tbuckley/cabot-search huggingface dataset:
Molecular subtypes of colorectal cancer in relation to disease survival.
Authors: Amanda I. Phipps, Paul J. Limburg, John A. Baron, Andrea N. Burnett-Hartman, Daniel J Weisenberger, Peter W. Laird, Frank A. Sinicrope, Christophe Rosty, Daniel D. Buchanan, John D. Potter, Polly A. Newcomb
Journal: Journal of Clinical Oncology (2014)

451 Background: Classifications for molecular subtypes of colorectal cancer based on microsatellite instability (MSI), the CpG island methylator phenotype (CIMP), and somatic mutations in BRAF V600E and KRAS have been proposed to reflect distinct pathways of colorectal tumorigenesis. We assessed the relationship between these subtype classifications and colorectal cancer survival in a population-based study. Methods: Tumor-markers were evaluated in incident colorectal cancer cases diagnosed between 1997-2007 in western Washington State. Cases were classified into pathway-based subtypes according to the following tumor-marker combinations: (1) traditional pathway [microsatellite stable / low MSI (MSS/MSI-L), non-CIMP, BRAF-wildtype, KRAS-wildtype, n = 631]; (2) MSI-high serrated (MSI-high, CIMP-positive, BRAF-mutated, KRAS-wildtype, N=100); (3) MSS/MSI-L serrated (MSS/MSI-L, CIMP-positive, BRAF-mutated, KRAS-wildtype, n = 55); (4) alternate pathway (MSS/MSI-L, non-CIMP, BRAF-wildtype, KRAS-mutated, n = 353); and (5) MSI-high familial (MSI-high, non-CIMP, BRAF-wildtype, KRAS-wildtype, n = 50). Multiple-imputation was used to classify tumor-marker status for cases with missing data on one to three markers. Differences in survival across subtypes were assessed through multivariable-adjusted Cox regression. Results: Relative to cases of the predominant traditional pathway subtype, cases with MSS/MSI-L serrated and alternate pathway tumor subtypes experienced statistically significantly worse disease-specific survival [hazard ratio (HR) = 2.25, 95% confidence interval (CI): 1.50-3.36 and HR = 1.39, 95% CI: 1.12-1.71, respectively]; cases with MSI-high familial tumors had the most favorable disease-specific prognosis (HR = 0.28, 95% CI: 0.12-0.64). With respect to overall survival, associations were similar but slightly attenuated. Conclusions: In this large, population-based study, colorectal cancer subtype classifications based on integrated pathways were associated with marked differences in survival, highlighting the significance of molecular heterogeneity in colorectal cancer.
Abstract 2083: Improvement in Coronary Flow Reserve is Associated With Late Recovery of Left Ventricular Function After Carvedilol Therapy in Patients with Idiopathic Dilated Cardiomyopathy
Authors: Kenichi Sugioka, Takeshi Hozumi, Yasuhiko Takemoto, Shoichi Ehara, Yasushi Kono, Keitaro Ogawa, Hiroki Oe, Yoshiki Matsumura, Ryo Otsuka, Hidetoshi Yoshitani, Junichi Yoshikawa, Minoru Yoshiyama
Journal: Circulation (2007)

