tbuckley/cabot-search huggingface dataset:
Abstract 20: Manipulating PHD2 to Promote Efficacy of Stem Cell Therapy for Myocardial Infarction
Authors: Wei Eric Wang, Dezhong Yang, Liangpeng Li, Yulan Peng, Wei Wang, Linda Ye, Dayue Duan, Xiongwen Chen, Steven R. Houser, Chunyu Zeng
Journal: Circulation Research (2014)

OBJECTIVE: Stem cell transplantation has had modest success as a treatment for myocardial infarction (MI). One of the limitations is the poor stem cell survival and function in the diseased microenvironment. We studied whether and how prolyl hydroxylase domain protein 2 (PHD2), a cellular oxygen sensor, enhances stem cell cardioprotective effects after transplantation into infarcted hearts. METHODS and RESULTS: Both adipose-derived stem cells (ADSCs) and bone marrow mesenchymal stem cells (BM-MSCs) were used. Stem cells were transduced with lentiviral short hairpin RNA to silence PHD2 (shPHD2) and intramyocardially injected into infarcted heart in mice. ADSCs reduced cardiomyocyte apoptosis, fibrosis, and infarct size (MI+ADSCs: 39.4±3.3%;MI+PBS: 48.4±4.5%) and improved cardiac function (MI+ADSCs: 43.8±5.6%; MI+PBS: 37.2±3.0%). shPHD2-ADSCs exerted significantly more protection (infarct size: 22.6±3.0%; LVEF: 67.3±6.8%; p&lt;0.05 vs. MI+ADSCs). PHD2 silencing induced greater ADSC survival (survival rate at 7 days post-transplantation: shPHD2-ADSCs: 14.7±4.2% vs. ADSCs: 3.4±0.8%, p&lt;0.05), which was abolished by HIF-1alpha silencing. No ADSC gave rise to cardiomyocyte and ADSCs induced cardioprotection was mainly induced by paracrine function. Conditioned medium from shPHD2-ADSCs decreased cardiomyocyte apoptosis. Insulin-like growth factor-1 (IGF-1) levels were 3.8 times higher in the conditioned medium of shPHD2-ADSCs than ADSCs, and depletion of IGF-1 attenuated the cardioprotective effects of shPHD2-ADSC-conditioned medium. NF-kappaB activation was induced by shPHD2 to stimulate IGF-1 secretion via binding to the IGF-1 gene promoter. A combination of HIF-1alpha silencing and IGF-1 neurtralization blocked the beneficial effects of shPHD2-ADSCs for MI. Similar findings were observed with BM-MSCs. CONCLUSIONS: PHD2 silencing promotes stem cell survival in infarcted hearts and enhances their paracrine function to protect cardiomyocytes. Its prosurvival effect on stem cells is HIF-1alpha dependent, while it enhances stem cell paracrine function through NF-kappaB-mediated IGF-1 upregulation. PHD2 silencing in stem cells may be a novel strategy for enhancing the effectiveness of stem cell therapy after MI.
Galactosyltransferase Isoenzyme II in the Detection of Pancreatic Cancer: Comparison with Radiologic, Endoscopic, and Serologic Tests
Authors: Daniel K. Podolsky, Mark S. McPhee, Elliot Alpert, Andrew L. Warshaw, Kurt J. Isselbacher
Journal: New England Journal of Medicine (1981)

We assessed the value of several serologic markers in detecting pancreatic carcinoma in a prospective study of 270 patients. The sensitivity and specificity of galactosyltransferase isoenzyme II (GT-II), carcinoembryonic antigen (CEA), alpha-fetoprotein, ferritin, C1q binding, and ribonuclease were determined. GT-II was the most sensitive (67.2 per cent) and specific (98.2 per cent) for discriminating between benign and malignant disease and was more sensitive and specific than CEA, the next most useful marker. Sensitivity was 64 per cent for ultrasound, 79.4 per cent for computerized body tomography (CBT), and 92.8 per cent for endoscopic retrograde cholangiopancreatography (ERCP). As a single test, only ERCP was more sensitive than GT-II, but more sensitive diagnoses resulted when GT-II was combined with ultrasound (92 per cent), CBT (88 per cent), or ERCP (100 per cent). Serum GT-II may be useful both by itself and in combination with imaging techniques in distinguishing benign from malignant pancreatic disease; however, this test does not discriminate between pancreatic carcinoma and other gastrointestinal neoplasms.
Combined analysis of two Phase II studies evaluating first-line erlotinib in NSCLC with EGFR mutation: JO22903/JO25567
Authors: Shinji Atagi, Koichi Goto, Takashi Seto, Nobuyuki Yamamoto, Tomohide Tamura, Kosei Tajima, Naohito Inagaki
Journal: Annals of Oncology (2015)
Prevention and Treatment of the Complications of Diabetes Mellitus
Authors: Charles M. Clark, D. Anthony Lee
Journal: New England Journal of Medicine (1995)

