tbuckley/cabot-search huggingface dataset:
Abstract 4505: Activity and avascular penetration of FTY720 (fingolimod) and its non-immune suppressant analogue (OSU2S) within three dimensional tissue culture model of colorectal cancer
Authors: Samir A. Zaahkouk, Serag Eldin I. Elbehairi, Aly F. El-Sayed, Sayed Bakry, Alaa Khedr, Hany A. Omar, Ahmed M. Al-Abd
Journal: Cancer Research (2015)

Abstract Fingolimod (FTY-720) and its non-immunosuppressive analogue (OSU2S) possess anticancer activity against hepatocellular carcinoma attributed to interference with protein kinase Cδ (PKCδ) signaling. Avascular penetration represents a major limitation for the treatment of solid tumors nonetheless colorectal cancer. Herein, we are assessing the differential antiproliferative activity of OSU2S compared to FTY720 against multicellular spheroids of HCT-116 and HT-29 colorectal cancer cell lines. In addition, we are comparing the avascular penetration properties of OSU2S to FTY720 within the avascular multicellular layers model. The IC50's of FTY720 and OSU2S were calculated in monolayer and spheroid culture models of HCT-116 and HT-29 cells using Emax model. Generally, OSU2S was found to be 1.5 to 3 folds more potent than FTY720 in both cell lines using monolayer and spheroid culture systems. The ratios between the IC50's of FTY720 in spheroid compared to monolayer cultures of HCT-116 and HT-29 cells were found to be to 5.7 and 3.4 folds, respectively. On the other hand, the ratios between the IC50's of OSU2S in spheroid compared to monolayer cultures of HCT-116 and HT-29 cells were found to be 4.5 and 3.4 folds, respectively. This might be attributed to avascular penetration problem for OSU2S and FTY720 in colorectal cancer. The pre-calculated IC50's of FTY720 and OSU2S induced significant increase in the cleaved fraction of PKCδ in both monolayer and spheroid model in HCT-116 and HT-29 cells. The influence of FTY720 and OSU2S on cell cycle analysis was studied using DNA flow cytometry analysis. Both FTY720 and OSU2S changed the cell cycle distribution of both HCT-116 and HT-29 cell lines in the monolayer culture and to a lesser extent in the spheroid culture model. The avascular penetration of OSU2S through multicellular layers of HCT-116 was 1.9 and 1.2 fold faster than FTY720 after 12 and 24 h of penetration, respectively. Also, OSU2S was faster than FTY720 in penetrating multicellular layers of HT-29 by 2.1 to 1.7 folds after 12 and 24 h of penetration, respectively. In conclusion, OSU2S possess better antiproliferative and avascular penetration profile within colorectal cancer cells compared to FTY720. Citation Format: Samir A. Zaahkouk, Serag Eldin I. Elbehairi, Aly F. El-Sayed, Sayed Bakry, Alaa Khedr, Hany A. Omar, Ahmed M. Al-Abd. Activity and avascular penetration of FTY720 (fingolimod) and its non-immune suppressant analogue (OSU2S) within three dimensional tissue culture model of colorectal 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 4505. doi:10.1158/1538-7445.AM2015-4505
Profiles of DNA methylation in colorectal cancer
Authors: G. Capella, J. Frigola, J. R. Germà, X. Solé, M. F. Paz, M. Esteller, V. Moreno, M. A. Peinado
Journal: Journal of Clinical Oncology (2004)

