bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunization with anti‐idiotype monoclonal antibodies bearing the internal image of the renal‐cell carcinoma‐associated antigen G250 induces specific cellular immune responses
Authors: Uemura Hirotsugu , Okajima Eigoro , Debruyne Frans M. J. , Oosterwijk Egbert 
Published: February 2007

AbstractWe have previously isolated and characterized 6 anti‐idiotype antibodies (Ab2s) directed against monoclonal antibody G250 (MAbG250) which reacts with a tumor‐associated antigen (TAA) expressed in a large proportion of human renal‐cell carcinomas (RCC). These 6 Ab2s (NUH31, 51, 71, 82, 91: IgG1, NUH44: IgG2a) showed MAbG250 binding site specificity and induction of anti‐TAA antibody resembling MAbG250 (so‐called Ab l') in rabbits, indicating that they are internal image antibodies. To investigate whether these Ab2s could induce G250‐TAA‐specific cell‐mediated immunity, delayed‐type hypersensitivity (DTH) tests were carried out with G250 antigen‐positive and/or ‐negative cells in the ears of BALB/c mice. Mice primed with Ab2 showed antigen‐specific DTH responses, whereas no significant DTH response was observed with G250‐negative cells. This antigen‐specific DTH could be transferred to naive mice by lymphocytes harvested from Ab2‐sensitized mice. In addition to the classical DTH responses observed 24 and 48 hr after tumor challenge, an early‐phase antigen‐specific hypersensitivity response was seen 2 hr after challenge. This early component of the specific hypersensitivity reaction but not the classical DTH could be transferred to naive mice by serum from Ab2‐sensitized mice, indicating that the early reaction was due to serum factors. These findings demonstrate that all Ab2s induced tumor‐specific cellular immune responses directed against human RCC, and suggest that they may be useful as RCC‐TAA surrogates, i.e., as tumor vaccines for RCC patients.
Effects of type‐I and ‐II interferons on 90K antigen expression in ovarian carcinoma cells
Authors: Marth Christian , Dreps Andreas , Natoli Clara , Zeimet Alain G. , Lang Thomas , Widschwendter Martin , Daxenbichler Günter , Ullrich Axel , Iacobelli Stefano 
Published: February 2007

AbstractAntigen 90K is produced by several tumor‐cell lines and by patients with cancer. Its function has not yet been clarified, although recent reports suggest that it plays a role in the tumor—host relationship—for example by stimulation of natural killer and lymphokine‐activated killer‐cell activity. Previous studies have indicated that 90K expression may be under the influence of interferon‐α. Here, we provide evidence that both interferon‐α and ‐γ can enhance the secretion of 90K and augment the level of specific mRNA expression in 3 ovarian carcinoma cell lines (OVCAR‐3, HTB‐77 and SKOV‐6). However, interferon‐γ leads to depletion of cellular 90K whereas interferon‐α increases both secreted and cellular 90K levels. In equimolar concentrations, Interferon‐α was always superior to interferon‐γ in augmenting 90K protein or mRNA levels. Combinations of TNF with interferon‐γ were highly synergistic both in reducing cell proliferation and in increasing 90K secretion and mRNA expression. This synergism was seen to a lesser extent with interferon‐α.
Intraperitoneal photodynamic therapy in the rat: Comparison of toxicity profiles for photofrin and mTHPC
Authors: Veenhuizen Ruth B. , Ruevekamp‐Helmers Marjan C. , Helmerhorst Theo J. M. , Kenemans Peter , Mooi Wolter J. , Marijnissen Johannes P. A. , Stewart Fiona A. 
Published: February 2007