Diabetes mellitus is a chronic disease characterized by hyperglycemia and by complications that include microvascular disease of the eye and kidney and a variety of clinical neuropathies.1 Although diabetes is also associated with premature macrovascular disease, this review is limited to a discussion of retinopathy, nephropathy, and neuropathy. The pathophysiology of these complications of diabetes was recently reviewed in the Journal. 1 The specific association of microvascular disease and neuropathy with diabetes and the relation of the two complications to the duration of diabetes suggest that they are linked to hyperglycemia or a concomitant metabolic abnormality. The Diabetes Control and Complications . . .
Toll-like receptor 2–expressing macrophages are required and sufficient for rhinovirus-induced airway inflammation
Authors: Mingyuan Han, Yutein Chung, Jun Young Hong, Charu Rajput, Jing Lei, Joanna L. Hinde, Qiang Chen, Steven P. Weng, J. Kelley Bentley, Marc B. Hershenson
Journal: Journal of Allergy and Clinical Immunology (2016)
Chemotherapy-Induced Acral Erythema
Authors: M Pirisi, G Soardo
Journal: New England Journal of Medicine (1994)

Figure 1. Chemotherapy-Induced Acral Erythema. Acral cyanosis can be seen in a 61-year-old woman with non-Hodgkin's lymphoma. The lesions developed while the patient had severe neutropenia during a course of therapy consisting of methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin. The disorder is characterized by intense, painful erythema of the palms and soles, often culminating in the formation of vesicles or bullae. Chemotherapeutic agents are one of the known causes.
CBIO-16NON-STEROIDAL ANTI-INFLAMMATORY DRUGS ENHANCE THE THERAPEUTIC EFFECTS OF TEMOZOLOMIDE AND RADIATION AGAINST MALIGNANT ASTROCYTIC TUMOR CELLS IN VITRO
Authors: Kosuke Katayama, Kenichiro Asano, Hiroki Ohkuma
Journal: Neuro-Oncology (2015)

BACKGROUND: The present study aimed to define the anti-tumor effects of aspirin (ASA) and celecoxib (CXB) alone or combined with temozolomide (TMZ) and/or irradiation (XRT), against C6, U87MG and T98G malignant astrocytic tumor cell lines in vitro. METHODS: Cell viability, cell cycles and apoptosis were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, flow cytometry and terminal deoxynucleotidyl transferase-mediated nick end-labeling assays, respectively. RESULTS: Aspirin and CXB exerted similar anti-tumor effects by inducing cell cycle arrest and apoptosis. Aspirin and CXB induced the G0/G1 and G2/M phases of cell cycle arrest respectively, in all three malignant astrocytic tumor cell lines, whereas ASA with TMZ induced G2/M cell cycle arrest in the C6 and U87MG lines. The viability of malignant astrocytic tumor cell lines was reduced more effectively by ASA or CXB when combined with TMZ and XRT than by any of these agents alone or by a combination of any two modalities in the C6 and T98G cell lines. CONCLUSIONS: Both ASA and CXB enhance the therapeutic effects of concomitant XRT and TMZ and thus might serve as a novel strategy for treating malignant astrocytic tumors.
Familial Hypopituitarism with Large Sella Turcica
Authors: John S. Parks, Alfred Tenore, Alfred M. Bongiovanni, Rebecca T. Kirkland
Journal: New England Journal of Medicine (1978)

We studied endocrine function in three siblings with short stature and enlargement of the sella turcica. Sellar volumes were 5.9, 3.7 and 4.0 standard deviations above age-specific means. Computed tomography or pneumoencephalography showed full sellae without suprasellar extension. Basal thyrotropin levels were low despite hypothyroidism and increments were less than 3 micromicron per milliliter after thyrotropin-releasing hormone injection. Stimulated growth hormone levels were less than 5 ng per milliliter, declining to less than 2 ng per milliliter after thyroxine treatment. Both thyroxine and growth hormone treatments were required for rapid growth. Impaired thyrotropin responses to thyrotropin-releasing hormone distinguish these patients from most cases of idiopathic or familial deficiency of thyrotropin and growth hormone. Persistent deficiency of growth hormone during thyroxine treatment indicates that the defects is not limited to thyrotropin structure or release. The findings are compatible with either familial neoplasia of the anterior pituitary or a regulatory defect promoting anterior pituitary-cell hyperplasia and inhibiting thyrotropin and growth hormone release.
Contrasting Epidemiology of Acute Rheumatic Fever and Acute Glomerulonephritis
Authors: Alan L. Bisno, Iris A. Pearce, Hershel P Wall, Max D. Moody, Gene H. Stollerman
Journal: New England Journal of Medicine (1970)

