bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential expression of thymosin genes in human tumors and in the developing human kidney
Authors: Hall Alan K. 
Published: February 2007

AbstractThymosins β4 and β10 are 2 structurally related polypeptides originally defined in the rat immune system. To date, no truly unambiguous functions have been formally ascribed to these small (<4.9 kDa) acidic proteins. Previous research has demonstrated relationships between expression of these genes and cell growth/differentiation. These observations prompted the present study which has used cDNA and synthetic oligonucleotide probes in combination with high‐performance liquid chromatography (HPLC) to examine the differential expression of these 2 genes in normal and neoplastic human tissues and in the developing human kidney. Low levels of β4 and β10 mRNA species prevailed in normal tissues; in contrast, these gene transcripts were notably more abundant in malignant renal tumors and in the normal human embryonic kidney. These findings show that the thymosin β4 and β10 genes are constitutively expressed at higher levels in embryonic/neoplastic as compared to normal/benign tissues and that thymosin in β10 in particular may be a new molecular marker for renal‐cell carcinoma as well as other malignancies.
Occurrence of antibodies TO L1, L2, E4 and E7 gene products of human papillomavirus types 6b, 16 and 18 among cervical cancer patients and controls
Authors: Köchel Heinrich G. , Monazahian Masyar , Sievert Kai , Höhne Michaela , Thomssen Christoph , Teichmann Alexander , Arendt Peter , Thomssen Reiner 
Published: February 2007

AbstractSera from 118 women of 33 to over 90 years of age, with or without a history of cervical squamous‐cell carcinoma, were examined for the presence of antibodies to HPV‐6b, HPV‐16 and HPV‐18 L1, L2, E4, and E7 gene products by the use of bacterially derived β‐Gal fusion proteins and Western‐blot analysis. Among the cervical cancer patients, 29/46 (63.0%) were positive for antibodies to E4 and/or E7 of HPV‐16 and/or E7 of HPV‐18. In contrast, only 2 of 31 (6.5%) non‐genital cancer patients and 4 of 41 (9.8%) healthy individuals were antibody‐positive for HPV‐16 E4 or E7, while antibodies to the homologous proteins of HPV‐18 could not be detected. Prevalence rates of antibodies to the HPV‐16/18 late proteins were 25/46 (54.3%) in the cervical carcinoma group, 13/31 (41.9%) among women with non‐genital cancer types, and 18/41 (43.9%) among normal, healthy individuals. Antibodies to HPV‐6b late gene products ranged between 6.5% and 12.2% in the different patient groups. Antibodies to HPV‐6b E4 and E7 were detected only once. By studying an additional control group of 207 women with a different age distribution, age‐dependence of antibodies to HPV gene products could be ruled out. Whereas antibodies to late proteins may indicate that, regardless of clinical stage, HPV infections are widespread among the female population, the striking difference between the prevalence rates of antibodies to early proteins of HPV‐16 and HPV‐18 among cervical cancer patients and controls (p < 0.001) supports the idea of the involvement of these virus types in carcinogenesis of the cervix.
Expression of cholecystokinin forms by medullary thyroid cancer
Authors: Poston G. J. , Draviam E. J. , Seitz Patricia K. , Rajaraman S. , Alexander R. W. , Cooper C. W. , Townsend C. M. , Thompson J. C. 
Published: February 2007

AbstractWe have studied the production and release of cholecystoklnin (CCK) forms by rat medullary thyroid cancer (MTC) in vivo. MTC cells were inoculated s.c. into 8 Wag‐Rij rats. One month later, after i.v. injection of calcium plasma levels of CCK, calcitonin and tissue contents of gastrln and calcitonin were determined by radioimmunoassay (RIA), immunocyto‐chemistry, and high‐pressure liquid chromatography (HPLC). The tumors were passed 4 times to 8 rats in 1‐month intervals fasting levels of CCK in control rats were unaffected by calcium stimulation, and in tumor‐bearing rats, plasma CCK was elevated in 3 out of 4 passages, falling to normal levels at the end of passage 4. Hypercalcemia had no effect on plasma levels of CCK in tumor‐bearing rats, but did stimulate the release of calcitonin in both control and some tumor‐bearing rats in later passages. CCK‐8 sulfate was found in all 4 tumor passages but not CCK‐33/39. We conclude that rat MTC synthesizes and releases CCK‐8, but unlike calcitonin, release of CCK appears unresponsive to calcium stimulation.
Growth inhibition of two solid tumors in mice, caused by polyamine depletion, is not attended by alterations in cell‐cycle phase distribution
Authors: Hessels J. , Kingma A. W. , Muskiet F. A. J. , Sarhan S. , Seiler N. 
Published: February 2007

