tbuckley/cabot-search huggingface dataset:
Effect of Glucocorticoids on Plasma Insulin
Authors: Michael Perley, David M. Kipnis
Journal: New England Journal of Medicine (1966)

ALTHOUGH the diabetogenic activity of adrenoglucocorticoids has been studied extensively in terms of increased gluconeogenesis and impaired peripheral glucose utilization1 2 3 4 the effects of these steroids on pancreatic islet-cell function have not received much attention. In the present study the effect of the synthetic glucocorticoid dexamethasone on the plasma insulin response of normal, mildly diabetic and acromegalic subjects to oral administration of glucose and intravenous administration of tolbutamide has been determined. In addition, since increased gluconeogenesis is a characteristic feature of glucocorticoid action, the effect on the response of insulin secretion to intravenously infused tolbutamide in mild hyperglycemia maintained by prolonged . . .
Telomere dysfunction in prostatic carcinogenesis: The crognostic importance of telomere length in HPIN (high-grade prostatic intraepithelial neoplasia)
Authors: Anthony M. Joshua, Bisera Vukovic, Ilan Braude, Andrew J. Evans, John R. Srigley, Jeremy A. Squire
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4992 

One of the major types of genetic instability in human malignancies is characterized by abnormal karyotypes, featuring both structural and numerical chromosome abnormalities and is termed chromosomal instability (CIN). CIN has been demonstrated in both carcinoma of the prostate (CaP) and high-grade prostatic intraepithelial neoplasia (HPIN). Both the chromosomal and genetic changes observed in HPIN are similar to those seen in primary CaP. Telomeres are the terminal repeated DNA sequence associated with specific binding proteins of eukaryotic chromosomes. Natural shortening of telomeres with each cell division has been thought to act as a mitotic clock limiting the replicative potential of the cell. Excessive telomere shortening leads to end-to-end chromosomal fusion thereby to unstable chromosomal rearrangements and cell death. This laboratory previously found a significant decrease in telomere length in both HPIN and CaP in comparison to normal prostatic epithelium and more erosion evident in HPIN in the discrete regions of the prostate containing CaP. Therefore we hypothesise that the loss of telomere integrity and the resulting chromosomal instability (CIN) is an early fundamental event in CaP oncogenesis and that measurement of telomere length in HPIN associated with telomere dysfunction will provide prognostic information about progression to CaP and clinical outcome. We have analysed sextant core biopsies from 80 patients with HPIN from 1998-2000 (41 diagnosed subsequently with CaP and 39 without CaP on rebiopsy) with a minimum clinical and pathological follow up of 4 years. To correlate the morphology of fluorescently labelled and DAPI-counterstained tissue sections containing HPIN, an adjacent H&E section has been obtained for each biopsy studied. To examine telomere length distribution within HPIN in the cohort, we have used quantitative fluorescence in-situ hybridisation (Q-FISH) analysis of interphase nuclei in paraffin embedded sections with directly labelled telomere specific PNA probes as the resulting fluorescence emission is known to be directly proportional to telomere length. Internal control probes for centromere intensity have also been used. Current pathways of HPIN to CaP involving genes such as PTEN and ETS transcription factors are simultaneously being investigated. Statistical associations between telomere length in the HPIN sample, gene detection and the subsequent diagnosis of cancer and the Gleason score will be reported. These analyses will help determine whether telomere erosion provides a useful biomarker for the development of prostate cancer and reveal mechanisms underlying genomic instability in this neoplasm.
Ultrastructural and Complement-Fixation Studies on Suspension Cultures Derived From Human Solid Tumors
Authors: Albert J. Dalton, Ursula Heine, Joan M. Kondratick, Dharam V. Ablashi, Elizabeth A. Blackham
Journal: JNCI Journal of the National Cancer Institute (1973)

A series of 42 individual cell cultures from 55 separate biopsies of human solid tumors have been made. Ten of these cell lines developed into suspension cultures at intervals of from 5 to 7 days to 3 months after the cultures were started. Four of these Iines were apparently derived from normal cells present in the stroma of the tumor. The derivation of the cells of the other 6 isolates is uncertain. In complementfixation tests of donor serum,S were negative for cytomegalovirus (CMY) antibodies and 5 were positive for Epstein-Barr virus (EBV) cnfibedles, In 8 of the 10 isolates, herpes-type virions were identified by electron microscopy. In the 2 isolates in which herpes-type virions were not found the donor sera were positive for CMY antibodies and negative for EBY antibodies. The serum of the donor of 1 isolate in which herpes-type virions were found was anticomplementary. Tubuloreticular modifications of the endoplasmic reticulum were present in some of the cells of all 10 isolates. The significance of these results is discussed in relation to the presently accepted view of the importance of EBY in the development of lymphoid suspension cultures.
Transmetatarsal Amputations and Arterial Surgery in Diabetic Patients
Authors: Frank C. Wheelock
Journal: New England Journal of Medicine (1961)

