bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence of haplotype insufficiency in human cells containing a germline mutation in BRCA1 or BRCA2
Authors: Buchholz Thomas A. , Wu Xifeng , Hussain Abu , Tucker Susan L. , Mills Gordon B. , Haffty Bruce , Bergh Sherry , Story Michael , Geara Fady B. , Brock William A. 
Published: September 2002

AbstractThe BRCA1 and BRCA2 gene products are thought to play important roles in the processing of DNA damage. To assess whether heterozygous mutations in these genes are associated with cellular radiosensitivity, we performed an in vitro radiation clonogenic survival assay on dermal fibroblasts obtained from 8 sequence‐proven BRCA heterozygotes (6 BRCA1, 2 BRCA2). These data were compared to results obtained from a previous set of 17 prospectively studied cancer patients who had a negligible risk for a BRCA mutation. In addition, results from radiation‐induced chromatid break assay performed on lymphocytes obtained from 9 BRCA heterozygotes (8 BRCA1, 1 BRCA2) were compared to results from a control group of 18 women with no cancer history. Results from both assays suggested that cells containing a heterozygous mutation in BRCA1 or BRCA2 were more radiosensitive than controls. For the fibroblast studies, the mean surviving fraction at 2 Gy (SF2) for carriers was 0.279 vs. 0.348 for the control set (p = 0.007). For the lymphocyte studies, the mean number of chromatid breaks after 125 cGy of radiation was 0.79 breaks per cell for the carriers vs. 0.45 for the controls (p = 0.0005). There was no apparent difference in the radiosensitivity between cells with BRCA1 vs. BRCA2 mutations (p = 0.769), although the small sample size minimizes the certainty of this observation. These preliminary results are consistent with a relationship between a germline mutation in BRCA1 or BRCA2 and a hypersensitivity to radiation. This phenotype could possibly predispose to an increased risk of radiation‐induced mutagenesis and carcinogenesis. © 2001 Wiley‐Liss, Inc.
Prevalence of high‐risk human papilloma virus types and its association with P53 codon 72 polymorphism in tobacco addicted oral squamous cell carcinoma (oscc) patients of Eastern India
Authors: Nagpal Jatin K. , Patnaik Srinivas , Das Bibhu R. 
Published: September 2002

AbstractHuman papillomavirus (HPV) infects the squamous epithelial cells of oral cavity and cervix leading to formation of warts that develops into the cancer. Human papillomavirus (HPV)‐16 and 18 encode E6 oncoprotein, which binds to and induces degradation of the tumour suppressor protein p53. A common polymorphism of p53, encoding either proline (Pro) or arginine (Arg) at position 72, affects the susceptibility of p53 to E6 mediated degradation in vivo. Oral cancer is a pressing problem in India due to the widespread habit of chewing betel quid, which plays an important role in etiology of this disease. In the present study an attempt has been made to analyze the genetic predisposition of the Indian population to HPV infection and oral carcinogenesis. In our study a total of 110 cases of Oral Cancer highly addicted to betel quid and tobacco chewing are analyzed for HPV 16/18 infection and its association with polymorphism at p53 codon 72. Of these a total number of 37 patients (33.6%) have shown the presence of HPV, among which the presence of HPV‐16, 18 and 16/18 coinfection is 22.7%, 14.5% and 10%, respectively. Our results also indicate that the p53 codon 72 genotype frequencies in Indian Oral Cancer patients are 0.55 (Arg) and 0.45 (Pro) as per Hardy‐Weinberg equilibrium. In our study, striking reduction in Pro/Pro allele frequency has been found in HPV positive cases, indicating Arg/Arg genotype to be more susceptible to HPV infection and oral carcinogenesis. © 2001 Wiley‐Liss, Inc.
Establishment of a non‐tumorigenic papillary thyroid cell line (FB‐2) carrying the RET/PTC1 rearrangement
Authors: Basolo Fulvio , Giannini Riccardo , Toniolo Antonio , Casalone Rosario , Nikiforova Marina , Pacini Furio , Elisei Rossella , Miccoli Paolo , Berti Piero , Faviana Pinuccia , Fiore Lisa , Monaco Carmen , Pierantoni Giovanna Maria , Fedele Monica , Nikiforov Yuri E. , Santoro Massimo , Fusco Alfredo 
Published: September 2002

