Laboratory Medicine Commons^™

Audit Of The Impact Of The Pause In The National Screening Service For Breast Cancer During The Covid-19 Pandemic, Ava Coakley

International Undergraduate Journal of Health Sciences

In Ireland there is a free national screening service for breast cancer called BreastCheck. BreastCheck invites women aged fifty to sixty-nine to have screening mammograms once every two years to detect any densities in their breast mammogram which could indicate breast cancer. If densities are seen on a mammogram a breast core is sampled and sent to a histopathology laboratory where a part of the tissue is examined by a consultant pathologist using a microscope. Further tests can then be performed on this sample if it is diagnosed as breast cancer. Tests include immunohistochemistry and dual in-situ hybridisation (DISH). BreastCheck …

Survival Prognostic Factors And Molecular Aspects In Extremity Soft Tissue Sarcoma, Bogdan Serban, Eugen Radu, Adrian Cursaru, Bogdan Stefan Cretu, Sergiu Andrei Iordache, Madalina Cirnu, Cosmin Florentin Niculae, Cătălin Florin Cîrstoiu

Journal of Mind and Medical Sciences

Soft tissue sarcomas are defined as relatively rare, wide-ranging mesenchymal tumors that present several forms of aggressive behavior. In order to improve the therapeutic result and thus the patient's prognosis, reliable diagnostic and evaluation tools are needed, capable of establishing the evolutive pattern of each patient. Materials and Methods. An analytical observational study was conducted in the period 2016-2023 in the Orthopedics Department of the Bucharest University Emergency Hospital, on patients diagnosed with soft tissue sarcoma. Data such as sex, age, site, size, depth, histotype, grade and margin status, vessel or bone involvement, adenopathies, adjuvant therapy, clinical findings, etc., were …

Genetic Alchemy Unveiled: Microrna-Mediated Gene Therapy As The Artisan Craft In The Battlefront Against Hepatocellular Carcinoma—A Comprehensive Chronicle Of Strategies And Innovations, Abduh Murshed, Mohammed A.H. Alnoud, Saleem Ahmad, Safir Ullah Khan, Mohammed Alissa, Meshari A. Alsuwat, Ahmed Ezzat Ahmed, Munir Ullah Khan

School of Graduate Studies Faculty Publications

Investigating therapeutic miRNAs is a rewarding endeavour for pharmaceutical companies. Since its discovery in 1993, our understanding of miRNA biology has advanced significantly. Numerous studies have emphasised the disruption of miRNA expression in various diseases, making them appealing candidates for innovative therapeutic approaches. Hepatocellular carcinoma (HCC) is a significant malignancy that poses a severe threat to human health, accounting for approximately 70%–85% of all malignant tumours. Currently, the efficacy of several HCC therapies is limited. Alterations in various biomacromolecules during HCC progression and their underlying mechanisms provide a basis for the investigation of novel and effective therapeutic approaches. MicroRNAs, also …

Differential Expression Of Wnt5a Long And Short Isoforms In Non-Muscle-Invasive Bladder Urothelial Carcinoma., Amy M Strope, Cody Phillips, Sabin Khadgi, Scott A Jenkinson, Karen T Coschigano, Ramiro Malgor

Oncology Articles

Wnt ligands belong to a family of secreted glycoproteins in which binding to a range of receptors/co-receptors activates several intracellular pathways. WNT5A, a member of the Wnt family, is classified as a non-canonical Wnt whose activation triggers planar cell polarity (PCP) and Ca+2 downstream pathways. Aberrant expression of WNT5A has been shown to play both protective and harmful roles in an array of conditions, such as inflammatory disease and cancer. In the present study, using histological, immunohistochemical, and molecular methods, we investigated the expression of two isoforms of WNT5A, WNT5A-Short (WNT5A-S) and WNT5A-Long (WNT5A-L) in bladder urothelial carcinoma (UC). Three …

Intrabiliary Metastasis Of Colorectal Mucinous Adenocarcinoma Mimicking Choledocholithiasis 18 Years After The Primary Tumor, Sumaya Abdul Ghaffar, David Pfau, Nikhil Madhuripan, Robert Christopher Harmon, Antonio Galvao Neto, Ana Luiza Gleisner

Faculty, Staff and Student Publications

This case report presents a 62-year-old male who had previously undergone curative colectomy and neoadjuvant chemotherapy in 2005 for colorectal cancer. He presented with jaundice, which was initially attributed to choledocholithiasis. After cholecystectomy and repeat ERCPs, hyperbilirubinemia persisted. There was persistent dilation of the right posterior duct on imaging, concerning for biliary stricture, possibly due to cholangiocarcinoma or intraductal papillary neoplasm. During a right posterior hepatectomy, a peripheral liver lesion was found in association with the dilated bile duct. On frozen evaluation, the lesion was found to be invasive adenocarcinoma. The final pathology was compatible with a metastatic mucinous adenocarcinoma …