AbstractWe studied the effect of polyamine depletion on growth and cell cycle characteristics of subcutaneously grown Lewis lung carcinoma (LLC) and fibrosarcoma (FIO 26) in mice. Polyamine depletion was achieved by inhibition of ornithine decarboxylase using 2‐(difluoromethyl)ornithine, limitation of exogenous polyamines by administration of a polyamine‐poor diet and decontamination of the gastrointestinal tract, and inhibition of endogenous polyamine reutilization by N, N'‐bis‐(2,3‐butadienyl)putrescine (MDL 72527). Determination of S‐phase cells was performed in tumor‐cell suspensions by flow cytometry and in tumor tissue sections by microscopy, following In vivo labelling with 5‐bromo‐2′‐deoxyuridine (BUdR). DNA synthesis rate was estimated from the Incorporation of in vivo‐injected [3H]‐thymidine (3H‐TdR). Both solid tumors almost completely stopped growing after access to polyamines was blocked. Growth inhibition was, however, not attended by changes in cell‐cycle‐phase distribution. Paradoxically, we measured increased in vivo 3H‐TdR incorporation rates and unaltered BUdR‐linked staining intensity in treated tumors. Injection of putrescine into treated LLC‐bearing mice resulted in an increase in intracellular putrescine and spermidine concentrations, a slight increase in the number of S‐phase cells and a marked drop in DNA synthesis rate within the following 9 hr.
HLA‐class‐I and‐class‐II expression on renal tumor xenografts and the relation to sensitivity for α‐IFN, γ‐IFN and TNF
Authors: Beniers A. J. M. C. , Peelen W. P. , Debruyne F. M. J. , Schalken J. A. 
Published: February 2007

AbstractIn this study we evaluated the usefulness of the histocom‐patibility leucocyte antigen (HLA) class‐I and class‐II expression on renal‐cell carcinoma (RCC) xenografts as predictive markers for response to cytokine therapy. Eight different RCC xenografts growing in BALBC nu/nu mice were treated with 0.5 or 5.0 ng/g recombinant human at‐or γ‐interferon (If N), or 500 ng/g recombinant human tumor necrosis factor (TNF). Modulation of HLA class‐I,‐II expression was evaluated immunohistochemically using the monoclonal antibodies (MAbs) W6.32 and B8.11.2 and at the mRNA level using the plasmids pDP001 and DR alpha 120. HLA class‐I expression in all lines was upregulated by α‐and γ‐IFN and was highest in the high‐IFN‐dose‐treated tumors. TNF also stimulated HLA‐class‐I expression and up‐regulated class‐I expression still further when combined with IFN. Highest up‐regulation of HLA‐class‐I in all tumors was measured in the alpha‐IFN‐5.0/TNF‐500‐ng/g‐treated mice, although this was not necessarily the treatment regimen resulting In the most pronounced effect on tumor growth. Hence, maximum up‐regulation of class‐I antigens at a given regimen was not always indicative for the highest achievable anti‐tumor effect. HLA‐class‐II expression which was present on only 3 of the untreated tumors was up‐regulated by both a and γ‐IFN. TNF itself did not up‐regulate class‐II expression but enhanced the class‐II expression on the α‐IFN‐treated tumors but not on the γ‐IFN‐treated tumors. Irrespective of the basic expression level, inducibility of both HLA‐class‐I and‐class‐II antigens appear to be correlated to the direct effects on growth of renal‐tumor xenografts towards α‐IFN, γ‐IFN and TNF. Modulation of HLA antigens was studied in the nude mouse, hence T‐cell‐mediated effector mechanisms cannot explain the good correlation between inducibility and response. Nonetheless, our studies indicate that the extent of modulation of HLA‐class‐I and‐II can serve as predictive marker for response to cytokine therapy, which may serve as a valuable criterion for inclusion of patients in cytokine treatment regimens.
Characterization of a cathepsin‐H‐like enzyme from a human melanoma cell line
Authors: Tsushima Hirofumi , Ueki Ayako , Matsuoka Yasuo , Mihara Hisashi , Hopsu‐Havu Väinö K. 
Published: February 2007

