tbuckley/cabot-search huggingface dataset:
Phase II study of erlotinib in metastatic or unresectable malignant peripheral nerve sheath tumors (MPNST)
Authors: K. H. Albritton, C. Rankin, C. M. Coffin, N. Ratner, G. T. Budd, S. M. Schuetze, R. L. Randall, J. E. Declue, E. C. Borden
Journal: Journal of Clinical Oncology (2006)

9518 Background: MPNSTs are rare soft tissue tumors (STS) that are relatively resistant to chemotherapy. 26% have epidermal growth factor receptor (EGFR) amplification. In preclinical studies, NF1/p53 murine MPNSTs in vitro are stimulated by EGF and inhibited by EGFR inhibitors. We proposed to assess response rate (RR) to erlotinib in adult patients with unresectable or metastatic MPNST. Methods: Patients (pts) were required to have measurable disease, Zubrod performance status (PS) &lt;3, adequate organ function, no prior EGFR therapy, and centrally reviewed confirmation of diagnosis. Treatment was erlotinib 150 mg by mouth daily, in continuous 28 day cycles. Disease evaluation was performed every 2 cycles. Results: 24 pts enrolled in 22 months, from 13 institutions. 20 pts were deemed eligible. Median age was 45.3 years; 50% had neurofibromatosis. At enrollment, 15 had a PS of 0–1, 18 had metastatic disease, and 19 had unresectable disease. Pts were heavily pretreated: 9 pts had ≥ 2 prior regimens, 6 pts had 1 prior regimen, and 4 pts had no prior chemotherapy (1 unknown). 19 of 20 pts were assessable for toxicity: 6 pts had grade 3 toxicities; only 1 was hematologic (anemia). Mild rash (in 15 pts) and fatigue (in 8 pts) were the most common side effects. 20 pts were evaluable for response: 1 had stable disease after first evaluation and 19 had no response. Median progression-free survival was 2 months. 14 patients have died; median overall survival was 4 months. Because no objective responses were observed in the first stage of the study, it was closed to further accrual. Conclusions: We were able to accrue pts with a rare STS to a phase II histology specific study through a single adult cooperative group. In spite of preclinical promise of EGFR inhibition, erlotinib does not appear to be active in MPNSTs. To further understand the role of EGFR in MPNST, we are assessing EGFR expression immunohistochemically and performing quantitative PCR for genes altered by EGFR stimulation/inhibition on pt tumors. No significant financial relationships to disclose.
Decline in Mortality in Acute Rheumatic Fever in New Haven, Connecticut, 1920–1948
Authors: Robert W. Quinn, Julia P. Quinn
Journal: New England Journal of Medicine (1951)

IT HAS been suspected for two decades or more, both in the United States and in England, that the prevalence of rheumatic fever is declining. It has not been easy to document the fact in this country, as this disease and rheumatic heart disease§ are not reportable here. However, some reliance can be placed on morbidity and mortality surveys, and by means of such methods, crude as they are, evidence is now beginning to accumulate that the decline in morbidity rates for rheumatic fever and mortality rates for rheumatic heart disease is an actuality. Studies confirming this impression began with . . .
Abstract 3348: Naïve rat umbilical cord matrix stem cells abrogate mammary tumor growth through markedly enhanced tumor immune responses
Authors: Atsushi Kawabata, Naomi Ohta, Garret Seiler, Marla Pyle, Deryl Troyer, Masaaki Tamura
Journal: Cancer Research (2011)