DIABETIC patients, for reasons not well understood at present, are much more liable than nondiabetic persons to develop arterial insufficiency of the lower extremities. Good diabetic control lessens the incidence of this major complication but does not obviate the problem. Much can be accomplished for these patients, in whom areas of gangrene or other signs of arterial insufficiency have developed, by means of arterial reconstruction. With the restoration of adequate circulation, claudication and rest pain will disappear, and areas of gangrene may either heal or be removed by simple local procedures. In other cases in which this cannot be done . . .
Etoposide (E) + epirebicin (E) + cisplatin (P) combination chemotherapy (EEP) In advanced gastric cancer: Negative impact on clinical outcome
Authors: E Díaz-Rubio, J Jimeno, E Aranda, B Massuti, C Camps, A Cervantes, J Dorta, J J Cruz Hernández, S Dominguez, A Anton
Journal: Annals of Oncology (1992)
Recurrent Acyclovir-Resistant Genital Herpes in an Immunocompetent Patient
Authors: Rhonda G. Kost, Edgar L. Hill, Michael Tigges, Stephen E. Straus
Journal: New England Journal of Medicine (1993)

Acyclovir has been widely used over the past decade as an effective and safe drug for the treatment of infections with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2)1. Resistance to acyclovir was initially noted only in studies of HSV infection in vitro and in animal models,2–4 then it was found in immunocompromised patients, and it has now become a well-documented clinical challenge to the care of patients infected with the human immunodeficiency virus (HIV)4–12. Acyclovir resistance has not been a problem to date in the treatment of immunocompetent people with HSV infection. Although . . .
Carcinoma of the Urinary Bladder after Treatment with Cyclophosphamide for Non-Hodgkin's Lymphoma
Authors: J Pedersen-Bjergaard, J Ersbøll, V L Hansen, B L Sørensen, K Christoffersen, K Hou-Jensen, N I Nissen, J B Knudsen, M M Hansen
Journal: New England Journal of Medicine (1988)

We observed nine cases of transitional-cell carcinoma of the urinary bladder among patients who had had long-term treatment of other cancers with cyclophosphamide. Seven of the bladder carcinomas occurred within a cohort of 471 patients treated for non-Hodgkin's lymphomas. In this cohort the relative risk of bladder cancer was 6.8 (95 percent confidence interval, 3.2 to 14.2). The cumulative risk (mean +/- SE) was 3.5 +/- 1.8 percent 8 years after the start of treatment with cyclophosphamide and 10.7 +/- 4.9 percent after 12 years. Three of the nine patients were 50 years of age or younger; seven died with progressive bladder cancer. Subsequently, an additional patient had acute nonlymphocytic leukemia. Hemorrhagic cystitis was observed in 33 patients (cumulative risk, 11.8 +/- 2.1 percent after five years). Development of carcinoma of the urinary bladder was not related to previous hemorrhagic cystitis. The results caution against long-term treatment with cyclophosphamide for diseases with a favorable prognosis.
Abstract 3085: MicroRNA-186 inhibition alters cell proliferation and colony formation in prostate cancer
Authors: Dominique Zilpha Jones, Katharine R. Hobbing, M. L. Schmidt, Geoffrey J. Clark, LaCreis R. Kidd
Journal: Cancer Research (2015)

