bluuebunny/crossref_metadata_2025_split huggingface dataset:
A role for the fyn oncogene in metastasis of methylcholanthrene‐induced fibrosarcoma a cells
Authors: Takayama Tetsuji , Mogi Yoshihiro , Kogawa Katsuhisa , Yoshizaki Naohito , Muramatsu Hirohito , Koike Kazuhiko , Semba Kentaro , Yamamoto Tadashi , Niitsu Yoshiro 
Published: February 2007

AbstractExpression of various oncogenes (ras, myc, erbB2, src, fyn, yes and sis) in a high‐metastatic clone (MH‐02) derived from a murine methylcholanthrene‐induced fibrosarcoma A (Meth A) was compared with those of its parent clone (ML‐01) by Northern blot analysis. Two oncogenes, fyn, belonging to the tyrosine‐kinase family, and sis, belonging to the cellular‐growth‐factor family, were found to have higher signals (3.6‐fold and 1.8‐fold respectively) in MH‐02 than in ML‐01 cells. To explore the possibility that higher expression of these oncogenes is involved in enhanced metastasis of the MH‐02 clone, ML‐01 was transfected by a fyn vector and the metastatic potential of the transfectant was examined. Mice administered fyn‐transfected ML‐01 cells had significantly increased metastatic nodules in the lung, as compared with those whose ML‐01 cells were transfected with control vector without the fyn gene. The result indicates that the fyn gene is one of the factors governing the metastatic potential of Meth A cells.
Cancer‐cell traffic in the liver. III. Lethal deformation of B16 melanoma cells in liver sinusoids
Authors: Barbera‐Guillem Emilio , Weiss Leonard 
Published: February 2007

AbstractIt has previously been shown that most of the B16 F10 melanoma cells delivered to the mouse liver via the portal vein are rapidly killed in periportal zone 1 of the sinusoids. Few intact viable cells reach pericentral zone 3 of the sinusoids and of these, only a very small proportion leave the liver to colonize the lungs. The hypothesis has been advanced that one nonexclusive, potential mechanism for cancer‐cell destruction in the liver is a result of the deformation of cancer cells when they enter vessels of smaller diameter than themselves. Where entry is associated with change in shape from spheroid to cylindrical, a mandatory increase in cancer‐cell surface area occurs, which is first apparent and utilizes surface membrane excess (rugosity). If this increase is insufficient, a real increase occurs which, if in excess of approximately 4%, results in lethal surface membrane rupture. This hypothesis predicts that, under these circumstances, cancer‐cell resistance to mechanical trauma is favored by small diameter and utilizable surface membrane excess. To test this hypothesis, the traffic of melanoma cells in the liver following portal‐vein injection has been observed by confocal microscopy and image reconstruction. In accordance with the hypothesis, non‐disrupted cells within the sinusoids have a smaller mean diameter than that of the original inoculum, and show evidence of utilization of surface membrane excess. The results indicate that deformation‐associated trauma, suffered by cancer cells on entry and residence in the microvasculature, may well be an important factor contributing to metastatic inefficiency.
Intravesical administration of indium‐111‐labelled hmfg2 monoclonal antibody in superficial bladder carcinomas
Authors: Bamias A. , Bowles M. J. , Krausz T. , Williams G. , Epenetos A. A. 
Published: February 2007

AbstractTumour‐associated HMFG2 monoclonal antibody (MAb) was labelled with indium‐111 and administered intravesically to 20 patients with known or suspected superficial bladder carcinoma. The antibody solution was kept in the bladder for 1 hr and was then washed out. Cystoscopy was performed at 2 and 24 hr after instillation. Radioactivity of tumour and normal tissue obtained from the bladder during cystoscopy and cells recovered from urine after the instillation were counted in a gamma‐counter. Conventional histology, immunocytochemistry and autoradiography were also performed. Mean uptake at 2 and at 24 hr was higher in tumours than in normal samples. Autoradiography showed selective accumulation of radioactivity in cells which expressed the antigen detected by the HMFG2 MAb. There was no correlation of tumour uptake with the grade of tumour. No radioactivity was found in the blood of patients after the instillation. Based on dosimetric calculations, however, the radiation dose that can be delivered to the tumours is not sufficient to be cytotoxic, possibly due to inadequate penetration and retention by tumour tissue. Nevertheless, the significant difference between antibody uptake by the tumours and that by normal urothelium, observed in our study, allow for the possibility of using this approach therapeutically.
Nk‐cell activity in patients with hpv16‐associated anogenital tumors: Defective recognition of hpv16‐harboring keratinocytes and restricted unresponsiveness to immunostimulatory cytokines
Authors: Malejczyk Jacek , Malejczyk Magdalena , Majewski Slawomir , Orth Gerard , Jablonska Stefania 
Published: February 2007

