Oncology Commons^™

The Molecular Biology And Treatment Of Malignant Melanoma With Brafv600 Mutations, Michael P. Mullane

Journal of Patient-Centered Research and Reviews

Since 2011, the treatment options for metastatic malignant melanoma have significantly changed. In that year, ipilimumab, an anti-CTLA4 monoclonal antibody, and vemurafenib, a potent inhibitor of mutated-BRAF (V600E and V600K), were approved by the U.S. Food and Drug Administration (FDA). In 2013, dabrafenib, another inhibitor of mutated-BRAF, and trametinib, a MEK inhibitor, were approved by the FDA. Most recently, combination therapy with dabrafenib and trametinib was approved. This article will describe a patient with metastatic malignant melanoma with BRAF^V600E who has responded very well to vemurafenib monotherapy. We will then explore the molecular basis, pharmacologic development and clinical outcomes …

Sentinel Lymph Node Biopsy In Head And Neck Melanoma: A Review, Martin Corsten, Stephanie Johnson-Obaseki

Journal of Patient-Centered Research and Reviews

The incidence of melanoma in the United States continues to rise. Head and neck melanomas comprise approximately 20% of all primary cutaneous melanomas. Sentinel lymph node (SLN) biopsy (SLNB) has become the standard of care for staging in melanoma. It has a number of advantages, including the addition of prognostic information, accurate staging, and the potential to add completion lymph node dissection (CLND) or adjuvant therapy when indicated. Furthermore, it may allow for the identification of patients who would benefit from inclusion in clinical trials; this advantage may be amplified based on the introduction of novel targeted therapies.

SLNB does …

Systematic Analysis Of A Xenograft Mice Model For Kshv+ Primary Effusion Lymphoma (Pel), Lu Dai, Jimena Trillo-Tinoco, Lihua Bai, Baoli Kang, Zengguang Xu, Xiaofei Wen, Luis Del Valle, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL), which arises preferentially in the setting of infection with human immunodeficiency virus (HIV). Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+) PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells …

Primary Care For Melanoma: Should We Be Screaming For Screening?, Dennis J. Baumgardner, Alexandria Rogers

Journal of Patient-Centered Research and Reviews

The incidence of cutaneous malignant melanoma continues to rise in the United States. This deadly disease is potentially curable if caught at an early stage, however screening programs remain controversial. The United States Preventive Services Task Force cites insufficient evidence to recommend screening, by total-body skin examination (TBSE), for early detection of cutaneous melanoma. While definitive studies may be cost-prohibitive in the United States, more recent evidence suggests that organized programs to increase TBSE reduce mortality from melanoma. The positive impact of TBSE, and education regarding risk reduction and skin self-examination, is most likely to be cost-effective in high-risk patients …

Targeted Therapy For Cutaneous Melanoma: Beyond Braf..., Michael A. Davies

Journal of Patient-Centered Research and Reviews

The development and regulatory approval of vemurafenib and dabrafenib for metastatic melanoma patients with activating BRAF mutations has demonstrated that personalized targeted therapy strategies can provide significant clinical benefit in this highly aggressive disease. However, these agents are not beneficial in patients who do not have activating BRAF mutations, representing over half of all melanoma patients. Recent studies have demonstrated that melanomas have the highest rate of somatic mutations among the major cancers. Based on this information, additional personalized treatment strategies are now in various stages of clinical development and testing. These efforts are being guided by the lessons learned …

A Rendezvous With An Unexpected Diagnosis, Helen C. Williams, Alexandria Rogers

Journal of Patient-Centered Research and Reviews

A personal account of skin cancer explores a caregiver’s emotional encounter with malignant melanoma, following her podiatrist’s initial diagnosis when she presented for an ingrown toenail.

Melanoma: Attacking On Many Fronts, Michael A. Thompson

Journal of Patient-Centered Research and Reviews

No abstract provided.

Genome-Wide Methylation Analyses In Glioblastoma Multiforme, Rose K. Lai, Yanwen Chen, Xiaowei Guan, Darryl Nousome, Charu Sharma, Peter Canoll, Jeffrey Bruce, Andrew E. Sloan, Etty Cortes, Jean-Paul Vonsattel, Tao Su, Lissette Delgado-Cruzata, Irina Gurvich, Regina M. Santella, Quinn Ostrom, Annette Lee, Peter Gregersen, Jill Barnholtz-Sloan

Publications and Research

Few studies had investigated genome-wide methylation in glioblastoma multiforme (GBM). Our goals were to study differential methylation across the genome in gene promoters using an array-based method, as well as repetitive elements using surrogate global methylation markers. The discovery sample set for this study consisted of 54 GBM from Columbia University and Case Western Reserve University, and 24 brain controls from the New York Brain Bank. We assembled a validation dataset using methylation data of 162 TCGA GBM and 140 brain controls from dbGAP. HumanMethylation27 Analysis Bead-Chips (Illumina) were used to interrogate 26,486 informative CpG sites in both the discovery …

Natural History Of Untreated Prostate Specific Antigen Radiorecurrent Prostate Cancer In Men With Favorable Prognostic Indicators, Andrew Renshaw

All Publications

No abstract provided.