Background: Beta-blocker therapy reverses left ventricular (LV) remodeling in patients with idiopathic dilated cardiomyopathy (IDC). Improvement in coronary circulation by beta-blocker could play a role in theses circumstances. This study investigated the relationship between change in coronary flow reserve (CFR), as a marker of coronary circulation, and subsequent improvement in LV ejection fraction (LVEF) at follow-up during carvedilol therapy in IDC patients. Methods: We studied 20 patients with IDC (mean age 56 ± 15 years, NYHA I–II) who were scheduled to receive carvedilol therapy. All patients were stabilized using an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker and diuretic treatment. Transthoracic Doppler echocardiography with intravenous infusion of adenosine triphosphate was used to assess CFR in the left anterior descending artery at baseline and after 1 month of treatment with carvedilol. A follow-up echocardiographic assessment of LVEF was done at 12 ± 6 months of treatment. The patients were classified by the degree of improvement in LVEF in the follow-up study, as Group A (LVEF change ≥10%) and Group B (LVEF change &lt;10%). Results: Although there was no significant difference in CFR between the 2 groups at baseline (Group A vs. Group B, 2.4 ± 1.0 vs. 2.2 ± 0.8; P =NS), CFR was significantly higher in Group A than in Group B at 1 month of therapy (3.7 ± 0.5 vs. 2.5 ± 0.9; P &lt;0.01). The magnitude of CFR change after 1 month of therapy was significantly greater in Group A than in Group B (1.3 ± 0.6 vs. 0.4 ± 0.5; P &lt;0.01). Logistic regression analysis revealed that CFR change predicted a significant improvement in LVEF at follow-up ( P &lt;0.05). Furthermore, a significant correlation was found between the change in CFR after 1 month and that in LVEF on follow-up (r=0.65, P &lt;0.01). Conclusions: This study demonstrated that early change in CFR is associated with subsequent improvement in LVEF, suggesting the potential predictive value of coronary circulation for subsequent LV reverse remodeling after beta-blocker therapy in patients with IDC.
Abstract 240: Inhibition of Glycogen Synthase Kinase 3 Beta Improves EPC Yield, Function and Ameliorates Arterial Repair Post-injury and Stenting
Authors: Benjamin Hibbert, Xiaoli Ma, Erik Holm, Ali Pourdjabbar, Katey Rayner, Yong-Xiang Chen, Jianfeng Sun, Edward O’Brien
Journal: Circulation (2007)

Endothelial progenitor cells (EPCs) are circulating undifferentiated pluripotent cells capable of reconstituting endothelium in vivo and diminishing lesion formation following arterial injury. We tested the hypothesis that treatment with a specific soluble GSK 3β-inhibitor (GSK3βi) would improve the in vitro yield and function of EPCs from patients with coronary artery disease (CAD) and augment their in vivo potential to improve arterial repair after injury and stent implantation. In vitro treatment with GSK3βi at 1× (IC50) and 2× (IC50) increased the number of cells that dual labelled for acLDL and UEA-1 lectin on day 7 (13.4±3.2 vs. 39.9±5.3 vs. 43.8±10.1; p &lt; 0.05). Furthermore, GSK3βi significantly augmented CAD-EPC survival to levels equal to those of healthy controls, increased VEGF secretion (7.1±1.6 vs 30.0±8.9, p&lt;0.05) and resulted in a 4× increase in adhesion (p&lt;0.05). Using Q-PCR, mRNA copy numbers for VLA-1,2,3,4 and 5 were assayed; however, only VLA-4 levels increased (4×, p&lt;0.01). Use of a VLA-4 specific blocking antibody confirmed that the improved EPC adhesion was specifically mediated by VLA-4. Finally, the effects of GSK 3β inhibition were tested in two in vivo models of arterial injury. CD-1 athymic nude mice underwent femoral artery wire injury and injection of CAD-EPCs that were either GSK3βi treated, untreated, or injection with vehicle alone. GSK3βi treated EPCs improved the ability of xenotransplanted cells to inhibit lesion formation when compared to untreated and vehicle arteries respectively (intima/media ratios: 0.3±0.1 vs. 5.3±1.2 vs 11.2±2.7 μm, p&lt;0.01). GSK3βi coated stents were inserted into rabbit carotid arteries. Fourteen days after stent deployment, GSK3βi stents resulted in a 44% increase in re-endothelialization (assessed by scanning electron microscopy and compared to vehicle coated stents; p&lt;0.01) and a 16% trend towards a reduction in neointima formation (p&lt;0.09). In summary, our data demonstrates that GSK3βi improves EPC function in vitro and ameliorates arterial repair following injury and stent insertion in vivo .
Osteomyelitis: A Review of Clinical Features, Therapeutic Considerations and Unusual Aspects
Authors: Francis A. Waldvogel, Gerald Medoff, Morton N. Swartz
Journal: New England Journal of Medicine (1970)

