COLLISION RELAPSE Trial
Ontology highlight
ABSTRACT:
DISEASE(S): Neoplasm Metastasis,Neoplasms, Second Primary,Liver Metastases,Liver Metastasis Colon Cancer,Chemotherapy Effect,Colorectal Cancer,Liver Neoplasms
PROVIDER: 60270 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:The PUMP-IT study is designed to prove the feasibility of HAIP chemotherapy with concomitant standard systemic chemotherapy (FOLFOX and FOLFIRI) in the Netherlands. This study will include patients with both unresectable CRLM and resectable CRLM with an indication for upfront systemic therapy (further referred to as potentially resectable CRLM), without extrahepatic metastases. The study will be performed in two tertiary referral centers in the Netherlands.
| 2351806 | ecrin-mdr-crc
Project description:Cellular senescence is associated with aging but also impacts various physiological and pathological processes such as embryonic development and wound healing. Factors secreted by senescent cells can affect their microenvironment, including local spreading of senescence. Acute severe liver disease is associated with hepatocyte senescence and frequently progresses to multi-organ failure. Why the latter occurs is poorly understood however, the presence of hepatic senescence is associated with poor prognosis and extrahepatic organ failure in acute liver disease. Here, using genetic mouse models of hepatocyte-specific senescence, we demonstrate senescence development in extrahepatic organs and associated organ dysfunction in response to liver senescence. In patients with acute indeterminate hepatitis, the extent of hepatocellular senescence predicts the occurrence of extrahepatic dysfunction, need for liver transplantation and mortality. We identify the Transforming Growth Factor β (TGFβ) pathway as a critical mediator of systemic spread of senescence and TGFβ inhibition blocks senescence transmission to other organs preventing renal dysfunction. Our results highlight the systemic consequences of organ-specific senescence which, independent of aging, contributes to multi-organ dysfunction.
2024-08-23 | GSE262705 | GEO
Project description:Cellular senescence is associated with aging but also impacts various physiological and pathological processes such as embryonic development and wound healing. Factors secreted by senescent cells can affect their microenvironment, including local spreading of senescence. Acute severe liver disease is associated with hepatocyte senescence and frequently progresses to multi-organ failure. Why the latter occurs is poorly understood however, the presence of hepatic senescence is associated with poor prognosis and extrahepatic organ failure in acute liver disease. Here, using genetic mouse models of hepatocyte-specific senescence, we demonstrate senescence development in extrahepatic organs and associated organ dysfunction in response to liver senescence. In patients with acute indeterminate hepatitis, the extent of hepatocellular senescence predicts the occurrence of extrahepatic dysfunction, need for liver transplantation and mortality. We identify the Transforming Growth Factor Beta (TGFbeta) pathway as a critical mediator of systemic spread of senescence and TGFbeta inhibition blocks senescence transmission to other organs preventing renal dysfunction. Our results highlight the systemic consequences of organ-specific senescence which, independent of aging, contributes to multi-organ dysfunction.
2024-08-23 | GSE267196 | GEO
Project description:The tumor microenvironment is distinctive in primary and secondary liver cancer. B cells represent an important component of immune infiltrates. Here, we demonstrated that B cells are an important regulator in hepatocellular carcinoma (HCC) and colorectal cancer liver metastasis (CRLM) microenvironments. B cells displayed distinct developmental trajectories in HCC and CRLM. Single-cell analysis revealed that IgG+ plasma cells preferentially accumulated in HCC while IgA+ plasma cells were preferentially enriched in CRLM. Mechanistically, IgG+ plasma cells in HCC were recruited by tumor-associated macrophages via the CXCR3-CXCL10 axis, whereas IgA+ plasma cells in CRLM were recruited by metastatic tumor cells via CCR10-CCL28 signaling. Functionally, IgG+ plasma cells preferentially promoted pro-tumorigenic macrophages formation in HCC, and IgA+ plasma cells preferentially induced granulocytic myeloid-derived suppressor cells activation in CRLM. Clinically, increased infiltration of IgG+ plasma cells and macrophages in HCC was correlated to worse survival, while increased intratumoral IgA+ plasma cells and neutrophils in CRLM indicated poor prognosis. Taken together, this study demonstrated plasma and myeloid cell-mediated immunosuppression in HCC and CRLM, suggesting that selectively modulating primary or secondary tumor-related immunosuppressive regulatory networks might reprogram the microenvironment and provide an immunotherapeutic strategy for treating liver cancer.
2023-09-17 | GSE243245 | GEO
Project description:The tumor microenvironment is distinctive in primary and secondary liver cancer. B cells represent an important component of immune infiltrates. Here, we demonstrated that B cells are an important regulator in hepatocellular carcinoma (HCC) and colorectal cancer liver metastasis (CRLM) microenvironments. B cells displayed distinct developmental trajectories in HCC and CRLM. Single-cell analysis revealed that IgG+ plasma cells preferentially accumulated in HCC while IgA+ plasma cells were preferentially enriched in CRLM. Mechanistically, IgG+ plasma cells in HCC were recruited by tumor-associated macrophages via the CXCR3-CXCL10 axis, whereas IgA+ plasma cells in CRLM were recruited by metastatic tumor cells via CCR10-CCL28 signaling. Functionally, IgG+ plasma cells preferentially promoted pro-tumorigenic macrophages formation in HCC, and IgA+ plasma cells preferentially induced granulocytic myeloid-derived suppressor cells activation in CRLM. Clinically, increased infiltration of IgG+ plasma cells and macrophages in HCC was correlated to worse survival, while increased intratumoral IgA+ plasma cells and neutrophils in CRLM indicated poor prognosis. Taken together, this study demonstrated plasma and myeloid cell-mediated immunosuppression in HCC and CRLM, suggesting that selectively modulating primary or secondary tumor-related immunosuppressive regulatory networks might reprogram the microenvironment and provide an immunotherapeutic strategy for treating liver cancer.
