Mutational landscape implicates epithelial-mesenchymal transition gene TGF-β2 mutations for uterine carcinosarcoma after adjuvant tamoxifen therapy for breast carcinoma.

Uterine carcinosarcoma (UCS) is a rare aggressive malignancy. Several reports previously described UCS occurring after tamoxifen therapy for breast carcinoma. However, the genetic landscape of tamoxifen-related UCS remains unclear.

Germline genetic patterns underlying familial rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren's syndrome highlight T cell-initiated autoimmunity.

Objectives: Familial aggregation of primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and co-aggregation of these autoimmune diseases (ADs) (also called familial autoimmunity) is well recognised. However, the genetic predisposition variants that explain this clustering remains poorly defined.

Methods: We used whole-exome sequencing on 31 families (9 pSS, 11 SLE, 6 RA and 5 mixed autoimmunity), followed by heterozygous filtering and cosegregation analysis of a family-focused approach to document rare variants predicted to be pathogenic by analysis.

Whole-Exome Sequencing Reveals Frequent Mutations in Chromatin Remodeling Genes in Mammary and Extramammary Paget's Diseases.

Paget's disease (PD) is an intraepidermal adenocarcinoma of the skin at the breast (mammary PD) or urogenital locations (extramammary PD [EMPD]). At present, there is lack of clarity on PD's pathogenesis, the relationship between its subtypes, and its lineage link with the underlying invasive carcinomas. Here we describe that mammary PD and EMPD have similar mutational profiles, with the most frequent recurrent mutations occurring in the chromatin remodeling genes, such as KMT2C (MLL3, 39%) and ARID2 (22%), with additional recurrent somatic mutations detected in genes previously not known to be mutated in cancers, such as CDCC168 (34%), FSIP2 (29%), CASP8AP2 (29%), and BIRC6 (24%).

Transcriptome analyses reveal FOXA1 dysregulation in mammary and extramammary Paget's disease.

Paget's disease (PD) is an uncommon intraepithelial adenocarcinoma with unknown pathogenesis. There are two anatomic subtypes: mammary (MPD) and extramammary (EMPD). Little is known about their molecular characteristics.

Mammary and Extramammary Paget's Disease Presented Different Expression Pattern of Steroid Hormone Receptors.

Background And Objectives: Paget's disease (PD) is a rare intraepithelial adenocarcinoma, which is composed of mammary (MPD) and extramammary Paget's disease (EMPD). Currently, the published literature contains scant data on expression pattern of steroid hormone receptors in MPD and EMPD.

Methods: Expression of estrogen receptor (ER) and androgen receptor (AR) was evaluated in 88 MPD and 72 EMPD by using immunohistochemical staining and H-score method.

Genotype Distribution of Human Papillomavirus among Women with Cervical Cytological Abnormalities or Invasive Squamous Cell Carcinoma in a High-Incidence Area of Esophageal Carcinoma in China.

Data of HPV genotype including 16 high-risk HPV (HR-HPV) and 4 low-risk HPV from 38,397 women with normal cytology, 1341 women with cervical cytology abnormalities, and 223 women with ISCC were retrospectively evaluated by a hospital-based study. The prevalence of high-risk HPV (HR-HPV) was 6.51%, 41.

Effect of 1,25-dihydroxyvitamin D3 on mast cells tryptase in asthmatic guinea pigs.

Objective: To explore the effect of 1,25-dihydroxyvitamin D3 on the mast cell tryptase (MCT) in asthmatic guinea pigs.

Methods: A total of 60 male or female healthy guinea pigs were randomly divided into control group (group A), asthmatic group (group B), and 1,25-dihydroxyvitamin D3 group (group C), with 20 cases in each group. To establish asthmatic guinea pig models, 1 mL peanut oil was filled into stomach in the morning in group A and group B, and 1 mL peanut oil with 1,25-dihydroxyvitamin D3 was filled into stomach in group C.

Therapeutic efficacy of combined BRAF and MEK inhibition in metastatic melanoma: a comprehensive network meta-analysis of randomized controlled trials.

Background: Several recent randomized clinical trials have preliminarily demonstrated that initial targeted therapy with combined BRAF and MEK inhibition is more effective in metastatic melanoma (MM) than single agent. To guide therapeutic decisions, we did a comprehensive network meta-analysis to identify evidence to robustly support whether combined BRAF and MEK inhibition is the best initial targeted therapeutic strategy for patients with MM.

