tbuckley/cabot-search huggingface dataset:
US needs $1.1bn to treat opioid addiction
Authors: Michael McCarthy
Journal: BMJ (2016)

President Barack Obama has proposed $1.1bn (£0.8bn; €1bn) in new funding to increase access to treatment for misuse of heroin and prescribed opioids, the White House said on 2 February.

Since the late 1990s, the US has seen the number of deaths related to prescription opioids and heroin use soar, reaching …
L’échoendoscopie de contraste harmonique pour le diagnostic différentiel des kystes du pancréas
Authors: M. Palazzo
Journal: Endoscopy (2015)

La découverte de kystes du pancréas sur une imagerie en coupes est une situation clinique de plus en plus fréquente. Les kystes mucineux (cystadénome mucineux et TIPMP) ont un potentiel de dégénérescence. La présence d’un nodule mural en échoendoscopie est une indication opératoire. La sensibilité de ce signe pour le diagnostic de malignité est excellente mais sa spécificité est moyenne. L’échoendoscopie de contraste harmonique est une technique permettant l’étude de la microvascularisation et permettrait la différenciation entre un pseudonodule tissulaire (mucus, débris nécrotique …) et un authentique nodule tissulaire tumoral. Le but de cette étude était d’évaluer l’intérêt de l’échoendoscopie de contraste pour le diagnostic différentiel des kystes du pancréas.
TCT-464 Comparison of Cutting Balloon Angioplasty for the Treatment of Restenosis with Bare Metal Stent; Neointimal Hyperplasia Tissue vs Neoatherosclerosis tissue
Authors: Maoto Habara, Kenya Nasu, Takahiko Suzuki, Mitsuyasu Terashima
Journal: Journal of the American College of Cardiology (2013)
<sup>18</sup>FDG‐PET/CT: 21st century approach to leukemic tumors in 124 cases
Authors: Isabel Cunningham, Brigett Kohno
Journal: American Journal of Hematology (2015)

Extramedullary tumors remain an obstacle to curing more acute leukemia patients. Their incidence is unknown because the presence of occult tumors that contribute to relapse is not routinely sought as in other cancers. No standard approach exists for treating tumors at most sites, apparent clinical response is typically followed by further tumors, and achievement of lengthy remission is uncommon. Body scanning with (18) FDG PET/CT now provides a means to identify the extent of occult tumors that enables directed tumor eradication and a way to evaluate tumor response. To evaluate its potential benefits, analysis was undertaken of 124 published cases scanned after apparent tumors were diagnosed. Clinical and radiologic exams underestimated extent of disease in over half of 100 cases. Among 70 cases that reported scans after various treatments, 70% achieved negative scans. Half relapsed subsequently but disease-free survivals up to 6 years were documented. These reported cases add to our knowledge of extramedullary leukemia in showing that further tumors are more likely than marrow relapse, clinical and radiologic evaluation of response is inadequate, intensive chemotherapy alone generally does not prevent progression and is associated with significant mortality, and tumor-directed plus systemic therapies appears the most effective approach, particularly to AML tumors. This analysis suggests this technology could increase our ability to eradicate all foci of leukemia, and identify tumors responsible for refractory, residual, and relapsed disease.
Early Introduction of Egg for Infants with Atopic Dermatitis to Prevent Egg Allergy: A Double-Blind Placebo-Controlled Randomized Clinical Trial
Authors: Osamu Natsume, Shigenori Kabashima, Junko Nakasato, Kiwako Yamamoto-Hanada, Masami Narita, Mai Kondo, Mayako Saito, Ai Kishino, Eisuke Inoue, Wakako Shinahara, Hiroshi Kido, Hirohisa Saito, Yukihiro Ohya
Journal: Journal of Allergy and Clinical Immunology (2016)
Allopurinol dose relative to renal function and risk of hypersensitivity reactions
Authors: Richard Day, Shuen-Iu Hung, Wen-Hung Chung
Journal: Annals of the Rheumatic Diseases (2016)

