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A phase I study of alternate-day administration of S-1 plus leucovorin with bevacizumab in patients with refractory metastatic colorectal cancer.

ABSTRACT: Interventions: alternate-day administration of S-1 plus leucovorin with bevacizumab Primary outcome(s): recommended dose Study Design: Single arm Non-randomized

DISEASE(S): Colorectal Cancer

PROVIDER: 2631419 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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RNA sequencing of trastuzumab plus pertuzumab-refractory tumor in a mouse xenograft model

Project description:We report RNA sequencing data of trastuzumab plus pertuzumab-refractory tumor in a mouse xenograft model.

2020-03-05 | GSE146380 | GEO

The Effects of 5-Fluorouracil/Leucovorin Chemotherapy on Cognitive Function in Mice

Project description:5-Fluorouracil (5-Fu) and leucovorin (LV) are often given in combination to treat colorectal cancer. 5-Fu/LV prevents cell proliferation by inhibiting thymidylate synthase, which catalyzes the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate. While 5-Fu has been shown to cause cognitive impairment, the synergistic effect of 5-Fu with LV has not been fully explored. The present investigation was designed to assess how the combination of 5-Fu and LV affect cognition in a murine model. Six-month-old male mice were used in this study; 15 mice received saline injections and 15 mice received 5-Fu/LV injections. One month after treatment, the elevated plus maze, Y-maze, and Morris water maze behavioral tasks were performed. Brains were then extracted, cryosectioned, and stained for CD68 to assay microglial activation and with tomato lectin to assay the vasculature. All animals were able to locate the visible and hidden platform locations in the water maze. However, a significant impairment in spatial memory retention was observed in the probe trial after the first day of hidden-platform training (first probe trial) in animals that received 5-Fu/LV, but these animals showed spatial memory retention by day 5. There were no significant increases in inflammation as measured by CD68, but 5-Fu/LV treatment did modulate blood vessel morphology. Tandem mass tag proteomics analysis identified 6,049 proteins, 7 of which were differentially expressed with a P-value of < 0.05 and a fold change of >1.5. The present data demonstrate that 5-Fu/LV increases anxiety and significantly impairs spatial memory retention.

2022-02-17 | PXD028899 | Pride

Phase II study of S-1, leucovorin plus bevacizumab in refractory colorectal cancer

Project description:Interventions: Oral S-1, leucovorin plus bevacizumab therapy Primary outcome(s): Disease control rate assessed by independent review committee Study Design: Single arm Non-randomized

| 2624484 | ecrin-mdr-crc

Characterization of hyperglycemia due to sub-chronic administration of red ginseng extract via comparative global proteomic analysis

Project description:Ginseng (Panax ginseng Meyer) is commonly used as an herbal remedy worldwide. Few studies have explored the possible physiological changes in the liver although patients often self-medicate with ginseng preparations, which may lead to exceeding the recommended dose for long-term administration. Here, we analyzed changes in the hepatic proteins of mouse livers using quantitative proteomics after sub-chronic administration of Korean red ginseng (KRG) extract (control group and 0.5, 1.0, and 2.0 g/kg KRG) using tandem mass tag (TMT) 6‐plex technology. The 1.0 and 2.0 g/kg KRG groups exhibited signs of liver injury, including increased levels of aspartate transaminase (AST) and alanine aminotransferase (ALT) in the serum. Furthermore, serum glucose levels were significantly higher following KRG administration compared with the control group. Based on the upregulated proteins found in the proteomic analysis, we found that increased cystathionin beta-synthase (CBS) and cystathionine gamma-lyase (CSE) levels promoted greater hydrogen sulfide (HRR2RRS) synthesis in the liver. This investigation provides novel evidence that14T sub-chronic administration of 4T14TKRG can elevate HRR2RRS production by increasing protein expression of CBS and CSE in the liver.

2021-09-10 | PXD023731 | Pride

A phase Ib/II study evaluating Fruquintinib plus 5-Fluorouracil/Leucovorin (5FU/LV) beyond progression on Fruquintinib monotherapy in metastatic colorectal cancer

Project description:Interventions: experimental group:Fruquintinib plus 5-Fluorouracil /Leucovorin Primary outcome(s): recommended phase 2 dose (RP2D);6-month overall survival rate Study Design: Single arm

| 2693103 | ecrin-mdr-crc

StUbEx PLUS in U2OS

Project description:StUbEx PLUS – a modified Stable tagged Ubiquitin Exchange system for Peptide Level purification and in-depth mapping of Ubiquitination Sites. Applying StUbEx PLUS to U2OS cells treated with proteasomal inhibitors MG132 or Bortezomib resulted in the identification of 41,582 sites mapping on 7,762 proteins. In addition, 72 proteins were identified with N-terminal protein ubiquitination.