Osteomyelitis Secondary to a Contiguous Focus of InfectionOsteomyelitis secondary to a contiguous focus of infection is a direct infection of bone from a source outside the body (exogenous) or a progressive and continuous spread of infection from a contiguous focus. Operative infection is an example of the former, and sinus disease, felons and burns of the latter. Precipitating factors (Table 4)Postoperative infections. Of the 96 postoperative infections in our series 79 were in patients who had had open reduction of fractures. Thirty-six of the infections occurred after internal fixation of hip fractures, and 43 after repair . . .
THE PLASMA PROTEINS IN RELATION TO BLOOD HYDRATION
Authors: F. S. Bruckman, J. P. Peters
Journal: Journal of Clinical Investigation (1930)

That extreme restriction of dietary protein results in reduction of serum proteins in rats has been demonstrated by Frisch, Mendel and Peters (1).In the preceding article of this series (2) it has been shown that a serum protein deficiency, in which the albumin fraction alone suffers, is regularly found in patients who have, as the result of disease, become seriously malnourished.Presumably, wastage of tissue proteins is the most important feature of such malnutrition.The appearance of edema in protein-starved rats was first observed by Kohman (3) and Maver (4), whose observations were confirmed by Frisch, Mendel and Peters (1).Furthermore, the occurrence of edema in famine areas has been noted repeatedly, especially during the world war, and has been ascribed by some to the effects of protein starvation (5, 6).It is also frequently observed in patients with wasting diseases.The discovery that malnutrition is regularly at- tended by serum albumin deficiency seems to afford a rational ex- planation of the development of edema.
Androgen receptor degradation (ARD) enhancers: a targeted therapy for hormone-refractory prostate cancer
Authors: Ching-Yuan Su, Brian Russell, Richard Cao, Hui-Kang Wang, Charles C-Y. Shih
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4710 

Prostate cancer is the second leading cancer death for men in the United States. The androgen receptor (AR) plays a critical role in the development of prostate cancer. Total androgen blockade through a combination of castration and antiandrogens is a conventional treatment for primary prostate cancer. However, the tumors almost always relapse and become hormone-refractory. AR continues to express and appears to overly express in many relapsed tumors. Residual androgenic activity of antiandrogens or the so-called “nonconventional AR ligands” have been attributed to the occurrence of hormone-refractory tumors. In this report, we demonstrated that a new group of compounds, ASCJ, inhibits AR functional activity through a novel mechanism, i.e., enhancing AR degradation, and may have potential for treating hormone-refractory prostate cancer. ASCJ compounds, derivatives of a natural compound, at concentrations ranging from 0.5 to 2.5 μM decreased AR protein expression in human prostate cancer LNCaP and CWR22 cell lines; a cycloheximide chase study showed that under the experimental conditions, ASCJ compounds enhanced AR degradation. Data derived from a mammalian two-hybrid protein assay illustrated that ASCJ compounds, unlike the classic antiandrogens (cyproterone acetate and hydroxyflutamide), did not interfere with AR dimerization and AR-coactivator (ARA70) interaction in the presence of androgens, indicating that ASCJ compounds possess an anti-AR mechanism significantly different from the conventional antiandrogens. At cellular level, ASCJ compounds alone at various concentrations were unable to stimulate AR transactivation, indicating an absence of “residual androgenic” activity in this new class of compounds. But at pharmacologically achievable concentrations, ASCJ compounds markedly inhibited androgen-induced transactivation of both wild type and mutant ARs (in LNCaP and CWR22 cells). ASCJ compounds also suppressed AR transcriptional activity induced by the “nonconventional AR ligands”, including estradiol and adrenal androgens (androstenediol or dehydroepiandrosterone), as well as classic antiandrogens (cyproterone acetate and hydroxyflutamide). In an LNCaP xenograft animal model, intraperitoneal injection of a lead ASCJ compound (at 100 mg/kg body weight, three times per week) significantly hindered prostate tumor growth. In conclusion, these data demonstrate that ASCJ compounds, which enhance AR degradation, are powerful AR functional inhibitors both in vitro and in vivo . Since most relapsed prostate cancers are AR-dependent and in many cases overly express AR, the ARD Enhancers such as ASCJ compounds, may be ideal drug candidate to be developed into a target-specific therapy for hormone-refractory prostate cancer.
A bisphosphonate, minodoronate, decreases both CXCR-4 expression in osteoblastic and osteolytic prostate cancer cells and their ability to grow in bone
Authors: Atsushi Mizokami, Sotaro Miwa, Jian Zhang, Evan T. Keller, Russell Taichman, Mikio Namiki
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