Studies of streptococcal infection in the mid-South, where acute rheumatic fever and pyoderma nephritis occur in the same population, suggest quantitative and qualitative factors tending to reduce the frequency of acute rheumatic fever. Quantitatively, beta-hemolytic streptococci isolated from ambulatory patients with pharyngitis at City of Memphis Hospitals were characterized by relatively low percentages of Group A and M-typable strains and weak immune responses. Qualitatively, throat strains fell into the M and T serotypes generally associated with skin infections rather than with pharyngitis. In addition, there was a temporal disparity between the occurrence of acute rheumatic fever and acute glomerulonephritis in patients admitted to these hospitals. Despite the frequent isolation of "skin strains" from the throat, rheumatic fever did not appear during the peak of the pyoderma season. These findings support the concept that "pyoderma strains" of streptococci are associated with little or no rheumatic fever.
Running retraining to treat lower limb injuries: a mixed-methods study of current evidence synthesised with expert opinion
Authors: C J Barton, D R Bonanno, J Carr, B S Neal, P Malliaras, A Franklyn-Miller, H B Menz
Journal: British Journal of Sports Medicine (2016)

Running-related injuries are highly prevalent.Synthesise published evidence with international expert opinion on the use of running retraining when treating lower limb injuries.Mixed methods.A systematic review of clinical and biomechanical findings related to running retraining interventions were synthesised and combined with semistructured interviews with 16 international experts covering clinical reasoning related to the implementation of running retraining.Limited evidence supports the effectiveness of transition from rearfoot to forefoot or midfoot strike and increase step rate or altering proximal mechanics in individuals with anterior exertional lower leg pain; and visual and verbal feedback to reduce hip adduction in females with patellofemoral pain. Despite the paucity of clinical evidence, experts recommended running retraining for: iliotibial band syndrome; plantar fasciopathy (fasciitis); Achilles, patellar, proximal hamstring and gluteal tendinopathy; calf pain; and medial tibial stress syndrome. Tailoring approaches to each injury and individual was recommended to optimise outcomes. Substantial evidence exists for the immediate biomechanical effects of running retraining interventions (46 studies), including evaluation of step rate and strike pattern manipulation, strategies to alter proximal kinematics and cues to reduce impact loading variables.Our synthesis of published evidence related to clinical outcomes and biomechanical effects with expert opinion indicates running retraining warrants consideration in the treatment of lower limb injuries in clinical practice.
Dissolution of Cholesterol Gallstones by Chenodeoxycholic Acid
Authors: Rudy G. Danzinger, Alan F. Hofmann, Leslie J. Schoenfield, Johnson L. Thistle
Journal: New England Journal of Medicine (1972)

Seven women with gallstones were given 0.75 to 4.5 g per day of chenodeoxycholic acid, a primary bile acid, to promote micellar solubilization of cholesterol in bile. In Case 1 three stones that had remained unchanged in size during six years of observations disappeared after six months of treatment. A single stone in Case 2 and multiple calculi in Cases 3 and 4 progressively grew smaller during 14 to 22 months of chenodeoxycholic acid administration. Gallstone size did not change in the other three. Chenodeoxycholic acid and total bile acid pool sizes (measured in two patients), which were reduced before therapy, were markedly expanded by chenodeoxycholic acid, and the ratio of bile acids and lecithin to cholesterol in bile increased in all patients. Liver function and morphology remained normal; moderate dose-related diarrhea occurred. Chenodeoxycholic acid may offer medical treatment for cholesterol cholelithiasis in man.
Predicative value of [18F]-FDG PET scan for pathological complete response to neoadjuvant chemotherapy in breast cancer
Authors: L. Favier, A. Berriolo-Riedinger, B. Coudert, C. Touzery, J. Riedinger, M. Toubeau, L. Arnould, F. Brunotte, P. Fumoleau
Journal: Journal of Clinical Oncology (2007)