AbstractToxicity studies for intraperitoneal photodynamic therapy (IPPDT) were performed in Wag/RijA rats, using specially designed light delivery blocks for proper light distribution and light dosimetry. A recently developed photosensitizer mesotetrahydroxyphenylchlorin (mTHPC), excited at 652‐nm wavelength, was compared with Photofrin (630 nm). Toxicity profiles for various sensitizer doses, light fluences and time intervals were investigated. A light fluence of 15 J ‐ cm−2delivered to the entire peritoneum 24 hr after 5 mg Photofrin per kg i.v. induced reversible impairment of intestinal, liver and kidney function. A dose of 0.2 mg mTHPC per kg i.v. followed by 6 J · cm−2at 72 hr appeared to be equitoxic to the intestines; however, functional tests revealed little effect for this mTHPC‐mediated IPPDT regime on liver or kidney. Histology demonstrated focal irreversible damage to the kidneys for both photosensitizers, not reflected in functional impairment. Light doses of 25 to 30 J. cm−2at 24 hr after Photofrin or 8–12 J · cm−2, 72 hr after mTHPC caused lethal toxicity in the first 2 weeks due to intestinal damage. Higher light doses caused a shock syndrome and rhabdomyolysis resulting in death within 20 hr for both photosensitizers. In conclusion, maximum tolerable schedules for whole‐abdomen IPPDT were defined for Photofrin and mTHPC. Both photosensitizers cause similar toxicity profiles depending on drug dose, light fluence and time interval.
Modifications of the anti‐oxidant metabolism during proliferation and differentiation of colon tumor cell lines
Authors: Bravard A. , Beaumatin J. , Dussaulx E. , Lesuffleur T. , Zweibaum A. , Luccioni C. 
Published: February 2007

AbstractThe anti‐oxidant metabolism was studied at different times after sub‐culture in 2 colon cell lines previously characterized for their growth and differentiation properties. The HT29 cell line is mainly composed of proliferative and undifferentiative cells, while the derived 5‐fluorouracil (FUra)‐adapted cells undergo growth‐dependent differentiation, which is complete at post‐confluence. In the 2 cell lines, all the anti‐oxidant parameters studied appeared to be related to proliferation, with increased activity of superoxide dismutase (SOD) 1 and 2, catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GSR), and glutathione transferase (GST), and decreased glucose‐6‐phosphate dehydrogenase (G6PD) activity and glutathione content, in parallel with slowing down of proliferation. At post‐confluence, these metabolic parameters remained stable, except for GPX activity, which continued to increase, and CAT activity, which decreased. The amounts of SOD1, SOD2 and CAT immunoreactive proteins, estimated by Western blotting, appeared to be correlated to their respective enzymatic activities, SOD1, CAT and GST activity and glutathione content, which remained at similar levels in the 2 cell lines for all times studied, appeared unrelated to the differentiation process. GSR and GPX activity, which was lower in FUraadapted than in parental cells only at post‐confluence, could be considered as markers of differentiated cells. The higher SOD2 and lower G6PD activity observed in FUra‐resistant cell in comparison with parental cells at all times after sub‐culture could be characteristic both of differentiative and of differentiated cells. Interestingly, cytogenetics have previously indicated that deletions of the long arm of chromosome 6, which carry the gene for SOD2, were frequently observed in parental but not in FUra‐adapted cells. These results demonstrate that modifications of the anti‐oxidant metabolism occur in relation with proliferation and differentiation, and suggest a particular role for SOD2 in these cellular processes.
Role of tumor‐derived fibroblasts in the growth of primary cultures of human breast‐cancer cells: Effects of epidermal growth factor and the somatostatin analogue octreotide
Authors: Hofland Leo J. , van der Burg Bart , van Eijck Casper H. J. , Sprij Diana M. , van Koetsveld Peter M. , Lamberts Steven W. J. 
Published: February 2007

