bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth Inhibition and Induction of Apoptosis in SHG‐44 Glioma Cells by Chinese Medicine Formula “Pingliu Keli”
Authors: Cao Peng , Cai Xueting , Lu Wuguang , Zhou Fei , Huo Jiege
Published: September 2010

The present study was carried out to evaluate the effects of the water extract of Chinese medicine “Pingliu Keli” (PK) on human glioma cell viability and apoptosis and to investigate its mechanisms of action in SHG‐44 cells. MTT assay showed that PK had a strong cytotoxic effect on SHG‐44 cells. The number of live cells was less than 20% after exposure to 90 μg/mL PK for 24 h. PK increased cytotoxicity of SHG‐44 cells in a dose‐dependent manner. PK caused arrest of SHG‐44 cells in G1 phase at low concentration and in G2 phase at high concentration. The percentage of apoptotic cells by flow cytometric analysis of the DNA‐stained cells increased to 38% and 52% after treatment with 72 and 108 μg/mL PK, respectively. In addition, PK increased the expression of proapoptotic protein (Bax) and decreased antiapoptotic protein (Bcl‐2), with a concomitant increase in the levels of cleaved caspase‐3, cleaved caspase‐9 and cleaved poly‐ADP‐ribose polymerase (PARP). These results suggest that PK has a significant apoptosis inducing effect on SHG‐44 glioma cells in vitro and caspase‐3 may act as a potential mediator in the process.
Use of Complementary and Alternative Medicine among People with Type 2 Diabetes in Taiwan: A Cross‐Sectional Survey
Authors: Chang Hsiao-yun Annie , Wallis Marianne , Tiralongo Evelin
Published: September 2010

Research into CAM use by people with diabetes is limited. This study explored CAM use among patients who attend diabetic clinics for followup treatment. Special attention was paid to patients′ changing patterns of CAM use before and after diagnosis with Type 2 diabetes, their experience of CAM use, and their management of CAM use with conventional medicines. A retrospective cross‐sectional survey (n = 326) was undertaken in three census regions in Taiwan, including metropolitan, urban, and rural areas in 2006‐7 (87.4% response rate). Participants reported extensive use of CAM with conventional medicines. The prevalence of CAM use was 22.7% before and 61.0% after diagnosis with Type 2 diabetes with nutritional supplements being the most commonly used CAM before and after diagnosis. However, the disclosure rate of CAM use to healthcare professionals remained low (24.6%), and lack of knowledge about CAM ingredients was common (63.4%). Awareness of the widespread use of CAM by people with Type 2 diabetes is crucial for healthcare professionals. The self‐administration of both conventional medicines and CAM without disclosure of CAM use to healthcare professionals may result in ineffective diabetes management and adverse effects. CAM information needs to be incorporated into clinical practice and patient and professional education.
Hyaluronan Deficiency in Tumor Stroma Impairs Macrophage Trafficking and Tumor Neovascularization
Authors: Kobayashi Nobutaka , Miyoshi Seiji , Mikami Takahide , Koyama Hiroshi , Kitazawa Masato , Takeoka Michiko , Sano Kenji , Amano Jun , Isogai Zenzo , Niida Shumpei , Oguri Kayoko , Okayama Minoru , McDonald John A. , Kimata Koji , Taniguchi Shun'ichiro , Itano Naoki
Published: September 2010

Despite the importance of stromal cells in tumor progression, our overall understanding of the molecular signals that regulate the complex cellular interactions within tumor stroma is limited. Here, we provide multiple lines of evidence that tumor-associated macrophages (TAM) preferentially traffic to stromal areas formed within tumors in a manner dependent on a hyaluronan (HA)–rich tumor microenvironment. To address the role of stroma-derived HA in macrophage recruitment, we disrupted the HA synthase 2 (Has2) gene in stromal fibroblasts using conditional gene targeting. The Has2 null fibroblasts showed severe impairment in recruiting macrophages when inoculated with tumor cells into nude mice, which shows the contribution of stroma-derived HA in intratumoral macrophage mobilization. Furthermore, a deficiency in stromal HA attenuated tumor angiogenesis and lymphangiogenesis concomitantly with impaired macrophage recruitment. Taken together, our results suggest that stromal HA serves as a microenvironmental signal for the recruitment of TAMs, which are key regulatory cells involved in tumor neovascularization. Cancer Res; 70(18); 7073–83. ©2010 AACR.
Quantitative Imaging of Lymphatic Function with Liposomal Indocyanine Green
Authors: Proulx Steven T. , Luciani Paola , Derzsi Stefanie , Rinderknecht Matthias , Mumprecht Viviane , Leroux Jean-Christophe , Detmar Michael
Published: September 2010

Lymphatic vessels play a major role in cancer progression and in postsurgical lymphedema, and several new therapeutic approaches targeting lymphatics are currently being developed. Thus, there is a critical need for quantitative imaging methods to measure lymphatic flow. Indocyanine green (ICG) has been used for optical imaging of the lymphatic system, but it is unstable in solution and may rapidly enter venous capillaries after local injection. We developed a novel liposomal formulation of ICG (LP-ICG), resulting in vastly improved stability in solution and an increased fluorescence signal with a shift toward longer wavelength absorption and emission. When injected intradermally to mice, LP-ICG was specifically taken up by lymphatic vessels and allowed improved visualization of deep lymph nodes. In a genetic mouse model of lymphatic dysfunction, injection of LP-ICG showed no enhancement of draining lymph nodes and slower clearance from the injection site. In mice bearing B16 luciferase-expressing melanomas expressing vascular endothelial growth factor-C (VEGF-C), sequential near-IR imaging of intradermally injected LP-ICG enabled quantification of lymphatic flow. Increased flow through draining lymph nodes was observed in mice bearing VEGF-C–expressing tumors without metastases, whereas a decreased flow pattern was seen in mice with a higher lymph node tumor burden. This new method will likely facilitate quantitative studies of lymphatic function in preclinical investigations and may also have potential for imaging of lymphedema or improved sentinel lymph detection in cancer. Cancer Res; 70(18); 7053–62. ©2010 AACR.
Antibody-Dependent Natural Killer Cell–Mediated Cytotoxicity Engendered by a Kinase-Inactive Human HER2 Adenovirus-Based Vaccination Mediates Resistance to Breast Tumors
Authors: Triulzi Chiara , Vertuani Simona , Curcio Claudia , Antognoli Agnese , Seibt Josef , Akusjärvi Göran , Wei Wei-Zen , Cavallo Federica , Kiessling Rolf
Published: September 2010

