Neoplasms Commons^™

Mir-155 Expression And Correlation With Clinical Outcome In Pediatric Aml: A Report From Children's Oncology Group., Ranjani Ramamurthy, Maya Hughes, Valerie Morris, Hamid Bolouri, Robert B. Gerbing, Yi-Cheng Wang, Michael R. Loken, Susana C. Raimondi, Betsy A. Hirsch, A S. Gamis, Vivian G. Oehler, Todd A. Alonzo, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Aberrant expression of microRNA-155 (miR-155) has been implicated in acute myeloid leukemia (AML) and associated with clinical outcome.

PROCEDURE: We evaluated miR-155 expression in 198 children with normal karyotype AML (NK-AML) enrolled in Children's Oncology Group (COG) AML trial AAML0531 and correlated miR-155 expression levels with disease characteristics and clinical outcome. Patients were divided into quartiles (Q1-Q4) based on miR-155 expression level, and disease characteristics were then evaluated and correlated with miR-155 expression.

RESULTS: MiR-155 expression varied over 4-log10-fold range relative to its expression in normal marrow with a median expression level of 0.825 (range 0.043-25.630) for the entire …

Erratum To: High Expression Of Myocyte Enhancer Factor 2c (Mef2c) Is Associated With Adverse-Risk Features And Poor Outcome In Pediatric Acute Myeloid Leukemia: A Report From The Children's Oncology Group., George S. Laszlo, Todd A. Alonzo, Chelsea J. Gudgeon, Kimberly H. Harrington, Alex Kentsis, Robert B. Gerbing, Yi-Cheng Wang, Rhonda E. Ries, Susana C. Raimondi, Betsy A. Hirsch, A S. Gamis, Soheil Meshinchi, Roland B. Walter

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

5-Hydroxymethylcytosine Localizes To Enhancer Elements And Is Associated With Survival In Glioblastoma Patients, Kevin C. Johnson, E. Andres Houseman, Jessica E. King, Katharine M. Von Herrmann, Camilo E. Fadu, Brock C. Christensen

Dartmouth Scholarship

Glioblastomas exhibit widespread molecular alterations including a highly distorted epigenome. Here, we resolve genome-wide 5-methylcytosine and 5-hydroxymethylcytosine in glioblastoma through parallel processing of DNA with bisulfite and oxidative bisulfite treatments. We apply a statistical algorithm to estimate 5-methylcytosine, 5-hydroxymethylcytosine and unmethylated proportions from methylation array data. We show that 5-hydroxymethylcytosine is depleted in glioblastoma compared with prefrontal cortex tissue. In addition, the genomic localization of 5-hydroxymethylcytosine in glioblastoma is associated with features of dynamic cell-identity regulation such as tissue-specific transcription and super-enhancers. Annotation of 5-hydroxymethylcytosine genomic distribution reveal significant associations with RNA regulatory processes, immune function, stem cell maintenance and …

Photothermal Therapy Improves The Efficacy Of A Mek Inhibitor In Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors., Elizabeth E. Sweeney, Rachel A. Burga, Chaoyang Li, Yuan Zhu, Rohan Fernandes

Pediatrics Faculty Publications

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive tumors with low survival rates and the leading cause of death in neurofibromatosis type 1 (NF1) patients under 40 years old. Surgical resection is the standard of care for MPNSTs, but is often incomplete and can generate loss of function, necessitating the development of novel treatment methods for this patient population. Here, we describe a novel combination therapy comprising MEK inhibition and nanoparticle-based photothermal therapy (PTT) for MPNSTs. MEK inhibitors block activity driven by Ras, an oncogene constitutively activated in NF1-associated MPNSTs, while PTT serves as a minimally invasive method to ablate …

Determining The Incidence And Factors Of Cardiotoxicity In Breast Cancer Patients Treated With Anthracycline And/Or Trastuzumab-Containing Regimen At Aurora Health Care, Stephanie Ghojallu, Matthew Rappelt, Han-Yang Chen, Ruth Perez, Lydia Garlie, Geoffrey Riddell, Yingying Gu, Jun Zhang, Rubina Qamar, Bijoy K. Khandheria, Arshad Jahangir, Yang Shi

Journal of Patient-Centered Research and Reviews

Background: Anthracycline and trastuzumab are common breast cancer treatments. While improving survival, they elevate risk of congestive heart failure. The incidence of cardiotoxicity (CTx) with these therapies varies in the literature from 10% to 59%, higher than those reported in clinical trials (4%–10%) that excluded patients with preexisting cardiovascular comorbidities. Studies have failed to establish consensus on the risk factors for CTx associated with these therapies.

