bluuebunny/crossref_metadata_2025_split huggingface dataset:
Li‐Fraumeni and Li‐Fraumeni—like syndrome among children diagnosed with pediatric cancer in Southern Brazil
Authors: Giacomazzi Juliana , Selistre Simone G. , Rossi Cristina , Alemar Barbara , Santos‐Silva Patricia , Pereira Fernando S. , Netto Cristina B. , Cossio Silvia L. , Roth Daniela E. , Brunetto Algemir L. , Zagonel‐Oliveira Marcelo , Martel‐Planche Ghyslaine , Goldim Jose R. , Hainaut Pierre , Camey Suzi A. , Ashton‐Prolla Patricia 
Published: October 2013

BACKGROUNDPediatric cancers are a feature in patients with Li‐Fraumeni syndrome and its variant Li‐Fraumeni–like syndrome (LFS/LFL). To the best of the authors' knowledge, TP53 germline mutations are currently the only molecular defect known to be associated with this disease. Recently, a specific germline mutation in this gene, p.R337H, has been reported at a high prevalence in Brazil.METHODSThe prevalence of LFS/LFL was investigated in children with cancer who were diagnosed with tumors on the LFS/LFL spectrum and in a small consecutive series of controls without cancer. The prevalence of the germline p.R337H mutation and of other germline TP53 mutations was investigated in a general group of children with cancer and exclusively in children fulfilling the clinical criteria for LFS/LFL, respectively.RESULTSAmong the 65 children without cancer, 1.5% had a family history of LFL whereas of the 292 children with cancer, 25.3% had a family history of LFL (P < .001). Screening for the p.R337H mutation identified 11 carriers (3.7%), 9 of whom were diagnosed with adrenocortical carcinomas (ACC) and 2 of whom were diagnosed with choroid plexus carcinomas. One of the ACC probands was homozygous mutant. The Brazilian founder haplotype and loss of heterozygosity at the p.R337H locus were present in all carriers. In addition, direct sequencing of the entire TP53 coding region and gene rearrangement analysis of probands fulfilling the criteria for LFL (Eeles 2 criteria, Birch and/or Chompret criteria) and who were negative for the p.R337H mutation revealed a DNA‐binding domain pathogenic mutation, p.G245S, in 1 child.CONCLUSIONSTP53 p.R337H testing should be offered to Brazilian children diagnosed with ACC and choroid plexus carcinoma. A significant percentage of children with cancer in southern Brazil fulfill the criteria for LFL and should be referred for genetic risk assessment. Cancer 2013;119:4341–4349. © 2013 American Cancer Society.
Identification of FOXM1‐induced epigenetic markers for head and neck squamous cell carcinomas
Authors: Hwang Sungjae , Mahadevan Swarna , Qadir Fatima , Hutchison Iain L. , Costea Daniela Elena , Neppelberg Evelyn , Liavaag Per Gunnar , Waseem Ahmad , Teh Muy‐Teck 
Published: October 2013

BACKGROUNDEpigenetic reprogramming of the methylome has been implicated in all stages of cancer evolution. It is now well accepted that cancer cells exploit epigenetic reprogramming, a mechanism that regulates stem/progenitor cell renewal and differentiation, to promote cancer initiation and progression. The oncogene FOXM1 has been implicated in all major forms of human cancer.METHODSWe have recently shown that aberrant upregulation of FOXM1 orchestrated a DNA methylation signature that mimics the cancer methylome landscape, from which we have identified a number of FOXM1‐induced epigenetic markers. Differential promoter methylation and gene expression in clinical specimens were measured using commercially available bisulfite conversion kits and absolute quantitative PCR, respectively.RESULTSHere, we investigated 8 FOXM1‐induced differentially methylated genes, SPCS1, FLNA, CHPF, GLT8D1, C6orf136, MGAT1, NDUFA10, and PAFAH1B3, using human head and neck tissue specimens donated by 2 geographically independent patient cohorts from Norway and the United Kingdom. Two genes (GLT8D1 and C6orf136) were found to be differentially expressed in head and neck squamous cell carcinomas (HNSCCs). Using methylation‐specific quantitative PCR, we confirmed that the promoters of GLT8D1 and C6orf136 were hypo‐ and hypermethylated, respectively, in HNSCC tissues.CONCLUSIONSGiven that epigenetic change precedes gene expression, methylation status of candidate genes identified from this study may represent a signature of premalignancy, rendering them potentially useful predictive biomarkers for precancer screening and/or therapeutic targets for cancer prevention. Cancer 2013;119:4249–4258. © 2013 American Cancer Society.
The cost implications of prostate cancer screening in the Medicare population
Authors: Ma Xiaomei , Wang Rong , Long Jessica B. , Ross Joseph S. , Soulos Pamela R. , Yu James B. , Makarov Danil V. , Gold Heather T. , Gross Cary P. 
Published: October 2013

