bluuebunny/crossref_metadata_2025_split huggingface dataset:
The p53 tumor‐suppressor gene and ras oncogene mutations in oral squamous‐cell carcinoma
Authors: Sakai Eiki , Rikimaru Koichi , Ueda Masayoshi , Matsumoto Yukie , Ishii Naoko , Enomoto Shoji , Yamamoto Hajime , Tsuchida Nobuo 
Published: February 2007

AbstractThe frequencies of mutations in the p53 tumor‐suppressor gene and ras proto‐oncogenes were investigated systematically in surgically resected oral squamous‐cell carcinomas (SCCs) using single‐strand conformation polymorphism (SSCP) and/or dot‐blot hybridization analysis of DNA fragments which had been amplified by the polymerase chain reaction (PCR). p53 gene mutations, within the region of exons 5 to 8, were detected in 17 out of 27 (63%) tumor specimens. The role of p53 mutations in cell‐line establishment was investigated. p53 gene mutations were detected in 5 out of 6 tissue samples from which cell lines were established and in 4 out of 5 specimens from which cell lines could not be established, suggesting that the presence of p53 gene mutations is not by itself sufficient for cell‐line establishment. Tumor samples were also analyzed for point mutational activation of the ras proto‐oncogenes. One out of 30 (3%) tumors showed an activating point mutation in codon 12 of H‐ras, this being consistent with reports from Europe and USA but not with any from India. Compared to frequencies of the other genetic changes so far reported for oral SCC, the p53 mutations have been observed most often to undergo genetic change. p53 gene mutation is thus intimately involved in the genesis of oral SCC and consequently should be useful as a marker for the diagnosis of this neoplasm. © 1992 Wiley‐Liss, Inc.
Neutralizing activity of human antibodies against the structural protein of human T‐cell lymphotropic virus type I
Authors: Inoue Yukiko , Kuroda Naotaka , Shiraki Hiroshi , Sato Hiroyuki , Maeda Yoshiaki 
Published: February 2007

AbstractWe have identified and mapped the regions responsible for neutralization in the human T‐cell leukemia virus type I (HTLV‐I) structural proteins by using region‐specific human antibodies derived from seropositive blood donors. We have obtained 18 kinds of region‐specific antibody (2 in the p 19 gag, 10 in the gp46 env and 6 in the gp21 env proteins) from seropositive human plasma by means of an affinity column coupled with the synthetic peptides corresponding to the antigenic regions of the HTLV‐I structural proteins. These antibodies were highly specific in ELISA using synthetic peptides as an antigen. Subsequently, we examined the neutralizing activity expressed by the inhibition of virion‐induced syncytium formation by region specific antibodies. Twelve of 16 antibodies derived from the env protein were able to inhibit syncytium formation induced by co‐cultivation of 8C cells with HTLV‐I antigen‐positive T cells. The antibodies derived from the p19 gag protein and the seronegative plasma used as the control showed no significant activity. The sequences recognized by the 10 neutralizing antibodies were sites corresponding to amino acids 20 to 49, 89 to 115, 136 to 160, 175 to 199, 213 to 236, 235 to 254, 277 to 292, 332 to 352, 350 to 386, 382 to 403, 426 to 448 and 458 to 488 from the amino terminal of the env protein. These observations suggest that the neutralizing epitopes were widely distributed in the env proteins of HTLV‐I. © 1992 Wiley‐Liss, Inc.
Establishment of a murine model of malignant mesothelioma
Authors: Davis M. R. , Manning L. S. , Whitaker D. , Garlepp M. J. , Robinson B. W. S. 
Published: February 2007

AbstractMalignant mesothelioma (MM) is an aggressive tumour of the serosal cavities which is associated with previous asbestos exposure and is generally found to be resistant to conventional forms of therapy. Adequate scientific and clinical assessment of this disease has been severely limited by the relatively low incidence of mesothelioma and the lack of representative cell lines and animal models. The purpose of this study was to develop an asbestos‐induced murine model of MM both as an in vivo‐passaged malignancy and as in vitro‐established cell lines. Such a model system would be invaluable for use in the study of various cellular, molecular and genetic aspects of the disease, and for the pre‐clinical evaluation of potential therapeutic agents. BALB/c and CBA mice were injected intraperitoneally with crocidolite asbestos. Seven to 25 months after exposure, 35% of the mice developed mesothelioma (5 BALB/c, 9 CBA), as determined by standard cytological and histological parameters. From these primary tumours, 12 continuously growing cell lines (5 BALB/c, 7 CBA) were established in culture. All have been confirmed as mesothelioma by cytological and ultrastructural (electron microscopy) analyses. These lines have been in culture for 7 to 24 months and have achieved passages above 32 (range 32 to 106). As in the human disease, the murine mesothelioma lines vary in their morphology and growth rates (doubling times ranging from 14 to 30 hr). All cell lines produced tumours when injected into syngeneic mice. © 1992 Wiley‐Liss, Inc.
Novobiocin‐induced accumulation of etoposide (VP‐16) in wehi‐3B D+ leukemia cells
Authors: Lorico Aureiio , Rappa Germana , Sartorelli Alan C. 
Published: February 2007

