tbuckley/cabot-search huggingface dataset:
Abstract 5379: Increased Myocardial Fatty Acid Uptake by Acyl-CoA Synthetase 1 Impairs Mitochondrial Function and Dynamics
Authors: Heiko Bugger, Xiao Xuan Hu, Joseph Tuinei, Heather Theobald, William L Holland, Genevieve Sparagna, Scott A Summers, Jean E Schaffer, E. Dale Abel
Journal: Circulation (2008)

Increased uptake and oxidation of fatty acids (FA) in diabetic hearts may contribute to mitochondrial dysfunction by promoting oxidative stress. To test this hypothesis, we investigated mice with cardiomyocyte-restricted overexpression of long-chain acyl-CoA synthetase 1 (MHC-ACS). In vivo PET studies revealed increased myocardial FA uptake (+120%; p&lt;0.05) in MHC-ACS. Unexpectedly, FA oxidation and myocellular triglyceride content were unchanged, and PPARα-regulated FAO genes and PGC-1α-regulated OXPHOS genes were unaltered. However, cardiac content of the phospholipid precursors ceramide (+260%; p&lt;0.05) and diacylglycerol (+40%; p&lt;0.05) were increased. Mitochondrial cardiolipin content was decreased (−25%; p&lt;0.05) and remodeled with substitution of 18:2 FA chains by unsaturated 22:6 FAs. Both ADP-stimulated mitochondrial O2 consumption (14.3±0.9 vs. 16.8±0.5 nmol/min/mgdw; p&lt;0.05) and ATP synthesis (24.2±1.4 vs. 31.8±1.6 nmol/min/mgdw; p&lt;0.05) were decreased in MHC-ACS in saponin-permeabilized cardiac fibers using palmitoyl-carnitine as a substrate. Mitochondrial superoxide production was increased by 75% (p&lt;0.05). Electron microscopy in 3 to 24 week-old mice revealed increased mitochondrial number, which was highest at 3 weeks (3wk +210%, 12wk +120%, 24wk +130%; all p&lt;0.05), and reduced mitochondrial size. Translocation of the mitochondrial fission protein dynamin-related protein 1 (Drp1) from cytosol to mitochondria was absent (p&lt;0.05) in MHC-ACS, but not in controls. Mitochondrial membrane content of the fission protein fission 1 and the fusion proteins mitofusin 1 and 2 were unchanged. These morphological changes are consistent with increased mitochondrial fission and reduced Drp1 likely represents an adaptive response. Thus remodeling of the myocardial lipid pool and mitochondrial membrane lipid composition are associated with impaired mitochondrial dynamics and represents a novel mechanism for lipid-induced mitochondrial dysfunction in the heart.
Recognition of human T-leukemia virus (HTLV-1) envelope by human CD4+ T- cell lines from HTLV-1 seronegative individuals: specificity and clonal heterogeneity
Authors: F Manca, G Li Pira, D Fenoglio, MT Valle, A Kunkl, A Ferraris, F Lancia, D Saverino, L Mortara, R Balderas
Journal: Blood (1995)
Abstract 1175: Curcumin may have anticancer effect by normalizing cancer metabolic pathway
Authors: Hideaki Takeyama, Hiromitsu Hayashi, Takayoshi Kaida, Kota Arima, Katsunobu Taki, Takaaki Higashi, Hirohisa Okabe, Hidetoshi Nitta, Daisuke Hashimoto, Akira Chikamoto, Toru Beppu, Hideo Baba
Journal: Cancer Research (2015)

