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Articles 6241 - 6270 of 8411
Full-Text Articles in Medical Specialties
Clinical Utility Of Lactate Dehydrogenase In Determining The Severity Of Hemolysis In Sickle Cell Anemia., Samir K. Ballas
Clinical Utility Of Lactate Dehydrogenase In Determining The Severity Of Hemolysis In Sickle Cell Anemia., Samir K. Ballas
Cardeza Foundation for Hematologic Research
No abstract provided.
Paracrine Effect Of Nrg1 And Hgf Drives Resistance To Mek Inhibitors In Metastatic Uveal Melanoma., Hanyin Cheng, Mizue Terai, Ken Kageyama, Shinji Ozaki, Peter Mccue, Takami Sato, Andrew E. Aplin
Paracrine Effect Of Nrg1 And Hgf Drives Resistance To Mek Inhibitors In Metastatic Uveal Melanoma., Hanyin Cheng, Mizue Terai, Ken Kageyama, Shinji Ozaki, Peter Mccue, Takami Sato, Andrew E. Aplin
Department of Cancer Biology Faculty Papers
Uveal melanoma patients with metastatic disease usually die within one year, emphasizing an urgent need to develop new treatment strategies for this cancer. MEK inhibitors improve survival in cutaneous melanoma patients but show only modest efficacy in metastatic uveal melanoma patients. In this study, we screened for growth factors that elicited resistance in newly characterized metastatic uveal melanoma cell lines to clinical-grade MEK inhibitors, trametinib and selumetinib. We show that neuregulin 1 (NRG1) and hepatocyte growth factor (HGF) provide resistance to MEK inhibition. Mechanistically, trametinib enhances the responsiveness to NRG1 and sustained HGF-mediated activation of AKT. Individually targeting ERBB3 and …
Surgeon Radiation Exposure In Hip Arthroscopy: A Prospective Analysis, John P. Salvo, Jake Zarah
Surgeon Radiation Exposure In Hip Arthroscopy: A Prospective Analysis, John P. Salvo, Jake Zarah
Rothman Institute Papers
Objectives: Hip arthroscopy is an established field within orthopaedic surgery. The majority of the procedures involve repairs of the acetabular labrum and arthroscopic treatment of femoroacetabular impingement (FAI). The procedures are being performed with increasing frequency annually. Fluoroscopic guidance is recommended during these procedures, and radiation exposure to the surgeon, staff, and patient remains a valid concern. The purpose of this study is to measure radiation exposure to the surgeon during hip arthroscopy and determine if this exposure remains below recommended annual occupational radiation exposure thresholds recommended by the International Committee on Radiological Protection (IRCP). Methods: Prospectively, radiation exposure was …
Medial Opening Wedge High Tibial Osteotomy: A Retrospective Review Of Patient Outcomes Over 10 Years, Fotios P. Tjoumakaris, Nicholas J. Lombardi, Bradford Tucker, Matthew D. Pepe
Medial Opening Wedge High Tibial Osteotomy: A Retrospective Review Of Patient Outcomes Over 10 Years, Fotios P. Tjoumakaris, Nicholas J. Lombardi, Bradford Tucker, Matthew D. Pepe
Rothman Institute Papers
Objectives: High tibial osteotomy (HTO) has become a well-established treatment for unicompartmental osteoarthritis of the knee. Over the last 30 years, various techniques have been introduced to advance this procedure. The purpose of this study is to review the outcomes of patients who received medial opening wedge HTO over the last ten years (2002-2012) using a modern, low profile, medially based fixation device. In addition, we sought to determine if obese patients had a less favorable outcome than their non-obese counterparts. Methods: Ninety-three patients were identified from a surgical database as having undergone a HTO for medial compartment osteoarthritis of …
Strategies For Searching The Internet For Orthopedic Surgeons: Tips And Tricks, Fatih Küçükdurmaz, Md, Terry Whipple, Md, Murat Bozkurt, Md, Daniel G. Kipnis, Msi
Strategies For Searching The Internet For Orthopedic Surgeons: Tips And Tricks, Fatih Küçükdurmaz, Md, Terry Whipple, Md, Murat Bozkurt, Md, Daniel G. Kipnis, Msi
Academic Commons and Scott Memorial Library Staff Papers and Presentations
Internet provides access to large amounts of information quickly, provides a flexible learning platform, and is easily accessible from anywhere, especially with new technologies. Web-based search engines and bibliographic databases, have already become part of a doctor's everyday life. However, even well-published researchers often fail to appreciate the background knowledge required to conduct a good literature search on the internet. Using the right techniques can improve the ability to search for relevant information This chapter briefly outlines the internet as an information resources such as Google, Google Scholar, PubMed, Cochrane for orthopedic surgeons. Also the subsequent sections of the chapter …
Long-Term Oncological Outcomes Of A Phase Ii Trial Of Neoadjuvant Chemohormonal Therapy Followed By Radical Prostatectomy For Patients With Clinically Localised, High-Risk Prostate Cancer., Jonathan L. Silberstein, Stephen A. Poon, Daniel D. Sjoberg, Alexandra C. Maschino, Andrew J. Vickers, Aaron Bernie, Badrinath R. Konety, William Kevin Kelly, James A. Eastham
Long-Term Oncological Outcomes Of A Phase Ii Trial Of Neoadjuvant Chemohormonal Therapy Followed By Radical Prostatectomy For Patients With Clinically Localised, High-Risk Prostate Cancer., Jonathan L. Silberstein, Stephen A. Poon, Daniel D. Sjoberg, Alexandra C. Maschino, Andrew J. Vickers, Aaron Bernie, Badrinath R. Konety, William Kevin Kelly, James A. Eastham
Department of Urology Faculty Papers
OBJECTIVE: To determine long-term oncological outcomes of radical prostatectomy (RP) after neoadjuvant chemohormonal therapy (CHT) for clinically localised, high-risk prostate cancer.
