This document summarizes the results of a study comparing the expression of cell surface antigens in different cell lineages between patients with myelodysplastic syndrome (MDS) and patients with idiopathic thrombocytopenic purpura (ITP) as a control group. The study found significant differences in the mean percentages of various antigens expressed in the granulocytic, erythroid, monocytic, and myeloid precursor lineages between MDS and ITP patients. Providing reference values for antigen expression patterns in MDS enhances the utility of flow cytometric analysis for diagnosing these patients.
A KRAS-variant is a Biomarker of Poor Outcome, Platinum Chemotherapy Resistan...UCLA
Germ-line variants in the 3′ untranslated region (3′UTR) of cancer genes disrupting microRNA (miRNA) regulation have recently been associated with cancer risk. A variant in the 3′UTR of the KRAS oncogene, referred to as the KRAS-variant, is associated with both cancer risk and altered tumor biology. Here we test the hypothesis that the KRAS-variant can act as a biomarker of outcome in epithelial ovarian cancer (EOC), and investigate the cause of altered outcome in KRAS-variant positive EOC patients. As this variant appears to be associated with tumor biology, we additionally test the hypothesis that this variant can be directly targeted to impact cell survival.
EOC patients with complete clinical data were genotyped for the KRAS-variant and analyzed for outcome (n=536), response to neoadjuvant chemotherapy (n=125), and platinum resistance (n=306). Outcome was separately analyzed for women with known BRCA mutations (n=79). Gene expression was analyzed on a subset of tumors with available tissue. Cell lines were employed to confirm altered sensitivity to chemotherapy with the KRAS-variant. The KRAS- variant was directly targeted through siRNA/miRNA oligonucleotides in cell lines and survival was measured.
Post-menopausal EOC patients with the KRAS-variant were significantly more likely to die of ovarian cancer by multivariate analysis (HR=1.67, 95% CI=1.09–2.57, p=0.019, n=279). Possibly explaining this finding, EOC patients with the KRAS-variant were significantly more likely to be platinum resistant (OR=3.18, CI=1.31–7.72, p=0.0106, n=291). Additionally, direct targeting of the KRAS-variant led to a significant reduction in EOC cell growth and survival in vitro.
These findings confirm the importance of the KRAS-variant in EOC, and indicate that the KRAS- variant is a biomarker of poor outcome in EOC likely due to platinum resistance. In addition, this work supports the hypothesis that these tumors have continued dependence on such 3′UTR lesions, and that direct targeting may be a viable future treatment approach.
Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecu...Joshua Mangerel
This document summarizes the results of a study that integrated genomic data to identify molecular subgroups in diffuse intrinsic pontine glioma (DIPG), a deadly childhood brain cancer. The study found that DIPG comprises three distinct subgroups - MYCN, silent, and H3-K27M - with differences in mutations, gene expression, methylation, and clinical features. A novel recurrent mutation was discovered in the ACVR1 gene in 20% of DIPGs. The identification of distinct molecular subgroups highlights the heterogeneity of DIPG and could help guide more targeted treatment approaches for this incurable cancer.
This study characterized the non-coding RNA landscape in head and neck squamous cell carcinoma (HNSCC) using RNA sequencing data from 422 HNSCC patients. 307 non-coding transcripts were found to be significantly correlated with patient survival, associated with mutations in cancer genes like TP53 and CDKN2A, and correlated with copy number variations in chromosomes 3, 5, 7, and 18. Experimental validation of 3 selected non-coding RNAs - lnc-JPH1-7, miR-654-3p, and piR-34736 - found their expression levels associated with tumor stage, HPV status, and other clinical characteristics. Modulation of lnc-JPH1-7 expression in cell lines
This study identified a recurrent amplification of the VEGFA gene locus in a subset of mouse and human hepatocellular carcinomas (HCC). Tumors with this amplification (Amppos) displayed distinct characteristics including higher proliferation, vessel density, and macrophage content compared to tumors without the amplification (Ampneg). Additionally, Amppos tumors had increased expression of VEGFA and other genes in the amplified region. Treatment with sorafenib, which targets VEGFR, was found to be particularly effective in inhibiting the growth of Amppos HCCs both in mouse models and human patients. This suggests VEGFA amplification could serve as a biomarker to identify HCC patients most likely to benefit from sorafenib or other
hMSH2 Gly322Asp (rs4987188) Single nucleotide polymorphism and the risk of br...Agriculture Journal IJOEAR
Aim: Breast cancer is the most common cancer in women both in the developed and less developed world. The reported study was designed to explore associations between hMSH2 - Gly322Asp (1032G>A, rs4987188) single nucleotide polymorphism (SNP) and the risk of breast carcinoma in the Polish women.
Material and methods: Blood samples were obtained from women with breast cancer (n=225), treated at the Department of Oncological Surgery and Breast Diseases, Polish Mother’s Memorial Hospital – Research Institute between the years 2005 and 2012. A control group included 220 cancer-free women. Genomic DNA was isolated and the SNP Gly322Asp of hMSH2 was determined by High-Resolution Melter method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each genotype and allele.
Results: This study revealed that single nucleotide polymorphism Gly322Asp of hMSH2 is associated with both breast cancer risk and grading. Moreover, it can be linked with breast carcinoma tumor size and lymph node status. The Asp allele in patients may be a risk factor for breast carcinoma (OR 5.12; 95% CI 3.77 –6.97, p<.0001).
Conclusions: Gly322Asp single nucleotide polymorphism of hMSH2 may be a risk factor of breast cancer in the Polish women.
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
This document analyzes the incidence, characteristics, and prognosis of acute myeloid leukemia (AML) cases with 11q23 abnormalities involving the MLL gene, as defined by the World Health Organization classification. In an analysis of 1897 cytogenetically analyzed AML cases, the incidence of MLL rearrangements was 2.8%. MLL rearrangements were more common in therapy-related AML, in patients under 60 years old, and in AML subtypes M4, M5a, and M5b. AML with MLL rearrangements had a worse prognosis than AML with intermediate risk cytogenetics but a similar prognosis to those with unfavorable cytogenetics. The median overall survival was significantly better
The document discusses PD-L1 expression in gliomas and the potential for blocking the PD-1/PD-L1 pathway as a new treatment strategy. It summarizes that PD-L1 is expressed in glioma cell lines and tumor tissues in approximately 44% of cases based on various studies. Higher PD-L1 expression is correlated with higher glioma grade. Blocking the PD-1/PD-L1 pathway has shown encouraging results in other cancers and offers hope as a new immunotherapy for gliomas given the role of this pathway in glioma progression and limiting the immune response against the tumors.
A KRAS-variant is a Biomarker of Poor Outcome, Platinum Chemotherapy Resistan...UCLA
Germ-line variants in the 3′ untranslated region (3′UTR) of cancer genes disrupting microRNA (miRNA) regulation have recently been associated with cancer risk. A variant in the 3′UTR of the KRAS oncogene, referred to as the KRAS-variant, is associated with both cancer risk and altered tumor biology. Here we test the hypothesis that the KRAS-variant can act as a biomarker of outcome in epithelial ovarian cancer (EOC), and investigate the cause of altered outcome in KRAS-variant positive EOC patients. As this variant appears to be associated with tumor biology, we additionally test the hypothesis that this variant can be directly targeted to impact cell survival.
EOC patients with complete clinical data were genotyped for the KRAS-variant and analyzed for outcome (n=536), response to neoadjuvant chemotherapy (n=125), and platinum resistance (n=306). Outcome was separately analyzed for women with known BRCA mutations (n=79). Gene expression was analyzed on a subset of tumors with available tissue. Cell lines were employed to confirm altered sensitivity to chemotherapy with the KRAS-variant. The KRAS- variant was directly targeted through siRNA/miRNA oligonucleotides in cell lines and survival was measured.
Post-menopausal EOC patients with the KRAS-variant were significantly more likely to die of ovarian cancer by multivariate analysis (HR=1.67, 95% CI=1.09–2.57, p=0.019, n=279). Possibly explaining this finding, EOC patients with the KRAS-variant were significantly more likely to be platinum resistant (OR=3.18, CI=1.31–7.72, p=0.0106, n=291). Additionally, direct targeting of the KRAS-variant led to a significant reduction in EOC cell growth and survival in vitro.
These findings confirm the importance of the KRAS-variant in EOC, and indicate that the KRAS- variant is a biomarker of poor outcome in EOC likely due to platinum resistance. In addition, this work supports the hypothesis that these tumors have continued dependence on such 3′UTR lesions, and that direct targeting may be a viable future treatment approach.
Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecu...Joshua Mangerel
This document summarizes the results of a study that integrated genomic data to identify molecular subgroups in diffuse intrinsic pontine glioma (DIPG), a deadly childhood brain cancer. The study found that DIPG comprises three distinct subgroups - MYCN, silent, and H3-K27M - with differences in mutations, gene expression, methylation, and clinical features. A novel recurrent mutation was discovered in the ACVR1 gene in 20% of DIPGs. The identification of distinct molecular subgroups highlights the heterogeneity of DIPG and could help guide more targeted treatment approaches for this incurable cancer.
This study characterized the non-coding RNA landscape in head and neck squamous cell carcinoma (HNSCC) using RNA sequencing data from 422 HNSCC patients. 307 non-coding transcripts were found to be significantly correlated with patient survival, associated with mutations in cancer genes like TP53 and CDKN2A, and correlated with copy number variations in chromosomes 3, 5, 7, and 18. Experimental validation of 3 selected non-coding RNAs - lnc-JPH1-7, miR-654-3p, and piR-34736 - found their expression levels associated with tumor stage, HPV status, and other clinical characteristics. Modulation of lnc-JPH1-7 expression in cell lines
This study identified a recurrent amplification of the VEGFA gene locus in a subset of mouse and human hepatocellular carcinomas (HCC). Tumors with this amplification (Amppos) displayed distinct characteristics including higher proliferation, vessel density, and macrophage content compared to tumors without the amplification (Ampneg). Additionally, Amppos tumors had increased expression of VEGFA and other genes in the amplified region. Treatment with sorafenib, which targets VEGFR, was found to be particularly effective in inhibiting the growth of Amppos HCCs both in mouse models and human patients. This suggests VEGFA amplification could serve as a biomarker to identify HCC patients most likely to benefit from sorafenib or other
hMSH2 Gly322Asp (rs4987188) Single nucleotide polymorphism and the risk of br...Agriculture Journal IJOEAR
Aim: Breast cancer is the most common cancer in women both in the developed and less developed world. The reported study was designed to explore associations between hMSH2 - Gly322Asp (1032G>A, rs4987188) single nucleotide polymorphism (SNP) and the risk of breast carcinoma in the Polish women.
