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Thomas Jefferson University

Kimmel Cancer Center Faculty Papers

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Full-Text Articles in Medicine and Health Sciences

Xpo1 Blockade With Kpt-330 Promotes Apoptosis In Cutaneous T-Cell Lymphoma By Activating The P53-P21 And P27 Pathways, Nitin Chakravarti, Amy Boles, Rachel Burzinski, Paola Sindaco, Colleen Isabelle, Kathleen Mcconnell, Anjali Mishra, Pierluigi Porcu Apr 2024

Xpo1 Blockade With Kpt-330 Promotes Apoptosis In Cutaneous T-Cell Lymphoma By Activating The P53-P21 And P27 Pathways, Nitin Chakravarti, Amy Boles, Rachel Burzinski, Paola Sindaco, Colleen Isabelle, Kathleen Mcconnell, Anjali Mishra, Pierluigi Porcu

Kimmel Cancer Center Faculty Papers

Dysregulated nuclear-cytoplasmic trafficking has been shown to play a role in oncogenesis in several types of solid tumors and hematological malignancies. Exportin 1 (XPO1) is responsible for the nuclear export of several proteins and RNA species, mainly tumor suppressors. KPT-330, a small molecule inhibitor of XPO1, is approved for treating relapsed multiple myeloma and diffuse large B-cell lymphoma. Cutaneous T-cell lymphoma (CTCL) is an extranodal non-Hodgkin lymphoma with an adverse prognosis and limited treatment options in advanced stages. The effect of therapeutically targeting XPO1 with KPT-330 in CTCL has not been established. We report that XPO1 expression is upregulated in …


Xaluritamig, A Steap1 × Cd3 Xmab 2+1 Immune Therapy For Metastatic Castration-Resistant Prostate Cancer: Results From Dose Exploration In A First-In-Human Study, William K. Kelly, Daniel C. Danila, Chia-Chi Lin, Jae-Lyun Lee, Nobuaki Matsubara, Patrick J. Ward, Andrew J. Armstrong, David Pook, Miso Kim, Tanya B. Dorff, Stefanie Fischer, Yung-Chang Lin, Lisa G. Horvath, Christopher Sumey, Zhao Yang, Gabor Jurida, Kristen M. Smith, Jamie N. Connarn, Hweixian L. Penny, Julia Stieglmaier, Leonard J. Appleman Oct 2023

Xaluritamig, A Steap1 × Cd3 Xmab 2+1 Immune Therapy For Metastatic Castration-Resistant Prostate Cancer: Results From Dose Exploration In A First-In-Human Study, William K. Kelly, Daniel C. Danila, Chia-Chi Lin, Jae-Lyun Lee, Nobuaki Matsubara, Patrick J. Ward, Andrew J. Armstrong, David Pook, Miso Kim, Tanya B. Dorff, Stefanie Fischer, Yung-Chang Lin, Lisa G. Horvath, Christopher Sumey, Zhao Yang, Gabor Jurida, Kristen M. Smith, Jamie N. Connarn, Hweixian L. Penny, Julia Stieglmaier, Leonard J. Appleman

Kimmel Cancer Center Faculty Papers

ABSTRACT : Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis of STEAP1-expressing cancer cells, such as those in advanced prostate cancer. This first-in-human study reports monotherapy dose exploration for patients with metastatic castration-resistant prostate cancer (mCRPC), primarily taxane pretreated. Ninety-seven patients received ≥1 intravenous dose ranging from 0.001 to 2.0 mg weekly or every 2 weeks. MTD was identified as 1.5 mg i.v. weekly via a 3-step dose. The most common treatment-related adverse events were cytokine release syndrome (CRS; 72%), fatigue (45%), and myalgia (34%). CRS occurred primarily during …


Exploring Breast Cancer Systemic Drug Therapy Patterns In Real-World Data, Julia O'Rourke, Jeff Warnick, John Doole, Luc De Keyser, Zuzanna Drebert, Olivia Wan, Courtney N Thompson, Jack W. London, Karen Fairchild, Matvey B. Palchuk Oct 2023

Exploring Breast Cancer Systemic Drug Therapy Patterns In Real-World Data, Julia O'Rourke, Jeff Warnick, John Doole, Luc De Keyser, Zuzanna Drebert, Olivia Wan, Courtney N Thompson, Jack W. London, Karen Fairchild, Matvey B. Palchuk

Kimmel Cancer Center Faculty Papers

PURPOSE: To explore medications and their administration patterns in real-world patients with breast cancer.