Cancer vaccines may have applications in the therapy and prevention of mammary carcinoma. To investigate such applications, we constructed a recombinant adenoviral vaccine expressing a kinase-inactive mutant form of human HER2 and introduced this into BALB/c wild-type (WT) or HER2 transgenic mice. Here, we report contributions by antibody responses and natural killer (NK) cells in tumor protection in this model. One i.p. vaccination protected WT mice from the HER2-expressing mouse carcinoma D2F2/E2. Half of the HER2 transgenic mice were protected fully and long term after preventive vaccination. Tumor growth in mice that eventually developed neoplastic lesions was delayed. Protection in WT and HER2 transgenic mice was associated with high or low levels of IgG2a antibodies, respectively, whereas CTLs were observed in WT but not in HER2 transgenic mice. Depleting CD4+ or CD8+ cells in vaccinated WT mice had limited effects, suggesting that protection was largely independent of CD4+ or CD8+ T cells. In contrast, antibody-mediated tumor rejection seemed to contribute significantly based on a loss of protection in mice deficient for Fc-γ RI/III or B cells. Further, a role for antibody-dependent cellular cytotoxicity (ADCC) mediated by NK cells was indicated by evidence that vaccine protection could be abolished by in vivo depletion of NK cells. Lastly, NK cells and immune sera purified from WT or HER2 transgenic mice exhibited efficient ADCC of HER2-expressing tumor cells in vitro. Our findings define a critical requirement for NK cells in vaccine-induced protection against HER2-expressing tumors. Cancer Res; 70(19); 7431–41. ©2010 AACR.
IFNγ Markedly Cooperates with Intratumoral Dendritic Cell Vaccine in Dog Tumor Models
Authors: Mito Kai , Sugiura Kikuya , Ueda Kana , Hori Takako , Akazawa Takashi , Yamate Jyoji , Nakagawa Hiroshi , Hatoya Shingo , Inaba Muneo , Inoue Norimitsu , Ikehara Susumu , Inaba Toshio
Published: September 2010

Dendritic cell (DC)–based immunotherapy can trigger effective immune responses against cancer in human patients. Although accompanied by little toxicity, further improvements are needed to optimize immune responses for fully satisfactory clinical outcomes. IFNγ, a potent inducer of T helper type 1 immune responses, is considered an important tool to realize improvements. In this study, we sought to clarify the effect of IFNγ on the maturation and activation of DCs and the clinical outcome of DC-based cancer therapy in dogs. In vitro experiments indicated that IFNγ significantly enhanced the expression of immune stimulatory molecules and interleukin-12 by DCs derived from canine monocytes. IFNγ also significantly strengthened DC-mediated growth suppression against tumor cell lines. DC inoculation with concomitant delivery of IFNγ into primary or recurrent tumors elicited significant clinical responses, including four complete responses and two partial responses against malignant tumors, also eliciting partial responses against benign but actively growing tumors. Together, our results indicate that combining IFNγ and DCs could induce strong immune responses against tumors, significantly improving clinical outcomes. The present study of dogs bearing common types of cancer in humans offers a unique line of support for the development of human cancer therapies. Cancer Res; 70(18); 7093–101. ©2010 AACR.
Evaluation of Breast Cancer Susceptibility Loci in Chinese Women
Authors: Long Jirong , Shu Xiao-Ou , Cai Qiuyin , Gao Yu-Tang , Zheng Ying , Li Guoliang , Li Chun , Gu Kai , Wen Wanqing , Xiang Yong-Bing , Lu Wei , Zheng Wei
Published: September 2010

Background: Recent genome-wide association studies (GWAS), mostly conducted among women of European ancestry, have identified 16 single-nucleotide polymorphisms (SNP) associated with breast cancer.

Methods: We evaluated these SNPs with the risk of breast cancer and further by estrogen receptor status in a population-based study of 6,498 cases and 3,999 controls in Chinese women. We also searched for novel genetic risk variants in four loci, 2q35, 5p12/MRPS30, 8q24.21, and 17q23.2/COX11, in a two-stage study. In stage I, 868 SNPs were analyzed in 2,073 cases and 2,084 controls. In stage II, 58 SNPs selected from stage I were evaluated, including 4,425 cases and 1,915 controls.

Results: Statistically significant associations (P < 0.05) were observed for eight GWAS-identified SNPs, including rs4973768 (3p24/SLC4A7), rs889312 (5q11.2MAP3K1), rs2046210 (6q25.1), rs1219648 (10q26.13/FGFR2), rs2981582 (10q26.13/FGFR2), rs3817198 (11p15.5/LSP1), rs8051542 (16q12.1/TOX3), and rs3803662 (16q12.1/TOX3). Two additional SNPs, rs10941679 (5p12/MRPS30) and rs13281615 (8q24.21), showed a marginally significant association. Some of these associations varied by estrogen receptor status. In the fine-mapping analysis, five SNPs showed a consistent association with breast cancer risk in both stages: rs10169372 (2q35), rs283720 (8q24.21), rs10515083 (17q23.2/COX11), rs16955329 (17q23.2/COX11), and rs2787487 (17q23.2/COX11).

