bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eradication of a disseminated mouse lymphoma by 1,3‐BIS(2‐chloroethyl)‐1‐nitrosourea is immunologically mediated and accompanied by de novo generation of anti‐tumor cytotoxicity
Authors: Sensi Marialuisa , Bergomi Marzia , Formelli Franca , Parmiani Giorgio 
Published: February 2007

AbstractThe anti‐tumor effect of 1, 3‐bis(2‐chloroethyl)‐I‐nitrosourea (BCNU) was examined in BALB/c mice bearing increasing burdens of a syngeneic lymphoma (YCB). A single i. p. injection of the drug resulted in over 75% of cures when given at day 3, 5, 7 or 10 after an i. v. inoculum of 104 YCB cells. The efficacy of BCNU on mice bearing large tumor burdens (from day 5 on) was not only due to its tumoricidal activity, but was immunologically mediated. Residual tumorigenic cells could be recovered in the livers of 5‐day tumor bearers (TB) up to 2 weeks after BCNU treatment and only a low percentage of cures could be achieved when BCNU was administered to nude mice. In addition, BCNU‐cured mice specifically rejected a lethal YC8 challenge and their splenocytes developed anti‐tumor cytotoxicity in response to in vitro stimulation with YC8 cells. During kinetic experiments a 2‐week period elapsed after BCNU injection before an anti‐tumor cytotoxic T‐lymphocyte (CTL) response could be generated by spleen cells of BCNU‐treated 5‐day TB. This period was characterized by immunosuppression as evaluated from impairment in the generation of lymphokine‐activated killer (LAK) cells or of allospecific primary CTL responses by spleen cells from BCNU‐treated 5‐day TB and BCNU‐treated normal mice. LAK cells first recovered and could be generated 7 days later, whereas primary allospecific CTL responses could only be detected by day 14. concomitantly with the generation of antitumor cytotoxicity by 5‐day TB. The development of secondary in vitro CTL responses, however, was permanently abrogated. Spleen cells from BALB/c mice immunized either with YC8 or with DBA/2 minor histocompatibility antigens and treated with BCNU I week after the last immunization failed to mount an in vitro CTL response to their immunizing antigen, even when the cultures were supplemented with recombinant interleukin‐2.
Degradation of alpha‐melanocyte stimulating hormone (alpha‐MSH) by CALLA/endopeptidase 24. 11 expressed by human melanoma cells in culture
Authors: Deschodt‐Lanckman Monique , Vanneste Yves , Loir Béatrice , Michel Alain , Libert Anita , Ghanem Ghanem , Lejeune Ferdinand 
Published: February 2007

AbstractThe common acute lymphoblastic leukemia antigen (CALLA) is identical to human endopeptidase 24.11 (E‐24.11) and is expressed on certain human melanoma lines. This work was conducted in order to investigate whether alphamelanocyte‐stimulating hormone (alpha‐MSH) could be a substrate for E‐24.11, its degradation leading to the negative alpha‐MSH radiobinding assay results observed with some CALLA‐positive cell lines. We used 3 human melanoma cell lines (GLL‐19, Mel Juso and G361) which lack receptors to alpha‐MSH and express CALLA, and, as a control, one CALLA‐negative melanoma cell line (HBL) with specific receptors for alpha‐MSH. Radioimmunoassays give evidence that alpha‐MSH was degraded in the presence of the 4 melanoma cell lines and that disappearance of the peptide was significantly reduced by phosphoramldon in 2 lines (GLL‐19 and G361). Upon incubation of alpha‐MSH with GLL‐19 and G361 cell membranes, 3 degradation products were completely abolished in the presence of phosphoramidon. Amino acid content analysis of alpha‐MSH fragments produced by purified E‐24.11 permitted identification of 6 peptide bonds in the sequence of alpha‐MSH susceptible to cleavage by the enzyme. It is concluded that alpha‐MSH is a substrate in vitro for purified E‐24.11 and for the enzyme present on the human melanoma cell lines GLL‐19 and G361, expressing a high level of endopeptidase activity. However, hydrolysis of alpha‐MSH by this enzyme does not seem to represent the main factor responsible for the apparent absence of receptors for the hormone on some cell lines.
Nutrition and cancer of the oral cavity and pharynx in north‐east italy
Authors: Franceschi Silvia , Bidoli Ettore , Barón Anna E. , Barra Salvatore , Talamini Renato , Serraino Diego , La Vecchia Carlo 
Published: February 2007