Material and methods: Blood samples were obtained from women with breast cancer (n=225), treated at the Department of Oncological Surgery and Breast Diseases, Polish Mother’s Memorial Hospital – Research Institute between the years 2005 and 2012. A control group included 220 cancer-free women. Genomic DNA was isolated and the SNP Gly322Asp of hMSH2 was determined by High-Resolution Melter method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each genotype and allele.
Results: This study revealed that single nucleotide polymorphism Gly322Asp of hMSH2 is associated with both breast cancer risk and grading. Moreover, it can be linked with breast carcinoma tumor size and lymph node status. The Asp allele in patients may be a risk factor for breast carcinoma (OR 5.12; 95% CI 3.77 –6.97, p<.0001).
Conclusions: Gly322Asp single nucleotide polymorphism of hMSH2 may be a risk factor of breast cancer in the Polish women.
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
This document analyzes the incidence, characteristics, and prognosis of acute myeloid leukemia (AML) cases with 11q23 abnormalities involving the MLL gene, as defined by the World Health Organization classification. In an analysis of 1897 cytogenetically analyzed AML cases, the incidence of MLL rearrangements was 2.8%. MLL rearrangements were more common in therapy-related AML, in patients under 60 years old, and in AML subtypes M4, M5a, and M5b. AML with MLL rearrangements had a worse prognosis than AML with intermediate risk cytogenetics but a similar prognosis to those with unfavorable cytogenetics. The median overall survival was significantly better
The document discusses PD-L1 expression in gliomas and the potential for blocking the PD-1/PD-L1 pathway as a new treatment strategy. It summarizes that PD-L1 is expressed in glioma cell lines and tumor tissues in approximately 44% of cases based on various studies. Higher PD-L1 expression is correlated with higher glioma grade. Blocking the PD-1/PD-L1 pathway has shown encouraging results in other cancers and offers hope as a new immunotherapy for gliomas given the role of this pathway in glioma progression and limiting the immune response against the tumors.
This document summarizes an investigation into the effects of AKT and P38 inhibitors on signaling pathways regulated by SPARC and PTEN in glioma cells. Four glioma cell lines and three non-cancerous cell lines were treated with an AKT inhibitor, three P38 inhibitors, or combinations. Changes in phosphorylated proteins downstream of these pathways were analyzed by western blot. Results showed that inhibitors reduced phosphorylated HSP27 in SPARC-positive cell lines, but not SPARC-negative lines, indicating SPARC regulates this pathway. Inhibitor effects also differed based on PTEN status, suggesting PTEN suppresses HSP27 phosphorylation. The study provides insight into signaling downstream of SPARC that
This study used high-density SNP microarrays to analyze chromosomal changes in 86 paired colorectal cancer and normal tissue samples from Bangladeshi patients. The researchers identified common regions of amplification on chromosomes 20q, 13q, 8q, and 5p and deletions on 18q, 17p, and 8p. They also detected mosaicism and different types of chromosomal abnormalities that could not be assessed by other methods. By matching genes in altered regions to drug databases, the researchers identified potential targeted therapies for personalized treatment based on a patient's cytogenetic profile. This represents an application of high-density SNP arrays for colorectal cancer cytogenetics and personalized treatment approaches.
SCIENCE TRANS MED Therapeutic targeting of the MYC signal by inhibition of hi...Selina Sutton
This document summarizes research finding that targeting the histone chaperone FACT may be an effective therapeutic strategy for neuroblastoma, especially those driven by MYCN amplification. The researchers found that FACT expression predicts poor prognosis in neuroblastoma patients. They also discovered that FACT and MYCN expression are regulated in a positive feedback loop, with MYCN transcriptionally activating FACT expression and vice versa. Inhibition of FACT using the small molecule CBL0137 reduced tumor progression in mouse models of neuroblastoma and showed strong synergy when combined with chemotherapy by blocking DNA damage repair. This suggests targeting FACT, particularly in combination with chemotherapy, may be a promising treatment approach for high-risk neuroblastoma.
This study evaluated the efficacy and toxicity of the Hyper-CVAD regimen in treating adult acute lymphocytic leukemia (ALL). 204 adult patients with newly diagnosed ALL received alternating cycles of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and high-dose methotrexate and cytarabine, along with central nervous system prophylaxis and supportive care. Results showed that 91% of patients achieved complete remission and the 5-year survival and complete remission rates were 39% and 38% respectively, demonstrating superior outcomes compared to previous regimens. The Hyper-CVAD regimen was found to be an effective therapy for adult ALL that
This document discusses directions and issues in the treatment of acute myeloid leukemia (AML). It addresses challenging existing treatment dogmas regarding chemotherapy drug doses and post-remission therapies. Specifically, it summarizes several studies investigating optimal dose levels of cytarabine and anthracyclines during induction and consolidation for AML. It also reviews evidence comparing the effectiveness of autologous stem cell transplantation versus chemotherapy alone as post-remission consolidation approaches. The document advocates moving beyond conventional chemotherapy regimens to more personalized precision medicine approaches for AML patients.
Association of common palb2 polymorphisms with ovarian cancer a case control ...IJARIIT
Background: The partner and localizer of breast cancer 2 (PALB2) has an essential role in BRCA2 mediated DNA
double-strand break repair by serving as a bridging molecule and acting as the physical and functional link between BRCA1&
2 proteins. Truncating mutations in the PALB2 gene are rare but are thought to be associated with increased risk of developing
breast and /or ovarian cancer in different populations. The present study was designed to investigate the variants of PALB2 and
their association with OC.
Material &Methods: A total of 150 histopathologically confirmed ovarian cancer patients and 250 healthy age matched controls
were collected. Three SNPs c.2794 G/A( rs45624036), c.1010 T/C(rs45494092), and c.1676A/G(rs152451) of PALB2 gene were
selected and genotyped by ARMS-PCR followed by agarose gel electrophoresis. Appropriate statistical tests were applied to test
for the significance of the results.
Results: A significant association of G/A (rs45624036) in inheritance models was observed & at the allelic level, the A allele
conferred four-fold increased risk compared to G allele. Regarding T/C (rs45494092) polymorphism all the models revealed an
association with OC and C allele showing eight-fold increased risk. With respect to A/G (rs152451) polymorphism, the protective
role was observed in tested inheritance models in OC patients.
The Haplo analysis for the combination of all the three variants revealed increased risk with A-T-A and G-C-G
haplotypes.(OR=4.50 ;95%CI 1.85-10.94;p=0.001,OR=26.36 ;95%CI 2.33 -297.91;p= 0.0085), whereas other haplotypes
conferred a protective role in OC.
Conclusions: The present study suggests an essential role of PALB2 in the etiology of ovarian cancer.
Vorinostat combined with DNMTi epigenetically controls the proliferation of l...MustafaFathy6
This study evaluated the effects of combining the histone deacetylase inhibitor (HDACi) vorinostat with other chemotherapeutic drugs on lung cancer cells. Vorinostat alone and in combination with carboplatin was most effective at reducing cell viability of A549 lung cancer cells. Global DNA methylation patterns varied depending on the drug combinations, with vorinostat and carboplatin causing hypomethylation and vorinostat and cyclophosphamide resulting in hypermethylation. The results suggest that combining epigenetic and chemotherapeutic drugs may be more effective at controlling lung cancer proliferation than single agents alone. However, more experiments are needed to confirm these findings.
This document summarizes a systematic review and meta-analysis that evaluated the prognostic impact of microRNAs (miRNAs) in patients with T cell acute lymphoblastic leukemia (T-ALL). Seventeen studies were included in the systematic review and sixteen were included in the meta-analysis. The meta-analysis found that overall miRNA expression was associated with a decreased risk of death by 7.1% in T-ALL patients. Upregulated miRNA expressions were associated with lower risk of death while downregulated expressions were associated with higher risk of death. The findings suggest that miRNA expression may help prognostic evaluation in T-ALL patients, although results were inconclusive.
EXPRESSION OF CK5 BASAL CYTOKERATIN DURING METASTATIC DEVELOPMENT OF BREAST C...ANCA MARIA CIMPEAN
Objective. Breast cancer is a one of the most common cancers in females worldwide. Basal cytokeratin CK5 represent the marker of progenitors for glandular and myoepithelial lineages of mammary epithelium. During epithelial differentiation there is a gradual decrease of CK5 expression. The purpose of this study was to compare the expression of basal cytokeratin CK5 vs hormone receptors, HER2, Ki67 and molecular subtypes immunohistochemically defined in the primary breast carcinoma of NST type and axillar lymph node metastasis. Material and Methods. We processed immunohistochemically 91 invasive breast carcinomas of NST type and their ipsilateral axillar lymph node metastasis (LNM). Results. The majority of primary tumors were evaluated as CK5 negative (78 cases/85.7%). The majority of cases were evaluated as Luminal B (50 cases/54.9%) and Luminal A (28 cases/30.8%) tumors. The HER2 subtype was confirmed in 8 cases/8.8%, 5NP in 3 cases/3.3% and Basal-like in 2 cases/2.2%. The parallel comparison of CK5 expression at both sites, primary and metastatic, revealed that this marker is not stable during metastatic progression. The molecular subtypes were not stable during metastatic process in 21 cases/23.1%. Conclusions. The majority of NST invasive ductal breast carcinomas are CK5 negative. The molecular subtypes and CK5 are not stable during metastatic process. Cancerous cells prefer to lose this marker in the lymph node environment. The presence of cases with simultaneous expression of CK5 and hormone receptors is an open field to debate the existence of other, transient molecular subtypes. We expect a further confirmation in larger study groups.
