bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical activity and renal cell cancer risk in a cohort of male smokers
Authors: Mahabir Somdat , Leitzmann Michael F. , Pietinen Pirjo , Albanes Demetrius , Virtamo Jarmo , Taylor Philip R. 
Published: June 2004

AbstractFew studies have examined exercise in relation to risk of renal cell cancer. We examined the association between leisure‐time and occupational physical activity and renal cell cancer in a cohort of 29,133 male smokers 50–69 years of age in the Alpha‐Tocopherol, Beta‐Carotene (ATBC) Cancer Prevention Study. Physical activity was assessed at baseline using a self‐administered questionnaire that inquired about usual level of physical activity during leisure‐time and at work during the past year. Cox proportional hazards modeling was used to adjust simultaneously for known or suspected risk factors for renal cell cancer. During 12 years (354,407 person‐years) of follow‐up, 210 incident cases of renal cell cancer were identified. In age‐adjusted analysis, the RRs of renal cell cancer in increasing categories of leisure‐time physical activity (light, moderate and heavy) were 1.0, 0.89 (95% CI = 0.67–1.17) and 0.38 (95% CI = 0.15–0.94), respectively (p‐value for trend = 0.06). After adjustment for body mass index, energy intake, smoking, hypertension, education and fruit and vegetable intake, the multivariate RRs of renal cell cancer in increasing categories of leisure‐time physical activity (light, moderate and heavy), were 1.0, 0.89 (95% CI = 0.66–1.19), and 0.46 (95% CI = 0.18–1.13) (p‐value for trend = 0.12). Occupational physical activity was unrelated to renal cell cancer risk. These data suggest that recreational physical activity may play a role in the prevention of renal cell cancer in men. © 2003 Wiley‐Liss, Inc.
3‐OH flavone inhibition of epidermal growth factor‐induced proliferaton through blocking prostaglandin E2 production
Authors: Shen Shing‐chuan , Ko Ching‐huai , Hsu Kuo‐chou , Chen Yen‐chou 
Published: June 2004

AbstractEpidermal growth factor (EGF) has been shown to induce proliferation in cells, however, the role of prostaglandin E2 (PGE2) plays in EGF‐induced proliferation in still unclear. EGF and PGE2 showed proliferation responses in epidermoid carcinoma cell A431 by MTT and [3H] thymidine incorporation assay. Activation of the EGF receptor and extracellular signal‐regulated protein kinases (ERK1/2), but not p38 and JNK, appeared 10 min after EGF treatment, whereas total amounts of ERK1/2, p38 and JNK remained unchanged in A431 cells, accompanied by induction of COX‐2 and PGE2 production. PD98059, a specific ERK1/2 inhibitor, inhibited EGF‐induced proliferation with concomitant decreases in ERK1/2 phosphorylation and COX‐2/PGE2 induction. Non‐steroid anti‐inflammatory drugs (NSAIDs) such as aspirin and diclofenac, a COX activity inhibitor, inhibited EGF‐induced proliferation by blocking PGE2 production. The addition of PGE2 reversed the inhibitory effects of PD98059, aspirin, and diclofenac on EGF‐induced proliferation. This suggests that COX‐2/PGE2 activation involves in EGF‐induced proliferation and locates at the downstream of ERK1/2 activation. Furthermore, the natural product, 3‐OH flavone, showed the most‐potent inhibitory activity on EGF‐induced proliferation among 9 structurally‐related compounds, and suppression of EGF receptor phosphorylation, ERK1/2 phosphorylation, and COX‐2/PGE2 production by 3‐OH flavone was identified. PGE2 addition attenuates the inhibitory activity of 3‐OH flavone on EGF‐induced proliferation by MTT assay and colony formation by soft agar assay. Additionally, 3‐OH flavone also showed more‐specific inhibition on EGF‐ than on fetal bovine serum (FBS)‐induced proliferation in A431 cells. Results of our present study provide evidence to demonstrate that PGE2 is an important downstream molecule in EGF‐induced proliferation, and 3‐OH flavone, which inhibits PGE2 production by blocking MAPK cascade, might reserve potential for development as an anti‐cancer drug. © 2003 Wiley‐Liss, Inc.
The role of angiogenesis, vascular maturation, regression and stroma infiltration in dormancy and growth of implanted MLS ovarian carcinoma spheroids
Authors: Gilead Assaf , Meir Gila , Neeman Michal 
Published: June 2004

