bluuebunny/crossref_metadata_2025_split huggingface dataset:
6‐(1‐Oxobutyl)‐5,8‐dimethoxy‐1,4‐naphthoquinone inhibits lewis lung cancer by antiangiogenesis and apoptosis
Authors: Lee Hyo Jeong , Lee Hyo‐Jung , Song Gyu‐Yong , Li Guangxun , Lee Jae‐Ho , Lü Junxuan , Kim Sung‐Hoon 
Published: February 2007

AbstractLung cancer is a leading cause of cancer mortality worldwide. Novel and nontoxic agents targeting angiogenesis and tumor cell proliferation and survival are desirable for lung cancer chemoprevention and treatment. Previously we have reported that 6‐(1‐oxobutyl)‐5,8‐dimethoxy‐1,4‐naphthoquinone (OXO) exhibits anti‐tumor activity against S‐180 sarcoma in vitro and in vivo. Here we studied the anti‐angiogenic and apoptogenic attributes of OXO in vitro and in vivo targeting lung cancer. In human umbilical vein endothelial cells (HUVECs), we show that OXO more potently inhibited VEGF‐stimulated than basic bFGF‐stimulated HUVEC proliferation and capillary differentiation. In Lewis lung carcinoma (LLC) cells, OXO not only induces S‐phase arrest and mitochondria/caspase‐9 pathway mediated apoptosis, but also effectively down‐regulated the hypoxia‐induced expression of HIF‐1α and VEGF at mRNA and protein levels in LLC and decreased VEGF secretion into conditioned culture media. OXO significantly reduced in vivo functional angiogenesis in the mouse Matrigel plug assay. Furthermore, OXO potently inhibited the growth of LLC cells inoculated on the flank of syngenic mice at dosages that did not affect their body weight. The in vivo anti‐cancer effect was associated with decreased HIF‐1α and VEGF expression, decreased microvessel density as well as a reduction of tumor cell proliferation and increased tumor cell apoptosis. Taken together, these results demonstrate that OXO exerts anti‐cancer activity through anti‐angiogenesis and tumor cell cycle arrest and apoptosis. These findings warrant additional studies of OXO as a novel agent for the chemoprevention and treatment of lung cancer. © 2007 Wiley‐Liss, Inc.
Expression of the IAP protein family is dysregulated in pancreatic cancer cells and is important for resistance to chemotherapy
Authors: Lopes Rita Bayer , Gangeswaran Rathi , McNeish Iain A. , Wang Yaohe , Lemoine Nick R. 
Published: February 2007

AbstractPancreatic cancer is one of the most aggressive human tumors with a 5‐year survival rate of only 3% and a striking resistance to chemotherapy and radiotherapy. The search for new therapeutic approaches includes strategies exploiting the deregulation of apoptotic pathways commonly found in cancer cells. The IAP proteins are inhibitors of apoptosis that have altered activity in numerous cancer types and are implicated in resistance to chemotherapy, and therefore are potentially interesting as therapeutic targets. We investigated alterations in the expression of IAPs and their inhibitors in pancreatic adenocarcinoma by using real‐time PCR, in situ hybridization and immunohistochemistry. We found differential expression of various IAPs in this malignancy, and particularly we observed overexpression of cIAP‐2, survivin, livin and XIAP. We also looked for correlations between the expression of IAPs and resistance to paclitaxel, doxorubicin, CDDP and 5‐fluorouracil, and found that resistance to these drugs correlates most significantly with expression of cIAP‐2. Using RNAi to downregulate these proteins we further confirmed that the levels of cIAP‐2 and XIAP influence the response to the anti‐cancer drugs, although only marginally for 5‐FU. We conclude that anti‐tumor strategies based on the inhibition of particular IAPs can be useful in targeting pancreatic adenocarcinoma. © 2007 Wiley‐Liss, Inc.
Genetic polymorphisms in the one‐carbon metabolism pathway and breast cancer risk: A population‐based case–control study and meta‐analyses
Authors: Lissowska Jolanta , Gaudet Mia M. , Brinton Louise A. , Chanock Stephen J. , Peplonska Beata , Welch Robert , Zatonski Witold , Szeszenia‐Dabrowska Neonila , Park Sue , Sherman Mark , Garcia‐Closas Montserrat 
Published: February 2007

