This study aimed to use karyometry to detect nuclear abnormalities in fallopian tube epithelium from women at high risk for ovarian cancer compared to low risk women. Karyometry involves high-resolution imaging and quantitative analysis of nuclear features too small to be seen by the human eye. The study found distinct deviations in nuclear features and signatures in fallopian tubes from high risk women carrying BRCA1/2 alterations compared to normal risk women. Specifically, measures of pixel optical density heterogeneity and very dark stained pixels showed a statistically significant shift, identifying an abnormal morphometric phenotype in high risk women. The results suggest karyometry may help detect early changes and improve ovarian cancer screening.
This study explored the role of miR-630 in enhancing the chemotherapeutic sensitivity of BRCA1 mutant triple-negative breast cancer (TNBC) cell lines. The researchers found that combining carboplatin and gemcitabine chemotherapy with the PARP inhibitor olaparib upregulated miR-630 expression in BRCA1 mutant MDA-MB-436 and HCC1937 TNBC cell lines. Overexpression of miR-630 suppressed cell proliferation, migration, and invasion, whereas inhibition of miR-630 increased these effects. Therefore, miR-630 plays an important tumor suppressor role in increasing the chemotherapeutic sensitivity of PARP inhibitors for BRCA1 mutant TNBC, which may be one mechanism of how PAR
This study investigated the correlation between clinicopathologic characteristics and the ratio of stromal tumor-infiltrating lymphocytes (sTILs) in 638 patients with breast cancer. sTIL ratio was positively correlated with histologic grade, HER2 expression, Ki-67 expression and P53 expression, and negatively correlated with estrogen and progesterone receptor expression. A prediction model for sTILs was established using clinicopathologic parameters, which showed a correlation of 0.574 between theoretical and actual sTIL values. A second model was developed to predict lymphocyte-predominant breast cancer that showed a correlation of 0.373 between theoretical and actual values.
The document describes an experiment that aimed to establish a model of cardiomyocyte hypertrophy using cultured neonatal rat cardiomyocytes treated with angiotensin II (Ang II). The effects of rutin treatment on various markers of hypertrophy were then observed. Rutin treatment inhibited Ang II-induced increases in cardiomyocyte surface area, intracellular calcium levels, and expression of hypertrophy marker proteins. Rutin also inhibited decreases in calcium ATPase activity and nitric oxide levels caused by Ang II. The results suggest rutin has protective effects against Ang II-induced cardiomyocyte hypertrophy, potentially by regulating intracellular calcium handling and nitric oxide signaling.
This document discusses the use of immunohistochemistry in breast pathology. It covers several topics:
1. Analyzing prognostic markers like hormone receptors in breast cancer and their predictive value.
2. Using myoepithelial cell markers to help solve diagnostic dilemmas and distinguish lesions.
3. Identifying tumor subtypes and assessing diagnoses using markers like luminal vs basal.
4. Evaluating cell populations in proliferative breast lesions and assessing neoplasia vs hyperplasia.
Association of common palb2 polymorphisms with ovarian cancer a case control ...IJARIIT
Background: The partner and localizer of breast cancer 2 (PALB2) has an essential role in BRCA2 mediated DNA
double-strand break repair by serving as a bridging molecule and acting as the physical and functional link between BRCA1&
2 proteins. Truncating mutations in the PALB2 gene are rare but are thought to be associated with increased risk of developing
breast and /or ovarian cancer in different populations. The present study was designed to investigate the variants of PALB2 and
their association with OC.
Material &Methods: A total of 150 histopathologically confirmed ovarian cancer patients and 250 healthy age matched controls
were collected. Three SNPs c.2794 G/A( rs45624036), c.1010 T/C(rs45494092), and c.1676A/G(rs152451) of PALB2 gene were
selected and genotyped by ARMS-PCR followed by agarose gel electrophoresis. Appropriate statistical tests were applied to test
for the significance of the results.
Results: A significant association of G/A (rs45624036) in inheritance models was observed & at the allelic level, the A allele
conferred four-fold increased risk compared to G allele. Regarding T/C (rs45494092) polymorphism all the models revealed an
association with OC and C allele showing eight-fold increased risk. With respect to A/G (rs152451) polymorphism, the protective
role was observed in tested inheritance models in OC patients.
The Haplo analysis for the combination of all the three variants revealed increased risk with A-T-A and G-C-G
haplotypes.(OR=4.50 ;95%CI 1.85-10.94;p=0.001,OR=26.36 ;95%CI 2.33 -297.91;p= 0.0085), whereas other haplotypes
conferred a protective role in OC.
Conclusions: The present study suggests an essential role of PALB2 in the etiology of ovarian cancer.
The document discusses molecular testing for breast cancer. It describes how molecular testing can provide insights into breast cancer subtypes, predict response to treatments, and assess recurrence risk. Several molecular tests are discussed, including Oncotype DX, Mammaprint, Prosigna, and tumor sequencing to identify actionable mutations. Molecular profiling is becoming increasingly important for personalized prevention, diagnosis, and treatment of breast cancer.
Breast Cancer Trials And Tribulations Revised Oct 09fondas vakalis
This document summarizes several clinical trials conducted by the NCIC CTG on breast cancer treatment:
1. Trial MA.5 from 1989-1993 compared CEF vs CMF chemotherapy and found improved DFS and OS with CEF.
2. Trial MA.12 from 1993-2000 randomized premenopausal women to 5 years of tamoxifen or placebo after chemotherapy. It found improved but not statistically significant DFS and OS with tamoxifen. Compliance was suboptimal.
3. Correlative studies explored prognostic biomarkers like OPN and insulin resistance from several trials. OPN levels correlated with survival and may help determine management.
This study explored the role of miR-630 in enhancing the chemotherapeutic sensitivity of BRCA1 mutant triple-negative breast cancer (TNBC) cell lines. The researchers found that combining carboplatin and gemcitabine chemotherapy with the PARP inhibitor olaparib upregulated miR-630 expression in BRCA1 mutant MDA-MB-436 and HCC1937 TNBC cell lines. Overexpression of miR-630 suppressed cell proliferation, migration, and invasion, whereas inhibition of miR-630 increased these effects. Therefore, miR-630 plays an important tumor suppressor role in increasing the chemotherapeutic sensitivity of PARP inhibitors for BRCA1 mutant TNBC, which may be one mechanism of how PAR
This study investigated the correlation between clinicopathologic characteristics and the ratio of stromal tumor-infiltrating lymphocytes (sTILs) in 638 patients with breast cancer. sTIL ratio was positively correlated with histologic grade, HER2 expression, Ki-67 expression and P53 expression, and negatively correlated with estrogen and progesterone receptor expression. A prediction model for sTILs was established using clinicopathologic parameters, which showed a correlation of 0.574 between theoretical and actual sTIL values. A second model was developed to predict lymphocyte-predominant breast cancer that showed a correlation of 0.373 between theoretical and actual values.
The document describes an experiment that aimed to establish a model of cardiomyocyte hypertrophy using cultured neonatal rat cardiomyocytes treated with angiotensin II (Ang II). The effects of rutin treatment on various markers of hypertrophy were then observed. Rutin treatment inhibited Ang II-induced increases in cardiomyocyte surface area, intracellular calcium levels, and expression of hypertrophy marker proteins. Rutin also inhibited decreases in calcium ATPase activity and nitric oxide levels caused by Ang II. The results suggest rutin has protective effects against Ang II-induced cardiomyocyte hypertrophy, potentially by regulating intracellular calcium handling and nitric oxide signaling.
This document discusses the use of immunohistochemistry in breast pathology. It covers several topics:
1. Analyzing prognostic markers like hormone receptors in breast cancer and their predictive value.
2. Using myoepithelial cell markers to help solve diagnostic dilemmas and distinguish lesions.
3. Identifying tumor subtypes and assessing diagnoses using markers like luminal vs basal.
4. Evaluating cell populations in proliferative breast lesions and assessing neoplasia vs hyperplasia.
Association of common palb2 polymorphisms with ovarian cancer a case control ...IJARIIT
Background: The partner and localizer of breast cancer 2 (PALB2) has an essential role in BRCA2 mediated DNA
double-strand break repair by serving as a bridging molecule and acting as the physical and functional link between BRCA1&
2 proteins. Truncating mutations in the PALB2 gene are rare but are thought to be associated with increased risk of developing
breast and /or ovarian cancer in different populations. The present study was designed to investigate the variants of PALB2 and
their association with OC.
Material &Methods: A total of 150 histopathologically confirmed ovarian cancer patients and 250 healthy age matched controls
were collected. Three SNPs c.2794 G/A( rs45624036), c.1010 T/C(rs45494092), and c.1676A/G(rs152451) of PALB2 gene were
selected and genotyped by ARMS-PCR followed by agarose gel electrophoresis. Appropriate statistical tests were applied to test
for the significance of the results.
Results: A significant association of G/A (rs45624036) in inheritance models was observed & at the allelic level, the A allele
conferred four-fold increased risk compared to G allele. Regarding T/C (rs45494092) polymorphism all the models revealed an
association with OC and C allele showing eight-fold increased risk. With respect to A/G (rs152451) polymorphism, the protective
role was observed in tested inheritance models in OC patients.
The Haplo analysis for the combination of all the three variants revealed increased risk with A-T-A and G-C-G
haplotypes.(OR=4.50 ;95%CI 1.85-10.94;p=0.001,OR=26.36 ;95%CI 2.33 -297.91;p= 0.0085), whereas other haplotypes
conferred a protective role in OC.
Conclusions: The present study suggests an essential role of PALB2 in the etiology of ovarian cancer.
The document discusses molecular testing for breast cancer. It describes how molecular testing can provide insights into breast cancer subtypes, predict response to treatments, and assess recurrence risk. Several molecular tests are discussed, including Oncotype DX, Mammaprint, Prosigna, and tumor sequencing to identify actionable mutations. Molecular profiling is becoming increasingly important for personalized prevention, diagnosis, and treatment of breast cancer.
Breast Cancer Trials And Tribulations Revised Oct 09fondas vakalis
This document summarizes several clinical trials conducted by the NCIC CTG on breast cancer treatment:
1. Trial MA.5 from 1989-1993 compared CEF vs CMF chemotherapy and found improved DFS and OS with CEF.
2. Trial MA.12 from 1993-2000 randomized premenopausal women to 5 years of tamoxifen or placebo after chemotherapy. It found improved but not statistically significant DFS and OS with tamoxifen. Compliance was suboptimal.
3. Correlative studies explored prognostic biomarkers like OPN and insulin resistance from several trials. OPN levels correlated with survival and may help determine management.
This document discusses tumor dormancy and mechanisms by which cancer cells can evade immune detection and elimination. It describes how some cancer cells enter a dormant state after disseminating from primary tumors and residing long-term in bone marrow niches without proliferating. These dormant disseminated tumor cells can later reactivate and form metastases. The document also outlines a mouse model using E0771 breast cancer cells expressing a model antigen (ovalbumin) to study interactions between dormant tumor cells in bone marrow and antigen-specific T cells, with the goal of developing non-toxic therapies to eliminate dormant tumor cells or prevent their outgrowth into metastases.
SHARE: Metastatic Breast Cancer: Cutting-Edge Research from National Cancer w...bkling
Patricia Steeg, PhD, Chief of Women's Cancers Section at the Center for Cancer Research at NCI, will present her novel research relating to metastatic breast cancer, including the development of experimental models of brain metastasis. Join SHARE and Dr. Steeg for this nformative webinar.
