bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphoinositide metabolism in a polyoma‐bk‐virus‐transformed pancreatic islet cell line: Evidence for constitutively activated phospholipase C
Authors: Giæver A. K. , Husom Haukland H. , Bertinussen A. , Vonen B. , Malm D. , Huseby N. E. , Florholmen J. 
Published: February 2007

AbstractWe have characterized the phosphoinositide metabolism in a polyoma‐BK‐virus‐transformed rat pancreatic islet cell line which has highly malignant characteristics, expresses viral T‐antigen and has lost insulin‐secreting capacity. After incorporation with [3H]linositol to isotopic equilibrium, all inositol metabolites were analyzed. When comared with normal pancreatic islets, increased levels of inositol 1,4,5‐trisphosphate (Ins‐ 1,4,5‐P3), inositol 1,3,4‐trisphosphates and inositol tetrakisphosphate (Ins‐P4), and decreased levels of phosphatidylinositol monophosphate (PIP) and phosphatidylinositol bisphosphate (PIP2) were found. The Ins‐1,4,5‐P3/PIP2 ratio increased, whereas the PIP2/PIP ratio was not altered after the transformation. In the pancreatic islet cell line there was a stable accumulation of inositol phosphates at 3.3 mM glucose. Glucose, KCL, cholecystokinin (CCK) and carbachol with and without LiCL were all without effect on the accumulation of inositol phosphates. Somatostatin inhibited the accumulation of inositol phosphates but a Ca2+‐free/EDTA solution did not. Preincubation with cholera toxin or pertussis toxin inhibited the accumulation of inositol phosphates at 3.3 mM glucose except for Ins‐P4, whereas no effect was obsewed on the phosphoinositides. NaF stimulated the accumulation of inositol phosphates, with a concomitant decrease in the phosphoinositides, whereas neomycin was without effect on the inositol phosphates. In normal pancreatic islets, pertussis toxin inhibited the CCK‐ induced increase in Ins‐ 1,4,5‐P3, whereas no effect was seen at 3.3 mM glucose. Finally, pertussis toxin inhibited the CCK‐ induced increase in the Ins‐ 1,4,5‐P3/PIP2 ratio in normal pancreatic islets. The same inhibition was also found in the pancreatic islet cell line at 3.3 mM glucose. We conclude that in the transformed pancreatic islet cell line the phosphoinositide hydrolysis is constitutively activated at the level of phospholipase C, with a substantial loss of regulatory control.
Gangliosides and organ‐specific metastatic colonization
Authors: Coulombe Josée , Pelletier Guy 
Published: February 2007

AbstractTo investigate whether metastatic specificity is associated with a variation in the ganglioside profile of the parent cell lines, we have analyzed and compared the ganglioside content of subcutaneous (s.c.) tumors to that of the corresponding metastases. C57BL/6 mice were injected with either the Lewis lung carcinoma (3LLc) or its cloned variants, M27, exclusively metastatic to the lung, and H59, metastasizing preferentially to the liver. Gangliosides were extracted, purified and separated on HPTLC. H59 liver metastases contained significantly more GM2 (27.80%) than the H59 s.c. tumor (7.6%). The ganglioside profiles of 3LLc or M27 s.c. tumors were no different from those of their corresponding metastases. GM2 predominated in the liver (90.8%) while GM3 (48.8%) and GM2 (33.8%) were prevalent in the lung. Unidentified gangliosides designated G1, G2, G4 and G5 were present in tumor cells but absent from normal lung and liver. This study indicates that the ganglioside compositions of the 3LLc cell line and of its M27 variant were not modified under the influence of different sites of growth. Furthermore, the ganglioside profiles of the metastases were distinct from those of their respective target organs. The results of these studies suggest a possible relationship between GM2 and the establishment of H59 metastases in the liver.
Effect of novobiocin on cisplatin cytotoxicity and dna interstrand cross‐link formation in a cisplatin‐resistant, small‐cell lung carcinoma cell line
Authors: De Jong Steven , Timmer‐Bosscha Hetty , De Vries Elisabeth G. E. , Mulder Nanno H. 
Published: February 2007

