Oncology Commons^™

Treatment Response Of Gingival Squamous-Cell Carcinoma To Palliative Intent Immunotherapy, Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson, James Gates

Department of Medical Oncology Faculty Papers

The use of PD-1 immune checkpoint inhibitor medications has become a common practice in the treatment of recurrent and metastatic head and neck squamous-cell carcinomas. Success in this setting has led to the investigation of their efficacy in locally advanced cases as a part of first-line therapy. In this report, we detail the treatment response to palliative intent immunotherapy of three geriatric patients with mandibular gingival squamous-cell carcinoma who decided against surgical intervention. Patient #1 was treated with pembrolizumab, a PD-1 inhibitor, and displayed complete clinical and radiologic response of the gingival mass after three months of treatment, which is …

The Classification Of Obesity Based On Metabolic Status Redefines The Readmission Of Non-Hodgkin’S Lymphoma-An Observational Study, Hang Dong, Honglin Guo, Jing Du, Yiping Cheng, Dawei Wang, Junming Han, Zinuo Yuan, Zhenyu Yao, Ran An, Xiaoqin Wu, Kyle L Poulsen, Zhixiang Wang, Shanshan Shao, Xiude Fan, Zhen Wang, Jiajun Zhao

Journal Articles

BACKGROUND: The relationship between obesity and non-Hodgkin's lymphoma (NHL) was controversial, which may be due to the crudeness definition of obesity based on body mass index (BMI). As obesity and metabolic abnormalities often coexist, we aimed to explore whether the classification of obesity based on metabolic status can help to evaluate the real impact of obesity on the readmission of NHL.

METHODS: In this retrospective cohort study, utilizing the 2018 Nationwide Readmissions Database, we identified NHL-related index hospitalizations and followed them for non-elective readmission. The patients with NHL were classified as metabolically healthy non-obese (MHNO) and obese (MHO) and metabolically …

Intensity Modulated Radiation Therapy With Stereotactic Body Radiation Therapy Boost For Unfavorable Prostate Cancer: Five-Year Outcomes, Michael Carrasquilla, Tamir Sholklapper, Abigail Pepin, Nicole Hodgins, Siyuan Lei, Abdul Rashid, Malika Danner, Alan Zwart, Grecia Bolanos, Marilyn Ayoob, Thomas Yung, Nima Aghdam, Brian Collins, Simeng Suy, Deepak Kumar, Ryan Hankins, Keith Kowalczyk, Nancy Dawson, Sean Collins

Einstein Health Papers

PURPOSE: Intensity-modulated radiation therapy (IMRT) with brachytherapy boost for unfavorable prostate cancer has been shown to improve biochemical relapse-free survival compared to IMRT alone. Stereotactic body radiation therapy (SBRT) is a less-invasive alternative to brachytherapy. Early outcomes utilizing SBRT boost suggest low rates of high-grade toxicity with a maintained patient-reported quality of life. Here, we report the 5-year progression-free survival (PFS) and prostate cancer-specific survival (PCSS) of patients treated with IMRT plus SBRT boost.

MATERIALS AND METHODS: Between 2008 and 2020, 255 patients with unfavorable prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided …

Social Determinants Of Health And Lung Cancer Surgery: A Qualitative Study, Dede K. Teteh, Betty Ferrell, Oluwatimilehin Okunowo, Aidea Downie, Loretta Erhunmwunsee, Susanne B. Montgomery, Dan J. Raz, Rick Kittles, Jae Y. Kim, Virginia Sun

Health Sciences and Kinesiology Faculty Articles

Introduction: Social determinants of health (SDOH) are non-clinical factors that may affect the outcomes of cancer patients. The purpose of this study was to describe the influence of SDOH factors on quality of life (QOL)-related outcomes for lung cancer surgery patients.