AbstractA novel human thyroid papillary carcinoma cell line (FB‐2) has been established and characterized. FB‐2 cells harbor the RET/PTC1 chimeric oncogene in which the RET kinase domain is fused to the H4 gene. FB‐2 cells neither formed colonies in semisolid media nor induced tumors after heterotransplant into severe combined immunodeficient mice. However, HMGI(Y), HMGI‐C and c‐myc genes, which are associated to thyroid cell transformation, were abundantly expressed in FB‐2 cells but not in normal thyroid cells. FB‐2 cells only partially retained the differentiated thyroid phenotype. In fact, the PAX‐8 gene, which codes for a transcriptional factor required for thyroid cell differentiation, was expressed, while thyroglobulin, TSH‐receptor and thyroperoxidase genes were not. Moreover, FB‐2 cells produced high levels of interleukin (IL)‐6 and IL‐8. © 2001 Wiley‐Liss, Inc.
A sequence repeat in the insulin‐like growth factor‐1 gene and risk of breast cancer
Authors: Missmer Stacey A. , Haiman Christopher A. , Hunter David J. , Willett Walter C. , Colditz Graham A. , Speizer Frank E. , Pollak Michael N. , Hankinson Susan E. 
Published: September 2002

AbstractInsulin‐like growth factor‐1 (IGF‐I), a potent mitogen, is hypothesized to influence breast cancer risk. In 3 previous studies, a polymorphism in the IGF‐1 gene (sequence repeat length) was associated with plasma IGF‐I level. We evaluated prospectively the relationships among a (CA)n repeat polymorphism in the IGF‐1 gene, IGF‐I level and breast cancer risk in a nested case‐control study conducted within the Nurses' Health Study. Blood samples were collected in 1989–1990; up to June 1994, we identified 463 cases of breast cancer. One to 2 controls were selected per case, matched by age, menopausal status, postmenopausal hormone use, month and time of day of blood collection and fasting status, for a total of 622 controls. Although no significant trend was observed, plasma IGF‐I levels were significantly lower among controls, with no copy of the 19 allele, compared with those homozygous for the 19 (CA)n repeat length (146 and 173 ng/ml, respectively; p‐value for pairwise mean comparison = 0.005). In conditional logistic regression, controlling for established breast cancer risk factors, we observed no significant association between (CA)n repeat length genotype and risk of breast cancer [compared with repeat genotype 19/19—18/19 genotype relative risk (RR) = 0.96, 95% confidence interval (CI) = 0.56–1.64; 18/20 genotype RR = 0.92, 95% CI = 0.39–2.19; 19/20 genotype RR = 1.16, 95% CI = 0.82–1.64; 19/21 genotype RR = 0.69, 95% CI = 0.42–1.14; 20/20 genotype RR = 0.55, 95% CI = 0.28–1.10; 20/21 genotype RR = 0.72, 95% CI = 0.29–1.79]. Results did not vary substantially when evaluated according to menopausal status, tumor receptor status or category of other breast cancer risk factors. Although a modest association cannot be excluded, our data do not support an important relation between this IGF‐1 gene polymorphism and breast cancer risk. © 2002 Wiley‐Liss, Inc.
Overexpression of the Wilms' tumor gene WT1 in de novo lung cancers
Authors: Oji Yusuke , Miyoshi Shinichiro , Maeda Hajime , Hayashi Seiji , Tamaki Hiroya , Nakatsuka Shin‐Ichi , Yao Masayuki , Takahashi Eigo , Nakano Yoko , Hirabayashi Hirohisa , Shintani Yasushi , Oka Yoshihiro , Tsuboi Akihiro , Hosen Naoki , Asada Momotaro , Fujioka Tatsuya , Murakami Masaki , Kanato Keisuke , Motomura Mari , Kim Eui Ho , Kawakami Manabu , Ikegame Kazuhiro , Ogawa Hiroyasu , Aozasa Katsuyuki , Kawase Ichiro , Sugiyama Haruo 
Published: September 2002

