tbuckley/cabot-search huggingface dataset:
Treatment of aggressive metastatic epithelioid hemangioendothelioma (HE) with a combination of weekly paclitaxel and lipossomal doxorubicin
Authors: E. J. Buarque
Journal: Journal of Clinical Oncology (2008)

21519 EH is a rare, intermediate grade vascular sarcoma sometimes very aggressive with many sites of metastatic disease. It was first described by Weiss and Enzinger and could appear anywhere (liver, lungs, spine, retroperitoneal, etc.). The concurrent involvement of multiple sites or disseminated metastasis as first diagnosis could mimic other neoplastic processes. There are very few reports of treatment and most of the cases are a surgical approach. It is important to document any medical treatment of this disease. This patient was a 19-year-old young woman that was first examined in June 2005 in an emergency room, due to excruciating pain in thoracic column, numbness in lower limbs and difficulty in walking. A CT scan showed a large tumor that completely destroyed T4 with medullar compression. She was submitted to surgery that removes more than 70% of the tumor, with decompression of the medulla and stabilization of the column. After the patient completed recovery, a full radiological examination showed multiple bone, lung and liver metastasis, the last one evolving more than 75% of the liver with nodules heavily vascularized. Histopathologic and immunochemical findings of the tumor tissue supported the diagnosis of EH (strong expression of CD 34, CD 31, factor VIII and vimetin). She began chemotherapy in August 2005 with a scheme used for angiosarcomas: weekly paclitaxel 65 mg/m2 three times with a week rest and lipossomal doxorubicin 40 mg/m2 each month. She had only hematologic toxicity grade 3 reversible with GSF-C. After the third cycle, she had no symptoms and the CT scan revealed a partial response with 50% reduction in lung and liver metastasis. She received the same chemo scheme until June 2006 when she began radiotherapy in thoracic column and initiated zoledronic acid once a month. She has been in control since then in very good health, reassuming her normal life. Her last control in December 2007 the CT scan showed stable images. This case report contributes to show that EH is responsive to chemotherapy and the new anti-angiogenic drugs could be another option to treat this aggressive disease. No significant financial relationships to disclose.
LSC 2012 abstract - Endothelial progenitor cells and the endothelin system
Authors: Susanna Desole, Florian Albrecht, Helene Vogelsinger, Katharina Cima, Christian Kähler
Journal: European Respiratory Journal (2012)

Bone-marrow–derived endothelial progenitor cells (EPCs) might play a key role in the formation of new vessels. Endothelin-1 (ET-1) is known to modulate different stages of neovascularisation. We investigated a potential link between the ET system and EPCs in pulmonary hypertension (PH).  EPCs were isolated from Sprague-Dawley rats and rat pulmonary artery (paECs) endothelial cells served as positive control. ET-A and B receptor expression and detection of prepro-ET and ET converting enzyme (ECE) mRNA were performed by RT-PCR.  In calcium (Ca2+) flux assays EPCs loaded with FURA-2 were exposed to ET-1 [10-6M and 10-8M]. For selective inhibition of receptor subtypes, EPCs were pre-incubated with ETRA (BQ123) or ETRB (BQ788) antagonists for 20 min before stimulation with ET-1.  EPCs express both ET-receptor subtypes. Both prepro-ET-1 and ECE encoding mRNA could be detected in EPC. In Ca2+ flux experiments addition of ET-1 elicited a significantly increased intracellular Ca2+ flux which could be inhibited by BQ123 (96%) and BQ788 (45%).  We proved for the first time the expression of both ETRA and ETRB and detected mRNA of prepro-ET and of ECE on EPCs. We also found that ET-1 activates Ca2+ flux in EPCs. In summary, our data reveal for the first time a link between EPC and the ET system.
Automated identification of abnormal respiratory ciliary motion in nasal biopsies
Authors: Shannon P. Quinn, Maliha J. Zahid, John R. Durkin, Richard J. Francis, Cecilia W. Lo, S. Chakra Chennubhotla
Journal: Science Translational Medicine (2015)