Clinical and experimental studies regarding the expression and diagnostic val...Enrique Moreno Gonzalez
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional Ig-like cell adhesion molecule that has a wide range of biological functions. According to previous reports, serum CEACAM1 is dysregulated in different malignant tumours and associated with tumour progression. However, the serum CEACAM1 expression in nonsmall-cell lung carcinomas (NSCLC) is unclear. The different expression ratio of CEACAM1-S and CEACAM1-L isoform has seldom been investigated in NSCLC. This research is intended to study the serum CEACAM1 and the ratio of CEACAM1-S/L isoforms in NSCLC.
This document provides guidelines for the management of endometrial cancer from several European medical societies. It covers epidemiology, risk assessment, surgery, lymph node staging, adjuvant therapy, and management of early, advanced, and recurrent disease. Key points include recommending total hysterectomy and bilateral salpingo-oophorectomy for staging without vaginal cuff resection for early-stage disease. It also supports consideration of sentinel lymph node biopsy for staging in select cases and ovarian preservation in certain low-risk premenopausal patients. Molecular testing is encouraged to further stratify prognosis, especially in high-grade tumors.
The document discusses criteria for evaluating genomic tests, including whether the test is clinically meaningful, how it was validated, reliability, practicality, and cost-effectiveness. It emphasizes that tests must provide value beyond traditional measures and require multiple studies as evidence. Genomic tests are developed through a process similar to drug development, starting with initial studies to develop relevant profiles which are then validated in additional studies with prospective design. Sources of variability must be rigorously controlled and clinical context is important.
This document describes a case of a 73-year-old man who presented with neurological symptoms and was found to have a brain lesion that was determined to be a solitary cerebral metastasis. Further investigation did not reveal the primary site. The patient underwent resection of the brain lesion, which was determined to be metastatic prostate cancer based on histopathology. Subsequent multiparametric MRI of the prostate revealed a lesion highly suggestive of prostate cancer. The document argues that multiparametric MRI of the prostate should be included in the diagnostic workup for patients presenting with cerebral metastases of unknown primary, as it may help identify occult prostate primary cancers earlier and guide more targeted treatment.
The document discusses classification and treatment of triple negative breast cancer (TNBC). It begins with an overview of TNBC classification including molecular subtypes. It then describes the clinical characteristics and prognosis of TNBC compared to other breast cancer types. Treatment options discussed include chemotherapy with taxanes and platinum agents shown to be effective. Other potential targeted therapies mentioned include PARP inhibitors, EGFR inhibitors, angiogenesis inhibitors, and tyrosine kinase inhibitors.
The document discusses molecular subtyping of breast cancer through gene expression profiling which has identified major subtypes including luminal A, luminal B, HER2-enriched, and basal-like. It describes the characteristic gene expressions and clinical features of each subtype. Molecular subtyping is shown to have prognostic and predictive relevance for breast cancer outcomes and treatment responses.
BRCA1 Promoter Methylation and Clinicopathological Characteristics in Sporadi...UniversitasGadjahMada
1) The study investigated BRCA1 promoter methylation and its association with clinicopathological characteristics in 56 Indonesian breast cancer patients.
2) BRCA1 promoter methylation was detected in 48 of 56 (85%) patients. Lower BRCA1 mRNA expression was associated with higher methylation levels, suggesting epigenetic silencing of BRCA1.
3) However, no significant associations were found between methylation levels, BRCA1 expression, and clinicopathological factors like tumor stage or size. This study provides the first analysis of BRCA1 methylation in an Indonesian breast cancer population.
This study examined the association between the ACE gene polymorphism and breast cancer risk among Bengalee Hindu females in West Bengal, India. The researchers analyzed samples from 108 breast cancer patients and 128 controls without cancer. They found that the frequency of the DD genotype was higher in patients (57.4%) than controls (25.0%), with a significant association between the DD genotype and increased breast cancer risk. Binary logistic analysis also found the DD genotype was associated with family history of breast cancer, fewer children, and longer-term contraceptive pill use among patients. The results suggest the DD genotype may be useful for determining breast cancer occurrence and prognosis in this population.
This document discusses molecular profiling of breast cancer. It begins by introducing breast cancer as the most common cancer in women. It then discusses traditional classifications based on histological and clinical features. However, up to half of hormone receptor positive cancers do not respond to treatment, showing clinical classifications are insufficient. Molecular profiling uses high-throughput techniques to better understand breast cancer biology and refine classifications. Gene expression profiling has identified major molecular subtypes, like luminal A/B, HER2-positive, and basal-like. Multigene assays provide prognostic and predictive information beyond traditional clinics-pathological factors. Several common assays are discussed, including Oncotype DX, Mammaprint, and PAM50. Next generation sequencing is also discussed for
Recently, a phase II clinical trial in hepatocellular carcinoma (HCC) has suggested that the combination of sorafenib and 5-fluorouracil (5-FU) is feasible and side effects are manageable. However, preclinical experimental data explaining the interaction mechanism(s) are lacking. Our objective is to investigate the anticancer efficacy and mechanism of combined sorafenib and 5-FU therapy in vitro in HCC cell lines MHCC97H and SMMC-7721.
New research studies presented at the 2011 Annual Meeting of the American Urological Association examine promising biomarkers and genetic tests for bladder and prostate cancers. Certain genetic variants on chromosomes 8q24 and 19q13 were found to be associated with higher rates of prostate cancer aggressiveness. Combining measurements of the PCA3 and TMPRSS2:ERG tests improved the sensitivity and accuracy of prostate cancer diagnosis compared to the PCA3 test alone. Additionally, a urine assay measuring TMPRSS2:ERG gene fusion levels correlated with higher pathologic stage, Gleason score, and Gleason upgrading in prostate cancer patients. The studies suggest newer diagnostic tests may help distinguish between indolent and aggressive forms of prostate and bladder cancers.
A germline mutation in the brca1 3'utr predicts stage iv breast cancerDavid W. Salzman
1) A variant in the 3' untranslated region (3'UTR) of the BRCA1 gene was found to predict increased risk of stage IV breast cancer.
2) In vitro luciferase assays showed the variant reduced BRCA1 expression and altered response to stimuli compared to the normal 3'UTR.
3) Analysis of breast tumor tissue found reduced BRCA1 expression in patients with the variant, and patients with the variant had a 4-fold increased risk of stage IV disease.
- Three major molecular assays have been developed for prognostic assessment of breast cancer: Oncotype DX, Mammaprint, and Prosigna.
- Oncotype DX uses a 21-gene signature to predict recurrence risk in ER+ breast cancer. Mammaprint uses a 70-gene signature and Prosigna uses the PAM50 intrinsic subtyping algorithm.
- Clinical trials have validated the use of these assays in lymph node positive and negative disease to predict chemotherapy benefit and guide treatment decisions. Ongoing research aims to further refine risk assessment and subclassify breast cancer.
The study found that a cell cycle progression (CCP) gene expression signature can differentiate indolent from aggressive prostate cancer and provide prognostic information beyond standard clinical parameters. Specifically:
1) Higher CCP scores, indicating more actively dividing cells, were associated with increased risk of biochemical recurrence after prostatectomy and death from prostate cancer in a conservatively managed cohort.
2) The CCP score was a strong univariate predictor of outcome and added significant prognostic information when combined with clinical factors like PSA and Gleason score in multivariate analyses.
3) The CCP score was robust across different patient populations and clinical settings and may help physicians select optimal treatment strategies at diagnosis.
Current and emerging biomarkers of breast cancerRD-Fasiha Ahsan
The document summarizes current and emerging biomarkers for breast cancer. It discusses established biomarkers like p53, HER2, BRCA1, and BRCA2, which are involved in processes like DNA damage response and repair. Emerging biomarkers discussed include Ki-67, which is involved in cell proliferation, and Cyclin D1, which regulates cell cycle. The document also reviews how certain foods and dietary components can influence these biomarkers and potentially reduce breast cancer risk by promoting apoptosis, DNA repair, and reducing inflammation. Maintaining a healthy diet and lifestyle is recommended for breast cancer prevention and treatment.
This journal club discusses a study examining the effect of metformin use on cancer treatment outcomes in diabetic breast cancer patients undergoing neoadjuvant chemotherapy. The study found that diabetic breast cancer patients taking metformin had a higher pathologic complete response rate to neoadjuvant chemotherapy compared to diabetic patients not taking metformin or non-diabetic patients. Metformin use was also associated with improved overall survival compared to non-metformin users and non-diabetic patients. The advantages of metformin include its low cost, wide therapeutic index, potential as a broad-spectrum anticancer drug, and safety profile.
The document discusses Ki-67, a protein marker used to measure tumor cell proliferation in breast cancer. It describes how to count Ki-67 immunoreactive cells, including counting only tumor cells and expressing the result as a percentage. Standardizing Ki-67 assessment procedures and scoring could improve reproducibility. Ki-67 is a useful prognostic marker in breast cancer, especially when combined with other clinical pathology factors.
EIS Technology: bioimpedance chronoamperometry in adjunct to screen the prost...ES-Teck India
Through the 6 tactile electrodes, a weak DC current is sending alternatively between 2 electrodes with a sequence and the EIS system is recording the electrical conductance of 11 pathways of the human body.
This study aimed to predict the risk of malignancy in women with adnexal masses using preoperative factors. The researchers analyzed 395 patients and found:
1) Tumor morphology on ultrasound, elevated serum CA 125 levels, presence of ascites, and older age were associated with higher risk of malignancy.
2) Patients with solid or complex masses and CA 125 > 35 U/mL had a positive predictive value of 84.7% for malignancy.
3) Purely cystic masses had a 100% negative predictive value for ruling out malignancy.
4) The combination of complex/solid mass and elevated CA 125 best defined patients at high risk of ovarian cancer.
This document discusses tumor dormancy and mechanisms by which cancer cells can evade immune detection and elimination. It describes how some cancer cells enter a dormant state after disseminating from primary tumors and residing long-term in bone marrow niches without proliferating. These dormant disseminated tumor cells can later reactivate and form metastases. The document also outlines a mouse model using E0771 breast cancer cells expressing a model antigen (ovalbumin) to study interactions between dormant tumor cells in bone marrow and antigen-specific T cells, with the goal of developing non-toxic therapies to eliminate dormant tumor cells or prevent their outgrowth into metastases.
SHARE: Metastatic Breast Cancer: Cutting-Edge Research from National Cancer w...bkling
Patricia Steeg, PhD, Chief of Women's Cancers Section at the Center for Cancer Research at NCI, will present her novel research relating to metastatic breast cancer, including the development of experimental models of brain metastasis. Join SHARE and Dr. Steeg for this nformative webinar.
Clinical and experimental studies regarding the expression and diagnostic val...Enrique Moreno Gonzalez
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional Ig-like cell adhesion molecule that has a wide range of biological functions. According to previous reports, serum CEACAM1 is dysregulated in different malignant tumours and associated with tumour progression. However, the serum CEACAM1 expression in nonsmall-cell lung carcinomas (NSCLC) is unclear. The different expression ratio of CEACAM1-S and CEACAM1-L isoform has seldom been investigated in NSCLC. This research is intended to study the serum CEACAM1 and the ratio of CEACAM1-S/L isoforms in NSCLC.
