A feasibility study of adjuvant therapy with FOLFOX plus Ca/Mg for the patient with colorectal cancer
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ABSTRACT: Interventions: FOLFOX4(L-OHP85mg/m2,l-LV100mg/m2x2, 5FU400mg/m2(bolus)x2, 5FU600mg/m2x2(civ)) or mFOLFOX6(L-OHP85mg/m2, l-LV200mg/m2, 5FU400mg/m2(bolus), 5FU2400mg/m2(civ)). Ca/Mg 0.8-1g (iv) x2 before and after L-OHP infusion Cycles of therapy are given every 2 weeks for 12 cycles
Primary outcome(s): the rate of completion of treatment as planned
Study Design: Single arm Non-randomized
Project description:Interventions: Oxaliplatin 130mg/m2 i.v. (day1) Capecitabine2,000mg/m2 ,p.o.(day1-14) Ca/Mg 0.8-1g/body i.v. x2 before and after L-OHP infusion (day1) Goshajinkigan 7.5g/body ,p.o.(day1-21) to be repeated every 3 weeks
Primary outcome(s): The rate of completion of treatment as planned
Study Design: Single arm Non-randomized
Project description:Interventions: FOLFOX4(L-OHP85mg/m2, l-LV100mg/m2x2, 5FU400mg/m2(bolus)x2, 5FU600mg/m2x2(civ)) or mFOLFOX6(L-OHP85mg/m2, l-LV200mg/m2, 5FU400mg/m2(bolus), 5FU240mg/m2(civ)).Cycles of chemotherapy are given every 2 weeks until PD or unacceptable toxicity occurred. Goshajinkigan(GJG) is given orally at a dose of 2.5 g three times a day for 26 weeks starting on the day of L-OHP infusion.
FOLFOX4(L-OHP85mg/m2, l-LV100mg/m2x2, 5FU400mg/m2(bolus)x2, 5FU600mg/m2x2(civ)) or mFOLFOX6(L-OHP85mg/m2, l-LV200mg/m2, 5FU400mg/m2(bolus), 5FU240mg/m2(civ)).Cycles of chemotherapy are given every 2 weeks until PD or unacceptable toxicity occurred. Placebo is given orally at a dose of 2.5 g three times a day for 26 weeks starting on the day of L-OHP infusion.
Primary outcome(s): The incidence of peripheral neurotoxicity ≥grade 2 after eight cycles of chemotherapy.
Study Design: Parallel Randomized
Project description:Between 2000 and 2015, mortality due to Alzheimer’s disease (AD) increased by 123%. No drugs have yet been approved to stop or slow the progression of AD. A delay of five years in the expression of AD would reduce the incidence rate by half. Thus, it is critical to develop novel prevention strategies to delay the onset of this common disease.
As an ancillary study conducted within a precision-based randomized trial (R01CA149633; PI, Dai & Yu]"), the investigators reduced Ca:Mg ratios to 2.3 through 3-month personalized Mg supplementation among those who consumed high Ca:Mg ratio diet, but otherwise in good general health. The investigators test the hypothesis that actively reducing the Ca:Mg ratio among those aged >65 years who consume high Ca:Mg ratio diets improves cognitive function compared to the placebo arm. The investigators further conduct molecular epidemiologic studies to understand the molecular mechanisms.
Project description:Our previous study revealed that influenza virus matrix protein 1 (M1)and matrix 2 (M2) interacted with canine RIG-I. However, the influence of these interactions remains in the mist. To explore these cellular transcriptome modulation induced by the interaction between CIV M1/M2 and canine RIG-I, here we carried out the comparative transcriptional RNA analysis of the overexpression of CIV M1/M2 along with canine RIG-I in HEK 293T cells.
Project description:To measure global gene expression in primary advanced colorectal cancer patients who have undergone fluorouracil, leucovorin and oxaliplatin (FOLFOX4) chemotherapy and screen valuable biomarkers to predict the effects of chemotherapy Samples from primary advanced colorectal cancer patients were collected. The effects of chemotherapy were evaluated, and patients were divided into an experimental group and a control group. All patients underwent standard FOLFOX4 regimen chemotherapy in four cycles after signing the chemotherapy agreement; subsequently, they were evaluated in accordance with the Response Evaluation Criteria In Solid Tumors (RECIST).Each samplewas collected immediately following resection. Each sample was divided in half: one half was fixed in formalin and embedded in paraffin; the other half floated in ice-cold phosphate-buffered saline and was stored in liquid nitrogen until total RNA extraction. CEL files available for only 16/30 samples. Remaining CEL files have been lost.
