Selenium in serum and neoplastic tissue in breast cancer: correlation with CEA

Trace element selenium (Se) is regarded to be a breast cancer preventive factor involved in multiple protective pathways. In all, 80 women with breast cancer who underwent a radical mastectomy were enrolled in the study. Serum Se and carcinoembryonic antigen levels were measured using a fluorometric and IRMA assay, respectively. Se tissue concentration was determined by a tissue extracting fluorometric assay. For statistical analysis purposes t-test was used and P-values <0.001 were regarded as statistically significant. Serum Se was 42.5±7.5 μg l−1 in breast cancer patients and 67.6±5.36 μg l−1 in the age-matched control group of healthy individuals. Serum carcinoembryonic antigen in patients was 10±1.7 U ml−1 (normal <2.5 U ml−1 in nonsmokers/<3.5 U ml−1 in smokers). A statistically significant difference was found for both serum Se and CEA between two groups studied (P<0.001). Neoplastic tissue Se concentration was 2660±210 mg g−1 tissue; its concentration in the adjacent non-neoplastic tissue was 680±110 mg g−1 tissue (P<0.001). An inverse relationship between Se and CEA serum levels was found in the two groups studied (r=−0.794). There was no correlation between serum/tissue Se concentration and stage of the disease. The decrease in serum Se concentration as well as its increased concentration in the neoplastic breast tissue is of great significance. These alterations may reflect part of the defence mechanisms against the carcinogenetic process

Ectopic expression of clusterin/apolipoprotein J or Bcl-2 decreases the sensitivity of HaCaT cells to toxic effects of ropivacaine

Journal URL: http://www.nature.com/cr/index.htm

Article chek2 pathogenic variants in greek breast cancer patients: Evidence for strong associations with estrogen receptor positivity, overuse of risk-reducing procedures and population founder effects

CHEK2 germline pathogenic variants predispose to breast cancer and possibly to other malignancies, with their spectrum and frequency being variable among populations. The majority of CHEK2-associated breast tumors are hormone receptor positive; however, relevant clinical outcomes are not well defined. Herein, we illustrate the histopathological characteristics and clinical outcomes of 52 Greek breast cancer patients who are CHEK2 carriers. Genetic analysis was performed by Sanger/massively parallel sequencing, followed by MLPA. Subsequent haplotype analysis investigated possible founder effects. Blood relatives were offered cascade testing. CHEK2 variant spectrum was characterized by variability, while influenced by founder effects. The majority of carriers, i.e., 60.8%, were diagnosed with breast cancer before the age of 45. Notably, 91.5% of breast tumors were hormone receptor positive. Hormone therapy and mastectomy at diagnosis seem to have a positive trend on overall survival, after a median follow-up of 9.5 years. Remarkably, 41.9% of patients underwent risk-reducing surgery, one third of which involved salpingo-oophorectomy. Nearly half of families responded to cascade testing. Our data highlight the need for guideline-adherent choices, based on the evidence that CHEK2 carriers are at moderate risk for breast cancer and no risk for ovarian cancer, while underscore the possible role of chemoprevention with tamoxifen. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

One in three highly selected Greek patients with breast cancer carries a loss-of-function variant in a cancer susceptibility gene

Background Gene panel testing has become the norm for assessing breast cancer (BC) susceptibility, but actual cancer risks conferred by genes included in panels are not established. Contrarily, deciphering the missing hereditability on BC, through identification of novel candidates, remains a challenge. We aimed to investigate the mutation prevalence and spectra in a highly selected cohort of Greek patients with BC, questioning an extensive number of genes, implicated in cancer predisposition and DNA repair, while calculating gene-specific BC risks that can ultimately lead to important associations. Methods To further discern BC susceptibility, a comprehensive 94-cancer gene panel was implemented in a cohort of 1382 Greek patients with BC, highly selected for strong family history and/or very young age (&lt;35 years) at diagnosis, followed by BC risk calculation, based on a case-control analysis. Results Herein, 31.5% of patients tested carried pathogenic variants (PVs) in 28 known, suspected or candidate BC predisposition genes. In total, 24.8% of the patients carried BRCA1/2 loss-of-function variants. An additional 6.7% carried PVs in additional genes, the vast majority of which can be offered meaningful clinical changes. Significant association to BC predisposition was observed for ATM, PALB2, TP53, RAD51C and CHEK2 PVs. Primarily, compared with controls, RAD51C PVs and CHEK2 damaging missense variants were associated with high (ORs 6.19 (Exome Aggregation Consortium (ExAC)) and 12.6 (Fabulous Ladies Over Seventy (FLOSSIES)), p&lt;0.01) and moderate BC risk (ORs 3.79 (ExAC) and 5.9 (FLOSSIES), p&lt;0.01), respectively. Conclusion Studying a large and unique cohort of highly selected patients with BC, deriving from a population with founder effects, provides important insight on distinct associations, pivotal for patient management. © 2020 Author(s) (or their employer(s)). Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Modulation of cisplatin cytotoxic activity against leiomyosarcoma cells by epigallocatechin-3-gallate

<p>The aim of this study was to investigate the cytotoxic effect cisplatin in combination with epigallocatechin-3-gallate (EGCG) on leiomyosarcoma cells (LMS cells) in order to identify a less toxic but equally effective alternative. Assays for cell proliferation, colony formation efficiency, induction of apoptosis and cell cycle arrest were performed using the IC₅₀ of cisplatin (8.6 μΜ) as a reference value and a concentration of EGCG (30 μΜ) that caused a non-significant reduction in cell proliferation. Pre-treatment of cells with EGCG for 24 h before the addition of cisplatin increased cytotoxicity up to 8.5% (<i>p</i> < 0.05) and the number of apoptotic cells by 40%. Epigallocatechin-3-gallate failed to alter S-phase cell cycle arrest induced by cisplatin and to modulate cisplatin effects on mitochondrial function. These results indicate that pre-treatment with EGCG could be used as an adjunctive therapy to maximise effectiveness of chemotherapy.</p

BRCA1 and BRCA2 germline testing in Cretan isolates reveals novel and strong founder effects

Germline BRCA1 and BRCA2 loss-of-function variants have been linked to increased breast and ovarian cancer risk, with more than 5,000 distinct pathogenic variants being reported worldwide. Among individuals of Greek descent, the BRCA1/2 variant spectrum is heterogeneous, but characterized by strong founder effects. As patients from certain geographical regions of Greece (like Crete) were underrepresented in previous studies, we hypothesized that isolated Cretans, a southern Greece islanders' population with distinct demographic, cultural and genetic features, could harbor founder BRCA1/2 mutations. A total of 304 breast or/and ovarian cancer patients of Cretan descent, fulfilling NCCN criteria for genetic testing, were tested by NGS or Sanger sequencing, followed by MLPA. Haplotype analysis was subsequently performed to investigate potential founder effects of recurrent alleles. Overall, 16.5% (50/304) of the tested patients carried 22 different pathogenic variants; 48% in BRCA1, 52% in BRCA2. Three variants, namely two in BRCA2 (Δexons 12 and 13 and c.7806-2A>T) and one in BRCA1 (c.5492del), constituting approximately half (48%) of all detected pathogenic variants, were shown to have a founder effect, with all carriers sharing common haplotypes. Remarkably, these variants were confined to Cretans and have not been identified in other regions of Greece. The high prevalence of specific BRCA1/2 pathogenic variants among Cretans, provides the possibility of cost- and time-efficient screening of the Cretan population. Integrating this knowledge in local public health services may have a significant impact on cancer prevention, and may serve as a starting point for the implementation of testing on a population level. © 2020 UIC