Medical Specialties Commons^™

Functional Analysis Of Human Beta Defensin-1: Novel Insight Into Its Role In Prostate Cancer, Rebecca S. Bullard

MUSC Theses and Dissertations

Prostate cancer is the second leading cause of cancer-related deaths in men in the United States. The molecular pathogenesis of this disease includes genetic alterations, infection, and exposure to inflammatory or dietary oxidants. Recently, research has focused on the role of host defense peptides in tumor immunity. Defensins, a highly conserved multigene family of proteins that possess antimicrobial and antiviral properties, play an essential role in innate and adaptive immunity. These peptides are categorized into alpha- and beta-defensins based upon the spacing and connection between the six conserved cysteine residues of the mature peptide. Human Beta Defensin-1 (hBD-1), an important …

Prolonged Hemophagocytic Lymphohistiocytosis Syndrome As An Initial Presentation Of Hodgkin Lymphoma: A Case Report., Kathryn Chan, Eric Behling, David S Strayer, William S Kocher, Scott K Dessain

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

INTRODUCTION: Hemophagocytic lymphohistiocytosis is an immune-mediated syndrome that typically has a rapidly progressive course that can result in pancytopenia, coagulopathy, multi-system organ failure and death. CASE PRESENTATION: A 57-year-old Caucasian woman was referred in fulminant hemophagocytic lymphohistiocytosis, with fever, pancytopenia, splenomegaly, mental status changes and respiratory failure. She was found to have stage IV classical Hodgkin lymphoma, in addition to Epstein-Barr virus and cytomegalovirus viremia. Her presentation was preceded by a 3-year prodrome consisting of cytopenia and fever that were partially controlled by steroids and azathioprine. CONCLUSION: Fulminant hemophagocytic lymphohistiocytosis may follow a prodromal phase that possesses features suggestive of …

Delineation Of Malignant Areas In Histological Images Of Head -Neck Cancer, Mutlu Mete

Theses and Dissertations

Histopathology remains one of the most critical steps in diagnosis and treatment of any kind of cancer. Recently, the improvements in imaging techniques led to the discovery of virtual histological slides, which in fact are high resolution images with a resolution of 0.25 μm/pixel. These images enabled researchers to investigate cancer cell morphologies at the finest level. Traditionally, assessment of tumor margins is done manually by a histopathologist. The procedure requires histological processing of the tumor and examining multiple tissue sections. The number of sections varies based on the size, location, and type of tumor. The recognition of cancer areas …

Beliefs, Perceptions, And Preferences For Treatment In Latinas With Breast Cancer, Barbara Ann Kreling

Walden Dissertations and Doctoral Studies

Research documents that breast cancer is the leading cause of death in Latina females. The exact numbers are unknown, but studies reveal that Latinas with breast cancer underuse recommended follow-up chemotherapy, decreasing their rates of survival. Although several factors may be responsible, cultural influences are a possible barrier. However, there is a gap in the literature about how culture affects decisions about breast cancer treatment. This focused ethnographic study examined the role of cultural beliefs and perceptions in the decision-making process for Latina women about whether or not to receive chemotherapy following a breast cancer diagnosis. Drawing from Douglas' cultural …

Living Past Your Expiration Date: A Phenomenological Study Of Living With Stage Iv Cancer Longer Than Expected, Cynthia Levine

Antioch University Dissertations & Theses

More treatment options exist today for persons diagnosed with terminal cancerextending lives longer than expected though there is little known about the psychosocial needs or resources for these individuals. This study describes the experience of living past the expiration date and still living with Stage IV cancer. A transcendental phenomenological approach was used to elucidate vivid expressions of this experience in a sample population of five Caucasian women. The women survived beyond their prognoses of an earlier expiration are not close to imminent death and are still living with incurable breast cancer metastases. The aim of this phenomenological inquiry is …

Maldi Mass Spectrometry Imaging For The Discovery Of Prostate Carcinoma Biomarkers, Lisa Harris Cazares