Purpose: We aim to determine the incidence and risk factors of CTx in breast cancer patients treated with anthracycline and/or trastuzumab at Aurora Health Care.

Methods: A retrospective review of patients with breast cancer …

Shorter Remission Telomere Length Predicts Delayed Neutrophil Recovery After Acute Myeloid Leukemia Therapy: A Report From The Children's Oncology Group., Robert B. Gerbing, Todd A. Alonzo, Lillian Sung, Alan S. Gamis, Soheil Meshinchi, Sharon E. Plon, Alison A. Bertuch, Maria M. Gramatges

Manuscripts, Articles, Book Chapters and Other Papers

Purpose Suboptimal outcomes for children with acute myeloid leukemia (AML) necessitate maximally intensive therapy. Consequently, serious adverse events, such as prolonged periods of profound myelosuppression, contribute to AML treatment-related mortality. Telomeres, the repetitive DNA-protein structures at chromosome ends, influence cellular replicative capacity in that critically short telomeres can induce cell senescence or apoptosis. Our objective was to evaluate the impact of telomere length on duration of post-therapy neutropenia in a pediatric AML cohort. Patients and Methods Patients were diagnosed with de novo AML, enrolled in Children's Oncology Group study AAML0531, and included those with (n = 53) and without (n …

Association Between Prolonged Neutropenia And Reduced Relapse Risk In Pediatric Aml: A Report From The Children's Oncology Group., Lillian Sung, Richard Aplenc, Todd A. Alonzo, Robert B. Gerbing, Yi-Cheng Wang, Soheil Meshinchi, A S. Gamis

Manuscripts, Articles, Book Chapters and Other Papers

Objective was to describe the relationship between the number of sterile site infections and duration of neutropenia during the first four cycles of chemotherapy and the risk of recurrence and overall survival in children with newly diagnosed acute myeloid leukemia (AML). AAML0531 was a Children's Oncology Group randomized phase 3 clinical trial that included 1022 children with de novo AML. For this analysis, we focused on non-Down syndrome favorable and standard risk patients who completed at least 4 cycles of chemotherapy without recurrence or withdrawal during protocol therapy. Those receiving hematopoietic stem cell transplantation in first remission were excluded. Five …

Processing Information After A Child's Cancer Diagnosis-How Parents Learn., Cheryl C. Rodgers, Kristin Stegenga, Janice S. Withycombe, Karen Sachse, Katherine Patterson Kelly

Manuscripts, Articles, Book Chapters and Other Papers

Parents of a child newly diagnosed with cancer must receive an extensive amount of information before their child's initial hospital discharge; however, little is known about best practices for providing this education. An interpretive descriptive study design was used to describe actual and preferred educational content, timing, and methods among parents of children newly diagnosed with cancer prior to their child's first hospital discharge. Twenty parents of children diagnosed with various malignancies participated in individual interviews 2 to 12 months after their child's diagnosis. Data were analyzed using constant comparative analysis. Education delivery occurred in a telling manner at diagnosis …

Constitutively Activated Pi3k Accelerates Tumor Initiation And Modifies Histopathology Of Breast Cancer, M. R. Sheen, J. D. Marotti, M. J. Allegrezza, M. Rutkowski, J. R. Conejo-Garcia, S. Fiering

Dartmouth Scholarship

The gene encoding phosphatidylinositol 3-kinase catalytic subunit α-isoform (PIK3CA, p110α) is frequently activated by mutation in human cancers. Based on detection in some breast cancer precursors, PIK3CA mutations have been proposed to have a role in tumor initiation. To investigate this hypothesis, we generated a novel mouse model with a Cre-recombinase regulated allele of p110α (myristoylated-p110α, myr-p110α) along with p53fl/fl deletion and KrasG12D also regulated by Cre-recombinase. After instillation of adenovirus-expressing Cre-recombinase into mammary ducts, we found that myr-p110α accelerated breast tumor initiation in a copy number-dependent manner. Breast tumors induced by p53fl/fl;KrasG12D with no or one copy of myr-p110α …