BACKGROUNDRecent debate about prostate‐specific antigen (PSA)‐based testing for prostate cancer screening among older men has rarely considered the cost of screening.METHODSA population‐based cohort of male Medicare beneficiaries aged 66 to 99 years, who had never been diagnosed with prostate cancer at the end of 2006 (n = 94,652), was assembled, and they were followed for 3 years to assess the cost of PSA screening and downstream procedures (biopsy, pathologic analysis, and hospitalization due to biopsy complications) at both the national and the hospital referral region (HRR) level.RESULTSApproximately 51.2% of men received PSA screening tests during the 3‐year period, with 2.9% undergoing biopsy. The annual expenditures on prostate cancer screening by the national fee‐for‐service Medicare program were $447 million in 2009 US dollars. The mean annual screening cost at the HRR level ranged from $17 to $62 per beneficiary. Downstream biopsy‐related procedures accounted for 72% of the overall screening costs and varied significantly across regions. Compared with men residing in HRRs that were in the lowest quartile for screening expenditures, men living in the highest HRR quartile were significantly more likely to be diagnosed with prostate cancer of any stage (incidence rate ratio [IRR] = 1.20, 95% confidence interval [CI] = 1.07‐1.35) and localized cancer (IRR = 1.30, 95% CI = 1.15‐1.47). The IRR for regional/metastasized cancer was also elevated, although not statistically significant (IRR = 1.31, 95% CI = 0.81‐2.11).CONCLUSIONSMedicare prostate cancer screening–related expenditures are substantial, vary considerably across regions, and are positively associated with rates of cancer diagnosis. Cancer 2014;120:96–102. © 2013 American Cancer Society.
Body mass and smoking are modifiable risk factors for recurrent bladder cancer
Authors: Wyszynski Asaf , Tanyos Sam A. , Rees Judy R. , Marsit Carmen J. , Kelsey Karl T. , Schned Alan R. , Pendleton Eben M. , Celaya Maria O. , Zens Michael S. , Karagas Margaret R. , Andrew Angeline S. 
Published: October 2013

BACKGROUNDIn the Western world, bladder cancer is the fourth most common cancer in men and the eighth most common in women. Recurrences frequently occur, and continued surveillance is necessary to identify and treat recurrent tumors. Efforts to identify risk factors that are potentially modifiable to reduce the rate of recurrence are needed.METHODSCigarette smoking behavior and body mass index were investigated at diagnosis for associations with bladder cancer recurrence in a population‐based study of 726 patients with bladder cancer in New Hampshire, United States. Patients diagnosed with non–muscle invasive urothelial cell carcinoma were followed to ascertain long‐term prognosis. Analysis of time to recurrence was performed using multivariate Cox regression models.RESULTSSmokers experienced shorter time to recurrence (continuing smoker hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 1.08‐2.13). Although being overweight (body mass index > 24.9 kg/m2) at diagnosis was not a strong independent factor (HR = 1.33, 95% CI = 0.94‐1.89), among continuing smokers, being overweight more than doubled the risk of recurrence compared to smokers of normal weight (HR = 2.67, 95% CI = 1.14‐6.28).CONCLUSIONSThese observational results suggest that adiposity is a risk factor for bladder cancer recurrence, particularly among tobacco users. Future intervention studies are warranted to evaluate whether both smoking cessation and weight reduction strategies reduce bladder tumor recurrences. Cancer 2014;120:408–414. © 2013 American Cancer Society.
Mediators of the resistance and aerobic exercise intervention effect on physical and general health in men undergoing androgen deprivation therapy for prostate cancer
Authors: Buffart Laurien M. , Galvão Daniel A. , Chinapaw Mai J. , Brug Johannes , Taaffe Dennis R. , Spry Nigel , Joseph David , Newton Robert U. 
Published: October 2013

