bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular endothelial growth factor‐D is a survival factor for human breast carcinoma cells
Authors: Akahane Manabu , Akahane Takemi , Matheny Shannon L. , Shah Amy , Okajima Eijiro , Thorgeirsson Unnur P. 
Published: September 2005

AbstractVascular endothelial growth factor‐D (VEGF‐D) stimulates growth of vascular and lymphatic endothelial cells by signaling through the tyrosine kinase receptors KDR (VEGFR‐2) and Flt‐4 (VEGFR‐3). In the present study, we examined the effects of VEGF‐D on apoptosis in human MCF‐7 and MDA‐MB‐231 breast carcinoma cells. Because VEGF‐D was not expressed constitutively in vitro, stable VEGF‐D transfectants were produced. The VEGF‐D‐expressing MCF‐7 and MDA‐MB‐231 lines displayed resistance to apoptosis induced by hypoxia, staurosporin and cycloheximide. Increased Bcl‐2 expression, decreased homogenous caspase activities and inhibition of poly(ADP‐ribose) polymerase cleavage were associated with inhibition of apoptosis in VEGF‐D‐expressing clones. Also, caspase‐3 activation was suppressed in the VEGF‐D expressing MDA‐MB‐231 clone. The antiapoptotic effect of VEGF‐D in vitro was recapitulated in vivo using VEGF‐D‐expressing MDA‐MB‐231 xenografts. The lack of VEGFR‐2 protein expression by Western blot and ineffectiveness of a neutralizing VEGFR‐2 antibody in eliminating the antiapoptotic effects of VEGF‐D suggest a different and yet unknown signaling mechanism. Our findings indicate that VEGF‐D has a novel function as a survival factor of breast carcinoma cells in addition to its established functions as an angiogenic and lymphangiogenic factor. © 2005 Wiley‐Liss, Inc.
Vascular endothelial growth factor–regulated ovarian cancer invasion and migration involves expression and activation of matrix metalloproteinases
Authors: Wang Feng‐qiang , So John , Reierstad Scott , Fishman David A. 
Published: September 2005

AbstractVascular endothelial growth factor (VEGF) expression is elevated in primary ovarian tumors and metastases. We examined the effect of VEGF on epithelial ovarian cancer (EOC) in vitro invasion and migration and underlying mechanisms. Using the Matrigel invasion assay and colloidal gold phagokinetic track assay, we found that VEGF induced EOC DOV13 invasion and migration in a matrix metalloproteinase (MMP)–dependent manner. Using Western blotting, we show that VEGF, at 20–80 ng/ml, induced secretion of pro‐MMP‐7 and pro‐MMP‐9 and activation of pro‐MMP‐2 in DOV13 conditioned medium in a concentration‐dependent manner. However, gelatinolytic activity and total MMP‐7 protein in DOV13 conditioned medium reached the maximum upon VEGF treatment at 20–40 ng/ml and decreased at higher‐concentration VEGF treatment (80 ng/ml), as shown by DQ‐gelatin degradation assay and ELISA. In addition to the effect on MMP secretion/activation, VEGF stimulated secretion of TIMP‐2; and blocking TIMP‐2 activity by an anti‐TIMP‐2 MAb significantly increased VEGF (80 ng/ml)–induced DOV13 invasion (p < 0.05), suggesting that VEGF may regulate MMP‐2 activity in DOV13 conditioned medium through TIMP‐2. Using real‐time PCR, we found that VEGF, at 20 ng/ml, significantly increased the expression of VEGFR‐1 and VEGFR‐2 by approximately 4‐fold and 31‐fold, respectively, compared to untreated control (p < 0.05). However, the inducing effect of VEGF on VEGFR‐2 expression and the internal expression of VEGF121 in DOV13 cells decreased with increasing of VEGF concentration, suggesting the existence of a negative feedback regulatory mechanism. In summary, our results indicate that VEGF may regulate EOC invasion and migration through VEGFR‐mediated secretion and activation of MMPs. © 2005 Wiley‐Liss, Inc.
CB694, a novel antimitotic with antitumor activities
Authors: Weiderhold Kimberly N. , Randall‐Hlubek Deborah A. , Polin Lisa A. , Hamel Ernest , Mooberry Susan L. 
Published: September 2005