2022-03-01 | PXD006092 | Pride

A randomized phase II study of S-1 plus oral leucovorin versus S-1 monotherapy in patients with gemcitabine-refractory advanced pancreatic cancer.

Project description:BackgroundWe evaluated the efficacy and toxicity of adding oral leucovorin (LV) to S-1 when compared with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer (PC).Patients and methodsGemcitabine-refractory PC patients were randomly assigned in a 1:1 ratio to receive S-1 at 40, 50, or 60 mg according to body surface area plus LV 25 mg, both given orally twice daily for 1 week, repeated every 2 weeks (SL group), or S-1 monotherapy at the same dose as the SL group for 4 weeks, repeated every 6 weeks (S-1 group). The primary end point was progression-free survival (PFS).ResultsAmong 142 patients enrolled, 140 were eligible for efficacy assessment (SL: n = 69 and S-1: n = 71). PFS was significantly longer in the SL group than in the S-1 group [median PFS, 3.8 versus 2.7 months; hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.37-0.85; P = 0.003]). The disease control rate was significantly higher in the SL group than in the S-1 group (91% versus 72%; P = 0.004). Overall survival (OS) was similar in both groups (median OS, 6.3 versus 6.1 months; HR, 0.82; 95% CI, 0.54-1.22; P = 0.463). After adjusting for patient background factors in a multivariate analysis, OS tended to be better in the SL group (HR, 0.71; 95% CI, 0.47-1.07; P = 0.099). Both treatments were well tolerated, although gastrointestinal toxicities were slightly more severe in the SL group.ConclusionThe addition of LV to S-1 significantly improved PFS in patients with gemcitabine-refractory advanced PC, and a phase III trial has been initiated in a similar setting.Clinical trials numberJapan Pharmaceutical Information Center: JapicCTI-111554.

| S-EPMC4769993 | biostudies-literature

Study of Oxaliplatin/5-FU/Leucovorin Plus Vatalanib Versus Oxaliplatin/5-FU/Leucovorin in Patients With Metastatic Colorectal Cancer.

Project description:To compare treatment with oxaliplatin/5-FU/leucovorin plus vatalanib versus oxaliplatin/5-FU/leucovorin plus placebo in patients with colorectal cancer that has spread to other organs and are seeking first chemotherapy treatment

| 2008963 | ecrin-mdr-crc

Gene expression profile in the liver of insulin-deficient mice with icv leptin administration

Project description:Analysis of gene expression in the liver of insulin-deficient mice regulated by icv leptin administration. Control group received icv PBS administration. Icv leptin administration ameliorates hyperglycemia in insulin-deficient mice. Our transcriptome data provides important aspects of the leptin’s anti-type 1 diabetes action. Mice were harvested 10 days after icv leptin administration (25ng/0.11uL/hour). Liver samples were quickly removed, frozen in liquid nitrogen and subsequently stored at –80ºC. RNAs were extracted by Qiagen mRNA extract kits (RNeasy plus). gDNA was eliminated in this procedure by gDNA eliminator column, which is included in Qiagen mRNA extract kits. Genomics and Microarray Core Facility at UT-Southwestern (http://microarray.swmed.edu/) checked RNA quality with Bioanalyzer Chip and processed the samples for hybridization with Illumina Mouse-6 V2 BeadChip (Illumina Inc., San Diego, CA).

2013-09-03 | E-GEOD-48598 | biostudies-arrayexpress

Study of Oxaliplatin/5-FU/Leucovorin Plus Vatalanib Versus Oxaliplatin/5-FU/Leucovorin in Patients With Previously Treated Metastatic Colorectal Cancer

Project description:The purpose of this study is to compare treatment with oxaliplatin/5-FU/leucovorin plus vatalanib versus oxaliplatin/5-FU/leucovorin plus placebo in patients with colorectal cancer that has spread to other organs and whose disease has worsened after treatment with irinotecan.

| 2008962 | ecrin-mdr-crc

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