AbstractEpidemiological evidence suggests that intake of folate and other B‐vitamins and genetic variants in the one‐carbon metabolism pathway could influence the risk of breast cancer. Previous studies have focused on 2 polymorphisms in the methylenetetrahydrofolate gene (MTHFR A222V and E429A); however, findings are inconclusive. In a large population‐based case–control study in Poland (2,386 cases, 2,502 controls), we investigated the association between breast cancer risk and 13 polymorphisms in 6 one‐carbon metabolism genes (MTHFR, MTR, MTRR, CBS, SHMT1 and SLC19A1). Data suggested an association between a nonsynonymous change in the gene coding for methionine synthase (MTR D919G) and reduced breast cancer risk: OR (95% CI) = 0.84 (0.73–0.96) and 0.85 (0.62–1.15) for heterozygous and homozygote variant genotypes, respectively, compared with common homozygotes; p‐trend = 0.01, false discovery rate = 0.14. We found no significant associations between other variants and breast cancer risk, including MTHFR A222V or E429A. Meta‐analyses including published studies of MTHFR A222V (8,330 cases and 10,825 controls) and E429A (6,521 cases and 8,515 controls) supported the lack of an overall association; however, studies suggested an increase in risk among premenopausal women. In conclusion, this report does not support a substantial overall association between the evaluated polymorphisms in the one‐carbon metabolism pathway and breast cancer risk. © 2007 Wiley‐Liss, Inc.
Immunohistochemical localization of matrix metallloproteinase 2 and its specific inhibitor timp‐2 in neoplastic tissues with monclonal antibodies
Authors: Höyhtyã Matti , Fripman Rafiae L , Komarek Daniel , Porter‐Jordan Kathleen , Stetler‐Stevenson William G. , Liotta Lance A. , Liang Chi‐Minjg 
Published: February 2007

AbstractMatrix metall oproteinase‐2 (MMP‐2), synthesized as a 631 amino‐acid proenzyme, is activated by cleavage of the first 80 amino acids and naturally inhibited by tissue inhibitor of metalloproteinase‐2 (TIMP‐2). We report here the production of MAbs against MMP‐2 and TIMP‐2 and their use in localizing the respective antigens on tumor tissues. The anti‐MMP‐2 MAb recognized the latent and activated MMP‐2 mutant protein (mutein) with C‐terminal deletion at amino acid 425, indicating that both N‐and C‐terminal amino acids of MMP‐2 are not important for its binding. The binding study of anti‐TIMP‐2 MAb, using several C‐terminally truncated TIMP‐2 muteins, showed that the amino acids 111–126 of TIMP‐2 are essential for the binding of this antibody. Besides their respective antigens, both MAbs also recognized the MMP‐2/TIMP‐2 complex. On frozen sections of breast tumor, anti‐MMP‐2 MAb stained mainly tumor‐cell cytoplasm with varying intensity, while anti‐TIMP‐2 MAb gave a stromal staining of varying intensity and a weak or absent staining of tumor‐cell cytoplasm, suggesting different localization of the proteins in these tumors. In addition, in 1/3 of the breast cases both antibodies also localized on tumor‐cell membranes. Similar cytoplasmic and stromal but not membrane staining patterns were observed in colon, gastric, endometrial, squamous‐cell, prostatic and ovarian carcinoma as well. Since MMP‐2 degrades type‐IV collagen, the major component of basement membranes, the differences between MMP‐2 and TIMP‐2 levels and localization in individual tumors may relate to the invasiveness of the tumor and thus provide predictive information. However, this aspect could not be discussed in this study because no biological and clinical parameters such as lymph‐node involvement or Dukes' stage of the tumors were available.
Increased tumorigenicity of human keratinocytes harboring human papillomavirus type 16 is associated with resistance to endogenous tumor necrosis factor‐α‐mediated growth limitation
Authors: Malejczyk Jacek , Malejczyk Magdalena , Majewski Slawomir , Breitburd Françoise , Luger Thomas A. , Jablonska Stefania , Orth Gerard 
Published: February 2007

