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PubMed Journals Articles About "Dietary Vulnerability Found Cancer Cells With Mutated Spliceosomes" RSS

06:35 EST 20th November 2019 | BioPortfolio

Dietary Vulnerability Found Cancer Cells With Mutated Spliceosomes PubMed articles on BioPortfolio. Our PubMed references draw on over 21 million records from the medical literature. Here you can see the latest Dietary Vulnerability Found Cancer Cells With Mutated Spliceosomes articles that have been published worldwide.

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Showing "Dietary vulnerability found cancer cells with mutated spliceosomes" PubMed Articles 1–25 of 50,000+

The formation of mutated IgM memory B cells in rat splenic marginal zones is an antigen dependent process.

Previous studies in rodents have indicated that only a minor fraction of the immunoglobulin heavy chain variable region (IGHV-Cμ) transcripts carry somatic mutations and are considered memory B cells. This is in marked contrast to humans where nearly all marginal zone B (MZ-B) cells are mutated. Here we show in rats that the proportion of mutated IgM+ MZ-B cells varies significantly between the various IGHV genes analyzed, ranging from 27% mutated IGHV5 transcripts to 65% mutated IGHV4 transcripts. The obs...


LKB1 deficiency renders non-small-cell lung cancer cells sensitive to ERK inhibitors.: ERK inhibitors in LKB1 mutated NSCLC.

Liver kinase B1 (LKB1/STK11) is one of the most mutated genes in non-small-cell lung cancer (NSCLC) accounting for about one third of cases and its activity is impaired in about half of KRAS mutated NSCLC. At present, these patients cannot benefit from any specific therapy.

The pharmalogical reactivation of p53 function improves breast tumor cell lysis by granzyme B and NK cells through induction of autophagy.

Cytotoxic T lymphocytes (CTL) and natural killer cells (NK)-mediated elimination of tumor cells is mostly dependent on Granzyme B apoptotic pathway, which is regulated by the wild type (wt) p53 protein. Because TP53 inactivating mutations, frequently found in human tumors, could interfere with Granzyme B-mediated cell death, the use of small molecules developed to reactivate wtp53 function in p53-mutated tumor cells could optimize their lysis by CTL or NK cells. Here, we show that the pharmalogical reactiva...


Hotspot SF3B1 mutations induce metabolic reprogramming and vulnerability to serine deprivation.

Cancer-associated mutations in the spliceosome gene SF3B1 create a neomorphic protein that produces aberrant mRNA splicing in hundreds of genes, but the ensuing biologic and therapeutic consequences of this missplicing are not well understood. Here we have provided evidence that aberrant splicing by mutant SF3B1 altered the transcriptome, proteome, and metabolome of human cells, leading to missplicing-associated downregulation of metabolic genes, decreased mitochondrial respiration, and suppression of the s...

Novel poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor, AZD2461, down-regulates VEGF and induces apoptosis in prostate cancer cells

Prostate cancer (Pca) is a heterogeneous disease, and current treatments are not based on molecular stratification. Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors have recently been found to be remarkably toxic to cells with defects in homologous recombination, particularly cells with BRCA-mutated backgrounds. Therefore, this preliminary study was designed to evaluate whether PTEN expression status could have an impact on the sensitivity of invasive Pca cells to the PARP inhibitor, AZ...

c-Met-dependent phosphorylation of RhoA plays a key role in gastric cancer tumorigenesis.

RhoA has been identified as having a gain-of-function mutation in approximately 20% of diffuse gastric cancer patients. However, the carcinogenic role of RhoA mutations in gastric cancer is unclear. In the present study, we report that RhoA directly interacts with c-Met and can be phosphorylated by c-Met at Y42 before subsequent K48-linked polyubiquitination and proteasome-mediated protein degradation. Y42C-mutated RhoA exhibits higher protein levels and promotes the proliferation and motility of gastric ca...

Effect of polyunsaturated fatty acids on proliferation and survival of prostate cancer cells.

Progression of prostate cancer to lethal forms is marked by emergence of hormone-independent proliferation of the cancer cells. Nutritional and epidemiological studies have indicated that prostate cancer progression is correlated with the consumption of polyunsaturated fatty acids (PUFA). To shed additional light on the cell-level mechanisms of the observed correlation, we compared the sensitivity of hormone-dependent and hormone-independent prostate cancer cells to growth medium supplementation with free P...

Change in mutation frequency at a TP53 hotspot during culture of ENU-mutagenised human lymphoblastoid cells.