BACKGROUNDThe objective of the current study was to identify mediators of the effects of a combined resistance and aerobic exercise program on perceived physical and general health in men undergoing androgen deprivation therapy for prostate cancer.METHODSIn total, 57 patients with prostate cancer undergoing androgen deprivation therapy were randomly assigned to 12 weeks of resistance and aerobic exercise or usual care. The outcome measures of physical and general health were assessed by standardized questionnaires. Linear regression analyses were conducted on the residual change scores of the variables. The mediating effects of fatigue, muscle strength, and functional performance on the intervention's effect on physical and general health were examined using the product of coefficients method. Bootstrapping was used to calculate the 95% confidence intervals (95% CIs).RESULTSThe exercise intervention was found to significantly improve physical (beta, 5.03; 95% CI, 1.01‐9.04) and general health (beta, 12.89; 95% CI, 2.24‐23.54). Upper body muscle strength and walking speed significantly mediated the intervention effect on physical health (beta, 2.65; 95% CI, 0.64‐5.54), accounting for 53% of the total effect. Walking speed and fatigue were found to be mediators in the intervention effect on general health (beta, 7.52; 95% CI, 2.16‐16.92), accounting for 51% of the total effect.CONCLUSIONSThe intervention effects on physical and general health were explained by different mediating mechanisms. Walking speed mediated the intervention effect on both physical and general health. The intervention effect on physical health was further mediated by upper body strength, whereas the effect on general health was mediated by fatigue. Cancer 2014;120:294–301. © 2013 American Cancer Society.
Trends in stage‐specific incidence rates for urothelial carcinoma of the bladder in the United States: 1988 to 2006
Authors: Nielsen Matthew E. , Smith Angela B. , Meyer Anne‐Marie , Kuo Tzy‐Mey , Tyree Seth , Kim William Y. , Milowsky Matthew I. , Pruthi Raj S. , Millikan Robert C. 
Published: October 2013

BACKGROUNDBladder cancer is notable for a striking heterogeneity of disease‐specific risks. Among the approximately 75% of incident cases found to be superficial to the muscularis propria at the time of presentation (non–muscle‐invasive bladder cancer), the risk of progression to the lethal phenotype of muscle‐invasive disease is strongly associated with stage and grade of disease. Given the suggestion of an increasing percentage of low‐risk cases in hospital‐based registry data in recent years, the authors hypothesized that population‐based data may reveal changes in the stage distribution of early‐stage cases.METHODSSurveillance, Epidemiology, and End Results (SEER) data were used to examine trends for the stage‐specific incidence of bladder cancer between 1988 and 2006, adjusted for age, race, and sex, using Joinpoint and nonparametric tests.RESULTSThe adjusted incidence rate of papillary noninvasive (Ta) predominantly low grade (77%) disease was found to increase from 5.52 to 9.09 per 100,000 population (P < .0001), with an average annual percentage change of +3.3. Over the same period, concomitant, albeit smaller, decreases were observed for flat in situ (Tis) and lamina propria‐invasive (T1) disease (2.57 to 1.19 and 6.65 to 4.61 per 100,000 population [both P < .0001]; average annual percent change of −5.0 and −1.6, respectively). The trend was most dramatic among patients in the oldest age strata, suggesting a previously unappreciated cohort phenomenon.CONCLUSIONSThe findings of the current study should motivate further epidemiological investigations of differential associations of genetic and environmental factors with different bladder cancer phenotypes as well as further scrutiny of clinical practice guideline recommendations for the growing subgroup of predominantly older patients with lower‐risk disease. Cancer 2014;120:86–95. © 2013 American Cancer Society.
Racial parities in outcomes after radiotherapy for head and neck cancer
Authors: Liu Gene‐Fu F. , Ranck Mark C. , Solanki Abhishek A. , Cao Hongyuan , Kolokythas Antonia , Wenig Barry L. , Chen Lucy , Ard Stephanie , Weichselbaum Ralph R. , Halpern Howard , Spiotto Michael T. 
Published: October 2013