Methods: Thirteen patients enrolled in a randomized trial of a dyadic self-management intervention were invited and agreed to participate in semi-structured key informant interviews at study completion (3 months post-discharge). A conventional content analysis approach was used to identify codes and themes that were derived from the interviews. Independent investigators coded the qualitative data, which were subsequently …

Tumor-Resident Lactobacillus Iners Confer Chemoradiation Resistance Through Lactate-Induced Metabolic Rewiring, Lauren E. Colbert, Molly B. El Alam, Rui Wang, Tatiana Karpinets, David Lo, Erica J. Lynn, Timothy A. Harris, Jacob H. Elnaggar, Kyoko Yoshida-Court, Katarina Tomasic, Julianna K. Bronk, Julie Sammouri, Ananta V. Yanamandra, Adilene V. Olvera, Lily G. Carlin, Travis Sims, Andrea Y. Delgado Medrano, Tatiana Cisneros Napravnik, Madison O'Hara, Daniel Lin, Chike O. Abana, Hannah X. Li, Patricia J. Eifel, Anuja Jhingran, Melissa Joyner, Lilie Lin, Lois M. Ramondetta, Andrew M. Futreal

School of Medicine Faculty Publications

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other …

Conditional Risks Of Biochemical Failure And Prostate Cancer-Specific Death In Patients Undergoing External Beam Radiotherapy: A Secondary Analysis Of 2 Randomized Clinical Trials, Gregory S. Alexander, Rebecca F Krc, James W Assif, Kai Sun, Jason K Molitoris, Phuoc Tran, Zaker Rana, Søren M Bentzen, Mark V Mishra

Department of Radiation Oncology Faculty Papers

IMPORTANCE: As patients achieve years of survival after treatment for prostate cancer, the risk of biochemical failure (BF) or prostate cancer-specific death (PCSD) may evolve over time, with clinical relevance to both patients and clinicians.

OBJECTIVE: To determine conditional BF-free survival, PSCD, and overall survival estimates for patients with low- or intermediate-risk prostate cancer enrolled in the Radiation Therapy Oncology Group (RTOG) 0126 and RTOG 0415 clinical trials. A secondary objective was to determine whether prognostic factors at diagnosis remain relevant at later points in follow-up.

DESIGN, SETTING, AND PARTICIPANTS: A pooled secondary analysis of patients treated with external-beam radiotherapy …

Unilateral Acute Iris Transillumination Syndrome With Glaucoma And Iris Pigment Epithelium Dispersion Simulating Iris Melanoma, Orlando Gonzalez Martinez, Carol L. Shields, Jerry Shields, Patricia Chévez-Barrios, Debbie Rigney Walley, Ralph C. Eagle Jr., Tatyana Milman

Wills Eye Hospital Papers

Purpose

To report a patient with a unilateral presentation of glaucoma, pain, and acute iris transillumination syndrome simulating iris melanoma.

Observations

A 53-year-old male presented with blurred vision and pain in his right eye several weeks following a respiratory sinus infection managed by oral azithromycin. Examination of the right eye was notable for elevated intraocular pressure of 46 mm Hg, an irregular mid-dilated pupil, and diffuse iris transillumination with pigmentary seeding on the iris surface, in the anterior chamber angle, and on the sclera, suspicious for diffuse iris melanoma with glaucoma and extrascleral extension. Ultrasound biomicroscopy (UBM) of the right …

