Neoplasms Commons^™

How Opportune Is Multigene Testing In Metastatic Colorectal Cancer? A Review, Cristina Orlov-Slavu, Andreea Parosanu, Mihaela Olaru, Dragos Serban, Ioana Paunica, Cornelia Nitipir

Journal of Mind and Medical Sciences

Personalized treatment in oncology is the most innovative method of care. The best method to establish personalized treatment is by genetic characterization of the malignant cell.

Theoretically, the more detailed the characterization, the more effective the choice of treatment becomes. Currently, there are fast and relatively low-cost options that allow such genetic characterization. However, test results sometimes do not detect targetable alterations and, even if they do detect, the use of the treatment-alteration combination does not always generate a satisfactory oncological response.

The present paper aims to answer two questions. First, how targetable can the most common gene alterations in …

The Molecular Mechanisms Linking Metabolic Syndrome To Endometrial And Breast Cancers, Andrada-Luciana Lazar, Romana Vulturar, Adriana Fodor, Olga Hilda Orasan, Camil-Horia Eusebiu Crișan, Cezar Login, Ioana Para, Vasile Negrean, Brandusa Tiperciuc, Angela Cozma

Journal of Mind and Medical Sciences

The metabolic syndrome represents a plethora of cardio-metabolic risk factors including obesity, arterial hypertension, atherogenic dyslipidemia, hyperglycemia, accompanied by pro-inflammatory and pro-thrombotic state. The metabolic syndrome is one of the key risk factors for certain types of cancer. Among these malignancies, breast cancer and endometrial neoplasms require special attention. Incriminated major causes for the development of breast and endometrial cancer in metabolic syndrome patients are: the pro-inflammatory status and related cytokines, adipokine imbalances, hyperestrogenism, growth factors, disturbances in cancer microenvironment, insulin resistance and hyperinsulinemia. The metabolic syndrome consists of molecular dysregulations that create a pro-oncogenic status. Our review aims at …

Alcohol Consumption Is Associated With Increased Cea Levels In Male Patients With Stage Iv Colorectal Cancer- A Single-Institution Retrospective Analysis, Lauren M. Keim, Alexander W. Praus, Walter S. Campbell, Kaeli K. Samson, Ashley M. Mohr, Martin Tobi, Benita L. Mcvicker

Graduate Medical Education Research Journal

Introduction: Alcohol use is an independent risk factor for liver metastasis, a major cause of morbidity and mortality in colorectal cancer (CRC) patients. Serum CEA level is an established prognostic indicator in CRC, yet the correlation with behavioral factors such as alcohol use remains to be defined. In a single-center review, we evaluated alcohol use, gender, and CEA levels in predicting advanced disease in CRC patients.

Methods: Retrospective analysis of UNMC patients diagnosed with CRC as the primary cancer between 2012-2019, stages I-IV, and age >19 with documentation of alcohol use. Univariable statistics were performed using Chi-Square and non-parametric tests. …

The Contribution Of Patient Reported Outcome Measures To Shared Decision-Making In Radiation Oncology At A Midwestern Comprehensive Cancer Center, Kellie Bodeker

Doctor of Philosophy in Translational Health Sciences Dissertations

Background. Chronic diseases, such as lung cancer, require a provider-patient relationship developed over time. This relationship fosters shared decision-making (SDM), a collaborative, dynamic information exchange and analysis between provider and patient regarding treatment and desired outcomes. Established benefits to SDM include an improved quality of life and decreased anxiety and depression. Despite established benefits, recent research suggests radiation oncologists are not engaging in SDM. A decision-aid tool utilizing patient reported outcome measures may increase SDM between radiation oncologists and patients with lung cancer. Patient-reported outcome measures, wherein the patient provides direct assessment of their health and quality of life, …

A Cancer Ubiquitome Landscape Identifies Metabolic Reprogramming As Target Of Parkin Tumor Suppression, Ekta Agarwal, Aaron R Goldman, Hsin-Yao Tang, Andrew V Kossenkov, Jagadish C Ghosh, Lucia Languino, Valentina Vaira, David W Speicher, Dario C Altieri