Conclusions: This study shows that approximately half of the SNPs initially reported from GWAS of breast cancer in European descendants can be directly replicated in Chinese. Our fine-mapping analyses revealed several candidates of risk variants that can be further evaluated in studies with a larger sample size.

Impact: Findings from this study may help guide future fine-mapping studies to identify causal variants for breast cancer. Cancer Epidemiol Biomarkers Prev; 19(9); 2357–65. ©2010 AACR.
Knowledge and Use of Finasteride for the Prevention of Prostate Cancer
Authors: Hamilton Robert J. , Kahwati Leila C. , Kinsinger Linda S.
Published: September 2010

Background: The knowledge about and use of chemopreventive agents for prostate cancer by physicians has not been described. The Prostate Cancer Prevention Trial (PCPT) showed that finasteride was effective in reducing the incidence of prostate cancer. We examined the influence of the PCPT on finasteride prescribing within the Veterans Health Administration (VHA).

Methods: We assessed trends on monthly new and total prescriptions for finasteride filled within the VHA from January 2000 to December 2005. Additionally, all VHA urologists and a random sample of VHA primary care physicians (PCP) were surveyed about their use of finasteride.

Results: The number of men starting finasteride grew over the study period. Publication of the PCPT was not significantly associated with any change in this pattern (P = 0.45). Fifty-seven percent of urologists and 40% of PCPs endorsed prescribing finasteride more frequently in 2006 than 5 years prior. However, among those who reported changing prescribing patterns, fewer than 2% reported being influenced by the PCPT. Sixty-four percent of urologists and 80% of PCPs never prescribe finasteride for prostate cancer chemoprevention; 55% of urologists cited concerns of inducing high-grade tumors, whereas 52% of PCPs did not know it could be used for chemoprevention.

Conclusions: The number of men starting finasteride in the VHA increased over time, but the change did not seem to be due to increased use of finasteride for chemoprevention. Publication of the PCPT seemed to have little influence over the study period.

Impact: Physicians may not readily accept the use of chemopreventive agents for prostate cancer. Cancer Epidemiol Biomarkers Prev; 19(9); 2164–71. ©2010 AACR.
Context-Dependent Effects of Genome-Wide Association Study Genotypes and Macroenvironment on Time to Biochemical (Prostate Specific Antigen) Failure after Prostatectomy
Authors: Rebbeck Timothy R. , Weber Anita L. , Walker Amy H. , Stefflova Klara , Tran Teo V. , Spangler Elaine , Chang Bao-Li , Zeigler-Johnson Charnita M.
Published: September 2010

Background: Disparities in cancer defined by race, age, or gender are well established. However, demographic metrics are surrogates for the complex contributions of genotypes, exposures, health care, socioeconomic and sociocultural environment, and many other factors. Macroenvironmental factors represent novel surrogates for exposures, lifestyle, and other factors that are difficult to measure but might influence cancer outcomes.

Methods: We applied a “multilevel molecular epidemiology” approach using a prospective cohort of 444 White prostate cancer cases who underwent prostatectomy and were followed until biochemical failure (BF) or censoring without BF. We applied Cox regression models to test for joint effects of 86 genome-wide association study–identified genotypes and macroenvironment contextual effects after geocoding all cases to their residential census tracts. All analyses were adjusted for age at diagnosis and tumor aggressiveness.

Results: Residents living in census tracts with a high proportion of older single heads of household, high rates of vacant housing, or high unemployment had shorter time until BF postsurgery after adjustment for patient age and tumor aggressiveness. After correction for multiple testing, genotypes alone did not predict time to BF, but interactions predicting time to BF were observed for MSMB (rs10993994) and percentage of older single heads of households (P = 0.0004), and for HNF1B/TCF2 (rs4430796) and census tract per capita income (P = 0.0002).

Conclusions: The context-specific macroenvironmental effects of genotype might improve the ability to identify groups that might experience poor prostate cancer outcomes.

Impact: Risk estimation and clinical translation of genotype information might require an understanding of both individual- and macroenvironment-level context. Cancer Epidemiol Biomarkers Prev; 19(9); 2115–23. ©2010 AACR.
Parental Decision Making about the HPV Vaccine
Authors: Allen Jennifer D. , Othus Megan K.D. , Shelton Rachel C. , Li Yi , Norman Nancy , Tom Laura , del Carmen Marcela G.
Published: September 2010

Background: Prophylactic human papillomavirus (HPV) vaccines are available, but uptake is suboptimal. Information on factors influencing parental decisions regarding vaccination will facilitate the development of successful interventions.

Methods: Parents of girls ages 9 to 17 years (n = 476; cooperation rate = 67%) from a panel of U.S. households completed online surveys between September 2007 and January 2008, documenting vaccine knowledge, attitudes, and intentions.

Results: Among those aware of the vaccine, 19% had already vaccinated their daughter(s), 34% intended to, 24% were undecided, and 24% had decided against vaccination. Awareness of HPV was high but knowledge levels were suboptimal (mean 72%, SEM 0.8%). Black and Hispanic parents were significantly less likely to be aware of the vaccine compared with White parents. In multivariate analyses, compared with parents who opposed vaccination, those who had already vaccinated their daughter(s) or who intended to do so had more positive attitudes, reported fewer barriers, and were more likely to perceive that family and friends would endorse vaccination. They also reported higher levels of trust in pharmaceutical companies that produce the vaccine.

