bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zoledronic Acid Markedly Improves Bone Mineral Density for Patients with Monoclonal Gammopathy of Undetermined Significance and Bone Loss
Authors: Berenson James R. , Yellin Ori , Boccia Ralph V. , Flam Marshall , Wong Siu-Fun , Batuman Olcay , Moezi Mehdi M. , Woytowitz Donald , Duvivier Herbert , Nassir Youram , Swift Regina A. 
Published: October 2008

Abstract
Purpose: Patients with monoclonal gammopathy of undetermined significance (MGUS) have increased rates of bone resorption, osteopenia, osteoporosis, and risk of fractures. This study was undertaken to determine the efficacy and safety of zoledronic acid for patients with MGUS and enhanced bone loss.
Experimental Design: In this phase II open-label study, 54 patients with MGUS and osteopenia or osteoporosis were administered zoledronic acid 4 mg i.v. at 0, 6, and 12 months. The primary efficacy end point was bone mineral density, assessed using a dual-energy X-ray absorptiometry scan in the lumbar (L)-spine done at screening and at 13 months (1 month after the final zoledronic acid infusion).
Results: At study end for all patients (N = 54), L-spine T-scores improved by a median of +0.27 (range, −0.38 to +3.91), corresponding to a median increase in bone mineral density of +15.0% (range, −18.0% to +1,140.0%; P &lt; 0.0001). Hip T-scores improved by a median of +0.10 (range, −2.40 to +2.03), corresponding to a median increase of +6.0% (range, −350.0% to +165.0%). During the study, no new fractures, osteonecrosis of the jaw, or significant renal adverse events were reported.
Conclusions: Zoledronic acid administered i.v. at a dosage of 4 mg every 6 months for three doses total was well-tolerated and substantially improved bone mineral density for patients with MGUS and bone loss. Zoledronic acid may be effective for the prevention of new fractures in this high-risk population.
Cotreatment with Vorinostat Enhances Activity of MK-0457 (VX-680) against Acute and Chronic Myelogenous Leukemia Cells
Authors: Fiskus Warren , Wang Yongchao , Joshi Rajeshree , Rao Rekha , Yang Yonghua , Chen Jianguang , Kolhe Ravindra , Balusu Ramesh , Eaton Kelly , Lee Pearl , Ustun Celalettin , Jillella Anand , Buser Carolyn A. , Peiper Stephen , Bhalla Kapil 
Published: October 2008

Abstract
Purpose: We determined the effects of vorinostat (suberoylanalide hydroxamic acid) and/or MK-0457 (VX-680), an Aurora kinase inhibitor on the cultured human (HL-60, OCI-AML3, and K562) and primary acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML), as well as on the murine pro-B BaF3 cells with ectopic expression of the unmutated and mutant forms of Bcr-Abl.
Experimental Design: Following exposure to MK-0457 and/or vorinostat, apoptosis, loss of viability, as well as activity and levels of Aurora kinase and Bcr-Abl proteins were determined.
Results: Treatment with MK-0457 decreased the phosphorylation of Aurora kinase substrates including serine (S)10 on histone H3 and survivin, and led to aberrant mitosis, DNA endoreduplication as well as apoptosis of the cultured human acute leukemia HL-60, OCI-AML3, and K562 cells. Combined treatment with vorinostat and MK-0457 resulted in greater attenuation of Aurora and Bcr-Abl (in K562) kinase activity and levels as well as synergistically induced apoptosis of OCI-AML3, HL-60, and K562 cells. MK-0457 plus vorinostat also induced synergistic apoptosis of BaF3 cells with ectopic overexpression of wild-type or mutant Bcr-Abl. Finally, cotreatment with MK-0457 and vorinostat induced more loss of viability of primary AML and imatinib-refractory CML than treatment with either agent alone, but exhibited minimal toxicity to normal CD34+ progenitor cells.
Conclusions: Combined in vitro treatment with MK-0457 and vorinostat is highly active against cultured and primary leukemia cells. These findings merit in vivo testing of the combination against human AML and CML cells, especially against imatinib mesylate–resistant Bcr-AblT315I–expressing CML Cells.
Androgen-Regulated and Highly Tumorigenic Human Prostate Cancer Cell Line Established from a Transplantable Primary CWR22 Tumor
Authors: Dagvadorj Ayush , Tan Shyh-Han , Liao Zhiyong , Cavalli Luciane R. , Haddad Bassem R. , Nevalainen Marja T. 
Published: October 2008

