tbuckley/cabot-search huggingface dataset:
Duplication and Adaptive Evolution of the Chalcone Synthase Genes of Dendranthema (Asteraceae)
Authors: Ji Yang, Jinxia Huang, Hongya Gu, Yang Zhong, Ziheng Yang
Journal: Molecular Biology and Evolution (2002)

Chalcone synthase (CHS) is a key enzyme in the biosynthesis of flavonoids, which are important for the pigmentation of flowers and act as attractants to the pollinators. Genes encoding CHS constitute a multigene family in which the copy number varies among plant species and functional divergence appears to have occurred repeatedly. Plants of the Dendranthema genus have white, yellow, and pink flowers, exhibiting considerable variation in flower color. In this article, 18 CHS genes from six Dendranthema species were sequenced. Two of them were found to be pseudogenes. The functional Dendranthema CHS genes formed three well-supported subfamilies: SF1, SF2, and SF3. The inferred phylogeny of the CHS genes of Dendranthema and Gerbera suggests that those genes originated as a result of duplications before divergence of these two genera, and the function of Dendranthema CHS genes have diverged in a similar fashion to the Gerbera CHS genes; i.e., the genes of SF1 and SF3 code for typical CHS enzymes expressed during different stages of development, whereas the genes of SF2 code for another enzyme that is different from CHS in substrate specificity and reaction. Relative rate tests revealed that the Dendranthema CHS genes significantly deviated from clocklike evolution at nonsynonymous sites. Maximum likelihood analysis showed that the nonsynonymous-synonymous (ω = dN/dS) rate ratio for the lineage ancestral to SF2 was much higher than for other lineages, with some sites having a ratio well above one. Positive selective pressure appears to have driven the divergence of SF2 from SF1 and SF3.
Stimulant Medication and Substance Use Outcomes
Authors: Kathryn L. Humphreys, Timothy Eng, Steve S. Lee
Journal: JAMA Psychiatry (2013)

Psychostimulant medication is an efficacious treatment for childhood attention-deficit/hyperactivity disorder, yet controversy remains regarding potential iatrogenic effects of stimulant medication, particularly with respect to increasing susceptibility to later substance use disorders. However, stimulant treatment was previously reported to reduce the risk of substance problems.To meta-analyze the longitudinal association between treatment with stimulant medication during childhood and later substance outcomes (ie, lifetime substance use and substance abuse or dependence).Studies published between January 1980 and February 2012 were identified using review articles, PubMed, and pertinent listservs.Studies with longitudinal designs in which medication treatment preceded the measurement of substance outcomes.Odds ratios were extracted or provided by the study authors. Odds ratios were obtained for lifetime use (ever used) and abuse or dependence status for alcohol, cocaine, marijuana, nicotine, and nonspecific drugs for 2565 participants from 15 different studies.Random-effects models estimated the overall association, and potential study moderators were examined.Separate random-effects analyses were conducted for each substance outcome, with the number of studies ranging from 3 to 11 for each outcome. Results suggested comparable outcomes between children with and without medication treatment history for any substance use and abuse or dependence outcome across all substance types.These results provide an important update and suggest that treatment of attention-deficit/hyperactivity disorder with stimulant medication neither protects nor increases the risk of later substance use disorders.
Phase II Study of Carboplatin and Pemetrexed for the Treatment of Platinum-Sensitive Recurrent Ovarian Cancer
Authors: Ursula A. Matulonis, Neil S. Horowitz, Susana M. Campos, Hang Lee, Julie Lee, Carolyn N. Krasner, Suzanne Berlin, Maria R. Roche, Linda R. Duska, Lauren Pereira, Deborah Kendall, Richard T. Penson
Journal: Journal of Clinical Oncology (2008)

