tbuckley/cabot-search huggingface dataset:
Association of Risk-Reducing Surgery in &lt;emph type="ital"&gt;BRCA1&lt;/emph&gt; or &lt;emph type="ital"&gt;BRCA2&lt;/emph&gt; Mutation Carriers With Cancer Risk and Mortality
Authors: Susan M. Domchek, Tara M. Friebel, Christian F. Singer, D. Gareth Evans, Henry T. Lynch, Claudine Isaacs, Judy E. Garber, Susan L. Neuhausen, Ellen Matloff, Rosalind Eeles, Gabriella Pichert, Laura Van T'veer, Nadine Tung, Jeffrey N. Weitzel, Fergus J. Couch, Wendy S. Rubinstein, Patricia A. Ganz, Mary B. Daly, Olufunmilayo I. Olopade, Gail Tomlinson, Joellen Schildkraut, Joanne L. Blum, Timothy R. Rebbeck
Journal: JAMA (2010)

Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer.To estimate risk and mortality reduction stratified by mutation and prior cancer status.Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009.Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality.No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer-specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer-specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]).Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.
Enhancing Chemotherapy Response with Sustained EphA2 Silencing Using Multistage Vector Delivery
Authors: Haifa Shen, Cristian Rodriguez-Aguayo, Rong Xu, Vianey Gonzalez-Villasana, Junhua Mai, Yi Huang, Guodong Zhang, Xiaojing Guo, Litao Bai, Guoting Qin, Xiaoyong Deng, Qingpo Li, Donald R. Erm, Burcu Aslan, Xuewu Liu, Jason Sakamoto, Arturo Chavez-Reyes, Hee-Dong Han, Anil K. Sood, Mauro Ferrari, Gabriel Lopez-Berestein
Journal: Clinical Cancer Research (2013)

RNA interference has the potential to specifically knockdown the expression of target genes and thereby transform cancer therapy. However, lack of effective delivery of siRNA has dramatically limited its in vivo applications. We have developed a multistage vector (MSV) system, composed of discoidal porous silicon particles loaded with nanotherapeutics, that directs effective delivery and sustained release of siRNA in tumor tissues. In this study, we evaluated therapeutic efficacy of MSV-loaded EphA2 siRNA (MSV/EphA2) with murine orthotopic models of metastatic ovarian cancers as a first step toward development of a new class of nanotherapeutics for the treatment of ovarian cancer.Tumor accumulation of MSV/EphA2 and sustained release of siRNA from MSV were analyzed after intravenous administration of MSV/siRNA. Nude mice with metastatic SKOV3ip2 tumors were treated with MSV/EphA2 and paclitaxel, and therapeutic efficacy was assessed. Mice with chemotherapy-resistant HeyA8 ovarian tumors were treated with a combination of MSV/EphA2 and docetaxel, and enhanced therapeutic efficacy was evaluated.Treatment of SKOV3ip2 tumor mice with MSV/EphA2 biweekly for 6 weeks resulted in dose-dependent (5, 10, and 15 μg/mice) reduction of tumor weight (36%, 64%, and 83%) and number of tumor nodules compared with the control groups. In addition, tumor growth was completely inhibited when mice were treated with MSV/EphA2 in combination with paclitaxel. Furthermore, combination treatment with MSV/EphA2 and docetaxel inhibited growth of HeyA8-MDR tumors, which were otherwise resistant to docetaxel treatment.These findings indicate that MSV/EphA2 merits further development as a novel therapeutic agent for ovarian cancer.
Kinetics of viral loads and risk of hepatitis B virus reactivation in hepatitis B core antibody-positive rheumatoid arthritis patients undergoing anti-tumour necrosis factor alpha therapy
Authors: Joung-Liang Lan, Yi-Ming Chen, Tsu-Yi Hsieh, Yi-Hsing Chen, Chia-Wei Hsieh, Der-Yuan Chen, Sheng-Shun Yang
Journal: Annals of the Rheumatic Diseases (2011)

