bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carrier frequency of mutation 657del5 in the NBS1 gene in a population of polish pediatric patients with sporadic lymphoid malignancies
Authors: Chrzanowska Krystyna H. , Piekutowska‐Abramczuk Dorota , Popowska Ewa , Gładkowska‐Dura Małgorzata , Małdyk Jadwiga , Syczewska Małgorzata , Krajewska‐Walasek Małgorzata , Goryluk‐Kozakiewicz Bożenna , Bubała Halina , Gadomski Artur , Gaworczyk Anna , Kazanowska Bernarda , Kołtan Andrzej , Kuźmicz Marta , Luszawska‐Kutrzeba Teresa , Maciejka‐Kapuścińska Lucyna , Stolarska Małgorzata , Stefańska Katarzyna , Sznurkowska Katarzyna , Wakulińska Anna , Wieczorek Maria , Szczepański Tomasz , Kowalczyk Jerzy 
Published: September 2005

AbstractNijmegen breakage syndrome (NBS) is a human autosomal recessive disease characterized by genomic instability and enhanced cancer predisposition, in particular to lymphoma and leukemia. Recently, significantly higher frequencies of heterozygous carriers of the Slavic founder NBS1 mutation, 657del5, were found in Russian children with sporadic lymphoid malignancies, and in Polish adults with non‐Hodgkin lymphoma (NHL). In addition, the substitution 643C>T (R215W) has also been found in excess among children with acute lymphoblastic leukemia (ALL). In an attempt to asses the contribution of both mutations to the development of sporadic lymphoid malignancies, we analyzed DNA samples from a large group of Polish pediatric patients. The NBS1 mutation 657del5 on one allele was found in 3 of 270 patients with ALL and 2 of 212 children and adolescents with NHL; no carrier was found among 63 patients with Hodgkin lymphoma (HL). No carriers of the variant R215W were detected in any studied group. The relative frequency of the 657del5 mutation was calculated from a total of 6,984 controls matched by place of patient residence, of whom 42 were found to be carriers (frequency = 0.006). In the analyzed population with malignancies, an increased odds ratio for the occurrence of mutation 657del5 was found in comparison with the control Polish population (OR range 1.48–1.85, 95% confidence interval 1.18–2.65). This finding indicates that the frequency of the mutation carriers was indeed increased in patients with ALL and NHL (p < 0.05). Nonetheless, NBS1 gene heterozygosity is not a major risk factor for lymphoid malignancies in childhood and adolescence. © 2005 Wiley‐Liss, Inc.
Characterization of the tumor suppressor gene WWOX in primary human oral squamous cell carcinomas
Authors: Pimenta Flávio J. , Gomes Dawidson A. , Perdigão Paolla F. , Barbosa Alvimar A. , Romano‐Silva Marco A. , Gomez Marcus V. , Aldaz C. Marcelo , De Marco Luiz , Gomez Ricardo S. 
Published: September 2005

AbstractOral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity, representing ˜90% of all oral carcinomas and accounting for 3–5% of all malignancies. The WWOX gene (WW‐domain containing oxidoreductase) is a candidate tumor suppressor gene located at 16q23.3–24.1, spanning the second most common fragile site, FRA16D. In this report, the role of the WWOX gene was investigated in 20 tumors and 10 normal oral mucosas, and we demonstrated an altered WWOX gene in 50% (10/20) of OSCCs. Using nested RT‐PCR, mRNA transcription was altered in 35% of the tumors, with the complete absence of transcripts in 2 samples as well as absence of exons 6–8 (2 tumors), exon 7 (1 tumor), exon 7 and exon 6–8 (1 tumor) and partial loss of exons 8 and 9 (1 tumor). To determine if the aberrant transcripts were translated, Western blots were performed in all samples; however, only the normal protein was detected. By immunohistochemistry, a reduction in Wwox protein expression was observed, affecting 40% of the tumors when compared with normal mucosa. In addition, a novel somatic mutation (S329F) was found. The presence of alterations in mRNA transcription correlated with the reduced expression of Wwox protein in the tumors. These results show that the WWOX gene is frequently altered in OSCC and may contribute to the carcinogenesis processes in oral cancer. © 2005 Wiley‐Liss, Inc.
Promoter hypermethylation of the potential tumor suppressor DAL‐1/4.1B gene in renal clear cell carcinoma
Authors: Yamada Daisuke , Kikuchi Shinji , Williams Yuko N. , Sakurai‐Yageta Mika , Masuda Mari , Maruyama Tomoko , Tomita Kyoichi , Gutmann David H. , Kakizoe Tadao , Kitamura Tadaichi , Kanai Yae , Murakami Yoshinori 
Published: September 2005

