Search results for "digestive system"
showing 10 items of 1747 documents
Assessment of intratumor immune-microenvironment in colorectal cancers with extranodal extension of nodal metastases
2018
Background: No data is available on the molecular background of the extra-nodal extension (ENE) of lymph node metastasis (LN) in colorectal cancer (CRC). Methods: A series of 22 ENE-positive CRCs was considered and three samples per case were selected (the primary CRC, an ENE-negative and an ENE-positive metastatic LN). Samples (n=66) were analysed by immunohistochemistry for PD-L1, CD4, CD8, CD68 and CD80. Fifteen out of twenty-two cases were further profiled through a hotspot multigene mutational custom panel, including 164 hotspot regions of AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN and TP53 genes. Results: A significantly higher percentage of CD4-, CD8- and CD68-pos…
Impact of BRAF and RAS mutations on first-line efficacy of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab: analysis of the FIRE-3 (AIO KRK-03…
2017
Abstract Background RAS and BRAF mutations have been identified as negative prognostic factors in metastatic colorectal cancer. Efficacy of 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) plus bevacizumab in patients with RAS-mutant tumours needs to be further evaluated. Whether to treat patients with BRAF-mutant tumours with either bevacizumab or anti-epidermal growth factor receptor (EGFR) antibodies remains unclear. Methods Patients treated within the FIRE-3 trial were retrospectively tested for BRAF and RAS mutations using formalin fixated paraffin embedded (FFPE) tumour material applying pyrosequencing for KRAS and NRAS exon 2, 3 and 4 mutations as far as for BRAF mutations. Survival …
Update of the statements on biology and clinical impact of occult hepatitis B virus infection
2019
In October 2018 a large number of international experts with complementary expertise came together in Taormina to participate in a workshop on occult hepatitis B virus infection (OBI). The objectives of the workshop were to review the existing knowledge on OBI, to identify issues that require further investigation, to highlight both existing controversies and newly emerging perspectives, and ultimately to update the statements previously agreed in 2008. This paper represents the output from the workshop.
Accumulation of MDSC and Th17 Cells in Patients with Metastatic Colorectal Cancer Predicts the Efficacy of a FOLFOX-Bevacizumab Drug Treatment Regimen
2016
Abstract Host immunity controls the development of colorectal cancer, and chemotherapy used to treat colorectal cancer is likely to recruit the host immune system at some level. Athough preclinical studies have argued that colorectal cancer drugs, such as 5-fluorouracil (5-FU) and oxaliplatin, exert such effects, their combination as employed in the oncology clinic has not been evaluated. Here, we report the results of prospective immunomonitoring of 25 metastatic colorectal cancer (mCRC) patients treated with a first-line combination regimen of 5-FU, oxaliplatin, and bevacizumab (FOLFOX–bevacizumab), as compared with 20 healthy volunteers. Before this therapy was initiated, T regulatory ce…
Baseline Splenic Volume as a Prognostic Biomarker of FOLFIRI Efficacy and a Surrogate Marker of MDSC Accumulation in Metastatic Colorectal Carcinoma
2020
Background: Predictive biomarkers of response to chemotherapy plus antiangiogenic for metastatic colorectal cancer (mCRC) are lacking. The objective of this study was to test the prognostic role of splenomegaly on baseline CT scan. Methods: This study is a sub-study of PRODIGE-9 study, which included 488 mCRC patients treated by 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) and bevacizumab in first line. The association between splenic volume, and PFS and OS was evaluated by univariate and multivariable Cox analyses. The relation between circulating monocytic Myeloid derived suppressor cells (mMDSC) and splenomegaly was also determined. Results: Baseline splenic volume >
The Current Landscape of Clinical Trials for Systemic Treatment of HCC
2021
Simple Summary Liver cancer is a life-threatening disease. Apart from surgery and catheter-guided therapies, drugs are a central pillar for its treatment. Clinical trials are research studies that are designed to evaluate the treatment effect of a given drug. Therefore, they are the driving force behind innovation and medical progress. One such innovation in the past years has been immunotherapy, which has become increasingly important for treating cancer. Recently, the first such therapy has been approved for the treatment of liver cancer. Current clinical trials are exploring the benefit of immunotherapy and other therapies for this disease. This article gives an overview of such trials p…
Phase Ib/II trial evaluating the safety, tolerability and immunological activity of durvalumab (MEDI4736) (anti-PD-L1) plus tremelimumab (anti-CTLA-4…
2018
Background 5-Fluorouracil plus irinotecan or oxaliplatin alone or in association with target therapy are standard first-line therapy for metastatic colorectal cancer (mCRC). Checkpoint inhibitors targeting PD-1/PD-L1 demonstrated efficacy on mCRC with microsatellite instability but remain ineffective alone in microsatellite stable tumour. 5-Fluorouracil and oxaliplatin were known to present immunogenic properties. Durvalumab (D) is a human monoclonal antibody (mAb) that inhibits binding of programmed cell death ligand 1 (PD-L1) to its receptor. Tremelimumab (T) is a mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). This study is designed to evaluate whether the …
Outcomes of BRAF V600E Pediatric Gliomas Treated With Targeted BRAF Inhibition.
2020
PURPOSE Children with pediatric gliomas harboring a BRAF V600E mutation have poor outcomes with current chemoradiotherapy strategies. Our aim was to study the role of targeted BRAF inhibition in these tumors. PATIENTS AND METHODS We collected clinical, imaging, molecular, and outcome information from patients with BRAF V600E–mutated glioma treated with BRAF inhibition across 29 centers from multiple countries. RESULTS Sixty-seven patients were treated with BRAF inhibition (pediatric low-grade gliomas [PLGGs], n = 56; pediatric high-grade gliomas [PHGGs], n = 11) for up to 5.6 years. Objective responses were observed in 80% of PLGGs, compared with 28% observed with conventional chemotherapy …
Alternative lengthening of telomeres (ALT) influences survival in soft tissue sarcomas: a systematic review with meta-analysis
2019
Background Alternative lengthening of telomeres (ALT) is a telomerase-independent mechanism used by a broad range of neoplasms to maintain telomere length, permitting uncontrolled replication during their progression. ALT has been described in different types of sarcoma, but a comprehensive analysis of its clinical significance is still lacking. Therefore, we provide here the first meta-analysis on this topic. Methods We searched SCOPUS and PubMed through July 2018 to identify all studies that investigated the prognostic role of ALT in sarcomas. We considered the risk of death (risk ratio, RR) calculated as the number of death vs. total participants during follow-up in ALT+ versus ALT- pati…
Pancreatic Ductal Adenocarcinoma (PDAC) Organoids: The Shining Light at the End of the Tunnel for Drug Response Prediction and Personalized Medicine.
2020
Simple Summary Pancreatic ductal adenocarcinoma (PDAC) causes massive medical problems because of late diagnosis and limited responsiveness to standard chemotherapeutic treatments. This makes PDAC one of the major causes of death by cancer. To address this problem, novel tools for early diagnosis and therapy are needed. The recent development of PDAC organoids, which represent micro-scale mini-tumors, offers promising new options for personalized drug-testing based on primary PDAC patient material. This overview article summarizes and discusses the current state-of-the-art in exploiting the organoid technology to improve clinical management of PDAC. Abstract Pancreatic ductal adenocarcinoma…