METHODS: A retrospective study was performed using TriNetX, a federated network of deidentified, Health Insurance Portability and Accountability Act-compliant data from 21 health care organizations across North America. Patients diagnosed with breast cancer between January 1, 2013, and May 31, 2022, were included. We investigated a rule-based and unsupervised learning algorithm to extract medications and their administration patterns. To group similar administration patterns, we used three features in k-means clustering: total number of administrations, median number of days between administrations, and standard deviation of the days …


Relative Burden Of Cancer And Noncancer Mortality Among Long-Term Survivors Of Breast, Prostate, And Colorectal Cancer In The Us, Madhav Kc, Jane Fan, Terry Hyslop, Sirad Hassan, Michael Cecchini, Shi-Yi Wang, Andrea Silber, Michael S. Leapman, Ira Leeds, Stephanie B. Wheeler, Lisa P. Spees, Cary P. Gross, Maryam Lustberg, Rachel A. Greenup, Amy C. Justice, Kevin C. Oeffinger, Michaela A. Dinan Jul 2023

Relative Burden Of Cancer And Noncancer Mortality Among Long-Term Survivors Of Breast, Prostate, And Colorectal Cancer In The Us, Madhav Kc, Jane Fan, Terry Hyslop, Sirad Hassan, Michael Cecchini, Shi-Yi Wang, Andrea Silber, Michael S. Leapman, Ira Leeds, Stephanie B. Wheeler, Lisa P. Spees, Cary P. Gross, Maryam Lustberg, Rachel A. Greenup, Amy C. Justice, Kevin C. Oeffinger, Michaela A. Dinan

Kimmel Cancer Center Faculty Papers

IMPORTANCE: Improvements in cancer outcomes have led to a need to better understand long-term oncologic and nononcologic outcomes and quantify cancer-specific vs noncancer-specific mortality risks among long-term survivors.

OBJECTIVE: To assess absolute and relative cancer-specific vs noncancer-specific mortality rates among long-term survivors of cancer, as well as associated risk factors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 627 702 patients in the Surveillance, Epidemiology, and End Results cancer registry with breast, prostate, or colorectal cancer who received a diagnosis between January 1, 2003, and December 31, 2014, who received definitive treatment for localized disease and who were alive 5 …


A Rare Metastatic Mesenteric Malignant Pecoma With Tsc2 Mutation Treated With Palliative Surgical Resection And Nab-Sirolimus: A Case Report, Luke Meredith, Timothy Chao, Avinoam Nevler, Atrayee Basu Mallick, Rajan Singla, Peter Mccue, Wilbur Bowne, Wei Jiang, Md, Phd Apr 2023

A Rare Metastatic Mesenteric Malignant Pecoma With Tsc2 Mutation Treated With Palliative Surgical Resection And Nab-Sirolimus: A Case Report, Luke Meredith, Timothy Chao, Avinoam Nevler, Atrayee Basu Mallick, Rajan Singla, Peter Mccue, Wilbur Bowne, Wei Jiang, Md, Phd

Kimmel Cancer Center Faculty Papers

BACKGROUND: Malignant perivascular epithelioid cell tumors (PEComas) are exceedingly rare malignant mesenchymal neoplasms with characteristic morphological and immunohistochemical (IHC) patterns. However, some malignant PEComas are poorly differentiated with atypical histopathological features, making a definitive diagnosis difficult. PEComas are most commonly found in females and often show either TSC1 or TSC2 alterations, which result in the activation of the mTOR pathway, or TFE3 fusions. Given these molecular characteristics, mTOR inhibitors have recently been approved by the FDA in the treatment of malignant PEComas, particularly in those with TSC1/2 alterations. Therefore, molecular analyses may be helpful for both the diagnostic workup of …


Parp Inhibitors For The Treatment Of Brca1/2-Mutated Metastatic Breast Cancer: A Systematic Review And Meta-Analysis, Ranju Kunwor, Daniel P. Silver, Maysa Abu-Khalaf Apr 2023

Parp Inhibitors For The Treatment Of Brca1/2-Mutated Metastatic Breast Cancer: A Systematic Review And Meta-Analysis, Ranju Kunwor, Daniel P. Silver, Maysa Abu-Khalaf

Kimmel Cancer Center Faculty Papers

BACKGROUND: The PARP inhibitors (PARPis) olaparib and talazoparib are currently approved for the treatment of deleterious germline BRCA1/2-mutated (gBRCA+) metastatic breast cancer (MBC). These approvals were based on improvements in progression-free survival (PFS) observed in two randomized controlled trials (RCTs). Other PARPis, such as veliparib and niraparib, have also been studied. We conducted this meta-analysis of RCTs to assess the PFS and overall survival (OS) benefits of PARPis in gBRCA + MBC.