A Proteogenomic Approach To Understanding Myc Function In Metastatic Medulloblastoma Tumors., Jerome A Staal, Yanxin Pei, Brian R. Rood

Pediatrics Faculty Publications

Brain tumors are the leading cause of cancer-related deaths in children, and medulloblastoma is the most prevalent malignant childhood/pediatric brain tumor. Providing effective treatment for these cancers, with minimal damage to the still-developing brain, remains one of the greatest challenges faced by clinicians. Understanding the diverse events driving tumor formation, maintenance, progression, and recurrence is necessary for identifying novel targeted therapeutics and improving survival of patients with this disease. Genomic copy number alteration data, together with clinical studies, identifies c-MYC amplification as an important risk factor associated with the most aggressive forms of medulloblastoma with marked metastatic potential. Yet despite …

Sulfatase 2 Facilitates Lymphangiogenesis In Breast Cancer By Regulating Vegf-D., Chenfang Zhu, Xiaoliang Qi, Xin Zhou, Xin Nie, Yan Gu

Surgery Faculty Publications

In our previous studies, sulfatase 2 (Sulf2) was found to upregulate vascular endothelial growth factor-D (VEGF-D) expression in breast cancer. As VEGF-D plays an important role in lymphangiogenesis, we hypothesized that Sulf2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D. To evaluate the functions of Sulf2 on lymphangiogenesis in breast cancer, proliferation, apoptosis, cell cycle, cell mobility and tube-formation of lymphatic endothelial cells (LECs) were measured in vitro. Lymphangiogenesis in nude mouse ears and breast cancer xenografts were examined in vivo. Furthermore, the expression levels of related signaling pathway genes were screened and verified in LECs. We found that Sulf2 …

Rationale And Design Of The Children's Oncology Group (Cog) Study Alte1621: A Randomized, Placebo-Controlled Trial To Determine If Low-Dose Carvedilol Can Prevent Anthracycline-Related Left Ventricular Remodeling In Childhood Cancer Survivors At High Risk For Developing Heart Failure., Saro H. Armenian, Melissa M. Hudson, Ming Hui Chen, Steven D. Colan, Lanie Lindenfeld, George Mills, Aida Siyahian, Sarah Gelehrter, Ha Dang, Wendy Hein, Daniel M M. Green, Leslie L. Robison, F Lennie Wong, Pamela S. Douglas, Smita Bhatia

Manuscripts, Articles, Book Chapters and Other Papers

Background: Anthracyclines are widely used in the treatment of childhood cancer. One of the well-recognized side-effects of anthracycline therapy is dose-dependent cardiomyopathy that may progress to heart failure (HF) years after completion of cancer-directed therapy. This study will evaluate the efficacy of low-dose beta-blocker (carvedilol) for HF risk reduction in childhood cancer survivors at highest risk for HF. The proposed intervention has the potential to significantly reduce chronic cardiac injury via interruption of neurohormonal systems responsible for left ventricular (LV) remodeling, resulting in improved cardiac function and decreased risk of HF. The intervention is informed by previous studies demonstrating efficacy …

Gastrointestinal Stromal Tumor (Gist) Of The Treitz’S Angle– A Very Rare Cause Of High Bowel Obstruction, Mădălina Elena Tobă, Dan Florin Ungureanu, Lota Corina Georgescu, Traian Pătraşcu

Journal of Mind and Medical Sciences

Gastrointestinal stromal tumors (GIST) are somewhat rare gastrointestinal tumors - approximately 1% to 3% incidence, but they are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs are usually found in the stomach or small intestine but can occur anywhere within the gastrointestinal tract, even in extremely uncommon locations like duodeno-jejunal flexure. Only 3% – 5% of GISTs are located in the duodenum and tumors occurring in the angle of Treitz are even rarer, most published studies being case reports. These tumors have a size ranging from small lesions to large masses and can cause digestive bleeding or high …

A Pilot Study Of Circulating Tumor Cells In Stage Iv Non-Small Cell Lung Carcinoma, Max Haid, Edward Chesna, Mary Theodoroff, Debra K. Spaeth, Cheruppolil R. Santhosh-Kumar, Zahid N. Dar

Journal of Patient-Centered Research and Reviews

Purpose

Measurement of the number of circulating tumor cells (CTCs) in the bloodstream has been shown to have prognostic significance in treating breast carcinoma. This pilot study was formulated to determine if stage IV non-small cell lung carcinomas similarly shed malignant cells into the circulation and if their presence has prognostic significance.