2023-06-19 | GSE235057 | GEO
Project description:Purpose: Our research aims to identify the expression, clinical value, biological significance and signaling pathway of KIAA1522 in colorectal carcinoma liver metastases (CRLM). Materials and Methods: To elucidate the role of KIAA1522 in CRC, its expression and survival analysis were assessed using GEPIA databases. Then we evaluated expression of KIAA1522 immunohistochemically in tissue samples of 57 patients with CRLM. The correlations between expression of KIAA1522 and clinical significance, prognosis of these 57 patients with CRLM were analyzed. Western blotting, CCK-8, colony formation, Flow cytometry, Transwell invasion, and wound healing assays were performed to explore the function of KIAA1522 in colon cancer cell lines. Finally, transcriptome sequencing and gene set enrichment analysis was used to identify the pathways involved. Results: Our results demonstrated that KIAA1522 was highly expressed in CRLM tissues and colon cancer cell lines, and expression of KIAA1522 in primary sites was significantly positively correlated with that in metastatic sites. Furthermore, KIAA1522 overexpression was associated with unfavorable clinicopathological characteristics. Survival analyses revealed that KIAA1522 overexpression predicted lower overall survival rates in patients with CRLM. Functional studies suggested that KIAA1522 facilitated proliferation, migration and invasion of colon cancer cell lines in vitro. Moreover, KIAA1522 upregulated the Notch signaling pathway, as confirmed by transcriptome sequencing and gene set enrichment analysis. Conclusion: In conclusion, these data suggest that upregulation of KIAA1522 might enhance tumorigenicity and metastasis of colon cancer cell lines through potentiating the Notch signaling pathway activity. Expression of KIAA1522 plays oncogenic roles in CRLM and might serve as a novel molecular target in CRLM treatment.
2022-12-31 | GSE174449 | GEO
Project description:The patients with non-resectable colorectal liver metastases (CRLM) have always being considered a particular subgroup of CRLM in which the therapeutic approach, is focused on strategies that allow a potential surgery like neoadjuvant systemic treatments. But, the underlying biology that causes this particular profile of spread in a proportion of patients that always recur and progress in the liver has not been properly characterized from a biological point of view. Unfortunately, these patients finally develop liver metastasis not amenable for local treatments and become refractory to systemic treatments even without developing extrahepatic liver metastases. As a result, liver transplantation (LT) is a potential for patients without extrahepatic involvement and nonresectable CRLM. There are several studies that aims to evaluate if LT increases overall survival compared to best alternative care. To our knowledge, none of these studies incorporate objectives focused on the underlying tumor biology of this particular population and the development of focused strategies including a dynamic disease monitoring and targeted treatments for this particular population.The METLIVER trial will permit to expand the genetic studies to the whole complexity of metastatic lesions and a more precise evaluation of their genetic heterogeneity. Moreover, it will help to precise the type of genetic analyses on liquid biopsies that can be designed for patients that will unfortunately relapse mostly with lung metastases after LT. Our proposal will maximize the opportunity to produce an unprecedented knowledge on CRLM evolution and will provide new opportunities for relapsed patients.
| 2732685 | ecrin-mdr-crc
Project description:For patients with initially unresectable colorectal liver metastasis (IU-CRLM) receiving effective conversion therapy, disease relapse after conversion hepatectomy is common due to the extensive tumor load. Yet, few studies have focused on the assessment and management of relapse after conversion hepatectomy for IU-CRLM. This study aimed to investigate the impact of surgical management for relapse after conversion hepatectomy in IU-CRLM.
| 2742045 | ecrin-mdr-crc
Project description:Primary Objective: The first objective of this study is to evaluate efficacy of adjuvant HAIP chemotherapy after repeat hepatectomy for recurrent CRLM in the Erasmus MC.
Secondary Objective(s): The second objective is to determine treatment related adverse events (grade III and higher).
Primary Objective: The first objective of this study is to evaluate efficacy of adjuvant HAIP chemotherapy after repeat hepatectomy for recurrent CRLM in the Erasmus MC.
| 2539639 | ecrin-mdr-crc
Project description:Neoadjuvant chemotherapy (NAC) has been of recent interest as an alternative to upfront surgery followed by adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). However, a subset of patients does not respond to NAC and may have been better managed by upfront surgery. Hence, there is an unmet need for accurate biomarkers for predicting NAC response in PDAC. This project aimed to identify upregulated proteins in tumor tissue from poor- and good-NAC responders.
2020-04-16 | PXD017051 | Pride