Medicine and Health Sciences Commons^™

Nfkb Disrupts Tissue Polarity In 3d By Preventing Integration Of Microenvironmental Signals, Sabine Becker-Weimann, Gaofeng Xiong, Saori Furuta, Ju Han, Irene Kuhn, Uri-David Akavia, Dana Pe'er, Mina J. Bissell, Ren Xu

Markey Cancer Center Faculty Publications

The microenvironment of cells controls their phenotype, and thereby the architecture of the emerging multicellular structure or tissue. We have reported more than a dozen microenvironmental factors whose signaling must be integrated in order to effect an organized, functional tissue morphology. However, the factors that prevent integration of signaling pathways that merge form and function are still largely unknown. We have identified nuclear factor kappa B (NFkB) as a transcriptional regulator that disrupts important microenvironmental cues necessary for tissue organization. We compared the gene expression of organized and disorganized epithelial cells of the HMT-3522 breast cancer progression series: the non-malignant …

Recommendations For High-Priority Research On Cancer-Related Fatigue In Children And Adults., Andrea M. Barsevick, Michael R. Irwin, Pamela Hinds, Andrew Miller, Ann Berger, Paul Jacobsen, Sonia Ancoli-Israel, Bryce B Reeve, Karen Mustian, Ann O'Mara, Jin-Shei Lai, Michael Fisch, David Cella

Department of Medical Oncology Faculty Papers

Over the past decades, some scientific progress has been made in understanding and treating cancer-related fatigue (CRF). However, three major problems have limited further progress: lack of agreement about measurement, inadequate understanding of the underlying biology, and problems in the conduct of clinical trials for CRF. This commentary reports the recommendations of a National Cancer Institute Clinical Trials Planning Meeting and an ongoing National Cancer Institute working group to address these problems so that high-priority research and clinical trials can be conducted to advance the science of CRF and its treatment. Recommendations to address measurement issues included revising the current …

Cyclin D1 Determines Estrogen Signaling In The Mammary Gland In Vivo., Mathew C Casimiro, Chenguang Wang, Z Li, Gabriele Disante, Nicole E Willmart, Sankar Addya, Lei Chen, Yang Liu, Michael P. Lisanti, Richard Pestell

Department of Cancer Biology Faculty Papers

The CCND1 gene, which is frequently overexpressed in cancers, encodes the regulatory subunit of a holoenzyme that phosphorylates the retinoblastoma protein. Although it is known that cyclin D1 regulates estrogen receptor (ER)α transactivation using heterologous reporter systems, the in vivo biological significance of cyclin D1 to estrogen-dependent signaling, and the molecular mechanisms by which cyclin D1 is involved, are yet to be elucidated. Herein, genome-wide expression profiling conducted of 17β-estradiol-treated castrated virgin mice deleted of the Ccnd1 gene demonstrated that cyclin D1 determines estrogen-dependent gene expression for 88% of estrogen-responsive genes in vivo. In addition, expression profiling of 17β-estradiol-stimulated cyclin …

Population Cancer Risks Associated With Coal Mining: A Systematic Review, Wiley D. Jenkins, W. Jay Christian, Georgia Mueller, K. Thomas Robbins

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: Coal is produced across 25 states and provides 42% of US energy. With production expected to increase 7.6% by 2035, proximate populations remain at risk of exposure to carcinogenic coal products such as silica dust and organic compounds. It is unclear if population exposure is associated with increased risk, or even which cancers have been studied in this regard.

METHODS: We performed a systematic review of English-language manuscripts published since 1980 to determine if coal mining exposure was associated with increased cancer risk (incidence and mortality).

RESULTS: Of 34 studies identified, 27 studied coal mining as an occupational exposure …

Circulating Tumor Dna To Monitor Metastatic Breast Cancer., Massimo Cristofanilli, Paolo Fortina

Kimmel Cancer Center Faculty Papers

No abstract provided.

Altered Drainage Patterns In Patients With Melanoma And Previous Axillary Dissection., Caitlyn M. Johnson, Charles Intenzo, Michael Mastrangelo, Kendra Feeney, Adam C. Berger

Department of Surgery Faculty Papers

The incidence of melanoma is increasing rapidly in the United States. Sentinel lymph node biopsy is an important diagnostic tool in the treatment and staging of melanoma. However, many patients with melanoma will have had lymph node surgery for previous melanoma or breast cancer. We set out to examine alterations in drainage patterns in patients with previous axillary dissection for breast cancer. We reviewed four patients with truncal and/or extremity melanomas and examined their lymphoscintigraphy and drainage patterns. Three patients with truncal melanoma mapped to cervical lymph nodes and a fourth patient with an arm melanoma mapped to her previously …

Prognostic Factors For Male Breast Cancer: Similarity To Female Counterparts, Edward Yu, Larry Stitt, Olga Vujovic, Kurian Joseph, Avi Assouline, Joseph Au, Jawaid Younus, Francisco Perera, Patricia Tai