Abstract Mesenchymal stem cells derived from the umbilical cord matrix (UCMSC) have great potential for therapeutic use in multiple diseases including cancer. We have demonstrated that un-engineered naïve human and rat UCMSC attenuate growth of several organ type tumors (Ayuzawa et al., Cancer Lett.2009; Ganta et al., Cancer Res, 2009, Doi et al., Cytotherapy 2010). Since UCMSC are easy to prepare in relatively large quantities and are poorly immunogenic in allogeneic transplantation, they are potentially useful in cancer therapy. However, the mechanism by which UCMSC attenuate tumor growth has not been studied rigorously. Hence, the objectives of this study were to examine the ability of UCMSC to control the growth of mammary tumors and to determine possible mechanisms by which UCMSC attenuate the tumor growth. Intratumoral injection of rat UCMSC markedly attenuated tumor growth of orthotopic Mat B III autografts in female F344 rat mammary gland. Histopathology of the tumors in the rat UCMSC group indicated that a large number of lymphocytes had infiltrated into the peritumoral area and were occasionally observed in the intratumoral area. Immunohistochemistry revealed that although CD3+ T lymphocytes were located mainly in the peritumoral area rather than in the intratumoral area, CD20+ cells were rarely seen suggesting that the majority of infiltrated lymphocytes in the rat UCMSC treated tumors were T cells. In addition, the treatment of rat UCMSC increased the CD 8+ cell infiltration throughout tumor tissue. CD68+ cells were scarcely observed in the tumors of the PBS control group but not in the rat UCMSC treated group. Transwell culture system-based in vitro migration assay revealed that rat UCMSC significantly enhanced migration of peripheral blood mononuclear cells. These results suggest that naïve rat UCMSC attenuated mammary tumor growth at least in part by markedly enhanced host immune responses against tumors. This research demonstrates that naïve rat UCMSC can be used as powerful anti-cancer therapeutic cells for breast cancer treatment. This work was supported by the Kansas State University (KSU) Terry C. Johnson Center for Basic Cancer Research, KSU CVM Dean's Fund, NIH P20 RR017686, p20 RR1556, R21CA135599 and Kansas Bioscience Authority research fund. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3348. doi:10.1158/1538-7445.AM2011-3348
Abstract 1292: β-catenin is activated in arsenic-transformed human bronchialepithelial cells and promotes angiogenesis .
Authors: Zhishan Wang, Brock Humphries, Chengfeng Yang
Journal: Cancer Research (2013)

Abstract Arsenic exposure represents a major health concern causing human cancers, yet the mechanism of arsenic carcinogenesis has not been elucidated. We and others recently reported that cell malignant transformation by arsenic is accompanied by epithelial to mesenchymal transition (EMT). However, the role of EMT in arsenic carcinogenesis is not well understood. Although previous studies showed that acute short term arsenic treatment stimulates angiogenesis, it remains to be determined whether cells that were malignantly transformed by long term arsenic exposure have a pro-angiogenic effect. The objective of this study was to investigate the effect of arsenic-transformed human bronchial epithelial cells that underwent EMT on angiogenesis and the underlying mechanism. It was found that the conditioned medium from arsenic-transformed cells strongly stimulated tube formation by human umbilical vein endothelial cells (HUVECs). Moreover, enhanced angiogenesis was detected in mouse xenograft tumor tissues resulting from inoculation of arsenic-transformed cells. Mechanistic studies revealed that β-catenin was activated in arsenic-transformed cells up-regulating its target gene expression including angiogenic-stimulating vascular endothelial growth factor (VEGF). Stably expressing microRNA-200b in arsenic-transformed cells that reversed EMT inhibited β-catenin activation, decreased VEGF expression and reduced tube formation by HUVECs. SiRNA knocking down β-catenin decreased VEGF expression. Adding a VEGF neutralizing antibody into the conditioned medium from arsenic-transformed cells impaired tube formation by HUVECs. It was further determined that the canonical Wnt signaling was not increased in arsenic-transformed cells. These findings suggest that EMT in arsenic-transformed cells promotes angiogenesis through activating β-catenin-VEGF pathway in the absence of elevated-canonical Wnt signaling. Citation Format: Zhishan Wang, Brock Humphries, Chengfeng Yang. β-catenin is activated in arsenic-transformed human bronchialepithelial cells and promotes angiogenesis . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1292. doi:10.1158/1538-7445.AM2013-1292
Abstract P2-02-06: Efficacy and Cost Benefit of Preoperative MRI in the Diagnostic Procedure for Operable Breast Cancer
Authors: Y Kojima, H Yamauchi, H Tsunoda, M Kikuchi, S Honda, A Yoshida, H Yagata, K Tsugawa, S. Nakamura
Journal: Cancer Research (2010)

