Polymorphism of Prolactin Gene and Its Association with Egg Production Trait in Four Commercial Chicken Lines

Δε διατίθεται περίληψη στα ελληνικάBroodiness is a behavioral trait observed in most common breeds of domestic fowl and due to its fundamental role in avian reproduction, it has been of great interest to poultry scientists, breeders and producers of hatching eggs. Prolactin gene (PRL) is generally accepted as crucial to the onset and maintenance of broodiness in birds and thus plays a crucial role in egg production. Therefore, the present study aimed to screen the Single Nucleotides Polymorphisms (SNPs) of prolactin gene in four commercial chicken lines namely Hubbard F15, Lohmann, Cobb500, and Avian48 using PCR and direct sequencing. A total number of forty chickens (ten females from each of the four commercial chicken lines) were used. Blood samples were collected aseptically from brachial (wing) vein of the chickens for genomic DNA extraction. PCR reaction was done using five pairs of primers, one sense (F) and one antisense (R) primer for each of the five exons of prolactin gene. Finally, DNA sequencing and Single Nucleotide Polymorphisms (SNPs) analysis was done using Laser gene Megalign program. The results showed three SNPs in Hubbard F15 chicken line; one synonymous SNP at the position 3838 bp (ACC/ACT-transition) in exon 2 while in exon 5, two SNPs were detected; one non-synonymous single nucleotide polymorphism at the position 7921bp (CCT/TCT-transition) which results in amino acid changes at codon positions 169 (P/S), and one synonymous single nucleotide polymorphism at the position 8187 bp T/ C. The study concluded that this SNP in PRL gene could be used as the potential molecular markers for egg production traits in chicken

Accurate metaheuristic deep convolutional structure for a robust human gait recognition

Gait recognition has become a developing technology in various security, industrial, medical, and military applications. This paper proposed a deep convolutional neural network (CNN) model to authenticate humans via their walking style. The proposed model has been applied to two commonly used standardized datasets, Chinese Academy of Sciences (CASIA) and Osaka University-Institute of Scientific and Industrial Research (OU-ISIR). After the silhouette images have been isolated from the gait image datasets, their features have been extracted using the proposed deep CNN and the traditional ones, including AlexNet, Inception (GoogleNet), VGGNet, ResNet50, and Xception. The best features were selected using genetic, grey wolf optimizer (GWO), particle swarm optimizer (PSO), and chi-square algorithms. Finally, recognize the selected features using the proposed deep neural network (DNN). Several performance evaluation parameters have been estimated to evaluate the model’s quality, including accuracy, specificity, sensitivity, false negative rate (FNR), and training time. Experiments have demonstrated that the suggested framework with a genetic feature selector outperforms previous selectors and recent research, scoring accuracy values of 99.46% and 99.09% for evaluating the CASIA and OU-ISIR datasets, respectively, in low time (19 seconds for training)

Tall Cell Carcinoma with Reversed Polarity:Case Report of a Rare Special Type of Breast Cancer and Review of the Literature

Background: Tall cell carcinoma of the breast with reversed polarity (TCCRP) is a rare type of invasive breast cancer with overlapping features with papillary thyroid carcinoma and a characteristic molecular profile. Few cases have been reported in the literature since the first case was described in 2003. Case presentation: We present the case of a 41-year-old female with a symptomatic left breast lump. Image-guided core biopsy was diagnosed as triple-negative apocrine carcinoma. Surgical excision revealed an invasive carcinoma with solid papillary pattern, nuclei arranged away from the basement membrane (reversed polarity) and luminal eosinophilic colloid-like material. The tumour was GATA3-, CK5-, CK14- and CK7-positive and TTF1-negative. Specialist opinion and the identification of hotspot mutations in the IDH2 p.Arg172 gene via PCR confirmed the diagnosis of TCCRP. Conclusions: TCCRP is a relatively recently recognised papillary epithelial neoplasm with characteristic morphological features and molecular profile. Due to its rarity, TCCRP can be diagnostically challenging, and features can be mistaken for benign and malignant lesions. Accurate diagnosis is important in effective treatment of this indolent malignant triple-negative breast cancer, which carries an excellent prognosis

