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Fluorouracil With or Without Mitomycin in Treating Patients With Peritoneal Cancer

ABSTRACT: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Randomized phase II trial to compare the effectiveness of fluorouracil with or without mitomycin in treating patients who have peritoneal cancer.

DISEASE(S): Colorectal Cancer,Colorectal Neoplasms,Carcinoma Of The Appendix,Primary Peritoneal Cavity Cancer

PROVIDER: 2005170 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Standard Therapy With or Without Surgery and Mitomycin C in Treating Patients With Advanced Limited Peritoneal Dissemination of Colon Cancer

Project description:RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Heating mitomycin C to several degrees above normal body temperature and infusing it into the area around the tumor may kill more tumor cells. Giving mitomycin C after surgery may kill any remaining tumor cells. It is not yet known whether standard therapy is more effective with or without surgery followed by mitomycin C. PURPOSE: This randomized phase III trial is studying standard therapy with or without surgery and mitomycin C in treating patients with advanced limited peritoneal dissemination of colon cancer

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Tailoring heated intra-peritoneal Mitomycin C for peritoneal metastases originating from colorectal carcinoma – A translational approach to improve survival

Project description:Patients with peritoneal metastases (PM) originating from colorectal carcinoma (CRC) are curatively treated by cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) with Mitomycin C (MMC). We aim to improve patient selection and personalize treatment for patients treated with HIPEC by predicting MMC sensitivity. MMC sensitivity was determined for 12 CRC cell lines using two separate assays. Thirty-seven genes related to the FA-BRCA pathway, ATM-ATR pathway and enzymatic activation of MMC were correlated on expression array platform to MMC sensitivity. Low sensitivity correlated with a decrease in BLM (p=0.01) and BRCA2 (p=0.02) on mRNA expression level. Both genes are part of the Fanconi Anaemia-BRCA (FA-BRCA) pathway and therefore, functionality of the FA-BRCA pathway in cell lines was determined using chromosomal breakage assay and Western Blot for key protein FANCD2. However, FA-BRCA pathway functionality showed no correlation to MMC sensitivity. BLM was further analysed by staining for the corresponding protein with immunohistochemistry (IHC) on both CRC cell lines and patient material. In cell lines, weak intensity staining by IHC correlated to high sensitivity (p=0.04) to MMC. High BLM protein expression was significantly correlated to a decreased survival in patients after CRS and HIPEC (p=0.04). We are the first to have found a possible predictive biomarker for PM with CRC.

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Project description:Pancreatic ductal adenocarcinoma (PDAC) frequently metastasizes into the peritoneum, which contributes to poor prognosis. Metastatic spreading is promoted by cancer cell plasticity, yet its regulation by the microenvironment is incompletely understood. Here, we show that the presence of hyaluronan and proteoglycan link protein-1 (HAPLN1) in the extracellular matrix enhances tumor cell plasticity and PDAC metastasis. Bioinformatic analysis showed that HAPLN1 expression is enriched in the basal PDAC subtype and associated with worse overall patient survival. In a mouse model for peritoneal carcinomatosis, HAPLN1-induced immunomodulation favored a more permissive microenvironment, which accelerated the peritoneal spread of tumor cells. Mechanistically, HAPLN1, via upregulation of tumor necrosis factor receptor 2 (TNFR2), promoted TNF-mediated upregulation of Hyaluronan (HA) production, facilitating EMT, stemness, invasion and immunomodulation. Extracellular HAPLN1 modified cancer cells and fibroblasts, rendering them more immunomodulatory. As such, we identified HAPLN1 as a prognostic marker and as a driver for peritoneal metastasis in PDAC.

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Eniluracil, Fluorouracil, and Oxaliplatin in Treating Patients With Advanced Colorectal Cancer

Project description:RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combining eniluracil, fluorouracil, and oxaliplatin in treating patients who have advanced colorectal cancer that has been treated previously.

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Transcription profiling of mouse lymphoma L5178Y cells treated with Mitomycin C - ILSI-HESI Genotoxicity Study - Mitomycin

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2004-05-13 | E-TOXM-8 | biostudies-arrayexpress

Fluorouracil and Leucovorin With or Without Oxaliplatin in Treating Patients With Recurrent Metastatic Colorectal Cancer

Project description:RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Randomized phase II trial to study the effectiveness of combining fluorouracil and leucovorin with or without oxaliplatin in treating patients who have recurrent metastatic colorectal cancer.

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Peritoneal Dialysis Induces Alterations In The Transcriptome Of Peritoneal Cells Before Detectible Peritoneal Functional Changes

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Gene expression profiles of peritoneal macrophages from Sphingosine 1-phosphate receptor type 1 (S1pr1) overexpressing mice against control mice.

Project description:Sphingosine 1-phosphate (S1P) is a lysosphingolipid with anti-atherogenic properties, but mechanisms underlying its effects remain unclear. We here analyzed the consequences of overexpressing the S1P receptor type 1 (S1pr1) on peritoneal macrophage gene expression. To amplify S1pr1 signaling in macrophages, double transgenic mice expressing mouse S1pr1 in mononuclear cells were constructed by crossing two lines. The S1pr1-KI line carries a transgenic cassette in the Rosa 26 locus harboring the mouse S1P1 cDNA and separated from the CAG promoter by a lox-Stop-lox insert. S1pr1-KI mice were then crossed to LysMCre mice expressing Cre recombinase under the control of the lysozyme M promoter, which drives macrophage expression. In the offspring the lox-Stop-lox insert is excised in Cre-expressing cells (macrophages), which induces cDNA expression driven by the CAG promoter. At 12 weeks of age, peritoneal leukocytes were isolated from S1pr1-LysMCre mice and control mice (S1pr1-KI) by peritoneal lavage and seeded in cell culture plates. After 2 h non-adherent cells were removed, total RNA was isolated from the remaining macrophages and subjected to microarray gene expression analysis.

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Single Arm Study Treating Patients of Peritoneal Surface Malignancy (Colorectal, Appendical, Pseudomyxoma, Gastric) With Cytoreductive Surgery and Hyperthermic Intraperitoneal Mitomycin-C

Project description:This is a clinical study investigating the new treatment of surgery combined with intraperitoneal mitomycin-C for patients with gastrointestinal cancer that has spread to the peritoneal (abdominal cavity) surface. Mitomycin-C to be used in this procedure is approved by the U.S. Food and Drug Administration (FDA)for many different cancers including gastrointestinal cancer. Giving mitomycin C via the intraperitoneal route is not FDA approved and is an investigation therapy. Cytoreductive surgery plus intraperitoneal chemotherapy can be offered as standard of care outside of a clinical trial. However, since this is an unproven and potentially more effective but a more toxic approach, the investigators are performing this procedure under an IRB approved clinical trial in order to better evaluate the risks and benefits of this approach. A standardized, evidence-based approach is currently lacking for patients with peritoneal surface malignancy from gastrointestinal origin. A clinical trial with surgical quality assurance and modern hyperthermic intraperitoneal chemotherapy incorporating critical assessment of disease burden, determinants of complete cytoreduction, treatment-related toxicity, quality of life and survival is imperative. Theoretically, cytoreductive surgery is performed to treat macroscopic disease, and hyperthermic intraperitoneal chemotherapy is used to treat microscopic residual disease with the objective of removing disease completely in a single procedure.

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Fluorouracil-Uracil and Leucovorin in Treating Elderly Patients With Metastatic Colorectal Cancer

Project description:RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of fluorouracil-uracil and leucovorin in treating elderly patients who have metastatic colorectal cancer.

| 2004008 | ecrin-mdr-crc

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