Abstract Purpose The role of preoperative MRI for operable breast cancer is controversial. In this study, we evaluate the efficacy of preoperative MRI as a diagnostic tool to determine the most appropriate procedure (i.e; mastectomy or partial mastectomy) for operable breast cancer patients and cost saving benefit from selecting the most appropriate procedure. Patients and Methods From January 2006 to December 2007, we retrospectively studied 1149 patients. All of these patients were diagnosed with breast cancer and consequently underwent mammography (MMG), ultrasound (US) and MRI before surgery so as to determine the optimal procedure. We extracted all the cases which required changes in procedures due to the MRI findings, and compared the radiological data to the clinical and pathological outcomes. Furthermore, we studied the overall cost differences between using MRI and not using MRI. Results In seventy seven cases, 6.7% of the total, operational changes were made because of preoperative MRI findings, which resulted in better operational outcomes. The main reason for procedural changes was the MRI findings revealed more extensive lesions, which pathologically proven to be in situ lesions. In some cases, additional lesions were pointed out by the MRI, which led us to avoid undertreatment. Among 77 cases, 69 were pathologically proven to have accurate radiological diagnosis and appropriate procedural change with MRI. The positive predictive value of preoperative MRI for partial resection was 99.1% and that for total mastectomy was 97.1%. The calculated cost difference for appropriate procedural change with MRI compared with not using MRI was $4,340. From our data, in 69 cases among 1149 received this appropriate change, $260 per case would be saved, which assumed to be more than $130 million in a year. Conclusion Adding preoperative MRI in the diagnostic procedures for the accurate operation in breast cancer might be effective. Usage of MRI preoperatively also save the inappropriate cost in breast cancer operations. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-02-06.
Prognostic Value of SUVmean in Oropharyngeal and Hypopharyngeal Cancers
Authors: Kyoungjune Pak, Gi Jeong Cheon, Keon Wook Kang, June-Key Chung, E. Edmund Kim, Dong Soo Lee
Journal: Clinical Nuclear Medicine (2014)

We investigated whether SUV parameters, from PET, can provide prognostic information for patients with oropharyngeal or hypopharyngeal cancer.Forty-eight patients with oropharyngeal or hypopharyngeal cancer who underwent PET before treatment were enrolled. A volume of interest was placed on PET images covering the entire tumor volume and metastatic lymph nodes, and the SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured.With the use of Kaplan-Meier analysis, age, SUVmean, MTV, and TLG predicted decreased disease-free survival (DFS). However, SUVmax was not associated with DFS. In multivariate analysis, the variables were included in 3 separate models. An SUVmean2.5 was an independent prognostic factor for DFS. Other SUV parameters, such as MTV and TLG, were associated with trends toward a decreasing DFS.SUVmean of PET was an independent prognostic factor for DFS in patients with oropharyngeal and hypopharyngeal cancer.
Abstract 4540: Development of a biochemical High Throughput Screening (HTS) assay for chemical inhibitors of MALT1, a target for lymphoma therapeutics.
Authors: Dayong Zhai, Chih-Wen Shu, Paul Diaz, John C. Reed
Journal: Cancer Research (2013)

Abstract MALT1 plays critical role in antigen receptor-mediated lymphocyte activation and lymphomagenesis. MALT1 acts both as a scaffold protein to recruit upstream signal transducers and as an intracellular cysteine protease with proteolytic activity that cleaves substrate proteins involved in NF-kB induction. Dysregulation of MALT1 activity occurs in lymphoma as a result of chromosomal translocations that fuse the catalytic domain of MALT1 with portions of BirC3 (c-IAP2). Previous studies have shown that MALT1’s proteolytic activity is required for its participation in NF-kB induction and for promoting cell viability of certain types of lymphomas, particularly the activated B-cell (ABC) type of diffuse large B-cell lymphoma. To lay a foundation for discovery of drug-like chemical inhibitors of MALT1, we developed a fluorescence-based, biochemical assay for measuring protease activity of MALT1 in vitro in 384 and 1,536 well formats. The assay components included recombinant purified full-length MALT1 protein, the MALT1-binding protein, Bcl-10, and the fluorigenic substrate Ac-LRSR-AMC (Ac-Leu-Arg-Ser-Arg-7-amino-4-methylcoumarin). Experiments showed that addition of Bcl-10 increases MALT1‘s protease activity up to 20-40 fold. The high throughput screening (HTS) assay was validated with excellent Z’ factors (&amp;gt;0.7) in both 384 and 1,536 well formats, with performance remaining robust for more than 6 hours, and thus suitable for screening of large chemical libraries. The HTS assay was validated by performing pilot screens with two small collections of compounds enriched in bioactive molecules (n = 1280 for LopacTM and 2000 for SpectrumTM library), yielding confirmed hit rates of 0.2 % and 0.7%, respectively. Counter-screening assays were also generated using other types of intracellular cysteine proteases, specifically Caspase-3 and Autophagin-1 (ATG4B), for eliminating non-specific inhibitors. Various supporting cell-based assays have also been generated to support hit characterization. In conclusion, we have generated a robust biochemical HTS assays for detection of chemical inhibitors of the MALT1 protease. We plan to utilize the HTS assay for screening large compound libraries as a starting point for discovery of novel therapeutics for treatment of lymphoma, autoimmunity, and allograft rejection. Citation Format: Dayong Zhai, Chih-Wen Shu, Paul Diaz, John C. Reed. Development of a biochemical High Throughput Screening (HTS) assay for chemical inhibitors of MALT1, a target for lymphoma therapeutics. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4540. doi:10.1158/1538-7445.AM2013-4540
Assessment of the early regenerative therapeutic response in graft versus host disease using high definition technology with virtual i-Scan chromoendoscopy
Authors: Marietta Iacucci, Andrew Daly, Ahsan Chaudhry, Peter Duggan, Xianyong Gui, Jonathan Love, Subrata Ghosh
Journal: Endoscopy (2013)