AbstractDuring the course of a mechanism‐based screening program aimed at identifying new antimitotic agents, a novel microtubule depolymerizing piperazine derivative, 1‐(5‐chloro‐2‐methoxybenzoyl)‐4‐(3‐chlorophenyl) piperazine, was identified. The compound, designated CB694, caused inhibition of proliferation of a wide range of cancer cell lines, with an average IC50 of 85 nM. A multidrug‐resistant cell line was sensitive to inhibition by CB694, suggesting that this compound is a poor substrate for transport by P‐glycoprotein. CB694 caused formation of abnormal mitotic structures in HeLa cells. Specifically, CB694 caused a concentration‐dependent increase in bipolar spindles with lagging chromosomes and, with slightly higher concentrations, formation of multipolar mitotic spindles. These mitotic abnormalities occurred at concentrations that did not cause significant changes in the appearance or quantity of interphase microtubules. Coincident with the formation of abnormal mitotic spindles, CB694 caused G2/M arrest. CB694 inhibited the assembly of purified tubulin with an IC50 of 2.3 μM. Colchicine binding was strongly inhibited by CB694, suggesting that it binds to tubulin at the colchicine site. Bcl‐2 phosphorylation and activation of ERK and JNK and caspase 3‐dependent cleavage of PARP were observed in MDA‐MB‐435 cells treated with CB694. CB694 caused phosphorylation of Aurora A within 8 hr of treatment, and increases in Aurora A protein levels were coincident with mitotic accumulation. The efficacy of CB694 against a syngeneic murine transplantable solid tumor, Mammary 16/C, was also evaluated. CB694 was well tolerated and showed antitumor activity. © 2005 Wiley‐Liss, Inc.
The steroid receptor RNA activator protein is expressed in breast tumor tissues
Authors: Chooniedass‐Kothari Shilpa , Hamedani Mohammad Kariminia , Troup Sandy , Hubé Florent , Leygue Etienne 
Published: September 2005

AbstractThe steroid receptor RNA activator (SRA) was originally described as the first functional noncoding RNA able to specifically coactivate the activity of steroid receptors. We previously demonstrated the existence in breast cancer cell lines of new SRA isoforms that, as opposed to the first cloned SRA RNA, encode for a 236–amino acid protein, SRAP. To investigate the possible implications of the coding SRA RNA and SRAP expression on breast cancer progression, we examined by Western blot analysis 74 primary breast tumors of patients subsequently treated with tamoxifen. Patients whose primary tumors were positive for SRAP expression (n = 24) had a significantly (Kaplan‐Meier survival curve p = 0.047) lower likelihood of dying from recurrent disease than SRAP‐negative patients (n = 50). We generated 2 cell lines, SRAP‐V5‐High.A and SRAP‐V5‐High.B, by stably overexpressing SRAP in the estrogen receptor‐positive MCF‐7 breast cancer cell line. Transient transfection experiments, performed using a luciferase reporter gene under the control of an estrogen‐responsive element, revealed decreased sensitivity to estradiol but no additional sensitivity to tamoxifen in SRAP‐overexpressing cells. Overall, our data suggest that the presence of both coding SRA RNA and its corresponding SRAP modifies the activity of estrogen receptor in breast cancer cells and that SRAP could be a new clinical marker for breast cancer. Further studies are needed to define the respective mechanisms of action and the roles of SRA RNA and protein in breast tumorigenesis and tumor progression. © 2005 Wiley‐Liss, Inc.
Aberrant expression of BARD1 in breast and ovarian cancers with poor prognosis
Authors: Wu Jian‐Yu , Vlastos Anne‐Therese , Pelte Marie‐Françoise , Caligo Maria‐Adelaide , Bianco Andrea , Krause Karl‐Heinz , Laurent Geoffrey J. , Irminger‐Finger Irmgard 
Published: September 2005

