Search results for "TUMORS"
showing 10 items of 1138 documents
Interleukin-30 feeds breast cancer stem cells via CXCL10 and IL23 autocrine loops and shapes immune contexture and host outcome
2021
BackgroundBreast cancer (BC) progression to metastatic disease is the leading cause of death in women worldwide. Metastasis is driven by cancer stem cells (CSCs) and signals from their microenvironment. Interleukin (IL) 30 promotes BC progression, and its expression correlates with disease recurrence and mortality. Whether it acts by regulating BCSCs is unknown and could have significant therapeutic implications.MethodsHuman (h) and murine (m) BCSCs were tested for their production of and response to IL30 by using flow cytometry, confocal microscopy, proliferation and sphere-formation assays, and PCR array. Immunocompetent mice were used to investigate the role of BCSC-derived IL30 on tumor…
Genetic and pharmacological modulation of DNA mismatch repair heterogeneous tumors promotes immune surveillance.
2023
Patients affected by colorectal cancer (CRC) with DNA mismatch repair deficiency (MMRd), often respond to immune checkpoint blockade therapies, while those with mismatch repair-proficient (MMRp) tumors generally do not. Interestingly, a subset of MMRp CRCs contains variable fractions of MMRd cells, but it is unknown how their presence impacts immune surveillance. We asked whether modulation of the MMRd fraction in MMR heterogeneous tumors acts as an endogenous cancer vaccine by promoting immune surveillance. To test this hypothesis, we use isogenic MMRp (Mlh1+/+) and MMRd (Mlh1-/-) mouse CRC cells. MMRp/MMRd cells mixed at different ratios are injected in immunocompetent mice and tumor reje…
Myeloid-Derived Suppressor Cells in Multiple Myeloma: Pre-Clinical Research and Translational Opportunities
2014
Immunosuppressive cells have been reported to play an important role in tumor-progression mainly because of their capability to promote immune-escape, angiogenesis, and metastasis. Among them, myeloid-derived suppressor cells (MDSCs) have been recently identified as immature myeloid cells, induced by tumor-associated inflammation, able to impair both innate and adaptive immunity. While murine MDSCs are usually identified by the expression of CD11b and Gr1, human MDSCs represent a more heterogeneous population characterized by the expression of CD33 and CD11b, low or no HLA-DR, and variable CD14 and CD15. In particular, the last two may alternatively identify monocyte-like or granulocyte-lik…
In the literature: February 2019
2019
Malignant pleural mesothelioma (MPM) is a rare and lethal cancer associated to asbestos exposure. Currently, the pemetrexed and cisplatin combination chemotherapy remains the only approved treatment. In the last 5 years, a growing knowledge on mesothelioma pathobiology has translated into the development of multiple novel therapeutic strategies.1 One of the largest reports of comprehensive genomic profiling of MPM was conducted by Bueno and colleagues. Using RNA-seq data, they identified four distinct molecular subtypes, and through exome analysis, they found that BAP1 , NF2 , TP53 , SETD2 , DDX3X , ULK2 , RYR2 , CFAP45 , SETDB1 and DDX51 were significantly mutated.2 In an article recently …
Why do results conflict regarding the prognostic value of the methylation status in colon cancers? The role of the preservation method.
2012
Abstract Background In colorectal carcinoma, extensive gene promoter hypermethylation is called the CpG island methylator phenotype (CIMP). Explaining why studies on CIMP and survival yield conflicting results is essential. Most experiments to measure DNA methylation rely on the sodium bisulfite conversion of unmethylated cytosines into uracils. No study has evaluated the performance of bisulfite conversion and methylation levels from matched cryo-preserved and Formalin-Fixed Paraffin Embedded (FFPE) samples using pyrosequencing. Methods Couples of matched cryo-preserved and FFPE samples from 40 colon adenocarcinomas were analyzed. Rates of bisulfite conversion and levels of methylation of …
In the literature: June 2020.
2020
Immunotherapy based on checkpoint blockade has revolutionised cancer treatment during last years. Whereas this approach fails in a relevant group of patients, the knowledge on tumour microenvironment (TME) opened the possibility to the use of additional therapeutic strategies to potentiate antitumour immunity, including depletion of protumourigenic or immune suppressive and activation of specific immune populations using agonistic antibodies. Nevertheless, due to the complexity of the TME, many of these strategies have been indiscriminately advanced to the clinic without clear mechanistic hypotheses. Nowadays, single-cell RNA sequencing (scRNA-seq)-based transcriptome analyses identify T ce…
Targeting MYCN in Pediatric and Adult Cancers
2021
The deregulation of theMYCfamily of oncogenes, includingc-MYC,MYCNandMYCLoccurs in many types of cancers, and is frequently associated with a poor prognosis. The majority of functional studies have focused onc-MYCdue to its broad expression profile in human cancers. The existence of highly conserved functional domains betweenMYCNandc-MYCsuggests thatMYCNparticipates in similar activities.MYCencodes a basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor (TF) whose central oncogenic role in many human cancers makes it a highly desirable therapeutic target. Historically, as a TF, MYC has been regarded as “undruggable”. Thus, recent efforts focus on investigating methods to indi…
Suppression of Mcl-1 via RNA interference sensitizes human hepatocellular carcinoma cells towards apoptosis induction
2006
Abstract Background Hepatocelluar carcinoma (HCC) is one of the most common cancers worldwide and a major cause of cancer-related mortality. HCC is highly resistant to currently available chemotherapeutic drugs. Defects in apoptosis signaling contribute to this resistance. Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 protein family which interferes with mitochondrial activation. In a previous study we have shown that Mcl-1 is highly expressed in tissues of human HCC. In this study, we manipulated expression of the Mcl-1 protein in HCC cells by RNA interference and analyzed its impact on apoptosis sensitivity of HCC cells in vitro. Methods RNA interference was per…
Erratum: Melanoma Unknown Primary Brain Metastasis Treatment With ECHO-7 Oncolytic Virus Rigvir: A Case Report
2018
Melanoma is considered an aggressive malignancy with a tendency of forming metastasis in the brain. Less than 10% of all melanoma cases present with unknown primary tumor location. This diagnose is yet to be fully understood, because there are only theoretical assumptions about the nature of the disease. Melanoma brain metastases have many severe side effects and, unfortunately, any disease related to the brain has limited therapeutic options due to the blood–brain barrier. The course of the disease after a treatment course is complicated to predict, and it is difficult to obtain long-lasting remission. In this report, we describe a female patient with unknown primary melanoma brain metasta…
Bortezomib: a new pro-apoptotic agent in cancer treatment.
2010
Bortezomib is a proteasome inhibitor. It targets the ubiquitin-proteasome pathway with subsequent inhibition of the degradation of proteins involved in cell cycle regulation and cancer cell survival. The best known molecular mechanism concerns the inhibition of IkappaB breakdown and the related stabilization of NFkappaB, thus preventing its translocation to the nucleus for the activation of downstream pathways. Bortezomib is the only drug in this class which has been approved for clinical use. It has shown an efficient antitumor effect in a phase III clinical trial (APEX) involving relapsed multiple myeloma patients. Response rate, time to progression and overall survival have been improved…