Key Words: molecular subtypes, invasive carcinoma NST type, basal cytokeratin.
CSF-Derived cell-free DNA for Diagnosis and Characterization of.pptxAmit Ghosh
This document discusses using cell-free DNA (cfDNA) derived from cerebrospinal fluid (CSF) for the diagnosis and characterization of central nervous system (CNS) malignant tumors. It begins by outlining current methods for molecular profiling of brain tumors, which rely on invasive biopsies and may not capture tumor heterogeneity. The document then reviews studies showing CSF-derived cfDNA is more sensitive than plasma for detecting brain neoplasms and can provide additional genetic information beyond tissue biopsies. It describes an ongoing pilot study analyzing CSF cfDNA in 100 brain tumor patients to diagnose tumors, represent heterogeneity, and monitor progression. The study aims to evaluate cfDNA analysis for guiding treatment and monitoring response. Overall, the document argues
HETEROGENEITY OF C ERB B FAMILY MEMBERS EXPRESSION IS RELATED TO CELL MORPHOL...ANCA MARIA CIMPEAN
This document summarizes a study examining the expression of HER2 and EGFR in pituitary adenomas and their relationship to hormone profiles. The study found that over one-third of pituitary adenomas expressed HER2, particularly prolactin-secreting adenomas. HER2 expression was also related to certain hormone co-expressions. Approximately half of adenomas expressed EGFR, which was correlated with GH-prolactin co-expression. The results suggest HER2 and EGFR expression may help define subclasses of pituitary adenomas and explain their clinical heterogeneity.
This study analyzed exome and genome sequences of 183 lung adenocarcinoma tumor/normal DNA pairs. It identified a mean exonic somatic mutation rate of 12.0 events/megabase and recurrent mutations in genes like U2AF1, RBM10 and ARID1A. Whole-genome analysis revealed frequent structural rearrangements including in-frame alterations in EGFR and SIK2 kinases. The candidate cancer genes identified may provide insights into lung adenocarcinoma pathogenesis and potential therapeutic targets.
This study examined the association between a FOXP3 gene polymorphism (rs3761548) and nondermatomal vitiligo in an Indian population. The researchers found that:
1) Female patients with the CC genotype were protected against vitiligo, while those with the CA genotype had a 3-fold higher risk of developing vitiligo.
2) No significant differences were observed between genotype frequencies in male patients and controls.
3) The results suggest the FOXP3 polymorphism may influence vitiligo susceptibility in women through altered regulatory T cell expression and function.
Proteomics Exploration of Chronic Lymphocytic Leukemia_Crimson PublishersCrimsonpublishersCancer
Chronic Lymphocytic Leukemia (CLL) is an adult heme malignancy characterized by the presence of mature-appearing CD5+ B cells in the blood, bone marrow, and secondary lymphoid organs [1]. In the United States, there will be an estimate of 20,720 new cases and 3,930 deaths according to the American Cancer Society statistics. Symptoms include swollen lymph nodes, frequent infections, and fatigue which negatively impacts the quality of life of people affected [1]. CLL is heterogeneous in its progression and clinical outcomes. Factors that contribute to the heterogeneity include the immunoglobulin heavy chain (IGHV) status and chromosomal aberrations [2,3]. There are two subtypes of CLL: Unmutated(U-CLL) and Mutated CLL(M-CLL). 40% and 60% of patients are diagnosed with unmutated and mutated CLL. U-CLL is characterized by the presence of CLL cells that have less than two percent of their IGHV mutated, whereas M-CLL cells have more than two percent mutated [4]. U-CLL is the more aggressive phenotype [2]. These cells have increased responsiveness to antigens that bind the B cell receptor (BCR) versus M-CLL cells [5]. M-CLL is the more indolent phenotype. Increased BCR signaling results in increased cell survival and proliferation [5].
Objective: The prognostic indictors of age-related poor outcomes in patients with acute myeloid leukemia (AML) are still controversial. The aim of this work was to provide comprehensive insights into the effect of different hemocytes and to investigate the association between age and clinical features in adult patients with AML.
Study Design: A retrospective study was performed to determine the role of age in the therapeutic outcomes of AML. A total of 166 newly diagnosed adult patients’ data from January 2015 to November 2019 in Zhongshan Hospital of Xiamen University were collected and analyzed.
Results: Older patients presented a poorer prognosis (p=0.001) with shorter overall survival, which is served as age-related outcomes. Binary logistic regression demonstrated that cytogenetic risk (OR=4.508, 95% CI 2.733–7.435), leukocyte (OR=7.410, 95% CI 1.139–5.910), and bone marrow blast cells (OR=3.261, 95% CI 1.075–5.615) were independent indictors for age-related prognosis. In addition, Kaplan-Meier curve also revealed that the above factors were associated with overall survival (all p values <0.001).
Conclusion: Cytogenetic risk, leukocyte, and bone marrow blast cells are dominant factors which account for the age-related poor outcomes and shorter overall survival in AML.
Keywords: acute myeloid leukemia, adult, cytogenetic risk, hemocyte, leukemia, overall survival
Targeted sequencing of 99 colorectal cancer samples identified frequent mutations in TP53 (65%), APC (36%), KRAS (35%), PIK3CA (19%), and other genes. EGFR mutations were associated with younger age of onset. EGFR or PIK3CA mutations were markers of poor disease-specific survival, and KRAS or PIK3CA mutations were associated with poor survival in TP53 wild-type cases. The findings provide novel prognostic insights and could help clinical decision-making for colorectal cancer patients in Saudi Arabia.
Yayan T. Sundara, Dokter di Klinik Jejaring Padjadjaran dan Master of Bio Medical Science Research dari Leiden University Medical Centrum, juga staff Departemen Pelayanan PT Rumah Sakit Padjadjaran
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.
Objective: The association between telomerase reverse transcriptase (TERT) promoter mutation and outcome of melanoma is unclear and controversial. We aim to conduct a meta-analysis and investigate whether the TERT promoter mutation is a prognostic factor of melanoma.
Study Design: Appropriate studies were searched in 3 databases: PubMed, Web of Science, and Embase. Pooled hazard ratios (HRs) were counted through random effects model.
Results: Heterogeneity was moderate in overall survival (OS) (I2=43.7%, p=0.059) and low in disease-free survival (DFS) (I2=0.0%, p=0.587). Sensitivity analysis indicated that the removal of any of the study did not affect the final results. Evidence for publication bias was not found (Begg’s test, p=0.281; Egger’s test, p=0.078). The pooled OS HRs from combined effects analysis was determined (HR 1.07; 95% CI 0.83–1.39, p=0.585), together with the pooled HRs of DFS (HR 1.65; 95% CI 1.02–2.66, p=0.042). TERT promoter mutation predicted a good outcome in meta-static melanoma patients (HR 0.66; 95% CI 0.46–0.96, p=0.042). The pooled HRs of combined mutation in TERT promoter and BRAF (HR 6.27; 95% CI 2.7–14.58, p=0.000) predicted a bad outcome in melanoma patients.
Conclusion: TERT promoter mutation significantly predicted poor DFS outcome but, on the contrary, predicted a good outcome in metastatic melanoma patients. The combined TERT promoter and BRAF mutation was a significant independent factor of OS in melanoma patients.
Keywords: melanoma; meta-analysis; mutation; prognosis; promoter regions, genetic; skin neoplasms; telomerase; TERT promoter mutation; TERT protein, human
This review article discusses the application of nanoscaffolds in mesenchymal stem cell-based therapy. It begins with an introduction about the need for regenerative medicine as an alternative to organ transplantation due to donor shortages. It describes mesenchymal stem cells and nanofibers/scaffolds as two essential components in regenerative medicine. Recently, the combination of mesenchymal stem cells and nanofibers/scaffolds has been utilized to obtain more homogeneous stem cell populations with higher proliferation rates and differentiation potential, which are important for regenerative medicine. The review then discusses topics such as the biology, sources, characterization, and isolation of mesenchymal stem cells. It also covers the
This document summarizes a study that analyzed antigen expression patterns in different subtypes of myelodysplastic syndromes (MDS) using flow cytometry. Bone marrow samples from 30 newly diagnosed MDS patients classified as refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), or refractory anemia with excess blasts (RAEB) were analyzed for antigen expression on granulocytic, monocytic, erythroid and lymphoid lineages. The study found no significant differences in antigen expression between subtypes for granulocytic lineages. For erythroid lineages, the percentage of CD71-positive cells was significantly lower in RAEB compared to R
This document summarizes an investigation into the effects of AKT and P38 inhibitors on signaling pathways regulated by SPARC and PTEN in glioma cells. Four glioma cell lines and three non-cancerous cell lines were treated with an AKT inhibitor, three P38 inhibitors, or combinations. Changes in phosphorylated proteins downstream of these pathways were analyzed by western blot. Results showed that inhibitors reduced phosphorylated HSP27 in SPARC-positive cell lines, but not SPARC-negative lines, indicating SPARC regulates this pathway. Inhibitor effects also differed based on PTEN status, suggesting PTEN suppresses HSP27 phosphorylation. The study provides insight into signaling downstream of SPARC that
This study used high-density SNP microarrays to analyze chromosomal changes in 86 paired colorectal cancer and normal tissue samples from Bangladeshi patients. The researchers identified common regions of amplification on chromosomes 20q, 13q, 8q, and 5p and deletions on 18q, 17p, and 8p. They also detected mosaicism and different types of chromosomal abnormalities that could not be assessed by other methods. By matching genes in altered regions to drug databases, the researchers identified potential targeted therapies for personalized treatment based on a patient's cytogenetic profile. This represents an application of high-density SNP arrays for colorectal cancer cytogenetics and personalized treatment approaches.