Concordance between ER, PR, Ki67, and HER2‐low expression in breast cancer by MammaTyper RT‐qPCR and immunohistochemistry:implications for the practising pathologist

Background: There are limited data on the role of multigene tests and their correlation with immunohistochemistry (IHC), especially on core biopsy. MammaTyper is a quantitative conformite Europeeanne (CE) marked, National Institute for Health and Care excellence (NICE) approved, in in vitro diagnostic quantitative real‐time polymerase chain reaction (RT‐qPCR) test for assessment of mRNA expression of four biomarkers (ESR1, PGR, ERBB2, MKI67).Methods: We evaluated the concordance of MammaTyper with oestrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 by IHC on 133 core needle biopsies of breast cancer. HER2 was positive if IHC 3+ or 2+ and fluorescence in situ hybridization (FISH)‐amplified. Global and hotspot Ki67 expression was analysed using a cutoff of ≥20% assessed manually and by digital image analysis. Agreements were expressed as overall percent agreement (OPA), positive percent agreement (PPA), negative percent agreement (NPA), and Cohen's kappa. Results: RT‐qPCR results of ESR1 were highly concordant with IHC with OPA of 94.7% using 1% cutoff and 91.7% when the low ER‐positive category was included. The PPA and NPA between RT‐qPCR and IHC for PR was 91.5% and 88.0%, respectively, when using the 1% cutoff. For ERBB2/HER2, the OPA was 95% and the PPA was 84.6%. 40 of 72 HER2 IHC score 0 tumours were classified as ERBB2 low. Best concordance between MKI67 by MammaTyper and Ki67 IHC was achieved using hotspot digital image analysis (OPA: 87.2%, PPA: 90.6%, NPA: 80%).Conclusion: RT‐qPCR‐based assessment of the mRNA expression of ESR1, PGR, ERBB2, and MKI67 showed high concordance with IHC, suggesting that the MammaTyper test on core needle biopsies represents a reliable, efficient, and reproducible alternative for breast cancer classification and refining HER2 low categorisation

Heterogeneity of germline variants in high risk breast and ovarian cancer susceptibility genes in India

Breast and ovarian cancers now account for one in three cancers in Indian women and their incidence is rising. Major differences in the clinical presentation of breast and ovarian cancers exist between India and the United Kingdom. For example, Indian patients with breast cancer typically present a decade earlier than in the UK. Reasons for this could be multifactorial, including differences in underlying biology, environmental risks, and other systematic factors including access to screening. One possible explanation lies in variable incidence or penetrance of germline mutations in genes such as BRCA1 and BRCA2. We performed a methodical database and literature review to investigate the prevalence and spectrum of high-risk cancer susceptibility genes in Indian patients with breast and ovarian cancers. We identified 148 articles, but most studies were small, with inconsistent inclusion criteria and based on heterogeneous technologies, so that mutation frequency could not be reliably ascertained. Data were also often lacking on penetrance, histopathology, and survival outcomes. After filtering out unsuitable studies, only 13 remained, comprising 1028 patients. Large-scale research studies are urgently needed to determine mutation prevalence, spectra, and clinico-pathological features, and hence derive guidelines for screening, treatment, and prevention specific to the Indian population

Profiling of Tumour-Infiltrating Lymphocytes and Tumour-Associated Macrophages in Ovarian Epithelial Cancer:Relation to Tumour Characteristics and Impact on Prognosis