AbstractPeripheral blood mononuclear cells (PBMC) from patients with active HPV16‐associated pre‐malignant and malignant anogenital lesions display a significantly decreased NK‐cell activity against HPV16‐harboring SKv keratinocytes (NK/SKv) while their cytotoxicity against erythroleukemic K562 cells (NK/K562) remains unaffected. A similar defect can also be seen in some healthy individuals displaying no symptoms of HPV infection (low responders). Analysis with specific Leu I la monoclonal antibodies (MAbs) has revealed that all patients as well as weakly responding control subjects had normal numbers of circulating CD 16+ NK cells. However, PBMC from patients with active disease and weakly responding controls displayed a significantly decreased ability to bind SKv cells. Binding of K562 was in the normal range. In patients in whom the lesions were successfully removed or regressed spontaneously (patients with no lesions), NK/SKv activity did not differ from that of normally responding healthy subjects and the ability of their PBMC to bind SKv cells was unaffected. To determine whether an abrogated NK/SKv cytotoxicity may be corrected by NK‐cell stimulatory cytokines, PBMC were pre‐incubated overnight with IL‐2 and interferon‐α. Both cytokines stimulated NK/K562 activity in all tested groups. Significant stimulation of NK/SKv activity was observed in PBMC from normal and weakly responding controls as well as patients with no lesions. No increase could be seen in patients with active disease. Evaluations of NK‐cell activity before and after surgical removal or spontaneous regression of the lesions showed normalization of primarily depressed NK/SKv activity. Malignant progression was associated with a significant drop in SKv cell killing. Our results suggest that abrogation of NK‐cell activity against HPV16‐harboring targets in patients with HPV16‐associated anogenital neoplasia is associated with restricted inability to recognize the disease‐specific target cells, and may depend on persistence of the lesions.
Loss of heterozygosity on chromosome 13 and its association with delayed growth of retinoblastoma
Authors: Kato Mitsuo V. , Ishizaki Kanji , Ejima Yosuke , Kaneko Akihiro , Tanooka Hiroshi , Sasaki Masao S. 
Published: February 2007

AbstractLoss of heterozygosity (LOH) on chromosome 13 and the age of patients at operation were studied in 46 cases of retinoblas‐toma (RB) tumors, of which 25 were hereditary and 21 were non‐hereditary. The frequency of LOH was 70% for all informative tumors, but significantly higher in non‐hereditary tumors (90%) than in hereditary ones (52%). Our results suggest that LOH might be involved in the initial somatic events in non‐hereditary tumors. Age at operation of patients with hereditary tumors was significantly lower than that of patients with non‐hereditary tumors. Even when tumors associated with a family history were omitted from among the hereditary cases, the difference was still significant. In the case of hereditary tumors, age at operation of LOH‐negative patients was significantly lower than that of LOH‐positive patients. When tumors associated with a family history were omitted, the difference was still significant. The delay in development of LOH‐positive tumors suggests that LOH for one chromosome 13 may be disadvantageous with respect to growth of RB tumors.
L‐myc Proto‐oncogene alleles and susceptibility to hepatocellular carcinoma
Authors: Taylor Jack A. , Bell Douglas A. , Nagorney David 
Published: February 2007

AbstractA common inherited RFLP of the L‐myc proto‐oncogene has been reported to correlate with cancer susceptibility or prognosis for some tumors. Using a PCR‐based RFLP assay on DNA extracted from peripheral blood samples, we determined the L‐myc EcoRI genotype of patients with HCC, patients with other liver tumors, and healthy controls. In this polymorphism there are 2 alleles, L and S, which define 3 possible genotypes: LL, LS, and SS. While the genotype distribution of patients with other liver tumors and healthy controls do not differ from one another, both differ significantly from the genotype distribution of patients with HCC. This difference is primarily the result of a low frequency of the SS genotype among HCC patients compared to controls or other liver tumor patients. Persons with the SS genotype appear to be protected against HCC and have roughly one‐ninth the risk of persons who carry one or more copies of the L allele. Within HCC cases, patients with different L‐myc genotypes show slight, but not statistically significant, differences in tumor characteristics and survival.
Expression of the c‐erbB‐3 gene product in gastric cancer
Authors: Sanidas E. E. , Filipe M. I. , Linehan J. , Lemoine N. R. , Gullick W. J. , Rajkumar T. , Levison D. A. 
Published: February 2007