SCIENCE TRANS MED Therapeutic targeting of the MYC signal by inhibition of hi...Selina Sutton
This document summarizes research finding that targeting the histone chaperone FACT may be an effective therapeutic strategy for neuroblastoma, especially those driven by MYCN amplification. The researchers found that FACT expression predicts poor prognosis in neuroblastoma patients. They also discovered that FACT and MYCN expression are regulated in a positive feedback loop, with MYCN transcriptionally activating FACT expression and vice versa. Inhibition of FACT using the small molecule CBL0137 reduced tumor progression in mouse models of neuroblastoma and showed strong synergy when combined with chemotherapy by blocking DNA damage repair. This suggests targeting FACT, particularly in combination with chemotherapy, may be a promising treatment approach for high-risk neuroblastoma.
This study evaluated the efficacy and toxicity of the Hyper-CVAD regimen in treating adult acute lymphocytic leukemia (ALL). 204 adult patients with newly diagnosed ALL received alternating cycles of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and high-dose methotrexate and cytarabine, along with central nervous system prophylaxis and supportive care. Results showed that 91% of patients achieved complete remission and the 5-year survival and complete remission rates were 39% and 38% respectively, demonstrating superior outcomes compared to previous regimens. The Hyper-CVAD regimen was found to be an effective therapy for adult ALL that
This document discusses directions and issues in the treatment of acute myeloid leukemia (AML). It addresses challenging existing treatment dogmas regarding chemotherapy drug doses and post-remission therapies. Specifically, it summarizes several studies investigating optimal dose levels of cytarabine and anthracyclines during induction and consolidation for AML. It also reviews evidence comparing the effectiveness of autologous stem cell transplantation versus chemotherapy alone as post-remission consolidation approaches. The document advocates moving beyond conventional chemotherapy regimens to more personalized precision medicine approaches for AML patients.
Association of common palb2 polymorphisms with ovarian cancer a case control ...IJARIIT
Background: The partner and localizer of breast cancer 2 (PALB2) has an essential role in BRCA2 mediated DNA
double-strand break repair by serving as a bridging molecule and acting as the physical and functional link between BRCA1&
2 proteins. Truncating mutations in the PALB2 gene are rare but are thought to be associated with increased risk of developing
breast and /or ovarian cancer in different populations. The present study was designed to investigate the variants of PALB2 and
their association with OC.
Material &Methods: A total of 150 histopathologically confirmed ovarian cancer patients and 250 healthy age matched controls
were collected. Three SNPs c.2794 G/A( rs45624036), c.1010 T/C(rs45494092), and c.1676A/G(rs152451) of PALB2 gene were
selected and genotyped by ARMS-PCR followed by agarose gel electrophoresis. Appropriate statistical tests were applied to test
for the significance of the results.
Results: A significant association of G/A (rs45624036) in inheritance models was observed & at the allelic level, the A allele
conferred four-fold increased risk compared to G allele. Regarding T/C (rs45494092) polymorphism all the models revealed an
association with OC and C allele showing eight-fold increased risk. With respect to A/G (rs152451) polymorphism, the protective
role was observed in tested inheritance models in OC patients.
The Haplo analysis for the combination of all the three variants revealed increased risk with A-T-A and G-C-G
haplotypes.(OR=4.50 ;95%CI 1.85-10.94;p=0.001,OR=26.36 ;95%CI 2.33 -297.91;p= 0.0085), whereas other haplotypes
conferred a protective role in OC.
Conclusions: The present study suggests an essential role of PALB2 in the etiology of ovarian cancer.
Vorinostat combined with DNMTi epigenetically controls the proliferation of l...MustafaFathy6
This study evaluated the effects of combining the histone deacetylase inhibitor (HDACi) vorinostat with other chemotherapeutic drugs on lung cancer cells. Vorinostat alone and in combination with carboplatin was most effective at reducing cell viability of A549 lung cancer cells. Global DNA methylation patterns varied depending on the drug combinations, with vorinostat and carboplatin causing hypomethylation and vorinostat and cyclophosphamide resulting in hypermethylation. The results suggest that combining epigenetic and chemotherapeutic drugs may be more effective at controlling lung cancer proliferation than single agents alone. However, more experiments are needed to confirm these findings.
This document summarizes a systematic review and meta-analysis that evaluated the prognostic impact of microRNAs (miRNAs) in patients with T cell acute lymphoblastic leukemia (T-ALL). Seventeen studies were included in the systematic review and sixteen were included in the meta-analysis. The meta-analysis found that overall miRNA expression was associated with a decreased risk of death by 7.1% in T-ALL patients. Upregulated miRNA expressions were associated with lower risk of death while downregulated expressions were associated with higher risk of death. The findings suggest that miRNA expression may help prognostic evaluation in T-ALL patients, although results were inconclusive.
EXPRESSION OF CK5 BASAL CYTOKERATIN DURING METASTATIC DEVELOPMENT OF BREAST C...ANCA MARIA CIMPEAN
Objective. Breast cancer is a one of the most common cancers in females worldwide. Basal cytokeratin CK5 represent the marker of progenitors for glandular and myoepithelial lineages of mammary epithelium. During epithelial differentiation there is a gradual decrease of CK5 expression. The purpose of this study was to compare the expression of basal cytokeratin CK5 vs hormone receptors, HER2, Ki67 and molecular subtypes immunohistochemically defined in the primary breast carcinoma of NST type and axillar lymph node metastasis. Material and Methods. We processed immunohistochemically 91 invasive breast carcinomas of NST type and their ipsilateral axillar lymph node metastasis (LNM). Results. The majority of primary tumors were evaluated as CK5 negative (78 cases/85.7%). The majority of cases were evaluated as Luminal B (50 cases/54.9%) and Luminal A (28 cases/30.8%) tumors. The HER2 subtype was confirmed in 8 cases/8.8%, 5NP in 3 cases/3.3% and Basal-like in 2 cases/2.2%. The parallel comparison of CK5 expression at both sites, primary and metastatic, revealed that this marker is not stable during metastatic progression. The molecular subtypes were not stable during metastatic process in 21 cases/23.1%. Conclusions. The majority of NST invasive ductal breast carcinomas are CK5 negative. The molecular subtypes and CK5 are not stable during metastatic process. Cancerous cells prefer to lose this marker in the lymph node environment. The presence of cases with simultaneous expression of CK5 and hormone receptors is an open field to debate the existence of other, transient molecular subtypes. We expect a further confirmation in larger study groups.
Key Words: molecular subtypes, invasive carcinoma NST type, basal cytokeratin.
CSF-Derived cell-free DNA for Diagnosis and Characterization of.pptxAmit Ghosh
This document discusses using cell-free DNA (cfDNA) derived from cerebrospinal fluid (CSF) for the diagnosis and characterization of central nervous system (CNS) malignant tumors. It begins by outlining current methods for molecular profiling of brain tumors, which rely on invasive biopsies and may not capture tumor heterogeneity. The document then reviews studies showing CSF-derived cfDNA is more sensitive than plasma for detecting brain neoplasms and can provide additional genetic information beyond tissue biopsies. It describes an ongoing pilot study analyzing CSF cfDNA in 100 brain tumor patients to diagnose tumors, represent heterogeneity, and monitor progression. The study aims to evaluate cfDNA analysis for guiding treatment and monitoring response. Overall, the document argues
HETEROGENEITY OF C ERB B FAMILY MEMBERS EXPRESSION IS RELATED TO CELL MORPHOL...ANCA MARIA CIMPEAN
This document summarizes a study examining the expression of HER2 and EGFR in pituitary adenomas and their relationship to hormone profiles. The study found that over one-third of pituitary adenomas expressed HER2, particularly prolactin-secreting adenomas. HER2 expression was also related to certain hormone co-expressions. Approximately half of adenomas expressed EGFR, which was correlated with GH-prolactin co-expression. The results suggest HER2 and EGFR expression may help define subclasses of pituitary adenomas and explain their clinical heterogeneity.
This study analyzed exome and genome sequences of 183 lung adenocarcinoma tumor/normal DNA pairs. It identified a mean exonic somatic mutation rate of 12.0 events/megabase and recurrent mutations in genes like U2AF1, RBM10 and ARID1A. Whole-genome analysis revealed frequent structural rearrangements including in-frame alterations in EGFR and SIK2 kinases. The candidate cancer genes identified may provide insights into lung adenocarcinoma pathogenesis and potential therapeutic targets.
This study examined the association between a FOXP3 gene polymorphism (rs3761548) and nondermatomal vitiligo in an Indian population. The researchers found that:
1) Female patients with the CC genotype were protected against vitiligo, while those with the CA genotype had a 3-fold higher risk of developing vitiligo.
2) No significant differences were observed between genotype frequencies in male patients and controls.
3) The results suggest the FOXP3 polymorphism may influence vitiligo susceptibility in women through altered regulatory T cell expression and function.
Proteomics Exploration of Chronic Lymphocytic Leukemia_Crimson PublishersCrimsonpublishersCancer
Chronic Lymphocytic Leukemia (CLL) is an adult heme malignancy characterized by the presence of mature-appearing CD5+ B cells in the blood, bone marrow, and secondary lymphoid organs [1]. In the United States, there will be an estimate of 20,720 new cases and 3,930 deaths according to the American Cancer Society statistics. Symptoms include swollen lymph nodes, frequent infections, and fatigue which negatively impacts the quality of life of people affected [1]. CLL is heterogeneous in its progression and clinical outcomes. Factors that contribute to the heterogeneity include the immunoglobulin heavy chain (IGHV) status and chromosomal aberrations [2,3]. There are two subtypes of CLL: Unmutated(U-CLL) and Mutated CLL(M-CLL). 40% and 60% of patients are diagnosed with unmutated and mutated CLL. U-CLL is characterized by the presence of CLL cells that have less than two percent of their IGHV mutated, whereas M-CLL cells have more than two percent mutated [4]. U-CLL is the more aggressive phenotype [2]. These cells have increased responsiveness to antigens that bind the B cell receptor (BCR) versus M-CLL cells [5]. M-CLL is the more indolent phenotype. Increased BCR signaling results in increased cell survival and proliferation [5].