Systemic Anticancer Therapy And Thromboembolic Outcomes In Hospitalized Patients With Cancer And Covid-19, Shuchi Gulati, Chih-Yuan Hsu, Surbhi Shah, Pankil K. Shah, Rebecca Zon, Susan Alsamarai, Joy Awosika, Ziad El-Bakouny, Babar Bashir, Alicia Beeghly, Stephanie Berg, Daniel De-La-Rosa-Martinez, Deborah B. Doroshow, Pamela C. Egan, Joshua Fein, Daniel B. Flora, Christopher R. Friese, Ariel Fromowitz, Elizabeth A. Griffiths, Clara Hwang, Chinmay Jani, Monika Joshi, Hina Khan, Elizabeth J. Klein, Natalie Knox Heater, Vadim S. Koshkin, Daniel H. Kwon, Chris Labaki, Tahir Latif, Rana R. Mckay, Gayathri Nagaraj, Elizabeth S. Nakasone, Taylor Nonato, Hyma V. Polimera, Matthew Puc, Pedram Razavi, Erika Ruiz-Garcia, Renee Maria Saliby, Aditi Shastri, Sunny R.K. Singh, Vicky Tagalakis, Diana Vilar-Compte, Lisa B. Weissmann, Cy R. Wilkins, Trisha M. Wise-Draper, Michael T. Wotman, James J. Yoon, Sanjay Mishra, Petros Grivas, Yu Shyr, Jeremy L. Warner, Jean M. Connors, Dimpy P. Shah, Rachel P. Rosovsky

Kimmel Cancer Center Faculty Papers

IMPORTANCE: Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.

OBJECTIVE: To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.

DESIGN, SETTING, AND PARTICIPANTS: This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.

EXPOSURE: Treatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune …

Her3 Targeting Augments The Efficacy Of Panobinostat In Claudin-Low Triple-Negative Breast Cancer Cells, Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu

School of Medicine Faculty Publications

Patients with triple-negative breast cancer (TNBC) have a poor prognosis and high relapse rate due to limited therapeutic options. This study was conducted to determine the mechanisms of action of panobinostat, a pan-inhibitor of histone deacetylase (HDAC) and FDA-approved medication for multiple myeloma, in TNBC and to provide a rationale for effective drug combinations against this aggressive disease. RNA sequencing analyses of the claudin-low (CL) TNBC (MDA-MB-231) cells untreated or treated with panobinostat were performed to identify the differentially expressed genes. Adaptive alterations in gene expression were analyzed and validated in additional CL TNBC cells. Tumor xenograft models were used …

Nivolumab And Ipilimumab In Combination With Radiotherapy In Patients With High-Risk Locally Advanced Squamous Cell Carcinoma Of The Head And Neck., Jennifer Johnson, Ioannis A. Vathiotis, Larry Harshyne, Ayesha Ali, Voichita Bar-Ad, Rita S. Axelrod, Emily Lorber, Joseph Curry, David Cognetti, Adam J. Luginbuhl, Madalina Tuluc, Scott W Keith, M.G. Mahoney, Athanassios Argiris

Department of Medical Oncology Faculty Papers

BACKGROUND: The combination of nivolumab and ipilimumab has been approved for the treatment of multiple solid tumors. This was a phase I study investigating definitive radioimmunotherapy (RIT) with nivolumab and ipilimumab for the treatment of locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN).

METHODS: Patients with newly diagnosed, stage IVA-IVB SCCHN eligible for cisplatin-based chemotherapy received nivolumab (3 mg/kg every 2 weeks for a total of 17 doses) and ipilimumab (1 mg/kg every 6 weeks for a total of 6 doses) starting 2 weeks prior to radiotherapy. The primary endpoint was safety of definitive RIT. Secondary …

Nanoparticle-Based Treatment Approaches For Skin Cancer: A Systematic Review., Michael Joseph Diaz, Nicole Natarelli, Shaliz Aflatooni, Sarah J. Aleman

School of Medicine Faculty Publications

Nanoparticles have shown marked promise as both antineoplastic agents and drug carriers. Despite strides made in immunomodulation, low success rates and toxicity remain limitations within the clinical oncology setting. In the present review, we assess advances in drug delivery nanoparticles, for systemic and topical use, in skin cancer treatment. A systematic review of controlled trials, meta-analyses, and Cochrane review articles was conducted. Eligibility criteria included: (1) a primary focus on nanoparticle utility for skin cancer; (2) available metrics on prevention and treatment outcomes; (3) detailed subject population; (4) English language; (5) archived as full-text journal articles. A total of 43 …