AbstractMLS ovarian epithelial carcinoma multicellular spheroids xenografted subcutaneously in CD‐1 nude mice displayed growth delay, or dormancy, of up to 52 days. In the study reported here, implanted MLS spheroids were used for testing the role of angiogenesis and vascular maturation in triggering the initiation of tumor progression. The kinetics and impact of neovascular maturation and functionality, in dormancy, and growth of MLS spheroid xenografts were studied noninvasively by BOLD contrast MRI. MR data were supported by histologic staining for biotinylated albumin as a blood pool marker and alpha‐smooth muscle actin (alpha‐SMA) as marker for perivascular mural cells. Although the tumor periphery showed higher levels of total and mature vasculature than normal skin, the fraction of mature out of the total vessels as detected by MRI vascular maturation index (VMIMRI) was significantly lower in the tumor both before and after tumor exit from dormancy. The neovasculature induced by the implanted spheroid was unstable and showed cycles of vessel growth and regression. Surprisingly, this instability was not restricted to the immature vessels, but rather included also regression of mature vessels. During dormancy, neovasculature was predominantly peripheral with no infiltration into the implanted spheroid. Infiltration of alpha‐SMA positive stroma cells into the spheroid was associated with functional vascularization and tumor growth. Thus, stroma infiltration and vascular maturation are an important checkpoint linking the angiogenic switch with initiation of tumor progression. © 2003 Wiley‐Liss, Inc.
Long term consequences of the 1944–1945 Dutch famine on the insulin‐like growth factor axis
Authors: Elias Sjoerd G. , Keinan‐Boker Lital , Peeters Petra H.M. , Van Gils Carla H. , Kaaks Rudolf , Grobbee Diederick E. , Van Noord Paulus A.H. 
Published: June 2004

AbstractThe insulin‐like growth factor axis is highly responsive to nutritional status and may be involved as one of the underlying mechanisms through which caloric restriction could affect cancer risk. High levels of circulating insulin‐like growth factor (IGF)‐I, or IGF‐I relative to IGF binding protein (IGFBP)‐3 have been related to various human cancer types. In a group of 87 postmenopausal women, we found that childhood exposure to the 1944–1945 Dutch famine was associated with increased plasma levels of IGF‐I and IGFBP‐3, whereas IGFBP‐1 and ‐2 levels were weakly decreased. These results are opposite to immediate responses seen under starvation and we hypothesize that this could indicate a permanent overshoot upon improvement of nutritional status after the famine. © 2003 Wiley‐Liss, Inc.
Rescue of death receptor and mitochondrial apoptosis signaling in resistant human NSCLC in vivo
Authors: Okouoyo Stella , Herzer Kerstin , Ucur Esat , Mattern Jürgen , Krammer Peter H. , Debatin Klaus‐Michael , Herr Ingrid 
Published: June 2004

AbstractNon small cell lung carcinoma (NSCLC) is a highly lethal malignancy that often becomes resistant to chemotherapy. To determine whether alterations in apoptotic signaling might contribute to such resistance, we established in vitro and in vivo models for sensitive and resistant human NSCLC. We found that resistance is due to multiple defects found in expression of CD95‐L, CD95 and members of the Bcl‐2 and IAP family, as well as caspase‐8, ‐9 and ‐3 as examined by immunohistochemistry, Western blot analysis, gene array analysis and functional assays. Failure to activate death receptor, as well as mitochondrial apoptosis signaling, points to a central role of caspases. To restore apoptosis signaling we transfected NSCLC xenografts on nude mice with caspase‐8 and ‐9. This treatment strongly induced apoptosis per se and sensitized the tumors to cisplatin‐induced cell death. Thus, these findings indicate that re‐expression of caspases might be an effective strategy to restore sensitivity for chemotherapy in NSCLC in vivo. © 2003 Wiley‐Liss, Inc.
Parathyroid hormone‐related protein (PTHrP) is responsible for production of bone metastasis, but not visceral metastasis, by human small cell lung cancer SBC‐5 cells in natural killer cell‐depleted SCID mice
Authors: Miki Toyokazu , Yano Seiji , Hanibuchi Masaki , Kanematsu Takanori , Muguruma Hiroaki , Sone Saburo 
Published: June 2004