Abstract Background: Cancer metabolism is a new and exciting field of biology that provides a fundamentally different approach to treating cancer. The characteristic of cancer metabolism is Warburg effect formation that is the glucose metabolism in the glycolytic pathway in aerobic environments. Specific high expression of PKM2 (Pyruvate kinase type M2) is indispensable to the Warburg effect formation. Curcumin is an ingredient of Termeric, and has a variety of bioactivity with less toxicity. Recently, an anti-cancer effect of Curcumin attracts attention, and various studies are conducted to investigate the bio-mechanisms as an anti-cancer agent. While Curcumin has been reported to provide an anti-cancer effect by suppressing NF-κB-COX pathway and/or the oxidative stress, its effect on cancer metabolism still remains unclear. Here, we investigated the mechanism of anti-cancer effects derived by Curcumin by focusing on cancer metabolism. Method: The anti-cancer effect of Curcumin was examined by growth-assay in HCC cell lines (HepG2 and HLF). To further assess the biological mechanism of Curcumin on cancer cells, the changes in cancer metabolic pathways such as pyruvate kinase type M2 (PKM2), glucose transporter1 (Glut1), glucose-6-phosphate dehydrogenase deficiency (G6PD), and Transketolase (TKT). Result: In growth assay, Curcumin treatment significantly suppressed cell growth of HepG2 cell. For the cancer metabolic pathways, Curcumin treatment induced a shift into PKM1 from PKM2 expression represented by decreased PKM2/1 ratio by real time PCR in HepG2 and HLF cells. Indeed, Glut1 and G6PD expressions were also suppressed by Curcumin treatment, whereas TKT expression was increased in HepG2 cell. Conclusion: Curcumin displayed anti-proliferative effects on HCC cell lines, and its anti-cancer effects may be due to normalize the cancer metabolic pathway represented by a shift into PKM1 from PKM2 expression. Citation Format: Hideaki Takeyama, Hiromitsu Hayashi, Takayoshi Kaida, Kota Arima, Katsunobu Taki, Takaaki Higashi, Hirohisa Okabe, Hidetoshi Nitta, Daisuke Hashimoto, Akira Chikamoto, Toru Beppu, Hideo Baba. Curcumin may have anticancer effect by normalizing cancer metabolic pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1175. doi:10.1158/1538-7445.AM2015-1175
Photodynamic therapy with TOOKAD in an orthotopic human prostate cancer xenografted in nude rat.
Authors: Dominique Blanc, Hervé Ficheux, Nathalie Just, Olivier Duchamp, Francis Bichat
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5187 

Background: Bacteriopheophorbide molecules are promising photosensitizers for photodynamic therapy (PDT) applications due to their absorption peaks in the near-infrared wavelengths. Tookad, palladium bacteriopheophorbide, has been successfully evaluated in several pre-clinical models. In this study, we have evaluated the anti-tumor effects of a PDT with Tookad in the PC3-M human prostate cancer model orthotopically xenografted in nude rat. Methods: The anti-tumor effects of PDT were evaluated by tumor growth inhibition measurements, histology and magnetic resonance imaging (MRI). PC3-M cells were injected in the prostate of nude rats at D0. Treatments started at D10 when the tumor size reaches a diameter of 5-10 mm. An optic fiber (5 mm active length) was inserted into the center of the tumor. Then, Tookad was infused through the tail vein over 3 min (267μl/kg/min) to deliver a dose of 2 mg/kg. Laser illumination (λ=763 nm) has started 5 min after the start of Tookad infusion. Laser energy varied from 50 to 205 J/cm and laser power was fixed at 200 mW/cm. Navelbine was used as positive control treatment. The rats were sacrificed at D13 and D31 for tumor weighing. Pimonidazol and Dextran-FITC were injected before sacrifice in order to perform functional histology (% of surface tumor necrosis, hypoxia and functional vessels). Moreover, three rats treated with Tookad and laser energy at 175 J/cm2 were imaged using a 4.7T MRI system at D9 (before treatment), D11 and D17. A panel of T1, T2 and T2*-weighted images sequences were applied in each rat for morphology, water apparent diffusion coefficient (ADC), level of oxygenation (R2*) and vascular perfusion (Ktrans) parameters quantification. Results: A significant anti-tumor effect was seen at D31 on the tumor weight of groups of rats treated with PDT at 125 J/cm2 and Navelbine compared to control (2.42g ± 1.42g and 3.04g ± 0.23g, versus 4.18g ± 0.41g respectively). The histological analyses of the tumors at D13 showed a significant increase of necrosis areas in all the Tookad+PDT treated groups (62 to 87 % of necrosis versus 8-20 % in vehicle treated and Navelbine treated groups). ADC and R2* MRI markers confirmed early response to treatment and onset of necrosis upon PDT treatment as soon as D1 post-treatment. In PDT treated rats, ADC dropped by 42% at D1 and re-increased at D7. R2* dropped by more than 50 % at D7. Conclusions: These results strongly suggest that PDT with Tookad is a treatment of interest for locally prostate cancer, and that MRI could provide suitable markers of PDT efficacy.
Effect of 5-FU on the expression of interferon receptor families of esophageal cancer cells
Authors: Yumiko Matsumura, Masakazu Yashiro, Hisahiro Tabuchi, Masaichi Ohira, Yoshito Yamashita, Masanao Yamazaki, Takeshi Hori, Bunzo Nakata, Tetsuji Sawada, Kiyoshi Maeda, Naoyoshi Onoda, Nobuya Yamada, Tetsuro Ishikawa, Kosei Hirakawa
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

