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A phase II non-randomized open labeled trial for preoperative circadian chronomodulated hepatic arterial infusion (HAI) chemotherapy combined with panitumumab for liver metastases from colorectal cancer.

ABSTRACT: Interventions: Chronomodulated HAI chemotherapy group The patients of this group will receive 6 cycles of chronomodulated HAI chemotherapy with 5-FU/LV/L-OHP before hepatectomy for liver metastases from colorectal cancer Chronomodulated HAI chemotherapy with Panitumumab group The patients of this group will receive 6 cycles of chronomodulated HAI chemotherapy with 5-FU/LV/L-OHP and Panitumumab before hepatectomy for liver metastases from colorectal cancer Primary outcome(s): Response rate Study Design: Parallel Non-randomized

DISEASE(S): Liver Metastases From Colorectal Cancer

PROVIDER: 2624492 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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study of medical treatment reactivity by the chemokine receptor (CXCR4)as 1st line treatment in patients with metastatic colorectal cancer

Project description:Interventions: CXCR4-CEC>=20 mFOLFOX6,Bevacizumab L-OHP:85mg/m2 5-FU(bolus):400mg/m2 l-LV:200mg/m2 5-FU(infusion):2,400mg/m2 Bevacizumab:5mg/m2 CXCR4-CEC>=20 mFOLFOX6,Panitumumab L-OHP:85mg/m2 5-FU(bolus):400mg/m2 l-LV:200mg/m2 5-FU(infusion):2,400mg/m2 Panitumumab :6mg/m2 CXCR4-CEC<20 mFOLFOX6,Bevacizumab L-OHP:85mg/m2 5-FU(bolus):400mg/m2 l-LV:200mg/m2 5-FU(infusion):2,400mg/m2 Bevacizumab:5mg/m2 CXCR4-CEC<20 mFOLFOX6,Panitumumab L-OHP:85mg/m2 5-FU(bolus):400mg/m2 l-LV:200mg/m2 5-FU(infusion):2,400mg/m2 Panitumumab :6mg/m2 Primary outcome(s): Progression-free survival Study Design: Parallel Randomized

| 2623948 | ecrin-mdr-crc

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

Safety and Efficacy Study of mFOLFOX6 + Panitumumab Combination Therapy and 5-FU/LV + Panitumumab Combination Therapy in Participants With Chemotherapy-naïve Unresectable Advanced Recurrent Colorectal Carcinoma

Project description:The purpose of this study is to exploratorily examine efficacy and safety in the participants with chemotherapy-naïve unresectable, advanced/recurrent colorectal carcinoma of Kirsten rat sarcoma-2 virus (KRAS) wild-type who have been treated with 6 cycles (2 weeks/cycle) of first-line mFOLFOX6 + panitumumab combination therapy and then assigned to two groups i.e., a group receiving 5-FU/LV + panitumumab combination therapy and a group receiving mFOLFOX6 + panitumumab combination therapy.

| 2181884 | ecrin-mdr-crc

Randomized phase III trial of surgery followed by mFOLFOX6 as adjuvant chemotherapy versus peri-operative mFOLFOX6 plus cetuximab for KRAS wild type resectable liver metastases of colorectal cancer

Project description:Interventions: Surgical hepatectomy followed by chemotherapy (mFOLFOX6) 12cycles. mFOLFOX6(L-OHP 85 mg/m2/biweekly, Levofolinate 200 mg/m2/biweekly, 5-FU/bolus 400 mg/m2/biweekly, 5-FU/continuous 2,400 mg/m2/biweekly) Pre-operative chemotherapy(mFOLFOX6 plus cetuximab) 6cycles followed by surgical hepatectomy followed by post-operative chemotherapy (mFOLFOX6 plus cetuximab) 6cycles. Cetuximab(loading dose 400mg/m2, 250 mg/m2/week), mFOLFOX6(L-OHP 85 mg/m2/biweekly, Levofolinate 200 mg/m2/biweekly, 5-FU/bolus 400 mg/m2/biweekly, 5-FU/continuous 2,400 mg/m2/biweekly) Primary outcome(s): Progression free survival Study Design: Parallel Randomized

| 2623200 | ecrin-mdr-crc

Neoaduvant chemotherapy woth FOLFOXIRI and anti-EGFR monoclonal antibody for colorectal cancer with liver metastasis

Project description:Interventions: day1:CPT-11(150mg/m2),L-OHP(65mg/m2),L-LV(200mg/m2) day1-2:5-FU(3200mg/m2)48hr civ, day1:Panitumumab(6mg/kg) or day1 and 7 cetuximab(400mg/m2) ever 2 weeks Primary outcome(s): R0 rejective rate Study Design: Single arm Non-randomized

| 2620819 | ecrin-mdr-crc

A Multicenter, Clinical Phase II study of FOLFOXIRI with Bevacizumab As First-line Therapy in Patients with Metastatic Colorectal Cancer.