AbstractWe previously established an osteolytic bone metastasis model with multiorgan dissemination in natural killer (NK) cell‐depleted severe combined immunodeficient (SCID) mice using human small cell lung cancer cells (SBC‐5), which highly express the parathyroid hormone‐related protein (PTHrP). In our present study, we evaluated the role of PTHrP on bone metastasis by SBC‐5 cells using anti‐PTHrP neutralizing antibody (Ab). Anti‐PTHrP Ab did not affect the proliferation or cytokine production of SBC‐5 cells in vitro. Repeated intravenous injection with anti‐PTHrP Ab inhibited the formation of bone metastasis in a dose‐dependent manner, while the same treatment had no significant effect on the metastasis to visceral organs (lung, liver, kidney and lymph node). In addition, treatment with anti‐PTHrP Ab improved the elevated serum calcium level, associated with inhibition of osteolytic bone metastasis, suggesting that anti‐PTHrP Ab inhibited bone metastasis via suppression of bone resorption probably by neutralizing PTHrP. These findings suggest that PTHrP is essential for bone metastasis, but not visceral metastasis, by small cell lung cancer SBC‐5 cells. © 2003 Wiley‐Liss, Inc.
Immunoscreening of a cDNA library from a lung cancer cell line using autologous patient serum: Identification of XAGE‐1b as a dominant antigen and its immunogenicity in lung adenocarcinoma
Authors: Ali Eldib Ali Mohamed , Ono Toshiro , Shimono Michihide , Kaneko Miho , Nakagawa Kazuhiko , Tanaka Ryo , Noguchi Yuji , Nakayama Eiichi 
Published: June 2004

AbstractBy serologic identification of antigens by recombinant expression cloning (SEREX) analysis using an autologous lung adenocarcinoma cell line, OU‐LU‐6, as a cDNA library source, we demonstrated that XAGE‐1 was the dominant antigen recognized by serum from a patient. By immunoscreening, we obtained 38 positive cDNA clones consisting of 16 genes designated as OY‐LC‐1 to ‐OY‐LC‐16. OY‐LC‐1, represented by 18 clones, was identical to XAGE‐1. OY‐LC‐2 to ‐16, represented by either a single or 2 clones, were identical to known genes shown to be ubiquitously expressed in various normal tissues. RT‐PCR analysis showed that of 4 XAGE‐1 transcripts—XAGE‐1a, b, c and d—XAGE‐1b was expressed in OU‐LU‐6 dominantly. Furthermore, XAGE‐1b mRNA was expressed in 4 of 10 lung cancer tissues, whereas no expression was observed in normal tissues. Of 4 XAGE‐1b mRNA positive cancer tissues, 3 were adenocarcinoma and one was poorly differentiated squamous cell carcinoma. Of 32 sera from lung cancer patients, 8 sera were reactive with the XAGE‐1b product. Those 8 sera were from patients with adenocarcinoma. These findings indicated strong immunogenicity of XAGE‐1b in lung adenocarcinoma and suggested its potential use as a target for vaccine‐based immunotherapies. © 2003 Wiley‐Liss, Inc.
Assessment of highly angiogenic and disseminated in the peripheral blood disease in breast cancer patients predicts for resistance to adjuvant chemotherapy and early relapse
Authors: Giatromanolaki Alexandra , Koukourakis Michael I. , Kakolyris Stelios , Mavroudis Dimitris , Kouroussis Charalambos , Mavroudi Chrysa , Perraki Maria , Sivridis Efthimios , Georgoulias Vassilis 
Published: June 2004