PATIENTS AND METHODS: In this phase II multicentre trial of patients with high-risk prostate cancer (PSA level >20 ng/mL, Gleason ≥8, or clinical stage ≥T3), androgen-deprivation therapy (goserelin acetate depot) and paclitaxel, carboplatin and estramustine were administered before RP. We report the long-term oncological outcomes of these patients and compared them to a contemporary cohort who met oncological inclusion criteria but received RP only.
RESULTS: In all, 34 patients were enrolled and followed for a median of 13.1 years. …
Kinase Independent Oncogenic Cyclin D1., Mathew C Casimiro, Andrew Arnold, Richard Pestell
Kinase Independent Oncogenic Cyclin D1., Mathew C Casimiro, Andrew Arnold, Richard Pestell
Kimmel Cancer Center Faculty Papers
No abstract provided.
Risk Analysis Of Prostate Cancer In Practical, A Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci., Ali Amin Al Olama, Sara Benlloch, Antonis C Antoniou, Graham G Giles, Gianluca Severi, David E Neal, Freddie C Hamdy, Jenny L Donovan, Kenneth Muir, Johanna Schleutker, Brian E Henderson, Christopher Haiman, Fredrick R Schumacher, Nora Pashayan, Paul D P Pharoah, Elaine A Ostrander, Janet L Stanford, Jyotsna Batra, Judith A Clements, Suzanne K Chambers, Maren Weischer, Børge G Nordestgaard, Sue A Ingles, Karina D Sorensen, Torben F Orntoft, Jong Y Park, Cezary Cybulski, Christiane Maier, Thilo Doerk, Joanne L Dickinson, Lisa Cannon-Albright, Hermann Brenner, Timothy R Rebbeck, Charnita Zeigler-Johnson, Tomonori Habuchi, Stephen N Thibodeau, Kathleen A Cooney, Pierre O Chappuis, Pierre Hutter, Radka P Kaneva, William D Foulkes, Maurice P Zeegers, Yong-Jie Lu, Hong-Wei Zhang, Robert Stephenson, Angela Cox, Melissa C Southey, Amanda B Spurdle, Liesel Fitzgerald, Daniel Leongamornlert, Edward Saunders, Malgorzata Tymrakiewicz, Michelle Guy, Tokhir Dadaev, Sarah J Little, Koveela Govindasami, Emma Sawyer, Rosemary Wilkinson, Kathleen Herkommer, John L Hopper, Aritaya Lophatonanon, Antje E Rinckleb, Zsofia Kote-Jarai, Rosalind A Eeles, Douglas F Easton
Risk Analysis Of Prostate Cancer In Practical, A Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci., Ali Amin Al Olama, Sara Benlloch, Antonis C Antoniou, Graham G Giles, Gianluca Severi, David E Neal, Freddie C Hamdy, Jenny L Donovan, Kenneth Muir, Johanna Schleutker, Brian E Henderson, Christopher Haiman, Fredrick R Schumacher, Nora Pashayan, Paul D P Pharoah, Elaine A Ostrander, Janet L Stanford, Jyotsna Batra, Judith A Clements, Suzanne K Chambers, Maren Weischer, Børge G Nordestgaard, Sue A Ingles, Karina D Sorensen, Torben F Orntoft, Jong Y Park, Cezary Cybulski, Christiane Maier, Thilo Doerk, Joanne L Dickinson, Lisa Cannon-Albright, Hermann Brenner, Timothy R Rebbeck, Charnita Zeigler-Johnson, Tomonori Habuchi, Stephen N Thibodeau, Kathleen A Cooney, Pierre O Chappuis, Pierre Hutter, Radka P Kaneva, William D Foulkes, Maurice P Zeegers, Yong-Jie Lu, Hong-Wei Zhang, Robert Stephenson, Angela Cox, Melissa C Southey, Amanda B Spurdle, Liesel Fitzgerald, Daniel Leongamornlert, Edward Saunders, Malgorzata Tymrakiewicz, Michelle Guy, Tokhir Dadaev, Sarah J Little, Koveela Govindasami, Emma Sawyer, Rosemary Wilkinson, Kathleen Herkommer, John L Hopper, Aritaya Lophatonanon, Antje E Rinckleb, Zsofia Kote-Jarai, Rosalind A Eeles, Douglas F Easton
Department of Medical Oncology Faculty Papers
BACKGROUND: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer.
