bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of P‐cadherin in gastric carcinomas and its reduction in tumor progression
Authors: Yasui Wataru , Sano Toshiaki , Nishimura Kenji , Kitadai Yasuhiko , Ji Zhong‐Qiang , Yokozaki Hiroshi , Ito Hisao , Tahara Eiichi 
Published: February 2007

AbstractThe expression of P‐cadherin, one of the Ca2+‐dependent cell‐cell adhesion molecules, in human gastric carcinomas was examined by Northern blotting, Western blotting and immuno‐histochemistry. P‐cadherin mRNA was expressed in all the gastric carcinoma tissues examined, whereas no message was detected in non‐neoplastic mucosa. By Western‐blot analysis, P‐cadherin protein was expressed in 83% and 29% of the well‐differentiated and poorly differentiated gastric adenocarcinomas, respectively, the incidence being significantly different. Immunohistochemically, P‐cadherin immunoreactivity was localized on the cell surface or the cell‐to‐cell borders of well‐differentiated adenocarcinomas. P‐cadherin was not detected in Borrmann's type‐4 or scirrhous carcinomas where the tumor cells proliferate diffusely with productive fibrosis. The level of P‐cadherin expression in stage‐2 carcinomas was significantly higher than in stage‐1 carcinomas. In the case of patients in stages 2 to 4, however, the level of P‐cadherin expression decreased as the stage progressed, the difference between stages 2 and 3 and between stages 3 and 4 being significant. Our findings suggest that P‐cadherin might play an important role in the development of well‐differentiated gastric adenocarcinomas and the decreased expression of P‐cadherin might be responsible for the infiltrative growth and progression of gastric carcinomas.
Breast cancer risk in mothers of multiple births
Authors: Hsieh Chung‐Chcng , Goldman Marlene , Pavia Maria , Trichopoulos Dimitrios , Ekbom Anders , Adami Hans‐Olov , Petridou Eleni 
Published: February 2007

AbstractData from an international case‐control study of breast cancer that was conducted in the 1960s were used to examine whether multiple births affect the risk of breast cancer in the mother. Among 2821 parous breast‐cancer patients, 88 had had one or more multiple births, whereas among 8882 controls 247 had had one or more multiple births; the logistic‐regression‐adjusted odds ratio (OR) was 1.21, the 95% confidence interval (Cl), 0.94 to 1.55. The OR was significantly elevated during the 15‐year period following the latest multiple birth (1.76; Cl, 1.12 to 2.75), but declined toward the null afterwards. A late first pregnancy imparted a substantially higher breast‐cancer risk when it was multiple rather than singleton; the OR was 2.34 for a multiple and 1.48 for a singleton first pregnancy when the cutoff point was 30 years, and 4.58 and 1.57, respectively, when the cutoff point was 35 years. Since multiple pregnancies are characterized by higher levels of pregnancy estrogens, the results of this study would be compatible with the hypothesis that these hormones may be responsible for the transient increase in breast–cancer risk following a term pregnancy and, in particular, a multiple term pregnancy. The long‐term reduction of breast‐cancer risk is probably due to a different mechanism, most likely the terminal differentiation of susceptible mammary‐gland cells.
Studies on the role of platelet eicosanoid metabolism and integrin αIIbβ3 in tumor‐cell‐induced platelet aggregation
Authors: Steinert Bruce W. , Tang Dean G. , Grossi Irma M. , Umbarger Lillian A. , Honn Kenneth V. 
Published: February 2007