3861 

Esophageal cancer is one of the highest malignancies. Recently, it has been diagnosed in earlier stage, and wide-ranged dissection of lymphnodes has improved their prognosis. However, overall survival rates are extremely poor, even though they are treated with combination therapy, such as surgical resection, radiation therapy, and chemotherapy. Much more effective strategy is desired to improve the survival rates. 5-FU is one of the common chemotherapeutic agents for esophageal cancer, and there have been quite a lot of investigations which is seeking for more effective combination therapy with other agents. Cytotoxic effect of 5-FU, such as the inhibition of DNA synthesis or RNA function, has been well known, and furthermore, it might remain other unknown working pathway. Recently interferons have been used as a biochemical modulator of the chemotherapy for esophageal cancer and some other malignancies. Though their effectiveness has been reported, their working pathway is still unknown. The purpose of this study is to find a new mechanism of 5-FU, and to develop a new combination therapy by analyzing 5-FU pathway. We used Affymetrix GeneChip arrays to find the effects of 5-FU exposure to the three cell lines of esophageal squamous cell carcinoma (SCC). Several genes whose expression commonly either increased or decreased among 12000 were identified following the 5-FU addition. Five interferon-related genes were up-regulated following the addition of 5-FU, including interferon receptor (IFNAR2) and interferon stimulated genes (ISG15K, ISG54K). These up-regulations were confirmed by RT-PCR. Based on these results, we investigated the anti-tumor effects of the simultaneous exposure to 5-FU with interferon alpha, beta and gamma. The growth of esophageal SCC cells was significantly decreased synergistically. The above findings indicated that 5-FU induced the stimulation of the interferon pathway in esophageal SCC cells following the up-regulation of interferon receptors, and suggested that the combination of 5-FU and interferon might be an efficacious method of treatment for esophageal cancer.
Abstract 89: Penn State Hershey: 4-Year Experience in Mild Therapeutic Hypothermia Program---Lessons Learned
Authors: Steven M Ettinger, Sandralee Blosser, Thomas Terndrup, Raymond Reichwein, Erin Sarfield, Sonya Bressler, Jill Burkholder, Michael Lazar, Edward Stephenson, Christopher L LaCoe, Patti A Wengert
Journal: Circulation (2011)

Introduction: Mild Therapeutic Hypothermia (MTH) improves neurological outcomes in patients (pts) following sudden cardiac arrest with return of spontaneous circulation (SCA-ROSC). The Penn State Hershey Medical Center assembled a multispecialty team and formalized a MTH program in October 2007. Indications were expanded to include pts presenting with cerebrovascular trauma (CVT) and stroke in addition to SCA-ROSC. Methods: A multidisciplinary team of nurses and physicians (Emergency Medicine, Interventional Cardiology and Neurology) along with EMS (Life Lion) reviewed the scientific literature and created educational programs that were provided to the critical care units in the hospital. An electronic order set was created to standardize protocol. Life Lion provided education to Emergency Medicine programs at regional hospitals. Results: From October 1, 2007-March 29, 2011, 149 pts were enrolled in the MTH program (97 men, mean age 61.4 yr; 52 women, mean age 58.0 yr). 100 pts were enrolled for SCA; 1 pt enrolled following ICD failure; 5 pts enrolled post-CABG (cooling with ECMO); and 43 pts were enrolled following CVT/stroke. SCA-ROSC ranged from 5-45 min. Cardiac rhythm at the time of first medical contact (FMC) was as follows: VFib/VT:58 pts; asystole/PEA:42 pts; NSR:49 pts. Time to cooling (target 33°C) ranged from 2.5 - 10 hours with 3 pts receiving pre-hospital cooling. 64 pts (43%) survived to hospital discharge. 85 pts died (57%). Pittsburgh cerebral-performance category (CPC) level I-II was observed in 54.7% (n=35); CPC Level III-V was observed in 35.9% (n=23). 21 pts were discharged to a rehab facility. Of pts with FMC rhythm VFib/VT (n=56) there were 26 deaths (survival rate 53.6%). Of pts with FMC rhythm Asystole/PEA (n=39) there were 31 deaths (survival rate 20.5%). Conclusion: The MTH program was successfully implemented at our institution in pts presenting with SCA-ROSC and CVT/stroke. Pts with FMC cardiac rhythm of VFib/VT demonstrated better survival and neurological outcomes with MTH as compared to pts with FMC cardiac rhythm of asystole/PEA. Elements that have contributed to the success of our program include: a multidisciplinary approach; nursing leadership with an educational focus; and standardization of medical order sets.
Abstract 2964: Histology-specific patterns of DNA methylation in Lynch-associated and sporadic ovarian cancer
Authors: Anni Niskakoski, Sippy Kaur, Synnove Staff, Laura Renkonen-Sinisalo, Heini Lassus, Heikki J. Järvinen, Jukka-Pekka Mecklin, Ralf Bützow, Päivi Peltomäki
Journal: Cancer Research (2015)

