Oncology Commons^™

Regulation Of Cellular Protein Phosphatase-1 (Pp1) By Phosphorylation Of The Cpi-17 Family, C-Kinase-Activated Pp1 Inhibitors., Masumi Eto

Department of Molecular Physiology and Biophysics Faculty Papers

The regulatory circuit controlling cellular protein phosphatase-1 (PP1), an abundant group of Ser/Thr phosphatases, involves phosphorylation of PP1-specific inhibitor proteins. Malfunctions of these inhibitor proteins have been linked to a variety of diseases, including cardiovascular disease and cancer. Upon phosphorylation at Thr(38), the 17-kDa PP1 inhibitor protein, CPI-17, selectively inhibits a specific form of PP1, myosin light chain phosphatase, which transduces multiple kinase signals into the phosphorylation of myosin II and other proteins. Here, the mechanisms underlying PP1 inhibition and the kinase/PP1 cross-talk mediated by CPI-17 and its related proteins, PHI, KEPI, and GBPI, are discussed.

Giant Synovial Cell Sarcoma Of The Thorax In A 46-Year-Old Man: A Case Report., Saulat Hasnain Fatimi, Taimur Saleem

Department of Surgery

Background:Although synovial cell sarcoma is a common tumor of the extremities, its occurrence in the thorax has been less frequently documented. Case Presentation: A 46-year-old Pakistani man presented with a 2 month history of progressively increasing cough and left lower chest pain. Initial evaluation was done using a chest x-ray, the Patient was found to have a large mass involving the lower portion of the left chest. A computed tomography scan was performed next which showed a large mass involving the left chest wall with invasion into the pericardium and left hemidiaphragm. En bloc surgical resection of the tumor …

Stromal Caveolin-1 Levels Predict Early Ductal Carcinoma In Situ Progression To Invasive Breast Carcinoma, A. K. Witkiewicz, A. Dasgupta, G. F. Schwartz, Kh H. Nguyen, H. R. Rui, M. P. Lisanti

Department of Cancer Biology Faculty Papers

With the increased use of screening mammography, the incidence of ductal carcinoma in situ (DCIS) has increased substantially and it currently accounts for 20-30% of newly diagnosed breast carcinomas in United States. Breast conserving therapy with or without radiotherapy is the accepted treatment for most cases of DCIS. However, the local recurrence rate with such therapy rages from 10 to 40% with half of these patients developing invasive carcinoma. Tamoxifen, used as an adjuvant systemic therapy for DCIS, does not increase overall survival and data on reduction of local recurrence rates are conflicting.

The current classification for DCIS based on …

Initial Tumor Metabolic Parameters (Maximum Suv And Metabolic Volume) Predict Death From Lung Cancer And Rapid Suv Decline Is Associated With Local Control, Maria Werner-Wasik, Edward Pequignot, Terry Hyslop, Brian Shulli, Ying Xiao, Mitchell Machtay, Amy Taylor, Walter Curran, Rita Axelrod

Department of Radiation Oncology Faculty Papers

Factors associated with local failure and death from lung cancer were evaluated based on post-treatment FDG-PET imaging in patients (pts) with non-small cell lung cancer (NSCLC).

PET-CT scans were obtained 6-8 weeks after thoracic RT and approximately every 3 months thereafter.

Mepe/Of45 Protects Cells From Dna Damage Induced Killing Via Stabilizing Chk1., Shuang Liu, Hongyan Wang, Xiang Wang, Lin Lu, Ning Gao, Peter S N Rowe, Baocheng Hu, Ya Wang

Department of Radiation Oncology Faculty Papers

Matrix extracellular phosphoglycoprotein/osteoblast factor 45 (MEPE/OF45) was cloned in 2000 with functions related to bone metabolism. We identified MEPE/OF45 for the first time as a new co-factor of CHK1 in mammalian cells to protect cells from DNA damage induced killing. We demonstrate here that MEPE/OF45 directly interacts with CHK1. Knocking down MEPE/OF45 decreases CHK1 levels and sensitizes the cells to DNA damage inducers such as ionizing radiation (IR) or camptothicin (CPT)-induced killing. Over-expressing wild-type MEPE/OF45, but not the mutant MEPE/OF45 (depleted the key domain to interact with CHK1) increases CHK1 levels in the cells and increases the resistance of the …

No Association Of Obesity And Type 2 Diabetes Mellitus Related Genetic Variants With Colon Cancer, Cheryl L. Thompson, Sarah J. Plummer, Thomas C. Tucker, Graham Casey, Li Li

Markey Cancer Center Faculty Publications

Background: Obesity and type 2 diabetes mellitus (T2D) are known risk factors for colon cancer. Recent reports from a number of genome wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with obesity and T2D. Here we tested the hypothesis that these SNPs may also be associated with risk of colon cancer.

