Search results for "Cancer Research"

High-SETD8 inactivates p53 in neuroblastoma

2017

Heterogeneity within and between primary colorectal carcinomas and matched metastases as revealed by analysis of Ki-ras and p53 mutations

2004

Analysis of the genetic status of Ki-ras and p53 in primary colorectal carcinomas and matched colorectal liver metastasis from 30 patients reveals an overall heterogeneity both within and between the two tumoral tissues. Both genes were found mutated with a similar frequency in both tissues; however, identical mutations in primary tumor and matched metastasis were found less frequently in the case of the Ki-ras than the p53 gene. Only in three cases the same p53 and Ki-ras mutations found in the primary tumor were found also in the metastasis. In several metastatic specimens the DNA bearing a mutation detected also in the primary tumor appears significantly less abundant than the wild-type …

Targeting HSP90 with the small molecule inhibitor AUY922 (luminespib) as a treatment strategy against hepatocellular carcinoma

2018

Hepatocellular carcinoma (HCC) is a highly malignant tumor that responds very poorly to existing therapies, most probably due to its extraordinary inter- and intra-tumor molecular heterogeneity. The modest therapeutic response to molecular targeted agents underlines the need for new therapeutic approaches for HCC. In our study, we took advantage of well-characterized human HCC cell lines, differing in transcriptomic subtypes, DNA mutation and amplification alterations, reflecting the heterogeneity of primary HCCs, to provide a preclinical evaluation of the specific heat shock protein 90 (HSP90) inhibitor AUY922 (luminespib). Indeed, HSP90 is highly expressed in different tumor types, but it…

Plausible Role of Estrogens in Pathogenesis, Progression and Therapy of Lung Cancer

2021

Malignant neoplasms are among the most common diseases and are responsible for the majority of deaths in the developed world. In contrast to men, available data show a clear upward trend in the incidence of lung cancer in women, making it almost as prevalent as breast cancer. Women might be more susceptible to the carcinogenic effect of tobacco smoke than men. Furthermore, available data indicate a much more frequent mutation of the tumor suppressor gene-p53 in non-small cell lung cancer (NSCLC) female patients compared to males. Another important factor, however, might lie in the female sex hormones, whose mitogenic or carcinogenic effect is well known. Epidemiologic data show a correlatio…

Molecular mechanisms of MYCN-dependent apoptosis and the MDM2-p53 pathway: an Achille’s heel to be exploited for the therapy of MYCN amplified neurob…

2012

The p53 oncosuppressor is very seldom mutated in neuroblastoma, but several mecha- nisms cooperate to its functional inactivation in this tumor. Increased MDM2 levels, due to genetic amplification or constitutive inhibition of p14ARF, significantly contribute to this event highlighting p53 reactivation as an attractive perspective for neuroblastoma treat- ment. In addition to its role in tumorigenesis, MYCN sensitizes untransformed and cancer cells to apoptosis. This is associated to a fine modulation of the MDM2-p53 pathway Indeed MYCN induces p53 and MDM2 transcription, and, by evoking a DNA damage response (DDR), it stabilizes p53 and its proapoptotic kinase Homeodomain Interacting Prote…

Testing for Lynch Syndrome in Endometrial Carcinoma: From Universal to Age-Selective MLH1 Methylation Analysis

2022

Simple Summary International guidelines recommend universal screening of endometrial carcinoma patients for Lynch syndrome, a hereditary cancer predisposition syndrome. Screening is based on mismatch repair protein immunohistochemistry and reflex MLH1 methylation analysis to exclude the likely sporadic cases of MMR deficiency. As sporadic MLH1 protein loss is common in endometrial carcinoma, the ability to target methylation testing would save efforts and costs. We discovered that limiting methylation testing to patients under 65 years would have significantly reduced the testing effort while maintaining a low false negative rate for MLH1-LS detection (0% and 3% in our clinic and registry-b…

Peroxisome Proliferator-Activated Receptors and Atherosclerosis

2011

The peroxisome proliferator-activated receptors (PPARs) represent the family of 3 nuclear receptor isoforms-PPARα, -γ, and -δ/β, which are encoded by different genes. As lipid sensors, they are primarily involved in regulation of lipid metabolism and subsequently in inflammation and atherosclerosis. Atherosclerosis considers accumulation of the cells and extracellular matrix in the vessel wall leading to the formation of atherosclerotic plaque, atherothrombosis, and other vascular complications. Besides existence of natural ligands for PPARs, their more potent synthetic ligands are fibrates and thiazolidindiones. Future investigations should now focus on the mechanisms of PPARs activation, …

Is HLA type a possible cancer risk modifier in Lynch syndrome?

2022

Lynch syndrome (LS) is the most common inherited cancer syndrome. It is inherited via a monoallelic germline variant in one of the DNA mismatch repair (MMR) genes. LS carriers have a broad 30-80% risk of developing various malignancies, and more precise, individual risk estimations would be of high clinical value, allowing tailored cancer prevention and surveillance. Due to MMR deficiency, LS cancers are characterized by the accumulation of frameshift mutations leading to highly immunogenic frameshift peptides (FSPs). Thus, immune surveillance is proposed to inhibit the outgrowth of MMR-deficient cell clones. Recent studies have shown that immunoediting during the evolution of MMR-deficient…

TRAIL acts synergistically with iron oxide nanocluster-mediated magneto- and photothermia

2019

International audience; Targeting TRAIL (Tumor necrosis factor (TNF)-Related Apoptosis-Inducing Ligand) receptors for cancer therapy remains challenging due to tumor cell resistance and poor preparations of TRAIL or its derivatives. Herein, to optimize its therapeutic use, TRAIL was grafted onto iron oxide nanoclusters (NCs) with the aim of increasing its pro-apoptotic potential through nanoparticle-mediated magnetic hyperthermia (MHT) or photothermia (PT). Methods: The nanovector, NC@TRAIL, was characterized in terms of size, grafting efficiency, and potential for MHT and PT. The therapeutic function was assessed on a TRAIL-resistant breast cancer cell line, MDA-MB-231, wild type (WT) or T…

Prognostic and Predictive Role of Tumor-Infiltrating Lymphocytes (TILs) in Ovarian Cancer

2022

In the last decade, tumor-infiltrating lymphocytes (TILs) have been recognized as clinically relevant prognostic markers for improved survival, providing the immunological basis for the development of new therapeutic strategies and showing a significant prognostic and predictive role in several malignancies, including ovarian cancer (OC). In fact, many OCs show TILs whose typology and degree of infiltration have been shown to be strongly correlated with prognosis and survival. The OC histological subtype with the higher presence of TILs is the high-grade serous carcinoma (HGSC) followed by the endometrioid subtype, whereas mucinous and clear cell OCs seem to contain a lower percentage of TI…