tbuckley/cabot-search huggingface dataset:
Quantitative Polymerase Chain Reaction for the Detection of Micrometastases in Patients With Breast Cancer
Authors: Martin J. Slade, Brendan M. Smith, H. Dudley Sinnett, Nicholas C.P. Cross, R. Charles Coombes
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Previous reports have indicated that reverse transcriptase polymerase chain reaction (RT-PCR) for cytokeratin 19 (CK-19) may be useful in the management of patients with breast cancer. However, the specificity of this technique is low, principally because of a high rate of false-positive results. To improve the specificity of this assay, we developed a quantitative RT-PCR methodology that enables an estimate to be made of the number of CK-19 transcripts in blood and bone marrow samples. PATIENTS AND METHODS: We examined 45 peripheral-blood samples and 30 bone marrow samples from patients with a variety of nonneoplastic conditions using nested RT-PCR for CK-19. We also examined bone marrow and peripheral-blood samples from 23 patients with primary breast cancer and peripheral-blood samples from 37 patients with metastatic breast cancer. The number of CK-19 transcripts was estimated in positive specimens by competitive PCR and normalized to the number of ABL transcripts as an internal control for the quality and quantity of cDNA. RT-PCR results were compared with the numbers of CK-19–positive cells detected by immunocytochemistry. RESULTS: Analysis of samples from patients without cancer enabled us to define an upper limit for the background ratio of CK-19 to ABL transcripts (1:1,000 for blood samples and 1:1,600 for bone marrow samples). Using these figures as cut-off points, elevated CK-19: ABL ratios were detected in peripheral-blood samples of 20 of 37 (54%) patients with metastatic breast cancer and in bone marrow samples of 14 of 23 (61%) patients with primary breast cancer. Only three of 23 (13%) primary breast cancer peripheral-blood samples and none of the control samples were positive by these criteria. Only two of 23 patients (9%) with primary breast cancer showed immunocytochemically detectable cells in the blood; 10 of 23 (43%) showed immunocytochemically detectable cells in the bone marrow. Of 36 patients with metastatic breast cancer, eight (22%) showed positive events. CONCLUSION: Quantitative RT-PCR for CK-19 detects a percentage of patients with breast cancer and may enable the progression or regression of the disease to be monitored.
Response to ketoconazole after failure of docetaxel in patients with advanced androgen-independent prostate cancer (AIPC).
Authors: G. W. Jean, S. Shah, S. V. Keisner, S. M. GressettUssery, J. Dowell
Journal: Journal of Clinical Oncology (2010)

e15052 Background: In AIPC, the combination of docetaxel and prednisone has been shown to increase overall survival and progression free survival. Ketoconazole is considered in patients with AIPC to improve symptoms and progression free survival (PFS). Currently, literature evaluating PSA response rates (RR) in patients who receive ketoconazole after docetaxel failure is lacking. Methods: This study evaluated patients with AIPC treated with ketoconazole between January 1, 1999 and September 30, 2009. Patients included in the analysis had failed androgen deprivation therapy and were subsequently initiated on ketoconazole. Nominal data was evaluated with Fisher's Exact Test and continuous data was evaluated with Mann Whitney U or log rank tests. The primary objective of this study was to evaluate PSA response (PSA decline >50% maintained at least 4 weeks) in patients receiving ketoconazole therapy with or without prior docetaxel therapy. Results: A total of 30 patients were included in the analysis. Mean baseline age in the groups with (n=15) and without (n=15) prior docetaxel therapy was 68.8 and 72 years, respectively. More patients in the prior docetaxel group had a performance status of 0 or 1 (80% vs. 47%; p=0.13). Most patients had received prior therapy with an antiandrogen (93.3% and 100%), and the percentage of patients who received antiandrogen withdrawal therapy was 13.3% and 33.3% in prior docetaxel and no prior docetaxel groups, respectively. Median baseline PSA and duration of ketoconazole therapy were similar between groups (109.4 ng/ml vs. 80.4 ng/ml and 5.8 vs. 6.9 months, respectively). PSA response rates were 66.7% in patients with prior docetaxel and 46.7% in patients without prior docetaxel (p=0.46). Median PFS of 7.2 vs. 7.4 months (p=0.85) were similar between groups. Conclusions: Patients receiving ketoconazole who have received prior docetaxel have similar response rates compared to patients who have not received prior docetaxel. No significant financial relationships to disclose.
Expression of Human T-Lymphocyte Antigens by Natural Killer Cells2
Authors: Joseph Kaplan, Denis M. Callewaert
Journal: JNCI Journal of the National Cancer Institute (1978)

