bluuebunny/crossref_metadata_2025_split huggingface dataset:
Possible regulation of soluble icam‐1 levels by interleukin‐1 in a sub‐set of breast cysts
Authors: Lai L. C. , Kadory S. , Cornell C. , Lennard T. W. J. 
Published: February 2007

AbstractThere are 2 main groups of breast cysts characterized by their intracystic sodium‐to‐potassium ratios. Women who have intracystic Na/K < 3 may have a higher risk of developing breast cancer than those who have intracystic Na/K > 3. The cell adhesion molecule, ICAM‐1, has been shown to be inducible by interleukin‐1 (IL‐1). Furthermore, ICAM‐1 may be involved in the progression of metastasis in certain malignancies. The aim of this study was to measure intracystic soluble ICAM‐1 (sICAMu‐l) and IL‐1 α/β levels and to assess the relationships between these substances. Wide‐ranging concentrations of sICAM‐1, IL‐1α and IL‐1β were found in breast‐cyst fluid. The high‐electrolyte‐ratio group had intracystic levels of sICAM‐1 and IL‐1β which were significantly higher than those of the low‐electrolyte‐ratio group. No significant difference was found between IL‐1α concentrations in the 2 groups of breast cysts. Strong positive correlations were found between sICAM‐1 and IL‐1α, sICAM‐1 and IL‐1β, and IL‐1α and IL‐1β. The significance of the higher concentrations of sICAM‐1 in the high‐electrolyte‐ratio group remains to be determined, but the results of this study suggest that sICAM‐1 levels in the high‐electrolyte‐ratio group may be regulated in part by IL‐1α and IL‐1β.
Evaluation of PAP and PSA gene expression in prostatic hyperplasia and prostatic carcinoma using northern‐blot analyses, in situ hybridization and immunohistochemical stainings with monoclonal and bispecific antibodies
Authors: Hakalahti Leena , Vihko Pirkko , Henttu Pirkko , Vihko Reijo , Autio‐Harmainen Helena , Soini Ylermi 
Published: February 2007

AbstractIn this report we have investigated levels of prostatic acid phosphatase (PAP) and prostate‐specific antigen (PSA) gene expression in prostatic carcinoma (Ca) and benign prostatic hyperplasia (BPH) specimens. Northern‐blot analyses of total prostatic mRNA indicated that there was a tendency towards lower amounts of PAP mRNA and PSA mRNA in the Ca specimens than in the BPH specimens, although, because of the great variation in the expression levels of both mRNAs, these differences were not statistically significant. In situ hybridization analyses clearly showed that both PAP and PSA mRNAs were confined to the columnar epithelial cells and that stromal cells were devoid of these mRNAs. In addition, PAP and PSA mRNAs were more abundant in BPH tissue than in adjacent Ca tissue within the same specimen. The levels of PAP and PSA enzymes were analyzed immunohistochemically using a bispecific antibody having high affinity for both PAP and PSA, and the results were compared with those obtained using monoclonal anti‐PAP and anti‐PSA antibodies. All 3 antibodies stained only epithelial cells and BPH tissue consistently gave more intense staining than Ca tissue. Furthermore, the anti‐PSA and the bispecific anti‐PAP‐PSA antibodies stained well or moderately differentiated Ca tissues more strongly than poorly differentiated Ca tissues. No PSA staining was detected in 3 and no PAP staining in 5 of the moderately or poorly differentiated carcinomas (grades II or III). Our results show that, in comparison with BPH tissue, prostatic Ca tissue is associated with significantly lower levels of mRNAs coding for the prostatic marker enzymes PAP and PSA, as well as with lower concentrations of these enzymes. Furthermore, dedifferentiation of prostate Ca is associated with a decrease in the level of intraprostatic PSA.
PCR detection and typing of genital papillomavirus in a new brunswick population
Authors: Kurz J. , Mitra K. , Adam R. , Miao X. , Coombs D. H. , Krause M. O. , Mackay J. S. , Isa N. N. 
Published: February 2007