Mutations in oncogenes or tumour suppressor genes cause increases in cell growth capacity. In some cases, fully malignant cancer cells develop after additional mutations occur in initially mutated cells. In such instances, the risk of cancer would increase in response to growth of these initially mutated cells. To ascertain whether such a situation might occur in cultured cells, three independent cultures of human lymphoblastoid GM00130 cells were treated with N-ethyl-N-nitrosourea to induce mutations, and ...

Antiproliferative and toxicogenomic effects of resveratrol in bladder cancer cells with different TP53 status.

The antitumor activity of resveratrol, a polyphenolic compound found mainly in grapes, has been studied in several types of cancer. In bladder cancer, its antiproliferative effects have already been demonstrated, however its mechanism of action is not completely understood. The aim of this study was to evaluate resveratrol antitumor activity (12.5, 25, 50, 100, 150, 200 and 250 μM) and its possible mechanisms of action in bladder tumor cells with different TP53 gene status (RT4, grade 1, TP53 wild type; 56...

The Impact of Diet on Breast Cancer Outcomes.

Breast cancer is the most common cancer in women, yet conclusive evidence of the effects of dietary modification in breast cancer survivors is lacking. Here, we summarize the literature and highlight important data regarding the association between dietary interventions and breast cancer outcomes.

Adult Dietary Fat Intake and Ovarian Cancer Risk.

The association of dietary fat intake with ovarian cancer risk has been inconsistent across populations. We examined dietary fat intake, overall and by type, and ovarian cancer risk in two prospective cohort studies. We assessed long-term dietary fat intake among Nurses' Health Study (NHS) and NHSII participants using food frequency questionnaires administered every 2-4 years beginning in 1984 and 1991, respectively. We examined cumulative energy-adjusted intake of total fat, specific types of fat (animal...

In vitro selective cytotoxicity of the dietary chalcone cardamonin (CD) on melanoma compared to healthy cells is mediated by apoptosis.

Malignant melanoma is an aggressive type of cancer and the deadliest form of skin cancer. Even though enormous efforts have been undertaken, in particular the treatment options against the metastasizing form are challenging and the prognosis is generally poor. A novel therapeutical approach is the application of secondary plant constituents occurring in food and food products. Herein, the effect of the dietary chalcone cardamonin, inter alia found in Alpinia species, was tested using human malignant melanom...

Identification of a catechol-type diphenylbutadiene as a tyrosinase-activated pro-oxidative chemosensitizer against melanoma A375 cells via GST inhibition.

Glutathione S-transferases (GSTs) play an active role in the development of drug-resistance by numerous cancer cells including melanoma cells, which is a major cause of chemotherapy failure. As part of our continuous effort to explore why dietary polyphenols bearing the catechol moiety (dietary catechols) show usually anticancer activity, a catechol-type diphenylbutadiene (3,4-DHB) was selected as a model of dietary catechols to probe whether they work as pro-oxidative chemosensitizers via GST inhibition in...

General and specified vulnerability to extreme temperatures among older adults.

Extreme temperatures pose significant risks to human health and well-being. Older adults are particularly at risk and their susceptibility is a function of vulnerability to general daily life circumstances and to specified events or threats. For the first time, this paper develops a combined general and specified approach to understand the determinants of vulnerability. The findings show that most participants exhibit high levels of heat-related vulnerability, followed by cold-related vulnerability and last...

LPS induces inflammatory chemokines via TLR-4 signalling and enhances the Warburg Effect in THP-1 cells.

The Warburg Effect has emerged as a potential drug target because, in some cancer cell lines, it is sufficient to subvert it in order to kill cancer cells. It has also been shown that the Warburg Effect occurs in innate immune cells upon infection. Innate immune cells play critical roles in the tumour microenvironment but the Warburg Effect is not fully understood in monocytes. Furthermore, it is important to understand the impact of infections on key players in the tumour microenvironment because inflammat...

Epigenetic Gene Regulation by Dietary Compounds in Cancer Prevention.

Traditionally, cancer has been viewed as a set of diseases that are driven by the accumulation of genetic mutations, but we now understand that disruptions in epigenetic regulatory mechanisms are prevalent in cancer as well. Unlike genetic mutations, however, epigenetic alterations are reversible, making them desirable therapeutic targets. The potential for diet, and bioactive dietary components, to target epigenetic pathways in cancer is now widely appreciated, but our understanding of how to utilize these...

Adherence to American Cancer Society and American Institute of Cancer Research dietary guidelines in overweight African American breast cancer survivors.

The American Cancer Society (ACS) and the American Institute for Cancer Research (AICR) each created dietary and physical activity guidelines to improve cancer survivorship. Despite African American breast cancer survivors (AABCS) having the lowest survival rates of any racial or ethnic group, limited information exists on their adherence to cancer-specific lifestyle recommendations. The study's purpose was to measure adherence to ACS/AICR dietary recommendations in AABCS.

