tbuckley/cabot-search huggingface dataset:
FDG PET/CT in Malignant Eccrine Spiradenoma
Authors: Gabriela Sanchez Petitto, Nawid M. Sarwari, Preetesh Jain, Michael Swaby, Modushudan Bhattacharjee
Journal: Clinical Nuclear Medicine (2016)

Malignant eccrine spiradenoma is very rare skin appendageal cancer. We report a 64-year-old man who presented with a 6-month history of a rapidly growing mass in his groin. Physical examination revealed a 10-cm, ulcerated, fungating mass involving the entire right ilioinguinal region. PET/CT scan demonstrated intense FDG-avid lesion in the inguinal region. Histopathology of the lesion was compatible with malignant eccrine spiradenoma. He required extensive tumor resection followed by chemotherapy and radiotherapy.
Preventing General Surgery Residency Attrition—It Is All About the Mentoring
Authors: Julie A. Freischlag, Michelle M. Silva
Journal: JAMA Surgery (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Evaluation of Enteral Versus Parenteral Feeding As Nutritional Support In Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Richard Lemal, Romain Guièze, Cécile Moluçon-Chabrot, Eric Hermet, Aurélie Ravinet, Cécile Combal, Aurélie Cabrespine, Jacques-Olivier Bay, Bouteloup Corinne
Journal: Blood (2011)
Carbohydrate-binding protein CLEC14A regulates VEGFR-2– and VEGFR-3–dependent signals during angiogenesis and lymphangiogenesis
Authors: Sungwoon Lee, Seung-Sik Rho, Hyojin Park, Jeong Ae Park, Jihye Kim, In-Kyu Lee, Gou Young Koh, Naoki Mochizuki, Young-Myeong Kim, Young-Guen Kwon
Journal: Journal of Clinical Investigation (2016)

Controlled angiogenesis and lymphangiogenesis are essential for tissue development, function, and repair. However, aberrant neovascularization is an essential pathogenic mechanism in many human diseases, including diseases involving tumor growth and survival. Here, we have demonstrated that mice deficient in C-type lectin family 14 member A (CLEC14A) display enhanced angiogenic sprouting and hemorrhage as well as enlarged jugular lymph sacs and lymphatic vessels. CLEC14A formed a complex with VEGFR-3 in endothelial cells (ECs), and CLEC14A KO resulted in a marked reduction in VEGFR-3 that was concomitant with increases in VEGFR-2 expression and downstream signaling. Implanted tumor growth was profoundly reduced in CLEC14A-KO mice compared with that seen in WT littermates, but tumor-bearing CLEC14A-KO mice died sooner. Tumors in CLEC14A-KO mice had increased numbers of nonfunctional blood vessels and severe hemorrhaging. Blockade of VEGFR-2 signaling suppressed these vascular abnormalities and enhanced the survival of tumor-bearing CLEC14A-KO mice. We conclude that CLEC14A acts in vascular homeostasis by fine-tuning VEGFR-2 and VEGFR-3 signaling in ECs, suggesting its relevance in the pathogenesis of angiogenesis-related human disorders.
Abstract 3066: Regulation of oncogenic Zeb1 by microRNA-23b in bladder cancer
Authors: Shahana Majid, Altaf A. Dar, Sharanjot Saini, Soichiro Yamamura, Varahram Shahryari, Yozo Mitsui, Yuichiro Tanaka, Rajvir Dahiya, Guoren Deng
Journal: Cancer Research (2015)