AbstractRenal clear cell carcinoma (RCCC) is a malignant tumor with poor prognosis caused by the high incidence of metastasis to distal organs. Although metastatic RCCC cells frequently show aberrant cytoskeletal organization, the underlying mechanism has not been elucidated. DAL‐1/4.1B is an actin‐binding protein implicated in the cytoskeleton‐associated processes, while its inactivation is frequently observed in lung and breast cancers and meningiomas, suggesting that 4.1B is a potential tumor suppressor. We studied a possible involvement of 4.1B in RCCCs and evaluated it as a clinical indicator. 4.1B protein was detected in the proximal convoluted tubules of human kidney, the presumed cell of origin of RCCC. On the other hand, loss or marked reduction of its expression was observed in 10 of 19 (53%) renal cell carcinoma (RCC) cells and 12 of 19 (63%) surgically resected RCCC by reverse transcription‐PCR. Bisulfite sequencing or bisulfite SSCP analyses revealed that the 4.1B promoter was methylated in 9 of 19 (47%) RCC cells and 25 of 55 (45%) surgically resected RCCC, and inversely correlated with 4.1B expression (p < 0.0001). Aberrant methylation appeared to be a relatively early event because more than 40% of the tumors with pT1a showed hypermethylation. Furthermore, 4.1B methylation correlated with a nuclear grade (p = 0.017) and a recurrence‐free survival (p = 0.0036) and provided an independent prognostic factor (p = 0.038, relative risk 10.5). These results indicate that the promoter methylation of the 4.1B is one of the most frequent epigenetic alterations in RCCC and could predict the metastatic recurrence of the surgically resected RCCC. © 2005 Wiley‐Liss, Inc.
Increase in skin cancer screening during a community‐based randomized intervention trial
Authors: Aitken Joanne F. , Youl Philippa H. , Janda Monika , Lowe John B , Ring Ian T. , Elwood Mark 
Published: September 2005

AbstractSurvival from cutaneous melanoma is mainly dependent on the thickness of the lesion at diagnosis. Skin screening may increase detection of thin lesions and hence improve survival. Within a community‐based randomized controlled trial of a population screening program for melanoma in Queensland, Australia, 9 communities were randomly assigned to the 3‐year intervention and 9 communities to the control group. Skin screening prevalence was monitored by cross‐sectional surveys at baseline, 1, 2 and 3 years into the intervention and 2 years later. At baseline, prevalence of whole‐body clinical skin examination was similar in intervention and control communities. In intervention communities, the prevalence of whole‐body skin examinations increased to 29.2%, an absolute difference of 18% from baseline, with a peak of 34.8% 2 years after baseline, and began to decline again at the end of the intervention period. The largest increases were seen in men and women ≥50 years. Uptake of screening did not differ according to melanoma risk factors; however, the decline in screening was less in participants who reported a number of melanoma risk factors. The prevalence of skin self‐examination remained stable during the intervention program. No changes were observed in the control communities. These results indicate that the intervention program significantly increased the prevalence of whole‐body clinical skin examinations in intervention communities. Once the intervention program ceased, and particularly after skin clinics ceased, levels of skin screening began to decline. The provision of specialized skin screening clinics may be needed to achieve sufficient screening rates should population based screening for skin cancer be considered. © 2005 Wiley‐Liss, Inc.
Incidence of bone and soft tissue sarcoma after radiotherapy: A cohort study of 295,712 Finnish cancer patients
Authors: Virtanen Anna , Pukkala Eero , Auvinen Anssi 
Published: September 2005

