tbuckley/cabot-search huggingface dataset:
FRI0224 Lymphoproliferative disorders in primary sjÖgren’s syndrome: a ten years follow-up study of 68 cases
Authors: C Botsios, P Sfriso, L Semerano, P Ostuni, C Grava, PF Gambari
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease chiefly involving salivary and lachrymal glands, associated with a high risk of developing non Hodgkin’s lymphoma (NHL) (about 44 times higher than in the general population), usually B-cell lymphomas of mucosa associated lymphoid tissue (MALT). Anyway, the most frequent histologic lesion of major salivary glands of pSS patients is myoephitelial sialadenitis (MESA). <h3>Objectives</h3> We longitudinally studied the prevalence and the clinical features of lymphoproliferative disorders in a large cohort of pSS patients throughout a 10-years follow-up period. <h3>Methods</h3> We evaluated 68 consecutive outpatients, affected by pSS according to the Fox’s criteria, followed since January 1987 to November 2000. Patients were divided into two groups, according to their autoantibodies pattern at the time of diagnosis: anti-Ro and/or La positive vs anti-Ro/La negative. We excluded patients affected either by secondary SS or associated to other connective tissue diseases and HCV infection, or by isolated keratoconjunctivitis sicca and those taking drugs causing sicca syndrome. We even calculated the relative risk on the basis of incidence rate of NHL as reported by Italian Cancer Registry. <h3>Results</h3> Lymphoproliferative disorders were diagnosed in 5 (7.35%) patients. Lymphoproliferation was significantly prevalent in the Ro/La positive group (p = 0.041). We recorded 2 cases of NHL of intermediate or low grade malignancy (1 rhinofaringeal plasmocytoma associated with glomerulonephritis and monoclonal crioglobulinemia and 1 parotid MALToma) and 3 pre-neoplastic disorders (2 cases of MESA and 1 case of renal lymphoproliferative disorder). The latter died of melanoma 4 years after the diagnosis of lymphoproliferative disorder. In all the cases the development of a lymphoproliferative disorder was associated with purpura, parotid swelling and low C4 levels, either at the time of diagnosis or during the follow-up. Kaplan-Meier rates analyses showed that MESA and NHL represented late occurring events in the course of pSS. According to our results, the relative risk (RR) to develop NHL was 36.1 for the whole group with pSS (p &lt; 0.001), while for the Ro and/or La positive group was 47.1. Ten years survivorship in pSS patients was not significantly lower with respect to the general population (86.5 vs 90%) calculated with the aid of life tables of the Italian general population (matched for age and sex). <h3>Conclusion</h3> Patients with purpura, parotid swelling, low C4 levels and cryoglobulinemia present an increased risk to develop lymphoproliferative disorders. These clinical and laboratory findings seem to identify a subgroup of patients with pSS which should be controlled and, maybe, treated in a different way.
Morphoproteomics of VEGF pathway mediators as evidence of reversible resistance to VEGF-TKIs demonstrated by expression of activated ERK and STAT3 in metastatic renal cell carcinoma (mRCC).
Authors: Shan Guo, Swetha Siddappa Yadav, Jamie Buryanek, Robert E Brown, Fangqian Ouyang, Robert J. Amato
Journal: Journal of Clinical Oncology (2013)

e15552 Background: Resistance to vascular endothelial growth factors (VEGF)-tyrosine kinase inhibitors (TKIs) (e.g., sunitinib, sorafenib) may be a result of changes in the tumor microenvironment and to the selection of resistant clones and permanent genetic changes. This has been demonstrated in mouse xenograft models where there was tumor shrinkage following reintroduction of sorafenib after a 1 week break (Zhang 2011 PLoS One). Methods: We applied morphoproteomic analysis to biopsy specimens of mRCC after a treatment break with VEGF-TKIs. Constitutive activation evidenced by expression (≤3) of p-extracellular signal-regulated kinase (ERK) 1/2 and p-signal transducer and activator of transcription (STAT) 3 in the nuclear compartments (≤3) indicates signaling through the VEGF pathway. Results: Strong overexpression of p-ERK1/2 and p-STAT3 with VEGF tyrosine kinase inhibitors indicates reactivation of the VEGF pathways (Table). Conclusions: Morphoproteomics confirms constitutive activation of the prosurvival ERK and STAT3 pathways after a treatment break indicating reversibility in resistance patterns to therapy with VEGF-TKIs indicating that the drugs can be reintroduced after having progressed on the same therapy. [Table: see text]
Transforming the Early Drug Development Paradigm at the National Cancer Institute: The Formation of NCI's Experimental Therapeutics Clinical Trials Network (ETCTN)
Authors: Holly A. Massett, Grace Mishkin, Jeffrey A. Moscow, Amy Gravell, Michael Steketee, Martha Kruhm, Sae H. Han, Barbara Barry, Michael Montello, James Zwiebel, Jeffrey S. Abrams, James H. Doroshow, S. Percy Ivy
Journal: Clinical Cancer Research (2019)