AbstractA previous report from this laboratory demonstrated that novobiocin produced supra‐additive cytotoxicity when combined with etoposide (VP‐16) or teniposide (VM‐26) in WEHI‐3B D+ and A549 cells. The increase in cytotoxicity was accompanied by an increase in the formation of drug‐stabilized protein‐DNA covalent complexes. We now report that novobiocin increased the amount of VP‐16‐induced covalent complexes between the 170 kDa form of topoisomerase II and DNA in WEHI‐3B D+ cells, as measured by the band‐depletion immuno‐blotting assay, while it did not affect the extractable topoisomerase II activity, measured by the unknotting of P4 phage DNA and by a DNA cleavage assay. Novobiocin progressively increased the steady‐state concentration of intracellular VP‐16. Removal of novobiocin resulted in a rapid return of VP‐16 to levels comparable to those seen with VP‐16 alone. The increased accumulation of VP‐16 was accounted for by an increase in the exchangeable fraction only. The novobiocin‐mediated increase in the steady‐state concentration of VP‐16 occurred whether novobiocin was added simultaneously with VP‐16 or was added after a steady‐state level of VP‐16 had been achieved. Novobiocin did not affect the initial rate of uptake of VP‐16; however, it inhibited the efflux of the epipodophyllotoxin. In fact, when cells were loaded with the same level of VP‐16 in the presence or absence of novobiocin, the efflux curves in the presence or absence of novobiocin were significantly different. We conclude that the inhibition of VP‐16 efflux by novobiocin is responsible for the increase in VP‐16 accumulation, leading to increased formation of VP‐16‐stabilized topoisomerase‐II‐DNA covalent complexes and increased cytotoxicity. © 1992 Wiley‐Liss, Inc.
Analysis of factors associated with the tumorigenic potential of 12 tumor clones derived from a single rat colon adenocarcinoma
Authors: Zennadi R. , Garrigue L. , Ringeard S. , Ménoret A. , Blanchardie P. , le Pendu J. 
Published: February 2007

AbstractWe analyzed several factors which could influence the immunogenicity of colon tumor cells, using a series of clones derived from a single chemically induced rat adenocarcinoma cell line. These clones display variable tumorigenic potential in syngeneic immunocompetent animals, and it has been established that in this model the tumorigenicity of the cells depends on their ability to escape immune surveillance. The results show an absence of relationship between tumorigenicity and expression of MHC‐class‐I antigens, cell adhesion to rat fibroblasts or fibroblast extracellular matrix. The secretion of latent and active TGFβ I appeared to be quite variable from one clone to the other, but was unrelated to tumorigenicity. Unexpectedly, some regressive clones produced elevated levels of this cytokine, suggesting that in this model, spontaneous secretion of TGFβ I is not sufficient to impair the immune system of the host. In contrast, the more tumorigenic clones were more resistant than less tumorigenic ones to cytotoxicity mediated by NK or LAK cells. They also showed arrest of cell proliferation after reaching confluence, something not observed in the less tumorigenic clones. Finally, the strongest relationship with tumorigenicity was found for expression of blood‐group carbohydrate antigens. Increased expression of blood‐group‐H antigen and, conversely, decreased expression of β‐galactoside precursors of this antigen correlated with increased tumorigenicity. © 1992 Wiley‐Liss, Inc.
Inhibition by squalene of the tumor‐promoting activity of 12‐O‐Tetradecanoylphorbol‐13‐acetate in mouse‐skin carcinogenesis
Authors: Murakoshi Michiaki , Nishino Hoyoku , Tokuda Harukuni , Iwashima Akio , Okuzumi Junichi , Kitano Hirokazu , Iwasaki Ryozo 
Published: February 2007