AbstractThe assessment of tumor molecular features in combination with the detection of occult malignant cells may provide important clinical information, beyond the standard staging of breast cancer. Using a nested RT‐PCR technique, we assessed prospectively the presence of cytokeratin‐19 (CK19) mRNA positive cells in the blood of 100 operated patients with breast cancer before the initiation of adjuvant chemotherapy and local radiotherapy. Tissue samples were prospectively collected and analyzed for estrogen (ER) and progesterone (PgR) receptor, c‐erbB‐2 overexpression, mutant‐p53 and bcl‐2 protein accumulation, proliferation index and microvessel density (MVD). CK‐19 mRNA‐positive cells were detected in the peripheral blood of 33% of patients. Simultaneous display of high intratumoral MVD and of CK‐19 mRNA‐positive cells, which characterized highly angiogenic and disseminated in the peripheral blood (HAD) disease was noted in 25% of patients. Detection of CK‐19 positive cells was significantly associated with increased MVD (p = 0.002). In univariate analysis (median follow‐up 30 months) CK19 mRNA detection and MVD were the most significant factors related to a short relapse‐free survival (RFS), (p < 0.0001). In multivariate analysis, CK19 positivity, high MVD and c‐erbB‐2 overexpression were the only significant and independent variables associated with relapse (p = 0.0005, 0.03 and 0.04, respectively). Patients with HAD had an expected relapse rate close to 70% vs. <5% in the remaining patients irrespectively of the used chemotherapy regimen. The simultaneous presence of high MVD and CK19‐positive cells in the blood of patients with early breast is linked with poor prognosis, which cannot be improved with standard chemotherapy regimens. © 2003 Wiley‐Liss, Inc.
Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma
Authors: Wakita Toshiaki , Hayashi Tatsuya , Nishioka Junji , Tamaru Hiroshi , Akita Nobuyuki , Asanuma Kunihiro , Kamada Haruhiko , Gabazza Esteban C. , Ido Masaru , Kawamura Juichi , Suzuki Koji 
Published: June 2004

AbstractProtein C inhibitor (PCI), a member of the serine protease inhibitor family, is produced in various human tissues, including the liver, kidney and testis. In addition to inhibiting the anticoagulant protein C pathway, PCI also inhibits urinary plasminogen activator (uPA), which is a well‐known mediator of tumor cell invasion. In the present study, to clarify the biologic significance of PCI in the kidney, we compared the expression of PCI between human renal cell carcinoma (RCC) tissue and nontumor kidney tissue. The PCI antigen level in RCC tissue was found to be significantly lower than in nontumor kidney tissue, and expression of PCI mRNA was detected in normal renal proximal tubular epithelial cells (RPTEC), but not in RCC or in an RCC cell line (Caki‐1 cells). No differences were detected between the nucleotide sequence of the major cis‐elements in the promoter region of the PCI gene from nontumor kidney and RCC tissues, RPTEC and Caki‐1 cells, an RPTEC‐derived RCC cell line. The in vitro invasiveness of Caki‐1 cells transfected with a PCI expression vector was significantly decreased compared to mock‐transfected Caki‐1 cells, and it was blocked in the presence of anti‐PCI antibody. Since PCI itself did not affect the proliferation rate of Caki‐1 cells or cell expression of uPA in vitro, the effect of uPA, PCI, heat‐inactivated PCI and plasminogen activator inhibitor (PAI)‐1 on the invasive potential of cultured RCC cells was evaluated. The in vitro invasiveness of Caki‐1 cells, which express uPA, was significantly enhanced by the addition of uPA, and it was inhibited by anti‐uPA antibody, PCI and PAI‐1, but not by heat‐inactivated PCI. In addition, uPA activity was significantly decreased and uPA‐PCI complex level was significantly increased in the culture medium of PCI expression vector‐transfected Caki‐1 cells as compared to mock‐transfected Caki‐1 cells. These findings strongly suggest that PCI regulates the invasive potential of RCC cells by inhibiting uPA secreted by these cells. The results of our study suggest that PCI might be a potential therapeutic agent for inhibiting renal tumor invasion. © 2003 Wiley‐Liss, Inc.
Chemoprotective effect of caffeic acid phenethyl ester on promotion in a medium‐term rat hepatocarcinogenesis assay
Authors: Carrasco‐Legleu Claudia E. , Márquez‐Rosado Lucrecia , Fattel‐Fazenda Samia , Arce‐Popoca Evelia , Pérez‐Carreón Julio I. , Villa‐Treviño Saúl 
Published: June 2004

