bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal trends in the incidence and survival of cancers of the upper aerodigestive tract in Ontario and the United States
Authors: Gupta Shlok , Kong Weidong , Peng Yingwei , Miao Qun , Mackillop William J. 
Published: June 2009

AbstractThe Ontario Cancer Registry (OCR) and the Surveillance, Epidemiology and End Results (SEER) databases were used to describe temporal trends in the incidence and survival of squamous cancers of the upper aerodigestive tract (UADT) in Ontario and the US between 1984 and 2001. Between the 1984–86 and 1999–01 periods, the age‐adjusted incidence rate of all first primary cancers of the UADT decreased from 11.6 (11.2–12.0) to 8.8 (8.5–9.1) in Ontario and 13.0 (12.7–13.3) to 10.2 (10.0–10.4) in the US. Significant decreases in incidence were observed in many UADT sites but there was no significant change in the incidence of cancer of the oropharynx in either the US or Canada. Over the same period, the 5‐year relative survival for all UADT cancers increased from 49.2% (47.2–51.2%) to 57.1%(55.0–59.1%) in Ontario and from 48.1% (46.9–49.3%) to 52.4% (51.2–53.6%) in the US. This significant improvement in the outcome of UADT cancer was largely due to a dramatic increase in the 5‐year relative survival for cancers of the oropharynx from 31.1% (27.1–35.1%) to 53.6% (49.3–57.9%) in Ontario and from 35.3% (32.9–37.8%) to 51.0% (48.7–53.3%) in the US. Smaller increases in survival were observed in cancers of the oral cavity, nasopharynx, and hypopharynx, but there was no evidence of any increase in survival for cancer of the larynx. These results are consistent with the hypothesis that there has been a major change in the etiology of cancer of the oropharynx in Canada and the US and a concomitant change in its response to therapy. © 2009 UICC
GLUT‐1 expression and response to chemoradiotherapy in rectal cancer
Authors: Brophy Sarah , Sheehan Katherine M. , McNamara Deborah A. , Deasy Joseph , Bouchier‐Hayes David J. , Kay Elaine W. 
Published: June 2009

AbstractPreoperative chemoradiotherapy is used in locally advanced rectal cancer to reduce local recurrence and improve operability, however a proportion of tumors do not undergo significant regression. Identification of predictive markers of response to chemoradiotherapy would improve patient selection and may allow response modification by targeting of specific pathways. The aim of this study was to determine whether expression of glucose transporter‐1 (GLUT‐1) and p53 in pretreatment rectal cancer biopsies was predictive of tumor response to chemoradiotherapy. Immunohistochemical staining for GLUT‐1 and p53 was performed on 69 pretreatment biopsies and compared to tumor response in the resected specimen as determined by the tumor regression grade (TRG) scoring system. GLUT‐1 expression was significantly associated with reduced response to chemoradiotherapy and increasing GLUT expression correlated with poorer response (p = 0.02). GLUT‐1 negative tumors had a 70% probability of good response (TRG3/4) compared to a 31% probability of good response in GLUT‐1 positive tumors. GLUT‐1 may be a useful predictive marker of response to chemoradiotherapy in rectal cancer. © 2009 UICC
EP300—A miRNA‐regulated metastasis suppressor gene in ductal adenocarcinomas of the pancreas
Authors: Mees Soeren Torge , Mardin Wolf Arif , Wendel Claudia , Baeumer Nicole , Willscher Edith , Senninger Norbert , Schleicher Christina , Colombo‐Benkmann Mario , Haier Joerg 
Published: June 2009

AbstractGenetic and epigenetic alterations during development of pancreatic ductal adenocarcinomas (PDACs) are well known. This study investigates genetic and epigenetic data together with tumor biology to find specific alterations responsible for metastasis formation. Using 16 human PDAC cell lines in a murine orthotopic PDAC model, local infiltration and metastatic spread were assessed by standardized dissemination scores. The cell lines were further classified into 3 hierarchical groups according to their metastatic potential. Their mRNA and microRNA (miRNA) expression was profiledviamRNA‐microarray as well as Taqman Low Density Array, and validated by single quantitative RT‐PCR and Western blotting. In the highly metastatic group, a significant induction of EP300 targeting miRNAs miR‐194 (fold change: 26.88), miR‐200b (fold change: 61.65), miR‐200c (fold change: 19.44) and miR‐429 (fold change: 21.67) (p< 0.05) was detected. Corresponding to this, decreased expression of EP300 mRNA (p< 0.0001) and protein (p< 0.05) were detected in the highly metastatic PDAC cell lines with liver metastases compared to the nonmetastatic or marginally metastatic cell lines, while no correlation with local tumor growth was found. In conclusion, epigenetic alterations with upregulated EP300 targeting miRNAs miR‐194, miR‐200b, miR‐200c and miR‐429 are related to reduced EP300 mRNA and protein in PDAC. These results demonstrate that miRNAs might be able to modulate the expression of metastasis‐specific suppressor genes and metastatic behavior in PDAC, suggesting diagnostic and therapeutic opportunities for EP300 and its targeting miRNAs in PDAC.
Estrogen‐induced interaction between KLF5 and estrogen receptor (ER) suppresses the function of ER in ER‐positive breast cancer cells
Authors: Guo Peng , Dong Xue‐Yuan , Zhao Ke‐Wen , Sun Xiaodong , Li Qunna , Dong Jin‐Tang 
Published: June 2009