2918 

Bisphosphonates (BPs) have already proven to be useful in the treatment of bone metastasis in prostate cancer (PCa) to affect not only osteoclast but may play have a direct anti-tumor effect. In the present study, the third generation BP, YM529 (minodoronate) was administered intra-peritoneally every week post-transplantation. Compared with non-treated group, both osteolytic and osteoblastic changes were inhibited both radiographically and histologically.demonstrating efficacy of YM529. In vitro, YM529 inhibited both the proliferation and invasion of both cell types in a dose-dependent manner. The SDF-1/CXCR-4 pathway is believed to play an important role in the establishment and progression of bone metastasis lesions as osteoblasts secrete SDF-1 and PCa cells express CXCR-4. We therefore investigated whether BPs may affect the SDF-1/CXCR-4 pathway. YM529 suppressed CXCR-4 expression in PC-3 and LNCaP-SF in a dose-dependent manner in vitro. Moreover, immunohistochemical analysis showed that YM529 also attenuated CXCR-4 expression in PC-3 and LNCaP-SF cells transplanted into tibia. In recent years, relation of various chemokine and its receptor are presented for cancer metastasis. These results suggest BPs may inhibit cancer cell invasion to bone matrix mediating through repression of CXCR-4 expression in bone metastasis lesion.
Efficacy Of Helicobacter Pylori Eradication For The First Line Treatment Of Immune Thrombocytopenia Patients With Moderate Thrombocytopenia
Authors: Hyo Jung Kim, Won Sik Lee, Hawk Kim, Jung-Hee Lee, Sang Min Lee, Sung Hwa Bae, Myung Soo Hyun, Je-Hwan Lee
Journal: Blood (2013)
Relationship between loss of heterozygosity, mutation of MTA1 gene and lymph node metastasis in non-small cell lung cancer
Authors: Jianjun Wang, Yuan Chen, Lurong Zhang
Journal: Cancer Research (2006)

2481   MTA1 (Metastasis-associated 1) gene has previously been found to be associated with progression to the metastatic state in various cancers. We investigated the loss of heterozygosity (LOH) and mutation of MTA1 gene in NSCLC (non-small cell lung cancer) related lymph node metastasis. Using three narrow spaced microsatellite markers(D14S62,D14S51,D14S1007), 40 primary NSCLC specimens and matched normal tissues were analyzed for LOH at MTA1 locus. The mutation of MTA1 gene was examined by PCR-SSCP and DNA sequencing. About 72.5 percent of NSCLC samples showed LOH in all of the informative markers tested. The rates of the three microsatellite markers were 30%,22.5% and 20%. More LOH events at markers D14S62 (P
解读《2005年精神与智力障碍法案》——可指导医生去帮助保护弱势群体
Authors: Andrew, Alonzi, Mike, Pringle, 卢杰
Journal: BMJ (2008)