Abstract MicroRNAs (miRs), key regulators of cancer-related genes, are dysregulated in many solid tumors, including prostate cancer. However, the role of miR-186 in prostate cancer (PCA) requires further elucidation. Previously, we observed mature miR-186-5p was significantly up-regulated in the serum collected from PCA patients (n = 15) diagnosed with aggressive PCA (stage III/IV) disease compared to disease-free men (n = 5). In addition, miR-186 expression was significantly up-regulated in metastatic PCA cells (PC3) compared to a normal prostate epithelial cell line (RWPE1). Putative and predicted miR-186 gene targets in various cancers include pro-apoptotic and tumor suppression-related genes (e.g., P2×7, FOXO1, AKAP12). We hypothesized that miR-186 inhibition will reduce the aggressive PCA phenotype. To test this hypothesis, PC3 cells were transiently transfected with miR-186 inhibitor and scramble control for 24hrs. Cell viability and colony formation of transfected cells were evaluated via the ATPlite Luminescence assay and soft agar assay. We also evaluated expression profiles of predicted miR-186 gene targets in PCA cell lines and transiently transfected PC3 cells using qRT-PCR. Transient inhibition of miR-186 repressed cellular proliferation and colony formation by 48-58% in 72-96hrs and 30% after 21 days, respectively. We observed a 1.6-2.24 fold up-regulation in ROCK1 gene expression in PC3 cells treated with miR-186 inhibitor. However, additional studies are needed to assess whether stable inhibition of miR-186 will increase PCA invasiveness by up-regulating ROCK1 using in vitro assays and murine models. Moreover, predicted miR-186 gene targets require validation using qRT-PCR, western blots and luciferase reporter assays. Such efforts may lead to the identification of novel biomarkers to improve diagnostic, prognostic and clinical management strategies. Citation Format: Dominique Zilpha Jones, Katharine R. Hobbing, M. L. Schmidt, Geoffrey J. Clark, LaCreis R. Kidd. MicroRNA-186 inhibition alters cell proliferation and colony formation in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3085. doi:10.1158/1538-7445.AM2015-3085
Pulmonary MicroRNA Expression Profiles Associated with Subchronic Aspergillus fumigatus Exposure
Authors: Tara L. Croston, Ajay P. Nayak, Angela R. Lemons, W.Travis Goldsmith, Michael L. Kashon, Dori M. Germolec, Donald H. Beezhold, Brett J. Green
Journal: Journal of Allergy and Clinical Immunology (2016)
Case 42-1793
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Edwin O. Wheeler, Benjamin Castleman
Journal: New England Journal of Medicine (1973)

Presentation of CaseA 44-year-old man was admitted to the hospital because of dyspnea.The patient had learned of a heart murmur in childhood and had been thin and physically less well than other children but had served in the armed forces 22 years before admission without mention of a cardiac problem. Several years before entry he consulted a physician because of awareness of his heart action and was reassured. He was well until three months before admission, when severe dyspnea developed over a period of approximately one week. A physician treated him for pneumonia, without improvement. He was admitted . . .
Skin Lipid Composition Varies Based on Clinical Subphenotypes in Adult European American Atopic Dermatitis Subjects
Authors: Arup K. Indra, Shan Li, Miguel Villarreal, Denise C. Babineau, Catherine Philpot, Gloria David, Mark Boguniewicz, Jon M. Hanifin, Donald Y.M. Leung, Eric L. Simpson, Lisa A. Beck
Journal: Journal of Allergy and Clinical Immunology (2016)
Case 28-1974
Authors: N. Paul Rosman, Fred H. Hochberg, Edward P. Richardson
Journal: New England Journal of Medicine (1974)

Presentation of CaseA 13-year-old girl was admitted to the hospital because of altered behavior and mood.She was well until two weeks previously, when she was noted to be apathetic, with inappropriate responses at times. She wandered away aimlessly on several occasions and was returned home by friends. One week before entry she became withdrawn. During the three days preceding admission she remained in bed and slept almost continuously.There were reports of the recent use of drugs among the patient's friends. She had ridden a horse on Cape Cod during the few months before admission; there was no . . .
Routine Pelvic Examinations in Asymptomatic Young Women
Authors: Julius Schachter, Mary-Ann Shafer, Myra Young, Mary Ott
Journal: New England Journal of Medicine (1996)

To the Editor: A first-catch urine sample from women may be an appropriate specimen for diagnosing chlamydial and gonococcal infection by DNA-amplification procedures.1,2 This noninvasive means of ...
IMPS-18OVERCOMING TGFβ-MEDIATED SUPPRESSION OF NK CELL CYTOTOXICITY IN MEDULLOBLASTOMA
Authors: Geoffrey Kannan, Srinivas Somanchi, Dean Lee
Journal: Neuro-Oncology (2015)