AbstractThe relation between dietary indicators and the risk of cancer of the oral cavity and pharynx was investigated in a case‐control study conducted in Pordenone province, north‐east Italy, on 302 cases (266 males and 36 females) and 699 controls admitted to hospital for acute, non‐neoplastic and non‐digestive disorders. Positive associations were observed, after allowing for occupation, smoking and drinking habits, with more frequent consumption of pasta or rice, polenta, cheese, eggs and pulses (odds ratios ‐ Ors = 1.6, 2.1, 1.9, 1.9 and 2.0 for highest vs. lowest tertile), whereas reduced ORs emerged in subjects reporting more frequent consumption of carrots, fresh tomatoes and green peppers (ORs = 0.6, 0.5 and 0.5, respectively). Higher frequency of daily meals was also associated with a significantly elevated OR (1.7 for ≥ 4 vs. ≤ 2 meals). The role of various indicator foods must be assessed in the context of the very high levels of alcohol consumption in the study area (≥ 8 alcoholic drinks/day in 2/3 cancer cases).
Prognostic importance of cellular dna content in head‐and‐neck squamous‐cell cancers. A comparison of retrospective and prospective series
Authors: Kearsley John H. , Bryson Greg , Battistutta Diana , Collins Russell J. 
Published: February 2007

AbstractFlow cytometric DNA‐ploidy measurements were performed on formalin‐fixed tumour specimens from 172 patients with squamous‐cell cancers (SCCs) of the head and neck region. One hundred and two samples were chosen retrospectively and a further 70 consecutive patients were analysed prospectively in order to assess the prognostic significance of DNA ploidy and DNA index (D1). There were no statistically significant differences between retrospective and prospective groups in regard to age, sex, TNM stage, ploidy or D1. Sixty‐seven percent of patients were aneuploid (65% retrospective; 71% prospective). The proportion of aneuploid tumours was significantly higher among poorly differentiated tumours. Survival analysis using Cox multivariate regression modelling revealed that DNA aneuploidy and increasing D1 were significant independent prognostic factors for both relapse‐free and overall survival. The relapse and death rates among aneuploid subjects were approximately 3 times as high as those for diploid subjects. Patients with a D1 >2.11 (hyper‐tetraploidy) experienced a 6.6‐fold higher death rate than diploid subjects. These results provide strong support for the incorporation of DNA ploidy profiles into the clinical management of patients with head and neck cancer.
Kaposi's sarcoma and non‐hodgkin's lymphoma in european aids cases. no excess risk of kaposi's sarcoma in mediterranean countries
Authors: Casabona Jordi , Melbye Mads , Biggar Robert J. 
Published: February 2007

