This study examined CXCL1 protein expression in 152 bladder tissue samples, including 142 cancer samples and 10 benign samples, using immunohistochemical staining. The key findings were:
1) CXCL1 protein expression was present in cancerous bladder tissues but entirely absent in benign bladder tissues.
2) CXCL1 expression was significantly higher in high-grade and high-stage tumors compared to low-grade and low-stage tumors.
3) Increased CXCL1 expression was associated with reduced disease-specific survival and overall survival.
So in summary, this study found that CXCL1 protein expression is increased in more aggressive bladder cancers and associated with poorer survival outcomes. This suggests CXCL1 may play a
Calcarea carbonica induces apoptosis in cancer cells in p53-dependent manner ...home
These observations delineate the significance of immuno-modulatory circuit during calcarea carbonicamediated
tumor apoptosis. The molecular mechanism identified may serve as a platform for involving calcarea
carbonica into immunotherapeutic strategies for effective tumor regression
1) T-regulatory cells (Tregs), which help suppress inflammation, were significantly lower in omental adipose tissue compared to subcutaneous adipose tissue in adults with obesity. 2) Lower levels of Tregs in omental adipose tissue were associated with higher fasting glucose levels and lower beta-cell function. 3) The study assessed immune cell populations like Tregs, macrophages, and T effector cells in different adipose tissue depots and their relationship to markers of type 2 diabetes risk.
Impaired mitochondrial beta-oxidation in patients with chronic hepatitis C: r...Enrique Moreno Gonzalez
Hepatic steatosis is often seen in patients with chronic hepatitis C (CH-C). It is still unclear whether these patients have an impaired mitochondrial β-oxidation. In this study we assessed mitochondrial β-oxidation in CH-C patients by investigating ketogenesis during fasting.
ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grad...Enrique Moreno Gonzalez
High-grade (WHO grade III and IV) astrocytomas are aggressive malignant brain tumors affecting humans with a high risk of recurrence in both children and adults. To date, limited information is available on the genetic and molecular alterations important in the onset and progression of pediatric high-grade astrocytomas and, even less, on the prognostic factors that influence long-term outcome in children with recurrence. A-to-I RNA editing is an essential post-transcriptional mechanism that can alter the nucleotide sequence of several RNAs and is
mediated by the ADAR enzymes. ADAR2 editing activity is particularly important in mammalian brain and is impaired in both adult and pediatric high-grade astrocytomas.
Moreover, we have recently shown that the recovered ADAR2 activity in high-grade astrocytomas inhibits in vivo tumor growth. The aim of the present study is to investigate whether changes may occur in ADAR2-mediated RNA editing profiles of relapsed highgrade astrocytomas compared to their respective specimens collected at diagnosis, in four pediatric patients.
Antioxidant-mediated up-regulation of OGG1 via NRF2 induction is associated ...Enrique Moreno Gonzalez
Estrogen metabolism-mediated oxidative stress is suggested to play an important role in estrogen-induced breast carcinogenesis. We have earlier demonstrated that antioxidants,
vitamin C (Vit C) and butylated hydroxyanisole (BHA) inhibit 17β-estradiol (E2)-mediated oxidative stress and oxidative DNA damage, and breast carcinogenesis in female August
Copenhagen Irish (ACI) rats. The objective of the present study was to characterize the mechanism by which above antioxidants prevent DNA damage during breast carcinogenesis.
Search for atoxic cereals: a single blind, cross-over study on the safety of...Enrique Moreno Gonzalez
Cereals of baking quality with absent or reduced toxicity are actively sought as alternative therapy to a gluten-free diet (GFD) for patients with coeliac disease (CD). Triticum monococcum, an ancient wheat, is a potential candidate having no toxicity in in-vitro and exvivo studies. The aim of our study was to investigate on the safety of administration of a single dose of gluten of Tm in patients with CD on GFD.
- The study examined malondialdehyde (MDA) levels and hematological parameters in 31 newly diagnosed cervical cancer patients at a hospital in India.
- MDA levels, which indicate oxidative stress, were found to be significantly higher in cervical cancer patients compared to healthy volunteers. MDA levels also differed between cancer grades.
- Hematological analysis found reduced red blood cell count and hemoglobin levels and increased white blood cell count in cervical cancer patients relative to normal levels.
- The results suggest that oxidative stress and hematological abnormalities are present at the initial clinical presentation of cervical cancer patients and that MDA may be a predictive marker for disease progression. Controlling oxidative stress and improving nutrition could help cervical cancer treatment
Variant G6PD levels promote tumor cell proliferation or apoptosis via the STA...Enrique Moreno Gonzalez
Glucose-6-phosphate dehydrogenase (G6PD), elevated in tumor cells, catalyzes the first reaction in the pentose-phosphate pathway. The regulation mechanism of G6PD and pathological change in human melanoma growth remains unknown.
Calcarea carbonica induces apoptosis in cancer cells in p53-dependent manner ...home
These observations delineate the significance of immuno-modulatory circuit during calcarea carbonicamediated
tumor apoptosis. The molecular mechanism identified may serve as a platform for involving calcarea
carbonica into immunotherapeutic strategies for effective tumor regression
1) T-regulatory cells (Tregs), which help suppress inflammation, were significantly lower in omental adipose tissue compared to subcutaneous adipose tissue in adults with obesity. 2) Lower levels of Tregs in omental adipose tissue were associated with higher fasting glucose levels and lower beta-cell function. 3) The study assessed immune cell populations like Tregs, macrophages, and T effector cells in different adipose tissue depots and their relationship to markers of type 2 diabetes risk.
Impaired mitochondrial beta-oxidation in patients with chronic hepatitis C: r...Enrique Moreno Gonzalez
Hepatic steatosis is often seen in patients with chronic hepatitis C (CH-C). It is still unclear whether these patients have an impaired mitochondrial β-oxidation. In this study we assessed mitochondrial β-oxidation in CH-C patients by investigating ketogenesis during fasting.
ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grad...Enrique Moreno Gonzalez
High-grade (WHO grade III and IV) astrocytomas are aggressive malignant brain tumors affecting humans with a high risk of recurrence in both children and adults. To date, limited information is available on the genetic and molecular alterations important in the onset and progression of pediatric high-grade astrocytomas and, even less, on the prognostic factors that influence long-term outcome in children with recurrence. A-to-I RNA editing is an essential post-transcriptional mechanism that can alter the nucleotide sequence of several RNAs and is
mediated by the ADAR enzymes. ADAR2 editing activity is particularly important in mammalian brain and is impaired in both adult and pediatric high-grade astrocytomas.
Moreover, we have recently shown that the recovered ADAR2 activity in high-grade astrocytomas inhibits in vivo tumor growth. The aim of the present study is to investigate whether changes may occur in ADAR2-mediated RNA editing profiles of relapsed highgrade astrocytomas compared to their respective specimens collected at diagnosis, in four pediatric patients.
Antioxidant-mediated up-regulation of OGG1 via NRF2 induction is associated ...Enrique Moreno Gonzalez
Estrogen metabolism-mediated oxidative stress is suggested to play an important role in estrogen-induced breast carcinogenesis. We have earlier demonstrated that antioxidants,
vitamin C (Vit C) and butylated hydroxyanisole (BHA) inhibit 17β-estradiol (E2)-mediated oxidative stress and oxidative DNA damage, and breast carcinogenesis in female August
Copenhagen Irish (ACI) rats. The objective of the present study was to characterize the mechanism by which above antioxidants prevent DNA damage during breast carcinogenesis.
Search for atoxic cereals: a single blind, cross-over study on the safety of...Enrique Moreno Gonzalez
Cereals of baking quality with absent or reduced toxicity are actively sought as alternative therapy to a gluten-free diet (GFD) for patients with coeliac disease (CD). Triticum monococcum, an ancient wheat, is a potential candidate having no toxicity in in-vitro and exvivo studies. The aim of our study was to investigate on the safety of administration of a single dose of gluten of Tm in patients with CD on GFD.
- The study examined malondialdehyde (MDA) levels and hematological parameters in 31 newly diagnosed cervical cancer patients at a hospital in India.
- MDA levels, which indicate oxidative stress, were found to be significantly higher in cervical cancer patients compared to healthy volunteers. MDA levels also differed between cancer grades.
- Hematological analysis found reduced red blood cell count and hemoglobin levels and increased white blood cell count in cervical cancer patients relative to normal levels.
- The results suggest that oxidative stress and hematological abnormalities are present at the initial clinical presentation of cervical cancer patients and that MDA may be a predictive marker for disease progression. Controlling oxidative stress and improving nutrition could help cervical cancer treatment
Variant G6PD levels promote tumor cell proliferation or apoptosis via the STA...Enrique Moreno Gonzalez
Glucose-6-phosphate dehydrogenase (G6PD), elevated in tumor cells, catalyzes the first reaction in the pentose-phosphate pathway. The regulation mechanism of G6PD and pathological change in human melanoma growth remains unknown.
A new assay for measuring chromosome instability (CIN) and identification of...Enrique Moreno Gonzalez
This document describes a new assay for measuring chromosome instability (CIN) using a human artificial chromosome (HAC) carrying a fluorescent marker. The assay allows quantification of HAC loss after drug treatment via flow cytometry. Several known anti-mitotic drugs were tested and found to increase HAC loss rates to varying degrees, with microtubule-stabilizing drugs taxol and peloruside A showing the highest increases in CIN. This new assay provides a simple and efficient way to screen drugs and identify those that elevate CIN, with the goal of developing new cancer therapies targeting chromosomally unstable tumors.
Cord Blood Mesenchymal Stem Cells Conditioned Media Suppress Epithelial Ovari...ijtsrd
MSC CM suppresses epithelial ovarian cancer cells in vitro in a concentration-dependent manner. When ovarian cancer cells were treated with MSC CM at concentrations of 100%, 75%, 50%, and 25% for 72 hours, cell morphology changes were observed including cell shrinkage, debris and reduced cell numbers compared to control. MTT assays showed reduced proliferation and Annexin V testing demonstrated increased early and late apoptosis. Cell cycle analysis found an increased sub-G1 phase, indicating apoptosis. Expression of embryonic stemness genes was also progressively suppressed in cancer cells treated with MSC CM compared to control. Therefore, MSC CM has potential as an ovarian cancer inhibitor by creating new treatment modalities.