AbstractKruppel‐like factor 5 (KLF5) is implicated in human breast cancer by frequent genomic deletion and expressional deregulation, but the molecular mechanisms by which KLF5 affects breast tumorigenesis are still unknown. This study was conducted to examine whether and how KLF5 affects the function of estrogen receptor (ER) in breast cancer cells. Using different cell lines, we found that restored expression of KLF5 inhibited estrogen‐promoted cell proliferation in ER‐positive MCF‐7 and T‐47D cell lines but had no effect on ER‐negative SK‐BR‐3 cells. Transcriptional activity of ER was also suppressed by KLF5, as detected by using estrogen‐stimulated ER responsive element‐mediated reporter assay and expression analysis of ER target genes including c‐MYC and Cathepsin D (CSTD). Chromatin immunoprecipitation assays showed that KLF5 inhibited ERα binding to the promoter of c‐myc and CSTD. Furthermore, estrogen induced an interaction between KLF5 and ERα. These results suggest that KLF5 inhibits the function of ERα in gene regulation and cell proliferation through protein interaction that interrupts the binding of ERα to target gene promoters to prevent target gene induction.
The influence of cosmetic breast augmentation on the stage distribution and prognosis of women subsequently diagnosed with breast cancer
Authors: Xie Lin , Brisson Jacques , Holowaty Eric J. , Villeneuve Paul J. , Mao Yang 
Published: June 2009

AbstractThis study aimed to determine whether cosmetic breast implants impair the early detection of breast cancer, and adversely influence survival. This analysis derives from a cohort of 24,558 women who received bilateral cosmetic breast implants, and 15,893 women who underwent other plastic surgery procedures at the same practices in Ontario and Quebec, Canada, between 1974 and 1989. Incident cancers and vital status through 1997 were determined by record linkage to the Canadian Cancer Registry and Canadian Mortality Database. Analyses are based on a total of 182 and 202 incident cases of breast cancer identified among the implant and control groups, respectively. Contingency table analyses were performed to test for differences in the stage distribution of breast cancers between the 2 groups. Potential differences in survival were evaluated using the Kaplan–Meier estimates and Cox proportional hazards models. Women who received breast implants were more likely to have advanced stage breast carcinoma relative to the other plastic surgery patients (crude and adjusted ps ≤ 0.01). No statistically significant differences in distributions between the implant and control patients were found for age at diagnosis, tumor size, histological type, period of diagnosis or length of follow‐up. The delayed diagnosis in augmented women did not appear to influence the overall prognosis. Breast cancer‐specific survival was similar in both groups (hazard ratio = 1.06; 95% confidence interval = 0.65–1.74). In conclusion, this study suggests that breast implants delay the detection of breast cancer, but there was no statistically significant difference in survival between the breast implant and other plastic surgery groups.
HDAC inhibitor valproic acid enhances tumor cell kill in adenovirus‐HSVtk mediated suicide gene therapy in HNSCC xenograft mouse model
Authors: Kothari Vishal , Joshi Ganesh , Nama Srikanth , Somasundaram Kumaravel , Mulherkar Rita 
Published: June 2009