AbstractExpression of the Wilms' tumor gene WT1 in de novo lung cancer was examined using quantitative real‐time RT‐PCR and immunohistochemistry. Overexpression of the WT1 gene was detected by RT‐PCR in 54/56 (96%) de novo non‐small cell lung cancers examined and confirmed by detection of WT1 protein with an anti‐WT1 antibody. Overexpression of the WT1 gene was also demonstrated in 5/6 (83%) de novo small cell lung cancers by immunohistochemistry. Furthermore, when the WT1 gene was examined for mutations by direct sequencing of genomic DNA in 7 lung cancers, no mutations were found. These results suggest that the nonmutated, wild‐type WT1 gene plays an important role in tumorigenesis of de novo lung cancers and may provide us with the rationale for new therapeutic strategies for lung cancer targeting the WT1 gene and its products. © 2002 Wiley‐Liss, Inc.
Personality characteristics and the risk of breast cancer: A prospective cohort study
Authors: Lillberg Kirsi , Verkasalo Pia K. , Kaprio Jaakko , Helenius Hans , Koskenvuo Markku 
Published: September 2002

AbstractVarious personality characteristics have been suggested to increase the risk of breast cancer but reliable epidemiologic data on this issue are limited. We prospectively investigated the relationship between personality characteristics and the risk of breast cancer in 12,499 Finnish women aged 18 years or more. In health questionnaires in 1975 and 1981, these women completed at least one of the following personality scales: Eysenck extroversion, Bortner type A behaviour and author‐constructed measure of hostility. They also reported about other potential breast cancer risk factors. From 1976–1996, 253 cases of breast cancer were identified by record linkage with the Finnish Cancer Registry. Proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). The multivariable HRs of breast cancer for women with intermediate level (scores 3–6) and high level (7–9) of extroversion in 1975 were 1.18 (95% CI 0.87–1.60) and 0.97 (95% CI 0.64–1.47), respectively, compared to those with low level (0–2). These results remained unaltered when the level of extroversion was determined as the average of the 1975 and 1981 reports. There was also no increase in breast cancer risk in relation to type A behaviour and hostility. Furthermore, we observed no substantial joint effects of personality characteristics on the risk of breast cancer. In conclusion, our data do not support the existence of an important role for personality in the aetiology of breast cancer. These findings are reassuring to those who have believed the contrary. © 2002 Wiley‐Liss, Inc.
Cancer incidence among Sami in Northern Finland, 1979–1998
Authors: Soininen Leena , Järvinen Sari , Pukkala Eero 
Published: September 2002