AbstractRadiotherapy is commonly used for treatment of malignant disease. As a consequence of radiotherapy, an increased risk of developing a second malignant neoplasm has been shown. However, little is known about the effects of radiation on developing sarcoma. The aim of this study was to examine the risk of developing a bone or soft tissue sarcoma after radiotherapy for a first primary cancer. The study population included all the patients with primary cancers of breast, cervix uteri, corpus uteri, lung, ovary, prostate, rectum and lymphoma diagnosed during 1953–2000 and identified from the Finnish Cancer Registry. Patients were followed up for subsequent sarcomas. The follow‐up yielded 1.5 million person‐years at risk and 147 sarcomas. Compared to the national incidence rates, after 10 years of follow‐up sarcoma risk was increased among patients who had received neither radiotherapy nor chemotherapy (standardised incidence ratio (SIR) 2.0, 95% CI 1.3–3.0), radiotherapy without chemotherapy (SIR 3.2, 95% CI 2.3–4.3), chemotherapy without radiotherapy (SIR 4.9, 95% CI 1.0–14.4), as well as combined radiotherapy and chemotherapy (SIR 3.4, 95% CI 0.4–12.5). For radiotherapy in ages below 55 the SIR was 4.2 (95% CI 2.9–5.8). In the adjusted regression analysis the rate ratio was 1.5 (95% CI 0.9–2.6) for the radiotherapy group. In conclusion, radiotherapy appears to be associated with an increased risk of developing sarcoma especially among younger patients. Further investigation is needed to clarify the dose–response of the preceding ionizing radiation. © 2005 Wiley‐Liss, Inc.
Mammalian lignans enterolactone and enterodiol, alone and in combination with the isoflavone genistein, do not promote the growth of MCF‐7 xenografts in ovariectomized athymic nude mice
Authors: Power Krista A. , Saarinen Niina M. , Chen Jian Min , Thompson Lilian U. 
Published: September 2005

AbstractThis study determined the effect of the mammalian lignans enterolactone (ENL) and enterodiol (END) alone and in combination with the isoflavone genistein (GEN) on the growth of MCF‐7 tumors in ovariectomized nude mice. Ovariectomized athymic nude mice with established MCF‐7 tumors were fed a basal diet (AIN‐93G) and divided into 5 groups that received daily subcutaneous injections (10 mg/kg body weight (BW)) of ENL, END, GEN, a mixture of these compounds (MIX), or vehicle as a negative control for 22 weeks. A positive control group was implanted with an estradiol pellet in order to establish an estrogenic tumor growth response. In the ENL‐ and END‐treated mice, palpable tumors regressed significantly by 91 and 83%, respectively, resulting in final tumors that were similar to the negative control tumors. However, tumor cell apoptosis was significantly enhanced by the lignans. In the GEN‐treated mice, tumors initially regressed significantly by 64% but regression ceased following prolonged treatment, resulting in final tumors that were significantly larger compared to negative control, ENL‐, and END‐treated mice, in part by increasing tumor cell proliferation. The MIX treatment significantly regressed palpable tumors by 87% similar to negative control group, with no effects on tumor cell apoptosis or proliferation. The isoflavone GEN alone promoted the growth of established MCF‐7 human breast cancer xenografts after prolonged treatment while the mammalian lignans ENL and END did not. When these phytoestrogens were given in combination, no tumor growth‐promoting effects were observed. © 2005 Wiley‐Liss, Inc.
Hormonal and reproductive factors and risk of glioma: A prospective cohort study
Authors: Silvera Stephanie A. Navarro , Miller Anthony B. , Rohan Thomas E. 
Published: September 2005

AbstractThe etiology of glioma, the most commonly diagnosed malignant brain tumor among adults in the United States, is poorly understood. Given the lower incidence rate of glioma in women than in men, it has been hypothesized that reproductive and hormonal factors may be involved in the etiology of glioma. We conducted a secondary analysis of data from the National Breast Screening Study, which included 89,835 Canadian women, aged 40–59 years at recruitment between 1980 and 1985. Linkages to national cancer and mortality databases yielded data on cancer incidence and deaths from all causes, respectively, with follow‐up ending between 1998 and 2000. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CI) for the association between hormonal and reproductive factors and risk of glioma. During a mean of 16.4 years of follow‐up, we observed 120 incident glioma cases. Compared with women with a relatively early age at menarche (≤12 years), women who were 13–14 years of age at menarche had a 64% increased risk of glioma (95% CI = 1.01–2.65), and women who were older than 14 years of age at menarche had a 66% increased risk of glioma (95% CI = 0.86–3.20, ptrend = 0.06). Age at first live birth, parity, menopausal status, use of oral contraceptive and use of hormone replacement therapy were not associated with altered glioma risk in our study population. Additional prospective studies are needed to confirm our findings. © 2005 Wiley‐Liss, Inc.
Antigen‐independent accumulation of activated effector/memory T lymphocytes into human and murine tumors
Authors: Joncker Nathalie T. , Marloie Marie‐Annick , Chernysheva Anna , Lonchay Christophe , Cuff Simone , Klijanienko Jerzy , Sigal‐Zafrani Brigitte , Vincent‐Salomon Anne , Sastre Xavier , Lantz Olivier 
Published: September 2005