AbstractIn the present study we have investigated the role of human breast‐cancer‐derived fibroblasts in the proliferation of primary cultures of epithelial cells derived from the same tumor. For this purpose, a co‐culture system, using Transwell tissue‐culture inserts with microporous membranes was employed. Fibroblasts and epithelial cells were enriched according to differences in their density on Percoll density gradients. The co‐culture system was first established using MCF‐7 breast cancer cells and a human fibroblast line (HF cells). Insulin, 17β‐estradiol, EGF and HF cells all significantly stimulated the growth of MCF‐7 breast cancer cells. The stimulatory effects of insulin, E2 and EGF were additive to the stimulatory effect of HF cells. These data suggest that (unique) factor(s), other than the above‐mentioned growth‐promoting compounds, are responsible for the growth‐promoting effects of fibroblasts. In half of the human breast cancers investigated, tumor‐derived fibroblasts stimulated tumor‐derived epithelial cell proliferation. EGF significantly stimulated epithelial cell proliferation in 4 out of 6 cultures. The stimulatory effects of fibroblasts and EGF were additive or synergistic, and were observed in the additional presence of FCS, again suggesting production of unique factor(s) by the fibroblasts, in one culture the fibroblasts significantly inhibited epithelial tumor‐cell proliferation. Conversely, the epithelial cells significantly stimulated proliferation of fibroblasts in 3 out of 3 cultures. The somatostatin analogue octreotide significantly inhibited epithelial cell proliferation by 46% in one tumor‐cell culture in the absence, but not in the presence, of fibroblasts. In one culture, octreotide significantly inhibited the proliferation of fibroblasts co‐cultured with epithelial cells. © 1995 Wiley‐Liss, Inc.
Nuclear DNA content and chromatin texture in multidrug‐resistant human leukemic cell lines
Authors: Dufer Jean , Millot‐Broguo Christine , Hamed Zohra Oum , Lialtaud‐Roger Francloise , Joly Philippe , Desplaces Andrée , Jardillier Jean‐Claude 
Published: February 2007

AbstractNuclear morphological alterations associated with multidrug resistance (MDR) were evaluated by image cytometry in various human leukemic cell sub‐lines: 3 cell lines with P‐gp‐mediated resistance (CEM‐VLB, HL60/Vinc, K562‐Dox), the non‐Pgp‐mediated MDR HL60/AR leukemic cell line with over‐expres‐sion of MRP, and the at‐MDR CEM‐VMI leukemic cell line with alteration of topoisomerase II. All these MDR cell sub‐lines were obtained by drug selection and were compared with their sensitive counterparts and with the hamster LR73‐R cell line obtained by transfection of mouse mdrl cDNA. All MDR cell sub‐lines obtained by drug selection displayed decreased DNA Feulgen stainability as compared with their respective sensitive parental cell line, a phenomenon not observed in the trans‐fected LR73‐R cells. Nuclear texture analysis on G0/G1‐selected cell nuclei revealed 2 types of textural phenotype. The first phenotype was characterized by chromatin decondensation with small but compact chromatin clumps, and was observed in drug‐selected P‐gp‐mediated MDR cells (CEM‐VLB, HL60‐Vinc, K562‐Dox) and in the non‐P‐gp‐mediated MDR HL60/AR cell line. The second phenotype was characterized by a condensed and homogeneous chromatin pattern, and was observed in the at‐MDR CEM‐VMI cell line. LR73‐R cells transfected with mdrl cDNA did not display any significant changes in textural pheno‐type as compared with sensitive LR73 cells, suggesting that P‐gp over‐expression alone cannot account for the cytological modi‐fications observed in MDR cells. These data suggest that multidrug resistance could be associated with specific nuclear morphological changes which appeared to be a consequence of alterations occurring during selection by cytotoxic drugs rather than of P‐gp over‐expression. © 1995 Wiley‐Liss, Inc.
High expression of udp‐n‐acetylglucosamine: β‐d mannoside β‐1, 4‐n‐acetylglucosaminyltransferase III (GnT‐III) in chronic myelogenous leukemia in blast crisis
Authors: Yoshimura Masafumi , Nishikawa Atsushi , Ihara Yoshito , Nishiura Tetsuo , Nakao Hirohisa , Kanayama Yoshio , Matuzawa Yuji , Taniguchi Naoyuki 
Published: February 2007

