tbuckley/cabot-search huggingface dataset:
CC-005 A confusing case of colitis
Authors: M Kumar, R Ravikumar, J Hossain
Journal: Gut (2010)

<h3>Introduction</h3> The common causes of acute bloody diarrhoea include infective gastroenteritis, inflammatory bowel disease, pseudomembranous colitis and ischaemic colitis. We present a case of refractory colitis in an elderly patient who did not respond to conventional treatment. <h3>Methods</h3> 75-year-old male patient presented with 2-day h/o bloody diarrhoea, vomiting and fever. Past medical history included diabetes and hypertension. Physical examination revealed mildly distended, non-tender, soft abdomen. Blood tests showed leucocytosis with neutrophilia and CRP 223. Stool culture was negative for clostridium toxin. Colonic obstruction and ischaemia were ruled out by CT scan. Sigmoidoscopy showed marked ulceration and cobblestone appearance with mucoid exudates in sigmoid colon suggesting IBD. Patient was commenced on corticosteroids. Histology showed crypt distortion and inflammatory changes, but H&amp;E staining showed characteristic owls-eye inclusion bodies. Immunohistochemistry confirmed owls eye inclusion bodies suggesting acute CMV colitis. CMV IgG antibodies were positive and CMV viralload PCR was 60×100 000 indicating acute viraemia. Patient was treated with IV Ganciclovir for 2 weeks and corticosteroids were stopped. Repeat colonic biopsies were negative for CMV inclusion bodies, but endoscopic appearances remain unchanged. Patient developed toxic megacolon, peritonitis and died as patient was unfit for surgery. <h3>Results</h3> In our patient, both serology and histology initially suggested a diagnosis of CMV colitis, although endoscopic appearances and histological features were indistinguishable from ulcerative colitis. Corticosteroids were stopped, as there was a risk of worsening CMV colitis due to immunosuppression by steroids. IV Ganciclovir did not improve symptoms suggesting ulcerative colitis as the cause of diarrhoea and CMV as an innocent bystander. <h3>Conclusion</h3> Primary CMV colitis is rare in immunocompetent patients. Most cases of CMV colitis have been reported in refractory, steroid resistant ulcerative colitis or HIV patients.1 Treatment with IV Ganciclovir results in improvement of ulcerative colitis.2 Our case demonstrates that distinguishing primary CMV colitis from ulcerative colitis with latent CMV infection can be difficult in immunocompetent patients and initiating right treatment can be challenging.
CT-011, Anti-PD-1 Antibody, Enhances Ex-Vivo T Cell Responses to Autologous Dendritic/Myeloma Fusion Vaccine Developed for the Treatment of Multiple Myeloma.
Authors: Jacalyn Rosenblatt, Brett Glotzbecker, Heidi Mills, Whitney Keefe, Kerry Wellenstein, Baldev Vasir, Zekui Wu, Corrine Zarwan, Michael Schickler, Rinat Rotem-Yehudar, Donald Kufe, David Avigan
Journal: Blood (2009)
Improved Outcomes of Low-Dose Cytarabine Regimen By Increased Dose and Duration of Cytarabine in Combination with Oral Etoposide for Elderly Acute Myeloid Leukemia
Authors: Seung-Hwan Shin, Seung-Ah Yahng, Jae-Ho Yoon, Byung-Sik Cho, Hee-Je Kim, Young-Woo Jeon, Sung-Eun Lee, Ki-Sung Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min
Journal: Blood (2015)
Impact of new chemotherapeutic and targeted agents on survival in stage IV non-small cell lung cancer.
