Medical Specialties Commons^™

Sonic Hedgehog Dependent Phosphorylation By Ck1Α And Grk2 Is Required For Ciliary Accumulation And Activation Of Smoothened, Yongbin Chen, Noriaki Sasai, Guoqiang Ma, Tao Yue, Jianhang Jia, James Briscoe, Jin Jiang

Markey Cancer Center Faculty Publications

Hedgehog (Hh) signaling regulates embryonic development and adult tissue homeostasis through the GPCR-like protein Smoothened (Smo), but how vertebrate Smo is activated remains poorly understood. In Drosophila, Hh dependent phosphorylation activates Smo. Whether this is also the case in vertebrates is unclear, owing to the marked sequence divergence between vertebrate and Drosophila Smo (dSmo) and the involvement of primary cilia in vertebrate Hh signaling. Here we demonstrate that mammalian Smo (mSmo) is activated through multi-site phosphorylation of its carboxyl-terminal tail by CK1α and GRK2. Phosphorylation of mSmo induces its active conformation and simultaneously promotes its ciliary accumulation. We demonstrate that …

Oncolog, Volume 56, Number 06, June 2011, John H. Mccool, Sunni Hoseman

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

• MD Anderson Celebrates 70th Anniversary: Its first clinical facility was a converted Army barracks, its first headquarters was renovated residential estate near downtown Houston, and its first cancer research was conducted by four scientists in a former horse stable
• Compass: Stage II or III Soft Tissue Sarcoma-Chemotherapy and radiation therapy before or after surgery benefit patients

Oral Ingestion Of Hexavalent Chromium Through Drinking Water And Cancer Mortality In An Industrial Area Of Greece - An Ecological Study, Athena Linos, Athanassios Petralias, Costas A. Christophi, Eleni Christoforidou, Paraskevi Kouroutou, Melina Stoltidis, Afroditi Veloudaki, Evangelia Tzala, Konstantinos C. Makris, Margaret R. Karagas

Dartmouth Scholarship

Background: Hexavalent chromium is a known carcinogen when inhaled, but its carcinogenic potential when orally ingested remains controversial. Water contaminated with hexavalent chromium is a worldwide problem, making this a question of significant public health importance.

Methods: We conducted an ecological mortality study within the Oinofita region of Greece, where water has been contaminated with hexavalent chromium. We calculated gender, age, and period standardized mortality ratios (SMRs) for all deaths, cancer deaths, and specific cancer types of Oinofita residents over an 11-year period (1999 - 2009), using the greater prefecture of Voiotia as the standard population.

Results: A total of …

Possible Role Of Death Receptor-Mediated Apoptosis By The E3 Ubiquitin Ligases Siah2 And Posh, Perry A. Christian, Michael V. Fiandalo, Steven R. Schwarze

Markey Cancer Center Faculty Publications

BACKGROUND: A functioning ubiquitin proteasome system (UPS) is essential for a number of diverse cellular processes and maintenance of overall cellular homeostasis. The ability of proteasome inhibitors, such as Velcade, to promote extrinsic apoptotic effects illustrates the importance of the ubiquitin proteasome system in the regulation of death receptor signaling. Here, we set out to define the UPS machinery, particularly the E3 ubiquitin ligases, that repress apoptosis through the extrinsic pathway. A cell-based genome-wide E3 ligase siRNA screen was established to monitor caspase-8 activity following the addition of TRAIL.

RESULTS: Data from the high-throughput screen revealed that targeting the RING-finger …

Four Year Experience Of Sarcoma Of Soft Tissues And Bones In A Tertiary Care Hospital And Review Of Literature, Tayyaba Z. Ansari, Nehal Masood, Asra Parekh, Rabab Z. Jafri, Syed N. Niamatullah, Adnan A. Zaidi, Masood Umer

Department of Medicine

Background:

Sarcoma encompasses an uncommon group of cancer and the data is insufficient from Pakistan. We report our four years experience of Sarcoma of soft tissues and bones.