Edward Yu

Abstract. Aim: To assess whether prognostic factors in male (MBC) and female (FBC) breast cancer have similar impact on survival. Patients and Methods: Charts for men and women diagnosed with breast cancer referred to the London Regional Cancer Program (LRCP) were reviewed. Patients with distant metastatic diseases were excluded. Data on prognostic factors including age, nodal status, resection margin, use of hormonal therapy, chemotherapy with/without hormone and radiation therapy (RT), overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were analyzed. Survival estimates were obtained using Kaplan-Meier methodology. The Cox regression interaction was used to compare male and female …

The Tweak Receptor Fn14 Is A Therapeutic Target In Melanoma: Immunotoxins Targeting Fn14 Receptor For Malignant Melanoma Treatment., Hong Zhou, Suhendan Ekmekcioglu, John W Marks, Khalid A Mohamedali, Kaushal Asrani, Keeley K Phillips, Sharron A N Brown, Emily Cheng, Michele B Weiss, Walter N Hittelman, Nhan L Tran, Hideo Yagita, Jeffrey A Winkles, Michael G Rosenblum

Department of Cancer Biology Faculty Papers

Fibroblast growth factor-inducible protein 14 (Fn14), the cell surface receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK), is overexpressed in various human solid tumor types and can be a negative prognostic indicator. We detected Fn14 expression in ∼60% of the melanoma cell lines we tested, including both B-Raf WT and B-Raf(V600E) lines. Tumor tissue microarray analysis indicated that Fn14 expression was low in normal skin, but elevated in 173/190 (92%) of primary melanoma specimens and in 86/150 (58%) of melanoma metastases tested. We generated both a chemical conjugate composed of the recombinant gelonin (rGel) toxin and the anti-Fn14 …

Feasibility Of Tomotherapy-Based Image-Guided Radiotherapy To Reduce Aspiration Risk In Patients With Non-Laryngeal And Non-Pharyngeal Head And Neck Cancer, Nam P. Nguyen, Lexie Smith-Raymond, Vincent Vinh-Hung, Paul Vos, Rick Davis, Anand Desai, Thomas Sroka

Dartmouth Scholarship

Purpose: The study aims to assess the feasibility of Tomotherapy-based image-guided radiotherapy (IGRT) to reduce the aspiration risk in patients with non-laryngeal and non-hypopharyngeal cancer. A retrospective review of 48 patients undergoing radiation for non-laryngeal and non-hypopharyngeal head and neck cancers was conducted. All patients had a modified barium swallow (MBS) prior to treatment, which was repeated one month following radiotherapy. Mean middle and inferior pharyngeal dose was recorded and correlated with the MBS results to determine aspiration risk.

Health-Related Quality Of Life And Life Satisfaction In Colorectal Cancer Survivors: Trajectories Of Adjustment, Jeff Dunn, Shu Kay Ng, William Breitbart, Joanne Aitken, Pip Youl, Peter D. Baade, Suzanne K. Chambers

Research outputs 2013

Background: This longitudinal study describes the five year trajectories of health-related quality of life (HR-QOL) and life satisfaction in long term colorectal cancer survivors.Patients and methods: A population-based sample of 1966 colorectal cancer survivors were surveyed at six time points from five months to five years post-diagnosis. Predictor variables were: socio-demographic variables, optimism; cancer threat appraisal; perceived social support. Quality of life was assessed with the Functional Assessment of Cancer Therapy-Colorectal (HR-QOL); and the Satisfaction with Life Scale. Growth mixture models were applied to identify trajectory classes and their predictors.Results: Distinct adjustment trajectories were identified for HR-QOL and life satisfaction. …

Characteristics And Quality Of Life Of Patients Presenting To Cancer Support Centres: Patient Rated Outcomes And Use Of Complementary Therapies, Bonnie J. Furzer, Kemi E. Wright, Anna S. Petterson, Karen E. Wallman, Timothy R. Ackland, David Jl Joske

Research outputs 2013

Background: In order to effectively target and provide individualised patient support strategies it is crucial to have a comprehensive picture of those presenting for services. The purpose of this study was to determine the characteristics and patient rated outcomes of individuals presenting to SolarisCare cancer support centres and their choices regarding complementary and integrated therapies (CIT).Methods: A cohort with a current or previous cancer diagnosis aged 18 - 87 years presenting to a SolarisCare centre during a 5-day period completed a questionnaire. Four SolarisCare centres participated in the trial including regional and metropolitan locations. Outcomes included medical and demographic characteristics, …

A Phase 1b Study Of Humanized Ks-Interleukin-2 (Huks-Il2) Immunocytokine With Cyclophosphamide In Patients With Epcam-Positive Advanced Solid Tumors., Joseph P Connor, Mihaela C Cristea, Nancy L Lewis, Lionel D Lewis, Philip B Komarnitsky, Maria R Mattiacci, Mildred Felder, Sarah Stewart, Josephine Harter, Jean Henslee-Downey, Daniel Kramer, Roland Neugebauer, Roger Stupp

Kimmel Cancer Center Faculty Papers

BACKGROUND: Humanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent.

METHODS: Phase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300 mg/m2 on day 1), and escalating doses of huKS-IL2 (0.5-4.0 mg/m2 IV continuous infusion over 4 hours) on days 2, 3, and 4 of each 21-day cycle. Safety, pharmacokinetic profile, immunogenicity, anti-tumor and biologic activity were evaluated.

RESULTS: Twenty-seven patients were treated …