AbstractTumor infiltrating lymphocytes (TIL) display activation markers and their presence is often associated with a favorable outcome. The role of tumor antigens in T cell recruitment into tumors is unclear. In an attempt to address this issue, we purified lymphocytes from breast tumor or nontumor, mammary tissue from patients, and normal mammary tissue from healthy individuals. In all groups, including healthy individuals, the majority of cells displayed an effector/memory (CD45RAlo/CD27+/−) phenotype and quite surprisingly the early and transient activation marker CD69, thus, questioning the tumor antigen specificity of TIL. Because the human repertoire is diverse, the T cells found in the tumors could recognize both self/tumor and environmental antigens through cross‐reactivity. To test this hypothesis, we used two anti‐male HY monospecific TCR transgenic mouse models. We found an infiltration of HY negative tumors by the CD4+ and CD8+ monoclonal T cells after priming with HY positive cells in the periphery. Thus, the presence of activated effector/memory T lymphocytes in tumors can be independent of reactivity against tumor antigens. These results suggest that to find activated effector T cells in a tissue does not always mean that a specific immune response is taking place. © 2005 Wiley‐Liss, Inc.
Methylation profile in tumor and sputum samples of lung cancer patients detected by spiral computed tomography: A nested case–control study
Authors: Cirincione Rosalia , Lintas Carla , Conte Davide , Mariani Luigi , Roz Luca , Vignola Antonio Maurizio , Pastorino Ugo , Sozzi Gabriella 
Published: September 2005

AbstractWe evaluated the aberrant promoter methylation profile of a panel of 3 genes in DNA from tumor and sputum samples, in view of a complementary approach to spiral computed tomography (CT) for early diagnosis of lung cancer. The aberrant promoter methylation of RARβ2, p16INK4A and RASSF1A genes was evaluated by methylation‐specific PCR in tumor samples of 29 CT‐detected lung cancer patients, of which 18 had tumor‐sputum pairs available for the analysis, and in the sputum samples from 112 cancer‐free heavy smokers enrolled in a spiral CT trial. In tumor samples from 29 spiral CT‐detected patients, promoter hypermethylation was identified in 19/29 (65.5%) cases for RARβ2, 12/29 (41.4%) for p16INK4A and 15/29 (51.7%) for RASSF1A. Twenty‐three of twenty‐nine (79.3%) samples of the tumors exhibited methylation in at least 1 gene. In the sputum samples of 18 patients, methylation was detected in 8/18 (44.4%) for RARβ2 and 1/18 (5%) for both RASSF1A and p16INK4A. At least 1 gene was methylated in 9/18 (50%) sputum samples. Promoter hypermethylation in sputum from 112 cancer‐free smokers was observed in 58/112 (51.7%) for RARβ2 and 20/112 (17.8%) for p16, whereas methylation of the RASSF1A gene was found in only 1/112 (0.9%) sputum sample. Our study indicates that a high frequency of hypermethylation for RARβ2, p16INK4A and RASSF1A promoters is present in spiral CT‐detected tumors, whereas promoter hypermethylation of this panel of genes in uninduced sputum has a limited diagnostic value in early lung cancer detection. © 2005 Wiley‐Liss, Inc.
Risk assessment for biochemical recurrence prior to radical prostatectomy: Significant enhancement contributed by human glandular kallikrein 2 (hK2) and free prostate specific antigen (PSA) in men with moderate PSA‐elevation in serum
Authors: Steuber Thomas , Vickers Andrew J. , Haese Alexander , Becker Charlotte , Pettersson Kim , Chun Felix K.‐H. , Kattan Michael W. , Eastham James A. , Scardino Peter T. , Huland Hartwig , Lilja Hans 
Published: September 2005