METHODS: We performed a systematic search for RCTs using the Cochrane Library, PubMed, Embase, and Web of Science databases up to March 2021. Only phase II and III …


The V8-10 Variant Isoform Of Cd44 Is Selectively Expressed In The Normal Human Colonic Stem Cell Niche And Frequently Is Overexpressed In Colon Carcinomas During Tumor Development, Bruce M. Boman, Vignesh Viswanathan, Caroline O B Facey, Jeremy Z Fields, James W Stave Mar 2023

The V8-10 Variant Isoform Of Cd44 Is Selectively Expressed In The Normal Human Colonic Stem Cell Niche And Frequently Is Overexpressed In Colon Carcinomas During Tumor Development, Bruce M. Boman, Vignesh Viswanathan, Caroline O B Facey, Jeremy Z Fields, James W Stave

Kimmel Cancer Center Faculty Papers

CD44 protein and its variant isoforms are expressed in cancer stem cells (CSCs), and various CD44 isoforms can have different functional roles in cells. Our goal was to investigate how different CD44 isoforms contribute to the emergence of stem cell (SC) overpopulation that drives colorectal cancer (CRC) development. Specific CD44 variant isoforms are selectively expressed in normal colonic SCs and become overexpressed in CRCs during tumor development. We created a unique panel of anti-CD44 rabbit genomic antibodies to 16 specific epitopes that span the entire length of the CD44 molecule. Our panel was used to comprehensively investigate the expression of …


Ros And Mirna Dysregulation In Ovarian Cancer Development, Angiogenesis And Therapeutic Resistance, David C Stieg, Yifang Wang, Ling-Zhi Liu, Bing-Hua Jiang Jun 2022

Ros And Mirna Dysregulation In Ovarian Cancer Development, Angiogenesis And Therapeutic Resistance, David C Stieg, Yifang Wang, Ling-Zhi Liu, Bing-Hua Jiang

Kimmel Cancer Center Faculty Papers

The diverse repertoires of cellular mechanisms that progress certain cancer types are being uncovered by recent research and leading to more effective treatment options. Ovarian cancer (OC) is among the most difficult cancers to treat. OC has limited treatment options, especially for patients diagnosed with late-stage OC. The dysregulation of miRNAs in OC plays a significant role in tumorigenesis through the alteration of a multitude of molecular processes. The development of OC can also be due to the utilization of endogenously derived reactive oxygen species (ROS) by activating signaling pathways such as PI3K/AKT and MAPK. Both miRNAs and ROS are …


Assessing The Coverage Of Us Cancer Center Primary Catchment Areas., Amy E Leader, Christopher Mcnair, Christina Yurick, Matthew Huesser, Elizabeth Schade, Emily E Stimmel, Caryn Lerman, Karen E Knudsen May 2022

Assessing The Coverage Of Us Cancer Center Primary Catchment Areas., Amy E Leader, Christopher Mcnair, Christina Yurick, Matthew Huesser, Elizabeth Schade, Emily E Stimmel, Caryn Lerman, Karen E Knudsen

Kimmel Cancer Center Faculty Papers

Background: Cancer centers are expected to engage communities and reduce the burden of cancer in their catchment areas. However, the extent to which cancer centers adequately reach the entire US population is unknown. Methods: We surveyed all members of the Association of American Cancer Institutes (N ¼ 102 cancer centers) to document and map each cancer center’s primary catchment area. Catchment area descriptions were aggregated to the county level. Catchment area coverage scores were calculated for each county and choropleths generated representing coverage across the US. Similar analyses were used to overlay US population density, cancer incidence, and cancer-related mortality …