AbstractThe Sami population living in Northern Finland represents a specific genetic background and a way of life that is different from other Finns. A cohort of 2,100 Sami and 4,174 non‐Sami people from the 2 northernmost municipalities of Finland on 31 December 1978 was identified from the national Population Register and followed up through the Finnish Cancer Registry for cancer incidence during 1979–1998. There were 111 cancer cases among the Sami, while the expected number based on the average cancer incidence in the Finnish population was 173. Among the non‐Sami cohort members, there were 226 cases of cancervs.224 expected cases. The Sami had significantly decreased incidence of cancers of the prostate [standardised incidence ratio (SIR) 0.25; 95% confidence interval (CI) 0.08–0.58] and breast (SIR 0.36; 95% CI 0.14–0.73), similarly for both localised and nonlocalised tumours. Low SIRs were also observed for bladder cancer (SIR 0.28; 97% CI 0.03–0.99) basal cell carcinoma of the skin (SIR 0.12; 95% CI 0.03–0.30) and other nonmelanoma skin cancers (SIR 0; 95% CI 0–0.63). In contrast to other subcategories of the Sami, the Skolts, whose lifestyle stems from areas that now belong to Russia, showed a nonreduced overall cancer risk and a significantly elevated risk for stomach cancer (SIR 3.8; 95% CI 1.5–7.8). The low cancer incidence among the other Sami populations in Finland cannot be fully explained by their specific way of life. It seems likely that the Sami ethnicity carries a reduced cancer incidence level. Although many Sami have been exposed to radioactive fallout from the nuclear weapon tests via their reindeer‐rich diet, this does not seem to affect their cancer risk. © 2002 Wiley‐Liss, Inc.
Increased emotional distress in daughters of breast cancer patients is associated with decreased natural cytotoxic activity, elevated levels of stress hormones and decreased secretion of Th1 cytokines
Authors: Cohen Miri , Klein Ehud , Kuten Abraham , Fried Geta , Zinder Oren , Pollack Shimon 
Published: September 2002

AbstractDBCP who are aware of their increased risk of developing breast cancer may suffer from high emotional distress. Chronic stress may interfere with NCA and low NCA is associated with increased cancer risk. We studied 80 DBCP and 47 age‐ and education‐matched healthy females (controls). Heparinized venous blood (30 ml) was drawn from all subjects between 8 and 9 A.M., and each participant answered a set of psychologic questionnaires. In addition, the first‐morning urine sample was collected. DBCP scored significantly higher in emotional distress compared to controls. Levels of stress hormones in DBCP were higher and in vitro secretion of IL‐2, IL‐12 and IFN‐γ lower compared to controls. NCA against NK‐resistant (MCF‐7, COLO‐205, U937) and NK‐sensitive (K562) cell lines was significantly lower in DBCP and much less augmented by in vitro preincubation with IL‐2 or IL‐12 compared to controls. NCA and in vitro Th1 cytokine secretion were inversely correlated with the degree of emotional distress and the level of stress hormones in blood or urine. High emotional distress and elevated levels of stress hormones are associated with impaired immune surveillance functions in DBCP. This may contribute to the increased risk of DBCP to develop breast cancer. An interventional trial to enhance coping and reduce stress levels may help to decrease the risk for breast cancer onset in DBCP. © 2002 Wiley‐Liss, Inc.
Inhibitory effects of the standardized extract (DA‐9601) of Artemisia asiatica Nakai on phorbol ester–induced ornithine decarboxylase activity, papilloma formation, cyclooxygenase‐2 expression, inducible nitric oxide synthase expression and nuclear transcription factor κB activation in mouse skin
Authors: Seo Hyo‐Joung , Park Kwang‐Kyun , Han Seong Su , Chung Won‐Yoon , Son Mi‐Won , Kim Won‐Bae , Surh Young‐Joon 
Published: September 2002

AbstractArtemisia asiatica Nakai has been used in traditional Asian medicine for the treatment of inflammatory and other disorders. Previous studies have revealed that the formulated ethanol extract (DA‐9601) of A. asiatica has pronounced antioxidative and antiinflammatory activities and exhibits cytoprotective effects against experimentally induced gastrointestinal, hepatic and pancreatic damage. In the present study, we assessed the inhibitory effect of DA‐9601 on tumor promotion, which is closely linked to inflammatory tissue damage. As an initial approach to evaluating the possible antitumor‐promoting potential of DA‐9601, its effects on TPA‐induced ear edema were examined in female ICR mice. Pretreatment of the inner surface of the mouse ear with DA‐9601 30 min prior to topical application of TPA inhibited ear edema at 5 hr. TPA‐stimulated expression of epidermal COX‐2 and iNOS was also mitigated by topical application of the same extract. Moreover, DA‐9601 abrogated the TPA‐mediated activation of NF‐κB/Rel and AP‐1 in mouse epidermis. Suppression of epidermal NF‐κB by DA‐9601 appeared to be mediated in part through inhibition of IκBα degradation, thereby blocking the nuclear translocation of p65, the functional subunit of NF‐κB. DA‐9601 also significantly suppressed TPA‐induced ODC activity and papilloma formation in mouse skin. Taken together, these findings suggest that DA‐9601 derived from A. asiatica possesses potential chemopreventive activities. © 2002 Wiley‐Liss, Inc.
Expression of maspin predicts poor prognosis in breast‐cancer patients
Authors: Umekita Yoshihisa , Ohi Yasuyo , Sagara Yoshiatsu , Yoshida Hiroki 
Published: September 2002