Department of Cancer Biology Faculty Papers

Changes in metabolism that affect mitochondrial and glycolytic networks are hallmarks of cancer, but their impact in disease is still elusive. Using global proteomics and ubiquitome screens, we now show that Parkin, an E3 ubiquitin ligase and key effector of mitophagy altered in Parkinson's disease, shuts off mitochondrial dynamics and inhibits the non-oxidative phase of the pentose phosphate pathway. This blocks tumor cell movements, creates metabolic and oxidative stress, and inhibits primary and metastatic tumor growth. Uniformly down-regulated in cancer patients, Parkin tumor suppression requires its E3 ligase function, is reversed by antioxidants, and is independent of mitophagy. These data …

Factors That Impact Outcome In Patients Post-Esophagectomy, Leona Jakupi

Theses and Graduate Projects

Background: Esophageal malignancy and severe benign esophageal disorders are now treated by esophagectomy. Although mortality rates after esophagectomy have progressively decreased, many patients continue to suffer from increasing problems despite advances in patient selection, surgical techniques, and postoperative care. The purpose of this research is to determine the perioperative variables that affect morbidity and mortality after esophagectomy.

Methods: A thorough search of Google Scholar, UpToDate, and the Lindell Library was conducted to find previously published papers describing the different outcomes related to esophagectomy. This research consulted a total of 30 reviews and two publications. The esophagus’s architecture, perioperative evaluations, surgical …

The Sulfur Microbial Diet And Risk Of Colorectal Cancer By Molecular Subtypes And Intratumoral Microbial Species In Adult Men, Daniel R. Sikavi, Long H. Nguyen, Koichiro Haruki, Tomotaka Ugai, Wenjie Ma, Dong D. Wang, Kelsey N. Thompson, Yan Yan, Tobyn Branck, Jeremy E. Wilkinson, Naohiko Akimoto, Rong Zhong, Mai Chan Lau, Kosuke Mima, Keisuke Kosumi, Teppei Morikawa, Eric B. Rimm, Wendy S. Garrett, Jacques Izard, Yin Cao, Mingyang Song, Curtis Huttenhower, Shuji Ogino, Andrew T. Chan

Department of Food Science and Technology: Faculty Publications

Introduction: We recently described the sulfur microbial diet, a pattern of intake associated with increased gut sulfur-metabolizing bacteria and incidence of distal colorectal cancer (CRC). We assessed whether this risk differed by CRC molecular subtypes or presence of intratumoral microbes involved in CRC pathogenesis (Fusobacterium nucleatum and Bifidobacterium spp.).

Methods: We performed Cox proportional hazards modeling to examine the association between the sulfur microbial diet and incidence of overall and distal CRC by molecular and microbial subtype in the Health Professionals Follow-Up Study (1986-2012).

Results: We documented 1,264 incident CRC cases among 48,246 men, approximately 40% …

The Microsatellite Instability High Endometrial Tumor Microenvironment And Identifying Predictive Biomarkers Of Response To Pembrolizumab, Jeffrey How

Dissertations and Theses (Open Access)

Objective: Half of patients with microsatellite instability high (MSI-H) endometrial cancer are treatment-refractory to pembrolizumab. We sought to evaluate the MSI-H endometrial tumor samples to examine differences in the tumor microenvironment (TME) and identify transcriptomic signatures associated with response/resistance to pembrolizumab. Methods: Archival tumor samples from MSI-H endometrial cancer patients treated at MD Anderson Cancer Center were obtained. Tissue samples originating from patients who did not receive pembrolizumab treatment (“untreated cohort ”; n = 11) were analyzed via RNA sequencing (RNA-seq). Pre-treatment archival tumor samples (“treated cohort”; n = 23) from patients who were later treated with pembrolizumab were collected …

Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Diagnosis Obscured By Concomitant Recreational Drug Use, Paige Lester Ms Ii, Adam M. Franks Md, William Rollyson Ms Iv, Jenna K. Barbour Md, Matthew B. Curry Md