AbstractA cathepsin‐H‐like enzyme has been isolated from cultured human melanoma cells (G 361 cell line). The enzyme is similar to cathepsin H(s) of normal tissues in molecular weight, enzymatic characteristics (substrates, inhibitors, pH optima, Km values), and immunoreactivity. The inactive form of the enzyme with a molecular mass of 40 kDa has been found in the culture medium. The inactive enzyme is activated by acid pH, pepsin, and cathepsin‐D‐like enzyme treatments and converted into a form with a molecular mass of 28 kDa. The activated extracellular cathepsin‐H‐like enzyme and the active intracellular enzyme exhibit the same characteristics. The melanoma‐derived cathepsin‐H‐like enzyme degrade fibrinogen and fibronectin, but not laminin or type‐IV collagen. We conclude that the extracellular cathepsin‐H‐like enzyme may have important functions, together with other proteinases, in the destruction of extracellular matrix components, thus enabling proliferation, migration, and metastasis to occur.
Results and conclusions of the national toxicology program's rodent carcinogenicity studies with sodium fluoride
Authors: Bucher John R. , Hejtmancik Milton R. , Toft John D. , Persing Ronald L. , Eustis Scot L. , Haseman Joseph K. 
Published: February 2007

AbstractThe US National Toxicology Program (NTP) has conducted toxicity and carcinogenicity studies with sodium fluoride administered in the drinking water to F344/N rats and B6C3F1 mice. The drinking water concentrations used in the 2‐year studies were 0, 25, 100, or 175 ppm sodium fluoride (equivalent to 0, 11, 45 or 79 ppm fluoride). Survival and weight gains of rats and mice were not affected by fluoride treatment. Animals receiving sodium fluoride developed effects typical of dental fluorosis, and female rats given 175 ppm had increased osteosclerosis. There were no Increases in neoplasms in female rats or in male or female mice that were attributed to sodium fluoride administration. There was equivocal evidence of carcinogenic activity of sodium fluoride in male rats based on the occurrence of a small number of osteosarcomas in treated animals.
Protein kinase C activity as marker for colorectal cancer
Authors: Sakanoue Youichirou , Hatada Takuya , Kusunoki Masato , Yanagi Hidenori , Yamamura Takehira , Utsunomiya Joji 
Published: February 2007

AbstractProtein kinase C (PKC) activity was measured in normal‐appearing colonic mucosa from patients undergoing colonic resection. Comparisons were made between cases with and without colorectal cancers. PKC activity in cytosolic and particulate fractions was significantly reduced in patients with colorectal cancer: 40 ± 9 and 114 ± 29 (pmol/min/mg) respectively, compared with patients without cancer; 129 ± 11 and 250 ± 38 (pmol/min/mg) (p < 0.05). Normal‐appearing colonic mucosa in patients with cancer showed significantly decreased total PKC activities in the cytosolic and particulate fractions compared with those In patients without cancer (10 ± I and 20 ± 3 vs. 30 ± 2 and 33 ± 6) (pmol/min/g tissue) (p < 0.05). The cellular distribution (% particulate fraction) of PKC activity in normal‐appearing mucosa in patients with cancer (64%) was higher than in patients without cancer (49%) (p < 0.05). Our data suggest that PKC activity may be used as a biological marker of risk of developing colorectal cancer or risk of bearing an asymptomatic tumor.
Spontaneous and induced abortions and risk of breast cancer
Authors: Parazzini Fabio , Negri Eva , La Vecchia Carlo 
Published: February 2007