Medulloblastoma is the most common pediatric central nervous system (CNS) malignancy, with generally favorable outcomes depending on the molecular subtype. However, current therapies have significant long-term neurologic morbidities, and recurrent/relapsed disease portends a dismal prognosis. Therefore, novel, innovative, and safe therapies are needed. Immune cell therapy is an appealing, targeted approach, and NK cells have shown activity against some adult CNS tumors. However, NK cell adoptive cell therapy may be susceptible to the immunosuppressive effects of TGFβ, either produced by the tumor or the surrounding microenvironment. We have developed a robust expansion platform that yields NK cells in sufficient numbers and cyotoxic potency for therapy. We now seek to overcome TGFβ-mediated suppression to enhance NK cell cytotoxicity for CNS tumors. We show that expanded NK cells are highly cytotoxic against medulloblastoma cell lines, but have diminished cytotoxicity toward medulloblastoma in the presence of soluble TGFβ. The decrease in cytotoxicity correlates with a decrease in NKG2D expression on the expanded NK cells, as has been described for freshly-obtained peripheral blood NK cells. However, we also show that NK cells can be expanded in the presence of TGFβ without affecting their proliferative rate, and that the presence of TGFβ alters the CD16 and KIR expression profile, while maintaining NKG2D levels. Furthermore, NK cells that are expanded in the presence of TGFβ are resistant to the immunosuppressive effects of additional TGFβ. We are also exploring genetic and pharmacologic approaches to generating TGFβ-resistance. Understanding the mechanisms of NK cell immunosuppression by medulloblastoma may lead to a better understanding of the disease, and improved pre-clinical models and clinical trials of NK cell adoptive therapy for medulloblastoma and other pediatric CNS malignancies.
Outcomes in patients hospitalized for heart failure and chronic obstructive pulmonary disease: differences in clinical profile and treatment between 2002 and 2009
Authors: Lidia Staszewsky, Laura Cortesi, Mauro Tettamanti, Gabrio Andrea Dal Bo, Ida Fortino, Angela Bortolotti, Luca Merlino, Roberto Latini, Maria Carla Roncaglioni, Marta Baviera
Journal: European Journal of Heart Failure (2016)
ATPS-54GENOMICALLY UNSTABLE GLIOBLASTOMA (U-GBM) SHOW EXQUISITE SENSITIVITY TO PARP INHIBITION
Authors: Kerrie McDonald, Swapna Joshi, Toni Rose Jue, Julia Yin, Mustafa Khasraw
Journal: Neuro-Oncology (2015)

BACKGROUND: The development of effective targeted drugs for the treatment of glioblastoma (GBM) represents a major unmet need. Veliparib (ABT-888; Abbvie) inhibits both PARP1 and PARP2 (poly[ADP-ribose] polymerase). The successful clinical application of veliparib and other PARP inhibitors (PARPi) will be assisted by the identification of predictive biomarkers. METHODS: We performed whole genome sequencing (WGS) on ten GBM specimens with matched normal DNA. Mutations were detected using qSNP and GATK and indels called with Pindel and GATK. Somatic structural variants were identified using the qSV package. We tested the efficacy of the combination of veliparib and radiotherapy (RT) in vitro using patient derived cell lines (PDCLs) and in vivo using our patient derived xenograft (PDX) model. RESULTS: Strikingly, in 2 patient samples denoted as G89 and G54, the mutation rate was at least 16-fold higher compared to the other 8 participants. G89 and G54 exhibited a large number of single nucleotide variants (SNVs), insertions, deletions and structural variant (SV) events (>2 million) when compared to the other 8 patient samples. The scale of genomic instability suggested defects in DNA maintenance, which could potentially define sensitivity to DNA damaging agents. Upon closer examination of the mutational profile of G89 and G54, mutations were found in at least one of the mismatch repair (MMR) genes: MLH1, MSH2, MSH6 and PMS2. We also detected mutations in other genes involved in DNA maintenance such as XRCC4, FANCA, FANCD2, ATR, RPA1, and REV3L. We designated these patients' GBM as U-GBM class. We found the U-GBM class of tumors, G89 and G54 to be hypersensitive to the combination of veliparib and RT, both in vitro and in vivo. CONCLUSION: Mutations in DNA maintenance pathways may be a method for selecting patients for therapies involving the combination of DNA damaging agents such as radiotherapy, and PARP inhibitors.
Abstract A09: Effects of Podocalyxin on neural stem/progenitor cells
Authors: Isabelle V. Leefa Chong San, Gaelle Prost, Ulrike Nuber
Journal: Cancer Research (2015)