Abstract Early drug development for cancer requires broad collaboration and skilled clinical investigators to enable enrollment of patients whose tumors have defined molecular profiles. To respond to these challenges, the National Cancer Institute (NCI) transformed its 60-year-old early-phase drug development program in 2014 into the Experimental Therapeutics Clinical Trials Network (ETCTN). The ETCTN is a consolidated, national network of 40+ academic institutions responsible for conducting more than 100 early-phase clinical trials. It promotes team science coordinated among basic, translational, and clinical investigators, emphasizing the inclusion of early career trialists. This perspective provides a brief overview of the ETCTN, summarizes its successes and challenges over its first grant funding cycle, and discusses the program's future directions. Measures indicated strong connectivity across the institutions, significant increases in investigator approval of the ETCTN scientific portfolio from years 1 to 4, and substantial research activity over 5 years, with 334 letters of intent submitted, 102 trials activated, and 3,570 patients accrued. The ETCTN's successful adoption relied heavily on the inclusion of senior investigators who have long-standing interactions with the NCI and a willingness to participate in a team science approach and to mentor early career investigators. In addition, NCI invested substantial resources in a centralized infrastructure to conduct trials and to support the inclusion of biomarkers in its studies. The ETCTN provides evidence that a collaborative national clinical trial network for early drug development is feasible and can address the demands of precision medicine approaches to oncologic clinical trials.
Oncogenic Rag GTPase signalling enhances B cell activation and drives follicular lymphoma sensitive to pharmacological inhibition of mTOR
Authors: Ana Ortega-Molina, Nerea Deleyto-Seldas, Joaquim Carreras, Alba Sanz, Cristina Lebrero-Fernández, Camino Menéndez, Andrew Vandenberg, Beatriz Fernández-Ruiz, Leyre Marín-Arraiza, Celia de la Calle Arregui, Ana Belén Plata-Gómez, Eduardo Caleiras, Alba de Martino, Nuria Martínez-Martín, Kevin Troulé, Elena Piñeiro-Yáñez, Naoya Nakamura, Shamzah Araf, Gabriel D. Victora, Jessica Okosun, Jude Fitzgibbon, Alejo Efeyan
Journal: Nature Metabolism (2019)
Endoscopic sclerotherapy under balloon-assisted enteroscopy for hemorrhagic jejunal varices after choledocho-jejunostomy
Authors: Kota Takashima, Shigenaga Matsui, Yoriaki Komeda, Tomoyuki Nagai, Sakurai Toshiharu, Hiroshi Kashida, Masatoshi Kudo
Journal: Endoscopy (2019)

Hemorrhage from varices in the jejunal loop after reconstruction of the biliary tract is quite rare. Portal hypertension due to extrahepatic portal vein stenosis or obstruction at the site of a previously performed choledocho-jejunostomy results in the formation of hepatoportal collaterals through the anastomosis, thus creating varices in the afferent loop that can rupture and hemorrhage [1] [2]. We present endoscopic sclerotherapy under balloon-assisted enteroscopy for hemorrhagic jejunal varices after choledocho-jejunostomy ([Video 1]).
Abstract 580: Detailed analysis of immune responses induced against patient-specific neoantigens using the <i>ex-vivo</i> induction protocol, NEO-STIM™
Authors: Divya Lenkala, Jessica Kohler, Brian McCarthy, Michael Nelson, Rachel DeBarge, Yvonne Ware, Yuting Huang, Janani Sridar, Yusuf Nasrullah, Dewi Hartjano, Asaf Poran, Sejuti Sengupta, Joost H. van den Berg, Matt Goldstein, Richard B. Gaynor, Marit M. van Buuren
Journal: Cancer Research (2019)