Exosome Shedding Is Concordant With Objective Treatment Response Rate And Stratifies Time To Progression In Treatment Naïve, Non-Resectable Hepatocellular Carcinoma, Kelley G. Núñez, Dorota Wyczechowska, Mina Hibino, Tyler Sandow, Juan Gimenez, Ali R. Koksal, Yucel Aydin, Srikanta Dash, Ari J. Cohen, Paul T. Thevenot

School of Medicine Faculty Publications

Translational strategies to characterize and monitor extracellular vesicles such as exosome (EX) shedding and the clinical impact of this data within hepatocellular carcinoma (HCC) remains unclear. In this study, EX shedding was assessed in early-stage HCC and evaluated as a stratification factor for time to progression (TTP) following first-cycle liver-directed therapy (LDT). Plasma EXs were isolated from HCC patients undergoing LDT using ultracentrifugation. Purified EXs were stained using markers CD9 and CD63 and quantified using an ImageStreamX flow cytometer. Circulating EXs expressing CD9 were isolated at 10-fold higher levels compared to CD63. The intensity of CD9+ EX shedding following LDT …

Ezh2 Cooperates With Brd4-Nut To Drive Nut Carcinoma Growth By Silencing Key Tumor Suppressor Genes, Yeying Huang, R Taylor Durall, Nhi M Luong, Hans J Hertzler, Julianna Huang, Prafulla C Gokhale, Brittaney A Leeper, Nicole S Persky, David E Root, Praju V Anekal, Paula D L M Montero Llopis, Clement N David, Jeffery L Kutok, Alejandra Raimondi, Karan Saluja, Jia Luo, Cynthia A Zahnow, Biniam Adane, Kimberly Stegmaier, Catherine E Hawkins, Christopher Ponne, Quan Le, Geoffrey I Shapiro, Madeleine E Lemieux, Kyle P Eagen, Christopher A French

Faculty, Staff and Student Publications

NUT carcinoma (NC) is an aggressive carcinoma driven by the BRD4-NUT fusion oncoprotein, which activates chromatin to promote expression of pro-growth genes. BET bromodomain inhibitors (BETi) are a promising treatment for NC that can impede BRD4-NUT’s ability to activate genes, but the efficacy of BETi as monotherapy are limited. Here, we demonstrated that EZH2, which silences genes through establishment of repressive chromatin, is a dependency in NC. Inhibition of EZH2 with the clinical compound tazemetostat (taz) potently blocked growth of NC cells. Epigenetic and transcriptomic analysis revealed that taz reversed the EZH2-specific H3K27me3 silencing mark and restored expression of multiple …

Inflammation In The Tumor-Adjacent Lung As A Predictor Of Clinical Outcome In Lung Adenocarcinoma, Igor Dolgalev, Hua Zhou, Nina Murrell, Hortense Le, Theodore Sakellaropoulos, Nicolas Coudray, Kelsey Zhu, Varshini Vasudevaraja, Anna Yeaton, Chandra Goparaju, Yonghua Li, Imran Sulaiman, Jun-Chieh J Tsay, Peter Meyn, Hussein Mohamed, Iris Sydney, Tomoe Shiomi, Sitharam Ramaswami, Navneet Narula, Ruth Kulicke, Fred P Davis, Nicolas Stransky, Gromoslaw A Smolen, Wei-Yi Cheng, James Cai, Salman Punekar, Vamsidhar Velcheti, Daniel H Sterman, J T Poirier, Ben Neel, Kwok-Kin Wong, Luis Chiriboga, Adriana Heguy, Thales Papagiannakopoulos, Bettina Nadorp, Matija Snuderl, Leopoldo N Segal, Andre L Moreira, Harvey I Pass, Aristotelis Tsirigos

Faculty, Staff and Student Publications

Approximately 30% of early-stage lung adenocarcinoma patients present with disease progression after successful surgical resection. Despite efforts of mapping the genetic landscape, there has been limited success in discovering predictive biomarkers of disease outcomes. Here we performed a systematic multi-omic assessment of 143 tumors and matched tumor-adjacent, histologically-normal lung tissue with long-term patient follow-up. Through histologic, mutational, and transcriptomic profiling of tumor and adjacent-normal tissue, we identified an inflammatory gene signature in tumor-adjacent tissue as the strongest clinical predictor of disease progression. Single-cell transcriptomic analysis demonstrated the progression-associated inflammatory signature was expressed in both immune and non-immune cells, and cell …