AbstractSafety, efficacy and enhanced transgene expression are the primary concerns while using any vector for gene therapy. One of the widely used vectors in clinical trials is adenovirus which provides a safe way to deliver the therapeutic gene. However, adenovirus has poor transduction efficiency in vivo since most tumor cells express low coxsackie and adenovirus receptors. Similarly transgene expression remains low, possibly because of the chromatization of adenoviral genome upon infection in eukaryotic cells, an effect mediated by histone deacetylases (HDACs). Using a recombinant adenovirus (Ad‐HSVtk) carrying the herpes simplex thymidine kinase (HSVtk) and GFP genes we demonstrate that HDAC inhibitor valproic acid can bring about an increase in CAR expression on host cells and thereby enhanced Ad‐HSVtk infectivity. It also resulted in an increase in transgene (HSVtk and GFP) expression. This, in turn, resulted in increased cell kill of HNSCC cells, following ganciclovir treatment in vitro as well as in vivo in a xenograft nude mouse model.
Forced cytochrome B gene mutation expression induces mitochondrial proliferation and prevents apoptosis in human uroepithelial SV‐HUC‐1 cells
Authors: Dasgupta Santanu , Hoque Mohammad Obaidul , Upadhyay Sunil , Sidransky David 
Published: June 2009

AbstractMitochondria encoded Cytochrome B (CYTB) gene mutations were reported in tumors of different anatomic origin but the functional significance of these mutations are not well studied. Earlier, we found a 7‐amino acid deletion mutation in the CYTB gene in a primary bladder cancer patient. In the present study, we overexpressed this 7‐amino acid deletion mutation of CYTB gene in SV‐40 transformed human uroepithelial HUC‐1 cells. The nuclear transcribed mitochondrial CYTB (mtCYTB) was targeted into the mitochondria and generated increased copies of mitochondria and mitochondrial COX‐I protein in the transfected HUC‐1 cells. The proapoptotic protein Bax largely remained confined to the cytoplasm of the mtCYTB transfected HUC‐1 cells without release of Cytochrome C. The downstream apoptotic proteins PARP also remained uncleaved along with increased Lamin B1 in the mtCYTB transfected cells. Our results demonstrate that forced overexpression of mtCYTB in transformed human uroepithelial HUC‐1 cells triggered mitochondrial proliferation and induction of an antiapoptotic signaling cascade favoring sustained cellular growth. Coding mitochondrial DNA mutations appear to have significant functional contribution in tumor progression. Published 2009 UICC.
Identification of cisplatin‐resistance related genes in head and neck squamous cell carcinoma
Authors: Yamano Yukio , Uzawa Katsuhiro , Saito Kengo , Nakashima Dai , Kasamatsu Atsushi , Koike Hirofumi , Kouzu Yukinao , Shinozuka Keiji , Nakatani Ken , Negoro Kenji , Fujita Shigeyuki , Tanzawa Hideki 
Published: June 2009

AbstractResistance to cisplatin is a major obstacle to successful treatment of head and neck squamous cell carcinoma (HNSCC). To investigate the molecular mechanism of this resistance, we compared the gene expression profiles between the cisplatin‐sensitive SCC cell lines (Sa‐3, H‐1 and KB) and the cisplatin‐resistant cell lines established from them (Sa‐3R, H‐1R and KB‐R) using Affymetrix U133 Plus 2.0 microarray. We identified 199 genes differentially expressed in each group. To identify important functional networks and ontologies to cisplatin resistance, the 199 genes were analyzed using the Ingenuity Pathway Analysis Tool. Fifty‐one of these genes were mapped to genetic networks, and we validated the top‐10 upregulated genes by real‐time reverse transcriptase‐polymerase chain reaction. Five novel genes, LUM, PDE3B, PDGF‐C, NRG1 and PKD2, showed excellent concordance with the microarray data. In 48 patients with oral SCC (OSCC), positive immunohistochemical staining for the five genes correlated with chemoresistance to cisplatin‐based combination chemotherapy. In addition, the expression of the five genes predicted the patient outcomes with chemotherapy. Furthermore, siRNA‐directed suppressed expression of the five genes resulted in enhanced susceptibility to cisplatin‐mediated apoptosis. These results suggested that these five novel genes have great potential for predicting the efficacy of cisplatin‐based chemotherapy against OSCC. Global gene analysis of cisplatin‐resistant cell lines may provide new insights into the mechanisms underlying clinical cisplatin resistance and improve the efficacy of chemotherapy for human HNSCC.
Precise detection of lymph node metastases in mouse rectal cancer by using 5‐aminolevulinic acid
Authors: Murayama Yasutoshi , Harada Yoshinori , Imaizumi Katsuichi , Dai Ping , Nakano Keimei , Okamoto Kazuma , Otsuji Eigo , Takamatsu Tetsuro 
Published: June 2009