METHODS: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history.
RESULTS: The prostate cancer risk for men in the top 1% of the …
Functional Neuroimaging Distinguishes Posttraumatic Stress Disorder From Traumatic Brain Injury In Focused And Large Community Datasets., Daniel G Amen, Cyrus A Raji, Kristen Willeumier, Derek Taylor, Robert Tarzwell, Andrew B. Newberg, Md, Theodore A Henderson
Functional Neuroimaging Distinguishes Posttraumatic Stress Disorder From Traumatic Brain Injury In Focused And Large Community Datasets., Daniel G Amen, Cyrus A Raji, Kristen Willeumier, Derek Taylor, Robert Tarzwell, Andrew B. Newberg, Md, Theodore A Henderson
Department of Radiology Faculty Papers
BACKGROUND: Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are highly heterogeneous and often present with overlapping symptomology, providing challenges in reliable classification and treatment. Single photon emission computed tomography (SPECT) may be advantageous in the diagnostic separation of these disorders when comorbid or clinically indistinct.
METHODS: Subjects were selected from a multisite database, where rest and on-task SPECT scans were obtained on a large group of neuropsychiatric patients. Two groups were analyzed: Group 1 with TBI (n=104), PTSD (n=104) or both (n=73) closely matched for demographics and comorbidity, compared to each other and healthy controls (N=116); Group 2 …
Role Of Phenol-Soluble Modulins In Formation Of Staphylococcus Aureus Biofilms In Synovial Fluid., Sana S Dastgheyb, Amer E Villaruz, Katherine Y Le, Vee Y Tan, Anthony C Duong, Som S Chatterjee, Gordon Y C Cheung, Hwang-Soo Joo, Noreen J Hickok, Michael Otto
Role Of Phenol-Soluble Modulins In Formation Of Staphylococcus Aureus Biofilms In Synovial Fluid., Sana S Dastgheyb, Amer E Villaruz, Katherine Y Le, Vee Y Tan, Anthony C Duong, Som S Chatterjee, Gordon Y C Cheung, Hwang-Soo Joo, Noreen J Hickok, Michael Otto
Department of Orthopaedic Surgery Faculty Papers
Staphylococcus aureus is a leading cause of prosthetic joint infections, which, as we recently showed, proceed with the involvement of biofilm-like clusters that cause recalcitrance to antibiotic treatment. Here we analyzed why these clusters grow extraordinarily large, reaching macroscopically visible extensions (>1 mm). We found that while specific S. aureus surface proteins are a prerequisite for agglomeration in synovial fluid, low activity of the Agr regulatory system and subsequent low production of the phenol-soluble modulin (PSM) surfactant peptides cause agglomerates to grow to exceptional dimensions. Our results indicate that PSMs function by disrupting interactions of biofilm matrix molecules, such …
Development And Implementation Of A Clinical Pathway Approach To Simulation-Based Training For Foregut Surgery., Kiyoyuki W. Miyasaka, Joseph Buchholz, Denise Lamarra, Giorgos C. Karakousis, Rajesh Aggarwal
Development And Implementation Of A Clinical Pathway Approach To Simulation-Based Training For Foregut Surgery., Kiyoyuki W. Miyasaka, Joseph Buchholz, Denise Lamarra, Giorgos C. Karakousis, Rajesh Aggarwal
Student Papers, Posters & Projects
INTRODUCTION: Contemporary demands on resident education call for integration of simulation. We designed and implemented a simulation-based curriculum for Post Graduate Year 1 surgery residents to teach technical and nontechnical skills within a clinical pathway approach for a foregut surgery patient, from outpatient visit through surgery and postoperative follow-up.