AbstractThe aim of this study was to evaluate the relationship between tumorigenicity of cell sublines derived from weakly tumorigenic SKv‐e and SKv‐I keratinocytes harboring human papillomavirus type 16 (HPV 16) and their susceptibility to autocrine growth limitation mediated by tumor necrosis factor‐α (TNF‐α). These sublines displayed different in vitro proliferative potential which correlated with tumorigenicity in nu/nu mice. Recombinant TNF‐α inhibited in vitro growth of weakly tumorigenic parental SKv cell lines while it did not affect proliferation of their respective highly tumorigenic sublines. Resistance to TNF‐α correlated with both increased in vitro proliferation and tumorigenicity. Anti‐TNF‐α antibodies (Ab) significantly increased in vitro proliferation of weakly tumorigenic parental SKv cells up to the levels of their highly tumorigenic sublines. Growth of highly tumorigenic SKv cells was not affected. On the other hand, proliferation of SKv cells was affected neither by transforming growth factor‐β (TGF‐β) nor by anti‐TGF‐β Ab. All SKv cell sublines tested spontaneously released TNF‐α, as evaluated by a specific radioimmunoassay; however, the levels of the endogenous cytokine were not related to their proliferative potential and tumorigenicity. An increased resistance to the anti‐proliferative effect of TNF‐α may be associated with decreased expression of TNF‐α receptors (TNF‐αR) inasmuch as evaluation of 125 I‐TNF‐α binding and Northern‐blot analysis of TNF‐αR‐specific mRNA showed that highly tumorigenic SKv cell sublines expressed significantly lower numbers of TNF‐αR than their respective parental cells. These results show that an increased tumorigenicity of HPV 16‐harboring SKv keratinocytes may be, at least partially, due to escape from autocrine TNF‐α‐mediated growth limitation.
Aberrant crypt foci and colon tumors in F344 rats have similar increases in proliferative activity
Authors: Pretlow Theresa P. , Cheyer Christopher , Ann O'Riordan Mary 
Published: February 2007

AbstractIncreased proliferative activity has been described frequently in the colons of animals treated with colon carcinogens and of patients at increased risk of colon cancer; it has been proposed as an intermediate biomarker of colon cancer. Aberrant crypt foci, microscopic lesions identified in whole‐mount preparations of colons, are thought to be putative pre‐neoplastic lesions. The present studies were carried out to evaluate the proliferative activity of aberrant crypt foci at several different time periods, and of tumors after a single dose of azoxymethane (AOM) in F344 rats. Rats were injected with 5‐bromo‐2′‐deoxyuridine (BUdR) 1 hr before killing. Aberrant crypt foci and tumors were identified and marked in the whole‐mount specimens, embedded in glycol methacrylate, and evaluated for histochemically demonstrable hexosaminidase activity. Hexosaminidase is known to be altered in over 95% of aberrant crypt foci. Serial sections were evaluated for BUdR incorporation immunohistochemically with a monoclonal antibody. The mean proliferative activity of aberrant crypt foci in the distal colons was found to be 'increased 3‐to 4‐fold over that of the adjacent normal crypts at every time period analyzed (4 to 36 weeks) and was comparable to that seen in benign and malignant colon tumors in the same animals. The observed increase in proliferative activity further supports the hypothesis that aberrant crypt foci are putative pre‐neoplastic lesions. Similar aberrant crypt foci, identified in human colons at increased risk of colon cancer, may provide important biomarkers for this common human cancer.
Hepatitis B and C virus infection as risk factors for hepatocellular carcinoma in Chinese: A case‐control study
Authors: Tsai Jung‐Fa , Jeng Jen‐Eing , Ho Mei‐Shang , Chang Wen‐Yu , Lin Zu‐Yau , Tsai Juei‐Hsiung 
Published: February 2007

AbstractTo assess whether hepatitis B and C virus infection were risk factors for hepatocellular carcinoma (HCC), antibody to hepatitis C virus (anti‐HCV), hepatitis B surface antigen and e antigen (HBsAg and HBeAg) were tested in 150 HCC patients. Another 150 case‐control pairs matched individually by sex and age were also enrolled. Univariate analysis demonstrated that both the anti‐HCV and the carrier status of HBsAg and HBeAg were significantly associated with HCC. Multi‐variate analysis revealed that both anti‐HCV and HBsAg were risk factors for HCC. The population‐attributable risk was estimated as 14.2% for anti‐HCV alone, 59.4% for HBsAg alone and 8.0% for both anti‐HCV and HBsAg in Taiwan. In conclusion, both hepatitis B and C virus infection are independent risk factors for HCC in Chinese in southern Taiwan.
Expression of glucose transporters in head‐and‐neck tumors
Authors: Mellanen P. , Minn H. , Grénman R. , Härkönen P. 
Published: February 2007

