Medical Specialties Commons^™

The Role Of Radiotherapy In The Complex Treatment Of Mycosis Fungoides; A Case Report, Laura Florentina Rebegea, Claudia-Elena Pavel, Nadejda Corobcean, Ana Maria Ilie, Dorel Firescu, Madalin Guliciuc, Elena Niculet, Mihaela Dumitru, Daniela Mihalache, Flavius Bulgaru, Roxana-Andreea Rahnea-Nita

Journal of Mind and Medical Sciences

Introduction. Mycosis fungoides (MF) is the most common form of primary cutaneous T-cell lymphoma. Radiotherapy induces excellent response rates in the treatment of localized or extensive lesions of MF, both as monotherapy and as part of a multidisciplinary treatment. Total skin irradiation with electrons or protons is available in a limited number of medical centers and is mainly used in patients with extensive MF. Case presentation. It is presented the case of a 47-year-old patient who developed erythematous papules and plaques on the chest, upper limbs, face and scalp, initially diagnosed as chronic eczema and treated with systemic corticotherapy, antihistamines …

Metachronous Mucinous Breast Carcinoma And Mucinous Pancreatic Cystadenoma In A Patient With Metabolic Comorbidities; Case Report And A Literature Review, Teodora Gabriela Alexescu, Irina Obada, Angela Cozma, Mirela Georgiana Perne, Olga Hilda Orasan, Vasile Negrean, Iacob Domsa, Victoria Ruta, Simina Felicia Țărmure

Journal of Mind and Medical Sciences

Mucinous breast carcinoma is a rare subtype of mammary neoplasm encountered in medical practice. It represents approximately 1-6% of all breast cancers and is more common in postmenopausal women. There are two subtypes of mucinous breast carcinoma: pure and mixed. We report the case of a 73-year-old Caucasian woman diagnosed with mucinous pancreatic cystadenoma in 2007. She underwent a surgical procedure involving pancreatectomy of the body and tail, along with multiple known cardiovascular and metabolic comorbidities. In November 2019, during a clinical-biological evaluation for associated diseases, a mucinous carcinoma of the right breast was accidentally detected and later confirmed through …

Advantages Of Mechanical Anastomosis In Rectal Cancer Surgery, Paul Șiancu, Adrian Boicean, Denisa Tănăsescu, Dan Bratu, Ciprian Tănăsescu

Journal of Mind and Medical Sciences

Rectal oncological pathology represents an increased degree of difficulty in terms of surgical approach. Along with the development of minimally invasive surgery, technology has also increased the options for performing digestive anastomoses. A significant increase has been observed among mechanical anastomoses. The evolution of mechanical sutures through the use of the stapler has become a true symbol of technological advancement, as they have led to improvements and effective gains in quality and productivity in suture making. The aim of this paper is to highlight the advantages of the use of staplers in rectal surgery, with their help achieving a lower …

Correlation Between Molecular Prognostic Factors And Bevacizumab Therapeutic Resistance In Patients With Metastatic Colorectal Cancer; The Avamet Study, Adrian Paul Suceveanu, Dragos Serban, Andreea Daniela Caloian, Georgeta Camelia Cozaru, Anca Chisoi, Anca Antonela Nicolau, Ioan Sergiu Micu, Andra Iulia Suceveanu

Journal of Mind and Medical Sciences

Objectives. Colorectal cancer is responsible for more than two million cases diagnosed annually. Despite early diagnosis through screening programs and adequate treatment, 25% of cases are diagnosed with metastatic disease while up to 50% of patients diagnosed early progress to metastatic disease. Materials and Methods. The study of 40 patients aims to identify the role of placental growth factor and heparin-binding growth factor as prognostic tools for current treatments involving resistance to bevacizumab in metastatic colorectal cancer. Results. Our results suggested that overall survival was influenced by serum fibroblast growth factor 1 levels. A cut-off value of 260.71 pg/ml was …

Medical And Psychological Management Of Patients With A History Of Surgical Treatment For Pancreatic Diseases, Magdalena Țone, Daniel Cochior, Oana Denisa Balalau, Tomescu Dana Rodica, Cristian Balalau, Teodora Mocan, Aurelian Udristoiu, Gabriel Petre Gorecki