Abstract Epithelial ovarian cancer is a heterogeneous group of cancers, and molecular tools are urgently needed for a better understanding and targeted management of this often lethal disease. Since epigenetic methods can offer new tools for the management of ovarian cancer, our aim was to investigate epigenetic mechanisms in ovarian tumorigenesis representing different histological types. Expression profiling of ovarian and endometrial cancer cell lines treated with demethylating agents as well as literature were used to select gene candidates for epigenetic regulation. A methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay was constructed for thirteen genes to study methylation in 104 (85 sporadic and 19 Lynch syndrome-associated) ovarian carcinomas. Increased methylation (hypermethylation) was characteristic of ovarian cancer tissues relative to the corresponding normal tissues and hypermethylation was consistently more prominent in non-serous than serous tumors. The highest frequencies of hypermethylation were detected in Lynch-associated clear cell ovarian carcinomas. An interesting finding among endometrioid ovarian carcinomas was a significant association of lower levels of methylation in HOXA9, RSK4 and SPARC with higher tumor grade; thus, the methylation patterns of high-grade endometrioid ovarian carcinomas resembled epigenetic characteristics of high-grade serous tumors. Overall, non-serous ovarian tumors of Lynch and sporadic origin (as opposed to serous tumors) showed frequent epigenetic inactivation in RSK4, SPARC, PROM1, HOXA10, HOXA9, WT1-AS, SFRP2, SFRP5, OPCML, and MIR34B. Our findings provide important new information regarding some critical genes affected by epigenetic dysregulation in ovarian tumorigenesis. The results will be utilized in future experiments aiming to define the genetic and epigenetic origins of ovarian carcinomas of different types. Citation Format: Anni Niskakoski, Sippy Kaur, Synnove Staff, Laura Renkonen-Sinisalo, Heini Lassus, Heikki J. Järvinen, Jukka-Pekka Mecklin, Ralf Bützow, Päivi Peltomäki. Histology-specific patterns of DNA methylation in Lynch-associated and sporadic ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2964. doi:10.1158/1538-7445.AM2015-2964
Cell proliferation and gene expression were regulated by contact between prostate cancer cells PC3 and primary osteoblasts in different stages of bone metastasis.
Authors: Jun Wang, Anait Levenson, Ted Thurn, Laura Simons, Robert L. Satcher
Journal: Cancer Research (2004)

3419   Bone is the most common target of prostate cancer metastasis. It has been postulated that a ‘vicious cycle’ between cancer cells and bone cells is established that leads to the formation of skeletal metastases. The interaction between prostate cancer cells and bone cells is an important step in this process, but is poorly characterized. Our hypothesis is that direct contact between cells (mediated by receptors) is required for metastasis formation in addition to interaction mediated by soluble factors. In order to explore the dynamic regulation in cell proliferation, gene expression profile and cell interaction between two cell populations, we established a co-culture system containing prostate cancer cell lines (PC3 or DU145) and primary cultures of osteoblasts (derived from rat bone marrow or from long bone). Different ratios (1:100, 1:10, 1:1 and 10:1) between prostate cancer cells and osteoblasts mimicked the different stages of metastasis development. Proliferation of two types of cells in the co-culture system was measured by labeling prostate cancer cells (or bone cells) with CSFE (Vybrant) dye, and quantitating the proportion of co-culture cells with flow cytometic analysis. Gene expression profiles were assayed with microarray. The results showed that proliferation of PC3 prostate cancer cells was suppressed by co-culturing with osteoblasts during the first 48 hours in comparison to prostate cancer cell culture alone. In contrast, PC3 prostate cancer cells stimulated proliferation of osteoblasts. Expression of uPA in prostate cancer cells was highly up-regulated in the co-culture system. Besides uPA, prostate cancer cells expressed many other potential mediators of osteoblastic metastasis, including endothelin-1, TGF-β2, BMP, IGFBP 1 and 3, prostate-specific antigen and FGF. Those factors stimulated proliferation and differentiation of osteoblasts, which expressed the bone formation markers type I collagen, alkaline phosphatase and osteocalcin. The osteoblastic metastasis-related genes were dynamically regulated during the progression of prostate cancer cells growth and proliferation when PC3 were co-cultured with osteoblasts. These results set a foundation for future studies that will identify receptors in osteoblasts and prostate cancer cells that mediate changes in proliferation and expression in response to contact in co-culture.
Abstract 16319: Physical Fitness Modifies the Predictive Impact of Weight Gain and Body Mass Index for Incident Atrial Fibrillation
Authors: Irene Grundvold, Per T Skretteberg, Sverre E Kjeldsen, Harald Arnesen, Johan Bodegard
Journal: Circulation (2011)