Objective: The prognostic indictors of age-related poor outcomes in patients with acute myeloid leukemia (AML) are still controversial. The aim of this work was to provide comprehensive insights into the effect of different hemocytes and to investigate the association between age and clinical features in adult patients with AML.
Study Design: A retrospective study was performed to determine the role of age in the therapeutic outcomes of AML. A total of 166 newly diagnosed adult patients’ data from January 2015 to November 2019 in Zhongshan Hospital of Xiamen University were collected and analyzed.
Results: Older patients presented a poorer prognosis (p=0.001) with shorter overall survival, which is served as age-related outcomes. Binary logistic regression demonstrated that cytogenetic risk (OR=4.508, 95% CI 2.733–7.435), leukocyte (OR=7.410, 95% CI 1.139–5.910), and bone marrow blast cells (OR=3.261, 95% CI 1.075–5.615) were independent indictors for age-related prognosis. In addition, Kaplan-Meier curve also revealed that the above factors were associated with overall survival (all p values <0.001).
Conclusion: Cytogenetic risk, leukocyte, and bone marrow blast cells are dominant factors which account for the age-related poor outcomes and shorter overall survival in AML.
Keywords: acute myeloid leukemia, adult, cytogenetic risk, hemocyte, leukemia, overall survival
Targeted sequencing of 99 colorectal cancer samples identified frequent mutations in TP53 (65%), APC (36%), KRAS (35%), PIK3CA (19%), and other genes. EGFR mutations were associated with younger age of onset. EGFR or PIK3CA mutations were markers of poor disease-specific survival, and KRAS or PIK3CA mutations were associated with poor survival in TP53 wild-type cases. The findings provide novel prognostic insights and could help clinical decision-making for colorectal cancer patients in Saudi Arabia.
Yayan T. Sundara, Dokter di Klinik Jejaring Padjadjaran dan Master of Bio Medical Science Research dari Leiden University Medical Centrum, juga staff Departemen Pelayanan PT Rumah Sakit Padjadjaran
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.
Objective: The association between telomerase reverse transcriptase (TERT) promoter mutation and outcome of melanoma is unclear and controversial. We aim to conduct a meta-analysis and investigate whether the TERT promoter mutation is a prognostic factor of melanoma.
Study Design: Appropriate studies were searched in 3 databases: PubMed, Web of Science, and Embase. Pooled hazard ratios (HRs) were counted through random effects model.
Results: Heterogeneity was moderate in overall survival (OS) (I2=43.7%, p=0.059) and low in disease-free survival (DFS) (I2=0.0%, p=0.587). Sensitivity analysis indicated that the removal of any of the study did not affect the final results. Evidence for publication bias was not found (Begg’s test, p=0.281; Egger’s test, p=0.078). The pooled OS HRs from combined effects analysis was determined (HR 1.07; 95% CI 0.83–1.39, p=0.585), together with the pooled HRs of DFS (HR 1.65; 95% CI 1.02–2.66, p=0.042). TERT promoter mutation predicted a good outcome in meta-static melanoma patients (HR 0.66; 95% CI 0.46–0.96, p=0.042). The pooled HRs of combined mutation in TERT promoter and BRAF (HR 6.27; 95% CI 2.7–14.58, p=0.000) predicted a bad outcome in melanoma patients.
Conclusion: TERT promoter mutation significantly predicted poor DFS outcome but, on the contrary, predicted a good outcome in metastatic melanoma patients. The combined TERT promoter and BRAF mutation was a significant independent factor of OS in melanoma patients.
Keywords: melanoma; meta-analysis; mutation; prognosis; promoter regions, genetic; skin neoplasms; telomerase; TERT promoter mutation; TERT protein, human
This review article discusses the application of nanoscaffolds in mesenchymal stem cell-based therapy. It begins with an introduction about the need for regenerative medicine as an alternative to organ transplantation due to donor shortages. It describes mesenchymal stem cells and nanofibers/scaffolds as two essential components in regenerative medicine. Recently, the combination of mesenchymal stem cells and nanofibers/scaffolds has been utilized to obtain more homogeneous stem cell populations with higher proliferation rates and differentiation potential, which are important for regenerative medicine. The review then discusses topics such as the biology, sources, characterization, and isolation of mesenchymal stem cells. It also covers the
This document summarizes a study that analyzed antigen expression patterns in different subtypes of myelodysplastic syndromes (MDS) using flow cytometry. Bone marrow samples from 30 newly diagnosed MDS patients classified as refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), or refractory anemia with excess blasts (RAEB) were analyzed for antigen expression on granulocytic, monocytic, erythroid and lymphoid lineages. The study found no significant differences in antigen expression between subtypes for granulocytic lineages. For erythroid lineages, the percentage of CD71-positive cells was significantly lower in RAEB compared to R
This study utilized flow cytometric immunophenotyping to analyze bone marrow samples from 30 newly diagnosed myelodysplastic syndrome (MDS) patients. Abnormalities were frequently observed in the granulocytic, monocytic, and erythroid lineages of MDS patients compared to controls. The most common abnormality in granulocytes was decreased expression of CD10. Low expressions of CD13 were most common in monocytes. The erythroid lineage commonly showed low expression of CD71 and CD235a. Flow cytometry provided supportive evidence of phenotypic abnormalities to aid in the diagnosis of MDS when morphological analysis alone was inconclusive.
This document summarizes the biology, properties, and clinical applications of mesenchymal stem cells (MSCs). It discusses that MSCs are adult stem cells that can be isolated from bone marrow and other tissues. MSCs are plastic-adherent and spindle-shaped cells that are multipotent, able to differentiate into osteoblasts, chondrocytes, and adipocytes. They participate in repairing tissues like bone, cartilage, muscle and fat. Due to their multipotency and immunosuppressive properties, MSCs are promising candidates for stem cell-based therapies. The document reviews the isolation, identification, niche, and differentiation potential of MSCs in detail.
This document summarizes research optimizing the transfection of umbilical cord mesenchymal stem cells (UC-MSCs) with minicircle plasmid DNA using Lipofectamine LTX. The researchers tested different ratios of plasmid to Lipofectamine LTX, volumes of transfection complexes, cell densities, and presence or absence of medium. They found that a 1:2 ratio of 3μg plasmid to 6μl Lipofectamine LTX, transfecting 50,000 cells with 150μl of the transfection complex in the presence of medium, resulted in the highest expression of the GFP reporter gene as observed by fluorescence microscopy 72 hours after transfection. Flow cytometry was also used to quantitatively measure transfection efficiency
The defendant's attorney filed a motion to suppress evidence in a case where the defendant, Kenny Boy, was arrested for physical control of a vehicle while intoxicated. The arrest was made based solely on an anonymous tip. The motion argues that an anonymous tip alone does not meet the standard of "indicia of reliability" required to justify stopping and detaining someone. Prior case law establishes that an anonymous tip must demonstrate reliability of the informant or be corroborated by officer observations to justify stopping someone. As the officer in this case did not observe any criminal activity or corroborate the tip before stopping the defendant, the attorney argues all evidence obtained from the stop should be suppressed as the result of an unlawful seizure.
Standar ini menetapkan spesifikasi untuk agregat ringan yang digunakan dalam pembuatan beton ringan struktural. Agregat harus memenuhi persyaratan komposisi kimia, sifat fisis, dan gradasi serta menghasilkan beton dengan kuat tekan dan kuat tarik tertentu. Agregat dapat berasal dari proses alami maupun buatan seperti lempung bekah, dan harus memiliki berat jenis rendah serta daya serap air terbatas.
This document provides the program for a public symposium on "DNA & Indigeneity: The Changing Role of Genetics in Indigenous Rights, Tribal Belonging, and Repatriation". The symposium includes sessions on constructing biogenetic identities and their limitations, the role of genetics in the repatriation of human remains, and challenges and directions for genetic research with Indigenous communities. Speakers include experts from various Indigenous communities and academic institutions discussing case studies and issues relating to the use of genetics in determining Indigenous identity and rights, as well as repatriation efforts.
This document discusses cognitive development throughout childhood, covering infancy, early childhood, middle childhood, and adolescence. It describes the major stages and abilities associated with each period, including sensorimotor learning in infancy, preoperational thinking in early childhood, concrete operational skills emerging in middle childhood, and formal operational abstract thinking in adolescence. The document also examines similarities and differences between stages, components and flaws of Piaget's model, language and intelligence testing, and effects of daycare on attachment.
This document discusses strengths theory and positive psychology. It defines strengths as pre-existing capacities that are authentic and energizing, enabling optimal functioning. Two main classification systems are described: Clifton StrengthsFinder measures 34 talent themes, while VIA Inventory of Strengths identifies 24 character strengths within six virtues. Well-being has three dimensions - emotional, psychological, and social - and flourishing involves high levels across all dimensions. Limitations in applying strengths approaches cross-culturally are noted.
I have extensive design and process development knowledge from personally producing 200mm and 300mm Applied Materials; Centura Single Wafer Upper Domes, Lower Domes, Chamber Liners, Susceptor Shafts, and Wafer Lift Shafts along with ASM 200mm & 300mm Process Chambers, Thermocouples, Support Rings, Spiders, and Pencil Shafts. I also have many years experience at Vertical Batch Processes such as TEL, SVG, Kokusai, as well as Horizontal Batch Processes. All of this hands on experience and knowledge has been the the key ingredient to enable me to be successful and well rounded in many areas of Production Management, Product Management, Sales and Large Lathe Quartz Fabrication.