Journal of Mind and Medical Sciences

Background. Pancreatic cancer, known for its high mortality rate and late diagnosis, remains a significant health concern. Surgery offers a potential therapeutic remedy, but it is only valid in the early stage of detection. Increasing risk factors and an aging population are expected to raise the incidence of pancreatic cancer, further challenging healthcare systems. Methods. The general objective of this study was to analyze doctors' experiences regarding the health status of patients with benign pancreatic pathology who underwent surgery and were admitted to CF2 Clinical Hospital in Bucharest. The research involved a specialized questionnaire addressing various aspects of patient health, …

Surgery Of The Colon; The Impact Of Colostomy And Postoperative Complications On Patients' Quality Of Life, Vlad Denis Constantin, Adrian Silaghi, Dragos Epistatu, Daniela Gabriela Bălan, Florin Silviu Groseanu, Denisa Mihaela Nedelcu, Ioana Paunica

Journal of Mind and Medical Sciences

Introduction. This study aims to evaluate the impact of stoma formation on the quality of life of patients undergoing colonic surgery, considering both emergency and elective procedures. Several factors (demographic data, Charlson comorbidity score, type of surgical intervention, duration of hospitalization, postoperative outcomes and complications, etc.) were analyzed to understand their influence on patients' well-being. Materials and Methods. A retrospective analysis was performed on patients who underwent colorectal surgery that required stoma formation. A total of 270 patients were included in the study, with 69.25% undergoing emergency surgery and 30.74% undergoing elective procedures. Results. The Charlson comorbidity score was significantly …

Low Anterior Rectal Resection; The Impact Of Anastomotic Fistula On Incidence And Severity Of Low Anterior Resection Syndrome, Georgiana Cotofana-Graure, Cecil Mirea, Silviu Daniel Preda, Stefan Patrascu, Tiberiu Stefanita Tenea-Cojan, Adina Turcu-Stiolica, Alexandru Munteanu, Vlad Padureanu, Dragos Margaritescu, Sandu Ramboiu, Dan Cartu, Valeriu Surlin, Petru Radu

Journal of Mind and Medical Sciences

Objectives. Low anterior resection is a common surgical procedure for rectal cancer, but it is associated with a distressing complication known as Low Anterior Resection Syndrome (LARS). The incidence of LARS varies, with severe symptoms persisting in some patients even years after surgery. This study aimed to investigate the association between anastomotic leak and LARS severity in rectal cancer patients. Methods. A retrospective analysis was conducted on 100 rectal cancer patients who underwent LAR between 2017 and 2021. Patients were categorized based on LARS questionnaire responses into groups with anastomotic leakage and LARS, LARS alone, or no LARS. Various factors, …

Ovarian Cancer Prevention And Screening – Where Do We Stand Today?, Cristina Bucur, Irina Balescu, Sorin Petrea, Bogdan Gaspar, Lucian Pop, Valentin Varlas, Adrian Hasegan, Marilena Stoian, Gabriel Petre Gorecki, Nicolae Bacalbasa

Journal of Mind and Medical Sciences

Widely recognized as the most deathful gynecologic malignancy affecting women worldwide, ovarian cancer has reported a significant decline in terms of prevalence and incidence in the last decades. This fact has been especially explained by to the use of menopausal hormonal therapy and of oral contraceptives in association with genetic, oncologic and gynecologic counseling. The aim of the current review is to discuss about actual ovarian cancer prevention and screening tools. For this reason, we reviewed several data related to ovarian cancer, such as: incidence and risk factors, histopathological types (epithelial with high- and low-grade serous carcinomas, clear cell carcinoma, …

Genetic And Serological Markers In Colorectal Cancer Surgery, Adrian Silaghi, Vlad Denis Constantin, Dragos Serban, Dragos Epistatu, Ioana Paunica, Daniela Gabriela Bălan, Laura Florentina Rebegea

Journal of Mind and Medical Sciences

Colon cancer is relatively asymptomatic in the early stages, the manifestations appearing and intensifying with the evolution of the disease, especially when associated with local and/or systemic complications. In such cases, surgical interventions are often emergency and involve more extensive operations (on metabolically and immune-stressed organisms), so that an early diagnosis (endoscopy, tumor markers, etc.) remains not only desirable but even a priority, especially in predisposed patients (genetic factors, lifestyle, etc.). As a consequence, the involvement of tumor markers in colon neoplasms has become more and more investigated in recent times. This review investigates the roles of serological and genetic …

Venous Thrombosis Associated With Pancreatic Cancer, Vlad Buică, Camelia Diaconu, Octavian Andronic