AbstractAccurate diagnosis of metastatic lymph nodes (LNs) is essential in choosing appropriate treatment for gastrointestinal carcinoma. Our aim was to evaluate the diagnostic power of 5‐aminolevulinic acid (5‐ALA) for LN metastasis in mouse rectal cancer. Colorectal cancer cell lines, isolated cells from normal LNs, and orthotopic mouse model incorporating enhanced green fluorescent protein‐tagged and untagged human rectal cancer cells were studied after 5‐ALA administration by using confocal microscopy, fluorescence stereomicroscopy, fluorescence lifetime imaging microscopy (FLIM), multichannel spectrophotometry and macroconfocal imaging system to precisely detect LN metastases. In vitro confocal microscopic analyses showed that all colorectal cancer cell lines tested were positive for 5‐ALA‐induced fluorescence, whereas isolated normal LN cells were negative. 5‐ALA‐induced protoporphyrin IX (PPIX) fluorescence, verified by FLIM and multichannel spectrophotometry, revealed LN metastases in mice‐bearing human rectal cancer cells. Occult LN metastases, unrecognized on white‐light imaging and simplified hematoxylin‐eosin analyses, were readily detectable on 5‐ALA‐induced PPIX fluorescence imaging. In vivo macroconfocal images clearly revealed PPIX‐fluorescence‐positive cancer cells in draining lymph vessels and nodes. Together with specific speckled patterns of PPIX‐fluorescence in metastatic lesions, the PPIX‐fluorescence intensity ratio of metastatic and nonmetastatic lesions discriminated metastasis with 100% sensitivity and 100% specificity in excised whole LN samples. These results show that fluorescence diagnosis with 5‐ALA is very accurate in the detection of LN micrometastases of mouse rectal cancer, suggesting that this feasible diagnostic approach is applicable to target sectioning of metastases of resected fresh whole node samples in pathology laboratories. © 2009 UICC
The association of plasma androgen levels with breast, ovarian and endometrial cancer risk factors among postmenopausal women
Authors: Danforth Kim N. , Eliassen A. Heather , Tworoger Shelley S. , Missmer Stacey A. , Barbieri Robert L. , Rosner Bernard A. , Colditz Graham A. , Hankinson Susan E. 
Published: June 2009

AbstractAlthough androgens may play an etiologic role in breast, ovarian and endometrial cancers, little is known about factors that influence circulating androgen levels. We conducted a cross‐sectional analysis among 646 postmenopausal women in the Nurses' Health Study to examine associations between adult risk factors for cancer, including the Rosner/Colditz breast cancer risk score, and plasma levels of testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). All analyses were adjusted for age, laboratory batch and other cancer risk factors. Free testosterone levels were 79% higher among women with a body mass index of ≥30 vs. <22 kg/m2 (p‐trend <0.01) and 25% higher among women with a waist circumference of >89 vs. ≤74 cm (p‐trend = 0.02). Consuming >30 g of alcohol a day vs. none was associated with a 31% increase in DHEA and 59% increase in DHEAS levels (p‐trend = 0.01 and <0.01, respectively). Smokers of ≥25 cigarettes per day had 35% higher androstenedione and 44% higher testosterone levels than never smokers (p‐value, F‐test = 0.03 and 0.01, respectively). No significant associations were observed for height or time since menopause with any androgen. Testosterone and free testosterone levels were ∼30% lower among women with a hysterectomy vs. without (both p‐values < 0.01). Overall breast cancer risk was not associated with any of the androgens. Thus, several risk factors, including body size, alcohol intake, smoking and hysterectomy, were related to androgen levels among postmenopausal women, while others, including height and time since menopause, were not. Future studies are needed to clarify further which lifestyle factors modulate androgen levels.
Bisphosphonates suppress insulin‐like growth factor 1‐induced angiogenesis via the HIF‐1α/VEGF signaling pathways in human breast cancer cells
Authors: Tang Xudong , Zhang Qunzhou , Shi Shihong , Yen Yun , Li Xiangyong , Zhang Yuefei , Zhou Keyuan , Le Anh D. 
Published: June 2009