Early-Onset/Young-Onset Colorectal Carcinoma: A Comparative Analysis Of Morphological Features And Biomarker Profile, Atif A. Hashmi, Mahnoor Aslam, Khushbakht Rashid, Abrahim H. Ali, Tanim Ud Dowlah, Umair Arshad Malik, Shamail Zia, Sunder Sham, Fazail Zia, Muhammad Irfan

Medical College Documents

Introduction: Colorectal carcinoma (CRC) is one of the most common cancers that involve the human body. Young-onset CRC (YO-CRC) or early-onset CRC (EO-CRC) is defined as CRC that develops before the age of 50 years, as opposed to CRC that is diagnosed after the age of 50, referred to as late-onset CRC (LO-CRC). EO-CRC is sparsely studied in our population. Therefore, in this study, we evaluated the clinicopathological parameters and biomarker profile of EO-CRC and compared them with those of LO-CRC.
Methods: This was a retrospective study conducted at the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan. A total …

High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin

School of Graduate Studies Faculty Publications

Background: Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. Methods: Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding …

Yes-Associated Protein-1 Overexpression In Ocular Surface Squamous Neoplasia; A Potential Diagnostic Marker And Therapeutic Target, Peter Julius, Stepfanie N. Siyumbwa, Fred Maate, Phyllis Moonga, Guobin Kang, Trevor Kaile, John T. West, Charles Wood, Peter C. Angeletti

School of Graduate Studies Faculty Publications

Yes-associated protein-1 (YAP-1) is a Hippo system transcription factor, which serves as an oncogene in squamous cell carcinoma, and several solid tumors when the Hippo pathway is dysregulated. Yet, the activity of YAP-1 in ocular surface squamous neoplasia (OSSN) has not been determined. Here, we investigate the relationship between YAP-1 overexpression and OSSN. Using a cross-sectional study design, we recruited 227 OSSN patients from the University Teaching Hospitals in Lusaka, Zambia. Immunohistochemistry was used to assess YAP-1 protein overexpression in tumor tissue relative to surrounding benign squamous epithelium. OSSN patient samples (preinvasive, n = 62, 27% and invasive, n = …

Enhancement Of Tki Sensitivity In Lung Adenocarcinoma Through M6a-Dependent Translational Repression Of Wnt Signaling By Circ-Fbxw7, Kai Li, Zi Yang Peng, Rui Wang, Xiang Li, Ning Du, Da Peng Liu, Jia Zhang, Yun Feng Zhang, Lei Ma, Ye Sun, Shou Ching Tang, Hong Ren, Yi Ping Yang, Xin Sun

School of Medicine Faculty Publications

Background: Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem. Methods: By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing …

Scutellaria Baicalensis Enhances 5-Fluorouracil-Based Chemotherapy Via Inhibition Of Proliferative Signaling Pathways, Haizhou Liu, Hui Liu, Zhiyi Zhou, Jessica Chung, Guojing Zhang, Jin Chang, Robert A Parise, Edward Chu, John C Schmitz

Abington Jefferson Health Papers

Fluoropyridine-based chemotherapy remains the most widely used treatment for colorectal cancer (CRC). In this study, we investigated the mechanism by which the natural product Scutellaria baicalensis (Huang Qin; HQ) and one of its main components baicalin enhanced 5-fluorouracil (5-FU) antitumor activity against CRC. Cell proliferation assays, cell cycle analysis, reverse-phase protein array (RPPA) analysis, immunoblot analysis, and qRT-PCR were performed to investigate the mechanism(s) of action of HQ and its active components on growth of CRC cells. HQ exhibited in vitro antiproliferative activity against drug resistant human CRC cells, against human and mouse CRC cells with different genetic backgrounds and …