Abstract MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by targeted repression of transcription and translation. In this study we show that miRNA-23b (miR-23b) acts as a tumor suppressor in bladder cancer. Quantitative real-time PCR analysis showed that miR-23b is significantly down-regulated in bladder cancer cell lines and tumor tissues compared to non-malignant cells and normal tissue samples. We also demonstrate that miR-23b expression has a potential to be diagnostic and prognostic biomarker in bladder cancer. High miR-23b expression is positively correlated with higher overall survival of bladder cancer patients as revealed by Kaplan-Meier analysis. ROC analysis showed that miR-23b expression can distinguish between normal and bladder cancer tissues. Further we elucidated the biological significance of miR-23b in bladder cancer. Over-expression of miR-23b in bladder cancer cells inhibited cell proliferation and impaired colony formation. Fluorescence activated cell sorting (FACS) analysis revealed that re-expression of miR-23b in bladder cancer cells induced G0/G1 cell cycle arrest and apoptosis while inhibiting cell migration and invasion. Luciferase reporter assays demonstrated that Zeb1, a crucial regulator of epithelial-to-mesenchymal transition (EMT), is a direct target of miR-23b in bladder cancer. These results show that loss of miR-23b confers a proliferative advantage and promotes bladder cancer cell migration and invasion. Furthermore, re-expression of miR-23b may be a beneficial therapeutic strategy for the treatment of human bladder cancer. Citation Format: Shahana Majid, Altaf A. Dar, Sharanjot Saini, Soichiro Yamamura, Varahram Shahryari, Yozo Mitsui, Yuichiro Tanaka, Rajvir Dahiya, Guoren Deng. Regulation of oncogenic Zeb1 by microRNA-23b in bladder cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3066. doi:10.1158/1538-7445.AM2015-3066
The Mutations SER2117→LEU, and TRP/TRP2063/64→MET/PHE in the Hydrophobic Spikes of the Factor V C2 Domain Lead to Tenacious Phospholipid Binding and Suggest a Mechanism through Which Phosphatidylserine Activates the Prothrombinase Complex.
Authors: Gary E. Gilbert, Valerie A. Novakovic, Randal J. Kaufman, Hongzhi Miao, Steven W. Pipe
Journal: Blood (2007)
461. Scale-Up and Manufacturing of High-Titer Foamy Virus Vector Containing Human CD18 for the Treatment of Leukocyte Adhesion Deficiency
Authors: Md Nasimuzzaman, Danielle Lynn, Rebecca Ernst, Michele Beuerlein, Scott Cross, Kevin Link, Carolyn Lutzko, Diana Nordling, David Russell, Punam Malik, Johannes C.M. Van der Loo
Journal: Molecular Therapy (2015)

Compared to other integrating viral vectors, foamy virus (FV) vectors have several distinct advantages as a gene transfer tool, including: the ability to carry larger expression cassettes, the increased stability due to a DNA genome formed in developing vector particles, and the random integration pattern without preference for promoter regions or active genes as is the case with gamma-retroviral and lentiviral vectors. In addition, the FV envelope has tropism for most cell types and is not associated with disease in humans. Combined, these properties make FV vectors the ideal candidate for gene therapy application. Proof of principle was provided by Bauer et al. (Nat. Med. 2008) showing cure of canine Leukocyte Adhesion Deficiency (LAD) using autologous CD34+ cells transduced with FV vector carrying the CD18 gene, without short or long-term adverse effects. Here we demonstrate the optimization of large scale manufacturing of FV vector carrying the human CD18 gene for the treatment of human LAD. As compared to the methods used in the canine LAD study, a 60-fold increase in FV-CD18 titer was observed using a combination of polyethylenimine (PEI) transfection and use of a codon-optimized gag, from approximately 1.70E+04 to 1.00E+06 Infectious Units/mL (IU/mL) on Raw 264.7 cells. An evaluation of purification strategies showed efficient vector purification and concentration of FV vector through a combination of heparin-affinity chromatography on the AKTA ready, a disposable fluid path chromatography unit, tangential flow filtration and ultracentrifugation, with an overall 5000-fold concentration and 20-30% recovery. This approach was compatible with large scale manufacturing in compliance with Good Manufacturing Practices (GMP). Although 5% DMSO is needed for optimal recovery of infectious FV vector from -80°C storage, highly concentrated vector can be diluted to reduce the DMSO concentration and toxicity to CD34+ cells, while maintaining effective transduction rates of up to 50%. This process is currently being finalized for clinical manufacturing in support of a Phase I trial for the treatment of LAD. Note: MN and DL equally contributed to this study.
277. Characterization of the Macrophage Response in Hematopoietic Stem Cell-Mediated Tissue Repair in Cystinosis
Authors: Swati Naphade, Shweta Joshi, Donald L. Durden, Stephanie Cherqui
Journal: Molecular Therapy (2015)