AbstractCaffeic acid phenethyl ester (CAPE), a natural honeybee product exhibits a spectrum of biological activities including anti‐microbial, anti‐inflammatory, antioxidant and anti‐tumoral actions. CAPE is also chemopreventive against intestinal, colon and skin cancer. Our aim was to extend the study of its chemoprotective features to the promotion of hepatocarcinogenesis. Male Wistar rats were subjected to a protocol under a modified promotion regimen of the resistant hepatocyte model. The altered hepatic foci (AHF) were quantitatively analyzed by histochemistry and image processing. When given during promotion, CAPE (20 mg/kg) decreased the expression of number and area γ‐glutamyl transpeptidase (GGT) positive AHF by 91% and 97%, respectively. When GGT expression was analyzed by RT‐PCR, CAPE drastically decreased and prevented expression of almost all GGT transcripts at this stage of the carcinogenic process. Glutathione S‐transferase placental form (GST‐P), another protein marker for preneoplastic lesions was measured by Western blot and a decrease of 82% was observed. Additionally, we evaluated the effect of CAPE on the expression of nuclear factor NF‐κB and found an 85% decrease in nuclear localization of the p65 subunit of NF‐κB; however, their repressor, IκBα was not modified. Our results showed that CAPE given during promotion in hepatocarcinogenesis protects against induction of GGT‐positive AHF, GST‐P protein, GGT mRNA expression and translocation of p65. This phenomenon was independent of IκBα degradation. © 2003 Wiley‐Liss, Inc.
Childhood leukemia and road traffic: A population‐based case‐control study
Authors: Crosignani Paolo , Tittarelli Andrea , Borgini Alessandro , Codazzi Tiziana , Rovelli Adriano , Porro Emma , Contiero Paolo , Bianchi Nadia , Tagliabue Giovanna , Fissi Rosaria , Rossitto Francesco , Berrino Franco 
Published: June 2004

AbstractTo assess the effect of road traffic exhaust on the risk of childhood leukemia, we carried out a population‐based case‐control study in the Province of Varese, northern Italy, covered by a population‐based cancer registry. All 120 incident cases from 1978–97 were included in the study. Four controls per case, matched by age and gender, were sampled from population files. As index of exposure to traffic exhaust we estimated the annual mean concentration of benzene outside the home using a Gaussian diffusion model. This model uses traffic density (vehicles/day) on nearby main roads, distance between roads and residence, and information on vehicle emissions and weather conditions to estimate benzene concentration. Compared to children whose homes was not exposed to road traffic emissions (<0.1 μg/m3 of benzene as estimated by the model), the risk of childhood leukemia was significantly higher (relative risk [RR] = 3.91; 95% confidence interval [CI] = 1.36–11.27) for heavily exposed children (over 10 μg/m3 estimated annual average). For the intermediate exposure group (0.1–10 μg/m3) the relative risk was 1.51 (95% CI = 0.91–2.51). These data, considered with other available evidence, suggest that motor traffic emissions can be involved in the etiology of childhood leukemia. © 2003 Wiley‐Liss, Inc.
Menstrual and reproductive factors and endometrial cancer risk: Results from a population‐based case‐control study in urban Shanghai
Authors: Xu Wang‐Hong , Xiang Yong‐Bing , Ruan Zhi‐Xian , Zheng Wei , Cheng Jia‐Rong , Dai Qi , Gao Yu‐Tang , Shu Xiao‐Ou 
Published: June 2004

