bluuebunny/crossref_metadata_2025 huggingface dataset:
Breath hydrogen and methane in populations at different risk for colon cancer
Authors: Marchand Loïc Le , Wilkens Lynne R. , Harwood Patricia , Cooney Robert V.
Published: February 2007

Results from laboratory and clinical studies have suggested that fermentation in the large bowel may play a protective role against colon cancer. Hydrogen and methane are end‐products of colonic fermentation that are absorbed into the bloodstream and excreted via expired air in the breath. Thus, breath levels of hydrogen and methane have been used as markers for this process. Breath levels of these gases were compared among 10 ethnic and sex groups that exhibit marked differences for colon cancer risk in Hawaii. Four end‐expiratory breath samples were used to characterize daily excretion of hydrogen and methane in a population‐based sample of 244 men and women. There was no significant difference in breath hydrogen or methane by sex or age. Hawaiians produced significantly more hydrogen than Filipinos, and Hawaiians and Caucasians more methane than the 3 Asian groups. These differences did not correlate with risk of colon cancer among these ethnic populations.
Association between expression of sialosyl‐Tn antigen and intestinalization of gastric carcinomas
Authors: Kushima Ryoji , Jancic Snezana , Hattori Takanori
Published: February 2007

We examined immunohistochemically the expression of sialosyl‐Tn antigen (STN) in 137 primary gastric carcinomas. In the non‐neoplastic mucosa, STN was expressed in all goblet cells, most absorptive cells and Paneth cells of intestinalized tubules, whereas it was not seen in the gastric mucosa proper. We evaluated the association between the mucin‐histochemical findings of intramucosal carcinomas and the STN‐expression. STN was expressed in 8 of 20 undifferentiated‐type carcinomas, all of which were mucin‐histochemically of the gastric type. STN was expressed in 25 of 51 differentiated‐type carcinomas, among which it was expressed in 3 of 12 gastric‐type, 11 of 17 intestinal‐type and 11 of 22 mixed‐type adenocarcinomas. The extent of STN expression in the intestinal‐type adenocarcinomas was significantly higher than in gastric‐type adenocarcinomas and undifferentiated‐type carcinomas, and that seen in mixed‐type adenocarcinomas was significantly higher than in the gastric‐type adenocarcinomas. We also examined STN expression in early and advanced carcinomas. As the depth of carcinoma invasion progressed, the extent of STN expression was significantly higher and its incidence was significantly higher. Our findings suggest that STN expression reflects intestinalization of the gastric mucosa, and that a kind of intestinal metaplasia occurs in progressing gastric carcinoma cells.
Hodgkin's disease: The protective effect of childbearing
Authors: Kravdal ØYstein , Hansen Svein
Published: February 2007

Register and census data for complete cohorts of Norwegian men and women born between 1935 and 1974 were used to examine the relationship between reproductive factors and the incidence of Hodgkin's disease (HD). Among 1.3 million men and 1.3 million women under observation, 695 male and 441 female cases of HD were diagnosed during the period of follow‐up. Our hazard model estimates showed that women, at a given age and in a given birth cohort, have an HD incidence inversely related to current parity. A clear relationship was found only for the nodular sclerosis subtype. In men, the risk of HD development was higher than that in childless women, and there was no parity effect. The lower HD incidence among high‐parity women could not be ascribed to their lower social status. Presumably, there is a still unidentified protective factor associated with the biology of childbearing, the effect of which possibly wears off with increasing length of time since childbirth. In addition, there are indications of a net effect of age at entry into motherhood, which may explain part of the estimated parity effect.
Expression and chromosomal assignment of PTPH1 gene encoding a cytosolic protein tyrosine phosphatase homologous to cytoskeletal‐associated proteins
Authors: Itoh Fumio , Ikuta Shigeo , Hinoda Yuji , Arimura Yoshiaki , Ohe Mutsumi , Adachi Masaaki , Ariyama Takeshi , Inazawa Johji , Imai Kohzoh , Yachi Akira
Published: February 2007

We have investigated the mRNA expression of 2 human protein tyrosine phosphatases with sequence homology to cytoskeletal proteins, PTPHI and PTPMEG. Northern‐blot analysis of PTPHI using poly (A)+ RNA from normal human colon tissue showed a low‐abundance message of 4.3 kb. Reverse‐transcriptase/polymerase‐chain reaction (RT‐PCR) was therefore used to detect it in a wide variety of cell lines including 9 colorectal, 5 gastric, 5 hepatic and 6 hematopoietic tumor cells. PTPHI mRNA was not detected only in Colo 320 cells over‐expressing c‐myc mRNA, among the colorectal cancer cell lines examined. When Colo 320 cells were incubated with 5 mM sodium butyrate for 5 days, PTPH I mRNA became detectable, concomitant with the marked decrease in the expression level of c‐myc mRNA. Moreover, the chromosomal localization of PTPHI gene was investigated by fluorescence in situ hybridization. Interestingly, PTPHI gene was mapped to 9q31 where the gene for Gorlin syndrome, a putative tumor suppressor gene, exists.
Effect of somatostatin analog RC‐160 and bombesin/gastrin releasing peptide antagonist RC‐3095 on growth of PC‐3 human prostate‐cancer xenografts in nude mice
Authors: Pinski Jacek , Schally Andrew V. , Halmos Gabor , Szepeshazi Karoly
Published: February 2007