Conclusions: Despite limited knowledge, most parents had decided to vaccinate their daughter(s). Given evidence of diminished access to information among Black and Hispanic parents, programs should focus on reaching these groups. Interventions should address parental concerns about behavioral consequences, reduce structural barriers, and promote the perception that vaccination is endorsed by significant others. Moreover, interventions may need to address mistrust of pharmaceutical companies.

Impact Statement: This study documents factors associated with parental decisions about HPV vaccination for their daughter(s) and provides direction for intervention development. Cancer Epidemiol Biomarkers Prev; 19(9); 2187–98. ©2010 AACR.
Patient Delay in Presentation of Possible Cancer Symptoms: The Contribution of Knowledge and Attitudes in a Population Sample from the United Kingdom
Authors: Simon Alice E. , Waller Jo , Robb Kathryn , Wardle Jane
Published: September 2010

Background: Qualitative studies implicate knowledge of cancer symptoms and attitudes towards help-seeking as important factors in patient delay. The present study uses quantitative data from a population-based survey to test the hypotheses that (a) a greater knowledge of early cancer symptoms is associated with a higher likelihood of having appraised a symptom as possibly due to cancer, and (b) more negative attitudes towards help-seeking are associated with a lower likelihood of having sought medical advice for that symptom.

Methods: Two thousand and seventy-one adults were asked whether they had experienced a symptom that they worried might be cancer in the past 3 months, and if so, whether they had seen a doctor. Respondents also completed the Cancer Awareness Measure (CAM) assessing symptom knowledge and barriers to help-seeking.

Results: Two hundred and thirty-six (11.4%) respondents reported having experienced a possible cancer symptom. In logistic regression analyses controlling for age, sex, and self-rated health, higher CAM symptom knowledge scores were associated with a greater likelihood of having experienced a possible cancer symptom (odds ratio = 1.09; 95% confidence interval, 1.01-1.17). Of those who had experienced a symptom, 75% (177/236) had seen a doctor. Higher scores on the CAM barriers scale were associated with being less likely to have seen a doctor (odds ratio, 0.74; 95% confidence interval, 0.63-0.87).

Conclusions: Better knowledge of the signs and symptoms of cancer might help people recognize possible cancer symptoms and therefore reduce appraisal delay, whereas more positive attitudes towards help-seeking might reduce behavioral delay.

Impact: Campaigns to educate the public about cancer symptoms and reduce help-seeking barriers could play a role in promoting early diagnosis. Cancer Epidemiol Biomarkers Prev; 19(9); 2272–7. ©2010 AACR.
The Screening of Volatile Markers for Hepatocellular Carcinoma
Authors: Qin Tao , Liu Hu , Song Qi , Song Geng , Wang Hong-zhi , Pan Yue-yin , Xiong Fu-xing , Gu Kang-sheng , Sun Guo-ping , Chen Zhen-dong
Published: September 2010

Background: Breath analysis became promising for noninvasive diagnoses of cancer with sophisticated spectrometry technology introduced. This study aimed to screen volatile markers for hepatocellular carcinoma (HCC).

Methods: Breath samples were collected from 30 HCC patients who were comorbid with type B hepatitis and cirrhosis and from 27 hepatocirrhosis patients and 36 healthy persons, both taken as controls. The volatile organic compounds in the samples were analyzed with gas chromatography/mass spectrometry and the markers were selected by comparing their levels between groups. Each of the markers was evaluated by receiver operating characteristic (ROC) curves and a discriminant function using the markers was established. The relationships of α-fetoprotein (AFP) levels and clinical stages with the concentrations of the markers were also investigated.

Results: 3-Hydroxy-2-butanone, styrene, and decane were screened as potential markers, among which 3-hydroxy-2-butanone was found to have the best diagnostic value. The diagnostic function using these markers had a sensitivity of 86.7% and a specificity of 91.7% between HCC patients and normal controls and a sensitivity of 83.3% and a specificity of 91.7% by cross-validation. No statistically significance (P > 0.05) was found for the concentration differences of these markers between HCC patients with AFP >400 or <400 μg/L or between stage I-II and stage III-IV patients.

Conclusion: These volatile organic compounds could be useful as breath markers of HCC patients, independent of AFP levels or clinical stages.

Impact: Breath analysis could be useful for early diagnosis of HCC, especially for AFP-negative HCC. Cancer Epidemiol Biomarkers Prev; 19(9); 2247–53. ©2010 AACR.
Plasma Coenzyme Q10 Levels and Postmenopausal Breast Cancer Risk: The Multiethnic Cohort Study
Authors: Chai Weiwen , Cooney Robert V. , Franke Adrian A. , Shvetsov Yurii B. , Caberto Christian P. , Wilkens Lynne R. , Le Marchand Loïc , Henderson Brian E. , Kolonel Laurence N. , Goodman Marc T.
Published: September 2010

Background: Coenzyme Q10 (CoQ10) is a component of the mitochondrial electron transport chain and is considered an important cellular antioxidant. Decreased circulating CoQ10 levels have been reported in women with breast cancer, but evidence is limited. We examined the association of plasma CoQ10 levels with postmenopausal breast cancer risk using prospectively collected blood samples.

Methods: Prediagnostic plasma levels of total CoQ10 were measured among 160 incident postmenopausal breast cancer cases and 289 controls in the Multiethnic Cohort Study. Cases and controls were individually matched on age, sex, ethnicity, study location (Hawaii or California), hormone replacement therapy use, date and time of specimen collection, and hours of fasting. Logistic regression was used to compute odds ratios and 95% confidence intervals.