Impact Of Homologous Recombination Status And Responses With Veliparib Combined With First-Line Chemotherapy In Ovarian Cancer In The Phase 3 Velia/Gog-3005 Study, Elizabeth M Swisher, Carol Aghajanian, David M O'Malley, Gini F Fleming, Scott H Kaufmann, Douglas A Levine, Michael J Birrer, Kathleen N Moore, Nick M Spirtos, Mark S Shahin, Thomas J Reid, Michael Friedlander, Karina Dahl Steffensen, Aikou Okamoto, Vasudha Sehgal, Peter J Ansell, Minh H Dinh, Michael A Bookman, Robert L Coleman May 2022

Impact Of Homologous Recombination Status And Responses With Veliparib Combined With First-Line Chemotherapy In Ovarian Cancer In The Phase 3 Velia/Gog-3005 Study, Elizabeth M Swisher, Carol Aghajanian, David M O'Malley, Gini F Fleming, Scott H Kaufmann, Douglas A Levine, Michael J Birrer, Kathleen N Moore, Nick M Spirtos, Mark S Shahin, Thomas J Reid, Michael Friedlander, Karina Dahl Steffensen, Aikou Okamoto, Vasudha Sehgal, Peter J Ansell, Minh H Dinh, Michael A Bookman, Robert L Coleman

Kimmel Cancer Center Faculty Papers

Objective: In the Phase 3 VELIA trial (NCT02470585), PARP inhibitor (PARPi) veliparib was combined with first-line chemotherapy and continued as maintenance for patients with ovarian carcinoma enrolled regardless of chemotherapy response or biomarker status. Here, we report exploratory analyses of the impact of homologous recombination deficient (HRD) or proficient (HRP) status on progression-free survival (PFS) and objective response rates during chemotherapy.

Methods: Women with Stage III-IV ovarian carcinoma were randomized to veliparib-throughout, veliparib-combination-only, or placebo. Stratification factors included timing of surgery and germline BRCA mutation status. HRD status was dichotomized at genomic instability score 33. During combination therapy, …


Assessment Of Regional Variability In Covid-19 Outcomes Among Patients With Cancer In The United States., Jessica E Hawley, Tianyi Sun, David D Chism, Narjust Duma, Julie C Fu, Na Tosha N Gatson, Sanjay Mishra, Ryan H Nguyen, Sonya A Reid, Oscar K Serrano, Sunny R K Singh, Neeta K Venepalli, Ziad Bakouny, Babar Bashir, Mehmet A Bilen, Paolo F Caimi, Toni K Choueiri, Scott J Dawsey, Leslie A Fecher, Daniel B Flora, Christopher R Friese, Michael J Glover, Cyndi J Gonzalez, Sharad Goyal, Thorvardur R Halfdanarson, Dawn L Hershman, Hina Khan, Chris Labaki, Mark A Lewis, Rana R Mckay, Ian Messing, Nathan A Pennell, Matthew Puc, Deepak Ravindranathan, Terence D Rhodes, Andrea V Rivera, John Roller, Gary K Schwartz, Sumit A Shah, Justin A Shaya, Mitrianna Streckfuss, Michael A Thompson, Elizabeth M Wulff-Burchfield, Zhuoer Xie, Peter Paul Yu, Jeremy L Warner, Dimpy P Shah, Benjamin French, Clara Hwang Jan 2022

Assessment Of Regional Variability In Covid-19 Outcomes Among Patients With Cancer In The United States., Jessica E Hawley, Tianyi Sun, David D Chism, Narjust Duma, Julie C Fu, Na Tosha N Gatson, Sanjay Mishra, Ryan H Nguyen, Sonya A Reid, Oscar K Serrano, Sunny R K Singh, Neeta K Venepalli, Ziad Bakouny, Babar Bashir, Mehmet A Bilen, Paolo F Caimi, Toni K Choueiri, Scott J Dawsey, Leslie A Fecher, Daniel B Flora, Christopher R Friese, Michael J Glover, Cyndi J Gonzalez, Sharad Goyal, Thorvardur R Halfdanarson, Dawn L Hershman, Hina Khan, Chris Labaki, Mark A Lewis, Rana R Mckay, Ian Messing, Nathan A Pennell, Matthew Puc, Deepak Ravindranathan, Terence D Rhodes, Andrea V Rivera, John Roller, Gary K Schwartz, Sumit A Shah, Justin A Shaya, Mitrianna Streckfuss, Michael A Thompson, Elizabeth M Wulff-Burchfield, Zhuoer Xie, Peter Paul Yu, Jeremy L Warner, Dimpy P Shah, Benjamin French, Clara Hwang

Kimmel Cancer Center Faculty Papers

Importance: The COVID-19 pandemic has had a distinct spatiotemporal pattern in the United States. Patients with cancer are at higher risk of severe complications from COVID-19, but it is not well known whether COVID-19 outcomes in this patient population were associated with geography.