AbstractThe purpose of our study was to evaluate the association of menstrual and reproductive factors with the risk of endometrial cancer. In a population‐based case‐control study conducted in urban Shanghai, in‐person interviews were completed for 833 women aged 30–69 years and an equal number of controls frequency‐matched to cases by age. All cases were newly diagnosed with endometrial cancer between January 1, 1997 and December 31, 2001. The unconditional logistic regression model was employed to derive the adjusted odds ratios (ORs) of endometrial cancer and 95% confidence intervals (CIs) in relation to menstrual and reproductive factors. Earlier menarche age, particularly among premenopausal women, and later menopausal age were associated with an elevated risk of endometrial cancer. A clear dose‐response relation between endometrial cancer risk and years of menstruation was observed (p for trend < 0.01). Compared to women ever having a pregnancy and women ever having had a live birth, respectively, nulligravity and nulliparity were both associated with a more than one‐fold elevated risk of endometrial cancer. Both completed (OR = 3.02, 95% CI 1.10–8.32 for women never having a complete pregnancy) and incomplete pregnancy (OR = 0.69, 95%CI 0.55–0.87) conferred a protective effect against endometrial cancer, and the protective effect appeared to increase with total number of pregnancies (p for trend = 0.01). The effect of pregnancy on endometrial cancer remained unchanged with increasing time since the last pregnancy. Stillbirth and age at first pregnancy was unrelated to endometrial cancer risk. Our study suggests that prolonged menstruation was related to an increased risk of endometrial cancer while pregnancy, including induced abortion, reduced the risk of endometrial cancer. © 2003 Wiley‐Liss, Inc.
HER‐2 receptor expression, localization, and activation in colorectal cancer cell lines and human tumors
Authors: Half Elizabeth , Broaddus Russell , Danenberg Kathleen D. , Danenberg Peter V. , Ayers Gregory D. , Sinicrope Frank A. 
Published: June 2004

AbstractThe HER‐2/neu oncogene encodes a 185 kD protein that is phosphorylated upon ligand binding to other HER/erbB members and regulates cell growth and differentiation. Given that HER‐2 receptor blockade can inhibit the growth of colon cancer cell lines and tumor xenografts, we investigated the frequency, localization and phosphorylation status of HER‐2 in colon cancer cell lines and in human tumors. Protein expression was analyzed in relation to mRNA levels, HER‐2 amplification, and clinicopathological variables. Colon cancer cell lines constitutively expressed HER‐2 proteins and none showed HER‐2 amplification by fluorescence in situ hybridization. Cell fractionation and immunoblotting showed HER‐2 in both the membrane and cytosolic compartments. Primary colorectal carcinomas (n = 96) and their metastases (n = 25) were examined by immunohistochemistry. Strong membrane HER‐2 staining was detected in 5 (5%) of primaries and in 3 (12%) metastases (p = 0.36). Membrane but not cytoplasmic localization was strongly associated with HER‐2 gene amplification (p = 0.007). Cytoplasmic HER‐2 staining was found in 61 (63.5%) of primary tumors and localization was confirmed by immunoelectron microscopy that also showed plasma membrane HER‐2. Using real‐time quantitative RT‐PCR, HER‐2 mRNA was increased in tumors with membrane compared to cytoplasmic staining (r = 0.66, p = 0.001). Cytoplasmic HER‐2 was associated with tumor differentiation (p = 0.018), but not other clinicopathological variables. By immunoblotting, heterogeneity was seen in HER‐2 levels with downregulation in 4 of 7 tumors relative to normal epithelia that uniformly expressed HER‐2. Phosphorylated HER‐2 was detected in approximately 50% of tumors and in normal mucosa. In conclusion, HER‐2 is expressed constitutively in colon cancer cell lines and demonstrates relatively distinct localization patterns in human tumors. Strong membrane immunoreactivity is associated with high levels of HER‐2 mRNA and gene amplification whereas cytoplasmic HER‐2 is detected frequently and seems to be a marker of tumor differentiation. © 2003 Wiley‐Liss, Inc.