AbstractPrior to the AIDS epidemic, Kaposi's sarcoma (non‐AIDS‐KS) in Europe was mainly a disease of elderly Mediterranean men. In 1989 AIDS data from 15 European countries were collected to study proportional trends in AIDS‐related Kaposi's sarcoma (AIDS‐KS) in order to determine whether specific factors in Southern Europe might be important in the development of KS among AIDS patients. Another AIDS‐related cancer, non‐Hodgkin's lymphoma (NHL) was included as a malignancy control. Of 22,367 AIDS cases reported, 3,779 (16.9%) were KS and 741 (3.3%) were NHL. A significant, continuous fall in the percentage of AIDS‐KS was seen for both homosexual men and other members of exposure groups during the period 1981‐89 (p‐trend <0.000l). The proportion with AIDS‐KS decreased from 40.5% in 1983 to 26.5% in 1988 in homosexual men and from 12.2 to 3.6% in other exposure groups, respectively. No significant change was observed in the proportion of NHL cases among any of the risk groups over time, although a tendency towards a slight increase was noted for homosexual men. Comparing proportional trends of KS and NHL geographically, no significant difference was found overall, by time or by exposure group. In conclusion, a specific decline is observed over time for AIDS‐KS. However, if geographically‐restricted factors are important in the development of non‐AIDS‐KS in Europe, the same factors do not appear to affect the risk of AIDS‐KS.
Enhancement by sulpiride of the inhibitory effects of cysteamine on gastric carcinogenesis induced by n‐methyl‐n'‐nitro‐n‐nitrosoguanidine in wistar rats
Authors: Tatsuta Masaharu , Iishi Hiroyasu , Baba Miyako , Nakaizumi Akihiko , Uehara Hiroyuki , Taniguchi Haruo 
Published: February 2007

AbstractThe effects of sulpiride on cysteamine inhibition of gastric carcinogenesis induced by N‐methyl‐N′‐nitro‐N‐nitroso‐guanidine (MNNG) and on the BUdR labelling index of gastric mucosa were investigated in inbred Wistar rats. After 25 weeks of oral treatment with MNNG, rats received one of the following alternate‐day injections: cysteamine (2 doses), cysteamine (2 doses) plus sulpiride or sulpiride. At week 52, prolonged administration of cysteamine significantly reduced the incidence of adenocarcinomas of the glandular stomach. Cysteamine at low dose had no effect on the incidence of gastric cancers, but a combination of low‐dose cysteamine and sulpiride caused a significantly greater reduction in the incidence of gastric cancers. Administration of sulpiride alone had no influence on gastric carcinogenesis. The labelling index of the antral mucosa was significantly lower in rats treated with high but not low doses of cysteamine. However, a combination of low‐dose cysteamine and sulpiride significantly decreased the labelling index of the antral mucosa. Our findings indicate that cysteamine suppressed gastric carcinogenesis and that sulpiride enhanced this inhibition. Because sulpiride is a dopamine antagonist, these findings also indicate that dopamine may play an important role in cysteamine inhibition of gastric carcinogenesis.
Role of activated c‐H‐ras Oncogene in the induction and progression of immortal liver epithelial cell lines derived from normal C3H mice
Authors: Lee Gang‐Hong , Sakai Ryuichi , Nagao Minako , Kitagawa Tomoyuki 
Published: February 2007

AbstractThe nature of 15 immortal mouse liver epithelial cell (MLEC) lines established from normal C3H mice was investigated specifically in terms of ras oncogene activation. Neither transforming activity nor point mutation within codon 61 of c‐H‐ras could be demonstrated in any of the cell lines by DNA transfection in a NIH/3T3 cell system or by the direct sequencing method after polymerase chain reaction, respectively. Acrylamide gel migration analysis of ras p2l products did not show any shift from the normal. Transplantation experiments demonstrated only 2 out of the 15 lines to be tu‐morigenic in nude mice. When 4 of the non‐tumorigenic MLEC lines were transfected with cloned activated c‐H‐ras containing a point mutation within codon 61, they all became tumorigenic, the resultant neoplasms being hepatocellular carcinomas often associated with albumin mRNA expression. Our results thus indicate that ras activation is not necessary for immortalization or even for transformation of mouse liver cells in culture, and that ras activation may be an event during the progression process in mouse hepatocarcinogene‐sis in vivo.
Heterotransplantation of human breast carcinomas in nude mice. Correlation between successful heterotransplants, poor prognosis and amplification of the her‐2/neu oncogene
Authors: Giovanella Beppino C. , Vardeman Dana M. , Williams Leo J. , Taylor D. Jane , De Ipolyi Peter D. , Greeff Pierre J. , Stehlin John S. , Ullrich Axel , Cailleau Relda , Slamon Dennis J. , Gary Howard E. 
Published: February 2007

