bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of protein kinase c and cytokines on the function and production of cytolytic granules in αCD3‐activated killer‐cell‐mediated killing of tumor cells
Authors: Wu Jennifer , Hargrove Myrthel E. , Ting Chou‐Chik , Shiver John 
Published: July 2010

AbstractThe effects of PMA and staurosporine (PKC depletor/antagonist) and IL‐2/IL4 were used to determine the role of PKC and cytokine on αCD3‐induced activated killer cells (CD3‐AK). The present study examines their effects on the production of BLT‐esterase and on the effector function of CD3‐AK cells as well as the cytolytic granules. The production of BLT‐esterase generally correlated with the cytolytic activity of CD3‐AK cells and was reduced by PKC depletor/inhibitor but increased by IL‐4. In studying the effector function of CD3‐AK cells, we found that adding PMA or SSP at the effector phase inhibited the PKC‐dependent slow lysis. PMA, but not SSP, also reduced fast lysis, which was shown to be a PKC‐independent event. Additional experiments were performed to determine the effect of PKC on the lytic granules and to ascertain whether PMA has other effects on the effector‐to‐target relationship unrelated to PKC. It was found that neither PMA nor SSP affects the function of cytolytic granules, as measured by hemolytic assay against anucleated target (SRBC). These findings indicate that PKC has no direct effect on the granules. During testing against the nucleated tumor target through a novel approach using non‐cytolytic surrogate killers, the lytic activity of the granules was inhibited by PMA, suggesting that exocytosis or delivery of granules to nucleated target cells may require mobilization of intracellular Ca2+ in the killer cells, and this process is inhibited by PMA. Our findings indicate that PKC and cytokines regulate the production but not the lytic activity of cytolytic granules. Nonetheless, delivery of cytolytic granules from killer cells to the nucleated tumor target appears to be a Ca2+‐dependent event unrelated to PKC.
c‐myc Gene activation as a permanent trait of RSV‐infected quail cells
Authors: Sovová Vlasta , Fidlerová Helena , Hlozánek I. , Friis R. 
Published: July 2010

AbstractA high level of c‐myc gene expression was found to be a constant feature of v‐src transformation. The c‐myc gene product was analyzed in quail embryo cells transformed by different mutants of Rous sarcoma virus (RSV) that were temperature‐sensitive with respect to various parameters of v‐src function. The high‐level expression of c‐myc proved not to be temperature‐sensitive: At both permissive (35°C) and non‐permissive (41°C) temperatures, the same high levels of c‐myc gene product were found for all RSV mutants tested. This result, in agreement with earlier evidence for a v‐src‐induced proliferative stimulus which was unaffected by ts mutants at the non‐permissive temperature, shows that certain v‐src functions have not yet been fully characterized.
T‐cell‐receptor engagement and tumor ICAM‐1 up‐regulation are required to by‐pass low susceptibility of melanoma cells to autologous CTL‐mediated lysis
Authors: Anichini Andrea , Mortarini Roberta , Parmiani Giorgio , Alberti Saverio , Mantovani Alberto 
Published: July 2010

AbstractTumor‐specific and non‐specific CD3+, TcRαβ+, CD8+ cytotoxic T‐cell (CTL) clones, isolated from tumor‐infiltrating lymphocytes (TIL) or peripheral blood lymphocytes (PBL) of a melanoma patient and allogeneic LAK cells, were used to investigate the requirements for bypassing the low lysability of some melanoma clones derived from an S.C. metastasis from which highly lysable clones were also obtained. Cytofluorimetric analysis showed that all melanoma clones expressed ICAM‐1, although to different extents, reaching a 10‐fold difference in fluorescence units, while HLA class‐1 antigens were similarly expressed. The differences in expression of ICAM‐1 among tumor clones correlated with differences in lysability, by both specific and non‐specific CTL, but were not large enough to affect lymphocyte‐tumor conjugate formation. Cytokine‐ or gene‐transfer‐mediated up‐regulation of ICAM‐1 did not induce de novo lysis of ICAM‐1low tumor cells; however, it markedly enhanced a low level of killing of the same cells by tumor‐specific, TcR‐dependent and HLA‐restricted CTL clones but not by non‐specific, TcR‐independent effectors. In addition, lysis of melanoma clones by any effector was similarly inhibited by anti‐ICAM‐1 and anti‐LFA‐1 antibodies. This indicates that by‐pass of low lysability of ICAM‐1low melanoma clones by CTL clones, after ICAM‐1 up‐regulation, is possible only if simultaneous LFA‐1 and TcR engagement takes place. In addition, these results suggest that the constitutive high level of expression of ICAM‐1 on the subset of ICAM‐1high melanoma cells must be only one of the factors contributing to the high lysability of these cells by any effector.
Over‐expression of c‐myc increases the sensitivity of epstein‐barr virus immortalized lymphoblastoid cells to non‐MHC‐restricted cytotoxicity
Authors: Cuomo Laura , Zhang Quian‐Jin , Torsteinsdottir Sigurbjörg , Klein George , Masucci Maria G. , Lombardi Luigia , Dalla‐Favera Riccardo 
Published: July 2010

