Search results for "Sms"
showing 10 items of 10610 documents
5-Fluorouracil and recombinant alpha interferon-2a in the treatment of advanced colorectal carcinoma: a dose optimization study
1990
A dose optimization study was carried out with the aim of identifying the maximally tolerated dose of recombinant alpha interferon-2a (raIFN-2a) in combination with 5-fluorouracil (5FU). 5FU was given at the dose of 750 mg/m2 over a 4-hour infusion on day 1- - greater than 5 followed by 750 mg/m2 weekly i.v. bolus. Recombinant aIFN-2a was started at 3 x 10(6) IU subcutaneously three times/week. 12 patients with advanced colorectal carcinoma were included in the study. 10 patients had previously received chemotherapy for advanced disease. Severe fatigue, most likely attributable to rIFN, was the dose-limiting toxicity. The dosage of raIFN-2a could not be further escalated above 12 x 10(6) IU…
Epigenomic landscape of human colorectal cancer unveils an aberrant core of pan-cancer enhancers orchestrated by YAP/TAZ
2021
Cancer is characterized by pervasive epigenetic alterations with enhancer dysfunction orchestrating the aberrant cancer transcriptional programs and transcriptional dependencies. Here, we epigenetically characterize human colorectal cancer (CRC) using de novo chromatin state discovery on a library of different patient-derived organoids. By exploring this resource, we unveil a tumor-specific deregulated enhancerome that is cancer cell-intrinsic and independent of interpatient heterogeneity. We show that the transcriptional coactivators YAP/TAZ act as key regulators of the conserved CRC gained enhancers. The same YAP/TAZ-bound enhancers display active chromatin profiles across diverse human t…
Can Immunogenic Chemotherapies Relieve Cancer Cell Resistance to Immune Checkpoint Inhibitors?
2019
The unprecedented clinical activity of checkpoint blockade in several types of cancers has formally demonstrated that anti-tumor immune responses are crucial in cancer therapy. Durable responses seen in patients treated with immune checkpoint inhibitors (ICI) show that they can trigger the establishment of long-lasting immunologic memory. This beneficial outcome is however achieved for a limited number of patients. In addition, late relapses are emerging suggesting the development of acquired resistances that compromise the anticancer efficacy of ICI. How can this be prevented through combination therapies? We here review the functions of immune checkpoints, the successes of ICI in treating…
Two-Week Aflibercept or Erlotinib Administration Does Not Induce Changes in Intestinal Morphology in Male Sprague–Dawley Rats But Aflibercept Affects…
2019
Gastrointestinal toxicity is a frequently observed adverse event during cancer treatment with traditional chemotherapeutics. Currently, traditional chemotherapeutics are often combined with targeted biologic agents. These biologics, however, possess a distinct toxicity profile, and they may also exacerbate the adverse effects of traditional chemotherapeutics. In this study, we aimed to characterize the gastrointestinal and metabolic changes after a 2-week treatment period with aflibercept, an antiangiogenic VEGFR decoy, and with erlotinib, a tyrosine-kinase inhibitor. Male rats were treated either with aflibercept or erlotinib for 2 weeks. During the 2-week treatment period, the animals in …
Exosomal microRNAs in liquid biopsies: future biomarkers for prostate cancer
2017
Abstract: Prostate cancer is the second most diagnosed cancer in males in the world. Plasma quantification of prostate-specific antigen substantially improved the early detection of prostate cancer, but still lacks the required specificity. Clinical management of prostate cancer needs advances in the development of new non-invasive biomarkers, ameliorating current diagnosis and prognosis and guiding therapeutic decisions. microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level. These miRNAs are expressed in the cells and are also present in cell-derived extracellular vesicles such as exosomes. Exosomes have been shown to act as…
PD-L1 Expression and Immune Cell Infiltration in Gastroenteropancreatic (GEP) and Non-GEP Neuroendocrine Neoplasms With High Proliferative Activity
2019
The potential of neuroendocrine neoplasms (NEN) to respond to checkpoint inhibitors is largely unknown and full of great expectations. Immunohistochemical (IHC) studies of programmed cell death ligand 1 (PD-L1) expression in the tumor microenvironment and its implications in predicting the response to checkpoint inhibition is a very active subject. Currently, the combined analysis of PD-L1 expression and tumor-associated immune cell (TAIC) infiltration is considered the best predictive marker of therapeutic response. Here we investigated the expression of PD-L1 on tumor cells (TC) and tumor-infiltrating immune cells (IC) by IHC in 68 NEN samples with a high proliferation rate (Ki-67 >20%…
Associations of epstein-barr virus-positive gastric adenocarcinoma with circulating mediators of inflammation and immune response
2018
Epstein-Barr virus (EBV)-positive gastric adenocarcinoma exhibits locally intense inflammation but systemic manifestations are uncertain. Our study examined whether circulating mediators of inflammation and immune response differ by tumor EBV status. From a Latvian series of 302 gastric cancer cases, we measured plasma levels of 92 immune-related proteins in the 28 patients with EBV-positive tumors and 34 patients with EBV-negative tumors. Eight markers were statistically significantly higher with tumor EBV positivity: chemokine C-C motif ligand (CCL) 20 (Odds Ratio (OR) = 3.6; p-trend = 0.001), chemokine C-X-C motif ligand 9 (OR = 3.6; p-trend = 0.003), programmed death-ligand 1 (PD-L1; OR…
Nano-Enhanced Cancer Immunotherapy: Immunology Encounters Nanotechnology
2020
Cancer immunotherapy utilizes the immune system to fight cancer and has already moved from the laboratory to clinical application. However, and despite excellent therapeutic outcomes in some hematological and solid cancers, the regular clinical use of cancer immunotherapies reveals major limitations. These include the lack of effective immune therapy options for some cancer types, unresponsiveness to treatment by many patients, evolving therapy resistance, the inaccessible and immunosuppressive nature of the tumor microenvironment (TME), and the risk of potentially life-threatening immune toxicities. Given the potential of nanotechnology to deliver, enhance, and fine-tune cancer immunothera…
Legume consumption and risk of all-cause, cardiovascular, and cancer mortality in the PREDIMED study.
2018
BACKGROUND & AIMS: Limited prospective studies have examined the association between legumes consumption and mortality, whereas scarce, if at all, previous studies have evaluated such associations taking into consideration specific grain legumes. We aimed to investigate the association between total legumes consumption and grain legumes species (dry beans, chickpeas, lentils, and fresh peas) with all-cause, cardiovascular disease (CVD), cancer and other-cause mortality among elderly Mediterranean individuals at high CVD risk. METHODS: We prospectively assessed 7216 participants from the PREvención con DIeta MEDiterránea study. Dietary intake was assessed at baseline and yearly during follow…
Fasciola spp: Mapping of the MF6 epitope and antigenic analysis of the MF6p/HDM family of heme-binding proteins
2017
MF6p/FhHDM-1 is a small cationic heme-binding protein which is recognized by the monoclonal antibody (mAb) MF6, and abundantly present in parenchymal cells and secreted antigens of Fasciola hepatica. Orthologs of this protein (MF6p/HDMs) also exist in other causal agents of important foodborne trematodiasis, such as Clonorchis sinensis, Opisthorchis viverrini and Paragonimus westermani. Considering that MF6p/FhHDM-1 is relevant for heme homeostasis in Fasciola and was reported to have immunomodulatory properties, this protein is expected to be a useful target for vaccination. Thus, in this study we mapped the epitope recognized by mAb MF6 and evaluated its antigenicity in sheep. The sequenc…