Methods:

This cross sectional study was carried out at Aga Khan University Hospital from 2004 to 2008. The Patients were divided into two groups from the outset i.e. initially diagnosed and relapsed group and separate sub group analysis was conducted.

Results:

Out of 93 newly diagnosed Patients, 58 belonged to bone sarcoma and 35 to soft tissue sarcoma group. While for relapsed Patients, 5 had soft tissue sarcoma and 9 had bone …

Multiple Courses Of Stereotactic Re-Irradiation In Recurrent Oligodendroglioma: A Case Report., Shannon Fogh, Charles Glass, David W Andrews, Maria Werner-Wasik

Department of Radiation Oncology Faculty Papers

INTRODUCTION: High grade gliomas are an insidious disease associated with an extremely poor prognosis. The role of re-irradiation for recurrent gliomas is unclear but several retrospective studies have indicated mild toxicity and modest outcomes with this regimen. With subsequent progression, it is unclear what options remain and more radiotherapy is rarely offered for fear of surpassing normal central nervous system tissue tolerance and causing significant side effects without significant benefit.

CASE PRESENTATION: In this report, we describe a 37-year-old Caucasian male initially diagnosed with a grade IV oligodendroglioma, who received multiple courses of re-irradiation and experienced a survival of 10 …

Frontiers Of Oncology: Biobanking Resources For The 21St Century, Jill Barnholtz-Sloan, Mark R. Chance

Faculty Scholarship

No abstract provided.

The Interplay Between Nf-Kappab And E2f1 Coordinately Regulates Inflammation And Metabolism In Human Cardiac Cells., Xavier Palomer, David Álvarez-Guardia, Mercy M Davidson, Tung O Chan, Arthur M Feldman, Manuel Vázquez-Carrera

Department of Medicine Faculty Papers

Pyruvate dehydrogenase kinase 4 (PDK4) inhibition by nuclear factor-κB (NF-κB) is related to a shift towards increased glycolysis during cardiac pathological processes such as cardiac hypertrophy and heart failure. The transcription factors estrogen-related receptor-α (ERRα) and peroxisome proliferator-activated receptor (PPAR) regulate PDK4 expression through the potent transcriptional coactivator PPARγ coactivator-1α (PGC-1α). NF-κB activation in AC16 cardiac cells inhibit ERRα and PPARβ/δ transcriptional activity, resulting in reduced PGC-1α and PDK4 expression, and an enhanced glucose oxidation rate. However, addition of the NF-κB inhibitor parthenolide to these cells prevents the downregulation of PDK4 expression but not ERRα and PPARβ/δ DNA binding activity, …

Mitostatin Is Down-Regulated In Human Prostate Cancer And Suppresses The Invasive Phenotype Of Prostate Cancer Cells., Matteo Fassan, Domenico D'Arca, Juraj Letko, Andrea Vecchione, Marina P Gardiman, Peter Mccue, Bernadette Wildemore, Massimo Rugge, Dolores Shupp-Byrne, Leonard G Gomella, Andrea Morrione, Renato V Iozzo, Raffaele Baffa

Kimmel Cancer Center Faculty Papers

MITOSTATIN, a novel putative tumor suppressor gene induced by decorin overexpression, is expressed in most normal human tissues but is markedly down-regulated in advanced stages of mammary and bladder carcinomas. Mitostatin negatively affects cell growth, induces cell death and regulates the expression and activation levels of Hsp27. In this study, we demonstrated that ectopic expression of Mitostatin in PC3, DU145, and LNCaP prostate cancer cells not only induced a significant reduction in cell growth, but also inhibited migration and invasion. Moreover, Mitostatin inhibited colony formation in soft-agar of PC3 and LNCaP cells as well as tumorigenicity of LNCaP cells in …

Risk Of Second Malignant Neoplasms Following Proton Arc Therapy And Volumetric Modulated Arc Therapy For Prostate Cancer, Laura A. Rechner

Dissertations and Theses (Open Access)

