A pilot study evaluating response to induction chemotherapy with oxaliplatin, capecitabine and bevacizumab in patients with extensive peritoneal carcinomatosis of colorectal origin.
Ontology highlight
ABSTRACT:
DISEASE(S): Induction Chemotherapy For Peritoneal Carcinomatosis Of Colorectal Cancer
PROVIDER: 2527556 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Peritoneal carcinomatosis (PC), a tumoral tumor of the peritoneum, is a frequent metastatic localization of colorectal cancer (CRC, 13%). Long regarded as a palliative situation, its management has progressed significantly with a curative treatment based on a complete cytoreduction surgery coupled with intraperitoneal hyperthermic chemotherapy. However current screening tools, tumor markers (ACE, CA19-9, CA125) and abdominopelvic CT scan are insufficient, to diagnose CP early. A non-invasive biomarker, more sensitive and more specific than currently available tumor markers, would be a major advance in oncology. Microparticles (MPs), vesicles from extracellular membrane budding in response to cell activation or apoptosis of different cell types, have been described as implicated in tumor progression, procoagulant activity associated with cancer, and initiation of metastatic niches. A specific microparticulate (microparticulosome) signature has been reported in patients with CRC, particularly in the presence of a thromboembolic event. However, there is currently no data on PMs and their involvement in CP. In addition, CP and surgery coupled with hyperthermic intraperitoneal chemotherapy are major risk factors for thromboembolic complications. The characterization of prothrombotic PMs is therefore essential to predict such event.
The main objective of this project is to characterize the microparticulate signature of CP of colorectal origin and to compare it with that of CP without CP. The secondary objectives are to compare the microparticulate signature obtained on peripheral venous samples and intraoperative tumor samples, evaluate the evolution of the microparticulate signature between the beginning and the end of the intervention, then correlate the peripheral signature to the oncological follow-up of the patients with CP and the occurrence of a thromboembolic event.
| 2307077 | ecrin-mdr-crc
Project description:Characterizations of ascites proteome from ovarian PC and gastric PC have demonstrated that ascites contains elevated pro-tumorigenic factors. Reasoning that the composition of ascitic fluid might offer insight into the memory of key biological events occurring intra-abdominally, we hypothesized that paracrine factors essential for survival and growth of peritoneal deposits are secreted into and circulate within ascitic fluid. Our data from cytokine array profile suggest that ascites contains biologically active ligands capable of supporting cellular functions of cancer cells. To decipher downstream signalling pathways activated in cancer cells when exposed to ascites, we performed gene expression analysis of Colo-205 and SNU-C1 cells upon exposure to PC ascites.
2022-02-22 | GSE189004 | GEO
Project description:Small RNA isolated from synovial fluid of the metacarpophalangeal joints of horses. Horses either had minimal signs of osteoarthritis based on macroscopic and microscopic joint scoring or early (mild) osteoarthritis. Differential expression of small non-coding RNAs was undertaken.
2020-06-30 | E-MTAB-8409 | biostudies-arrayexpress
Project description:Characterizations of ascites proteome from ovarian PC and gastric PC have demonstrated that ascites contains elevated pro-tumorigenic factors. Reasoning that the composition of ascitic fluid might offer insight into the memory of key biological events occurring intra-abdominally, we hypothesized that paracrine factors essential for survival and growth of peritoneal deposits are secreted into and circulate within ascitic fluid. Our data suggest that ascites contains biologically active ligands capable of supporting cellular functions of cancer cells.
2022-02-22 | GSE189168 | GEO
Project description:How epigenetic deregulation affects gene expression patterns in subclones of the same tumor is poorly known. Peritoneal Carcinomatosis (PC) is a condition in which multiple metastases of the same abdominal tumor develop in the peritoneal cavity and intra-peritoneal organs, thus defining different ecosystems of the same cancer. PITCHER addresses the variations in epigenetically regulated gene expression between different subclones of PC in relation with cell mechanoresponses, providing insights on how cancer epigenetic landscapes evolve under environmental pressures and on strategies used by cancer cells to adapt to the transition from one ecosystem to the other.