Cystinosis is a lysosomal storage disorder resulting from genetic mutations in the ubiquitously expressed CTNS gene, which encodes the lysosomal transmembrane transporter called cystinosin. In the absence of functional cystinosin, cystine accumulates in all tissues of the body, eventually depositing as crystals. Thus, cystinosis is a multisystemic degenerative disorder, with end-stage kidney failure as the cardinal manifestation. Our previous work has shown that transplantation of syngeneic wild-type hematopoietic stem cells (HSCs) in the mouse model of cystinosis, Ctns-/- mice, was effective in treating cystinosis and led to long-term tissue preservation. Our study clearly established that transplanted HSCs integrated abundantly into all tissues and differentiated into tissue-resident macrophages, such as Kupffer cells in the liver, microglia in the brain, and dendritic cells in the kidney. Addressing the cellular mechanism, we showed that HSC-derived macrophages corrected the genetic defect by delivering functional cystinosin to adjacent host Ctns-/- cells via long intercellular bridges called tunneling nanotubes (TNTs). In the kidney, TNTs were shown to transfer cystinosin-containing lysosomes from transplanted interstitial macrophages into diseased proximal tubular cells directly across the dense, continuous, and formidable barrier of the tubular basement membrane. This is the first demonstration of correction of a genetic lysosomal defect by vesicular exchange via TNTs and suggests broader potential for HSC transplantation for other disorders due to defective vesicular proteins. Overall, correlation between differentiation of HSCs into macrophages and improved biochemical, functional, and anatomical outcomes post-transplantation suggest that macrophages are key mediators of tissue repair. To test this hypothesis and to characterize the molecular protagonists involved, Ctns-/- mice have been transplanted with HSCs isolated from mouse strains that are deficient in macrophage differentiation. This work will open new perspectives in regenerative medicine that could spur the development of novel stem cell-based therapy.
144. Development of Novel Dicer- and Ago2-Independent Small Hairpin RNAs
Authors: Shin-ichiro Ohno, Karen Itano, Yuichirou Harada, Koutaro Asada, Keiki Oikawa, Mike Kashiwazako, Sudo Katsuko, Masakatsu Takanashi, Norihiko Ikeda, Masahiko Kuroda
Journal: Molecular Therapy (2016)

The innate cytokine response to nucleic acid is the most challenging problem confronting the practical use of nucleic acid medicine. The degree of stimulation of the innate cytokine response strongly depends on the length of the nucleic acid. In this study, we developed a 30-nucleotide single-strand RNA, termed "guide hairpin RNA (ghRNA, ghR)", that has a physiological function similar to that of miRNA and siRNA. The ghRNA caused no innate cytokine response either in vitro or in vivo. In addition, its structure does not contain a passenger strand seed sequence, reducing the unwanted gene repression relative to existing short RNA reagents. Systemic and local injection of ghRNA-form miR-34a (ghR-34a) suppressed tumor growth in a mouse model of RAS-induced lung cancer. Furthermore, ghR-34a functioned in a Dicer- and Ago2-independent manner. This novel RNA interference (RNAi) technology may provide a novel, safe, and effective nucleic acid drug platform that will increase the clinical usefulness of nucleic acid therapy.
Diffusion-MRI and angiogenic profiling in patients with advanced well-differentiated pancreatic neuroendocrine tumors treated with everolimus
Authors: C.A. Cella, F. Spada, S. Galdy, A.M. Frezza, M. Catapano, L. Funicelli, P. Mancuso, L. Zorzino, D. Radice, A. Calleri, N. Fazio
Journal: Annals of Oncology (2015)
196. AAV-Mediated Gene Replacement Therapy in Mouse Model of Tuberous Sclerosis
Authors: Shilpa Prabhakar, Xuan Zhang, June Goto, Miguel Sena-Esteves, Vijaya Ramesh, Roderick Bronson, John W. Chen, Anat O. Stemmer-Rachamimov, David J. Kwiatkowski, Xandra O. Breakefield
Journal: Molecular Therapy (2015)