Journal of Mind and Medical Sciences

Introduction. Cancer-associated thrombosis is a significant prognostic marker in pancreatic neoplasia, with a venous thromboembolism incidence of 17-34%. This study focuses on cancer-associated thrombosis risk factors, screening scores, and treatment options. Materials and Methods. Comprehensive database searches were conducted across Web of Science, PubMed, Reaxys, ScienceDirect, and Scopus. Results. Of the 37 articles reviewed, findings include splanchnic vein thrombosis correlating with pancreatic complications and survival rates. Gender differences in cancer-associated thrombosis risk were inconclusive, while African Americans showed a higher incidence of pulmonary embolism. Various cancer-associated thrombosis staging scores were evaluated, with ONKOTEV score outperforming Khorana. Direct oral anticoagulants were …

Diabetic Patients And Postoperative Complications In Colorectal Surgery, Ioana Paunica, Adrian Silaghi, Daniela Gabriela Bălan, Bogdan Socea, Cristian Balalau, Florin Silviu Groseanu, George Alexandru Popescu, Dragos Epistatu, Vlad Denis Constantin

Journal of Mind and Medical Sciences

Diabetes mellitus is one of the most common comorbidities of patients undergoing surgery. Colorectal surgery is frequently associated with postoperative complications, and diabetic patients represent a population that presents a high risk of developing such complications. Understanding the interrelationships between neoplastic disease and diabetes, as well as the pathophysiological mechanisms underlying postoperative complications, are essential for effective therapeutic management. Genetic predispositions, alterations in the gut microbiota, inflammatory response, ischemic, thrombotic and infectious processes contribute significantly to the development of severe surgical complications, such as anastomotic fistulas. Postoperative ileus, characterized by gastrointestinal dysmotility, is common in diabetic patients due to neuropathic …

Phase I Trial Of Single-Photon Emission Computed Tomography-Guided Liver-Directed Radiotherapy For Patients With Low Functional Liver Volume, Enoch Chang, Franklin C L Wong, Beth A Chasen, William D Erwin, Prajnan Das, Emma B Holliday, Albert C Koong, Ethan B Ludmir, Bruce D Minsky, Sonal S Noticewala, Grace L Smith, Cullen M Taniguchi, Maria J Rodriguez, Sam Beddar, Rachael M Martin-Paulpeter, Joshua S Niedzielski, Gabriel O Sawakuchi, Emil Schueler, Luis A Perles, Lianchun Xiao, Janio Szklaruk, Peter C Park, Arvind N Dasari, Ahmed O Kaseb, Bryan K Kee, Sunyoung S Lee, Michael J Overman, Jason A Willis, Robert A Wolff, Ching-Wei D Tzeng, Jean-Nicolas Vauthey, Eugene J Koay

Faculty, Staff and Student Publications

BACKGROUND: Traditional constraints specify that 700 cc of liver should be spared a hepatotoxic dose when delivering liver-directed radiotherapy to reduce the risk of inducing liver failure. We investigated the role of single-photon emission computed tomography (SPECT) to identify and preferentially avoid functional liver during liver-directed radiation treatment planning in patients with preserved liver function but limited functional liver volume after receiving prior hepatotoxic chemotherapy or surgical resection.

METHODS: This phase I trial with a 3 + 3 design evaluated the safety of liver-directed radiotherapy using escalating functional liver radiation dose constraints in patients with liver metastases. Dose-limiting toxicities were …

Pathological Response In Resectable Non-Small Cell Lung Cancer: A Systematic Literature Review And Meta-Analysis, Nathalie A Waser, Melanie Quintana, Bernd Schweikert, Jamie E Chaft, Lindsay Berry, Ahmed Adam, Lien Vo, John R Penrod, Joseph Fiore, Donald A Berry, Sarah Goring

Faculty, Staff and Student Publications

BACKGROUND: Surrogate endpoints for overall survival in patients with resectable non-small cell lung cancer receiving neoadjuvant therapy are needed to provide earlier treatment outcome indicators and accelerate drug approval. This study's main objectives were to investigate the association among pathological complete response, major pathological response, event-free survival and overall survival and to determine whether treatment effects on pathological complete response and event-free survival correlate with treatment effects on overall survival.