AbstractThe pattern of c‐erbB‐3 gene product was studied in 91 advanced gastric carcinomas, adjacent hyperplastic mucosa, intestinal metaplasia and dysplasia and in normal controls, using immunohistochemistry in archival material. All tumours showed positive c‐erbB‐3 staining in both cytoplasm and membrane. No significant differences of expression were observed between intestinal and diffuse‐type carcinomas or any other clinical parameters. Of interest is the expression in the adjacent mucosa, which is extensive, cytoplasmic, and of lower intensity than in the tumours. Further studies are currently being carried out to clarify the role of this protein in tumour behaviour and gastric carcinogenesis.
Pharmacokinetics and biological responses after treatment of the rat R‐1 rhabdomyosarcoma with methotrexate
Authors: Kipp J. B. A. , Leyva A. , Van Gennip A. H. , Kal H. B. 
Published: February 2007

AbstractTime relationships of drug concentrations in tissue of a transplantable rat rhabdomyosarcoma and of tumour responses up to 120 hr after treatment with methotrexate (MTX) were analysed and compared. MTX was shown to be retained within the tumour in a substantial concentration for several days, although no evidence of MTX polyglutamation was obtained. The response data confirm that MTX is active in the tumour for up to at least 3 days after injection. Within the first day after MTX treatment the nucleotide pools are only partly depleted. This indicates that the inhibition of DNA synthesis is still incomplete at the time when salvage precursors in increasing amounts are becoming available from decaying cells. From flow cytometric analysis of cell‐cycle progression it is concluded that subsequent cohorts arriving in early S‐phase were retarded, but not inhibited, in their progression through the S phase. At 3 days after MTX treatment the mean rate of cell‐cycle progression as well as the relative clonogenic capacity were maximally reduced to 30% and 1% of control values, respectively. From 3 to 5 days the rate of cell‐cycle progression was gradually restored, whereas from day 5 onwards the clonogenic capacity increased at a high rate corresponding to the proliferation rate of exponentially growing rhabdomyosarcoma cells in culture. However, a continuous reduction of cell recovery lasting for at least 12 days after treatment contributed to an 8‐day delay in tumour volume growth.
Infection with a transforming growth factor α anti‐sense retroviral expression vector reduces the in vitro growth and transformation of a human colon cancer cell line
Authors: Ciardiello Fortunato , Bianco Catcrina , Normanno Nicola , Baldassarre Gustavo , Pepe Stefano , Tortora Giampaolo , Bianco A. Raffaele , Salomon David S. 
Published: February 2007

AbstractTransforming growth factor α (TGFα) is a growth factor produced by colon cancer cells which may function as an autocrine growth regulator. Therefore, the proliferation and transformation of colon cancer cells might be attenuated by blocking the production of endogenous TGFα. GEO cells, from a human colon carcinoma cell line that expresses TGFα and functional epidermal growth factor (EGF) receptors, were infected with a replication‐defective, recombinant amphotropic retroviral expression vector containing the neomycin‐resistance gene and a 435‐bp Apal‐EcoRI coding fragment of the human TGF α cDNA oriented in the 3′ to 5′ direction under the transcriptional control of the heavy‐metal‐inducible mouse metallothionein 1 promoter. Following antibiotic selection, G418‐resistant colonies were pooled and expanded into a cell line (GEO TGFα AS cells). A 50 to 70% inhibition in the production of secreted and cell‐associated TGFα protein was observed in GEO TGFα AS cells that had been maintained in CdCI2‐supplemented medium. Moreover, a growth inhibition of 70% and 50% was observed in CdCI2‐treated GEO TGFα AS cells under anchorage‐dependent and anchorage‐independent culture conditions, respectively. In contrast, CdCI2 treatment of parental GEO cells had no significant effect upon these parameters. Our results suggest that TGFα may be involved in modulating the in vitro cell growth and transformation of human colon cancer cells that express both this growth factor and its cognate receptor.
Therapy of mouse mammary carcinomas with vincristine and doxorubicin encapsulated in sterically stabilized liposomes
Authors: Vaage Jan , Donovan Dorothy , Mayhew Eric , Uster Paul , Woodle Martin 
Published: February 2007

