bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced interaction between tubulin and microtubule‐associated protein 2 via inhibition of MAP kinase and CDC2 kinase by paclitaxel
Authors: Nishio Kazuto , Arioka Hitoshi , Ishida Tomoyuki , Fukumoto Hisao , Kurokawa Hirokazu , Sata Makoto , Ohata Masahiro , Saijo Nagahiro 
Published: February 2007

AbstractPaclitaxel, an anti‐mitotic anti‐cancer agent, is active against solid tumors. The inhibition of depolymerization and promotion of microtubular assembly are essential for the anti‐tumor activity of paclitaxel. Microtubule‐associated proteins (MAPs) co‐polymerize with tubulin and play some roles in microtubular dynamics. We examined the effect of paclitaxel on the interaction between tubulin and MAPs. Human lung‐cancer cells, PC‐14, were synchronized to G1/S border by the thymidine‐double‐block technique. After release from exposure to thymidine, the cells were treated briefly with 2 nM paclitaxel and the levels of α and β tubulins and MAPs were examined after various times. Immunoblot analysis of paclitaxel‐treated cells showed no changes in the overall expression of α and β tubulins, microtubule‐associated protein 2 (MAP2) or MAPs in comparison with controls. The samples were immunoprecipitated with anti‐α‐ and anti‐β‐tubulin antibodies and reblotted with an anti‐MAP2 antibody, which showed that the amount of co‐immuno‐precipitated MAP2 in the synchronized cells, were increased by the brief paclitaxel treatment. These results suggest that paclitaxel treatment enhances the interaction between α and β tubulins and MAP2. Since the phosphorylation state of MAP2 regulates the affinity of MAP2 for tubulins, and mitogen‐activated protein (MAP) kinase is considered to be one of the kinases responsible for MAP2 phosphorylation, the effect of paclitaxel treatment on the MAP‐kinase activity of synchronized PC‐14 cells was examined. Two bands with molecular masses of 42 and 44 kDa were detected by an “intra‐gel” MAP‐kinase assay using myelin basic protein as the substrate. Paclitaxel treatment inhibited the MAP‐kinase activity of PC‐14 cells and inhibition was maximal at the G2/M phase of the cell cycle. Similar, concentration‐dependent inhibition by paclitaxel of cellular MAP kinase of human synchronized small‐cell lung carcinoma, H69, was observed. No inhibition of the MAP kinase of the paclitaxel‐resistant sub‐line H69/T×1 by paclitaxel was observed, suggesting that some change of the MAP‐kinase cascade had occurred in these cells. No direct inhibition of MAP‐kinase activity by paclitaxel was observed in the cell‐free assay (in vitro), suggesting that paclitaxel did not inhibit MAP kinase directly. Since it has been speculated that p34cdc2 kinase is also a kinase that phosphorylates MAP2, the effect of paclitaxel treatment on the p34cdc:2‐kinase activity of synchronized PC‐14 and PC‐9 cells was examined. Paclitaxel inhibited p34cdc2‐kinase activation at the G2/M phase. These results suggest that paclitaxel inhibited MAP kinase and p34cdc2 kinase in vivo indirectly. These actions of paclitaxel may be responsible for the increased affinity between MAP2 and tubulins that it induces. © 1995 Wiley‐Liss, Inc.
Fibroblast growth factor 3 is tumorigenic for mouse mammary cells orthotopically implanted in nude mice
Authors: Hajitou Amin , Calberg‐Bacq Claire‐ M. 
Published: February 2007