METHODS: A comprehensive systematic literature review was conducted to identify neoadjuvant studies in resectable non-small cell lung cancer. Analysis at the patient level using frequentist and Bayesian random effects (hazard …

Quorum-Sensing Agr System Of Staphylococcus Aureus Primes Gene Expression For Protection From Lethal Oxidative Stress, Magdalena Podkowik, Andrew I Perault, Gregory Putzel, Andrew Pountain, Jisun Kim, Ashley L Dumont, Erin E Zwack, Robert J Ulrich, Theodora K Karagounis, Chunyi Zhou, Andreas F Haag, Julia Shenderovich, Gregory A Wasserman, Junbeom Kwon, John Chen, Anthony R Richardson, Jeffrey N Weiser, Carla R Nowosad, Desmond S Lun, Dane Parker, Alejandro Pironti, Xilin Zhao, Karl Drlica, Itai Yanai, Victor J Torres, Bo Shopsin

Faculty, Staff and Student Publications

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr resulted in decreased ATP levels and growth, despite increased rates of respiration or fermentation at appropriate oxygen tensions, suggesting that Δagr cells undergo a shift towards a hyperactive metabolic …

Overexpression Of Fatty Acid Synthase Upregulates Glutamine–Fructose-6-Phosphate Transaminase 1 And O-Linked N-Acetylglucosamine Transferase To Increase O-Glcnac Protein Glycosylation And Promote Colorectal Cancer Growth, James Drury, Mariah E. Geisen, Josiane Weber Tessmann, Piotr G. Rychahou, Courtney O. Kelson

Markey Cancer Center Faculty Publications

Fatty acid synthesis has been extensively investigated as a therapeutic target in cancers, including colorectal cancer (CRC). Fatty acid synthase (FASN), a key enzyme of de novo lipid synthesis, is significantly upregulated in CRC, and therapeutic approaches of targeting this enzyme are currently being tested in multiple clinical trials. However, the mechanisms behind the pro- oncogenic action of FASN are still not completely understood. Here, for the first time, we show that overexpression of FASN increases the expression of glutamine–fructose-6-phosphate transaminase 1 (GFPT1) and O-linked N-acetylglucosamine transferase (OGT), enzymes involved in hexosamine metabolism, and the level of O-GlcNAcylation in vitro …

Mir4435-2hg As A Possible Novel Predictive Biomarker Of Chemotherapy Response And Death In Pediatric B-Cell All, Yulieth Torres-Llanos, Jovanny Zabaleta, Nataly Cruz-Rodriguez, Sandra Quijano, Paula Carolina Guzmán, Iliana De Los Reyes, Nathaly Poveda-Garavito, Ana Infante, Liliana Lopez-Kleine, Alba Lucía Combita

School of Medicine Faculty Publications

Introduction: Although B-cell acute lymphoblastic leukemia (B-cell ALL) survival rates have improved in recent years, Hispanic children continue to have poorer survival rates. There are few tools available to identify at the time of diagnosis whether the patient will respond to induction therapy. Our goal was to identify predictive biomarkers of treatment response, which could also serve as prognostic biomarkers of death, by identifying methylated and differentially expressed genes between patients with positive minimal residual disease (MRD+) and negative minimal residual disease (MRD-). Methods: DNA and RNA were extracted from tumor blasts separated by immunomagnetic columns. Illumina MethlationEPIC and mRNA …

Financial Hardship And Neighborhood Socioeconomic Disadvantage In Long-Term Childhood Cancer Survivors, Alex J Fauer, Weiyu Qiu, I-Chan Huang, Patricia A Ganz, Jacqueline N Casillas, K Robin Yabroff, Gregory T Armstrong, Wendy Leisenring, Rebecca Howell, Carrie R Howell, Anne C Kirchhoff, Yutaka Yasui, Paul C Nathan

Faculty, Staff and Student Publications

Background: Long-term survivors of childhood cancer face elevated risk for financial hardship. We evaluate whether childhood cancer survivors live in areas of greater deprivation and the association with self-reported financial hardships.