AbstractThis study tested the therapeutic effects of vincristine sulfate and doxorubicin hydrochloride, each drug in 2 different formulations: (i) as a solution in saline, and (ii) encapsulated in sterically stabilized, long‐circulating liposomes composed of hydroge‐natedsoy‐phosphatidylcholine/cholesterol/polyethylene‐glycer‐ol‐distearoyl‐ phosphatidylethanolamine. The 4 drug preparations were used to treat s.c. implants of the mouse mammary carcinoma MC2. The drugs were given by i.v. injection over 15 to 18 days, starting 3 days after tumor implantation. The single‐drug therapeutic effects of vincristine (S‐VCR) and doxorubicin (Doxil) in liposomes were compared, and the 2 preparations were also tested in alternate and in simultaneous combinations. These new liposome formulations of vincristine and doxorubicin were significantly more effective than the free drugs in curing the mice. Alternate, semi‐weekly injection of both drugs gave the best therapeutic effect. Prolonged circulation time with increased accumulation in tumors are considered likely reasons for the improved therapeutic efficacy of both drugs when encapsulated in these liposomes.
Characterization of four new cell lines derived from small‐cell gastrointestinal carcinoma
Authors: Fujiwara Takato , Motoyama Teiichi , Ishihara Noriko , Watanabe Hidenobu , Kumanishi Toshiro , Kato Kanefusa , Ichinose Hiroshi , Nagatsu Toshiharu 
Published: February 2007

AbstractFour human small‐cell gastrointestinal carcinoma cell lines were established from tumor tissues of patients with esopha‐geal, gastric or rectal cancer, and were studied morphologically and biochemically in comparison with small‐cell lung carcinoma (SCLC) cell lines and common gastric cancer cell lines. Cells from all the small‐cell gastrointestinal carcinoma lines were as small as classic SCLC cells and had characteristic neurosecre‐tory granules. Cells from only one line grew as tightly packed spherical aggregates of floating cells, and those of the other 3 grew attached to substrate. Although high levels of creatine kinase brain isoenzyme (CK‐BB) were detected in all 4 cell lines, 2 of them showed low levels of aromatic L‐amino‐acid decarbox‐ylase and 3 had low levels of neuron‐specific enolase (NSE). None of the lines showed simultaneous elevation of enzymes. C‐myc, N‐myc, and L‐myc were not amplified in any of the cell lines, but c‐myc mRNA was expressed in 2 lines. Our findings indicate that all small‐cell gastrointestinal carcinoma cells examined belong to the variant type which is used in the classification of SCLC. Furthermore, the ECC18 line, derived from esopha‐geal cancer, seemed to be of true endocrine cell origin, while the 3 other small‐cell gastrointestinal carcinoma lines seemed to arise via neoplastic neometaplasia from adenocarcinoma cells to endocrine cells.
Possible role of activated ras genes in human esophageal carcinogenesis
Authors: Galiana C. , Fusco A. , Martel N. , Nishihira T. , Hirohashi S. , Yamasaki H. 
Published: February 2007

AbstractActivation by point mutation of the H‐, K‐ and N‐ras genes is found in many tumors. However, no such mutation has yet been found in human esophageal carcinomas from various parts of the world. We have confirmed the absence of mutation at codons 12, 13 and 61 of K‐ and N‐ras and at codons 12 and 61 of H‐ras in 25 primary tumors obtained in France. In contrast, among 7 human esophageal carcinoma cell lines (TE1, TE2, TE3, TE8, TE9, TE TE10, TE 13) with different degrees of tumorigenicity in nude mice, 3 highly tumorigenic lines (TE1, TE2 and TE8) exhibited activation of ras oncogenes; 2 showed a G35 to A35 transition of K‐ras gene and one a H‐ras G35 to T35 transversion. Since these cell lines had been established from tumors of Japanese patients from Sendai, we examined 3 primary esophageal tumors from Tokyo and 19 from Sendai, including the primary tumors from which the TE cell lines had been derived. No ras mutation was detected, which suggests that the ras gene mutations in the TE cell lines are either due to their long‐term culture or that only a small portion of the original tumors contained such mutations. In order to directly examine the effect of ras gene mutation, one of the non‐tumorigenic cell lines, TE 13, was transfected with a plasmid coding for a mutated H‐ras gene (G35 to T35). Transfected clones expressing high levels of mutated ras gene were able to induce tumors in nude mice. Thus, although no primary human esophageal tumor contained mutated ras genes, our studies do not exclude a significant role of mutated ras genes in cell proliferation and malignant transformation of human esophageal cells.
Effect of reactive oxygen intermediates on the in vitro invasive capacity of tumor cells and liver metastasis in mice
Authors: Nonaka Yasuyuki , Iwagaki Hiromi , Kimura Toshikazu , Fuchimoto Sadanori , Orita Kunzo 
Published: February 2007