BACKGROUNDAlthough black patients experience worse outcomes after treatment for squamous cell carcinoma of the head and neck (HNSCC), these conclusions were based on populations in which blacks comprised a minority of patients. The objective of the current study was to determine the impact of race on outcomes in patients with HNSCC who received radiotherapy at an institution in which blacks comprised the majority of patients.METHODSIn this retrospective cohort study, the authors reviewed 366 black patients and 236 white patients who had nonmetastatic HNSCC for which they received radiotherapy between 1990 and 2012. The primary study outcome measures were locoregional control, freedom from distant metastasis, progression‐free survival, and overall survival.RESULTSThe median follow‐up was 18.3 months for all patients. The 2‐year locoregional control rate was 71.9% for black patients compared with 64.2% for white patients (hazard ratio, 0.72; P = .03). There was no difference between blacks and whites regarding 2‐year freedom from distant metastasis, progression‐free survival, or overall survival. Among the patients who had stage III through IVB disease, blacks and whites had similar outcomes. On multivariate analysis, race was not statistically significant for locoregional control, freedom from distant metastasis, progression‐free survival, or overall survival. Despite these similar outcomes, black patients had worse socioeconomic factors and increased comorbidities but had similar treatment compliance compared with white patients.CONCLUSIONSWith more adverse prognostic factors, black patients experienced oncologic outcomes similar to the outcomes of white patients after receiving radiotherapy for HNSCC. The current data suggest that centers that treat large percentages of minority patients who receive radiotherapy for HNSCCs may overcome existing health care disparities through improved treatment compliance. Cancer 2014;120:244–252. © 2013 American Cancer Society.
Hepatocyte nuclear factor‐1β is not a specific marker of clear cell carcinoma in serous effusions
Authors: Davidson Ben 
Published: October 2013

BACKGROUNDThe transcription factor hepatocyte nuclear factor‐1β (HNF1β) has been reported to be a specific clear cell carcinoma marker, but its role in the diagnosis of serous effusions is largely unexplored. The objective of this study was to assess the diagnostic role of 2 commercial antibodies against HNF1β in effusion specimens.METHODSEffusions (n = 101), consisting of 43 ovarian adenocarcinomas (26 serous, 14 clear cell, 3 endometrioid), 37 nonovarian adenocarcinomas, 10 malignant mesotheliomas, 2 nonepithelial cancers, and 9 reactive specimens, were immunostained using antibodies from Santa Cruz Biotechnology Inc (Santa Cruz, Calif) and Atlas Antibodies AB (Stockholm, Sweden).RESULTSUse of the Santa Cruz antibody was associated with cytoplasmic or background staining in some specimens, whereas distinct staining with minimal background was observed using the Atlas antibody. The Santa Cruz antibody performed better in differentiating clear cell carcinoma from serous ovarian carcinoma and breast carcinoma, whereas staining was consistently negative in benign and malignant mesotheliomas using both antibodies. Distinct nuclear expression of HNF1β was observed in lung and gastrointestinal carcinomas, most often using the Atlas antibody.CONCLUSIONSThe HNF1β antibody from Atlas performed better than its counterpart from Santa Cruz in terms of staining quality, but was less specific for clear cell carcinoma. Although HNF1β may be of diagnostic value in differentiating clear cell from serous carcinoma in cases with proven genital origin, the role of this marker is questionable in the differential diagnosis between the former tumors and adenocarcinomas of other origin, particularly in the setting of metastasis from an unknown primary tumor. Cancer (Cancer Cytopathol) 2014;122:153–8. © 2013 American Cancer Society.
Label‐retaining, quiescent globose basal cells are found in the olfactory epithelium
Authors: Jang Woochan , Chen Xueyan , Flis Daniel , Harris Margaret , Schwob James E. 
Published: October 2013

