Caffeic acid phenethyl ester activates pro-apoptotic and epithelial-mesenchymal transition-related genes in ovarian cancer cells A2780 and A2780cis.

Ovarian cancer is a highly aggressive pathology, displaying a poor prognosis and chemoresistance to classical therapy. The present study was conducted to evaluate the effect of caffeic acid phenethyl ester (CAPE) on survival of ovarian cancer cell lines, A2780 (sensitive to cisplatin) and A2780cis (resistant to cisplatin). MTT assay was used to evaluate cell viability, while the apoptotic processes were examined by flow cytometry and qRT-PCR. A reduction of cell proliferation and activation of the apoptosis was observed in both cell lines. qRT-PCR evaluation demonstrated the activation of the pro-apoptotic genes (BAD, CASP8, FAS, FADD, p53) in both cell lines. The limited therapeutic effect in A2780 cells is explained by the activation of epithelial-mesenchymal transition-related genes (ZEB1, ZEB2, or TGFBB1) as displayed by Ingenuity Network analysis. Overall data suggest that CAPE can be used as an alternative in sensitizing cells to chemotherapy.

The role of histamine and its receptors in breast cancer: from pathology to therapeutic targets.

Breast cancer is the most common malignancy in women, and despite the development of new treatment methods and the decreasing mortality rate in recent years, one of the clinical problems in breast cancer treatment is chronic inflammation in the tumor microenvironment. Histamine, an inflammatory mediator, is produced by tumor cells and can induce chronic inflammation and the growth of some tumors by recruiting inflammatory cells. It can also affect tumor physiopathology, antitumor treatment efficiency, and patient survival. Antihistamines, as histamine receptor antagonists, play a role in modulating the effects of these receptors in tumor cells and can affect some treatment methods for breast cancer therapy; in this review, we investigate the role of histamine, its receptors, and antihistamines in breast cancer pathology and treatment methods.

Expression profiles of miR-196, miR-132, miR-146a, and miR-134 in human colorectal cancer tissues in accordance with their clinical significance : Comparison regarding KRAS mutation.

BACKGROUND: Colorectal cancer (CRC) is among the most widespread malignancies in the world. MicroRNA (miRNA) has been identified as an important modulator of the biological processes of the cells. This group of noncoding RNAs also has a pivotal function in the growth and development of human cancers, including CRC. Among these miRNAs, miR-196, miR-132, miR-146a, and miR-134 have fundamental impacts on the regulation of cancers. The current study aimed to investigate the involvement of these miRNAs in CRC patients. METHODS: In this study, 50 pairs of tumor and tumor margin samples of CRC patients were investigated to assess the expression levels of miR-196, miR-132, miR-146a, and miR-134 in this cancer. For this purpose, firstly, quantitative real-time PCR (qRT-PCR) was applied. Also, KRAS mutation and clinicopathological characteristics of the CRC patients were analyzed in the study groups. RESULTS: The findings demonstrated the overexpression of miR-196 (P-value = 0.0045) and miR-146a (P-value = 0.0033) in tumor tissues compared to controls. Conversely, the expression levels of miR-132 (P-value = 0.00032) and miR-134 (P-value < 0.0001) were downregulated in tumor tissues. Also, miR-146a was the only miRNA with significant expression change in the case of the KRAS gene mutation. Interestingly, the expression ratio of these miRNAs was significantly associated with some of the clinicopathological features of the patients, such as lymph node and distant metastases. CONCLUSION: Our data demonstrated that these miRNAs appear to be promising novel biomarkers for early diagnosis of CRC and may pave the way for the future establishment of novel therapeutic options for CRC.

Rational Development of Liquid Biopsy Analysis in Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is known for its variable clinical behavior and outcome, including heterogeneity in developing relapse or metastasis. Recent data highlighted the potential of somatic mutations as promising biomarkers for risk stratification in RCC. Likewise, the analysis of circulating tumor DNA (ctDNA) for such informative somatic mutations (liquid biopsy) is considered an important advance for precision oncology in RCC, allowing to monitor molecular disease evolution in real time. However, our knowledge about the utility of ctDNA analysis in RCC is limited, in part due to the lack of RCC-appropriate assays for ctDNA analysis. Here, by interrogating different blood compartments in xenograft models, we identified plasma cell-free (cf) DNA and extracellular vesicles (ev) DNA enriched for RCC-associated ctDNA. Additionally, we developed sensitive targeted sequencing and bioinformatics workflows capable of detecting somatic mutations in RCC-relevant genes with allele frequencies ≥ 0.5%. Applying this assay to patient-matched tumor and liquid biopsies, we captured tumor mutations in cf- and ev-DNA fractions isolated from the blood, highlighting the potentials of both fractions for ctDNA analysis. Overall, our study presents an RCC-appropriate sequencing assay and workflow for ctDNA analysis and provides a proof of principle as to the feasibility of detecting tumor-specific mutations in liquid biopsy in RCC patients.

A novel TNFRSF1A gene mutation in a patient with tumor necrosis factor receptor-associated periodic syndrome.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a periodic fever syndrome inherited in an autosomal dominant fashion. It stems from mutations in the TNFRSF1A (accession number: NM_001065) gene expressing the receptor for tumor necrosis factor α. A patient with TRAPS may present with prolonged episodes of fever attacks, abdominal pain, severe myalgia, and painful erythema on the trunk or extremities. Here, we report an 8-year-old boy with febrile attacks occurring every 1-2months and continuing for 3-4days. The patient experienced 40°C-fever attacks without chills. Approximately 80% of fever attacks were accompanied by abdominal manifestations. Direct sequencing analysis was used to assess the genomic DNA of the patient, and a heterozygous R426L mutation in exon 10 of the TNFRSF1A gene in an autosomal dominant inheritance fashion was identified. Further genetic analyses were also carried out on his parents. Due to the fact that the mutation was not inherited from the parents, it was likely that R426L was a de novo and novel mutation in the TNFRSF1A gene, which can trigger TRAPS or TRAPS-like symptoms.

MicroRNAs as regulators of apoptosis mechanisms in cancer.

MicroRNAs or miRNAs are small non-coding RNAs that regulate gene expression. Their discovery has brought new knowledge in biological processes of cancer. Involvement of miRNAs in cancer development includes several major pathways from cell transformation to tumor cell development, metastasis and resistance to treatment. The first part of this review discusses miRNAs function in the intrinsic and extrinsic pathways of apoptosis. Due to the fact that many miRNAs that regulate apoptosis have been shown to play a major role in tumor cell resistance to treatment, in the second part of the review we aim at discussing miRNAs potential in becoming curative molecules.