tbuckley/cabot-search huggingface dataset:
Cost Implications and Complications of Overtreatment of Low-Risk Prostate Cancer in the United States
Authors: Ayal A. Aizer, Xiangmei Gu, Ming-Hui Chen, Toni K. Choueiri, Neil E. Martin, Jason A. Efstathiou, Andrew S. Hyatt, Powell L. Graham, Quoc-Dien Trinh, Jim C. Hu, Paul L. Nguyen
Journal: Journal of the National Comprehensive Cancer Network (2015)

Background: Evidence-based consensus guidelines recommend only observation for men with low-risk prostate cancer and life expectancy less than 10 years. This report describes the incidence, drivers, cost, and morbidity of overtreatment of low-risk prostate cancer within the United States. Methods: The SEER-Medicare Program was used to identify 11,744 men aged 66 years or older diagnosed with low-risk prostate cancer in 2004 through 2007. Overtreatment of prostate cancer was defined as definitive treatment of a patient with a life expectancy of less than 10 years. Expected survival was estimated using NCCN methodology. Costs were the amount paid by Medicare in years after minus year before diagnosis. Toxicities were relevant Medicare diagnoses/interventions. P values are 2-sided. Results: Of 3001 men with low-risk prostate cancer and a life expectancy of less than 10 years, 2011 men (67%) were overtreated. On multivariable logistic regression, overtreated men were more likely to be married (odds ratio [OR], 1.29; 95% CI, 1.05–1.59; P=.02), reside in affluent regions (P<.001), and harbor more advanced disease at diagnosis (P<.001). Two-year toxicity was greater in overtreated patients (P<.001). Relative to active surveillance/watchful waiting/observation, the median additional cost per definitive treatment was $18,827 over 5 years; the cumulative annual cost attributable to overtreatment in the United States was $58.7 million. The ability to avoid treating the 80% of men with low-grade disease who will never die of prostate cancer would save $1.32 billion per year nationally. Conclusions: Overtreatment of low-risk prostate cancer is partially driven by sociodemographic factors and occurs frequently, with marked impact on patient quality of life and health-related costs.
The World report on ageing and health: a policy framework for healthy ageing
Authors: John R Beard, Alana Officer, Islene Araujo de Carvalho, Ritu Sadana, Anne Margriet Pot, Jean-Pierre Michel, Peter Lloyd-Sherlock, JoAnne E Epping-Jordan, G M E E (Geeske) Peeters, Wahyu Retno Mahanani, Jotheeswaran Amuthavalli Thiyagarajan, Somnath Chatterji
Journal: The Lancet (2015)
Electron Microscopy of Cell Transformation by R-35 Rat Virus and Comparative Morphology With Other Oncogenic Viruses&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G. Schidlovsky, M. Ahmed, S. Slattery, G. Lowry
Journal: JNCI Journal of the National Cancer Institute (1972)

Morphological alterations of all major cell organelles were detected by the in situ fixation technique in R-35 virus-induced transformation of normal rat mammary cells in vitro. The extent of the alterations provided visual testimony to the complexity and interdependence of the biochemical occurrences during cell transformation and virus synthesis. C-type R-35 virus particles were synthesized only by transformed cells which had already undergone structural changes in their surface, nuclei, mitochondria, polyribosomes, endoplasmic reticulum, and Golgi apparatus. Short spikes (50 A) were found on the surface of Mason-Pfizer monkey virus and FL-74 feline leukemia virus. These were compared with the long spikes (100 A) on mouse mammary tumor virus. The R-35 rat mammary virus appeared to have a smooth surface.
Abstract 5390: The Endothelial Nitric Oxide Synthase Enhancer AVE9488 Increases Circulating Endothelial Progenitor Cells and Prevents Heart Failure Early after Myocardial Infarction
Authors: Thomas Thum, Felix Fleissner, Daniela Fraccarollo, Georg Ertl, Johann Bauersachs
Journal: Circulation (2008)

We studied the effects of AVE9488, a novel endothelial nitric oxide synthase (eNOS) expression enhancer on endothelial progenitor cells (EPC) mobilizing pathways in bone marrow, EPC function and im...
Gemcitabine for patients with chronic renal failure on hemodialysis
Authors: M. Matsuda
Journal: Journal of Clinical Oncology (2007)