AbstractEpstein‐Barr virus (EBV)‐carrying Burkitt lymphoma (BL) lines which maintain the phenotypic characteristics of the in vivo tumor cells are more sensitive to natural (NK), interferonactivated (IAK) and IL‐2‐activated (LAK) cytotoxicity than EBV‐immortalized lymphoblastoid cell lines (LCL) of normal B‐cell origin. All BL cells carry chromosomal translocations which lead to deregulated expression of the c‐myc oncogene. LCLs transfected with constitutively active c‐myc alleles display changes in growth properties and surface phenotype. In this study, we have examined the effect of c‐myc deregulation on the sensitivity of LCLs to NK, IAK and LAK effectors. C‐myctransfected LCLs showed an increased sensitivity to lysis which correlated with the level of c‐myc expression. Expression of HLA class I and sensitivity to allospecific and EBV‐specific cytotoxic T‐lymphocytes (CTL) remained unchanged. Transfection of a constitutively active v‐H‐ras gene, which also induces changes in growth properties and cell‐surface phenotype, did not alter the sensitivity of LCLs to NK or LAK cytotoxicity.
Antenatal risk factors for malignant brain tumours in new south wales children
Authors: McCredie Margaret , Maisonneuve Patrick , Boyle Peter 
Published: July 2010

AbstractA population‐based case‐control study of incident primary malignant brain tumours diagnosed during 1985 to 1989 in children aged 0 to 14 years was carried out in the coastal conurbation of New South Wales comprising Sydney, Wollon‐gong and Newcastle in the period 1988 to 1990. Personal interviews were conducted using a structured questionnaire with mothers of 82 cases and 164 control children individually matched to the cases by sex and age. Among the hypotheses being examined were those related to exposure to parental tobacco smoke, N‐nitroso compounds and possible protection from sources of vitamin C. No link was found with tobacco smoking by the mother before or during pregnancy. While exposure during pregnancy of the mother to tobacco smoke of the father appeared to double the risk of childhood brain tumours and a similar risk was found for father (but not mother) smoking before the index pregnancy, there was no “dose‐response” and the increased risk was confined to data supplied by the mother (rather than the father himself). The risk of childhood brain tumours rose with reported increasing consumption, during pregnancy, of cured meats, which have high levels of N‐nitroso compounds (or their precursors), and fell with rising consumption of vegetables. No association was found between the risk of childhood brain tumours and family history of epilepsy, cancer, or tumours of the nervous system, parental irradiation, previous miscarriage or procedures carried out during pregnancy, maternal consumption of antihistamines, barbiturates or diuretics, or maternal contact with cats or farm‐life during pregnancy. © 1994 Wiley‐Liss, Inc.
Perinatal and early postnatal risk factors for malignant brain tumours in New South Wales children
Authors: McCredie Margaret , Maisonneuve Patrick , Boyle Peter 
Published: July 2010

AbstractA population‐based case‐control study of incident primary malignant brain tumours diagnosed during 1985–1989 in children aged 0 to 14 years was carried out in the coastal conurbation of New South Wales comprising Sydney, Wollon‐gong and Newcastle in the period 1988 to 1990. Personal interviews were conducted using a structured questionnaire with mothers of 82 cases and 164 control children individually matched to the cases by sex and age. Among the hypotheses examined were those related to: N‐nitroso compounds (sources included diet, dummies, medications, tobacco smoke); factors associated with the birth of the child; trauma to the head; and irradiation (X‐rays and electromagnetic radiation through electric blankets or water beds). Reported ever‐use of a dummy increased the risk of childhood brain tumours (OR = 2.9, 95% CI 1.6 to 5.4), although there did not appear to be any consistent indication of rising risk with reported increased levels of use. Compared with children who had never used a dummy, categories of use during the first year of life of a maximum of “no more than I hour per day or night”, “several hours per day or night”, and “most of the day or night” had statistically significant odds ratios of 2.6, 3.4, and 2.7 respectively. Consumption of fruit by the child before the age of one appeared to be protective. No association was found between childhood brain tumours and birth weight, being the first‐born child, or factors linked with the child's birth; head injuries; exposure to X‐rays; contact with horses, or living on a farm; pesticide treatment of the house during the child's lifetime; or exposure to burning incense. © 1994 Wiley‐Liss, Inc.
Significance of epidermal growth factor receptor expression in primary human endometrial cancer
Authors: Scambia Giovanni , Panici Pierluigi Benedetti , Ferrandina Gabriella , Battaglia Francesco , Distefano Mariagrazia , D'Andrea Giorgia , De Vincenzo Rosa , Maneschi Francesco , Ranelletti Franco Oreste , Mancuso Salvatore 
Published: July 2010