Methods: We genotyped nine SNPs reported in GWAS of obesity and/or T2D, including SNPs in HHEX, KCNJ11, SLC30A8, FTO, CDKN2, CDKAL1, TCF2, and the rs9300039 SNP in an intergenic region, in 561 colon cancer cases and 721 population controls.

Results: None of these SNPs were …

Expression And Function Of Hypoxia Inducible Factor-1 Alpha In Human Melanoma Under Non-Hypoxic Conditions, Caroline N. Mills, Sandeep S. Joshi, Richard M. Niles

Biochemistry and Microbiology

Background

Hypoxia inducible factor-1 alpha (HIF-1α) protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP), vertical growth phase (VGP) and metastatic (MET) melanomas.

Results

HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part …

Doxorubicin Loaded Polymeric Nanoparticulate Delivery System To Overcome Drug Resistance In Osteosarcoma, Michiro Susa, Arun K. Iyer, Keinosuke Ryu, Francis J. Hornicek, Henry Mankin, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Background: Drug resistance is a primary hindrance for the efficiency of chemotherapy against osteosarcoma. Although chemotherapy has improved the prognosis of osteosarcoma patients dramatically after introduction of neo-adjuvant therapy in the early 1980's, the outcome has since reached plateau at approximately 70% for 5 year survival. The remaining 30% of the patients eventually develop resistance to multiple types of chemotherapy. In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure incurred from multidrug resistant (MDR) tumor cells, we explored the possibility of loading doxorubicin onto biocompatible, lipid-modified dextran-based polymeric nanoparticles and evaluated the …

Solution Structure Of The Inhibitory Phosphorylation Domain Of Myosin Phosphatase Targeting Subunit 1., Shunsuke Mori, Ryou Iwaoka, Masumi Eto, Shin-Ya Ohki

Department of Molecular Physiology and Biophysics Faculty Papers

Cell motility, such as smooth muscle contraction and cell migration, is controlled by the reversible phosphorylation of the regulatory light chain of myosin II and other cytoskeletal proteins. Mounting evidence suggests that in smooth muscle cells and other types of cells in vertebrates, myosin phosphatase (MP) plays an important role in controlling the phosphorylation of myosin II as well as other cytoskeletal proteins, including ezrin, moesin, and radixin.1 MP is a holoenzyme consisting of a catalytic subunit of a type-1 Ser/Thr phosphatase (PP1C) delta isoform, a myosin phosphatase targeting subunit 1 (MYPT1), and an accessory subunit M21. In this ternary …

Is Extended Volume Of External Beam Irradiation Beneficial In Post-Esophagectomy High Risk Patients Receiving Combined Chemoradiation Therapy?, E. Yu, A. R. Dar, R. Ash, G. Videtic, P. Truong, L. Stitt, A. Tomiak, M. Vincent, R. Malthaner, I. Craig, E. Brecevic, W. Kocha, R. Inculet, M. Lefcoe

Edward Yu

OBJECTIVE: To assess the value of extended volume irradiation with anastomotic coverage in high risk resected esophageal cancer patients. METHOD: A retrospective study was undertaken at LRCC from 1989-1999 for high risk resected esophageal cancer patients. Adjuvant treatments consisted of 4 cycles of chemotherapy (epirubicin/fluorouracil/cisplatin or cisplatin/fluorouracil), and local regional irradiation with or without coverage of the anastomotic site. Radiation dose ranged from 45-60Gy at 1.8-2.0 Gy/fraction given with initial anterior-posterior/posterior-anterior arrangement with either extended (with anastomotic coverage) or small (without anastomotic coverage) field followed by oblique fields for boost. RESULT: One hundred eighty-eight charts were reviewed. Seventy-two patients were …

Robot Assisted Ultrasound Imaged Guided Interstitial Lung Brachytherapy In A Porcine Model, Richard A. Malthaner, Edward Yu, Jerry J. Battista, Chris Blake, Donal Downey, Aaron Fenster

Edward Yu

We set out to see if permanent interstitial brachytherapy seeds could be safely and reproducibly inserted thoracoscopicaly with the ZEUS Robotic system and intraoperative ultrasound into in-vivo porcine lungs.