CRISPR editing of sftb-1/SF3B1 in Caenorhabditis elegans allows the identification of synthetic interactions with cancer-related mutations and the chemical inhibition of splicing.

SF3B1 is the most frequently mutated splicing factor in cancer. Mutations in SF3B1 likely confer clonal advantages to cancer cells but they may also confer vulnerabilities that can be therapeutically targeted. SF3B1 cancer mutations can be maintained in homozygosis in C. elegans, allowing synthetic lethal screens with a homogeneous population of animals. These mutations cause alternative splicing (AS) defects in C. elegans, as it occurs in SF3B1-mutated human cells. In a screen, we identified RNAi of U2 snR...

Stilbenoid-mediated Epigenetic Activation of SEMAPHORIN 3A in Breast Cancer Cells Involves Changes in Dynamic Interactions of DNA with DNMT3A and NF1C Transcription Factor.

Loci-specific increase in DNA methylation occurs in cancer and may underlie gene silencing. We investigate whether dietary stilbenoids, resveratrol and pterostilbene, exert time-dependent effects on DNA methylation patterns and specifically methylation-silenced tumor suppressor genes in breast cancer cells.

SOX17 in cellular reprogramming and cancer.

SOX17 is a transcription factor directing the specification and development of the primitive endoderm, primitive germ cells, definitive endoderm and, subsequently, is involved in the cardiovascular system and several endoderm-derived organs. The analysis of cancer genome sequencing data classified SOX17 as mutated cancer driver gene in endometrial cancer. These studies identified hotspot missense mutations within its DNA binding and transactivation domains. In somatic cell reprogramming, structure-based pro...

FANCM, RAD1, CHEK1 and TP53I3 act as BRCA-like tumor suppressors and are mutated in hereditary ovarian cancer.

Although 25% of ovarian cancer cases are due to inherited factors, most of the genetic risk remains unexplained. We previously identified candidate genes through germline whole exome sequencing of BRCA1/BRCA2 negative ovarian cancer patients with familial risk. Here, we performed functional assessment to determine whether they act as BRCA-like tumor suppressors. Seven candidate risk genes were targeted by siRNA for mRNA depletion followed by functional assays for clonogenic survival, cytotoxicity to DNA dam...

Modulation of miR-34a in curcumin-induced antiproliferation of prostate cancer cells.

Curcumin is a phytochemical which exhibits significant inhibitory effect in multiple cancers including prostate cancer. MicroRNA-34a (miR-34a) was found to be a master tumor suppressor miRNA and regulated the growth of cancer cells. To date, however, the role of miR-34a in the anticancer action of curcumin against prostate cancer has been rarely reported. In the present study, we showed that curcumin altered the expression of cell cycle-related genes (cyclin D1, PCNA, and p21) and inhibited the proliferatio...

Cancer-associated mutation abolishes the impact of TRIM21 on the invasion of breast cancer cells.

TRIM21 mediates the ubiquitination and proteasomal degradation of Snail, a master regulator of the epithelial to mesenchymal transition, and suppresses the migration and invasion of breast cancer cells. R64Q, a breast cancer-associated TRIM21 mutation, abolishes the interaction between TRIM21 and Snail, and the TRIM21-mediated ubiquitination and degradation of Snail. More importantly, comparing to the xenograft tumors derived from MDA-MB-231 cells with the wild-type TRIM21, xenograft tumors derived from MDA...

Functional Dominance of CHIP-Mutated Hematopoietic Stem Cells in Patients Undergoing Autologous Transplantation.

Clonal hematopoiesis of indeterminate potential (CHIP) is caused by recurrent somatic mutations leading to clonal blood cell expansion. However, direct evidence of the fitness of CHIP-mutated human hematopoietic stem cells (HSCs) in blood reconstitution is lacking. Because myeloablative treatment and transplantation enforce stress on HSCs, we followed 81 patients with solid tumors or lymphoid diseases undergoing autologous stem cell transplantation (ASCT) for the development of CHIP. We found a high inciden...

Tanshinone IIA-mediated inhibition on miR-125b/STARD13 axis attenuates the stemness and enhances adriamycin sensitivity of breast cancer cells.

The roles of Tanshinone IIA in regulating the stemness of tumor cells remain unclear. This work aims to explore the roles and underlying mechanisms of Tanshinone IIA in breast cancer cell stemness. We found that Tanshinone IIA attenuated the stemness of breast cancer cells, evident by downregulating the expression of stemness markers, hindering the capacity of spheroid formation and decreasing the CD24/CD44 sub-population in a concentration-dependent manner. Additionally, Tanshinone IIA enhanced adriamycin ...


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