Nude mice bearing xenografts of the androgen‐independent human prostate‐cancer cell line PC‐3 were treated for 4 weeks with somatostatin analog RC‐160, bombesin/gastrin‐releasing peptide (GRP) antagonist (RC‐3095), or the combination of both peptides. In the first experiment, treatment was started when the tumors measured approximately 10 mm3. Tumor volumes and weights were reduced by about 40% by RC‐160 or RC‐3095 administered by s.c. injections at doses of 100 μg/day/ animal and 20 μg/day/animal respectively. The combination of RC‐3095 with RC‐160 did not further potentiate suppression of tumor growth, but histologically the ratio of apoptotic and mitotic indices was significantly higher in the groups treated with the combination than in the other groups. Serum gastrin levels were significantly reduced in all treated groups. Therapy with RC‐160 or the combination also significantly decreased serum growth‐hormone levels. Specific high‐affinity binding sites for bombesin, somatostatin and epidermal growth factor (EGF) were found on the tumor membranes. Receptors for EGF were significantly down‐regulated by treatment with RC‐3095, RC‐160 and a combination of both analogs. Tumors from mice treated with RC‐160 showed a significant increase in maximal binding capacity for somatostatin as compared with control tumors, demonstrating the absence of down‐regulation. In the second experiment, treatment was started when the tumors were well developed and measured approximately 90 mm3. No significant reduction in volume, weight and growth rate of tumors was found in the groups treated with RC‐160 or RC‐3095. Our results suggest that somatostatin analog RC‐160 and bombesin/GRP antagonist RC‐3095 can inhibit the growth of androgen‐independent prostate cancer when the therapy is started at an early stage of tumor development.
p53 protein accumulation and gene mutations in human glioma cell lines
Authors: Anker Lars , Ohgaki Hiroko , Ludeke Barbara I. , Herrmann Hans‐Dietrich , Kleihues Paul , Westphal Manfred
Published: February 2007

Mutations in, and aberrant expression of, the p53 tumor suppressor gene were assessed in 17 cell lines derived from human malignant brain tumors (glioblastoma multiforme). Ex‐ons 5 through 8 were screened by single strand conformational polymorphism analysis (SSCP), followed by direct DNA sequencing. Mutations were found in 6 of 17 glioma cell lines, i.e., at a frequency similar to that found in primary malignant gliomas. Loss of the wild type allele was observed in 4 of the mutated cell lines. Two cell lines had the same mutation (CGG → TGG; Arg → Trp) in codon 248. Five of 6 mutations were transitions, 4 of which occurred at CpG dinucleotides. In one cell line a 10‐bp deletion at the intron 4/exon 5 junction was found. Five of 6 glioma cell lines contained a mutation identical to that in the respective primary tumor despite prolonged in vitro culture (140‐221 passages). Thus, the acquisition of p53 mutations during culture appears to be infrequent. Two cell lines derived from heterozygous tumors maintained the wild type p53 allele during long term culture. p53 protein levels were assessed by immunofluorescence cytochemistry and immunoprecipitation followed by Western blot analysis and revealed elevated levels of the p53 protein, although to a variable extent, in all cell lines with p53 mutations. A marked p53 protein accumulation was also observed in two cell lines lacking p53 mutations in exons 5 through 8, indicating that a prolonged half life of the gene product is not solely dependent on an aberrant coding sequence. The remaining cell lines had either low levels or no detectable p53 protein; one of the latter contained a gross rearrangement of the p53 gene. Our results suggest that with respect to p53 gene status, glioma cell lines usually resemble the original tumors and may, therefore, be suitable for studying the biological changes associated with p53 mutations in glial tumors.
Allogeneic blood transfusion reduces murine pulmonary natural killer (NK) activity and enhances lung metastasis of a syngeneic tumour
Authors: Clarke P. Jane , Burton Robert C. , Wood Kathryn J.
Published: February 2007

A model was established whereby CS7BL/6 (B6) blood injected i.v. into C3H mice 7 days prior to i.v. injection of syngeneic UV‐2237 tumour cells significantly increased the number of pulmonary metastases counted 21 days later as compared with levels observed in mice treated with saline, C3H or NZW blood or SRBC. This regimen of B6 allogeneic blood transfusion of C3H mice also significantly depressed splenic and pulmonary NK activity as assayed by lysis of 51Cr YAC‐1 in vitro and by clearance of 111In YAC‐1 in vivo respectively. Anti‐asialo GMI treatment, which depletes NK activity in vivo, and Poly I:C treatment, which enhances NK activity in vivo, were associated with significantly increased and decreased pulmonary metastasis of UV‐2237, respectively, in C3H mice. Depletion of CD4+ and CD8+ T cells had no effect. Cyclophosphamide pretreatment which, among other effects, depletes NK cells, significantly increased pulmonary metastasis of UV‐2237 in C3H mice. This was corrected by adoptive transfer of normal C3H spleen cells but not spleen cells from anti‐asialo GM 1 ‐treated C3H mice or B6‐blood‐transfused C3H mice. Furthermore, a 1:1 mixture of normal C3H spleen cells with spleen cells from B6‐blood‐transfused C3H mice also failed to reconstitute the cyclophosphamide‐pre‐treated C3H mice. We conclude that allogeneic blood transfusion augments pulmonary metastasis of the UV‐2237 sarcoma in C3H mice and that the mechanism involves suppression of NK activity.
Patterns of allele losses suggest the existence of five distinct regions of loh on chromosome 17 in breast cancer
Authors: Kirchweger Regina , Zeillinger Robert , Schneeberger Christian , Speiser Paul , Louason Geneviève , Theillet Charles
Published: February 2007

