Publications by authors named "Nadeem Zafar"

Background: High-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated if smoking and/or drinking augment the molecular mechanisms of cervical carcinogenesis and defined a potential therapeutic approach for their attenuation.

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The application of extracellular vesicles, particularly exosomes (EXs), is rapidly expanding in the field of medicine, owing to their remarkable properties as natural carriers of biological cargo. This study investigates utilization of exosomes derived from stromal cells of tumor adjacent normal tissues (NAF-EXs) for personalized medicine, which can be derived at the time of diagnosis by endoscopic ultrasound. Herein, we show that exosomes (EXs) derived from NAFs demonstrate differential bio-physical characteristics, efficient cellular internalization, drug loading efficiency, pancreatic tumor targeting and delivery of payloads.

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Food and nutrition insecurity exist at an alarming rate in the US educational system, ranging from 17% among K-12 students up to 58.8% among university students. Many Muslim American students face food and nutrition insecurity due, in part, to a lack of acknowledgment of student adherence to halal dietary guidelines and the availability of certified halal options at school.

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Anchorage-independent survival after intravasation of cancer cells from the primary tumor site represents a critical step in metastasis. Here, we reveal new insights into how MUC13-mediated anoikis resistance, coupled with survival of colorectal tumor cells, leads to distant metastasis. We found that MUC13 targets a potent transcriptional coactivator, YAP1, and drives its nuclear translocation via forming a novel survival complex, which in turn augments the levels of pro-survival and metastasis-associated genes.

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Background: The correlation between head and neck squamous cell carcinoma (SCC) and human papillomavirus (HPV) has been of great interest. We aimed to study immunoexpression of the p16 (p16) antigen, a surrogate marker for high-risk HPV infection, in oropharyngeal SCC among veterans to estimate HPV-related cancer and survival. Secondary aims included stratification of race and ethnicity, degree of tobacco and alcohol use, tumor location, stage, and age at diagnosis.

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Background: Lip and oral squamous cell carcinoma maintains a significant disease burden in Pakistan. The latest research on cancer focuses more on the role of body's immune response in tumour progression and spread rather than on the nature of neoplastic cells. Tumour-infiltrating lymphocytes constitute a major part of the tumour microenvironment and infiltration of tumour stroma by cytotoxic T-cells are known to limit the tumour progression in various malignancies, such as colorectal and stomach cancers.

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Patient safety education is a mandated Common Program Requirement of the Accreditation Council for Graduate Medical Education and for the Royal College of Physicians and Surgeons of Canada in all medical residency and fellowship programs. Although many hospitals and healthcare environments have general patient safety education tools for trainees, few to none focus on the unique training milieu of pathologists, including a mix of highly automated and manual error-prone processes, frequent multiplicity of events, and lack of direct patient relationships for error disclosure. We established a national Association of Pathology Chairs-Program Directors Section Workgroup focused on patient safety education for pathology trainees entitled Training Residents in Patient Safety (TRIPS).

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Objective: To determine the frequency of ancillary pulmonary signs and their relation to the severity of disease seen on high-resolution computed tomography of chest in patients of coronavirus disease-2019 pneumonia.

Methods: The observational descriptive study was conducted at the Armed Forces Institute of Radiology and Imaging, Rawalpindi, Pakistan, from March to July 2020, and included in place of comprised all coronavirus disease-2019 patients who were found positive on reverse transcription-polymerase chain reaction-and were referred to have high-resolution computed tomography of chest. Ancillary pulmonary findings in addition to typical features of coronavirus disease-2019 pneumonia were recorded.

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Spontaneous pneumomediastinum with COVID pneumonia is a rare occurrence with or without accompanying subcutaneous emphysema or pneumothorax. The aim of this study was to establish relation of this complication to severity of lung disease and its clinical outcome. The study was conducted for a period of seven months from April to October 2020 in the CT Department of Armed Forces Institute of Radiology and Imaging (AFIRI), Rawalpindi, Pakistan.

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Objective: To test the germline oncogenic mutations in BRCA1 and BRCA2 genes, associated with triple-negative breast cancer (TNBC) patients under study, by targeted sequencing of their DNA with next-generation sequencing (NGS) platform.

Study Design: Cross-sectional observational study.

Place And Duration Of Study: Histopathology Department, Armed Forces Institute of Pathology (AFIP) Rawalpindi, Pakistan from May to June 2020.

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The coronavirus disease 2019 (COVID-19) pandemic, an infection caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), has led to more than 771,000 deaths worldwide. Tobacco smoking is a major known risk factor for severe illness and even death from many respiratory infections. The effects of smoking on COVID-19 are currently controversial.

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The use of social media at academic conferences is expanding, and platforms such as Twitter are used to share meeting content with the world. Pathology conferences are no exception, and recently, pathology organizations have promoted social media as a way to enhance meeting exposure. A social media committee was formed ad hoc to implement strategies to enhance social media involvement and coverage at the 2018 and 2019 annual meetings of the Association of Pathology Chairs.