AbstractMutations in tumor‐suppressor gene BARD1 have been found in inherited and spontaneous breast, ovarian and uterine cancers. BARD1 plays a critical role in DNA repair and ubiquitination as binding partner of BRCA1, with which it colocalizes to nuclear dots. Independently of BRCA1, BARD1 can induce p53‐dependent apoptosis in response to genotoxic stress. Therefore, BARD1 or p53 might be defective in cancer cells spared from apoptosis. We investigated BARD1 and p53 expression in ovarian, breast and non‐small‐cell lung cancers. BARD1 expression was highly upregulated and cytoplasmic in most cancer cells, while weak nuclear staining was observed in the surrounding normal tissue. Maximal BARD1 expression was associated with the most malignant ovarian cancer, clear cell carcinoma. In breast cancer, BARD1 expression was correlated with poor differentiation and large tumor size, established factors of poor prognosis, as well as short disease‐free survival. In contrast to breast and ovarian cancers, no correlation of BARD1 expression with either grade or stage could be determined for lung cancer. RT‐PCR, performed on 10 ovarian cancers, revealed absence of the 5′ portion of the BARD1 transcript in 7 tumors, and sequencing of the remaining 3 identified a missense mutation (A1291G) resulting in an amino acid change of glutamine 406 to arginine. These data suggest that genetic and epigenetic changes might lead to elevated cytoplasmic expression of BARD1 and that cytoplasmic BARD1 might be a poor prognostic factor for breast and ovarian cancers. © 2005 Wiley‐Liss, Inc.
Regulation of prostate cell collagen receptors by malignant transformation
Authors: Mirtti Tuomas , Nylund Camilla , Lehtonen Janika , Hiekkanen Heikki , Nissinen Liisa , Kallajoki Markku , Alanen Kalle , Gullberg Donald , Heino Jyrki 
Published: September 2005

AbstractCell adhesion receptors, including the integrin‐type collagen receptors (α1β1, α2β1, α10β1 and α11β1) participate in cancer progression and invasion. Quantitative RT‐PCR indicated that all 4 receptors are abundantly expressed in sarcoma‐derived cell lines, whereas most carcinoma‐derived cells express α1β1 and α2β1 only. This was surprising because α11β1 has been connected previously to the progression of lung adenocarcinomas. To test the hypothesis that α11 expression may not persist in cultured cancer cells we analyzed fresh tissue samples of 104 total prostatectomies, keeping in mind that prostate cancer cell lines showed negligible α11 mRNA levels. In prostate α2 expression was significantly lower in poorly differentiated carcinomas when compared to benign lesions (p = 0.0331). In immunohistochemistry the protein levels of α2 integrin decreased significantly (p = 0.0001) and the protein levels of α11 subunit increased significantly (p = 0.029) with the increasing grade of carcinoma. Thus α11β1 may replace α2β1 during tumor progression. Our observations support the idea that α11β1 may be expressed in tumors but the corresponding cell lines may lose the expression of this integrin. Previous studies have shown that in cell culture androgen receptor (AR) controls α2β1 expression. We measured AR mRNA levels and the number of AR positive nuclei in the prostate samples and the results showed a significant correlation between α2β1 and AR. Androgen receptors may control the mechanisms regulating integrin expression in prostate. © 2005 Wiley‐Liss, Inc.
Steroid hormone receptors and coregulators in endocrine‐resistant and estrogen‐independent breast cancer cells
Authors: Sarvilinna Nanna , Eronen Heli , Miettinen Susanna , Vienonen Annika , Ylikomi Timo 
Published: September 2005