Allopurinol dose relative to renal function and risk of hypersensitivity reactionsWe thank Dr Corrado Campochiaro for the comments 1 on our paper examining the risks for severe cutaneous adverse reactions (SCAR) to allopurinol. 2 Dr Campochiaro notes that the ratio of baseline dose of allopurinol to glomerular filtration rate was not different to controls without allopurinol-SCAR in our patients with renal impairment (estimated glomerular filtration rate (eGFR) <30 mL/min) compared with Stamp et al, 3 who found a higher ratio in their patients with SCAR.First, Dr Campochiaro asks if any of our subjects were being dialysed as this reduces plasma oxypurinol concentrations.They were not.There is a difference in the two studies, however, that might explain this apparent contrast, apart from the additional point made by Dr Campochiaro that our patients had worse renal function than the patients in the Stamp et al study.In our study, the ratio of dose to eGFR is that on presentation with SCAR.We do not have data on starting doses for our patients or controls.This contrasts with Stamp et al who have starting doses as well as doses at the time of SCAR.Larger prospective controlled studies examining the hypothesis of Stamp et al that lower commencing doses in relation to eGFR might reduce the risk of allopurinol-SCAR are needed.
Phase I clinical trial of XK469 in patients with chemo-refractory solid tumors
Authors: A. M. Alousi, R. Parchment, R. Boinpally, S. Gadgeel, R. Weigand, J. McCormick, P. Lorusso
Journal: Journal of Clinical Oncology (2004)

2020 Background: XK469 is a member of the quinoxaline family of antitumor agents. Based on encouraging pre-clinical data, a phase I trial was conducted to determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD). Methods: We used a 2B accelerated titration (AT) schema with drug administered as a 5- minute IV infusion days 1–5 every 21-days. Starting dose was 9 mg/m2. Results: 19 patients (18 evaluable) (median age of 57 years, median performance status of 1) were enrolled. 14/ 19 patients were heavily pretreated receiving > 3 previous chemotherapies and 10/ 19 received prior radiation therapy. At 260mg/m2/day, 1/ 6 patients experienced a DLT- grade 4 neutropenia. The following non- DLT's (grade 2 or higher) were observed: grade 3 neutropenia and thrombocytopenia (1 patient), grade 2 fatigue (1 patient) and grade 2 alopecia (1 patient). GI toxicity was mild and limited to grade 1 nausea (3 patients) and grade 1 vomiting (1 patient). At dose level 12 (346 mg/m2/day), 2/ 2 patients experienced DLT's with one episode of febrile neutropenia and one grade 3 infection. The projected MTD is 260mg/m2/day. XK469 peak plasma levels and systemic exposure were proportional to dose from 9 to 346 mg/m2/day indicating that the drug exhibits linear pharmacokinetics. However, secondary peaks in the PK profiles and a rapid decline in drug level from 23 to 24 hours occurred in some patients. Drug infusion in the afternoon followed by dense sampling of levels during the elimination phase confirmed the hypothesis that the drug was being sequestered in the biliary system resulting in fluctuating drug levels. An in vitro prediction model for MTD that uses drug sensitivity of CFU-GM successfully predicted the MTD and individual patient risk for neutropenia. To date, there have been no responses to therapy. Conclusions: The 2B AT design proved efficient, successfully identifying MTD with only 19 patients despite 12 dose escalations. Traditional PK sampling designs were inadequate to describe XK469 disposition. Stem cell assays can be used to predict MTD and individual patients' neutropenic risk. No significant financial relationships to disclose.
Sequential therapy with vinorelbine followed by gemcitabine in patients with metastatic non-small cell lung cancer (NSCLC), performance status (PS) 2 or elderly with comorbidities: A multicenter phase II trial
Authors: J. Latreille, V. Hirsh, H. Kreisman, P. Desjardins, L. M. Ofiara, R. Whittom, S. Fox, M. D. Palayew
Journal: Journal of Clinical Oncology (2004)