Rabbit antisera against human T-lymphocyte and B-lymphocyte antigens (anti-HTLA and anti-HBLA, respectively) were used to characterize natural killer (NK) cells mediating spontaneous cell-mediated cytotoxicity for myelogenous leukemia cell line K562 as measured in a 51Cr-release assay. NK activity of lymphocyte suspensions was abrogated by incubation of the suspensions in anti-HTLA plus complement but not by incubation in anti-HBLA plus complement. The effect of anti-HTLA was due to removal of NK cells rather than antigen-antibody complex inhibition of NK cells inasmuch as lytic complement was necessary. The results indicated that NK cells were HTLA+-HBLA- and thus supported the concept that NK cells are T-cells.
Phase III randomized double-blind study to evaluate the efficacy of a polycarbophil-based vaginal moisturizer in women with breast cancer.
Authors: C L Loprinzi, S Abu-Ghazaleh, J A Sloan, C vanHaelst-Pisani, A M Hammer, K M Rowland, M Law, H E Windschitl, J S Kaur, N Ellison
Journal: Journal of Clinical Oncology (1997)

PURPOSE Vaginal dryness and dyspareunia are significant estrogen-depletion symptoms that affect many breast cancer survivors. The present trial was developed to evaluate the nonhormonal vaginal lubricating preparation, Replens, for alleviating these symptoms. MATERIALS AND METHODS A double-blind, crossover, randomized clinical trial was developed. Patients received 4 weeks of Replens (Columbia Research Laboratories, Rockville Centre, NY) followed by a 1-week washout period followed by 4 weeks of a placebo lubricating product, or vice versa. Weekly patient-completed diaries were used for measuring efficacies and toxicities of therapy. RESULTS The 45 assessable patients provided well-balanced treatment groups. During the first 4 weeks, average vaginal dryness decreased by 62% and 64% in the placebo and Replens groups, respectively (P = .3). Average dyspareunia scores also improved by 41% and 60%, respectively (P = .05). Crossover analysis indicated that the bulk of the beneficial effects appeared within the first 2 weeks of the first treatment and remained constant thereafter. Both treatments were relatively well tolerated. CONCLUSION Both Replens and the placebo appear to substantially ameliorate vaginal dryness and dyspareunia in breast cancer survivors.
An algorithm based on one or two nasal samples is accurate to identify persistent nasal carriers of Staphylococcus aureus
Authors: P.O. Verhoeven, F. Grattard, A. Carricajo, F. Lucht, C. Cazorla, O. Garraud, B. Pozzetto, P. Berthelot
Journal: Clinical Microbiology and Infection (2011)
Abstract 3257: NME1 mediates a switch in expression of beta integrin subunits that correlates with prolonged patient survival
Authors: M. Kathryn Leonard, Marian Novak, Xiuwei Yang, Alexey Belkin, David Kaetzel
Journal: Cancer Research (2015)