Chromosome 17 is a frequent target during breast‐cancer formation and progression. It has been shown to be affected by allele losses at multiple sites, as well as by DNA amplification. Our aim was to delineate a map of the genetic alterations on chromosome 17 in a given set of breast tumors. To this end we analyzed 151 pairs of tumor and cognate lymphocyte DNAs by Southern blotting with 5 RFLP or VNTR probes and by PCR at 8 CA repeat polymorphic loci for LOHs. Moreover, we studied DNA amplification of the evi2, erbB2, thra1, gcsf and rara genes. Data presented here point strongly to the existence of 5 distinct regions of allele losses on chromosome 17:2 on 17p, 3 on 17q. Of the 2 regions on 17p, one involves tp53 while the second is located more distally toward the telomere. LOH was found in 45.9% and 58.8% respectively. The 3 regions on 17q are located: (i) on the proximal portion of the long arm band q21, corresponding to the brcal region; (ii) in a central region defined by the marker D17S74; (iii) on the distal part of 17q (band q25) characterized by losses of the marker D17S24. Each of these regions presented respectively allele losses in 47.5%, 33.3% and 40.8% of the informative tumors. Whereas some tumors presented patterns of LOH consistent with the loss of a complete chromosomal arm or of large portions of the chromosome, a high proportion of the analyzed tumors showed interstitial losses. Amplifications were found in 15% of the tumors and were centered around erbB2. An altered chromosome 17 (bearing an LOH or a DNA amplification) was found in more than 80% of the breast tumor set analyzed here and multiple anomalies affecting this chromosome were often detected in the same sample.
The effect of GM‐CSF and G‐CSF on the growth of human osteosarcoma cells in vitro and in vivo
Authors: Thacker J. Dean , Dedhar Shoukat , Hogge Donna E.
Published: February 2007

The human osteosarcoma cell line, MG63, responds both to GM‐CSF and to G‐CSF in vitro. To assess the significance of these observations to tumor growth in vivo, MG63 cells were engineered by retroviral infection to produce human GM‐CSF or G‐CSF. These retrovirally infected cells become autostimulatory as measured by increased [3H]‐thymidine incorporation (3‐to 7‐fold) and anchorage‐independent colony formation (7‐to 10‐fold) as compared with uninfected MG63 cells or cells infected with control (neor) retrovirus. The increased proliferation induced by exogenous GM‐CSF or G‐CSF on uninfected MG63 cells in both assays could be completely inhibited by anti‐GM‐CSF or anti‐G‐CSF antibodies, while the same antibodies only partially abrogated proliferation by the growth‐factor‐producing cells. None of 34 nude or SCID mice developed tumors when injected s.c. with uninfected or neor‐virus‐infected cells. In contrast, all 30 mice injected with GM‐CSF‐or G‐CSF‐producing MG63 cells developed tumors which were G418‐resistant and factor‐producing. Tumor cell DNA showed a polyclonal retroviral integration pattern indistinguishable from that in the DNA of cells injected into mice. Tumors that formed following injection of a mixture of G418‐resistant, GM‐CSF‐producing cells and cells infected with virus containing only the hygror gene contained hygromycin‐resistant cells in the same proportion as was present in the original cell mixture. These data indicate that GM‐CSF and G‐CSF can support the growth of an osteosarcoma cell line both in vitro and in vivo whether the factor is supplied by autocrine production or from exogenous sources.
The MHC class‐II and CD44 molecules are involved in the induction of tumour necrosis factor (TNF) gene expression by human monocytes stimulated with tumour cells
Authors: Zembala Marek , Siedlar Maciej , Ruggiero Irena , Wieckiewicz Jerzy , Mytar Bozena , Mattei Maurizio , Colizzi Vittorio
Published: February 2007

Tumour necrosis factor alpha (TNF) mRNA is detected in the macrophage infiltrate surrounding the tumour, but the cellular/ molecular interactions leading to TNF gene expression in macrophages are unknown. The in vitro system in which human blood monocytes are stimulated with human cancer cells for TNF release was used to study such interactions. Monoclonal antibodies (MAbs) against various adhesion molecules (LFA‐I, LFA‐3, (CAM‐I, VNR, VLAβI chain) were unable to block TNF production in co‐culture of monocytes with a human pancreatic carcinoma (HPC) cell line. However, anti‐CD44 and anti‐HLA‐DR MAbs effectively blocked TNF release and TNF‐mRNA induction in monocytes. Pre‐incubation of monocytes with anti‐HLA‐DR and tumour cells with anti‐CD44 MAbs had a similar effect. It was concluded that CD44 molecules are involved in tumour‐monocyte interactions and that HLA‐DR determinants of monocytes are engaged in signal transduction for TNF gene activation. These findings may suggest that certain surface determinants of tumour cells act as ligands for MHC class‐II molecules and induce TNF production in monocytes.
Anti‐proliferative and anti‐estrogenic effects of ICI 164,384 and ICI 182,780 in 4‐OH‐tamoxifen‐resistant human breast‐cancer cells
Authors: Coopman Peter , Garcia Marcel , Brünner Nils , Derocq Danielle , Clarke Robert , Rochefort Henri
Published: February 2007

The effects of the anti‐estrogens 4‐hydroxytamoxifen (OHTam), ICI 164,384 and ICI 182,780 were tested on the MCF‐7/LCC2 breast‐carcinoma cell line, which grows significantly in the presence of OHTam and serves as a model for studying anti‐estrogen resistance of estrogen‐receptor‐positive breast cancer. Cell proliferation and cathepsin‐D secretion were strongly inhibited by either ICI 182,780 or ICI 164,384 alone or ICI 164,384 in combination with 17‐p‐estradiol (E2) or OHTam. ICI 164,384 alone did not affect the cathepsin‐D and pS2 mRNA levels, but antagonized the stimulatory effects of E2 or OHTam on these 2 mRNAs. OHTam was more effective than E2 in increasing cathepsin‐D mRNA levels, supporting the idea that anti‐estrogen‐resistant breast cancer continues to over‐express cathepsin‐D. These data show that the steroidal anti‐estrogens ICI 164,384 and ICI 182,780 retain their ability to inhibit cell proliferation and the estrogen‐responsiveness of cathepsin‐D and pS2 genes in the OHTam‐resistant MCF‐7/ LCC2 cell line. These pure anti‐estrogens may thus be efficient second‐line treatments of some Tamoxifen‐resistant tumors.
Analysis of HLA‐DR expression on keratinocytes in cervical neoplasia
Authors: Coleman Nicholas , Stanley Margaret A.
Published: February 2007

