bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection and isolation of antigen‐specific immune complexes from sera of melanoma patients
Authors: Wong Jan H. , Xu Shihong , Saxton Romaine E. , Gupta Rishab K. , Morton Donald L. 
Published: February 2007

AbstractDetection of antigen‐specific circulating immune complexes (IC) in sera from cancer patients provides an approach for defining tumor antigens that induce a host immune response and could prove useful for purposes of immunoprognosis. In the present study, a sandwich ELISA was developed to detect antigen‐specific IC in cancer patients, utilizing a murine monoclonal antibody designated MAb JSI. The MAb was produced by cell fusion using standard hybridoma technology following immunization with a partially purified fetal antigen that had been isolated from the spent culture medium of a melanoma cell line. The partially purified antigen appeared to be broadly expressed on melanomas, sarcomas, and carcinomas. The MAb was mass‐produced in pristine‐primed mice. MAb JSI reacted with the cultured melanoma cell M14 but not the autologous lymphoblastoid cell L14. Following purification by ammonium sulfate precipitation, the MAb was immobilized on polystyrene plates and utilized to capture antigen‐specific immune complexes from sera of melanoma patients which were detected with anti‐human globulins. The second antibody in the sandwich was shown to be endogenous human IgG. Antigen‐specific immune complexes were present in melanoma patients but only infrequently in sera from normal individuals and patients with active autoimmune disease. Antigen‐specific immune complexes detected in melanoma sera were isolated by affinity chromatography utilizing the MAb JSI. The assay described in this report is simple and reproducible, without plate effect (p = 0.97) or time effect (p = 0.34) and could provide a useful new approach to examine the role of antigen‐specific circulating immune complex analysis in cancer patients.
Simultaneous monitoring of P53 protein and dna content of colorectal adenocarcinomas by flow cytometry
Authors: Remvikos Y. , Laurent‐Puig P. , Salmon R. J. , Frelat G. , Dutrillaux B. , Thomas G. 
Published: February 2007

AbstractThe p53 transformation‐related gene is located on 17p, a chromosomal segment frequently under‐represented in colorectal adenocarcinoma karyotypes. We have developed a flow cytometric method for detection of its gene product on isolated nuclei by indirect immunofluorescence. Criteria for defining the presence of p53 were established, using parameters related to the difference of fluorescence obtained by incubating nuclei with a specific monoclonal antibody (MAB) versus isotypic control. This method allowed simultaneous quantitation of p53 and DNA in tumor nuclei to be made. Twenty‐two of the 41 tumors analyzed (54%) were found to overexpress p53 when compared to 13 normal mucosa specimens. Repeated preparations from different fragments of the same tumor gave reproducible results for the 21 cases tested. p53 was detected in a higher proportion of disseminated tumors (64%) compared to localized disease (39%), but the difference did not reach statistical significance (X2 = 2.4, p > 0.10). Tumors containing aneuploid cell subpopulations were also more frequently positive (65%) than diploid ones (20%), the difference being significant (Fisher's exact test, p < 0.03). This dual parameter flow cytometric method, evaluating both DNA ploidy and p53 expression, may prove useful in identifying different biological subgroups of colorectal cancer.
Transcriptional down‐regulation of the rearranged c‐myc expression in murine cell hybrids between a plasmacytoma and a T‐cell lymphoma
Authors: Oikawa Tsuneyuki , Kondoh Nobuo , Fujita Hisakazu , Satoh Chiharu , Li Song Zhi , Yoshida Michihiro C. , Imamura Masahiro , Onoé Kazunori , Kuzumaki Noboru 
Published: February 2007

AbstractRegulation of the rearranged and non‐rearranged c‐myc expression was studied in murine cell hybrids (SBWI and SBWII) between plasmacytoma (S194) and T‐cell lymphoma (BWS147) cells. Expression of the rearranged c‐myc of heterogeneous mRNA sizes (1.8 ∼ 2.4 kb) was markedly down‐regulated in these hybrids regardiess of retention of the gene. On the other hand, expression of the non‐rearranged c‐myc (2.4 kb) was not significantly affected in these hybrids. Treatment of SBWI hybrid ceiis with cycloheximide enhanced the non‐rearranged c‐myc 2‐ to 4‐fold but did not release the down‐regulation of the rearranged c‐myc at all, suggesting that the down‐regulation of the rearranged c‐myc in the hybrid cells was mainly at a transcriptional rather than a post‐transcriptional level. This was supported by the results of nuclear run‐on assay: the high level of run‐on transcripts in S194 cells declined in SBWI hybrid cells comparable to the level in BW5147 cells. The rearranged c‐myc was hemi‐methylated in S194 cells and the pattern was the same in SBWI hybrid cells. Furthermore, down‐regulation of the rearranged c‐myc in the hybrid was also not restored by treatment with 5‐azacytidine (5‐AzaC), 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) or forskolin, suggesting no causative involvement of DNA methylation or protein phosphorylation in down‐regulation. Higher DNase I sensitivity of the rearranged c‐myc in S194 cells decreased to a similar extent to that of the non‐rearranged c‐myc after cell fusion with BW5147 cells. These results suggest that expression of the rearranged c‐myc is down‐regulated at the level of transcription in murine cell hybrids between a plasmacytoma and a T‐cell lymphoma, probably by changing chromatin configuration around the gene from the open to the closed state.
Heterogeneity of polyoma tumors in hamsters: Analysis of cytoskeletal proteins and viral gene expression
Authors: Combette J. M. , Sappino A. P. , Türler H. 
Published: February 2007