This document provides guidelines for the management of endometrial cancer from several European medical societies. It covers epidemiology, risk assessment, surgery, lymph node staging, adjuvant therapy, and management of early, advanced, and recurrent disease. Key points include recommending total hysterectomy and bilateral salpingo-oophorectomy for staging without vaginal cuff resection for early-stage disease. It also supports consideration of sentinel lymph node biopsy for staging in select cases and ovarian preservation in certain low-risk premenopausal patients. Molecular testing is encouraged to further stratify prognosis, especially in high-grade tumors.
The document discusses criteria for evaluating genomic tests, including whether the test is clinically meaningful, how it was validated, reliability, practicality, and cost-effectiveness. It emphasizes that tests must provide value beyond traditional measures and require multiple studies as evidence. Genomic tests are developed through a process similar to drug development, starting with initial studies to develop relevant profiles which are then validated in additional studies with prospective design. Sources of variability must be rigorously controlled and clinical context is important.
This document describes a case of a 73-year-old man who presented with neurological symptoms and was found to have a brain lesion that was determined to be a solitary cerebral metastasis. Further investigation did not reveal the primary site. The patient underwent resection of the brain lesion, which was determined to be metastatic prostate cancer based on histopathology. Subsequent multiparametric MRI of the prostate revealed a lesion highly suggestive of prostate cancer. The document argues that multiparametric MRI of the prostate should be included in the diagnostic workup for patients presenting with cerebral metastases of unknown primary, as it may help identify occult prostate primary cancers earlier and guide more targeted treatment.
The document discusses classification and treatment of triple negative breast cancer (TNBC). It begins with an overview of TNBC classification including molecular subtypes. It then describes the clinical characteristics and prognosis of TNBC compared to other breast cancer types. Treatment options discussed include chemotherapy with taxanes and platinum agents shown to be effective. Other potential targeted therapies mentioned include PARP inhibitors, EGFR inhibitors, angiogenesis inhibitors, and tyrosine kinase inhibitors.
The document discusses molecular subtyping of breast cancer through gene expression profiling which has identified major subtypes including luminal A, luminal B, HER2-enriched, and basal-like. It describes the characteristic gene expressions and clinical features of each subtype. Molecular subtyping is shown to have prognostic and predictive relevance for breast cancer outcomes and treatment responses.
BRCA1 Promoter Methylation and Clinicopathological Characteristics in Sporadi...UniversitasGadjahMada
1) The study investigated BRCA1 promoter methylation and its association with clinicopathological characteristics in 56 Indonesian breast cancer patients.
2) BRCA1 promoter methylation was detected in 48 of 56 (85%) patients. Lower BRCA1 mRNA expression was associated with higher methylation levels, suggesting epigenetic silencing of BRCA1.
3) However, no significant associations were found between methylation levels, BRCA1 expression, and clinicopathological factors like tumor stage or size. This study provides the first analysis of BRCA1 methylation in an Indonesian breast cancer population.
This study examined the association between the ACE gene polymorphism and breast cancer risk among Bengalee Hindu females in West Bengal, India. The researchers analyzed samples from 108 breast cancer patients and 128 controls without cancer. They found that the frequency of the DD genotype was higher in patients (57.4%) than controls (25.0%), with a significant association between the DD genotype and increased breast cancer risk. Binary logistic analysis also found the DD genotype was associated with family history of breast cancer, fewer children, and longer-term contraceptive pill use among patients. The results suggest the DD genotype may be useful for determining breast cancer occurrence and prognosis in this population.
This document discusses molecular profiling of breast cancer. It begins by introducing breast cancer as the most common cancer in women. It then discusses traditional classifications based on histological and clinical features. However, up to half of hormone receptor positive cancers do not respond to treatment, showing clinical classifications are insufficient. Molecular profiling uses high-throughput techniques to better understand breast cancer biology and refine classifications. Gene expression profiling has identified major molecular subtypes, like luminal A/B, HER2-positive, and basal-like. Multigene assays provide prognostic and predictive information beyond traditional clinics-pathological factors. Several common assays are discussed, including Oncotype DX, Mammaprint, and PAM50. Next generation sequencing is also discussed for
Recently, a phase II clinical trial in hepatocellular carcinoma (HCC) has suggested that the combination of sorafenib and 5-fluorouracil (5-FU) is feasible and side effects are manageable. However, preclinical experimental data explaining the interaction mechanism(s) are lacking. Our objective is to investigate the anticancer efficacy and mechanism of combined sorafenib and 5-FU therapy in vitro in HCC cell lines MHCC97H and SMMC-7721.
New research studies presented at the 2011 Annual Meeting of the American Urological Association examine promising biomarkers and genetic tests for bladder and prostate cancers. Certain genetic variants on chromosomes 8q24 and 19q13 were found to be associated with higher rates of prostate cancer aggressiveness. Combining measurements of the PCA3 and TMPRSS2:ERG tests improved the sensitivity and accuracy of prostate cancer diagnosis compared to the PCA3 test alone. Additionally, a urine assay measuring TMPRSS2:ERG gene fusion levels correlated with higher pathologic stage, Gleason score, and Gleason upgrading in prostate cancer patients. The studies suggest newer diagnostic tests may help distinguish between indolent and aggressive forms of prostate and bladder cancers.
A germline mutation in the brca1 3'utr predicts stage iv breast cancerDavid W. Salzman
1) A variant in the 3' untranslated region (3'UTR) of the BRCA1 gene was found to predict increased risk of stage IV breast cancer.
2) In vitro luciferase assays showed the variant reduced BRCA1 expression and altered response to stimuli compared to the normal 3'UTR.
3) Analysis of breast tumor tissue found reduced BRCA1 expression in patients with the variant, and patients with the variant had a 4-fold increased risk of stage IV disease.
- Three major molecular assays have been developed for prognostic assessment of breast cancer: Oncotype DX, Mammaprint, and Prosigna.
- Oncotype DX uses a 21-gene signature to predict recurrence risk in ER+ breast cancer. Mammaprint uses a 70-gene signature and Prosigna uses the PAM50 intrinsic subtyping algorithm.
- Clinical trials have validated the use of these assays in lymph node positive and negative disease to predict chemotherapy benefit and guide treatment decisions. Ongoing research aims to further refine risk assessment and subclassify breast cancer.
The study found that a cell cycle progression (CCP) gene expression signature can differentiate indolent from aggressive prostate cancer and provide prognostic information beyond standard clinical parameters. Specifically:
1) Higher CCP scores, indicating more actively dividing cells, were associated with increased risk of biochemical recurrence after prostatectomy and death from prostate cancer in a conservatively managed cohort.
2) The CCP score was a strong univariate predictor of outcome and added significant prognostic information when combined with clinical factors like PSA and Gleason score in multivariate analyses.
3) The CCP score was robust across different patient populations and clinical settings and may help physicians select optimal treatment strategies at diagnosis.
Current and emerging biomarkers of breast cancerRD-Fasiha Ahsan
The document summarizes current and emerging biomarkers for breast cancer. It discusses established biomarkers like p53, HER2, BRCA1, and BRCA2, which are involved in processes like DNA damage response and repair. Emerging biomarkers discussed include Ki-67, which is involved in cell proliferation, and Cyclin D1, which regulates cell cycle. The document also reviews how certain foods and dietary components can influence these biomarkers and potentially reduce breast cancer risk by promoting apoptosis, DNA repair, and reducing inflammation. Maintaining a healthy diet and lifestyle is recommended for breast cancer prevention and treatment.
This journal club discusses a study examining the effect of metformin use on cancer treatment outcomes in diabetic breast cancer patients undergoing neoadjuvant chemotherapy. The study found that diabetic breast cancer patients taking metformin had a higher pathologic complete response rate to neoadjuvant chemotherapy compared to diabetic patients not taking metformin or non-diabetic patients. Metformin use was also associated with improved overall survival compared to non-metformin users and non-diabetic patients. The advantages of metformin include its low cost, wide therapeutic index, potential as a broad-spectrum anticancer drug, and safety profile.
The document discusses Ki-67, a protein marker used to measure tumor cell proliferation in breast cancer. It describes how to count Ki-67 immunoreactive cells, including counting only tumor cells and expressing the result as a percentage. Standardizing Ki-67 assessment procedures and scoring could improve reproducibility. Ki-67 is a useful prognostic marker in breast cancer, especially when combined with other clinical pathology factors.
EIS Technology: bioimpedance chronoamperometry in adjunct to screen the prost...ES-Teck India
Through the 6 tactile electrodes, a weak DC current is sending alternatively between 2 electrodes with a sequence and the EIS system is recording the electrical conductance of 11 pathways of the human body.
This study aimed to predict the risk of malignancy in women with adnexal masses using preoperative factors. The researchers analyzed 395 patients and found:
1) Tumor morphology on ultrasound, elevated serum CA 125 levels, presence of ascites, and older age were associated with higher risk of malignancy.
2) Patients with solid or complex masses and CA 125 > 35 U/mL had a positive predictive value of 84.7% for malignancy.
3) Purely cystic masses had a 100% negative predictive value for ruling out malignancy.
4) The combination of complex/solid mass and elevated CA 125 best defined patients at high risk of ovarian cancer.
New research studies presented at the 2011 Annual Meeting of the American Urological Association examine promising biomarkers and genetic tests for bladder and prostate cancers. Certain genetic variants on chromosomes 8q24 and 19q13 were found to be associated with higher rates of prostate cancer aggressiveness. Combining measurements of the PCA3 and TMPRSS2:ERG tests improved the sensitivity and accuracy of prostate cancer diagnosis compared to the PCA3 test alone. Additionally, a urine assay measuring TMPRSS2:ERG gene fusion levels correlated with higher pathologic stage, Gleason score, and Gleason upgrading in prostate cancer patients. The studies suggest newer diagnostic tests may help distinguish between indolent and aggressive forms of prostate and bladder cancers.
Colorectal cancer is the second leading cause of cancer death in western countries. Early detection through screening can prevent over 50% of deaths, but screening rates remain low. Current noninvasive screening methods like fecal occult blood tests (FOBT) have limitations in sensitivity and specificity. Blood markers like CEA, LASA, and CA19-9 are not adequate screening tools. Stool markers show more promise, like immunochemical FOBT, colonocytes, and stool DNA testing which can detect mutations. While promising, stool DNA testing needs more research on cost effectiveness and patient acceptance before being recommended for general screening. Overall, no single marker is sufficient for screening and early detection remains a challenge.
Toward Integrated Clinical and Gene Expression Profiles for Breast Cancer Pro...CSCJournals
Breast cancer patients with the same diagnostic and clinical prognostic profile can have markedly different clinical outcome. This difference is possibly caused by the limitation of current breast cancer prognostic indices, which group molecularly distinct patients into similar clinical classes based mainly on morphological of disease. Traditional clinical based prognosis models were discovered contain some restriction to address the heterogeneity of breast cancer. The invention of microarray technology and its ability to simultaneously interrogate thousands genes has changed the paradigm of molecular classification of human cancers as well as it shifted clinical prognosis model to broader prospect. Numerous studies have revealed the potential value of gene expression signatures in examining the risk of disease recurrence. However, currently most of these studies attempted to implement genetic marker based prognostic models to replace the traditional clinical markers, yet neglecting the rich information contain in clinical information. Therefore, this research took an effort to integrate both clinical and microarray data in order to obtain accurate breast cancer prognosis, by taking into account that these data complements each other. This article presents a review of the development of breast cancer prognosis models, concentrating precisely on clinical and gene expression profiles. The literature is reviewed in an explicit machine learning framework, which include the elements of feature selection and classification techniques.