AbstractPlatelet eicosanoid metabolism resulting from tumor‐cell‐induced platelet aggregation (TCIPA) was examined in a homologous in vitro system. Rat Walker 256 carcinosarcoma cells induced the aggregation of rat platelets via a thrombin‐dependent mechanism with concomitant production of eicosanoid metabolites (e.g., 12‐HETE, TXA2. TCIPA was dependent on the concentration of tumor cells inducing aggregation, as well as cyclooxygenase and lipoxygenase products. Cyclooxygen‐ase inhibitors, but not lipoxygenase inhibitors, blocked platelet aggregation induced in vitro by a low concentration of agonist. At a high agonist concentration, neither cyclooxygenase nor lipoxygenase inhibitors alone affected platelet aggregation; however, the combined inhibition of both the cyclooxygenase and lipoxygenase pathways resulted in subsequent inhibition of platelet aggregation regardless of agonist concentration. The extent of platelet TXA2 and 12‐HETE biosynthesis was likewise dependent on and correlated with agonist concentration. The inhibitors used in this study did not significantly inhibit protein kinase C activity at the doses tested. Platelet surface glycoproteins αIIbβ3 play an important role in platelet aggregation. The effect of platelet cyclooxygenase and lipoxygenase inhibition in regulating αIIbβ3 surface expression was examined by flow cytometric analysis. Thrombin stimulation of washed rat platelets resulted in significantly increased surface expression of platelet αIIbβ3 integrin complex. The enhanced surface expression was not inhibited by a cyclooxygenase inhibitor (aspirin), a thromboxane synthase inhibitor (CGS‐14854) or a throm‐boxane receptor antagonist (SQ 29,548), nor was it stimulated by a thromboxane A2 mimic (pinane‐thromboxane A2). However, αIIbβ3 expression was blocked by lipoxygenase inhibition and stereospecifically increased by the platelet lipoxygenase metabolite 12(S)‐HETE. These results suggest that both the platelet lipoxygenase and cyclooxygenase pathways are important for TCIPA but that different mechanisms of action are involved.
12(S)‐hete promotes tumor‐cell adhesion by increasing surface expression of αVβ3 integrins on endothelial cells
Authors: Tang D. G. , Grossi I. M. , Chen Y. Q. , Diglio C. A. , Honn K. V. 
Published: February 2007

AbstractThe present work was undertaken to investigate the regulatory role of 12(S)‐HETE, a lipoxygenase metabolite of arachidonic acid, in the surface expression of αvβ3 integrin receptors in endothelial cells (rat aortic endothelial cells, or RAEC). Several monoclonal and polyclonal antibodies localized αvβ3 in focal adhesions in both subconfluent and post‐confluent RAEC. RAEC αvβ3 integrins were further characterized by immunoblotting and immunoprecipitation. 12(S)‐HETE, but not 12(R)‐HETE or other lipoxygenase‐derived hydroxy fatty acids, induced a dose‐dependent increase in αvβ3 surface expression in RAEC, which was antagonized by prostacyclin or its analog iloprost as well as by 13‐HODE, a 15‐lipoxygenase product of linoleic acid. 12(S)‐HETE promoted RAEC adhesion to vitronectin, an effect inhibited by antibodies against αvβ3 12(S)‐HETE also promoted tumor‐cell (W256 carcinosarcoma) adhesion to vitronectin, which was inhibited by various antibodies against αIIbβ3 but not by an antibody against αv. W256 adhesion to 12(S)‐HETE‐treated RAEC demonstrated a significant increase, which was inhibited by anti‐αv, ‐β3, or ‐αvβ3antibodies and by 13‐HODE. Western blotting, immunoprecipitation and reverse transcription‐polymerase chain reaction indicated that W256 carcinosarcoma cells expressed αIIbβ3 integrins but not αvβ3. The results suggest that the lipoxygenase metabolites [i.e., 12(S)‐HETE and 13‐HODE] play a significant role in modulating tumor‐cell interactions with en'dothelium by enhancing endothelial cell integrin (e.g., αvβ3)expression.
Role of aminopeptidase N (CD13) in tumor‐cell invasion and extracellular matrix degradation
Authors: Saiki Ikuo , Yoneda Junya , Azuma Ichiro , Fujii Hideji , Abe Fuminori , Nakajima Motowo , Tsuruo Takashi 
Published: February 2007