AbstractWe have used a broad range of primers for HPV detection, using the polymerase chain reaction (PCR) so as to compare PCR typing of HPV with the results of cytological diagnosis in a New Brunswick population referred to the out‐patient clinic of the Saint John Regional Hospital. The primers selected were found to be capable of amplification with high efficiency, therefore we did not perform further hybridization analysis for specific identification of HPV types. Amplification of selected fragments for detection of HPV 6, 11, 16, 18, 31 and 33 was obtained from cervical swabs collected from 154 patients. Microscopic examination was performed in duplicate samples and the results compared with the DNA‐typing analysis. HPV of any of the above types was detected in 43 out of 154 patients. Among these, 32 patients showed single or multiple infections with “high‐risk” HPV strains 16, 18, 31 or 33. Cytologically normal or atypical samples with any of the HPV types tested amounted to 17%, but increased to 56% in patients with CIN I, and to 100% in patients with CIN II or III. Prevalence of “high‐risk” types alone increased from 15% and 10%, for normal and atypical cases respectively, to 48% for CIN I, 75% for CIN II and 100% for CIN III. Our results indicate that HPV detection and typing by this simple procedure can be a valuable indicator of cancer progression and thus can help to identify individuals at high risk in pre‐malignant stages of the disease.
CIS‐diamminedichloroplatinum(II) inhibits p34cdc2 protein kinase in human lung‐cancer cells
Authors: Nishio Kazuto , Fujiwara Yasuhiro , Miyahara Yuki , Takeda Yuichiro , Ohira Tatsuo , Kubota Naohiro , Ohta Sei , Funayama Yasunori , Ogasawara Hayato , Saijo Nagahiro , Ohata Masahiro 
Published: February 2007

Abstractcis‐Diamminedichloroplatinum(II) (CDDP) induced G2‐phase arrest in PC‐9 human cancer cells. To elucidate how CDDP acts on cell‐cycle regulation, we analyzed the effect of CDDP on cell‐cycle regulators such as p34cdc2 protein kinase. p34cdc2 protein kinase activity was maximum in G2 phase and decreased after G2/M transition in synchronized PC‐9 human lung cancer cells. Evidence for a phosphorylated p34cdc2 protein kinase complexed with cyclin B was obtained from cells in G2 phase and the p34cdc2 protein kinase appeared to be dephosphorylated at M phase. After exposure to CDDP in G, phase, PC‐9 cells were arrested in G2 phase. The activation of p34cdc2 protein kinase was inhibited by CDDP. Cyclin A and wee‐1 kinase were not affected by the exposure to CDDP. Cyclin B was degraded in M phase in PC‐9 cells. Exposure to CDDP did not affect the degradation of cyclin B. Our data suggest that the effect of CDDP on cell‐cycle phase might be regulated by the dephosphorylation of p34cdc2 protein kinase. To determine whether the p34cdc2 protein kinase is a primary target for CDDP, we examined the direct effect of CDDP on tyrosine dephosphorylation of p34cdc2 protein kinase in cellular extracts. Cell lysates from synchronized PC‐9 in G2 phase were immunoprecipitated with p 13‐Sepharose beads. In vitro dephosphorylation of phosphotyrosine of p34cdc2 protein kinase was observed after exposure to okadaic acid in a concentration‐dependent manner. The dephosphorylation of p34cdc2 protein kinase by okadaic acid was inhibited by CDDP. We hypothesize that inhibition of p34cdc2 dephorphorylation by CDDP is important for its growth‐inhibiting properties.
The influence of angiogenesis inhibitor AGM‐1470 on immune system status and tumor growth in vitro
Authors: Schoof Deric D. , Obando J. Antonio , Cusack James C. , Goedegebuure Peter S. , Eberlein Timothy J. , Brem Harold 
Published: February 2007