Authors: J. L. Yu, C. E. Simmons, C. Victor, D. Han, S. Hogeveen, N. B. Leighl, S. Verma
Journal: Journal of Clinical Oncology (2011)

e18015 Background: Significant advances in the systemic management of metastatic non-small cell lung cancer (NSCLC) have occurred over the past decade, with options now including multiple lines of chemotherapy, EGFR inhibitors, and anti-angiogenic agents. Improvements in overall survival have been demonstrated in randomized controlled trials comparing these newer agents to best supportive care (BSC) or standard therapy. This study examined uptake of these therapies in general practice and their impact on survival. Methods: This retrospective cohort study compared demographic, treatment and survival data among 987 patients diagnosed with stage IV NSCLC at two institutions in 1998, 2003, and 2008. Cohorts were selected based on intervals when doublet chemotherapy, second line chemotherapy, and targeted agents were incorporated into the standard treatment regimen. Results: The proportion of patients receiving systemic therapy increased over time (20% in 1998, 42% in 2008). Treated patients diagnosed in 2008 were more likely to receive ≥2 lines of systemic therapy (60% vs. 7% in 1998). Overall survival improved significantly across cohorts (P <0.001), with 2 year survival rates of 0.3% in 1998, 4% in 2003, and 15% in 2008. After controlling for other variables, risk of death was diminished by 55% in patients receiving 1 line of systemic therapy and 72% in those receiving ≥2 lines, compared with BSC alone. Elderly patients (age ≥70 years) were also more likely to receive systemic therapy over time, with improved overall survival (P <0.001). Conclusions: Over the past decade, there has been increased use of systemic therapy in stage IV NSCLC patients, including the elderly. This has been associated with significantly improved overall survival.
Intracellular Microreactors as Artificial Organelles to Conduct Multiple Enzymatic Reactions Simultaneously
Authors: María Godoy‐Gallardo, Cédric Labay, Michelle M. T. Jansman, Pramod K. Ek, Leticia Hosta‐Rigau
Journal: Advanced Healthcare Materials (2016)

The creation of artificial organelles is a new paradigm in medical therapy that aims to substitute for missing cellular function by replenishing a specific cellular task. Artificial organelles tackle the challenge of mimicking metabolism, which is the set of chemical reactions that occur within a cell, mainly catalyzed by enzymes. So far, the few reported carriers able to conduct enzymatic reactions intracellularly are based on single-compartment carriers. However, cell organelles outperform by conducting multiple reactions simultaneously within confined sub-compartments. Here, the field of artificial organelles is advanced by reporting the assembly of a microreactor consisting of polymer capsules entrapping gold nanoclusters (AuNCs) and liposomes as sub-compartments. The fluorescence properties of AuNCs are employed to monitor the microreactors uptake by macrophages. Encapsulation is demonstrated and functionality of microreactors with trypsin (TRP) and horseradish peroxidase (HRP)-loaded liposomes is preserved. Multiple enzymatic reactions taking place simultaneously is demonstrated by exposing macrophages with the internalized microreactors to bis-(benzyloxycarbonyl-Ile-Pro-Arg)-Rho-110 and Amplex Red substrates, which are specific for TRP and HRP, respectively. Conversion of the substrates into the respective fluorescent products is observed. This report on the first microreactor conducting multiple enzymatic reactions simultaneously inside a cell is a considerable step in the field of artificial organelles.
Brentuximab Vedotin (SGN-35) Enables Successful Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Relapsed/Refractory Hodgkin Lymphoma
Authors: Robert W. Chen, Stephen J. Forman, Joycelynne Palmer, Ni-Chun Tsai, Leslie Popplewell, Maria L Delioukina, Torres Alejandra, Bernadette Pulone, Eileen P. Smith, Auayporn P. Nademanee, Chatchada Karanes, Paul O'Donnell, David G. Maloney, Len Farol, Schickwann Tsai, Laurie E. Grove, Ajay K. Gopal
Journal: Blood (2011)
PTH-044 Poor sleep quality in irritable bowel syndrome: a comparison with healthy adult controls
Authors: G Sisson, C Junghans, I Bjarnason
Journal: Gut (2010)

<h3>Introduction</h3> Irritable bowel syndrome (IBS) is a common disorder resulting in a wide range of abdominal and bowel symptoms which often have an impact on quality of life (QOL). Poor sleep quality also affects QOL and is a recognised feature of inflammatory bowel disease as well as other medical and psychiatric disorders.12 Although poor sleep quality is reported in IBS little is known about its prevalence. Here we compare sleep quality in IBS with health controls using the Pittsburgh Sleep Quality Index (PSQI) a standardised and validated quantitative measure of sleep quality.1 <h3>Methods</h3> Consecutive patients with a diagnosis of IBS attending the outpatient gastroenterology department of Kings College Hospital were recruited. Healthy controls were recruited from hospital staff and students on a voluntary basis. All patients and controls gave informed written consent. Exclusion criteria were night shift work, current or past sleep disorder, inflammatory bowel disease (IBD) or other significant health problem that may affect sleep (IBS was excluded from the control group). All patients completed the a health and life style questionnaire and a PSQI which gives a quantitative sleep quality score from 1 to 21 with a higher score representing a worse sleep quality. Cases and controls were compared using the Mann–Whitney U test in Stata 8 statistical software. <h3>Results</h3> A total of 90 subjects, 63 patients and 27 controls were recruited. The mean PSQI was 9.6 and 4.4 in IBS and control subjects, respectively (CI 8.6 to 10.7 and 3.5 to 5.4). (p&lt;0.0001). <h3>Conclusion</h3> This study is the first to demonstrate and quantitate poor sleep quality in patients with IBS when compared to healthy controls. Poor sleep quality appears to be yet another manifestation of the multi-organ involvement of the disease and may add further to the reduced QOL seen in IBS.