Theses and Dissertations in Biomedical Sciences

The elucidation of new biological markers of prostate cancer (PCa) should aid in the detection, and prognosis of this disease. Diagnostic decision making by pathologists in prostate cancer is highly dependent on tissue morphology. The ability to localize disease-specific molecular changes in tissue would help improve this critical pathology decision making process. Direct profiling of proteins in tissue sections using MALDI imaging mass spectrometry (MALDI-IMS) has the power to link molecular detail to morphological and pathological changes, enhancing the ability to identify candidates for new specific biomarkers. However, critical questions remain regarding the integration of this technique with clinical decision …

Evaluation Of Human Prolactin, Its Antagonist, And Antagonist-Based Fusion Proteins As Chemopreventative And Therapeutic Agents, Seth Tomblyn

All Dissertations

Cancer is a collection of diseases with many different manifestations and is the second leading cause of death in the United States. Breast cancer accounts for nearly one third of cancer diagnosis in women. Prolactin (PRL) functions as a lactogen and as a mammary gland differentiation factor. PRL acts in an autocrine/paracrine manner within the mammary gland and in breast tumors which implies PRL may be involved in breast cancer progression. This is corroborated by the PRLR over-expression in breast cancer cells lines and the majority of patient biopsies. These reasons make PRL and PRLR attractive targets for breast cancer …

Characterization Of The Anti-Angiogenic Properties Of Kdr-Ig4-7 And Its Variants As Potential Anti-Cancer Therapeutics, Jang Pyo Park

All Dissertations

Beginning with the development of an embryo and throughout one's adult life angiogenesis plays an essential role for organ growth and repair. The balancing of pro-angiogenic factors to anti-angiogenic factors is what regulates the process of angiogenesis. When this balance is disrupted in one direction or the other, numerous disorders can occur including ocular and inflammatory diseases and, in particular, tumor growth and metastasis. Therefore, inhibition of angiogenesis has become an effective therapy for arresting the growth of tumors.
A key regulator of angiogenesis involves vascular endothelial growth factor (VEGF) and its receptor, VEGFR-2 (KDR). The binding of VEGF to …

Interventional Options For Malignant Upper Gi Obstruction, 2nd Ed, James R. Ouellette, Lisa Patterson, Paula M. Termuhlen

Department of Surgery Faculty Publications

Background

Patients with unresectable cancers of the upper gastrointestinal tract often suffer severe symptoms due to pain, nausea and vomiting, weight loss, cachexia, and poor food tolerance. This can be related to gastric and duodenal cancers causing intrinsic obstruction of the intestinal lumen or pancreatic and biliary cancers causing extrinsic biliary compression. Management options vary depending on the site of obstruction, the patient’s functional status, the patient-defined goals of care, and estimated prognosis. Fast Fact #45 discussed medical management options. This Fact Fact reviews interventional approaches for upper GI obstructions, especially when further radiation, chemotherapy, medical management, or curative surgical …

Breast Cancer In Pakistan - Awareness And Early Detection, Saba Sohail, Shams Nadeem Alam

Department of Radiology

No abstract provided.

Adaptive Radiotherapy Planning On Decreasing Gross Tumor Volumes As Seen On Megavoltage Computed Tomography Images., Curtis Woodford, Slav Yartsev, R. Dar, Glenn Bauman, Jacob Van Dyk

Oncology Publications

PURPOSE: To evaluate gross tumor volume (GTV) changes for patients with non-small-cell lung cancer by using daily megavoltage (MV) computed tomography (CT) studies acquired before each treatment fraction on helical tomotherapy and to relate the potential benefit of adaptive image-guided radiotherapy to changes in GTV.