AbstractAdjunctive chemotherapy with bisphosphonates has been reported to delay bone metastasis and improve overall survival in breast cancer. Aside from its antiresorptive effect, bisphosphonates exhibit antitumor activities, in vitro and in vivo, via several mechanisms, including antiangiogenesis. In this study, we investigated the potential molecular mechanisms underlying the antiangiogenic effect of non–nitrogen‐containing and nitrogen‐containing bisphosphonates, clodronate and pamidronate, respectively, in insulin‐like growth factor (IGF)‐1 responsive human breast cancer cells. We tested whether bisphosphonates had any effects on hypoxia‐inducible factor (HIF)‐1α/vascular endothelial growth factor (VEGF) axis that plays a pivotal role in tumor angiogenesis, and our results showed that both pamidronate and clodronate significantly suppressed IGF‐1‐induced HIF‐1α protein accumulation and VEGF expression in MCF‐7 cells. Mechanistically, we found that either pamidronate or clodronate did not affect mRNA expression of HIF‐1α, but they apparently promoted the degradation of IGF‐1‐induced HIF‐1α protein. Meanwhile, we found that the presence of pamidronate and clodronate led to a dose‐dependent decease in the newly‐synthesized HIF‐1α protein induced by IGF‐1 in breast cancer cells after proteasomal inhibition, thus, indirectly reflecting the inhibition of protein synthesis. In addition, our results indicated that the inhibitory effects of bisphosphonates on the HIF‐1α/VEGF axis are associated with the inhibition of the phosphoinositide 3‐kinase/AKT/mammalian target of rapamycin signaling pathways. Consistently, we demonstrated that pamidronate and clodronate functionally abrogated both in vitro and in vivo tumor angiogenesis induced by IGF‐1‐stimulated MCF‐7 cells. These findings have highlighted an important mechanism of the pharmacological action of bisphosphonates in the inhibition of tumor angiogenesis in breast cancer cells.
Evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005
Authors: Le Stang N. , Belot A. , Gilg Soit Ilg A. , Rolland P. , Astoul P. , Bara S. , Brochard P. , Danzon A. , Delafosse P. , Grosclaude P. , Guizard A.‐V. , Imbernon E. , Lapôtre‐Ledoux B. , Ligier K. , Molinié F. , Pairon J.‐C. , Sauleau E.‐A. , Trétarre B. , Velten M. , Bossard N. , Goldberg M. , Launoy G. , Galateau‐Sallé F. 
Published: June 2009

AbstractThe evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005 was analysed using data derived from the French network of cancer registries (FRANCIM) and the French National Mesothelioma Surveillance Program (PNSM). Mesothelioma proportions in pleural cancers were calculated by diagnosis year in the 1980–2000 period. Our results suggest that the incidences of pleural cancer and mesothelioma levelled off in French men since 2000 and continued to increase in French women. A decrease of the annual pleural cancer incidence average in men was noticed (−3.4% of annual rate of change) between 2000 and 2005. The proportion of pleural cancers that were mesothelioma was unchanged between 1980 and 2003 with an average of 86%. The age standardised incidence rate of pleural mesothelioma remained relatively stable between 1998 and 2005 with a slight falling trend. For women, the age standardised incidence rate of pleural cancers and mesothelioma increased during the period 1998–2005. Additionally, the proportion of pleural cancers that were mesothelioma increased during the same period of time. Finally, the increased trend observed in the incidence of pleural mesothelioma and cancers in women is credibly due to their under diagnosis in the 1980–1997 period. The comparison between the French incidence and the American and British ones shows that the decreasing trend in incidence of mesothelioma and pleural cancers in French men since 2000 is potentially associated with a lower amphibole consumption and by the implementation of safety regulations at work from 1977.
Attitudes to HPV vaccination among parents of children aged 12‐15 years—A population‐based survey in Sweden
Authors: Dahlström Lisen A. , Tran Trung N. , Lundholm Cecilia , Young Cecilia , Sundström Karin , Sparén Pär 
Published: June 2009

AbstractIn this population‐based survey undertaken in Sweden in 2007, we investigated correlates of attitudes to human papillomavirus (HPV) vaccination among parents of children aged 12–15 years. We invited 16,000 parents of girls and 4,000 parents of boys, randomly selected from the Swedish population. Response rates were 70 and 69%, respectively. Multinomial logistic regression models were applied to investigate correlates of acceptability to HPV vaccination. Among studied parents, 76% were willing to vaccinate their child if the vaccine is for free and 63% were willing to vaccinate even if the vaccine comes with a cost. Having heard of HPV was associated with both willingness to vaccinate if the vaccine is free (odds ratio [OR]: 1.42; 95% confidence interval [CI]: 1.21–1.66) and willingness to vaccinate even if the vaccine is not free (OR: 1.96; 95% CI: 1.75–2.20) compared with those who never heard of HPV. Beliefs about vaccine safety and efficacy were also strong correlates of willingness to vaccinate. Parents born outside Europe and those with higher education were less willing to vaccinate if the vaccine is not free. In conclusion, the willingness to vaccinate was reasonably high and cost did not appear to be a major barrier. Information about vaccine safety and efficacy is important and parents need information about HPV and the HPV vaccine.