7119 Background: Vinorelbine (V) and Gemcitabine (G) are active, well tolerated agents in NSCLC. They have different mechanisms of action and are easily administered on an outpatient basis. Methods: Forty-four patients (pts), 42 evaluable, were entered between August 2001 and May 2003. They received V 30 mg/m2 i.v. on Days 1 and 8 every three weeks, two cycles for stable disease (SD) or one (1) cycle after best response (BR) followed by G 1000 mg/m2 i.v. on Days 1 and 8 every three weeks, two cycles for SD or one cycle after BR. Then stable pts continued until progressive disease (PD) on V or G according to pts' preference. Thirty seven pts had stage IV and five pts stage IIIB disease, 32 males, 10 females, median age 75, 21 pts with ECOG PS 2, 17 pts with ECOG PS 1, and 4 pts with ECOG PS 0. Pts' comorbidities were cardiovascular, pulmonary, or neurological. Results: A total of 124 cycles of V were administered, median of 3 cycles per pt and 69 cycles of G, median of 1 cycle per pt. Sixteen pts (38 %) achieved partial response (PR), 11 pts on V and 5 pts on G, eleven pts (26.7 %) had SD, 7 pts on V and 4 pts on G. Of 24 pts with PD on V, three pts (12.5 %) responded to G. Median time to first PD was 3.5 months. Median survival has surpassed six months and eight pts (19 %) already survived over one year. Thirteen pts are still alive after six months of minimal follow-up. Toxicity was minimal, six pts had grade 2 leukopenia, two pts received red cell transfusions, no grade 3 or 4 toxicities were reported. Three pts had grade 2 fatigue and anorexia and one pt had grade 2 neuropathy. Conclusion: Our regimen offers an excellent palliative treatment with minimal toxicity for elderly pts with comorbidities or pts with poor PS. Sponsored by GlaxoSmithKline. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline
Prolyl Hydroxylase 3 Attenuates MCL-1–Mediated ATP Production to Suppress the Metastatic Potential of Colorectal Cancer Cells
Authors: Praveenkumar Radhakrishnan, Nadine Ruh, Jonathan M. Harnoss, Judit Kiss, Martin Mollenhauer, Anna-Lena Scherr, Lisa K. Platzer, Thomas Schmidt, Klaus Podar, Joseph T. Opferman, Juergen Weitz, Henning Schulze-Bergkamen, Bruno C. Koehler, Alexis Ulrich, Martin Schneider
Journal: Cancer Research (2016)

Hypoxia is a common feature of solid tumors. Prolyl hydroxylase enzymes (PHD1-3) are molecular oxygen sensors that regulate hypoxia-inducible factor activity, but their functions in metastatic disease remain unclear. Here, we assessed the significance of PHD enzymes during the metastatic spread of colorectal cancer. PHD expression analysis in 124 colorectal cancer patients revealed that reduced tumoral expression of PHD3 correlated with increased frequency of distant metastases and poor outcome. Tumorigenicity and metastatic potential of colorectal tumor cells over and underexpressing PHD3 were investigated in orthotopic and heterotopic tumor models. PHD3 overexpression in a syngeneic tumor model resulted in fewer liver metastases, whereas PHD3 knockdown induced tumor spread. The migration of PHD3-overexpressing tumor cells was also attenuated in vitro Conversely, migratory potential and colony formation were enhanced in PHD3-deficient cells, and this phenotype was associated with enhanced mitochondrial ATP production. Furthermore, the effects of PHD3 deficiency were accompanied by increased mitochondrial expression of the BCL-2 family member, member myeloid cell leukemia sequence 1 (MCL-1), and could be reversed by simultaneous inhibition of MCL-1. MCL-1 protein expression was likewise enhanced in human colorectal tumors expressing low levels of PHD3. Therefore, we demonstrate that downregulation of PHD3 augments metastatic spread in human colorectal cancer and identify MCL-1 as a novel downstream effector of oxygen sensing. Importantly, these findings offer new insight into the possible, context-specific deleterious effects of pharmacologic PHD inhibition. Cancer Res; 76(8); 2219-30. ©2016 AACR.
Intrathymic Restriction and Peripheral Expansion of the T-Cell Repertoire in Omenn Syndrome
Authors: Simona Signorini, Luisa Imberti, Silvia Pirovano, Anna Villa, Fabio Facchetti, Marco Ungari, Fabio Bozzi, Alberto Albertini, Alberto G. Ugazio, Paolo Vezzoni, Luigi D. Notarangelo
Journal: Blood (1999)
Abstract 15607: Renal Artery Stenting Causes Acute Proximal Tubule Dysfunction
Authors: Grant W Reed, Katherine Hoetzl, Steven T Haller, Pamela Brewster, Joseph I Shapiro, Christopher J Cooper
Journal: Circulation (2010)