METHODS AND MATERIALS: Seventeen patients were prescribed 30 fractions of radiotherapy on helical tomotherapy for non-small-cell lung cancer at London Regional Cancer Program from Dec 2005 to March 2007. The GTV was contoured on the daily MVCT studies of each patient. Adapted plans were created using merged MVCT-kilovoltage CT image sets to investigate the advantages …

Anti-Tumor Effect Of Doxycycline On Glioblastoma Cells, Andrea Wang-Gillam, Eric Siegel, Debra A. Mayes, Laura F. Hutchins, Yi-Hong Zhou

Neuroscience, Cell Biology & Physiology Faculty Publications

AIM: Glioblastoma multiforme (GBM) is the most common primary brain tumor in humans, and it is highly invasive. Doxycycline, first identified as an antimicrobial agent, is a nonspecific inhibitor of matrix metalloproteinases (MMPs). Our objective was to investigate the anti-MMP effect of doxycycline at therapeutically acceptable levels on glioma cells in vitro.

METHODS: The MTT assay was used to determine the anti-proliferative effects of doxycycline. MMP2 activity and expression were determined by gelatinase zymography and real-time quantitative RT-PCR, respectively. Cell invasion was assessed by Matrigel invasion assay.

RESULTS: Doxycycline exerted mild anti-proliferative effects on all three glioma cell lines …

Understanding Barriers For Adherence To Follow-Up Care For Abnormal Pap Tests, Katherine S. Eggleston, Ann L. Coker, Irene Prabhu Das, Suzanne T. Cordray, Kathryn J. Luchok

CRVAW Faculty Journal Articles

Objective: Approximately 4000 women annually will die from preventable and treatable cervical cancer. Failure to adhere to follow-up recommendations after an abnormal Pap test can lead to development of cervical cancer. This paper summarizes the body of literature on adherence to follow-up after an abnormal Pap test in order to facilitate development of interventions

to decrease morbidity and mortality due to cervical cancer.

Methods: We conducted a comprehensive search of published literature addressing risk factors for adherence or interventions to improve adherence following an abnormal Pap test as the outcome. We included peer-reviewed original research conducted in the …

Oncolog, Volume 52, Number 11, November 2007, Diane Witter, Karen Stuyck, Garth Powis Dphil

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Outsmarting Brain Cancer
• Protecting the Heart
• House Call: Recognize the Signs of Ovarian Cancer
• DiaLog: Advancing Drug Design in Academia, by Garth Powis, DPhil, Director, Center for Targeted Therapy, Chair, Department of Experimental Therapeutics

Eltrombopag For The Treatment Of Chronic Idiopathic Thrombocytopenic Purpura, James Bussel, Bhabita Mayer, Nicole Stone, Michael Arning, Drew Provan, Mansoor Saleh

Haematology and Oncology, East Africa

Background: The pathogenesis of chronic idiopathic thrombocytopenic purpura (ITP) involves antibody-mediated platelet destruction and reduced platelet production. Stimulation of platelet production may be an effective treatment for this disorder.

Methods: We conducted a trial in which 118 adults with chronic ITP and platelet counts of less than 30,000 per cubic millimeter who had had relapses or whose platelet count was refractory to at least one standard treatment for ITP were randomly assigned to receive the oral thrombopoietin-receptor agonist eltrombopag (30, 50, or 75 mg daily) or placebo. The primary end point was a platelet count of 50,000 or more per …

Chemotherapy And Survival For Patients With Multiple Myeloma: Findings From A Large Nationwide And Population-Based Cohort, Nidhi Rohatgi, Xianglin L. Du, Ann L. Coker, Lemuel L. Moye, Michael Wang, Shenying Fang

CRVAW Faculty Journal Articles

Objective: To assess the patterns of chemotherapy use for patients with multiple myeloma and to determine if chemotherapy is effective in prolonging survival outside the clinical trial settings.

Methods: We studied a nationwide and population-based retrospective cohort of 4902 patients ≥65 years of age with stage II or III multiple myeloma from 1992 to 1999, identified from the Surveillance, Epidemiology, and End-Results-Medicare data. Multivariate logistic regression was used to estimate the odds ratio of receiving chemotherapy and Cox proportional hazard model was used to estimate the hazard ratio of mortality associated with chemotherapy.