Palliative gastrectomy in asymptomatic metastatic esophagogastric cancer (EGC): does it make sense?
Authors: G. Musettini, C. Caparello, C. Vivaldi, G. Pasquini, M. Lencioni, I. Petrini, L. Fornaro, E. Vasile, A. Falcone
Journal: Annals of Oncology (2015)
276. PAX4 Gene Transfer Induces α-to-β Cell Transdifferentiation and Ameliorates Hyperglycemia
Authors: Yanqing Zhang, Genevieve Fava, Hongjun Wang, Franck Mauvais-Jarvis, Vivian Fonseca, Hongju Wu
Journal: Molecular Therapy (2015)

The transcription factor Pax4 plays a critical role in the determination of the lineage of insulin-producing β-cells versus glucagon-producing α-cells during endocrine pancreas development. In this study, we explored whether Pax4 gene transfer into α-cells could convert them into functional β-cells, and thus provide therapeutic benefits for insulin-deficient diabetes. To accomplish that, we developed an adenoviral vector encoding CMV promoter driven human Pax4, Ad5.Pax4, and examined its functionality in the clonal α-cell line, aTC1.9. Our results showed that Pax4 induced insulin expression and reduced glucagon expression in aTC1.9 cells. More importantly, these cells exhibited functional glucose-stimulated insulin secretion, a key feature of functional β-cells. When injected into streptozotocin-induced diabetic mice, the Pax4-treated aTC1.9 cells significantly reduced blood glucose within 24 hours, and the mice showed better glucose tolerance, supporting that Pax4 gene transfer into aTC1.9 cells resulted in the formation of functional β-cells. Furthermore, treatment of primary human islets with Ad5. Pax4 resulted in significantly improved β-cell function. Although in the experimental setting, we were not able to distinguish pre-existing β-cells from converted β-cells, detection of triple positive cells (glucagon+/Pax4+/Insulin+) argued for the presence of α-to-β cell transitioning. This was further supported by quantification of glucagon and insulin double positive (bi-hormonal) cells, of which the number of bi-hormonal cells in Pax4-treated human islets was significantly higher than that in control groups. Finally, we found that direct administration of Ad5. Pax4 into the pancreas of insulin-deficient mice had therapeutic benefits. The significantly improved β-cell function in both human islets and mouse pancreas was consistent with Pax4-induced α-to-β cell conversion, although Pax4-mediated β-cell protection could have contributed as well. Taken together, our data demonstrate that manipulating Pax4 gene expression in α-cells represents a novel and viable therapeutic strategy for the treatment of insulin deficient diabetes.