AbstractThe activity and mRNA expression of UDP‐N‐acetylglucosamine: β‐D mannoside β‐1,4‐N‐acetylglucosaminyl transferase III (GnT‐III: EC 2.4.1.144) were investigated in hematological malignancies. GnT‐III activity was elevated in patients with chronic myelogenous leukemia (CML) in blast crisis and patients with multiple myeloma (MM), as compared to normal healthy subjects and patients with other hematological malignancies including CML in chronic phase. The GnT‐III transcript was the same size in leukemic cells from various hematological diseases and cell lines, while expression of the transcript was not found to correlate significantly with enzyme activity, implying that posttranslational modification might regulate the activity of GnT‐III. Southernblot analysis showed no significant variation in the structure and position of the GnT‐III genome, indicating that the gene is present as a single copy without isoforms. Furthermore, analyses by immunoprecipitation and Western blot revealed that high GnT‐III activity in KU812 cell, a CML cell line, resulted in an increase in E4‐PHA binding to CD45, a major surface glycoprotein of the leukocyte, indicating that more bisecting GlcNAc was added to CD45 catalyzed by elevated GnT‐III.
Inhibition of bispecific monoclonal antibody (bsAb)‐targeted cytolysis by human anti‐mouse antibodies in ovarian carcinoma patients treated with bsAb‐targeted activated T‐lymphocytes
Authors: Lamers Cor H. J. , Gratama Jan W. , Warnaar Sven O. , Stoter Gerrit , Bolhuis Reinder L. H. 
Published: February 2007

AbstractT lymphocytes of 8 patients with ovarian cancer were targeted to the tumor cells using F(ab')2 fragments of a bispecific monoclonal antibody (bsAb), specific for CD3 (a component of the T lymphocyte receptor for antigen) and for the folate receptor MOv 18 (overexpressed by ovarian carcinoma cells) as part of a phase l/II study. Phase I (days 0 to 3) consisted of increasing intraperitoneal (i.p.) numbers (106−109) of bsAbtargeted T lymphocytes plus lowdose interleukin‐2 (IL‐2). Phase II (days 6 to 13, and 27 to 33) consisted of daily i.p. infusions of 109 targeted T lymphocytes, 2 mg soluble bsAb, and lowdose IL‐2. Using enzymelinked immunosorbent assays (ELISA), human antimouse antibodies (HAMA) were detected in all patients: in the serum from day 13 onwards and in the peritoneal fluid from day 20 onwards. A significant proportion of the HAMA appeared to be directed against the idiotypes of the bsAb specific for CD3 and MOv18, as suggested by (I) the clearly higher ELISA titers against OC/TR bsAb as compared to those against a monoclonal antibody (MAb) with unrelated specificity, and (2) failure to abrogate the capacity of peritoneal fluid containing HAMA to block the binding of OC/TR bsAb to MOv18+ or CD3+ cells by absorption of human antimouse IgG‐framework antibodies in peritoneal fluid to immobilized mouse IgG. The OC/TR‐targeted cytolysis of the MOv18+ ovarian carcinoma cell line lgrov‐1 by autologous T lymphocytes was inhibited by peritoneal fluid samples containing relatively high HAMA titers. Such inhibitory activity was never detected at the start of phase II, but coincided with the last series of i.p. infusions of targeted T lymphocytes in 2 patients.
A low incidence of p53 mutations in pre‐malignant lesions of the oral cavity from non‐tobacco users
Authors: Lazarus P. , Garewal H. S. , Sciuuba J. , Zwiebel N. , Calcagnotto A. , Fair A. , Schaefer S. , Richie J. P. 
Published: February 2007