A Novel Radiation-Induced P53 Mutation Is Not Implicated In Radiation Resistance Via A Dominant-Negative Effect., Yunguang Sun, Carey Jeanne Myers, Adam Dicker Md, Phd, Bo Lu, Md

Department of Radiation Oncology Faculty Papers

Understanding the mutations that confer radiation resistance is crucial to developing mechanisms to subvert this resistance. Here we describe the creation of a radiation resistant cell line and characterization of a novel p53 mutation. Treatment with 20 Gy radiation was used to induce mutations in the H460 lung cancer cell line; radiation resistance was confirmed by clonogenic assay. Limited sequencing was performed on the resistant cells created and compared to the parent cell line, leading to the identification of a novel mutation (del) at the end of the DNA binding domain of p53. Levels of p53, phospho-p53, p21, total caspase …

Response Assessment Of Novottf-100a Versus Best Physician's Choice Chemotherapy In Recurrent Glioblastoma, Eric T. Wong, Edwin Lok, Kenneth D. Swanson, Shiva Gautam, Herbert H. Engelhard, Frank Lieberman, Sophie Taillibert, Zvi Ram, John L. Villano

Markey Cancer Center Faculty Publications

The NovoTTF-100A device emits frequency-tuned alternating electric fields that interfere with tumor cell mitosis. In phase III trial for recurrent glioblastomas, NovoTTF-100A was shown to have equivalent efficacy and less toxicity when compared to Best Physician's Choice (BPC) chemotherapy. We analyzed the characteristics of responders and nonresponders in both cohorts to determine the characteristics of response and potential predictive factors. Tumor response and progression were determined by Macdonald criteria. Time to response, response duration, progression-free survival (PFS) ± Simon-Makuch correction, overall survival (OS), prognostic factors, and relative hazard rates were compared between responders and nonresponders. Median response duration was 7.3 …

Epicatechin Stimulates Mitochondrial Activity And Selectively Sensitizes Cancer Cells To Radiation, Hosam A. Elbaz, Icksoo Lee, Deborah A. Antwih, Jenney Liu, Maik Hüttemann, Steven P. Zielske

Center for Molecular Medicine and Genetics

Radiotherapy is the treatment of choice for solid tumors including pancreatic cancer, but the effectiveness of treatment is limited by radiation resistance. Resistance to chemotherapy or radiotherapy is associated with reduced mitochondrial respiration and drugs that stimulate mitochondrial respiration may decrease radiation resistance. The objectives of this study were to evaluate the potential of (-)-epicatechin to stimulate mitochondrial respiration in cancer cells and to selectively sensitize cancer cells to radiation. We investigated the natural compound (-)-epicatechin for effects on mitochondrial respiration and radiation resistance of pancreatic and glioblastoma cancer cells using a Clark type oxygen electrode, clonogenic survival assays, and …

Radiation Exposure Of Patients By Cone Beam Ct During Endobronchial Navigation - A Phantom Study, Wolfgang Hohenforst-Schmidt, Rosemarie Banckwitz, Paul Zarogoulidis, Thomas Vogl, Kaid Darwiche, Eugene Goldberg, Haidong Huang, Michael Simoff, Qiang Li, Robert Browning, Lutz Freitag, J. Francis Turner, Patrick Le Pivert, Lonny Yarmus, Konstantinos Zarogoulidis, Johannes Brachmann

Internal Medicine Faculty Publications

Rationale: Cone Beam Computed Tomography imaging has become increasingly important in many fields of interventional therapies. Objective: Lung navigation study which is an uncommon soft tissue approach. Methods: As no effective organ radiation dose levels were available for this kind of Cone Beam Computed Tomography application we simulated in our DynaCT (Siemens AG, Forchheim, Germany) suite 2 measurements including 3D acquisition and again for 3D acquisition and 4 endobronchial navigation maneuvers under fluoroscopy towards a nodule after the 8th segmentation in the right upper lobe over a total period of 20 minutes (min). These figures reflect the average complexity and …

Influence Networks Based On Coexpression Improve Drug Target Discovery For The Development Of Novel Cancer Therapeutics, Nadia M. Penrod, Jason H. Moore

Dartmouth Scholarship

Background: Thedemandfornovelmolecularlytargeteddrugswillcontinuetoriseaswemoveforwardtowardthe goal of personalizing cancer treatment to the molecular signature of individual tumors. However, the identification of targets and combinations of targets that can be safely and effectively modulated is one of the greatest challenges facing the drug discovery process. A promising approach is to use biological networks to prioritize targets based on their relative positions to one another, a property that affects their ability to maintain network integrity and propagate information-flow. Here, we introduce influence networks and demonstrate how they can be used to generate influence scores as a network-based metric to rank genes as potential drug targets. …

Has The Use Of Computers In Radiation Therapy Improved The Accuracy In Radiation Dose Delivery?, Jacob Van Dyk, Jerry J. Battista Dr.

