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
Sct promoter methylation is a highly discriminative biomarker for lungredpel dot com
Sct promoter methylation is a highly discriminative biomarker for lung
for more ieee paper / full abstract / implementation , just visit www.redpel.com
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.
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.
Sct promoter methylation is a highly discriminative biomarker for lungredpel dot com
Sct promoter methylation is a highly discriminative biomarker for lung
for more ieee paper / full abstract / implementation , just visit www.redpel.com
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.
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.
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.
Geriatric Care at a Time of Accelerated Aging in the World Population and Eme...science journals
It is a well-known fact that the world population has been aging since mid-20th century. The number of older people aged 60 years and above has more than quadrupled since 1950’s and older people’s share of the world population reached 11.7 percent in 2013.
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.
Expanding treatment platform in m crc bayer - asyut 2018Mohamed Abdulla
Describes the different therapeutic approach to patients with metastatic colorectal cancer in the 3rd subsequent treatment line with especial emphasis on the role of regorafenib and how to manipulate the adverse events while not compromise the outcome.
Ohio State's 2016 ASH Review Blood and Marrow Trasplantation (with Turning Po...OSUCCC - James
Ohio State’s 2016 ASH Review
Blood and Marrow Transplantation
Basem M. William, MD, MRCP(UK), FACP
Assistant Professor of Internal Medicine
Blood and Marrow Transplant Program
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.
Clinical Genomics for Personalized Cancer Medicine: Recent Advances, Challeng...Yoon Sup Choi
I reviewed recent advances, challenges, and opportunities to implement clinical cancer genomics. Case studies of advanced systems, such as Foundation Medicine, MI-ONCOSEQ are introduced for benchmark. A few fundamental limitations to establish personalized oncology are also discussed.
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.
Geriatric Care at a Time of Accelerated Aging in the World Population and Eme...science journals
It is a well-known fact that the world population has been aging since mid-20th century. The number of older people aged 60 years and above has more than quadrupled since 1950’s and older people’s share of the world population reached 11.7 percent in 2013.
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.
Expanding treatment platform in m crc bayer - asyut 2018Mohamed Abdulla
Describes the different therapeutic approach to patients with metastatic colorectal cancer in the 3rd subsequent treatment line with especial emphasis on the role of regorafenib and how to manipulate the adverse events while not compromise the outcome.
Ohio State's 2016 ASH Review Blood and Marrow Trasplantation (with Turning Po...OSUCCC - James
Ohio State’s 2016 ASH Review
Blood and Marrow Transplantation
Basem M. William, MD, MRCP(UK), FACP
Assistant Professor of Internal Medicine
Blood and Marrow Transplant Program
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.
Clinical Genomics for Personalized Cancer Medicine: Recent Advances, Challeng...Yoon Sup Choi
I reviewed recent advances, challenges, and opportunities to implement clinical cancer genomics. Case studies of advanced systems, such as Foundation Medicine, MI-ONCOSEQ are introduced for benchmark. A few fundamental limitations to establish personalized oncology are also discussed.
This presentation summarises a basic Computational Fluid Dynamics project that analyses aerodynamic flow over a Formula rear wing, and goes on to analyse a slotted rear wing solution, which is commonly used for efficient wing performance.
Purpose: An inherited mutation in KRAS (LCS6-variant or rs61764370) results in altered control of the KRAS oncogene. We studied this biomarker’s correlation to anti-EGFR monoclonal antibody (mAb) therapy
response in patients with metastatic colorectal cancer.
Experimental Design: LCS6-variant and KRAS/BRAF mutational status was determined in 512 patients
with metastatic colorectal cancer treated with salvage anti-EGFR mAb therapy, and findings correlated with
outcome. Reporters were tested in colon cancer cell lines to evaluate the differential response of the LCS6-
variant allele to therapy exposure.
Results: In this study, 21.2% (109 of 512) of patients with metastatic colorectal cancer had the LCS6-
variant (TG/GG), which was found twice as frequently in the BRAF-mutated versus the wild-type (WT) group
(P = 0.03). LCS6-variant patients had significantly longer progression- free survival (PFS) with anti-EGFR
mAb monotherapy treatment in the whole cohort (16.85 vs. 7.85 weeks; P = 0.019) and in the double WT
(KRAS and BRAF) patient population (18 vs. 10.4 weeks; P = 0.039). Combination therapy (mAbs plus
chemotherapy) led to improved PFS and overall survival (OS) for nonvariant patients, and brought their
outcome to levels comparable with LCS6-variant patients receiving anti-EGFR mAb monotherapy. Combination
therapy did not lead to improved PFS or OS for LCS6-variant patients. Cell line studies confirmed a
unique response of the LCS6-variant allele to both anti-EGFR mAb monotherapy and chemotherapy.
Conclusions: LCS6-variant patients with metastatic colorectal cancer have an excellent response to anti-EGFR
mAb monotherapy, without any benefit from the addition of chemotherapy. These findings further confirm
the importance of thismutation as a biomarker of anti-EGFR mAb response in patients with metastatic colorectal cancer, and warrant further prospective confirmation.
Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell...semualkaira
anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy
Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell...semualkaira
anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy. Several studies reported a sex disparity
in ASCC prognosis showing a better survival for female compared
to men. Methods: we examined 1,380 patients with ASCC who received comprehensive genomic profiling as part of routine clinical
care and present key
Proteogenomic analysis of human colon cancer reveals new therapeutic opportun...Gul Muneer
We performed the first proteogenomic study on a prospectively collected colon cancer cohort. Comparative proteomic and phosphoproteomic analysis of paired tumor and normal adjacent tissues produced a catalog of colon cancer-associated proteins and phosphosites, including known and putative new biomarkers, drug targets, and cancer/testis antigens. Proteogenomic integration not only prioritized genomically inferred targets, such as copy-number drivers and mutation-derived neoantigens, but also yielded novel findings. Phosphoproteomics data associated Rb phosphorylation with increased proliferation and decreased apoptosis in colon cancer, which explains why this classical tumor suppressor is amplified in colon tumors and suggests a rationale for targeting Rb phosphorylation in colon cancer. Proteomics identified an association between decreased CD8 T cell infiltration and increased glycolysis in microsatellite instability-high (MSI-H) tumors, suggesting glycolysis as a potential target to overcome the resistance of MSI-H tumors to immune checkpoint blockade. Proteogenomics presents new avenues for biological discoveries and therapeutic development.
Gastric Cancer and the Role of Hedgehog- Interacting Protein One as a Prognos...CrimsonpublishersCancer
Hedgehog (Hh) signaling has been linked to foregut development since its initial discovery in Drosophila. The mammalian genome expresses three (3) Hh ligands, with sonic hedgehog (Shh) level of expression is highest in the mucosa of the embryonic and adult foregut. Hedgehog signaling aberrant activation is associated with pathological consequences in a range of human cancer. Hedgehog signaling is of pivotal role in homeostasis, neoplastic transformation, and gastrointestinal cancer development. The ability to track these cell types in tumor micro-environment broadens options for the more efficient screening of subjects predisposed to eventually developing gastric cancer as well as to expand opportunities for prophylactic therapy once atrophic gastritis develops. The Hedgehog-interacting protein (HHIP) gene is an essential homolog for multiple developmental processes. However, the expression and clinical correlation of HHIP in gastric cancer (GC) has not thoroughly been investigated. There is need to explore the expression of HHIP in gastric cancer (GC) and evaluate its clinicopathological and functional correlation.