Development and Validation of a Two-Site Immunoradiometric assay for Glypican...Premier Publishers
This study aimed to develop and validate an immunoradiometric assay (IRMA) to measure glypican-3 (GPC3) levels in plasma samples and evaluate its diagnostic potential for hepatocellular carcinoma (HCC). The researchers established an IRMA to measure GPC3 and compared its performance to a commercial ELISA kit using plasma samples from 150 HCC patients, 150 hepatitis C patients, and 150 healthy controls. The IRMA showed better diagnostic accuracy than the ELISA kit for distinguishing HCC patients from controls and hepatitis C patients based on receiver operating characteristic analysis. Using the optimized IRMA, the study found that GPC3 levels could help discriminate HCC from hepatitis C with high sensitivity and specificity and was a
This document summarizes a study examining the expression of Thomsen-Friedenreich antigen (TF-antigen), a mucin-type glycoprotein, in human esophageal squamous cell carcinoma (ESCC) using peanut agglutinin (PNA) binding. The study found increased levels of TF-antigen in the serum and tissues of ESCC patients compared to normal individuals. TF-antigen levels did not differ between well, moderately, and poorly differentiated ESCC grades and did not decrease after therapy. Expression of TF-antigen increased with histological progression and was localized to the Golgi apparatus and cell membrane in ESCC tissues. The study establishes TF-antigen as a potential diagnostic marker for ES
Determining the intrinsic quality of a summary (for Automatic Summarization E...Nishita Jaykumar
The document discusses factors that contribute to the quality of summaries generated by an automatic summarization system. It examines how the topic being summarized, source documents, and summarization method all impact the results. The system is evaluated by comparing summary content to curated medical resources to determine how well the high-level information is conveyed in a condensed format.
OSU-03012 sensitizes breast cancers to lapatinib-induced cell killing: a role...Enrique Moreno Gonzalez
Lapatinib is characterized as an ErbB1/ErbB2 dual inhibitor and has recently been approved for the treatment of metastatic breast cancer. In this study, we examined mechanisms
associated with enhancing the activity of lapatinib via combination with other therapies.
Expression of a LINE-1 endonuclease variant in gastric cancer: its associatio...Enrique Moreno Gonzalez
Long interspersed nuclear element-1 (LINE-1 or L1), the most abundant and only autonomously active family of non-LTR retrotransposons in the human genome, expressed not only in the germ lines but also in somatic tissues. It contributes to genetic instability, aging, and age-related diseases, such as cancer. Our previous study identified in human gastric adenocarcinoma an upregulated transcript GCRG213, which shared 88% homology with human LI sequence and contained a putative conserved apurinic/apyrimidinic endonucleas1 domain.
HDAC4 and HDAC7 Promote Breast and Ovarian Cancer Cell Migration by Regulatin...CrimsonpublishersCancer
Breast and ovarian cancer have been remained as a highly malignant tumor among women, posing a serious threat to women health worldwide. In this study, we were aimed to investigate the underlying mechanism of breast and ovarian cancer cell migration. Wound healing assay showed that MDA-MB-231and C13* have higher migration potential compare with MCF-7 and OV2078 cells, as well as regulated epithelial-mesenchymal transition (EMT) marker. We found that HDAC4 and HADC7 mRNA are up regulated in MDA-MB-231 and C13* cells. Moreover, target HDAC4 and HDAC7 by TSA or shRNA block MDA-MB-231and C13* migration. These results reveal a new link between HDACs and EMT in the regulation of breast and ovarian cancer migration.
Cancer Precision Medicine Physiological Function of C MYC as Targeted Moleculeijtsrd
The genome represents a design for creating the body, with each one being different. In cancer genomic medicine, many genes are simultaneously examined using mainly cancer tissues the oncogene panel test , and gene mutations are revealed. Cancer treatments are then initiated according to each individual's constitution and medical condition based on gene mutations. A system for cancer genome medical treatment is currently being developed. In the treatment of several cancer types, the "oncogene test with an oncogene companion diagnosis" is already being performed as a standard test using cancer tissue to detect one or several gene mutations. Precision Medicine discovering unique therapies that treat an individual's cancer based on the specific abnormalities, i.e. germline or somatic mutations of their tumors. In this paper, we will explain the biological role of C MYC and emphasize the importance of C MYC as a target factor in cancer precision medicine. The functional activated C MYC for cell proliferation and tumorigenesis is potential candidate as anti oncogenic molecule. Takuma Hayashi | Ikuo Konishi "Cancer Precision Medicine: Physiological Function of C-MYC as Targeted Molecule" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-5 , August 2019, URL: https://www.ijtsrd.com/papers/ijtsrd28030.pdfPaper URL: https://www.ijtsrd.com/medicine/other/28030/cancer-precision-medicine-physiological-function-of-c-myc-as-targeted-molecule/takuma-hayashi
Gene expression analysis of a Helicobacter pyloriinfected and high-salt diet-...Enrique Moreno Gonzalez
Helicobacter pylori (H. pylori) infection and excessive salt intake are known as important risk factors for stomach cancer in humans. However, interactions of these two factors with gene expression profiles during gastric carcinogenesis remain unclear. In the present study, we investigated the global gene expression associated with stomach carcinogenesis and prognosis of human gastric cancer using a mouse model.
This document summarizes two recent studies on prognostic biomarkers for hepatocellular carcinoma (HCC). The first study found that high levels of C-reactive protein (CRP), an inflammatory marker, predicts poor long-term survival for patients with HCC undergoing nonsurgical treatments. The second study found that low levels of CD4+ cytotoxic T lymphocytes (CTLs), part of the immune system, predicts poor outcomes and high recurrence rates for HCC patients. Both inflammatory and immunological markers may provide prognostic information to supplement current clinical staging systems for HCC. However, more research is still needed to validate the prognostic value of these biomarkers.
This study examined promoter hypermethylation of the hmlh1 gene in esophageal cancer patients from Kashmir, India. The researchers collected tumor and normal tissue samples from 50 cancer patients and 20 controls. DNA was extracted from the samples and treated to detect methylation levels. Methylation-specific PCR was performed using methylated and unmethylated primers. The frequency of hmlh1 promoter hypermethylation was 56% in cancer tissues and 15% in normal tissues, which was a statistically significant difference. The results suggest aberrant hmlh1 promoter hypermethylation may play a role in esophageal carcinogenesis in this high-risk population.
ResQu: A Framework for Automatic Evaluation of Knowledge-Driven Automatic Sum...Nishita Jaykumar
Automatic generation of summaries that capture the salient aspects of a search resultset
(i.e., automatic summarization) has become an important task in biomedical research. Automatic
summarization offers an avenue for overcoming the information overload problem
prevalent in large online digital libraries. However, across many of the knowledge-driven
approaches for automatic summarization it is not always clear which features highly impact
or influence the quality of a summary. Instead, there has been considerable focus on
utilizing schema knowledge to facilitate browsing and exploration of generated summaries
a posteriori. Informative features should not be ignored, since they could be utilized to
help optimize the models that generate these semantic summaries in the first place.
In this research, we adopt a leave-one-out approach to assess the impact of various
features on the quality of automatically generated summaries that contain structured background
knowledge. We first create the gold standard summaries, using information-theoretic
methods, by extraction and validation, then the semantic summaries are transformed into
an equivalent textual format. Finally, various similarity metrics, such as cosine similarity,
euclidean distance, and Jensen-Shannon divergence are computed under different feature
combinations, to assess summary quality against the textual gold standard. We report on
the relative importance of the various features used to automatically generate the semantic
summaries in a biomedical application. Our evaluation suggests that the proposed approach
is an effective automatic
Compound A inhibits bladder cancer growth through multiple mechanisms:
1) It functions as both a glucocorticoid receptor agonist and androgen receptor antagonist, inhibiting proliferation and inducing apoptosis in bladder cancer cells expressing both receptors.
2) It promotes interactions between the glucocorticoid receptor and nuclear factor-κB, inducing glucocorticoid receptor-mediated transrepression of genes related to invasion, migration and inflammation.
3) In mouse models, Compound A more strongly suppresses tumor growth than dexamethasone or hydroxyflutamide alone, indicating its dual receptor effects are more beneficial than targeting individual receptors.
Molecular Detection of Epstein-Barr Virus and Human Cytomegalovirus Antigen E...CrimsonpublishersCancer
Breast cancer is a leading cause of death among women worldwide. The association between Epstein-Barr Virus (EBV) and Human Cytomegalovirus (HCMV) and breast cancer risk still remains controversial making it difficult to determine whether either, both or neither virus is causally associated with breast cancer. The aim of this study was to detect EBV and the expression of the Immediate Early Antigen (IE) of HCMV in breast cancer in Sudanese women.
LCS101 (Protectival) Research Pubclications Abstractsyellowman
This document contains abstracts from multiple research publications on the botanical formula LCS101 and its potential effects in cancer treatment and reducing chemotherapy side effects. One study found LCS101 significantly reduced anemia, leukopenia, and neutropenia in breast cancer patients undergoing chemotherapy compared to a placebo. Another study found LCS101 selectively inhibited the growth of breast, colon, and prostate cancer cell lines while having no effect on normal cells. A third study found LCS101 increased the anticancer effects of doxorubicin and 5-FU on breast cancer cells but protected normal cells from chemotherapy-induced death.
11.relationship between the levels of serum thyroid hormones and the risk of ...Alexander Decker
This study examined the relationship between serum thyroid hormone levels and the risk of breast cancer. The study analyzed thyroid hormone and antibody levels in 100 breast cancer patients and 75 control individuals without breast or thyroid disease. The mean values for thyroid hormones (T3, T4) and anti-thyroid peroxidase antibodies were significantly higher in breast cancer patients compared to controls. The results indicate an increased prevalence of autoimmune and non-autoimmune thyroid diseases in breast cancer patients, suggesting that abnormal thyroid gland characteristics may influence breast cancer progression.
1) Glyceollin I is a phytochemical that can reverse epithelial to mesenchymal transition (EMT) in letrozole-resistant breast cancer cells by inhibiting the zinc finger E-box binding homeobox 1 (ZEB1) transcription factor.
2) Treatment of letrozole-resistant breast cancer cells (LTLT-Ca cells) with glyceollin I led to decreased proliferation, invasion, and migration in vitro as well as weaker ZEB1 and N-cadherin staining and stronger E-cadherin staining in vivo.
3) Glyceollin I treatment of LTLT-Ca cells caused a 3.39-fold
Black cohosh has been shown to inhibit the growth of both estrogen-dependent and estrogen-independent breast cancer cell lines. It appears to exert these effects through multiple mechanisms, including weak antagonism of estrogen receptors, induction of apoptosis through caspase activation, and cell cycle arrest. Extracts of black cohosh inhibited proliferation in a dose-dependent manner and induced apoptosis in breast cancer cells through both genomic and non-genomic mechanisms due to its various active components.
Fatty liver index correlates with non-alcoholic fatty liver disease, but not ...Enrique Moreno Gonzalez
Fatty liver index (FLI) was recently established to predict non-alcoholic fatty liver disease (NAFLD) in general population, which is known to be associated with coronary artery atherosclerotic disease (CAD).
This study aims to investigate whether FLI correlates with NAFLD and with newly diagnosed CAD in a special Chinese population who underwent coronary angiography.
Sox2 suppresses the invasiveness of breast cancer cells via a mechanism that ...Enrique Moreno Gonzalez
Sox2, an embryonic stem cell marker, is aberrantly expressed in a subset of breast cancer (BC). While the aberrant expression of Sox2 has been shown to significantly correlate with a number of clinicopathologic parameters in BC, its biological significance in BC is incompletely understood.