AbstractThe expression of glucose transporter genes (GLUTI‐4) was studied in 20 head‐and‐neck tumors of 18 patients. All tumors—16 of which were squamous‐cell carcinomas (SCC)—expressed GLUTI and/or GLUT3 mRNA, while detectable levels of GLUT2 or GLUT4 mRNA were not observed. The signals for GLUTI and GLUT3 mRNAs varied markedly throughout the SCC tumor population but no clear relationship with the grade of differentiation was found. The high GLUT expression observed in some tumors was, not associated with amplification or rearrangement of the corresponding genes. Immunohistochemistry of 5 SCCs showed that GLUTI protein was located in tumor‐cell membranes in relation to the level of mRNA expression. We conclude that both GLUTI and GLUT3 are involved in basal glucose uptake of extracranial head‐and‐neck tumors. The increased expression of these high‐affinity GLUT isoforms may be related to the growth maintenance of cancer tissue in cases of limited supply of substrate e.g., in poorly vascularized tumor areas.
Frequency and characterization of p53 mutations in primary and metastatic human prostate cancer
Authors: Dinjens Winand N. M. , Van Der Weiden Marcel M. , Schroeder Fritz H. , Bosman Fred T. , Trapman Jan 
Published: February 2007

AbstractWe have studied the frequency of mutations in the p53 gene in human prostate cancer. The investigated material consisted of 20 primary‐tumor tissue specimens, obtained by transurethral resection and tissue specimens of 15 lymph‐node metastases, obtained at total prostatectomy. The applied methods encompassed immunohistochemistry on frozen sections, using the monoclonal antibody PAb 1801, and single‐strand conformation polymorphism (SSCP) analysis, after amplification of single exon sequences by PCR, on exons 5 to 8 of the p53 gene. The mutations, leading to aberrantly migrating bands in the PCRSSCP analysis, wereidentified by direct sequencing of the PCR product. Immunohistochemical and PCR‐SSCP analysis were completely confirmative. In the primary tumors, mutations were found in 10% of the specimens (codons 232 and 273), and in lymph‐node metastases in 15% of the specimens (codons 248 and 273). In one case (codon 273), the same mutation was found both in the primary tumor and in the lymph‐node metastasis. Our results show that p53 mutations are infrequent in both primary and metastatic prostate tumors. In addition, they indicate that there is no strict correlation between p53 mutation and tumor metastasis.
A repertoire of monoclonal antibodies reveals extensive epitope heterogeneity in CEA purified from neoplasms originating from different organs
Authors: Hernando Juan José , Von Kleist Sabine , Grunert Fritz 
Published: February 2007

AbstractThe heterogeneity of carcinoembryonic antigen (CEA) from 5 individual hepatic metastases of tumours originating in different organs (I colon, I stomach and 3 breast adenocarcinomas) was analyzed with a repertoire of 56 αCEA murine MAbs. In each tumour preparation, the MAbs disclosed 2 distinct molecular species displaying remarkable variability in their apparent molecular weights (e.g. 130–170 kDa for the fast‐migrating CEA variant and 180–260 kDa for the slowly‐migrating one). After chemical deglycosylation this heterogeneity was abolished and 2 main proteins of 84 and 64 kDa were generated; the difference in their molecular weights could not be accounted for by differential glycosylation. Although 3 of the analyzed preparations were derived from individual adenocarcinomas of the breast, the glycosylated molecules differed considerably from one another, in their relative molecular mass. The MAbs used showed essentially 3 different recognition patterns according to their reactivity either with both CEA molecular weight variants, or just with the higher or the lower one. In a quantitative comparison of the immunoprecipitation yields of the MAbs with CEA, considerable immunological variability (ranging up to 26‐fold), as well as preferential expression of CEA epitopes, could be demonstrated among the 5 different preparations. Here again no uniform epitope presentation could be observed among the 3 breast tumours thus far tested. Comparison of the precipitation yields with the glycosylated and deglycosylated CEA species revealed that, whereas the CEA antigenic heterogeneity remained in some cases unchanged, most of the MAbs exhibited, in carbohydrate‐free CEA, the appearance of a new heterogeneity.
The influence of local tissue environment on epithelial basement membrane continuity in colorectal carcinomas
Authors: Hewitt Robert E. , Keeble William , Powe Desmond G. , Williamson Richard J. , Turner David R. 
Published: February 2007