Abstract
Purpose: One of the major obstacles in understanding the molecular mechanisms underlying the transition of prostate cancer growth from androgen dependency to a hormone-refractory state is the lack of androgen-regulated and tumorigenic human prostate cancer cell lines.
Experimental Design: We have established and characterized a new human prostate cancer cell line, CWR22Pc, derived from the primary CWR22 human prostate xenograft tumors.
Results: The growth of CWR22Pc cells is induced markedly by dihydrotestosterone, and CWR22Pc cells express high levels of androgen receptor (AR) and prostate-specific antigen (PSA). Importantly, PSA expression in CWR22Pc cells is regulated by androgens. Stat5a/b, Stat3, Akt, and mitogen-activated protein kinase were constitutively active or cytokine inducible in CWR22Pc cells. The AR in CWR22Pc cells contains the H874Y mutation, but not the exon 3 duplication or other mutations. When inoculated subcutaneously into dihydrotestosterone-supplemented castrated nude mice, large tumors formed rapidly in 20 of 20 mice, whereas no tumors developed in mice without circulating dihydrotestosterone. Moreover, the serum PSA levels correlated with the tumor volumes. When androgens were withdrawn from the CWR22Pc tumors grown in nude mice, the tumors initially shrank but regrew back as androgen-independent tumors.
Conclusions: This androgen-regulated and tumorigenic human prostate cancer cell line provides a valuable tool for studies on androgen regulation of prostate cancer cells and on the molecular mechanisms taking place in growth promotion of prostate cancer when androgens are withdrawn from the growth environment. CWR22Pc cells also provide a model system for studies on the regulation of transcriptional activity of mutated H874YAR in a prostate cancer cell context.
A Phase I-II Study of Docetaxel and Atrasentan in Men with Castration-Resistant Metastatic Prostate Cancer
Authors: Armstrong Andrew J. , Creel Patricia , Turnbull James , Moore Cassandra , Jaffe Tracy A. , Haley Sherri , Petros William , Yenser Sarah , Gockerman Jon P. , Sleep Darryl , Hurwitz Herbert , George Daniel J. 
Published: October 2008

Abstract
Purpose: The primary aims of this phase I-II study were to determine the maximum tolerated dose, dose-limiting toxicity, pharmacokinetics, and preliminary efficacy of the combination of docetaxel and the endothelin A receptor antagonist atrasentan as first-line treatment for men with metastatic castration-resistant prostate cancer.
Experimental Design: Patients were treated with docetaxel at doses ranging from 60 to 75 mg/m2 every 21 days, with daily oral atrasentan 10 mg starting on day 3. Patients were treated until evidence of disease progression or unacceptable toxicity.
Results: Thirty-one patients were enrolled over three docetaxel dose levels (8 at 60 mg/m2, 19 at 70 mg/m2, and 4 at 75 mg/m2) including dose expansion at 70 mg/m2. The maximum tolerated dose of docetaxel was 70 to 75 mg/m2. Drug-related grade 3-4 toxicities included neutropenia (50-63%) and febrile neutropenia (16-25%); other grade 1-2 toxicities included fatigue, peripheral edema, diarrhea, headache, rhinitis, anorexia, and nausea. Confirmed prostate-specific antigen (PSA) responses were observed in 23% [95% confidence interval (95% CI), 10-41%]; the rate of &gt;30% declines in PSA was 35% (95% CI, 19-55%). Median overall survival was 17.6 months (95% CI, 13.0-23.2) and median progression-free survival was 4.2 months (95% CI, 2.3-5.8). Significant declines in bone alkaline phosphatase and serum N-telopeptides were observed with therapy.
Conclusions: The maximum tolerated dose of every-3-week docetaxel with 10 mg atrasentan is 70 to 75 mg/m2. Overall survival and progression-free survival are comparable to that seen with docetaxel and prednisone, whereas the rates of PSA decline are slightly lower than expected. A phase III study of this combination with prednisone has been initiated and is ongoing.
CASP3 Polymorphisms and Risk of Squamous Cell Carcinoma of the Head and Neck
Authors: Chen Kexin , Zhao Hui , Hu Zhibin , Wang Li-E , Zhang Wei , Sturgis Erich M. , Wei Qingyi 
Published: October 2008