Abstract Podocalyxin (PODXL) is a highly glycosylated and sialylated protein found mainly on podocytes and up-regulated in various types of tumors. Known to be a marker of hematopoietic progenitors and pluripotent stem cells, PODXL is also increasingly considered a marker of malignancy in several aggressive tumor types. Though the exact role of PODXL in tumors is not yet established, it has increasingly been shown in vitro to be involved in cell migration and invasion. We found Podxl to be highly expressed in murine tumorigenic neural stem/progenitor cells. To investigate effects of elevated Podxl levels in neural stem/progenitor cells (NSPs), Podxl or an empty control construct were over-expressed in these cells. Podxl-overexpressing NSPs did not form brain tumors upon intracranial transplantations, indicating that high levels of this gene alone are not sufficient for tumorigenesis. In vitro studies however revealed how Podxl might contribute to the development and /or maintenance of tumors. Podxl overexpression had a positive effect on cell number, sphere formation and cell viability. To find out how Podxl exerts its pro-survival effects, the proteome of Podxl-overexpressing and empty control NSPs was analysed by mass spectrometry. These experiments revealed an up-regulation of Annexin A2, a calcium-regulated phospholipid binding protein interacting with the cytoskeleton and extracellular matrix. In addition to elevated Annexin A2 protein levels, we also found increased transcript levels indicating that PODXL stimulates expression of the Annexin A2 gene. NSPs lacking Annexin A2 and overexpressing Podxl are less viable than wild type Podxl-overexpressing NSPs, suggesting that PODXL-mediated pro-survival effects can at least in part be explained by increased Annexin A2 levels. We are now investigating how Podxl and Annexin A2 mechanistically interact to enhance cell viability Citation Format: Isabelle V. Leefa Chong San, Gaelle Prost, Ulrike Nuber. Effects of Podocalyxin on neural stem/progenitor cells. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr A09.
Edi-3, a new independent prognostic factor in ovarian cancer
Authors: A. Mustea, D. Koensgen, W. Lichtenegger, C. Pirvulescu, P. M. Sun, A. Thomas, E. Lausch, E. Steiner, J. G. Hengstler, J. Sehouli
Journal: Journal of Clinical Oncology (2007)

10585 Background: Recently, we have identified for the first time a new putative phosphodiesterase named edi-3 that correlates with tumorigenesis in endometrial cancer. In the present study we analyzed the prognostic relevance of edi-3 in ovarian cancer. Methods: Edi-3 mRNA expression was measured by quantitative RT-PCR (TaqMan) in 62 patients with primary ovarian cancer. All patients signed informed consent, approved by the Clinical Review Board and Ethics Committee of the Medical University Berlin, Charité, Germany. The tumor specimens were collected according to the Tumor Bank Ovarian Cancer standard operating procedures. A validated systematic intraoperative documentation tool was used for the detailed documentation of all surgical procedures. Using the multivariate proportional hazard model we analyzed whether edi-3 predicts survival independent from FIGO-stage, grading, postoperative residual disease and histological type. Results: Edi-3 expression is associated with survival in the univariate Cox model (hazards ratio [HR]: 1.488, 95% confidence interval [CI]: 1.131 - 1.959, P=0.005). Interestingly, edi-3 was also predictive in the multivariate proportional hazard model adjusted for the conventional clinical factors (HR: 1.521, CI: 1.107 - 2.090, P=0.010). Conclusions: Edi-3 is a new independent prognostic factor in primary ovarian cancer with HR=1.5 (P=0.010). Its function, a possible role in inositol phosphate metabolism, will be further explored in a multi-instutional setting. No significant financial relationships to disclose.
Risk Factors for Hip Fracture in Black Women
Authors: Jeane Ann Grisso, Jennifer L. Kelsey, Brian L. Strom, Linda A. O'Brien, Greg Maislin, Karin LaPann, Lisa Samelson, Susie Hoffman
Journal: New England Journal of Medicine (1994)

Although more than 1 percent of black women 80 years of age or older have hip fractures each year, little is known about risk factors for hip fracture in these women.
Sentinel node biopsy versus complete axillary clearance in breast cancer: The patients' point of view. Results of a prospective survey
Authors: S. Giard, P. Carpentier, C. Bercez, C. Dedourge
Journal: Journal of Clinical Oncology (2004)

750 Background: Sentinel node biopsy (SNB) seems to be associated with less morbidity than axillary clearance (AC) in early breast cancer. The aim of this study is to evaluated the patients' self-perception of SNB as compared to AC. Methods: Two different questionnaires were built, one for SNB and one for AC patients (pts). Each one contained 3 different domains : pts knowledge, perception of the different technique outcomes, consequences on the day-to-day life : psychological and physical morbidity.Questionnaires were mailed to pts operated on from 01.2001 to 03.2003 (mean delay after surgery : 15 months, range : 7–34 months). Results: Questionnaires were returned by 272/368 pts ( 74%). Three groups of pts were evaluated : group A (n=143) : pts with SNB without AC, group B (n=50) : pts with SNB followed by AC, group C (n= 79) : pts with AC only. Conclusions: Although uncontrolled, this prospective study shows that pts' point of view is significantly more negative after SNB with AC than after SNB or AC alone. No significant financial relationships to disclose.