Pancreatic cancer has a high mortality rate because it is often diagnosed late after metastasizing. Early detection is difficult because symptoms usually do not appear until it has spread. This paper aims to integrate multi-omic data like genomics, proteomics, and imaging into a predictive model to better classify pancreatic cancer patients. The goal is to identify novel biomarkers and pathways to advance early detection and personalized treatment.
This study aimed to develop an unbiased RNA profiling approach for the early detection of colorectal cancer (CRC) and advanced adenomas (AA) using blood samples. The researchers combined a literature review with microarray analysis of circulating RNA purified from plasma to identify RNA biomarker panels. They tested the panels on two cohorts, detecting CRC with 75% sensitivity and 93% specificity using an 8-gene panel, and detecting AA with 60% sensitivity and 87% specificity using a 2-gene panel. The study demonstrates the feasibility of unbiased molecular diagnosis of CRC and AA from blood and introduces circulating RNA profiling as a potential non-invasive screening approach.
Nuclear imaging techniques play various roles in prostate cancer assessment and management. Conventional bone scintigraphy using technetium-99m is effective for detecting bone metastases, though it lacks specificity. PET tracers like FDG have limited utility in prostate cancer due to typically low glucose metabolism in prostate tumors. However, PET may help stage more aggressive primary tumors or locate recurrent disease when conventional imaging is negative. Newer tracers targeting prostate-specific membrane antigen (PSMA) show promise, with radioimmunoscintigraphy using Indium-111-capromab demonstrating reasonable sensitivity and specificity for detecting prostate cancer lesions.
Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell...semualkaira
anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy
Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell...semualkaira
anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy. Several studies reported a sex disparity
in ASCC prognosis showing a better survival for female compared
to men. Methods: we examined 1,380 patients with ASCC who received comprehensive genomic profiling as part of routine clinical
care and present key
Understanding Uterine Cancer Treatment Optionsbkling
Join Dr. Bhavana Pothuri, gynecologic oncologist at NYU Langone Medical Center, as she breaks down the different types of uterine cancer treatments available to patients based on their particular diagnosis. Learn about new research and treatment updates, options for when cancer recurs, side effects, and more.
This document presents a study on developing an automated screening technique for cervical cancer using differential interference contrast microscopy and machine learning algorithms. The study aims to differentiate between normal, pre-invasive, and invasive cervical cells based on their morphological features in images. A total of 50 patient samples will be analyzed over 18 months. Statistical analysis will be conducted to calculate sensitivity, specificity, and predictive values of the new screening method. Preliminary results found a sensitivity of 90%, 70%, and 100% for normal, pre-cancer, and cancer cells respectively. The study aims to develop a fast and effective automated cervical cancer screening tool.
This document provides an overview and updates on prostate cancer pharmacotherapies. It discusses the anatomy and physiology of the prostate, risk factors for prostate cancer like diet and genetics, screening methods including PSA tests and digital rectal exams, diagnostic workup involving imaging and biopsies, tumor staging using Gleason scores and TNM classification, and treatment strategies at different stages including radiation, surgery, and hormone therapies. Controversies around PSA screening and increasing legal risks for failure to diagnose are also reviewed.
International Journal of Biometrics and Bioinformatics(IJBB) Volume (3) Issue...CSCJournals
This document reviews approaches for predicting breast cancer prognosis using both clinical data and gene expression profiles. Traditional prognosis models rely mainly on clinical factors like age, tumor size, and lymph node status, but can fail to distinguish molecularly distinct subgroups. Gene expression profiling via microarray technology has improved molecular classification and shown promise for prognosis. However, most studies have focused on gene signatures without fully leveraging clinical data. Integrating clinical and gene expression data may enhance accuracy by accounting for their complementary nature. The review discusses feature selection and classification methods applied to both data types, as well as related work on data integration. The goal is to develop an improved prognosis model that incorporates both clinical and molecular factors.
Diagonsis of cancer through saliva.pptxZaidAhmad42
Human saliva is an ideal body fluid for developing non-invasive diagnostics. Saliva contains naturally-occurring nanoparticles with unique structural and biochemical characteristics.
A convenient clinical nomogram for small intestine adenocarcinomanguyên anh doanh
The document describes a study that developed a nomogram to predict cancer-specific survival for patients with small-intestine adenocarcinoma. Researchers analyzed data on 4,971 patients from the SEER database and identified 8 factors associated with survival: age, sex, marital status, insurance status, grade, stage, surgery status, and chemotherapy. These factors were used to create a nomogram that assigns a score to each variable to predict 3- and 5-year survival probabilities. Validation tests found the nomogram predicted survival more accurately than the AJCC staging system and closely matched actual survival rates.
Prostate cancer molecular bio markers seminarHarshaR35
This document discusses various molecular biomarkers for prostate cancer that have been approved by regulatory agencies or are under investigation. It begins by providing background on prostate cancer statistics and the rationale for biomarkers. It then discusses currently approved blood-based biomarkers like PSA, PHI, and 4Kscore. Circulating tumor cells and cell-free DNA are also mentioned. Finally, it briefly summarizes urine-based biomarkers like PCA3 and potential new serum protein panels. In general, the document reviews both established and emerging liquid and tissue-based biomarkers that could improve prostate cancer screening, diagnosis, and monitoring.
DIFFERENT IMAGING MODALITIES USED FOR THE DETECTION OF PROSTATE CANCER – A RE...IRJET Journal
The document discusses various imaging modalities used to detect prostate cancer, including multiparametric ultrasound, multiparametric MRI, MRI-ultrasound fusion imaging, and positron emission tomography. It provides details on prostate anatomy, cancer grading, and treatment options to provide context. The modalities are compared in terms of their ability to detect characteristics like tissue alterations, angiogenesis, and metastatic spread. Limitations and potential improvements to the modalities are also reviewed.
- The Personalized OncoGenomics (POG) program at the British Columbia Cancer Agency conducted whole-genome analysis on tumors from 100 patients with advanced or incurable cancers to inform treatment decisions.
- Fresh tumor and blood samples were obtained from patients and underwent whole-genome and RNA sequencing. Computational analysis identified potential driver mutations, genes and pathways.
- A multidisciplinary team discussed genomic findings weekly and established guidelines for interpreting and communicating results to integrate them into patient care. Genomic findings were considered actionable in 55 of 78 cases that underwent whole-genome analysis, and motivated treatment changes in 23 cases.
- The experience demonstrated that a multidisciplinary team can implement an approach where whole-genome
Similar to Karyometry Identifies a Distinguishing Fallopian Tube Epithelium Phenotype in Subjects at High Risk for Ovarian Cancer (20)
BACKGROUND: Sequential Epstein-Barr virus (EBV)–positive B cell lymphoma to the initial diagnosis of angioimmunoblastic T cell lymphoma (AITL) is very rare, the exact mechanism and standard therapy of which is still being explored. CASE: A 50-year-old man was admitted to our hospital in January 2014 with a three-week history of enlargement of multiple lymph nodes. His initial pathological evaluation indicated AILT. The reactivation of EBV was observed during the immunosuppression therapy for AITL, accompanied by onset of subcutaneous nodules proven to be EBV-positive diffuse large B cell lymphoma (DLBCL) based on the pathological findings of rebiopsy. The patient was successfully treated with chidamide, a histone deacetylase (HDAC) inhibitor, and rituximab.
Conclusion: The sufficient surveillance for serum EBV and repeat biopsy is necessary for patients with AITL, and this treatment modality may become an active option.
Keywords: angioimmunoblastic T cell lymphoma, Epstein-Barr virus, HDAC inhibitor, non-Hodgkin lymphoma, peripheral T cell lymphoma
The study investigated the protective effects of losartan, an angiotensin II type 1 receptor blocker, on intestinal ischemia-reperfusion injury in rats. Forty rats were divided into four groups: sham operation, ischemia, ischemia/reperfusion (I/R), and I/R + losartan treatment. Biochemical markers and histopathological analysis of the jejunum tissue were performed. Losartan treatment reduced oxidative stress markers, inflammation, and apoptosis compared to the I/R group. This suggests losartan may protect against intestinal damage caused by ischemia-reperfusion injury.
Objective: The association between telomerase reverse transcriptase (TERT) promoter mutation and outcome of melanoma is unclear and controversial. We aim to conduct a meta-analysis and investigate whether the TERT promoter mutation is a prognostic factor of melanoma.
Study Design: Appropriate studies were searched in 3 databases: PubMed, Web of Science, and Embase. Pooled hazard ratios (HRs) were counted through random effects model.
Results: Heterogeneity was moderate in overall survival (OS) (I2=43.7%, p=0.059) and low in disease-free survival (DFS) (I2=0.0%, p=0.587). Sensitivity analysis indicated that the removal of any of the study did not affect the final results. Evidence for publication bias was not found (Begg’s test, p=0.281; Egger’s test, p=0.078). The pooled OS HRs from combined effects analysis was determined (HR 1.07; 95% CI 0.83–1.39, p=0.585), together with the pooled HRs of DFS (HR 1.65; 95% CI 1.02–2.66, p=0.042). TERT promoter mutation predicted a good outcome in meta-static melanoma patients (HR 0.66; 95% CI 0.46–0.96, p=0.042). The pooled HRs of combined mutation in TERT promoter and BRAF (HR 6.27; 95% CI 2.7–14.58, p=0.000) predicted a bad outcome in melanoma patients.
Conclusion: TERT promoter mutation significantly predicted poor DFS outcome but, on the contrary, predicted a good outcome in metastatic melanoma patients. The combined TERT promoter and BRAF mutation was a significant independent factor of OS in melanoma patients.
Keywords: melanoma; meta-analysis; mutation; prognosis; promoter regions, genetic; skin neoplasms; telomerase; TERT promoter mutation; TERT protein, human
Objective: In order to reduce complications accompanied with dental implant restoration, this study strives to prepare a novel sealant and lubricant that can be used in dental implant systems as well as to evaluate its characteristics.
Study Design: Chitosan (CS), β-glycerophosphate pentahydrate (β-GP), and nano silver (nAg) were used to prepare thermosensitive hydrogel. According to the different volume ratios of CS to β-GP, 3 experimental groups were established, namely 16/4, 13/7, and 10/10 groups. Their morphology, composition, and chemical properties were analyzed via SEM, EDS, and FTIR. In addition, the effect of the hydrogel on the stability of dental implant-abutment connection was investigated by removal torque test combined with dynamic cyclic loading experiment. The maximum fracture load was measured under different lubricating conditions by electronic universal testing machine. The cytotoxicity and in vitro antibacterial effect of the hydrogel were examined respectively by CCK-8 test and the spread plate method.
Results: The CS/β-GP/nAg thermosensitive hydro-gel was successfully prepared in this study, which was found to be a porous structure through SEM. The removal torque test and the dynamic cyclic loading experiment showed that the removal torque of the experimental group was greater than that of the control group. Furthermore, the single load-to-fracture test indicated that the 16/4 group had the greatest maximum bearing load. The in vitro cytotoxicity test using rat bone marrow stromal cells (rBMSCs) and human gingival fibroblast cells (hGFCs) showed no cytotoxicity in all 3 groups. The 3 experimental groups had obvious antibacterial effects against E. coli, S. aureus, and P. gingivalis.