We have investigated the expression in vivo and in vitro of HLA‐DR in pre‐invasive squamous‐cell neoplasia of the uterine cervix. Immunohistochemistry of cervical biopsies demonstrated HLA‐DR expression by cervical keratinocytes in 50% of cases of high‐grade squamous intra‐epithelial neoplasia, although the molecule was rarely expressed in low‐grade squamous intra‐epithelial neoplasia and was absent from normal ectocervical cells. HLA‐DR‐positive high‐grade lesions were associated with significantly greater numbers of T lymphocytes in the immediately sub‐epithelial stroma than were the HLA‐DR‐negative high‐grade lesions. In vitro HLA‐DR expression was absent from normal ectocervical epithelium, and from the HPV type 16 containing cell lines W12 (representing low‐grade squamous intra‐epithelial neoplasia) and CaSki and SiHa (each representing high‐grade squamous intra‐epithelial neoplasia), both in monolayer and in organotypic raft culture. HLA‐DR expression was induced in all cell types following recombinant interferon gamma treatment. Our data suggest that the expression of HLA‐DR by keratinocytes in some high‐grade cervical lesions in vivo may be due to local induction of the molecule by pro‐inflammatory cytokines released by immunocompetent cells. The functional significance of HLA‐DR positivity in enabling an effective host immune response to neoplastic cervical keratinocytes remains unclear.
Parathyroid hormone‐related protein and human papillomavirus in gynecological tumors
Authors: Mackenzie Sharon L. , Gillespie Matthew T. , Scurry James P. , Planner Robert S. , Martin T. John , Danks Janine A.
Published: February 2007

The presence of parathyroid hormone‐related protein (PTHrP) and human papillomavirus (HPV) in a series of gynecological tumors from 131 unselected patients was examined. PTHrP was localized immunohistochemically using a highly specific rabbit polyclonal anti‐serum against PTHrP(1–16). The results confirmed that gynecological malignancies, although rarely associated with humoral hypercalcemia of malignancy (HHM), stained for PTHrP in a majority of the squamous‐cell carcinomas (SCC) at all sites, but only in a minority of adenocarcinomas, and then in areas of squamous metaplasia. This included a series of endometrial tumors. Detection of HPV types was achieved using a polymerase‐chain‐reaction (PCR) detection system enabling the detection of HPV types 6, 11, 16, 18,31,33 and 45. PTHrP production was not directly related to HPV infection, but correlated with the type of tumor.
Coordinate enhancement of gelatinase a mRNA and activity levels in human fibroblasts in response to breast‐adenocarcinoma cells
Authors: Noël Agnès C. , Polette Myriam , Lewalle Jean‐Marc , Munaut Carine , Emonard Hervé P. , Birembaut Philippe , Foidart Jean‐Michel
Published: February 2007

Gelatinases/type‐IV collagenases are metalloproteinases involved in some carcinoma invasion and metastatic processes. The exact cellular source of the 72‐kDa gelatinase A is controversial. We have analyzed the expression of mRNA coding for gelatinase A in vivo by in situ hybridization on breast‐cancer tissues. The mRNA for gelatinase A was present in fibroblasts. We have therefore evaluated the gelatinase‐A activity in vitro, in co‐cultures of different breast adenocarcinoma cell lines and human fibroblasts. In monoculture, none of the tumor cells tested produced detectable amounts of gelatinase A. The gelatinase‐A activity was enhanced in cultures of fibroblasts maintained in the presence of MDA‐MB 231 or SKBR3 cells, or their conditioned medium. This increased enzymatic activity was evidenced both in the culture medium and in the membrane fraction and was paralleled by enhancement of the steady‐state levels of mRNA. These results are an in vitro demonstration of a regulation of fibroblasts gelatinase‐A production by soluble factors secreted by breast‐tumor cells.
Chromosomal deletions in anaplastic meningiomas suggest multiple regions outside chromosome 22 as important in tumor progression
Authors: Lindblom Annika , Ruttledge Martin , Collins V. Peter , Nordenskjöld Magnus , Dumanski Jan P.
Published: February 2007

Meningioma is a common, usually benign, sporadic and solitary tumor of the meninges covering the central nervous system. Meningiomas can become malignant, and such anaplastic tumors are associated with a high rate of recurrence and death from the disease. We analyzed 16 sporadic, anaplastic meningiomas for loss of alleles on the majority of chromosomal arms, in order to define regions in the genome which may be important for tumor progression. Loss of genetic material was observed on all but 2 chromosomes studied. While loss of heterozygozity (LOH) from chromosome 22 was the most frequent finding, LOH from the short arm of chromosome I was the second most common lesion occurring preferentially in tumors from men, and at a frequency almost as high as for LOH on chromosome 22. This suggests the existence of a tumor‐suppressor locus on Ip involved in meningioma carcinogenesis. Three tumor samples from one large, anaplastic tumor, each with distinct histopathological characteristics, were studied. All 3 samples showed deletions on 22q and Ip. However, only one tumor sample, with the most malignant histopathological phenotype, displayed, in addition to 22q and Ip, deletions on 9q and 17p. This case suggests that the latter 2 chromosomal regions may harbor genes which contribute to the progression of meningioma.
Sexually transmitted agents and cervical neoplasia in colombia and Spain
Authors: de Sanjosé S. , Muñoz N. , Bosch F. X. , Reimann K. , Pedersen N. S. , Orfila J. , Ascunce N. , González L. C. , Tafur L. , Gili M. , Lette I. , Viladiu P. , Tormo M. J. , Moreo P. , Shah K. , Wahren B.
Published: February 2007