Methods: The databases of PubMed and trial registries were researched for randomized clinical trials of targeted therapy.

Levels of microRNA-181b and plasminogen activator inhibitor-1 are associated with hypertensive disorders complicating pregnancy.

The aim of the present study was to explore the association between the expression of microRNA (miRNA)-181b and plasminogen activator inhibitor-1 (PAI-1) in the placental tissue of pregnant females with a hypertensive disorder complicating pregnancy (HDCP). Placental tissue samples were obtained from 48 patients with HDCP and 40 females with a normal pregnancy. The levels of miRNA-181b and PAI-1 mRNA were determined by the reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

Synchronous uterine carcinosarcoma and contralateral breast cancer after tamoxifen therapy: a case report.

Uterine carcinosarcoma (malignant mixed Müllerian tumor, MMMT) is a rare aggressive malignant tumor, which demonstrates both malignant epithelial (carcinoma) and mesenchymal (sarcoma) components. Synchronous uterine carcinosarcoma and contralateral breast cancer in patient received tamoxifen treatment had not been reported. We present a case of uterine carcinosarcoma co-occurrenced with contralateral breast cancer in a 56-year-old nulliparous, obese breast cancer patient, who had been treated with tamoxifen for 5 years.

Genotype distribution of human papillomavirus in women with abnormal cervical cytology in an esophageal carcinoma high incidence area of China.

Infection with human papillomavirus (HPV) could affect genesis of both cervical and esophageal cancers. The type-specific distribution of HPV in cervical cytology abnormalities of women has remained unclear in Shantou, an esophageal cancer high-incidence area of China. Data from 22,617 women who were subjected to cervical HPV DNA testing with simultaneous cervical cytological examination during 2009-2013 were therefore here retrospectively evaluated in a hospital-based study.

Esophageal squamous cell carcinoma and gastric cardia adenocarcinoma shared susceptibility locus in PLCE1: a meta-analysis.

Background And Objective: Two recent genome-wide association studies have identified a shared susceptibility variation PLCE1 rs2274223 for esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA). Subsequent case-control studies have reported this association in other populations. However, the findings were controversial and the effect remains undetermined.

Alcohol dehydrogenase-1B Arg47His polymorphism and upper aerodigestive tract cancer risk: a meta-analysis including 24,252 subjects.

Background: Cancers of the upper aerodigestive tract (UADT) include malignant tumors of the oral cavity, pharynx, larynx, and esophagus, account for approximately 4% of all new cancers in world. Alcohol drinking is an established risk factor for UADT cancers, and the rate of alcohol metabolism could significantly been influenced by genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) His47Arg (rs1229984). To evaluate whether combined evidence shows ADH1B His47Arg as a common genetic variant that influenced the risk of UADT cancers, we considered all available studies in a meta-analysis.

Meta-analysis of ADH1B and ALDH2 polymorphisms and esophageal cancer risk in China.

Aim: To evaluate whether alcohol dehydrogenase-1B (ADH1B) His47Arg and aldehyde dehydrogenase-2 (ALDH2) Glu487Lys polymorphism is involved in the esophageal squamous cell carcinoma (ESCC) risk in Chinese Han population.

Methods: Seven studies of ADH1B and ALDH2 genotypes in Chinese Han population in 1450 cases and 2459 controls were included for meta-analysis. Stratified analyses were carried out to determine the gene-alcohol and gene-gene interaction with ESCC risk.

ADH1B Arg47His polymorphism is associated with esophageal cancer risk in high-incidence Asian population: evidence from a meta-analysis.

Background And Objectives: Incidence of Esophageal squamous cell carcinoma (ESCC) is prevalent in Asian populations, especially in the ones from the "Asian esophageal cancer belt" along the Silk Road and the ones from East Asia (including Japan). Silk Road and Eastern Asia population genetics are relevant to the ancient population migration from central China. The Arg47His (rs1229984) polymorphism of ADH1B is the highest in East Asians, and ancient migrations along the Silk Road were thought to be contributive to a frequent ADH1B*47His allele in Central Asians.

Hypoxia-inducible factor-1alpha induces the coronary collaterals for coronary artery disease.

Background: Marked variability exists in coronary artery collaterals in patients with ischemic heart disease. Multiple factors are thought to play a role in collateral development; however, the contribution of hypoxia inducible factor-1alpha (HIF-1alpha), which is a transcriptional activator that functions as a master regulator of oxygen homeostasis, is not completely clear. It could play an important role in modulating collateral development.