ABSTRACTThe vertebrate olfactory epithelium (OE) is known for its ability to renew itself throughout life as well as to reconstitute after injury. Although this remarkable capacity demonstrates the persistence of stem cells and multipotent progenitor cells, their nature in the OE remains undefined and controversial, as both horizontal basal cells (HBCs) and globose basal cells (GBCs) have features in common with each other and with stem cells in other tissues. Here, we investigate whether some among the population of GBCs satisfy a key feature of stem cells, i.e., mitotic quiescence with retention of thymidine analogue label and activation by injury. Accordingly, we demonstrate that some GBCs express p27Kip1, a member of the Kip/Cip family of cyclin‐dependent kinase inhibitors. In addition, some GBCs retain bromodeoxyuridine or ethynyldeoxyuridine for an extended period when the pulse is administered in neonates followed by a 1‐month chase. Their identity as GBCs was confirmed by electron microscopy. All spared GBCs express Ki‐67 in the methyl bromide (MeBr)‐lesioned OE initially after lesion, indicating that the label‐retaining (LR) GBCs are activated in response to injury. LR‐GBCs reappear during the acute recovery period following MeBr exposure, as demonstrated with 2‐ or 4‐week chase periods after labeling. Taken together, our data demonstrate the existence of LR‐GBCs that are seemingly activated in response to epithelial injury and then re‐established after the initial phase of recovery is completed. In this regard, some among the GBCs satisfy a common criterion for functioning like stem cells. J. Comp. Neurol. 522:731–749, 2014. © 2013 Wiley Periodicals, Inc.
Functional anatomy of the fiddler crab compound eye (Uca vomeris: Ocypodidae, Brachyura, Decapoda)
Authors: Alkaladi Ali , Zeil Jochen 
Published: October 2013

ABSTRACTWe describe the structural organization of the ommatidium in the compound eye of the fiddler crab, Uca vomeris, at both the light‐ and the electron‐microscopy levels. We pay particular attention to the organization of the optical system, the retinular cells, the rhabdom, and of pigment cells. Although the fiddler crab compound eye is of the apposition type, typical for Brachyuran crabs, we identify a number of novel, functionally relevant aspects of ommatidial organization that have not previously been described. The flat corneal facet lenses provide the main focusing power and therefore must contain a gradient of refractive index. Each ommatidium has the typical set of eight retinular cells, with a distal retinular cell R8 lying close to the proximal tip of the crystalline cone. R8 is shaped into four lobes, which are separated by proximal extensions of the four crystalline cone cells and of distal extensions of retinular cells R1–R7. The microvilli in the R8 rhabdom are not aligned in a uniform direction, while the microvilli of the main rhabdom show the typical crustacean pattern of alternating bands of horizontally (R3, R4, R7) and vertically aligned microvilli (R1, R2, R5, R6). We describe in detail the distribution and structural properties of screening pigment granules in the two types of pigment cells and in the retinular cells in the equatorial eye. We discuss the functional significance of this fine‐structural organization of the fiddler crab compound eye in relation to visual processing and visual ecology. J. Comp. Neurol. 522:1264–1283, 2014. © 2013 Wiley Periodicals, Inc.
Natural and lesion‐induced decrease in cell proliferation in the medial nucleus of the trapezoid body during hearing development
Authors: Saliu Aminat , Adise Shana , Xian Sandy , Kudelska Kamila , Rodríguez‐Contreras Adrián 
Published: October 2013

ABSTRACTThe functional interactions between neurons and glial cells that are important for nervous system function are presumably established during development from the activity of progenitor cells. In this study we examined proliferation of progenitor cells in the medial nucleus of the trapezoid body (MNTB) located in the rat auditory brainstem. We performed DNA synthesis labeling experiments to demonstrate changes in cell proliferation activity during postnatal stages of development. An increase in cell proliferation correlated with MNTB growth and the presence of S100β‐positive astrocytes among MNTB neurons. In additional experiments we analyzed the fate of newly born cells. At perinatal ages, newly born cells colabeled with the astrocyte marker S100β in higher numbers than when cells were generated at postnatal day 6. Furthermore, we identified newly born cells that were colabeled with caspase‐3 immunohistochemistry and performed comparative experiments to demonstrate that there is a natural decrease in cell proliferation activity during postnatal development in rats, mice, gerbils, and ferrets. Lastly, we found that there is a stronger decrease in MNTB cell proliferation after performing bilateral lesions of the auditory periphery in rats. Altogether, these results identify important stages in the development of astrocytes in the MNTB and provide evidence that the proliferative activity of the progenitor cells is developmentally regulated. We propose that the developmental reduction in cell proliferation may reflect coordinated signaling between the auditory brainstem and the auditory periphery. J. Comp. Neurol. 522:971–985, 2014. © 2013 Wiley Periodicals, Inc.