AbstractRadioreceptorial assessment of EGFR expression was prospectively performed on 60 primary human endometrial tumors. Of these, 26 were EGFR‐positive while 13 expressed high EGFR levels. High EGFR levels correlated well with poor histopatho‐logical grading. No correlation with histopathological type, stage, myometrial invasion, lymph‐node involvement or steroid hormone receptor status was observed. Disease‐free survival rate was significantly shorter in the cases with high than in the cases with low EGFR levels. These results suggest a potential role of EGFR expression assessment in prognostic characterization of endometrial cancer patients. © 1994 Wiley‐Liss, Inc.
High prevalence of neutralizing activity to helicobacter pylori cytotoxin in serum of gastric‐carcinoma patients
Authors: Hirai Masamichi , Azuma Takeshi , Ito Shigeji , Kato Takuji , Kohli Yoshihiro , Fujiki Norio 
Published: July 2010

AbstractHelicobacter pylori infection is causally related to chronic type‐B gastritis, and may also be associated with an increased risk of gastric carcinoma. Vacuolating cytotoxin, which is an 87‐kDa protein secreted by H. pylori, induces eukaryotic cell vacuolation in vitro. To determine whether there is an association between H. pylori vacuolating cytotoxin and gastric carcinoma, we investigated several characteristics of H. pylori infection, i.e., isolation of H. pylori from gastric biopsies, antibodies specific for H. pylori, detection of neutralizing activity to vacuolating cytotoxin in serum and immunological detection of cytotoxin by serum. Out of 6 sera from gastric‐carcinoma patients, all showed the neutralizing activity to vacuolating cytotoxin, in contrast to 3 of 5 sera from peptic‐ulcer patients. Normal individuals showed no neutralizing activity. All sera possessing the neutralizing activity recognized an 87‐kDa protein band by Western blot analysis. Our results confirmed that cytotoxin‐neutralizing activity in human sera was associated with immunodetection of an 87‐kDa protein. To further evaluate neutralizing activity in serum from gastric‐carcinoma patients, we retrospectively analyzed frozen‐stocked serum samples from 22 gastric‐carcinoma patients. Sera from 21 of these 22 patients exhibited neutralizing activity. These sera were also checked for antibodies to H. pylori, using an ELISA; 16 sera showed positive results. Our results indicate that detection of cytotoxin‐neutralizing activity in sera is strongly associated with H. pylori infection, and probably with gastric carcinoma, and is also of interest in the diagnosis of H. pylori infection. © 1994 Wiley‐Liss, Inc.
Preferential usage of T‐cell receptor αβ variable regions among tumor‐infiltrating lymphocytes in primary human malignant melanomas
Authors: Straten Per Thor , Schøller Jørgen , Hou‐Jensen Klaus , Zeuthen Jesper 
Published: July 2010

AbstractThe usage of T‐cell‐receptor (TCR) αβ variable (V) regions among tumor infiltrating lymphocytes (TILs) in primary human malignant melanomas was characterized using a method based on the polymerase chain reaction (PCR). A panel of 57 different variable‐region primers specific for the TCR Vα 1–29 and Vβ 1–28 was designed, and a semi‐quantitative PCR method applicable to formalin‐fixed, paraffin‐embedded tissues was developed. This semi‐quantitative method was demonstrated to be reproducible and to be useful for the assessment of Vα‐ and Vβ‐gene‐family usage in formalin‐fixed, paraffin‐embedded tissue samples. A total of 9 different histopathologically characterized primary tumors were analyzed in this study. The TILs in these tumors were found to preferentially express certain TCR Vα and Vβ regions. The differential usage of certain Vα regions was very pronounced as illustrated by Vα4, which was highly expressed in 3/8 tumors, and Vα22, which was highly expressed in 4/8 tumors. For comparison, specific highly expressed Vα regions in control samples of peripheral‐blood lymphocytes rarely exceded 10%. The most highly expressed VB region was Vβ8, which was highly expressed in 2/8 tumors. For the highly expressed Vα4 and Vα22 and Vβ8 regions, the high levels may be explained by the in situ clonal or oligoclonal expansion of TIL. In one specific case, the high expression of Vβ8 was due to expansion of a single clone of TILs, as evidenced by a fully readable sequence of the CDR3 (V‐D‐J) region, determined by direct sequencing of the PCR product corresponding to Vβ8. In contrast, sequence analysis of Vα22, which was expressed in the same tumor sample at similar levels, demonstrated the simultaneous presence of 3 different CDR3 (V‐J) sequences derived from Vα22 transcripts of exactly the same length. The observed preferential use of TCR Vα and Vβ regions suggests the in situ clonal expansion of specific populations of T‐cells, possibly reactive with melanoma‐associated peptides presented by HLA molecules. The preferential use of TCR Vα and Vβ regions may imply the involvement of a limited number of shared melanoma‐associated peptides. © 1994 Wiley‐Liss, Inc.
Altered homologous and heterologous gap‐junctional intercellular communication in primary human liver tumors associated with aberrant protein localization but not gene mutation of connexin 32
Authors: Krutovskikh V. , Mazzoleni G. , Mironov N. , Omori Y. , Aguelon A.‐M. , Mesnil M. , Berger F. , Partensky C. , Yamasaki H. 
Published: July 2010