An objective, computational method to quantitatively identify ciliary motion in digital videos of cells from patients with ciliopathies can be used for diagnosis.
A Translational Phase 2 Study of Cabozantinib in Men with Metastatic Castration Resistant Prostate Cancer with Visceral Metastases with Characterization of Circulating Tumor Cells and Large Oncosomes
Authors: E.M. Posadas, M. Tighiouart, Y. Lu, D. Di Vizio, D. Hoffman, L. Green, K. Scher, M. Sievert, A. Oppenheim, N. Moldawer, B. Knudsen, M. Freeman, N. Bhowmick, A. Rogatko, H. Tseng, L.W.K. Chung, R.A. Figlin
Journal: Annals of Oncology (2014)
Atrial Fibrillation in Patients With Brugada Syndrome
Authors: Kengo F. Kusano, Makiko Taniyama, Kazufumi Nakamura, Daiji Miura, Kimikazu Banba, Satoshi Nagase, Hiroshi Morita, Nobuhiro Nishii, Atsuyuki Watanabe, Takeshi Tada, Masato Murakami, Kohei Miyaji, Shigeki Hiramatsu, Koji Nakagawa, Masamichi Tanaka, Aya Miura, Hideo Kimura, Soichiro Fuke, Wakako Sumita, Satoru Sakuragi, Shigemi Urakawa, Jun Iwasaki, Tohru Ohe
Journal: Journal of the American College of Cardiology (2008)
Effect of Dietary Corn Bran and Autohydrolyzed Lignin on 3,2′-Dimethyl-4-aminobiphenyl-Induced Intestinal Carcinogenesis in Male F344 Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: B S Reddy, Y Maeura, M Wayman
Journal: JNCI Journal of the National Cancer Institute (1983)

The effect of dietary corn bran and autohydrolyzed lignin on 3,2'-dimethyl-4-aminobiphenyl (DMAB)-induced intestinal carcinogenesis was studied in male inbred F344 rats. Groups of weanling rats were fed semipurified diets containing 15% corn bran or 7.5% lignin or a semipurified diet without these fibers (control diet). At 7 weeks of age, all animals, except vehicle-treated controls, were given sc injections of 50 mg DMAB/kg body weight/week for 20 weeks. All animals were autopsied 20 weeks after the last injection of DMAB. The incidence of colon tumors (percentage of animals with tumors) and colon tumor multiplicity (tumors/animal) were increased in rats fed the corn bran diet as compared to the tumor incidence and multiplicity in rats fed the control diet. The incidence of small intestinal tumors was slightly lower in rats fed the corn bran diet as compared to the incidence in rats fed the control diet. The concentrations (mg/g dry feces) of fecal deoxycholic acid and total bile acids and the daily output of fecal deoxycholic acid, lithocholic acid, hyodeoxycholic acid, and total bile acids were increased in rats fed the corn bran diet as compared to the concentrations and daily output in rats fed the control diet. The incidence and multiplicity of small intestinal tumors as well as the number of colon adenocarcinomas per tumor-bearing animal were lower in animals fed the lignin diet than in those fed the control diet. Lignin had no effect on the concentrations of fecal bile acids, but the daily output of total bile acids was increased in animals fed the lignin diet as compared to the daily output in rats fed the control diet. This study thus indicates that the protection against colon cancer depends on the type of fiber.
Colorectal cancer risk factors in patients with serrated polyposis syndrome: a large multicentre study
Authors: Sabela Carballal, Daniel Rodríguez-Alcalde, Leticia Moreira, Luis Hernández, Lorena Rodríguez, Francisco Rodríguez-Moranta, Victoria Gonzalo, Luis Bujanda, Xavier Bessa, Carmen Poves, Joaquin Cubiella, Inés Castro, Mariano González, Eloísa Moya, Susana Oquiñena, Joan Clofent, Enrique Quintero, Pilar Esteban, Virginia Piñol, Francisco Javier Fernández, Rodrigo Jover, Lucía Cid, María López-Cerón, Miriam Cuatrecasas, Jorge López-Vicente, Maria Liz Leoz, Liseth Rivero-Sánchez, Antoni Castells, María Pellisé, Francesc Balaguer
Journal: Gut (2015)