PITCHER is a network of 10 teams from Lyon, Grenoble and Marseille, based on data and specimen collection of patients who have undergone a surgery for a peritoneal carcinomatosis of ovarian or colorectal origin. PC lesions and eventually matched specimens of primary tumors will be collected in the same patients at the time of the surgery or eventually retrieved from already existing samples. Epigenetic landscapes will be analyzed by a bioinformatics pipeline combining exome sequencing, transcriptome and methylome to identify "epigenetic hotspots", and their variations across lesions will be evaluated. These analyses will be realized in fresh (when available) or pre-existing samples. When possible, organoid cultures and animal models will be derived from multicellular structures in peritoneal fluids and membrane, cytoskeletal and nucleoskeletal mechanoresponses will be characterized using Atomic Force Microscopy. The role of tumor axonogenesis, a process of neo-formation of axon fibers in tumors, will be addressed. Experimental studies of cell responses to therapy will be performed to derive mathematical predictive models. All components will be integrated in a systems biology map of PC.
| 2364325 | ecrin-mdr-crc
Project description:Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). Studies in human MS and its animal model experimental autoimmune encephalomyelitis (EAE) have shown that new abnormal vessels develop in demyelinating plaques through pathological neo-angiogenesis, which exacerbates MS/EAE pathology by contributing to the leakage of serum components and infiltration of immune cells into the CNS. However, the cellular origin and the signaling pathways underlying this pathology remain poorly understood. Here, using single-cell RNA sequencing and validation with in situ hybridization and immunofluorescence, we discovered that neo-angiogenesis is initiated specifically by venous endothelial cells during EAE. Moreover, we identified VEGF-A signaling as the primary driver of neo-angiogenesis in EAE, as treatment with the VEGF-A blocking antibody, bevacizumab, ameliorated the EAE pathology by reducing neo-angiogenesis in vivo. Our findings may lead to the development of novel therapeutics designed to reduce neo-angiogenesis and improve long-term neurological deficits in MS.
2023-03-14 | GSE210776 | GEO
Project description:Primary objectives: Parte 1: SAFETY RUN-IN PART
Determinar la Dosis Máxima Tolerada (DMT) y la Dosis Recomendada de Fase II (DRF2) de MSC1936369B combinado con FOLFIRI como tratamiento de segunda línea en pacientes con Cáncer colorrectal metastásico con K-Ras mutado (CCRm).
Parte 2: PARTE DE ASIGNACIÓN ALEATORIZADA FASE II
Valorar la actividad anti-tumoral de MSC1936369B combinado con FOLFIRI como tratamiento de segunda línea en pacientes con CCRm K-Ras mutado en términos de Supervivencia libre de progresión (SLP).
Primary endpoints: Safety Run-in Part
Toxicidad limitante de dosis (TLD) utilizando los Criterios Comunes de Terminología NCI para Acontecimientos Adversos v3.0 (CTCAE), evaluada durante el primer ciclo de tratamiento. Se utilizará el número y la incidencia de TLDs por nivel de dosis en el análisis estadístico primario de la Safety Run-in Part.
Parte de Asignación Aleatorizada Fase II
Tiempo de supervivencia libre de progresión (SLP), definido como el tiempo (en meses) desde la fecha de asignación aleatorizada hasta la primera progresión de la enfermedad según lo notificado y documentado por el investigador (ej., progresión radiológica por RECIST v1.0) o muerte por cualquier causa. Se censurará la SLP en el momento de posterior tratamiento antes de la progresión. En el análisis estadístico principal de la Parte de Asignación Aleatorizada Fase II se utilizará la Razón de Riesgo (RR) de la SLP del grupo experimental versus el grupo control.
| 2527070 | ecrin-mdr-crc
Project description:The aberrant activation of HER2 has a pivotal role in bone metastasis implantation and progression in several tumor types, in-cluding prostate cancer (PC). Trastuzumab and other anti-HER2 therapies, such as lapatinib, have been used in human breast cancer HER2 positive. Although HER2 overexpression has been reported in PC, anti-HER2 therapy response has revealed conflicting results. We investigated the potential of lapatinib in inhibiting cell migration and inducing apoptosis in two human (LNCaP and PC3) and two canine PC cell lines (PC1 and PC2). Cell migration and apoptosis were evaluated by Annexin V/PI analysis after lapatinib treatment. The transcriptome analysis of all cell lines before and after treatment with lapatinib was also performed. We found increased apoptosis and migration inhibition in LNCaP cells (androgen-sensitive cell line), while PC1, PC2, and PC3 cells showed no alterations after the treatment. The transcriptome analysis of LNCaP and PC3 cell lines showed 158 dysregulated transcripts in common, while PC1 and PC2 cell lines presented 82. At the doses of lapatinib used, we observed transcriptional modifications in all cell lines. PI3K/AKT/mTOR pathway were enriched in human PC cells, while canine PC cells showed en-richment of tyrosine kinase antitumor response and HER2-related pathways. In canine PC cells, the apoptosis failed after lapatinib treatment, possibly due to the downregulation of MAPK genes. Prostate cancer cells insensitive to androgens may be resistant to lapatinib through PI3K gene dysregulation. The association of lapatinib with PI3K inhibitors may provide a more effective anti-tumor response and clinical benefits to PC patients.
2023-11-30 | E-MTAB-13551 | biostudies-arrayexpress