AbstractFibroblast growth factor‐3 (Fgf‐3) is involved in mouse mammary tumorigenesis since the Fgf‐3 gene is a main target for mouse mammary tumor virus (MMTV) insertional activation. Its action has been correlated with the appearance of pregnancy‐dependent tumors. We describe here the effects on normal mouse mammary EF43 cells of the short Fgf‐3 protein form which enters the secretory pathway. The genes, Fgf‐3 AUG or Fgf‐4 for comparison, were introduced in the mammary cells by means of retroviral vectors. Fgf‐3 expression did not modify EF43 cell morphology, had no effect on growth in soft agar nor on the inhibitory action exerted on cell growth by TGF‐β; however, it allowed the cells to grow under low serum conditions in the absence of insulin and EGF. The Fgf‐3‐expressing cells were not tumorigenic in nude mice when injected s.c., but tumors developed when the cells were implanted in the mammary gland. The tumors appeared after some latency; they had a slow growth phase followed by a phase of increased growth rate. An identical tumoral growth pattern was observed in ovariectomized nude mice. These results show that the secreted Fgf‐3 form can initiate tumorigenesis and that the induced tumors are hormone‐independent. The mammary‐gland environment, however, is required for the EF43 cells to grow and differentiate. During that process, which resembles natural cell growth during mammary‐gland development at pregnancy, the cells could pass through a stage which is specifically sensitive to Fgf‐3. © 1995 Wiley‐Liss, Inc.
Expression of estrogen, progesterone and epidermal growth factor receptors in primary and metastatic breast cancer
Authors: van Agthoven Ton , Timmermans Mieke , Dorssers Lambert C. J. , Henzen‐Logmans Sonja C. 
Published: February 2007

AbstractThe prognostic value of epidermal growth factor receptor (EGFR) expression and its biological role in estrogen receptor‐positive (ER+) and ER‐negative (ER−) primary breast cancer is controversial. In this study, distributions of ER, progesterone receptor and EGFR have been established using immunohisto‐chemistry in both primary breast tumors and their matched axillary lymph node metastases of 26 patients or their matched distant metastases of 2 patients. In addition, 5 patients with bilateral breast cancer were studied. ER+ tumor cells were detected in 22 (69%) and EGFR+ tumor cells were detected in 11 (34%) primary breast carcinomas. Expression of ER and EGFR was inverse regarding the individual tumor cells in both primary tumors and metastases. Relationship of EGFR expression with poorly differentiated and large breast tumors was observed. Furthermore, primary tumors with a predominant lobular component were ER+ and, with one exception, EGFR−. Invasive ductal carcinomas were more frequently EGFR+. No apparent differences in receptor expression were observed between primary tumors and lymph node metastases or chro‐nously or metachronously occurring bilateral breast cancers. Only one ER+ primary tumor showed a switch to EGFR expression in the involved lymph node. Our study shows that a shift in receptor phenotype between primary tumors and lymph node metastases is a rare event and, thus, additional analyses of involved lymph nodes will not likely serve as a better predictor for response to anti‐estrogen therapy. We conclude that expression of EGFR is not a prerequisite for development of metastases. © 1995 Wiley‐Liss, Inc.
High frequency of K‐ras mutations in normal appearing lung tissues and sputum of patients with lung cancer
Authors: Yakubovskaya Marina S. , Spiegelman Vladimir , Luo Feng C. , Malaev Serge , Salnev Alexander , Zborovskaya Irina , Gasparyan Alexander , Polotsky Boris , Machaladze Zurab , Trachtenberg Alexander C. , Belitsky Gennady A. , Ronai Zeev 
Published: February 2007