Abstract 4465: Sequential combination of docetaxel with a novel SHP-1 agonist enhanced anti-tumor effect in triple negative breast cancer cells
Authors: Ling-Min Tseng, Chun-Yu Liu, Shiu-Ping Yang, Wan-Lun Wang, Jung-Chen Su, Chia-Yun Wu, Chung-Wai Shiau, Kuen-Feng Chen
Journal: Cancer Research (2015)

Abstract Background: Interfering the oncogenic STAT3 signaling is considered as promising anti-cancer strategy. STAT3 signaling can be negatively regulated by the protein tyrosine phosphatase SHP-1 through direct dephosphorylation of p-STAT3 (Tyr705). Our previous studies have confirmed SC-43 as a novel SHP-1 enhancer which down-regulate p-STAT3 and STAT3-related downstream effectors (Breast Cancer Research 2013). Here, we tested the efficacy of SC-43 in combination with docetaxel in triple negative breast cancer cells. Methods: TNBC cell lines (HCC-1937, MDA-MB-468, MDA-MB-231) were used for in vitro studies. Cell viability was examined by MTT assay. Combination index was determined using Calcusyn anaysis. Apoptosis was examined by flow cytometry and western blot. Signal transduction pathways in cells were assessed by western blot. In vivo efficacy of SC-43 in combination with docetaxel was tested in nude mice with breast cancer xenografts. Results: Sequential combination of docetaxel with SC-43 showed enhanced anti-proliferative activity in all tested TNBC cells. Synergistic effect was demonstrated when docetaxel combined with SC-43 at a dose ratio of 1 to 10, showing combination index below 1.0. Sub-G1 and western blot analysis showed that SC-43 enhanced docetaxel-induced apoptosis. In addition, combining SC-43 with docetaxel efficiently suppressed p-STAT3 and downstream effectors. Ectopic expression of STAT3 reduced the enhanced cytotoxicity by the combination therapy. Previous studies has shown SC-43 enhanced SHP-1 activity, here we showed that SC-43 in combination with docetaxel significantly enhanced SHP-1 activity. More importantly, intraperitoneal injection of SC-43 with tri-weekly docetaxel showed enhanced anti-tumor growth in xenografted tumor mice. Conclusion: Our results suggest that the novel SHP-1 agonist SC-43 enhanced docetaxel-induced cytotoxic killing by SHP-1 dependent STAT3 inhibition in human triple negative breast cancer cells. (Supported by Yen Tjing-Ling Medical Foundation CI-104-07; NSC-102-2325-B-075-006 and MOST 103-2325-B-075-002; and MOHW103-TD-B-111-02) Citation Format: Ling-Min Tseng, Chun-Yu Liu, Shiu-Ping Yang, Wan-Lun Wang, Jung-Chen Su, Chia-Yun Wu, Chung-Wai Shiau, Kuen-Feng Chen. Sequential combination of docetaxel with a novel SHP-1 agonist enhanced anti-tumor effect in triple negative breast cancer cells. [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 4465. doi:10.1158/1538-7445.AM2015-4465
438. Human, Pig and Mouse IFITMs Partially Restrict Pseudotyped Lentiviral Vectors
Authors: Andrew L. Hornick, Ni Li, Mayumi Oakland, Paul B. McCray, Patrick L. Sinn
Journal: Molecular Therapy (2016)

Lentiviral vectors are increasingly used in clinical trials to treat genetic diseases. Our research has focused on strategies to improve lentiviral gene transfer efficiency in the airways. Previously we demonstrated that a feline immunodeficiency virus (FIV)-based lentiviral vector pseudotyped with the baculovirus envelope glycoprotein GP64 (GP64-FIV) efficiently transduced mouse nasal epithelia in vivo but transduced mouse intrapulmonary airways with ten-fold less efficiency. Here, we demonstrate that a family of proteins with antiviral activity, interferon induced transmembrane proteins (IFITMs), are more highly expressed in the mouse intrapulmonary airways as compared to the nasal airways. Using GP64 and VSV-G pseudotyped FIV, we show that expression of mouse IFITM1, IFITM2, and IFITM3 restricts gene transfer. Further we show that both the nasal and intrapulmonary airways of IFITM locus knockout mice are more efficiently transduced by GP64-FIV than their heterozygous littermates. In anticipation of transitioning our studies into pig models of airway disease and clinical trials in humans, we investigated the ability of pig and human IFITMs to restrict lentiviral gene transfer. We observed that both human and pig IFITMs partially restricted both VSV-G-FIV and GP64-FIV transduction in vitro. These results implicate the IFITM proteins as restriction factors that can limit lentiviral gene transfer to airway epithelia. The findings are relevant to future pre-clinical and clinical airway gene therapy trials using lentiviral-based vectors.