A new assay for measuring chromosome instability (CIN) and identification of...Enrique Moreno Gonzalez
This document describes a new assay for measuring chromosome instability (CIN) using a human artificial chromosome (HAC) carrying a fluorescent marker. The assay allows quantification of HAC loss after drug treatment via flow cytometry. Several known anti-mitotic drugs were tested and found to increase HAC loss rates to varying degrees, with microtubule-stabilizing drugs taxol and peloruside A showing the highest increases in CIN. This new assay provides a simple and efficient way to screen drugs and identify those that elevate CIN, with the goal of developing new cancer therapies targeting chromosomally unstable tumors.
Cord Blood Mesenchymal Stem Cells Conditioned Media Suppress Epithelial Ovari...ijtsrd
MSC CM suppresses epithelial ovarian cancer cells in vitro in a concentration-dependent manner. When ovarian cancer cells were treated with MSC CM at concentrations of 100%, 75%, 50%, and 25% for 72 hours, cell morphology changes were observed including cell shrinkage, debris and reduced cell numbers compared to control. MTT assays showed reduced proliferation and Annexin V testing demonstrated increased early and late apoptosis. Cell cycle analysis found an increased sub-G1 phase, indicating apoptosis. Expression of embryonic stemness genes was also progressively suppressed in cancer cells treated with MSC CM compared to control. Therefore, MSC CM has potential as an ovarian cancer inhibitor by creating new treatment modalities.
Development and Validation of a Two-Site Immunoradiometric assay for Glypican...Premier Publishers
This study aimed to develop and validate an immunoradiometric assay (IRMA) to measure glypican-3 (GPC3) levels in plasma samples and evaluate its diagnostic potential for hepatocellular carcinoma (HCC). The researchers established an IRMA to measure GPC3 and compared its performance to a commercial ELISA kit using plasma samples from 150 HCC patients, 150 hepatitis C patients, and 150 healthy controls. The IRMA showed better diagnostic accuracy than the ELISA kit for distinguishing HCC patients from controls and hepatitis C patients based on receiver operating characteristic analysis. Using the optimized IRMA, the study found that GPC3 levels could help discriminate HCC from hepatitis C with high sensitivity and specificity and was a
This document summarizes a study examining the expression of Thomsen-Friedenreich antigen (TF-antigen), a mucin-type glycoprotein, in human esophageal squamous cell carcinoma (ESCC) using peanut agglutinin (PNA) binding. The study found increased levels of TF-antigen in the serum and tissues of ESCC patients compared to normal individuals. TF-antigen levels did not differ between well, moderately, and poorly differentiated ESCC grades and did not decrease after therapy. Expression of TF-antigen increased with histological progression and was localized to the Golgi apparatus and cell membrane in ESCC tissues. The study establishes TF-antigen as a potential diagnostic marker for ES
Determining the intrinsic quality of a summary (for Automatic Summarization E...Nishita Jaykumar
The document discusses factors that contribute to the quality of summaries generated by an automatic summarization system. It examines how the topic being summarized, source documents, and summarization method all impact the results. The system is evaluated by comparing summary content to curated medical resources to determine how well the high-level information is conveyed in a condensed format.
OSU-03012 sensitizes breast cancers to lapatinib-induced cell killing: a role...Enrique Moreno Gonzalez
Lapatinib is characterized as an ErbB1/ErbB2 dual inhibitor and has recently been approved for the treatment of metastatic breast cancer. In this study, we examined mechanisms
associated with enhancing the activity of lapatinib via combination with other therapies.
Expression of a LINE-1 endonuclease variant in gastric cancer: its associatio...Enrique Moreno Gonzalez
Long interspersed nuclear element-1 (LINE-1 or L1), the most abundant and only autonomously active family of non-LTR retrotransposons in the human genome, expressed not only in the germ lines but also in somatic tissues. It contributes to genetic instability, aging, and age-related diseases, such as cancer. Our previous study identified in human gastric adenocarcinoma an upregulated transcript GCRG213, which shared 88% homology with human LI sequence and contained a putative conserved apurinic/apyrimidinic endonucleas1 domain.
HDAC4 and HDAC7 Promote Breast and Ovarian Cancer Cell Migration by Regulatin...CrimsonpublishersCancer
Breast and ovarian cancer have been remained as a highly malignant tumor among women, posing a serious threat to women health worldwide. In this study, we were aimed to investigate the underlying mechanism of breast and ovarian cancer cell migration. Wound healing assay showed that MDA-MB-231and C13* have higher migration potential compare with MCF-7 and OV2078 cells, as well as regulated epithelial-mesenchymal transition (EMT) marker. We found that HDAC4 and HADC7 mRNA are up regulated in MDA-MB-231 and C13* cells. Moreover, target HDAC4 and HDAC7 by TSA or shRNA block MDA-MB-231and C13* migration. These results reveal a new link between HDACs and EMT in the regulation of breast and ovarian cancer migration.
Cancer Precision Medicine Physiological Function of C MYC as Targeted Moleculeijtsrd
The genome represents a design for creating the body, with each one being different. In cancer genomic medicine, many genes are simultaneously examined using mainly cancer tissues the oncogene panel test , and gene mutations are revealed. Cancer treatments are then initiated according to each individual's constitution and medical condition based on gene mutations. A system for cancer genome medical treatment is currently being developed. In the treatment of several cancer types, the "oncogene test with an oncogene companion diagnosis" is already being performed as a standard test using cancer tissue to detect one or several gene mutations. Precision Medicine discovering unique therapies that treat an individual's cancer based on the specific abnormalities, i.e. germline or somatic mutations of their tumors. In this paper, we will explain the biological role of C MYC and emphasize the importance of C MYC as a target factor in cancer precision medicine. The functional activated C MYC for cell proliferation and tumorigenesis is potential candidate as anti oncogenic molecule. Takuma Hayashi | Ikuo Konishi "Cancer Precision Medicine: Physiological Function of C-MYC as Targeted Molecule" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-5 , August 2019, URL: https://www.ijtsrd.com/papers/ijtsrd28030.pdfPaper URL: https://www.ijtsrd.com/medicine/other/28030/cancer-precision-medicine-physiological-function-of-c-myc-as-targeted-molecule/takuma-hayashi
Gene expression analysis of a Helicobacter pyloriinfected and high-salt diet-...Enrique Moreno Gonzalez
Helicobacter pylori (H. pylori) infection and excessive salt intake are known as important risk factors for stomach cancer in humans. However, interactions of these two factors with gene expression profiles during gastric carcinogenesis remain unclear. In the present study, we investigated the global gene expression associated with stomach carcinogenesis and prognosis of human gastric cancer using a mouse model.
This document summarizes two recent studies on prognostic biomarkers for hepatocellular carcinoma (HCC). The first study found that high levels of C-reactive protein (CRP), an inflammatory marker, predicts poor long-term survival for patients with HCC undergoing nonsurgical treatments. The second study found that low levels of CD4+ cytotoxic T lymphocytes (CTLs), part of the immune system, predicts poor outcomes and high recurrence rates for HCC patients. Both inflammatory and immunological markers may provide prognostic information to supplement current clinical staging systems for HCC. However, more research is still needed to validate the prognostic value of these biomarkers.
This study examined promoter hypermethylation of the hmlh1 gene in esophageal cancer patients from Kashmir, India. The researchers collected tumor and normal tissue samples from 50 cancer patients and 20 controls. DNA was extracted from the samples and treated to detect methylation levels. Methylation-specific PCR was performed using methylated and unmethylated primers. The frequency of hmlh1 promoter hypermethylation was 56% in cancer tissues and 15% in normal tissues, which was a statistically significant difference. The results suggest aberrant hmlh1 promoter hypermethylation may play a role in esophageal carcinogenesis in this high-risk population.
ResQu: A Framework for Automatic Evaluation of Knowledge-Driven Automatic Sum...Nishita Jaykumar
Automatic generation of summaries that capture the salient aspects of a search resultset
(i.e., automatic summarization) has become an important task in biomedical research. Automatic
summarization offers an avenue for overcoming the information overload problem
prevalent in large online digital libraries. However, across many of the knowledge-driven
approaches for automatic summarization it is not always clear which features highly impact
or influence the quality of a summary. Instead, there has been considerable focus on
utilizing schema knowledge to facilitate browsing and exploration of generated summaries
a posteriori. Informative features should not be ignored, since they could be utilized to
help optimize the models that generate these semantic summaries in the first place.
In this research, we adopt a leave-one-out approach to assess the impact of various
features on the quality of automatically generated summaries that contain structured background
knowledge. We first create the gold standard summaries, using information-theoretic
methods, by extraction and validation, then the semantic summaries are transformed into
an equivalent textual format. Finally, various similarity metrics, such as cosine similarity,
euclidean distance, and Jensen-Shannon divergence are computed under different feature
combinations, to assess summary quality against the textual gold standard. We report on
the relative importance of the various features used to automatically generate the semantic
summaries in a biomedical application. Our evaluation suggests that the proposed approach
is an effective automatic
Compound A inhibits bladder cancer growth through multiple mechanisms:
1) It functions as both a glucocorticoid receptor agonist and androgen receptor antagonist, inhibiting proliferation and inducing apoptosis in bladder cancer cells expressing both receptors.
2) It promotes interactions between the glucocorticoid receptor and nuclear factor-κB, inducing glucocorticoid receptor-mediated transrepression of genes related to invasion, migration and inflammation.
3) In mouse models, Compound A more strongly suppresses tumor growth than dexamethasone or hydroxyflutamide alone, indicating its dual receptor effects are more beneficial than targeting individual receptors.
Molecular Detection of Epstein-Barr Virus and Human Cytomegalovirus Antigen E...CrimsonpublishersCancer
Breast cancer is a leading cause of death among women worldwide. The association between Epstein-Barr Virus (EBV) and Human Cytomegalovirus (HCMV) and breast cancer risk still remains controversial making it difficult to determine whether either, both or neither virus is causally associated with breast cancer. The aim of this study was to detect EBV and the expression of the Immediate Early Antigen (IE) of HCMV in breast cancer in Sudanese women.
LCS101 (Protectival) Research Pubclications Abstractsyellowman
This document contains abstracts from multiple research publications on the botanical formula LCS101 and its potential effects in cancer treatment and reducing chemotherapy side effects. One study found LCS101 significantly reduced anemia, leukopenia, and neutropenia in breast cancer patients undergoing chemotherapy compared to a placebo. Another study found LCS101 selectively inhibited the growth of breast, colon, and prostate cancer cell lines while having no effect on normal cells. A third study found LCS101 increased the anticancer effects of doxorubicin and 5-FU on breast cancer cells but protected normal cells from chemotherapy-induced death.
11.relationship between the levels of serum thyroid hormones and the risk of ...Alexander Decker
This study examined the relationship between serum thyroid hormone levels and the risk of breast cancer. The study analyzed thyroid hormone and antibody levels in 100 breast cancer patients and 75 control individuals without breast or thyroid disease. The mean values for thyroid hormones (T3, T4) and anti-thyroid peroxidase antibodies were significantly higher in breast cancer patients compared to controls. The results indicate an increased prevalence of autoimmune and non-autoimmune thyroid diseases in breast cancer patients, suggesting that abnormal thyroid gland characteristics may influence breast cancer progression.
1) Glyceollin I is a phytochemical that can reverse epithelial to mesenchymal transition (EMT) in letrozole-resistant breast cancer cells by inhibiting the zinc finger E-box binding homeobox 1 (ZEB1) transcription factor.