Abstract
Purpose: Caspase-3 plays a central role in executing cell apoptosis and thus in carcinogenesis, but little is known about the role of CASP3 variants in susceptibility to SCCHN.
Experimental Design: Genotype and haplotypes of the first intron (rs4647601:G&gt;T and rs4647602:C&gt;A) and 5′-untranslated region (UTR; rs4647603:G&gt;A) of CASP3 (NT_022792.17) were determined for 930 SCCHN patients and 993 cancer-free controls in a U.S. non-Hispanic white population. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated in multivariate logistic regression analysis.
Results: We found that the CASP3 rs4647601:TT variant genotype was associated with an increased risk of SCCHN (adjusted OR, 1.32; 95% CI, 1.00-1.73) compared with the GG genotype. This risk was more evident in the subgroups of younger (≤56 years) subjects, males, and never smokers with a significant trend for increased risk with increased number of variant T allele (P &lt; 0.05 for all). However, these risks were not found for other two SNPs. Furthermore, individuals with two copies of haplotypes TCG or GCA were found to have a significant increased risk of SCCHN (OR, 1.31; 95% CI, 1.07-1.61) compared with the other haplotypes, and this risk was more evident in less advanced diseases (OR, 1.45; 95% CI, 1.11-1.89) than in the advanced diseases (OR, 1.22; 95% CI, 0.96-1.54).
Conclusions: These results suggested that genetic variation in CASP3 may contribute to SCCHN risk. Larger studies are needed to confirm our findings.
Phase I Study of Epigenetic Modulation with 5-Azacytidine and Valproic Acid in Patients with Advanced Cancers
Authors: Braiteh Fadi , Soriano Andres O. , Garcia-Manero Guillermo , Hong David , Johnson Marcella M. , Silva Leandro De Padua , Yang Hui , Alexander Stefanie , Wolff Johannes , Kurzrock Razelle 
Published: October 2008

Abstract
Purpose: 5-Azacytidine (5-AZA) is a DNA-hypomethylating agent. Valproic acid is a histone deacetylase inhibitor. Combining hypomethylating agents and histone deacetylase inhibitors produces synergistic anticancer activity in vitro and in vivo. On the basis of this evidence, we conducted a phase I study of the combination of 5-AZA and valproic acid in patients with advanced cancers.
Experimental Design: 5-AZA was administered s.c. daily for 10 days. Valproic acid was given orally daily with a goal to titrate to plasma levels of 75 to 100 μg/mL (therapeutic for seizures). Cycles were 28 days long. 5-AZA was started at 20 mg/m2 and escalated using an adaptive algorithm based on the toxicity profile in the prior cohort (6 + 6 design). Peripheral blood mononuclear cell global DNA methylation and histone H3 acetylation were estimated with the long interspersed nucleotide elements pyrosequencing assay and Western blots, respectively, on days 1 and 10 of each cycle when patients agreed to provide them.
Results: Fifty-five patients were enrolled. Median age was 60 years (range, 12-77 years). The maximum tolerated dose was 75 mg/m2 of 5-AZA in combination with valproic acid. Dose-limiting toxicities were neutropenic fever and thrombocytopenia, which occurred at a dose of 94 mg/m2 of 5-AZA. Stable disease lasting 4 to 12 months (median, 6 months) was observed in 14 patients (25%). A significant decrease in global DNA methylation and induction of histone acetylation were observed.
Conclusion: The combination of 5-AZA and valproic acid is safe at doses up to 75 mg/m2 for 5-AZA in patients with advanced malignancies.
Integrin Agonists as Adjuvants in Chemotherapy for Melanoma
Authors: Schwartz Martin A. , McRoberts Kevin , Coyner Matthew , Andarawewa Kumari L. , Frierson Henry F. , Sanders John M. , Swenson Stephen , Markland Frank , Conaway Mark R. , Theodorescu Dan 
Published: October 2008

