Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Patient-tailored Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Peritoneal Metastases (OrganoHIPEC)

ABSTRACT: The objective of this clinical trial is to demonstrate that cytoreductive surgery and patient-tailored hyperthermic intra-peritoneal chemotherapy (HIPEC) will increase efficacy in controlling peritoneal disease. Tridimensional cell cultures (organoids) derived from colorectal cancer peritoneal metastases are used to select the most active drugs in an in vitro HIPEC model on individual-patient level, based on the hypothesis that resistance to drug(s) routinely used for intraperitoneal delivery can explain peritoneal relapse after combined treatment, depending on the individual tumor biology;

DISEASE(S): Neoplasm Metastasis,Peritoneal Metastases From Colorectal Cancer

PROVIDER: 107304 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

ACCESS DATA

Json Xml

Similar Datasets

Response Prediction of Hyperthermic Intraperitoneal Chemotherapy in Gastro- Intestinal Cancer

Project description:Patients with gastric or colon cancer with peritoneal carcinomatosis will receive a biopsy of the tumor during their primary curative surgery. The operation is performed according to standard and includes resection of the primary tumor and any metastases and followed by HIPEC (Intraperitoneal hyperthermic chemoperfusion) according to the respective hospital standard. Organoid cultures from the biopsies are established in the research laboratory. Various chemotherapeutic agents are tested on these tumor organoids in the laboratory and the tumor organoids are analyzed in detail with regard to genetic alterations in order to find alterations that can be addressed, if necessary, by means of targeted drugs against peritoneal carcinomatosis.

| 2517 | ecrin-mdr-crc

Exploiting a subtype-specific mitochondrial vulnerability for successful treatment of colorectal peritoneal metastases

Project description:Peritoneal metastases (PM) in colorectal cancer (CRC) present a significant challenge due to limited treatment options and poor patient prognosis. While cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) offers curative potential for selected patients, its overall benefit remains limited compared to surgery alone. In this study we show that the majority of CRC-PM represent the CMS4-subtype. Despite CRS-HIPEC treatment, CMS4 patients had high rates of recurrent disease and mortality, indicating limited effectiveness of the treatment. To explore alternative treatment approaches, we queried large-scale compound screens and discovered the copper (Cu)-ionophore elesclomol (ES) as a highly effective agent against CMS4-specific disease models. ES exhibited rapid and selective cytotoxicity against CMS4 cells by targeting the oxidative phosphorylation machinery. CMS4 cells had reduced absolute mitochondrial content and lower expression of genes involved in oxidative phosphorylation, making them vulnerable to ES-induced cytotoxicity. Short exposures to ES combined with Cu (ES-Cu) resulted in near-complete growth inhibition of cancer cells, suggesting its potential for HIPEC-like intra-abdominal treatment procedures. Furthermore, ES-Cu demonstrated efficacy in preclinical models of PM, including CRC-PM and ovarian cancer organoids, and a HIPEC rat model of PM. These findings highlight ES-Cu as promising candidate for the local treatment of CRC-PM, with broader implications for other cancer types characterized by high incidence of PM.

2024-05-01 | GSE242676 | GEO

Response Prediction of Hyperthermic Intraperitoneal Chemotherapy in gastro-intestinal Cancer (Hi-STEP1)

Project description:Interventions: Group 1: During primary curative surgery for gastric or colon carcinoma with synchronous or metachronous peritoneal carcinomatosis, the peritoneal carcinomatosis index (PCI) is determined and biopsies of the PC foci are taken before resection. Surgery is performed according to standard and includes both resection of the primarius and any metastases present and (as far as possible) complete cytoreductive surgery (CCS 0-1) by peritonectomy of the affected sites, followed by HIPEC according to the respective hospital standard. After 6 months, a planned re-operation (laparoscopy/laparotomy) may be performed, depending on the local standard at the respective study center. If a macroscopic PC recurrence is detected, the PCI will be recalculated and a new (as far as possible) complete cytoreductive surgery (CCS 0-1) will be performed by peritonectomy of the affected sites followed by HIPEC according to the respective hospital standard. The aim of this pilot study is to generate patient-derived tumor organoid models as well as orthotopic mouse models from peritoneal carcinomatosis lesions and to investigate their response to different therapies. Based on the findings of the pilot study, a main clinical trial will then be designed. Aims of the study are: 1. to describe individualized HIPEC regimens in vitro based on organoid response to therapy and next generation sequencing (NGS) data. 2. the evaluation of individualized HIPEC regimens in vivo in an orthotopic mouse model. 3. the collection of the oncological courses of the patients in the context of the standard tumor follow-up and comparison with the models. Primary outcome(s): The primary endpoint is to analyze the predictive accuracy of patient-generated tumor organoids (PDOs) for predicting response to HIPEC treatment in patients with peritoneal carcinomatosis (PC). Study Design: Allocation: ; Masking: ; Control: ; Assignment: ; Study design purpose: treatment

| 2761505 | ecrin-mdr-crc

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.