2) Treatment of letrozole-resistant breast cancer cells (LTLT-Ca cells) with glyceollin I led to decreased proliferation, invasion, and migration in vitro as well as weaker ZEB1 and N-cadherin staining and stronger E-cadherin staining in vivo.
3) Glyceollin I treatment of LTLT-Ca cells caused a 3.39-fold
Black cohosh has been shown to inhibit the growth of both estrogen-dependent and estrogen-independent breast cancer cell lines. It appears to exert these effects through multiple mechanisms, including weak antagonism of estrogen receptors, induction of apoptosis through caspase activation, and cell cycle arrest. Extracts of black cohosh inhibited proliferation in a dose-dependent manner and induced apoptosis in breast cancer cells through both genomic and non-genomic mechanisms due to its various active components.
Fatty liver index correlates with non-alcoholic fatty liver disease, but not ...Enrique Moreno Gonzalez
Fatty liver index (FLI) was recently established to predict non-alcoholic fatty liver disease (NAFLD) in general population, which is known to be associated with coronary artery atherosclerotic disease (CAD).
This study aims to investigate whether FLI correlates with NAFLD and with newly diagnosed CAD in a special Chinese population who underwent coronary angiography.
Sox2 suppresses the invasiveness of breast cancer cells via a mechanism that ...Enrique Moreno Gonzalez
Sox2, an embryonic stem cell marker, is aberrantly expressed in a subset of breast cancer (BC). While the aberrant expression of Sox2 has been shown to significantly correlate with a number of clinicopathologic parameters in BC, its biological significance in BC is incompletely understood.
Nitroglycerin 0.4% ointment vs placebo in the treatment of pain resulting fro...Enrique Moreno Gonzalez
This randomized, double-blind, placebo-controlled study compared nitroglycerin (NTG) 0.4% ointment to placebo for treating pain from chronic anal fissures. 247 patients applied either NTG or placebo ointment twice daily for 21 days. The primary outcome was change in pain levels from days 14-18. While the prespecified analysis found no difference, post hoc analyses found NTG reduced pain more than placebo. Headache was the most common side effect. This was the first such study to control for analgesics used to treat NTG-induced headaches, finding NTG 0.4% effectively reduced chronic anal fissure pain compared to placebo.
Anti-lymphangiogenic properties of mTOR inhibitors in head and neck squamous ...Enrique Moreno Gonzalez
Tumor dissemination to cervical lymph nodes via lymphatics represents the first step in the metastasis of head and neck squamous cell carcinoma (HNSCC) and is the most significant predictor of tumor recurrence decreasing survival by 50%. The lymphatic suppressing properties of mTOR inhibitors are not yet well understood.
Perceived benefits and barriers to exercise for recently treated patients wit...Enrique Moreno Gonzalez
Understanding the physical activity experiences of patients with multiple myeloma (MM) is essential to inform the development of evidence-based interventions and to quantify the benefits of physical activity. The aim of this study was to gain an in-depth understanding of the physical activity experiences and perceived benefits and barriers to physical activity for patients with MM.
The cysteinyl leukotriene 2 receptor contributes to all-trans retinoic acid-i...Enrique Moreno Gonzalez
Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory mediators that are increased in samples from patients with inflammatory bowel diseases (IBDs). Individuals with IBDs have enhanced susceptibility to colon carcinogenesis. In colorectal cancer, the balance between the pro-mitogenic cysteinyl leukotriene 1 receptor (CysLT1R) and the differentiation-promoting cysteinyl leukotriene 2 receptor (CysLT2R) is lost. Further, our previous data indicate that patients with high CysLT1R and low CysLT2R expression have a poor prognosis. In this study, we examined whether the balance between CysLT1R and CysLT2R could be restored by treatment with the cancer chemopreventive agent all-trans retinoic acid (ATRA).
Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on...Enrique Moreno Gonzalez
Melanoma represents one of the most aggressive and therapeutically challenging malignancies as it often gives rise to metastases and develops resistance to classical chemotherapeutic agents. Although diverse therapies have been generated, no major improvement of the patient prognosis has been noticed. One promising alternative to the conventional therapeutic approaches currently available is the inactivation of proteins essential for survival and/or progression of melanomas by means of RNA interference. Survivin and cyclin B1, both involved in cell survival and proliferation and frequently deregulated in human cancers, are good candidate target genes for siRNA mediated therapeutics.
Intensity-modulated radiotherapy with simultaneous modulated accelerated boos...Enrique Moreno Gonzalez
To present our experience of intensity-modulated radiotherapy (IMRT) with simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC).
Clinical features and outcome of cryptogenic hepatocellular carcinoma compare...Enrique Moreno Gonzalez
Cryptogenic hepatocellular carcinoma (HCC) is thought to arise due to non-alcoholic fatty liver disease (NAFLD). This study investigated the prevalence, clinical features, and outcomes of cryptogenic HCC and compared them with those of HCC related to hepatitis B virus infection (HBV-HCC), hepatitis C virus infection (HCV-HCC), and alcohol (ALCHCC) in Korea.
Intraepithelial lymphocyte distribution differs between the bulb and the seco...Enrique Moreno Gonzalez
Evaluation of intraepithelial duodenal lymphocytosis (IDL) is important in celiac disease (CD). There is no established cut-off value for increased number of IELs in the bulb. We therefore investigated the relation between IEL counts in the bulb and duodenal specimens in non-celiac subjects.
Antibiotic exposure and the development of coeliac disease: a nationwide case...Enrique Moreno Gonzalez
The intestinal microbiota has been proposed to play a pathogenic role in coeliac disease (CD). Although antibiotics are common environmental factors with a profound impact on intestinal microbiota, data on antibiotic use as a risk factor for subsequent CD development are scarce.
A phase I/II trial to evaluate the safety, feasibility and activity of salvag...Enrique Moreno Gonzalez
The current standard treatment of patients with relapsed or refractory diffuse large cell B-Cell lymphoma (DLBCL) primarily consists of intensified salvage therapy and, if the disease is chemo-sensitive, high dose therapy followed with autologous stem cell transplantation. In the rituximab era however, this treatment approach has shown only limited benefit. In particular, patients relapsing after rituximab-containing primary treatment have an adverse prognosis, especially if this occurs within the first year after therapy or if the disease is primarily refractory. Therefore there is an ultimate need for improved salvage treatment approaches.
Association between variations in the fat mass and obesity-associated gene an...Enrique Moreno Gonzalez
It is clear that genetic variations in the fat mass and obesity-associated (FTO) gene affect body mass index and the risk of obesity. Given the mounting evidence showing a positive association between obesity and pancreatic cancer, this study aimed to investigate the relation between variants in the FTO gene, obesity and pancreatic cancer risk.
Frizzled-8 receptor is activated by the Wnt-2 ligand in non-small cell lung c...Enrique Moreno Gonzalez
This document summarizes a research study that investigated the activation of Wnt-2 signaling through the Frizzled-8 receptor in non-small cell lung cancer (NSCLC). The study found a correlation between increased expression of Wnt-2 and Frizzled-8 in lung cancer tissue samples. A novel dominant-negative Wnt-2 construct (dnhWnt-2) inhibited Wnt-2 signaling activation and reduced colony formation of NSCLC cells in vitro and tumor growth in a mouse xenograft model. The dnhWnt-2 construct may provide a new therapeutic approach for targeting the Wnt pathway in lung cancer.
Implication from thyroid function decreasing during chemotherapy in breast ca...Enrique Moreno Gonzalez
Thyroid hormones have been shown to regulate breast cancer cells growth, the absence or reduction of thyroid hormones in cells could provoke a proliferation arrest in G0-G1 or weak mitochondrial activity, which makes cells insensitive to therapies for cancers through transforming into low metabolism status. This biological phenomenon may help explain why treatment efficacy and prognosis vary among breast cancer patients having hypothyroid, hyperthyroid and normal function. Nevertheless, the abnormal thyroid function in breast cancer patients has been considered being mainly caused by thyroid diseases, few studied influence of chemotherapy on thyroid function and whether its alteration during chemotherapy can influence the respose to chemotherapy is still unclear. So, we aimed to find the alterations of thyroid function and non-thyroidal illness syndrome (NTIS) prevalence druing chemotherapy in breast cancer patients, and investigate the influence of thyroid hormones on chemotherapeutic efficacy.
Overexpression of peptide deformylase in breast, colon, and lung cancersEnrique Moreno Gonzalez
Human mitochondrial peptide deformylase (PDF) has been proposed as a novel cancer therapeutic target. However, very little is known about its expression and regulation in human tissues. The purpose of this study was to characterize the expression pattern of PDF in cancerous tissues and to identify mechanisms that regulate its expression.
Induction of chromosome instability and stomach cancer by altering the expres...Enrique Moreno Gonzalez
There are strong indications for a causal association between areca-nut consumption and cancers. In Meghalaya, India, the variety of areca-nut is used as raw and unprocessed form whose chemical composition and pharmacological actions have been reported. Yet we know little on the initial pathway involved in areca-nut associated carcinogenesis since it is difficult to assess its effects on genetic alterations without interference of other compounding factors. Therefore, present study was undertaken in mice to verify the ability of raw areca-nut (RAN) to induce cancer and to monitor the expression of certain genes involved in carcinogenesis. This study was not intended to isolate any active ingredients from the RAN and to look its action.
If the many beneficial effects of the chemokines can be preserved, such efforts hold great promise for uncovering new therapies for inflammatory and immunologic disease
Optimal schedule of Bacillus Calmette-Guerin for non-muscle-invasive bladder ...Enrique Moreno Gonzalez
To explore the necessity of maintenance, efficacy of low-dose and superiority of various combination therapies of Bacillus Calmette-Guérin (BCG) in treatment of superficial bladder cancer (BCa).
Two of the most catastrophic global pandemics in history, the Black Death and AIDS, are connected by chemokines. During the Black Death pandemic in the 14th century, which killed over 50% of Europe's population, the Mediterranean region suffered heavy casualties. Interestingly, populations from this region are resistant to HIV-1. This resistance is due to a genetic mutation found in some individuals that prevents the CCR5 protein, which HIV-1 uses to enter immune cells, from functioning properly. This same mutation provided benefits against both the plague and HIV/AIDS.
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.
Claudin 1 expression in basal-like breast cancer is related to patient ageEnrique Moreno Gonzalez
Defects in tight junctions, gate-keepers of the integrity of the epidermal barrier function, are known to contribute to cancer development. As such, enhancing our understanding of how the expression of proteins involved in these junctions is regulated in cancer, remains a priority. Although the expression of one of these proteins, claudin 1, is down regulated in most invasive human breast cancers (HBC), we have recently shown that high levels of claudin 1, characterized tumors belonging to the very aggressive basal-like breast cancer (BLBC) subtype. In these tumors, the claudin 1.