Objective: To quantify spatiotemporal variation in COVID-19 outcomes among patients with cancer.

Design, Setting, and Participants: This registry-based retrospective cohort study included patients with a historical diagnosis of invasive malignant neoplasm and laboratory-confirmed SARS-CoV-2 infection between March and November 2020. Data were collected from cancer care delivery centers in the United States.

Exposures: Patient residence was categorized …


Potential Immunomodulatory Properties Of Biologically Active Components Of Spices Against Sars-Cov-2 And Pan Β-Coronaviruses, Sourodip Sengupta, Debina Bhattacharyya, Grishma Kasle, Souvik Karmakar, Omkar Sahu, Anirban Ganguly, Sankar Addya, Jayasri Das Sarma Aug 2021

Potential Immunomodulatory Properties Of Biologically Active Components Of Spices Against Sars-Cov-2 And Pan Β-Coronaviruses, Sourodip Sengupta, Debina Bhattacharyya, Grishma Kasle, Souvik Karmakar, Omkar Sahu, Anirban Ganguly, Sankar Addya, Jayasri Das Sarma

Kimmel Cancer Center Faculty Papers

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced COVID-19 has emerged as a defining global health crisis in current times. Data from the World Health Organization shows demographic variations in COVID-19 severity and lethality. Diet may play a significant role in providing beneficial host cell factors contributing to immunity against deadly SARS-CoV-2 pathogenesis. Spices are essential components of the diet that possess anti-inflammatory, antioxidant, and antiviral properties. Hyperinflammation, an aberrant systemic inflammation associated with pneumonia, acute respiratory failure, and multiorgan dysfunction, is a major clinical outcome in COVID-19. Knowing the beneficial properties of spices, we hypothesize that spice-derived bioactive components …


Returning To Sport: Female Athletes Living With And Beyond Cancer., Anna L. Schwartz, Christopher Terry Aug 2021

Returning To Sport: Female Athletes Living With And Beyond Cancer., Anna L. Schwartz, Christopher Terry

Kimmel Cancer Center Faculty Papers

Many athletes living with and beyond cancer can continue to train and, in some cases, compete during treatment. Following cancer treatment, athletes can return to competitive sport but need to learn to adapt their physical strength and training to the lingering effects of cancer. It is critical for oncology healthcare providers to use the principles of assess, refer and advise to exercise oncology programs that are appropriate for the individual. Managing side effects of treatment is key to being able to train during and immediately following cancer treatment. Keen attention to fatigue is important at any point in the cancer …


Digital Literacy At An Urban Cancer Center: Implications For Technology Use And Vulnerable Patients, Amy Leader, Lisa M. Capparella, L. Waldman, Ba, Rebecca Cammy, Alison Petok, Rebecca Dean, Ayako Shimada, Liana Yocavitch, Kristin L. Rising, Gregory Garber, Brooke Worster, Adam Dicker Aug 2021

Digital Literacy At An Urban Cancer Center: Implications For Technology Use And Vulnerable Patients, Amy Leader, Lisa M. Capparella, L. Waldman, Ba, Rebecca Cammy, Alison Petok, Rebecca Dean, Ayako Shimada, Liana Yocavitch, Kristin L. Rising, Gregory Garber, Brooke Worster, Adam Dicker

Kimmel Cancer Center Faculty Papers

PURPOSE: eHealth literacy, or the ability to seek, find, understand, and appraise health information from electronic sources, has become increasingly relevant in the era of COVID-19, when so many aspects of patient care became dependent on technology. We aimed to understand eHealth literacy among a diverse sample of patients with cancer and discuss ways for health systems and cancer centers to ensure that all patients have access to high-quality care.