METHODS: The 3-day curriculum for groups of 6 residents comprises a combination of standardized patient encounters, didactic sessions, and hands-on training. The curriculum is underpinned by a summative simulation "pathway" repeated on days 1 and 3. The "pathway" is a series of simulated preoperative, intraoperative, and postoperative encounters in following up …
Nrg Oncology/Rtog 0921: A Phase 2 Study Of Postoperative Intensity-Modulated Radiotherapy With Concurrent Cisplatin And Bevacizumab Followed By Carboplatin And Paclitaxel For Patients With Endometrial Cancer., Akila N. Viswanathan, Jennifer Moughan, Brigitte E. Miller, Ying Xiao, Anuja Jhingran, Lorraine Portelance, Walter R. Bosch, Ursula A. Matulonis, Neil S. Horowitz, Robert S S. Mannel, Luis Souhami, Beth A. Erickson, Kathryn A. Winter, William Small, David K. Gaffney
Nrg Oncology/Rtog 0921: A Phase 2 Study Of Postoperative Intensity-Modulated Radiotherapy With Concurrent Cisplatin And Bevacizumab Followed By Carboplatin And Paclitaxel For Patients With Endometrial Cancer., Akila N. Viswanathan, Jennifer Moughan, Brigitte E. Miller, Ying Xiao, Anuja Jhingran, Lorraine Portelance, Walter R. Bosch, Ursula A. Matulonis, Neil S. Horowitz, Robert S S. Mannel, Luis Souhami, Beth A. Erickson, Kathryn A. Winter, William Small, David K. Gaffney
Department of Radiation Oncology Faculty Papers
BACKGROUND: The current study was conducted to assess acute and late adverse events (AEs), overall survival (OS), pelvic failure, regional failure, distant failure, and disease-free survival in a prospective phase 2 clinical trial of bevacizumab and pelvic intensity-modulated radiotherapy (IMRT) with chemotherapy in patients with high-risk endometrial cancer.
METHODS: Patients underwent a hysterectomy and lymph node removal, and had ≥1 of the following high-risk factors: grade 3 carcinoma with >50% myometrial invasion, grade 2 or 3 disease with any cervical stromal invasion, or known extrauterine extension confined to the pelvis. Treatment included pelvic IMRT and concurrent cisplatin on days 1 …
Current Management Of Heart Failure: When To Refer To Heart Failure Specialist And When Hospice Is The Best Option., Behnam Bozorgnia, Paul J. Mather
Current Management Of Heart Failure: When To Refer To Heart Failure Specialist And When Hospice Is The Best Option., Behnam Bozorgnia, Paul J. Mather
Division of Cardiology Faculty Papers
Heart failure is a common syndrome caused by different abnormalities of the cardiovascular system that result in impairment of the ventricles in filling or ejecting blood. It is one of the most common causes of hospitalization in the United States, with a very high cost to the health care system. This article focuses on the causes of left ventricle dysfunction and the presentation and management of heart failure, both acute and chronic.
Pain Management Strategies In Hand Surgery., Constantinos Ketonis, Md, Phd, Asif M Ilyas, Frederic Liss
Pain Management Strategies In Hand Surgery., Constantinos Ketonis, Md, Phd, Asif M Ilyas, Frederic Liss
Department of Orthopaedic Surgery Faculty Papers
Modern anesthetic agents have allowed for the rapid expansion of ambulatory surgery, particularly in hand surgery. The choice between general anesthesia, peripheral regional blocks, regional intravenous anesthesia (Bier block), local block with sedation, and the recently popularized wide-awake hand surgery depends on several variables, including the type and duration of the procedure and patient characteristics, coexisting conditions, location, and expected length of the procedure. This article discusses the various perioperative and postoperative analgesic options to optimize the hand surgical patients' experience.