AbstractTo evaluate the possible use of mutant ras as a biomarker for lung cancer, we have analyzed “normal appearing” lung tissue, lung tumor, lung metastases and sputum samples from patients with non‐small cell lung cancer (NSCLC). As a control, we used lung tissue and sputum samples from patients without oncological diseases or lung disorders. Our analyses were performed with the aid of enriched PCR (EPCR), a method which enables detection of ras mutation even if present at low incidence. EPCR identified K‐ras codon 12 mutations in 10% of lung tissues obtained from patients with no lung diseases, whereas the same mutation was detected in 60% of samples of normal appearing lung tissues obtained from patients with NSCLC, 62% of NSCLC tumors and 80% of metastases. Analysis of sputum samples of patients with NSCLC identified 47% to harbor mutant ras allele, whereas 12.5% of controls diagnosed with non‐oncological lung diseases carried this mutation. Most of these mutations were detected with the aid of EPCR only, indicating that a minority of cells in a given sample harbor this mutation. The ability to detect K‐ras codon 12 mutation in 60% of lung tissue samples and in 47% of sputum samples taken from patients with lung cancer (as compared with 10% and 12.5% of respective controls) points to the potential use of ras mutation as a biomarker for exposure and possible identification of patients who may be at a higher risk of developing lung cancer. © 1995 Wiley‐Liss, Inc.
Invasive phenotype of MCF10A cells overexpressing c‐Ha‐ras and c‐erbB‐2 oncogenes
Authors: Giunciuglio Daniela , Culty Martine , Fassina Gianfranco , Masiello Luciana , Melchiori Antonella , Paglialunga Giuseppina , Arand Gloria , Ciardiello Fortunato , Basolo Fulvio , Thompson Erik W. , Albini Adriana 
Published: February 2007

AbstractInfection with erbB‐2 (E) of Ha‐roj (H) oncogene‐transfected cells has been previously shown to cooperatively induce anchorage‐independent growth of the MCF10A human mammary epithelial cell line in vitro, but not to induce nude mouse tumorigenicity. Here we show that oncogene‐transformed MCF10A are able to halt in the lungs of nude mice, a sign of organ colonization potential. We have therefore studied the transformants for in vitro migratory and invasive properties known to correlate with the metastatic potential of human mammary carcinoma cells in nude mice. MCF10A transfected with Ha‐ras, infected with a recombinant retroviral vector containing the human c‐erbB‐2 proto‐oncogene (MCF10A‐HE cells), show a higher invasive index than either the single transfectant (MCF10A‐H) or MCF10A‐erbB‐2 (MCF10A‐E) cells in the Boyden chamber chemotaxis and chemoinvasion assays. The MCF10A‐HE cells also adopted an invasive stellate growth pattern when plated or embedded in Matrigel, in contrast to the spherical colonies formed by the single transformants MCF10A‐H, MCF10A‐E, and the parental cells. Dot‐blot analysis of gelatinase A and TIMP‐2 mRNA levels revealed increasing gelatinase A mRNA levels (HE > E > H > MCF10A) and reduced TIMP‐2 expression in both single and double transformants. Furthermore, MCF10A‐HE cells show more MMP‐2 activity than parental MCF 10A cells or the single transformants. CD44 analysis revealed differential isoform banding for the MCF10A‐HE cells compared to parental ceils, MCF10A‐H and MCF10A‐E, accompanied by increased binding of hyaluronan by the double transformants. Our results indicate that erbB‐2 and Ha‐ros co‐expression can induce a more aggressive phenotype in vitro, representative of the malignancy of mammary carcinomas. © 1995 Wiley‐Liss, Inc.
Anti‐tumor activity of tumor necrosis factor in combination with interferon‐γ is not affected by prior tolerization
Authors: Takahashi Nozomi , Fiers Walter , Brouckaert Peter 
Published: February 2007

AbstractRepetitive administration of low doses of tumor necrosis factor (TNF) results in a state of selective tolerance to some of its effects. We have demonstrated that tolerance does not impair the therapeutic efficacy of TNF against a syngeneic murine B16BL6 melanoma and allows a complete cure. Another study, performed with a distinct tumor model, came to apparently contradictory results. To clarify this, we investigated whether the outcome depended on the tumor type and on the inclusion of interferon‐γ (IFNγ) in the treatment. Three syngeneic tumors of different histological origin, i.e., B16BL6 melanoma, Lewis lung carcinoma (LLC) and EL4 lymphoma, were compared in C57BL/6 mice. The anti‐tumor efficacy of TNF against BI6BL6 and EL4 was not impaired in tolerant mice, but the effect of TNF against LLC was slightly, though significantly, reduced. Inclusion of IFNγ in the treatment regimen, however, abolished this difference and resulted in complete cure for all 3 tumor systems. As therapeutically optimal doses were lethal in normal mice, only tolerance allowed a long‐term cure. We conclude that the influence of tolerance on the anti‐tumor activity of TNF as a single agent depends on the tumor type; in combination therapy with IFNγ, however, tolerance allowed us to dissociate lethal toxicity from anti‐tumor activity, irrespective of the tumor type tested. © 1995 Wiley‐Liss, Inc.
Prostate‐specific antigen activates single‐chain urokinase‐type plasminogen activator
Authors: Yoshida Etsuo , Ohmura Sayuri , Sugiki Masahiko , Maruyama Masugi , Mihara Hisashi 
Published: February 2007