15189 Background: Numerous studies of gemcitabine (GEM) as an agent for advanced pancreatic carcinoma (APC) have been reported. Although significant and/or unexpected toxicities of GEM have been reported even at low doses in patients (pts) with impaired renal function, no dosing recommendations have been developed for chronic renal failure (CRF). Methods: In this report, we present five APC pts with CRF and discuss the use of GEM for pts on hemodialysis (HD). Results: CASE 1. A-74-year old man with CRF (not on HD) received GEM (800 mg) on days 1 and 8. Grade 3 hematological toxicity (neutropenia and thrombocytopenia) occurred on day 9, which recovered immediately after HD was performed. Ten courses of GEM (800 mg x q2w) with HD initiated 6 h after administration have since been administered without any side effects. CASE 2. A-48-year old man underwent Whipple’s operation and received GEM (1000 mg x3 q4w) as adjuvant chemotherapy. After 10 cycles, he developed hemolytic uremic syndrome (HUS), which recovered immediately after performance of HD. HD was initiated 24 h after GEM (1000 mg), and this sequence was repeated 53 times until recurrence occurred. CASE 3. A-78-year old woman with recurrent pancreatic carcinoma developed HUS after 29 cycles of GEM (800 mg x q2w). After remission of HUS by starting HD, GEM was commenced again (HD was initiated 24 h after GEM at 1000mg x q2w), and has been administered 18 times. Both CASE 4 (a 65-year- old woman) and CASE 5 (a 56-year-old man) are APC pts with a long history of HD. Although HD was initiated within 24 h after GEM (1000mg) administration, Grade 3 hematological toxicity (neutropenia and leukocytopenia) occurred in these pts and we had to give up GEM after several courses. Conclusions: GEM (800–1000 mg) can be administered safely to pts with CRF on HD, especially soon after commencing HD, as long as HD is initiated within 24 h after GEM administration. In pts with a long history of HD, however, GEM should be administered with caution. No significant financial relationships to disclose.
High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma
Authors: Carla Hebert, Kathleen Norris, Mark A Scheper, Nikolaos Nikitakis, John J Sauk
Journal: Molecular Cancer (2007)

Abstract Background HMGA2 expression has been shown to be associated with enhanced selective chemosensitivity towards the topoisomerase (topo) II inhibitor, doxorubicin, in cancer cells. Although the roles of signaling cascades and proteins as regulatory factors in development, neoplasia and adaptation to the environment are becoming well established, evidence for the involvement of regulatory small RNA molecules, such as microRNAs (miRNAs) as important regulators of both transcriptional and posttranscriptional gene silencing is presently mounting. Results Here we report that HMGA2 expression in head and neck squamous cell carcinoma (HNSCC) cells is regulated in part by miRNA-98 (miR-98). Albeit HMGA2 is associated with enhanced selective chemosensitivity towards topoisomerase (topo) II inhibitor, doxorubicin in HNSCC, the expression of HMGA2 is thwarted by hypoxia. This is accompanied by enhanced expression of miRNA-98 and other miRNAs, which predictably target HMGA2. Moreover, we show that transfection of pre-miR-98™ during normoxia diminishes HMGA2 and potentiates resistance to doxorubicin and cisplatin. These findings implicate the role of a miRNA as a key element in modulating tumors in variable microenvironments. Conclusion These studies validate the observation that HMGA2 plays a prominent role in governing genotoxic responses. However, this may only represent cells growing under normal oxygen tensions. The demonstration that miRNA profiles are altered during hypoxia and repress a genotoxic response indicates that changes in microenvironment in eukaryotes mimic those of lower species and plants, where, for example, abiotic stresses regulate the expression of thousands of genes in plants at both transcriptional and posttranscriptional levels through a number of miRNAs and other small regulatory RNAs.
Prevention of Recurrent Spontaneous Abortions by Leukocyte Transfusions
Authors: C G Taylor, W Page Faulk, J A McIntyre
Journal: Journal of the Royal Society of Medicine (1985)

One hundred and thirty-nine couples referred because of recurrent abortions with no obvious cause were assessed for genetic similarity using the HLA major histocompatibility system. Comparison with 103 fertile control couples demonstrated that a much higher proportion of couples in the abortion group shared two or more HLA antigens. Using this criterion, 44 wives out of the 139 couples referred, when compared with a child-bearing group, appeared to share a greater than expected number of histocompatibility antigens and were therefore considered suitable for treatment. Twenty-eight wives have received treatment with white cell infusions from erythrocyte-compatible donors and so far they have delivered 17 babies plus 2 second babies. Another 3 wives are pregnant beyond their previous dates for abortions (1 first and 2 second pregnancies). There have been 5 failures (4 first pregnancy and 1 second pregnancy); one of these was treated a second time and has now successfully delivered. Seven couples are awaiting conception. Of the patients who have become pregnant, 81.5% have had successful deliveries. No adverse transfusion reactions have been observed.
Histogenesis and Dose Dependence of &lt;italic&gt;N&lt;/italic&gt;-Methyl-&lt;italic&gt;N&lt;/italic&gt;-nitrosourea-Induced Carcinoma in a Localized Area of the Hamster Trachea&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: P J Becci, H J Thompson, C J Grubbs, R C Moon
Journal: JNCI Journal of the National Cancer Institute (1980)