Objective To investigate the kinetics of hepatitis B virus (HBV) viral loads and HBV reactivation in rheumatoid arthritis (RA) patients undergoing therapy with tumour necrosis factor alpha (TNFα) inhibitors. Methods The authors investigated the virological, serological and biochemical evidence of HBV reactivation in 88 RA patients receiving anti-TNFα therapy. Levels of HBV surface (HBs) antigen (Ag), anti-HBV core (HBc)-IgG and anti-HBs antibody (Ab) were detected by electrochemiluminescence immunoassay, and viral loads were determined by real-time PCR assay. Results In a total of 88 HBcAb-positive patients, 18 (20.5%) patients were HBsAg-positive, 12 (13.6%) patients were HBsAg-negative/HBsAb-negative and 58 (65.9%) patients were HBsAg-negative/HBsAb-positive before starting anti-TNFα therapy. Among HBsAg-positive patients receiving anti-TNFα therapy, HBV reactivation was documented in none of 10 patients who received lamivudine pre-emptive therapy and serum viral loads significantly decreased (mean±SEM, 153 860±80 120 IU/ml at baseline vs 313±235 IU/ml after 12 months antiviral therapy, p&lt;0.001), paralleling the decrease in serum aminotransferase levels. In contrast, five (62.5%) of eight patients without antiviral prophylaxis developed HBV reactivation, viral loads significantly increased after anti-TNFα therapy (9375±5924 IU/ml vs 49 710 000±40 535 000 IU/ml, p&lt;0.001), and markedly declined after antiviral therapy (49 710 000±40 535 000 IU/ml vs 6382±2424 IU/ml, p&lt;0.001). Baseline viral loads were detectable in four (33.3%) of 12 patients who had HBsAg-negative/HBsAb-negative status, and one developed HBV reactivation after anti-TNFα therapy. Conclusion HBV reactivation can occur in both HBsAg-positive and HBsAg-negative/HBcAb-positive patients with detectable HBV DNA, so-called occult HBV infection, during anti-TNFα therapy. Antiviral prophylaxis may effectively reduce HBV reactivation in HBsAg-positive RA patients undergoing anti-TNFα therapy.
Untying the Gordian knot: policies, practices, and ethical issues related to banking of umbilical cord blood
Authors: Joanne Kurtzberg, Anne Drapkin Lyerly, Jeremy Sugarman
Journal: Journal of Clinical Investigation (2005)

Since the first successful transplantation of umbilical cord blood in 1988, cord blood has become an important source of hematopoietic stem and progenitor cells for the treatment of blood and genetic disorders. Significant progress has been accompanied by challenges for scientists, ethicists, and health policy makers. With the recent recognition of the need for a national system for the collection, banking, distribution, and use of cord blood and the increasing focus on cord blood as an alternative to embryos as a source of tissue for regenerative medicine, cord blood has garnered significant attention. We review the development of cord blood banking and transplantation and then discuss the scientific and ethical issues influencing both established and investigational practices surrounding cord blood collection, banking, and use.
Effect of edema on segmental vascular resistance in isolated lamb lungs determined by micropuncture.
Authors: J U Raj, P Chen
Journal: Circulation Research (1987)

We have studied the mechanical effects of fluid accumulation on the pulmonary vasculature in 28 isolated blood perfused lungs of newborn lambs. Vascular resistance in the pulmonary arteries, microvessels, and veins was determined by micropuncture measurement of microvascular pressures, and regional distribution of blood flow in the lungs was determined using radiolabelled microspheres both before and after the development of varying degrees of hydrostatic edema. Edema was induced by raising venous pressure. During measurements, alveolar and venous pressures were kept constant at 7 and 8 cm H2O, respectively, as well as lung blood flow (540 +/- 107 ml/min). All vascular pressures were referenced to the superior surface of the lung, site of all micropunctures. Active vasomotor changes were eliminated by addition of papaverine to the perfusate. Under baseline nonedematous conditions in the absence of vasomotor tone, 17% of the total pressure drop was in arteries, 41% was in microvessels, and 42% was in veins. With the development of alveolar edema (80 +/- 13% weight gain), there was no change in total or segmental vascular resistance, but after 148 +/- 97% weight gain, total pulmonary vascular resistance increased by 74%. Segmental pressure drop increased in arteries by 172% and in microvessels by 132% but decreased by 22% in the venous segment. Regional distribution of blood flow remained unchanged. Possible mechanisms for increased resistance to blood flow may be compression of small arterioles and venules (less than 20 micron diameter) by liquid cuffs and/or occlusion of microvessels by the weight of alveolar liquid.
Targeting Cyst Initiation in ADPKD
Authors: Stephanie J. Leuenroth, Craig M. Crews
Journal: Journal of the American Society of Nephrology (2009)