AbstractFor colorectal carcinomas, there is evidence that marked discontinuity of the epithelial basement membrane (EBM) is associated with higher malignant potential. Since the meta‐static process appears to be selective, more discontinuous EBMs might be expected in secondary rather than in primary tumours. To test this prediction, we examined a series of 60 cases of colorectal carcinoma for which samples of lymph‐node or liver metastases were available. Sections were immunocyto‐chemically stained for laminin, and the continuity of tumour EBM was then assessed by observational rating as well as by detailed morphometric analysis for a sample of cases. Contrary to the above prediction, we find that EBMs tend to be more continuous in secondary tumours than in corresponding primary tumours. These results could be explained by the possibility that local tissue environmental factors have a major influence on EBM continuity. Supporting evidence comes from our previous observation that EBM is very discontinuous at the advancing edge of primary colorectal carcinomas, where the tumour is adjacent to collagen‐I‐deficient stroma. Further evidence from the present study is that the EBM is extremely discontinuous at the interface between metastases and specialised parenchymal tissue, but more continuous at the interface between metastases and stromal connective tissue. Since basement membranes affect the differentiation and behaviour of adjacent cells, these findings suggest that host tissues may influence invasive activity through their effects on EBM continuity.
TNF accelerates the S‐phase of the cell cycle in tumor cells
Authors: Volland Sabine , Amtmann Eberhard , Sauer Gerhard 
Published: February 2007

AbstractThe reduction of glucose supply induced the killing of tumor cells by tumor necrosis factor (TNF) in vivo and in vitro. In contrast, normal cell lines were resistant to TNF regardless of the presence or absence of glucose. Epidermal growth factor (EGF) did not exert a cytotoxic effect on tumor cells in the absence of glucose. Therefore, the killing mechanism of TNF under conditions of reduced glucose supply was investigated. Flow cytometry experiments and studies of kinetics revealed that the S‐phase of the cell cycle was prolonged in the absence of glucose. After TNF treatment, the S‐phase was found to be shortened and the rate of H‐thymidine incorporation into DNA was increased, whereas EGF failed to exert such an effect. DNA synthesis and entry into mitosis are known to be regulated by cyclin A. In serum‐starved tumor cells (HeLa) we have observed increased cyclin A synthesis within 10 hr, in parallel with enhancement of DNA synthesis and shortening of the S‐phase after TNF treatment. We conclude that, under conditions of low glucose supply, TNF can assume the role of a growth factor in transformed cells.
Incidence of female breast cancer in relation to prevalence of risk factors in Denmark
Authors: Ewertz Marianne , Duffy Stephen W. 
Published: February 2007

AbstractThe extent to which changes in prevalence of risk determinants for female breast cancer could explain the temporal variation in incidence was examined using incidence figures from Denmark for the years 1943–1989. Significant increases in incidence were observed for more recent time periods and birth cohorts. Using deviance statistics from Poisson regression measures of variability explained, only a small proportion of the increase in incidence could be accounted for by fertility rates, average age at menarche and exposure to exogenous hormones. Dietary factors, on the other hand, accounted for the greater proportion of the variation observed by time period or birth cohort. In particular, there was a strong positive association of incidence with alcohol consumption and a negative association with carbohydrate intake.
Risk of genital human papillomavirus infection in women with human immunodeficiency virus‐induced immunosuppression
Authors: Ho Gloria Y. F. , Burk Robert D. , Fleming Irene , Klein Robert S. 
Published: February 2007

AbstractThis study examined the risk factors for genital human papillomavirus (HPV) infection, including HIV‐related immunosuppression as well as demographic and behavioral factors. Subjects were 207 women with known HIV serologic status, the majority of whom were intravenous drug users recruited from a methadone treatment program in the Bronx, New York. A structured questionnaire interview, cervico‐vaginal lavage, and CD4 cell measurements we're obtained. HPV genomes in the cervico‐vaginal cells were detected by Southern‐blot hybridization. HPV prevalence was 23% among HIV seronegatives, 45% among HIV seropositives with CD4 percent >20 and 61% among HIV seropositives with CD4 percent ≤20. Multivariate analysis identified the following independent risk factors that were significantly associated with HPV positivity: HIV‐related immunosuppression, <35 years of age, and never used oral contraceptive pills. HIV‐related immunosuppression was also associated with a stronger Southern‐blot signal strength. HIV infection, however, did not increase the susceptibility to HPV infection with the oncogenic types (16, 18, 31, 33 and 35). Women with HIV infection or immunosuppression had a higher prevalence of HPV infection with the oncogenic types, but they also had an increased prevalence of infection with other HPV types as compared to the HIV‐seronegative women. The results suggest that HIV‐related immunosuppression increases the risk of genital HPV infection and has an effect on HPV replication.