Post-Operative Extended Volume External Beam Radiation Therapy Is Safe For High Risk Esophageal Cancer Patients, Edward Yu, Patricia Tai, Jawaid Younus, Richard Malthaner, Larry Stitt, Pauline Truong, George Rodrigues, Robert Ash, Rashid Dar, Anna Tomiak, Mark Vincent, Walter Kocha, Brian Dingle, Richard Inculet

Edward Yu

Post-operative radiation therapy (RT) (1) and post-operative chemoradiation (2) have been used for esophageal cancer patients deemed high risk for recurrence after esophagectomy. Defining opitmal RT target volume after esophagectomy is difficult due to significant changes in patient anatomy and function. Some radiationon cologists advocated the inclusion of the anastomotic site within the irradiation volume due to concerns for potential increased relapse risk, while others did not subscribe to this practice due to concerns for increased treatment related toxicity. We have previously reported patient outcome benefit using extended volume RT In management with high risk esophageal cancer patients underwent esopagectomy(3). …

Extended Vs. Small Field Irradiation In High Risk Post Esophagectomy Patients Receiving Combined Chemoradiation Therapy: A Decade Experience In Treatment Of Esophageal Cancer, Edward Yu, Patricia Tai, George Rodrigues, Robert Ash, Larry Stitt, Rashid A. Dar, Pauline Truong, Gregory M. Videtic, Richard Malthaner, Richard Inculet, Anna Tomiak, Jawaid Younus, Brian Dingle, Walter Kocha, Mark Vincent

Edward Yu

OBJECTIVE: To assess the impact of extended field irradiation with anastomotic coverage on local recurrence in high risk resected esophageal cancerpatients. METHODS: From 1989-1999, high risk resected esophageal cancer cases receiving post-resection chemoradiation were reviewed. Adjuvant chemotherapy consisted of four cycles of fluorouracil-based regimens. Loco-regional irradiation with or without coverage of anastomotic site had radiation a dose range from 45-60 Gyat 1.8-2.0 Gy/fraction given with initial anterior-posterior/posterior-anterior arrangement with either extended (with anastomotic coverage), or small (without anastomotic coverage) field followed by oblique fields for boost. RESULTS: One hundred eighty-eight charts were reviewed. Seventy-two patients were eligible for post-resection chemoradiation. …

Evaluation Of Intra-And Inter-Fraction Motion In Breast Radiotherapy Using Electronic Portal Imaging Cine Loops, Chrison Lee, Edward Yu, Tomas Kron

Edward Yu

Parallel tangent breast irradiation is commonly used postbreast conservation surgery for early breast cancer patient without lymph node involvement to improve local disease control. Intra-fractional and inter-fractional variabilities are often presented in daily treatment setup. The present pilot study used Electronic Portal Imaging (EPI) to evaluate intra-and inter-fraction motion in patients undergoing simple breast tangent radiotherapy.

Ppar Agonists Down-Regulate The Expression Of Atp10c Mrna During Adipogenesis, A Peretich, Maria Cekanova Ms, Rndr, Phd, S Hurst, Sj Baek, Madhu Dahr

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

No abstract provided.

Ppar Agonists Down-Regulate The Expression Of Atp10c Mrna During Adipogenesis, A Peretich, Maria Cekanova Ms, Rndr, Phd, S Hurst, Sj Baek, Madhu Dahr

Maria Cekanova MS, RNDr, PhD

No abstract provided.

Malignant Phyllodes Tumour As An Intracystic Growth With Osteosarcomatous Differentiation, Shaista Afzal Saeed, Imrana Masroor

Department of Radiology

Phyllodes tumour is an uncommon fibro epithelial tumour of breast that often presents clinically as a rapidly enlarging lump. On mammography it appears as a soft tissue density well circumscribed mass. Ultrasound shows it to be a solid hypoechoic mass with small cystic spaces. A case of malignant phyllodes tumour with an atypical appearance of intracystic tumour on sonography is reported with pertinent imaging features and histopathological diagnostic criteria. The tumour had undergone osteosarcomatous differentiation.

Imrt Commissioning: Multiple Institution Planning And Dosimetry Comparisons, A Report From Aapm Task Group 119., Gary A Ezzell, Jay W Burmeister, Nesrin Dogan, Thomas J Losasso, James G Mechalakos, Dimitris Mihailidis, Andrea Molineu, Jatinder R Palta, Chester R Ramsey, Bill J Salter, Jie Shi, Ping Xia, Ning J Yue, Ying Xiao, Phd

Department of Radiation Oncology Faculty Papers

AAPM Task Group 119 has produced quantitative confidence limits as baseline expectation values for IMRT commissioning. A set of test cases was developed to assess the overall accuracy of planning and delivery of IMRT treatments. Each test uses contours of targets and avoidance structures drawn within rectangular phantoms. These tests were planned, delivered, measured, and analyzed by nine facilities using a variety of IMRT planning and delivery systems. Each facility had passed the Radiological Physics Center credentialing tests for IMRT. The agreement between the planned and measured doses was determined using ion chamber dosimetry in high and low dose regions, …