With approximately 12.5 million people worldwide affected by autosomal dominant polycystic kidney disease (ADPKD), one hopes we are now at the beginning of multiple therapeutic breakthroughs. ADPKD is a hereditary disorder caused by a genetic defect in either polycystin-1 ( PKD1 ; PC1) or polycystin-2 ( PKD2 ; PC2) that leads to progressive kidney cyst formation and enlargement. The resulting high cystic burden in the kidney destroys the normal parenchyma and ultimately results in ESRD for the majority of patients. Although many of the cellular events leading to cystogenesis are not yet identified, the process can be roughly divided into the following stages after somatic inactivation of the remaining normal PKD allele through loss of heterozygosity: Loss of calcium-mediated cellular quiescence leading to an initial proliferative phase of tubule epithelial cells; out-pocketing of the tubule wall and eventual cyst separation from the parent nephron; and continued cell growth, fluid secretion, and progressive expansion of isolated cysts.

Tremendous progress has been made in understanding the various biologic mechanisms responsible for these pathologic stages of cyst formation and growth that range from the identification of the primary cilia as a mechanosensor mediating PC1/PC2 calcium influx to various perturbations of fluid regulation and cell proliferation. Because many proteins associated with these processes have been identified, we have multiple cellular targets to examine for pharmacologic intervention strategies, some of which are already under investigation.

When considering the stages of cystogenesis as described already, it is clear that many small molecule therapeutic agents have focused on cysts that are in the continued growth and expansion phase or the isolated cyst. There are several promising agents that either are under development or are already in clinical trials to reduce the …
Distribution of Tetraphenylporphinesulfonate and Tetracarboxyphenylporphine in Tumor-Bearing Mice<xref ref-type="fn" rid="FN2">2</xref>
Authors: D. A. Musser, J. M. Wagner, N. Datta-Gupta
Journal: JNCI Journal of the National Cancer Institute (1978)

The tumor-localizing potential of the free-base porphyrins tetracarboxyphenylporphine (TCPP) and tetraphenylporphinesulfonate (TPPS4) was Investigated In DBA/2Ha mice bearing solid L1210 tumors and Ha:ICR mice bearing sarcoma 180 tumors. At certain doses and times after administration, both compounds localized appreciably more in neoplastic tissue than in most other tissues. Maximal uptake of TPPS4 in tumor tissue was noted by 24 hours, after which its concentration remained constant. TCPP exhibited a maximum concentration in tumors 48 hours post injection followed by a decline through 72 hours. Substantial amounts of TPPS4 were localized in the kidney at most times and doses studied, whereas TCPP was localized primarily in the lung. Lowering the dose of TPPS4 did not alter the overall distribution pattern but did improve the tumor:kidney and tumor:tissue ratios. Lower doses of TCPP had the opposite effect. Tumor:lung and tumor:tlssue ratios were decreased in the L1210 tumor system. Tumor: lung ratios also decreased In the sarcoma 180 system, but tumor:tissue ratios increased. The greatest tumor:kidney ratio achieved with the use of TPPS4 was approximately 2:1 at a dose of 1 mg/kg in the L1210 system. The highest tumor:lung ratio achieved with TCPP was 2:1 at a dose of 10 mg/kg against the sarcoma 180. The substantial extratumor localization of both compounds might restrict their use as tumorvisualizing via fluorescence agents; however, the concentrations of both TCPP and TPPS4 found in the tumors and the high tumor:muscle ratios found at most doses of TCPP and TPPS4 suggest that both compounds may be useful as phototherapeutlc agent.
Randomized Assessment of Ticagrelor Versus Prasugrel Antiplatelet Effects in Patients With Diabetes
Authors: Dimitrios Alexopoulos, Ioanna Xanthopoulou, Eleni Mavronasiou, Katerina Stavrou, Argyro Siapika, Evropi Tsoni, Periklis Davlouros
Journal: Diabetes Care (2013)