Results: Plasma CoQ10 levels were positively associated with breast cancer risk, overall (P = 0.04). The association was stronger after women diagnosed within 1 year of blood draw were excluded to eliminate possible preclinical cases (odds ratio for the highest versus the lowest tertile, 2.26; 95% confidence interval, 1.22-4.19; P for trend = 0.01).

Conclusions: Higher CoQ10 levels in postmenopausal women may be associated with increased breast cancer risk.

Impact: A potential role for CoQ10 in the development and progression of breast cancer has been postulated, but epidemiologic evidence is lacking. Findings from this prospective cohort study add to the limited literature, indicating the potential positive association of circulating CoQ10 with postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev; 19(9); 2351–6. ©2010 AACR.
Postdiagnosis Diet Quality Is Inversely Related to a Biomarker of Inflammation among Breast Cancer Survivors
Authors: George Stephanie M. , Neuhouser Marian L. , Mayne Susan T. , Irwin Melinda L. , Albanes Demetrius , Gail Mitchell H. , Alfano Catherine M. , Bernstein Leslie , McTiernan Anne , Reedy Jill , Smith Ashley W. , Ulrich Cornelia M. , Ballard-Barbash Rachel
Published: September 2010

Background: Inflammation and immune response have potential prognostic implications for breast cancer survivors. We examined how postdiagnosis diet quality is cross-sectionally related to biomarkers of inflammation and adipose-derived hormones among breast cancer survivors and determined whether physical activity or body size modified any observed associations.

Methods: Participants included 746 women diagnosed with stage 0 to IIIA breast cancer. Thirty months after diagnosis, the women completed food frequency questionnaires. We scored diet quality with the Healthy Eating Index (HEI)-2005. Serum concentrations of C-reactive protein (CRP), serum amyloid A, leptin, and adiponectin were measured in fasting 30 mL blood samples. Log biomarker values were regressed on quartiles of HEI-2005 scores in multivariate models, and β scores were exponentiated and expressed as geometric means within quartiles of HEI-2005 scores.

Results: Women with better versus poor quality postdiagnosis diets, as defined by higher HEI-2005 scores (Q4 versus Q1), had lower concentrations of CRP (1.6 mg/L versus 2.5 mg/L), but no significant difference in concentrations of serum amyloid A, leptin, or adiponectin. Among women not engaging in recreational physical activity after diagnosis, better diet quality was associated with lower CRP concentrations (2.5 mg/L versus 5.0 mg/L), but no association was observed among women engaging in any recreational physical activity (1.4 mg/L versus 1.6 mg/L; P heterogeneity = 0.03).

Conclusions: Among breast cancer survivors, a better-quality diet seems to be associated with lower levels of chronic inflammation.

Impact: Lower levels of chronic inflammation have been associated with improved survival after breast cancer. Cancer Epidemiol Biomarkers Prev; 19(9); 2220–8. ©2010 AACR.
Survival of Women with Colon Cancer in Relation to Precancer Anthropometric Characteristics: the Iowa Women's Health Study
Authors: Prizment Anna E. , Flood Andrew , Anderson Kristin E. , Folsom Aaron R.
Published: September 2010

Background: We hypothesized that precancer anthropometric variables are associated with mortality among women who developed colon cancer in a prospective cohort, the Iowa Women's Health Study (IWHS).

Methods: From 1986 to 2005, 1,096 incident cases of colon cancer were identified (mean age at diagnosis, 73 years). Anthropometric characteristics were self-measured before colon cancer diagnosis (in 1986). Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for all-cause and colon-cancer mortality, adjusted for age at cancer diagnosis, stage, education, smoking status, and pack-years of smoking.

Results: During the follow-up of up to 20 years, 493 women died; 289 had colon cancer as the underlying cause. The HRs of all-cause death were increased for the highest versus lowest tertile for weight (HR, 1.39; 95% CI, 1.10-1.76; P trend = 0.005); waist to hip ratio (WHR; HR, 1.36; 95% CI, 1.08-1.72; P trend = 0.008), and waist (HR, 1.45; 95% CI, 1.15-1.82; P trend = 0.001). Compared with that for body mass index (BMI) of 18.5 to 24.9 kg/m2, HRs were increased for BMI ≥30 kg/m2 (HR, 1.45; 95% CI, 1.14-1.85) and for the few women with BMI <18.5 kg/m2 (HR, 1.89; 95% CI, 1.01-3.53). Colon cancer mortality was positively associated with WHR and waist: HR, 1.37 (95% CI, 1.02;1.85; P trend = 0.04) and 1.34 (95% CI, 1.01-1.80; P trend = 0.05), respectively, for the highest versus lowest tertile.

Conclusion: Greater precancer anthropometric measures and BMI <18.5 kg/m2 predicted poorer survival among colon cancer patients. Higher abdominal adiposity measured by WHR and waist was associated with increased risk of colon cancer death.

Impact: Prediagnostic obesity may be a modifiable risk factor for death in colon cancer patients. Cancer Epidemiol Biomarkers Prev; 19(9); 2229–37. ©2010 AACR.
Jumonji Domain Containing 1A Is a Novel Prognostic Marker for Colorectal Cancer: In vivo Identification from Hypoxic Tumor Cells
Authors: Uemura Mamoru , Yamamoto Hirofumi , Takemasa Ichiro , Mimori Koshi , Hemmi Hideyuki , Mizushima Tsunekazu , Ikeda Masataka , Sekimoto Mitsugu , Matsuura Nariaki , Doki Yuichiro , Mori Masaki
Published: September 2010

Purpose: This study aimed to identify novel hypoxia-inducible and prognostic markers in vivo from hypoxic tumor cells.