Abstract Expression of the metastasis suppressor NME1 in melanoma is associated with reduced cellular motility and invasion in vitro and metastasis in vivo, but the molecular mechanisms underlying this activity are not completely understood. Herein we report a novel mechanism through which NME1 modulates focal adhesion dynamics via regulation of integrin β1. Stable expression of NME1 significantly altered focal adhesion turnover at the cell periphery. Interestingly, over-expression of NME1 resulted in a switch in from predominantly fast recycling α4β1 integrins to slower recycling αvβ3 integrins. Contrary to its regulation of other cell surface receptors, the inhibition of integrin β1 by NME1 was found to occur at the transcriptional level rather than through dynamin-mediated endocytosis. This effect of NME1 required both its 3-5′ exonuclease and nucleoside diphosphate kinase (NDPK) activities, which are also required for its metastasis suppressor activities in vivo. Furthermore, an inverse correlation was observed between NME1 and integrin β1 mRNA in a large cohort of primary melanoma biopsies. The inverse correlation of NME1 and integrin β1 RNA was also a strong predictor of prolonged distant disease-free and overall survival in patients with the basal-like subtype of breast carcinoma. Together, these data strongly suggest NME1 suppresses metastasis of human melanoma and some types of breast cancers by inhibiting integrin β1 expression, which reduces recycling of focal adhesions and suppresses cell motility. Citation Format: M. Kathryn Leonard, Marian Novak, Xiuwei Yang, Alexey Belkin, David Kaetzel. NME1 mediates a switch in expression of beta integrin subunits that correlates with prolonged patient survival. [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 3257. doi:10.1158/1538-7445.AM2015-3257
Lymphocyte Transformation in Epithelium2
Authors: Warren Andrew
Journal: JNCI Journal of the National Cancer Institute (1965)

Journal Article Lymphocyte Transformation in Epithelium Get access Warren Andrew, Ph.D., M.D. Warren Andrew, Ph.D., M.D. Chairman Department of Anatomy, Indiana University School of Medicine, Indianapolis, Indiana Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 35, Issue 1, July 1965, Pages 113–237, https://doi.org/10.1093/jnci/35.1.113 Published: 01 July 1965 Article history Received: 28 December 1964 Published: 01 July 1965
Referrals, attendance, delivery, and response in an integrated pulmonary rehabilitation pathway
Authors: Lauren Hogg, Rachel Garrod, Hannah Thornton, Lynn McDonnell, Helene Bellas, Craig Davidson, Patrick White
Journal: European Respiratory Journal (2011)

Introduction: Pulmonary rehabilitation is the most effective COPD treatment in improving quality of life. Access to PR is variable and rates of completion are relatively low at 35%. In this study of an integrated system-wide PR service we report on outcome, referral rates, and predictors of attendance and completion.

Method: Routine data were gathered prospectively on demography, rolling or stand alone courses, spirometry, walking distance, quality of life, BMI, and referrer, in patients referred for PR between April 2008 and October 2010. Predictors of attendance and course completion were sought using multiple regression.

Results: 1563 patients were referred, 1117 attended for assessment and 593 (38%) completed a PR course. Referred patients were of similar age and sex as the COPD population from which they were referred but were more severely affected. All PR programme types showed significant improvements in walking distance and quality of life, reaching the minimum clinically important difference. Twice weekly courses were more effective. Patients who were depressed (OR 0.75, CI 0.63-0.90), had a higher MRC dyspnea score (OR 00.76, CI 0.63-0.91), were from lower socio-economic groups (OR 0.98,CI 0.97-0.99), or were referred by GPs (OR 0.57, CI 0.35-0.94) were less likely to complete courses. Drop-out was not affected by venue, once or twice weekly courses, or rolling or stand-alone programmes.

Conclusions: Pulmonary rehabilitation is effective in real-world clinical practice achieving results comparable to clinical trials. We have identified patients in whom special intervention may be required to overcome the obstacles that place them at greater risk of not completing PR.
Minute Virus of Mice. II. Prevalence, Epidemiology, and Occurrence as a Contaminant of Transplanted Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: John C. Parker, Michael J. Collins, Sue S. Cross, Wallace P. Rowe
Journal: JNCI Journal of the National Cancer Institute (1970)

Journal Article Minute Virus of Mice. II. Prevalence, Epidemiology, and Occurrence as a Contaminant of Transplanted Tumors Get access John C. Parker, John C. Parker Microbiological Assodates, Inc., Bethesda, Maryland 20014, and Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,4Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael J. Collins, Jr., Michael J. Collins, Jr. Microbiological Assodates, Inc., Bethesda, Maryland 20014, and Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,4Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Sue S. Cross, Sue S. Cross Microbiological Assodates, Inc., Bethesda, Maryland 20014, and Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,4Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Wallace P. Rowe Wallace P. Rowe Microbiological Assodates, Inc., Bethesda, Maryland 20014, and Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,4Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 45, Issue 2, August 1970, Pages 305–310, https://doi.org/10.1093/jnci/45.2.305 Published: 01 August 1970 Article history Received: 09 February 1970 Accepted: 13 April 1970 Published: 01 August 1970
Molecular Pathogenesis of Hepatocellular Carcinoma
Authors: Daniel Wai-Hung Ho, Regina Cheuk-Lam Lo, Lo-Kong Chan, Irene Oi-Lin Ng
Journal: Liver Cancer (2016)