The risk of second malignant neoplasms (SMNs) following prostate radiotherapy is a concern due to the large population of survivors and decreasing age at diagnosis. It is known that parallel-opposed beam proton therapy carries a lower risk than photon IMRT. However, a comparison of SMN risk following proton and photon arc therapies has not previously been reported. The purpose of this study was to predict the ratio of excess relative risk (RRR) of SMN incidence following proton arc therapy to that after volumetric modulated arc therapy (VMAT). Additionally, we investigated the impact of margin size and the effect …

Patient Characteristics And Outcomes Of Gastrointestinal Stromal Tumor Patients Undergoing Imatinib Plasma Level Testing, Laura Nolden

Dissertations and Theses (Open Access)

Although gastrointestinal stromal tumor (GIST) is effectively treated with imatinib, there are a number of clinical challenges in the optimal treatment of these patients. The plasma steady-state trough level of imatinib has been proposed to correlate with clinical outcome. Plasma imatinib level may be affected by a number of patient characteristics. Additionally, the ideal plasma trough concentration of imatinib is likely to vary based on the KIT genotype (genotype determines imatinib binding affinity) of the individual patient. Patients’ genotype or plasma imatinib level may influence the type and duration of response that is appreciable by clinical evaluation.

The objectives of …

The Association Between Cancer-Related-Fatigue, Response To Fatigue Treatment, And Cytokines And Their Receptors, In Patients With Advanced Cancer, Sriram Yennu

Dissertations and Theses (Open Access)

Background: Inflammation is implicated in the development of cancer related fatigue (CRF). However there is limited literature on the mediators of inflammation (namely), cytokines and their receptors, associated with clinically significant fatigue and response to treatment.

Methods: We reviewed 37 advanced cancer patients with fatigue (≥4/10), who participated in two Randomized Controlled Trials, of anti-inflammatory agents (Thalidomide and Dexamethasone) for CRF. Responders showed improvement in FACIT-F subscale at the end of study (Day 15). Baseline patient characteristics and symptoms were assessed by FACIT-F, ESAS; serum cytokines [IL-1β and receptor antagonist (IL-1RA), IL-6, IL-6R, TNF-α and sTNF-R1 and R2, IL-8, …

Randomized Phase Iii Trial Of Paclitaxel/Carboplatin With Or Without Pf-3512676 (Toll-Like Receptor 9 Agonist) As First-Line Treatment For Advanced Non–Small-Cell Lung Cancer, Vera Hirsh, Luis Paz-Ares, Michael Boyer, Rafael Rosell, Gary Middleton, Wilfried Eberhardt, Aleksandra Szczesna, Pavel Reiterer, Mansoor Saleh, Oscar Arrieta

Haematology and Oncology, East Africa

Purpose: This phase III study examined efficacy of the synthetic Toll-like receptor 9–activating oligodeoxynucleotide PF-3512676 in combination with standard paclitaxel/carboplatin chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC).

Patients and Methods: Chemotherapy-naive patients with stage IIIB or IV NSCLC were randomly assigned (1:1) to receive up to six courses of paclitaxel/carboplatin (intravenous paclitaxel 200 mg/m2 and carboplatin at area under the [concentration-time] curve 6 on day 1 of a 3-week cycle) alone (control arm) or in combination with 0.2 mg/kg subcutaneous PF-3512676 on days 8 and 15 (investigational arm). Primary end point was overall survival (OS).

Results: Baseline demographics …

Modeling Mortality Rates For Leukemia Between Men And Women In The United States, Blessed Quansah

UNLV Theses, Dissertations, Professional Papers, and Capstones

Leukemia related deaths increased dramatically over the last forty years. Leukemia is a malignant disease or cancer of the bone marrow and blood. It is characterized by the uncontrolled accumulation of blood cells. Leukemia is divided into two categories: myelogenous or lymphocytic, each of which can be acute or chronic. The terms, myelogenous or lymphocytic denote the cell type involved.

In this thesis, the proposed modeling techniques are applied to leukemia deaths data from the Surveillance Epidemiology and End Results (SEER). In particular, annual deaths data from 1969 to 2007 are used in the data analysis, which includes three major …

Early Toxicity Predicts Long-Term Survival In High-Grade Glioma., Y. R. Lawrence, M Wang, Adam Dicker, David W Andrews, Walter J Curran, J M Michalski, L Souhami, W-Ka Yung, M Mehta

Department of Radiation Oncology Faculty Papers

BACKGROUND: Patients with high-grade gliomas are treated with surgery followed by chemoradiation. The risk factors and implications of neurological side effects are not known.