Purpose More efficacious, less toxic combinations are needed to treat platinum-sensitive recurrent epithelial ovarian cancer (EOC). Pemetrexed is a multitargeted antifolate with manageable toxicity and has been combined with carboplatin to treat other cancers. Patients and Methods This is a phase II study of carboplatin area under the curve 5 with pemetrexed 500 mg/m 2 administered intravenously on day 1 every 21 days for six cycles or for up to eight cycles if clinical benefit occurred. Eligible patients had platinum-sensitive recurrent EOC, peritoneal serous cancer, or fallopian tube cancer. The primary objective was to determine response rate defined by Response Evaluation Criteria in Solid Tumors; other end points included toxicities, progression-free survival (PFS), and overall survival (OS). Results Forty-five patients were accrued; 44 patients received treatment. Overall response rate was 51.1%; there were no complete responses (0%), 23 confirmed partial responses (51.1%), two unconfirmed partial responses (4.4%), 14 patients with stable disease (31.1%), and two patients with progressive disease after two cycles (4.4%). Grade 3 and 4 hematologic toxicities included neutropenia (41%), thrombocytopenia (23%), and anemia (9%); there were no episodes of febrile neutropenia. Grade 3 and 4 nonhematologic toxicities included fatigue (11%), nausea (5%), vomiting (5%), diarrhea (5%), syncope (5%), and pulmonary embolism (5%). Median PFS time was 7.57 months (95% CI, 6.44 to 10.18 months), mean OS time was 20.3 months, and median OS has not yet been reached with a mean follow-up time of 15.3 months. Conclusion Carboplatin/pemetrexed is a well-tolerated regimen with activity in platinum-sensitive recurrent EOC; further testing of this regimen in platinum-sensitive EOC patients is warranted.
Amyloidosis: Pathogenesis and New Therapeutic Options
Authors: Giampaolo Merlini, David C. Seldin, Morie A. Gertz
Journal: Journal of Clinical Oncology (2011)

The systemic amyloidoses are a group of complex diseases caused by tissue deposition of misfolded proteins that results in progressive organ damage. The most common type, immunoglobulin light chain amyloidosis (AL), is caused by clonal plasma cells that produce misfolded light chains. The purpose of this review is to provide up-to-date information on diagnosis and treatment options for AL amyloidosis. Early, accurate diagnosis is the key to effective therapy, and unequivocal identification of the amyloidogenic protein may require advanced technologies and expertise. Prognosis is dominated by the extent of cardiac involvement, and cardiac staging directs the choice of therapy. Treatment for AL amyloidosis is highly individualized, determined on the basis of age, organ dysfunction, and regimen toxicities, and should be guided by biomarkers of hematologic and cardiac response. Alkylator-based chemotherapy is effective in almost two thirds of patients. Novel agents are also active, and trials are ongoing to establish their optimal use. Treatment algorithms will continue to be refined through controlled trials. Advances in basic research have led to the identification of new drug targets and therapeutic approaches, which will be integrated with chemotherapy in the future.
Palettes of Vaccines and Immunostimulatory Monoclonal Antibodies for Combination
Authors: Ignacio Melero, Ivan Martinez-Forero, Juan Dubrot, Natalia Suarez, Asis Palazón, Lieping Chen
Journal: Clinical Cancer Research (2009)

Various monoclonal antibodies (mAb) target immune system molecules to enhance immunity by costimulating T cells (i.e., CD137, OX40, CD40, GITR) or interfering in coinhibitory signals (i.e., CTLA-4, PD-1). These powerful agents can be guided by cancer vaccines to enhance immunity against tumor but not self tissues. Clinically powerful therapeutic synergies are at hand.
Mechanisms of Plaque Formation and Rupture
Authors: Jacob Fog Bentzon, Fumiyuki Otsuka, Renu Virmani, Erling Falk
Journal: Circulation Research (2014)

Atherosclerosis causes clinical disease through luminal narrowing or by precipitating thrombi that obstruct blood flow to the heart (coronary heart disease), brain (ischemic stroke), or lower extremities (peripheral vascular disease). The most common of these manifestations is coronary heart disease, including stable angina pectoris and the acute coronary syndromes. Atherosclerosis is a lipoprotein-driven disease that leads to plaque formation at specific sites of the arterial tree through intimal inflammation, necrosis, fibrosis, and calcification. After decades of indolent progression, such plaques may suddenly cause life-threatening coronary thrombosis presenting as an acute coronary syndrome. Most often, the culprit morphology is plaque rupture with exposure of highly thrombogenic, red cell-rich necrotic core material. The permissive structural requirement for this to occur is an extremely thin fibrous cap, and thus, ruptures occur mainly among lesions defined as thin-cap fibroatheromas. Also common are thrombi forming on lesions without rupture (plaque erosion), most often on pathological intimal thickening or fibroatheromas. However, the mechanisms involved in plaque erosion remain largely unknown, although coronary spasm is suspected. The calcified nodule has been suggested as a rare cause of coronary thrombosis in highly calcified and tortious arteries in older individuals. To characterize the severity and prognosis of plaques, several terms are used. Plaque burden denotes the extent of disease, whereas plaque activity is an ambiguous term, which may refer to one of several processes that characterize progression. Plaque vulnerability describes the short-term risk of precipitating symptomatic thrombosis. In this review, we discuss mechanisms of atherosclerotic plaque initiation and progression; how plaques suddenly precipitate life-threatening thrombi; and the concepts of plaque burden, activity, and vulnerability.
Hormone Replacement Therapy and Survival After Colorectal Cancer Diagnosis
Authors: Jennifer A. Chan, Jeffrey A. Meyerhardt, Andrew T. Chan, Edward L. Giovannucci, Graham A. Colditz, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2006)