The pathogenesis of hepatocellular carcinoma (HCC) is a multistep process involving the progressive accumulation of molecular alterations pinpointing different molecular and cellular events. The next-generation sequencing technology is facilitating the global and systematic evaluation of molecular landscapes in HCC. There is emerging evidence supporting the importance of cancer metabolism and tumor microenvironment in providing a favorable and supportive niche to expedite HCC development. Moreover, recent studies have identified distinct surface markers of cancer stem cell (CSC) in HCC, and they also put forward the profound involvement of altered signaling pathways and epigenetic modifications in CSCs, in addition to the concomitant drug resistance and metastasis. Taken together, multiple key genetic and non-genetic factors, as well as liver CSCs, result in the development and progression of HCC.
Abstract 82: Regulation Of Frataxin By HIF-1 In The Ischemic Diabetic Heart
Authors: Raj H Amin, Abdullah AlAsmari, Gayani Nanayakkari, John Quindry, Shavanthi Mouli, Haitham Eldoumani, Graham McGinnis, Xiaoyu Fu
Journal: Circulation Research (2014)

Background: Diabetes is at epidemic proportions, with the major form of fatality due to congestive heart failure triggered by myocardial infarction (MI). The impaired insulin signalling in the diabetic heart leads to myocardial energy dysregulation that compromises the cardioprotective mechanism against ischemic injury. Therefore understanding how mitochondrial energetics is altered in the diabetic ischemic heart would greatly advance the knowledge base for improving outcomes from heart failure in diabetic patients. Methods/Findings: We observed that db/db mice (leptin deficient, type 2 diabetic mice) have increased infarction size (&gt;30%) compared to wild type mice after ischemia/reperfusion (IR) injury by TTC stain. We also found that activity of Hypoxia inducible factor-1 (HIF1) is involved in the cardioprotective response to ischemia, is impaired in db/db hearts. HIF1 is known to transcriptionally regulate genes involved in myocardial energetics. We recently found that HIF1 transcriptionally regulates the mitochondrial protein frataxin (Fxn) in cardiomyocytes as determined by luciferase assays (&gt;3 fold). In vitro studies indicate that hypoxic conditions increase Fxn protein expression in cardiomyocytes as determined by western analysis (2 fold). Fxn plays an important role in the Fe-S cluster biogenesis required for aconitase, succinate dehydrogenase and complexes in the mitochondria. Interestingly, we observed decreased expression of Fxn in the ischemic diabetic heart. Conclusion: we postulate that attenuated HIF1-Fxn signalling in ischemic diabetic heart leads to abnormally enlarged infarction size in response to IR. The decline in HIF-1 activity in response to hypoxia was further validated in cardiomyocytes cultured in high glucose media. The significance for Fxn against hypoxic injury was confirmed by utilizing overexpressed Fxn cardiomyocytes via MTT, ATP and aconitase activity assays. Current and future work: currently we are attempting to identify the HIF response element (HRE) in Fxn promoter to further validate the transcriptional activity of HIF1. In addition, we are completing the IR surgeries on HIF1 KO mice to address the cardioprotective nature of HIF1-Fxn signalling against MI.
Investigation of possible cytokine induction in peripheral blood mononuclear cells by heat-stable serotypes of Campylobacter jejuni
Authors: S. Chatzipanagiotou, M. Michalopoulou, I. Marinou, F. Boufidou, E. Papavasileiou, E. Trikka-Graphakos, E. Kabouri, C. Nicolaou, N.J. Legakis
Journal: Clinical Microbiology and Infection (2005)
Cardiac bioimpedance during exercise testing in patients with idiopathic pulmonary arterial hypertension
Authors: Ralf Kaiser, Christian Frantz, Kerstin Hadasch, Christian Lensch, Robert Bals, Heinrike Wilkens
Journal: European Respiratory Journal (2011)