AbstractFour hundred and thirty‐three human breast carcinomas and 23 cell lines derived from human breast carcinomas were heterotransplanted in nude mice. Twenty‐eight tumors and 13 cell lines took and could be serially transplanted. Their human origin was established by isozyme analysis performed on successive passages. Sixteen primary infiltrating duct‐cell carcinomas (PIDC) took, from a total of 262 transplanted (6.1%). This is in striking contrast to the >50% rate of takes of most major cancers of epithelial origin. All 16 PIDC growing in nude mice were highly cellular and lacked desmoplastic hyperplasia. The clinical prognosis of the PIDC patients whose tumors were successfully transplanted was poor. Ten of 16 (63%) died of their disease within 3 years, compared to only 49 (20%) of the 246 PIDC patients whose tumors did not take in nude mice. This could not be attributed to later stage disease of the tumors that took, because only 15% of these patients had 4 or more positive axillary lymph nodes as opposed to 28% of the patients whose tumors did not take. Sixty‐four percent of the breast carcinomas growing in nude mice exhibited amplification of the HER‐2/neu oncogene which is also correlated with poor prognosis in human breast cancer. It is possible that the nude mouse is more susceptible to a population of highly invasive and lethal breast carcinomas.
Human ovarian cancer xenografts in nude mice: Characterization and analysis of antigen expression
Authors: Molthoff Carla F. M. , Calame Johannes J. , Pinedo Herbert M. , Boven Epie 
Published: February 2007

AbstractWe have characterized 13 different human ovarian cancer xenografts grown subcutaneously in nude mice. The tumor lines represented 5 histological subtypes: serous (4), mucinous (4), clear‐cell carcinoma (1), carcinosarcoma (1) and undifferentiated (3). The specific histology and the degree of differentiation resembled those of the original patients' tumors and were maintained upon serial transfer. Volume doubling times of the xenografts ranged from 3.5 to 15 days. The xenografts were also analyzed for their antigen expression using 20 monoclonal antibodies (MAbs) reactive with 15 tumor‐associated antigens. Immunohistochemical examination of tissue sections showed a positive reaction pattern with MAbs 115D8, 140C1, 139H2, 175C5, HMFG1 and HMFG2, each recognizing episialin, as well as with MAbs AUA1, 358.4.32 and 199‐157 in xenografts of the serous, mucinous and clear‐cell carcinoma subtype. MAb OC125 was reactive with xenografts of the serous subtypes. Other antibodies, such as 494 and OV‐TL3 infrequently demonstrated positive reactions. Reactivity of all MAbs was low in the carcinosarcoma and undifferentiated tumor lines. With the exception of AUA1, 495 and I26E5, all MAbs revealed a heterogeneous staining pattern. MAbs against episialin and OC125 predominantly stained the apical site of the tumor cells. Strongest reactivity with almost all histological subtypes was observed with MAbs 115D8, 140C1, 139H2 and AUA1. In cases where we were able to compare the patients' tumor tissue with the respective xenografts, retention of antigen expression was demonstrated in each instance. Release of tumor‐associated antigens was shown for CA125 in 2 serous‐tumor lines, for CA15.3 in I serous‐tumor line, and for CEA in 3 lines of the mucinous subtype. This panel of human tumor xenografts could be a valuable tool to determine the potential usefulness of MAb‐guided therapy in ovarian cancer.
Counteraction of estradiol‐induced activation of tissue‐type plasminogen activator in a human breast cancer cell line by an anti‐estrogen, LY117018
Authors: Uchiumi T. , Mizoguchi H. , Hagino Y. , Kohno K. , Kuwano M. 
Published: February 2007