Purpose Postmenopausal estrogen use has been shown to decrease the incidence of colorectal cancer, but there is limited information regarding the effect of estrogen use on survival after diagnosis of colorectal cancer. Participants and Methods We examined the influence of postmenopausal estrogen use on mortality among 834 women participating in the Nurses' Health Study who were diagnosed with colorectal cancer between 1976 and 2000 and observed until death or June 2004, whichever came first. Colorectal cancer–specific mortality and overall mortality according to categories of hormone use were assessed. Cox proportional hazards models were used to calculate hazard ratios (HRs) adjusted for other risk factors for cancer survival. Results Postmenopausal estrogen use before diagnosis of colorectal cancer was associated with significant reduction in mortality. Compared with women with no prior estrogen use, those reporting current use before diagnosis had an adjusted HR of 0.64 (95% CI, 0.47 to 0.88) for colorectal cancer–specific mortality and 0.74 (95% CI, 0.56 to 0.97) for overall mortality. This inverse association between hormone use and mortality was most evident among women whose duration of use was less than 5 years. Longer durations and past use were not associated with significant survival benefit. Assessment of estrogen use after diagnosis demonstrated similar findings. Conclusion Current postmenopausal estrogen use before diagnosis of colorectal cancer was associated with improved colorectal cancer–specific and overall mortality. This benefit was principally limited to women who initiated estrogens within 5 years of diagnosis. Additional efforts to understand mechanisms through which estrogens influence colorectal carcinogenesis and cancer progression seem warranted.
Determination of Left Ventricular Preload and Afterload by Quantitative Echocardiography in Man
Authors: ROBERT A. RATSHIN, CHARLES E. RACKLEY, RICHARD O. RUSSELL
Journal: Circulation Research (1974)

Left ventricular circumferential wall stress at end-diastole (preload) and at the end of isovolumic left ventricular contraction (afterload) was calculated in 48 subjects with chronic myocardial and valvular heart disease by using left ventricular internal dimensions and wall thickness measured by quantitative echocardiography, left ventricular end-diastolic pressure, and aortic end-diastolic pressure. These calculations were then compared with similar determinations made using quantitative angiocardiography. Left ventricular preload and afterload determined by quantitative echocardiography and quantitative angiocardiography correlated significantly ( r = 0.978 and 0.864, respectively). Left ventricular preloads of 30 x 10 3 dynes/cm 2 in subjects with mitral stenosis and 39 x 10 3 dynes/cm 2 in subjects with coronary artery disease unassociated with left ventricular dysfunction or mitral regurgitation were close to or within the normal range (32 x 10 3 ± 4 x 10 3 dynes/cm 2 ). Left ventricular preload in subjects with compensated volume overload was comparable with the angiocardio-graphically calculated values of 63 x 10 3 , 57 x 10 3 , and 53 x 10 3 dynes/cm 2 in subjects with coronary artery disease plus mitral regurgitation, mitral regurgitation, and aortic regurgitation, respectively. Left ventricular preload was most elevated in subjects with coronary artery disease associated with segmental left ventricular dyskinesis or akinesis. No significant differences in left ventricular afterload were noted between subject groups, although those with hypertrophic cardiac disease had the lowest calculated values. Quantitative echocardiography is an accurate technique for measuring left ventricular circumferential wall stress (preload and afterload) when left ventricular end-diastolic pressure and aortic end-diastolic pressure can be obtained.
Abstract 261: The novel Akt inhibitor API-1 induces c-FLIP degradation and synergizes with TRAIL to augment apoptosis independent of Akt inhibition
Authors: Bo Li, Hui Rentsch, Ping Yue, Mingwei Chen, Fadlo R. Khuri, Shiyong Sun
Journal: Cancer Research (2012)