Marshall Journal of Medicine

Anti-NMDA receptor encephalitis (aNMDAre) is a relatively newly discovered autoimmune and inflammatory disorder affecting the limbic system. It has a clinical course that includes Prodromal, Psychiatric, Unresponsive and Hyperkinetic stages. These stages are often confused with mental health issues in the medical literature, but they also share symptoms of various drug intoxication and withdrawal states. Implicit bias in physicians regarding substance use disorder and patient demographics can impair delivery of care and outcomes in patients with aNMDAre, especially in an environment of recreational drug use. When clinical presentation aligns, this diagnosis should be investigated as soon as possible, even in …

External Beam Radiation Therapy Carries Lower Risk Of Sexual Dysfunction As Compared To Radical Prostatectomy In Treatment Of Patients With Localized Prostate Cancer, Aamod S. Dekhne

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Donovan JL, Hamdy FC, Lane JA, et al. Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med. 2016;375(15):1425-1437. https://doi.org/10.1056/NEJMoa1606221

for a patient with localized prostate cancer and concerns regarding future sexual dysfunction.

Microrna-26a-5p As A Potential Predictive Factor For Determining The Effectiveness Of Trastuzumab Therapy In Her-2 Positive Breast Cancer Patients, Sadra Samavarchi Tehrani, Ehsan Zaboli, Farzin Sadeghi, Soraya Khafri, Ansar Karimian, Mahnoosh Rafie, Hadi Parsian

BioMedicine

Background: Breast cancer (BC) is known as the most prevalence type of cancer among women. Trastuzumab, as a cancer drug, has been used broadly in human epidermal growth factor receptor 2 (HER-2) positive BC patients. On the other hand, accumulating evidence has demonstrated that microRNAs involved in pathogenesis BC. Hence, we aimed to investigate the effect of trastuzumab on the expression levels of microRNA-26a in HER-2positiveBC patients.

Methods: This study was conducted on HER-2 positive BC patients and HER-2 Negative BC patients. Serum expression of microRNA-26a were detected by real-time PCR. Then, we assessed the correlation of microRNA-26a level with …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

University Scholar Projects

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to …

Low Dose Doxorubicin Inhibits Immune Checkpoint Upregulation In Acute Leukemias, Bradley C. Stockard

Research Days

Background: Evasion of drug and immune response in therapy-resistant leukemic stem cells (LSCs) is a major cause of relapse. A previous study has identified an alternative mechanism of action for low-dose doxorubicin (DXR) that inhibits upregulation of immune checkpoints (IC) in LSCs.

Objectives/Goal: The objective of this study is to establish the DXR dose range that will achieve the inhibition of immune checkpoint expression in leukemic cell lines.

Methods/Design: Cells were analyzed for expression of CTLA-4, LAG-3, PD-1, TIGIT, and TIM-3 via flow cytometry. Analysis was performed on days 3, 5, and 8 of treatment at concentrations identified as low, …

A Pediatric Case Of Treatment-Related Myelodysplastic Syndrome While On Therapy For Pre-B All, Sara Mcelroy

Research Days

Background: Treatment-related myelodysplastic syndrome (t-MDS) is a known, but rare, late effect of cancer therapy, specifically radiation, alkylating agents or topoisomerase II inhibitors. When secondary to treatment with alkylating agents, t-MDS typically occurs 4 to 7 years after therapy, and common cytogenetics include chromosomes 5 and 7 abnormalities. Treatment in children with t-MDS is typically allogeneic stem cell transplant, but the prognosis remains poor.

Objectives/Goal: To describe a rare case of a pediatric patient who developed t-MDS while receiving treatment for Pre-B Cell Acute Lymphoblastic Leukemia (pre-B ALL) and to outline the treatment regimen that he received.

Methods/Design: Case Report …

Replication Protein A (Rpa) Targeting Of Uracil Dna Glycosylase (Ung2), Derek Chen, Brian P Weiser

Rowan-Virtua Research Day

Replication Protein A (RPA) is a single stranded DNA binding protein which stabilizes ssDNA for replication and repair. One function of RPA is to bind the DNA repair enzyme uracil DNA glycosylase (UNG2) and direct its activity towards ssDNA dsDNA junctions.

