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Background: In this study, the role of claudins in cancer progression was explored among breast cancer-affected women.Methodology: Two cohorts (discovery and validated) of breast cancer-affected women were used. In discovery cohort, 90 freshly excised breast tumor tissues along with adjacent cancer free specimens were collected at the time of surgery. These specimens were processed for RNA isolation and complementary DNA synthesis. After designing primers for claudin 3, claudin 4, and claudin 7, these sequences were synthesized from Macrogen, Korea. Claudin expression in respective tumors and controls was assessed using quantitative reverse transcription polymerase chain reaction. Any probable correlation of these molecules with various clinicopathological parameters was explored. For validation, a publicly available dataset of 2088 breast cancer patients was accessed. Claudin expression of these patients was analyzed for given clinical parameters and compared with earlier findings of discovery cohort.Results: Discovery cohort comprised 17% luminal A, 63% luminal B, 8% human epidermal growth factor receptor 2 enrich, and 12% triple-negative breast cancer tumor. High claudin 3 expression was significantly correlated with tumor size >2 cm and menopausal status. Claudin 7 expression was upregulated among poorly differentiated tumor patients. Both claudins 3/4 showed significant correlation with tumor grade, stage, size, and metastasis. Claudin-low subtype was also found in 18% of the cohort.Conclusion: Claudins impart a significant role in cell differentiation and disease progression. Hence, claudin cluster can be ascertained as the disease biomarkers for breast cancer. [ABSTRACT FROM AUTHOR]

Circadian clock associates with several cellular processes, which are important in molecular carcinogenesis. Accordingly, aberrant expression of BMAL1 and CLOCK (core components of circadian pathway) has been identified in cancers. In present study, transcript expression of BMAL1 and CLOCK was assessed, and proteins interactions were mapped, in colorectal cancer (CRC). Low BMAL1 gene expression was observed in tumors as compared to normal tissue samples from GSE39582, GSE21510 and TCGA publicly available datasets for CRC. BMAL1 and CLOCK were suppressed in APC low (WNT activated) and MYC high tumors. Moreover, BMAL1 was slightly upregulated in TGFß-activated and BRAF-mutated tumors, whereas CLOCK was overexpressed in KRAS-mutated tumors. Protein interaction network of the core circadian molecules identified important CRC-related proteins physically associating with BMAL1 and CLOCK. Therefore, expressional correlation of circadian drivers with frequently altered pathways in CRC as well as interactions of BMAL1 and CLOCK with physiologically functional proteins highlight their importance in CRC while paving way for in depth study of circadian pathway in oncogenesis. [ABSTRACT FROM AUTHOR]

YAP1 plays a key role as a transcriptional coactivator in the Hippo pathway. Based on conflicting reports regarding YAP1 function in cancer, this study discerned its role in breast carcinogenesis. First, a systematic review of salient breast cancer studies targeting YAP1 dysregulation was performed. Additionally, freshly excised tumor specimens of approximately 200 breast cancer patients were processed for quantification of YAP1 expression at mRNA and protein levels using quantitative PCR and immunohistochemistry, respectively. YAP1 expression was nine folds higher in tumors versus controls and significantly associated with metastasis (p < 0.05) and poor survival in Pakistani breast cancer patients. These findings establish the role of YAP1 overexpression in tumorigenesis and metastasis. Hence, YAP1 inhibition may be considered a possible therapeutic strategy. [ABSTRACT FROM AUTHOR]

The article focuses on coronaviridae family is a broad emerging group of Ribonucleic Acid viruses that has affected humans repeatedly in the past few decades. Topics include the coagulation dysfunction is leading to life-threatening complications as disseminated intravascular coagulation and multiple organ failure in some patients, the diagnosis and treatment intervention are pivotal to management, and the limitations are of concern in resource-limited developing countries as Pakistan.