3728 Background: DNA methylation profiles in cancer cells are characterized by an overall decrease in the level of 5-methylcytosine and regional hypermethylation on particular CpG islands. We have addressed the concurrent study of DNA hyper- and hypomethylation and the analysis of its possible correlates with other features in a series of human colorectal cancers. Methods: DNA methylation profiles in sporadic colorectal carcinomas (n=98), synchronous adenoma-carcinoma pairs (n=11) and their paired normal mucosa were analyzed by using the Amplification of Inter-Methylated Sites (AIMS) method. A total of 208 anonymous methylated tags were evaluated for differential methylation. Global indices of hyper- and hypomethylation were calculated. Also MSI, K-ras, p53 mutations and hypermethylation at specific genes were assessed. Results: All adenomas and carcinomas displayed altered patterns of DNA methylation in reference to the normal tissue. In average, 24% of the represented tags were differentially methylated in carcinomas in regard to the normal pair with an overall prevalence of hypomethylations (14.6%) to hypermethylations (9.6%). Carcinomas exhibited higher (9.6%) levels of hypermethylation than adenomas (7.1%) but similar levels of hypomethylation. Hypermethylation correlated with female sex, advanced tumor stage and number of hypermethylated genes. Hierarchical cluster analysis revealed two main patterns of DNA methylation that were associated to particular mutational spectra in the K-ras and the p53 genes. In both groups correlates of hypomethylation or hypermethylation with survival were observed. Discussion: DNA hypermethylation and hypomethylation appear to play different roles in colorectal tumor progression and correlate with overall survival in subgroups with specific genetic and epigenetic signatures. No significant financial relationships to disclose.
Emotional and psychological peculiarities of compliance of patients with bronchial asthma
Authors: Larisa V. Bogovin, Victor P. Kolosov
Journal: European Respiratory Journal (2011)

Background: Compliance is one of the major factors of achieving asthma control. Emotional and psychological peculiarities of compliance in patients with bronchial asthma (BA) have not been studied enough.

Aim: To study clinical-functional and psycho-emotional peculiarities of patients with BA depending on compliance.

Methods: 91 patients with mild to moderate BA at the age of 36±1.1 years were examined. Women comprised 65%. Minnesota Multiphasic Personality Inventory (MMPI), Hospital Anxiety and Depression Scale (HADS), Self-estimation scale developed by Spilberger-Hanin, and TAS for alexitimia were used.

Results: The patients were divided into groups considering compliance: the 1st group consisted of patients with positive compliance (PC), they followed all doctor's recommendations during the year; the 2nd group included the patients with negative compliance (NC), they either absolutely or partially did not follow the recommendations. The patients with NC had a more intense degree of BA severity (69%) and were of an older age (p<0,002). Higher values were revealed in the 2nd group by TAS, scales of depression, personal and reactive anxiety. The average profile of a personality by MMPI scales in BA patients with NC was higher than the standard one. A high risk of psychopathologic reactions was revealed in the patients of this group (impulsiveness, nonconformity, nonstereotipeness). The patients of this group had inner tension, nervousness, aloofness, which can intensify psychosomatic disorders.

Conclusion: For BA patients with NC it is necessary to create a psychotherapeutic environment in the hospital as well as an individual approach to recommendations and their explanation.
Implementation of the California Oncology Emergency Preparedness Plan (COEPP): Updated results of an ASCO-supported state oncology society (SOS) project for patient (PT) protection
Authors: R. A. Moss, C. A. Presant, M. Lamb, S. Tucker, F. Howard
Journal: Journal of Clinical Oncology (2007)

17003 Background: Following the Katrina disaster MOASC began developing a plan to provide continuity of care to cancer PT in the event of a disaster. ASCO provided grant support to further develop the plan and begin implementation. COEPP included oncologist (ONC) and PT education and enrollment, developing a simple, portable, PT owned data storage system, ensuring drug availability, establishing offsite data storage, and implementing a communications system. This report updates the progress and problems encountered in this process. Methods: A committee was formed to develop the plan. ONC were educated through the MOASC website and meetings. A PT wallet card (WC) was developed as an initial method to store clinical data. Drug companies were contacted to provide support and emergency drugs. Communication avenues were identified. Attitudes of ONC were surveyed through interviews. Results: ONC readily agreed to join the COEPP. The PT WC have recently begun to be distributed. PT have been enthusiastic to participate. HIPPA compliant digital storage is being explored, but lack of standardization remains a problem. These efforts have required considerable time expenditures by committee members. Drug companies have expressed enthusiasm, and to date, one company has provided a sizable grant. Drug manufacturers and drug wholesalers have separate emergency plans for determining who is responsible for ensuring drug availability to PT and storing current distribution data. However, ONC membership in COEPP continues to increase, and WC have been widely accepted by PT indicating success of the initial part of the program. Educational materials and WC examples will be distributed at the poster. Conclusions: COEPP, while still early in development, is becoming a successful model of emergency preparedness to protect continuity of care for cancer PT. Adequate funding is required for network development, coordination, legal protections, eventual digitization of treatment records, coordination of drug availability, and ONC and PT educational materials. With grants, this model plan can be implemented in other regions by SOS. No significant financial relationships to disclose.
Cost-Effectiveness Analysis of Abiraterone and Sipuleucel-T in Asymptomatic Metastatic Castration-Resistant Prostate Cancer
Authors: Cynthia L. Gong, Joel W. Hay
Journal: Journal of the National Comprehensive Cancer Network (2014)