AbstractSqualene inhibited the effect of tumor promoter 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), such as increased 32Pi incorporation into phospholipids of HeLa cell membrane, induction of Epstein‐Barr‐virus early antigen in Raji cell and induction of ornithine decarboxylase in mouse skin. Squalene also markedly suppressed the promoting activity of TPA on skin carcinogenesis in 7, 12‐dimethylbenz[a]anthracene‐initiated mice. © 1992 Wiley‐Liss, Inc.
The development of human tumor‐cell resistance to TNF‐α does not confer resistance to cytokine‐induced cellular cytotoxic mechanisms
Authors: Zyad Abdelmajid , Branellec Didier , Mahé Yann , Tursz Thomas , Chouaib Salem 
Published: February 2007

AbstractWe have derived a TNF‐α‐resistant clone (RA‐I) from the parental TNF‐sensitive human breast‐adenocarcinoma cell line (MCF‐7). The acquisition of TNF‐resistance was not associated with endogenous TNF production or with differential levels of TNF receptors since both MCF‐7 and RA‐1 display comparable TNF‐receptor expression. We have investigated the relationship between acquisition of resistance to TNF and susceptibility to lysis by cytokine‐activated effectors. Experiments were performed using human peripheral‐blood monocytes stimulated with IL‐2, IFN or GM‐CSF, and lymphokine‐activated killer cells as effector cytotoxic cells. Our data indicate that both TNF‐resistant (RA‐I) and TNF‐sensitive (MCF‐7) cells were killed by IL‐2‐activated monocytes. Incubation of monocytes with IFN also resulted in the activation of their tumoricidal activity against MCF‐7 and RA‐I. When stimulated monocytes were pre‐incubated in the presence of a TNF‐specific neutralizing monoclonal antibody, prior to co‐culture with target cells, no effect on their lytic capacity was observed. Thus, the monocyte killing does not appear to involve the membrane form of TNF. These observations suggest that, in our experimental system, IL‐2 and IFN are able to induce non‐TNF‐mediated mechanisms of cytotoxicity by monocytes. Experiments performed using GM‐CSF and LPS for monocyte stimulation indicate that, although both reagents were efficient in inducing the membrane form of TNF on monocytes, they did not enhance the cell‐killing capacity towards MCF‐7 and RA‐1 targets. Furthermore, using IL‐2‐stimulated LGL as effector cells, we show in this study that the TNF‐resistant clone RA‐1 was as sensitive as MCF‐7 to human LAK cells. © 1992 Wiley‐Liss, Inc.
Cancer‐cell traffic in the liver. I. Growth kinetics of cancer cells after portal‐vein delivery
Authors: Barbera‐Guillem Emilio , Smith Isabel , Weiss Leonard 
Published: February 2007

AbstractFollowing the intrasplenic injection of B16F10 melanoma cells into mice, at first single cells, and later multicellular tumor foci were observed at different times in the liver. Cell numbers and tumor volumes were determined over the next 12 days, by confocal microscopy of thick liver sections. Fifteen minutes after injection, approximately 20% of the melanoma cells were identified in the liver microvasculature; after 48 hr, only 0.68% of these retained morphologic integrity; by 5 days only 0.13% of the originally detected cells incorporated BUdR; and, by 12 days, these subsequently grew into tumor nodules. Tumor volume changes with time were not exponential and, following a non‐replicative period during the first 2½ days, the volume doubling times increased from approximately 8 to 39 hr at 12 days. BUdR incorporation indicated that this was probably due to a diminishing proliferative fraction in the cancer‐cell population. When animals were killed at 12 days, tumor foci were centered on the liver sinusoids and appeared to represent expansive growth of arrested cells, with no evidence of parenchymal invasion by migrating cancer cells, in spite of the absence of a subendothelial basement membrane. Our direct observations indicate that, in this model system, the post‐delivery phase of hepatic colonization is characterized by high levels of inefficiency with respect to cancer‐cell survival, growth and extravasation. © 1992 Wiley‐Liss, Inc.
Analysis of anti‐tax antibody of HTLV‐I carriers in an endemic area in Japan
Authors: Shioiri Shigemasa , Tachibana Nobuyoshi , Okayama Akihiko , Ishihara Shiro , Tsuda Kazunori , Essex Max , Stuver Sherri O. , Mueller Nancy 
Published: February 2007