505 Background: To evaluate, in breast cancer patients treated by neoadjuvant chemotherapy, the early predictive value of the FDG uptake decrease for the assessment of the pathological complete response (pCR). Methods: Forty seven women with non metastatic with conventional imaging, non inflammatory, large or locally advanced breast cancer were included. Pathological tumour regression determined on surgical resection specimens served as the gold standard for the assessment of the neoadjuvant chemotherapy response. According to the Sataloff classification, patients were classified in two groups: patients with a pathological complete response (pCR) and patients with a pathological non complete response (non pCR). FDG uptake of breast lesions was evaluated before and after the first course of neoadjuvant chemotherapy, using Standard Uptake Value maximum (SUV) corrected by body surface area and glycaemia. Relations between baseline [ 18 F]-FDG uptake and clinical, histopathological and biological parameters were assessed by Mann-Whitney test. Predictive value of the FDG decrease for the assessment of the pCR was studied with logistic regression analysis. Results: An elevated baseline SUV was found independently associated with a high mitotic activity (p&lt;0.002), tumour grading (p&lt;0.004), high score of nuclear pleomorphism (p= 0.03) and positive hormonal receptor status (p&lt;0.005). After completion of chemotherapy, 11 (23%) of the 47 breast tumours examined at surgery showed a pCR while 36 (77%) showed a non pCR. The relative decrease (ΔSUV) after the first course of neoadjuvant chemotherapy was significantly greater in the pCR group than in the non pCR group (p&lt; 10 -4 ). A SUV decrease of 85.4% ± 21.9% in pCR patients versus 22.6% ± 36.6% in non pCR patients was found. ΔSUV&lt;-60% predicted pCR with an accuracy of 87%. With multivariate logistic regression analyses, ΔSUV&lt;-60% was the only predictive factor of the pCR Conclusions: In breast cancer patients treated by neoadjuvant chemotherapy, the FDG uptake decrease, after only one course of treatment, is an early and powerful predictor of the pCR. No significant financial relationships to disclose.
Modulation of IL-6 Release Subsequent to Airway Poly I:C Administration
Authors: KarryAnne K. Belanger, Walter C. Spear, Barbara A. Rolls, Spotswood Miller, Bing Tian, Gracie Vargas, Massoud Motamedi, Istvan Boldogh, Allan Brasier, Bill T. Ameredes
Journal: Journal of Allergy and Clinical Immunology (2016)
Treatment of Choice in Cancer of the Uterine Corpus
Authors: John B. Graham
Journal: New England Journal of Medicine (1956)

CANCER of the uterine corpus can be successfully treated in a number of ways. However, there is no unanimity concerning the best therapy. The following discussion is intended to evaluate the different methods and to aid in the development of a plan for the treatment of this disease.The types of treatment now employed are: total hysterectomy by either the abdominal or the vaginal route; radiotherapy; a combination of these two; and radical hysterectomy. These can be evaluated by their applicability, primary mortality and five-year survival without evidence of disease. Because the various methods of treatment are not equally applicable, . . .
Academic cancer researchers’ perspective on a federally mandated centralized comprehensive database of all cancer clinical trials results
Authors: Y. Novik, L. Escalon, L. Rolnitzky
Journal: Journal of Clinical Oncology (2009)

e17576 Background: Campbell et al. (2002) examined the data sharing habits of geneticists and other life scientists from universities that receive funding from the NIH and found that genetics researchers are refusing to share results with colleagues, hindering the ability to replicate published results. This has not been explored in cancer research. Data sharing, data transparency, and collaboration adds value to research by reducing redundancy (time, resources, exposing trial participants to unnecessary risk). In cancer research there are existing results databases from the NCI to caBIG. The purpose of this study is to ascertain from the perspective of academic cancer researchers whether there is a need for a federally mandated comprehensive database of all cancer clinical trial results. Methods: The 11 question online questionnaire addressed data sharing. Responses are presented as percents of respondents who agree with each statement accompanied by 95% confidence intervals (CI). The 24 respondents included physicians, research nurses, regulatory staff, data management, and administration who work in cancer research in an academic setting. Results: Overall, 92% (95% CI, 74–98%) agree that a centralized comprehensive database will reduce redundancy, 100% (95% CI, 86–100%) agree that disclosing results to fellow researchers will help researchers to design better cancer clinical trials, and 96% (95% CI, 80–99%) agree that there is a need for a federally mandated comprehensive database of all clinical trial results. On database access 100% (95% CI, 86–100%) agree for academic researchers, 58% (95% CI, 39–76%) agree for the pharmaceutical industry, 50% (95% CI, 31–69%) agree for trial participants, 29% (95% CI, 15–49%) agree for the public, and 21% (95% CI, 9–40%) agree for media. Conclusions: This study is a step in exploring how the academic cancer research community feels about data sharing. The study population is small and limited to a single institution. To support generalizability of the findings, it is necessary to enlarge the population by increasing the number of participants from the chosen institution and/or to include other academic institutions in future studies. No significant financial relationships to disclose.
Early mortality in multiple myeloma: the time-dependent impact of comorbidity: A population-based study in 621 real-life patients
Authors: Rafael Ríos‐Tamayo, Juan Sáinz, Joaquín Martínez‐López, José Manuel Puerta, Daysi‐Yoe‐Ling Chang, Teresa Rodríguez, Pilar Garrido, José Luís García de Veas, Antonio Romero, Lucía Moratalla, Elisa López‐Fernández, Pedro Antonio González, María José Sánchez, José Juan Jiménez‐Moleón, Manuel Jurado, Juan José Lahuerta
Journal: American Journal of Hematology (2016)