Serrated polyposis syndrome (SPS) is associated with an increased colorectal cancer (CRC) risk, although the magnitude of the risk remains uncertain. Whereas intensive endoscopic surveillance for CRC prevention is advised, predictors that identify patients who have high CRC risk remain unknown. We performed a multicentre nationwide study aimed at describing the CRC risk in patients with SPS and identifying clinicopathological predictors independently associated with CRC.From March 2013 through September 2014, patients with SPS were retrospectively recruited at 18 Spanish centres. Data were collected from medical, endoscopy and histopathology reports. Multivariate logistic regression was performed to identify CRC risk factors.In 296 patients with SPS with a median follow-up time of 45 months (IQR 26-79.7), a median of 26 (IQR 18.2-40.7) serrated polyps and 3 (IQR 1-6) adenomas per patient were detected. Forty-seven patients (15.8%) developed CRC at a mean age of 53.9±12.8, and 4 out of 47 (8.5%) tumours were detected during surveillance (cumulative CRC incidence 1.9%). Patients with >2 sessile serrated adenomas/polyps (SSA/Ps) proximal to splenic flexure and ≥1 proximal SSA/P with high-grade dysplasia were independent CRC risk factors (incremental OR=2, 95% CI 1.22 to 3.24, p=0.006). Patients with no risk factors showed a 55% decrease in CRC risk (OR=0.45, 95% CI 0.24 to 0.86, p=0.01).Patients with SPS have an increased risk of CRC, although lower than previously published. Close colonoscopy surveillance in experienced centres show a low risk of developing CRC (1.9% in 5 years). Specific polyp features (SSA/P histology, proximal location and presence of high-grade dysplasia) should be used to guide clinical management.
Role of priority setting in implementing universal health coverage
Authors: Yot Teerawattananon, Alia Luz, Churnrurtai Kanchanachitra, Sripen Tantivess
Journal: BMJ (2016)

When is a country financially ready to implement universal health coverage (UHC), a health policy designed to ensure that all citizens receive the health services they need without financial hardship? Since no standard set of essential health services or a defined benefits package for universal coverage exists, determining financial readiness is challenging. Health priorities must be set knowing what services are to be provided, to whom they will be provided, and how. Priority setting helps determine the financial requirements for UHC, and thus the financial capacity of a country to adopt it. Setting priorities also helps decide on the benefits package that is feasible given current resource constraints. Countries can deliver a limited benefits package and identify priorities for expansion should additional resources become available. In either scenario, priority setting is essential for any country committed to universal coverage. Priority setting can be explicit or implicit. Governments should favour explicit rationing, wherein the decisions and their justifications are clear, rather than strategies of implicit rationing such as denial, deterrence, deflection, delay, and dilution. In 2015, the UN General Assembly made a global commitment to UHC and the sustainable development goals. 4 As such, more emerging economies will commit to UHC. Explicit priority setting, however, requires dedicated resources, which are more readily available in wealthier countries. In 1912, Norwaywas the first country to introduce UHC. Several other high income countries followed, but 64 years passed before Cuba became the first middle income country to introduce UHC legislation in 1976. By 2015, 58 countries had achieved universal coverage, of which 22 did so while they were low or middle income countries (LMICs). 5 Thus, the challenge that remains is supporting countries with limited capacity to implement UHC and set priorities explicitly. Health priority setting in support of UHC requires capacity and resources, as well as persuasive evidence to justify decisions (figure). This involves two major steps: evidence generation and use of evidence in resource allocation, programme management, and quality assurance. Priority setting in health systems is complicated by a wide range of political, economic, ethical, and sociocultural factors. An explicit process requires four building blocks (box).
Phase I study of NPI-2358 (a novel vascular disrupting agent) in patients with solid tumors and lymphomas
Authors: A. C. Mita, L. K. Yee, K. P. Papadopoulos, E. I. Heath, O. Romero, G. K. Lloyd, G. Cropp, M. A. Spear, M. M. Mita, P. M. LoRusso
Journal: Journal of Clinical Oncology (2008)

