Risk of second primary cancer among breast cancer patients: A systematic review and meta-analysis

ObjectivesThe aim of this study was to estimate the extra risk of second primary cancer among breast cancer patients.Methods and materialsThis is a systematic review. A comprehensive search of literature was performed in PubMed, Web of Science, Cochrane library, and Scopus. The search included all published studies up to October 2022. This systematic review included studies published in the English language that reported the risk of second primary non-breast cancer [i.e., standardized incidence ratio (SIR)] among breast cancer patients older than 15 years. After evaluating the methodological quality of the selected studies, SIRs were pooled with consideration of heterogeneity among studies. The estimates were pooled by age and time since the diagnosis of primary breast cancer for both sexes (male and female). Age was categorized based on before 50 years and after 50 years, and time was categorized as duration of less than and more than 10 years, respectively.ResultsFrom 2,484 articles, 30 articles were eligible for inclusion in the systematic review and meta-analysis. The studies varied in terms of population, number of cases, study design, setting, and year of implementation of the research. The estimated SIR for men and women was 1.28 (95% CI: 1.18, 1.38) and 1.27 (95% CI: 1.15, 1.39), respectively. Women diagnosed with breast cancer before menopause [SIR: 1.52 (95% CI: 1.34, 1.71) vs. 1.21 (95% CI: 1.08, 1.34)] as well as women after 10 years since their breast cancer diagnosis [1.33 (95% CI: 1.22, 1.431) vs. 1.24 (95% CI: 1.10, 1.37)] were at a higher risk of developing second primary cancer. Among men, while there were no differences in risk based on age, with the increase of time, the risk of second primary cancer was reduced [SIR: 1.22 (95% CI: 1.12, 1.33) vs. 1.00 (95% CI: 0.79, 1.22)].ConclusionThere is an extra risk of second primary cancer among breast cancer patients. The extra risk should be considered for further screening and preventive measures among this population.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=336062, identifier (CRD42022336062)

ANKRD54 preferentially selects Bruton's Tyrosine Kinase (BTK) from a Human Src-Homology 3 (SH3) domain library

Bruton's Tyrosine Kinase (BTK) is a cytoplasmic protein tyrosine kinase with a fundamental role in B-lymphocyte development and activation. The nucleocytoplasmic shuttling of BTK is specifically modulated by the Ankyrin Repeat Domain 54 (ANKRD54) protein and the interaction is known to be exclusively SH3-dependent. To identify the spectrum of the ANKRD54 SH3-interactome, we applied phage-display screening of a library containing all the 296 human SH3 domains. The BTK-SH3 domain was the prime interactor. Quantitative western blotting analysis demonstrated the accuracy of the screening procedure. Revealing the spectrum and specificity of ANKRD54-interactome is a critical step toward functional analysis in cells and tissues.Peer reviewe

The highly attenuated oncolytic recombinant vaccinia virus GLV-1h68: comparative genomic features and the contribution of F14.5L inactivation

As a new anticancer treatment option, vaccinia virus (VACV) has shown remarkable antitumor activities (oncolysis) in preclinical studies, but potential infection of other organs remains a safety concern. We present here genome comparisons between the de novo sequence of GLV-1h68, a recombinant VACV, and other VACVs. The identified differences in open reading frames (ORFs) include genes encoding host-range selection, virulence and immune modulation proteins, e.g., ankyrin-like proteins, serine proteinase inhibitor SPI-2/CrmA, tumor necrosis factor (TNF) receptor homolog CrmC, semaphorin-like and interleukin-1 receptor homolog proteins. Phylogenetic analyses indicate that GLV-1h68 is closest to Lister strains but has lost several ORFs present in its parental LIVP strain, including genes encoding CrmE and a viral Golgi anti-apoptotic protein, v-GAAP. The reduced pathogenicity of GLV-1h68 is confirmed in male mice bearing C6 rat glioma and in immunocompetent mice bearing B16-F10 murine melanoma. The contribution of foreign gene expression cassettes in the F14.5L, J2R and A56R loci is analyzed, in particular the contribution of F14.5L inactivation to the reduced virulence is demonstrated by comparing the virulence of GLV-1h68 with its F14.5L-null and revertant viruses. GLV-1h68 is a promising engineered VACV variant for anticancer therapy with tumor-specific replication, reduced pathogenicity and benign tissue tropism