This document summarizes research on anaplastic large cell lymphoma (ALCL) associated with breast implants. The researchers established three new cell lines from patient biopsy specimens to study the unique biology of this cancer. Characterization found chromosomal abnormalities but no common genetic translocations. The cancer cells showed markers of T-cells and antigen presentation. Studies revealed strong activation of STAT3 signaling related to increased interleukin-6 and decreased SHP-1 phosphatase, suggesting a mechanism of cell survival. Inhibiting STAT3 or treating with chemotherapy killed the cancer cells in vitro, indicating potential new therapies for this disease. The cell lines provide models to further understand breast implant-associated ALCL and identify effective treatments.
Triple negative breast cancer (TNBC) accounts for 15-25% of breast cancer cases and has a poor prognosis due to a lack of molecular targets. The study characterized expression of the lactate transporter MCT1 and its ancillary protein CD-147 in murine TNBC 4T1 cells. MCT1 and CD-147 were expressed on the cell membrane. L-lactate uptake followed Michaelis-Menten kinetics and was inhibited by the MCT1 inhibitor AR-155858, indicating MCT1's role in uptake. Further studies are needed to investigate MCT1 inhibition as a potential TNBC therapy.
Transcriptome Analysis of Spontaneous PDFJanaya Shelly
This document summarizes an analysis of gene expression in mouse lung tumors using RNA sequencing. Five mouse lung tumors - two spontaneous and three genetically engineered - were analyzed along with normal lung tissue. The top expressing genes in each tumor type were identified and their biological functions analyzed. Spontaneous tumors were associated with homeostatic processes while engineered tumors exhibited genes related to metastasis and immune response. The study aims to gain insights into lung cancer genetics using mouse models.
Sipuleucel-T (Provenge) is an autologous cellular immunotherapy for asymptomatic metastatic prostate cancer. It consists of autologous dendritic cells activated ex vivo with a recombinant fusion protein and infused back to the patient to stimulate an immune response against prostate cancer cells. Clinical trials demonstrated a significant survival benefit for patients treated with Sipuleucel-T compared to placebo. Dendreon is preparing for the commercial launch of Provenge in the US and EU, which will require a major manufacturing and logistics effort to process and deliver the personalized immunotherapy to thousands of patients.
Cancer testis antigens and NY-BR-1 expression in primary breast cancer: prog...Enrique Moreno Gonzalez
Cancer–testis antigens (CTA) comprise a family of proteins, which are physiologically expressed in adult human tissues solely in testicular germ cells and occasionally placenta. However, CTA expression has been reported in various malignancies. CTAs have been identified by their ability to elicit autologous cellular and or serological immune responses, and are considered potential targets for cancer immunotherapy. The breast differentiation antigen NY-BR-1, expressed specifically in normal and malignant breast tissue, has also immunogenic properties. Here we evaluated the expression patterns of CTAs and NY-BR-1 in breast cancer in correlation to clinico-pathological parameters in order to determine their possible impact as prognostic factors.
Benefit of Serum-Thymidine Kinase 1 Concentration for Risk Assessment from Ga...eshaasini
This meta-analysis examined 27 studies to determine if serum thymidine kinase 1 concentration (STK1p) can provide benefit for risk assessment of gastric neoplasm progression to gastric carcinoma (GC) and for evaluating GC treatment effects. The studies included 1,909 GC patients, 1,229 gastric neoplasm patients, and 2,260 tumor-free individuals. The results showed that STK1p levels increased significantly from tumor-free to superficial gastritis to chronic gastritis to atrophic gastritis to gastric ulcer to GC. STK1p levels in 251 GC patients declined significantly by 66% one month after surgery compared to pre-surgery levels. This suggests that STK1p has
Benefit of Serum-Thymidine Kinase 1 Concentration for Risk Assessment from Ga...semualkaira
Human Thymidine kinase 1 (hTK1), a key enzyme involved in the DNA synthesis during S-phase of the cell cycle and upregulation of cell proliferation, thus it is reliable tumor proliferating biomarker for assessment of tumor proliferation rate in serum and in tissue in oncology. This meta-analysis is investigation whether the serum TK1 concentration(STK1p)based on hTK1-IgY-polyclonal-antibody can provide a benefit for risk assessment from gastric neoplasm progression to gastric carcinoma (GC) as well as for evaluation of treatment effect in GC.
Benefit of Serum-Thymidine Kinase 1 Concentration for Risk Assessment from Ga...semualkaira
Human Thymidine kinase 1 (hTK1), a key enzyme involved in the DNA synthesis during S-phase of the cell cycle and upregulation of cell proliferation, thus it is reliable tumor proliferating biomarker for assessment of tumor proliferation rate in serum and in tissue in oncology. This meta-analysis is investigation whether the serum TK1 concentration(STK1p)based on hTK1-IgY-polyclonal-antibody can provide a benefit for risk assessment from gastric neoplasm progression to gastric carcinoma (GC) as well as for evaluation of treatment effect in GC.
Benefit of Serum-Thymidine Kinase 1 Concentration for Risk Assessment from Ga...semualkaira
Human Thymidine kinase 1 (hTK1), a key enzyme involved in the DNA synthesis during S-phase of the cell cycle and upregulation of cell proliferation, thus it is reliable tumor proliferating biomarker for assessment of tumor proliferation rate in serum and in tissue in oncology. This meta-analysis is investigation whether the serum TK1 concentration(STK1p)based on hTK1-IgY-polyclonal-antibody can provide a benefit for risk assessment from gastric neoplasm progression to gastric carcinoma (GC) as well as for evaluation of treatment effect in GC.
Expression profile of BRCA1 and BRCA2 genes in premenopausal Mexican women wi...Erwin Chiquete, MD, PhD
Gloria Loredo-Pozos, Erwin Chiquete,
Antonio Oceguera-Villanueva, Arturo Panduro,
Fernando Siller-Lo´pez, Martha E. Ramos-Márquez
Low BRCA1 gene expression is associated with
increased invasiveness and influences the response of
breast carcinoma (BC) to chemotherapeutics. However,
expression of BRCA1 and BRCA2 genes has not been
completely characterized in premenopausal BC. We analyzed
the clinical and immunohistochemical correlates of
BRCA1 and BRCA2 expression in young BC women. We
studied 62 women (mean age 38.8 years) who developed
BC before the age of 45 years. BRCA1 and BRCA2 mRNA
expression was assessed by reverse transcriptase-polymerase
chain reaction (RT-PCR) and that of HER-2 and
p53 proteins by immunohistochemistry. Body mass index
(BMI) C27 (52%) and a declared family history of BC
(26%) were the main risk factors. Ductal infiltrative adenocarcinoma
was found in 86% of the cases (tumor size
[5 cm in 48%). Disease stages I–IV occurred in 2, 40, 55,
and 3%, respectively (73% implicating lymph nodes).
Women aged B35 years (24%) had more family history of
cervical cancer, stage III/IV disease, HER-2 positivity, and
lower BRCA1 expression than older women (P-.05).
BRCA1 and BRCA2 expression correlated in healthy, but
not in tumor tissues (TT). Neither BRCA1 nor BRCA2
expression was associated with tumor histology, differentiation,
nodal metastasis or p53 and HER-2 expression.
After multivariate analysis, only disease stage explained
BRCA1 mRNA levels in the lowest quartile. Premenopausal
BC has aggressive clinical and molecular
characteristics. Low BRCA1 mRNA expression is associated
mainly with younger ages and advanced clinical stage
of premenopausal BC. BRCA2 expression is not associated
with disease severity in young BC women.
This document provides personal and professional information about Dr. Teh-Ying Chou. It summarizes her educational background, current positions, work experience, research interests and topics. Her research focuses on the pathobiology of lung diseases, including studies on EGFR mutations in lung cancer patients treated with gefitinib, genetic profiling of in situ and invasive lung adenocarcinomas, and the role of Clusterin in epithelial-mesenchymal transitions and metastasis of lung cancer cells. She has published papers on biomarkers for acute respiratory distress syndrome outcomes and the predictive value of EGFR mutations for gefitinib treatment responses in lung cancer.
1. Sipuleucel-T (Provenge) is an autologous cellular immunotherapy for asymptomatic metastatic prostate cancer that works by activating antigen-presenting cells and T-cells against prostatic acid phosphatase.
2. Clinical trials showed Provenge improved overall survival in metastatic castration-resistant prostate cancer patients.
3. Manufacturing and delivering Provenge presents logistical challenges due to its personalized nature that Dendreon aims to address through an advanced planning system and partnerships.
1) The study found that the tumor protein p53 regulates the expression of the immune checkpoint protein PDL1 (programmed death ligand 1) via the microRNA miR-34.
2) Delivery of miR-34a in a mouse model of lung cancer using a liposomal formulation (MRX34) reduced PDL1 expression in tumors and increased tumor-infiltrating immune cells.
3) Combining MRX34 with radiation therapy further increased immune cell numbers in tumors and showed potential as a novel cancer therapeutic approach.
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...daranisaha
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database.
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...eshaasini
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...semualkaira
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database.
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...semualkaira
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database.
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...semualkaira
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database
Similar to Chemokine (C-X-C) ligand 1 (CXCL1) protein expression is increased in aggressive bladder cancers (20)
Incidence of pneumonia and risk factors among patients with head and neck can...Enrique Moreno Gonzalez
This study investigated the incidence and patient- and treatment-related risk factors related to pneumonia acquired during radiotherapy (PNRT) in head and neck cancer (HNC) patients.
Acute myeloid leukemia (AML) is a hematopoietic malignancy with a dismal outcome in the majority of cases. A detailed understanding of the genetic alterations and gene expression changes that contribute to its pathogenesis is important to improve prognostication, disease monitoring, and therapy. In this context, leukemia-associated misexpression of microRNAs (miRNAs) has been studied, but no coherent picture has emerged yet, thus warranting further investigations.
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.
Differences in microRNA expression during tumor development in the transition...Enrique Moreno Gonzalez
The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate.
Multicentric and multifocal versus unifocal breast cancer: differences in the...Enrique Moreno Gonzalez
This study compared the expression of E-cadherin, β-catenin, and MUC1 in multicentric/multifocal breast cancers versus unifocal breast cancers of identical tumor size and grade. The study found significantly downregulated expression of E-cadherin in multicentric/multifocal cancers compared to unifocal cancers. In contrast, no significant differences were seen in β-catenin expression between the two groups. Within the unifocal group, E-cadherin and β-catenin expression were positively correlated, but this was not seen in the multicentric/multifocal group. The results suggest multicentric/multifocal and unifocal breast cancers differ in E-
The life in sight application study (LISA): design of a randomized controlled...Enrique Moreno Gonzalez
It is widely recognized that spiritual care plays an important role in physical and psychosocial well-being of cancer patients, but there is little evidence based research on the effects of spiritual care. We will conduct a randomized controlled trial on spiritual care using a brief structured interview scheme supported by an e-application. The aim is to examine whether an assisted reflection on life events and ultimate life goals can improve quality of life of cancer patients.
Assessment of preoperative exercise capacity in hepatocellular carcinoma pati...Enrique Moreno Gonzalez
Cardiopulmonary exercise testing measures oxygen uptake at increasing levels of work and predicts cardiopulmonary performance under conditions of stress, such as after abdominal surgery. Dynamic assessment of preoperative exercise capacity may be a useful predictor of postoperative prognosis. This study examined the relationship between preoperative exercise capacity and event-free survival in hepatocellular carcinoma (HCC) patients with chronic liver injury who underwent hepatectomy.