AbstractMurine polyomavirus‐induced hamster tumors revealed an unexpected heterogeneity with respect to patterns of cytoskeletal proteins expressed in different visceral and subcutaneous tumors and with respect to viral gene expression early during tumor outgrowth. All tumors analyzed expressed vimentin. Desmin was found in all heart tumors, to variable degrees in kidney tumors and in trace amounts only in I out of 4 s.c. tumors. The α‐smooth‐muscle actin isoform was observed in heart tumors only and was restricted to structures that we interpret as being proliferating pericytes or proliferating smooth‐muscle cells of the media. in kidneys of infected newborn animals and before the appearance of macroscopic tumors, viral early mRNAs were transcribed from free viral genomes. In tumor tissue the size of the viral transcripts was altered, suggesting that they were transcribed from integrated viral DNA. Since in each tumor discrete bands of viral RNAs were detected, individual tumors arose presumably from single cells and one functional integration event. In contrast, in situ hybridizations of kidney tissue and tumors showed large quantitative differences in viral gene expression not only between different tumors but also between individual cells of the same tumor.
Enhancement of the antiproliferative activity of cis‐diamminedichloroplatinum(II) by quercetin
Authors: Hofmann Johann , Fiebig Heiner H. , Winterhalter Bernd R. , Berger Dietmar P. , Grunicke Hans 
Published: February 2007

AbstractWe have shown previously that the flavonoid quercetin (3,3′,4′,5,7‐pentahydroxyflavone) enhances the antiproliferative activity of cis‐diamminedichloroplatinum(II) (cis‐DDP) in vitro. In order to investigate whether this observation could be exploited in cancer treatment, we tested this drug combination in human tumor xenografts. The established human large‐cell cancer of the lung (LXFL 529) was implanted s.c. into nude mice. Tumors were allowed to grow to a mean diameter of approximately 5 mm and the animals were subsequently treated intraperitoneally with quercetin, cis‐DDP or a combination of both. Treatment was given 3 times at 3‐day intervals. Twenty milligrams quercetin per kg body weight caused no inhibition in tumor growth compared to untreated controls; 3 mg cis‐DDP per kg body weight with the same time schedule reduced tumor growth, compared to quercetin‐treated and control animals. Concomitant treatment with 20 mg quercetin and 3 mg cis‐DDP per kg body weight reduced tumor growth to a significantly greater degree than cis‐DDP alone. Toxicity of this treatment was relatively low as determined by measurements of the body weight of the mice. A combination of 4 mg or 5 mg cis‐DDP with 20 mg quercetin per kg body weight also reduced tumor growth compared to single cis‐DDP treatment. The toxicity of treatment with these increased doses was high, as shown by the high lethality and the loss of body weight of surviving animals.
Cessation of autonomous proliferation of mouse lymphoma EL4 by fusion with a T cell line
Authors: Kubota Koichi , Katoh Hideki 
Published: February 2007

AbstractBenzanthracene‐induced C57BL/6 (H‐2b) mouse T‐cell lymphoma EL4 (a thymidine kinase‐deficient cell line) was fused by using polyethylene glycol with an Mlsa (Mls for minor lymphocyte stimulatory) antigen‐dependent T cell line, which was designated G4 and had been derived from a C3H/He mouse (H‐2k), and the fused cells were cultured in HAT medium. Although no growing cells appeared in most of these fusions, we consistently obtained growth‐arrested H‐2Kb‐positive cells from the fused cell populations by the panning method. The cells were tetraploid and were able to proliferate in response to Mlsa antigen. Three H‐2Kb‐positive clones, isolated by limiting dilution from three different fusions, were shown to be EL4 × G4 hybrids, because (I) they had both H‐2k and H‐2b antigens; (2) each of the clones had one submetacentric chromosome which was a marker chromosome of EL4, and they were tetraploid with modal chromosome numbers of 74, 78, and 79, respectively; (3) they had 4 isozymes of both parental cells. These results indicate that EL4 lymphoma cells cease to proliferate when fused with T cell line G4. The malignant phenotype of lymphoma EL4 is thus suppressed at the level of cell transformation by the introduction of the G4 cell genome.
N‐myc gene is amplified in alveolar rhabdomyosarcomas (RMS) but not in embryonal RMS
Authors: Dias P. , Kumar P. , Marsden H. B. , Gattamaneni H. R. , Heighway J. , Kumar S. 
Published: February 2007