Methods: We performed a cross-sectional analysis of data from the Childhood Cancer Survivor Study between 1970 and 1999 and self-reported financial information from 2017 to 2019. We measured neighborhood deprivation with the Area Deprivation Index (ADI) based on current zip code. Financial hardship was measured with validated surveys that captured behavioral, material and financial sacrifice, and psychological hardship. Bivariate analyses described neighborhood differences between survivors and siblings. Generalized linear …

Interaction Of High-Fat Diet And Brain Trauma Alters Adipose Tissue Macrophages And Brain Microglia Associated With Exacerbated Cognitive Dysfunction, Rebecca J Henry, James P Barrett, Maria Vaida, Niaz Z Khan, Oleg Makarevich, Rodney M Ritzel, Alan I Faden, Bogdan A Stoica

Faculty, Staff and Student Publications

Obesity increases the morbidity and mortality of traumatic brain injury (TBI). Detailed analyses of transcriptomic changes in the brain and adipose tissue were performed to elucidate the interactive effects between high-fat diet-induced obesity (DIO) and TBI. Adult male mice were fed a high-fat diet (HFD) for 12 weeks prior to experimental TBI and continuing after injury. High-throughput transcriptomic analysis using Nanostring panels of the total visceral adipose tissue (VAT) and cellular components in the brain, followed by unsupervised clustering, principal component analysis, and IPA pathway analysis were used to determine shifts in gene expression patterns and molecular pathway activity. Cellular …

Nestedbd: Bayesian Inference Of Phylogenetic Trees From Single-Cell Copy Number Profiles Under A Birth-Death Model, Yushu Liu, Mohammadamin Edrisi, Zhi Yan, Huw A Ogilvie, Luay Nakhleh

Faculty, Staff and Student Publications

Copy number aberrations (CNAs) are ubiquitous in many types of cancer. Inferring CNAs from cancer genomic data could help shed light on the initiation, progression, and potential treatment of cancer. While such data have traditionally been available via “bulk sequencing,” the more recently introduced techniques for single-cell DNA sequencing (scDNAseq) provide the type of data that makes CNA inference possible at the single-cell resolution. We introduce a new birth-death evolutionary model of CNAs and a Bayesian method, NestedBD, for the inference of evolutionary trees (topologies and branch lengths with relative mutation rates) from single-cell data. We evaluated NestedBD’s performance using …

Sars-Cov-2 Omicron: Viral Evolution, Immune Evasion, And Alternative Durable Therapeutic Strategies, Hailong Guo, Sha Ha, Jason W Botten, Kai Xu, Ningyan Zhang, Zhiqiang An, William R Strohl, John W Shiver, Tong-Ming Fu

Faculty, Staff and Student Publications

Since the SARS-CoV-2 Omicron virus has gained dominance worldwide, its continual evolution with unpredictable mutations and patterns has revoked all authorized immunotherapeutics. Rapid viral evolution has also necessitated several rounds of vaccine updates in order to provide adequate immune protection. It remains imperative to understand how Omicron evolves into different subvariants and causes immune escape as this could help reevaluate the current intervention strategies mostly implemented in the clinics as emergency measures to counter the pandemic and, importantly, develop new solutions. Here, we provide a review focusing on the major events of Omicron viral evolution, including the features of spike …

Aso Author Reflections: Outcomes Of Hepatic Artery-Based Therapies And Systemic Multiagent Chemotherapy In Unresectable Colorectal Liver Metastases: A Systematic Review And Meta-Analysis, Lee M. Ocuin

Faculty Scholarship

No abstract provided.

Direct Implantation Of Patient Brain Tumor Cells Into Matching Locations In Mouse Brains For Patient-Derived Orthotopic Xenograft Model Development, Lin Qi, Patricia Baxter, Mari Kogiso, Huiyuan Zhang, Frank K Braun, Holly Lindsay, Sibo Zhao, Sophie Xiao, Aalaa Sanad Abdallah, Milagros Suarez, Zilu Huang, Wan Yee Teo, Litian Yu, Xiumei Zhao, Zhigang Liu, Yulun Huang, Jack M Su, Tsz-Kwong Man, Ching C Lau, Laszlo Perlaky, Yuchen Du, Xiao-Nan Li

Center for Medical Ethics and Health Policy Staff Publications

Background: Despite multimodality therapies, the prognosis of patients with malignant brain tumors remains extremely poor. One of the major obstacles that hinders development of effective therapies is the limited availability of clinically relevant and biologically accurate (CRBA) mouse models.

Methods: We have developed a freehand surgical technique that allows for rapid and safe injection of fresh human brain tumor specimens directly into the matching locations (cerebrum, cerebellum, or brainstem) in the brains of SCID mice.