The effect of the number of weekly intratracheal Instillations of N-methyl-N-nitrosourea (MNU) on induction of tracheal tumors was studied in male noninbred Syrian golden hamsters. The histogenesis of metaplastic and neoplastic lesions was also characterized. Treatment of hamsters once weekly for either 6, 8, 10, 12, or 14 weeks with a 0.5% solution of MNU resulted in the induction of a 0, 6, 11, 26, and 42% incidence of carcinoma, respectively, at 6 months after the first MNU treatment. Of the carcinomas induced, 87% were combined epidermoid and adenocarcinomas, whereas 13% were epidermoid carcinomas. In animals killed 1 week following either 1, 3, 6, 8, 10, 12, or 14 treatments, a continuum of metaplastic and neoplastic changes was observed that correlated well with the cancer incidence exhibited at the termination of the study. Mucous cells were found to be of prime importance in the development of the metaplastic and neoplastic tracheal lesions observed.
Fifteen-year survival and recurrence rates after radiotherapy for localized prostate cancer.
Authors: J A Eastham, M W Kattan, S Groshen, P T Scardino, E Rogers, C E Carlton, S P Lerner
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine 15-year survival and recurrence rates after radiotherapy for localized prostate cancer. METHODS One hundred thirty-six patients with clinically localized prostate cancer treated from 1966 to 1974 with interstitial gold seed and external-beam irradiation were evaluated to determine the probability of recurrence and survival &gt; or = 15 years after therapy. All patients were surgically staged with pelvic lymphadenectomy and none received hormonal therapy before relapse. RESULTS Overall, 60 patients (44%) have never recurred, although 57% (34 of 60) of these same patients have died of causes other than prostate cancer. Local progression developed in 39% of patients and distant metastases in 42%. At 15 years, the probability of dying of prostate cancer was 33%+/-8% (% +/- 2SE) and of all causes was 72%+/-8%. In clinical stage A2 and B, 29%+/-9% of patients died of their cancer within 15 years, compared with 57%+/-21% in stage C1, while only 18%+/-8% with clinical stage A2 and B and negative lymph nodes died of cancer within this period. In contrast, the prostate cancer mortality rate at 15 years was high for patients with positive nodes regardless of the stage of the primary tumor (73% for A2 and B; 71% for C1). Patients with nodal metastases, poorly differentiated tumors, and advanced local disease all had a significantly (P &lt; .0001) increased risk of cancer death. CONCLUSION The cancer-specific mortality rate for patients with stage A2 and B tumors and negative nodes compares favorably with other series of patients treated with radiation therapy and &gt; or = 15 years' follow-up evaluation. While local progression rates are high and associated with a substantial risk of prostate cancer death, many patients live with the disease and ultimately die of causes other than prostate cancer.
Cystic Fibrosis. Third Edition
Authors: H. Heijerman
Journal: European Respiratory Journal (2008)

Edited by M. Hodson, D. Geddes, A. Bush    Published by Hodder Arnold, London, UK    Pages: 503. Price: £99.00. ISBN: 978-0-340-90758-0

Cystic Fibrosis. Third Edition    Although published as a third edition, this new book is completely different from the previous editions.

It offers an up-to-date, concise overview of all clinical aspects and the clinically relevant science of cystic fibrosis (CF). CF is a …
Evidence of an epigenetic origin for high-risk 1q21 copy number aberrations in multiple myeloma
Authors: Jeffrey R. Sawyer, Erming Tian, Christoph J. Heuck, Donald J. Johann, Joshua Epstein, Charles M. Swanson, Janet L. Lukacs, Regina Lichti Binz, Marian Johnson, Gael Sammartino, Maurizio Zangari, Faith E. Davies, Frits van Rhee, Gareth J. Morgan, Bart Barlogie
Journal: Blood (2015)
Primordial Germ Cell Proliferation in Fetal Testes in Mouse Strains With High and Low Incidences of Congenital Testicular Teratomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Takehiko Noguchi, Leroy C. Stevens
Journal: JNCI Journal of the National Cancer Institute (1982)