Dpp8 Selective Inhibitor Tominostat As A Novel And Broad-Spectrum Anticancer Agent Against Hematological Malignancies, Shohei Kikuchi, Akinori Wada, Yusuke Kamihara, Kosuke Okazaki, Paras Jawaid, Mati Ur Rehman, Eiji Kobayashi, Takeshi Susukida, Tomoki Minemura, Yoshimi Nabe

Department of Biological & Biomedical Sciences

DPP8/9 inhibition induces either pyroptotic or apoptotic cell death in hematological malignancies. We previously reported that treatment with the DPP8/9 inhibitor 1G244 resulted in apoptotic cell death in myeloma, and our current study further evaluates the mechanism of action of 1G244 in different blood cancer cell lines. Specifically, 1G244 inhibited DPP9 to induce GSDMD-mediated-pyroptosis at low concentrations and inhibited DPP8 to cause caspase-3-mediated-apoptosis at high concentrations. HCK expression is necessary to induce susceptibility to pyroptosis but does not participate in the induction of apoptosis. To further characterize this DPP8-dependent broad-spectrum apoptosis induction effect, we evaluated the potential antineoplastic role for …

Lingual Alveolar Soft Part Sarcoma In A 78-Year-Old Woman: A Case Report And Comprehensive Review Of The Literature From 1952 To 2022, Aliaksandr Aksionau, Nestor Enriquez Dela Cruz, Andrew T Meram, Hugo Cuellar-Saenz, Jillian R Aveni, Hidehiro Takei

Faculty, Staff and Student Publications

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare translocation-related soft tissue sarcoma, occurring mainly in the limbs and trunk in young adults and adolescents. ASPS is rarely seen in the head and neck and one fourth of those cases described are tongue primary. Given its nonspecific symptoms, clinical findings, and rarity in this location, lingual ASPS (L-ASPS) has been reported to be commonly misdiagnosed as various benign tumors, leading to adverse outcomes.

METHODS: We report a case of L-ASPS occurring in the oldest (78 years) female patient published to date and comprehensively review the literature from 1952 to 2022. …

Epstein-Barr Virus-Associated Lymphoepithelial Carcinoma Arising In The Parotid Gland: A Case Report And Literature Review, Akinobu Kubota, Nobuyuki Bandoh, Takashi Goto, Ken-Ichi Matsumoto, Tomomi Yamaguchi-Ishochi, Yasutaka Kato, Hiroshi Nishihara, Hidehiro Takei

Faculty, Staff and Student Publications

A 60-year-old woman presented with a 3-year history of a slow-growing, painless mass in their left parotid gland. Ultrasonography revealed a well-circumscribed, lobulated, hypoechoic mass measuring 19x12x10 mm in the left parotid gland. Computed tomography revealed a well-circumscribed, solid mass with homogeneous enhancement. Fluorodeoxyglucose-positron emission tomography revealed uptake by the tumor but no uptake in other organs, including the nasopharynx. The patient underwent superficial parotidectomy with adequate safety margins and selective neck dissection followed by radiotherapy. No facial paralysis or recurrence of the tumor had been observed as of 20 months post-operation. Histologically, the tumor was composed of sheets of …

B-Lymphoblastic Leukemia With Burkitt-Like Morphology And Aberrant Myeloperoxidase Expression: A Diagnostic Conundrum, Karen A Nahmod, Wei Wang, Karan Saluja, Zhenya Tang, L Jeffrey Medeiros, Beenu Thakral

Faculty, Staff and Student Publications

No abstract provided.

Pathologic Predictors Of Response To Treatment Of Immune Checkpoint Inhibitor-Induced Kidney Injury, Ala Abudayyeh, Liye Suo, Heather Lin, Omar Mamlouk, Noha Abdel-Wahab, Amanda Tchakarov

Faculty, Staff and Student Publications

Background: Immune-related adverse events are a management challenge in patients receiving immune checkpoint inhibitors (ICIs). The most common renal immune-related adverse event, acute interstitial nephritis (AIN), is associated with patient morbidity and mortality. AIN, characterized by infiltration of renal tissue with immune cells, may be analogous to kidney transplant rejection. We evaluated clinical variables and pathologic findings to identify predictors of renal response and overall survival (OS) in patients with ICI-induced AIN. Design, setting, participants, and measurements: We reviewed the records and biopsy specimens of all 35 patients treated for ICI-induced AIN at our institution, between August 2007 and August …

Ahcc® Supplementation To Support Immune Function To Clear Persistent Human Papillomavirus Infections, Judith A Smith, Anjali A Gaikwad, Lata Mathew, Barbara Rech, Jonathan P Faro, Joseph A Lucci, Yu Bai, Randall J Olsen, Teresa T Byrd

Faculty, Staff and Student Publications

OBJECTIVE: To determine the efficacy, safety, and durability of the use of AHCC supplementation for 6 months to support the host immune system to clear high-risk human papillomavirus (HPV) infections. The AHCC supplement is a proprietary, standardized extract of cultured lentinula edodes mycelia (AHCC