METHODS: Acute and late ≥ grade 3 neurological toxicities (NTs) were analysed among 2761 patients from 14 RTOG trials accrued from 1983 to 2003. The association between acute and late toxicity was analysed using a stepwise logistic regression model. The association between the occurrence of acute NT and survival was analysed as an independent variable.

RESULTS: There were 2610 analysable patients (86% glioblastoma, 10% anaplastic astrocytoma). All received a systemic agent during radiation (83% chemotherapy, 17% …

Structured Algorithm For Error Reduction In Chemotherapy Administration, Marianne Bundalian Tejada

Nursing Faculty Presentations

Purpose. To develop an evidence-based structured algorithm tool that might be used by nursing leaders at a cancer center to decrease chemotherapy medication errors.

Background. In spite of available technology and known factors resulting in medication errors, chemotherapy errors remain the major cause of iatrogenic patient morbidity in hospitals (Gilbar, 2001; Heidt et al., 2001 ). A major risk factor for chemotherapy errors is lack of standardization in administration (ordering, dispensing, administration, monitoring). Failure to identify necessary staff skills/aptitude required to prevent errors may also be problematic.

Significance. Use of the developed algorithm may lead to development of evidence-based strategies …

Antidepressants And Breast And Ovarian Cancer Risk: A Review Of The Literature And Researchers' Financial Associations With Industry, Lisa Cosgrove, Ling Shi, David E. Creasey, Maria Anaya-Mckivergan, Jessica A. Myers, Krista F. Huybrechts

Counseling, School Psychology & Sport Faculty Publication Series

Background

Antidepressant (AD) use has been purported to increase the risk of breast and ovarian cancer, although both epidemiological and pre-clinical studies have reported mixed results [1]–[6]. Previous studies in a variety of biomedical fields have found that financial ties to drug companies are associated with favorable study conclusions [7].

Methods and Findings

We searched English-language articles in MEDLINE, PsychINFO, the Science Citations Index and the Cochrane Central Register of Controlled Clinical Trials (through November 2010). A total of 61 articles that assessed the relationship between breast and ovarian cancer and AD use and articles that examined the effect of …

Oncolog, Volume 56, Number 04-05, April-May 2011, Zach Bohannan, Bryan Tutt

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

• Understanding and Managing Multiple Endocrine Neoplasia Syndromes: Endocrine tumors caused by multiple endocrine neoplasia syndromes (MEN) pose a dual threat-both from the tumors' potential for growth or metastasis and from their hormonal secretions
• Two-Stage Resection and Improved Chemotherapy Regimens Lengthen Survival for Patients with Lever Metastasis from Colorectal Cancer
• HOUSE CALL: Saving a Life by Donating Stem Cells: Fact about stem cell transplants
• IN BRIEF: Study Reveals How EZH2 Protein Promotes Breast Tumor-Initiating Cell Growth

Sunitinib Plus Paclitaxel Versus Bevacizumab Plus Paclitaxel For First-Line Treatment Of Patients With Advanced Breast Cancer: A Phase Iii, Randomized, Open-Label Trial, Nicholas Robert, Mansoor Saleh, Devchand Paul, Daniele Generali, Laurent Gressot, Mehmet Copur, Adam Brufsky, Susan Minton, Jeffrey Giguere, John W. Smith Ii

Haematology and Oncology, East Africa

Introduction: A multicenter, open-label phase III study was conducted to test whether sunitinib plus paclitaxel prolongs progression-free survival (PFS) compared with bevacizumab plus paclitaxel as first-line treatment for patients with HER2− advanced breast cancer.