METHODS: A cross-sectional survey of patients with cancer and caregivers was conducted at an NCI-designated cancer center to assess access to the Internet, smartphone ownership, use of mobile apps, willingness …


Virtual Connectivity During Quarantine: The Role Of Social Media For Radiation Oncology During Covid-19, Miriam A Knoll, Mudit Chowdhary, Adam Dicker, Thomas Eichler Oct 2020

Virtual Connectivity During Quarantine: The Role Of Social Media For Radiation Oncology During Covid-19, Miriam A Knoll, Mudit Chowdhary, Adam Dicker, Thomas Eichler

Kimmel Cancer Center Faculty Papers

No abstract provided.


Health Insurance Coverage Disruptions And Cancer Care And Outcomes: Systematic Review Of Published Research, K Robin Yabroff, Katherine Reeder-Hayes, Jingxuan Zhao, Michael T Halpern, Ana Maria Lopez, Leon Bernal-Mizrachi, Anderson B Collier, Joan Neuner, Jonathan Phillips, William Blackstock, Manali Patel Jul 2020

Health Insurance Coverage Disruptions And Cancer Care And Outcomes: Systematic Review Of Published Research, K Robin Yabroff, Katherine Reeder-Hayes, Jingxuan Zhao, Michael T Halpern, Ana Maria Lopez, Leon Bernal-Mizrachi, Anderson B Collier, Joan Neuner, Jonathan Phillips, William Blackstock, Manali Patel

Kimmel Cancer Center Faculty Papers

BACKGROUND: Lack of health insurance coverage is associated with poor access and receipt of cancer care and survival in the United States. Disruptions in coverage are common among low-income populations, but little is known about associations of disruptions with cancer care, including prevention, screening, and treatment, as well as outcomes of stage at diagnosis and survival.

METHODS: We conducted a systematic review of studies of health insurance coverage disruptions and cancer care and outcomes published between 1980 and 2019. We used the PubMed, EMBASE, Scopus, and CINAHL databases and identified 29 observational studies. Study characteristics and key findings were abstracted …


Identification Of A Developmental Gene Expression Signature, Including Hox Genes, For The Normal Human Colonic Crypt Stem Cell Niche: Overexpression Of The Signature Parallels Stem Cell Overpopulation During Colon Tumorigenesis., Seema Bhatlekar, Sankar Addya, Moreh Salunek, Christopher R Orr, Saul Surrey, Steven E. Mckenzie, Jeremy Z Fields, Bruce M Boman Jan 2014

Identification Of A Developmental Gene Expression Signature, Including Hox Genes, For The Normal Human Colonic Crypt Stem Cell Niche: Overexpression Of The Signature Parallels Stem Cell Overpopulation During Colon Tumorigenesis., Seema Bhatlekar, Sankar Addya, Moreh Salunek, Christopher R Orr, Saul Surrey, Steven E. Mckenzie, Jeremy Z Fields, Bruce M Boman

Kimmel Cancer Center Faculty Papers

Our goal was to identify a unique gene expression signature for human colonic stem cells (SCs). Accordingly, we determined the gene expression pattern for a known SC-enriched region--the crypt bottom. Colonic crypts and isolated crypt subsections (top, middle, and bottom) were purified from fresh, normal, human, surgical specimens. We then used an innovative strategy that used two-color microarrays (∼18,500 genes) to compare gene expression in the crypt bottom with expression in the other crypt subsections (middle or top). Array results were validated by PCR and immunostaining. About 25% of genes analyzed were expressed in crypts: 88 preferentially in the bottom, …


Circulating Tumor Dna To Monitor Metastatic Breast Cancer., Massimo Cristofanilli, Paolo Fortina Jul 2013

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

Kimmel Cancer Center Faculty Papers

No abstract provided.


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 Jan 2013

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 …


Lymph Node Ratio Is An Important And Independent Prognostic Factor For Patients With Stage Iii Melanoma, Adam C. Berger, Michael Fierro, John C. Kairys, David Berd, Takami Sato, Jocelyn Andrel, Terry Hyslop, Michael J. Mastrangelo Jan 2012

Lymph Node Ratio Is An Important And Independent Prognostic Factor For Patients With Stage Iii Melanoma, Adam C. Berger, Michael Fierro, John C. Kairys, David Berd, Takami Sato, Jocelyn Andrel, Terry Hyslop, Michael J. Mastrangelo

Kimmel Cancer Center Faculty Papers

INTRODUCTION:

The incidence of melanoma is dramatically increasing worldwide. We hypothesized that the ratio of metastatic to examined lymph node ratio (LNR) would be the most important prognostic factor for stage III patients.