Conclusion: A nontoxic antibacterial CS/β-GP/nAg thermosensitive hydrogel for lubricating purpose was successfully fabricated. When the volume ratio of CS to β-GP was 16/4, this thermosensitive hydrogel demonstrated better sealing and lubricating abilities and had a positive influence on the reliability of dental implant-abutment connection.
Keywords: abutment, dental implant, dental implant restoration, dental sealant, lubrication, thermosensitive hydrogel
Objective: To investigate the bond strength of resin-modified glass ionomer enhanced with bioactive glass (Activa BioActive-Base/Liner) to composite resin using different dental adhesive systems.
Study Design: In this study, Activa BioActive-Base/Liner (ABA/BL) was placed in cylindrical cavities formed in acrylic blocks. In blocks divided into 6 groups according to the adhesive system to be applied, two-step etch-and-rinse Gluma 2 Bond (Heraeus Kulzer, Germany), one-step self-etch Gluma Self Etch (Heraeus Kulzer), universal system Gluma Universal (Heraeus Kulzer), two-step self-etch Clearfil SE Protect (Kuraray, Japan), one-step self-etch Clearfil S3 Bond Plus (Kuraray), and universal system Clearfil S3 Bond Universal (Kuraray) adhesive systems were applied on ABA/BL. After composite resin (3M ESPE Filtek Ultimate) was applied to the prepared surfaces, the specimens were placed in a universal test device and shear bond strength test was determined. Fracture types were evaluated using a stereomicroscope and scanning electron microscope. Data were analyzed by Shapiro-Wilk, two-way ANOVA, Kruskal-Wallis, and Post-Hoc Multiple Comparisons tests.
Results: In terms of bond strength values, the highest bond value was seen in the two-step self-etch (Clearfil SE Protect) group, and the lowest bond strength value was seen in the universal system (Clearfil S3 Bond Universal) group. There was no statistically significant difference between the adhesive agent groups in terms of bond strength values (p>0.05).
Conclusion: It is thought that choosing the two-step self-etch technique as an adhesive system when resin-modified glass ionomer enhanced with bioactive glass (ABA/BL) is used as the pulp capping/base material will be more appropriate in terms of bond strength.
Keywords: adhesive systems, bioactive materials, bond strength, cariostatic agents, composite resins, dental materials, fluorides, glass ionomer, glass ionomer cements, materials testing, vital pulp therapy
Objective: To analyze the sonographic features of different histopathological subtypes of borderline ovarian tumors (BOTs) confirmed by pathology, and to study the ultrasound performances of various types in borderline ovarian tumors.
Study Design: Retrospective analysis was performed on the pathological results and ultrasound projection findings of 129 patients diagnosed as BOTs by ultrasound department of our hospital from January 2012 to November 2019. All patients were confirmed by surgical pathology and scanned consecutively by the investigators using transabdominal or transvaginal ultrasound examination.
Results: Serous borderline tumors (SBOTs) were observed, and the prevalence rate (53%) was significantly higher than that of other subtypes, and the probability of bilateral lesions was higher (40%). The sonogram often showed ultrasound features of papillary neoplasm in the lesion and good internal echo (p<0.05). Mucinous borderline ovarian tumors (MBOTs) were mostly unilateral lesions (86%). The prevalence was second only to SBOTs. Histomorphological examinations were divided into gastrointestinal-type and endocervical-type. Among them, the gastrointestinal type of MBOTs were mostly unilateral, and their incidence was higher than that of endocervical-type of MBOTs. Compared with other pathological subtypes, the gastrointestinal type is more likely to show the sonographic characteristics of huge space occupying in the pelvic and abdominal cavity (mean diameter >10 cm), polycystic, multiple septums, and poor internal echo (p<0.05). The ultrasonographic features of the endocervical-type of MBOTs were similar to those of SBOTs. Compared with gastrointestinal type, the sonographic images showed smaller lesion diameter, less septal or cyst, and more papillary excrescences in the tumor (p<0.05). The borderline clear cell tumor is the intermediate transition between the clear cell adenofibroma and the clear cell carcinoma. The clinical manifestations are diverse and lack specificity. The histology of sonography was mainly solid, and the multiple microcapsules were honeycomb-like. It can also be shown as cystic. Among the 169 patients with BOTs, 20 cases of SBOTs, 17 cases of MBOTs, and 10 cases of other rare subtypes were complicated with other diseases or multiple subtypes. This study did not find significant ultrasonic characteristics were used for distinguish them from other subtypes.
Conclusion: BOTs is a common disease in women during the reproductive period. It is characterized by the development of malignant tumors. Its clinical and pathological subtypes are complex and diverse. It leads many doctors to use the terms “large pelvic mass” and “solid ovarian mass” for diagnosis because of their lack of experience and understanding.
Keywords: adenocarcinoma, mucinous; adenocarcinoma, serous; borderline ovarian tumors; diagnostic imaging; ovarian neoplasms; papillary neoplasms; prognosis; transvaginal ultrasound, ultrasonography
Objective: To evaluate the results of the effect of nebivolol on tibial bone defect and graft application in new bone development in the rat.
Study Design: Thirty Wistar albino rats were divided into 3 groups. In the Control group, tibia bone defect was created without any treatment. In the Defect+ Graft group, allograft treatment was performed by forming a 6 mm tibial bone defect. In the Defect+Graft+ Nebivolol group, alloplastic bone graft was placed in the calvarial bone defect and then nebivolol (0.34 mg/mL solution/day) treatment was intraperitoneally applied for 28 days.
Results: Histopathological examination revealed inflammation in the defect area, congestion in the vessels, degeneration in collagen fibers, and an increase in osteoclast cells. There was an increase in inflammation and blood vessel structure in graft application, and osteoblastic activity matrix formation after reorganization nebivolol application in collagen fibers. Osteonectin expression was positive in the collagen fiber and matrix, starting in the Graft group, in osteoblasts, whereas in the Nebivolol group, osteoblasts increased in osteocytes and new bone formation.
Conclusion: Nebivolol is thought to have a positive effect on osteoinductive bone growth factors and contribute to the cell-matrix interaction, in addition to the supporting effect of the graft with its antioxidative effect.
Keywords: allograft; bone; bone regeneration; disease models, animal; nebivolol; orthopedic procedures; osteonectin; rats; tibia; tibial defect
Objective: The prognostic indictors of age-related poor outcomes in patients with acute myeloid leukemia (AML) are still controversial. The aim of this work was to provide comprehensive insights into the effect of different hemocytes and to investigate the association between age and clinical features in adult patients with AML.
Study Design: A retrospective study was performed to determine the role of age in the therapeutic outcomes of AML. A total of 166 newly diagnosed adult patients’ data from January 2015 to November 2019 in Zhongshan Hospital of Xiamen University were collected and analyzed.
Results: Older patients presented a poorer prognosis (p=0.001) with shorter overall survival, which is served as age-related outcomes. Binary logistic regression demonstrated that cytogenetic risk (OR=4.508, 95% CI 2.733–7.435), leukocyte (OR=7.410, 95% CI 1.139–5.910), and bone marrow blast cells (OR=3.261, 95% CI 1.075–5.615) were independent indictors for age-related prognosis. In addition, Kaplan-Meier curve also revealed that the above factors were associated with overall survival (all p values <0.001).
Conclusion: Cytogenetic risk, leukocyte, and bone marrow blast cells are dominant factors which account for the age-related poor outcomes and shorter overall survival in AML.
Keywords: acute myeloid leukemia, adult, cytogenetic risk, hemocyte, leukemia, overall survival
This study investigated the effects of intracoronary nicorandil and tirofiban on no-reflow phenomenon and clinical outcomes in 438 patients with acute coronary syndrome undergoing percutaneous coronary intervention. Both nicorandil and tirofiban improved TIMI blood flow grades after PCI, with TIMI grade 3 flow in 85.2% and 81.4% of patients respectively. There was no significant difference in major adverse cardiac events between the two groups. The study concluded that intracoronary nicorandil can improve coronary perfusion in ACS patients, but its effect on long-term prognosis requires further research.
Objective: To identify interstitial cells of Cajal (ICC) in the common bile duct of Kunming mice.
Study Design: Common bile ducts obtained from the Kunming mice were prepared for immunohistochemical investigations using the c-kit antibody. Immunoelectron microscopy was used to detect the expression of c-kit in the ICC of the common bile duct. Transmission electron microscopy showed ultrastructure of ICC in the murine bile duct. Reverse transcription–polymerase chain reaction (RT-PCR) and western blot were used to confirm the expression of mRNA specific for the c-kit gene and production of c-kit protein in the Kunming mice common bile duct.
Results: Immunohistochemistry revealed that ICC in the murine common bile duct are c-kit positive and the ICC are located in the tela submucosa and the tunica muscularis of the murine common bile duct and do not connect with each other. Immunoelectron microscopy confirmed the expression of Kit by ICC in the murine common bile duct. Transmission electron microscopy showed that ICC in the murine common bile duct have long processes, abundant mitochondria, plenty of smooth endoplasmic reticulum (sER), a lot of lysosomes, and dense bodies. The caveolae of ICC are distinctive. At the same time, RT-PCR indicated that the Kunming mice common bile duct expressed mRNA specific for the c-kit gene, and western blot analysis showed the evidence of production of c-kit protein in the Kunming mice common bile duct.
Conclusion: ICC are found in the Kunming mice common bile duct, which is likely to lead to the development of motility study of the common bile duct.
Keywords: common bile duct; electron microscopy; immuno-electron microscopy; interstitial cells of Cajal; intestines; smooth muscle; tyrosine kinase receptor (c-kit)
Objective: To study the effects of resveratrol in neuronal structures in traumatic brain injury (TBI).
Study Design: Thirty rats were categorized as (1) control group (n=10), saline solution administered i.p. for 14 days, (2) TBI group (n=10), trauma induced by weight-drop model on brain, and (3) TBI+Resveratrol group (n=10), 15 minutes after injury the rats were given resveratrol (10 μmoL/kg/i.p.) for 14 days. At the end of the experiment the cerebellum was excised for routine paraffin tissue protocol. Blood samples were tested for serum biochemical markers (MDA, SOD, CAT, and GSH-x).
Results: SOD, GPx, and CAT values were lowest in the TBI group. MDA and histological scores of dilations in vessels, inflammation, degeneration in neurons, apoptosis in microglia, ADAMTS8, and GFAP expressions were highest in the TBI group. Sections of the control group showed normal cerebellar histology. The trauma group showed degenerated ganglion layer, pyknotic and apoptotic Purkinje cell nuclei. Vascular thrombus was seen in the substantia alba and substantia grisea. In the Trauma+Resveratrol group, most pa- thologies observed in the TBI group were improved. In the control group, GFAP protein was expressed in granular cells, axons, dendrites, Purkinje cells, and microglia cells. In the trauma group, increased GFAP expression was observed in glial processes, neurons, and Purkinje cells. In the Trauma+Resveratrol group, GFAP was expressed in molecular layer and glial processes. In the control group, ADAMTS-4 activity was observed in granulosa layer, glial cells, and Purkinje cells. In the trauma group, ADAMTS-4 expression was positive in Purkinje cells and glial cells. In the Trauma+ Resveratrol group, ADAMTS-4 was expressed in Purkinje cells, granular cells, and glial cells.