Results: Using this technique, we successfully developed 188 PDOX models from 408 brain tumor patient samples (both high-and low-grade) with a success rate of 72.3% …

Efficient Gene Knockout And Genetic Interaction Screening Using The In4mer Crispr/Cas12a Multiplex Knockout Platform, Nazanin Esmaeili Anvar, Chenchu Lin, Xingdi Ma, Lori L Wilson, Ryan Steger, Annabel K Sangree, Medina Colic, Sidney H Wang, John G Doench, Traver Hart

Faculty, Staff and Student Publications

Genetic interactions mediate the emergence of phenotype from genotype, but technologies for combinatorial genetic perturbation in mammalian cells are challenging to scale. Here, we identify background-independent paralog synthetic lethals from previous CRISPR genetic interaction screens, and find that the Cas12a platform provides superior sensitivity and assay replicability. We develop the in4mer Cas12a platform that uses arrays of four independent guide RNAs targeting the same or different genes. We construct a genome-scale library, Inzolia, that is ~30% smaller than a typical CRISPR/Cas9 library while also targeting ~4000 paralog pairs. Screens in cancer cells demonstrate discrimination of core and context-dependent essential genes …

Utility Of Clinical Next Generation Sequencing Tests In Kit/Pdgfra/Sdh Wild-Type Gastrointestinal Stromal Tumors, Ryan A Denu, Cissimol P Joseph, Elizabeth S Urquiola, Precious S Byrd, Richard K Yang, Ravin Ratan, Maria Alejandra Zarzour, Anthony P Conley, Dejka M Araujo, Vinod Ravi, Elise F Nassif Haddad, Michael S Nakazawa, Shreyaskumar Patel, Wei-Lien Wang, Alexander J Lazar, Neeta Somaiah

Faculty, Staff and Student Publications

Objective: The vast majority of gastrointestinal stromal tumors (GISTs) are driven by activating mutations in KIT, PDGFRA, or components of the succinate dehydrogenase (SDH) complex (SDHA, SDHB, SDHC, and SDHD genes). A small fraction of GISTs lack alterations in KIT, PDGFRA, and SDH. We aimed to further characterize the clinical and genomic characteristics of these so-called "triple-negative" GISTs.

Methods: We extracted clinical and genomic data from patients seen at MD Anderson Cancer Center with a diagnosis of GIST and available clinical next generation sequencing data to identify "triple-negative" patients.

Results: Of …

Impact Of Fall Education To Oncology Staff On Oncology Patient Fall Rates, Danni Sloane

Articles, Abstracts, and Reports

Significance & Background

Falls and fall-related injuries impact patients' health outcomes and are the most commonly reported adverse event in hospitals. Patient falls also affect reimbursement rates and can increase length of stay by about 6.3 days and increase undue patient harm. An increase of patients falls on the medical and surgical oncology acute care units have caused undue physical harm, increased moral distress, mental fatigue, and burnout in nurses; as well as placing financial burdens on the healthcare system. Implementing fall education and interventions aligns with national patient safety goals, is a top-priority project, is in alignment with the …

New Insights Into Macrophage Polarization And Its Prognostic Role In Patients With Colorectal Cancer Liver Metastasis, Isha Khanduri, Harufumi Maki, Anuj Verma, Riham Katkhuda, Gayathri Anandappa, Renganayaki Pandurengan, Shanyu Zhang, Alicia Mejia, Zhimin Tong, Luisa M Solis Soto, Akshaya Jadhav, Ignacio I Wistuba, David Menter, Scott Kopetz, Edwin R Parra, Jean-Nicolas Vauthey, Dipen M Maru

Faculty, Staff and Student Publications

Background: As liver metastasis is the most common cause of mortality in patients with colorectal cancer, studying colorectal cancer liver metastasis (CLM) microenvironment is essential for improved understanding of tumor biology and to identify novel therapeutic targets.

Methods: We used a multiplex immunofluorescence platform to study tumor associated macrophage (TAM) polarization and adaptive T cell subtypes in tumor samples from 105 CLM patients (49 without and 56 with preoperative chemotherapy).

Results: CLM exhibited M2 macrophage polarization, and helper T cells were the prevalent adaptive T cell subtype. The density of total, M2 and TGFβ-expressing macrophages, and regulatory T cells was …

Multi-Institution Single Geometry Plan Complexity Characteristics Based On Iroc Phantoms, Vimal Desai, Zacariah Labby, Wesley Culberson, Larry Dewerd, Stephen Kry

Department of Radiation Oncology Faculty Papers

BACKGROUND: Clinical intensity modulated radiation therapy plans have been described using various complexity metrics to help identify problematic radiotherapy plans. Most previous studies related to the quantification of plan complexity and their utility have relied on institution-specific plans which can be highly variable depending on the machines, planning techniques, delivery modalities, and measurement devices used. In this work, 1723 plans treating one of only four standardized geometries were simultaneously analyzed to investigate how radiation plan complexity metrics vary across four different sets of common objectives.