AbstractStudies were performed to determine whether novobiocin can be used to enhance cisplatin (CDDP) cytotoxicity in a human small‐cell lung carcinoma cell line, GLC4/CDDP, resistant to CDDP. Continuous incubation with novobiocin enhanced the cytotoxicity of CDDP treatment 1.9‐fold in the parental cell line GLC4, but had no effect on its cytotoxicity in the resistant cell line GLC4/CDDP. Short incubation with novobiocin enhanced the cytotoxicity of CDDP treatment in GLC4 and GLC4/CDDP by a factor of 4.1 and 2.8, respectively. Using the latter schedule, the amount of CDDP‐induced DNA interstrand cross‐links (DNA ISC) at 4 hr as well as at 24 hr after novobiocin and CDDP treatment was higher in GLC4 than in GLC4/CDDP. In this case, the amount of DNA ISC had increased 1.6‐fold in GLC4and 1.3‐fold in GLC4/CDDP at 4hr, and 2.7‐fold and 1.4‐fold, respectively, in these cell lines at 24 hr after treatment compared to CDDP treatment alone. Our results suggest an effect of novobiocin on the formation of DNA ISC. The decreased efficacy of novobiocin, an inhibitor of DNA topoisomerase (Topo) II catalytic activity, in GLC4/CDDP may be due to the increased Topo II activity previously found in the resistant cells. In the present study, we showed that increased Topo II activity was not due to changes in amounts of Topo II in nuclei or nuclear extracts of GLC4/CDDP. Further analysis of the chromatin, that includes Topo II, showed that the chromatin in nuclei of GLC4/CDDP was more sensitive to micrococcal nuclease digestion than GLC4. In addition, the amount of a 56‐kDa protein was increased 2‐fold in nuclei and nuclear matrices from GLC4/CDDP. The reduced efficacy of novobiocin to increase the CDDP cytotoxicity as well as the formation of DNA ISC in GLC4/CDDP compared to GLC4 may be due to changes in the chromatin structure of the resistant cells.
Induction of the fundic mucosa‐specific glycolipid with dimethylformamide in gastric‐cancer cell lines
Authors: Dohi Taeko , Nakasuji Miyuki , Oshima Mieko 
Published: February 2007

AbstractWe have previously reported that a glycolipid GalNAcβ I‐4[NeuAcα2‐3]Galβ I‐4GlcNAcβ I ‐3Galβ I‐4Glc‐Cer named NGM‐I is present specifically in the human gastric fundic mucosa, but not in other organs. In gastric‐cancer tissue and cancer cell lines, this glycolipid completely disappears. These findings imply that NGM‐I is expressed only in well‐differentiated fundic mucosa. The purpose of this study is to examine the expression of NGM‐I as a differentiation‐related molecule. A gastric cell line AZ52I was cultured in the medium with various reagents which had been reported to induce differentiation in cancer cells. The growth of AZ52I was suppressed by the addition of 0.8% dimethylformamide (DMF) to the medium, but not by addition of dimethylsulfoxide (DMSO), retinoic acid or butyric acid. In the ganglioside fraction of the cells cultured with DMF. a glycolipid regarded as NGM‐I which had not been present before treatment was detected using a monoclonal antibody. Suppression of the proliferation of AZ52I by eliminating the serum from the medium could not induce the expression of NGM‐I. A colonic cell line treated with DMF also failed to express the glycolipid. The synthase activity of NGM‐I was elevated in the AZ52I cells treated with DMF, but not with DMSO. These results demonstrate that the expression of NGM‐I is induced by DMF specifically in gastric‐cancer cells, and suggest the possibility that NGM‐I is a differentiation‐related molecule.
Incidence pattern of thyroid cancer in norway: Influence of birth cohort and time period
Authors: Akslen Lars A. , Haldorsen Tor , Thoresen Steinar Ø. , Glattre Eystein 
Published: February 2007