Patients and Methods: Patients with HER2− advanced breast cancer who were disease free for ≥ 12 months after adjuvant taxane treatment were randomized (1:1; planned enrollment 740 patients) to receive intravenous (I.V.) paclitaxel 90 mg/m2 every week for 3 weeks in 4-week cycles plus either sunitinib 25 to 37.5 mg every day or bevacizumab 10 mg/kg I.V. every 2 weeks.

Results: The trial was terminated early …

In Vitro Migration Of Cytotoxic T Lymphocyte Derived From A Colon Carcinoma Patient Is Dependent On Ccl2 And Ccr2., Klara Berencsi, Pyapalli Rani, Tianqian Zhang, Laura Gross, Michael Mastrangelo, Neal J Meropol, Dorothee Herlyn, Rajasekharan Somasundaram

Department of Medical Oncology Faculty Papers

BACKGROUND: Infiltration of colorectal carcinomas (CRC) with T-cells has been associated with good prognosis. There are some indications that chemokines could be involved in T-cell infiltration of tumors. Selective modulation of chemokine activity at the tumor site could attract immune cells resulting in tumor growth inhibition. In mouse tumor model systems, gene therapy with chemokines or administration of antibody (Ab)-chemokine fusion proteins have provided potent immune mediated tumor rejection which was mediated by infiltrating T cells at the tumor site. To develop such immunotherapeutic strategies for cancer patients, one must identify chemokines and their receptors involved in T-cell migration toward …

Renal Thrombotic Microangiopathy In Mice With Combined Deletion Of Endocytic Recycling Regulators Ehd3 And Ehd4., Manju George, Mark A. Rainey, Mayumi Naramura, Kirk W. Foster, Melissa S. Holzapfel, Laura L. Willoughby, Guoguang Ying, Rasna M. Goswami, Channabasavaiah B. Gurumurthy, Vimla Band, Simon C. Satchell, Hamid Band

Journal Articles: Eppley Institute

Eps15 Homology Domain-containing 3 (EHD3), a member of the EHD protein family that regulates endocytic recycling, is the first protein reported to be specifically expressed in the glomerular endothelium in the kidney; therefore we generated Ehd3(-/-) mice and assessed renal development and pathology. Ehd3(-/-) animals showed no overt defects, and exhibited no proteinuria or glomerular pathology. However, as the expression of EHD4, a related family member, was elevated in the glomerular endothelium of Ehd3(-/-) mice and suggested functional compensation, we generated and analyzed Ehd3(-/-); Ehd4(-/-) mice. These mice were smaller, possessed smaller and paler kidneys, were proteinuric and died between …

Racial/Ethnic Disparities In Survival Among Men Diagnosed With Prostate Cancer In Texas, Arica L. White, Ann L. Coker, Xianglin L. Du, Katherine S. Eggleston, Melanie Williams

CRVAW Faculty Journal Articles

BACKGROUND:

To the authors' knowledge, few studies to date have examined racial differences in prostate cancer survival while controlling for socioeconomic status (SES). No such studies have examined this association in Texas, a large state with significant ethnic and racial diversity. The objective of this analysis was to determine whether racial disparities in survival for men diagnosed with prostate cancer in Texas from 1995 through 2002 remained after adjusting for SES, rural residence, and stage of disease.

METHODS:

A cohort of 87,449 men who were diagnosed with prostate cancer was identified from the Texas Cancer Registry. The SES measure was …

Results Of Re-Excision For Inadequate Margins Following Partial Mastectomy For Carcinoma Of The Breast, Aaron D. Bleznak Md, Facs, Christine W. Du Md, Samuel Steerman Md, Elizabeth Dellers Md

Department of Surgery

No abstract provided.