IMPACT of Therapeutic Strategy and Time to Therapy Initiation on Clinical Evolution in Higher-Risk Myelodysplastic Syndromes. a Report from Erasme Study
Authors: Julia Montoro, Rosa Coll, David Valcarcel, Mar Tormo, Maria Calbacho, Teresa Bernal, Alfonso Fernandez, Joaquin Sanchez, Manuel Albors, Montserrat Arnan, Edgardo Barranco, Montse Rafel, Regina Garcia
Journal: Blood (2014)
Innovative Phase I/II Statistical Design in Combination Chemotherapy That Combines Toxicity and Efficacy Parameters to Increase Study Efficiency: Bendamustine and Idarubicin in De Novo Adult AML
Authors: Jack M. Lionberger, Kathleen Shannon Dorcy, Carol Dean, Nathan Holm, Bart Lee Scott, J. Kyle Wathen, Elihu H. Estey, John M. Pagel
Journal: Blood (2011)
Abstract LB-191: Association of anti-estrogen therapy in breast cancer patients and subsequent risk of rheumatoid arthritis: An electronic health record study
Authors: Matthew K. Breitenstein, Ming-Fen Ho, Richard M. Weinshilboum, James R. Cerhan, Jyotishman Pathak, Tim Bongartz, Liewei Wang, James N. Ingle
Journal: Cancer Research (2015)

Abstract Background: The use of anti-estrogen (AE) therapies (selective estrogen receptor modulators [SERMs], aromatase inhibitors [AIs]) in breast cancer (BC) patients was recently associated with risk of developing rheumatoid arthritis (RA) (J Rheum 2015;42:55-9). We attempted to replicate and extend these results using electronic health record (EHR) enhanced cancer registry data that assessed specific AE therapies and also accounted for potential confounding by age, smoking status, and chemotherapy use. Methods: Using cancer registry and EHR data, we identified a cohort of BC patients who were newly diagnosed and treated at Mayo Clinic Rochester from 1998-2011 and had no previous diagnosis of RA. Smoking status at diagnosis, BC treatments and RA at diagnosis and during follow-up were identified using validated EHR-based algorithms. Hazard ratios (HRs) and 95% confidence intervals (CI) from a multivariate Cox model were used to estimate the association of AE use with risk of RA, controlling for age, smoking status at BC diagnosis, and BC chemotherapy use. Results: The analytic cohort of 9,244 newly diagnosed BC patients treated and followed at Mayo Clinic had a median age at diagnosis of 59 years (range 18-97); 32% were smokers; and 29% were treated with chemotherapy. During a median follow-up of 49 months (range 1-191), 19 patients developed RA. Compared to BC patients not receiving any AE therapy, those receiving AI monotherapy, but not SERM monotherapy or both SERMs and AIs, were at significantly increased risk of developing RA (Table). AE Therapy# of RA Cases / # patientsHR* (95% CI)P-valueNo AE therapy6/4,0711.00 (reference)SERMs only5/2,5371.20 (0.36 - 3.95)0.77AIs only5/7126.37 (1.77 - 22.92)0.005SERMs then AIs3/1,8750.90AI then SERMs0/490.91 (0.21 - 3.86)*Adjusted for age, smoking status and use of chemotherapy Conclusions: Our findings indicate that the use of AIs for BC therapy, but not SERMs or SERMs followed by AIs, is associated with increased risk for development of RA, when controlling for smoking status and use of chemotherapy. While needing replication, these findings suggest a specific role for AIs in RA development and suggest pathways that could be targeted to prevent this potential treatment complication. Citation Format: Matthew K. Breitenstein, Ming-Fen Ho, Richard M. Weinshilboum, James R. Cerhan, Jyotishman Pathak, Tim Bongartz, Liewei Wang, James N. Ingle. Association of anti-estrogen therapy in breast cancer patients and subsequent risk of rheumatoid arthritis: An electronic health record study. [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 LB-191. doi:10.1158/1538-7445.AM2015-LB-191
Randomized phase II study of gemcitabine monotherapy versus gemcitabine with an EPA-enriched oral supplement in advanced pancreatic cancer.
