Medicine and Health Sciences Commons^™

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 …

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 …

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)

• 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

Systematic Review Of Baseline Low-Dose Ct Lung Cancer Screening., Michael Lock

Michael Lock

The purpose of this systematic review was to provide physicians and patients with a synthesis of the available data and an assessment of the operating characteristics associated with baseline LDCT screening for lung cancer. Various databases, meeting abstracts, clinical trials in progress, and major textbooks for relevant data from 1966 to 2006 were searched for relevant studies. The median value of sensitivity, specificity, positive predictive value and negative predictive value were 81%, 81%, 8% and 99%, respectively. Of the studies that compared LDCT with other lung cancer screening maneuvers, it was found that LDCT detected a greater number of cancerous …

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 and Research Publications

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 …

Nodal Ratios In Node-Positive Breast Cancer—Long-Term Study To Clarify Discrepancy Of Role Of Supraclavicular And Axillary Regional Radiotherapy, Patricia Tai, Kurian Joseph, Evgeny Sadikov, Shazia Mahmood, Francis Lien, Edward Yu

Edward Yu

Purpose: To study the absolute number of involved nodes/the number of nodes examined or the nodal ratio (NR) in breast cancer. The primary study endpoint was to evaluate the role of supraclavicular and axillary radiotherapy (SART) according to the NR. Methods and materials: From the Saskatchewan provincial registry of 1981-1995, the charts of 5,996 consecutive patients were retrieved to collect detailed prognostic factors. Among these patients, 1,985 were node positive. Because the NRs are more reliable the greater the number of nodes examined, we analyzed 1,255 patients with > or =10 nodes examined. Of these 1,255 patients, 667, 389, and 199 …

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)

• 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

The Return Of Research Results To Participants: Pilot Questionnaire Of Adolescents And Parents Of Children With Cancer, Conrad Fernandez, Darcy Santor, Charles Weijer, Caron Strahlendorf, Albert Moghrabi, Rebecca Pentz, Jun Gao, Eric Kodish

Charles Weijer

PURPOSE: The offer to return research results to participants is increasingly recognized as an ethical obligation, although few researchers routinely return results. We examined the needs and attitudes of parents of children with cancer and of adolescents with cancer to the return of research results.

METHODS: Seven experts in research ethics scored content validity on parent and adolescent questionnaires previously developed through focus group and phone interviews. The questionnaires were revised and provided to 30 parents and 10 adolescents in a tertiary care oncology setting.

RESULTS: The content validity index for individual questions and the overall questionnaires scored as 0.86 …

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)

• 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

Disease-Specific Survival For Limited-Stage Small-Cell Lung Cancer Affected By Statistical Method Of Assessment, Patricia Tai, Judith-Anne Chapman, Edward Yu, Dennie Jones, Changhong Yu, Fei Yuan, Lee Sang-Joon

Edward Yu

Background: In general, prognosis and impact of prognostic/predictive factors are assessed with Kaplan-Meier plots and/or the Cox proportional hazard model. There might be substantive differences from the results using these models for the same patients, if different statistical methods were used, for example, Boag log-normal (cure-rate model), or log-normal survival analysis. Methods: Cohort of 244 limited-stage small-cell lung cancer patients, were accrued between 1981 and 1998, and followed to the end of 2005. The endpoint was death with or from lung cancer, for disease-specific survival (DSS). DSS at 1-, 3- and 5-years, with 95% confidence limits, are reported for all …

Oncolog, Volume 52, Number 02, February 2007, Diane Witter

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

• New Findings on Aspirin and Heart Attacks
• Kicking Off a Trend: Cancer-Related Deaths Decline
• House Call: Working Out How to Lower Your Risk of Cancer

Labour And Perinatal Outcome In Women At Term With One Previous Lower-Segment Caesarean: A Review Of 1000 Consecutive Cases, Siti Zawiah Omar

Siti Zawiah Omar

Objective: To compare the outcome in 1000 women at term with one lower transverse Caesarean that was suitable for a trial of labour. Methods: One thousand consecutive women with one previous scar suitable for a trial of labour delivering in our centre from June 2002 to December 2005 were identified from the labour ward register. Data were retrieved from patients' charts, and neonatal admissions were determined. Results: In the study, 76.8% of women underwent a trial of labour, with a 71.2% vaginal birth rate. Hospital stay was shorter with a trial of labour. The three perinatal deaths (0.4%; P = …

3d Thoracoscopic Ultrasound Volume Measurement Validation In An Ex Vivo And In Vivo Porcine Model Of Lung Tumours, V. Hornblower, E. Yu, A. Fenster, J. Battista, R. Malthaner

Edward Yu

The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial "tumours" were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the "tumours" were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the …

Management Of Anthracycline Extravasation Injuries, David J. Reeves

Scholarship and Professional Work – COPHS

OBJECTIVE: To review the evidence for the management of anthracycline extravasation and determine the optimal treatment of such injuries.

DATA SOURCES: A search of MEDLINE (1966–February 2007) and International Pharmaceutical Abstracts (1970–February 2007) was performed using the search terms anthracyclines and extravasation.

DATA SYNTHESIS: Extravasation of anthracyclines can have devastating effects. After infiltration of these drugs into the interstitial tissue, damage may range from mild erythema and pain to severe tissue necrosis. Many agents have been studied in the management of these injuries; however, few have demonstrated efficacy and treatment remains controversial. Nonpharmacologic modalities shown to limit extravasation injuries include …