AbstractProstate‐specific antigen (PSA) increases in the plasma of patients with prostate cancer, and has therefore been used as a reliable tumor marker. It has been demonstrated that prostate cancer cells over‐express urokinase‐type plasminogen activator (uPA), which plays an important role in tumor invasion and metastasis. We found that PSA converts the single‐chain pro‐form of urokinase‐type plasminogen activator (scuPA) to an active 2–chain form. The active 2–chain uPA generated from scuPA by PSA was measured by hydrolyzation of S‐2444, a synthetic substrate for uPA. PSA activated scuPA time‐ and dose‐dependently. SDS‐PAGE analysis revealed that, after incubation with PSA, the intensity of the 55–kDa band of scuPA decreased concomitantly with increases in the intensity of the 2 bands at 33 kDa and 22 kDa. Amino‐acid‐sequence analysis indicated that PSA cleaved Lys158‐Ile159, which corresponds with the site cleaved by plasmin. PSA did not enhance or impair the activity of the 2–chain form of uPA. These findings imply that PSA could be an initiator of the protease cascade involved in prostate‐cancer invasion and metastasis. © 1995 Wiley‐Liss, Inc.
Malignant lymphoma induction in rabbits by intravenous inoculation of Epstein‐Barr‐virus‐related herpesvirus from HTLV‐II‐transformed cynomolgus leukocyte cell line (Si‐IIA)
Authors: Hayashi Kazuhiko , Koirala Tirtha R. , Ino Hideo , Chen Hong‐Li , Ohara Nobuya , Teramoto Norihiro , Yoshino Tadashi , Takahashi Kiyoshi , Yamada Masao , Nil Shiro , Miyamoto Kanji , Fujimoto Koji , Yoshikawa Yasuhiro , Akagi Tadaatsu 
Published: February 2007

AbstractMaignant lymphomas, which were usually of T‐cell type, were Induced in 10 of 13 (77%) male rabbits (Japanese white, 8/10; New Zealand white, 2/3) inoculated i.v. with HTLV‐II‐transformed simian (Cynomolgus) leukocyte cell line (Si‐IIA) cells. Of 7 rabbits injected with cell‐free pellets from Si‐IIA cultures, 5 also developed malignant lymphoma (15–28 days). Lymphoma development was completely inhibited by inactivation of cell‐free pellets from Si‐IIA culture with ethyl ether and was almost suppressed by neutralization of the cell‐free pellets with anti‐Si‐IIA sera. Herpesvirus particles were discovered very rarely in Si‐IIA cells, in addition to C‐type virus particles, by electron microscopy. Si‐IIA cells were positive for Epstein‐Barr‐virus(EBV)‐associated nuclear antigen (EBNA) by immunofluo‐resconce (IF) test. Antibody response to viral capsid antigen of EBV was also detected in sera from rabbits inoculated with Si‐IIA. EBV‐encoded RNA‐I (EBER‐I) was demonstrated in Si‐IIA, the tumor tissues and all rabbit tumor cell lines by in situ hybridization. EBV DNA was also detected in Si‐IIA and rabbit lymphoma cell lines by polymerase chain reaction (PCR) and Southern blotting. However, EBV DNA was amplified only by some primers complementary to human EBV sequence (B95–8), but not by other primers. Integration of HTLV‐II provirus genome could not be detected in Si‐IIA‐induced rabbit tumor cells. Moreover, no lymphoma was induced by inoculation of HTLV‐IIC and MOT (other HTLV‐II‐producing human cell lines), B95‐8 (EBV‐producing cell line) or TALL‐1 and peripheral leukocytes from normal Cynomolgus (controls). Neither Herpesvirus saimiri nor H. ateles (simian oncogenic viruses) were detected in Si‐IIA cells by IF test. These data suggest that the high rate of lymphoma induction in rabbits may not be caused by HTLV‐II, human EBV (B95–8) or well‐known simian oncogenic viruses, but by EBV‐related herpesvirus derived from Si‐IIA cells or HTLV‐IIA cells, with which Si‐IIA was established. The availability of this animal model promises to clarify the role of EBV in human lymphoma and provides a means of studying prophylactic and therapeutic regimens. © 1995 Wiley‐Liss, Inc.
Familial clustering of breast cancer: Possible interaction between dna repair proficiency and radiation exposure in the development of breast cancer
Authors: Helzlsouer Kathy J. , Harris Emily L. , Parshad R. , Fogel Sandy , Bigbee William L. , Sanford Katherine K. 
Published: February 2007