Authors: Makoto Ueno, Satoshi Kobayashi, Shinichi Ohkawa, Ryo Kameda, Tomoko Andou, Kazuya Sugimori, Haruo Miwa, Ryonho Ko, Katsuaki Tanaka, Masataka Taguri, Satoshi Morita
Journal: Journal of Clinical Oncology (2013)

e15109 Background: Gemcitabine is one of the standard chemotherapeutic agents for pancreatic cancer. Pancreatic cancer is often associated with cachexia. It had been reported that eicosapentaenoic acid (EPA) reduces proinflammatory cytokines, leading to improvement of cachexia. This study aimed to evaluate the efficacy and safety of gemcitabine with an EPA-enriched oral supplement in patients with unresectable pancreatic cancer. Methods: This phase II study consisted of patients (pts) who were randomly categorized into Arm A (1000 mg/m 2 gemcitabine was administered on days 1, 8, and 15, every 4 weeks while an EPA-enriched oral supplement (Prosure, EPA 1056mg per pack) was taken daily at the maximum of 2 packs) or Arm B (gemcitabine monotherapy) at a 2:1 ratio. The primary endpoint was the evaluation of the 1-year survival. The sample size of 66 pts was chosen based on the randomized phase II selection design by Simon et al. (1985). The design suggests a correct selection probability of 80% if 1-year survival probabilities are 35% and 25% for two treatment arms. Results: From May 2010 to Oct. 2011, randomized 66 pts were examined (Arm A: 43, B: 23). The 1-year survival probability of Arm A was 35% while Arm B was 19%. The median survival times were 8.2 and 9.7 months, respectively. The hazard ratio was 0.79 [95%CI 0.46-1.37]; (p=0.40). The toxicities were mild and insignificant in both arms. Grade 3/4 toxicities (A/B %) included: neutropenia, 20.9/13.0; leukocytopenia, 30.2/21.7; hemoglobin, 14.0/8.7; thrombocytopenia, 9.3/8.7; nausea, 11.6/0.0; and diarrhea, 0/4.3. Although survival curve did not show significant differences, delayed effect was observed in Arm A. According to subgroup analyses, more beneficial effects were observed in men and pancreatic body-tail patients who took a lot of supplements (Table). Conclusions: Gemcitabine with an EPA-enriched oral supplement in advanced pancreatic cancer may be effective, and further phase III trial is needed. Clinical trial information: UMIN000003658. [Table: see text]
Blood Traffic of Endothelial, Mesenchymal, Hematopoietic and Lin-/CD45-CD34+AC133+CXCR4+ Progenitor Cell Subsets Show Different Patterns in Pre-Fibrotic and Fibrotic Primary Myelofibrosis
Authors: Mario Ojeda-Uribe, Christophe Desterke, Laura Jung, Pierre Bories, Hanna Sovalat, Laurent Mauvieux, Jean Claude Eisenmann, Bruno Lioure, Marie-Caroline Le Bousse-Kerdiles
Journal: Blood (2014)
The 21st Century Cures Act — A View from the NIH
Authors: Kathy L. Hudson, Francis S. Collins
Journal: New England Journal of Medicine (2016)

the political costs of gutting the entire ACA is too high, states may be the ones crafting the future of federal health care reform.Reforms undertaken by Massachusetts in 2006 greatly influenced federal reforms in the ACA.State-driven reforms enacted under innovation waivers could similarly foreshadow the future of U.S. health care reform.
Relationship and predictive role of the dual expression of FGFR and IL8 in metastatic renal cell carcinoma (mRCC)
Authors: C. Mosillo, R. Iacovelli, M. De Tursi, A. Ciardi, C. Carella, C. Natoli, G. Naso, E. Corstesi
Journal: Annals of Oncology (2015)