bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcome of colorectal cancer patients treated with human monoclonal anti‐idiotypic antibody
Authors: Denton Gavin W. L. , Durrant Lindy G. , Hardcastle Jack D. , Austin Eric B. , Sewell Herb F. , Robins R. Adrian 
Published: February 2007

AbstractA human monoclonal anti‐idiotypic antibody (105AD7) has been developed which mimics a colorectal‐tumour‐associated antigen and induces cellular anti‐colorectal tumour immune responses in animals. Thirteen patients with advanced colorectal cancer were immunized with 105AD7 and their survival was compared with that of a contemporary group of unimmunized patients with similar disease status. No toxicity related to anti‐idiotype immunization was seen. Cellular responses to anti‐idiotypic immunization were indicated by lymphocyte proliferation to gp72‐positive tumour cells, and production of interleukin‐2; anti‐tumour antibodies were not detected. Median survival following diagnosis of advanced disease of immunized patients was 12 months, compared with 4 months in unimmunized patients. The improved survival of immunized patients in this study without associated toxicity suggests that 105AD7 immunization may have considerable potential for immunotherapy of colorectal cancer. © Wiley‐Liss, Inc.
Invasion depth is the most important prognostic factor for transitional‐cell carcinoma in a prospective trial of radical cystectomy and adjuvant chemotherapy
Authors: Mazzucchelli Luca , Bacchi Marisa , Studer Urs E. , Markwalder Regula , Sonntag Roland W. , Kraft Rainer 
Published: February 2007

AbstractThe aim of this prospective study was to examine the prognostic pathomorphological factors in urothelial cancer of the urinary bladder. Clinical and morphological variables were evaluated by univariate and multivariate analysis in 70 patients with invasive transitional‐cell carcinoma of the bladder (pTI‐pT4a). The patients were treated according to a prospective program consisting of radical cystectomy and pelvic‐node dissection, either alone or followed by adjuvant cisplatinum chemotherapy. Nodal status was pN0 in 89% of the patients. The median follow‐up time was 5.75 years and the 5‐year survival was 58%. Among the morphologic variables, deep invasion of the bladder wall and squamous differentiation indicated a poorer prognosis. Differentiation grade, pattern of growth (infiltrating versus expanding), angioinvasive growth, glandular differentiation and concomitant prostate carcinoma (pT1) were not significative factors for survival. By contrast, a significant reduction in mortality rate was found in patients with concomitant carcinoma in situ. Multivariate analysis confirmed that depth of invasion is an independent prognostic factor of outcome. The results confirm the primary importance of tumor stage in the prediction of survival after radical cystectomy. © Wiley‐Liss, Inc.
Aberrations of tumor‐suppressor genes (p53, apc, mcc and Rb) in esophageal squamous‐cell carcinoma
Authors: Maesawa Chihaya , Tamura Gen , Suzuki Yasushi , Ogasawara Satoshi , Ishida Kaoru , Saito Kazuyoshi , Satodate Ryoichi 
Published: February 2007

AbstractLoss of heterozygosity at 4 tumor‐suppressor gene loci (p53, apc, mcc and Rb) was investigated using polymerase chain reactions, in 49 esophageal squamous‐cell carcinoma specimens from patients who had undergone curative resection. Mutations in the p53 gene within exons 5 to 8 were also examined. LOH was detected in 9 (43%) of 21 p53 genes, 16 (55%) of 29 apc genes, 10 (48%) of 21 mcc genes, and 13 (52%) of 25 Rb genes for which heterozygosity could be determined. Mutations in the p53 gene were detected in 18 (36%) of 49 cases and were significantly more frequent in stage‐III tumors and in tumors exhibiting DNA aneuploidy. In 5 cases where heterozygosity could be determined for all the loci, all had 2 or more aberrations. Additionally, a heterozygous deletion of p53 gene was associated with a mutation of the remaining allele in 8 (89%) of 9 cases. Short‐term relapse within 3 to 12 months occurred significantly more frequently in patients having tumors with both p53 aberrations (p < 0.05). Thus, aberration of tumor‐suppressor genes was a frequent occurrence in esophageal squamous‐cell carcinoma and inactivation of the p53 gene may contribute to the progression of this tumor. © Wiley‐Liss, Inc.
Early‐life risk indicators of gastric cancer. A population‐based case‐control study in sweden
Authors: Hansson Lars‐Erik , Baron John , Nyrén Olof , Bergström Reinhold , Wolk Alicja , Lindgren Anders , Adami Hans‐Olov 
Published: February 2007