Conclusion: GFAP and ADAMTS-4 proteins may be involved in regeneration of damaged astroglial cells and other glial cells, Purkinje cells, and synaptic extensions. We suggest that antioxidative drugs such as resveratrol may be alternative target agents in neurological disease.
Keywords: ADAMTS-4, brain, cerebellum, GFAP, rat, resveratrol, traumatic brain injury
Objective: To evaluate the antibacterial effects of 4 different cavity disinfectants on Streptococcus mutans, Lactobacillus acidophilus, and Enterococcus faecalis bacteria in different time periods.
Study Design: The antibacterial effects of Cavity Cleanser, Tubulicid Red Label, Chloraxid 2%, and Oxygenated Water cavity disinfectant solutions on E. faecalis (ATCC 29212), S. mutans (ATCC 25175), and L. acidophilus (RSKK 03037) bacterial strains were evaluated by disk diffusion method. In the study where vancomycin antibiogram disc constituted the positive control group, physiological saline solution was used as the negative control group. Standard, sterile, blank antibiogram discs of 5 mm in diameter, in which 15 μL of each material were added, were placed on agar plates at 2.5–3 cm intervals. The inhibition zone diameters formed around the discs that were left to incubate for 24–48 hours at 37°C were measured in millimeters. Statistical analysis of the data was performed using one-way analysis of variance, Kolmogorov-Smirnov, Levene, and Bonferroni tests.
Results: At the end of the study the solutions tested showed a statistically significant antibacterial effect on all bacterial strains used (p<0.05). Cavity Cleanser disinfectant containing 2% chlorhexidine showed the highest antibacterial effect on S. mutans and L. acidophilus, and benzalkonium-containing Tubulicid Red disinfectant on E. faecalis.
Conclusion: The antibacterial effect of all cavity disinfectants used in the study was found to be higher at the end of the 48th hour than at the end of the 24th hour, but there was no statistically significant difference (p>0.05).
Keywords: antibacterial agents; antibacterial effect; cavity disinfectants; chlorhexidine; contamination; dental caries; disinfection; disc diffusion; gram-negative bacteria; gram-positive bacteria
Objective: To probe into the influence of miR-21 on the proliferation as well as apoptosis of oral squamous cell carcinoma (OSCC) and its causative role.
Study Design: We adopted microarray for detecting the differentially expressed genes in OSCC tumor tis-sues and paracancerous tissues. We assessed the link of miR-21 expression with tumor size, lymph node metastasis, and tumor differentiation. We employed CCK-8 and EdU assay for detecting the impact of miR-21 inhibitor and miR-21 mimic on Cal-27 cell proliferation, as well as TUNEL and AnnexinV-FITC/PI double staining for detecting miR-21 expression on cell apoptosis. We forecasted the possible target of miR-21 via TargetScan, as well as detected the interaction of miR-21 with PTEN via luciferase reporter experiment. The function of miR-21 expression in PTEN signaling pathway was monitored via western blot. We constructed PTEN overexpression plasmid and conducted rescue experiment to evaluate overexpressed PTEN on miR-21–induced proliferation.
Results: Microarray and RT-qPCR indicated that miR-21 expression increased demonstrably in OSCC. Subsequently, statistical analysis showed that miR-21 expression was plainly correlated with tumor size, lymph node metastasis, tumor differentiation, and smoking history. CCK-8 and EdU method exhibited that miR-21 mimics manifestly promoted Cal-27 cell proliferation, while miR-21 inhibitor blatantly inhibited Cal-27 cell proliferation. TUNEL and V-FITC/PI double staining assay showed that miR-21 inhibitor conspicuously promoted Cal-27 cell apoptosis. CCK-8 and EdU assay exhibited that overexpressed PTEN abolished the pro-proliferation influence of miR-21 mimic. TUNEL and V-FITC/PI experiments pointed out that knocking down PTEN abrogated the pro-apoptosis impact of miR-21 inhibitor.
Conclusion: miR-21 contributes to OSCC cell proliferation via targeting PTEN and inhibits its apoptosis.
Keywords: Akt/PKB signaling pathway; apoptosis; biomarkers, tumor; carcinoma, squamous cell; cell line, tumor; cell proliferation; microRNAs; miR-21; miRNA-21; mouth neoplasms; oral cancer; oral squamous cell carcinoma; proliferation; real time PCR
This study examined the effects of prolonged simvastatin (SIM) treatment on ischemia-reperfusion (I/R) induced acute kidney injury in rats. Rats were divided into four groups: sham, ischemia, I/R, and I/R+SIM treated. The I/R group showed intense inflammation, necrosis, and apoptosis in kidney tissue. The I/R+SIM group showed reduced inflammation and tissue damage. Biochemical analysis found increased oxidative stress and inflammation markers in the ischemia and I/R groups compared to control, but levels in the I/R+SIM group were similar to control. Histological analysis also showed more damage in ischemia and I/R groups versus control, while the I/R+
Objective: To investigate the changes in the retina due to deltamethrin toxicity and the process in cell inflammation and apoptosis.
Study Design: Sixteen Wistar albino rats were randomly divided into two groups as control (n=8) and deltamethrin (n=8) groups. Saline was given to the control group, and 0.5 mL of 5 mg/kg deltamethrin was given to the deltamethrin group for 14 days each. Blood was collected for biochemical analysis. Retinal tissue was processed for histological examination.
Results: Compared to the control group, MDA levels were high while GSH and CAT levels were low in the deltamethrin group. Histopathological analysis showed spaces between the pigment epithelium, irregularity in the delimiting membrane, degenerated ganglion, cone and bacillus cell, pyknotic nuclei, thinned inner limitation membrane, and thickened vascular wall. The control group showed FAS expression in the pigment layer limiting membranes, in the nuclei of many cone and bacillus cells, and ganglion cells in the control group sections. In the deltamethrin group, FAS expression was observed in the inner and outer limiting membranes of the pigment epithelium, cone and bacillus cells, and ganglion cell nuclei. In the control group, negative NOS expression in the pigment epithelium and outer limiting membranes, internal limitation membrane, and ganglion cells in the cone and bacillus cell nuclei were observed. In the deltamethrin group, NOS expression was positive in the pigment epithelium, cone and bacillus, and ganglion cell nuclei.
Conclusion: We suggest that deltamethrin toxicity induced apoptotic process due to increased inflammation in the retina and may cause visual impairment as a result of neural damage.
Keywords: deltamethrin, FAS, insecticides, NOS, nitric oxide synthase, retina
Objective: Tongue squamous cell carcinoma (TSCC) is a prominent type of oral cancer. Despite the numerous research studies on SCC and microRNAs (miRs), the relation between TSCC and miR-135b-5p is poorly discussed. This experiment aims to find out the possible effect of miR-135b-5p on TSCC with the network of its downstream genes.
Study Design: TSCC tissues and adjacent normal tissues were harvested. Then, expression of miR-135b-5p and AT-rich interactive domain‑containing protein 1A gene (ARID1A) and the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT) pathway was analyzed. After the transfection of miR-135b-5p inhibitor and its negative control into TSCC cells, functional assays were employed to measure cell proliferation, apoptosis, and cycle. Next, the target relation between miR-135b-5p and ARID1A was confirmed. In addition, the fact that miR-135b-5p promoted TSCC development via mediating ARID1A was demonstrated by functional rescue experiment.
Results: miR-135b-5p was upregulated in TSCC tissues and cells, while ARID1A was suppressed (p< 0.05). Silenced miR-135b-5p discouraged TSCC cell proliferation, improved apoptosis, induced cell cycle arrest, and increased ARID1A expression while inactivating the PI3K/AKT axis (p<0.05). Furthermore, knockdown of ARID1A reversed the impacts on TSCC cell proliferation and apoptosis exerted by silencing miR-135b-5p.
Conclusion: This research supported that silenced miR-135b-5p impeded TSCC proliferation and apoptosis by promoting ARID1A and inactivating the PI3K/AKT axis, which may provide some indications for TSCC alleviation.
Keywords: apoptosis; ARID1A; ARID1A protein, human; carcinoma, squamous cell; cell line, tumor; cell proliferation; drug resistance, neoplasm; microRNA-135b-5p; microRNAs; PI3K/AKT pathway; neoplasm metastasis; neoplastic stem cells; proliferation; protein binding; tongue; tongue squamous cell carcinoma
Objective: To investigate the immunohistochemical staining of hypoxia-inducible factor 1-alpha (HIF-1α) and Ki-67 expression in the placenta of pregnant women with placenta previa and placenta accreta.
Study Design: Thirty placentas (10 normotensive, 10 placenta previa, and 10 placenta accreta) were processed for routine histological tissue processing. The biochemical parameters of patients were recorded. Placentas were stained with hematoxylin-eosin and HIF-1α and Ki-67 immunostaining.
Results: Normal histology was observed in placentas of normotensive pregnant women. Placenta previa sections showed increased syncytial knots, intervillous hemorrhage, fibrin accumulation, and hyalinization. In placenta accreta sections, increased syncytial nodes, vascular dilation/congestion, fibrin accumulation, and hyalinization were observed. Normotensive placentas showed no HIF-1α expression. In placenta previa tissues, high HIF-1α expression was observed in vascular endothelial cells, villous stromal cells, and syncytial knots. High HIF-1α expression was recorded in villous stromal cells and cytotrophoblast cells in placenta accreta. In normotensive placental tissues, no Ki-67 expression was observed. In placenta previa sections, high Ki-67 expression was observed mostly in root villi stromal cells and some endothelial cells. High Ki-67 expression was observed mostly in villi stromal cells of placenta accreta.
Conclusion: It is thought that HIF-1α is an important regulatory gene in the development of villus in trophoblast invasion such as placenta accreta and previa, while Ki-67 will play a key role in the development of abnormal placenta with its stimulating effect on inflammatory cell development and angiogenesis in accreta and preeclampsia.
This study investigated the effects of spinal cord injury on the bladder tissue of rats. Twenty rats were divided into a control group and spinal cord injury (SCI) group. The SCI group exhibited statistically higher levels of oxidative stress markers (MDA, MPO), epithelial degeneration, vascular dilation, inflammation, and expression of VEGF and APAF-1 compared to the control group. The SCI group also had lower levels of the antioxidant GSH. Histological examination of the SCI group showed degeneration of epithelial cells, thickened fibrosis, dilated blood vessels, and increased VEGF and APAF-1 expression compared to the control group. The results suggest that spinal cord injury leads to increased oxidative stress, inflammation and apoptosis in
Objective: To investigate the effect of sildenafil on reducing the impact of hepatic ischemia/reperfusion (HIR) injury established by Pringle maneuver on the heart of rats.
Study Design: Forty Wistar albino rats were divided into 4 groups: Sham (laparotomy only), Control (laparotomy following sildenafil application), IR (ischemia/reperfusion injured by HIR), and IR+SIL (injured by HIR following sildenafil application). Ischemia was developed by clamping the hepatoduodenal ligament for 30 minutes; then reperfusion was applied for 30 minutes. Sildenafil (single dose of 50 mg/kg) was administered by oral gavage for 15 minutes before ischemia. Blood samples of rats were collected from Sham and Control groups at 60 minutes and from IR and IR+SIL groups at 30 minutes after initiation of reperfusion for biochemical analysis. Meanwhile, heart tissues were sampled for biochemical analysis. Malondialdehyde (MDA) and total antioxidant capacity (TAC) in serum samples and TAC, total oxidative capacity (TOC), and oxidative stress index in heart tissues were examined biochemically.