UNG2 removes uracil bases from DNA which can appear through dUMP misincorporation or through cytosine deamination. If uracil is present instead of a cytosine, then the original GC pair becomes a GU pair. The uracil will then base pair to adenine in the replicated daughter strand. This results in a GC → AT mutation that could contribute to cancer …

The Effect Of Carfilzomib And Bortezomib Based Regimes On Cardiotoxicity In Multiple Myeloma Patients At Cooper University Hospital, Ami Patel, Tulin Budak-Alpdogan, Stalam Tapati

Rowan-Virtua Research Day

Introduction

• Multiple myeloma (MM) is a cancer of plasma cells, which is a white blood cell that normally produces antibodies
• Treatment in patients younger than 65 years old is typically high dose chemotherapy, usually with bortezomib based regimens or lenalidomide dexamethasone, followed by a stem cell transplant
• For patients with relapsed myeloma, carfilzomib is usually the treatment of choice
• Carfilzomib is a highly selective, irreversible proteasome inhibitor that binds to the 20 S proteasome. Several studies have illustrated that carfilzomib has been associated with cardiovascular adverse events (CVAE).
• Current literature on the role and effect of bortezomib on cardiotoxicity is …

Novel Technology Enables Diagnostic Ultrasound Machine To Treat Hepatocellular Carcinoma In Mice, Ryan Morrison, Mrigendra B. Karmacharya, Chandra M. Sehgal

Rowan-Virtua Research Day

An off-the-shelf diagnostic transducer (ULTRASONIX C5-2) was modified with custom-built circuitry to enable the transducer to produce therapeutic ultrasound in order to ablate hepatocellular carcinomas grown in immunodeficient athymic nude mice (25-35 g; Charles River Laboratories, Wilmington, MA, USA). The therapeutic antivascular ultrasound (AVUS) produced by the off-the-shelf abdominal transducer was unfocused, continuous 2.8MHz ultrasound targeting contrast-enhancing perflutren lipid microbubbles within tumor vasculature. Previous research with a dedicated physiotherapy ultrasound machine (D150 Plus, Dynatronics Corp., Salt Lake City, UT, USA) targeting similar hepatocellular carcinomas showed disrupted tumor neovasculature and irreparable dilation of tumor capillaries with subsequent intercellular edema and hemorrhage.1-3 …

Phyllodes Tumor Containing Invasive Ductal Carcinoma: A Rare Case Description & Review Of Literature, Kathryn Eckert, John Ground, Alyssa Imperatore, Victoria Tiedemann, Linda Szczurek

Rowan-Virtua Research Day

Phyllodes tumors are uncommon, often benign, malignancies of the breast and account for approximately 0.5% of all breast malignancies. These tumors were first described in 1838 by Johannes Muller as cystosarcoma phyllodes and were later more aptly renamed phyllodes tumors (as they were neither cystic nor sarcomatous).(1) As a mixed connective tissue and epithelial tumor, these behave similar to benign fibroadenomas, though their growth is much more rapid and they tend to occur in older patients.(2) Hallmarked by their large size at presentation, these tumors average between 4 and 7 cm at the time of diagnosis. The only known risk …

Assessment Of Factors Preventing Adequate Decline In Cervical Cancer Rates Amongst Minority Women In New Jersey, Rosie Wenrich, Jillian Baker

Rowan-Virtua Research Day

Background

• Nationally declining cervical cancer rates are still high amongst minority women in NJ, with Hispanic women being affected the most.

• The Human Papilloma Virus (HPV) is the most common sexually transmitted infection and can lead to cervical cancer

• Administration of the 9-valent HPV vaccine can prevent infection and progression to cancer

• Regular cervical cancer screenings allow for better outcomes

• Various barriers prevent people with a cervix receiving the vaccine

• Various barriers prevent people with a cervix aged >/= 30 from receiving regular cervical cancer screenings

Conclusions

• Improved physician recommendation is required for the …

Barriers To Lung Cancer Screening Among African American Males Aged 50-70 In The United States, Edward Marines

Rowan-Virtua Research Day

Objectives:

• Identify the different barriers to lung cancer screening among African American males
• Examine potential methods of increasing access and participation within this population