Oncolog Volume 54, Number 11/12, November/December 2009, Dawn Chalaire, Joe Munch

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

• Treating Neurofibromatosis
• Personalized Therapy for Lung Cancer
• House Call: Genetic Screening for Cancer Risks Gives Patients Options

Effect Of Interval To Definitive Breast Surgery On Clinical Presentation And Survival In Early-Stage Invasive Breast Cancer, Olga Vujovic, Edward Yu, Anil Cherian, Francisco Perera, A. Dar, Larry Stitt, A. Hammond

Edward Yu

Purpose: To examine the effect of clinical presentation and interval to breast surgery on local recurrence and survival in early-stage breast cancer. Methods and materials: The data from 397 patients with Stage T1-T2N0 breast carcinoma treated with conservative surgery and breast radiotherapy between 1985 and 1992 were reviewed at the London Regional Cancer Program. The clinical presentation consisted of a mammogram finding or a palpable lump. The intervals from clinical presentation to definitive breast surgery used for analysis were 0-4, >4-12, and >12 weeks. The Kaplan-Meier estimates of the time to local recurrence, disease-free survival, and cause-specific survival were determined …

Accelerated Fractionation In Inoperable Non-Small Cell Lung Cancer. A Phase I/Ii Study, Edward Yu, Luis Souhami, Julio Guerra, Brenda Clark, Carole Gingras, Palma Fava

Edward Yu

Background: A prospective, single-treatment-arm, Phase I/II trial was performed to determine the tumor response to an accelerated regimen and assess the feasibility and toxic effects of this approach in patients with inoperable non-small cell lung cancer (NSCLC). Methods: Thirty-seven previously untreated patients with inoperable NSCLC who had no evidence of metastatic disease entered the study. All patients were able to walk and had disease that was measurable or assessable. Patients with palpable supraclavicular disease and weight loss were also eligible. Radiation therapy consisted of an altered fractionation regimen with a concomitant boost technique. The original lung volume received a dose …

Decarboxylation Of L-Dopa And 5-Hydroxytryptophan In Dispersed Rat Pancreas Acinar Cells, E. Yu, L. Stern, A. Tenenhouse

Edward Yu

Amino acid decarboxylation activity in dispersed rat pancreas acinar cells and fractions derived by differential centrifugation of homogenate of these cells was studied. The rate of decarboxylation was measured by determining the rate of production of the [3H]-amine from [3H]-amino acid or the rate of production of 14CO2 from the [14C]-carboxy-labelled amino acid. Only the hydroxylated amino acids L-dopa and 5-hydroxytryptophan are decarboxylated by intact dispersed pancreas acinar cells or cell homogenates at all pH values and amino acid concentrations tested. The decarboxylase activity is located exclusively in the cell cytosol. Each substrate competitively inhibits the decarboxylation of the other …

Wnt Pathway Reprogramming During Human Embryonal Carcinoma Differentiation And Potential For Therapeutic Targeting, Grace E. Snow, Allison C. Kasper, Alexander M. Busch, Elisabeth Schwarz, Katherine E. Ewings, Thomas Bee, Michael J. Spinella, Ethan Dmitrovsky, Sarah J. Freemantle

Dartmouth Scholarship

Testicular germ cell tumors (TGCTs) are classified as seminonas or non-seminomas of which a major subset is embryonal carcinoma (EC) that can differentiate into diverse tissues. The pluripotent nature of human ECs resembles that of embryonic stem (ES) cells. Many Wnt signalling species are regulated during differentiation of TGCT-derived EC cells. This study comprehensively investigated expression profiles of Wnt signalling components regulated during induced differentiation of EC cells and explored the role of key components in maintaining pluripotency.

Ethnic Disparities In Cervical Cancer Survival Among Texas Women, Ann L. Coker, Christopher P. Desimone, Katherine S. Eggleston, Arica L. White, Melanie Williams

CRVAW Faculty Journal Articles

Objective: The aim of this work was to determine whether minority women are more likely to die of cervical cancer. A population-based cohort study was performed using Texas Cancer Registry (TCR) data from 1998 to 2002.

Methods: A total of 5,166 women with cervical cancer were identified during 1998–2002 through the TCR. Measures of socioeconomic status (SES) and urbanization were created using census block group-level data. Multilevel logistic regression was used to calculate the odds of dying from cervical cancer by race, and Cox proportional hazards modeling was used for cervical cancer-specific survival analysis.