Project description:Carcinoma-associated mesenchymal stem cells (CA-MSCs) are critical stromal progenitor cells within the tumor microenvironment. We previously demonstrated that CA-MSCs differentially express BMP genes, promote tumor cell growth, increase cancer ‘stemness’ and chemotherapy resistance. Here we use RNA sequencing of normal omental MSCs and ovarian CA-MSCs to demonstrate CA-MSCs have global changes in gene expression. Using these expression profiles we create a unique predictive algorithm to classify CA-MSCs. Our classifier, accurately distinguishes normal omental, ovary and bone marrow MSCs from ovarian cancer CA-MSCs. Suggesting broad applicability, the model correctly classifies pancreatic and endometrial cancer CA-MSCs and distinguishes cancer associated fibroblasts (CAFs) from CA-MSCs. Using this classifier, we definitively demonstrate ovarian CA-MSCs arise from tumor mediated reprograming of local tissue MSCs. While cancer cells alone cannot induce a CA-MSC phenotype, the in vivo ovarian tumor micoenvironment (TME) can reprogram omental or ovary MSCs to protumorigenic CA-MSC (classifier score of >0.96). In vitro studies suggest that both tumor secreted factors and hypoxia are critical to induce the CA-MSC phenotype. Interestingly, while the breast cancer TME can reprogram BM MSCs into CA-MSCs, the ovarian TME cannot, demonstrating for the first time that tumor mediated CA-MSC conversion is tissue and cancer type dependent. Together these findings (1) provide a critical tool to define CA-MSCs and (2) highlight cancer cell influence on distinct normal tissues providing powerful insights into the mechanisms underlying cancer specific metastatic niche formation. Carcinoma-associated mesenchymal stem cells (CA-MSCs) are critical stromal progenitor cells within the tumor microenvironment. We previously demonstrated that CA-MSCs differentially express BMP genes, promote tumor cell growth, increase cancer ‘stemness’ and chemotherapy resistance. Here we use RNA sequencing of normal omental MSCs and ovarian CA-MSCs to demonstrate CA-MSCs have global changes in gene expression. Using these expression profiles we create a unique predictive algorithm to classify CA-MSCs. Our classifier, accurately distinguishes normal omental, ovary and bone marrow MSCs from ovarian cancer CA-MSCs. Suggesting broad applicability, the model correctly classifies pancreatic and endometrial cancer CA-MSCs and distinguishes cancer associated fibroblasts (CAFs) from CA-MSCs. Using this classifier, we definitively demonstrate ovarian CA-MSCs arise from tumor mediated reprograming of local tissue MSCs. While cancer cells alone cannot induce a CA-MSC phenotype, the in vivo ovarian tumor micoenvironment (TME) can reprogram omental or ovary MSCs to protumorigenic CA-MSC (classifier score of >0.96). In vitro studies suggest that both tumor secreted factors and hypoxia are critical to induce the CA-MSC phenotype. Interestingly, while the breast cancer TME can reprogram BM MSCs into CA-MSCs, the ovarian TME cannot, demonstrating for the first time that tumor mediated CA-MSC conversion is tissue and cancer type dependent. Together these findings (1) provide a critical tool to define CA-MSCs and (2) highlight cancer cell influence on distinct normal tissues providing powerful insights into the mechanisms underlying cancer specific metastatic niche formation.
Project description:We characterized the marine natural product cortistatin A (CA) as an inhibitor of CDK8 to determine whether pharmacologic inhibition of CDK8 regulates super-enhancer function and inhibits AML proliferation. In this series, we use ChIP-seq of H3K27ac, H3K4me1, MED1, CDK8, BRD4, and RNA polymerase II (PolII) to examine enhancer occupancy and transcriptional response to CA in human cells lines.