Of patients diagnosed with prostate cancer, 0% to 20% experience disease progression to metastatic castration-resistant prostate cancer (mCRPC). Recently, 4 novel therapies have been introduced for the treatment of mCRPC; of these, abiraterone and sipuleucel-T have been studied in the asymptomatic, pre-docetaxel population. Both have shown clinical benefits compared with placebo. This study evaluated the cost-effectiveness of abiraterone acetate and sipuleucel-T compared with prednisone in asymptomatic, pre-docetaxel mCRPC from a US societal perspective. A Markov model was constructed to simulate stable disease, progressed disease, and death. Survival and event rates were derived from published clinical trial data. Costs were derived from the literature and government reimbursement schedules. Outcomes were measured as average cost-effectiveness ratios (ACERs), incremental cost-effectiveness ratios (ICERs), and net monetary benefits (NMBs). One-way and probabilistic sensitivity analyses were conducted to test the robustness of the model. The base-case ACER was $114K/quality-adjusted life-years (QALY) for abiraterone, $85K/QALY for sipuleucel-T, and $31K/QALY for prednisone. The base-case ICER was $389K/QALY for abiraterone and $547K/QALY for sipuleucel-T. Prednisone dominates both abiraterone and sipuleucel-T in terms of NMB at willingness-to-pay (WTP) thresholds of $400K or less. One-way sensitivity analyses revealed that the model was most sensitive to overall survival and utility inputs. Probabilistic sensitivity analyses showed abiraterone to be cost-effective 50% or more of the time at a WTP of greater than $400K, whereas sipuleucel-T was cost-effective 50% or more of the time at a WTP of greater than $270K. Neither abiraterone nor sipuleucel-T was found to be cost-effective compared with prednisone in the treatment of asymptomatic, pre-docetaxel mCRPC.
Scientists Generate 3D Images of Cardiac Cell Connectors
Authors: Tracy Hampton
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Public Health Milestone
Journal: JAMA (1995)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Association of Maternal Prepregnancy Dyslipidemia With Adult Offspring Dyslipidemia in Excess of Anthropometric, Lifestyle, and Genetic Factors in the Framingham Heart Study
Authors: Michael M. Mendelson, Asya Lyass, Christopher J. O’Donnell, Ralph B. D’Agostino, Daniel Levy
Journal: JAMA Cardiology (2016)