Abstract Background: Neoantigens are tumor-specific antigens that have been shown to be critical in the anti-tumor immune response. These antigens are not subject to central immune tolerance and are therefore potentially more immunogenic than tumor-associated antigens. The goal of our studies is to assess the immunogenic potential of high-quality neoantigen targets, as defined through our bioinformatic engine RECON®, as well as perform detailed characterization of the induced T cell responses towards these neoantigen targets. Methods: Patient-specific neoantigens were predicted using our bioinformatic engine RECON. The predicted high quality neoantigens were utilized in our proprietary ex-vivo stimulation protocol NEO-STIM to assess immunogenicity. NEO-STIM is used to prime, activate and expand memory and de novo T cell responses from both the CD4+ as well as the CD8+ compartment. In-depth analysis was performed to characterize the specificity, functionality (cytokine production and cytolytic capacity) and diversity of the induced T cell responses. Results: Here we present the successful induction of memory and de novo CD8+ T cell responses in PBMCs isolated by leukapheresis from three patients using NEO-STIM (2 with melanoma &amp; 1 with NSCLC). We then deeply characterize the induced CD8+ T cell responses of one of the melanoma patients and show that these responses are functional, specific and have cytolytic capacity. Furthermore, we use paired single cell RNA and TCR sequencing to assess the diversity and gene expression profile of these responses. Conclusions: NEO-STIM is a novel platform to understand the immunogenic potential of high-quality neoantigen-targets in detail. Moreover, this platform can be utilized to generate T cell products for adoptive cell therapy for patients with a variety of solid and liquid tumors. Citation Format: Divya Lenkala, Jessica Kohler, Brian McCarthy, Michael Nelson, Rachel DeBarge, Yvonne Ware, Yuting Huang, Janani Sridar, Yusuf Nasrullah, Dewi Hartjano, Asaf Poran, Sejuti Sengupta, Joost H. van den Berg, Matt Goldstein, Richard B. Gaynor, Marit M. van Buuren. Detailed analysis of immune responses induced against patient-specific neoantigens using the ex-vivo induction protocol, NEO-STIM™ [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 580.
Economic Impact and Healthcare Utilization in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) in Routine Clinical Care in the United States (US) - a Claims Database Study
Authors: Aaron Galaznik, Jill A Bell, Laurie Hamilton, Augustina Ogbonnaya, Kristin Hennenfent, Michael T. Eaddy, Yaping Shou
Journal: Blood (2017)
Prognostic value of inositol polyphosphate-5-phosphatase expression in recurrent and metastatic cutaneous squamous cell carcinoma
Authors: Connor J. Maly, Helen J.L. Cumsky, Collin M. Costello, Jessica E. Schmidt, Richard J. Butterfield, Nan Zhang, David J. DiCaudo, Steven A. Nelson, Maxwell L. Smith, Shari A. Ochoa, Christian L. Baum, Thomas H. Nagel, Mark R. Pittelkow, Aleksandar Sekulic, Aaron R. Mangold
Journal: Journal of the American Academy of Dermatology (2019)
Tips on transitioning out of elite sport (judo): the athlete’s perspective
Authors: Patrick Dawson
Journal: British Journal of Sports Medicine (2019)

From the moment I started judo, I was obsessed. I started from a non-competitive sporting background at the age of 16 years old. I was extremely lucky as I walked into (what was at the time) the most successful judo club in Britain and fell in love with the sport (see figure 1). I pretty much stopped doing everything else as soon as I started doing judo!



Figure 1 
Technical practice with training partner, photo credits to Richard Goulding.



The two best results that I had in my career were World Cup gold medals in Buenos Aires in 2013 and in February 2014 in Sofia, Bulgaria. At that time, the world number 1 that I fought was pretty much unbeaten. These were two very good days!

### Sport becoming the essence of you

Any athlete who chooses to compete and train full-time makes their sport a way of life. It is the reason you get up, you eat and you sleep. There’s a great moral code that goes alongside judo and in its purest form, it is a pretty good way to a holistic lifestyle.