The development of genital ridges in mouse strains was compared with high and low susceptibility to teratocarcinogenesis. The number of dividing primordial germ cells (PGC) was low at 12 days of gestation. The number increased sharply at 13 days and decreased precipitously by 15 days of gestation. The period of high mitotic activity closely paralleled the period of susceptibility to experimentally induced teratocarcinogenesis. Testes that had a long proliferative period had a higher incidence of teratomas than those that had a short proliferative period. A group of fetuses was identified that had markedly fewer than normal PGC. The incidence of teratomas in this group was very high, and nearly all growths were bilateral.
Subsets of CD34+ cells and rapid hematopoietic recovery after peripheral-blood stem-cell transplantation.
Authors: M W Dercksen, S Rodenhuis, M K Dirkson, W P Schaasberg, J W Baars, E van der Wall, I C Slaper-Cortenbach, H M Pinedo, A E Von dem Borne, C E van der Schoot
Journal: Journal of Clinical Oncology (1995)

To study whether there is a relationship between transplanted cell dose and rate of hematopoietic recovery after peripheral-blood stem-cell (PBSC) transplantation, and to obtain an indication whether specific subsets of CD34+ cell populations contribute to rapid recovery of neutrophils or platelets.Based on data from 59 patients, we calculated for each day after PBSC transplantation the dose of CD34+ cells that resulted in rapid recovery of either neutrophils or platelets in the majority (> 70%) of patients. Using dual-color flow cytometry, subsets of peripheral-blood CD34+ cells were quantified and the numbers of CD34+ cells belonging to each of the reinfused subsets correlated with hematopoietic recovery following high-dose chemotherapy.The calculated threshold values with a high probability of engraftment showed a steep dose-effect relationship between CD34+ cell dose and time to recovery of both neutrophils or platelets. Predominantly CD34+ cells with the phenotype of myeloid precursors were mobilized. A minority of CD34+ cells expressed the erythroid and megakaryocytic lineage-associated antigens and a low but distinct population of CD34+ cells expressed antigens associated with multipotent stem cells. Analysis showed that the number of CD34+CD33- cells (r = -.74, P < .05), as well as the number of CD34+CD41+ cells (r = -.81, P < .005), correlated significantly better with time to neutrophil and platelet recovery, respectively, than with the total number of CD34+ cells (r = -.55 and r = -.56, respectively).The numbers of CD34+CD33- cells and CD34+CD41+ cells may help to predict short-term repopulation capacity of PBSCs, especially when relatively low numbers of CD34+ cells per kilogram are reinfused.
Co-morbidities and cardiovascular medications are the best predictors of mortality in patients with obesity-associated hypoventilation treated with long-term non-invasive ventilation
Authors: Jean-Christian Borel, Benoit Burel, Renaud Tamisier, Sonia Dias-Domingos, Patrick Levy, Jean-Louis Pepin
Journal: European Respiratory Journal (2012)

Rationale:  NIV is largely used to treat patients with obesity-associated hypoventilation (OH). The impact of comorbidities, their medications and NIV compliance on survival of these patients remain unexplored.   Methods:  A Cohort of OH patients initiated on NIV between March 2003 and July 2008. Anthropometry, diurnal and nocturnal respiratory parameters, comorbidities, medications, conditions of NIV initiation and NIV compliance were used as covariates. Survival curves were estimated by the Kaplan–Meier method. Univariate and multivariate Cox models allowed estimating predictive factors of mortality.   Results:  In 107 patients (56% women, mean follow-up of 43±14 months) NIV was initiated in acute conditions in 36%. The 1, 2, 3-year survival rates were 99, 85, 82% respectively. In univariate analysis, death was associated with older age (>61 yrs), low FEV1 (   Conclusion:  Cardiovascular comorbidities represent the main factor predicting mortality in NIV-treated OH patients. In this population, NIV should be used among a combination of treatment modalities allowing a reduction in cardiovascular risk.
Controversies in the Locoregional Management of Head and Neck Cancer
Authors: David M. Brizel, William Lydiatt, A. Dimitrios Colevas
Journal: Journal of the National Comprehensive Cancer Network (2011)