Overexpression of YAP 1 contributes to progressive features and poor prognosi...Enrique Moreno Gonzalez
Yes-associated protein 1 (YAP 1), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene in multiple tumors. However, the expression dynamics of YAP 1 in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance are unclear.
CXCR7 is induced by hypoxia and mediates glioma cell migration towards SDF-1a...Enrique Moreno Gonzalez
Glioblastomas, the most common and malignant brain tumors of the central nervous system, exhibit high invasive capacity, which hinders effective therapy. Therefore, intense efforts aimed at improved therapeutics are ongoing to delineate the molecular mechanisms governing glioma cell migration and invasion.
Abnormal expression of Pygopus 2 correlates with a malignant phenotype in hum...Enrique Moreno Gonzalez
Pygopus 2 (Pygo2) is a Pygo family member and an important component of the Wnt signaling transcriptional complex. Despite this data, no clinical studies investigating Pygo2 expression in lung cancer have yet been reported.
Differentiation of irradiation and cetuximab induced skin reactions in patien...Enrique Moreno Gonzalez
In order to improve the clinical outcome of patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) not being capable to receive platinum-based chemoradiation, radiotherapy can be intensified by addition of cetuximab, a monoclonal antibody that blocks the epidermal growth factor receptor (EGFR). The radioimmunotherapy with cetuximab is a feasible treatment option showing a favourable toxicity profile. The most frequent side effect of radiotherapy is radiation dermatitis, the most common side effect of treatment with cetuximab is acneiform rash. Incidence and severity of these frequent, often overlapping and sometimes limiting skin reactions, however, are not well explored. A clinical and molecular differentiation between radiogenic skin reactions and skin reactions caused by cetuximab which may correlate with outcome, have never been described before.
Cholestasis induces reversible accumulation of periplakin in mouse liverEnrique Moreno Gonzalez
Periplakin (PPL) is a rod-shaped cytolinker protein thought to connect cellular adhesion junctional complexes to cytoskeletal filaments. PPL serves as a structural component of the cornified envelope in the skin and interacts with various types of proteins in cultured cells; its level decreases dramatically during tumorigenic progression in human epithelial tissues. Despite these intriguing observations, the physiological roles of PPL, especially in noncutaneous tissues, are still largely unknown. Because we observed a marked fluctuation of PPL expression in mouse liver in association with the bile acid receptor farnesoid X receptor (FXR) and cholestasis, we sought to characterize the role of PPL in the liver and determine its contributions to the etiology and pathogenesis of cholestasis.
Functional p53 is required for rapid restoration of daunorubicin-induced lesi...Enrique Moreno Gonzalez
This document summarizes a research article that studied the role of p53 in daunorubicin (DNR)-induced lesions in the spleen. The key findings were:
1) DNR treatment caused more rapid cell death and weight loss in the spleens of wild type mice compared to p53-null mice.
2) While wild type mouse spleens recovered normal morphology 8 days after DNR treatment, p53-null mouse spleens still had large necrotic lesions.
3) DNR treatment increased p21 levels in wild type mice but not p53-null mice, indicating p53 is required for p21 induction.
4) The results suggest p53
Post-diagnosis hemoglobin change associates with overall survival of multiple...Enrique Moreno Gonzalez
Anemia refers to low hemoglobin (Hb) level and is a risk factor of cancer patient survival. The National Comprehensive Cancer Network recently suggested that post-diagnosis Hb change, regardless of baseline Hb level, indicates the potential presence of anemia. However, there is no epidemiological study evaluating whether Hb change has direct prognostic values for cancer patients at the population level.
Cost-effectiveness of MRI for breast cancer screening in BRCA1/2 mutation car...Enrique Moreno Gonzalez
Women with mutations in BRCA1 or BRCA2 are at high risk of developing breast cancer and, in British Columbia, Canada, are offered screening with both magnetic resonance imaging (MRI) and mammography to facilitate early detection. MRI is more sensitive than mammography but is more costly and produces more false positive results. The purpose of this study was to calculate the cost-effectiveness of MRI screening for breast cancer in BRCA1/2 mutation carriers in a Canadian setting.
Este documento presenta la laudatio del Dr. Enrique Moreno González, quien recibe el grado de Doctor Honoris Causa de la Universidad de Málaga. Resalta la trayectoria académica y profesional del Dr. Moreno, incluyendo sus logros en cirugía hepática y de trasplantes, sus cargos y distinciones, y su dedicación a la enseñanza. El orador destaca al Dr. Moreno como pionero quirúrgico, maestro, y persona comprometida con mejorar la atención médica a través
Environment inside even a small tumor is characterized by total (anoxia) or partial oxygen deprivation, hypoxia. It has been shown that radiotherapy and some conventional chemotherapies may be less effective in hypoxia, and therefore it is important to investigate how different drugs act in different microenvironments. In this study we perform a large screening of the effects of 19 clinically used or experimental chemotherapeutic drugs on four different cell lines in conditions of normoxia, hypoxia and anoxia.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
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).
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Clinic ^%[+27633867063*Abortion Pills For Sale In Tembisa Central19various
Clinic ^%[+27633867063*Abortion Pills For Sale In Tembisa Central Clinic ^%[+27633867063*Abortion Pills For Sale In Tembisa CentralClinic ^%[+27633867063*Abortion Pills For Sale In Tembisa CentralClinic ^%[+27633867063*Abortion Pills For Sale In Tembisa CentralClinic ^%[+27633867063*Abortion Pills For Sale In Tembisa Central
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
2. Chemokine (C-X-C) ligand 1 (CXCL1) protein
expression is increased in aggressive bladder cancers
Makito Miyake1
Email: Makito.miyake@orlandohealth.com
Adrienne Lawton2
Email: Adrienne.lawton@orlandohealth.com
Steve Goodison3
Email: goodison.steve@gmail.com
Virginia Urquidi3
Email: Virginia.urquidi@gmail.com
Evan Gomes-Giacoia1
Email: Evan.gomesgiacoia@orlandohealth.com
Ge Zhang1
Email: Ge.zhang@orlandohealth.com
Shanti Ross1
Email: Shanti.ross@orlandohealth.com
Jeongsoon Kim1
Email: Jeongsoon.kim@orlandohealth.com
Charles J Rosser1,3,*
Email: deacdoc@aol.com
1
Cancer Research Institute, Orlando Health, Orlando, FL 32827, USA
2
Department of Pathology, Orlando Health, Orlando, FL 32806, USA
3
Nonagen Bioscience Corporation, Orlando, FL 32827, USA
*
Corresponding author. Cancer Research Institute, Orlando Health, Orlando, FL
32827, USA
Abstract
Background
Chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), may regulate tumor
epithelial-stromal interactions that facilitate tumor growth and invasion. Studies have linked
CXCL1 expression to gastric, colon and skin cancers, but limited studies to date have
described CXCL1 protein expression in human bladder cancer (BCa) tissues.
3. Methods
CXCL1 protein expression was examined in 152 bladder tissue specimens (142 BCa) by
immunohistochemical staining. The expression of CXCL1 was scored by assigning a
combined score based on the proportion of cells staining and intensity of staining. CXCL1
expression patterns were correlated with clinicopathological features and follow-up data.
Results
CXCL1 protein expression was present in cancerous tissues, but was entirely absent in benign
tissue. CXCL1 combined immunostaining score was significantly higher in high-grade
tumors relative to low-grade tumors (p = 0.012). Similarly, CXCL1 combined
immunostaining score was higher in high stage tumors (T2-T4) than in low-grade tumors
(Ta-T1) (p < 0.0001). An increase in the combined immunostaining score of CXCL1 was also
associated with reduced disease-specific survival.
Conclusion
To date, this is the largest study describing increased CXCL1 protein expression in more
aggressive phenotypes in human BCa. Further studies are warranted to define the role
CXCL1 plays in bladder carcinogenesis and progression.
Keywords
Bladder cancer, Chemokine ligand 1 (CXCL1), Tumor grade, Tumor stage
Background
Chemokines are known to be critical mediators of the inflammatory response by regulating
the recruitment of immune cells from both the innate and adaptive immune systems to
diseased tissues. Dysregulated expression and activity of certain chemokines has been
implicated in the initiation and progression of several cancers. Specifically, the chronic
exposure of cells to a chemokine-rich milieu is associated with macrophage and T cell
accumulation, chronic activation of macrophages, abnormal angiogenesis, and DNA damage
due to the presence of reactive oxygen species [1,2]. Furthermore, chemokines have been
known to regulate multiple processes associated with tumor progression including primary
tumor growth, tumor angiogenesis and development of metastatic disease, thus some reports
have linked chemokines to more aggressive cancers [3,4]. One chemokine of interest is
chemokine (C-X-C) ligand 1 (CXCL1), also known as growth-regulated oncogene-alpha or
melanoma growth stimulatory activity, alpha. CXCL1 has been reported to be overexpressed
in colon, skin and breast cancers [5-8], but only one study to date has reported on the
expression pattern of CXCL1 protein in human bladder tumors. Herein, we report the largest
study assessing CXCL1 expression patterns in human bladder cancer (BCa) tissues.
4. Methods
Under MD Anderson Cancer Center Orlando/Orlando Health Institutional Review Board
approval with waiver of informed consent, 142 bladder tumor paraffin blocks and 10 benign
bladder paraffin blocks dating from 2002–2009 were identified in the Department of
Pathology archives at Orlando Health, Inc. The clinicopathologic variables of the study
cohort are shown in Table 1. All paraffin blocks were examined by H&E for histological
verification of disease status.
Table 1 Demographic and clinicopathologic characteristics of 152 subjects comprising
IHC study cohort
IHC cohort
BCa (%) n = 142 Controls (%) n = 10
Median Age (range, y) 73 (30–94) 29 (15–48)
Median Age (range, y) 73 (30–94) 29 (15–48)
Race
Caucasian 134 (94%) N/A
African American 5 (4%) N/A
Other 3 (2%) N/A
Median follow-up (months) 13 11
Clinical stage
Tis 16 (11%)
Ta 6 (4%)
T1 60 (42%)
≥T2 60 (42%)
Tumor grade
Low 11 (8%)
High 131 (92%)
Abbreviations: IHC immunohistochemistry, BCa bladder cancer, N/A not available.
Immunohistochemistry staining
Paraffin blocks were cut (5 µm sections) and placed on a Superfrost Plus Microslide. Sections
were deparaffinized followed by antigen retrieval using citric acid buffer (pH 6.0, 950
C for 20
minutes). Slides were treated with 1% hydrogen peroxide in methanol to block endogenous
peroxidase activity. After 20 minutes of blocking in 1% bovine serum albumin (BSA), the
slides were incubated overnight at 40
C with anti-human CXCL1 antibody (sc-1374; goat
polyclonal, dilution 1/250 in 1% BSA) from Santa Cruz Biotechnology (Santa Cruz, CA).