AbstractThe tumor suppressor genemaspinhas been reported to inhibit the invasiveness and motility of breast cancer cells. It has been reported that maspin is expressed in normal human mammary epithelial cells but is downregulated during cancer progression, and that p53 could induce maspin expression by transcriptional activation. However, to date, the clinical significance of maspin expression and its correlation with p53 protein expression in human breast cancer patients have not been elucidated. One hundred and sixty‐eight female patients diagnosed with invasive ductal carcinoma, who had undergone a mastectomy (154 patients) or breast‐conserving surgery (14 patients), were followed up for 15–119 months (median: 87 months) postoperatively. Immunoreactivity for maspin and p53 antibodies with paraffin‐embedded carcinoma tissue was investigated using labeled streptavidin‐biotin methods. Tumors with more than 20% of positive cells were considered positive for the expression of maspin. The expression of maspin in carcinoma cells was found in 27.4% (46 of 168) and significantly correlated with larger tumor size (p= 0.008), higher histologic grade (p= 0.0001) and positive p53 status (p= 0.003). A significant inverse relationship was observed between the expression of maspin and estrogen receptor (p= 0.0004) or progesterone receptor status (p= 0.02). Univariate analysis by log‐rank test revealed a significant association between the expression of maspin and shorter relapse‐free survival (p< 0.0001) and overall survival (p< 0.0001). According to Cox's multivariate analysis, the expression of maspin had the most significant effect in relapse‐free survival (p< 0.0001) and overall survival (p< 0.0001) followed by lymph node status. In turn, the expression of maspin in 58 cases of ductal carcinomain situwere also investigated to explore whether the downregulation of maspin through cancer progression are true or not. However, there were no positive cases in our series. These results seem to be contrary to previous reports defining maspin as a tumor suppressor gene. Although more precise characterization of the maspin expression, especially gene analysis is essential, the present investigation suggests that the expression of maspin is not downregulated through malignant progression and that the immunohistochemic detection of maspin in carcinoma cells may be helpful for selecting the group of breast cancer patients with an aggressive phenotype. © 2002 Wiley‐Liss, Inc.
Spontaneously formed tumorigenic hybrids of Meth A sarcoma and macrophages grow faster and are better vascularized than the parental tumor
Authors: Busund Lill‐Tove R. , Killie Mette K. , Bartnes Kristian , Seljelid Rolf 
Published: September 2002

AbstractMacrophages and Meth A sarcoma cells spontaneously fuse and give rise to tumorigenic hybrid cell lines with a mixed phenotype. We report here that the hybrid tumors grow faster and have a strikingly better developed vasculature than the parent sarcoma. Thus, electron microscopy and immunohistochemical analysis revealed that in the most active areas of neovascularization, the tumors that emerged from inocula of monoclonal hybrid cell populations had a microvessel density nearly twice that of Meth A tumors after 1 week of growth. Moreover, the proportion of vessels associated with pericytes, detected by staining for smooth muscle α‐actin, was 3 times higher in the hybrid tumors, attesting to the more advanced differentiation of their vasculature. The collagenous stroma component was also more extensive in the hybrid tumors. Concentration of the angiogenic proteins vascular endothelial growth factor (VEGF) and transforming growth factor‐β (TGF‐β) were significantly higher in supernatants of hybrid cell cultures compared with Meth A cultures. These observations indicate that the growth advantage of the hybrid tumors over the parental sarcoma is due to a higher angiogenic capacity. Because the malignant features of many tumors correlate with angiogenesis and because macrophages are known to be major producers of angiogenic factors, our data open the possibility that the intense neovascularization of highly aggressive cancers in some cases reflects the acquisition of macrophage traits by heterotypic cell fusion. © 2002 Wiley‐Liss, Inc.
Overexpression of Bcl‐2 in squamous cell carcinoma of the larynx: A marker of radioresistance
Authors: Condon Luke T. , Ashman James N.E. , Ell Stephen R. , Stafford Nicholas D. , Greenman John , Cawkwell Lynn 
Published: September 2002