Results: Of 4902 patients with stage II …

Selective Repression Of Retinoic Acid Target Genes By Rip140 During Induced Tumor Cell Differentiation Of Pluripotent Human Embryonal Carcinoma Cells, Kelly C. Heim, Kristina A. White, Dexin Deng, Craig R. Tomlinson, Jason Moore, Sarah Freemantle, Michael Spinella

Dartmouth Scholarship

The use of retinoids as anti-cancer agents has been limited due to resistance and low efficacy. The dynamics of nuclear receptor coregulation are incompletely understood. Cell-and context-specific activities of nuclear receptors may be in part due to distinct coregulator complexes recruited to distinct subsets of target genes. RIP140 (also called NRIP1) is a ligand-dependent corepressor that is inducible with retinoic acid (RA). We had previously shown that RIP140 limits RA induced tumor cell differentiation of embryonal carcinoma; the pluriopotent stem cells of testicular germ cell tumors. This implies that RIP140 represses key genes required for RA-mediated tumor cell differentiation. Identification …

Infiltrating Ductal Carcinoma Breast With Central Necrosis Closely Mimicking Ductal Carcinoma In Situ (Comedo Type): A Case Series, Shahid Pervez, Hassan Khan

Department of Pathology and Laboratory Medicine

Here we present a series of infiltrative ductal carcinoma breast cases (infiltrative ductal carcinoma with central necrosis) so closely mimicking 'DCIS with central comedo necrosis' that on initial morphological analysis these foci of tumors were labeled as DCIS (high grade, comedo). However on further histological work up and by using immunohistochemistry (IHC) for myoepithelial markers it was later confirmed that these were foci of infiltrative ductal carcinoma breast with central necrosis. This case series gives the realization that a breast carcinoma may be partly or entirely DCIS like yet invasive. In such a dilemma IHC especially for assessment of myoepithelial …

Phosphorylation-Induced Conformational Switching Of Cpi-17 Produces A Potent Myosin Phosphatase Inhibitor, Masumi Eto, Toshio Kitazawa, Fumiko Matsuzawa, Sei-Ichi Aikawa, Jason A. Kirkbride, Noriyoshi Isozumi, Yumi Nishimura, David L. Brautigan, Shin-Ya Ohki

Department of Molecular Physiology and Biophysics Faculty Papers

Phosphorylation of endogenous inhibitor proteins specific for type-1 Ser/Thr phosphatase (PP1) provides a mechanism for reciprocal coordination of kinase and phosphatase activities. Phosphorylation of Thr38 in the inhibitor protein CPI-17 transduces G-protein-mediated signaling into a > 1000-fold increase of inhibitory potency toward myosin phosphatase. We show here the solution NMR structure of phospho-T38-CPI-17 with r. m. s. d. of 0.36 ± 0.06 Å for the backbone secondary structure, which reveals how phosphorylation triggers a conformational change and exposes the PP1 inhibitory surface. This active conformation is stabilized by the formation of a hydrophobic core of intercalated side-chains, which is not formed …

Let-7 Expression Defines Two Differentiation Stages Of Cancer, Scott Shell, Sun-Mi Park, Amir Reza Radjabi, Robert Schickel, Emily Kistner, David Jewell

Dartmouth Scholarship

The early phases of carcinogenesis resemble embryonic development, often involving the reexpression of embryonic mesenchymal genes. The NCI60 panel of human tumor cell lines can genetically be subdivided into two superclusters (SCs) that correspond to CD95 Type I and II cells. SC1 cells are characterized by a mesenchymal and SC2 cells by an epithelial gene signature, suggesting that SC1 cells represent less differentiated, advanced stages of cancer. miRNAs are small 20- to 22-nucleotide-long noncoding RNAs that inhibit gene expression at the posttranscriptional level. By performing miRNA expression analysis on 10 Type I and 10 Type II cells, we have determined …

Effects Of Colon Cancer Risk Counseling For First-Degree Relatives, Karen Glanz, Alana D. Steffen, Lauren Taglialatela

Faculty Articles

Background: Individuals with a first-degree relative who has had colorectal cancer are at increased risk for colorectal cancer and thus can benefit from early detection. Tailored risk counseling may increase adherence to screening guidelines in these persons. The present study evaluated a culturally sensitive Colon Cancer Risk Counseling (CCRC) intervention for relatives of colorectal cancer patients.

