Histone deacetylase inhibitors dysregulate DNA repair proteins and antagonize metastasis-associated processes

ConclusionHDACi suppress the epithelial –mesenchymal transition (EMT) and compromise the DNA integrity of cancer cells. These data encourage further testing of HDACi against tumor cells.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research

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Conclusions: Our findings demonstrate that Regorafenib enhanced radiosensitivity of breast cancer cells by inhibiting the expression of multiple receptor tyrosine kinases, VEGF-mediated angiogenesis and DNA damage response in TNBC. Therefore, combining Regorafenib with radiation and antiangiogenic agents will be beneficial and effective in controlling TNBC. PMID: 32052681 [PubMed - as supplied by publisher]
Source: International Journal of Radiation Biology - Category: Radiology Tags: Int J Radiat Biol Source Type: research
RARITAN, N.J., February 3, 2020 – The Janssen Pharmaceutical Companies of Johnson &Johnson announced today multiple data presentations from a robust solid tumor portfolio that will be featured at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, taking place February 13-15 in San Francisco. Company-sponsored data presentations will include clinical results for ERLEADA® (apalutamide) and niraparib in prostate cancer; and BALVERSA™ (erdafitinib) in bladder cancer. “We are committed to improving outcomes in patients with prostate and bladder cancer where high unmet ...
Source: Johnson and Johnson - Category: Pharmaceuticals Tags: Innovation Source Type: news
CONCLUSION: HDACi suppress the epithelial-mesenchymal transition (EMT) and compromise the DNA integrity of cancer cells. These data encourage further testing of HDACi against tumor cells. PMID: 31932908 [PubMed - as supplied by publisher]
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: J Cancer Res Clin Oncol Source Type: research
Abstract Cancer stem cell like cells (CSCs) present a challenge in the management of cancers due to their involvement in the development of resistance against various chemotherapeutic agents. Over expression of ABCG2 transporter gene is one of the factors responsible for drug resistance in CSCs, which causes efflux of therapeutic drugs from these cells. The development of inhibitors against CSCs has not achieved any significant success, till date. In this work, we have evaluated the anti-proliferative activity of curcumin (Cur) and quinacrine (QC) against CSCs using in vitro model system. Cur and QC synergisticall...
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research
In this study, PC4 downregulation was observed in a significant proportion of mammary tissues obtained from Breast cancer patient samples as well as in a subset of highly invasive and metastatic Breast cancer patient-derived cell lines. We have identified a miRNA, miR-29a which potentially reduce the expression of PC4 both in RNA and protein level. This miR-29a was found to be indeed overexpressed in a substantial number of Breast cancer patient samples and cell lines as well, suggesting one of the key mechanisms of PC4 downregulation. Stable Knockdown of PC4 in MCF7 cells induced its migratory as well as invasive properti...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
ConclusionTogether, our results suggest that high expression ofPRKDC facilitates breast cancer cell growth via regulation of p38 MAPK signaling, and is a prognostic marker for poor survival in breast cancer patients.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research
Abstract Homologous recombination deficiency conferred by alterations in BRCA1 or BRCA2 are common in breast tumors and can drive sensitivity to platinum chemotherapy and PARP inhibitors. Alterations in nucleotide excision repair (NER) activity can also impact sensitivity to DNA damaging agents, but NER activity in breast cancer has been poorly characterized. Here, we apply a novel immunofluorescence-based cellular NER assay to screen a large panel of breast epithelial and cancer cell lines. Although the majority of breast cancer models are NER proficient, we identify an example of a breast cancer cell line with p...
Source: DNA Repair - Category: Genetics & Stem Cells Authors: Tags: DNA Repair (Amst) Source Type: research
In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, our observations suggest epithelial CTSS expression may be prognostic of improved outcome in TNBC. Improved outcome observed with HER2+ at the gene expression level furthermore suggests CTSS may be prognostic of improved outcome in ER- cancers as a whole. Lastly, from the context of these patients receiving adjuvant therapy and as a result of its association with BL1 subgroup CTSS may be elevated in patients with defects in DNA damage repair pathways, indicating it may be predictive of tumour sensitivity to DNA damaging agents. PMID: 31346333 [PubMed]
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
In this study, we investigated the molecular mechanisms by which the human TNBC cell line MDA-MB-231, expressing PD-L1, responds to atezolizumab, using RNA-Seq. Transcriptome analysis revealed 388 upregulated and 362 downregulated genes in response to atezolizumab treatment. The expression of selected genes, from RNA-Seq data, was subsequently validated using RT-qPCR in the MDA-MB-231 and MDA-MB-468 TNBC cells following atezolizumab treatment. Bioinformatics analysis revealed that atezolizumab downregulates genes promoting cell migration/invasion and metastasis, epithelial-mesenchymal transition (EMT), cell growth/prolifer...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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