Head and neck cancer (HNC) is a heterogeneous combination of various sites and types of disease. This manuscript elaborates on 3 important and current issues: the emerging role of human papilloma virus (HPV) in oropharyngeal cancer (OPC), current considerations in systemic therapy for advanced disease, and evolving treatment of the neck. Exogenous carcinogens, most notably tobacco, have classically been implicated in the development of HNC. A large increase in the incidence of OPC has occurred in the past few decades, predominantly in nontobacco users, and is caused by HPV. This disease is unique in many respects and presents an opportunity for novel therapeutic approaches. Because the prognosis for HPV-related HNC is better, regardless of whether surgery or radiation is used as the primary therapy, the reduction of treatment-related morbidity has assumed increasing importance and provides unique opportunities and challenges for de-escalation of therapies. Radiotherapy (RT) and concurrent cisplatin is the most commonly used nonsurgical platform for locally advanced disease. New data suggest that viable alternatives exist to the typical 3 cycles of bolus high-dose cisplatin. The role of RT and concurrent taxanes remains less understood. Similarly, the value of integrating epidermal growth factor inhibition and concurrent chemoradiation is under continuing investigation. The use of PET scanning is changing the traditional use of adjuvant neck dissection after RT or chemoradiation. Recent data support the use of surgery in the presence of a positive posttreatment PET, and observation in the setting of a negative posttreatment scan.
Involvement of PKCeta activation in cigarette smoke extract induced apoptosis in human lung fibroblasts (MRC-5 cell)
Authors: Jeong-Woong Park, Sun Young Kyung, Sung Hwan Jeong
Journal: European Respiratory Journal (2014)

Cigarette smoke, a major risk factor in emphysema, causes cell death by incompletely understood mechanisms. We demonstrated cigarette smoke extract (CSE) induced caspases activation in human lung fibroblasts (MRC-5 cells). PKCeta was activated in MRC-5 cells exposed to CSE, translocated from cytosol to membrane fraction.The aim of this study was to investigate the involvement of protein kinase Ceta activation in CSE induced extrinsic apoptotic pathway. Lactate dehydrogenase (LDH) release was measured using a cytotoxicity detection kit. Colorimetric MTT assay was used as a measure of cell viability. Overexpression of wild-type (wt) PKCetadecreased cell viability, as assessed by colorimetric MTT assay in MRC-5 cells exposed to 20% CSE for >12 h compared to the LacZ-infected MRC-5 cells.LDH release following CSE exposure was significantly increased inwtPKCetainfected MRC-5 cells compared to the control. We demonstrated that CSE induced expression of caspases-3/caspase-8 cleavage by Western immunoblot analysis in MRC-5 cells and wt PKCeta significantly increased expression of caspases-3/caspase-8 compared to the control LacZ. On the other hand, dominant-negative (dn) PKCeta inhibited apoptosis in MRC-5 cells exposed to CSE showing decreased expression of caspases-3/caspase-8 compared to the control LacZ. PKCeta activationplays a role in the extrinsic apoptotic pathway of MRC-5 cells induced by CSE. These results suggest thatmodulation of PKCetamayhave therapeutic potential in the prevention of smoke-related lung injury.
Farm dust decreases Th2 driven allergic airway inflammation in mice: A role for airway TLR2 and TLR4?
Authors: P. Robbe, M.J. Blacquière, D.S. Postma, W. Timens, M. Geerlings, A. Bufe, O. Holst, E. von Mutuis, M.N. Hylkema
Journal: European Respiratory Journal (2011)

Exposure to farm dust is known to decrease allergic inflammation in an ovalbumin mouse model for asthma. However, the underlying mechanisms of this protection are not known. With the focus on the role of epithelium in this process, we investigated whether farm dust also protects against allergic airway inflammation in a more clinically relevant house dust mite (HDM) asthma mouse model.

Dust from different farms in Germany was collected and pooled. BALB/c mice were exposed intranasally 4 times/week for 5 weeks to PBS or farm dust (1 mg/ml, 50 μl/day), followed by PBS or HDM (2.5 mg/ml, 10 μl/day). IgE levels, inflammatory cells, cytokines (CC chemokine ligand (CCL)20, thymic stromal lymphopoietin (TSLP) and Th2) and Toll-like receptor (TLR)2 and TLR4 expression on epithelial cells were assessed.

Farm dust+HDM exposed mice had lower levels of HDM-specific IgE in serum, eosinophilic inflammation, and Th2 cytokines in lungs than HDM exposed mice. Expression of TLR2 and 4 in epithelium, and CCL20 and TSLP levels in lung tissue were lower in farm dust exposed than HDM exposed mice. Additionally, we observed less spindle shaped CD68+ cells beneath the epithelial basement membrane in farm dust exposed mice.

Lower expression of TLR2 and 4 in epithelium after farm dust exposure may explain the lower levels epithelial cell-derived cytokines CCL20 and TSLP. These lower CCL20 and TSLP levels could have prevented the recruitment of antigen presenting cells as evidenced by the spindle shaped CD68+ cells, as well as the skewing towards a Th2 response. Hence, lower expression of TLR2 and 4 may contribute to the observed protection against HDM-induced allergic inflammation in farm dust-exposed mice.