Abstract
Purpose: Metastatic melanomas are generally resistant to chemotherapy and radiation, even when wild-type for p53. These tumors often grow in small nests where many of the cells have little contact with extracellular matrix (ECM). Previous work showed that M21 melanomas undergo apoptosis in response to chemotherapy when cells are adherent to ECM but not in suspension. Thus, reduced integrin-dependent adhesion to ECM could mediate therapy resistance. The goal of this study was to test whether stimulation of integrin signaling could increase chemotherapeutic efficacy.
Experimental Design: Colony forming assays and survival assays were used to test the responses of melanoma lines in vitro. Severe combined immunodeficient mice with subcutaneous human melanomas received chemotherapy with or without reagents that stimulate integrin signaling; tumor volume was then monitored over time.
Results: Clonal growth assays confirmed that M21 cells showed reduced sensitivity to the chemotherapeutic drug 1-β-d-arabinofuranosylcytosine (araC). When five additional primary melanoma lines were screened, 80% showed higher sensitivity when adherent compared with suspended. Subcutaneous M21 tumors in vivo showed minimal ECM between tumor cells. To evaluate the importance of integrin signaling in chemoresistance in this model, mice were treated with araC, with or without the multivalent snake venom disintegrin contortrostatin or the activating anti-β1 integrin antibody TS2/16. Although araC, TS2/16, or contortrostatin alone had little effect on M21 tumor growth, combining araC with either integrin signaling reagents strongly reduced growth (P = 0001).
Conclusions: Loss of integrin-mediated adhesion is rate limiting for therapeutic response in this model. Combining chemotherapy with reagents that stimulate integrin signaling may therefore provide a new approach to therapy.
Effect of Low Temperature on Mechanical Properties of Bidirectional Glass Fiber Composites
Authors: Shrivastava A.K. , Nazir Hussain Md. 
Published: October 2008

In this article, low temperature and its degradative influence on the material together with hygro-thermal effect are highlighted. Hygrothermal factor is a major environmental factor experienced by the composites. An attempt has been made to study the mechanical properties of bidirectional glass cloth specimens exposed to low temperature and humid condition. Tensile strength records its highest value after 10 days exposure at -55°C, compressive strength at 0°C exposure increases but after 10 days exposure at -55°C decreases, shear strength of exposed specimen at 0°C increases, flexural strength of exposed specimen at -55°C increases and records its highest value of 10 days exposed specimen. Further, it has been observed that the strength of the composite is in the following order: Compressive strength of specimen<shear strength of specimen<tensile strength of specimen<flexural strength of specimen. In this article an attempt has been made to study effect of low temperature on mechanical properties of bidirectional glass fiber composites.
Making Diabetes Self-management Education Culturally Relevant for Filipino Americans in Hawaii
Authors: Finucane Melissa L. , McMullen Carmit K. 
Published: October 2008

Purpose The purpose of this study was to identify the cultural val- ues, traditions, and perceptions of diabetes risk and self- care among Filipino Americans in Hawaii with type 2 diabetes that facilitate or impede engagement in diabetes self-management behaviors and education classes. Methods This qualitative study used 2 rounds of semistructured focus groups and interviews. Participants included 15 patients with type 2 diabetes recruited from a large health-maintenance organization in Hawaii and 7 health care and cultural experts recruited from the community. The taped and transcribed focus groups and interviews were coded thematically. Participants evaluated example materials for diabetes self-management education (DSME) with Filipino Americans. Results Several aspects of Filipino American culture were identi- fied as central to understanding the challenges of engag- ing in self-management behaviors and DSME: (1) undertaking self-management while prioritizing the fam- ily and maintaining social relationships, (2) modifying diet while upholding valued symbolic and social mean- ings of food, (3) participating in storytelling in the face of stigma associated with diabetes, and (4) reconciling spiritual and biomedical interpretations of disease causa- lity and its management. Respondents also emphasized therole of several qualitative aspects of perceived risk (eg, dread, control) in moderating their behaviors. Participants suggested ways to make DSME culturally relevant. Conclusions Awareness of cultural values and qualitative aspects of perceived risk that influence Filipino Americans' engage- ment in diabetes self-care behaviors and classes may help to improve teaching methods, materials, and recruitment strategies
Low Testosterone and the Association With Type 2 Diabetes
Authors: Farrell JoAnne B. , Deshmukh Anjali , Baghaie Ali A. 
Published: October 2008

Purpose The purpose of this article is to describe androgen deficiency in men, the consequences of this clinically underdiagnosed endocrine disorder, and its relationship to the metabolic syndrome and the association with type 2 diabetes. An overview of prevalence, screening, diagnosis, treatment, and monitoring of male hypogonadism is presented. Method Established guidelines were used to provide definition, diagnosis, treatment, and monitoring information for male hypogonadism. A literature review from 1990 to 2007 revealed study findings that identify the link between low testosterone in men and the development of type 2 diabetes. The following databases were used to review and analyze the current literature: CINAHL, PubMed, and MEDLINE. Results An analysis of 26 studies was completed. The key findings in all of these studies show that there is a link between low levels of testosterone and an adverse metabolic profile (ie, obesity and insulin resistance). There is evidence that hypogonadism is associated with metabolic syndrome and type 2 diabetes in men. Conclusion Male hypogonadism is a clinical condition that affects a significant number of men in the United States and can affect up to 50% of men diagnosed with type 2 diabetes. The implications for diabetes educators are two-fold: first, there is a high prevalence of low testosterone in men with type 2 diabetes, and second, educators need to have a better understanding of this disease state to provide instructional guidance for their patients and to coordinate care with other clinicians.
Diabetes Training of Community Health Workers Serving Native Hawaiians and Pacific People
Authors: Look Mele A. , Baumhofer Nicole K. , Ng-Osorio Jackie , Furubayashi Jill K. , Kimata Chieko 
Published: October 2008