AbstractLY117018 is a non‐steroid anti‐estrogen which exhibits about 100 times higher affinity for estrogen receptor than tamoxifen, another anti‐estrogen. The cell line ES‐1, which was isolated from human breast cancer MCF‐7 cells, was highly sensitive to the cytocidal action of estradiol. Growth of ES‐I cells was inhibited by 10−8M 17 β‐estradiol, a concentration that stimulated the growth of parental MCF‐7 cells. The estradiol‐induced growth inhibition of ES‐1 cells was almost completely reversed by treatment with LY 117018, but not by treatment with tamoxifen. The relative binding affinity of LYI17018 for estradiol receptor was equal to that of estradiol in both MCF‐7 and ES‐1 cells. Treatment of ES‐1 cells with estradiol specifically induced tissue‐type plasminogen activator (t‐PA), whereas such estradiol‐induced activation was not observed in parental MCF‐7 cells. Quantitative immunoreac‐tive assays and Northern blot analysis showed that estradiol‐induced expression of t‐PA was blocked by LYI 17018 in ES‐1 cells. The inhibitory effect of tamoxifen was about 100 times lower than that of LYI 17018. The inhibition of t‐PA gene expression by LYI 17018 might be due to competitive inhibition with estradiol in estradiol receptor binding.
Regressing nude mouse grafts of burkitt's lymphoma×lymphoblastoid cell hybrids show deregulation of the c‐myc gene and expression of the EBV latent membrane protein
Authors: Wolf Jürgen , Klevenz Britta , Pawlita Michael , Komitowski Dimitrij , Moldenhauer Gerd , Hausen Harald Zur 
Published: February 2007

AbstractSomatic cell hybrids between the malignant Burkitt lymphoma cell line BL 60 and the non‐malignant Epstein‐Barr virus (EBV) immortalized lymphoblastoid cell line (LCL) IARC 277 demonstrate the deregulated c‐myc transcription pattern of the parental BL cell line during exponential growth in tissue culture. Subcutaneous nude mouse grafts of these hybrids, however, completely regress after an initial growth phase. To investigate whether regression of these grafts is mediated by a down‐regulation of the BL‐60‐derived deregulated c‐myc gene in vivo, c‐myc transcription was analyzed in growing versus regressing hybrid grafts. In the initial growth phase as well as during regression, these grafts showed the deregulated c‐myc expression pattern of the parental BL cell line with highly abundant c‐myc transcripts originating from the BL specific translocation chromosome 8q+. Our results question the significance of c‐myc deregulation for an unlimited in vivo growth potential of B‐lymphoblastoid cells. To further characterize the hybrids, surface expression of B‐cell‐specific antigens was analyzed on the hybrids and shown to correspond to that of the parental LCL. In addition, transcription of the gene encoding for the EBV latent membrane protein (LMP) as well as histological features were analyzed in growing versus regressing hybrid grafts. The LMP gene, which is down‐regulated in the tumors produced by the parental BL cells, was expressed in the hybrid grafts as well as in the parental LCL grafts. This finding might be compatible with a host response of the nude mouse against LMP. The histological analysis, however, which revealed massive necrosis in the center of the regressing grafts without pronounced inflammatory infiltrates, rather points to a hypoxemic process leading to graft regression.
Receptor‐mediated endocytosis and recycling of alpha‐fetoprotein in human B‐lymphoma and T‐leukemia cells
Authors: Torres Juan M. , Geuskens Maurice , Uriel Jose 
Published: February 2007