I always give 110% of myself to achieve all company goals and objectives to further grow and prosper the business. I am always aggressive to improve efficiencies in all areas and to streamline product lines and fabrication processes. From R&D and team efforts, to thinking outside the box to optimize output from every angle possible. This was achieved through 35 years of knowledge and hands on experience with quartz large lathe and bench fabrication.
The document summarizes cognitive development throughout childhood from infancy to adolescence. It discusses Piaget's stages of cognitive development, including the sensorimotor stage in infancy where children learn through their senses and actions. In early childhood, children develop symbolic thinking and theory of mind. Middle childhood is characterized by concrete operational thought, while adolescence involves formal operational thinking and advanced information processing. The document also reviews factors that influence language development and intelligence testing in children.
Role of Flow Cytometric Immunophenotyping in Plasma Cell DyscrasiasApollo Hospitals
Immunophenotyping is being routinely used for the diagnosis of leukemias. With the advent of specific markers for plasma cells, it has become possible to differentiate between benign and malignant plasma cells based on their immunophenotypic profile. The enhanced use of immunophenotyping in plasma cells dyscrasias may help to categorize the borderline cases which can not be done with morphology alone. Also the immunophenotypic profiling of plasma cells would help in Minimal Residual Disease (MRD) evaluation of patients on treatment of multiple myeloma (MM).
Minimal Residual Disease in Acute lymphoblastic leukemiaDr. Liza Bulsara
This document discusses minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL). It provides information on several key points:
1. MRD refers to small amounts of leukemia cells that can be detected through sensitive laboratory techniques like flow cytometry and PCR, but not through standard morphology.
2. Various methods for detecting MRD are discussed, including immunophenotyping, PCR, FISH, and cytogenetics. PCR can detect a single malignant cell among 100,000 normal cells and is the most sensitive method.
3. MRD levels determined at different time points during treatment have prognostic significance and can be used for risk stratification and determining the need for treatment intensification or reduction. Monitoring
Background: Tuberculous meningitis is defined as an inflammatory response to mycobacterial bacterial infection of the pia, arachnoid and CSF of the subarachnoid space. It is a dangerous form of extrapulmonary tuberculosis because it can cause permanent neurological disabilities and even death. Stroke is a devastating complication which further increase the morbidity and mortality in the disease. Matrix metalloproteinases are endopeptidases which degrade all the components of the extracellular matrix and thus have potential to disrupt blood brain barrier and cause CNS damage. Matrix metalloproteinases have been associated with pathophysiology of ischemic stroke. MMP levels in serum and CSF have also been seen to rise with advancing stage of TBM. So it is postulated that MMP may have role in the pathophysiology of stroke in TBM and may serve as a biomarker to predict stroke in TBM. Aims: To compare Serum Matrix metalloproteinase-9 in patients with Tuberculous Meningitis with and without Stroke and correlate it with various clinical, biochemical and radiological features of TBM. Methods: 40 Patients of probable or definite TBM and 40 age and sex matched patients of TBM with clinical stroke were enrolled in the study and formed two groups i.e. cases and controls. The two groups were compared for various clinical parameters, biochemical parameters (CSF cytology, glucose and protein), neuroimaging parameters and serum MMP-9 levels. Serum MMP-9 was estimated by ELISA method. Results: Serum MMP-9 levels were (224 ± 261.627 ng/ml) in cases and (157.23 ± 197.155 ng/ml) controls, which though higher in cases but no difference was statistically significant (p value 0.157) between two groups. Also there was no correlation between the serum MMP-9 levels and various clinical features (duration of illness, fever, headache, vomiting, weight loss, seizure, hemiparesis), CSF characteristics (protein, sugar and cytology) and radiological findings (tuberculoma, and hydrocephalus). Conclusion: we conclude that MMP-9 levels is not correlated with occurrence of stroke in TBM. MMP-9 levels were not increased with severity of disease, complications and outcomes.
Recent advances in treatment of Myelodysplastic Syndrome. Dr. Zhijian Xiaospa718
The document discusses recent advances in the treatment of myelodysplastic syndrome (MDS). It covers several key points:
1) Patient characteristics like age, performance status, and comorbidities are important considerations in determining treatment approach and ability to tolerate intensive therapies.
2) Treatment strategies for lower-risk and higher-risk MDS aim to improve blood counts, quality of life, delay disease progression, and prolong survival.
3) Supportive care focuses on reducing morbidity from low blood counts while active therapies aim to alter the natural history of MDS and improve survival.
4) Allogeneic stem cell transplantation remains the only potentially curative treatment but the decision to transplant requires considering age,
Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement M Dominici1, K Le Blanc2, I Mueller3, I Slaper-Cortenbach4, FC Marini5, DS Krause6, RJ Deans7, A Keating8, DJ Prockop9 and EM Horwitz10
Cost Effectiveness Analysis for Targeted Therapy in Patients with Acute Myelo...Madeleine Lee
This study aimed to evaluate the cost-effectiveness of using targeted therapies compared to standard chemotherapy for treating acute myeloid leukemia (AML) patients. The study developed Markov models to analyze the costs and effects of the different treatment strategies. It reviewed literature on clinical trials of several targeted therapies approved since 2017 for AML, including FLT3 inhibitors, IDH inhibitors, and others. The results indicated that for ineligible patients, targeted therapies may be a cost-effective alternative to intensive chemotherapy, based on an incremental cost-effectiveness ratio analysis. However, more detailed cohort studies are still needed to evaluate outcomes based on patient characteristics and multiple treatment approaches.
Dr. maryalice stetler stevenson lymphoma mrdHitham Esam
Flow cytometry can be used to detect minimal residual disease (MRD) in plasma cell neoplasms such as multiple myeloma. It provides both prognostic information and a way to measure response to drug therapies. Several factors are important for obtaining high quality flow cytometry results, including using bone marrow aspirates within 24 hours of collection, lysing red blood cells, acquiring sufficient events, and using standardized staining and gating strategies. Detection of MRD by flow post-treatment is predictive of patient outcomes and can guide clinical decision making.
Dr. nahla farahat immunophenotyping of multiple myeloma Hitham Esam
Plasma cell myeloma is a heterogeneous group of neoplasms characterized by expansion of clonal plasma cells in the bone marrow. Flow cytometry is useful for diagnosing and monitoring plasma cell disorders by confirming the clonal nature of plasma cells and differentiating disorders. Normal plasma cells are CD38bright, CD138+, CD19+ and CD45dim, while myeloma cells typically show aberrant expression including CD19, CD27 and CD45 underexpression and CD28, CD33, CD56 and CD117 overexpression. A minimum of 100 clonal plasma cell events should be acquired to accurately assess disease. The presence of more than 5% residual normal plasma cells can differentiate MGUS from myeloma.
Gene expression profiling reveals molecularly and clinically distinct subtype...Yu Liang
This study used gene expression profiling to analyze molecular subtypes of glioblastoma multiforme (GBM), the most common and aggressive form of brain cancer. The analysis revealed:
1) Distinct gene expression patterns between GBM tumors and normal brain tissue, as well as between GBMs and lower-grade oligodendroglial tumors.
2) Significant differences in gene expression among individual GBM tumors, particularly in genes related to angiogenesis, immune response, and extracellular matrix remodeling.
3) Gene expression patterns of samples from the same GBM tumor were more similar to each other than to other tumors, even when the samples had divergent histologies.
4) A set of 70 genes associated
The Impact of Lymph Node Dissection on Survival in Intermediate- and High-Ris...semualkaira
Aimed to evaluate the therapeutic effect of pelvic lymph node dissection (PLND) on survival and determine the predictors of lymph node involvement (LNI) in patients with intermediate- or high-risk prostate cancer (PCa) treated with Radical Prostatectomy
The Impact of Lymph Node Dissection on Survival in Intermediate- and High-Ris...semualkaira
Aimed to evaluate the therapeutic effect of pelvic lymph node dissection (PLND) on survival and determine the
predictors of lymph node involvement (LNI) in patients with intermediate- or high-risk prostate cancer (PCa) treated with Radical
Prostatectomy
This document discusses monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), which are precursor states of multiple myeloma. It provides definitions and risk factors for progression from MGUS to myeloma. Genetic and molecular insights into disease progression are explored, including primary and secondary genetic events. Management strategies for MGUS and SMM are reviewed, including risk stratification and criteria for high-risk SMM. Ongoing research into clonal evolution and the tumor microenvironment shed light on myelomagenesis. The first randomized trial to show a benefit of early treatment in high-risk SMM is summarized.
The Prognostic Model of Differentiation-Related Lncrna Based on Bioinformatic...semualkaira
Differentiation status of glioma cells correlated with prognosis and Tumor-Immune Microenvironment (TIME) in patients with gliomas. This study aimed to identify differentiation-related long non-coding RNAs (DRlncRNAs) that can be used to predict the outcome and the response to immunotherapy in patients with gliomas.
The Prognostic Model of Differentiation-Related Lncrna Based on Bioinformatic...eshaasini
Differentiation status of glioma cells correlated with prognosis and Tumor-Immune Microenvironment (TIME) in patients with gliomas. This study aimed to identify difDifferentiation status of glioma cells correlated with prognosis and Tumor-Immune Microenvironment (TIME) in patients with gliomas. This study aimed to identify differentiation-related long non-coding RNAs (DRlncRNAs) that can be used to predict the outcome and the response to immunotherapy in patients with gliomas.ferentiation-related long non-coding RNAs (DRlncRNAs) that can be used to predict the outcome and the response to immunotherapy in patients with gliomas.
The Prognostic Model of Differentiation-Related Lncrna Based on Bioinformatic...semualkaira
Differentiation status of glioma cells correlated with prognosis and Tumor-Immune Microenvironment (TIME) in patients with gliomas. This study aimed to identify differentiation-related long non-coding RNAs (DRlncRNAs) that can be used to predict the outcome and the response to immunotherapy in patients with gliomas.