AbstractResistance to hormonal therapy is often a problem in the treatment of breast cancer patients. It has been suggested that resistance could be explained by altered nuclear hormone receptor or coregulator levels or inappropriately increased agonist activity of selective estrogen receptor modulator (SERM). To test these hypotheses, we have established novel MCF‐7 cell line‐derived in vitro models of anti‐estrogen‐ and progestin‐resistant and estrogen‐independent breast cancer by long‐term culture in the presence of toremifene and medroxyprogesterone acetate (MPA) and in the absence of estradiol, respectively. Using cell growth and multiprobe ribonuclease protection assays, the expression of 5 nuclear hormone receptors and 9 coregulators as well as the alterations in the cell proliferation and target gene transcription in response to hormonal treatments were studied. Progesterone receptor (PR) expression was decreased and silencing mediator for retinoid acid and thyroid hormone receptors (SMRT) and amplified in breast cancer‐1 (AIB1) expression increased in anti‐estrogen‐resistant cells. Estrogen caused PR and ERβ upregulation in all cell lines, but we did not observe increased agonist activity of anti‐estrogen measured by regulation of these estrogen target genes. Basal ERα levels and estrogenic growth response were decreased and p300/CBP‐associated factor (pCAF) and AIB1 upregulated by estrogen in progestin‐resistant cells, but coregulator levels were unchanged. Estrogen‐independent cells were still estrogen‐responsive and PR, nuclear receptor corepressor (N‐CoR) and SMRT expression was increased whereas steroid receptor coactivator‐1 (SRC‐1a) and CBP‐related protein p300 (p300) expression decreased. Their growth was inhibited by toremifene, but estradiol was able to abrogate this effect, which might have interesting clinical implications concerning the use of postmenopausal hormone replacement therapy. © 2005 Wiley‐Liss, Inc.
Identification of a glioma antigen, GARC‐1, using cytotoxic T lymphocytes induced by HSV cancer vaccine
Authors: Iizuka Yukihiko , Kojima Hidefumi , Kobata Tetsuji , Kawase Takeshi , Kawakami Yutaka , Toda Masahiro 
Published: September 2005

AbstractDespite several ongoing clinical trials of immunotherapies against glioma, few glioma‐specific antigens recognized by cytotoxic T lymphocytes (CTLs) have been identified. We recently demonstrated that intratumoral inoculation with herpes simplex virus (HSV) as a cancer vaccine activates tumor‐specific CTLs. To identify glioma antigens recognized by CTLs, we used the HSV cancer vaccine to vaccinate mice harboring a syngeneic mouse glioma cell line, GL261. From the splenocytes of the immunized mice, we generated an H‐2Db‐restricted CTL line, GCL‐1, that was specific for GL261. Then, a cDNA expression library generated from GL261 was screened with GCL‐1, and a new gene encoding glioma antigen, GARC‐1, was isolated. Sequence analysis revealed that the GARC‐1 gene isolated from GL261 had a point mutation causing an amino acid change (Asp to Asn at position 81). T‐cell epitope analysis revealed that the mutated peptide GARC‐177–85 (AALLNKLYA) but not the wild‐type peptide (AALLDKLYA), was recognized by GCL‐1. These results suggest that HSV cancer vaccination may be a useful method for inducing tumor‐specific CTLs and identifying tumor antigens. Furthermore, this GL261/GARC‐1 murine glioma model may be useful for the development of immunotherapy for brain tumors. © 2005 Wiley‐Liss, Inc.
Cancer risk among Danish women with cosmetic breast implants
Authors: Friis Søren , Hölmich Lisbet R. , McLaughlin Joseph K. , Kjøller Kim , Fryzek Jon P. , Henriksen Trine F. , Olsen Jørgen H. 
Published: September 2005