AbstractWe have investigated the effect of monoclonal antibodies (MAbs) specific for aminopeptidase N/CD13 on the invasion of human metastatic tumor cells into reconstituted basement membrane (Matrigel). The invasion of human metastatic tumor cells (SN12M renal‐cell carcinoma, HT1080 fibrosarcoma and A375M melanoma) into Matrigel‐coated filters was inhibited by an anti‐CD 13 MAb, WM15, in a concentration‐dependent manner. However, this MAb did not have any effect on tumor‐cell adhesion and migration to the extracellular matrices, which may be involved in tumor‐cell invasion. MAb WM15 inhibited the degradation of type‐IV collagen by tumor cells in a concentration‐dependent manner. We also found that WM15 inhibited hydrolysing activities towards substrates of aminopeptidases in 3 different tumor cells. Since our previous study indicated that bestatin, an aminopeptidase inhibitor, was able to inhibit tumor‐cell invasion, as well as aminopeptidase activities of murine and human metastatic tumor cells, cell‐surface aminopeptidase N/CD13 may be partly involved in the activation mechanism for type‐IV collagenolysis to achieve tumor‐cell invasion, and anti‐CD13 MAb WM15 may inhibit tumor‐cell invasion through a mechanism involving its inhibitory action on the aminopeptidase N in tumor cells.
Spontaneous and induced differentiation of human melanoma cells
Authors: Valyi‐Nagy Istvan , Shih Ie‐Ming , Györfi Tibor , Greenstein David , Juhasz Istvan , Herlyn Meenhard , Elder David E. 
Published: February 2007

AbstractMalignant melanoma cells can differentiate spontaneously in vivo and in vitro into cells with a finite lifespan. Analysis of differentiating cells from primary melanomas in culture revealed a flat, fibroblast‐like morphology and expression of the fibroblast‐associated marker leucine aminopeptidase (LAP). Differentiation was also observed in a minor sub‐population of permanent cell lines derived from metastatic lesions. An experimental model of melanoma cell differentiation was then developed, using the pyrimidine analog bromodeoxyuridine (BUdR). BUdR‐treated cells had a flat morphology, were contact‐inhibited, had up to 20‐fold increased surface area, expressed LAP, no longer proliferated anchorage‐independently in soft agar, and 3 out of 4 cell lines were non‐tumorigenic in athymic nude mice. Our results show that models of differentiation of melanoma cells can be established that help to define pathways of differentiation.
In situ evaluation of the relationship between epidermal‐growth‐factor‐receptor status and tumor‐cell proliferation in colon carcinomas
Authors: Porschen Rainer , Classen Susanne , Kahle Yvonne , Borchard Franz 
Published: February 2007

AbstractThe association between the expression of the epidermal‐growth‐factor receptor (EGFR) and tumor proliferation was studied in 69 resected human adenocarcinomas of the colon. EGFR was detected immunohistochemically using the monoclonal antibody (MAb) EGFRI. Tumor‐cell proliferation was assessed with the MAb Ki‐67 directed against a proliferation‐associated nuclear antigen expressed only in proliferating cells. The percentage of Ki‐67‐positive tumor cells (Ki‐67 index) was evaluated by the point‐counting method. Forty‐seven carcinomas contained detectable EGFR immunoreactivity. Statistical analysis failed to reveal correlations between the EGFR status and T, N and M stages or tumor differentiation. The mean Ki‐67 index did not differ between EGFR‐positive and ‐negative carcinomas. Seven tumors contained clearly distinguishable areas with different EGFR staining intensity. In these tumors with a locally heterogeneous EGFR expression, tumor proliferation also did not correlate with EGFR immunoreactivity. These in situ observations suggest that EGFR expression may not play an important role in the growth regulation of human colonic carcinomas.
Histologic grading in soft‐tissue sarcomas. An analysis of 194 cases including agnor count and mast‐cell count
Authors: Tomita Y. , Aozasa K. , Myoui A. , Kuratsu S. , Matsumoto K. , Uchida A. , Ono K. 
Published: February 2007