Case‐control studies of cervical intra‐epithelial neoplasia grade III (CIN III) and of invasive cervical cancer were carried out in Spain and Colombia to assess the relationship between cervical cancer and 6 common sexually transmitted agents (STAs). The CIN‐III studies included 525 cases and 512 controls matched for age and for the place of recruitment; the invasive‐cancer studies included 373 historically confirmed cases of squamous‐cell carcinoma and 357 age‐stratified controls selected randomly from the populations that generated the cases. Antibodies to Chlamydia trachomatis, Neisseria gonorrhoeas, Treponemo pallidum, herpes simplex virus type II (HSV‐2) and cytomegalovirus (CMV) were tested in 88% of the women. Cervical scrapes were examined for HPV DNA in 63% of the women using a polymerase‐chain‐reaction assay (PCR). Among controls, the highest antibody prevalence was to CMV (96.5%), followed by HSV‐2 (31.4%) and C. trachomatis (23.3%). For all STAs, the sera‐prevalence was markedly higher in Colombia than in Spain both for cases and for controls. After adjustment for the presence of HPV DNA, C. trachomatis was the only STA associated with CIN III in both countries; Spain and Colombia. In both countries, the risk of CIN III increased with increasing of C. trachomatis antibody titers. Among Spanish women, an increase in risk of invasive carcinoma was found for those with antibodies to N. gonorrhoeae; those with antibodies to HSV‐2 and those with antibodies to C. trachomatis. These associations were present only in HPV‐DNA‐negative women. Among HPV‐DNA‐positive women, none of the STAs considered were associated with cervical neoplasia. Our findings could be interpreted as indicating that past infections with HSV‐2, N. gonorrhoeae and C. trachomatis are surrogate markers of HPV, but because HPV DNA may have escaped detection, we cannot exclude that these STAs are also of separate etiologicaf significance.
Antigenic profile of mucosal melanoma lesions
Authors: Kageshita Toshiro , Kimura Toru , Yoshii Akira , Hirai Shunji , Ono Tomomichi , Ferrone Soldano
Published: February 2007

Ten primary and 6 metastatic mucosal melanoma lesions were tested, utilizing the immunoperoxidase reaction with a panel of 26 monoclonal antibodies (MAbs). The latter included MAbs recognizing membrane‐bound and cytoplasmic‐melanoma‐associated antigens, adhesion molecules and their receptors, and HLA Class‐I and Class‐II antigens. The melanoma lesions displayed differential reactivity with the panel of MAbs. Mucosal melanoma lesions differ from other types of melanoma in their antigenic profile, since they are the only type of melanoma to display a higher expression of p97 MAA, CEA‐MAA and NGF‐R in primary lesions than in metastatic ones. Furthermore, the pattern of HMW‐MAA expression in mucosal melanoma lesions is different from that in nodular and uveal melanoma lesions and only partly resembles that observed in acral lentiginous melanoma lesions. Like other types of melanoma, mucosal melanoma lesions display a heterogeneous expression of HLA antigens, a selective loss of reactivity with some of the anti‐HLA Class‐I MAbs and a higher frequency of abnormalities in HLA Class‐I antigen expression in metastatic than in primary lesions. Expression of HMW‐MAA, 110‐kDa MAA, p97 MAA, CEA‐MAA, NGF‐R and GD2 ganglioside in primary melanoma lesions was found to be associated with a poor prognosis. Although preliminary in nature, these results suggest that analysis of mucosal melanoma lesions with MAbs, in conjunction with information about the clinical course of the disease, will contribute to determine the biological and clinical significance of the distinct characteristics of the antigenic profile of mucosal melanoma lesions.
Three exceptional IgH/myc‐translocation‐carrying rat immunocytomas have breakpoints 50 to 80 kb 5′ of c‐myc
Authors: Axelson Håkan , Panda Chinmay Kumar , Klein George
Published: February 2007

The spontaneously arising immunocytoma of the Louvain rat (RIC) carries a consistent chromosomal translocation between chromosomes 6 and 7. This translocation juxtaposes immunoglobulin heavy chain and c‐myc sequences. In an earlier study on 14 RIC tumors, we found that the translocation breakpoint is located within 1.5 kb immediately upstream of c‐myc in 10 of the tumors. Here we describe 3 exceptional tumors that had no rearrangement within 20 kb 5′ of c‐myc. Using pulsed‐field gel electrophoresis we show that the translocation breakpoints in these tumors are located 50–80 kb 5′. of c‐myc and that c‐myc rearranges to the 3′ end of the IgH cluster.
Inhibition of gastrin‐induced proliferation of AR4–2j cells by calcium channel antagonists
Authors: Bertrand Viviane , Bastié Marie‐José , Vaysse Nicole , Pradayrol Lucien
Published: February 2007

The exact intracellular mechanisms by which gastrin enhances the proliferation of AR4–2J cells, a tumor pancreatic acinar cell line, are not precisely known. Calcium has long been considered as an intracellular signal involved in growth‐regulatory control of many cell types. Moreover, Ca++ channel blockers show growth‐suppressing effects in most proliferating cells. In the present study, we analyzed the role of nifedipine, a voltage‐dependent Ca++ channel antagonist, on AR4–2J cells which possess well‐defined voltage‐dependent Ca++ channels. The results showed that 10 nM gastrin induced a transient rise in intracellular calcium (Ca++), followed by a sustained phase which was dependent upon a Ca++ influx operating through nifedipine‐dependent and‐independent Ca++ channels. Both influxes are necessary for reloading the agonist‐sensitive Ca,++ pools. In parallel, we demonstrated that nifedipine at doses of I μM and 3 μM preferentially blocked the increase in cell number elicited by 10 nM gastrin and 0.1 μM Bay K 8644, a Ca++ channel agonist, suggesting that voltage‐sensitive Ca++ channel activity was required for gastrin‐stimulated mitogenesis. Moreover, nifedipine had no effect on the proliferation of AR4–2J cells growing in serum‐free medium, indicating that this drug did not simply exert a toxic effect. Therefore, Ca++ influx through voltage‐dependent Ca++ channels might be an important initial step representing a component of a synergistic cooperation between different signal transduction pathways involved in gastrin‐regulated growth.
Modulation of cytostatic drugs by nifedipine in two heterotransplanted human testicular‐cancer cell lines differing in their sensitivity to standard agents
Authors: Bokemeyer Carsen , Dunn Theresa , Harstrick Andreas , Lerch T. , Poliwoda Hubert , Schmoll Hans‐Joachim
Published: February 2007