AbstractThe incidence of thyroid cancer in Norway increased about 2‐fold for both sexes during the period 1955 to 1989 (4691 cases). In the last 5‐year period, however, a decline was observed, especially among females. The ratio between age‐ adjusted incidence rates in Northern Norway compared with Southern Norway was 1.6 for females and 1.5 for males, and the incidence pattern during the period was similar in the 2 regions. The analysis of age‐cohort‐period models showed a strong cohort effect in both sexes. The reason for this is not clear, although radiation treatment during childhood and dietary habits may possibly be involved. A weaker but statistically significant and transient period effect was also present, giving relatively higher incidence rates, especially in the 1970s. Although this result may be consistent with an influence of radioactive fallout in the northern area, more detailed studies are needed.
Linkage mapping in familial breast cancer: Improved localisation of a susceptibility locus on chromosome 17q12‐21
Authors: Porter D. E. , Cohen B. B. , Wallace M. R. , Carothers A. , Steel C. M. 
Published: February 2007

AbstractFifteen pedigrees with a total of 75 cases of breast cancer, 10 of ovarian cancer and 53 of other cancers have been collected. Polymorphic markers on chromosome 17q have been screened to locate a putative breast‐cancer gene using DNA from relevant individuals within these families. Pairwise LOD scores have been calculated for markers CMM86, NM23, 42D6 and MFD188. The maximal summated LOD for the 15 families 4.45 at 8 = 0.025 using 42D6. All cases of bilateral breast cancer and ovarian cancer appear to be linked to this region. Recalculating LOD scores on the assumption of linkage in these cases increases the maximal rummated LOD to 5.62 at 8 = 0.025 using 4206. A genetic exclusion map of critical recombinants linked families suggests that the gene is flanked by markers 42D6 and MFD188, a region 5 to 10 cm in length.
Evaluation of the new (1987) TNM classification for thoracic esophageal tumors
Authors: Kato Hoichi , Tachimori Yuji , Watanabe Hiroshi , Iizuka Toshifumi 
Published: February 2007

AbstractA total of 351 patients with thoracic esophageal carcinoma were prospectively classified according to the new (1987) TNM classification. Sixty‐two patients received chemotherapy and/or radiotherapy without surgery. Esophagectomy was performed on 291 patients, among whom 139 underwent cervical, mediastinal and abdominal lymph adenectomy (3‐field dissection). The number of stage IIB patients was unnaturally small, and the 3‐year survival rates of stages IIA and IIB were similar. The survival curves for patients of T, N and M categories distributed well except for those of stages IIA and IIB. Numbers of patients in N and pN categories and those in M and pM categories showed poor coincidence. The 5‐year survival rate for MI patients (IO.Wo) was too good, which suggested the mingling of patients with rather better prognosis. When MI (LYM) patients were excluded from M I, the 3‐year survival rate fell to 0.3%. The 5‐year survival rate for pM I (LYM) patients who underwent 3‐field dissection was 38.2%. Survival rates and numbers of positive nodes showed negative correlation in patients who underwent 3‐field dissection. According to these results, we propose the following revision in the next TNM classification: (I) to group stage IIA and stage IIB together to form Stage II; (2) to include cervical and coeliac lymph nodes among the regional lymph nodes, or to designate metastasis in non‐regional lymph nodes separately from metastasis in viscera; and (3) to divide N I into N1 and N2 according to the number of positive lymph nodes.
Different roles for phenacetin and paracetamol in cancer of the kidney and renal pelvis
Authors: McCredie Margaret , Stewart J. H. , Day N. E. 
Published: February 2007