AbstractIn order to establish a new histologic grading system for STS, we evaluated histologic prognostic factors. For this purpose, we selected 194 patients with STS: 31 in the upper extremities, 63 in the trunk, and 100 in lower extremities. All the patients were treated by surgery, followed by chemotherapy in 74 cases, radiotherapy in 11, chemotherapy and radiotherapy in 30, or no adjuvant treatment in 79. Histologic factors evaluated were mitotic count, extent of necrosis, cellularity, cellular pleomorphism, extent of myxoid change, sclerosis, non‐specific histologic diagnosis, counting of reaction product in silver stain for nucleolar organizer regions (AgNOR) and mast‐cell counts. Univariate analysis revealed mitotic count, necrosis, cellularity, cellular pleomorphism, non‐specific histologic classification, AgNOR count and mast‐cell count to be significantly related to prognosis. Multivariate analysis revealed that AgNOR count, cellularity and necrosis were independent prognostic factors. A new grading system was introduced: low‐grade, intermediate‐grade and high‐grade. The survival between each group were significantly different; the 5‐year‐survival rate in patients of the low‐, intermediate‐ and high‐grade groups was 87%, 74% and 35% respectively. Our findings suggest that this histologic grading system may be useful for making therapeutic decisions.
Establishment and characterization of a human gastric scirrhous carcinoma cell line in serum‐free chemically defined medium
Authors: Yanagihara Kazuyoshi , Kamada Nanao , Tsumuraya Masaru , Amano Fumio 
Published: February 2007

AbstractWe have established a human gastric scirrhous carcinoma cell line (designated as HSC‐43) in a serum‐free chemically defined medium (CDM) without any polypeptide growth factor, from a primary tumor of a 56‐year‐old male patient. HSC‐43 cells grew in vitro in adherence with a population doubling time of 55 hr, and had the cytological properties of mucinous epithelial tumor cells. Cytogenetic analysis of the cells revealed pseudo‐tetraploidy, with structural abnormalities of deletion at chromosome Iq25 and with 3 marker chromosomes. Some cells had retained features of signet‐ring cells and caused fibroblastic proliferation when transplanted into athymic nude mice. The possible involvement of transforming growth factor‐α(TGF‐α), and its receptor, the epidermal‐growth‐factor receptor (EGFR), on the growth of HSC‐43 cells was studied. Synthesis and secretion of TGF‐α by HSC‐43 cells were confirmed by biological assay and enzyme‐linked immunosorbent assay. Radioreceptor analysis showed the presence of receptors for EGF in HSC‐43 cells. Proliferation of HSC‐43 cells was inhibited by antibodies against TGF‐α and/or the EGFR. However, neither TGF‐α nor epidermal growth factor (EGF) was effective in stimulating the cell growth of HSC‐43 cells, irrespective of the cell density when supplemented exogenously. Our data suggest that TGF‐α and EGFR play a role in the autocrine growth of HSC‐43 cells. This may be another example of growth regulation of gastric carcinoma.
Very frequent loss of heterozygosity throughout chromosome 17 in sporadic ovarian carcinoma
Authors: Foulkes William D. , Black Donald M. , Solomon Ellen , Trowsdale John , Stamp Gordon W. H. 
Published: February 2007