AbstractThe available epidemiologic evidence does not support a carcinogenic effect of silicone breast implants on breast or other cancers. Data on cancer risk other than breast cancer are limited and few studies have assessed cancer risk beyond 10–15 years after breast implantation. We extended follow‐up of our earlier cohort study of Danish women with cosmetic breast implants by 7 years, yielding 30 years of follow‐up for women with longest implant duration. The study population consisted of women who underwent cosmetic breast implant surgery at private clinics of plastic surgery (n = 1,653) or public hospitals (n = 1,110), and a control group of women who attended private clinics for other plastic surgery (n = 1,736), between 1973–95. Cancer incidence through 2002 was ascertained using the Danish Cancer Registry. Risk evaluation was based on computation of standardized incidence ratios (SIR) and Cox proportional hazards models, adjusting for age, calendar period and reproductive history. We observed 163 cancers among women with breast implants compared to 136.7 expected based on general population rates (SIR = 1.2; 95% confidence interval [CI] = 1.0–1.4), during a mean follow‐up period of 14.4 years (range = 0–30 years). Women with breast implants experienced a reduced risk of breast cancer (SIR = 0.7; 95% CI = 0.5–1.0), and an increased risk of non‐melanoma skin cancer (SIR = 2.1; 95% CI = 1.5–2.7). Stratification by age at implantation, calendar year at implantation and time since implantation showed no clear trends, however, the statistical precision was limited in these analyses. When excluding non‐melanoma skin cancer, the SIR for cancer overall was 1.0 (95% CI = 0.8–1.2). With respect to other site‐specific cancers, no significantly increased or decreased SIR were observed. Similar results were found when directly comparing women who had implants at private clinics with women who attended private clinics for other plastic surgery, with rate ratios for cancer overall, breast cancer and non‐melanoma skin cancer of 1.1 (95% CI = 0.8–1.6), 0.7 (95% CI = 0.4–1.3) and 1.5 (95% CI = 0.8–2.7), respectively. In conclusion, our study lends further support to the accumulating evidence that silicone breast implants are not carcinogenic. Reasons for the consistently reported deficit of breast cancer among women with breast implants remain unclear, whereas increased exposure to sunlight may explain the excess occurrence of non‐melanoma skin cancer. We found no indication of delayed diagnosis of breast cancer due to the presence of breast implants. © 2005 Wiley‐Liss, Inc.
The Brn‐3b POU family transcription factor represses plakoglobin gene expression in human breast cancer cells
Authors: Samady Laila , Faulkes David J. , Budhram‐Mahadeo Vishwanie , Ndisang Daniel , Potter Eyck , Brabant Georg , Latchman David S. 
Published: September 2005

AbstractThe Brn‐3b transcription factor has been shown to be overexpressed in human breast cancer cells and contributes toward cell growth regulation. Using micro‐arrays, more than 50 cancer‐related genes regulated by Brn‐3b in human breast cancer cells have been identified. For example, Brn‐3b activates the cell cycle regulator CDK4 that provides a mechanism by which Brn‐3b controls the growth of breast cancer cells. Here, we show that Brn‐3b regulates plakoglobin (γ‐catenin), a member of the catenin family involved in cell‐cell adhesion and signal transduction. Brn‐3b expression inversely correlates with plakoglobin expression at both mRNA and protein levels in breast cancer cell lines and human breast biopsies. In contrast, no significant correlation was observed between Brn‐3b expression and β‐catenin, or between Brn‐3b expression and E‐cadherin expression. Brn‐3b represses the plakoglobin promoter via a Brn‐3 consensus binding site contained within the region −965 to −593 relative to the transcriptional start site. Both repression of the promoter and binding of Brn‐3b are lost when this site is mutated. To our knowledge, this is the first time that a Brn‐3b POU family transcription factor has been shown to regulate a member of the catenin family, which provides insight into the molecular mechanisms by which Brn‐3b expression may favour breast cancer progression and tumor invasion. © 2005 Wiley‐Liss, Inc.
Cancer risk among patients with multiple sclerosis: A population‐based register study
Authors: Nielsen Nete Munk , Rostgaard Klaus , Rasmussen Søren , Koch‐Henriksen Nils , Storm Hans H. , Melbye Mads , Hjalgrim Henrik 
Published: September 2005