Novel Cross Talk Between Igf-Ir And Ddr1 Regulates Igf-Ir Trafficking, Signaling And Biological Responses., Roberta Malaguarnera, Maria Luisa Nicolosi, Antonella Sacco, Alaide Morcavallo, Veronica Vella, Concetta Voci, Michela Spatuzza, Shi-Qiong Xu, Renato V Iozzo, Riccardo Vigneri, Andrea Morrione, Antonino Belfiore
Novel Cross Talk Between Igf-Ir And Ddr1 Regulates Igf-Ir Trafficking, Signaling And Biological Responses., Roberta Malaguarnera, Maria Luisa Nicolosi, Antonella Sacco, Alaide Morcavallo, Veronica Vella, Concetta Voci, Michela Spatuzza, Shi-Qiong Xu, Renato V Iozzo, Riccardo Vigneri, Andrea Morrione, Antonino Belfiore
Kimmel Cancer Center Faculty Papers
The insulin-like growth factor-I receptor (IGF-IR), plays a key role in regulating mammalian development and growth, and is frequently deregulated in cancer contributing to tumor initiation and progression. Discoidin domain receptor 1 (DDR1), a collagen receptor tyrosine-kinase, is as well frequently overexpressed in cancer and implicated in cancer progression. Thus, we investigated whether a functional cross-talk between the IGF-IR and DDR1 exists and plays any role in cancer progression.Using human breast cancer cells we found that DDR1 constitutively associated with the IGF-IR. However, this interaction was enhanced by IGF-I stimulation, which promoted rapid DDR1 tyrosine-phosphorylation and co-internalization with the IGF-IR. …
Selective Impact Of Cdk4/6 Suppression On Patient-Derived Models Of Pancreatic Cancer., Agnieszka K Witkiewicz, Nicholas A Borja, Jorge Franco, Jonathan Brody, Md, Charles Yeo, John Mansour, Michael A Choti, Peter Mccue, Erik S Knudsen
Selective Impact Of Cdk4/6 Suppression On Patient-Derived Models Of Pancreatic Cancer., Agnieszka K Witkiewicz, Nicholas A Borja, Jorge Franco, Jonathan Brody, Md, Charles Yeo, John Mansour, Michael A Choti, Peter Mccue, Erik S Knudsen
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Pancreatic ductal adenocarcinoma (PDA) harbors an exceedingly poor prognosis, and is generally considered a therapy-recalcitrant disease due to poor response to conventional chemotherapy coupled with non-actionable genetic drivers (e.g. KRAS mutations). However, PDA frequently loses p16ink4a, thereby leading to deregulation of CDK4/6. Surprisingly, in established cell models and xenografts, CDK4/6 inhibition has a modest effect on proliferation and resistance develops rapidly. To determine if such weak response was an intrinsic feature of PDA, we developed primary tumor explants that maintain the tumor environment and recapitulate feuture of primary PDA. The CDK4/6 inhibitor PD-0332991 was highly efficient at suppressing proliferation in …
Treatment For Inclusion Body Myositis, Michael R. Rose, Katherine Jones, Kevin Leong, Maggie C. Walter, James Miller, Marinos Dalakas, Ruth Brassington, Robert Griggs
Treatment For Inclusion Body Myositis, Michael R. Rose, Katherine Jones, Kevin Leong, Maggie C. Walter, James Miller, Marinos Dalakas, Ruth Brassington, Robert Griggs
Department of Neurology Faculty Papers
Background Inclusion body myositis (IBM) is a late-onset inflammatory muscle disease (myopathy) associated with progressive proximal and distal limb muscle atrophy and weakness. Treatment options have attempted to target inflammatory and atrophic features of this condition (for example with immunosuppressive and immunomodulating drugs, anabolic steroids, and antioxidant treatments), although as yet there is no known effective treatment for reversing or minimising the progression of inclusion body myositis. In this review we have considered the benefits, adverse effects, and costs of treatment in targeting cardinal effects of the condition, namely muscle atrophy, weakness, and functional impairment. Objectives To assess the effects …
Taranis Functions With Cyclin A And Cdk1 In A Novel Arousal Center To Control Sleep In Drosophila., Dinis J.S. Afonso, Die Liu, Daniel R. Machado, Huihui Pan, James E.C. Jepson, Dragana Rogulja, Kyunghee Koh
Taranis Functions With Cyclin A And Cdk1 In A Novel Arousal Center To Control Sleep In Drosophila., Dinis J.S. Afonso, Die Liu, Daniel R. Machado, Huihui Pan, James E.C. Jepson, Dragana Rogulja, Kyunghee Koh
Department of Neuroscience Faculty Papers