AbstractThe capacity of peripheral blood lymphocytes to repair X‐ray‐induced DNA damage, manifest as chromatid damage 30‐90 min after G2‐phase X‐irradiation, was measured among available members of a family exhibiting a cluster of breast‐cancer cases occurring in one generation. The cancer patients had been exposed to repeated chest fluoroscopic examinations during early childhood and adolescence. The development of breast cancer was correlated with DNA repair proficiency and history of radiation exposure. The results of the family study provide preliminary support for the hypothesis that a deficiency in repair of X‐irradiation DNA damage may be a susceptibility factor for the development of breast cancer. This hypothesis, however, requires confirmation in a larger study. Studying the combined effect of susceptibility factors and environmental exposures may enhance our knowledge of the etiology of breast cancer and provide leads for effective prevention strategies aimed at reducing exposures or altering susceptibility to unavoidable exposures. © 1995 Wiley‐Liss, Inc.
Expression of mage genes in transitional‐cell carcinomas of the urinary bladder
Authors: Patard Jean‐Jacques , Brasseur Francis , Gil‐Diez Sixtina , Radvanyi François , Marchand Marie , François Philippe , Abi‐Aad Antoine , Van Cangh Paul , Abbou Clément Claude , Chopin Dominique , Boon Thierry 
Published: February 2007

AbstractHuman genes MAGE‐1 and MAGE‐3 code for distinct antigens, which are recognized on melanoma cells by autologous cytolytic T lymphocytes (CTL). These antigens may constitute useful targets for anti‐cancer immunotherapy, since no expression of MAGE genes has been observed in normal tissues other than testis. Out of 57 samples of primary transitional‐cell carcinomas of the bladder, 12 (21%) expressed MAGE‐1 and 20 (35%) expressed MAGE‐3. All but one of the tumors expressing MAGE‐1 also expressed MAGE‐3. Genes MAGE‐2 and MAGE‐4, which are closely related to MAGE‐1 and MAGE‐3, were expressed by 30% and 33% of the tumors respectively. MAGE expression was more frequent in advanced tumor stages: 61% of the invasive tumors (stage ± T2) were positive for expression of at least one of the four genes, whereas only 28% of the superficial tumors (stages Ta and Tl) expressed these genes. © 1995 Wiley‐Liss, Inc.
Expression of platelet‐derived endothelial cell growth factor/thymidine phosphorylase in human breast cancer
Authors: Toi Masakazu , Hosnina Seigo , Taniguchi Tadaaki , Yamamoto Yutaka , Ishitsuka Hideo , Tominaga Takeshi 
Published: February 2007