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder due to mutations in either TSC1 or TSC2 that affects many organs with hamartomas and tumors. TSC-associated brain lesions include cortical heterotopias, tubers, subependymal nodules, and decreased myelination. Neurologic manifestations include epilepsy, hydrocephalus, mental retardation and autism. Here, we describe a new mouse model of TSC brain lesions in which complete loss of Tsc1 is achieved in multiple cell types in the brain in a stochastic pattern starting from the time of birth. Injection of an adeno-associated virus (AAV) vector encoding Cre recombinase into the cerebral ventricles of mice homozygous for a floxed Tsc1 conditional allele on P0 led to reduced survival, and pathologic findings of enlarged neurons, cortical heterotopias, subependymal nodules, and hydrocephalus. Although several other models of TSC brain disease exist, this model is unique in that the pathology reflects a variety of TSC-associated brain lesions involving different numbers and types of cells in different animals. This model provides a valuable and unique addition for therapeutic assessment. In addition, we have assessed the benefit of gene therapy in a related mouse model of Tsc1 in which the encoded gene product, hamartin is lost in most brain neurons at embryonic day 12. An adeno-associated virus (AAV) vector expressing a tagged form of hamartin was injected into the cerebral ventricles of newborn pups with the genotype Tsc1cc (homozygous for a conditional floxed Tsc1 allele) Syn-Cre+ (with Cre under the synapsin promoter). The AAV rh8 serotype gave widespread delivery of the tagged hamartin to brain cells. Treated mice showed an improvement in survival, from a mean of 22 days in non-injected Tsc1ccSynIcre+ mice to 52 days in hamartin AAV vector-injected, with improved weight gain and normalized behavior. Pathologic studies showed a reduction in neuron enlargement in comparison to untreated mutant littermates. Hence, we show that gene therapy is an effective approach in this mouse model of TSC. Our strategy for delivery has the advantage of single application, and AAV vectors are known to have minimal to nil toxicity in clinical trials for other neurologic conditions.
Inotuzumab Ozogamicin (IO) Is An Effective Salvage Therapy That Allows for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Remission in Patients with Advanced Acute Lymphoblastic Leukemia (ALL)
Authors: Partow Kebriaei, Kaci Wilhelm, Farhad Ravandi, Rima M. Saliba, Marcos De Lima, Stefan O Ciurea, Laura L. Worth, Susan O'Brien, Deborah A. Thomas, Richard Champlin, Hagop M. Kantarjian
Journal: Blood (2011)
Thrombotic Complications in Ph'-Negative Myeloproliferative Neoplasms - 10-Year Experience of A Medical Center in Asian Area
Authors: Yi-Sheng Chou, Ri-Dong Bai, Chung-Jen Teng, Ying-Chung Hong, Chun-Yu Liu, Yuan-Bin Yu, Liang-Tsai Hsiao, Jin-Hwang Liu, Hui-Chi Hsu, Tzeon-Jye Chiou, Po-Min Chen, Cheng-Hwai Tzeng, Jyh-Pyng Gau
Journal: Blood (2011)
Regional hyperthermia (RHT) as an innovative treatment component: RHT combined with gemcitabine (G) and cisplatin (CIS) in G-pretreated advanced pancreatic cancer (APC).
Authors: K. Tschoep-Lechner, N. Dieterle, S. Abdel-Rahman, L. Lindner, C. Salat, S. Ehrke, B. Weber, C. J. Bruns, V. Heinemann, U. Mansmann, R. D. Issels
Journal: Journal of Clinical Oncology (2011)

