Search results for "Intestinal Cancer"
showing 10 items of 60 documents
Therapeutic drug monitoring as a tool to optimize 5-FU-based chemotherapy in gastrointestinal cancer patients older than 75 years.
2019
Abstract Aims Most clinical trials exclude elderly people, leading to a limited understanding of the benefit-to-risk ratio in this population. Despite existing data regarding the oncological management of elderly receiving fluorouracil (5-FU)-based regimen, our objective was to investigate 5-FU exposure/toxicity relationship in patients ≥75 years and compare the effectiveness of 5-FU therapeutic drug monitoring between elderly and younger patients. Methods Hundred fifty-four patients (31 of whom are older than 75 years) with gastrointestinal cancers, who were to receive 5-FU–based regimens, were included in our study. At cycle 1 (C1), the 5-FU dose was calculated using patient's body surfac…
Whole-blood transcriptome profiling reveals signatures of metformin and its therapeutic response
2020
Metformin, a biguanide agent, is the first-line treatment for type 2 diabetes mellitus due to its glucose-lowering effect. Despite its wide application in the treatment of multiple health conditions, the glycemic response to metformin is highly variable, emphasizing the need for reliable biomarkers. We chose the RNA-Seq-based comparative transcriptomics approach to evaluate the systemic effect of metformin and highlight potential predictive biomarkers of metformin response in drug-naive volunteers with type 2 diabetes in vivo. The longitudinal blood-derived transcriptome analysis revealed metformin-induced differential expression of novel and previously described genes involved in cholester…
The shared frameshift mutation landscape of microsatellite-unstable cancers suggests immunoediting during tumor evolution
2020
The immune system can recognize and attack cancer cells, especially those with a high load of mutation-induced neoantigens. Such neoantigens are abundant in DNA mismatch repair (MMR)-deficient, microsatellite-unstable (MSI) cancers. MMR deficiency leads to insertion/deletion (indel) mutations at coding microsatellites (cMS) and to neoantigen-inducing translational frameshifts. Here, we develop a tool to quantify frameshift mutations in MSI colorectal and endometrial cancer. Our results show that frameshift mutation frequency is negatively correlated to the predicted immunogenicity of the resulting peptides, suggesting counterselection of cell clones with highly immunogenic frameshift peptid…
Trifluridine/tipiracil : an emerging strategy for the management of gastrointestinal cancers
2018
Fluoropyrimidines are currently the backbone of treatment for gastrointestinal (GI) cancers but development of resistance to these agents remains a major problem. Trifluridine/tipiracil is an oral chemotherapeutic agent recently approved for third-line treatment of chemorefractory metastatic colorectal cancer. This article reviews the clinical value of trifluridine/tipiracil as a monotherapy, including recent trials in GI cancers, and the potential benefit of combining it with other agents in patients with GI cancers, including the preclinical rationale for combination therapy and recently completed and ongoing clinical trials. Data gathered so far suggest that trifluridine/tipiracil has t…
The McCAVE Trial: Vanucizumab plus mFOLFOX‐6 Versus Bevacizumab plus mFOLFOX‐6 in Patients with Previously Untreated Metastatic Colorectal Carcinoma …
2019
Abstract Background Bevacizumab, a VEGF‐A inhibitor, in combination with chemotherapy, has proven to increase progression‐free survival (PFS) and overall survival in multiple lines of therapy of metastatic colorectal cancer (mCRC). The angiogenic factor angiopoetin‐2 (Ang‐2) is associated with poor prognosis in many cancers, including mCRC. Preclinical models demonstrate improved activity when inhibiting both VEGF‐A and Ang‐2, suggesting that the dual VEGF‐A and Ang‐2 blocker vanucizumab (RO5520985 or RG‐7221) may improve clinical outcomes. This phase II trial evaluated the efficacy of vanucizumab plus modified (m)FOLFOX‐6 (folinic acid (leucovorin), fluorouracil (5‐FU) and oxaliplatin) ver…
Protease‐activated receptor signaling in intestinal permeability regulation
2019
Protease-activated receptors (PARs) are a unique class of G-protein-coupled transmembrane receptors, which revolutionized the perception of proteases from degradative enzymes to context-specific signaling factors. Although PARs are traditionally known to affect several vascular responses, recent investigations have started to pinpoint the functional role of PAR signaling in the gastrointestinal (GI) tract. This organ is exposed to the highest number of proteases, either from the gut lumen or from the mucosa. Luminal proteases include the host's digestive enzymes and the proteases released by the commensal microbiota, while mucosal proteases entail extravascular clotting factors and the enzy…
Mitochondrial D310 mutations in colorectal adenomas: an early but not causative genetic event during colorectal carcinogenesis.
2008
Somatic mutations of the D310 sequence of the mitochondrial DNA are reported in human cancers, including colorectal cancers (CRC). The presence of these mutations at early or late steps of colorectal carcinogenesis is unknown. Their prevalence increased significantly with the number of cytosines in the D310 sequence of the matched normal tissue (D310 polymorphism), suggesting that this polymorphism could be a risk factor for CRC. The aim of this study was (i) to investigate the prevalence of D310 mutations in 64 colorectal adenomas and 36 liver metastases from 15 CRC patients, (ii) to assess the relation between D310 polymorphism and the risk of colorectal adenoma in a case-control study in…
Expression of Female Sex Hormone Receptors, Connective Tissue Growth Factor and HER2 in Gallbladder Cancer
2019
AbstractGallbladder cancer (GBC) is a highly malignant tumor with poorly understood etiology. An insight into phenotypic features of this malignancy may add to the knowledge of its carcinogenesis and pave the way to new therapeutic approaches. We assessed the expression of female sex hormone receptors (ERα, ERβ, PR), connective tissue growth factor (CTGF) and HER2 in GBC, and adjacent normal tissue (NT), and determined their prognostic impact. Immunohistochemical (IHC) expression of all biomarkers was performed in formalin-fixed, paraffin-embedded specimens in 60 Caucasian GBC patients (51 women and 9 men). ERβ, cytoPR and CTGF expression were found in 89%, 27%, 91% of GBC, and in 63%, 87%,…
Early stage human colorectal cancer: prognostic value of nm23-H1 protein overexpression
1997
Nm23 gene codifies for a nucleoside diphosphate kinase allowing the intracellular transduction of the signals. In colorectal cancer nm23 protein expression seems related to the progression of the disease. By immunohistochemistry we have studied the intracytoplasmatic nm23 H1 protein expression in 20 patients affected by colorectal cancer at initial stage. In 12 cases it resulted elevated and in four the disease recurred. The overexpression was not correlated with other prognostic factors. Nm23 H1-positive patients affected by colorectal cancer at initial stage could be considered at risk for disease recurrence and included in a more frequent follow-up protocol.
Illness perception and affective symptoms in gastrointestinal cancer patients: A moderated mediation analysis of meaning in life and coping.
2019
Objective The character of the mediational relations between illness perception and affective symptoms often depends on the coping strategies used by patients. For example, these relationships may be moderated by meaning in life that plays a buffering role against the negative consequences of cancer. This study examined moderated mediation effects of meaning in life and coping on the relationship between illness perception and affective symptoms in cancer patients. Methods In this cross-sectional research, 317 gastrointestinal cancer patients who were undergoing chemotherapy, radiotherapy, or combined therapy treatments were examined. They completed measures of illness perception, affective…