Ankyrin domains across the Tree of Life

Ankyrin (ANK) repeats are one of the most common amino acid sequence motifs that mediate interactions between proteins of myriad sizes, shapes and functions. We assess their widespread abundance in Bacteria and Archaea for the first time and demonstrate in Bacteria that lifestyle, rather than phylogenetic history, is a predictor of ANK repeat abundance. Unrelated organisms that forge facultative and obligate symbioses with eukaryotes show enrichment for ANK repeats in comparison to free-living bacteria. The reduced genomes of obligate intracellular bacteria remarkably contain a higher fraction of ANK repeat proteins than other lifestyles, and the number of ANK repeats in each protein is augmented in comparison to other bacteria. Taken together, these results reevaluate the concept that ANK repeats are signature features of eukaryotic proteins and support the hypothesis that intracellular bacteria broadly employ ANK repeats for structure-function relationships with the eukaryotic host cell

Identification of a New Rhoptry Neck Complex RON9/RON10 in the Apicomplexa Parasite Toxoplasma gondii

Apicomplexan parasites secrete and inject into the host cell the content of specialized secretory organelles called rhoptries, which take part into critical processes such as host cell invasion and modulation of the host cell immune response. The rhoptries are structurally and functionally divided into two compartments. The apical duct contains rhoptry neck (RON) proteins that are conserved in Apicomplexa and are involved in formation of the moving junction (MJ) driving parasite invasion. The posterior bulb contains rhoptry proteins (ROPs) unique to an individual genus and, once injected in the host cell act as effector proteins to co-opt host processes and modulate parasite growth and virulence. We describe here two new RON proteins of Toxoplasma gondii, RON9 and RON10, which form a high molecular mass complex. In contrast to the other RONs described to date, this complex was not detected at the MJ during invasion and therefore was not associated to the MJ complex RON2/4/5/8. Disruptions of either RON9 or RON10 gene leads to the retention of the partner in the ER followed by subsequent degradation, suggesting that the RON9/RON10 complex formation is required for proper sorting to the rhoptries. Finally, we show that the absence of RON9/RON10 has no significant impact on the morphology of rhoptry, on the invasion and growth in fibroblasts in vitro or on virulence in vivo. The conservation of RON9 and RON10 in Coccidia and Cryptosporidia suggests a specific relation with development in intestinal epithelial cells

Effect of Aqueous Berberis integerrima Extract on Fatty Liver and Triglyceridemia

Introdution: Nowadays, hyperlipidemia and fatty liver disease are one of the urbanity disorders. Medicinal plants regarding benefit effects traditionally had special role in health of society. So, this study was done to evaluate the effect of Berberis integerrima extract on hypertriglyceridemia and fatty liver disease improvement. Methods: This interventional clinical study was done on 188 patients with hypertriglyceridemia (108 male, 80 female) with the age range of 20-70 years and 21 patients with fatty liver disorder. The patients had received 200-250 ml Berberis integerrima extract before sleep for 45- 60 days without any changes in diet regime, exercise activity and administration of anti-hyperlipidemic drugs. After 60 days, triglyceride levels through experiment and fatty liver grade via sonography were evaluated. SPSS statistical software (ver.16) and statistical tests of t-test and Wilcoxon were used for the result analysis and (P < 0/05) were considered significant. Results Blood Triglyceride levels were 292±34 and 200±31 mg.dl-1 before and after Berberis integerrima extract administration in males; whereas the levels were 258±31 and 175±30 mg.dl-1 before and after Berberis integerrima extract administration in females, which showed significant decrease in both gender (p=0.05). From 21 patients with fatty liver disease after Berberis integerrima extract administration, 6 cases with fatty liver grade II were shown grade I and 15 cases with fatty liver grade I were shown normal grade ( P=0.01 ). Conclusion: Regarding the obtained results, Berberis integerrima extract caused significant decrease in hypertriglyceridemia and fatty liver disorder