Chronic Obstructive Pulmonary Disease Is Associated With Worse Oncologic Outcomes In Early-Stage Resected Pancreatic And Periampullary Cancers, Rachel Huang, Emma Hammelef, Matthew Sabitsky, Carolyn Ream, Saed Khalilieh, Nitzan Zohar, Harish Lavu, Wilbur B. Bowne, Charles J. Yeo, Avinoam Nevler

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is the 3rd leading cause of cancer mortality in the United States. Hypoxic and hypercapnic tumor microenvironments have been suggested to promote tumor aggressiveness. The objective of this study was to evaluate the association between chronic obstructive pulmonary disease (COPD) and oncologic survival outcomes in patients with early-stage PDAC and periampullary cancers. In this case-control study, patients who underwent a pancreaticoduodenectomy during 2014–2021 were assessed. Demographic, perioperative, histologic, and oncologic data were collected. A total of 503 PDAC and periampullary adenocarcinoma patients were identified, 257 males and 246 females, with a mean age of 68.1 (±9.8) …

Covid-19 Severity And Cardiovascular Outcomes In Sars-Cov-2-Infected Patients With Cancer And Cardiovascular Disease, Melissa Y.Y. Moey, Cassandra Hennessy, Benjamin French, Jeremy L. Warner, Matthew D. Tucker, Daniel J. Hausrath, Dimpy P. Shah, Jeanne M. Decara, Ziad Bakouny, Chris Labaki, Toni K. Choueiri, Susan Dent, Nausheen Akhter, Roohi Ismail-Khan, Lisa Tachiki, David Slosky, Tamar S. Polonsky, Joy A. Awosika, Audrey Crago, Trisha Wise-Draper, Nino Balanchivadze, Clara Hwang, Leslie A. Fecher, Cyndi Gonzalez Gomez, Brandon Hayes-Lattin, Michael J. Glover, Sumit A. Shah, Dharmesh Gopalakrishnan, Elizabeth A. Griffiths, Daniel H. Kwon, Vadim S. Koshkin, Sana Mahmood, Babar Bashir, Taylor Nonato, Pedram Razavi, Rana R. Mckay, Gayathri Nagaraj, Eric Oligino, Matthew Puc, Polina Tregubenko, Elizabeth M. Wulff-Burchfield, Zhuoer Xie, Thorvardur R. Halfdanarson, Dimitrios Farmakiotis, Elizabeth J. Klein, Elizabeth V. Robilotti, Gregory J. Riely, Jean-Bernard Durand, Salim S. Hayek, Lavanya Kondapalli, Stephanie Berg, Timothy E. O'Connor, Mehmet A. Bilen, Cecilia Castellano, Melissa K. Accordino, Blau Sibel, Lisa B. Weissmann, Chinmay Jani, Daniel B. Flora, Lawrence Rudski, Miriam Santos Dutra, Bouganim Nathaniel, Erika Ruíz-García, Diana Vilar-Compte, Shilpa Gupta, Alicia Morgans, Anju Nohria

Kimmel Cancer Center Faculty Papers

BACKGROUND: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited.

OBJECTIVES: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF.

METHODS: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD

RESULTS: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity …

Association Of Smoking And Respiratory Disease History With Pancreatic Pathologies Requiring Surgical Resection, Carolyn Ream, Matthew Sabitsky, Rachel Huang, Emma Hammelef, Theresa P. Yeo, Harish Lavu, Charles J. Yeo, Wilbur Bowne, Avinoam Nevler

Student Papers, Posters & Projects

Background: The purpose of this study was to examine the relationship between various respiratory conditions, including hypercapnic respiratory disease, and a multitude of resected pancreatic lesions. Methods: This retrospective case-control study queried a prospectively maintained database of patients who underwent pancreaticoduodenectomy between January 2015 and October 2021. Patient data, including smoking history, medical history, and pathology reports, were recorded. Patients with no smoking history and no concomitant respiratory conditions were designated as the control group. Results: A total of 723 patients with complete clinical and pathological data were identified. Male current smokers showed increased rates of PDAC (OR 2.33, 95% …