在英国，《2005年精神与智力障碍法案》于2007年10月1日起开始完全实施与执行，这有助于保护那些无法自行做出决定的人们，并鼓励他们参与到这些决定中来。虽然这给医生提出了一些新的挑战，但也可帮助医生判断在不同情况下采取何种合法行为。
Genetic Modifiers Of Beta-Thalassaemia Associated With Management Without Blood Transfusion: Ten Years Experience
Authors: Saqib Hussain Ansari, Tahir S Shamsi, Mohammed Tahir Khan, Saima Munzir, Sajida Erum, Kousar Perveen, Sadia Parveen, Tasneem Farzana, Mushtaq Ashraf
Journal: Blood (2013)
Hepatic responses in antioxidant system and histoarchitecture to zinc in 1,2-dimethyl hydrazine intoxicated male Sprague Dawley rats.
Authors: Avdesh Avdesh, Praveen nair, vijayta Dani, Devendra Dhawan
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

B69 

The present study evaluated the effects of zinc on hepatic antioxidant defense system and histoarchitecture during 1, 2-dimethyl hydrazine (DMH) induced hepatotoxicity in male sprague dawley rats .DMH is a chemical carcinogen specifically used to induce colon carcinogenesis. For this experiment the rats were segregated into four groups viz., normal control, DMH treated, Zinc treated, DMH +Zinc treated. Hepatotoxicity was induced through weekly subcutaneous injections of DMH (30mg/kg body weight) for 8 weeks. Zinc in the form of zinc sulphate was supplemented to rats a dose level of 227mg/l in drinking water, ad libitum for the entire duration of the study. Increased lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) was accompanied by a decrease in catalase activity. Administration of zinc to DMH treated rats slightly decreased the lipid peroxidation level, significant decrease in SOD with simultaneous enhancement of catalase. Histopathological studies from DMH treated rats revealed disorganization of liver histoarchitecture. However zinc treatment to DMH treated rats greatly restored normalcy in the liver histoarchitecture, with no apparent signs of abnormalcy. Atomic absorption spectroscopic studies revealed a significant decrease in concentration of zinc in serum following DMH treatment, which upon zinc supplementation were recovered to near normal levels. In conclusion, the results of this study suggest that zinc has a beneficial effect during the hepatotoxic conditions.    Keywords: Hepatotoxicity, Antioxidant status, Zinc.
Abstract 15362: Impact of Morphological Characteristics of Ruptured Fibrous Cap Assessed by Optical Coherence Tomography on Creatinin Kinase Elevation in Acute Coronary Syndrome
Authors: Taishi Yonetsu, Tesumin Lee, Tadashi Murai, Kenji Koura, Takamitsu Takagi, Toshiyuki Iwai, Keiichi Hishikari, Tsunekazu Kakuta
Journal: Circulation (2011)

Backgrounds: Plaque rupture has been reported as a major cause of acute coronary syndrome. Recent study suggested the association between the morphology of ruptured cap and clinical presentation. O...
Acute Myeloid Leukemia With t(8;21)/RUNX1-RUNX1T1 demonstrate a High Number Of Secondary Genetic Lesions: Frequency and Impact On Clinical Outcome
Authors: Maria Theresa Krauth, Christiane Eder, Tamara Alpermann, Wolfgang Kern, Claudia Haferlach, Torsten Haferlach, Susanne Schnittger
Journal: Blood (2013)
Abstract 4033: EMS Agencies Implemented the 2005 AHA Guidelines for CPR and ECC an Average of 416 Days after Their Release
Authors: Blair L Bigham, Kent Koprowicz, John A Stouffer, Tom P Aufderheide, Stuart Donn, Judy Powell, Daniel P Davis, Sarah Nafziger, Brian Suffoletto, Ahamed Idris, Mike Helbock, Laurie J Morrison
Journal: Circulation (2008)