AbstractFrequent loss of heterozygosity (LOH) on both arms of chromosome 17 has been described in ovarian carcinoma (OC) by a number of groups, and the recent fine mapping of an inherited breast‐ovarian cancer gene (brcAl) to a small region at 17q 12–21 has focused interest on this area. We studied 28 sporadic OCs with 21 markers at 18 loci on chromosome 17 (5 on 17p and 13 on 17q). LOH on 17p was 78%, and always involved p53. In 86% of cases showing LOH, all informative markers on chromosome 17 showed reduction to homozygosity. Using 6 markers flanking the brcAI locus on 17q, LOH was 75%, but only one tumour showed LOH with telomeric retention. The data therefore suggest that small deletions on chromosome 17 are very uncommon in sporadic OC. No genomic rearrangements by Southern blotting were seen in the brcAl candidate gene estradiol 17β dehydrogenase 2 (17hsd2), or in erbB2, prohibitin (phb) and nmel (previously nm23‐HI). LOH on chromosome 17 was more common in high‐grade, late‐stage carcinomas, and no LOH was seen in any benign or borderline tumour. This study has clearly demonstrated that LOH at any one site on chromosome 17 is most commonly explained by LOH over the whole of the chromosome. We consider possible reasons for the absence of small deletions on chromosome 17 in OC.
Prognostic significance of human papillomavirus genomes (type‐16, ‐18) and aberrant expression of p53 protein in human esophageal cancer
Authors: Furihata Mutsuo , Ohtsuki Yuji , Ogoshi Shohei , Takahashi Akira , Tamiya Tatsuo , Ogata Takuro 
Published: February 2007

AbstractThe presence and distribution of human papillomavirus (HPV) DNA or of increased expression of the p53 protein were determined in 71 patients with esophageal squamous‐cell carcinoma (SCC) by in situ hybridization with biotinylated DNA probes for HPV‐16, ‐18,‐31 and ‐33, and immunohistochemical techniques using antibody to p53 protein. Of 71 patients from Kochi prefecture, 24 (Group I) were positive for HPV DNA, including 10 for HPV type‐16 and 14 for HPV type‐18; in contrast, none were positive for HPV‐31 or ‐33. Of the remaining 47 patients, 24 (Group II) showed positive nuclear staining in cancer cells with p53 antibody. The group of 23 patients with neither HPV nor p53 expression (Group III) had a significantly better survival rate than Group I or II. These results suggest that HPV‐16 and ‐18 may play a role in the pathogenesis of esophageal SCC, particularly with regard to its striking geographical distribution; that esophageal cancers do occur in the absence of HPV infection when over‐expression of p53 is present; and that the presence of HPV infection and over‐expression of p53 may each be a factor indicating a relatively poor prognosis.
Appearance of amplified thymidylate synthase or dihydrofolate reductase genes in stage‐IV breast‐cancer patients receiving endocrine treatment
Authors: Lönn Ulf , Lönn Sigrid , Stenkvist Björn 
Published: February 2007

AbstractWe have examined the appearance of amplification of 2 genes involved in resistance to chemotherapy (thymidylate synthase, dihydrofolate reductase) in patients receiving endocrine treatment. Chronological tumor samples were obtained from breast‐cancer patients with clinical stage‐IV disease, using fine‐needle biopsies. The presence of amplification of thymidylate synthase and dihydrofolate reductase was determined using PCR in 185 fine‐needle biopsies from 37 patients. None of the initial samples of each patient showed amplification. However, in 7 of the 37 patients (19%) we detected development of gene amplification: in 2 cases of thymidylate synthase and in 5 cases of dihydrofolate reductase. Five of the 7 patients with amplification were receiving second‐line endocrine treatment after failing to respond to tamoxifen.
Prevalence of G‐TO‐T transversions among K‐ras oncogene mutations in human colorectal tumors in Yugoslavia
Authors: Urošević Nadežda , Dujić Aleksandar , Krtolica Koviljka , Škaro‐Milić Andjelija , Knežević‐Ušaj Slavica 
Published: February 2007