Social Determinants Of Health Among Family Caregiver Centered Outcomes In Lung Cancer: A Systematic Review, Dede K. Teteh, Madeleine Love, Marissa Ericson, Marissa Chan, Tanyanika Phillips, Aroona Toor, Betty Ferrell, Loretta Erhunmwunsee, Susanne B. Montgomery, Virginia Sun, Jae Y. Kim

Health Sciences and Kinesiology Faculty Articles

Background: Lung cancer is the leading cause of cancer death globally. Both lung cancer patients and family caregivers (FCGs) have unmet quality of life (QOL) needs. An understudied topic in lung cancer research is the role of social determinants of health (SDOH) on QOL outcomes for this population. The purpose of this review was to explore the state of research on SDOH FCGs centered outcomes in lung cancer.

Methods: The databases PubMed/MEDLINE, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and American Psychological Association (APA) PsycInfo were searched for peer-reviewed manuscripts evaluating defined SDOH domains on …

Echinomycin As A Promising Therapeutic Agent Against Kshv-Related Malignancies, Jungang Chen, Zhen Lin, Jiao Song, Karlie Plaisance-Bonstaff, Jennifer James, Shengyu Mu, Steven R. Post, Lu Dai, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL), which preferentially arise in immunocompromised patients while lack of effective therapeutic options. Oncoproteins Myc and hypoxia-inducible factor-1α (HIF1α) have been found closely related to KSHV infection, replication and oncogenesis. However, the strategies of dual targeting these two oncoproteins have never been developed and tested for treatments of KSHV-related malignancies. In the current study, we report that treatment of echinomycin dramatically regresses cell growth both in vitro-cultured KSHV + tumor cells and in vivo KS or PEL xenograft mice models, …

Symptom Management Care Pathway Adaptation Process And Specific Adaptation Decisions, Emily Vettese, Farha Sherani, Allison A. King, Lolie Yu, Catherine Aftandilian, Christina Baggott, Vibhuti Agarwal, Ramamoorthy Nagasubramanian, Kara M. Kelly, David R. Freyer, Etan Orgel, Scott M. Bradfield, Wade Kyono, Michael Roth, Lisa M. Klesges, Melissa Beauchemin, Allison Grimes, George Tomlinson, L. Lee Dupuis, Lillian Sung

School of Medicine Faculty Publications

BACKGROUND: There is substantial heterogeneity in symptom management provided to pediatric patients with cancer. The primary objective was to describe the adaptation process and specific adaptation decisions related to symptom management care pathways based on clinical practice guidelines. The secondary objective evaluated if institutional factors were associated with adaptation decisions. METHODS: Fourteen previously developed symptom management care pathway templates were reviewed by an institutional adaptation team composed of two clinicians at each of 10 institutions. They worked through each statement for all care pathway templates sequentially. The institutional adaptation team made the decision to adopt, adapt or reject each statement, …

Met Alterations Are Associated With Osimertinib Resistance In Egfr Mutant Lung Cancers, A Meta-Analysis, Annie Le, Marissa Viola, Jun Wang

Research Day

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) that has been used to treat EGFR mutant lung cancers, especially those with EGFR T790M mutation. Resistance to osimertinib is likely associated with acquired genetic alterations in these cancer cells. Mesenchymal epithelial transition (MET) is a tyrosine kinase and its amplification is frequently seen in osimertinib resistant patients. To investigate whether the presence of MET alteration is associated with osimertinib resistance, a meta-analysis was conducted using published observations of EGFR mutant lung cancer patients treated with osimertinib. Frequencies of MET alterations are variable, ranging from 0-43% in osimertinib resistant patients. MET alteration …

Upregulation Of Cell Surface Glycoproteins In Correlation With Kshv Lana In The Kaposi Sarcoma Tumor Microenvironment, Sara R. Privatt, Owen Ngalamika, Jianshui Zhang, Qinsheng Li, Charles Wood, John T. West