This study investigated the relationship between tumor characteristics and somatostatin receptor 2 (SSTR2) expression in 81 patients with meningioma. Univariate and multivariate analyses found that older age (>65), larger tumor size (>3 cm), and female sex were associated with poorer overall survival. However, there was no association found between SSTR2 expression levels (negative, weakly positive, strongly positive) and overall survival or other tumor characteristics. Therefore, further research is needed to understand the role of SSTR2 receptor expression in meningiomas beyond its diagnostic value.
The document discusses key changes in the 5th edition of the WHO brain tumor classification:
- It recognizes 22 new tumor types and revises the terminology for 13 tumor types.
- It takes a new approach to classify gliomas, glioneuronal tumors, and neuronal tumors into 6 families including adult and pediatric diffuse low-grade gliomas.
- Grading is no longer entirely histological and incorporates molecular alterations. Factors like CDKN2A deletion can result in grade 4 even with low-grade histology.
- Terms like "anaplastic" have been removed and grading uses numerical scales instead of descriptive terms.
WHO BRAIN TUMOR CLASSIFICATION 5th EDITIONKanhu Charan
The document summarizes some of the key changes in the 2021 5th edition of the WHO brain tumor classification compared to previous editions. Some notable changes include recognizing the distinction between adult and pediatric diffuse gliomas, adding 22 new tumor types, revising the terminology for 13 tumor types, introducing essential and desirable diagnostic criteria, and classifying tumors based on a combination of histopathological and molecular features. Sellar tumors, meningiomas, and ependymomas were also revised in the new classification system.
This study examined the prevalence of cryptococcal meningitis (CM) among people living with HIV/AIDS (PLHAs) at a hospital in southern Odisha, India. Of 112 clinically diagnosed CM patients, 16 cases were confirmed via cerebrospinal fluid analysis, showing a prevalence of 14.3%. Males aged 21-40 were most commonly affected. The most common symptoms were fever, headache, altered sensorium, and neck stiffness. CD4 T-lymphocyte counts were below 100 cells/μl in 93.7% of confirmed cases. All patients responded initially to antifungal therapy but 2 died during hospitalization and 4 were lost to follow up. Early diagnosis and treatment of CM is
Similar to Range Determination of Antigen Expression in (20)
Prevalence of cryptococcal meningitis among people living with human immunode...
Range Determination of Antigen Expression in
1. 19IRANIAN JOURNAL OF BLOOD AND CANCER Volume 6 Number 1 Autumn 2013
Range Determination of Antigen Expression in
Myeloid, Erythroid and Lymphoid Cell Lineages
among Patients with Myelodysplastic Syndrome
Hashem Boroojerdi M1
*, Daneshvar N2
, Ghoraishizadeh P3
, Ramasamy R2
,
Seman Z1
, Noor S1
1. Pathology department, Faculty of Medical and Health Science, University Putra Malaysia.
2. Institute of Bioscience, University Putra Malaysia, Selangor, Malaysia.
3. Pathology department, Faculty of Medical and Health Science, University Putra Malaysia.
*Corresponding Author: Hashem Boroojerdi M, Email: mohadese_b84@yahoo.com
Submitted: 21-03-2013 , Accepted: 18-08-2013
Abstract
Background: Myelodysplastic syndrome is a mixed clonal disorder of bone marrow progenitor cells. Understanding
the pattern of the different lineage-specific, immature, and mature markers in myelodysplastic syndrome will help in
setting-up the frame of reference to diagnose.
Patients and Methods: We compared 60 bone marrow samples from 30 newly-diagnosed patients with
myelodysplastic syndrome and 30 patients with idiopathic thrombocytopenic purpura as the control to perform a
quantitative analysis of the antigen expression patterns in granulocytic, monocytic, erythroid and lymphoid lineages
and myeloid precursors.
Results: Quantitative analysis of CD markers, showed that the mean percentages of CD33, CD13, CD11b, HLA-
DR, CD10 and CD34 positive granulocytes were 91%, 84.98%, 77.20%, 14.59%, 40.34% and 34.25%, respectively
in myelodysplastic syndrome and 96.89%, 91.57%, 81.47%, 10.56%, 58.30% and 32.37%, respectively in idiopathic
thrombocytopenic purpura. Flow cytometric analysis of erythroid lineage showed the mean percentage of CD71
in myelodysplastic syndrome and idiopathic thrombocytopenic purpura cases to be 64.54% and 83%, respectively.
Investigation of antigen expression in the myeloid precursors of myelodysplastic syndrome patients showed the
mean proportions of: 19.89%, 59.53%, 57.26%, 69.24%, 60.64% and 23.43% for CD117, CD34, HLA-DR, CD33, CD13
and CD11b, respectively. Also, idiopathic thrombocytopenic purpura cases showed the mean percentages of 11.73%,
45.67%, 58.90%, 74.28%, 70.16% and 15.66% for CD117, CD34, HLA-DR, CD33, CD13 and CD11b, respectively.
Conclusion: There is no doubt that providing the reference values for an antigen expression pattern among
myelodysplastic syndrome cases enhances the utility of flow cytometric analysis interpretation among these patients.
Keywords: Myelodysplastic syndromes, flow cytometry, immunophenotyping, antigen expression.
Introduction
Myelodysplastic Syndrome (MDS) is a
heterogeneous cluster of diseases characterized
by ineffective haematopoiesis, which leads to
the peripheral cytopenia of one, two or all three
(myeloid, erythroid and megakaryocytic) lineages 1,2
.
The clinical presentation of constant cytopenia
supported with a morphological examination of the
bone marrow (BM) is the conventional tool in the
diagnosis of MDS. Because of certain limitations,
the morphological findings in MDS patients are not
always trustworthy 3
. Analysis of the cell lineages
and expression pattern of antigens can provide a
characteristic model of the disease. These findings
lead to the more accurate diagnosis of this
disorder as they also support the morphological
diagnosis4
. Furthermore, immunophenotypic
analysis is easier and faster as compared to
conventional MDS diagnostic methods 5
.
Patients and Methods
Thirty patients with newly diagnosed MDS were
examined in this study. Samples from patients
with MDS were collected from February 2009 to
November 2010 at Hospital Kuala Lumpur (HKL).
IJBC 2013;1: 19-26
ORIGINAL ARTICLE
2. 20 IRANIAN JOURNAL OF BLOOD AND CANCER
This study was approved by the Faculty of Medicine
and Health Sciences and performed at University
Putra Malaysia (UPM). Information about the MDS
and control groups is summarized in Table 1. The
pattern of antibody we used in this study which
is listed in Table 2 was based on van Lochem et
al. suggestion 6
. The technique that was used for
labeling the cells was according to Li et al. study 7
.
More details have been described in our previous
study 8
. For all variables in this study a descriptive
analysis was performed. Differences between
groups were tested by student t-test. For all
statistical tests, statistical significance was defined
by a p value of 0.05 or less 9
. Antigenic difference
assessment was performed by comparing the mean
of the gated population fluorescence with that of
the control.
Results
Flow cytometric immunophenotyping
Granulocytic lineage
The mean percentages of CD33, CD13, CD11b,
HLA-DR, CD10 and CD34 positive granulocytes were
91%, 84.98%, 77.20%, 14.59%, 40.34% and 34.25%,
respectively, among MDS and 96.89%, 91.57%,
81.47%, 10.56%, 58.30% and 32.37%, respectively,
among non-MDS patients. Table 3 shows the
percentages of different antigens in granulocytic
lineage in MDS and non-MDS patients.
Erythroid lineage in MDS and non-MDS
Flow cytometric analysis of erythroid lineage
showed the mean percentage of CD71 in MDS and
non-MDS cases to be 64.54% and 83%, respectively.
In addition, CD235a-positive and CD71/CD235a-
positive erythroid precursors showed mean
percentages of 35.96% and 6.61%, respectively, in
MDS cases, as compared to 52.83% and 10.48%,
respectively, in non-MDS cases. Table 4 shows
the percentages of different antigens in erythroid
lineage in MDS and non-MDS cases.
Monocytic lineage in MDS and non-MDS
In this study the mean proportions of CD14,
CD33, CD13, CD34 and HLA-DR were 65.89%,
79.92%, 74.04%, 44.43%, 36.25% in MDS and
74.36%, 86.57%, 87.74%, 45.30%, 38.86% in non-
MDS cases. Table 5 shows the percentages of
different antigens on monocytic lineage in MDS
and non-MDS.
Myeloid precursors in MDS and non-MDS
Investigation of antigen expression in myeloid
precursors of MDS patients showed the mean
Table 1: Demographics of the MDS and control groups.
Patient Group
MDS 30
Gender 20 Males and 10 Females
Median age 52 years old
Race 9 Malays and 21 Chinese
Control Group
ITP 30
Gender 13 Males and 18 Females
Median age 40 years old
Race 12 Malays and 18 Chinese
Table 2: The monoclonal antibody‐panel used in this study
CD19‐FITC / CD20‐PE / CD45‐PerCP‐Cy5.5 / CD10‐APC
CD71‐FITC / CD235a‐PE / CD45‐PerCP‐Cy5.5 / CD117‐AP
CD14‐FITC / CD33‐PE / CD45‐PerCP‐Cy5.5 / CD34‐APC
HLA‐DR‐FITC / CD13‐PE / CD45‐PerCP‐Cy5.5 / CD11bAPC
Hashem Boroojerdi et al.
3. 21Volume 6 Number 1 Autumn 2013
proportions of: CD117 (19.89%), CD34 (59.53%),
HLA-DR (57.26%), CD33 (69.24%), CD13 (60.64%)
and CD11b (23.43%). In non-MDS cases, the mean
percentages of CD117 (11.73%), CD34 (45.67%),
HLA-DR (58.90%), CD33 (74.28%), CD13 (70.16%)
and CD11b (15.66%) were detected. Table 6 shows
the percentages of different antigens in myeloid
precursors in MDS and non-MDS cases.