Methods

Patients with stage IV non-small cell lung carcinomas were tested once for CTCs in 7.5 ml of their blood prior to receiving any treatments. A proprietary blood collection kit produced by Veridex LLC (Raritan, NJ), which manufactures the instrument that performs the immunomagnetic CELLSEARCH^® CTC assay, …

Metastatic Pancreatic Adenocarcinoma During Pregnancy., Jessica Davis, Showkat Bashir, Helmae Wubneh, Marie L. Borum

Surgery Faculty Publications

We present a rare case of metastatic pancreatic adenocarcinoma diagnosed antepartum. A high index of suspicion must be maintained to diagnose pancreatic cancer during pregnancy. We recommend a thorough history and physical and aggressive pursuit of sensitive imaging in patients with persistent symptoms. If pancreatic adenocarcinoma is diagnosed, a multidisciplinary approach that focuses on patient goals should be undertaken. The effect of pregnancy on tumor growth rates is unknown.

Repetitive, Pre-Anesthetic Fasting And Malnutrition In A Pediatric Oncology Population Undergoing Radiation Therapy, Laura P. Santibáñez

Dissertations and Theses (Open Access)

Background: Pediatric oncology patients often experience nutritional status changes, particularly malnutrition, which may adversely affect their outcomes. Although the consequences of malnutrition are elucidated, its causes remain unclear. A possible cause of malnutrition in pediatric oncology patients is repetitive, pre-anesthetic fasting prior to non-invasive procedures and treatments, such as anesthesia-assisted radiation therapy (AART). This exploratory study investigated the association between repetitive, pre-anesthetic fasting and non-fasting days and malnutrition in pediatric oncology patients receiving AART.

Procedure: A retrospective cohort of 138 pediatric oncology patients (£ 10 years of age) who received any type of radiation therapy (RT) with or without anesthesia …

Asymptomatic Left Ventricular Myxoma In A 12-Year-Old Male., Meghan Chlebowski, James O'Brien, Casey Hertzenberg, Jonathan B. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Cardiac myxoma is the most common cardiac tumor in patients of all ages; the majority are encountered as single left atrial tumors. Left ventricular myxomas are exceedingly rare, having been recorded in a small number of case reports involving children worldwide. We report a case of a left ventricular myxoma with left ventricular outflow tract obstruction in a previously healthy, asymptomatic adolescent black male. Transthoracic echocardiograms revealed a single, large (2.5 × 5-cm), lobulated, mobile mass within the left ventricular cavity that oscillated into the outflow tract, thereby causing moderate obstruction during systole. Advanced images delineated the location and tissue …

Elevated Mtss1 Expression Associated With Metastasis And Poor Prognosis Of Residual Hepatitis B-Related Hepatocellular Carcinoma, Xiu-Yan Huang, Zi-Li Huang, Bin Xu, Zi Chen

Dartmouth Scholarship

Background: Hepatectomy generally offers the best chance of long-term survival for patients with hepatocellular carcinoma (HCC). Many studies have shown that hepatectomy accelerates tumor metastasis, but the mechanism remains unclear.

Methods: An orthotopic nude mice model with palliative HCC hepatectomy was performed in this study. Metastasis-related genes in tumor following resection were screened; HCC invasion, metastasis, and some molecular alterations were examined in vivo and in vitro. Clinical significance of key gene mRNA expression was also analyzed.

Thyroid Cancer And Tumor Collaborative Registry (Tccr)., Oleg Shats, Whitney Goldner, Jianmin Feng, Alexander Sherman, Russell B. Smith, Simon Sherman

Journal Articles: Eppley Institute

A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software …

The Influence Of Mir-99a On Mtor Signaling Regulation In Colorectal Cancer Cell Lines., Jonathan Rice

Electronic Theses and Dissertations

Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of death. These are staggering statistics for a disease that can essentially be cured if caught early and the pathology is favorable to therapeutic intervention. There is currently a drastic decrease in five year survival as the cancer stage increases from locally confined disease to metastatic disease. These statistics suggest that although some strides have been made with colon cancer screening and early intervention, there is still much room for improvement in both screening and treatment of CRC. One of the pathways that have …