Next, the slides were incubated with 2 µg/mL of biotinylated anti-goat IgG secondary
antibody (Vector Laboratories, Burlingame, CA) for 30 minutes at room temperature.
Subsequently, the sections were stained using Standard Ultra-Sensitive ABC Peroxidase
Staining kit (Pierce/Thermo Fisher Scientific, San Jose, CA) and 3, 3′- diaminobenzidine
(DAB; Vector Laboratories), counterstained by hematoxyline, dehydrated, and mounted with
a cover slide. Mouse xenograft tumors from the human prostate cancer cell line PC-3, known
to stain strongly for CXCL1 [9] were used as a positive control.
5. Quantification of CXCL1 expression of bladder cancer
Using light microscopy, two investigators (MM and AL), who were blinded to patients’ data,
interpreted immunostaining results. The sections were analyzed and staining assessed using a
semiquantitative grading system based on a previous report by Eck et al. [10]. Briefly, the
location of immunoreactivity (e.g., nuclear, cytoplasm, cell membrane, and stroma) was
noted. The expression level of CXCL1 was scored by assigning a proportion score and an
intensity score. The proportion of CXCL1-positive cells was scored in four grades and
represented the estimated proportion of immunoractive cells (0 = 0% of cells; 1 = 1% to 40%;
2 = 41% to 75% and 3 = 76% to 100%). The intensity was scored and represented the average
intensity of positive cells (0 = none; 1 = weak; 2 = intermediate and 3 = strong). The
proportion and intensity scores were added to obtain a combined immunostaining score for
the expression of CXCL1, which ranged from 0 to 6 (0, none; 1–2, low; 3–4, moderate; and
5–6, high). A third investigator (CJR) reviewed discrepancies and rendered a final score.
Statistical analyses
Correlation between the pathologic variables and CXCL1 levels was analyzed using Chi-
square test. Disease-specific survival (DSS) and overall survival (OS) curves were obtained
using the Kaplan-Meier method, and compared by the log-rank test for each prognostic
variable. Variables with effect on survival in univariate analysis were included in the Cox
proportional hazard regression model. Multivariate analysis was performed to identify
independent prognostic variables using a stepwise Cox proportional hazards regression
model. IBM SPSS Version 21 (SPSS Inc., Chicago, IL) and PRISM software version 5.00
(San Diego, CA) were utilized for statistical analyses and plotting the data, respectively.
Statistical significance in this study was set at p < 0.05 and all reported p values were 2-sided.
Results
We set out to analyze CXCL1 protein levels in benign and cancerous bladder tissue samples
using immunohistochemical staining. In benign bladder tissues, CXCL1 expression was
entirely absent (Figure 1A). Conversely, in tumor tissue, varying CXCL1 expression was
found in both epithelial and stromal components of the tissue (Figure 1B). Within the stroma,
CXCL1 immunoreactivity was diffuse and was not associated with any specific cell types.
Within the epithelia, CXCL1 immunoreactivity was localized to the cytoplasm. In many
cases we were able to compare cancerous epithelia cells and tumor-adjacent, histologically
benign epithelial cells within the same tissue section. Interestingly, tumor-adjacent urothelia
also expressed high levels of CXCL1 (Figure 1C), suggesting that in urothelial components,
early molecular changes occur well before morphological changes become evident. This
finding supports the ‘field-effect’ phenomenon that has been used to describe a change in the
entire urothelium once a carcinoma lesion is established [11].
Figure 1 Expression of CXCL1 protein in human bladder. Representative staining of
benign bladder tissue A, bladder cancer B, and tumor-adjacent normal urothelia within
section with cancer C. All images were captured at 200× or 400× magnification.
Based on the combined immunostaining score, CXCL1 protein expression was significantly
different between low-grade and high-grade tumors (p = 0.01). Some 7% of low-grade
tumors exhibited ‘high’ staining, whereas 46% of high-grade tumors had ‘high’ staining
6. (Figure 2A). Similarly, higher stage tumors (e.g., MIBC stages T2-T4) had significantly
higher CXCL1 expression (p < 0.0001) than lower stage counterparts (e.g., NMIBC stages
Ta-T1). For example, 63% of T2-T4 tumors had ‘high’ CXCL1 staining, compared to only
18% of Ta-T1 tumors (Figure 2B).
Figure 2 Expression of CXCL1 protein in high-grade and high stage human bladder
cancer. A, Representative staining of low-grade bladder tumor and high-grade bladder tumor.
Bar graph illustrates combined immunostaining score for CXCL1 expression according to
tumor grade. B, Representative staining of non-muscle invasive bladder cancer (pT1) and
muscle invasive bladder cancer (pT3). Bar graph illustrates combined immunostaining score
for CXCL1 expression according to tumor stage. All images were captured at 400×
magnification. *, p < 0.01 and ***, p < 0.0001.
Due to reduce numbers of cancer samples with ‘none’ or ‘low’ combined immunostaining
score, these two groups were combined for subsequent survival analysis. Univariate Cox
analysis revealed that increased CXCL1 expression represents a poor prognostic factor
regarding DSS (Figure 3A) and OS (Figure 3B) (p = 0.0013 and p = 0.0042, respectively).
Reduced DSS and OS were also associated with MIBC (p < 0.0001 and p = 0.0015,
respectively) (Table 2). MIBC was also an independent risk factor for DSS and OS (p = 0.001
and p = 0.001, respectively) in multivariate analyses (Table 3).
Figure 3 Probability of bladder cancer specific survival according to CXCL1 staining
patterns. ‘High’ combined immunostaing score for CXCL1 was associated with a significant
reduction in (A) disease-specific survival and (B) overall survival (Log-rank test).
7. Table 2 Univariate analysis of disease specific survival and overall survival
Variables Disease-specific survival Overall survival
N HR 95% CI p HR 95% CI p
Age (yrs)
≤ 65 35 1 1
> 65 107 1.88 0.69–5.08 0.21 2.03 0.78–5.25 0.15
Sex
Male 115 1 1
Female 27 1.45 0.47–4.46 0.52 1.3 0.44–3.86 0.63
Tumor grade
Low 11 1 1
High 131 2.97 0.42–20.90 0.27 2.99 0.46–19.58 0.25
Stage
NMIBC 82 1 1
MIBC 60 11.78 4.71–29.43 <0.0001 8.83 3.65–21.32 0.0015
Combined immunostaining score for CXCL1
None / Low 34 1 1
Moderate 53 3.45 0.84–14.13 0.085 2.68 0.76–9.50 0.13
High 55 5.73 1.92–17.10 0.0018 4.63 1.60–13.37 0.0047
Abbreviations: HR Hazard ratio, 95% CI 95% confidence interval, NMIBC Non-muscle invasive bladder cancer, MIBC Muscle invasive bladder
cancer.
8. Table 3 Multivariate analysis of disease specific survival and overall survival
Variables
Disease-specific survival Overall survival
N HR 95% CI p HR 95% CI p
Stage
NMIBC 82 1 1
MIBC 60 13.61 2.79–66.39 0.001 7.63 2.25–25.92 0.001
Combined immunostaining score for CXCL1
None / Low 34 1 1
Moderate 53 1.57 0.17–14.58 0.69 1.17 0.21–6.36 0.86
High 55 3.05 0.34–27.16 0.32 2.08 0.39–10.98 0.39
HR Hazard ratio, 95% CI 95% confidence interval, NMIBC Non-muscle invasive bladder cancer, MIBC Muscle invasive bladder cancer.
9. Discussion
With an estimated 70,980 newly diagnosed cases of BCa and 14,330 deaths in 2012, cancer
of the urinary bladder is the second most common genitourinary malignancy in the U.S. and
among the five most common malignancies worldwide [12]. Urothelial carcinoma, the most
prevalent histologic subtype, accounts for 90% of all BCa in the US [13]. More than 70% of
newly diagnosed BCa are NMIBC at first presentation and treatment can be curative with
transurethral resection with or without adjuvant intravesical therapy. NMIBC possesses a
high recurrence rate (~70%) but a low progression rate (~15%) and an excellent 5-year
survival rate of 94% [14]. Some thirty percent of patients are diagnosed with MIBC or
advanced BCa. MIBC cases are usually treated by radical cystectomy or external beam
radiation therapy with concomitant chemotherapy. The 5-year survival in these patients does
not exceed 50% [15]. Our understanding regarding the carcinogenesis and progression of
BCa is still limited. Better insight into the molecular background of BCa is needed in hopes
of improving outcomes. Reports have linked BCa initiation to chronic inflammation [16,17],
and the dysregulated expression and activity of certain chemokines has been implicated in the
potential progression from an inflammatory environment to cancer initiation [3,4]. This
chronic inflammatory milieu is associated with macrophage and T cell accumulation, chronic
activation of macrophages, abnormal angiogenesis, and DNA damage due to the presence of
reactive oxygen species [1,2].
CXCL1 has been reported to be overexpressed in gastric, colon, skin and renal cancers [5-
8,18]. However, its presence has also been negatively associated with non-small cell lung
cancers [19], attesting to its complex role in tumorigenesis and angiogenesis. CXCL1 protein
expression had not previously been intensely investigated in BCa, but it is functionally
closely related to interleukin 8 (IL-8), which has been widely studied in BCa [20-22].
One other study supports the association of CXCL1 in more aggressive BCa. Based on
proteomic profiling of bladder cancer cell lines, Kawanishi et al. monitored urinary CXCL1
obtained from 67 patients with BCa [23]. The study showed that urinary CXCL1 levels were
significantly higher in patients with MIBC relative to NMIBC (p = 0.0028), and that CXCL1
was an independent factor for predicting the invasive phenotype.
We report the first large-scale study assessing CXCL1 protein expression in human bladder
tumor tissues. Increased expression of CXCL1 was evident in higher grade and higher stage
bladder tumors. Furthermore, higher CXCL1 levels were associated with a reduction in
disease-specific survival. Similar survival results have been reported in gastric cancer [24],
breast cancer [25] and melanoma [26,27]. These findings support a role for CXCL1 in
bladder tumor initiation and progression, and further studies are underway to better define the
influence of CXCL1 in BCa. While no previous CXCL1 protein studies had been reported in
bladder tumors, a number of studies have profiled the BCa transcriptome. In order to
investigate the specific pattern of CXCL1 mRNA expression in bladder tissue we analyzed
three publicly available datasets [28-30] using Oncomine 3.0 [31]. Our data-mining analyses
illustrated CXCL1 expression in BCa tissues, and revealed a significant elevation of CXCL1
in MIBC compared to NMIBC (Figure 4), further substantiating our findings that CXCL1
was noted to be significantly different between NMIBC vs. MIBC. Data related to tumor
grade were not available for analysis.
10. Figure 4 CXCL1 mRNA expression in human bladder cancer from publically available
datasets. Three public datasets containing transcriptome profiles of bladder tumor tissues
were obtained and analyzed for CXCL1 expression using Oncomine 3.0. Mean relative
mRNA levels for CXCL1 in muscle invasive bladder cancer cases was significantly elevated
compared to non-muscle invasive bladder cancer cases (Sanchez-Carbayo et al., p = 1.72-6
[28], Dyrskjot et al. p = 3.77-6
[29], and Lee et al., p = 1.12-4
[30]).