AbstractWe studied the role of reactive oxygen intermediates (ROls) in experimental liver metastasis induced in mice by the inoculation of COLON 26‐M5 murine colon cancer cells, a highly metastatic variant of COLON 26 cells, and the effect of ROIs on the invasive capacity of the cells in an in vitro chemo‐invasion assay model using reconstituted basement membrane matrigel. We also measured the release of ROIs from cells using electron spin resonance (ESR) spectrometry. Hydroxyl radicals (.OH) were constitutively released from the cells. This release was augmented by pre‐treatment with phorbol 12‐myristate 13‐acetate (PMA). In experimental liver metastasis in CDF1 mice, the administration of recombinant human superoxide dismu‐tase (r‐hSOD) significantly increased the number of metastatic nodules, while administration of catalase significantly inhibited metastasis formation. In vitro pre‐treatment of cells with PMA significantly increased the number of metastatic nodules. Invasive capacity of the cells was markedly augmented by pre‐treatment with PMA. PMA‐induced augmentation was significantly inhibited by the simultaneous addition of r‐hSOD to the assay. Catalase had no significant effect. Our findings suggest that ROIs play an important role in tumor invasion and metastasis, and that hydrogen peroxide (H2O2) may contribute to the retention or extravasation of circulating tumor cells. Furthermore, the superoxide anion (O2 ‐) released by tumor cells may play an important role in basement membrane degradation.
Increased yield in GST‐P‐positive liver pre‐neoplastic foci induced by dena or enu in rats pre‐treated with estradiol or tamoxifen
Authors: Servais P. , Galand P. 
Published: February 2007

AbstractWe investigated the mechanisms by which partial hepatec‐tomy (PH) increases the ability of chemical hepatocarcinogens to induce pre‐neoplastic liver foci. Comparison of the effects of pre‐treatment with PH, estradiol (E2) or tamoxifen (TAM) on the yield in glutathione‐S‐transferase(GST‐P)‐positive pre‐neoplastic foci in rat liver induced by subsequent treatment with ethylnitrosourea (ENU) or diethylnitrosamine (DENA) showed that pre‐treatment with E2 increased the yield in foci induced by subsequent treatment with ENU or DENA, as compared with that in animals not pre‐treated, the increase being of similar magnitude with either carcinogen. Compared with that of PH, the effect of the hormone was much more pronounced than would be expected from the relative mito‐genic effect of the hormonal and surgical pre‐treatments if the mitotic rate were the cause. On the other hand, the average volume of pre‐neoplastic liver lesions in rats treated with ENU or DENA was 2.5 to 5.0 times higher than in rats not pre‐treated whenever PH was included in the pre‐treatment, whereas it was not affected by any other pre‐treatment.
Transplantation of colon carcinoma into granulation tissue induces an invasive morphotype
Authors: Dingemans Koert P. , Zeeman‐Boeschoten Ingrid M. , Keep Robert F. , Das Pranab K. 
Published: February 2007

AbstractThe stroma surrounding many malignant tumors resembles granulation tissue. To test the hypothesis that such stroma stimulates tumor invasiveness, we compared, by electron microscopy and immunohistochemistry, the growth patterns of CC531 rat colon adenocarcinoma in 2 experimental situations: (i) after transplantation into the undisturbed subcutaneous connective tissue of rats, and (ii) after transplantation into experimentally induced subcutaneous granulation tissue in rats. For the latter experimental situation, a subcutaneous „tissue chamber”︁ was designed allowing fragments of tumor tissue to be transplanted into the very center of developing granulation tissue. In the undisturbed subcutaneous tissue, the whole tumor was generally encapsulated, and the tumor cells were arranged in compact groups with a strong tendency to form acini. In the pre‐formed granulation tissue, on the other hand, the tumor tissue closely matched descriptions of invasive colon carcinomas in the literature and met the criteria for the „invasive morphotype”︁. In this situation, the tumor consisted of thin, unorganized, widely dispersed strands of irregular tumor cells with numerous protrusions that deeply penetrated the surrounding matrix. Our results show that an invasive morphotype can be evoked by pre‐inducing granulation tissue at the transplantation site.