Experimental Design: Using carbonic anhydrase 9 and CD34 as a guide for hypoxic tumor cells, laser capture microdissection was used to isolate colorectal cancer (CRC) liver metastases. The samples were analyzed by microarray analysis, in parallel with five CRC cell lines cultured under hypoxic conditions. To evaluate the prognostic impact of the expression of certain genes, samples from a total of 356 CRC patients were analyzed by microarray or quantitative reverse transcription-PCR. In vitro mechanistic studies and in vivo therapeutic experiments were also done about a histone H3 Lys9 demethylase, Jumonji domain containing 1A (JMJD1A).

Results: Several candidate genes were identified by microarray analysis of liver metastases and culturing of CRC cells under hypoxic conditions. Among them, we found that JMJD1A was a novel independent prognostic factor for CRC (P = 0.013). In vitro assays revealed that loss of JMJD1A by small interfering RNA treatment was associated with a reduction of proliferative activity and decrease in invasion of CRC cell lines. Furthermore, treatment with an adenovirus system for antisense JMJD1A construct displayed prominent therapeutic effects when injected into established tumor xenografts of the CRC cell lines HCT116 and DLD1.

Conclusions: JMJD1A is a useful biomarker for hypoxic tumor cells and a prognostic marker that could be a promising therapeutic target against CRC. Clin Cancer Res; 16(18); 4636–46. ©2010 AACR.
Inhibitory Effect of Silibinin against Azoxymethane-Induced Colon Tumorigenesis in A/J Mice
Authors: Ravichandran Kameswaran , Velmurugan Balaiya , Gu Mallikarjuna , Singh Rana P. , Agarwal Rajesh
Published: September 2010

Purpose: Colorectal cancer is the second leading cause of cancer-associated deaths, which suggests that more effort is needed to prevent/control this disease. Herein, for the first time, we investigate in vivo the efficacy of silibinin against azoxymethane-induced colon tumorigenesis in A/J mice.

Experimental Design: Five-week-old male mice were gavaged with vehicle or silibinin (250 and 750 mg/kg) for 25 weeks starting 2 weeks before initiation with azoxymethane (pretreatment regime) or for 16 weeks starting 2 weeks after the last azoxymethane injection (posttreatment regime). The mice were then sacrificed, and colon tissues were examined for tumor multiplicity and size, and molecular markers for proliferation, apoptosis, inflammation, and angiogenesis.

Results: Silibinin feeding showed a dose-dependent decrease in azoxymethane-induced colon tumorigenesis with stronger efficacy in pretreatment versus posttreatment regimen. Mechanistic studies in tissue samples showed that silibinin inhibits cell proliferation as evident by a decrease (P < 0.001) in proliferating cell nuclear antigen and cyclin D1, and increased Cip1/p21 levels. Silibinin also decreased (P < 0.001) the levels of inducible nitric oxide synthase, cyclooxygenase-2, and vascular endothelial growth factor, suggesting its anti-inflammatory and antiangiogenic potential in this model. Further, silibinin increased cleaved caspase-3 and poly(ADP-ribose) polymerase levels, indicating its apoptotic effect. In other studies, colonic mucosa and tumors expressed high levels of β-catenin, insulin-like growth factor-1 receptorβ, phospho Glycogen synthase kinase-3β, and phospho protein kinase B/pAkt proteins in azoxymethane-treated mice, which were strongly lowered (P < 0.001) by silibinin treatment. Moreover, azoxymethane reduced insulin-like growth factor binding protein-3 protein level, which was enhanced by silibinin.

Conclusions: Silibinin targets β-catenin and IGF-1Rβ pathways for its chemopreventive efficacy against azoxymethane-induced colon carcinogenesis in A/J mice. Overall, these results support the translational potential of silibinin in colorectal cancer chemoprevention. Clin Cancer Res; 16(18); 4595–606. ©2010 AACR.
Attained Educational Level and Incident Atherothrombotic Events in Low- and Middle-Income Compared With High-Income Countries
Authors: Goyal Abhinav , Bhatt Deepak L. , Steg P. Gabriel , Gersh Bernard J. , Alberts Mark J. , Ohman E. Magnus , Corbalán Ramón , Eagle Kim A. , Gaxiola Efrain , Gao Runlin , Goto Shinya , D'Agostino Ralph B. , Califf Robert M. , Smith Sidney C. , Wilson Peter W.F. ,   for the Reduction of Atherothrombosis for Continued Health (REACH) Registry Investigators
Published: September 2010

Background—

Studies report a protective effect of higher attained educational level (AEL) on cardiovascular outcomes. However, most of these studies have been conducted in high-income countries (HICs) and lack representation from low- and middle-income countries (LMICs), which bear >80% of the global burden of cardiovascular disease.

Methods and Results—

The Reduction of Atherothrombosis for Continued Health (REACH) Registry is a prospective study of 67 888 subjects with either established atherothrombotic (coronary, cerebrovascular, and/or peripheral arterial) disease or multiple atherothrombotic risk factors enrolled from 5587 physician practices in 44 countries. At baseline, AEL (0 to 8 years, 9 to 12 years, trade or technical school, and university) was self-reported for 61 332 subjects. Outcomes included the baseline prevalence of atherothrombotic risk factors and the rate of incident cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) through 23 months across AEL groups, stratified by sex and world region (LMICs or HICs). Educational attainment was inversely associated with age and diabetes mellitus and directly associated with hypercholesterolemia in all subjects. However, for other risk factors such as obesity, smoking, hypertension, and baseline burden of vascular disease, AEL was protective (inversely associated) in HICs but not protective in LMICs. The protective effect of greater AEL on incident cardiovascular events was strongest in men from HICs (
P
<0.0001), more modest in women from HICs (
P
=0.0026) and in men from LMICs (
P
=0.082), and essentially absent in women from LMICs (
P
=0.32).