AbstractWe have investigated the expression of platelet‐derived endothelial‐cell growth factor/thymidine phosphorylase (PD‐ECGF/dThdPase) in human breast‐cancer tissues by the immunocytochemical method using anti‐PD‐ECGF/dThdPase monoclonal antibody. Out of 100 invasive‐ductal‐carcinoma tissue samples, 39 (39%) were evaluated as PD‐ECGF/dThdPase‐positive. The expression of PD‐ECGF/dThdPase was identified mainly in the cytoplasma of tumor cells. The expression of PD‐ECGF/dThdPase was significantly associated with the microvessel density assessed by immunostaining to factor‐VIII‐related‐antigen (p < 0.05). However, there was no correlation between expression of PD‐ECGF/dThdPase and menopausal status, tumor size, axillary lymph‐node metastases, hormone‐receptor status, epidermal‐growth‐factor receptor, or erb‐B‐2‐protein and p53‐protein expression. We suggest that expression of PD‐ECGF/dThdPase plays an important role in the promotion of angiogenesis in human breast cancer. © 1995 Wiley‐Liss, Inc.
Comparative analysis of p53 gene mutations and protein accumulation in human non‐small‐cell lung cancer
Authors: Top Bert , Mooi Wolter J. , Klaver Siegina G. , Boerrigter Lucie , Wisman Peter , Elbers Hans R. J. , Visser Sjoerd , Rodenhuis Sjoerd 
Published: February 2007

AbstractA series of 54 resected primary non‐small‐cell lung carcinomas was analyzed for p53 gene mutations and for p53 protein accumulation and the findings were correlated with clinical parameters. Mutations in exons 5 through 8 of the p53 gene were identified by a denaturing gradient gel electrophoresis (DGGE) assay and cycle sequencing, whereas p53 protein accumulation was detected in paraffin‐embedded tissue by immunostaining using 2 different murine monoclonal antibodies (MAbs) (BP53‐12 and DO7). A p53 gene mutation and/or p53 protein accumulation was found in 37 of 54 tumors. Mis‐sense mutations were closely associated with positive immunostaining, which was intense in 15 out of 17 cases with a mutation. In 10 tumors, obvious p53 accumulation was detected in the absence of mutations in exons 5 through 8. Conversely, only one of 8 p53 non‐sense mutations led to detectable p53 accumulation. The most frequent single base changes were G → T transversions and C → T transitions. The presence of a p53 alteration was not related to age, tumor size, stage or histology. However, we found a significant inverse correlation between p53 alterations and the presence of a K‐ras mutation. This was reflected in the overall postoperative survival data: patients with p53 alterations in their tumors tended to have a better prognosis than those without a p53 alteration; however, this difference was lost when cases with a K‐ras mutation were omitted from the analysis. © 1995 Wiley‐Liss, Inc.
Chromosome‐9 loss detected by fluorescence in situ hybridization in bladder cancer
Authors: Sauter Guido , Moch Holger , Carroll Peter , Kerschmann Russel , Mihatsch Michael J. , Waldman Frederic M. 
Published: February 2007

AbstractA loss of chromosome‐9 material is one of the most frequent genomic aberrations known in bladder cancer. In order to better understand the role of chromosome‐9 losses in bladder cancer, 125 formalin‐fixed and 37 unfixed bladder tumors were examined using fluorescence in situ hybridization (FISH). A repetitive probe for a pericentromeric region on 9q12 (pHUR98) was applied for chromosome‐9 copy‐number enumeration. Under‐representation of chromosome 9 was found in 74 of 162 cases. There was no association between loss of chromosome 9 and increased grade or stage, papillary growth pattern, p53 protein expression, or tumor‐cell proliferation (Ki‐67). These data show that chromosome‐9 loss is an early event in bladder‐cancer development, occuring independently of p53 alterations. In order to determine the prevalence of large sub‐regional chromosome‐9 deletions, dual hybridizations with pHUR 98 and cosmid probes for 9q34, 9q22, and 9p21 were performed. Partial deletion was detected in only 1 of 36 cases for 9q34 and in 1 of 24 cases for 9p21. Surprisingly, amplification of the interferon alpha locus on 9p21 was seen in 1 of 24 tumors. The finding of 9p amplification may indicate the site of an oncogene relevant for bladder cancer. © 1995 Wiley‐Liss, Inc.