AbstractThe relationship between spontaneous or induced abortion and the risk of breast cancer was analyzed in a case‐control study conducted in the greater Milan area on 2,394 cases of breast cancer and 2,218 controls in hospital for a spectrum of acute conditions, not gynecological, hormonal or neoplastic. No consistent relationship emerged between spontaneous or induced abortion and breast cancer: compared with women reporting no abortions (spontaneous or induced), the multivariate relative risk (RR) was 1.0 (95% confidence interval, Cl, 0.9 to 1.2) in those reporting one abortion and 0.9 (95% Cl 0.7 to 1.0) in those reporting two or more. This lack of association was consistent in strata of age and parity, including younger women. We further analyzed the risk of breast cancer associated with an abortion before and after full‐term pregnancy. Compared with parous women reporting no induced or spontaneous abortions, those who had an abortion before their first full‐term pregnancy had about a 20% higher risk of breast cancer. This finding, however, was not statistically significant (RR 1.2, 95% Cl 0.9 to 1.7). No increased risk was observed in women who had had a first abortion after a full‐term pregnancy (RR 0.9, 95% Cl 0.8 to 1.0). This study does not support the hypothesis that spontaneous or induced abortion appreciably Influences subsequent breast‐cancer risk.
Monoclonal antibodies against Galα 1 −4Galß 1 −4Glc(Pk, CD77) produced with a synthetic glycoconjugate as immunogen: Reactivity with carbohydrates, with fresh frozen human tissues and hematopoietic tumors
Authors: Oosterwlik Egbert , Kalisiak Angela , Wakka Jeannette C. , Scheinberg David A. , Old Lloyd J. 
Published: February 2007

AbstractThe purpose of this study was to isolate mouse monoclonal antibodies (MAbs) recognizing Galα I ‐4Galβ I −4Glc (Pk. CD77), which has been described as a Burkitt's‐lym homa‐associated using a synthetic glycoconjugate as immunogen and a filter immunoplaque screening assay. One MAb (PK67) was characterized by immuno‐thin‐layer chromatography, ELISA and competition assays using neutral glycolipids from various sources and a variety of carbohydrates and glycoproteins. Epitope analysis showed that all 3 carbohydrate moieties are required in PK67 binding. No cross‐reactivity was observed with closely related carbohydrate structures, with the exception of Galα I ‐4Ga1β I ‐4GlcNAc. However, the reactivity with this structure was several orders of magnitude lower than with Pk. lmmunohistochemical analysis of fresh‐frozen tissue specimens showed that Gb3, is widely expressed: prominent staining was observed in many normal tissues, e.g., kidney and gastric tissue and on capillary endothelial cells. In lymph nodes, very weak staining of a few B cells was observed. Flow cytometric analysis of hematopoietic neoplasms showed Gb, expression on B‐cell neoplasms, particularly those with committed 8‐cell phenotype indicating that, in addition to earlier reports of Gb3, expression on Burkitt's lymphoma, Gb3, is present on other committed B‐cell neoplasms.
Relationships between epithelial basement membrane staining patterns in primary colorectal carcinomas and the extent of tumour spread
Authors: Hewitt Robert E. , Powe Desmond G. , Griffin Nicholas R. , Turner David R. 
Published: February 2007