Lymphoid lineage in MDS and non-MDS cases
The mean ranges for CD19/CD10-positive,
CD19/CD20-positive, CD20/CD10-positive and
CD19 were 4.14%, 12.20%, 3.13%, and 14.69%,
respectively, in MDS and 3.19%, 13.93%, 3.08%,
and 15.57%, respectively, in non-MDS cases. Table
7 shows the percentages of different antigens in
lymphoid lineage in MDS and non-MDS cases.
Table 3: Percentages of different antigens in granulocytic lineage in MDS and non‐MDS patients.
Variable Group Mean percentage SD P values
CD13
MDS 84.98 10.77 0.006
non‐MDS 91.57 6.49
CD34
MDS 34.25 6.76 0.218
non‐MDS 32.37 4.81
CD10 MDS 40.34 16.19 0.000
non‐MDS 58.30 5.98
HLA‐DR MDS 14.59 7.73 0.029
non‐MDS 10.56 3.66
CD33 MDS 91 22.21 0.005
non‐MDS 96.89 10.18
CD11b MDS 77.20 17.45 0.210
non‐MDS 81.47 5.99
Table 4: Percentages of different antigens on erythroid lineage in MDS and non‐MDS patients.
Variable Group Mean percentage SD P values
CD71
MDS 64.54 18.68 0.000
non‐MDS 83 7.05
CD235a
MDS 35.96 13.03 0.000
non‐MDS 52.83 7.98
CD71/CD235a‐positive MDS 6.61 3.75 0.000
non‐MDS 10.48 3.23
Range Determination of Antigen Expression ...
4. 22 IRANIAN JOURNAL OF BLOOD AND CANCER
Discussion
MDS is one of the common BM disorders among
elderly population. Incidence of MDS in general
population is about 3.5–4 per 100,000 people
per year 10
. Analyzing the pattern of different
CD markers in MDSs will help to set the frame of
reference for identification of MDS 4. These ranges
provide a basis for comparing the results from
various institutes. In addition, it helps to combine
such results on patients from several institutes,
and will provide the methodology and equipment
that are matching at all sites. Describing a range for
antigen expression can also be useful in evaluating
each individual patient. With a panel of thirteen
monoclonal antibodies, including monoclonal
antibodies against CD45, CD71, CD235a, CD117,
HLA-DR, CD13, CD11b, CD14, CD33, CD34, CD19,
CD20, and CD10 quantitative flow cytometric
analysis of various cell lineage specific antigens
were achieved in this study. We examined antigen
expression pattern of erythroid, granulocytic,
monocytic, lymphoid lineages and myeloid
precursors in thirty patients with newly-diagnosed
MDS. The results were compared with the BM
samples of patients affected by disorders with no
BM involvement (ITP) 9
.
The gold standard for the MDS diagnosis is based
on morphology but sometimes morphological
diagnosis may not be enough 11,12
. Different
studies have indicated that neoplastic cells in MDS
demonstrate decreased or increased expression
of some CD markers. They also have shown the
maturational asynchrony in expression of different
antigens in MDS. In fact, abnormal expression
patterns of different antigens have been reported
Table 5: Percentages of different antigens on monocytic lineage in MDS and non‐MDS cases.
Variable Group Mean percentage SD P values
CD34
MDS 44.43 11.53 0.755
non‐MDS 45.30 9.69
HLA‐DR
MDS 36.25 11.72 0.376
non‐MDS 38.86 10.65
CD19 MDS 31.64 10.12 0.350
non‐MDS 31.29 9.04
HLA‐DR/CD11b‐positive MDS 32.49 8.00 0.024
non‐MDS 28.47 5.04
CD14 MDS 65.89 21.53 0.337
non‐MDS 74.36 9.65
CD33 MDS 79.92 16.80 0.099
non‐MDS 86.57 8.62
CD14/CD34‐positive MDS 35.98 15.86 0.037
non‐MDS 29.21 6.48
CD13 MDS 74.04 23.90 0.005
non‐MDS 87.74 5.90
Hashem Boroojerdi et al.
5. 23Volume 6 Number 1 Autumn 2013
several times in MDS cases 5, 12-16
. But to the best of
our knowledge there is no report about the mean
percentage of different CD markers on various cell
lineages in MDS patients. Previous studies have just
mentionedthedecreasing,increasingandabnormal
expression of different CD markers on different cell
lineages. For instance, low mean percentage of
CD13 and CD33 on granulocytes and monocytes has
been reported before 5,8,12,13
. In addition, a lower
mean percentage of CD10+ on granulocytes has
been found in MDS patients 5,12,15,16
. Wells et al. 15
,
showed the maintenance of CD34 expression on
mature granulocytes. In a series of 115 MDS cases,
they reported retention of CD34 expression on
differentiatinggranulocytes15
.Wangetal.17
,studied
immunophenotypic characteristics of BM samples
from 48 MDS patients. They found the abnormal
expression of CD13/CD11b on granulocytes of MDS
patients but the difference between MDS and non-
MDS cases was not statistically significant 17
. Other
studies have shown decreased CD14 expression
on monocytes of MDS patients 12,15
. Wells et al. 15
,
found a variety of myeloid and monocytic abnormal
antigenic patterns in MDS, atypical maintenance
of HLA-DR in subpopulations of maturing myeloid
cells, aberrant development in a subpopulation of
monocytes that decrease CD11b presentation on
maturing granulocyte and monocytes 15
. Antigen
expression pattern of erythroid precursors has
been investigated by the researchers as well. Based
on previous findings flow cytometric analysis
of erythroid progenitors from MDS patients
have indicated decreased CD71 and CD235a/CD71
presentation compared to those from normal BM 16,
18
. Xu et al.19
analyzed the Immunophenotypic features
of erythroid progenitors to evaluate their diagnostic
application in MDS. They showed low expression
of CD71 in erythroid precursors of MDS patients.
Chopra et al.20
, investigated the BM aspirates of
57 suspected MDS and 31 normal controls by five-
Table 6: Percentages of different antigens in myeloid precursors in MDS and non‐MDS patients.
Variable
Group
Mean percentage
SD P values
CD33
MDS 69.24 22.21 0.263
non‐MDS 74.28 10.18
CD34
MDS 59.53 19.33 0.002
non‐MDS 45.67 12.06
CD13 MDS 60.64 20.35 0.031
non‐MDS 70.16 11.78
HLA‐DR MDS 54.26 2033 0.355
non‐MDS 58.90 18.16
HLA‐DR/CD11b‐positive MDS 22.40 13.65 0.000
non‐MDS 9.22 5.48
CD117 MDS 19.89 9.70 0.000
non‐MDS 11.73 6.05
CD11b MDS 23.43 14.27 0.012
non‐MDS 15.66 8.02
Range Determination of Antigen Expression ...
6. 24 IRANIAN JOURNAL OF BLOOD AND CANCER
color flow cytometry. They showed significantly
lower expression of CD71 on CD235a of erythroid
precursors and in MDS cases 20
.
Also, several studies have reported the
phenotypic changes occurring in the myeloid
precursors of MDS patients. Arroyo et al. 21, 22
,
and 23
reported an increase in myeloid precursors
CD34 and CD38 expression in MDS. Ogata
et al. 23
, also reported finding an increase in
myeloid precursors CD11b expression23
. Samuel
et al.24
, also showed, reduced or increased
CD33 expression on myeloid precursors.
CD117 is another antigen that is expressed
on hematopoietic progenitors and immature
myeloid cells. CD117 has been shown to be normal
or increased in myeloid precursor cells in MDS
patients 24
. Kussick et al.14
, showed increased CD34,
HLA-DR, CD11b+, CD117, and CD11b expression
on myeloid precursors in MDS when compared to
non-MDS cases. On the other hand, decrease of
HLA-DR, CD33 and CD13 on myeloid precursors
has been reported in MDS cases compared to
non-MDS cases14
. Ogata et al .23
, also indicated the
rise of CD11b expression on myeloid precursors.
Previous studies have indicated enhancement of
CD38 expression on myeloid precursors in MDS
cases 21, 22,23
. Although, our results support the
previous studies the aim of this study was showing
the mean percentage of each CD markers included
in our panel. There is no doubt, that having the
reference values for an antigen expression pattern
of various cell lineages in MDS will enhance the
utility of flow cytometric analysis. In addition,
using reference values will improve the accuracy
of flow cytometric analysis by mixing variation
due to race, gender, and age. In the absence of
previously published estimates, we now report
establishment of reference values for antigen
expression patterns in various cell lineages of MDS
cases. In conclusion, this study has determined the
range of antigen expression on myeloid, erythroid
and lymphoid cell lineages in MDS patients that
may be useful in interpretation of laboratory and
clinical findings. In addition, our result can be used
as a reference for antigen expression patterns for
the diagnosis of MDS, and also help to distinguish
MDS from other diseases. Although this study was
successfully completed some limitations were
observed. First of all, the number of MDS cases
was very low in Malaysia. Secondly, no normal
individuals volunteered to give BM sample for the
study so in this study we used the ITP cases as the
control. We think these cases were suitable enough
to be as a control because they did not show any
BM involvement.
Conclusion
There is no doubt that providing the reference
values for an antigen expression pattern among
myelodysplastic syndrome cases enhances the
utility of flow cytometric analysis interpretation
among these patients.
Table 7: Percentages of different antigens in lymphoid lineage in MDS and non‐MDS patients.
Variable Group Mean percentage SD P values
CD19
MDS 14.69 5.34 0.510
non‐MDS 15.57 4.86
CD19/CD10‐positive
MDS 4.14 3.85 0.530
non‐MDS 3.19 5.70
CD19/CD20‐positive MDS 12.20 2.26 0.094
non‐MDS 13.93 2.05
CD20/CD10‐positive MDS 3.13 1.97 0.925
non‐MDS 3.08 2.09
Hashem Boroojerdi et al.
7. 25Volume 6 Number 1 Autumn 2013
Acknowledgements
We would like to thank Dr Raudhawati Osman as
the head of the hematology unit in Hospital Kuala
Lumpur for allowing us to collect and conduct this
study and Madam Lee Siew Moi, for the assistance
in sample collection.
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