Introduction: The incidence of both atrial fibrillation (AF) and obesity is increasing in the general population, and lifestyle intervention is recommended. We tested the hypothesis that measured p...
The UCLA-University of Utah epidemiologic survey of autism: prevalence
Authors: E R Ritvo, B J Freeman, C Pingree, A Mason-Brothers, L Jorde, W R Jenson, W M McMahon, P B Petersen, A Mo, A Ritvo
Journal: American Journal of Psychiatry (1989)

The authors conducted an epidemiologic survey in Utah using a four-level ascertainment system, blind current diagnostic assessments, and DSM-III criteria. Of 483 individuals ascertained, 241 were diagnosed as having autism. The best estimate for the prevalence rate was 4 per 10,000 population. Autism was not associated with parental education, occupation, racial origin, or religion. Sixty-six percent of the autistic subjects scored below 70 on standardized IQ tests, and females scored proportionately lower than males. Twenty (9.7%) of 207 families had more than one autistic sibling, which supports the authors' previous finding that there may be a familial subtype of autism.
Abstract 17914: C-Reactive Protein and Sleep Apnea Symptoms in World Trade Center Responders
Authors: Miriam L Fishman, Rupa L Iyengar, Simonette T Sawit, Cynara Maceda, Jacqueline O'Boyle, Jessica Dweck, Jacqueline Moline, Mary Ann McLaughlin
Journal: Circulation (2011)

Background Obstructive sleep apnea (OSA) is particularly prevalent in patients with cardiovascular disease (CVD). OSA is not an isolated sleep disturbance: the extent of its role as a causative agent in development and progression of CVD is under investigation. The hypoxemic stress that occurs during apneas leads to systemic inflammation and studies have shown correlations in the severity of OSA and the elevation of high-sensitivity C-reactive protein (CRP). We seek to characterize the association of CRP and patients at risk for OSA as assessed by the Berlin Questionnaire (BQ) and hypothesize that a positive relationship might improve diagnosis of OSA. Methods We evaluated 1,976 participants in the Law Enforcement Cardiac Screening Program, a subset of the World Trade Center Medical Monitoring and Treatment Program. Abnormal CRP is defined as CRP &gt;/= 2 mg/L. Subjects with a positive response in 2 of the 3 categories from the Berlin Questionnaire are considered to be at high risk for OSA. We used chi-squared test and multivariate binary logistic regression in SPSS 19.0 to analyze the relationship between CRP and risk for OSA. Results Mean age is 46.77 ± 5.38 years and mean CRP is 3.26 ± 6.29. CRP &gt;/= 2 was significantly related to high risk for OSA, p = 0.001. When adjusted for age, gender, and family history of coronary artery disease, CRP &gt;/= 2 and risk for OSA are still significantly correlated ( p &lt; 0.001). Conclusion CRP &gt;/= 2 is associated with being at high risk for OSA. This association may trigger more practitioners to screen their patients with high CRP values for OSA. The presence of a positive inflammatory marker with its implications for systemic disease may encourage patients to undergo the time-consuming diagnosis of and to be adherent to the cumbersome treatment of OSA, potentially resulting in improvement of their cardiovascular health, an exciting area for further research. Funding Source: NY Fraternal Order of Police, via Office of the NY Attorney General Charity Fund.
Factitious psychosis: phenomenology, family history, and long-term outcome of nine patients
Authors: H G Pope, J M Jonas, B Jones
Journal: American Journal of Psychiatry (1982)

Factitious psychological symptoms are defined in DSM-III as symptoms that are under the patient's voluntary control. Using specific criteria for the presence of voluntary control, the authors identified a cohort of 9 patients with factitious psychotic symptoms from among 219 patients consecutively admitted to a research ward for psychotic disorders. The phenomenology and family history of the patients suggested that they were a homogeneous group. All had similar DSM-III personality disorders, and most had a remarkably poor long-term outcome.