It has been postulated that prasugrel might be the preferred treatment option in diabetes mellitus (DM) patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We aimed to compare the pharmacodynamic action of ticagrelor versus prasugrel.In a prospective, single-center, single-blind, crossover study, 30 consecutive ACS patients with DM who had been pretreated with clopidogrel were randomized to either 90 mg ticagrelor twice daily or 10 mg prasugrel once daily with a 15-day treatment period. Platelet reactivity (PR) was assessed with the VerifyNow P2Y12 function assay, measured in P2Y12 reaction units (PRU).PR was significantly lower after ticagrelor (45.2 PRU [95% CI 27.4-63.1]) compared with prasugrel (80.8 PRU [63.0-98.7]), with a least squares mean difference of -35.6 PRU (-55.2 to -15.9, P = 0.001). High PR rate was 0% for ticagrelor and 3.3% for prasugrel (P = 1.0).In DM patients with ACS who had been pretreated with clopidogrel and who undergo PCI, ticagrelor achieves a significantly higher platelet inhibition than prasugrel. Both antiplatelet agents effectively treat high PR. The relevance of these findings to the clinical efficacy and safety of ticagrelor and prasugrel in DM patients needs further elucidation.
Effectiveness and safety of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine in HIV-1-infected adults in Cameroon: open-label multicentre trial
Authors: Christian Laurent, Charles Kouanfack, Sinata Koulla-Shiro, Nathalie Nkoué, Anke Bourgeois, Alexandra Calmy, Bernadette Lactuock, Viviane Nzeusseu, Rose Mougnutou, Gilles Peytavin, Florian Liégeois, Eric Nerrienet, Michèle Tardy, Martine Peeters, Isabelle Andrieux-Meyer, Léopold Zekeng, Michel Kazatchkine, Eitel Mpoudi-Ngolé, Eric Delaporte
Journal: The Lancet (2004)
DRUG-ELUTING VERSUS BARE-METAL STENTS IN TREATMENT OF DIABETIC PATIENTS WITH ACUTE CORONARY SYNDROMES: ANALYSIS FROM THE RANDOMIZED ACUITY TRIAL
Authors: Karthik K. Challa, Eugenia Nikolsky, Roxana Mehran, Alexandra J. Lansky, George D. Dangas, Adriano Caixeta, Brent T. McLaurin, David A. Cox, Jeffrey W. Moses, Frederick Feit, Monica Embacher, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2010)
Psoriasis Area and Severity Index 75 rate of classical inpatient dithranol therapy under daily life conditions
Authors: C. Painsi, M. Patscheider, M. Inzinger, R. Huegel, B. Lange-Asschenfeldt, F. Quehenberger, P. Wolf
Journal: British Journal of Dermatology (2015)