Cll Metabolism Is Regulated By Prognostic Factors, Modulated By Stroma And Abrogated By Pi3k Inhibition, Hima Vangapandu

Dissertations and Theses (Open Access)

Metabolism of chronic lymphocytic leukemia (CLL), a disease characterized by the relentless accumulation of mature B cells has been little explored. Bone marrow stromal cells provide a survival benefit to CLL cells, in part through PI3K/AKT pathway. Compared with proliferative B-cell lines, metabolic fluxes of oxygen and lactate were low in quiescent malignant B lymphocytes from CLL patients. Glycolysis (extracellular acidification rate, ECAR) was consistently low in CLL samples, but oxygen consumption (OCR) varied considerably. Higher OCR was associated with poor prognostic factors such as ZAP 70 positivity, unmutated IgVH, high β2M levels, and higher Rai stage. Co-culture with the …

A Mir-200c/141-Bmi1 Autoregulatory Loop Regulates Oncogenic Activity Of Bmi1 In Cancer Cells., Mingu Kang, Manjari Dimri, Goberdhan P. Dimri

Biochemistry and Molecular Medicine Faculty Publications

MicroRNAs (miRNAs) are known to function as oncomiRs or tumor suppressors and are important noncoding RNA regulators of oncogenesis. The miR-200c/141 locus on chromosome 12 encodes miR-200c and miR-141, two members of the miR-200 family, which have been shown to function as tumor suppressive miRNAs by targeting multiple oncogenic factors such as polycomb group protein BMI1. Here, we show that BMI1 reciprocally functions as a transcriptional repressor of the miR-200c/141 cluster and that BMI1 inhibitors upregulate expression of miR-200c and miR-141. Our data suggest that BMI1 binds to the miR-200c/141 promoter and regulates it through transcription factor binding motifs E-box …

Single-Nucleotide Polymorphisms In Psca And The Risk Of Breast Cancer In A Chinese Population., Meng Wang, Xijing Wang, Sidney W. Fu, Zhijun Dai, Tianbo Jin, + 10 Additional Authors

Medicine Faculty Publications

This study explored the associations between common PSCA single-nucleotide polymorphisms (rs2294008, rs2978974, and rs2976392) and breast cancer among 560 breast cancer cases and 583 controls (Chinese Han women). We found rs2294008 was significantly associated with a high risk of breast cancer (homozygote model, odds ratio [OR]: 1.67, 95% confidence interval [CI]: 1.06–2.59; recessive, OR: 1.64, 95% CI: 1.06–2.53). And stratification by menopausal status revealed an association of the minor allele of rs2294008 with breast cancer risk among premenopausal (homozygote model, OR: 2.41, 95% CI: 1.03–5.66; recessive, OR: 2.80, 95 % CI: 1.21–6.47) and postmenopausal women (allele model, OR: 1.29, 95% …

Neurocognitive Dysfunction In Brain Tumor Patients Following Radiation Therapy: A Review Of Biological Hypotheses, Current Treatment Outcomes, And Novel Therapeutic Strategies, Raj Singh

Marshall Journal of Medicine

Given the difficulty of surgical resection of brain neoplasms located adjacent to vital structures of the brain as well as the challenges posed by the blood-brain-barrier for the efficacy of chemotherapeutic agents, whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) are often turned to for patients with brain metastases as well as primary brain neoplasms. Though radiation therapy may be successful in local control of these tumors, many patients experience treatment-related neurocognitive issues later in life. In this review, we examine cognitive dysfunction in brain tumor patients following radiation therapy, with an emphasis on the pediatric population. Articles were …

Dc Beadm1™: Towards An Optimal Transcatheter Hepatic Tumour Therapy., Andrew L Lewis, Matthew R Dreher, Vincent O'Byrne, David Grey, Marcus Caine, Anthony Dunn, Yiqing Tang, Brenda Hall, Kirk D Fowers, Carmen Gacchina Johnson, Karun V. Sharma, Bradford J Wood

Pediatrics Faculty Publications

Clinical use of DC Bead™ loaded with doxorubicin (DEBDOX™) or irinotecan (DEBIRI™), for the treatment of primary and secondary tumours of the liver respectively, is showing great promise. Recently there has been a tendency to select smaller bead size ranges to treat tumours in an effort to allow more drug dose to be administered, improve tumoural penetration and resultant drug delivery and tumour coverage. Herein we describe the development and performance characterisation of a new DC Bead size range (DC BeadM1 (TM), 70-150 μm) capable of an increased bead delivery in the distal vasculature, corresponding to greater tumour coverage and …