AbstractDNA from 13 (6 alveolar and 7 embryonal) childhood rhabdomyosarcomas (RMS) was examined to determine the incidence and prognostic relevance of N‐ and c‐myc genes. Southern analysis showed 5‐ to 20‐fold amplification of N‐myc gene in 4 of 6 alveolar but in none of 7 embryonal RMS (p < 0.04; Fisher's exact test). The number of children who died with multiple‐ and single‐copy N‐myc gene was 4/4 and 5/9 respectively (p > 0.05; Chi‐squared test). There was no statistically significant correlation between N‐myc amplification and age, gender, site, stage or survival time. There was no amplification or gross rearrangement of c‐myc in any of the 13 RMS.
General primer‐mediated polymerase chain reaction permits the detection of sequenced and still unsequenced human papillomavirus genotypes in cervical scrapes and carcinomas
Authors: Van Den Brule Adriaan J. C. , Snijders Peter J. F. , Gordijn Roel L. J. , Bleker Otto P. , Meijer Chris J. L. M. , Walboomers Jan M. M. 
Published: February 2007

AbstractA newly developed general primer‐mediated polymerase chain reaction (GP‐PCR) was used for the detection of a broad spectrum of Human Papilloma‐virus (HPV) genotypes, including unsequenced types, in cytologically normal and abnormal cervical smears and in biopsies of cervical carcinomas. This PCR method used different general primer sets, located in strongly conserved E1 and L1 regions of the HPV genome. Comparison between results of GP‐PCR and HPV‐type‐specific PCR (TS‐PCR) revealed an increase in overall HPV prevalence to 25%, 80% and 88% in scrapes with normally, slightly and severely dysplastic cells, respectively. Unsequenced HPV types were detected in 11% of cytologically normal swabs and in up to 30% of scrapes with dysplastic cells. Further characterization showed that unsequenced types concern HPV 13, 30, 31, 45, 51 and some other, possibly unknown HPV types. More than 90% of carcinomas in situ and invasive cervical carcinomas contained HPV. In the latter, only HPV16 and HPV18 were present. HPV16 was most frequently found in both normal and dysplastic cells, the rate being highest in neoplastic tissue. These results indicate that GP‐PCR is a powerful approach for detecting as yet uncharacterized HPV types associated with neoplastic transformation of cervical squamous cell epithelium.
Expression of the gene coding for human prostate‐specific antigen and related hGK‐1 in benign and malignant tumors of the human prostate
Authors: Henttu P. , Lukkarinen O. , Vihko P. 
Published: February 2007

AbstractHuman glandular kallikrein‐1 gene (hGK‐1) is closely related to the gene of human prostate‐specific antigen (PSA) and both genes are expressed in the human prostate. We have studied PSA and hGK‐1 mRNAs in human prostatic tissue samples from patients with benign prostatic hyperplasia (BPH) or adenocarcinoma (CA), using Northern and slot‐blot analysis in order to gain insight into the expression of these highly similar genes. Multiple mRNAs were found to originate from both genes. The major mRNA species of 1.6 kb accounted for 57% to 76% of the total coding capacity for PSA in different tissue specimens, but a variant mRNA species of 1.9 kb was also abundant. Most of the BPH samples contained marked amounts of an aberrant 0.9 kb mRNA, and long PSA mRNAs of 6.1 kb, 4.5 kb and 3.1 kb were found in elevated amounts in some of the CA samples. The amount of PSA mRNAs that would produce aberrant PSA proteins if translated into protein varied from 18% to 38% in these tissue samples. The major mRNA species originating from hGK‐1 was of 1.6 kb, but other less abundant mRNA species could also be observed. The amount of PSA and hGK‐1 mRNAs was determined from slot blots hybridized with specific oligonucleotide probes. No significant differences could be found in the PSA gene expression between BPH and CA samples. The total amount of the PSA mRNAs in all the different BPH specimens was fairly similar, but there was a 3‐fold difference between the highest and lowest PSA mRNA levels in the CA samples. The hGK‐1 mRNA levels in the BPH specimens studied demonstrated greater variance than the PSA mRNA levels in the same samples. The correlation between PSA gene and hGK‐1 expression in the BPH samples was good, suggesting that there are similarities in the regulation of these genes. However, the lack of correlation between the amounts of PSA and hGK‐1 mRNAs in the CA samples except in sample CI indicates that there are also differences in the gene regulation. The observed 3.7‐ to 6.5‐fold excess of PSA mRNAs as compared with the amount of hGK‐1 mRNAs present in the same tissue specimen also indicated differences in the cis‐ or trans‐acting regulatory elements of these genes.
O‐linked mucin‐type glycoproteins in normal and malignant colon mucosa: Lack of T‐antigen expression and accumulation of tn and sialosyl‐Tn antigens in carcinomas
Authors: Ørntoft Torben F. , Harving Niels , Langkilde Niels C. 
Published: February 2007