School of Medicine Faculty Publications

HIV-associated epidemic Kaposi sarcoma (EpKS) remains one of the most prevalent cancers in sub-Saharan Africa despite the widespread uptake of anti-retroviral therapy and HIV-1 suppression. In an effort to define potential therapeutic targets against KS tumors, we analyzed previously published KS bulk tumor transcriptomics to identify cell surface biomarkers. In addition to upregulated gene expression (>6-fold) in the EpKS tumor microenvironment, biomarkers were selected for correlation with KSHV latency-associated nuclear antigen (LANA) expression. The cell surface glycoprotein genes identified were KDR, FLT4, ADAM12, UNC5A, ZP2, and OX40, as well as the endothelial lineage determinants Prox-1 and CD34. Each protein …

Enhanced Ca2+-Channeling Complex Formation At The Er-Mitochondria Interface Underlies The Pathogenesis Of Alcohol-Associated Liver Disease, Themis Thoudam, Dipanjan Chanda, Jung Yi Lee, Min Kyo Jung, Ibotombi Singh Sinam, Byung Gyu Kim, Bo Yoon Park, Woong Hee Kwon, Hyo Jeong Kim, Myeongjin Kim, Chae Won Lim, Hoyul Lee, Yang Hoon Huh, Caroline A. Miller, Romil Saxena, Nicholas J. Skill, Nazmul Huda, Praveen Kusumanchi, Jing Ma, Zhihong Yang, Min Ji Kim, Ji Young Mun, Robert A. Harris, Jae Han Jeon, Suthat Liangpunsakul, In Kyu Lee

School of Medicine Faculty Publications

Ca2+ overload-induced mitochondrial dysfunction is considered as a major contributing factor in the pathogenesis of alcohol-associated liver disease (ALD). However, the initiating factors that drive mitochondrial Ca2+ accumulation in ALD remain elusive. Here, we demonstrate that an aberrant increase in hepatic GRP75-mediated mitochondria-associated ER membrane (MAM) Ca2+-channeling (MCC) complex formation promotes mitochondrial dysfunction in vitro and in male mouse model of ALD. Unbiased transcriptomic analysis reveals PDK4 as a prominently inducible MAM kinase in ALD. Analysis of human ALD cohorts further corroborate these findings. Additional mass spectrometry analysis unveils GRP75 as a downstream phosphorylation target of PDK4. Conversely, non-phosphorylatable GRP75 …

Progranulin Oncogenic Network In Solid Tumors, Elisa Ventura, Giacomo Ducci, Reyes Benot Dominguez, Valentina Ruggiero, Antonino Belfiore, Elena Sacco, Marco Vanoni, Renato V. Iozzo, Antonio Giordano, Andrea Morrione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Progranulin is a pleiotropic growth factor with important physiological roles in embryogenesis and maintenance of adult tissue homeostasis. While-progranulin deficiency is associated with a broad range of pathological conditions affecting the brain, such as frontotemporal dementia and neuronal ceroid lipofuscinosis, progranulin upregulation characterizes many tumors, including brain tumors, multiple myeloma, leiomyosarcoma, mesothelioma and epithelial cancers such as ovarian, liver, breast, bladder, adrenal, prostate and kidney carcinomas. The increase of progranulin levels in tumors might have diagnostic and prognostic significance. In cancer, progranulin has a pro-tumorigenic role by promoting cancer cell proliferation, migration, invasiveness, anchorage-independent growth and resistance to chemotherapy. In …

Disparities In Access To Cancer Diagnostics In Asean Member Countries, Nicole Rose I. Alberto, Isabelle Rose I. Alberto, Corinna Victoria M. Puyat, Maria Alexandra R. Antonio, Frances Dominique V. Ho, Edward Christopher Dee, Brandon A. Mahal, Michelle Ann B. Eala