AbstractExposures early in life seem to play an important role in the development of gastric cancer, but their nature is not well understood. In a population‐based case‐control study, we examined weight, height and body‐mass index (BMI) at the age of 20 as well as indices of socioeconomic conditions. Face‐to‐face interviews were conducted with 338 of 456 eligible histologically confirmed gastric cancer patients and 679 of 880 eligible control subjects, sampled from population registers and frequency matched by age and gender. Gastric cancer risk was negatively associated with height. Risk was positively associated with weight at age 20 in both sexes. The highest BMI‐quartile was associated with an increased risk. This association between BMI and risk was confined to BMI at age 20, and disappeared for BMI 20 years prior to interview. High socioeconomic status (SES) as well as long education carried a decreased risk of gastric cancer. Number of siblings was positively associated with risk. Factors related to short stature and high adolescent body weight are associated with an increased risk of gastric cancer, as is a high number of siblings. These factors may reflect influences of dietary patterns early in life. © Wiley‐Liss, Inc.
Multiple sub‐sets of Cd4+ and Cd8+ cytotoxic T‐cell clones directed to autologous human melanoma identified by cytokine profiles
Authors: Maccalli Cristina , Mortarini Roberta , Parmiani Giorgio , Anichini Andrea 
Published: February 2007

AbstractCD4+ and CD8+ cytotoxic T‐cell (CTL) clones, selected for T‐ceII‐receptor (TcR)‐dependent lysis of the autologous tumor and isolated from peripheral‐blood lymphocytes (PBL) or tumor‐infiltrating lymphocytes (TIL) of 3 melanoma patients, were characterized for the pattern of 13 different cytokines released by antibody‐ or tumor‐mediated triggering. Induction or enhancement of cytokine release by anti‐CD3 monoclonal antibody (MAb) led to the identification of 2 major sub‐sets of CD8+ CTL clones on the basis of production of IL‐4. Within the 2 groups of IL‐4‐producing or non‐producing clones, further sub‐sets could be identified on the basts of differential production of IL‐1 p, IL‐2, IL‐6, IL‐8, IL‐10, TNF‐α, TNF β and IFN‐γ. A similar analysis performed on a panel of CD4+ CTL clones indicated multiple patterns consistent with at least 4 major sub‐sets, but further complexity was evident in each sub‐set on the basis of differential production of IL‐1, IL2, IL‐6, IL‐10 and G‐CSF. The cytokine profile of CD4+ and CD8+ clones, as determined after anti‐CD3 stimulation, was different from the pattern seen after co‐culture with autologous tumor, since many clones released cytokines such as IL‐4, IL‐10, IFN‐α and‐β, TNF‐γ and GM‐CSF after activation with only 1 of the 2 stimuli. These results indicate that CD4+ and CD8+ CTL clones reacting to human melanoma belong to a highly complex repertoire of functional subsets characterized by distinct cytokine profiles. In addition, the cytokine pattern of each T‐cell sub‐set can be modulated by changing the activation signals delivered to the T cell. © Wiley‐Liss, Inc.
DNA base modifications in renal chromatin of wistar rats treated with a renal carcinogen, ferric nitrilotriacetate
Authors: Toyokuni Shinya , Mori Toshiaki , Dizdaroglu Miral 
Published: February 2007

AbstractFerric nitrilotriacetate (Fe‐NTA) causes renal proximal tubular necrosis, a consequence of iron ion‐mediated free‐radical‐associated damage, that finally leads to a high incidence of renal ad en oca re in dm a in male rats and mice. We have investigated the levels of typical hydroxyl radical‐induced DNA base modifications in renal chromatin of male Wistar rats treated with a single or repeated administrations of Fe‐NTA. Five pyrimidine‐derived and 5 purine‐derived modified DNA bases were identified and quantified by gas chromatography/mass spectrometry with selected‐ion monitoring. The modified bases were 5‐hydroxy‐5‐methylhydantoin, 5‐(hydroxymethyl)uracil, 5‐hydroxy‐cytosine, thymine glycol, 5,6‐dihydroxyuraril, 4,6‐diamino‐5‐form‐amidopyrimidine, 8‐hydroxyadenine, xanthine, 2‐hydroxyadenine and 8‐hydroxyguanine. The amounts of most of these compounds were significantly increased over control levels in renal chromatin of Fe‐NTA‐treated rats as measured 3 and 24 hr after treatment. Elevated levels of modified bases were accompanied by proximal tubular necrosis. On the 19th day, however, accumulation of modified DNA bases was not observed. Morphologically, scattered karyomegaiic cells were seen in the proximal tubules, but necrosis was rarely found. Some of the identified DNA base lesions are known to be promutagenic., although others have not been investigated. Presence of modified DNA bases concomitant with necrosis and regeneration of the renal proximal tubules may be a critical step in Fe‐NTA‐induced carcinogenesis. © Wiley‐Liss, Inc.
Reproductive history and cancer of the biliary tract in women
Authors: Moerman Clara J. , Berns Mary P. H. , de Messqita H. Bas Bueno , Runia Sytske 
Published: February 2007