Background:  The effects of renal artery stenting on renal function are not well understood. N-acetyl-β-D-glucosaminidase (NAG) is released from injured proximal tubule cells, and β-2-Microglobulin (B2M) reabsorption is dependent on proximal tubule function. We investigated if urine NAG and B2M are elevated at baseline in patients with renal artery stenosis, and if levels increase following stenting.   Methods:  Urine samples were collected from 30 healthy adults (Normals), 30 patients with atherosclerosis and risk factors for renal disease but not renal artery stenosis (Atherosclerosis), and 72 patients with stenosis undergoing renal artery stenting (RAS). In the RAS group, additional samples were obtained 24 hours and one month post procedure. Samples were measured by ELISA and corrected for urine creatinine. Statistical analysis was performed on the natural log transformed data of matched pairs, reported as mean±SD.   Results:  NAG was higher in RAS than in Atherosclerosis (1.4±1.5 U/g vs. 0.69±0.74 U/g; p=0.0066), and higher in Atherosclerosis than in Normals (0.38±0.37 U/g; p=0.0017 compared to Atherosclerosis, p=0.0001 compared to RAS). Likewise, B2M was higher in RAS than in Atherosclerosis (−3.2±2.2 μg/L vs. −4.2±0.86 μg/L; p=0.031), and higher in Atherosclerosis than in Normals (−5.6±1.30 μg/L; p=0.0019 compared to Atherosclerosis, p   Conclusions:  Proximal tubule injury is commonplace in patients with renal artery stenosis and is not fully attributable to risk factors such as atherosclerosis. Proximal tubule function appears to worsen in the 24 hours following stenting, but returns to baseline by one month.
Virus-Induced Duodenal Adenomas in Guinea Fowl
Authors: T T Kirev, I A Toshkov, Z M Mladenov
Journal: JNCI Journal of the National Cancer Institute (1987)

Polypous growths of the duodenal mucosa were induced in guinea fowls after iv inoculation o virus strain Pts-56. The growths developed in about 60% of the experimental birds after a latent period of 4-6 months. The chronologic study of the alterations in the duodenal mucosa revealed consecutive occurrence of focal lymphoid cell infiltrations of the propria, restricted crypt hyperplasia, and enlargement of the villi followed by the formation of tubulovillous and tubulous adenomas. The virus-induced neoplasia of the guinea fowl duodenal mucosa morphologically closely resembled small intestinal adenomas in humans. Their formal genesis was similar to that of experimental intestinal tumors induced by chemical carcinogens.
Abstract 14194: Is the High Prevalence of Atrial Fibrillation in End Stage Renal Disease Related to the Hemodialysis Procedure Itself?
Authors: Maurits S Buiten, M. K De Bie, J. I Rotmans, B Gabreels, W van Dorp, L. Van Erven, T.J. Rabelink, M.J. Schalij, J.W. Jukema
Journal: Circulation (2012)