Results: Serum MDA levels were elevated significantly in the IR and IR+SIL groups as compared to the sham group. Sildenafil treatment inhibited MDA increase considerably in the IR+SIL group as compared to the IR group. Serum TAC levels were elevated significantly in the sildenafil and control groups (compared with sham groups) and in the IR+SIL group (compared with the IR group). TAC levels detected in heart tissue increased significantly in the IR group as compared to the sham group; however, sildenafil treatment had no effect on this increase.
Conclusion: Heart tissue was affected by HIR. It was revealed that sildenafil treatment may prevent the oxidative stress via increasing serum TAC levels in both control and IR+SIL groups.
Objective: To examine the oropharynx of patients with ectodermal dysplasia showing maxillary retrusion and mandibular protrusion with a short and concave facial structure using cone-beam computed tomography method. Ectodermal dysplasia refers to the congenital disorder defined by the abnormal development of the structure originating from the ectoderm.
Study Design: In order to examine the oropharynx airway, measurements and statistical evaluations were made in 3 levels in sagittal and transversal directions on three-dimensional cone beam computed tomography images obtained from 14 individuals divided into 2 groups as Ectodermal Dysplasia group (n=7) and Control group (n=7).
Results: As a result of statistical analysis, no statistically significant difference was found between the groups at any level or direction in metric measurements performed on all 3 planes taken at the sagittal and transversal levels (p>0.05).
Conclusion: Our findings on ectodermal dysplasia are similar to Class III malpositions that show similarity with ectodermal dysplasia.
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Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
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Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
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www.agostodourado.com
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ABDOMINAL TRAUMA in pediatrics part one.drhasanrajab
Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
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• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
2. Volume 43, Number 2/April 2021 45
Distinct Fallopian Phenotype in High-Risk Patients
and the number of very dark stained pixels) showed a
pronounced shift from normal in high-risk nuclei and
represent a statistically significant difference (p<0.05)
at the nuclear level.
CONCLUSION: Karyometry detected an abnormal mor-
phometric phenotype in nuclei of fallopian tube epitheli-
um from women at high risk for disease as compared to
normal controls. (Anal Quant Cytopathol Histpathol
2021;43:44–51)
Keywords: BRCA1 genes, BRCA2 genes, carcino-
ma, fallopian tube, karyometry, karyometric image
analysis, ovarian cancer, ovarian epithelial carcino-
ma.
Ovarian cancer is the most lethal gynecological
malignancy in women and is responsible for 5%
of all cancer-related deaths in females.1 When de-
tected in early stages, the 5-year survival rate is
as high as 90%.1 Unfortunately, only 15% of cases
are diagnosed at this stage, and ovarian cancer
typically progresses to later, more aggressive stages
before detection in the majority of cases, thereby
resulting in a substantial drop in 5-year survival to
less than 40%.1
Women with mutations in breast cancer sus-
ceptibility genes, BRCA1 and BRCA2, have a 40%
and 18% lifetime ovarian cancer risk, respective-
ly.2 For these women, twice yearly screening has
been advised in the hope that ovarian cancers
might be detected early. Current screening tech-
niques including pelvic examination, transvaginal
ultrasound (TVU), and CA125 blood marker mea-
surement, however, have very poor specificity and
sensitivity.3 Furthermore, annual screening by TVU
and CA125 in high-risk populations is grossly inef-
ficient at detecting the disease in its early stages.4
Because of the limitations in ovarian cancer screen-
ing, it is recommended that women at high risk
for the disease undergo radical preventative mea-
sures, such as a prophylactic bilateral salpingo-
oophorectomy (BSO), when they have either com-
pleted childbearing or by age 35–45.5
Bilateral salpingo-oophorectomy, or the removal
of both ovaries and fallopian tubes, has been asso-
ciated with an 80% reduction in not only ovarian
cancer risk, but also fallopian tube and peritoneal
cancer risk.5 Although removal of the ovaries and
fallopian tubes is an effective method of ovarian
cancer prevention, it is accompanied by adverse
sequelae, including loss of fertility, sudden onset
of menopause, and rapid loss of bone mineraliza-
tion.6 In order to decrease the need for such harm-
ful surgeries, more efficient screening techniques
are required to accurately identify individuals har-
boring lesions at risk for malignant transformation
and to use these techniques to detect the disease in
its early, more curable stages.
Karyometry is a form of digital microscopy
that allows for quantitative analysis of diagnostic
images. All digital images are represented by dis-
crete points or picture elements known as pixels.
Electronically examining images on a pixel-by-
pixel basis offers novel, objective information and
descriptive features that are not readily visible to
the human eye. The difference between visual and
computed features can be demonstrated by read
ing printed text. Although one can recognize visu-
al information like letters, words, and language,
more complex information, such as the relative
frequency of occurrence of one letter compared to
another, is overlooked. The relative frequencies of
certain letters or vowels compared to others, how-
ever, characterize the text while providing objec-
tive and computed descriptive features. Similarly,
examining the two-dimensional spatial and statis
tical distribution of pixels in a digitized image
produces computed descriptive features. Through
the power of variance-analytic procedures, nu-
merical representations of these features allow
for subtle, yet consistent, differences to be iden-
tified between images. The computer processing
of digitally represented histopathologic images
provides the unique opportunity to collect quan
titative, numerical data from an otherwise qualita-
tive source.
Karyometry can ascertain chromatin abnormali-
ties at the nuclear level by utilizing high-resolution
computer imaging analyses. It is designed to ex-
tract karyometric features that are undetectable to
the human eye, thereby providing a level of sen-
sitivity that allows the fine detection of variability
between samples despite the natural heterogene-
ity of nuclei.7 Not only does karyometry have the
ability to accurately detect nuclear abnormalities,
it also has provided objective and statistically valid
measures of chemopreventive efficacy in vivo. For
example, a statistically significant change toward
normalization in the karyometric features in the
ovary and fallopian tube epithelium in women at
increased risk for ovarian cancer treated with the
progestin levonorgestrel supported the notion that
progestins may act as chemopreventive agents
against ovarian and fallopian tube cancer.8 Similar
A
RTICLES
3. 46 Analytical and Quantitative Cytopathology and Histopathology®
Russell et al
studies investigating chemopreventive efficacy of
vitamin A in sun-damaged skin have shown that
karyometry analysis can provide more objective
measures of chemopreventive efficacy.9,10
When pathologists microscopically examine tu-
mor biopsies, they generally assign a grade based
on how abnormal the cells appear to visual inspec-
tion. On the other hand, digital analysis of biopsy
images through karyometry can provide the abil-
ity to compute and document certain features that
are too small to be appreciated by visual observa-
tion. For example, a previous study using karyo-
metry on ovarian surface epithelium discovered
that histologically normal-appearing epithelium
in women at high risk for ovarian cancer, as well
as in the normal epithelium adjacent to ovarian
cancer, harbors abnormal submicroscopic changes
in the nuclear chromatin, thus suggesting poten-
tial for malignancy.11 Furthermore, studies utiliz-
ing karyometry have uncovered similar significant
relationships between slight changes in the nuclei
of normal, preinvasive, and invasive lesions in var-
ious other tissues including breast, rectal, urinary
tract, prostate and skin.11-16 The ability to detect
distinct changes in nuclear chromatin pattern
between normal, preinvasive, and invasive lesions
provides the opportunity to characterize samples
in a progression curve. In fact, karyometry has
been shown to accurately detect the progression
of precancerous lesions of actinic keratosis to ag-
gressive squamous cell carcinomas through the
comparison of karyometric features.17 Although
further research is required, karyometry possesses
the potential of being an instrumental screening
technique for cancers of many different origins.
It is a widely supported theory that the cell of
origin for many high-grade ovarian cancers may
originate from the fallopian tube epithelium rath-
er than ovarian epithelium.18 This makes the fal-
lopian tube an attractive target for ovarian cancer
screening and prevention. In the current study, we
sought to determine whether karyometry might
be useful in detecting nuclear abnormalities of the
fallopian tube epithelium in women carrying the
BRCA1 or BRCA2 mutation at high risk for ovar-
ian cancer as compared to women with normal risk
factors. The ability to evaluate nuclear abnormali-
ties of fallopian tube epithelium through karyom-
etry may provide a more accurate assessment of
ovarian cancer risk beyond a simple genetic test
for BRCA mutations. Therefore, karyometry could
result in more individualized assessment of dis-
ease risk and the avoidance of unnecessary and
harmful procedures. It may even lead to the detec-
tion of preneoplastic lesions, resulting in appropri-
ate preventative measures and early surgical inter-
vention and, in this way, become a useful element
of precision oncology.
Materials and Methods
Sample Collection
A portion of fallopian tubes included in this ret-
rospective study were collected from an archive
of de-identified samples and received exemptions
from the Human Subjects Review Committees at
the University of Arizona and NorthShore Univer-
sity HealthSystem in Chicago. The remaining sam-
ples were collected under IRB protocol, utilizing
the U.S. common rule and obtaining patient con-
sent when appropriate. All materials were trans-
ferred to the University of Arizona from the Pa
thology Department at NorthShore University
HealthSystem (Evanston Hospital) on the basis of
a material transfer agreement between these two
institutions.
The “normal risk” fallopian tubes were collect-
ed from women who lacked BRCA1 or BRCA2
mutations or a strong family history of breast and
ovarian cancer and underwent a salpingectomy
for benign gynecologic indications. The “high risk”
fallopian tubes were collected from women who
were positive for BRCA1 or BRCA2 mutations
and who underwent surgery for ovarian cancer
risk reduction. All high-risk cases were examined
carefully by pathologists to rule out the presence
of any neoplasia, including the presence of atypia,
STIC lesions, and cancers. They were therefore
confirmed to be histologically normal, and any
abnormality detected by karyometry was therefore
occurring prior to any histologic transformation.
Tissue Preparation
A total of 15 fallopian tubes were collected, con-
sisting of 8 tubes from women at high risk due to
BRCA1 and BRCA2 gene mutations and 7 tubes
from women at normal risk. Tissue fixation and
staining was strictly controlled to prevent unnec-
essary sources of variability. Tissues underwent
standard fixation in 10% neutral buffered formalin,
followed by paraffin embedding. They were then
sectioned at 5-micron thickness and stained with a
reproducible procedure using synthetic hematox-
ylin and eosin. Human tonsil tissue was utilized
in order to maintain quality control during the
4. Volume 43, Number 2/April 2021 47
Distinct Fallopian Phenotype in High-Risk Patients
staining procedure.7 Images of the fallopian tube
epithelium were captured at high magnification
(100:1) with a high-quality video microscope, utiliz-
ing a high numerical aperture (1.40) apochromatic
oil immersion objective. Images were recorded at
4 to 6 pixels per micron and consisted of a random
accumulation of well-defined nuclei that did not
overlap.7
Karyometric Protocol
Images were analyzed using a semi-automated
segmentation program with manual correction,
thereby isolating individual nuclei for further in-
vestigation.19 Segmentation of nuclei was a cru-
cial step in quantitative image analysis because
any error in defining nuclear borders would have
modified the values utilized by karyometric fea-
tures. For segmentation, an image-processing al-
gorithm was applied for object recognition. This
resulted in chain codes that outlined each indi-
vidual nucleus, thereby specifying the pixels that
generated the nuclear border. Interactive correc-
tions were required throughout the segmentation
process since a single algorithm rarely segments
all nuclei correctly. This program isolated, on aver-
age, 158 nuclei per fallopian tube for a total of 1,257
nuclei in the high-risk group. Likewise, an average
of 172 nuclei per fallopian tube for a total of 1,205
nuclei were isolated in the normal-risk group. Fig-
ure 1 provides a sample representative image of
the fallopian tube epithelium after nuclear seg
mentation.