Project description:Interventions: [Induction treatment:FOLFOXIRI+BV] Administered for a maximum of 12 cycles. BV: 5mg/kg (d.i.v.) L-OHP: 85 mg/sq.m (d.i.v.) CPT-11:165mg/sq.m (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks. [Maintenance treatment:5-FU/LV+BV] BV:5mg/kg (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks. Primary outcome(s): Progression-free survival (PFS) at 10 months; by investigator-reported measurements. Study Design: Single arm Non-randomized

| 2629147 | ecrin-mdr-crc

An elemental diet protects mouse salivary glands from 5-fluorouracil-induced atrophy.

Project description:In cancer patients, an elemental diet (ED) reduces adverse effects of chemotherapy, including oral mucositis. However, the detailed mechanism(s) of the healing effects of an ED remains unclear. In this study, the protective effects of the ED, Elental®, were examined against 5-fluorouracil (5-FU)-induced oral mucositis and salivary gland atrophy in mice. Mucositis was induced in female ICR mice by injection of 5-FU. The mice were orally administered Elental® (ED group) or saline (control group). After treatment, whole transcriptome analysis and network analysis were conducted to understand the mechanism(s) of action of Elental® against oral mucositis. Whole transcriptome analysis and Ingenuity Pathways Analysis (IPA) data suggested that Elental® contributed to the recovery of mitochondrial function in 5-FU-damaged salivary glands.

2022-05-05 | GSE196407 | GEO

Gunma study - Oxaliplatin-based chemotherapy and Avastin following Irinotecan-based chemotherapy with Erbitux in metastatic colorectal cancer

Project description:Interventions: first line chemotherpy FOLFIRI+Cetuximab (Cetuximab 500mg/m2/bi-week CPT-11 150mg/m2/bi-week l-LV 200mg/m2/bi-week 5-FU/bolus 400mg/m2/bi-week 5-FU/infusional 2,400mg/m2/bi-week (day 1-3)) FOLFIRI+Cetuximab second line chemotherapy (1) mFOLFOX6+Bevacizumab (Bevacizumab 5mg/kg/bi-week L-OHP 85mg/m2/bi-week l-LV 200mg/m2/bi-week 5-FU/bolus 400mg/m2/bi-week 5-FU/infusional 2,400mg/m2/bi-week (day 1-3)) second line chemotherapy (2) XELOX+Bevacizumab (Bevacizumab 7.5mg/kg/tri-week L-OHP 130mg/m2/tri-week Capecitabine 2000mg/m2/day/2 (day 1-15)) Primary outcome(s): Total Progression free survival (PFS1+PFS2): PFS during first-line (PFS1) and PFS during second-line (PFS2) Study Design: Single arm Non-randomized

| 2622536 | ecrin-mdr-crc

Intratumor transforming growth factor-β signaling with extracellular matrix-related gene regulation marks chemotherapy-resistant gastric cancer

Project description:Drug-tolerant persister (DTP) cells remain following chemotherapy and can cause cancer relapse. However, it is unclear when acquired resistance to chemotherapy emerges. Here, we compared the gene expression profiles of gastric cancer patient-derived cells (GC PDCs) and their respective xenograft tumors with different sensitivities to 5-fluorouracil (5-FU) by using immunodeficient female BALB/c-nu mice. RNA sequencing analysis of 5-FU-treated PDCs demonstrated that DNA replication/cell cycle-related genes were transiently induced in the earlier phase of DTP cell emergence, while extracellular matrix (ECM)-related genes were sustainably upregulated during long-term cell survival in 5-FU-resistant residual tumors. NicheNet analysis, which uncovers cell-cell signal interactions, indicated the transforming growth factor-β (TGF-β) pathway as the upstream regulator in response to 5-FU treatment. This induced ECM-related gene expression in the 5-FU-resistant tumor model. In the 5-FU-resistant residual tumors, there was a marked upregulation of cancer cell-derived TGF-β1 expression and increased phosphorylation of SMAD3, a downstream regulator of the TGF-β receptor. By contrast, these responses were not observed in a 5-FU-sensitive tumor model. We further found that TGF-β-related upregulation of ECM genes was preferentially observed in non-responders to chemotherapy with 5-FU and/or oxaliplatin among 22 patient-derived xenograft tumors. These observations suggest that chemotherapy-induced activation of the TGF-β1/SMAD3/ECM-related gene axis is a potential biomarker for the emergence of drug resistance in GCs.

2024-05-30 | GSE264144 | GEO

Ribo-seq of human colorectal cancer cell line HCT116/L-OHP against HCT116

Project description:Oxaliplatin (L-OHP) serves as a standard chemotherapy for colorectal cancer, while the drug resistance is still a considerable challenge. Dysregulation of lncRNA is involved in cancer and recent translatomics has found some alleged lncRNA actually contained small open reading frames and could encode short peptides. This ribosome footprint profiling (Ribo-seq) was a paired-end sequencing and aimed to investigate whether lncRNA could regulate oxaliplatin resistance in colorectal cancer by encoding short peptides.

2021-11-12 | E-MTAB-10805 | biostudies-arrayexpress

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