AbstractSquamous cell carcinoma of the larynx can be treated using radiotherapy or surgery, either alone or in combination. Radiotherapy is preferred for early‐stage tumours, as it spares the larynx and therefore preserves speech and swallowing. Unfortunately, approximately 15% of tumours treated this way will prove to be radioresistant, as manifest by tumour recurrence within the original radiotherapy field over the ensuing 12 months. By causing extensive DNA damage, radiotherapy aims to induce apoptosis and tumour regression. Our hypothesis was that defects in the mechanisms that recognise DNA damage, induce cell cycle arrest or control apoptosis, either alone or in combination, may be responsible for radioresistance. We therefore undertook an immunohistochemic analysis of pretreatment biopsies of radioresistant (n = 8) and radiosensitive (n = 13) laryngeal tumours. To minimise the impact of confounding factors, strict inclusion criteria were observed; all tumours were of the glottic subsite and all recurrences developed within 12 months of radiotherapy at the site of the original tumour. The expression of key proteins involved in DNA damage recognition (p53), cell cycle arrest (ATM, p16 and p21/WAF1) and apoptosis (Bcl‐2 and BAX) were studied. Ki‐67 was also assessed as a marker of cell proliferation to exclude low mitotic rate as a cause of radioresistance. A statistically significant correlation was observed between overexpression of Bcl‐2 and radioresistance (p = 0.003, Fisher's exact test). We hypothesise that overexpression of the anti‐apoptotic protein Bcl‐2 allows tumour cells with extensive radiation‐induced DNA damage to continue proliferating; the absence of an appropriate apoptotic response manifests clinically as radioresistance. © 2002 Wiley‐Liss, Inc.
Prevalence of human papillomavirus in cervical cancer: A multicenter study in China
Authors: Lo Keith W.K. , Wong Y.F. , Chan May K.M. , Li James C.B. , Poon J.S. , Wang Vivian W. , Zhu S.N. , Zhang T.M. , He Z.G. , Wu Q.L. , Li G.D. , Tam John S.L. , Kahn T. , Lam P. , Cheung T.H. , Chung Tony K.H. 
Published: September 2002

AbstractA large‐scale epidemiologic survey on the prevalence of different types of human papillomavirus (HPV) in cervical cancer in China is indicated because of the implications for the development of diagnostic probes and vaccines against cervical cancer. A total of 809 cervical cancer specimens were collected from 5 regions in China including Shanghai, Guangzhou, Sichuan, Beijing and Hong Kong. HPV DNA was detected in 83.7% of the specimens. HPV‐16 was present in 79.6%, HPV‐18 in 7.5%, HPV‐52 in 2.6% and HPV‐58 in 3.8% of all HPV‐positive specimens. The prevalences of HPV‐16 and HPV‐18 in Hong Kong were 61.7 and 14.8%, respectively, representing a lower HPV‐16 and a higher HPV‐18 proportion compared with the other regions. HPV‐16 remained the most common HPV infection in both squamous cell carcinoma (SCC) and adenocarcinoma (AC). The proportion of HPV‐18 infection was significantly higher in AC than in SCC. © 2002 Wiley‐Liss, Inc.