Vertebral Metastasis As The Initial Manifestation Of Colon Cancer, Tushina Jain, Renee Williams, Benjamin Liechty, Lea Ann Chen

Medicine Faculty Publications

Oncology guidelines currently recommend against performing colonoscopies in the workup of adenocarcinoma of unknown primary unless colonic malignancy is otherwise suggested by clinical signs or symptoms. We present 2 cases of metastatic colonic adenocarcinoma that presented only with neurologic symptoms from vertebral metastasis. Although bony metastases are a rare presentation of colon cancer and colonoscopy is not warranted in the initial workup of adenocarcinoma of unknown primary, we describe these cases as a reminder that bony metastases do not rule out a colon cancer diagnosis.

Spatial And Temporal Homogeneity Of Driver Mutations In Diffuse Intrinsic Pontine Glioma., Hamid Nikbakht, Eshini Panditharatna, Leonie G Mikael, Rui Li, Tenzin Gayden, Alan Siu, Javad Nazarian, + 17 More

Neurological Surgery Faculty Publications

Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly paediatric brain tumours where needle biopsies help guide diagnosis and targeted therapies. To address spatial heterogeneity, here we analyse 134 specimens from various neuroanatomical structures of whole autopsy brains from nine DIPG patients. Evolutionary reconstruction indicates histone 3 (H3) K27M-including H3.2K27M-mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). Later oncogenic alterations arise in sub-clones and often …

Validation Of Metabolic Alterations In Microscale Cell Culture Lysates Using Hydrophilic Interaction Liquid Chromatography (Hilic)-Tandem Mass Spectrometry-Based Metabolomics, Venugopal Gunda, Fang Yu, Pankaj K. Singh

Journal Articles: Eppley Institute

By standard convention, in order to increase the efficacy of metabolite detection from cell culture lysates, metabolite extracts from a large quantity of cells are utilized for multiple reaction monitoring-based metabolomic studies. Metabolomics from a small number of cell extracts offers a potential economical alternative to increased cell numbers, in turn increasing the utility of cell culture-based metabolomics. However, the effect of reduced cell numbers on targeted metabolomic profiling is relatively unstudied. Considering the limited knowledge available of the feasibility and accuracy of microscale cell culture metabolomics, the present study analyzes differences in metabolomic profiles of different cell numbers of …

Overcoming Treatment Resistance In Heterogeneous Tumors, Nikhil Hebbar

Theses and Dissertations--Toxicology and Cancer Biology

Most primary tumors are heterogeneous and are often composed of therapy-sensitive and emerging therapy-resistant cancer cells. Rather unexpectedly, treatment of therapy-sensitive tumor cells in heterogeneous tumor microenvironments resulted in apoptosis of the therapy-resistant cancer cells. We identified a novel Par-4 amino-terminal fragment (PAF, which includes amino acids 1-131 of Par-4) that is produced and released by therapy-sensitive cancer cells following therapy-induced caspase-dependent cleavage of the tumor suppressor Par-4. PAF caused paracrine apoptosis in therapy-resistant cancer cells. Unlike Par-4-inducible apoptosis, which is dependent on the cell surface GRP78 receptor, PAF produced cancer-selective apoptosis independent of cell surface GRP78 function. Par-4 contains …

Tmsb4y Is A Candidate Tumor Suppressor On The Y Chromosome And Is Deleted In Male Breast Cancer., Hong Yuen Wong, Grace M Wang, Sarah Croessmann, Daniel J Zabransky, Anita Aggarwal, Min-Ling Liu, + 10 More

Pathology Faculty Publications

Male breast cancer comprises less than 1% of breast cancer diagnoses. Although estrogen exposure has been causally linked to the development of female breast cancers, the etiology of male breast cancer is unclear. Here, we show via fluorescence in situ hybridization (FISH) and droplet digital PCR (ddPCR) that the Y chromosome was clonally lost at a frequency of ~16% (5/31) in two independent cohorts of male breast cancer patients. We also show somatic loss of the Y chromosome gene TMSB4Y in a male breast tumor, confirming prior reports of loss at this locus in male breast cancers. To further understand …