AbstractTo determine the incidence of pS3 mutations in pre‐malignant lesions of the oral cavity from individuals without prior history of tobacco use, we have analyzed the conserved regions of the pS3 gene (exons 5‐9) in archival oral cavity lesion specimens obtained from patients with varied tobacco use histories, by polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) and DNA sequencing analysis. Twenty‐six lesions were analyzed from 14 patients, with multiple lesions obtained from 8 patients. Six of these patients used tobacco, (3 being cigarette smokers, 1 ex‐cigarette smoker, 1 moderate cigar smoker and 1 snuff chewer). The remaining 8 patients had no prior history of tobacco use. Thirteen of the pre‐malignant lesions exhibited severe dysplasia, 9 exhibited moderate dysplasia and 4 exhibited mild dysplasia. Four of the 26 lesions exhibited pS3 mutations, each being from a tobacco user. None of the 13 lesions from never‐tobacco users exhibited pS3 mutations. There was a significantly higher p53 mutation incidence in pre‐malignant lesions from tobacco users (including ex‐smokers) than in non‐tobacco users as well as in cigarette smokers plus snuff chewers than in non‐tobacco users. Two of the mutations were observed in lesions exhibiting severe dysplasia: I in a lesion exhibiting moderate dysplasia and I in a lesion exhibiting mild dysplasia. These data suggest that pS3 mutation may be a very early event in oral cavity tumor progression and demonstrate that pre‐malignant lesions obtained from non‐tobacco users do not exhibit pS3 mutations.
Risk of subsequent malignant neoplasms among 470,000 cancer patients in Finland, 1953‐1991
Authors: Sankila Risto , Pukkala Eero , Teppo Lyly 
Published: February 2007

AbstractBecause of increasing numbers of incident cancers and improving survival rates, more and more cancer patients are at risk of subsequent primary malignant neoplasms. The potential carcinogenicity of cancer therapies raises further concern regarding this unwanted long‐term side effect. The objective of this cancer‐registry‐based study was to assess the trends in the risk of subsequent primary malignancies among cancer patients on a nationwide public‐health level. The 470,000 cancer patients registered between 1953 and 1991 in Finland were followed up for subsequent primary neoplasms, and 19,800 subsequent malignant neoplasms were observed, yielding an overall standardized incidence ratio (SIR) of 1.00 for men and 1.25 for women. Substantial variation was observed in the SIR by the site of subsequent malignancy. The adjusted relative risk derived from multiple regression analyses showed only a slight increase by follow‐up interval. Overall, the excess relative risk of subsequent malignancies was low, since the majority of cancer patients are old and at low relative risk. Patients under the age of 50 years, however, were at 70% increased risk, and the overall relative risk increased by 50% from the 1950s to the 1980s. Subsequent neoplasms among cancer patients do not pose a major public‐health problem, but the possibility of subsequent cancers must be borne in mind in decisions concerning therapy and in clinical follow‐up.
Analysis of the NF2 tumor‐suppressor gene and of chromosome 22 deletions in gliomas
Authors: Hoano‐Xuan Khě , Meree Philippe , Vega Felipe , Hugot Jean‐Pierre , Cornu Philippe , Delattre Jean‐Yves , Poisson Michel , Thomas Gilles , Delattre Olivier 
Published: February 2007