Oncolog, Volume 56, Number 03, March 2011, Bryan Tutt, Joe Munch

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

• Glioblastoma Cure Remains Elusive Despite Treatment Advances: Aggressive surgery followed by radiation therapy and chemo-therapy offers hope of long-term survival for some patients with glioblastoma, but for most glioblastoma patients, the prognosis is poor
• Assessing and Addressing the Biological Effects of Stress in Cancer Patients: Stress has long been linked to cancer progression. But the precise mechanisms by which stress exacts its pro-tumor effects are not fully understood
• MD Anderson One of Four Centers to Test Cancer Cell Detection Chip: A new test that could monitor the effectiveness of cancer treatment
• HOUSE CALL: Yoga and Tai Chi: Two distinct disciplines …

Epidermal Growth Factor Receptor Overexpression In Resected Pancreatic Cancer, Amit Mahipal, Mary J. Mcdonald, Agnieszka Witkiewicz, Brian I. Carr

Department of Medical Oncology Faculty Papers

Conclusions:

Membrane EGFR overexpression is associated with poorer clinical outcomes in patients with pancreatic cancer receiving adjuvant therapy post resection.

Cytoplasmic EGFR overexpression is not associated with clinical outcomes.

Regulation Of The Androgen Receptor By Set9-Mediated Methylation., Luke Gaughan, Jacqueline Stockley, Nan Wang, Stuart R C Mccracken, Achim Treumann, Kelly Armstrong, Fadhel Shaheen, Kate Watt, Iain J Mcewan, Chenguang Wang, Richard Pestell, Craig N Robson

Kimmel Cancer Center Faculty Papers

The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors that plays a critical role in regulating expression of genes involved in prostate development and transformation. Upon hormone binding, the AR associates with numerous co-regulator proteins that regulate the activation status of target genes via flux to the post-translational modification status of histones and the receptor. Here we show that the AR interacts with and is directly methylated by the histone methyltransferase enzyme SET9. Methylation of the AR on lysine 632 is necessary for enhancing transcriptional activity of the receptor by facilitating both inter-domain …

Phase I Study Of 'Dose-Dense' Pemetrexed Plus Carboplatin/Radiotherapy For Locally Advanced Non-Small Cell Lung Carcinoma., Xinglei Shen, Albert Denittis, Maria Werner-Wasik, Rita Axelrod, Paul Gilman, Thomas Meyer, Joseph Treat, Walter J Curran, Mitchell Machtay

Department of Radiation Oncology Faculty Papers

BACKGROUND: This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC).

METHODS: Eligible patients had Stage III or IV (oligometastatic) NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6) during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1) of pemetrexed was 300 mg/m2. Following the finding of dose limiting toxicity (DLT) in dose level 1, an amended dose level …

Intradiploic Epidermoid Cyst Overlying The Torcula: A Surgical Challenge, Amad Naseer Khan, Salema Khalid, Ather Enam

Medical College Documents

Intradiploic tumours are rare, slow growing tumours that can present in many different ways, including a painless lump, tenderness, headache and rarely with focal neurological signs. The authors present the case of a gentleman in whom the tumour presented in an unusual location and presented a surgical challenge. The major take home message from this case report is that an epidermoid cyst overlying the torcula is to be approached with great caution and care and is without doubt a surgical challenge.

Pediatric Ethics Guidelines For Hereditary Medullary Thyroid Cancer, M. Sara Rosenthal, Douglas S. Diekema

Internal Medicine Faculty Publications

Hereditary medullary thyroid cancer is an aggressive cancer for which there is no standard effective systemic therapy, but which can be prevented through genetic screening and prophylactic thyroidectomy. Although this cancer accounts for roughly 17% of all pediatric thyroid cancers, a significant percentage of affected families do not "accept" screening, while many gene carriers delay or refuse prophylactic thyroid surgery for their children. Current genetic screening practices in medullary thyroid cancer are inadequate; more than 50% of index patients with hereditary medullary thyroid cancer present with a thyroid mass; up to 75% have distant metastasis. These proposed pediatric ethics guidelines …

Oncolog, Volume 56, Number 02, February 2011, Joe Munch, John Lebas

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

• Risk-Based Cancer Screening: M.D. Anderson's revised guidelines offer more precise individualized recommendations on screening for common cancers.
• Screen Guidelines in Brief
• Electronic Navigation Biopsy for Peripheral Lung Lesion Diagnosis
• House Call: Couples and Cancer: Cancer-Related Issues Can Disrupt Relationships
• in Brief: Researchers Find Glioblastoma's Resistance to Treatment Rooted in Immunosuppression