AbstractThe synthetic angiogenesis modulator‐1470 O‐(chloroacetyl‐carbomoyl, AGM‐1470) is a potent inhibitor of neovascularization. We have investigated the potential influence of this inhibitor in tumor immunobiology using both in vivo and in vitro models. Mice given a single tail‐vein injection of tumor cells were later treated with AGM‐1470 by s.c. injection. After tumor injection, the lungs were evaluated for macroscopic tumor nodules. AGM‐1470 significantly reduced the development of macroscopic pulmonary disease but did not eliminate disease. However, tumor‐bearing mice treated with AGM‐1470 had significantly reduced spleen weight compared to controls. To determine if the observed decrease in spleen weight in the treated animals was associated with immunosuppression, we studied the possible immunomodulatory effects of AGM‐1470. AGM‐1470 induced no changes in spleen‐cell viability compared to controls. However, addition of angioinhibin at the beginning of IL‐2‐induced spleen‐cell activation significantly inhibited the development of NK‐mediated tumor‐cell killing. Similarly, splenic T‐cell proliferation induced by a mitogenic monoclonal antibody to murine T cells was significantly inhibited when activated in the presence of AGM‐1470. The in vitro studies were extended by evaluation of immune system status in tumor‐bearing mice treated with AGM‐1470. In vivo therapy with AGM‐1470 did not significantly change the mean splenic lymphocyte counts and CD4/CD8 ratios from control values. In addition, the induction of splenic NK‐mediated tumor killing with IL‐2 as well as mitogen‐induced T‐cell activation was not significantly different from control values. These results suggest that AGM‐1470 inhibits tumor growth by blocking neovascularization and may, under certain conditions of drug administration, inhibit immune system function.
Flunarizine as a modulator of doxorubicin resistance in human colon‐adenocarcinoma cells
Authors: Silvestrini Rosella , Zaffaroni Nadia , Costa Aurora , Orlandi Linda , Villa Raffaella , Hendriks Hans R. 
Published: February 2007

AbstractThe potential of the calcium‐entry blocker flunarizine in modulating the cytotoxicity of doxorubicin was investigated in human colon‐adenocarcinoma cell lines sensitive to (LoVo) or with experimentally induced resistance (LoVo/DX) to doxorubicin. Exposure to 1 to 2 m̈g/ml flunarizine for intervals of up to 24 hr did not affect cell survival in either line. Simultaneous exposure to flunarizine and doxorubicin for 1 hr selectively enhanced doxorubicin activity in the resistant cell line and not in the sensitive cell line. In particular, the doxorubicin concentration able to reduce cell survival by 50% dropped to one third. Moreover, simultaneous exposure to flunarizine significantly increased intracellular doxorubicin accumulation, as evaluated by fluorescence spectrophotometry. Again, flow‐cytometric analysis showed hyperpolarization of the membrane in resistant cells, starting from 15 min of exposure to 2 m̈g/ml flunarizine. Finally, in LoVo/DX cells, which normally express gpl70, a 24‐hr treatment with flunarizine markedly reduced the immuno‐reactivity of cells with 2 monoclonal antibodies (MAb57 and MRK16) directed against different external epitopes of the glycoprotein. The results from our study indicate the ability of flunarizine to positively modulate doxorubicin‐resistance in human colon‐adenocarcinoma cells expressing the multidrug‐resistance phenotype.
Importance of mevalonate‐derived products in the control of HMG‐CoA reductase activity and growth of human lung adenocarcinoma cell line a549
Authors: Bennis Faïza , Favre Gilles , Gaillard Francis Le , Soula Georges 
Published: February 2007

AbstractHMG‐CoA reductase catalyzes the synthesis of mevalonate, a crucial intermediate in the biosynthesis of cholesterol and non‐sterol isoprenoid compounds essential for cell growth. The HMG‐CoA reductase activity of the A549 tumor cell line is higher than that of normal human fibroblasts. This deregulation in mevalonate needs was not due to an alteration in the activated state of the enzyme by short‐term regulation. We show that the HMG‐CoA reductase in A549 cell line was subject to a multivalent feedback control. A high fraction (40%) of the reductase activity was devoted to non‐sterol products. In contrast, normal fibroblasts had only 15–20% of the reductase activity that generated non‐sterol products. We also show that cholesterol and at least one of the non‐sterol products are necessary for optimal cell growth of A549 cells. Our data strongly suggest that A549 cells produce more non‐sterol substances which may be related to increased requirements of mevalonate for upregulated cell growth.
Role of cell cholesterol in modulating vincristine uptake and resistance
Authors: Pallarés‐Trujillo J. , Domènech C. , Grau‐Oliete M. R. , Rivera‐Fillat M. P. 
Published: February 2007