Abstract API-1 is a novel small molecule inhibitor of Akt, which acts by binding to Akt and preventing its membrane translocation, and has promising preclinical antitumor activity. In this study, we reveal a novel function of API-1 in regulation of c-FLIP levels and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, independent of Akt inhibition. API-1 effectively induced apoptosis in tested cancer cell lines including activation of caspase-8 and caspase-9. It reduced the levels of c-FLIP without increasing the expression of DR4 or DR5. Accordingly, it synergized with TRAIL to induce apoptosis. Enforced expression of ectopic c-FLIP did not attenuate API-1-induced apoptosis, but inhibited its ability to enhance TRAIL-induced apoptosis. These data indicate that downregulation of c-FLIP mediates enhancement of TRAIL-induced apoptosis by API-1, but is not sufficient for API-1-induced apoptosis. API-1-induced reduction of c-FLIP could be blocked by the proteasome inhibitor MG132. Moreover, API-1 increased c-FLIP ubiquitination and decreased c-FLIP stability. These data together suggest that API-1 downregulates c-FLIP by facilitating its ubiquitination and proteasome-mediated degradation. Since other Akt inhibitors including API-2 and MK2206 had minimal effects on reducing c-FLIP and enhancement of TRAIL-induced apoptosis, it is likely that API-1 reduces c-FLIP and enhances TRAIL-induced apoptosis independent of its Akt-inhibitory activity. (This study was supported by the Georgia Cancer Coalition Distinguished Cancer Scholar award and National Cancer Institute NIH SPORE P50 grant CA128613. F.R.K. and S-Y.S. are Georgia Cancer Coalition Distinguished Cancer Scholars) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 261. doi:1538-7445.AM2012-261
Impact of Molecular Staging Methods in Primary Melanoma: Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) of Ultrasound-Guided Aspirate of the Sentinel Node Does Not Improve Diagnostic Accuracy, But RT-PCR of Peripheral Blood Does Predict Survival
Authors: Christiane A. Voit, Gregor Schäfer-Hesterberg, Martina Kron, Alexander C.J. van Akkooi, Juergen Rademaker, Ansgar Lukowsky, Alfred Schoengen, Markus Schwürzer-Voit, Wolfram Sterry, Markus Krause, Joachim Röwert-Huber, Alexander M.M. Eggermont
Journal: Journal of Clinical Oncology (2008)

Purpose This study analyzes (1) the value of tyrosinase reverse-transcriptase polymerase chain reaction (RT-PCR) of aspirates obtained by ultrasound-guided fine-needle aspiration cytology (US-FNAC) of sentinel nodes (SNs) in patients with melanoma before sentinel lymph node biopsy (SLNB) and (2) the value of RT-PCR of blood samples of all SLNB patients. Patients and Methods Between 2001 and 2003, 127 patients with melanoma (median Breslow depth, 2.1 mm) underwent SLNB. FNAC was performed in all SNs of all patients pre- and post-SLNB. The aspirates were partly shock-frozen for RT-PCR and were partly used for standard cytology. Peripheral blood was collected at the time of SLNB and at every outpatient visit thereafter. Results Thirty-four (23%) of 120 SNs were positive for melanoma. SN involvement was predicted by US-FNAC with a sensitivity of 82% and a specificity of 72%. Additional tyrosinase RT-PCR revealed the same sensitivity of 82% and a specificity of 72%. At a median follow-up time of 40 months from first blood sample, peripheral-blood RT-PCR was a significant independent predictor of disease-free survival (DFS) and overall survival (OS; P &lt; .001). Conclusion US-FNAC is highly accurate and eliminates the need for SLNB in 16% of all SLNB patients. RT-PCR of the aspirate or excised SN does not improve sensitivity or specificity. RT-PCR of blood samples predicts DFS and OS.
A comparative study of three occlusive dressings in the treatment of full-thickness wounds in pigs
Authors: Magnus S. Ågren, Patricia M. Mertza, Lennart Franzén
Journal: Journal of the American Academy of Dermatology (1997)