Our study has several limitations. Though we are able to demonstrate a significant difference
in the protein expression of CXCL1 in benign tissues compared to cancerous tissues, our
benign cohort was quite small (n = 8). Furthermore, we had a limited range of low-grade
tumors (n = 11) thus hampering detailed statistical analysis of our cohort. Lastly, follow-up
data of our BCa subjects was relatively short (median follow-up 13 months), which limits
long term prognostication. Additional studies are underway taking these limitations into
consideration.
Conclusions
Our study demonstrated that CXCL1 protein is specifically expressed in human bladder
carcinomas and that increased expression is associated with high-grade and high stage BCa,
and with reduced DSS. Further studies may provide insight into the molecular mechanisms
associated with a proinflammatory microenvironment that may contribute to cancer
development and progression. Knowledge of the role of CXCL1 in tumor progression may
facilitate the design of new therapeutic approaches that inhibit tumor cell growth through
selective perturbation of CXCL1 function.
Abbreviations
CXCL1, Chemokine (C-X-C) ligand 1; BCa, Bladder cancer; HR, Hazard rate; CI,
Confidence interval; NMIBC, Non-muscle invasive bladder cancer; MIBC, Muscle invasive
bladder cancer.
Competing interests
The following authors declare that they have no competing interests. Makito Miyake,
Adrienne Lawton, Ge Zhang, Shanti Ross, Jeongsoon Kim, Evan Gomes Giacoia.
The following authors declare that they have a competing interest. Steve Goodison –
affiliated with Nonagen Bioscience Corp., Virginia Urquidi – affiliated with Nonagen
Bioscience Corp., Charles J Rosser – affiliated with Nonagen Bioscience Corp.
Authors’ contribution
MM carried out IHC staining, reviewed IHC staining, performed statistical analysis and
drafted M&M section of the manuscript. AL reviewed IHC staining. GZ, JK and EGG carried
out IHC staining. SR collected and organized clinical data. SG participated in study design
and helped to draft the manuscript. VU collected and organize array data present in Figure 4.
CJR conceived the study, and participated in its design and coordination and helped to draft
the manuscript. All authors read and approved the final manuscript.
11. Acknowledgements
The work was supported by research grants from Florida Department of Health James and
Esther King Team Science Award 10KT-01 (CJR).
References
1. Moll NM, Cossoy MB, Fisher E, Staugaitis SM, Tucky BH, Rietsch AM, Chang A, Fox
RJ, Trapp BD, Ransohoff RM: Imaging correlates of leukocyte accumulation and
CXCR4/CXCL12 in multiple sclerosis. Arch Neurol 2009, 66:44–53.
2. Gillitzer R, Goebeler M: Chemokines in cutaneous wound healing. J Leukoc Biol 2001,
69:513–521.
3. Hembruff SL, Cheng N: Chemokine signaling in cancer: Implications on the tumor
microenvironment and therapeutic targeting. Cancer Ther. 2009, 7:254–267.
4. Hannelien V, Karel G, Jo VD, Sofie S: The role of CXC chemokines in the transition of
chronic inflammation to esophageal and gastric cancer. Biochim Biophys Acta 1825,
2012:117–129.
5. Verbeke H, Struyf S, Laureys G, Van Damme J: The expression and role of CXC
chemokines in colorectal cancer. Cytokine Growth Factor Rev 2011, 22:345–358.
6. Dhawan P, Richmond A: Role of CXCL1 in tumorigenesis of melanoma. J Leukoc Biol
2002, 72:9–18.
7. Vazquez-Martin A, Colomer R, Menendez JA: Protein array technology to detect HER2
(erbB-2)-induced 'cytokine signature' in breast cancer. Eur J Cancer 2007, 43:1117–
1124.
8. Lerebours F, Vacher S, Andrieu C, Espie M, Marty M, Lidereau R, Bieche I: NF-kappa B
genes have a major role in inflammatory breast cancer. BMC Cancer 2008, 8:41.
9. Engl T, Relja B, Blumenberg C, Müller I, Ringel EM, Beecken WD, Jonas D, Blaheta RA:
Prostate tumor CXC-chemokine profile correlates with cell adhesion to endothelium
and extracellular matrix. Life Sci 2006, 78:1784–1793.
10. Eck M, Schmausser B, Scheller K, Brändlein S, Müller-Hermelink HK: Pleiotropic
effects of CXC chemokines in gastric carcinoma: differences in CXCL8 and CXCL1
expression between diffuse and intestinal types of gastric carcinoma. Clin Exp Immunol
2003, 134:508–515.
11. Jones TD, Wang M, Eble JN, MacLennan GT, Lopez-Beltran A, Zhang S, Cocco A,
Cheng L: Molecular evidence supporting field effect in urothelial carcinogenesis. Clin
Cancer Res 2005, 11:6512–6519.
12. Siegel R, Naishadham D, Jemal A: Cancer statistics, 2013. CA Cancer J Clin 2013,
63:11–30.
12. 13. Kaufman DS, Shipley WU, Feldman AS: Bladder cancer. Lancet 2009, 374:239–249.
14. Brausi M, Witjes JA, Lamm D, Persad R, Palou J, Colombel M, Buckley R, Soloway M,
Akaza H, Böhle A: A review of current guidelines and best practice recommendations
for the management of nonmuscle invasive bladder cancer by the International Bladder
Cancer Group. J Urol 2011, 186:2158–2167.
15. Stenzl A, Cowan NC, De Santis M, Kuczyk MA, Merseburger AS, Ribal MJ, Sherif A,
Witjes JA, European Association of Urology (EAU): Treatment of muscle-invasive and
metastatic bladder cancer: update of the EAU guidelines. Eur Urol 2011, 59:1009–1018.
16. Yang H, Gu J, Lin X, Grossman HB, Ye Y, Dinney CP, Wu X: Profiling of genetic
variations in inflammation pathway genes in relation to bladder cancer predisposition.
Clin Cancer Res 2008, 14:2236–2244.
17. Leibovici D, Grossman HB, Dinney CP, Millikan RE, Lerner S, Wang Y, Gu J, Dong Q,
Wu X: Polymorphisms in inflammation genes and bladder cancer: from initiation to
recurrence, progression, and survival. J Clin Oncol 2005, 23:5746–5756.
18. Mestas J, Burdick MD, Reckamp K, Pantuck A, Figlin RA, et al: The role of
CXCR2/CXCR2 ligand biological axis in renal cell carcinoma. J Immunol 2005,
175:5351–5357.
19. Baird AM, Gray SG, O'Byrne KJ: Epigenetics underpinning the regulation of the
CXC (ELR+) chemokines in non-small cell lung cancer. PLoS One 2011, 27:6.
20. Izawa JI, Slaton JW, Kedar D, Karashima T, Perrotte P, Czerniak B, Grossman HB,
Dinney CP: Differential expression of progression-related genes in the evolution of
superficial to invasive transitional cell carcinoma of the bladder. Oncol Rep 2001, 8:9–
15.
21. Reis ST, Leite KR, Piovesan LF, Pontes-Junior J, Viana NI, Abe DK, Crippa A, Moura
CM, Adonias SP, Srougi M, Dall'Oglio MF: Increased expression of MMP-9 and IL-8 are
correlated with poor prognosis of Bladder Cancer. BMC Urol 2012, 12:18.
22. Inoue K, Slaton JW, Kim SJ, Perrotte P, Eve BY, Bar-Eli M, Radinsky R, Dinney CP:
Interleukin 8 expression regulates tumorigenicity and metastasis in human bladder
cancer. Cancer Res 2000, 60:2290–2299.
23. Kawanishi H, Matsui Y, Ito M, Watanabe J, Takahashi T, Nishizawa K, Nishiyama H,
Kamoto T, Mikami Y, Tanaka Y, Jung G, Akiyama H, Nobumasa H, Guilford P, Reeve A,
Okuno Y, Tsujimoto G, Nakamura E, Ogawa O: Secreted CXCL1 is a potential mediator
and marker of the tumor invasion of bladder cancer. Clin Cancer Res 2008, 14:2579–
2587.
24. Cheng WL, Wang CS, Huang YH, Tsai MM, Liang Y, Lin KH: Overexpression of
CXCL1 and its receptor CXCR2 promote tumor invasion in gastric cancer. Ann Oncol
2011, 22:2267–2276.
13. 25. Bièche I, Chavey C, Andrieu C, Busson M, Vacher S, Le Corre L, Guinebretière JM,
Burlinchon S, Lidereau R, Lazennec G: CXC chemokines located in the 4q21 region are
up-regulated in breast cancer. Endocr Relat Cancer 2007, 14:1039–1052.
26. Middleman BR, Friedman M, Lawson DH, DeRose PB, Cohen C: Melanoma growth
stimulatory activity in primary malignant melanoma: prognostic significance. Mod
Pathol 2002, 15:532–537.
27. Luan J, Shattuck-Brandt R, Haghnegahdar H, Owen JD, Strieter R, Burdick M, Nirodi C,
Beauchamp D, Johnson KN, Richmond A: Mechanism and biological significance of
constitutive expression of MGSA/GRO chemokines in malignant melanoma tumor
progression. J Leukoc Biol 1997, 62:588–597.
28. Sanchez-Carbayo M, Socci ND, Lozano J, Saint F, Cordon-Cardo C: Defining molecular
profiles of poor outcome in patients with invasive bladder cancer using oligonucleotide
microarrays. J Clin Oncol 2006, 24:778–789.
29. Dyrskjøt L, Zieger K, Real FX, Malats N, Carrato A, Hurst C, Kotwal S, Knowles M,
Malmström PU, de la Torre M, Wester K, Allory Y, Vordos D, Caillault A, Radvanyi F, Hein
AM, Jensen JL, Jensen KM, Marcussen N, Orntoft TF: Gene expression signatures predict
outcome in non-muscle-invasive bladder carcinoma: a multicenter validation study. Clin
Cancer Res 2007, 13:3545–3551.
30. Lee JS, Leem SH, Lee SY, Kim SC, Park ES, Kim SB, Kim SK, Kim YJ, Kim WJ, Chu
IS: Expression signature of E2F1 and its associated genes predict superficial to invasive
progression of bladder tumors. J Clin Oncol 2010, 28:2660–2667.
31. Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey
A, Chinnaiyan AM: ONCOMINE: a cancer microarray database and integrated data-
mining platform. Neoplasia 2004, 6:1–6.
14. Normal urothelia Bladder Cancer (pT1 Low grade)
100 m
Figure 1
Adjacent normal urothelia
Bladder Cancer (pT2 High grade)
200 200
400400
Cancer cells
100 m
Figure 1
15. pTa Low grade pTa High grade
100 m
Figure 2
pT1 High grade pT3 High grade
400 400
100 m
400 400
Low High
0
20
40
60
80
100
None
Low
Mod
High
(%) *
CXCL1
expression
Tumor Grade
Percentageoftotalcases
Ta-1 T2-4
0
20
40
60
80
100
None
Low
Mod
High
(%)
CXCL1
expression
***
Tumor stage
Percentageoftotalcases
Figure 2