3525 Background: NPI-2358 is a novel vascular disrupting agent (VDA) acting on tubulin dimerization that destabilizes tumor vascular endothelial cells and has cytotoxic activity. NPI-2358 selectively induces tumor vascular collapse and tumor regression in murine tumor models and potentiates other oncology agents. Preclinical data suggest NPI-2358 may have advantages in terms of safety profile and activity. Methods: Dose escalation of NPI-2358 was conducted in a phase I trial enrolling patients with advanced solid tumors and lymphomas. Patients were treated with a weekly IV infusion of NPI-2358 for 3 weeks in 4-week cycles. The study utilized a dynamic accelerated dose titration (DADT) design in which the dose of NPI-2358 would be escalated in cohorts from 2 mg/m2 to a recommended phase II Dose (RP2D). Any cohort could consist of 1 patient provided no ≥ Grade 2 adverse event (AE) is reported in the prior cohort. If a ≥ Grade 2 AE is reported in the prior cohort, the cohort consisted of at least 3 patients. In addition to weekly safety monitoring, ECG, ECHO and PK were obtained on D1 & D15. DCE-MRI were utilized to assess changes in tumor blood flow. Results: 25 subjects were enrolled. 30 mg/m2 was selected as the RP2D (predicted minimum efficacious dose = 7.5 mg/m2), based on toxicities of nausea, vomiting, fatigue, fever, tumor pain and transient elevations in blood pressure. DCE-MRI demonstrated decreases in Ktrans beginning at 13.5 mg/m2, and a 16–54% decrease in patients evaluated at 30 mg/m2. Five patients had stable disease for two or more cycles: pancreatic adenocarcinoma (4 cycles), colorectal carcinoma (2 cycles), anal squamous cell carcinoma (3 cycles), adrenalcortical carcinoma (2 cycles) and melanoma (2 cycles). Average Cmax and AUClast have increased from 34 to 468 ng/ml, and from 101 to 1518 ng/ml*hr respectively. No drug accumulation was observed. For all patients T1/2 was 5.3 ±2.8 h, CL was 37.3±28 L/h and Vss was 214±63 L. Conclusions: NPI-2358 generally produced modest toxicity at the RP2D, which was significantly above the predicted efficacious dose and elicited decreases in tumor blood flow by DCE-MRI. Cmax and AUC increased with dose, without drug accumulation. NPI-2358 is currently entering Phase 1b/2 trials in solid tumor malignancies. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Nereus Nereus Nereus Nereus
Survival data of 87 adenocarcinomas of the pancreas
Authors: V. Casneuf, P. Demetter, L. Delrue, B. de Hemptinne, M. Peeters
Journal: Journal of Clinical Oncology (2005)

4248 Background: Pancreatic adenocarcinoma carries one of the worst prognoses among all cancers. This study aimed to determine the exact disease free and overall survival data of patients with a pancreatic adenocarcinoma, who underwent an intentive curative resection in our institution between 1992 and 2003. Methods: A retrospective analysis of survival data of consecutive cases of adenocarcinoma of the pancreas was performed. Patients of whom medical files and survival data could be traced until November 2004 or until date of death were included. Disease free survival (DFS) was defined as the time period between date of surgery until clinical, biochemical, radiological and/or pathological evidence of tumor activity. Overall survival (OS) was calculated from surgery until death or survival in November 2004. Differences in mean DFS and OS were analysed using ANOVA of the logarithmic transformation of the variable. Results: Eighty-seven patients were included: 58 men and 29 women. Mean age at diagnosis was 60.8 years (range 32–80). Eighteen patients were alive at the time of writing. Four patients died within 2 months postoperative due to cardiopulmonary complications and are excluded from the analysis. The pathological classification according to UICC (6th edition) was 9 T1, 16 T2, 49 T3, 3 T4 and 6 TX. Twenty-eight were N0, 43 N1 and 12 NX. Mean DFS for T1 was 25.7 months (95% CI 3.8–47.7), for T2 21.8 months (95% CI 8.0–35.5), for T3 16.9 months (95% CI 11.6–22.1) and for T4 5.0 months (range 2–8). These differences were not significant. Mean OS for T1 was 31.1 months (95%CI 11.1–51.1), for T2 33.0 months (95%CI 16.7–49.2), for T3 19.3 months (95%CI 15.3–23.3) and for T4 9.6 months (range 3–17). There were no significant differences found. Mean DFS for N0 [23.2 months (95%CI14.2–32.3)] was significant different from N1 [11.3 months (95%CI 6.5–16.2)](F=6.18, P<0.05). Also a significant difference was found between mean OS for NO [28.6 months (95%CI 20.6–36.7)] and for N1 [20.0 months (95%CI 13.8–26.3)](F=4.36, P<0.05). Conclusion: No difference was found in DFS and OS according to T-status. A significant better DFS and OS was found in node-negative pancreatic adenocarcinomas. No significant financial relationships to disclose.
Association between primary biliary cirrhosis and coeliac disease Primary biliary cirrhosis and coeliac disease: a study of relative prevalences Reply
Authors: W DICKEY, S A MCMILLAN, H M FIDLER, P BUTLER, A K BURROUGHS, N MCINTYRE, C BUNN, M MCMORROW, R WALMSLEY, J DOOLEY, J G C KINGHAM, D R PARKER
Journal: Gut (1998)
Emergence of an Epidermis-Associated Cell Surface Antigen In Epithelial Cells of the Rat Urinary Bladder in Carcinogenesis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Takashi Masuko, Yoshiyuki Hashimoto
Journal: JNCI Journal of the National Cancer Institute (1981)