PURPOSE: To assess the treatment plan complexity characteristics of plans developed for Imaging and Radiation …

Chromosomal 3q Amplicon Encodes Essential Regulators Of Secretory Vesicles That Drive Secretory Addiction In Cancer, Xiaochao Tan, Shike Wang, Guan-Yu Xiao, Chao Wu, Xin Liu, Biyao Zhou, Jiang Yu, Dzifa Yawa Duose, Yuanxin Xi, Jing Wang, Kunika Gupta, Apar Pataer, Jack A Roth, Michael P Kim, Fengju Chen, Chad J Creighton, William K Russell, Jonathan M Kurie

Faculty, Staff and Student Publications

Cancer cells exhibit heightened secretory states that drive tumor progression. Here, we identify a chromosome 3q amplicon that serves as a platform for secretory regulation in cancer. The 3q amplicon encodes multiple Golgi-resident proteins, including the scaffold Golgi integral membrane protein 4 (GOLIM4) and the ion channel ATPase Secretory Pathway Ca2+ Transporting 1 (ATP2C1). We show that GOLIM4 recruits ATP2C1 and Golgi phosphoprotein 3 (GOLPH3) to coordinate calcium-dependent cargo loading and Golgi membrane bending and vesicle scission. GOLIM4 depletion disrupts the protein complex, resulting in a secretory blockade that inhibits the progression of 3q-amplified malignancies. In addition to its role …

Evolution Of Chromosome-Arm Aberrations In Breast Cancer Through Genetic Network Rewiring, Elena Kuzmin, Toby M Baker, Tom Lesluyes, Jean Monlong, Kento T Abe, Paula P Coelho, Michael Schwartz, Joseph Del Corpo, Dongmei Zou, Genevieve Morin, Alain Pacis, Yang Yang, Constanza Martinez, Jarrett Barber, Hellen Kuasne, Rui Li, Mathieu Bourgey, Anne-Marie Fortier, Peter G Davison, Atilla Omeroglu, Marie-Christine Guiot, Quaid Morris, Claudia L Kleinman, Sidong Huang, Anne-Claude Gingras, Jiannis Ragoussis, Guillaume Bourque, Peter Van Loo, Morag Park

Faculty, Staff and Student Publications

The basal breast cancer subtype is enriched for triple-negative breast cancer (TNBC) and displays consistent large chromosomal deletions. Here, we characterize evolution and maintenance of chromosome 4p (chr4p) loss in basal breast cancer. Analysis of The Cancer Genome Atlas data shows recurrent deletion of chr4p in basal breast cancer. Phylogenetic analysis of a panel of 23 primary tumor/patient-derived xenograft basal breast cancers reveals early evolution of chr4p deletion. Mechanistically we show that chr4p loss is associated with enhanced proliferation. Gene function studies identify an unknown gene, C4orf19, within chr4p, which suppresses proliferation when overexpressed-a member of the PDCD10-GCKIII kinase module …

Xpo1 Blockade With Kpt-330 Promotes Apoptosis In Cutaneous T-Cell Lymphoma By Activating The P53-P21 And P27 Pathways, Nitin Chakravarti, Amy Boles, Rachel Burzinski, Paola Sindaco, Colleen Isabelle, Kathleen Mcconnell, Anjali Mishra, Pierluigi Porcu

Kimmel Cancer Center Faculty Papers

Dysregulated nuclear-cytoplasmic trafficking has been shown to play a role in oncogenesis in several types of solid tumors and hematological malignancies. Exportin 1 (XPO1) is responsible for the nuclear export of several proteins and RNA species, mainly tumor suppressors. KPT-330, a small molecule inhibitor of XPO1, is approved for treating relapsed multiple myeloma and diffuse large B-cell lymphoma. Cutaneous T-cell lymphoma (CTCL) is an extranodal non-Hodgkin lymphoma with an adverse prognosis and limited treatment options in advanced stages. The effect of therapeutically targeting XPO1 with KPT-330 in CTCL has not been established. We report that XPO1 expression is upregulated in …