AbstractThe kinetics of iodinated human alpha‐fetoprotein (AFP) binding and uptake by 2 human neoplastic lymphoid cell lines (CEM and RAJI) have been studied. Three saturation plateaus were obtained by incubating CEM and RAJI cells at 4°C with 125I‐AFP at different concentrations. Scatchard analysis suggested the presence of 3 types of receptor site with different affinities and capacities on cells of both lines. AFP binding was inhibited by unlabelled human and bovine AFP, and to a lesser extent by human serum albumin (SAH); no significant competition was observed with human transferrin (Tf) or ovalbumin (Ova). Pulse‐chase experiments showed that 125I‐AFP was released practically undegraded from the cells. Covalent conjugates of AFP and Tf with horseradish peroxidase (HRP) were used to follow the endocytosis and intracellular pathway of these serum proteins by electron microscopy. Both proteins were observed in coated vesicles, endosomes and a tubular vesicular network localized in the Golgi‐centrosphere region. SAH‐HRP was internalized to a much lesser extent. Ova‐HRP was poorly internalized and was observed in lysosome‐like organelles.
Dominance of metastatically competent cells in primary murine breast neoplasms is necessary for distant metastatic spread
Authors: Theodorescu D. , Cornil I. , Sheehan C. , Man S. , Kerbel R. S. 
Published: February 2007

AbstractWe have previously shown, using tumor cell populations genetically tagged by random integrations of plasmid DNA, that metastatically‐competent clonal cell variants have a strong growth advantage within primary tumors over their non‐metastatic counterparts. As a result, primary tumors can become overgrown by the progeny of such cells, a process referred to as “clonal dominance” of primary tumors by metastatically‐competent cells. Because of the well‐known “metastatic inefficiency” of the multi‐step cascade process of spread and growth, clonal dominance within primary tumors may be necessary for distant metastatic spread or increase the probability of its occurrence. To examine this hypothesis mice were inoculated s.c. with mixtures of non‐metastatic and genetically tagged, metastatically‐competent mouse mammary carcinoma cells in defined ratios, but always containing an excess of the unmarked non‐metastatic population. Progressive overgrowth of the metastatic subpopulation was monitored as a function of time by Southern analysis of DNA obtained from mixed primary tumors. This allowed us to evaluate the effects that surgical removal of the primary tumor had before, during and after effective clonal dominance, and what influence this had on the subsequent formation of distant metastases. Surgical removal of primary tumors before metastatic clonal dominance resulted in a low (0‐25%) frequency of lung metastases, whereas removal just 1 or 2 weeks later during or after clonal dominance was achieved resulted in a high (75‐100%) frequency of such metastases. Our results support the hypothesis that dominance of primary tumors by metastatically competent cells may be necessary for distant metastatic spread, and also suggest that clonal interactions play a significant role in modulating the metastatic ability of tumor cells in vivo.
Protein kinase C activation by anthracyclines in swiss 3T3 cells
Authors: Lanzi Cinzia , Gambetta Romolo Achille , Perego Paola , Banfi Patrizia , Franzi Aimarita , Guazzoni Lorena , Zunino Franco 
Published: February 2007

AbstractThe effects of the anti‐cancer anthracyclines doxorubicin and daunorubicin on the activity of protein kinase C (PKC) were examined in intact Swiss 3T3 cells. The 2 drugs stimulated the phosphorylation of an 80K phosphoprotein found to be identical to that generated in response to the PKC activator 12‐O‐tetradecanoylphorbol‐13‐acetate as indicated by gel electrophoresis and peptide mapping. The effect of doxorubicin was dose‐dependent in the range 10−5 to 10−3 M and was not associated with a detectable translocation of PKC activity from cytosol to the cell membrane. Doxorubicin and daunorubicin were found to increase the incorporation of phosphate into phosphatide acid, phosphatidylinositol 4‐monophosphate and phosphatidyl inositol 4,5‐bisphosphate. In addition, the anthracyclines induced a rise in inositol phosphates, thus indicating a stimulation of the breakdown of phosphoinositides. These data are consistent with an indirect mechanism of PKC activation by anthracyclines. We propose that diacylglycerol, which is derived from the hydrolysis of phospholipids, (including the phosphoinositides), by activation of phospholipases, could mediate PKC activation. The described effects, involving cell‐signal‐transducing pathways, emphasize a new aspect of the cellular actions of these anti‐tumor agents.