Background: The Coronavirus disease (COVID-19) pandemic has shaken the world. So far, CT has emerged as main stay of imaging whereas the local data on radiographic features of COVID-19 is sparse. Methods: Prospective study includes 402 chest X rays (CXRs) of 105 patients presenting with symptoms of COVID-19. The nature of abnormality, distribution and lung zone involvement was documented. Following British Society of Thoracic Imaging (BSTI) guidelines, CXRs were grouped into classic/ probable COVID-19, indeterminate, non-COVID-19 and normal categories. The lung involvement was scored according to modified Radiographic Assessment of Lung Edema (RALE) scoring. The follow up radiographs were assessed for disease progression and improvement. Results: Seventy-six males and 29 females with mean age of 50 years were included in our study. 47 out of 105 baseline radiographs were categorized as classic/ probable COVID-19, 26 as indeterminate, 7 as Non-COVID-19 and 25 as normal. 75 patients were positive and 30 were negative on RT-PCR testing. The sensitivity of CXR in diagnosing COVID-19 is 84%. The worsening radiographic features and higher RALE score correlates with longer hospital stay, ICU admissions and mortality. The ground glass opacities and consolidations in peripheral distribution involving bilateral mid and lower zones are the predominant findings of COVID-19 in Pakistani population. Conclusion: Combination of bilateral peripheral ground glass opacities and consolidations are the cardinal feature of COVID-19 on CXRs. The diagnostic categories described by BSTI correlates with PCR results in Pakistani population. The worsening radiographic findings correspond to poor prognosis; hence serial radiographs can be used for assessing disease course. [ABSTRACT FROM AUTHOR]

Background: Initiation, promotion, progression, and metastasis of mammary tumors are mediated by dysregulation of multiple genes involved in various signaling pathways. Expressional variation of these molecules significantly influences cancer cell proliferation in breast cancer.Aims and Objectives: In the current study, tumor necrosis factor-alpha (TNF-α) and its downstream effector nuclear factor kappa-B1 (NF-κB1) mean transcript levels were explored and associated with molecular subtypes in breast cancer cohort of Pakistan. Freshly excised tumors (n = 150) along with background tissues were collected for RNA isolation and cDNA synthesis.Materials and Methods: Quantitative polymerase chain reaction was carried out for quantification of TNF-α, NF-κB1, and β-actin gene transcripts along with estrogen receptor, progesterone receptor, HER2, and Ki-67, followed by statistical analysis.Results: For TNF-α and NF-κB1, 95% and 77% of the cohort was found to be positive, respectively. Both of these molecules were found to be significantly upregulated in tumors when compared against their respective controls (P < 0.0001). Association of TNF-α and NF-κB1 with late clinical stages, poorly differentiated tumors, increased tumor size, nodal involvement, and metastasis was observed to be statistically significant (P < 0.05). Strong positive correlation was established between TNF-α and NF-κB1(r = 0.465, P< 0.05). Moreover, mean transcript levels of TNF-α and NF-κB1 were significantly elevated in Luminal A and Luminal B subtypes of breast cancer patients, respectively.Conclusion: Strong positive correlation between TNF-α and NF-κB1 proposed the putative role of these molecules as prognostic biomarkers in breast cancer. [ABSTRACT FROM AUTHOR]

Background: Genetic and expression anomaly of HER-2 have been frequently observed in different cancers. However, an overall association of HER-2 polymorphism (Ile655Val) with available cancer studies has not yet been explored. In the present study, a probable correlation of HER-2 Ile655Val polymorphism with 6 major types of cancers including breast, lung, gastric, ovarian, thyroid and uterine has been collectively assessed. Methodology: Extensive data mining was performed using online available medical research databanks including Pubmed, Ovid, Med-line and Embase. Research articles were retrieved based on common keywords "HER-2, polymorphism, (SNP) and cancer (including breast, gastric, lung, ovarian, thyroid and uterine). A database was maintained and updated for case control studies of HER-2 genotype Ile655Val (rs1136201) information until February 2015. Based on selection criteria, a total of 41 studies containing 37,111 subjects (17845 patients, 19266 controls) were selected for thorough insight about HER-2. Results: A significant risk association of HER-2 He655Val polymorphism was observed in different types of cancer using various genetic models (co-dominant heterogeneous Ile/Val vs. He/He; OR=1.1, 95% Cl = 1.01-1.16, P = 0.01 and dominant; OR = 1.12, 95% Cl = 1.03-1.20, P = 0.0003). Interestingly, a strong correlation of Ne655Val heterogeneity was seen in the stratified subgroup of different population including African-American (co-dominant homogenous Val/Val vs. He/He; OR = 8.7, 95% Cl = 2.5-30.4, P = 0.0001, dominant; OR = 1.3, 95% Cl = 1.03-1.7, P = 0.003; recessive; OR = 8.3, 95% Cl = 2.4-28, P = 0.0002), Caucasians (co-dominant heterogeneous Ile/Val vs lie/ lie; OR = 1.1, 95% Cl = 1.0-1.2, P= 0.03, dominant; OR = 1.12, 95% Cl = 1.0-1.2, P = 0.01). However, in Asian ethnic group, Ne655Val polymorphism lacked a significant association with cancer. This may be attributed to limited studies explored so far. Conclusion: In summary, the current study reveals a significant association between cancer susceptibility and the HER-2 He655Val polymorphism in all genetic models. [ABSTRACT FROM AUTHOR]