Sleep is an essential and conserved behavior whose regulation at the molecular and anatomical level remains to be elucidated. Here, we identify TARANIS (TARA), a Drosophila homolog of the Trip-Br (SERTAD) family of transcriptional coregulators, as a molecule that is required for normal sleep patterns. Through a forward-genetic screen, we isolated tara as a novel sleep gene associated with a marked reduction in sleep amount. Targeted knockdown of tara suggests that it functions in cholinergic neurons to promote sleep. tara encodes a conserved cell-cycle protein that contains a Cyclin A (CycA)-binding homology domain. TARA regulates CycA protein levels and genetically …
Pleiotropic Effects Of Bitter Taste Receptors On [Ca2+]I Mobilization, Hyperpolarization, And Relaxation Of Human Airway Smooth Muscle Cells., Blanca Camoretti-Mercado, Susan H Pauer, Hwan Mee Yong, Dan'elle C Smith, Deepak A. Deshpande, Phd, Steven S An, Stephen B Liggett
Pleiotropic Effects Of Bitter Taste Receptors On [Ca2+]I Mobilization, Hyperpolarization, And Relaxation Of Human Airway Smooth Muscle Cells., Blanca Camoretti-Mercado, Susan H Pauer, Hwan Mee Yong, Dan'elle C Smith, Deepak A. Deshpande, Phd, Steven S An, Stephen B Liggett
Center for Translational Medicine Faculty Papers
Asthma is characterized by airway inflammation and airflow obstruction from human airway smooth muscle (HASM) constriction due to increased local bronchoconstrictive substances. We have recently found bitter taste receptors (TAS2Rs) on HASM, which increase [Ca2+]i and relax the muscle. We report here that some, but not all, TAS2R agonists decrease [Ca2+]i and relax HASM contracted by G-protein coupled receptors (GPCRs) that stimulate [Ca2+]i. This suggests both a second pathway by which TAS2Rs relax, and, a heterogeneity of the response phenotype. We utilized eight TAS2R agonists and five procontractile GPCR agonists in cultured HASM cells. We find that heterogeneity in the …
Deregulation Of Mir-34b/Sox2 Predicts Prostate Cancer Progression., Irene Forno, Stefano Ferrero, Maria Veronica Russo, Giacomo Gazzano, Sara Giangiobbe, Emanuele Montanari, Alberto Del Nero, Bernardo Rocco, Giancarlo Albo, Lucia R Languino, Dario C Altieri, Valentina Vaira, Silvano Bosari
Deregulation Of Mir-34b/Sox2 Predicts Prostate Cancer Progression., Irene Forno, Stefano Ferrero, Maria Veronica Russo, Giacomo Gazzano, Sara Giangiobbe, Emanuele Montanari, Alberto Del Nero, Bernardo Rocco, Giancarlo Albo, Lucia R Languino, Dario C Altieri, Valentina Vaira, Silvano Bosari
Department of Cancer Biology Faculty Papers
Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was …
Chromatin To Clinic: The Molecular Rationale For Parp1 Inhibitor Function., Felix Y. Feng, Johann S. De Bono, Mark A. Rubin, Karen E Knudsen
Chromatin To Clinic: The Molecular Rationale For Parp1 Inhibitor Function., Felix Y. Feng, Johann S. De Bono, Mark A. Rubin, Karen E Knudsen
Department of Cancer Biology Faculty Papers
Poly(ADP-ribose) polymerase 1 (PARP1) inhibitors were recently shown to have potential clinical impact in a number of disease settings, particularly as related to cancer therapy, treatment for cardiovascular dysfunction, and suppression of inflammation. The molecular basis for PARP1 inhibitor function is complex, and appears to depend on the dual roles of PARP1 in DNA damage repair and transcriptional regulation. Here, the mechanisms by which PARP-1 inhibitors elicit clinical response are discussed, and strategies for translating the preclinical elucidation of PARP-1 function into advances in disease management are reviewed.
Obesity-Induced Adipokine Imbalance Impairs Mouse Pulmonary Vascular Endothelial Function And Primes The Lung For Injury., Dilip Shah, Freddy Romero, Michelle Duong, Nadan Wang, Bishnuhari Paudyal, Benjamin T Suratt, Caleb B Kallen, Jianxin Sun, Ying Zhu, Kenneth Walsh, Ross Summer
Obesity-Induced Adipokine Imbalance Impairs Mouse Pulmonary Vascular Endothelial Function And Primes The Lung For Injury., Dilip Shah, Freddy Romero, Michelle Duong, Nadan Wang, Bishnuhari Paudyal, Benjamin T Suratt, Caleb B Kallen, Jianxin Sun, Ying Zhu, Kenneth Walsh, Ross Summer
Center for Translational Medicine Faculty Papers
Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for …
Network-Based Stratification Analysis Of 13 Major Cancer Types Using Mutations In Panels Of Cancer Genes., Xue Zhong, Hushan Yang, Shuyang Zhao, Yu Shyr, Bingshan Li
Network-Based Stratification Analysis Of 13 Major Cancer Types Using Mutations In Panels Of Cancer Genes., Xue Zhong, Hushan Yang, Shuyang Zhao, Yu Shyr, Bingshan Li
Department of Medical Oncology Faculty Papers