AbstractRecurrent deletions of chromosome fragments observed in neoplasms are thought to participate in tumor development through the inactivation of tumor‐suppressor genes. In gliomas, the most frequent deletions involve chromosome arms 9p, 10q, 17p, 19q and 22q. We have analysed deletions of chromosome 22 in gliomas by studying loss of heterozygosity (LOH) at 8 microsatellite loci. LOH for this chromosome fragment was observed in 17/70 (24%) cases, most of them encompassing the region which encodes the gene altered in neurofibromatosis 2 (NF2), an inherited disease which predisposes to tumors of the nervous system. To investigate the possible involvement of the NF2 tumor‐suppressor gene in the tumorigenesis of gliomas, we searched for alterations in its genomic structure and in its mature transcript. Northern‐blot and reverse transcriptase‐PCR experiments showed that the NF2 transcript is expressed and does not demonstrate obvious structural alterations. Moreover, analysis, at the genomic level, of the 16 coding exons of the NF2 gene by denaturing gradient gel electrophoresis failed to detect any somatically acquired point mutations. Altogether, these data strongly suggest that, although gliomas demonstrate recurrent chromosome 22 deletions most frequently encompassing the NF2 region, the NF2 gene is not altered in these tumors.
Proteolytic enzymes at various stages of oncogenic transformation of rat fibroblasts. I. Aspartyl and cysteine proteinases
Authors: Solovyeva N. I. , Balayevskaya T. O. , Dilakyan E. A. , Zakamaldina‐Zama T. A. , Pozdnev V. F. , Topol L. Z. , Kisseljov F. L. 
Published: February 2007

AbstractAspartyl and cysteine proteinases at distinct stages of carcinogenesis were analyzed in rat embryo fibroblasts, sequentially immortalized and transformed by 2 different genes: the early region of simian adenovirus SA7 and c‐Ha‐ros oncogene. The dynamics of expression and distribution of proteinases throughout the transformation process were examined. It was shown that in immortalized and transformed cells the activities of the aspartyl and cysteine proteinases were expressed to a variable degree and that the expression was dependent on cell‐propagation time in vitro. The increase in activity both of cathepsin‐D‐like aspartyl proteinase and of cathepsin‐L‐ and ‐B‐like cysteine proteinases in cell lysates was correlated with the stages of fibroblast transformation (immortalization and tumorigenic transformation). In all cell types the major part of cysteine proteinases was localized inside the cell, while the cathepsin‐D‐like proteinase was apparently predominant among secreted proteinases. The cathepsin‐L‐like proteinase accounts for the major part of the cysteine‐proteinase activity as measured by Z‐Phe‐Arg‐MCA hydrolysis. We suggest that considerable portions of the cathepsin‐D‐ and ‐L‐like proteinases in all cell lines studied are secreted as a complex with inhibitor(s) and that inhibitor expression plays an important role in regulating the activity of cathepsin‐D‐like proteinase at different stages of transformation. Cathepsin‐L‐like proteinase is probably secreted in the precursor form.
Effect of VK framework‐1 glycosylation on the binding affinity of lymphoma‐specific murine and chimeric LL2 antibodies and its potential use as a novel conjugation site
Authors: Leung Shui‐On , Dion Arnold S. , Pellegrini Matthew C. , Losman Michele J. , Grebenau Ruth C. , Goldenberg David M. , Hansen Hans J. 
Published: February 2007

AbstractA potential asparagine (Asn)‐linked glycosylation site was identified in the VK FRI sequence of an anti‐B lymphoma monoclonal antibody (MAb), LL2. SDS‐PAGE analysis and endo‐F treatment of both murine and chimeric LL2 antibodies indicated that this site was glycosylated; however, no differences in the binding affinity to Raji cells were observed between the native murine LL2 and the endo‐F‐deglycosylated murine LL2 antibodies. Elimination of the glycosylation site from the chimeric LL2 antibody was accomplished by an Asn to Gin mutation in the tri‐acceptor site found in the light chain. The resultant aglycosylated chimeric LL2 exhibited a similar Raji cell binding affinity to that of the glycosylated form. The results are in agreement with computer modeling studies which suggested the lack of interactions between the oligosaccharide moiety and the CDRs. The finding is interesting because it enables a wider choice of human framework sequences, which in most cases do not have a corresponding glycosylation site, for the humaniza‐tion of the LL2 VK domain, as well as a greater latitude of host expression systems. Most importantly, the LL2 VK carbohydrate moiety might be used as a novel conjugation site for drugs and radionuclides without compromising the immunoreactivity of the antibody.