Multiple myeloma is a heterogeneous disease with variable survival; this variability cannot be fully explained by the current systems of risk stratification. Early mortality remains a serious obstacle to further improve the trend toward increased survival demonstrated in recent years. However, the definition of early mortality is not standardized yet. Importantly, no study has focused on the impact of comorbidity on early mortality in multiple myeloma to date. Therefore, we analyzed the role of baseline comorbidity in a large population-based cohort of 621 real-life myeloma patients over a 31-year period. To evaluate early mortality, a sequential multivariate regression model at 2, 6, and 12 months from diagnosis was performed. It was demonstrated that comorbidity had an independent impact on early mortality, which is differential and time-dependent. Besides renal failure, respiratory disease at 2 months, liver disease at 6 months, and hepatitis virus C infection at 12 months, were, respectively, associated with early mortality, adjusting for other well-established prognostic factors. On the other hand, the long-term monitoring in our study points out a modest downward trend in early mortality over time. This is the first single institution population-based study aiming to assess the impact of comorbidity on early mortality in multiple myeloma. It is suggested that early mortality should be analyzed at three key time points (2, 6, and 12 months), in order to allow comparisons between studies. Comorbidity plays a critical role in the outcome of myeloma patients in terms of early mortality. Am. J. Hematol. 91:700-704, 2016. © 2016 Wiley Periodicals, Inc.
Expression of Opioid Peptides in Tumors
Authors: D G Bostwick, W E Null, D Holmes, E Weber, J D Barchas, K G Bensch
Journal: New England Journal of Medicine (1987)

We looked for opioid peptides and their precursors in 108 tumors of both neuroendocrine and nonneuroendocrine origin, using a monoclonal "pan-opioid" antibody, 3-E7, which recognizes the tetrapeptide Tyr-Gly-Gly-Phe (the sequence responsible for pharmacologic activity in all known opioid peptides), in conjunction with polyclonal antibodies directed against representative peptides of each of the three precursors (alpha-endorphin, [met]enkephalin-Arg-Gly-Leu, and dynorphin B). Using the avidin-biotin immunoperoxidase technique, we observed consistent cytoplasmic immunoreactivity (at least focally) in all of 15 adrenal pheochromocytomas, all of 6 thyroid medullary carcinomas, and all of 5 pituitary adenomas. Opioid staining was also observed in parathyroid adenomas (8 of 9), pancreatic islet-cell tumors (7 of 10), carcinoid tumors from various sites (18 of 26), and paragangliomas (1 of 2). There was no immunoreactivity in pulmonary small-cell carcinomas, Merkel-cell tumors of skin, neuroblastomas, or any of the non-neuroendocrine tumors examined. The expression of alpha-endorphin, [met]enkephalin-Arg-Gly-Leu, and dynorphin B varied from tumor to tumor; however, positive staining with the "pan-opioid" antibody was found in each tumor containing at least one of the three precursors. Opioid peptide immunoreactivity was also detected in non-neoplastic cells of the adrenal medulla, pancreatic islets, pituitary, intestinal and bronchial mucosa, and intestinal myenteric plexuses. We conclude that opioid expression within tumors is most likely due to enhanced expression of a normal cell product and that opioid peptides are useful markers of neuroendocrine differentiation in many tumors.
Associations between dimensions of religious commitment and mental health reported in the American Journal of Psychiatry and Archives of General Psychiatry: 1978-1989
Authors: D B Larson, K A Sherrill, J S Lyons, F C Craigie, S B Thielman, M A Greenwold, S S Larson
Journal: American Journal of Psychiatry (1992)

The authors assessed all measures of religious commitment (N = 139) reported in research studies published in the American Journal of Psychiatry and Archives of General Psychiatry in 1978 through 1989 (N less than 35). For nearly two-thirds of the measures, the studies either made no hypotheses or reported no results concerning the relationship of religious commitment to mental health status. For the great majority of the measures assessed, the studies reported a positive relationship between religious commitment and mental health.