AbstractA population‐based case‐control study of kidney cancer was carried out in New South Wales using data from structured interviews with 489 cases of renal‐cell cancer and 147 cases of renal pelvic cancer diagnosed in 1989 and 1990, together with 523 controls from the electoral rolls. This study showed that the risk of renal pelvic cancer was increased by phenacetin/aspirin compound analgesics (RR = 12.2; 95% CI 6.8‐22.2) to a far greater extent than by paracetamol (RR = 1.3; 95% CI 0.7‐2.4; not significant). There was a doubling of risk (RR = 2.0; 95% CI 0.94.4) in the highest tertile of paracetamol taken in any form compared with values for non‐users of any type of analgesic. By contrast, the risk of renal‐cell cancer appeared to be increased to a similar degree by phenacetin/aspirin compound analgesics (RR = 1.4; 95% CI 0.9‐2.3) and paracetamol taken in any form (RR = 1.5; 95% CI 1.0‐2.3). When both drugs were treated as alternative forms of the same risk factor, the risk was increased by 1.7 (95% CI 1.2‐2.4). On this evidence, we postulate that phenacetin/aspirin compounds are weakly carcinogenic in the renal parenchyma through the metabolic conversion of phenacetin to paracetamol, and potently carcinogenic in the renal pelvis by different or additional pathways involving renal papillary necrosis. In addition, there is an indication of a weak link between paracetamol and renal pelvic cancer.
K‐ras mutations in human adenocarcinoma of the lung: Association with smoking and occupational exposure to asbestos
Authors: Husgafvel‐Pursiainen K. , Hackman P. , Ridanpää M. , Anttila S. , Karjalainen A. , Partanen T. , Taikina‐Aho O. , Heikkilä L. , Vainio H. 
Published: February 2007

AbstractWe investigated point mutational activation of the ras genes (K‐ras codons 12, 13 and 61; N‐ras codons 12, 13 and 61; H‐ras codons 12 and 61) in primary, resected lung cancer by dot blotting and oligonucleotide hybridization. K‐ras mutations were found in 14 (29%) of the 48 lung tumour specimens examined, but no N‐ras or H‐ras mutations were found. The highest frequency of K‐ras mutation was observed in adenocarcinoma: 12 of the 21 samples studied (57%) had a mutation, which is one of the highest frequencies reported for lung adenocarcinoma. The commonest type of mutation in these lung tumour samples consisted of transversions: we observed 11, of which 8 (57% of all mutations) were G to T transversions. Most of the 48 patients studied had a history of heavy smoking, either with or without evidence of occupational exposure to asbestos. Statistical analysis revealed‐in addition to the highly significant association between the adenocarcinoma type of lung cancer and K‐ras mutation‐a clear association of K‐ras mutations with heavy life‐time smoking (≥50 pack‐years of cigarette smoking; odds ratio (OR) 4.9, 90% CI 1.2 ‐ 19.5, multivariate analysis). In addition, occupational asbestos exposure showed an elevated, but non‐significant, OR of 2.2 (90% CI 0.6 ‐ 8.7) with the presence of K‐ras mutation. We conclude that the occurrence of K‐ras mutations in adenocarcinoma of the lung is frequent, and that such mutations are associated with heavy life‐time exposure to tobacco smoke, possibly in combination with occupational exposure to asbestos fibres.
Decreased expression of DCC mRNA in human colorectal cancers
Authors: Itoh Fumio , Hinoda Yuji , Ohe Mutsumi , Ohe Yasuo , Ban Toshihiro , Endo Takao , And Kohzoh Imai , Yachi Akira 
Published: February 2007