Aim Of Study: Increased expression of human epidermal growth factor receptor type 2 (HER2) is significantly associated with poor prognosis in breast cancer patients. However, data on HER2 at transcript levels in Pakistani mammary tumor affected females is still limited. In the current study, HER2 transcripts were explored in breast cancer cohort and correlated with various clinical parameters.Materials and Methods: Freshly excised tumors along with adjacent normal background tissues of 94 patients were collected at the time of surgery and immediately stored in RNAlater ® solution. Clinical data for these samples (disease stage, grade, age, and menopausal status) was also retrieved after a subsequent follow-up. Isolation of RNA and cDNA synthesis was done using an already established protocol. HER2 expression was evaluated using the quantitative real-time polymerase chain reaction (qRT-PCR) technique while β-actin was used as an internal control.Results: In the given cohort, 31 (33%) patients were found positive for HER2. These tumors showed a pronounced increase in HER2 as compared to controls (P = 0.0004). Interestingly, the significant relevance of high HER2 mRNA among moderately differentiated tumor tissues in comparison to controls was also observed (P = 0.02). A significant association of HER2 levels with premenopausal status was also reported.Conclusion: Based on these findings, early screening of HER2 using qRT-PCR should be incorporated for breast cancer patients of Pakistani population diagnosis. [ABSTRACT FROM AUTHOR]

Background: B-cell lymphoma 2 is involved in various cancers including breast carcinoma. Its expression in breast cancer has been associated with good prognostic factors such as hormone receptor expression, low Ki-67, low grade, and earlier stage. It is also considered to be an independent prognostic factor for luminal and triple-negative tumors., Objective: We aimed to determine the expression of B-cell lymphoma 2 (BCL2) in different molecular subtypes of invasive ductal carcinoma of breast and its association with prognostic indicators., Materials and Methods: Fifty samples of invasive carcinoma of breast, no special type (NST), were categorized into molecular subtypes according to immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67 and then evaluated for BCL2 expression. The expression of BCL2 was correlated with ER, PR, HER2, and Ki-67 and compared between luminal and nonluminal subtypes., Results: The BCL2 expression was seen in 68% of the cases with a significant association with ER, PR, and luminal subtypes. No significant association of BCL2 expression was seen with grade, HER2 and Ki-67 status of the tumor, or age group of the patients. BCL2 expression is significantly associated with ER, PR, and luminal subtypes in breast cancer., Conclusion: BCL2 is a marker of good prognosis in invasive carcinoma of breast, NST., Competing Interests: None

Background/aim: In the current study, the role of plexin B1 in breast cancer metastasis was explored., Materials and Methods: Freshly-excised tumours along with background tissues of affected patients (n=121) were collected from Pakistani hospitals and processed for RNA isolation and cDNA synthesis. Using quantitative polymerase chain reaction, expression of plexin B1 was evaluated and correlated with clinicopathological parameters. Furthermore, involvement of plexin B1 in metastasis was explored by generating gene knockdown in MDA-MB-231 and MCF-7 breast cancer cells., Results: Poorly-differentiated tumours showed low plexin B1 expression in comparison to well-differentiated ones. Similarly, reduced plexin B1 expression correlated positively with advanced tumour stage and metastasis. Loss of plexin B1 significantly reduced cell adhesion in comparison with respective control cell lines (p<0.05). Knockdown of plexin B1 in MDA-MB-231 cells led to a remarkable increase in cell motility in contrast to the respective control., Conclusion: Loss of plexin B1 expression might play a pivotal role in enhancing the metastatic potential of breast cancer cells., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Constitutive activation of Sonic hedgehog (SHH) has been observed in different types of cancers. In the present study, expressional profiling of SHH in a breast cancer cohort (n=150) of a Pakistani population and its association with different molecular subtypes have been explored., Materials and Methods: qRT-PCR and IHC were performed for expression analysis of SHH and its association with ER, PR, HER2 and Ki-67 were also statistically analyzed., Results: A significant over-expression of SHH was observed in tumor tissues in comparison to their respective controls (p<0.0001). A strong positive correlation was seen between SHH and proliferation marker (r=0.635, p=0). SHH expression was significantly high among patients with advanced tumor grade, stage, nodal involvement and metastasis. Furthermore, both luminal-B and triple-negative subtypes of cohort showed increased expression of SHH., Conclusion: Based on these findings, SHH may be used as a potential biomarker for breast carcinogenesis., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)