Following segmentation, 93 karyometric features
were used to analyze nuclear chromatin pattern.
Global features are the simplest and utilized all
pixels localized in a single nucleus, including such
characteristics as “nuclear area,” “nucleocytoplas-
mic ratio,” “measures of roundness of a nucleus,”
and “total optical absorbance.” These features rep-
resent individual nuclei as a whole and can be
classified as zero-order relationships. First- and
second-order features investigate the differences
or similarities between adjacent pixels, thereby
analyzing the 2-dimensional relationships of con-
tiguous pixels to determine chromatin patterns.
For example, several features summarize chroma
tin pattern by utilizing “pixel run length” or “mean
pixel absorbance.” Finally, the associations of sev-
eral nuclei throughout a sample are organized
into third-order relationships.20 Essentially, the fea-
tures classified in higher-ordered groups are as-
sociated with more complex linear combinations.
A more descriptive list of the 93 features has been
published previously.11
Statistical Analysis
The 93 karyometric features collectively created
the “nuclear signature,” and data were normalized
to provide comparable data sets. Furthermore,
“nuclear abnormality” was calculated by averag-
ing the standard deviations for all 93 features of
each nucleus.7 The nuclear signature expresses
the values and correlations among all measured
karyometric features, thereby providing a quanti-
tative approach that can discriminate malignancy-
associated changes in the nuclear chromatin from
benign. When using karyometric features to detect
nuclear abnormalities in a tissue biopsy, values
are normalized to a reference data set and ex
pressed in units of standard deviation, or z-value.
The magnitude of z-value for each feature mea-
sures its deviation from a normal reference set.
Normalized values add stability and provide data
that can be compared to similar samples. The z-
values averaged over all 93 karyometric features
offer a measure of “nuclear abnormality.”
In many cases the nuclear abnormality value
is not particularly sensitive, given that not all 93
karyometric features change between samples. A
Kruskal-Wallis test was utilized to ascertain the
Figure 1 The representative image illustrates nuclei of fallopian
tube epithelium that were randomly selected for further analysis.
Images of the fallopian tube epithelium were captured at high
magnification (100:1) with a high-quality video microscope
utilizing a high numerical aperture (1.40) apochromatic oil
immersion objective. The white outlines represent chain codes
that defined the border of each nucleus during segmentation.
5. 48 Analytical and Quantitative Cytopathology and Histopathology®
Russell et al
significance of very small deviations in data sets
in order to detect the submicroscopic differences
that cannot be appreciated by visual analysis
alone. Since there are 93 statistical tests being
performed, it is necessary to apply a multiple-test
correction such as the Bonferroni correction and
the Benjamini-Hochberg procedure to control for
false positives.21,22 In this work we selected features
with statistically significant value differences, at
p values <0.0001, which allows for a Bonferroni
correction. This test identified several important
features with statistically significant differences
between the high-risk group and the normal-risk
group.
These karyometric features identified by the
Kruskal-Wallis test were then used to construct
the linear discriminant function for separating the
two groups.20 A discriminant function analysis is
widely used in problems of categorizing obser-
vations into different groups, often called classi-
fication problems in statistics. Using the selected
features, a discriminant function analysis builds
a classification rule—in this case, high risk and
normal risk—by developing a function that can
separate different groups. Descriptive statistics
can characterize a set of nuclei by the numeric
values of their features. Finally, Wilks’ lambda
was used to determine a difference between the
nuclear abnormality in high-risk and normal-risk
fallopian tube samples with p value <0.05.
Results
Figure 2 plots the nuclear signature of the sam
ples, i.e., the standardized scores of 93 features, for
normal-risk fallopian tube epithelium (top panel)
and for high-risk fallopian tube epithelium (bot
tom panel). It shows that the nuclear feature dis-
tribution of high-risk cases demonstrates a distinct
deviation from that of normal-risk cases. Wilks’
lambda was reduced to 0.63, thereby providing
evidence of a definite difference between high-risk
and normal-risk fallopian tube features. Discrimi-
nant function analysis highlighted two of the most
segregating karyometric features, including pixel
optical density heterogeneity and the number of
very-dark-stained pixels. The feature “pixel optical
density heterogeneity” measured the degree of
diversity in the pixel optical density, and the fea-
ture “number of very-dark-stained pixels” mea-
sured the total number of dark-stained pixels in
the nucleus. Figure 3 displays the distribution
of discriminant function scores for nuclei from
Figure 2
The graphs represent the
nuclear signatures for
both high-risk (bottom) and
normal-risk (top) groups. Each
bar represents a single
karyometric feature and
provides a quantitative value
for the 93 global features
selected in the karyometric
analysis. In other words, each
bar represents a z-value that
was calculated using the
absolute difference of the
corresponding reference
feature mean divided by the
corresponding standard
deviation for the reference
feature. There are marked
abnormalities in at-risk from
normal, as seen by the
variation in z-values.
6. Volume 43, Number 2/April 2021 49
Distinct Fallopian Phenotype in High-Risk Patients
high-risk cases (in black) and for nuclei from
normal-risk cases (in grey). It clearly shows that
the discriminant function for high-risk nuclei dis-
played a pronounced shift (p<0.05) away from
that of normal-risk cases, towards lower (more
negative) values. Additionally, utilizing these two
segregating karyometric features in a bivariate plot
with 95% ellipses for the case mean values dem-
onstrated a statistically significant difference (p<
0.05) between the two experimental groups at the
nuclear level (Figure 4). It was observed that nu
clei from high-risk tissues, falling onto the upper
portion of Figure 4, had lower values of the pixel
optical density heterogeneity than those from nor-
mal risk tissues.
Discussion
This small, exploratory study was designed to
assess whether or not karyometric analysis could
detect changes in the nuclear chromatin pattern of
fallopian tube epithelium from women at high risk
for ovarian cancer. The results suggest that there
were, in fact, detectable and significant changes in
the chromatin signature of tubes in the high-risk
group as compared to the normal-risk controls.
As illustrated in Figure 2, there was a distinct dif-
ference in the nuclear signature of fallopian tube
epithelium of high-risk samples as compared to
normal controls. Changes in the nuclear signature
could represent the earliest transformation of histo-
logically normal-appearing tissue to premalignant
lesions. Previous studies confirmed that seemingly
normal tissue might harbor premalignant lesions
that can be detected through nuclear karyometry.12
For example, research conducted by Anderson et al
uncovered significant differences between nuclei in
normal-appearing breast tissue containing remote
cancer as compared to nuclei in breast tissue with
no cancer.12 These differences indicate a deviation
from normal, thereby suggesting the potential to
progress to malignancy.
Pixel optical density heterogeneity and the num-
ber of very-dark-stained pixels were computed as
the most segregated karyometric features. In fact,
these features provided statistically significant evi-
dence that nuclear chromatin patterns in high-risk
women differed from those in normal-risk controls
(Figure 4). When cells undergo molecular changes,
they develop altered chromatin structure. By utiliz
ing karyometric nuclear analysis, it is possible to
characterize chromatin patterns by describing the
organization of pixel combinations.23
It is widely appreciated that BRCA1 or BRCA2
mutations predispose women to high-grade serous
ovarian cancer and that the fallopian tubes are
believed to be the origin of disease.18 Therefore,
abnormalities between the nuclear signatures of
fallopian tubes from women with these mutations
and normal controls were anticipated. Given the
preliminary nature of this study, one of the weak-
nesses is the small number of samples analyzed. In
the future, we hope to expand upon this research
and analyze, in a blinded fashion, a much larger
number of fallopian tubes in order to better under-
Figure 3
The distribution of normalized
discriminant function scores
for the nuclei of fallopian
tube epithelium representing
women at normal risk cases
(in grey) and women at high
risk cases (in black). The
discriminant analysis utilized
only karyometric features that
maximally reduced Wilks’
lambda (i.e., maximally
separated high-risk from
normal-risk epithelium). There
is a significant separation of the two curves (p<0.05). A shift to the lower score values as seen in the black bars indicates higher deviation
from normal.
7. 50 Analytical and Quantitative Cytopathology and Histopathology®
Russell et al
stand the difference between high-risk and normal-
risk nuclear features.
Finally, we are collaborating with biomedical
engineers at the University of Arizona in the de-
velopment of a novel miniature endoscopic de-
vice that can be threaded through the vagina and
into the fallopian tubes to collect fallopian tube
cells. This revolutionary device would eliminate
the need to surgically remove the tubes in order
to accurately assess cancer risk. With the assis-
tance of this device, we are hopeful that karyom-
etry can offer a novel and noninvasive mechanism
for ovarian cancer screening, thereby encouraging
noninvasive prevention strategies and early detec-
tion of the disease, ultimately contributing to pre
cision oncology in gynecological malignancies.
Acknowledegments
This research was supported in part by a grant
from the National Cancer Institute (Arizona Can-
cer Center Support Grant CA023074), Bethesda,
Maryland. The authors also gratefully acknowl-
edge support from Humberto and Czarina Lopez,
Tucson, Arizona; The Jim Click Family Foundation,
Tucson, Arizona; and the J. Russell Skelton Fam-
ily, Phoenix, Arizona. In addition, we would like
to dedicate the present work to our brilliant co-
author, Peter Bartels, Ph.D., one of the founding
fathers of quantitative histopathology, who con-
tinued to be productive and amazingly creative
through his last days. He will forever be missed
and revered.
Contributions
Dr. Samantha Russell collated the karyometric
data and composed the manuscript. Dr. Gustavo
Rodriguez collected all the participant tissue sam-
ples, facilitated the production of the histopatho-
logical slides, and provided scientific input to the
project and manuscript. Dr. Hao Helen Zhang pro-
vided statistical advising, data interpretation, and
assistance throughout the editing process. Michael
Yozwiak provided oversight on the segmentation
of the microscopic studies and input into the inter-
pretation of the generated data. Dr. Charmi Patel
provided histopathological review of all samples
and input into selection of microscopic images
for karyometric analyses. Dr. Melody Maarouf
provided the segmentation of all histopathological
specimens. Hubert Bartels collected and main-
tained all analytical data. Dr. Jennifer Barton par-
ticipated in the discussion, interpretation of study
data, and editing of the manuscript as well as
potential application to the future collection of
tissue samples. Ahyoung Amy Kim provided sta-
tistical input throughout the editing process and
participated in the discussion. Sri Saii Atluri partic-
ipated in discussion of data and has been integral
in continuing segmentation of fallopian tubes for
future projects. Dr. Peter Bartels presided over the
final statistical analyses and the interpretation of
results. Dr. David Alberts developed experimental
design, supervised all laboratory functions, and
provided major input into the manuscript drafts.
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