Drug resistance is an important clinical problem in testicular cancer patients with relapsed or refractory disease after first‐line chemotherapy. Here we report that the relative reduction in tumour volume in nude mice heterotransplanted with either H 12.1 or H 23.1 human testicular cancer cell lines was significantly increased by addition of the calcium antagonist nifedipine to the maximum tolerated dose (MTD) of cisplatin (DDP). The mean reduction in relative tumour volume at day 30 (rVR) reached statistical significance for both cell lines following combination therapy of DDP with nifedipine compared to DDP alone (55 ± 7% versus 12 ± 4% for H 23.1 and 60 ± 9% vs. 24 ± 4% for H 12.1). The synergistic anti‐tumour activity of DDP with nifedipine has also been confirmed in H 12.1 cells in vitro. However, in vivo, this combination was associated with a concordant increase in therapeutic toxicity. In contrast, no improvement in in vivo anti‐tumour activity was obtained by combining similar dose‐schedules of nifedipine with the MTD of epirubicin, or with MTDs of vinblastine or etoposide. These results are in agreement with our immunohistochemical finding that H 12.1 and H 23.1 do not over‐express the Pgp 170 grycoprotein which mediates the multiple drug resistance (MDR) phenotype and involves both anthracyclines and vinblastine, but not DDP. We conclude that another Pgp‐MDR modulator, nifedipine, is able to increase the anti‐tumour activity of DDP in vivo and in vitro via a specific but as yet unknown mechanism, which is most likely not MDR‐related. However, the increased anti‐tumour activity is, in vivo, associated with a considerable increase in overall toxicity. Further studies are necessary to decrease therapeutic toxicity, before clinically relevant models for modifiers of DDP‐resistance could possibly be applied to patients.
Karyotypic pattern of pancreatic adenocarcinomas correlates with survival and tumour grade
Authors: Johansson Bertil , Bardi Georgia , Pandis Nikos , Gorunova Ludmila , Bäckman Pia Lena , Mandahl Nils , Dawiskiba Sigmund , Andrén‐Sandberg åke , Heim Sverre , Mitelman Felix
Published: February 2007

The relationship between cytogenetic findings and clinico‐histopathological parameters was assessed in 29 patients with pancreatic adenocarcinoma. Karyotypic analysis revealed normal karyotypes (N) in 8 carcinomas and abnormal karyotypes (A) in 21. Within the A group, 8 cases had simple chromosome abnormalities (As), i.e., only one numerical or structural aberration, whereas 13 had complex changes with multiple numerical and structural abnormalities (Ac). No significant differences between the N and A groups were detected in terms of tumour grade, clinical stage, type of surgery performed, tumour site or size or the patient's age and survival. A correlation analysis between groups As and Ac revealed a significant difference with regard to grade, poorly differentiated carcinomas being more frequent in the Ac group. Patients in the Ac group had also a significantly shorter survival time than those in the As group. None of the other potentially prognostic parameters, i.e., grade, tumour site, stage and type of surgery performed, correlated significantly with clinical outcome. © 1994 Wiley‐Liss, Inc.
Increased production of immune activation marker neopterin by colony‐stimulating factors in gynecological cancer patients
Authors: Marth Christian , Weiss Günther , Koza Astrid , Reibnegger Gilbert , Daxenbichler Günter , Zeimet Alain G. , Fuchs Dietmar , Wachter Helmut , Dapunt Otto
Published: February 2007

Granulocyte colony‐stimulating factor (G‐CSF) and granulo‐cyte‐macrophage colony‐stimulating factor (GM‐CSF) have recently been introduced in the treatment of chemotherapy‐induced neutropenia. Effects of these CSFs on the cellular immune system were evaluated in 38 neutropenic gynecological cancer patients during chemotherapy. In addition to restoring the leukocyte count, GM‐CSF‐to a greater extent than G‐CSF—also induced neopterin, a sensitive marker of macro‐phages activated by interferons. This effect was confirmed in vitro by investigating the effects of these CSFs on interferon‐γ‐mediated pathways in THP‐1 human myelomonocytic cells. The results suggest activation of immune effector cells by GM‐CSF. © 1994 Wiley‐Liss, Inc.
Regulation of ICAM‐1 (CD54) expression in human breast cancer cell lines by interleukin 6 and fibroblast‐derived factors
Authors: Hutchins David , Steel C. Michael
Published: February 2007