AbstractIn colorectal cancer an association has been found between lack of epithelial basement membrane (EBM) immunostaining in the tumour centre and more extensive malignant spread. Interestingly, ultrastructural investigations suggest that EBM loss at the tumour periphery may be part of an invasive mechanism. To further assess the significance of EBM deficiencies in different tumour areas, we carried out a detailed study of the basement membrane laminin immunostaining patterns in 130 cases of colorectal carcinoma. We find that discontinuous EBM staining in the tumour centre is associated with poor tumour differentiation (p < 0.005). presence of lymph‐node metastases (p < 0.02), and more advanced Dukes stage (p < 0.02). The latter association is strengthened by excluding cases in which numerous polymorphonuclear leukocytes (PMNs) are present adjacent to EBM breaks, suggesting that these inflammatory cells are a confounding factor. Discontinuous EBM staining is more frequently observed in tumour deep to muscularis propria than in submucosal tumour (p < 0.02). indicating intra‐tumoral variation. At the tumour periphery, extensive EBM discontinuity shows no association with lymph‐node involvement, but is linked with deeper local invasion (p < 0.05). While EBM staining patterns around central and peripheral tumour glands are related (p < 0.001). staining around peripheral glands is almost invariably more discontinuous. However, EBM lack at the tumour periphery is not as absolute as previously suggested, since in 18% of tumours fewer than 25% of peripheral tumour glands show EBM breaks. This appears consistent with the hypothesis that invasive changes at the tumour periphery are temporary and reversible.
Glutathione and cellular response of ACNU‐resistant rat glioma sublines to drugs and radiation
Authors: Saito Yuji , Hotta Takuhiro , Mikami Takasi , Kurisu Kaoru , Yamada Kenji , Kiya Katuzou , Kawamoto Keiichi , Uozumi Tohru , Nakada Yosihiro 
Published: February 2007

AbstractThree ACNU‐resistant sublines (R1, R3 and R12) from rat glioma 9L cells showed cross‐resistance to vinblastine, adriamycin, and VP‐16. Among these, the R3 subline also acquired radioresistance under aerobic conditions. Total glutathione levels In these sublines were elevated 2‐to 3‐fold. Treatment of the cells with BSO, a specific inhibitor of GSH synthesis, resulted in decreased intracellular total glutathione levels in all 4 cell lines to about 10% of control levels. However, sensitivity to radiation or to chemicals did not change accordingly. Treatment of 9L cells with OTZ, a precursor of cystelne, resulted in a rise in intracellular GSH levels but it did not correlate with sensitivity to X‐ray or to ACNU. These results suggest that, in terms of cellular sensitivity to radiation or ACNU, total glutathione level alone cannot serve as a predictive indicator.
Effect of N1,N14‐bis‐(ethyl)‐homospermine (BE‐4–4‐4) on the growth of U‐251 MG and SF‐188 human brain tumor cells
Authors: Basu Hirak S. , Pellarin Malgorzata , Feuerstein Burt G. , Deen Dennis F. , Marton Laurence J. 
Published: February 2007

AbstractWe studied the effects of the spermine analogue N,N14‐bis‐(ethyl)‐homospermine (BE‐4–4‐4) on growth, survival and polyamine levels in cultured U‐251 MG and SF‐188 human brain tumor cells. After 48 hr of treatment at concentrations of 1 μM or higher, BE‐4–4‐4 accumulated in cells with a concomitant decrease in intracellular putrescine, spermldine and spermine concentrations. Growth inhibition by 10 μM BE‐4–4‐4 began at 6 hr and peaked between 16 and 24 hr. The analogue was also increasingly cytotoxic with doses between 1 and 10 μM and with treatment times between 16 and 48 hr. Polyamines added 1 day after BE‐4–4‐4 lowered the intracellular concentrations of the analogue but did not reverse its growth‐inhibitory activity. When added simultaneously with the analogue, however, polyamines caused a decrease in analogue concentration that was accompanied by a block to the growth Inhibition. BE‐4–4‐4 has a higher affinity for DNA than spermine has, but is less able to aggregate DNA. Its growth‐inhibitory and cytotoxic effects support our hypothesis that polyamine analogues that enter cells and replace natural polyamines at DNA binding sites, without fulfilling their biologic functions, should act as antiproliferative agents.
Immunological characterization of the epstein‐barr virus phosphoprotein pp58 and deoxyribonuclease expressed in the baculovirus expression system
Authors: Chen Hai‐Feng , Sauter Marlies , Haiss Peter , Müller‐Lantzsch N. 
Published: February 2007