Oncology Publications

Purpose: It is well recognized that computer technology has had a major impact on the practice of radiation oncology. This paper addresses the question as to how these computer advances have specifically impacted the accuracy of radiation dose delivery to the patient. Methods: A review was undertaken of all the key steps in the radiation treatment process ranging from machine calibration to patient treatment verification and irradiation. Using a semi-quantitative scale, each stage in the process was analysed from the point of view of gains in treatment accuracy. Results: Our critical review indicated that computerization related to digital medical imaging …

A Melanin-Independent Interaction Between Mc1r And Met Signalling Pathways Is Required For Hgf-Dependent Melanoma, Agnieszka Wolnicka-Głubisz, Faith M. Strickland, Albert Wielgus, Miriam Anver, Glenn Merlino, Edward C. De Fabo, Frances P. Noonan

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Melanocortin 1 receptor (MC1R) signaling stimulates black eumelanin production through a cAMP-dependent pathway. MC1R polymorphisms can impair this process, resulting in a predominance of red phaeomelanin. The red hair, fair skin and UV sensitive phenotype is a well-described melanoma risk factor. MC1R polymorphisms also confer melanoma risk independent of pigment. We investigated the effect of Mc1r deficiency in a mouse model of UV-induced melanoma. C57BL/6-Mc1r+/+-HGF transgenic mice have a characteristic hyperpigmented black phenotype with extra-follicular dermal melanocytes located at the dermal/epidermal junction. UVB induces melanoma, independent of melanin pigmentation, but UVA-induced and spontaneous melanomas are dependent on black eumelanin. We …

Targeting Fibroblast Activation Protein In Tumor Stroma With Chimeric Antigen Receptor T Cells Can Inhibit Tumor Growth And Augment Host Immunity Without Severe Toxicity., Liang-Chuan S. Wang, Albert Lo, John Scholler, Jing Sun, Rajrupa S. Majumdar, Veena Kapoor, Michael Antzis, Cody E. Cotner, Laura A. Johnson, Amy C. Durham, Charalambos C. Solomides, Md, Carl H. June, Ellen Puré, Steven M. Albelda

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The majority of chimeric antigen receptor (CAR) T-cell research has focused on attacking cancer cells. Here, we show that targeting the tumor-promoting, nontransformed stromal cells using CAR T cells may offer several advantages. We developed a retroviral CAR construct specific for the mouse fibroblast activation protein (FAP), comprising a single-chain Fv FAP [monoclonal antibody (mAb) 73.3] with the CD8α hinge and transmembrane regions, and the human CD3ζ and 4-1BB activation domains. The transduced muFAP-CAR mouse T cells secreted IFN-γ and killed FAP-expressing 3T3 target cells specifically. Adoptively transferred 73.3-FAP-CAR mouse T cells selectively reduced FAP(hi) stromal cells and inhibited the …

Oncolog, Volume 59, Number 02, February 2014, Sarah Bronson, Kathryn L. Hale, Bryan Tutt, M. Yeoman

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

• New Approaches Revolutionize the Treatment of Advanced Melanoma: Recent breakthroughs in immunotherapy and targeted therapy have improved outcomes for patients with advanced melanoma
• Comprehensive Tobacco Treatment Approach Helps Patients Quit on Their Terms: Kicking a tobacco habit is a formidable task. Quitting tobacco after a diagnosis of cancer, can be even more difficult
• Targeted Drug Shows Promise Against Advanced Breast Cancer: Adding the experimental kinase inhibitor palbociclib to standard hormonal therapy may delay disease progression in patients with advanced breast cancer that is estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER@) negative
• HOUSE CALL: Avoiding Food-Drug …

Measuring Patient Satisfaction In Multidisciplinary Cancer Centers: Optimize Use Of Results To Effect Change And Improve Processes, Mary-Kate Cellmer, Bs

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Jefferson¹s Kimmel Cancer Center¹s multidisciplinary centers were established in 1994. The centers are a collaborative effort among radiation oncologists, medical oncologists, surgeons and other specialists involved in leading-edge cancer treatments.

The multidisciplinary center sees patients on the following days:

• Monday: Brain and Metastatic Uveal Melanoma
• Tuesday: Thoracic/Aerodigestive and Senior Adult Oncology
• Wednesday: Genitourinary and Liver
• Thursday: Small Renal Mass
• Friday: Senior Adult Oncology

Relationships Between Parenting Self-Efficacy And Distress In Parents With And Without Cancer, Julie Marie Cessna

USF Tampa Graduate Theses and Dissertations

Despite the relatively large number of parents with cancer, relatively little is known about the extent to which having cancer affects the parenting experience. Qualitative studies have identified issues and concerns that create distress among parents with cancer, but quantitative studies have yet to be conducted. Studies demonstrate that parents with cancer experience psychological distress, and that parenting self-efficacy is related to psychological distress among parents without cancer. However, no study to date has examined the relationships between parenting self-efficacy and psychological distress among parents with cancer. This study sought to address these gaps in the literature by comparing parents …