Inbred ACI/N rats were treated with a selective urinary bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamin (BBN). Two cell surface antigens on the epithelial cells of the bladder, normal bladder epithelium (NBE) antigen unique to normal epithelial cells of the bladder and BC-SK antigen specific for bladder cancer and epidermis, were periodically assayed by mixed hemadsorption test with the typing sera against each antigen. Treatment with BBN for 8 or more weeks induced papillomas or cancers that expressed a definite level of BC-SK antigen, whereas a 4-week treatment did not render the bladder cells with a significant level of this antigen. In general, the level of NBE antigen in bladder cells was not altered by the BBN treatment. In vitro culture of bladder cells of BBN-treated rats resulted in an increase in the level of BC-SK antigen as opposed to a decrease in the NBE antigen level. BC-SK antigen was not detected in epidermal cells of rats younger than 3 days, but it emerged in these cells by in vitro culture for longer than 4 days.
Safety and efficacy of biosimilar epoetins
Authors: H. Schellekens, D. Khayat
Journal: Journal of Clinical Oncology (2004)

8224 Background: Patents of innovator biopharmaceutical products, such as epoetin, are starting to expire allowing biosimilar versions of these products to eventually enter European and American markets. Generic drugs typically gain market approval via an abridged procedure demonstrating physicochemical similarity and bioequivalence. This concept cannot be applied to biopharmaceuticals because current analytical methods are inadequate to fully characterize these complex proteins. Ambiguous requirements for biosimilar products to gain approval for these markets have some manufacturers of biosimilar epoetins planning large, lengthy Phase III trials similar to those of an innovator product, while others expect to gain approval for all indications with a small study in Chronic Renal Failure (CRF) patients. This study compared biosimilar epoetin products to epoetin alfa and evaluated the quality and rigor of clinical studies performed with these products. Methods: Epoetin preparations marketed outside western markets were analyzed by high performance liquid chromatography, western blot, radioimmunoassay, in vitro and in vivo bioassays and isoelectric focusing. Clinical studies were assessed for: target population; study scope and design; quality and rigor. Results: Products differed widely in composition, did not always meet self-declared specifications and exhibited batch-to-batch variation. Results from in vivo bioassays ranged from 71–216% of specified bioactivity; some products tested comparable to epoetin alfa. The main target population was CRF patients, only 2 studies targeted cancer patients. The average per study was 89 patients and duration of 19 weeks. Of the 22 studies analyzed, most were uncontrolled, with 4 placebo-controlled and 4 competitor-controlled, including 1 crossover study. Tachyphylaxis, consistent with antibody formation, was reported in 1 study. Conclusions: The epoetins analyzed were variable and often mislabeled, which could cause under or overdosing of patients and undesired clinical effects. The clinical studies were not rigorous enough to demonstrate safety and efficacy of a biopharmaceutical product, highlighting the need to define strict standards. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotech Johnson & Johnson
Abstract 10808: Speckle Tracking And Conventional Doppler Analysis Of Cardiac Function In Small For Gestational Age Infants
Authors: Arvind Sehgal, Tejas Doctor, Samuel Menahem
Journal: Circulation (2013)

Aims: Speckle derived strain echocardiography is an emerging technique for assessing cardiac function. Small for gestational age infants are characterised by perinatal mortality and morbidity. The ...