AbstractAlthough reproductive factors have been shown to be related to the composition of bile and functioning of the biliary system, their relationship with biliary tract cancer has not been studied in detail. Between 1984 and 1987 we conducted a case‐control study of 75 women with cancer of the biliary tract and 252 controls from the general population. An interviewer‐administered questionnaire was used to collect information on reproductive history. The information was obtained from the responders themselves (direct response) or from relatives (indirect response). Our results indicate that younger age at menarche, early age at first pregnancy, higher number of pregnancies and prolonged fertility may enhance the risk of cancer of the biliary tract. Overall, increased exposure to endogenous oestrogens and progesterone constitutes a higher risk. © 1994 Wiley‐Liss, Inc.
Time trends of lung and larynx cancers in Italy
Authors: Capocaccia Riccardo , Micheli Andrea , Berrino Franco , Gatta Gemma , Sant Milena , Ruzza Maria Rosa , Valente Fulvia , Verdecchia Arduino 
Published: February 2007

AbstractDuring the period 1970‐1989, age‐adjusted mortality rates for lung cancer in Italy increased by more than 50%, while rates for larynx cancer in males decreased by approximately 13%. This study aims to interpret this difference, which seems to contradict the finding that cigarette smoking is a common major risk factor for both lung and larynx cancer. To this end, we jointly analyzed the time trends of incidence, survival and mortality. We first examined survival data taken from the population‐based Lombardy Cancer Registry (northern Italy). Based on data referring to 860 incident cases of larynx cancer, diagnosed during the period 1976‐1987, we estimated a 3% annual increase in relative survival. By contrast, no significant period effect was observed for survival rates of 2,259 incident cases of lung cancer.National incidence rates were estimated using official mortality data and the above‐described survival data. Age‐adjusted estimated incidence rates increased, from 1970 to 1989, for both cancer sites: +55% for male lung, +56% for female lung, and +22% for male larynx. Moreover, the patterns of birth‐cohort effect, which are diverging for mortality, are nearly parallel with regard to incidence. This analysis suggests that a substantial improvement in survival of larynx cancer patients may largely explain the differences in mortality trends for cancer of lung and larynx. © 1994 Wiley‐Liss, Inc.
Multiple loci on human chromosome 11 control tumorigenicity of BK virus transformed cells
Authors: Sabbioni Silvia , Negrini Massimo , Possati Laura , Bonfatti Alessandra , Corallini Alfredo , Sensi Alberto , Stanbridge Eric J. , Barbanti‐Brodano Giuseppe 
Published: February 2007

AbstractBK virus (BKV) is a human papovavirus that readily transforms rodent cells, but not human cells, to a neoplastic phenotype, suggesting that tumor‐suppressor functions expressed in human cells control BKV oncogenicity. Transfer of a normal human chromosome 11 to BKV‐transformed mouse cells suppresses the malignant phenotype. In this report we map the regions of chromosome involved in tumor suppression. Transfer of chromosome 11 to the BKV‐transformed hamster cell line HKBK produces monochromosomic hybrids retaining only portions of the transferred human chromosome. We have compared the tumorigenicity of the hybrids with the molecular mapping of chromosome 11 retained regions. This analysis indicated that 3 regions of human chromosome 11, 11p15.5, 11p13 and 11q13, cooperate in tumor suppression. However, 11q13 seems the most important, since all the HKBK/H11‐induced tumors analysed had lost this region, whereas 11p15.5 and 11p13 were sometimes retained. The chromosomal regions identified in this study are deleted in several types of human tumors, suggesting that the BKV transformation system specifically detects tumor‐suppressor genes on chromosome 11 that are involved in human oncogenesis. This model may be of use in isolating and cloning such genes. The results of this report raise the possibility that BKV may have a synergistic tumorigenic effect in human cells where tumor‐suppressor genes controlling its oncogenk potential are inactivated. © 1994 Wiley‐Liss, Inc.
Mechanism of inhibition of fadu hypopharyngeal carcinoma cell growth by tetraphenylphosphonium chloride
Authors: Rideout Darryl , Bustamante Andres , Patel Jasmin 
Published: February 2007