AbstractThe relationship between cell‐membrane permeability to vincristine and cholesterol/phospholipid levels was studied in L5I7SY murine leukemic lymphoblasts and in 2 multidrug‐resistant cell sublines, VCR/P60 and VCR/P200, which expressed increasing levels of vincristine resistance. The uptake of 3H‐vincristine was measured in all cell lines and in cholesterol‐depleted and ‐reloaded L5178Y and VCR/P200 cells. The initial rate of drug entry in resistant cells was lower than that measured in the parental cell line and it decreased as the relative resistance increased. An increment of cholesterol content, characterized in resistant cells, was directly proportional to the relative resistance to vincristine. Cholesterol depletion in both sensitive and resistant cells resulted in an increase in the rate of vincristine uptake, which reverted to the respective basal levels when each cell line was cholesterol‐reloaded. The rate of drug uptake was inversely correlated with the molar ratio of cholesterol to phospholipids. Although both VCR/P cell sublines, but not the sensitive parental cells, expressed the P‐glycoprotein in their plasma membrane, there were no differences in drug efflux and retention between resistant and parental cells. These results indicate that cholesterol modulates the permeation of vincristine through the plasma membrane and strongly suggest that increased levels of cholesterol/ phospholipid account for the lower drug accumulation and greater resistance in these multidrug‐resistant cells.
Specific expression of the pancreatic‐secretory‐trypsin‐inhibitor (PSTI) gene in hepatocellular carcinoma
Authors: Ohmachi Yoshitaka , Murata Atsuo , Yasuda Tadashi , Yasuda Takushi , Monden Morito , Mori Takesada , Ogawa Michio , Matsubara Kenichi 
Published: February 2007

AbstractTwenty hepatocellular carcinomas (HCC) were analyzed by Northern blotting to test the expression of pancreatic secretory trypsin inhibitor (PSTI). This gene was expressed in all HCCs, but not in other tumors, including mammary, thyroid, pulmonary and ovarian cancers. Some gastric and colonic cancers weakly expressed PSTI. Among cell lines examined in a similar manner, PSTI was expressed in all of 4 derived from hepatoma. On the other hand, among 15 cell lines derived from cancers other than hepatoma, only 3, derived from pancreatic, colonic and gastric cancers, weakly expressed PSTI. A CAT assay using a deletion set of the 5′ region from the cloned PSTI gene has shown that in hepatoma cell lines, the expression of this gene is dependent on the presence of 2 regulatory regions that include an IL‐6 responsive element and an AP‐1‐binding site. However, in non‐hepatoma cell lines, the 2 regulatory regions are not necessary for expression. The blood level of PSTI in 27 patients with HCC was significantly increased, and it was positively correlated with tumor size, suggesting that specific expression of PSTI in HCC causes this effect and that elevated blood level of PSTI without inflammation indicates the presence of HCC.
Intratumoral microvessel density and L53 protein: Correlation with metastasis in head‐and‐neck squamous‐cell carcinoma
Authors: Gasparini Giampietro , Weidner Noel , Maluta Sergio , Pozza Franco , Boracchi Patrizia , Mezzetti Maura , Testolin Alessandro , Bevilacqua Pierantonio 
Published: February 2007

AbstractSquamous‐cell carcinoma of the head and neck includes a heterogeneous group of tumours of the upper air and food passages for which prognosis is difficult to assess. In fact, patients in comparable stages may have diverse clinical courses and responses to similar treatments. In order to better define the prognosis of each patient there is therefore a need to identify novel biological markers which reflect more accurately growth rate, progression and metastatic potential of each tumour. We assessed whether metastases correlate with micro‐vessel counts (i.e. intratumoral vascularity) using the CD‐31 monoclonal antibody (MAb) and p53 mutant protein expression, determined in the primary by immunocytochemical methods in 70 patients with locally advanced head and neck cancer. Patients were treated with concurrent chemo‐radiotherapy; 50 of these presented loco‐regional node metastasis at diagnosis whereas 3 cases, initially node‐negative, developed distant metastasis during the period of observation. No feature was predictive for objective response to treatment. The overall mean and median blood vessel density at “hot spots” was 37.42 and 36, respectively, and 57% of the tumours expressed p53 mutant proteins. These 2 biological markers were significantly associated. Patients with metastases (loco‐regional and distant) had a significantly higher mean blood‐vessel density than those without tumour spread. Also, patients with p53‐positive (+/ + +) tumours had a significantly higher incidence of metastasis than those with negative ones. Multivariate analysis showed that both vascularity and stage, but not p53 expression, are significant and independent predictors of metastasis in this series.
Expression of αB‐crystallin in human brain tumors
Authors: Aoyama Akira , Steiger Rudolf H. , Fröhli Erika , Schäper Reinhold , Deimling Andreas , Wiestler Otmar D. , Klemenz Roman 
Published: February 2007