AbstractSera from 1197 adult residents in Miyazaki district, an area in Japan endemic for human T‐cell leukemia virus type I (HTLV‐I), were tested for anti‐Tax antibody by the recombinant Tax (r‐Tax) Western blot assay. Among HTLV‐I‐seropositive individuals, including 21.5% of 484 males and 28.6% of 713 females, the prevalence of anti‐Tax antibody were 59.6% and 58.3% respectively, with no apparent difference in age. There was a significant 6‐fold difference in the prevalence of anti‐Tax among seropositive subjects with titer > 1:8192 (84.6%) compared with those with the lowest titer of 1:16 (14.3%), suggesting the increased production of antibodies to viral structural proteins in anti‐Tax‐positive individuals. Furthermore, among those anti‐Tax‐positive subjects, the intensity of serum reactivity to r‐Tax protein in the high antibody titer (1:1024 or higher) group was significantly stronger than that in the lower antibody titer (1:512 or lower) group. We also found that 1.6% (14/889) of individuals without detectable levels of HTLV‐I antibody had anti‐Tax antibody. HTLV‐I pro‐viral DNA signals could not be detected in DNA sample from the lymphocytes of these individuals by the nested polymerase chain reaction method. Further evaluation is needed to clarify the significance of an anti‐Tax‐only status population in which HTLV‐I is endemic.
Basic fibroblast growth factor in human pheochromocytoma: A biochemical and immunohistochemical study
Authors: Statuto M. , Ennas M. G. , Zamboni G. , Bonetti F. , Pea M. , Bernardello F. , Pozzi A. , Rusnati M. , Gualandris A. , Presta M. 
Published: February 2007

AbstractBiopsies of human normal adrenal medulla, adrenal pheochromocytoma, and chemodectoma were studied for the presence of basic fibroblast growth factor (bFGF). An immunoreactive Mr 18,000 bFGF‐like molecule was detected both in normal and neoplastic tissues. This molecule was identified as bFGF on the basis of its molecular weight, its affinity for heparin, and its capacity to induce plasminogen activator production in cultured endothelial GM 7373 cells. The levels of immunoreactive and biologically active bFGF appeared to be significantly higher in the extracts of adrenal pheochromocytoma and chemodectoma than in the extracts of normal adrenal medulla. bFGF immunostaining was detectable in the nuclei of chief (Type‐I) cells and of endothelial cells both in normal adrenal medulla and in pheochromocytoma. Cytoplasmic bFGF positivity of endothelial cells was also observed in pheochromocytoma but not in normal tissue. The data are in keeping with the hypothesis that bFGF may exert autocrine and paracrine functions in the growth and neovascularization of human pheochromocytoma.
ras Gene mutations and hpv infection are common in human laryngeal carcinoma
Authors: Anwar Khurshid , Nakakuki Kazuya , Naiki Hironobu , Inuzuka Manabu 
Published: February 2007

AbstractTo evaluate the role of ras activation and human papillomavirus (HPV) infection in laryngeal carcinoma, we analyzed tumor DNA from 43 cases, including 25 primary laryngeal tumors, 12 lymph‐node and one skin metastases, and 5 recurrent laryngeal carcinomas. Thirteen normal laryngeal tissues and 7 benign laryngeal nodule biopsy specimens along with normal tissue surrounding laryngeal carcinoma in 2 cases were also included. The polymerase‐chain‐reaction technique was used to amplify DNA fragments containing codon 12 and 61 of H‐, K‐ and N‐ras, also HPV 16, 18 and 33 DNA, subsequently hybridized with sequence‐specific oligonucleotides. DNA samples from 22 patients with laryngeal carcinoma revealed ras mutations (18 in N‐ras codon 12, 6 in H‐ras codon 61, and 3 in K‐ras codon 61). Likewise, HPV DNA was found in 16 cases (HPV 16, 18 and 33 in 3 cases, 14 cases and 1 case respectively). ras mutations were significantly higher in metastatic tumors (10 of 13 cases) than in primary (11 of 25 cases) and recurrent laryngeal carcinomas (1 of 5 cases). HPV DNA was detected in 60% of recurrent, 44% of primary and 15% of metastatic tumors. Only 2 of the 13 normal laryngeal tissues and 1 out of 7 laryngeal nodule specimens were found to contain HPV DNA. These results suggest that ras activation, especially in N‐ras codon 12.1 (GGT → AGT) and HPV infection are 2 important factors in (multistage) laryngeal carcinogenesis. The ras mutation may be associated with metastatic ability of the tumor.
Bcl‐2 proto‐oncogene expression in epstein‐barr‐virus‐associated nasopharyngeal carcinoma
Authors: Lu Qi‐Long , Elia G. , Lucas S. , Alero Thomas J. 
Published: February 2007