Dyslipidemia in young adults in the United States during their childbearing years is common, and the consequences for the next generation are poorly understood. Further understanding of the harmful consequences of elevated low-density lipoprotein cholesterol (LDL-C) levels in young adults may help to inform population screening and management strategies.To examine whether adult levels of serum LDL-C are associated with maternal prepregnancy LDL-C levels beyond that attributable to inherited genetic sequence polymorphisms, diet, physical activity, and body mass index.The Framingham Heart Study is a multigenerational, population-based inception cohort initiated in 1948 in Framingham, Massachusetts. In this study of families, the analyses included 538 parent-offspring pairs with parental LDL-C levels measured in the study prior to the offspring's birth. Parental prebirth, parental concurrent, and adult offspring assessments occurred in 1971-1983, 1998-2001, and 2002-2005, respectively. Data analyses were conducted between March 1, 2013, and May 30, 2015.Maternal prepregnancy LDL-C levels compared with paternal prepregnancy and parental concurrent LDL-C levels in association with adult offspring LDL-C levels.Adult offspring LDL-C levels were examined as both a continuous and dichotomous outcome (using a threshold of 130 mg/dL).Among the 538 parent-offspring pairs, there were 241 mother-offspring and 297 father-offspring pairs with a mean (SD) offspring age of 26 (3) years. Adult offspring LDL-C levels were associated with maternal prepregnancy LDL-C levels after adjustment for family relatedness and offspring lifestyle, anthropometric factors, and inherited genetic variants (β = 0.32 [SE, 0.05] mg/dL; P < .001). After multivariable adjustment, adults who had been exposed to elevated maternal prepregnancy LDL-C levels were at a 3.8 (95% CI, 1.5-9.8) times higher odds of having elevated LDL-C levels (P = .005) and had an adjusted LDL-C level of 18 mg/dL (95% CI, 9-27 mg/dL) higher than did those without such exposure. Maternal prepregnancy LDL-C levels explained 13% of the variation in adult offspring LDL-C levels beyond common genetic variants and classic risk factors for elevated LDL-C levels.Adult offspring dyslipidemia is associated with maternal prepregnancy dyslipidemia in excess of measured lifestyle, anthropometric, and inherited genetic factors. The findings support the possibility of a maternal epigenetic contribution to cardiovascular disease risk in the general population. Further research is warranted to determine whether ongoing public health efforts to identify and reduce dyslipidemia in young adults prior to their childbearing years may have additional potential health benefits for the subsequent generation.
Genitourinary tuberculosis and its association with infertility in women
Authors: Chitra Iravatham, Prasad Chelluri, Hidayath Hussain, Ansari Shoeb, VijayKumar Marri
Journal: European Respiratory Journal (2011)

Introduction:  Infertility is a stressful event especially for women having both psychological and social impact.  Causes can be broadly classified under genetic, unknown etiology, environmental factors or of infectious origin.   Aim:  Retrospective analysis for cause of unexplained infertility in women.   Materials and methods:  Between 2008-2010, 200 female patients between age group 18 to 80 (mean age - 30.03) presenting with recurrent urinary tract infection not responding to antibiotics, irregular period and unexplained infertility were clinically evaluated.  Investigations included radiological and routine laboratory workup, monteux test, with screening for presence of Acid fast bacilli (AFB) done on early morning urine sample for three consecutive days.AFB culture was not done.   Result:  Of the total 200 patients AFB was positive in (n- 120) 60% of female patients, of which (39%)were in productive age group of 18 to 25 years with history of infertility, apart from chronic urinary tract infection.  Risk factors in older age group seen was Diabetes and other constitutional disorders.  Monteux positivity correlated with AFB positive patients.  Treatment with Anti TB treatment (ATT) under DOTS had a positive response with (n-15) 12.5% (age group 18-25) having reversal of symptoms and subsequent conception.   Conclusion:  Thus early detection and treatment can have a positive impact on prognosis.  Education on healthy life style management for women can help in restoring their health.
Changes in Oxygen Uptake-Work Rate Relationship as A Compensatory Mechanism in Patients with Heart Failure.
Authors: Haruki Itoh, Masato Nakamura, Chieko Ikeda, Etsuko Yanagisawa, Fumihiko Hatogai, Makoto Iwadare, Koichi Taniguchi
Journal: Circulation (1992)