AbstractThe mRNA expression levels of DCC gene, which is cloned from the deleted region of chromosome 18q in colorectal cancers and thought to be a tumor‐suppressor gene, was evaluated in tissue specimens surgically resected from patients with colorectal cancer by RT‐PCR. This method was chosen as the expression level of DCC mRNA is below the detectable level for Northern‐blot analysis. Semi‐quantitative measurements of DCC mRNA were performed based on a standard curve defined by serial dilution of DCC cDNA. As a result, the expression level of DCC mRNA was found to be lower in 17 out of 30 colorectal cancers than in adjacent non‐cancerous tissues. Inclusion of smooth muscle in tissue specimens was observed to have little disturbing effect on comparisons between cancerous and non‐cancerous regions. In addition, all 4 specimens of colorectal cancer with liver metastasis showed the decreased expression level of DCC mRNA, suggesting that functional loss of DCC in cancerous tissues may play an important role in metastatic events.
Thymosin β‐10 expression in melanoma cell lines and melanocytic lesions: A new progression marker for human cutaneous melanoma
Authors: Weterman Marian A. J. , Van Muijen Goos N. P. , Ruiter Dirk J. , Bloemers Henri P. J. 
Published: February 2007

AbstractWhen screening a subtraction library for sequences that were specifically expressed in highly metastatic human melanoma cell lines, a cDNA clone was isolated encoding thymosin β‐10. We found that expression of thymosin β‐10 mRNA was associated with metastatic behavior of various human melanoma cell lines in nude mice. Furthermore, Northern blot analysis showed that also in freshly harvested human melanocytic lesions thymosin β‐10 was differentially expressed. Although expression of thymosin β‐10 was also examined in other non‐melanoma model systems and materials, no clear relation could be established with metastatic potential or malignancy. Therefore, we conclude that thymosin β‐10 can be considered as a new progression marker for human cutaneous melanoma.
A monoclonal anti‐idiotypic antibody with an internal image of a “phosphatidylinositol‐like” structure derived from anti‐“phosphatidylinositol‐like” igg from the sera of patients with proliferative malignancies
Authors: Faiderbe S. , Chagnaud J. L. , Geffard M. 
Published: February 2007

AbstractUsing an enzyme‐linked immunosorbent assay (ELISA) with phosphatidylinositol (Ptdlns) coated on well‐plates, high levels of anti‐“Ptdlns‐like” autoantibodies (autoAbs) have been previously described in sera of cancer patients. These anti‐“Ptdlns‐like” autoAbs were purified and injected into BALB/c mice. A monoclonal anti‐idiotypic antibody (Ab2), internal image of human endogenous “Ptdlns‐like” structure called AIPI, was selected. Then the immunological binding in sera of cancer patients was evaluated on AIPI coated on well‐plates. Using this indirect ELISA method, we found a statistically highly significant immunological binding in sera of patients with epithelial tumors, which correlated with that previously found with the Ptdlns molecule coated on well‐plates. Moreover, AIPI mimics an endogenous structure closely associated with Ptdlns specifically encountered in epithelial proliferative disease.
Inhibition of growth‐factor‐activated proliferation by anti‐estrogens and effects on early gene expression of mcf‐7 cells
Authors: Wosikowski Katja , Küng Willy , Hasmann Max , Löser Roland , Eppenberger Urs 
Published: February 2007

AbstractRecently, it was reported that the anti‐estrogen tamoxifen not only inhibits estradiol‐stimulated growth of MCF‐7 cells but also significantly reduces the proliferation rate of cells stimulated by growth factors. We have confirmed this finding and also shown that the new anti‐estrogen droloxifene inhibits the proliferation of epidermal growth factor (EGF) and insulin‐like growth factor‐I (IGF‐I)‐stimulated MCF‐7 cells. The growth‐factor‐induced proliferation was inhibited in a dose‐dependent manner by the anti‐estrogens in the complete absence of estrogen and FCS. Of the anti‐estrogens, droloxifene was considerably more potent than tamoxifen. Because the exprersion of the proto‐oncogenes c‐fos and c‐myc has been considered a key event in development of the mitogenic response, we examined the effects of anti‐estrogens on c‐myc and c‐fos gene expression. We included in these investigations the steroidal anti‐estrogen ICI 164,384 because this compound has no or very little estrogenic activity. The studies revealed that all 3 antiestrogens transiently induced c‐myc mRNA expression. However, the anti‐estrogens inhibited estradiol‐induced c‐myc mRNA expression, although with different potencies. Pre‐incubation of MCF‐7 cells with droloxifene and tamoxifen resulted in elevated levels of growth‐factor‐induced c‐myc mRNA expression. In contrast, the anti‐estrogens did not induce c‐fos mRNA or affect the expression of c‐fos mRNA induced by growth factors. In conclusion, non‐steroidal anti‐estrogens inhibit growth‐factor‐stimulated proliferation of MCF‐7 cells without inhibitinggrowth‐factor‐induced c‐myc or c‐fos mRNA expression.
Increased radioresistance of ejras‐transformed human osteosarcoma cells and its modulation by lovastatin, an inhibitor of p21ras isoprenylation
Authors: Miller Alexandra C. , Kariko Katalin , Myers Charles E. , Clark Edward P. , Samid Dvorit 
Published: February 2007