e14524 Background: There is ongoing debate on the treatment benefit of gemcitabine (G) plus cisplatin (CIS) compared to G alone in firstline treatment of APC. However, from preclinical research it is proven that cytotoxicity of both drugs – G and CIS – is enhanced by heat exposure at 40 to 42°C. Here we show first clinical data on the combination of G plus CIS with RHT (Tmax 42°C) as secondline treatment in APC patients with G-refractory disease. Methods: Pts with locally advanced (n=2) or metastatic (n=21) pancreatic cancer with relapse after G firstline chemotherapy were retrospectively analysed. Pts received 8 cycles of G (1,000mg/m2) on day 1 and CIS (25mg/m2) combined with RHT (Tmax: 42°C) using the BSD -2000 hyperthermia system (BSD Medical Corporation, Salt Lake City, UT, USA) on days 2 + 4, biweekly according to an institutional protocol (nr. 79/98). CT scans were performed after 4, 8 and every 2 months thereafter. For endpoints we analysed toxicity and progression free survival (TTP2 defined as time from start of second-line therapy until progression of disease or death; [primary]) and overall survival and best clinical response (secondary). TTP1 was defined as time from start first-line therapy until progression of disease. Results: Between 10/99 and 08/08 overall 23 pts received a median of 5 G+CIS with RHT cycles (range 1-12). Pt characteristics: male 74%, female 26%; median age 60 yrs; majority of pts (n= 17) had ECOG 0/1 (74 %). Hematological toxicity grade 3/4 (NCI toxicity criteria): no grade 4 toxicity, grade 3 anemia (n=6), grade 3 leucopenia (n=3). Hyperthermia-associated toxicity: discomfort (n=5), power-related pain (n=13), position-related pain (n=15). Best clinical response (CR+PR+SD): 50% (16/23 pts evaluable; 0 CR, 1 PR, 7 SD). Median TTP1 was 5.9 mts (95% CI: 2.6-9.2), median TTP2 was 4,3 mts (95% CI: 1.2-7.4) and OS was 12.9 mts (95% CI: 9.9-15.9). Conclusions: G plus CIS with RHT is clinically active in G-pre-treated APC, with an acceptable safety profile. A prospective controlled phase II clinical trial of G+CIS+ RHT (EudraCT: 2005-003855-11) using this setting is currently recruiting.
Acral lentiginous melanoma in Hawaii: Characterization of the mTOR pathway in the non-Caucasian population.
Authors: S. Y. Morita, S. Jim, C. A. Lum, D. E. Hemmings, J. Davis
Journal: Journal of Clinical Oncology (2011)

8592 Background: Although, acral lentiginous melanoma (ALM) is the least common subtype among patients with melanoma, there is a higher preponderance in the non-Caucasian population. ALM has been proposed to have a different pathogenesis. Recent studies have profiled the importance of the mTOR (mammalian target of rapamycin) pathway in carcinogenesis. However, characterization of this pathway in a multi-ethnic ALM population has not been reported. The Pacific Basin provides a unique opportunity to study diseases in non-Caucasian patients. We elected to determine the frequency of mTOR pathway involvement in ALM. Methods: IRB approval was obtained for this retrospective analysis. From 1992 to 2010, 20 non-Caucasian patients (9-Filipino, 4-Micronesian, 4-Samoan, 1-Thai, 1-unspecified Pacific Islander and 1-Vietnamese) histologically confirmed to have ALM were evaluated at a tertiary institution. Data including age, gender, tumor location, Breslow thickness, Clark level, ulceration, regression, and mitoses per mm squared were compiled. Immunohistochemical expression for mTOR and eIF4E (eukaryotic initiation factor 4E) proteins was performed on formalin-fixed/ paraffin-embedded archived biospecimens (primary lesions). Both m-TOR and eIF4e expression were graded on a scale from 0 (absent) to 2 (high). Results: Our results demonstrated that the mTOR protein 14/20 (70%) and eIF4E protein 9/20 (45%) were highly expressed. Demographics of the non-Caucasian cohort include mean age of 69.6 years old (range 48-89) and male gender 10/20 (50%). Tumor location principally involved the foot 19/20 (95%); mean Breslow thickness was 4.36 mm (range 1.6-10.0), Clark IV or higher 16/20 (80%), ulceration 16/20 (80%), regression 20/20 (100%), and mean mitoses per mm squared was 8.5 (range 1-30). Conclusions: Non-Caucasian patients with ALM were found to have a high prevalence of effectors involving the mTOR pathway. Nearly half of our cohort had thick primary lesions with a high propensity for ulceration. This is the first study to our knowledge that has examined the mTOR pathway in a non-Caucasian population of ALM patients. This is compelling data that may be applied to the metastatic phenotype in future trials.
EBV-Specific Micro-RNA Via Exosome: A Key Inter-Cellular machinery between EBV+ Tumor and Tumor-Surrounding Immune Cells?
Authors: Kazuaki Yokoyama, Lu Jun, Takae Toyoshima, Hozumi Katsuto, Takashi Yahata, Kiyoshi Ando, Ai Kotani
Journal: Blood (2012)