AbstractMost models to predict biochemical recurrence (BCR) of prostate cancer use pretreatment serum prostate‐specific antigen (PSA), clinical stage and prostate biopsy Gleason grade. We investigated whether human glandular kallikrein 2 (hK2) and free prostate‐specific antigen (fPSA) measured in pretreatment serum enhance prediction. We retrospectively measured total PSA (tPSA), fPSA and hK2 in preoperative serum samples from 461 men with localized prostate cancer treated with radical prostatectomy between 1999 and 2001. We developed a regression model to predict BCR using preoperative tPSA, clinical stage and biopsy Gleason grade. We then compared the predictive accuracy of this “base” model with a model with fPSA and hK2 as additional predictors. BCR was observed in 90 patients (20%), including 48 patients with a pretreatment tPSA ≤ 14 ng/ml (13%), and 28 patients (10%) with a pretreatment tPSA ≤ 10 ng/ml. Overall, the predictive accuracy of the base model (bootstrap‐corrected concordance index of 0.813) was not improved after the addition of fPSA or hK2 (0.818). However, for men with moderate tPSA‐elevation (tPSA ≤ 10 ng/ml), addition of fPSA and hK2 data increased predictive accuracy (from a base model concordance index of 0.756–0.815, p = 0.005). The improvement in accuracy was not sensitive to the threshold for “moderately elevated” PSA. For patients with a moderate tPSA‐elevation (tPSA ≤ 10 ng/ml), which closely corresponds to concurrent disease demographics, BCR‐prediction was enhanced when fPSA and hK2 were added to the conventional model. Measurements of fPSA and hK2 improve on our ability to counsel patients prior to treatment as to their risk of BCR. © 2005 Wiley‐Liss, Inc.
Gene expression profiles relate to SS18/SSX fusion type in synovial sarcoma
Authors: Fernebro Josefin , Francis Princy , Edén Patrik , Borg Åke , Panagopoulos Ioannis , Mertens Fredrik , Vallon‐Christersson Johan , Åkerman Måns , Rydholm Anders , Bauer Henrik CF , Mandahl Nils , Nilbert Mef 
Published: September 2005

AbstractWe applied 27k spotted cDNA microarray slides to assess gene expression profiles in 26 samples from 24 patients with synovial sarcomas (SS). The data were analyzed in relation to histopathologic type, cytogenetic aberrations, gene fusion type and development of distant metastases. Supervised analysis based on gene fusion type in 12 SS with SS18/SSX1 and 9 with SS18/SSX2 revealed significant differences in gene expression profiles. Among the discriminators were several genes that have previously been found to be upregulated in SS, including AXL, ZIC2, SPAG7, AGRN, FOXC1, NCAM1 and multiple metallothioneins. Histopathology and degree of cytogenetic complexity did not significantly influence expression, whereas a genetic signature that related to development of metastases could be discerned, albeit with a high false‐positive rate. In conclusion, our findings demonstrate differentially expressed genes for the 2 major gene fusion variants in SS, SS18/SSX1 and SS18/SSX2, and thereby suggest that these result in different downstream effects. © 2005 Wiley‐Liss, Inc.
Cross‐sectional analysis of oncogenic HPV viral load and cervical intraepithelial neoplasia
Authors: Flores Roberto , Papenfuss Mary , Klimecki Walter T. , Giuliano Anna R. 
Published: September 2005

AbstractIn human papillomavirus (HPV)‐associated carcinogenesis, HPV infection characteristics such as viral load may play an important role in lesion development. The purpose of this study was to determine the association between quantitative assessment of oncogenic HPV viral load, and abnormal cytology among women residing along the United States–Mexico border. A cross‐sectional study of 2,319 women was conducted between 1997 and 1998. Viral load of oncogenic HPV types (16, 18, 31, 39, 45, 51, 52, and 58) was measured among 173 HPV (+) women using quantitative real‐time PCR. Overall, HPV 16, 31, 52 and 58 showed the highest viral load. Single type infection had higher viral loads compared to multiple type infections. HPV viral load declined significantly (p = 0.04) with age. No significant association was observed with other known HPV risk factors such as oral contraceptive use, parity, sexual and STD history. Viral load was independently associated with degree of cervical lesions. An adjusted odds ratio (AOR) of 4.7 for the association between increasing total viral load and Atypical Squamous Cells of Undetermined Significance (ASCUS)/Atypical Glandular Cells of Undetermined Significance (AGUS) was observed (p for trend <0.01). Increased risk of low‐grade SIL was observed with higher viral load compared with HPV negative women (AOR = 47.7 for total viral load; AOR = 37.1 for HPV viral load not including HPV16, and AOR = 25.9 for HPV16 viral load). Likewise, increased risk of high‐grade SIL with higher viral loads was observed (AOR = 58.4 for high total viral load compared with HPV negative women, AOR = 58.1 for HPV viral load not including HPV16, and AOR = 69.8 for HPV16 high viral load). Results from this study suggest a dose–response relationship between increasing oncogenic HPV viral load and risk of LSIL and HSIL. © 2005 Wiley‐Liss, Inc.