To assess the compensatory change in oxygen uptake (VO2) kinetics during exercise in patients with heart failure, we performed cardiopulmonary exercise testing using a cycle ergometer in 29 cardiac patients and 18 normal subjects. The work rate increased linearly (1w/6sec) after a 4 min, 20w warm-up. The ratio of increase in VO2 to increase in work rate (delta VO2/delta WR) was determined by linear regression of VO2 plots. Cardiac output by dye dilution method and plasma norepinephrine concentration (NE) were measured at rest and 20w warm-up. VO2 at rest and at 20w warm-up and delta VO2/delta WR decreased significantly with increasing severity in NYHA functional classification. delta VO2/delta WR showed significant negative correlation to the difference in NE levels at rest and at 20w (r = -0.69, p less than 0.001). The delta values of arteriovenous O2 content difference, calculated using Fick's principle, and cardiac index from rest to 20w warm-up failed to show significant relationship to delta VO2/delta WR. These results suggest that the decrease in VO2 requirement in heart failure patients is due probably to blood redistribution during exercise as a compensatory mechanism for exercise intolerance.
Susceptibility of Unfertilized and Fertilized Mouse Eggs to Simian Virus 40 and Moloney Sarcoma Virus&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: W. Sawicki, W. Baranska, H. Koprowski
 4
Journal: JNCI Journal of the National Cancer Institute (1971)

Unfertilized one-celled mouse eggs infected with simian virus 40 (SV40), SV40 DNA, or Moloney sarcoma virus (MSV) and cultivated in vitro for 3–4 days showed no changes in morphology or kinetics of development as compared with uninfected controls. Mouse embryos infected with SV40 DNA at the two-celled stage showed retarded development, whereas those infected at the morula stage developed normally to the blastula stage in vitro. No harmful effect was observed after infection with MSV of either two-celled fertilized eggs or morulae. Infectious viruses could be rescued from unfertilized eggs and embryos infected with SV40, SV40 DNA, and MSV after 3–4 days of cocultivation of the eggs with susceptible somatic cells.
Predictors of early, intermediate, and late recurrences in randomized phase III trial of adjuvant chemotherapy versus chemoimmunotherapy for locally advanced gastric cancer after curative surgery: Final results of 15-year follow-up
Authors: Y. Moon, H. Jeung, S. Rha, N. Yoo, J. Roh, S. Noh, J. Min, B. Kim, H. Chung
Journal: Journal of Clinical Oncology (2008)

4562 Background: We evaluated predictors correlated with the timing of recurrence from 15-year followed phase III trial of adjuvant chemotherapy versus chemoimmunotherapy for locally advanced gastric cancer (LAGC) (Hei Cheul Jeung, etc. Annals of Oncology, 2007). Methods: The current study included two hundred eighty patients from a randomized trial of adjuvant chemotherapy (5-fluorouracil plus adriamycin) ±immunotherapy [polyadenylic-polyuridylic acid (poly A:U)] for LAGC after D2–3 curative resection. The timing of recurrence was classfied into early (≤ 2 years after surgery), intermediate (2∼5 years), and late (> 5 years) recurrences. Bivariate and multivariate analyses were performed to determine the predictors correlated with the timing of recurrence. Results: The median follow-up period was 92 months (range, 7∼260). The early, intermediate, and late recurrence rates were 26.4%(74 of 280 total), 17.5%(36 of 206 two-year recurrence-free survivors), 12.4% (21 of 170 five-year recurrence-free survivors), respectively. The dominant recurrence pattern was peritoneal carcinomatosis during early and intermediate period but distant metastasis for late period. In bivariate analysis, poly A:U immunotherapy, tumor differentiation [well differentiated (D) vs moderately D vs poorly D or signet ring cell vs undifferentiate], tumor invasion (T1–2 vs T3–4), lymph node involvement (N0–1 vs N2 vs N3), and stage (IB-IIIB vs IVM0) were significant (p<0.05) for early recurrence; however, only tumor invasion and stage were significant (P<0.05) for intermediate and late recurrences. In multivariate analysis of predictors for early recurrence, poly A:U [hazard ratio (HR)=1.90; p=0.007], histology (HR=2.51; p=0.000), and stage (HR=2.39; p=0.003) were significant. Conclusions: In patients with gastric carcinoma treated with D2–3 gastrectomy and adjuvant therapy, treatment factor such as poly A:U immunotherapy as well as tumor factors affected early recurrence. However, intermediate and late recurrences were only influenced by tumor factors, not by treatment factor. No significant financial relationships to disclose.