BACKGROUND: Cancers are complex diseases with heterogeneous genetic causes and clinical outcomes. It is critical to classify patients into subtypes and associate the subtypes with clinical outcomes for better prognosis and treatment. Large-scale studies have comprehensively identified somatic mutations across multiple tumor types, providing rich datasets for classifying patients based on genomic mutations. One challenge associated with this task is that mutations are rarely shared across patients. Network-based stratification (NBS) approaches have been proposed to overcome this challenge and used to classify tumors based on exome-level mutations. In routine research and clinical applications, however, usually only a small panel of …
Trop-2 Is Up-Regulated In Invasive Prostate Cancer And Displaces Fak From Focal Contacts., Marco Trerotola, Kirat K Ganguly, Ladan Fazli, Carmine Fedele, Huimin Lu, Anindita Dutta, Qin Liu, Tiziana De Angelis, Luke W Riddell, Natalia A Riobo, Martin E Gleave, Amina Zoubeidi, Richard Pestell, Dario C Altieri, Lucia R Languino
Trop-2 Is Up-Regulated In Invasive Prostate Cancer And Displaces Fak From Focal Contacts., Marco Trerotola, Kirat K Ganguly, Ladan Fazli, Carmine Fedele, Huimin Lu, Anindita Dutta, Qin Liu, Tiziana De Angelis, Luke W Riddell, Natalia A Riobo, Martin E Gleave, Amina Zoubeidi, Richard Pestell, Dario C Altieri, Lucia R Languino
Department of Urology Faculty Papers
In this study, we show that the transmembrane glycoprotein Trop-2 is up-regulated in human prostate cancer (PCa) with extracapsular extension (stages pT3/pT4) as compared to organ-confined (stage pT2) PCa. Consistent with this evidence, Trop-2 expression is found to be increased in metastatic prostate tumors of Transgenic Adenocarcinoma of Mouse Prostate mice and to strongly correlate with α5β1 integrin levels. Using PCa cells, we show that Trop-2 specifically associates with the α5 integrin subunit, as binding to α3 is not observed, and that Trop-2 displaces focal adhesion kinase from focal contacts. In support of the role of Trop-2 as a promoter …
Doxycycline Down-Regulates Dna-Pk And Radiosensitizes Tumor Initiating Cells: Implications For More Effective Radiation Therapy., Rebecca Lamb, Marco Fiorillo, Amy Chadwick, Bela Ozsvari, Kimberly J Reeves, Duncan L Smith, Robert B Clarke, Sacha J Howell, Anna Rita Cappello, Ubaldo E. Martinez-Outshoorn, Md, Maria Peiris-Pagès, Federica Sotgia, Michael P Lisanti
Doxycycline Down-Regulates Dna-Pk And Radiosensitizes Tumor Initiating Cells: Implications For More Effective Radiation Therapy., Rebecca Lamb, Marco Fiorillo, Amy Chadwick, Bela Ozsvari, Kimberly J Reeves, Duncan L Smith, Robert B Clarke, Sacha J Howell, Anna Rita Cappello, Ubaldo E. Martinez-Outshoorn, Md, Maria Peiris-Pagès, Federica Sotgia, Michael P Lisanti
Kimmel Cancer Center Faculty Papers
DNA-PK is an enzyme that is required for proper DNA-repair and is thought to confer radio-resistance in cancer cells. As a consequence, it is a high-profile validated target for new pharmaceutical development. However, no FDA-approved DNA-PK inhibitors have emerged, despite many years of drug discovery and lead optimization. This is largely because existing DNA-PK inhibitors suffer from poor pharmacokinetics. They are not well absorbed and/or are unstable, with a short plasma half-life. Here, we identified the first FDA-approved DNA-PK inhibitor by "chemical proteomics". In an effort to understand how doxycycline targets cancer stem-like cells (CSCs), we serendipitously discovered that doxycycline …
Do I Buy It? How Aidettm Training Changes Residents’ Values About Communication Skills In Doctor-Patient Interactions, Andrea Braverman, Phd, Austin Katona, B.Sc., Elisabeth Kunkel, Md, Leo Katz, Md, Matthew Keller, Md, Constantine Daskalakis, Sc.D, Jennifer Jasmine Arfaa, Phd, Mhsa
Do I Buy It? How Aidettm Training Changes Residents’ Values About Communication Skills In Doctor-Patient Interactions, Andrea Braverman, Phd, Austin Katona, B.Sc., Elisabeth Kunkel, Md, Leo Katz, Md, Matthew Keller, Md, Constantine Daskalakis, Sc.D, Jennifer Jasmine Arfaa, Phd, Mhsa
Department of Obstetrics and Gynecology Presentations and Grand Rounds
OBJECTIVES
Acquiring communication and interpersonal skills is an important part of providing patient-centered care and improving patient satisfaction. This study explores whether residents’ own values about patient communication change over time.