AbstractCationic phosphonium salts are interesting because they inhibit the proliferation of carcinoma cells more than untransformed epithelial cells in vitro. This differential anti‐proliferative effect has been used to identify phosphonium salts and other lipophilic cations that later demonstrated effects in animals. Using 6 carcinoma‐derived and 2 untransformed epithelial cell lines, tetraphenylphosphonium chloride (TPP) and other cat‐ionic aryl phosphonium salts (CAPS) demonstrated a growth inhibition pattern similar to that of cation rhodamine 123, suggesting that CAPS may inhibit mitochondrial function. We tested this hypothesis for the effect of phosphonium salt TPP on FaDu human hypopharyngeal carcinoma cells. TPP inhibited the proliferation of FaDu carcinoma cells at submicromolar concentrations. Uptake of 3H‐TPP by FaDu cells was partially inhibited in medium containing high K+ and fully inhibited by valinomycin in this medium, indicating that TPP accumulates preferentially in mitochondria, and to a lesser extent in the cytoplasm. FaDu cells exposed to TPP exhibited damage to mitochondrial inner membranes, reduced ATP/ADP ratios, decreased oxygen uptake rates and decreased mitochondrial membrane potentials. The treated cells secreted lactate more rapidly than untreated controls and exhibited hypersensitivity to 2‐deoxyglucose, an inhibitor of glycolysis. TPP's antimitochondrial effects apparently enhance cytoplasmic glycolysis. In conclusion, TPP inhibits FaDu carcinoma cell growth by inhibiting mitochondrial respiration and ATP synthesis. Cationic phosphonium salts that inhibit carcinoma cell growth through anti‐mitochondrial effects might be used to treat solid tumors without the risk of secondary tumors associated with agents affecting nuclear DNA. © 1994 Wiley‐Liss, Inc.
Interleukin‐6 serum levels in patients with gynecological tumors
Authors: Scambia Giovanni , Testa Ugo , Panici Pierluigi Bendetti , Martucci Robert , Foti Elvira , Petrini Marina , Amoroso Mariangela , Masciullo Valeria , Peschle Cesare , Mancuso Salvatore 
Published: February 2007

AbstractSerum levels of IL‐6 were evaluated in a large group of patients with benign or malignant gynecological tumors. The results obtained were correlated with the patients' clinicopathological features and follow‐up data. Using a highly sensitive immunoenzymatic method for the evaluation of serum IL‐6 levels, we observed that > 5% of normal healthy women exhibited values within the range of 1.9‐6 pg/ml. Using a cut‐off of pg/ml, elevated levels of serum IL‐6 were found in 53% of 45 patients with primary epithelial ovarian cancer and less frequently in patients with endometrial and cervical cancer (37% and 10% respectively). Elevated levels of IL‐6 were occasionally seen in patients with benign disease. IL‐6 serum levels appeared to be less sensitive than CA 125 in ovarian cancer diagnosis. In cancer patients, increased IL‐6 serum levels were related to the presence of the tumor since all post‐operative patients exhibited a marked decrease. In patients with advanced ovarian cancer post‐operative levels of IL‐6 correlated with residual disease. Very high levels of IL‐6 were observed in the ascitic fluid of9 ovarian cancer patients, but IL‐6 mRNA was not detected in tumor cells. This suggests that the increased production of IL‐6 observed in ovarian cancer is reactive. Higher levels of IL‐6 were found in patients unresponsive to chemotherapy, as compared with responsive ones. Univariate analysis of survival data suggests that increased IL‐6 serum levels correlate with negative prognosis. © 1994 Wiley‐Liss, Inc.
p53 mutations in human tumors with chimeric EWS/FLI/1 genes
Authors: Hamelin Richard , Zucman Jessica , Melot Thomas , Delatre Olivier , Thomas Gilles 
Published: February 2007