Early evidence suggests a strong impact of tumour-infiltrating lymphocytes (TILs) on both the prognosis and clinical behaviour of ovarian cancer. Proven associations, however, have not yet translated to successful immunotherapies and further work in the field is urgently needed. We aimed to analyse the tumour microenvironment of a well-characterised cohort of ovarian cancer samples. Tumour markers were selected owing to their comparative underrepresentation in the current literature. Paraffin-embedded, formalin-fixed tumour tissue blocks of 138 patients representative of the population and including early stage disease were identified, stained for CD3, CD20, CD68 and CD163 and analysed for both the stromal and intertumoral components. Data were statistically analysed in relation to clinical details, histological subtype, borderline vs. malignant status, survival and management received. Mean stromal CD3, total CD3 count, mean stromal CD20 and total CD20 count all correlated negatively with survival. Malignant ovarian tumours consistently demonstrated significantly higher infiltration of all analysed immune cells than borderline tumours. Assessment of the stromal compartment produced a considerably higher proportion of significant results when compared to the intra-tumoural infiltrates. Customary assessment of solely intra-tumoural cells in advanced stage disease patients undergoing primary debulking surgery should be challenged, with recommendations for future scoring systems provided

TEM8/ANTXR1-specific CAR T cells mediate toxicity in vivo

Engineering T-cells to express receptors specific for antigens present on tumour tissue is proving a highly effective treatment for some leukaemias. However, extending this to solid tumours requires antigens that can be safely and effectively targeted. TEM8, a marker overexpressed on the vasculature of some solid tumours, has been proposed as one such target. A recent report stated that T-cells engineered to express a TEM8-specific chimeric antigen receptor (CAR), when injected into mouse models of triple negative breast cancer, are both safe and effective in controlling tumour growth. Here we report contrasting data with a panel of TEM8-specific CAR-T-cells including one generated from the same antibody used in the other study. We found that the CAR-T-cells demonstrated clear TEM8-specific cytotoxic and cytokine release responses in vitro, but when injected into healthy C57BL6 and NSG mice they rapidly and selectively disappeared from the circulation and in most cases caused rapid toxicity. Infusing CAR-T-cells into a TEM8-knockout mouse indicated that selective loss of cells from the circulation was due to targeting of TEM8 in healthy tissues. Histological analysis of mice treated with a TEM8-specific CAR revealed evidence of inflammation in the lung and spleen with large collections of infiltrating neutrophils. Therefore our data raise concerns over potential on-target off-tumour toxicity with CARs targeting TEM8 and these should be considered carefully before embarking upon clinical trials with such agents

Loss of CSMD1 expression is associated with high tumour grade and poor survival in invasive ductal breast carcinoma

International audienceCUB and SUSHI multiple domain protein 1 () is a candidate tumour suppressor gene that maps to chromosome 8p23, a region deleted in many tumour types including 50% of breast cancers. CSMD1 has homologies to proteins implicated in carcinogenesis. We aimed to study the expression pattern of the CSMD1 protein and evaluate its prognostic importance in invasive ductal carcinoma (IDC). An anti-CSMD1 antibody was developed and validated. The expression pattern of CSMD1 in normal breast and IDC samples was investigated by immunohistochemistry in 275 patients. Univariate and multivariate Cox regression analyses were performed. In normal breast duct epithelial cells, luminal, membranous and cytoplasmic CSMD1 staining was identified. Reduced expression of CSMD1 was detected in 79/275 (28.7%) of IDC cases. Low CSMD1 expression was significantly associated with high tumour grade ( = 0.003). CSMD1 expression was associated with overall survival (OS; HR = 0.607, 95%CI: 0.4-0.91,  = 0.018) but not with disease-free survival (DFS; HR = 0.81, 95%CI: 0.46-1.43,  = 0.48). Multivariate analysis showed that CSMD1, together with Nottingham Prognostic Index, was considered an independent predictor of OS (HR = 0.607, 95%CI: 0.4-0.91,  = 0.018) but not DFS (HR = 0.84, 95%CI: 0.46-1.5,  = 0.573). Reduction of CSMD1 expression was significantly associated with high tumour grade and decreased OS. Therefore, our results support the idea that is a tumour suppressor gene and suggest its possible use as a new prognostic biomarker. The membrane expression pattern of CSMD1 suggests that it may be a receptor or co-receptor involved in the process of signal transduction