AbstractThe open reading frames of the phosphoprotein pp58 (BMRF1) and the deoxyribonuclease (BGLF5) of the Epstein‐Barr‐virus (EBV) strain M‐ABA were cloned in the baculovirus expression vectors pAc373 and pAc360 and expressed in the Spodoptera frugiperda (SF158) insect cells. The recombinant phosphoprotein pp58 expressed in SF158 cells was recognized by the anti‐pp58 rabbit anti‐sera which were generated by immunizing rabbits with a TrpE‐BMRF1 fusion protein expressed in E. coli. DNA‐cellulose chromatography showed that the recombinant pp58 exhibited DNA‐binding activities. Immunofluorescence, immunoblot and ELISA analysis indicated that sera from patients with nasopharyngeal carcinoma (NPC) contained antibodies against pp58. The recombinant EBV DNase expressed in SF158 cells was recognized by the anti‐EBV DNase rabbit anti‐sera which were generated by immunizing rabbits with a TrpE‐C‐termlnal part of BGLF5 fusion protein expressed in E. coli. The anti‐EBV DNase rabbit anti‐sera recognized also a protein of about 52 kDa in the EBV‐harboring human B‐cell lines Raji, Jijoye, 895–8, M‐ABA and BL74 induced by TPA and n‐butyrate. The recombinant EBV DNase exhibited exonuclease and endonuclease activities, a requirement for magnesium, and a high pH optimum (8.0). Its enzyme activities could be inhibited by sera from NPC patients and anti‐EBV DNase rabbit anti‐sera. Comparable studies of Raji EBV‐DNase and recombinant EBV‐DNase implied that recombinant EBV‐DNase could also be used in the enzyme activity assay for the detection of NPC. In contrast to the enzyme inhibition test, immunofluorescence and immunoblot analysis demonstrated that the recombinant EBV DNase exhibited only a weak immunological reaction with NPC sera.
Natural killer‐cell activity under conditions reflective of tumor micro‐environment
Authors: Loeffler David A. , Heppner Gloria H. , Juneau Paul L. 
Published: February 2007

AbstractNatural‐killer(NK) activity was examined in the presence of low oxygen tension, low glucose concentration and acidic pH, to determine whether physical conditions present in the tumor micro‐environment could play a role in down‐regulating cytolytic activity of tumor‐infiltrating lymphocytes with NK phenotype. Anoxia (0% O2), but not hypoxia (1% O2), significantly reduced NK activity, as did acidic pH (6.4 or 6.7). Low glucose concentration (6 mg/dl) did not impair NK activity. Combinations of either moderate (1% O2, 26 mg/dl glucose, pH 6.7) or extreme (0% O2, 6 mg/dl glucose, pH 6.4) alteration of physical conditions significantly reduced NK activity. This study indicates that the physico‐chemical conditions present within solid tumors are capable of down‐regulating NK activity.
A recombinant vaccinia virus expressing human carcinoembryonic antigen (CEA)
Authors: Kaufman Howard , Schlom Jeffrey , Kantor Judy 
Published: February 2007

AbstractCarcinoembryonic antigen (CEA) is a 180‐kDa glycoprotein expressed on most gastrointestinal carcinomas. A 2.4‐kb cDNA clone, containing the complete coding sequence, was isolated from a human colon tumor cell library and inserted into a vaccinia virus genome. This newly developed construct was characterized by Southern blotting, DNA hybridization studies, and polymerase chain reaction analysis. The CEA gene was stably integrated into the vaccinia virus thymidine kinase gene. The recombinant was efficiently replicated upon serial passages in cell cultures and in animals. The recombinant virus expresses on the surface of infected cells a protein product recognized by a monoclonal antibody (COL‐1) directed against CEA. Immunization of mice with the vaccinia construct elicited a humoral immune response against CEA. Pilot studies also showed that administration of the recombinant CEA vaccinia construct was able to greatly reduce the growth In mice of a syngeneic murine colon adenocarcinoma which had been transduced with the human CEA gene. The use of this new recombinant CEA vaccinia construct may thus provide an approach in the specific active immunotherapy of human G1 cancer and other CEA expressing carcinoma types.