Methods: A randomized trial evaluated personalized CCRC sessions with print materials and follow-up phone calls compared with a comparable General Health Counseling (GHC) intervention. One hundred and seventy-six siblings and children of colorectal cancer patients, living in Hawaii, were assessed at baseline and 4 …

Clear Cell Carcinoma Of Ovary With Associated Mucinous Cystadenoma And Endometriosis, Zeeshan Uddin, Nausheen Yaqoob, Naila Kayani, Sheema H. Hasan

Department of Pathology and Laboratory Medicine

A 45 year old woman presented with right sided ovarian mass with multiple omental deposits and liver metastases. The right ovary was enlarged and showed a partly cystic partly solid cut surface. Histological picture showed clear cell carcinoma with areas of mucinous cystadenoma and endometriosis. Clear cell carcinoma is known to be associated with endometriosis. To the best of author's knowledge, it's association with mucinous cystadenoma has been described only once in the literature, where clear cell carcinoma was shown to be associated with mucinous cystadenoma without any evidence of endometriosis.

Clinical Features And Management Of Merkel Cell Carcinoma, Ahmed Nadeem Abbasi

Department of Radiation Oncology

Merkel cell carcinoma (MCC) is an aggressive dermal tumour of neuroendocrine origin. MCC is a rare tumour and all information pertaining to its behaviour, therapy and prognosis is based on retrospective reports. The two potentially curative treatment modalities are surgery and radiotherapy. It is a rare, highly malignant primary skin tumour, originally called "trabecular carcinoma" of the skin. MCC poses a challenge to the clinician because of its rarity and poor prognosis. The optimal therapy is customised and tailored for each individual patient with the appropriate use of operative resection and radiation therapy. This review covers reports from several authors …

The Modifier Of Min 2 (Mom2) Locus: Embryonic Lethality Of A Mutation In The Atp5a1 Gene Suggests A Novel Mechanism Of Polyp Suppression., Amy A Baran, Karen A Silverman, Joseph Zeskand, Revati Koratkar, Ashley Palmer, Kristen Mccullen, Walter J Curran, Tina Bocker Edmonston, Linda D Siracusa, Arthur M Buchberg

Kimmel Cancer Center Faculty Papers

Inactivation of the APC gene is considered the initiating event in human colorectal cancer. Modifier genes that influence the penetrance of mutations in tumor-suppressor genes hold great potential for preventing the development of cancer. The mechanism by which modifier genes alter adenoma incidence can be readily studied in mice that inherit mutations in the Apc gene. We identified a new modifier locus of ApcMin-induced intestinal tumorigenesis called Modifier of Min 2 (Mom2). The polyp-resistant Mom2R phenotype resulted from a spontaneous mutation and linkage analysis localized Mom2 to distal chromosome 18. To obtain recombinant chromosomes for use in refining the Mom2 …

Oncolog, Volume 52, Number 04/05, April/May 2007, Manny Gonzales, Diane Witter, Moshe Frenkel Md

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Endocrine Center Unites Specialists
• Prescribing Hormone Replacement: What Now?
• House Call: Writing for Wellness: Keeping a Journal\
• DiaLog: What Your Patients Aren’t Telling You, by Moshe Frenkel, MD, Associate Professor, Medical Director, Integrative Medicine Program

Sociodemographic Characteristics And Diabetes Predict Invalid Self-Reported Non-Smoking In A Population-Based Study Of U.S. Adults, Monica A. Fisher, George W. Taylor, Brent J. Shelton, Sara M. Debanne

Markey Cancer Center Faculty Publications

BACKGROUND: Nearly all studies reporting smoking status collect self-reported data. The objective of this study was to assess sociodemographic characteristics and selected, common smoking-related diseases as predictors of invalid reporting of non-smoking. Valid self-reported smoking may be related to the degree to which smoking is a behavior that is not tolerated by the smoker's social group.