In 2005, the AHA released guidelines to improve survival rates from out-of-hospital cardiac arrest (OHCA). We sought to determine if, and when, EMS agencies participating in the Resuscitation Outco...
Abstract 11025: Cardiovascular Disease Mortality Among Black and White Women With Ductal Carcinoma in Situ of the Breast
Authors: Amy Berkman, Bernard Cole, Philip A Ades, Samantha Dickey, Stephen T Higgins, Amy Trentham-Dietz, Brian L Sprague, Susan G Lakoski
Journal: Circulation (2014)

Background: Ductal carcinoma in situ (DCIS) of the breast represents 15-20% of new breast cancer diagnoses in the United States annually and the incidence has been escalating since the 1970s. Long-term competing risks of cardiovascular disease (CVD) mortality, as well as racial differences in outcomes among US women with DCIS are unknown. Methods: Case data from the years 1978-2010 was abstracted using SEER*Stat software available through the National Cancer Institute from the 2010 SEER (Surveillance, Epidemiology and End Reports) registries. We evaluated CVD, breast cancer, and all-cause mortality using cumulative incidence rates and hazard ratios (HRs). Results: A total of 12,173 deaths were observed over a median follow up time of 9.2 years with 33% of deaths due to CVD and 8% due to breast cancer. The cumulative incidences of CVD death at 5, 10, and 20 years of follow up were 2.0% (95% CI 1.8-2.1), 5.1% (CI 4.9-5.3), and 13.2% (CI 12.8-13.7), respectively. The highest incidence of CVD mortality were found in women diagnosed with DCIS between 1978-1983 with 5, 10, and 20 year incidence of 5.0% (CI 3.9-6.1), 10.2% (CI 8.6-11.7), and 21.1% (CI 19.0-23.2), respectively. When stratifying by age at diagnosis, cumulative incidences of CVD death were highest among women diagnosed at age ≥ 70. Compared to white women, black women tended to have higher risk of death, especially among women diagnosed at young age; for those aged 40-49 at diagnosis, the HR for CVD mortality was 9.83 (95% CI 4.56-21.17). Conclusions: Among women diagnosed with DCIS, the risk of dying from CVD was greater than breast cancer at 20 years, with the incidence of CVD most pronounced among women diagnosed in an earlier treatment era (1978-1983) and older age. Black women had greater risks of dying from CVD compared to white women for all years, with this disparity decreasing with advanced age.
EGFR Mutation of Tumor and Serum in Gefitinib-Treated Patients with Chemotherapy-Naive Non–small Cell Lung Cancer
Authors: Hideharu Kimura, Kazuo Kasahara, Kazuhiko Shibata, Takashi Sone, Akihiro Yoshimoto, Toshiyuki Kita, Yukari Ichikawa, Yuko Waseda, Kazuyoshi Watanabe, Hiroki Shiarasaki, Yoshihisa Ishiura, Masayuki Mizuguchi, Yasuto Nakatsumi, Tatsuhiko Kashii, Masashi Kobayashi, Hideo Kunitoh, Tomohide Tamura, Kazuto Nishio, Masaki Fujimura, Shinji Nakao
Journal: Journal of Thoracic Oncology (2006)
Anti–PD-1–Related Pneumonitis during Cancer Immunotherapy
Authors: Mizuki Nishino, Lynette M. Sholl, Hiroto Hatabu, Nikhil H. Ramaiya, F. Stephen Hodi
Journal: New England Journal of Medicine (2015)

Among three patients with melanoma receiving anti–PD-1 antibodies, the use of checkpoint blockers led to the development of serious autoimmune pneumonitis, a potentially lethal complication.
Abstract 15615: Outcomes of Catheter Ablation of Ventricular Tachycardia in Patients with Arrhythmogenic Right Ventricular Dysplasia
Authors: Binu Philips, Srinivasa Madhavan, Cynthia James, Crystal Tichnell, Brittney Murray, Darshan Dalal, Aditya Bhonsale, Saman Nazarian, Daniel P. Judge, Stuart D. Russell, Theodore Abraham, Hugh Calkins, Harikrishna Tandri
Journal: Circulation (2011)

Binu Philips, 2011 Finalist and Presenting Author