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Background: Cancer progression and metastasis is profoundly influenced by protein kinase D1 (PKD1) and metastasis-associated protein 1 (MTA1) in addition to other pathways. However, the nature of regulatory relationship between the PKD1 and MTA1, and its resulting impact on cancer metastasis remains unknown. Here we present evidence to establish that PKD1 is an upstream regulatory kinase of MTA1.

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Background: Poor prognosis of pancreatic cancer (PanCa) is associated with lack of an effective early diagnostic biomarker. This study elucidates significance of MUC13, as a diagnostic/prognostic marker of PanCa.

Methods: MUC13 was assessed in tissues using our in-house generated anti-MUC13 mouse monoclonal antibody and analyzed for clinical correlation by immunohistochemistry, immunoblotting, RT-PCR, computational and submicron scale mass-density fluctuation analyses, ROC and Kaplan Meir curve analyses.

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The oncocytic variant of prostatic adenocarcinoma is exceptionally rare with only 4 cases reported in the English literature. Little is known about the clinical behavior of this variant of prostatic adenocarcinoma, because of the exceptionally low number of reported cases. The 2016 World Health Organization Classification of Tumors of Prostate does not recognize the oncocytic variant, again likely related to the exceptional paucity of reported cases.

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Ormeloxifene is a clinically approved selective estrogen receptor modulator, which has also shown excellent anticancer activity, thus it can be an ideal repurposing pharmacophore. Herein, we report therapeutic effects of ormeloxifene on prostate cancer and elucidate a novel molecular mechanism of its anticancer activity. Ormeloxifene treatment inhibited epithelial-to-mesenchymal transition (EMT) process as evident by repression of N-cadherin, Slug, Snail, vimentin, MMPs (MMP2 and MMP3), β-catenin/TCF-4 transcriptional activity, and induced the expression of pGSK3β.

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Duchenne muscular dystrophy (DMD) is a neuromuscular disease that predominantly affects boys as a result of mutation(s) in the dystrophin gene. DMD is characterized by musculoskeletal and cardiopulmonary complications, resulting in shorter life-span. Boys afflicted by DMD typically exhibit symptoms within 3-5 years of age and declining physical functions before attaining puberty.

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There is a higher rate of HPV infection and cervical cancer incidence and mortality in underserved US population who reside in Appalachian mountain region compared to Northern Plains. Social and behavioral factors such as smoking and alcohol consumption are for such a high incidence. However, by and large, the reasons for these discrepancies lie in the reluctance of the underserved population to adopt preventive measures such as prophylactic Human papilloma virus (HPV) vaccines and Pap smear screening that have significantly reduced the incidence and mortality rate of cervical cancer in Caucasian women.

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Peripheral T-cell lymphomas (PTCLs) represent a relatively uncommon heterogeneous group of non-Hodgkin's lymphomas (NHLs) with an aggressive clinical course and poor prognosis. Anthracycline-based multiagent chemotherapy with or without radiation therapy followed by first-line consolidation with high-dose therapy followed by autologous stem cell rescue (HDT/ASCR) is the standard approach to most of the patients with newly diagnosed PTCL. Relapsed or refractory disease is managed with second-line systemic therapy followed by HDT/ASCR or allogeneic stem cell transplant, based on the patient's eligibility for transplant.

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Docetaxel (Dtxl) is currently the most common therapeutic option for prostate cancer (PC). However, adverse side effects and problems associated with chemo-resistance limit its therapeutic outcome in clinical settings. A targeted nanoparticle system to improve its delivery to and activity at the tumor site could be an attractive strategy for PC therapy.

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Diffuse large B-cell lymphomas (DLBCL) are now considered a heterogeneous group of distinct molecular subtypes (germinal center B-cell DLBCL, activated B-cell DLBCL, and primary mediastinal large B-cell lymphoma (PMBL) with varied natural history and response to therapy. In addition, a subset of patients with DLBCL have concurrent MYC and/or BCL2 gene rearrangements (double-hit lymphomas; DHL) and others have a dual expression of both MYC and BCL2 proteins (double-expressing DLBCL; DEL). The standard of care for the treatment of patients with PMBL, DHL, or DEL has not been established.

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Cervical cancer is one of the most common cancers among women worldwide. Current standards of care for cervical cancer includes surgery, radiation, and chemotherapy. Conventional chemotherapy fails to elicit therapeutic responses and causes severe systemic toxicity.

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Background: Dry tap is an annoying experience in bone marrow (BM) findings, especially in cases where the diagnosis may hinge on BM findings. This study was conducted to determine, on, the basis of bone marrow (BM) trephine biopsy, the frequency of various underlying conditions causing a dry tap, among different age groups.

Methods: It was a descriptive study carried out at PAF hospital Mianwali, Pakistan from 1" Jan 2009 to 31 Dec 2012.

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Pancreatic cancer is the fourth most prevalent cancer with about an 85% mortality rate; thus, an utmost need exists to discover new therapeutic modalities that would enhance therapy outcomes of this disease with minimal or no side effects. Ormeloxifene (ORM), a synthetic molecule, has exhibited potent anti-cancer effects through inhibition of important oncogenic and proliferation signaling pathways. However, the anti-cancer efficacy of ORM can be further improved by developing its nanoformulation, which will also offer tumor specific targeted delivery.

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