METHODS:

We retrospectively reviewed our institutional database of melanoma patients and identified 168 patients who underwent lymph node dissection (LND) for stage III disease between 1993 and 2007. Patients were divided into three groups based on LNR (≤10%, n = 93; 10-≤25%, n = 45; and >25%, n = 30). Univariate and multivariate analysis was performed using Cox proportional hazards model.

RESULTS:

The median survival time of …


Whole-Exome Sequencing Of Dna From Peripheral Blood Mononuclear Cells (Pbmc) And Ebv-Transformed Lymphocytes From The Same Donor., Eric R Londin, Margaret A Keller, Michael R D'Andrea, Kathleen Delgrosso, Adam Ertel, Saul Surrey, Paolo Fortina Sep 2011

Whole-Exome Sequencing Of Dna From Peripheral Blood Mononuclear Cells (Pbmc) And Ebv-Transformed Lymphocytes From The Same Donor., Eric R Londin, Margaret A Keller, Michael R D'Andrea, Kathleen Delgrosso, Adam Ertel, Saul Surrey, Paolo Fortina

Kimmel Cancer Center Faculty Papers

BACKGROUND: The creation of lymphoblastoid cell lines (LCLs) through Epstein-Barr virus (EBV) transformation of B-lymphocytes can result in a valuable biomaterial for cell biology research and a renewable source of DNA. While LCLs have been used extensively in cellular and genetic studies, the process of cell transformation and expansion during culturing may introduce genomic changes that may impact their use and the interpretation of subsequent genetic findings.

RESULTS: We performed whole exome sequencing on a tetrad family using DNA derived from peripheral blood mononuclear cells (PBMCs) and LCLs from each individual. We generated over 4.7 GB of mappable sequence to …


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 May 2011

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 …


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 Mar 2011

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 …


Biological Rationale For The Use Of Dna Methyltransferase Inhibitors As New Strategy For Modulation Of Tumor Response To Chemotherapy And Radiation., Giovanni L Gravina, Claudio Festuccia, Francesco Marampon, Vladimir M Popov, Richard G Pestell, Bianca M Zani, Vincenzo Tombolini Nov 2010

Biological Rationale For The Use Of Dna Methyltransferase Inhibitors As New Strategy For Modulation Of Tumor Response To Chemotherapy And Radiation., Giovanni L Gravina, Claudio Festuccia, Francesco Marampon, Vladimir M Popov, Richard G Pestell, Bianca M Zani, Vincenzo Tombolini

Kimmel Cancer Center Faculty Papers

Epigenetic modifications play a key role in the patho-physiology of many tumors and the current use of agents targeting epigenetic changes has become a topic of intense interest in cancer research. DNA methyltransferase (DNMT) inhibitors represent a promising class of epigenetic modulators. Research performed yielded promising anti-tumorigenic activity for these agents in vitro and in vivo against a variety of hematologic and solid tumors. These epigenetic modulators cause cell cycle and growth arrest, differentiation and apoptosis. Rationale for combining these agents with cytotoxic therapy or radiation is straightforward since the use of DNMT inhibitor offers greatly improved access for cytotoxic …


Assessment Of Epidermal Growth Factor Receptor (Egfr) Expression In Human Meningioma., A Gabriella Wernicke, Adam P Dicker, Michal Whiton, Jana Ivanidze, Terry Hyslop, Elizabeth H Hammond, Arie Perry, David W Andrews, Lawrence Kenyon May 2010

Assessment Of Epidermal Growth Factor Receptor (Egfr) Expression In Human Meningioma., A Gabriella Wernicke, Adam P Dicker, Michal Whiton, Jana Ivanidze, Terry Hyslop, Elizabeth H Hammond, Arie Perry, David W Andrews, Lawrence Kenyon

Kimmel Cancer Center Faculty Papers

PURPOSE: This study explores whether meningioma expresses epidermal growth factor receptor (EGFR) and determines if there is a correlation between the WHO grade of this tumor and the degree of EGFR expression.