AbstractAlterations in ras oncogene expression have been associated with increased cellular resistance to ionizing radiation. As an extension of studies with murine cell models, we have now explored the radioresponses of human osteosarcoma (HOS) sub‐clones that differ in their EJras expression. Quantitative analysis revealed a tight correlation between the amounts of ras‐encoded mRNA and p21 produced, and the degree of cell radioresistance. Interestingly, treatment of the ras‐transformed cells with lovastatin, an inhibitor of p21ras post‐translational processing via the mevalonate pathway, markedly decreased their radioresistance. Under the experimental conditions used, lovastatin prevented the membrane association, but not the biosynthesis, of p21. The decline in radiation resistance following lovastatin treatment could not be attributed to perturbation of cholesterol metabolism or to non‐specific cell‐cycle effects. In agreement, lovastatin did not alter the radiation responses of control HOS cells that do not express EJras, or those with an activated met oncogene. The results indicate that elevation in ras gene expression can lead to increased radioresistance of human tumor cells. It appears, however, that p21ras membrane localization is critical for maintenance of the radioresistant phenotype, thus providing a target for pharmacological intervention.
Establishment of l1210 leukemia cells resistant to the distamycin‐a derivative (FCE 24517): Characterization and cross‐resistance studies
Authors: Geroni Cristina , Pesenti Enrico , Tagliabue Giovanna , Ballinari Dario , Mongelli Nicola , Broggini Massimo , Erba Eugenio , D'Incalci Maurizio , Spreafico Federico , Grandi Maria 
Published: February 2007

AbstractN‐deformyl‐N‐[4‐N,N‐bis(2‐chloroethylamino)benzoyl] distamycin‐A (FCE 24517) is a new cytotoxic anti‐tumor agent in phase‐I clinical trials. We have isolated stable FCE‐24517‐resistant cell sublines from murine leukemia L1210 cells by in vitro exposure to the drug. FCE 24517 selects a mixed population of resistant cells: the L1210/245171 cell line in vitro was in fact resistant to the selecting agent (RI 48.3), as well as to L‐PAM (RI 5.4) and DX (RI 8.6) and over‐expressed the mdr‐I gene. When L1210/245171 cells were implanted in vivo and evaluated for sensitivity to the same agents, resistance was observed only to FCE 24517 and partially to L‐PAM. whereas DX had the same anti‐tumor efficacy as on the sensitive line. The clone derived from the above subline (L1210/245172) was resistant to FCE 24517, distamycin‐A and other cytotoxic compounds bearing the distamycin‐A skeleton, and fully sensitive to DX and other anti‐tumor compounds involved in the multi‐drug resistance mechanisms, with a complete disappearance of the mdr phenotype. L1210/245172 cell line is partially cross‐resistant to L‐PAM, this resistance being accounted for by higher GSH intracellular levels, which however do not influence the resistance to FCE 24517. In fact, BSO treatment was capable of significantly modifying only the cytotoxicity of L‐PAM. Our data suggest that L1210/245172 cells present a mechanism of resistance specific for FCE 24517 and related molecules.