Purpose: In idiopathic pulmonary arterial hypertension (IPAH) right ventricular insufficiency develops due to pressure overload. Furthermore left ventricular function is reduced by chronic underfilling.  Hemodynamics are monitored by echocardiography and cardiac catheterisation. This may describe cardiac function only insufficient, as hemodynamics may change during exercise and balance between right and left ventricular function might change due to development of a septal shift.  Methods: Spiroergometry testing was performed in 20 healthy volunteers and 21 patients with IPAH. Cardiac performance was determined using a cardiac bioimpedance instrument.  Results: Patients with IPAH tolerated less workload (54.3±37 vs. 177.4±90W). Ejection fraction (EF) at baseline was comparable to control. During exercise the increase of EF was diminished in IPAH (62.1±8 vs. 67.4±5%) and maximal cardiac index (CI) was significantly lower (5.2±2 vs. 9.0±3,7l/min/qm). Enddiastolic volume (EDI) showed a trend to decreased values (102.9±41 vs. 128.8±53ml/qm), while stroke index was markedly reduced (53.5±17 vs. 72.0±21ml/qm). Peakflow during ejection was decreased (387.7±126 vs. 559.0±180ml/min/qm) as well as flow acceleration (ACI, 153.5±61 vs. 217.1±71/sec2).  Conclusions: In patients with IPAH, stroke volume and CI were reduced. The diminished filling is represented by reduced EDI, resulting in less increase of contractility as shown by reduced peak flow and ACI. Patients with IPAH were not able to compensate the lack of contractility by heart rate, resulting in lower CI. Left ventricular underfilling affects cardiac performance during exercise, and inotropic response is reduced in patients with IPAH.
The Pressure–Volume Curve Is Greatly Modified by Recruitment
Authors: KEITH G. HICKLING
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

A mathematical model of the ARDS lung, with simulated gravitational superimposed pressure, evaluated the effect of varying alveolar threshold opening pressures (TOP), PEEP and peak inspiratory pressure (PIP) on the static pressure-volume (PV) curve. The lower inflection point (Pflex) was affected by SP and TOP, and did not accurately indicate PEEP required to prevent end-expiratory collapse. Reinflation of collapsed lung units (recruitment) continued on the linear portion of the PV curve, which had a slope at any volume greater than the total compliance of aerated alveoli. As recruitment diminished, the reduced PV slope could produce an upper Pflex at 20 to 30 cm H2O pressure. An upper Pflex caused by alveolar overdistension could be modified or eliminated by recruitment with high TOP. With constant PIP as PEEP increased, and TOP range of 5 to 60 cm H2O, PEEP to prevent end-expiratory collapse was indicated by minimum PV slope above 20 cm H2O, minimum hysteresis, and maximum volume at a pressure of 20 cm H2O. With constant inflation volume as PEEP increased, the effect on PV slope was unpredictable. Although increased PV slope indicated recruitment, maximum PV slope usually underestimated PEEP required to prevent end-expiratory collapse. Therefore, with this model the PV curve did not reliably predict optimal ventilator settings.
New horizons for cutaneous microbiology: the role of biofilms in dermatological disease
Authors: N. Vlassova, A. Han, J.M. Zenilman, G. James, G.S. Lazarus
Journal: British Journal of Dermatology (2011)

Human skin is colonized by bacteria. The development of new genomic microbiological techniques has revealed that the bacterial ecology of human skin is far more complex than previously imagined and includes many fastidious or noncultivable bacterial species which are found on both normal and diseased skin. In nature, the predominant bacterial phenotype on epithelial surfaces is that of organisms organized within a biofilm. This contrasts with the widely held belief that bacteria are planktonic, i.e. free-floating single cells. Biofilms are sessile bacterial communities encased in an extracellular matrix that have a well-developed communication system and can regulate bacterial growth and metabolism, confer resistance to antimicrobials and to host inflammatory cells, and alter host metabolism. Biofilms have been observed on healthy skin and in a number of dermatological conditions, including some that were previously thought not to have an infectious aetiology. Here we review the concept of biofilms and their role in cutaneous health and disease.