The gastrointestinal tract is the second most commonly involved organ system in graft versus host disease (GvHD) following allogeneic stem cell transplantation, and its involvement is associated with a worse prognosis [1] [2]. White light endoscopy findings are nonspecific and often unhelpful in the diagnosis of GvHD and evaluation of its response to therapy. Conventional histological examination of intestinal biopsy samples still represents the gold standard in GvHD diagnosis [3]. Moreover, after allogeneic stem cell transplantation, it could be potentially dangerous to carry out multiple biopsies and may require transfusion of erythrocytes, platelets, or coagulation factors. Here, we describe novel endoscopic findings associated with healing of the colonic mucosa in a patient with GvHD, obtained by high definition (HD +) technology with i-Scan virtual chromoendoscopy (Pentax Medical, Tokyo, Japan).
SAT0442 Standardised core indicators of musculoskeletal health across europe: The eumusc.net project
Authors: A.D. Woolf, J. Erwin, L. Carmona
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> EUMUSC.NET is a three year project to raise and harmonise quality and equity of care of rheumatic diseases and other musculoskeletal conditions across the 27 EU Member States. A key objective of the EUMUSC.NET project is to provide evidence at a country level of the impact of Musculoskeletal Conditions in terms of health, social, employment and economic measures. In order to achieve this goal EUMUSC.NET set out to develop a set of core indicators that could provide the basis for measuring the impact of musculoskeletal health in each country on a consistent and regular basis and enable comparions to be made between Member States. <h3>Objectives</h3> To develop a set of core indicators to consistently measure the health, social, employment and economic impact of musculoskeletal health on countries in the EU27. <h3>Methods</h3> The set of core indicators was developed by a working group with representatives from 11 EU Member States. This group: Conducted a review of previous work on indicators for MSCand a review of national, European and international indicator sets for relevance to MSC; Consulted with experts including those from the UK Department of Health, the Centre for Public Health Forecasting and Fit for Work on development of the core indicator set; Developed a criteria for selection of indicators to include in a core set; Reviewed the availability and accessibility of data from national, European and international data sets; Drew up a draft set of core indicators for consultation with the working group and the wider EUMUSC network (representing 22 organisations across the EU). <h3>Results</h3> A core indicator set of 38 indicators across 8 domains was developed. These domains are: Incidence &amp; prevalence, Health services utilisation, Hospital services utilisation, Human resources, Disability &amp; social consequence, Health related quality of life, Co-morbidity and Population health. <h3>Conclusions</h3> The development of a set of core indicators for the collection of comparable, accessible, relevant data from across the EU Member States to measure the impact of MSCis a key step in achieving equity and quality of care for MSCacross Europe. The indicators can be used for the effective surveillance of MSCand will be an important tool for needs assessment, progress monitoring, planning and priority setting for MSCacross the Union. <h3>Disclosure of Interest</h3> None Declared
Polymicrobial Etiology of Acute Pelvic Inflammatory Disease
Authors: David A. Eschenbach, Thomas M. Buchanan, Helen M. Pollock, Patricia S. Forsyth, E. Russell Alexander, Juey-shin Lin, San-pin Wang, Berttina B. Wentworth, William M. McCormack, King K. Holmes
Journal: New England Journal of Medicine (1975)