STUDY DESIGN: This was a randomized, double-blind, placebo-controlled study (CTN: NCT02405533) in 50 women over 30 years of age with confirmed persistent high-risk HPV infections for greater than 2 years. Patients were randomized to placebo once daily for 12 months (N = 25) or AHCC 3-g supplementation by mouth once daily on empty stomach for 6 …

Primary Effusion Lymphoma: A Clinicopathological Study Of 70 Cases, Zhihong Hu, Zenggang Pan, Weina Chen, Yang Shi, Wei Wang, Ji Yuan, Endi Wang, Shanxiang Zhang, Habibe Kurt, Brenda Mai, Xiaohui Zhang, Hui Liu, Adan A Rios, Hilary Y Ma, Nghia D Nguyen, L Jeffrey Medeiros, Shimin Hu

Faculty, Staff and Student Publications

Primary effusion lymphoma (PEL) is a rare type of large B-cell lymphoma associated with human herpesvirus 8 (HHV8) infection. Patients with PEL usually present with an effusion, but occasionally with an extracavitary mass. In this study, we reported a cohort of 70 patients with PEL: 67 men and 3 women with a median age of 46 years (range 26–91). Of these, 56 (80%) patients had human immunodeficiency virus (HIV) infection, eight were HIV-negative, and six had unknown HIV status. Nineteen (27%) patients had Kaposi sarcoma. Thirty-five (50%) patients presented with effusion only, 27 (39%) had an extracavitary mass or masses …

Bispecific Human Il2-Ccr4 Immunotoxin Targets Human Cutaneous T-Cell Lymphoma, Haoyu Wang, Zhaohui Wang, Huiping Zhang, Zeng Qi, Ariel C Johnson, David Mathes, Elizabeth A Pomfret, Erin Rubin, Christene A Huang, Zhirui Wang

Faculty, Staff and Student Publications

The majority of clinically diagnosed cutaneous T‐cell lymphomas (CTCL) highly express the cell‐surface markers CC chemokine receptor 4 (CCR4) and/or CD25. Recently, we have developed diphtheria toxin‐based recombinant Ontak®‐like human IL2 fusion toxin (IL2 fusion toxin) and anti‐human CCR4 immunotoxin (CCR4 IT). In this study, we first compared the efficacy of the CCR4 IT vs IL2 fusion toxin for targeting human CD25+CCR4+ CTCL. We demonstrated that CCR4 IT was more effective than IL2 fusion toxin. We further constructed an IL2‐CCR4 bispecific IT. The bispecific IT was significantly more effective than either IL2 fusion toxin or CCR4 IT alone. The bispecific …

A Validated Composite Organ And Hematologic Response Model For Early Assessment Of Treatment Outcomes In Light Chain Amyloidosis, Surbhi Sidana, Paolo Milani, Moritz Binder, Marco Basset, Nidhi Tandon, Andrea Foli, Angela Dispenzieri, Morie A Gertz, Suzanne R Hayman, Francis K Buadi, Martha Q Lacy, Prashant Kapoor, Nelson Leung, S Vincent Rajkumar, Giampaolo Merlini, Giovanni Palladini, Shaji K Kumar

Faculty, Staff and Student Publications

Newly diagnosed AL amyloidosis patients were evaluated to develop a model for early assessment of treatment benefit at 6 months, integrating both hematologic (HR) and organ response (OR) assessment (testing cohort, Mayo: n = 473; validation cohort, Pavia: n = 575). Multiple OR were assessed as follows: All OR (AOR): response in all organs, mixed OR (MOR): response in some organs, no OR (NOR)]. AOR rates at 6 months improved with deepening HR; complete response (CR; 38%, 35%), very good partial response (VGPR; 30%, 26%), and partial response (PR; 16%, 21%), respectively. A composite HR/OR (CHOR) model was developed using …

Epstein-Barr Virus-Positive Large Cell Neuroendocrine Carcinoma Of The Nasopharynx: Report Of One Case And Review Of The Literature, Zhenjian Cai, Mei Lin, Angel I Blanco, Jing Liu, Hui Zhu

Faculty, Staff and Student Publications

Epstein-Barr Virus (EBV)-positive neuroendocrine carcinoma (NEC) of the nasopharynx is exceedingly rare, only two cases have been reported in the literature. While EBV infection is strongly associated with nasopharyngeal carcinoma, which is carcinoma with squamous differentiation, the link between EBV and NEC is not well known, and can be diagnostically challenging. In this study, we report the third case of EBV-positive large cell NEC of nasopharynx with neck lymph node metastasis. The patient was treated with combined radiation and chemotherapy and showed complete clinical and radiological response. Similar treatment response has been reported in another patient with high stage EBV-positive …