METHODS: Following institutional review board approval, 113 meningioma specimens from 89 patients were chosen. Of these, 85 were used for final analysis. After a blinded review, immunohistochemical stains for EGFR were performed. Staining intensity (SI) was scored on a scale 0-3 (from no staining to strong staining). Staining percentage of immunoreactive cells (SP) was scored 1-5 (from the least to the maximum percent of the specimen staining). Immunohistochemical …


Elongation Factor 1 Alpha Interacts With Phospho-Akt In Breast Cancer Cells And Regulates Their Proliferation, Survival And Motility., Luisa Pecorari, Oriano Marin, Chiara Silvestri, Olivia Candini, Elena Rossi, Clara Guerzoni, Sara Cattelani, Samanta A Mariani, Francesca Corradini, Giovanna Ferrari-Amorotti, Laura Cortesi, Rita Bussolari, Giuseppe Raschellà, Massimo R Federico, Bruno Calabretta Jan 2009

Elongation Factor 1 Alpha Interacts With Phospho-Akt In Breast Cancer Cells And Regulates Their Proliferation, Survival And Motility., Luisa Pecorari, Oriano Marin, Chiara Silvestri, Olivia Candini, Elena Rossi, Clara Guerzoni, Sara Cattelani, Samanta A Mariani, Francesca Corradini, Giovanna Ferrari-Amorotti, Laura Cortesi, Rita Bussolari, Giuseppe Raschellà, Massimo R Federico, Bruno Calabretta

Kimmel Cancer Center Faculty Papers

BACKGROUND: Akt/PKB is a serine/threonine kinase that has attracted much attention because of its central role in regulating cell proliferation, survival, motility and angiogenesis. Activation of Akt in breast cancer portends aggressive tumour behaviour, resistance to hormone-, chemo-, and radiotherapy-induced apoptosis and it is correlated with decreased overall survival. Recent studies have identified novel tumor-specific substrates of Akt that may provide new diagnostic and prognostic markers and serve as therapeutic targets. This study was undertaken to identify pAkt-interacting proteins and to assess their biological roles in breast cancer cells. RESULTS: We confirmed that one of the pAkt interacting proteins is …


Distinct P53 Acetylation Cassettes Differentially Influence Gene-Expression Patterns And Cell Fate., Chad D Knights, Jason Catania, Simone Di Giovanni, Selen Muratoglu, Ricardo Perez, Amber Swartzbeck, Andrew A Quong, Xiaojing Zhang, Terry Beerman, Richard Pestell, Maria Laura Avantaggiati May 2006

Distinct P53 Acetylation Cassettes Differentially Influence Gene-Expression Patterns And Cell Fate., Chad D Knights, Jason Catania, Simone Di Giovanni, Selen Muratoglu, Ricardo Perez, Amber Swartzbeck, Andrew A Quong, Xiaojing Zhang, Terry Beerman, Richard Pestell, Maria Laura Avantaggiati

Kimmel Cancer Center Faculty Papers

The activity of the p53 gene product is regulated by a plethora of posttranslational modifications. An open question is whether such posttranslational changes act redundantly or dependently upon one another. We show that a functional interference between specific acetylated and phosphorylated residues of p53 influences cell fate. Acetylation of lysine 320 (K320) prevents phosphorylation of crucial serines in the NH(2)-terminal region of p53; only allows activation of genes containing high-affinity p53 binding sites, such as p21/WAF; and promotes cell survival after DNA damage. In contrast, acetylation of K373 leads to hyperphosphorylation of p53 NH(2)-terminal residues and enhances the interaction with …


All-1/Mll1, A Homologue Of Drosophila Trithorax, Modifies Chromatin And Is Directly Involved In Infant Acute Leukaemia., E Canaani, T Nakamura, T Rozovskaia, S T Smith, T Mori, C M Croce, Alexander Mazo Feb 2004

All-1/Mll1, A Homologue Of Drosophila Trithorax, Modifies Chromatin And Is Directly Involved In Infant Acute Leukaemia., E Canaani, T Nakamura, T Rozovskaia, S T Smith, T Mori, C M Croce, Alexander Mazo

Kimmel Cancer Center Faculty Papers

Rearrangements of the ALL-1/MLL1 gene underlie the majority of infant acute leukaemias, as well as of therapy-related leukaemias developing in cancer patients treated with inhibitors of topoisomerase II, such as VP16 and doxorubicin. The rearrangements fuse ALL-1 to any of >50 partner genes or to itself. Here, we describe the unique features of ALL-1-associated leukaemias, and recent progress in understanding molecular mechanisms involved in the activity of the ALL-1 protein and of its Drosophila homologue TRITHORAX.