Little objective information is available on the influence of occlusive dressings on the healing of cutaneous full-thickness wounds.Our purpose was to examine the effects of three occlusive dressings-two hydrocolloid dressings (Comfeel Ulcer Dressing, Coloplast A/S, Espergaerder, Denmark [hydrocolloid dressing A] and DuoDERM; ConvaTec, Princeton, N.J. [hydrocolloid dressing B]) and one polyurethane film dressing (OpSite, Smith & Nephew, Hull, U.K. [film dressing])-on tissue reactions, degree of inflammation, wound contraction, and epithelialization in full-thickness wounds in domestic pigs.Standardized 20 mm full-thickness punch biopsy wounds were treated for 10 days. Healing was assessed by light microscopy and by planimetry.Material from both hydrocolloid dressings was phagocytosed as indicated by the presence of foam cells in the granulation tissue. Granulomatous tissue reactions around extracellular vacuoles were found in 10 of 12 hydrocolloid dressing B-treated wounds compared with one in hydrocolloid dressing A-treated wounds and in none of the 10 film dressing-treated wounds (p < 0.0001). Inflammation was significantly (p < 0.002) more pronounced in hydrocolloid dressing B-treated wounds. The extracellular vacuoles in the hydrocolloid dressing B group contained dressing material as demonstrated by Fourier transform infrared microscopy. There was a tendency (p < 0.07) towards a delayed entry into the contraction phase with hydrocolloid dressing B, but there was no significant difference in epithelialization between the three dressings.Wound tissue reactions to different hydrocolloid dressings vary depending on composition. The tissue reactions had no significant effect on wound contraction or epithelialization.
Association of <i>BRCA1</i> Mutations With Occult Primary Ovarian Insufficiency: A Possible Explanation for the Link Between Infertility and Breast/Ovarian Cancer Risks
Authors: Kutluk Oktay, Ja Yeon Kim, David Barad, Samir N. Babayev
Journal: Journal of Clinical Oncology (2009)

Purpose Germline mutations in BRCA genes are associated with breast and ovarian cancer susceptibility. Because infertility is associated with breast and ovarian cancer risks, we hypothesized that the mutations in the BRCA gene may be associated with low response to fertility treatments. Methods We performed ovarian stimulation in 126 women with breast cancer by using letrozole and gonadotropins for the purpose of fertility preservation by embryo or oocyte cryopreservation. As surrogates of ovarian reserve, the oocyte yield and the incidence of low response were compared with ovarian stimulation according to BRCA mutation status. Results Of the 82 women who met the inclusion criteria, 47 women (57%) had undergone BRCA testing, and 14 had a mutation in BRCA genes, of which two were of clinically undetermined significance. In BRCA mutation–positive patients, low ovarian response rate was significantly higher compared with BRCA mutation–negative patients (33.3 v 3.3%; P = .014) and with BRCA-untested women (2.9%; P = .012). All BRCA mutation–positive low responders had BRCA1 mutations, but low response was not encountered in women who were only BRCA2 mutation positive. Compared with controls, BRCA1 mutation– but not BRCA2 mutation–positive women produced lower numbers of eggs (7.4 [95% CI, 3.1 to 17.7] v 12.4 [95% CI, 10.8 to 14.2]; P = .025) and had as many as 38.3 times the odds ratio of low response (95% CI, 4.1 to 353.4; P = .001). Conclusion BRCA1 mutations are associated with occult primary ovarian insufficiency. This finding may, at least in part, explain the link between infertility and breast/ovarian cancer risks.
Adjuvant treatment of severe acute pancreatitis with C1 esterase inhibitor concentrate after haematopoietic stem cell transplantation
Authors: D T Schneider, W Nurnberger, H Stannigel, H Bonig, U Gobel
Journal: Gut (1999)

<h3>BACKGROUND</h3> With an incidence of 4%, acute pancreatitis is a common complication of bone marrow or peripheral haematopoietic stem cell transplantation, which contributes significantly to morbidity and mortality in these patients. In most cases, the pathogenesis of acute pancreatitis cannot be attributed to a single pathogenetic factor, as treatment toxicity, acute graft versus host disease, infection, and cholestasis may all contribute. Acute pancreatitis is characterised by inflammation and activation of digestive proenzymes leading to autodigestive destruction of the pancreas and systemic activation of protease cascades including the complement system. <h3>AIM</h3> To describe the effects of human C1 esterase inhibitor in two children, who developed severe acute pancreatitis with considerable complement activation after allogeneic haematopoietic stem cell transplantation. <h3>METHODS</h3> Both children showed clinical features resembling those observed in capillary leakage syndrome. In both patients, treatment with C1 esterase inhibitor concentrate contributed to a rapid clinical stabilisation. <h3>CONCLUSIONS</h3> These observations strongly support the proposed pathophysiological concept that early treatment with C1 esterase inhibitor interferes with the activation of the complement system in acute pancreatitis. Inhibition of complement activation prevents its adverse effects on vascular function and permeability, and thus stabilises intravascular fluid status and prevents multiorgan failure in acute pancreatitis.