AbstractGap‐junctional intercellular communication (GJIC) in 20 primary human liver tumors with different degrees of malignancy has been studied at the functional and molecular levels. When GJIC capacity was determined by dye‐transfer assay performed directly with freshly removed tumor tissue, significant reduction was found in all samples, regardless of their morphology. In addition, a selective lack of GJIC between tumor and surrounding non‐tumorous cells was observed in some cases, probably due to the physical separation between them resulting from encapsulation of tumors. There was, however, no essential change in the level of expression of the major liver gap‐junction protein, connexin (ex) 32, in liver tumors as measured by Northern and Western blot analyses. Immunohistochemical study revealed aberrant localization of ex 32 in the majority of malignant liver tumors. Instead of cytoplasmic membrane localization at intercellular contacts, ex 32 was detected mainly either intracytoplasmically or in plasma membrane free from contact with other cells. We did not detect any mutation in the coding sequence of the ex 32 gene from any of the human liver tumors we tested. Thus it is likely that the aberrant localization of ex 32 in tumor cells is due to disruption of the mechanisms for establishment of this protein into gap‐junction plaques, rather than to structural abnormality of the ex 32 protein itself. Another member of the connexin family, ex 43, not detectable in non‐tumorigenic hepatocytes, was expressed in several tumors, especially in invasive areas, but was detected in only a few tumor cells and was localized intracytoplasmically, suggesting that ex 43 protein is not involved in GJIC in the tumors. © 1994 Wiley‐Liss, Inc.
Nuclear DNA content, proliferating‐cell nuclear antigen (PCNA) and p53 immunostaining in predicting progression of laryngeal cancer in situ lesions
Authors: Munck‐Wikland Eva , Edström Staffan , Jungmark Eva , Kuylenstierna Richard , Lindholm Johan , Auer Gert 
Published: July 2010

AbstractSquamous epithelial cancer in situ (CIS) of the upper aerodi‐gastric tract is a histopathologically well‐defined condition. However, in clinical practice, morphological grading of dysplasia is difficult and shows large variability. The biology of CIS remains enigmatic, and there is yet no reliable way to predict whether a CIS lesion will progress to invasive cancer, remain stable or regress. In the search for markers able to foretell clinical outcome, we performed image DNA cytometry (ICM) and immunohistochemical staining for PCNA as well as p53 in 38 laryngeal CIS lesions, of which 9 progressed to invasive cancer. The majority of the CIS lesions displayed high‐grade DNA aberration, a high PCNA‐positive rate, and every third lesion was p53‐poskive by immunostaining. The lesions which progressed to invasive cancer showed a clear tendency towards more pronounced DNA aberration, a higher percentage of intense PCNA staining and more frequent p53 positivity. By combining the results from the analyses of DNA, PCNA and p53 in a prognostic index for each individual case, we correctly classified 82% of the lesions as progressors or non‐progressors. © 1994 Wiley‐Liss, Inc.
Induction and promotion of forestomach tumors by sodium nitrite in combination with ascorbic acid or sodium ascorbate in rats with or without N‐metuyl‐N′‐nitro‐N‐nitrosoguanidine pre‐treatment
Authors: Yoshida Yasunori , Hirose Masao , Takaba Katsumi , Kimura Juki , Pito Nobuyuki 
Published: July 2010