Four human breast cancer cell lines (T47D, ZR‐75‐1, MCF7D and HS578T) were examined for the effects of cytokines on expression of cell surface antigens. Interferon (IFN)γ up‐regulated the expression of 1CAM‐1 (CD54) in all the cell lines and coordinately up‐regulated both CD54 and CD40 expression in T47D. Tumour necrosis factor (TNF)α, interieukin (IL)Iα ILIβ and IL6 also up‐regulated the expression of CD54 in all the cell lines but CD40 was unaffected. Levels of expression of CD IIa, CDI8, CD49b, CD58 and CD71 were unaltered by these cytokines. Conditioned medium (CM) generated from human fibroblasts, and Fn particular from foetal cells, was highly effective in up‐regulating expression of ICAM‐I but not of CD40 in the breast cancer cell lines. 1CAM‐1 induction correlated with IL6 bioactivity in these CMs. Combinations of IL6 with other cytokines, such as ILI, resulted in further increases in ICAM‐1 expression. Our observations suggest that IL6 is involved in intercellular signalling between mesenchyme and breast cancer epithelium. © 1994 Wiley‐Liss, Inc.
Glycolipids of germ cell tumors: Extended globo‐series glycolipids are a hallmark of human embryonal carcinoma cells
Authors: Wenk Jonathan , Andrews Peter W. , Casper Jochen , Hata Jun‐Ichi , Pera Martin F. , von Keitz Alexander , Damjanov Ivan , Fenderson Bruce A.
Published: February 2007

Glycolipids of human germ cell tumor lines were analyzed co define the most common immunohistochemical profiles of embryonal carcinoma (EC), differentiated derivatives of EC, yolk sac carcinoma (YC) and choriocarcinoma (CC). Glycolipid composition was examined by high‐performance thin‐layer chromatography (HPTLC) combined with Immunostaining with a panel of anti‐carbohydrate monoclonal antibodies (MAbs). All EC cell lines were found to contain high levels of globo‐series glycolipids, including globotriosylceramide (Gb3), globoside (Gb4), Gb5 (Ga1β1 ± 1Gb4) and GL7 (sialyl Ga1β1 ± 3Gb4). Somatic differentiated derivatives (e.g., EC cells treated with retinoic acid) contained decreased levels of globo‐series glycolipids and increased levels of lacto‐ and ganglio‐series glycolipids, including GD3, GT3 and GD2. CC cell lines contained relatively large amounts of Gb3 but did not contain extended globo‐series glycolipids GbS and GL7. CC cell lines also contained a macroglycolipid reactive with the antibody to SSEA‐1 (Lex). Glycolipids were not detected in two YC cell lines, while other YC cell lines contained globo‐series core glycolipids (Gb3 and Gb4) and gangliosides. We conclude that EC, YC and CC have distinct patterns of membrane glycolipid expression that can be identified by HPTLC and immunostaining. Our results indicate that globo‐series glycolipids GbS and GL7, which carry stage‐specific embryonic antigens 3 and 4 (SSEA‐3 and SSEA‐4), are a hallmark of human EC cells. Cell lines derived from human germ cell tumors that do not express Gb5 and GL7 deserve to be re‐evaluated, since they may represent different stem cells, most likely equivalent to somatic cells and their developmentally committed precursors (e.g., neuroblasts). © 1994 Wiley‐Liss, Inc.
Emergence and Composition of Trichoptera from Karst Habitats, Plitvice Lakes Region, Croatia
Authors: Previšić Ana , Kerovec Mladen , Kučinić Mladen
Published: February 2007

Adult Trichoptera were observed at the Plitvice Lakes, Croatia during two years (2000 and 2001) using pyramid‐type emergence traps. A total of 1350 individuals and 37 species were collected. Throughout the study, the emergence patterns showed only minor variations regarding differences in particular habitats. During 2000 most species emerged in June, and in 2001 in May. The complete emergence period is shown for all collected species and studied in detail for abundant species. Excluding Allogamus uncatus, all abundant species emerged in summer, with most exhibiting a long emergence period. Rhyacophila fasciata had the longest emergence period in both years of the study and also showed winter activity. Trichopteran diversity and equitability were calculated and trophic relationships of the collected species were identified for each sampling site in order to obtain better insight into trichopteran community structure. Results indicated that the trichopteran community could be grouped according to travertine barriers and stream habitat types. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A Data Reduction Exercise to Detect Threshold Samples for Regression Models to Predict Key Water Variables
Authors: Håkanson Lars
Published: February 2007

Inherent uncertainties in empirical data limit our understanding of interrelationships among variables and constrain our possibilities to identify critical thresholds as well as our possibilities to develop practically useful predictive models for water management. This work concerns key water variables for water management and the first aim is to utilize a very comprehensive set of data set for Ringkobing Fjord, Denmark. The paper first presents the methods and data used, then a reference regression for chlorophyll, coefficients of variation (CV = SD/MV; MV = mean value; SD = standard deviation) for a variety of water variables and how these CV‐values influence n, the number of data used to determine coastal area characteristic mean or median values (note that the interest here is not on the conditions in sampling bottle but on the conditions in entire coastal areas, the ecosystem perspective). The main part of the work presents a data reduction exercise including a definition of an error function where the focus is on “large N”, i.e., the number of data in a regression. The results are summarized in a diagram relating the error in the regression to different water variables with different inherent CVs in rivers, lakes and coastal areas. Given the inherently high CV‐values of many of these water variables, more samples than generally taken in most regular monitoring programs are needed if scientific unassailable conclusions are to be made concerning interrelationships among the variables and to produce scientifically meaningful information to detect critical ecosystem changes and threshold values. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Oxidized phosphatidylcholine is a marker for neuroinflammation in multiple sclerosis brain
Authors: Qin J. , Goswami R. , Balabanov R. , Dawson G.
Published: February 2007