We studied 204 women with acute pelvic inflammatory disease to delineate further the causes of that illness. Gonococci were recovered from 91. Gonococcal pili antibody rose or fell significantly in 12 of 18 patients with positive cultures and only two of 19 who had negative cultures and smears for Neisseria gonorrhaoea(P smaller than 0.005). N. gonorrhoeae was found in peritoneal exudate from eight of 21 patients with, and none of 33 without, cervical gonococcal infection. Among patients with severe disease, other bacteria were recovered from peritoneal exudates from five of 16 with, and 19 of 22 without, cervical gonococcal infection (P smaller than 0.025). Mixed anaerobic and aerobic bacterial peritoneal infection was common in nongonococcal pelvic disease. The most common species recovered were Bacteroides fragilis, peptostreptococci, and peptococci. Tuboperitoneal gonococcal infection probably causes pelvic inflammatory disease in most patients with cervical gonococcal infection, whereas polymicrobial tuboperitoneal infection probably causes most nongonococcal cases.A series of 204 women with acute pelvic inflammatory disease (PID) were studied to determine the microorganisms responsible for infection. Endocervical and blood cultures were performed. 91 of the 204 had gonococci recovered from cervical material. Among those whose cultures grew Neisseria gonorrhoeae, gonococcal pili rose or fell significantly in 12 of 18 patients with positive cultures and in only 2 of 19 who cultured negative (P .005). Peritoneal exudated bore N. gonorrhoeae in 8 of 21 patients with, and none of 33 without, cervical gonococcal infection. Other bacteria, including Bacteroides, peptostreptococci, and peptococci, were cultured from peritoneal exudates in 5 of 16 with and 19 of 22 without cervical gonococcal infection (P .025). When cervical gonococci are found, PID is probably caused by tuboperitoneal gonococci infection, whereas nongonococcal cases are probably caused by mixed, polymicrobial infections of the tuboperitoneum.
Prevention of Premature Birth
Authors: Robert L. Goldenberg, Dwight J. Rouse
Journal: New England Journal of Medicine (1998)

Preterm birth, which occurs in 11 percent of all pregnancies, is responsible for the majority of neonatal deaths and nearly one half of all cases of congenital neurologic disability, including cerebral palsy.1 Although all births before 37 weeks of gestation are considered premature, births before 32 weeks' gestation (2 percent of all births) account for most neonatal deaths and disorders.2 State and national vital statistics indicate that the incidence of preterm birth has risen over the past 15 years (Figure 1), and it remains twice as high among black women as among white women.35 Preterm birth is commonly categorized . . .
Radiation exposure during complex endovascular repair of the aorta
Authors: S. Kelly, M. Albayati, D. Gallagher, R. Dourado, A. Patel, P. Saha, A. Bajwa, T. El-Sayed, R. Salter, S. Abisi, T. Carrell, B. Modarai
Journal: International Journal of Surgery (2015)
UTILIDAD DE LA ENTEROSCOPIA DE BALÓN SIMPLE PARA EL ESTUDIO DE LA PATOLOGÍA DEL INTESTINO DELGADO
Authors: B Álvarez-Cuenllas, J Espinel Díez, LM Vaquero, E Pinedo, R Díez
Journal: Endoscopy (2013)

Introducción: la enteroscopia de balón simple (EBS) es una técnica cada vez más difundida, que permite la exploración de la mayor parte del intestino delgado. Objetivo: Analizar la utilidad diagnóstica-terapéutica de la EBS en la patología del intestino delgado. Material y Métodos: Análisis retrospectivo de las EBS realizadas en nuestro Hospital (Septiembre 2007-Junio 2013). Se analizaron las indicaciones, hallazgos, terapéutica, complicaciones y curso clínico posterior. Resultados: Se incluyeron 107 pacientes (edad media: 59,4 años, rango 15 – 84), 56,1% varones. Se realizaron 124 EBS (90 por vía oral, 34 por vía rectal). En 17 pacientes por ambas vías. La indicación más frecuente fue la HDOO (60 pacientes). En 48 pacientes (44,8%) la EBS fue normal. En 28 pacientes se encontraron angiodisplasias, siendo ésta la patología más frecuente, tratándose con argón todos los casos. Dos pacientes fueron diagnosticados de enfermedad celíaca, 6 de enfermedad de Crohn y 5 de tumores de intestino delgado. Se realizó polipectomía múltiple en 6 pacientes con síndrome de Peutz-Jeghers o PAF. Se colocó prótesis enteral con ayuda del EBS en 2 pacientes; se tomaron biopsias en 32 y se realizó dilatación de estenosis en uno. Se advirtieron 4 complicaciones: 2 casos de sangrado resueltos con tratamiento endoscópico y 2 casos de perforación. La EBS fue de utilidad clínica (aportó un diagnóstico, la terapéutica cambio el curso clínico) en 74 pacientes (69,1%). En 7, el problema no fue resuelto y en 26, por falta de datos evolutivos, desconocemos los Resultados: La prueba fue más eficaz en los sujetos con menor edad (72,4 vs. 79,3 años; p = 0,09). Conclusión: La EBS es una técnica eficaz y segura para el estudio y/o tratamiento de las enfermedades del intestino delgado. Aporta una incuestionable utilidad clínica en el curso evolutivo de la mayoría de los pacientes.