Background. Atrial fibrillation (AF) is common in patients with end stage renal disease (ESRD) and is associated with an increased risk of complications such as stroke. Pathophysiology might be rel...
Possible correlation between SOCS1 methylation and EGFR exon 19 mutation but not exon 21 mutation in Chinese NSCLC patients
Authors: S. Lee, T. Mok, H. Li, A. Yim, I. Wan, K. C. Lam, A. Chan, K. F. To, Q. Tao
Journal: Journal of Clinical Oncology (2007)

18113 Background: Suppressor of cytokine signaling-1 (SOCS1) and -3 (SOCS3) interact with the epidermal growth factor receptor (EGFR) to bring about the ubiquination and degradation of the receptor. Silencing of SOCS1 and SOCS3 by methylation was postulated to regulate the IL-6R/JAK-mediated STAT3 activation. Its relationship to EGFR and EGFR mutations in lung cancer remains unclear. Here, we examined the relationship between EGFR mutations and methylation of SOCS1 and SOCS3 in Chinese NSCLC patients. Methods: EGFR mutations were assessed in DNAs from microdissected tumor cells. PCR products were purified and sequenced using the BigDye Terminator Cycle Sequencing Kit (Applied Biosystem) and the ABI 3100 Genetic Analyzer. For methylation analyses of SOCS1 and SOCS3, DNAs were extracted from paraffin sections of tumor tissues, bisulfite treated and analyzed by methylation- specific PCR (MSP). Results: Data is available from 9 lung cancer cell lines and 20 tumor samples. Five EGFR-wild type cell lines had methylation for SOCS1. We found EGFR exon 19 mutation in 5 (25%) tumors, exon 21 mutation (L858R) in 2 (10%) tumors, and 1 (5%) tumor had double mutations. Four of 5 (80%) tumors with exon 19 mutation and none (0%) of the tumors with exon 21 mutation had SOCS1 methylation, comparing to only 2 of 12 (17%) EGFR-wild type tumors had SOCS1 methylation. SOCS3 methylation was not detected in any of the primary tumors or cell lines. Conclusions: Our preliminary findings suggest that SOCS1 methylation might be positively correlated with EGFR exon 19 mutation but exclusive from exon 21 mutation. A following study with larger sample size is currently under way. SOCS1 methylation may explain the better tumor response associated with EGFR exon 19 mutation. No significant financial relationships to disclose.
Phase II clinical trial of imatinib mesylate in therapy of KIT and/or PDGF-Rα-expressing Ewing sarcoma family of tumors (ESFT) and desmoplastic small round cell tumors (DSRCT)
Authors: J. Chao, G. T. Budd, P. Chu, P. Frankel, D. Garcia, M. Junqueira, G. Somlo, J. Sato, W. A. Chow
Journal: Journal of Clinical Oncology (2008)