2015-12-01 | GSE50494 | GEO

Project description:Genetic alterations in peritoneal metastatic tumors of patients receiving HIPEC

| PRJNA891798 | ENA

An Audit of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Project description:Peritoneal carcinomatosis is a common event in the natural history of colorectal and other digestive tract cancers. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provides a promising therapeutic option for highly selected patients with peritoneal carcinomatosis arising from different malignancies such as colorectal cancer, gastric cancer, ovarian cancer, or peritoneal mesothelioma with improvement of both patient survival and quality of life. CRS, i.e., removal of all visible metastatic abdominal and pelvic disease with peritonectomy along with HIPEC (for 90 min at a temperature of 42º C) and/or early postoperative intraperitoneal chemotherapy (EPIC) in order to eradicate all microscopic metastasis. CRS with HIPEC is a long and complex procedure with significant blood and fluid loss during debulking, hemodynamic, hematological, and metabolic alterations before and during the HIPEC phase, and even in the early postoperative period, with resultant significant morbidity and mortality. Despite that most of the reported patients are in American Society of Anesthesiologist class I and II, without significant comorbidities or systemic disorder; the morbidity and mortality ranges from 12 to 65% in these procedures, so a well coordinated team of anesthesiologist, surgeons and intensivist and other ancillary services can result in good outcome. This study will see the challenges faced by the team regarding the pathophysiological alterations during the CRS with HIPEC in the perioperative period.

| 2213760 | ecrin-mdr-crc

Radical Colorectal Resection and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Locally Advanced Colorectal Cancer

Project description:The efficacy of HIPEC in prevention of local recurrence, distant metastasis or peritoneal metastasis in locally advanced colorectal cancer is not definite. The hypothesis of the trial is that radical colorectal resection plus HIPEC is superior to only radical colorectal resection in terms of overall survival.

| 2219583 | ecrin-mdr-crc

Modular automated microfluidic cell culture platform reduces glycolytic stress in cerebral cortex organoids

Project description:Organ-on-a-chip systems combine microfluidics, cell biology, and tissue engineering to culture 3D organ-specific in vitro models that recapitulate the biology and physiology of their in vivo counterparts. Here, we have developed a multiplex platform that automates the culture of individual organoids in isolated microenvironments at user-defined media flow rates. Programmable workflows allow the use of multiple reagent reservoirs that may be applied to direct differentiation, study temporal variables, and grow cultures long term. Novel techniques in polydimethylsiloxane (PDMS) chip fabrication are described here that enable features on the upper and lower planes of a single PDMS substrate. RNA sequencing (RNA-seq) analysis of automated cerebral cortex organoid cultures shows benefits in reducing glycolytic and endoplasmic reticulum stress compared to conventional in vitro cell cultures.

2022-07-14 | GSE207894 | GEO

Cytoreduction Followed by Normothermic Versus Hyperthermic Intraperitoneal Intraoperative Chemoperfusion (HIPEC): a Study in Peritoneal Carcinomatosis

Project description:Peritoneal carcinomatosis from appendix or colon (large bowel) cancer is treated in suitable patients with surgery followed by instillation of heated chemotherapy inside the abdominal cavity. This procedure is termed ‘Hyperthermic intraoperative Peritoneal Chemoperfusion’ or HIPEC. Many center perform HIPEC with high dose oxaliplatin, a standard chemotherapy drug active against colon cancer, administered during 30 minutes at 41°C. The hypothesis of this study is, that chemoperfusion at normal (37.5°C) temperature but longer duration (90 minutes) may be safer and at least as efficient. Patients will be treated with one of three possible HIPEC regimens using oxaliplatin: high dose, 30 min, 41°C; high dose, 30 min, 37.5°C; or low dose, 90 min, 37.5°C. The outcome parameters are pharmacokinetic and pharmacodynamic: using specialized techniques, tissue penetration of chemotherapy and cancer cell kill effects will be compared in order to establish the safest and most active HIPEC regimen.

| 2123613 | ecrin-mdr-crc

Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [Bulk RNA-Seq]

Project description:Peritoneal carcinomatosis (PC) originating from colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Metastasis is the major cause of death in patients with CRC whereas primary locoregionally circumscribed tumors are mostly curable. Due to the lack of appropriate and realistic mouse models for metastasis of CRC until recently, the research about metastasis of these tumors and possible therapeutic options is still in its infancy. With the establishment of murine CRC tumor organoids, mouse models were established which realistically mimic the process of tumor cell metastasis to the liver and the lung. However, to date no appropriate model for PC is described. Here, we establish a realistic model for peritoneal metastasis of colorectal cancer upon surgical transplantation of tumor organoids into the cecum wall. This mouse model for PC recapitulates human PC which makes it an ideal model for research of the biology of metastasis of colorectal cancer to the peritoneal cavity and for its usage for preclinical drug screening as well as for the evaluation of new therapeutic approaches which are highly needed in clinical reality.

2022-06-27 | GSE202454 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data