Purpose Training of community health workers (CHWs) serving Native Hawaiian and Pacific People about diabetes prevention, control, and management was identified as a priority in a needs assessment of health agencies in Hawai`i. Methods Principles from Community-Based Participatory Research provided a framework to develop and implement a 4-hour training curriculum. The curriculum developers incorporated teaching strategies shown to be effective with this population and included culturally relevant material. Nineteen health organizations participated in the training that reached 111 CHWs over a 3-year period. Results Based on comparison of pre- and post-diabetes knowledge test results, the training participants showed significant gain in diabetes knowledge. Conclusions A culturally tailored diabetes education gives CHWs the relevant knowledge and tools to participate in the delivery of diabetes education to a minority group experiencing disparate health outcomes. A community-based method facilitated development of seminar content and delivery strategies.
Psychosocial Factors Related to Diet Among Women with Recent Gestational Diabetes Opportunities for Intervention
Authors: Zehle Katharina , Smith Ben J. , Chey Tien , McLean Mark , Bauman Adrian E. , Wah Cheung N. 
Published: October 2008

Purpose This study investigated postpartum dietary behaviors among women with recent gestational diabetes mellitus (GDM), the cognitive and social factors related to these, and preferred types of lifestyle support, in order improve the development of diabetes prevention strategies for this group. Methods Participants were a random sample of 226 women diagnosed with GDM in the prior 6 to 24 months. Telephone surveys were used to evaluate dietary behaviors, self-efficacy, social support, perceived barriers to healthy eating, and preferred methods of lifestyle support. Results Only 5% of the respondents consumed 5 servings/day of vegetables and 44% consumed 2 or more servings/day of fruit. Fried food was eaten at least twice per week by 26% of women and 50% usually consumed full-fat milk. Higher vegetable consumption was associated with self-efficacy to cook healthy foods, reporting that a healthy diet is not a difficult change and that dislike of healthy foods by other household members is not a barrier. Fruit consumption was positively related to self-efficacy when busy and when not reporting a dislike of healthy foods by others at home. Advice from a dietitian and telephone support from a health educator were the most preferred forms of health assistance. Conclusions Dietary risks factors are prevalent among women with recent GDM. Confidence and skills in cooking healthy foods, along with family food preferences and time pressures, are important influences on eating habits. Dietary change programs, informed by the beliefs and circumstances of this high-risk population, need to be developed.
Culturally Tailored Intervention for Rural African Americans With Type 2 Diabetes
Authors: Utz Sharon W. , Williams Ishan C. , Jones Randy , Hinton Ivora , Alexander Gina , Yan Guofen , Moore Cynthia , Blankenship Jean , Steeves Richard , Norman Oliver M. 
Published: October 2008

Purpose The purpose of this pilot study was to evaluate a culturally tailored intervention for rural African Americans. Social Cognitive Theory provided the framework for the study. Methods Twenty-two participants were recruited and randomly assigned to either Group or Individual diabetes self-management (DSME). Group DSME included story-telling, hands-on activities, and problem-solving exercises. Individual DSME sessions focused on goal-setting and problem-solving strategies. Sessions were offered in an accessible community center over a 10-week period. Results Outcomes included glycosylated hemoglobin (A1C), self-care actions, self-efficacy level, goal attainment, and satisfaction with DSME. Participants in both Group and Individual DSME improved slightly over the 3-month period in self-care activities, A1C level, and goal attainment. Although differences were not statistically significant, trends indicate improved scores on dietary actions, foot care, goal attainment, and empowerment for those experiencing Group DSME. Conclusions The culturally tailored approach was well received by all participants. Improvements among those receiving Individual DSME may indicate that brief sessions using a culturally tailored approach could enhance self-care and glycemic control. Additional testing among more participants over a longer time period is recommended.