Multiple sclerosis (MS) is a common autoimmune neurodegenerative disease of unknown cause, which results in inflammation and plaques of demyelination in brain and eventual axonal degeneration. We report the novel presence of oxidized phosphatidylcholine [1‐palmitoyl‐2‐(5′‐oxo)valeryl‐sn‐glycero‐3‐phosphorylcholine (POVPC)], a lipid associated with inflammatory diseases such as atherosclerosis and lung disease, in the brain of MS patients. The OxPC epitope was detected by Western blotting with the E06 monoclonal antibody. E06‐positive lipid was present in the highest amounts in MS plaques, which also showed evidence of low‐molecular‐weight (15‐kDa) OxPC‐modified protein. E06 reactivity did not change with post‐mortem interval, and E06‐positive lipids were largely absent from control tissue. We then used a second monoclonal antibody (AB1‐2, which recognizes the E06/T15 idiotype and therefore detects the presence of antibody to OxPC) to show that MS brain samples were strongly positive for the 50‐kDa antibody heavy chain. We also showed that isoelectric focussing of the oligoclonal IgG characteristic of MS revealed some immunoglobulin bands that Western blotted with the AB1‐2 antibody. Spinal cords from mice induced to undergo experimental allergic encephalomyelitis (EAE) also showed strong AB1‐2 reactivity by both immunocytochemistry and Western blot analysis. We therefore conclude that we can detect both OxPC and 15‐kDa protein modified by OxPC and the antibody to the antibody to OxPC (antiidiotype) in pathological tissue and suggest that this could play a role in the progression of MS. © 2007 Wiley‐Liss, Inc.
Pyruvate recycling in cultured neurons from cerebellum
Authors: Olstad Elisabeth , Olsen Grethe M. , Qu Hong , Sonnewald Ursula
Published: February 2007

Pyruvate recycling is a pathway for complete oxidation of glutamate. The cellular location and the physiological significance of such recycling has been debated during the last decade. The present study was aimed at elucidating whether recycling takes place in neuron‐enriched cultures of dissociated cerebella, consisting mainly of glutamatergic granule cells, some GABAergic neurons, and few astrocytes. These cultures and cultures of astrocytes from cerebellum were incubated in medium containing [U‐13C]glutamate, and cell extracts were analyzed by gas chromatography and mass spectrometry. Additionally, in the case of the neuron‐enriched cultures, a magnetic resonance (MR) spectrum was obtained. It could be shown that the atom percentage excess of the isotopomer representing pyruvate recycling in glutamate (M + 4) was similar for astrocytes and neuron‐enriched cultures. However, the latter showed more recycling in glutamine (synthesized in the small fraction of astrocytes) than the pure astrocyte cultures, whereas the reverse was the case for aspartate. In fact, the atom percentage excess of the isotopomer representing pyruvate recycling in glutamine was slightly but significantly higher than that in glutamate in the neuron‐enriched cultures. It can be concluded that pyruvate recycling is clearly present in neurons, and this was verified by MR spectroscopy. © 2007 Wiley‐Liss, Inc.
Adenosine inhibits voltage‐dependent Ca2+influx in cone photoreceptor terminals of the tiger salamander retina
Authors: Stella Salvatore L. , Hu Wanda D. , Vila Alejandro , Brecha Nicholas C.
Published: February 2007

Endogenous adenosine has already been shown to inhibit transmitter release from the rod synapse by suppressing Ca2+influx through voltage‐gated Ca2+channels. However, it is not clear how adenosine modulates the cone synapse. Cone photoreceptors, like rod photoreceptors, also possess L‐type Ca2+channels that regulate the release of L‐glutamate. To assess the impact of adenosine on Ca2+influx though voltage‐gated Ca2+channels in cone terminals, whole‐cell perforated‐patch clamp recording and Ca2+imaging with fluo‐4 were used on isolated cones and salamander retinal slices. Synaptic markers (VAMP and piccolo) and activity‐dependent dye labeling revealed that tiger salamander cone terminals contain a broad, vesicle‐filled cytoplasmic extension at the base of the somatic compartment, which is unlike rod terminals that contain one or more thin axons, each terminating in a large bulbous synaptic terminal. The spatiotemporal Ca2+responses of the cone terminals do not differ significantly from the Ca2+responses of the soma or inner segment like that observed in rods. Whole‐cell recording of cone ICaand Ca2+imaging of synaptic terminals in cones demonstrate that adenosine inhibited both ICaand the depolarization‐evoked Ca2+increase in cone terminals in a dose‐dependent manner from 1 to 50 μM. These results indicate that, as in rods, adenosine's ability to suppress voltage‐dependent Ca2+channels at the cone synapse will limit the amount of L‐glutamate released. Therefore, adenosine has an inhibitory effect on L‐glutamate release at the first synapse, which likely favors elevated adenosine levels in the dark or during dark‐adapted conditions. © 2007 Wiley‐Liss, Inc.
A recombinant human IgM promotes myelin repair after a single, very low dose
Authors: Warrington Arthur E. , Bieber Allan J. , Ciric Bogoljub , Pease Larry R. , Van Keulen Virginia , Rodriguez Moses
Published: February 2007

A recombinant human monoclonal IgM, rHIgM22, promotes the synthesis of new myelin when used to treat several animal models of demyelination. rHIgM22 binds to myelin and the surface of oligodendrocytes and accumulates at central nervous system lesions in vivo. The minimal dose of monoclonal IgM required to promote remyelination has a direct bearing on the proposed mechanism of action. A dose ranging study using rHIgM22 was performed in mice with chronic virus‐induced demyelination, a model of chronic progressive multiple sclerosis. The lowest tested dose of rHIgM22 effective at promoting spinal cord remyelination was a single 500‐ng intraperitoneal bolus injection. A time course study of spinal cord repair performed in chronically demyelinated mice revealed that remyelination plateaued by 5 weeks following treatment with rHIgM22. Two doses of rHIgM22 spaced 5 weeks apart did not increase the extent of remyelination over a single dose. The half‐life of rHIgM22 in the mouse systemic circulation was determined to be 15 hr; the human IgM serum concentration was close to zero by 48 hr following antibody administration. We propose that the specificity of rHIgM22 for myelin on living tissue targets the antibody to demyelinated lesions, initiating a long‐term reparative effect on the central nervous system. © 2007 Wiley‐Liss, Inc.