Conclusion—

In contrast to HICs, higher AEL may not be protective against cardiovascular events in LMICs, particularly in women.
Scimitar Syndrome
Authors: Vida Vladimiro L. , Padalino Massimo A. , Boccuzzo Giovanna , Tarja Erjon , Berggren Hakan , Carrel Thierry , Çiçek Sertaç , Crupi Giancarlo , Di Carlo Duccio , Di Donato Roberto , Fragata José , Hazekamp Mark , Hraska Viktor , Maruszewski Bohdan , Metras Dominique , Pozzi Marco , Pretre Rene , Rubay Jean , Sairanen Heikki , Sarris George , Schreiber Christian , Meyns Bart , Tlaskal Tomas , Urban Andreas , Thiene Gaetano , Stellin Giovanni
Published: September 2010

Background—

Scimitar syndrome is a rare congenital heart disease. To evaluate the surgical results, we embarked on the European Congenital Heart Surgeons Association (ECHSA) multicentric study.

Methods and Results—

From January 1997 to December 2007, we collected data on 68 patients who underwent surgery for scimitar syndrome. Primary outcomes included hospital mortality and the efficacy of repair at follow-up. Median age at surgery was 1.4 years (interquartile range, 0.46 to 7.92 years). Forty-four patients (64%) presented with symptoms. Surgical repair included intraatrial baffle in 38 patients (56%; group 1) and reimplantation of the scimitar vein onto the left atrium in 21 patients (31%; group 2). Eight patients underwent right pneumectomy, and 1 had a right lower lobe lobectomy (group 3). Four patients died in hospital (5.9%; 1 patient in group 1, 2.6%; 3 patients in group 3, 33%). Median follow-up time was 4.5 years. There were 2 late deaths (3.1%) resulting from severe pulmonary arterial hypertension. Freedom from scimitar drainage stenosis at 13 years was 83.8% in group 1 and 85.8% in group 2. Four patients in group 1 were reoperated, and 3 patients (2 in group 1 [6%] and 1 in group 2 [4.8%]) required balloon dilation/stenting for scimitar drainage stenosis.

Conclusions—

The surgical treatment of this rare syndrome is safe and effective. The majority of patients were asymptomatic at the follow-up control. There were a relatively high incidence of residual scimitar drainage stenosis that is similar between the 2 reported corrective surgical techniques used.
Genetic Deficiency of Plasminogen Activator Inhibitor-1 Promotes Cardiac Fibrosis in Aged Mice
Authors: Ghosh Asish K. , Bradham William S. , Gleaves Linda A. , De Taeye Bart , Murphy Sheila B. , Covington Joseph W. , Vaughan Douglas E.
Published: September 2010

Background—

Elevated levels of plasminogen activator inhibitor-1 (PAI-1), a potent inhibitor of urokinase plasminogen activator and tissue plasminogen activator, are implicated in the pathogenesis of tissue fibrosis. Paradoxically, lack of PAI-1 in the heart is associated with the development of cardiac fibrosis in aged mice. However, the molecular basis of cardiac fibrosis in aged PAI-1–deficient mice is unknown. Here, we investigated the molecular and cellular bases of myocardial fibrosis.

Methods and Results—

Histological evaluation of myocardial tissues derived from aged PAI-1–deficient mice revealed myocardial fibrosis resulting from excessive accumulation of collagen. Immunohistochemical characterization revealed that the levels of matrix metalloproteinase-2, matrix metalloproteinase-9, and transforming growth factor-β1/2 and the number of Mac3-positive and fibroblast specific protein-1–positive cells were significantly elevated in aged PAI-1–deficient myocardial tissues compared with controls. Zymographic analysis revealed that matrix metalloproteinase-2 enzymatic activity was elevated in PAI-1–deficient mouse cardiac endothelial cells. Real-time quantitative polymerase chain reaction analyses of RNA from myocardial tissues revealed the upregulation of profibrotic markers in aged PAI-1–deficient mice. The numbers of phosphorylated Smad2–, phosphorylated Smad3–, and phosphorylated ERK1/2 MAPK–, but not pAkt/PKB–, positive cells were significantly increased in PAI-1–deficient myocardial tissues. Western blot and immunocytochemical analysis revealed that PAI-1–deficient mouse cardiac endothelial cells were more susceptible to endothelial-to-mesenchymal transition in response to transforming growth factor-β2.

Conclusions—

These results indicate that spontaneous activation of both Smad and non-Smad transforming growth factor-β signaling may contribute to profibrotic responses in aged PAI-1–deficient mice hearts and establish a possible link between endothelial-to-mesenchymal transition and cardiac fibrosis in PAI-1–deficient mice.
Disability or Learning Difficulty? Politicians or Educators? Constructing Special Education in Finland and the United States
Authors: Jahnukainen Markku , Itkonen Tiina
Published: September 2010

This article examines institutional arrangements, disability constructions, and policy designs in Finland and the United States. In the US disability is constructed from a medical, diagnosis-driven discrepancy model, and politicians operating in an“equal opportunity” and“civil rights” framework shape policy. In Finland, diagnostic labels are rarely used, and students are referred to as experiencing academic difficulty. Policies are more strongly shaped by educators than politicians.
Change in Disability Classification: Redrawing Categorical Boundaries in SpecialEducation in the United States and Germany, 1920‐2005
Authors: Powell Justin J.W.
Published: September 2010