AbstractWe have previously shown that αB‐crystallin is a heat‐shock protein which specifically accumulates in response to the expression of c‐Ha‐ras and v‐mos oncogenes in mouse NIH 3T3 fibroblasts. Elevated levels of αB‐crystallin mRNA or protein were shown to be associated with pathological conditions of the brain. Therefore, we have examined the expression of αB‐crystallin in normal human brains and brain tumors by Western blot analysis. αB‐crystallin is moderately expressed in adult but not fetal brain. Elevated levels of αB‐crystallin expression are observed in glial tumors such as astrocytoma, glioblastoma multiforme, and oligodendroglioma. αB‐crystallin in these tumors is predominately unphosphorylated. High amounts of accumulated aB‐crystallin in astrocytic tumors are preferentially found in the more aggressive stages. Glioblastoma multiforme is exceptional in that high αB‐crystallin expression is observed in only one half of the analyzed samples whereas no aB‐crystallin could be detected in the other. These results indicate that αB‐crystallin may be a useful biochemical marker for studying the pathogenesis of various human brain tumors.
Helicobacter pylori infection in japanese patients with adenocarcinoma of the stomach
Authors: Blaser Martin J. , Kobayashi Kensuke , Cover Timothy L. , Cao Ping , Feurer Irene D. , Pérez‐pérez Guillermo I. 
Published: February 2007

AbstractTo examine the association of Helicobacter pylori infection with adenocarcinoma of the stomach in Japanese patients, we studied 29 patients and 58 matched controls. Ascertainment of H. pylori status was based on the presence of specific IgG to H. pylori. For the entire group, an association of this infection with gastric adenocarcinoma was suggested but not statistically significant. For patients in a putatively high‐risk subgroup (non‐cardia tumors and age ≤70 years), the association was significant. Assays detecting serum IgA to whole H. pylori cells and cytotoxin, IgG to cytotoxin and Hp54K (the heat‐shock protein homolog) and serum neutralization of cytotoxin activity each showed clear differences between H. pylori‐infected and uninfected persons in this population. However, for none of these assays was there a significant difference between values for H. pylori‐infected persons with or without gastric cancer. Thus, while H. pylori infection was associated with non‐cardia gastric cancer in Japanese persons ≤70 years of age, use of these additional serologic markers did not define additional factors that might be associated with increased risk.
Gamma‐globulin modulates growth of EBV‐derived B‐cell tumors in scid mice reconstituted with human lymphocytes
Authors: Abedi Mohammad R. , Christensson Birger , Al‐Masud Salahuddin , Hammarström Lennart , Smith C. I. 
Published: February 2007

AbstractThe effect of weekly γ‐globulin injection on the development of human B‐cell tumors was studied in 120 mice with severe combined immunodeficiency (SCID). The mice were injected intraperitoneally (i.p.) with human peripheral mononuclear cells (PBMC) from 6 different Epstein‐Barr virus (EBV)‐seropositive donors. Animals repopulated with cells from 5 donors received γ‐globulin or saline for 20 weeks and were followed up to 24 weeks after reconstitution. A delay in the appearance of fatal EBV‐derived human B‐cell tumors was noticed in the γ‐globulin‐treated groups as compared to the controls. In a separate experiment, the effect of γ‐globulin treatment during the initial 4 weeks after reconstitution was compared to treatment from week 5 to week 8 as well as to a continuous 20‐week treatment. The results from this experiment showed that B‐cell tumor growth could be prevented just as efficiently when the animals were treated only during the first 4 weeks. In contrast, no preventive effect was seen when the first γ‐globulin dose was given at the beginning of week 5 after reconstitution. Our results indicate that γ‐globulin reduces the frequency of EBV‐derived B‐cell tumor development and suggest that SCID mice repopulated with human cells represent a useful in vivo model for evaluation of the prophylactic and/or therapeutic effects of immunomodulatory treatments in lymphoproliferative disorders associated with immunosuppression.