10547 Background: The prognosis in metastatic or recurrent ESFT remains poor despite the success of multiagent chemotherapy for localized tumors. In a Children’s Oncology Group phase II study (Ped. Blood Cancer Jan 2007 Epub) use of imatinib mesylate led to one partial response in 34 patients with ESFT or DSRCT. This was similar to another series (Proc ASCO. 22:9001, 2004) in which 0/13 patients with ESFT had a 4 month progression-free survival while receiving imatinib mesylate. We have previously shown that the receptor tyrosine kinases (RTKs), KIT and platelet-derived growth factor receptor-α (PDGF-Rα), are expressed on ESFT cell lines, and inhibition of RTK function with imatinib mesylate induced dose-dependent apoptosis after 48 hours of treatment (Proc AACR. 43:1668a, 2002). We carried out an open-label, Phase II trial to evaluate the effectiveness of imatinib mesylate for patients with recurrent ESFT or DSRCT that express the KIT and/or PDGF receptors. Methods: Patients ≥ 16 years of age with recurrent ESFT or DSRCT were selected for immunohistochemical evidence of expression ≥ 2+/4+ for either KIT or PDGF-Rα. A Simon two-stage design was employed. Imatinib mesylate was administered orally 400 mg twice/day for 28 days/course. Primary endpoint was response. Results: 36 patients were screened and 16 met eligibility criteria for KIT or PDGF-Rα expression. A total of 7 were enrolled and evaluated. One patient with PNET and 2+/4+ PDGRα and 1+/4+ KIT expression had a partial response after 6 courses with eventual progression 185 days after enrollment. 4 patients had confirmed progression after 1 cycle (range 18–49 days). Two patients were not evaluable due to one early death and one refusing further treatment prior to finishing one course. Toxicities included one patient with grade 3 nausea, one with grade 3 vomiting, one with grade 3 hypokalemia, and one patient with grade 4 anemia. Conclusions: This study intended to enrich the population with molecular factors that potentially predict response. Given the poor prognosis in patients with metastatic or recurrent ESFT, further studies with imatinib mesylate or other novel KIT and PDGF-Rα inhibitors are warranted in patients with KIT or PDGF-Rα expressing tumors. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis
A phase I study of the oral platinum agent satraplatin (S) in with capecitabine (C) in patients (pts) with advanced solid malignancies
Authors: K. Wisinski, M. Mulcahy, T. M. Kuzel, A. B. Benson, M. Agulnik, G. R. MacVicar, D. Desai, S. Yun, M. Petrone, W. Gradishar
Journal: Journal of Clinical Oncology (2008)

13554 Background: S, an oral platinum (P) compound, has single agent anti-tumor activity. C, an oral pro-drug of 5-FU, has efficacy against many solid tumors. Furthermore, P agents and 5-FU have synergistic activity in a variety of tumor types. Methods: The primary objective was to determine the maximally tolerated dose (MTD) of concurrent S and C. Secondary objectives were to evaluate the safety and efficacy of S and C. C was dosed at 825mg/m2 bid on days 1–14 of each 21 day cycle. S was given qd on days 1–5 starting at 60mg/m2 for the first cohort. If dose limiting toxicity (DLT) was not observed, the S dose was escalated by increments of 20mg/m2 for subsequent cohorts. Cycle 1 DLT was defined as ≥ grade (gr) 3 neutropenia or thrombocytopenia lasting for ≥5 days or gr 4 neutropenia with fever. Persistent gr 2 neuropathy or ≥gr 3 non- hematologic toxicities including neuropathy, gastrointestinal or renal toxicity were also DLTs. Eligible pts had treatment refractory metastatic/unresectable solid tumors, ECOG performance status ≤2, and adequate hematologic parameters and organ function. Prior exposure to C, 5-FU or P agents was allowed. Results: 22 pts (14 male; 8 female) were enrolled. Median age was 58 years (range 27–77) and 73% were Caucasian. All pts received at least 1 dose of study drug and had data available for toxicity. 6 DLTs occurred (2 DLTs at dose level 4). Therefore, S 100mg/m2 was the MTD. DLTs were predominantly gr 3 or 4 thrombocytopenia, but also included 1 pt each with gr 3 palmar-plantar erythrodysesthesia, febrile neutropenia and vomiting. Of the 18 pts for whom all data is available, adverse events (AEs) occurred in 83%. 72% had gr 3 or 4 AE with 61% having a serious AE. The majority of AEs were related to S and resulted in discontinuations of S in 33%. In addition, 20% pts had dose reductions and 52% had dose delays. Thrombocytopenia was the most frequent AE with 42% of pts having ≥ gr 3 events. 2 deaths due to disease progression were reported. Of 11 evaluable pts, no complete or partial responses were seen. Stable disease was noted in 54% of pts. Conclusions: The combination of S and C has significant toxicity in advanced solid tumors. The MTD for S was 100mg/m2. No complete or partial responses were seen. Additional data will be provided at the time of presentation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GPC Biotech, Inc Roche GPC Biotech, Inc GPC Biotech, Inc Roche