How do we make sense of considerable cultural differences and change in disability classification? How are disability’s categorical boundaries being redrawn in special education to realign with shifting paradigms of normality? Based in particular on the case of provided services to students “with special educational needs,” this analysis examines classification systems of student disability and their categorical boundaries in the United States and Germany. Sketching the origins and evolution of special education categories from 1920 to 2005, the comparison shows how categorical boundaries have been redrawn, giving rise to new groups of students.
The Globalization of Disability Protests, 1970‐2005: Pushing the Limits of Cross-Cultural Research?
Authors: Barnartt Sharon
Published: September 2010

This paper examines political protests related to disability issues which occurred since 1970. It examines almost 700 protests outside the US and over 1200 within the US. The data come from media reports and organization websites. Results show that US protests increased after 1984 while non-US protests increased substantially after 1989. The largest numbers of non-US protests occurred in the UK and Canada. US protests are proportionally more likely than non-US protests to be cross-disability or to relate to mobility impairments, while outside of the US disability-specific protests, especially those related to blindness and deafness, are more common. American protests are more likely to target governments as opposed to non-governmental targets than were non-US protests. Factors relating to disability as well as methodological limitations are considered in explaining these differences.
The Role of Executive Time Horizons in State Response to AIDS in Africa
Authors: Kim Yi Dionne
Published: September 2010

In this article the author argues that politicians’ time horizons affect the differing levels of state intervention against AIDS. Using data measuring government spending, AIDS policy, and political constraints, the author tests the presumption that the leader of a country can determine a country’s level of AIDS intervention. She looks at countries in eastern and southern Africa to explore the relationship between political institutions that constrain an executive’s time horizon (i.e., competitive elections) and the level of the state’s efforts in the fight against AIDS. Her primary hypothesis is that an executive with a shorter time horizon is less likely to create policy or devote resources to intervene against AIDS. The author finds that lengthening an executive’s time horizon increases the level of government spending on health but that executives with shorter time horizons tended to have more comprehensive AIDS policy than their counterparts with longer time horizons.
The work and health process in the sugarcane agroindustry in Franca, Brazil
Authors: de Souza Lourenço Edvânia Ângela , Fenner Bertani Iris
Published: September 2010

This study aimed to discuss the interrelation between social determinants and the health conditions of workers in the sugarcane agroindustry in the region of Franca, in the countryside of São Paulo State, Brazil, from 2005 to 2006, considering the present socio-economic, historical, political and cultural conditions.
Utilization Potential of Waste from Window Joints for Particleboard
Authors: Çolak Semra , Nemli Gökay , Demirkir Cenk , Aydin Ismail , Demirel Samet
Published: September 2010

The aim of this study was to determine some technological properties of particleboard made from the waste from window joints. The effect of board density, adhesive amount, and paint presence on the properties of particleboard was investigated. Increasing density and adhesive amount significantly improved their mechanical properties and surface roughness, but negatively affected their thickness swelling. Removing of the paint from the particle resulted in better mechanical properties, but poorer (higher) surface roughness values. This treatment did not statistically affect the thickness swelling. Based on the results, it is proved that the waste of window joints has a potential as raw material for the manufacture of particleboard.
Integrating epidemic dynamics with daily commuting networks: building a multilayer framework to assess influenza A (H1N1) intervention policies
Authors: Tsai Yu-Shiuan , Huang Chung-Yuan , Wen Tzai-Hung , Sun Chuen-Tsai , Yen Muh-Yong
Published: September 2010

We describe an innovative simulation framework that combines daily commuting network data with a commonly used population-based transmission model to assess the impacts of various interventions on epidemic dynamics in Taiwan. Called the Multilayer Epidemic Dynamics Simulator (MEDSim), our proposed framework has four contact structures: within age group, between age groups, daily commute, and nationwide interaction. To test model flexibility and generalizability, we simulated outbreak locations and intervention scenarios for the 2009 swine-origin influenza A (H1N1) epidemic. Our results indicate that lower transmission rates and earlier intervention activation times did not reduce total numbers of infected cases, but did delay peak times. When the transmission rate was decreased by a minimum of 70%, significant epidemic peak delays were observed when interventions were activated before new case number 50; no significant effects were noted when the transmission rate was decreased by less than 30%. Observed peaks occurred more quickly when initial outbreaks took place in urban rather than rural areas. According to our results, the MEDSim provides insights that reflect the dynamic processes of epidemics under different intervention scenarios, thus clarifying the effects of complex contact structures on disease transmission dynamics.
Moving From Separate, to Equal, to Equitable Schooling: Revisiting School Desegregation Policies
Authors: McPherson Ezella
Published: September 2010

For over a century after the 1896 Plessy v. Ferguson decision, researchers have been grappling with how to effectively implement educational reform policies to provide students with an equal education in American schools. This literature review examines previous school desegregation cases and school desegregation plans to investigate how schools have been unsuccessful in fully implementing desegregation plans. The paper discusses the role that social and political factors played in prohibiting schools from fully desegregating in the South. It ends with some suggestions on moving from equal to equitable schooling inside and outside of the Southern region of the United States.
Information (and library) science at City University London; 50 years of educational development
Authors: Robinson Lyn , Bawden David
Published: September 2010

The development of education for information and library science at City University London over a 50-year period is described in this article. The development of the Masters course in Information Science, and the later equivalent courses in Library Science and in Information Management in the Cultural Sector are described in detail, together with shorter-lived Masters courses in pharmaceutical and health information. The rationale for changes to the courses, and the influence of the professional and educational contexts, are analysed. Issues emerging from this analysis are discussed in seven themes: the nature of the discipline; the library/information spectrum; the student group; the academic/professional balance; curriculum design; local and global issues; and teaching methods. The discussions of the courses are set in the wider context of changes in library/information education over the period in the UK and worldwide.