Journal Article Psoriasis Area and Severity Index 75 rate of classical inpatient dithranol therapy under daily life conditions Get access C. Painsi, C. Painsi Department of Dermatology State Hospital Klagenfurt Klagenfurt AustriaResearch Unit for Photodermatology Department of Dermatology Medical University of Graz Auenbrugger Platz 8 A‐8036 Graz Austria Search for other works by this author on: Oxford Academic Google Scholar M. Patscheider, M. Patscheider Department of Dermatology State Hospital Klagenfurt Klagenfurt Austria Search for other works by this author on: Oxford Academic Google Scholar M. Inzinger, M. Inzinger Research Unit for Photodermatology Department of Dermatology Medical University of Graz Auenbrugger Platz 8 A‐8036 Graz Austria Search for other works by this author on: Oxford Academic Google Scholar R. Huegel, R. Huegel Department of Dermatology State Hospital Klagenfurt Klagenfurt Austria Search for other works by this author on: Oxford Academic Google Scholar B. Lange‐Asschenfeldt, B. Lange‐Asschenfeldt Department of Dermatology State Hospital Klagenfurt Klagenfurt AustriaDepartment of Dermatology, Venereology and Allergology Charité, Universitätsmedizin Berlin Berlin Germany Search for other works by this author on: Oxford Academic Google Scholar F. Quehenberger, F. Quehenberger Institute for Medical Informatics, Statistics and Documentation Medical University of Graz Graz Austria Search for other works by this author on: Oxford Academic Google Scholar P. Wolf P. Wolf Research Unit for Photodermatology Department of Dermatology Medical University of Graz Auenbrugger Platz 8 A‐8036 Graz Austria Correspondence: Peter Wolf. E‐mail: peter.wolf@medunigraz.at Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 3, 1 September 2015, Pages 815–817, https://doi.org/10.1111/bjd.13744 Published: 01 September 2015
S146 Microvascular endothelial cell apoptosis and dysregulation of Vascular Endothelial Growth Factor Receptor 2 (VEGF-R2) in response to cigarette smoke. New insights into the pathogenesis of emphysema
Authors: L. S. Mackay, S. Dodd, W. Tomlinson, I. Dougall, H. Walden, B. Isherwood, A. Gardner, L. Borthwick, K. P. Brown, M. Foster, A. J. Fisher, P. A. Corris
Journal: Thorax (2010)

Microvascular injury may be a primary mechanism in the pathogenesis of emphysema. Rats treated with a VEGF-R2 antagonist develop emphysema that is caspase-3 dependent. Additionally, patients with emphysema have reduced VEGF. We hypothesised that cigarette smoke injury may disrupt homeostatic vascular repair mechanisms and investigated VEGF-R2 expression and endothelial apoptosis in the pulmonary microvasculature of patients with emphysema. <h3>Methods</h3> Microvascular endothelial cells were isolated from explanted peripheral lung tissue from four patients with emphysema undergoing transplantation. Cells were characterised via flow cytometry and confocal microscopy. Concurrent immunolocalisation of CD31, VEGF, VEGF-R2 and caspase-3 was performed on peripheral lung tissue from each patient and expression compared with that in excess normal lung tissue obtained from lobectomies. Isolated endothelial cells were treated with freshly prepared cigarette smoke extract (CSE) (3%) for 0, 24, 48, 72 h and expression of VEGF-R2 investigated via q-PCR. A cell permeable caspase-3 substrate, NucView 488 (Biotium), which is cleaved by the enzyme to form a high-affinity fluorescent DNA binding dye, was used to detect apoptosis via live cell imaging in response to CSE (0–12%) over 64 h. <h3>Results</h3> Isolated cells at low passage (P3-P6) expressed high levels of CD31, negligible CD90 and inducible CD62 confirming them as microvascular endothelial cells. VEGF-R2 expression was significantly reduced (68%; n=4, p&lt;0.01) following treatment with 3% CSE at 48 h, compared with unstimulated cells. Live cell imaging demonstrated that cells underwent apoptosis in response to low dose CSE (3%, 1 h treatment) at 24 h (p=0.05) compared with unstimulated cells. Immunohistochemical analysis revealed reduced CD31 expression in the alveolar bed of emphysema tissue, indicating capillary loss. Regional alveolar expression of VEGF-R2 was also reduced compared with non-emphysematous tissue. Caspase-3 staining revealed positive cells in the alveolar bed, a sub-population of these indicating the presence of apoptotic endothelial cells in severe emphysema. <h3>Conclusions</h3> Microvascular endothelial cells isolated from individuals with emphysema undergo accelerated apoptosis and down-regulate VEGF-R2 in response to CSE. These findings were consistent with the immunohistochemical analysis of emphysema tissue. This may represent a maladaptive response to CSE injury in susceptible individuals and be important in the pathogenesis of emphysema.
Enucleation Versus Plaque Irradiation for Choroidal Melanoma
Authors: Bradley R. Straatsma, Stuart L. Fine, John D. Earle, Barbara S. Hawkins, Marie Diener-West, Jack A. McLaughlin, Matthew D. Davis, Thomas E. Davis, James Eltringham, Frederick L. Ferris, J. Donald M. Gass, Lael C. Gatewood, Robert J. Levine, Robert W. Makuch
Journal: Ophthalmology (1988)