AbstractCancer occurrence in patients with multiple sclerosis (MS) has been little studied, but associations with brain tumours, breast cancer, Hodgkin lymphoma and nasopharyngeal carcinoma have been suggested. We took advantage of population‐based registers of MS and cancer to assess the risk of cancer following diagnosis of MS. Patients registered in the Danish Multiple Sclerosis Register were linked with the Danish Cancer Register to obtain information on cancer occurrence. The ratio of the observed to the number of expected cancers based on population‐based incidence rates, i.e., the standardised incidence ratio (SIR), served as measure of the relative cancer risk. A database comprising all Danish women born after April 1, 1935, with information on all live‐born children, was used in the analyses of breast cancer to adjust for reproductive factors. Overall 1,037 cancers were observed in 11,817 MS patients during 153,875 person‐years of follow‐up vs. an expected number of 1,098 (SIR = 0.94 [95% confidence interval CI: (0.89–1.00)]. The risk of brain tumours and Hodgkin lymphoma was not increased. A 16% overall reduced cancer risk in men with MS was explained by reduced numbers of cancers of the digestive, respiratory and genital organs. Though the overall cancer risk was not increased [SIR = 1.01(0.94–1.09), n = 676], female MS patients had an increased risk of breast cancer [SIR = 1.21 (1.05–1.39), n = 193]. Adjusting for parity and age at first child delivery did not change this risk estimate materially. In general MS patients are not at increased risk of cancer. Women with MS, however, seem to have a small excess risk of breast cancer, which cannot be attributed to reduced parity or delayed first child birth. © 2005 Wiley‐Liss, Inc.
Associations between 5,10‐methylenetetrahydrofolate reductase codon 677 and 1298 genetic polymorphisms and environmental factors with reference to susceptibility to colorectal cancer: A case‐control study in an Indian population
Authors: Wang Jingwen , Gajalakshmi Vendhan , Jiang Jing , Kuriki Kiyonori , Suzuki Sadao , Nagaya Teruo , Nakamura Seiichi , Akasaka Susumu , Ishikawa Hideki , Tokudome Shinkan 
Published: September 2005

AbstractAlthough the incidence rate of colorectal cancer is very low, and rectal cancer remains more common in India, a significant increase in its incidence has been reported for both men and women over the last 2 decades. We evaluated MTHFR genetic susceptibility and common environmental risk factors in the development of colon and rectal cancer, and assessed the interactions between gene and environmental factors with colorectal cancer in a case‐control study in the Indian population. The study included 59 colon cancer cases, 243 rectal cancer cases and 291 controls. The variant MTHFR 677T allele is rare, while the 1298C allele is common among Indians. MTHFR 677T showed no association with colon cancer (OR = 0.82; 95% CI 0.28–2.05) and a nonstatistically significantly elevated risk with rectal cancer (OR = 1.51; 95% CI 0.86–2.68), and MTHFR 1298 CC genotype was found to be associated with a significantly decreased risk for both colon cancer (OR = 0.30, 95% CI 0.09–0.81) and rectal cancer (OR = 0.43, 95% CI 0.23–0.80). High intake of nonfried vegetables or fruits was inversely associated with both colon and rectal cancer risk. Especially, the combination of a high intake of nonfried vegetables and MTHFR 1298CC genotype was associated with the lowest rectal cancer risk (OR = 0.22, 95% CI 0.09–0.52). Regarding alcohol consumption, indigenous Indian alcohol drinkers (OR = 2.26, 95% CI 0.86–6.36), and those consuming alcohol for duration more than 20 years (OR = 1.55, 95% CI 0.73–3.33), were at a somewhat higher rectal cancer risk. Moreover, the consumed alcohol amount (gram‐years) may be also associated with colon or rectal cancer risk. © 2005 Wiley‐Liss, Inc.