AbstractHuman colorectal carcinoma tissue sampled from 37 patients, routinely graded into Dukes' stages A, B and C and histologically examined for the level of differentiation, were analyzed for the presence of point mutations in the K‐ras oncogene. Seventeen cases out of the 37 analyzed were found to have a mutation in either the 12th or the 13th codon of the K‐ras gene, giving an overall frequency of mutation of 46%. The incidence of mutations in Dukes' stages A, B and C was 33, 46 and 58% respectively. Although the frequency of mutation appears to be similar to that reported for the USA population, the spectrum of point mutations in codons 12 and 13 of the K‐ras gene in the Yugoslav population appears to differ significantly. G‐to‐T trans‐versions make up 77% of all mutations present, with the distribution as follows: 18% at the first base and 59% at the second base of codons 12 and 13. G‐to‐A transitions at the second base is the only other mutation identified, occurring mainly in codon 13 in colorectal tumors of all 3 stages.
Expression of MaTu‐MN protein in human tumor cultures and in clinical specimens
Authors: Závada J. , Závadová Z. , Pastoreková S. , Čiampor F. , Pastorek J. , Zelník V. 
Published: February 2007

AbstractMaTu is a novel agent which may be of relevance in human oncogenesis, and has 2 components. One of them, the exogenous MX (coding for protein p58X), is transmissible to human fibroblasts, to HeLa and to HeLa × fibroblast (H/F) hybrids. The other component, MN, is a cellular gene. Its product, the protein p54/58N, is inducible by infecting HeLa cells with MX or by growing them in dense cultures. This p54/58N appears to be a tumor‐associated antigen: it is expressed in HeLa and in tumorigenic cells (H/F‐T), but not in fibroblasts or in non‐tumorigenic hybrid cells (H/F‐N). Proteins related to p54/58N were also found on immunoblots prepared from human carcinomas of ovary, endometrium and uterine cervix, but not from normal tissues from corresponding organs or from placenta. Using genetically engineered MN protein, we developed a radioimmunoassay for MN‐specific antibodies, and for quantitative determination of MN proteins in cell extracts. In HeLa cells infected with MX we observed conspicuous ultrastructural alterations: formation of abundant filaments on the cell surface and amplification of mitochondria. Using immunogold‐staining, we visualized the p54/58N on the surface microvilli and in the nucleus, particularly in nucleoli.
Effect of bombesin, gastrin‐releasing peptide (GRP)(14–27) and bombesin/GRP receptor antagonist RC‐3095 on growth of nitrosamine‐induced pancreatic cancers in hamsters
Authors: Szepeshazi Karoly , Halmos Gabor , Schally Andrew V. , Groot Kate 
Published: February 2007

AbstractFemale Syrian golden hamsters with N‐nitroso‐bis (2‐oxopropyl) amine (BOP)‐induced pancreatic cancers were treated for 2 months with bombesin/gastrin‐releasing peptide (GRP) antagonist D‐Tpi6, Leu13Ψ(CH2NH)Leu14 bombesin(6‐14) (RC‐3095). Bombesin and GRP(14–27) were also administered alone and in combination with the antagonist RC‐3095. RC‐3095 exerted a dose‐dependent inhibitory effect on growth of pancreatic cancers. The number of animals with pancreatic cancers was significantly lower in the group treated with 60 μg/day of RC‐3095 and the weight of tumorous pancreata was reduced. Administration of bombesin or GRP alone did not stimulate the growth of pancreatic tumors and, in fact, had a slightly suppressive effect on cancers which was significant only in Experiment I. Bombesin and GRP (14–27) given together with RC‐3095 did not nullify the inhibitory effect of the antagonist on pancreatic cancer growth. Actually, a greater inhibition of pancreatic tumors was observed after administration of RC‐3095 together with bombesin or GRP, than with RC‐3095 alone. The mechanism of action of bombesin, GRP, and bombesin antagonists on pancreatic cancers appears to be complex. The inhibitory effect of bombesin antagonists on pancreatic cancer growth was accompanied by a decrease in the binding capacity of EGF receptors in tumor membranes. Administration of bombesin also caused a down‐regulation of EGF receptors and the greatest decrease in binding capacity of EGF receptors was observed after treatment with RC‐3095 in combination with GRP. Inhibition of pancreatic cancer can thus be tentatively explained by some common pathways in the action of bombesin, GRP and their antagonists, that could be mediated by interference with EGF‐receptor mechanisms.