Little else mattered, and so I didn’t have the answers for how an athlete should prepare for the time that comes along when the motivation and drive by which you define yourself changes. This is specifically relevant to judo because it is an individual fighting sport. You don’t get …
From skeletal muscle weakness to functional outcomes following critical illness: a translational biology perspective
Authors: Jane Batt, Margaret S Herridge, Claudia C dos Santos
Journal: Thorax (2019)

Intensive care unit acquired weakness (ICUAW) is now a well-known entity complicating critical illness. It increases mortality and in the critical illness survivor it is associated with physical disability, substantially increased health resource utilisation and healthcare costs. Skeletal muscle wasting is a key driver of ICUAW and physical functional outcomes in both the short and long term. To date, there is no intervention that can universally and consistently prevent muscle loss during critical illness, or enhance its recovery following intensive care unit discharge, to improve physical function. Clinical trials of early mobilisation or exercise training, or enhanced nutritional support have generated inconsistent results and we have no effective pharmacological interventions. This review will delineate our current understanding of the mechanisms underpinning the development and persistence of skeletal muscle loss and dysfunction in the critically ill individual, highlighting recent discoveries and clinical observations, and utilisation of this knowledge in the development of novel therapeutics.
Hospitalization of hyperglycemic lung cancer patients during treatment
Authors: B. E. Martin, F. Mott, J. Song
Journal: Journal of Clinical Oncology (2009)

9560 Background: Approximately 20 million Americans have type 2 diabetes mellitus. This same group is at significant risk of developing malignancy. Evidence suggest that diabetics with colon and breast cancer experience inferior treatment outcomes. There are few direct comparisons of treatment outcome and/or treatment tolerability in those with and without hyperglycemia. There are no such comparisons in lung cancer patients. We anticipate those with hyperglycemia will tolerate treatment less well than those with euglycemia. With this premise, we assessed hospitalization risk between lung cancer patients with normal or elevated baseline serum glucose (BSG) prior to initial chemotherapy cycle. Methods: After obtaining institutional IRB approval, tumor registry analysis identified 364 consecutive individuals diagnosed with lung cancer between 2005 and 2007 at our institution. One hundred and fifteen were excluded: 71 not treated, 17 duplicate entries, 16 stage 1A lung cancer, 8 missing data, 2 glucose under 60 mg/dl, 1 admitted for chemotherapy. Demographic and cancer specific data were obtained from the registry. Chart review yielded: BSG, date of first chemotherapy cycle, date of hospitalization, neutrophil count at admission, radiation therapy 30 days before/after treatment. Data presented was analyzed using multivariate logistic regression. We utilized WHO strata for fasting whole blood glucose measurements. Those presenting with grade 3 (or greater) neutropenia were excluded. Results: See Table . Conclusions: Lung cancer patients with hyperglycemia are more likely to be hospitalized in the 30 days following their first cycle of cytotoxic chemotherapy. We used the WHO glucose strata to analyze our data. Compared to those with normal BSG, those with BSG between 110 and 126 mg/dl were twice as likely to be hospitalized, and those with BSG over 126 mg/dl had four times the risk. We feel this simple metric will improve clinician's treatment decisions. Prospective analysis of diabetic cancer outcomes is needed. [Table: see text] No significant financial relationships to disclose.
Concomitant weekly carboplatin (CB) and paclitaxel (P) with pelvic radiotherapy (RT) for the treatment of advanced cervical cancer (ACC): A FNCLCC gynecologic group phase I trial
Authors: C. Lhomme, T. Petit, R. Largillier, F. Mayer, A. Floquet, A. Rey, M. Jimenez, C. Haie-Meder
Journal: Journal of Clinical Oncology (2007)