Ateneo School of Medicine and Public Health Publications

Diagnostics, including laboratory tests, medical and nuclear imaging, and molecular testing, are essential in the diagnosis and management of cancer to optimize clinical outcomes. With the continuous rise in cancer mortality and morbidity in the Association of Southeast Asian Nations (ASEAN), there exists a critical need to evaluate the accessibility of cancer diagnostics in the region so as to direct multifaceted interventions that will address regional inequities and inadequacies in cancer care. This paper identifies existing gaps in service delivery, health workforce, health information systems, leadership and governance, and financing and how these contribute to disparities in access to cancer …

Clinical Practice Guideline Recommendation Summaries For Pediatric Oncology Health Care Professionals: A Qualitative Study, Nancy Santesso, Melissa Beauchemin, Paula D. Robinson, Alexandra M. Walsh, Aaron J. Sugalski, Tammy Lo, Ha Dang, Brian T. Fisher, Allison C. Grimes, Andrea Rothfus Wrightson, Lolie C. Yu, Lillian Sung, L. Lee Dupuis

School of Medicine Faculty Publications

Objective To develop a summary format of clinical practice guideline (CPG) recommendations to improve understandability among health care professionals. Methods We developed a summary format based on current research and used the "Think Aloud"technique in one-on-one cognitive interviews to iteratively improve it. Interviews of health care professionals from Children's Oncology Group-member, National Cancer Institute Community Oncology Research Program sites were conducted. After every five interviews (a round), responses were reviewed, and changes made to the format until it was well understood and no new, substantive suggestions for revision were raised. We took a directed (deductive) approach to content analysis of …

Quitting Smoking After A Cancer Diagnosis Is Associated With High-Risk Neutrophil-To-Lymphocyte Ratio Among Tobacco Use-Related Cancer Survivors, You Lu, Katherine Kwong, James Wells, Andrea Edwards, Zhong Chen, Tung-Sung Tseng, Kun Zhang

School of Public Health Faculty Publications

Quitting smoking could potentially minimize the risk of a high neutrophil-to-lymphocyte ratio (NLR) among tobacco use-related (TUR) cancer survivors. A total of 1263 TUR cancer survivors aged 20 to 85 years old were investigated using data from the National Health and Nutritional Examination Survey 1999-2018. The primary outcome was the NLR, which was defined as having two levels: high-risk (≥ 3) and low-risk (< 3). The association between smoking cessation time and a high-risk NLR level was analyzed using weighted logistic regression models. Overall, the current smoking rate of TUR cancer survivors was found to be 21.7%. Older age (75 years above), gender and respiratory-related cancers are covariables associated with high risk of NLR levels for individual who identified as Non-Hispanic White (NHW). Non-Hispanic Black (NHB) (n = 27) who quit smoking after a cancer diagnosis were associated with the highest risk of a high NLR (OR 4.83, 95% CI 1.40-16.61, p = 0.01) compared to NHB nonsmokers (n = 139). These findings suggest that the risk of a high NLR level is strongly associated with the time of smoking cessation in NHB TUR cancer survivors. As a result, NHB TUR cancer survivors should quit smoking as soon as possible because the benefits of quitting smoking were observed over the 5 year period following smoking cessation.

Spontaneous Large Volume Hemothorax Managed With A Small-Bore Chest Tube, Moiz Salahuddin, Samia Ayub

Department of Medicine

A 67-year-old male with metastatic lung cancer presented with acute shortness of breath and increasing oxygen requirements. He had a decreasing hemoglobin for which he required red blood cell transfusions. His chest x-ray showed near complete white-out of the left lung. Bedside ultrasound (Handheld Sonostar C4PL) showed a large pleural effusion with swirling echogenic material suggestive of plankton sign. The pleural effusion was aspirated and showed frank blood, after which a small-bore chest tube (SBCT) was inserted. A total of 3200ml of blood was drained with the SBCT. There was complete clearance of the pleural space, and no further blood …