Concomitant Retrograde Coronary Venous Infusion Of Basic Fibroblast Growth Factor Enhances Engraftment And Differentiation Of Bone Marrow Mesenchymal Stem Cells For Cardiac Repair After Myocardial Infarction., Xiao Wang, Lei Zhen, Huangtai Miao, Qiwei Sun, Ya Yang, Bin Que, Edmundo Patricio Lopes Lao, Xingxin Wu, Hongmei Ren, Shutian Shi, Wayne Bond Lau, Xin-Liang Ma, Changsheng Ma, Shaoping Nie
Concomitant Retrograde Coronary Venous Infusion Of Basic Fibroblast Growth Factor Enhances Engraftment And Differentiation Of Bone Marrow Mesenchymal Stem Cells For Cardiac Repair After Myocardial Infarction., Xiao Wang, Lei Zhen, Huangtai Miao, Qiwei Sun, Ya Yang, Bin Que, Edmundo Patricio Lopes Lao, Xingxin Wu, Hongmei Ren, Shutian Shi, Wayne Bond Lau, Xin-Liang Ma, Changsheng Ma, Shaoping Nie
Department of Emergency Medicine Faculty Papers
AIM: Basic fibroblast growth factor (bFGF) increases the migration and viability of bone marrow mesenchymal stem cells (MSCs) in vitro. Retrograde coronary venous infusion can provide both increased regional bFGF concentrations and homogeneous cell dissemination. We determined whether retrograde delivery of bFGF enhances the potency of transplanted MSCs for cardiac repair in a canine infarct model.
METHODS AND RESULTS: Under hypoxic conditions, cellular migration was significantly increased in MSCs co-cultured with bFGF compared to vascular endothelial growth factor or insulin-like growth factor, and bFGF promoted MSCs differentiation into a cardiomyocyte phenotype. A canine infarct model was employed by coronary ligation. …
Parametric Mapping Of Contrasted Ovarian Transvaginal Sonography., Katrina Korhonen, Ryan Moore, Andrej Lyshchik, Arthur C. Fleischer
Parametric Mapping Of Contrasted Ovarian Transvaginal Sonography., Katrina Korhonen, Ryan Moore, Andrej Lyshchik, Arthur C. Fleischer
Department of Radiology Faculty Papers
The purpose of this study was to assess the accuracy of parametric analysis of transvaginal contrast-enhanced ultrasound (TV-CEUS) for distinguishing benign versus malignant ovarian masses. A total of 48 ovarian masses (37 benign and 11 borderline/malignant) were examined with TV-CEUS (Definity; Lantheus, North Billerica, MA; Philips iU22; Philips Medical Systems, Bothell, WA). Parametric images were created offline with a quantification software (Bracco Suisse SA, Geneva, Switzerland) with map color scales adjusted such that abnormal hemodynamics were represented by the color red and the presence of any red color could be used to differentiate benign and malignant tumors. Using these map …
Desmin Common Mutation Is Associated With Multi-Systemic Disease Manifestations And Depletion Of Mitochondria And Mitochondrial Dna., Elizabeth M. Mccormick, Lawrence C. Kenyon, Marni J. Falk
Desmin Common Mutation Is Associated With Multi-Systemic Disease Manifestations And Depletion Of Mitochondria And Mitochondrial Dna., Elizabeth M. Mccormick, Lawrence C. Kenyon, Marni J. Falk
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Desmin (DES) is a major muscle scaffolding protein that also functions to anchor mitochondria. Pathogenic DES mutations, however, have not previously been recognized as a cause of multi-systemic mitochondrial disease. Here, we describe a 45-year-old man who presented to The Children's Hospital of Philadelphia Mitochondrial-Genetics Diagnostic Clinic for evaluation of progressive cardiac, neuromuscular, gastrointestinal, and mood disorders. Muscle biopsy at age 45 was remarkable for cytoplasmic bodies, as well as ragged red fibers and SDH positive/COX negative fibers that were suggestive of a mitochondrial myopathy. Muscle also showed significant reductions in mitochondrial content (16% of control mean for citrate synthase …
The Effects Of Formalized Team Training On Transitions In Patient Care In The Otolaryngology Head And Neck Surgery Residency, Natalie Vercillo, Md, David Cognetti, Md, Brittany Czarick, Pa-C, Heather Rozencwaig, Crnp, Troy Derose, Crnp, Rnfa, Ancc-C, Maurits Boon, Md
The Effects Of Formalized Team Training On Transitions In Patient Care In The Otolaryngology Head And Neck Surgery Residency, Natalie Vercillo, Md, David Cognetti, Md, Brittany Czarick, Pa-C, Heather Rozencwaig, Crnp, Troy Derose, Crnp, Rnfa, Ancc-C, Maurits Boon, Md
Department of Otolaryngology - Head and Neck Surgery Presentations and Grand Rounds
BACKGROUND
With increasing regulations from the ACGME for resident work hours, the number of patient care hand-offs inevitably rises. Work hour restrictions have the potential to significantly reduce the incidence of medical mistakes related to excessive fatigue only if the transitions of care are do not create further errors as a result of miscommunication. For this reason, transitions of care must be thorough and complete, yet efficient as patient care must not cease during these hand-off periods.
At Thomas Jefferson University Hospital, the Otolaryngology-Head and Neck Surgery service has both a full inpatient census and consult census. Given the trend …