5542 Background: Standard primary treatment for locally ACC is RT with concomitant chemotherapy (CT). CB and P are radiosensitizers with in vitro synergistic action. Methods: Patients (pts) with FIGO stage IIB-IVA negative paraaortic lymph nodes cervical cancer were treated with 6 weekly cycles of CT during pelvic RT (45 Gy) and brachytherapy (BT) according to Table 1 . Each dose escalation step followed a 30-day period of observation on cohorts of 3 to 6 pts depending on dose limiting toxicity (DLT): toxic death; garde (G) 4 neutropenia &gt; 1 week; G 4 toxicity (other hematologic or non-hematologic); any toxicity requiring = 1 week delay in RT, or &gt; 2 dose reductions of CT, or G 3/4 hematologic toxicity &gt; 3 weeks after treatment’s end; unendurable G 3 non hematologic toxicity. Results: 23 pts were included by 5 centers in 5 dose levels (L). Stage distribution: IIB (10), III (11), IVA (2); 20 epidermoid and 3 adenocarcinoma; ECOG: 0 (16), 1 (7). 22 pts received the 6 planned cycles. Median dose of irradiation was 45 Gy (43.2–50) with no toxicity related interruption. 17 pts underwent BT, 2 had hysterectomy and 1 received complementary external irradiation 12 Gy. CT dose reduction was necessary in 4 pts (cycle 5 or 6) and cycles postponed for 10 pts (cycle. 5 or 6). One pt experienced paclitaxel allergy at L1. G 3 anemia and/or neutropenia were reported in 11 pts and G 4 neutropenia = 1 week in 2 pts. Radiodermatitis occurred in 5 pts, asthenia in 3 and nausea in 1. One DLT was observed: unendurable G 3 asthenia + G 3 neutropenia and leucopenia at L3. Clinical and radiological complete response was obtained in 13 pts, 5 PRs and 2 SDs in 20 evaluable pts. Conclusions: Acceptable toxicity and optimal irradiation were possible at L4 in 7 pts. These doses are recommended for future phase II studies of concomitant CT/RT in ACC. [Table: see text] No significant financial relationships to disclose.
Effects of intralesional <sup>32</sup>P in refractory patients with head and neck tumors
Authors: W. C. Dempke, B. Gunawardena, B. Hesselt, R. Linke, K. A. Alimi
Journal: Journal of Clinical Oncology (2007)

16529 Background: The clinical outcome of refractory head and neck cancer patients remains poor despite novel treatment strategies. In this pilot study we investigated the efficacy of intratumoral injection of 32-P chromic phosphate in 14 patients with refractory head and neck cancers in terms of response rates and overall survival. Methods: Fourteen patients (median age: 59 years) with either cytostatic drug-resistant tumors or tumors known to be primarily chemotherapy-resistant were entered into the study. After sonographic determination of the tumor volume, 32-P chromic phosphate (74–555 MBq) was injected into the central part of the tumor under sonographic guidance. Follow-up investigations included serial scintigraphy, sonographic examinations, and hematologic studies. Results: Injection of 32-P chromic phosphate into refractory head and neck tumors resulted in remarkable regression. The median survival of all patients was 7.8 months (range: 4–16). The response rate (partial response) was 57% (8 patients). However, 6 patients (43%) did not respond to the treatment. In 3 patients thrombocytopenia (grade I/II) was observed, but no other side effects were apparent. Significant pathologic and anatomic changes within the tumor tissue were demonstrated. In all cases examined, formation of a cyst within the area of central activity, surrounded by a centrifugal necrotic ring and a marginal fibrotic structure, was found. Conclusions: Lack of persistent systemic or local side effects, as well as noteworthy efficacy, are properties of this novel regional treatment modality with 32-P chromic phosphate. This modality deserves consideration for further clinical trials. No significant financial relationships to disclose.
Redox dual-stimuli responsive drug delivery systems for improving tumor-targeting ability and reducing adverse side effects
Authors: Ruirui Li, Feifei Peng, Jia Cai, Dandan Yang, Peng Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2019)

Cancer is a big challenge that has plagued the human beings for ages and one of the most effective treatments is chemotherapy. However, the low tumor-targeting ability limits the wide clinical application of chemotherapy. The microenvironment plays a critical role in many aspects of tumor genesis. It generates the tumor vasculature and it is highly implicated in the progression to metastasis. To maintain a suitable environment for tumor progression, there are special microenvironment in tumor cell, such as low pH, high level of glutathione (GSH) and reactive oxygen species (ROS), and more special enzymes, which is different to normal cell. Microenvironment-targeted therapy strategy could create new opportunities for therapeutic targeting. Compared to other targeting strategies, microenvironment-targeted therapy strategy will control the drug release into tumor cells more accurately. Redox responsive drug delivery systems (DDSs) are developed based on the high level of GSH in tumor cells. However, there are also GSH in normal cell though its level is lower. In order to control the release of drugs more accurately and reduce side effects, other drug release stimuli have been introduced to redox responsive DDSs. Under the synergistic reaction of two stimuli, redox dual-stimuli responsive DDSs will control the release of drugs more accurately and quickly and even increase the accumulation. This review summarizes strategies of redox dual-stimuli responsive DDSs such as pH, light, enzyme, ROS, and magnetic guide to delivery chemotherapeutic agents more accurately, aiming at providing new ideas for further promoting the drug release, enhancing tumor-targeting and improving anticancer effects. To better illustrate the redox dual-stimuli responsive DDS, preparations of carriers are also briefly described in the review.