METHODS: True smoking was defined as having serum cotinine of 15+ng/ml. 1483 "true" smokers 45+ years of age with self-reported smoking and serum cotinine data from the Mobile Examination Center were identified in the third National Health and Nutrition Examination Survey. Invalid non-smoking was …

Colon Carcinoma Cells Harboring Pik3ca Mutations Display Resistance To Growth Factor Deprivation Induced Apoptosis., J. Wang, Karen Kuropatwinski, Jennie Hauser, Michael R. Rossi, Yunfei Zhou, Alexis Conway, Julie L.C. Kan, Neil W. Gibson, James K.V. Willson, John K. Cowell, Michael G. Brattain

Journal Articles: Eppley Institute

PIK3CA, encoding the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), is mutated in a variety of human cancers. We screened the colon cancer cell lines previously established in our laboratory for PIK3CA mutations and found that four of them harbored gain of function mutations. We have now compared a panel of mutant and wild-type cell lines for cell proliferation and survival in response to stress. There was little difference in PI3K activity between mutant PIK3CA-bearing cells (mutant cells) and wild-type PIK3CA-bearing cells (wild-type cells) under optimal growth conditions. However, the mutant cells showed constitutive PI3K activity during growth factor deprivation …

Association Of The Tensin N-Terminal Protein-Tyrosine Phosphatase Domain With The Alpha Isoform Of Protein Phosphatase-1 In Focal Adhesions, Masumi Eto, Jason Kirkbride, Elizabeth Elliott, Su Hao Lo, David L. Brautigan

Department of Molecular Physiology and Biophysics Faculty Papers

Focal adhesions attach cultured cells to the extracellular matrix, and we found endogenous protein phosphatase-1alpha isoform (PP1alpha) localized in adhesions across the entire area of adherent fibroblasts. However, in fibroblasts migrating into a scrape wound or spreading after replating PP1alpha did not appear in adhesions near the leading edge but was recruited into other adhesions coincident in time and space with incorporation of tensin. Endogenous tensin and PP1alpha co-precipitated from cell lysates with isoform-specific PP1 antibodies. Chemical cross-linking of focal adhesion preparations with Lomant's reagent demonstrated molecular proximity of endogenous PP1alpha and tensin, whereas neither focal adhesion kinase nor vinculin …

Oncolog, Volume 52, Number 03, March 2007, Sunni Hosemann, Karen Stuyck, Elizabeth L. Travis Phd

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• New Approaches for Advanced Melanoma
• Helping Patients Stop Smoking
• House Call: Simple Skin Cancer Prevention
• DiaLog: Toward Gender Equity in Academic Medicine, by Elizabeth Travis, PhD, Associate Vice President, Women Faculty Programs

Impact Of Morbid Obesity On Outcome Of Laparoscopic Splenectomy., Edward P Dominguez, Yong U Choi, Bradford G Scott, Alan M. Yahanda Md, Facs, Edward A Graviss, John F Sweeney

PCI Publications and Projects

BACKGROUND: Because of the obesity epidemic, surgeons are operating on morbidly obese patients in increasing numbers. The aim of this study was to evaluate the impact of morbid obesity on the outcome of laparoscopic splenectomy.

METHODS: The study group consisted of 120 consecutive patients who underwent laparoscopic splenectomy for benign and malignant disease from March 1996 to May 2005. These patients were retrospectively divided into three groups. Group 1 had a body mass index (BMI) < 30. Group 2 patients had a BMI > or = 30 and < 40 and were considered obese. Group 3 had a BMI > or = 40 and were considered morbidly obese. Data including surgical approach (laparoscopic vs. hand-assisted), operative time, conversion rate, estimated blood …