Results: After adjusting for age, SES, …

The Effects Of Field-Of-View And Patient Size On Ct Numbers From Cone-Beam Computed Tomography., Katrina Y T Seet, Arvand Barghi, Slav Yartsev, Jacob Van Dyk

Oncology Publications

Cone-beam computed tomography (CBCT) is used for patient alignment before treatment and is ideal for use in adaptive radiotherapy to account for tumor shrinkage, organ deformation and weight loss. However, CBCT images are prone to artifacts such as streaking and cupping effects, reducing image quality and CT number accuracy. Our goal was to determine the optimum combination of cone-beam imaging options to increase the accuracy of image CT numbers. Several phantoms with and without inserts of known relative electron densities were imaged using the Varian on-board imaging system. It was found that CT numbers are most influenced by the selection …

What Factors Predict Outcome At Relapse After Previous Esophagectomy And Adjuvant Therapy In High-Risk Esophageal Cancer?, Edward Yu, Patricia Tai, Richard Malthaner, Larry Stitt, George Rodrigues, Rashid Dar, Brian Yaremko, Jawaid Younus, Michael Sanatani, Mark Vincent, Brian Dingle, Dalilah Fortin, Richard Inculet

Oncology Presentations

Management of patients who have disease relapse after completion of surgery and adjuvant chemo-radiation (CRT) is controversial.

Some oncologists would advocate intensive therapeutic intervention due to promising experience on treatment for recurrence disease while others would recommend palliative support due to the concerns for poor patient outcome post disease recurrence.

In Addition, it is not clear if patient outcome is improved post adjuvant CRT when patients at risk have resection margin involvement and if time interval to recurrence can affect patient survival post relapse.

The present study was conducted to determine what factors will affect patient outcome at relapse after …

Determination Of Complication Rate Of Picc Lines In Oncological Patients, Ghulam Haider, Shiyam Kumar, Basit Salam, Nehal Masood, Asim Jamal, Yasmeen Abdul Rasheed

Department of Radiation Oncology

OBJECTIVE: To determine the complication rate of (PICCs) peripherally inserted central catheters in cancer patients with a 1 year prospective cohort study.

METHODS: All PICCs inserted in adult cancer patients in Radiology Department of The Aga Khan University Hospital were followed prospectively till removed or patient expired and pattern of complications noted.

RESULTS: One hundred and fourty six PICCs were inserted over a period of 1 year and followed for a total of 3329 catheter-days; median placement, 14 days: range 3-218 days. Of these 67 (32.8%) PICCs were complicated and removed earlier, for a rate of 14.4/1000 PICC-days. Patients with …

Oncolog Volume 54, Number 10, October 2009, John Lebas, Bryan Tutt

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

• Early Testicular Cancer
• Metastatic Rectal Cancer
• House Call: What Is Pancreatic Cancer?

What Factors Predict Outcome At Relapse After Previous Esophagectomy And Adjuvant Therapy In High-Risk Esophageal Cancer?, Edward Yu, Patricia Tai, Richard Malthaner, Larry Stitt, George Rodrigues, Rashid Dar, Brian Yaremko, Jawaid Younus, Michael Sanatani, Mark Vincent, Brian Dingle, Dalilah Fortin, Richard Inculet

Edward Yu

Management of patients who have disease relapse after completion of surgery and adjuvant chemo-radiation (CRT) is controversial. Some oncologists would advocate intensive therapeutic intervention due to promising experience on treatment for recurrence disease while others would recommend palliative support due to the concerns for poor patient outcome post disease recurrence. In Addition, it is not clear if patient outcome is improved post adjuvant CRT when patients at risk have resection margin involvement and if time interval to recurrence can affect patient survival post relapse. The present study was conducted to determine what factors will affect patient outcome at relapse after …

Effects Of Genistein Following Fractionated Lung Irradiation In Mice., Andrea E Para, Andrea Bezjak, Ivan W T Yeung, Jacob Van Dyk, Richard P Hill

Oncology Publications

BACKGROUND AND PURPOSE: This study investigated protection of lung injury by genistein following fractionated doses of radiation and its effect on tumor response.

MATERIAL AND METHODS: C3H/HeJ mice were irradiated (100 kVp X-rays) with 9 fractions of 3.1 Gy over 30 days (approximately equivalent to 10 Gy single dose) and were maintained on a genistein diet ( approximately 10mg/kg). Damage was assessed over 28 weeks in lung cells by a cytokinesis block micronucleus (MN) assay and by changes in breathing rate and histology. Tumor protection was assessed using a colony assay to determine cell survival following in situ irradiation of …