AbstractThe Ewing family of tumors is recurrently characterized at the molecular level by the presence of a fusion transcript between the EWS gene on chromosome 22 and either the FL‐I or ERG genes, 2 closely related members of the Ets family of transcription factors. We have investigated 12 primary human tumors, II xenografts and II cell lines, which have been shown to express chimeric EWS transcripts in search of p53 mutations. Fragments of exons 5 to 8 and the corresponding consensus splice sequences were amplified by PCR and analyzed by denaturing gradient gel electrophoresis (DGGE). In 12 of 34 samples p53 mutations were detected (including 4 samples with multiple p53 mutations). The distribution of the mutations in the various samples was as follows: primary tumors 2/12; cell lines 5/11; xenografts 5/11. No correlation between the presence or absence of p53 mutations and the presence of a specific EWS chimeric transcript was observed. In addition, we observed that p53 mutations were almost always associated with a second hit (either deletion or second mutation) on the other p53 allele. © 1994 Wiley‐Liss, Inc.
Evaluation of the secretory component as a prognostic variable in colorectal carcinoma
Authors: Koretz Karin , Schlag Peter , Quentmeier Armin , Möller Peter 
Published: February 2007

AbstractExpression of the secretory component (SC) of IgA was investigated in normal colonic mucosa, in adenomas and in 188 colon carcinomas. Of the carcinoma patients, 149 underwent potentially curative surgical treatment. In particular, it was of interest to determine whether pathohistological or clinical parameters showed any association with the mode of SC expression in carcinomas. Irrespective of anatomical site, normal colon mucosa was generally SC‐positive. Normal epithelium, however, displayed microheterogeneity in SC content, which was related to columnar and goblet‐cell type and micro‐topographical site, implying a subtle regulatory mechanism. In contrast to adenomas, which were evenly SC‐positive and showed focally weak SC expression in only 2 out of 20 cases, carcinomas were rather heterogeneous in their SC‐expression pattern. In all, 48 carcinomas were entirely positive, 48 were completely negative and the remaining 92 showed various patterns of heterogeneous SC expression. The mode of SC expression was correlated with tumor staging, i.e., complete absence of SC was more often found in Dukes' C and D groups. In addition, the presence of SC in carcinomas was statistically correlated with the mucinous type. The mode of SC expression was not correlated with tumor grading and tumor location. The rate of disease‐free survival and the risk of tumor‐related death revealed a significant correlation with the mode of SC expression when patients who had received potentially curative or non‐curative treatment were included in the log‐rank test. Absence or low levels of SC expression were more frequent in the group that suffered a tumor relapse than in the recurrence‐free cohort. Tumor‐related death was more frequent when primaries were characterized by absence or low levels of SC expression. We conclude that absence or low levels of SC expression are an unfavorable prognostic variable in colorectal carcinoma. © 1994 Wiley‐Liss, Inc.
Effects of urinary trypsin inhibitor on the invasion of reconstituted basement membranes by ovarian cancer cells
Authors: Kobayashi H. , Fujie M. , Shinohara H. , Ohi H. , Sugimura M. , Terao T. 
Published: February 2007

AbstractUsing the human ovarian cancer cell line HOC‐I, we investigated the effects of urinary trypsin inhibitor (UTI) purified from human urine and its related synthetic peptides on the invasive potential of cancer cells in an in vitro assay. Invasiveness of tumor cells was determined using a modified Boyden chamber and a reconstituted basement membrane Matrigel. Three peptides (peptide 1, peptide 2, and peptide 3), representing sequences within UTI, were synthesized. HOC‐I cells showed detectable and reproducible levels of expression of surface urokinase‐type plasminogen activator (uPA) and plasminogen/plasmin by cell ELISAs and enzyme assays. UTI was found to strongly inhibit plasmin and human leukocyte elastase (HLE). Peptide 2 and peptide 3 specifically inhibit HLE and plasmin activity respectively. Peptide 1 has essentially no inhibitory activity. Treatment with UTI and peptide 3 reduces the incidence of invasion, whereas peptide 1 and peptide 2 do not affect invasion. The inhibitory effect on cell invasion is dose‐dependent. The proteolytic enzyme plasmin may be involved in human ovarian cancer invasion in extracellular matrix degradation, and the use of UTI and peptide 3 that inhibits plasmin specifically reduces invasion by tumor cells. © 1994 Wiley‐Liss, Inc.