AbstractIn experiment I, short‐term effects of combined treatment with anti‐oxidants, sodium ascorbate (NaAsA) and sodium nitrite (NaNO2) on forestomach cell proliferation were examined in F344 male rats. Groups of 5 animals aged 6 weeks were treated for 4 weeks with 0.8% catechol, 0.8% hydroquinone, 1% tert butyl‐hydroquinone (TBHQ), 2% gallic acid or 2% pyrogallor alone or in combination with 0.3% NaNO2 in the drinking water and/or I % NaAsA in the diet. The thicknesses of forestomach mucosa in rats treated with anti‐oxidants and NaNO2 in combination were greater than those with antioxidant alone and additional NaAsA treatment further enhanced the thickening of mucosa. It was noteworthy that values for mucosae of animals treated with NaNO2 and NaAsA without anti‐oxidant were similar to those for anti‐oxidants. In experiment 2, effects of combined treatment with NaAsA or ascorbic acid '(AsA) and NaNO2 on carcinogenesis were examined in F344 male rats with or without N‐methyl‐N' ‐nitro‐N‐nitrosogua‐nidine (MNNG) pre‐treatment. Groups of 20 or 15 rats, respectively, aged 6 weeks, were given a single intra‐gastric administration of I SO mg/kg body weight of MNNG in DMSOwater =1:1 or the vehicle alone by stomach tube. Starting I week later, they received supplements of I % NaAsA or I % AsA in the diet and 0.3% NaNOz in drinking water in combination, each of the individual chemicals alone, or basal diet until the end of week 52. In MNNG‐treated animals, incidences of forestomach papillomas and carcinomas were significantly enhanced in the NaNO2 alone group (84 and 47%, respectively) as compared with the basal diet group (30 and 10%), with further significant increase in carcinomas occurring with additional NaAsA (79%, p < 0.05) or AsA (85%, p < 0.05) treatment. In animals without MNNG, all animals in the NaNO2 group demonstrated mild hyperplasia, additional administration of NaAsA or AsA remarkably enhancing the grade of hyperplasia, and resulting in 53% and 20% incidences, respectively, of papillomas. Thus NaNO2 was demonstrated to exert promoter action for forestomach carcinogenesis, with NaAsA and AsA acting as co‐promoters. The results strongly indicate that combined treatment with NaAsA or AsA and NaNO2 may induce forestomach carcinomas in the long term. © 1994 WUey‐Liss, Inc.
Receptor‐mediated cyotoxicity of a‐MSH fragments containing melphalan in a human melanoma cell line
Authors: Morandini R. , Suli‐Vargha H. , Libert A. , Loir B. , Botyánszki J. , Medzihradszky K. , Ghanem G. 
Published: July 2010

AbstractFour α‐MSH drug conjugates have been synthesized, 2 C‐terminal (Pep 3 and 4) and 2 central fragments (Pep I and 2), the latter being the 4–10 sequence known to be the main α‐MSH‐receptor‐recognition site. Melphalan was introduced into each sequence at different locations. Their ability to recognize α‐MSH receptors as well as their cytotoxic effects were compared in 3 cell lines: melanoma, carcinoma and fibroblast cells. Pep I and 2 were able to specifically bind to MSH receptors on melanoma cells by displacing labelled a‐MSH from its binding sites at concentrations similar to the 4–10 heptapeptide sequence known to contain the main receptor‐recognition site. They subsequently penetrate the cell, most probably by a receptor internalization mechanism, since about half of their effect could be inhibited by competition at the receptor level. Significant and selective cytotoxic effects to melanoma cells could be observed after only 2 hr exposure to the drug conjugates. Interestingly, these 2 conjugates, differing only in melphalan position, showed completely different cytotoxic/ in terms of IC50 values, Pep I being 24 times more toxic to all cells; but the 2 were equally specific to melanoma cells. However, they both were less toxic to all cells than melphalan itself. Furthermore, Pep I and 2 were able to block the receptor and, unlike Pep 3 and 4, their cytotoxic effect could be significantly inhibited by an α‐MSH agonist. Pep 3 and 4 were 5 to 10 times less toxic than melphalan to melanoma and carcinoma cells and 50 times less to fibroblast cells, and did not show any cell‐type selectivity. They were less toxic than Pep I to melanoma and carcinoma cells by a factor of 2, but equally toxic to fibroblasts. In contrast, they were more toxic than Pep 2 to fibroblasts, melanoma and carcinoma by a factor of 3, 10 and 24 respectively. Our data strongly suggest a receptor‐mediated cytotoxicity mechanism occurring with a‐MSH central fragments in human melanoma cells due to the presence of α‐MSH‐specific receptors. This mechanism appeared to be both peptide‐ and cell‐type‐specific.