AbstractThe bcl‐2 proto‐oncogene product inhibits apoptosis. Increased levels of bcl‐2 protein are associated with prolonged B‐cell survival and have been demonstrated in a high proportion of follicular B‐cell lymphoma. Recent studies have shown that bcl‐2 protein expression in B cells immortalized by Epstein‐Barr virus (EBV) in vitro is up‐regulated by the EBV‐latency‐associated antigen, latent membrane protein (LMP) I. The epithelial malignancy, undifferentiated nasopharyngeal carcinoma (UNPC), has a well‐established association with EBV and the tumour cells characteristically display a restricted latent viral phenotype including LMP I. This study has investigated the relationship between the presence of EBV DNA, EBV phenotypic profiles and bcl‐2 protein expression in conventionally processed and cryopreserved samples of NPC using in situ hybridization, immunocytochemical and immunoblotting techniques. bcl‐2 was detected in most (80%) samples of UNPC as well as in 1/3 samples of keratinizing NPC and 2/2 samples of nasopharyngeal adenocarcinoma. However, no close correlation was found between the presence of EBV DNA, and profiles for LMP I and bcl‐2 protein expression in 45 UNPC. In addition, bcl‐2 protein was shown to be selectively expressed in the basal compartment of normal nasopharyngeal epithelia. bcl‐2 protein expression has not been reported previously in malignant tumours of epithelial origin. The findings in this study implicate a role for bcl‐2 both in normal keratinocyte differentiation and in the pathogenesis of epithelial malignancy.
Flow cytometry in comparison with mitotic index in predicting disease outcome in transitional‐cell bladder cancer
Authors: Lipponen P. K. , Nordling S. , Eskelinen M. J. , Jauhiainen K. , Terho R. , Harju E. 
Published: February 2007

AbstractThe DNA content and S‐phase fraction were measured by flow cytometry in 448 tumour biopsy specimens from transitional‐cell bladder cancer (TCC). The samples were also analyzed for mitotic index, WHO grade and papillary status, and histological and flow cytometric data were then correlated to clinical behaviour of turnours during a mean follow‐up period of 9.9 years. TNM classification, WHO grade, papillary status, mitotic index, DNA ploidy and S phase fraction were significantly interrelated. Twenty‐four percent of tumours showed heterogeneous DNA indices when measured from multiple samples (measured in 94 cases). Of the histological parameters, independent predictors of progression in superficial tumours were the S‐phase fraction and mitotic index. In superficial tumours, S‐phase fraction and the mitotic index included all the available independent prognostic information in survival analysis, whereas in muscle‐invasive tumours T category was the most important prognostic factor. The results suggest that DNA ploidy has no independent prognostic value in transitional‐cell bladder cancer, whereas proliferation indices (SPF, mitotic index) are important prognostic factors. Accordingly, malignancy classification of papillary bladder tumours can be based on proliferation indices alone. Nodular tumours run an unfavourable course and their malignancy grading by flow cytometry or by mitotic index is not relevant.
Fundal atrophic gastritis as a risk factor for gastric cancer
Authors: Tatsuta Masaharu , Iishi Hiroyasu , Nakaizumi Akihiko , Okuda Shigeru , Taniguchi Haruo , Hiyama Tomohiko , Tsukuma Andhideaki , Oshima Akira 
Published: February 2007

AbstractThe role of atrophic gastritis of the gastric corpus (fundal atrophic gastritis) as a high‐risk factor was investigated by studying operative findings and follow‐up data on 690 patients with benign gastric diseases recorded at the Osaka Cancer Registry. The extent of fundal atrophic gastritis was determined by the endoscopic Congo red test. The patients were followed‐up from the time of endoscopic examination (1968 to 1976) to December 31, 1987. The vital status of 654 patients (94.8%) at the end of the observation period was determined. During the follow‐up period, 22 patients were found to have gastric cancer. The extent of fundal atrophic gastritis was shown to be closely related with the risk of developing gastric cancer. Patients who had been diagnosed as having severe fundal atrophic gastritis showed significantly higher risk of gastric cancer than patients who had been diagnosed as having little or no fundal atrophic gastritis (5.76‐fold, calculated with adjustments for age, sex and the follow‐up period). A positive linear relationship was found between the risk of developing gastric cancer and the extent of fundal atrophic gastritis. The observed number of gastric cancers was compared with the expected number calculated from the incidence in Osaka Prefecture. Analysis of the results showed that the observed and expected numbers of gastric cancers in patients with severe fundal atrophic gastritis were 11 and 4.8, respectively, the ratio of observed to expected numbers being 2.3 (p < 0.05). These findings indicate that severe fundal atrophic gastritis is a major risk factor for gastric cancer.