AbstractThe expression of carbohydrate core‐structures on O‐linked glycoproteins was examined in fetal (n = 6), infantile (n = 2), normal adult (n = 15), and malignant (n = 22) colorectal tissue by means of monoclonal antibodies (MAbs) specific for Tn (Ga1NAcα1‐O‐R), sialosyl‐Tn (NeuAcα2‐6Ga1NAcα1‐O‐R), and T (Ga1β‐3GalNAcα1‐O‐R) antigens. Immunolabelling of solubilized malignant tissue, separated by SDS‐PAGE, showed expression of Tn and sialosyl‐Tn antigens on 3 molecules of similar mw (230, 210, and 170 kDa), whereas no T antigens could be detected. Immunohistochemical techniques showed that fetal colon mucosa expressed Tn antigens but no sialosyl‐Tn antigens. Infantile colon mucosa, however, expressed Tn as well as sialosyl‐Tn antigens, and normal adult colon mucosa cells expressed no Tn antigens but sialosyl‐Tn in 2 out of 6 biopsies from cecum, which indicates occurrence post partum of α‐6‐NeuAc‐transferase. Endothelium in normal adult mucosa showed expression of both Tn and sialosyl‐Tn antigens; 82% of carcinoma tissue sections expressed Tn antigens, and 73% expressed sialosyl‐Tn antigens in mucin or cytoplasm, or on luminal cell membranes. T antigens could be detected neither in normal mucosa cells at any stage of development, nor in carcinomas. The possibility exists that this could be due to masking of T antigen. Mucin‐type blood‐group A antigens which contain an internal T‐disaccharide were demonstrated in 4 out of 4 A1 tumors by means of MAb HH5. However, urea‐containing SDS‐PAGE analysis demonstrated an HH5 binding to molecules different from those binding anti‐Tn. In remote morphologically normal and abnormal crypts in colons from carcinoma patients, both Tn and sialosyl‐Tn antigens were expressed in secreted mucin in 40% of the cases. The data indicate an expression of O‐linked Tn and sialosyl‐Tn core structures in fetal and infantile colon and in colorectal carcinomas.
Detection of somatic mutations in tumours of diverse types by DNA fingerprinting with M13 phage DNA
Authors: Hayward Nicholas , Chen Philip , Nancarrow Derek , Kearsley John , Smith Peter , Kidson Chev , Ellem Kay 
Published: February 2007

AbstractHybridization of M13 phage DNA to Southern blots of human DNA produces an individual‐specific DNA fingerprint. In this study, tumour and lymphocyte DNA from a series of patients with melanoma, Merkel‐cell carcinoma, Burkitt's lymphoma and Wilms' tumour was probed with M13 DNA to detect somatic mutations in the DNA of the tumours. Somatic changes were observed in tumour DNA of 16 out of the 28 cases examined. This frequency compared favourably with the frequency with which tumour‐specific changes have been found when using the Jeffreys DNA fingerprinting probe 33.15, and demonstrates that M13 DNA provides a useful additional probe for the study of somatic changes in tumours. The finding that multiple DNA fragments were lost or gained in DNA fingerprints from individual tumours indicates a marked degree of complexity in the genetic changes involved in the evolution of certain human cancers.
Plantar melanoma: Is the incidence of melanoma of the sole of the foot really higher in blacks than whites?
Authors: Stevens Nancy G. , Liff Jonathan M. , Weiss Noel S. 
Published: February 2007

AbstractThe overall incidence of malignant melanoma in black populations is considerably lower than that in whites. There have been repeated suggestions in the literature that black persons may have an increased incidence of melanoma of the sole, relative to whites, because among blacks with melanoma there is a high proportion with tumors of the sole of the foot. Whether this observed difference in site distribution represents a difference in incidence rates has never been demonstrated. Data on cancer incidence from 2 areas, western Washington State (1974–1983) and metropolitan Atlanta (1975–1984), were analyzed to examine this question. The annual area‐ and age‐adjusted incidence of plantar melanoma was 1.7 per million per year for blacks and 2.0 per million per year for whites (relative risk for blacks as compared with whites = 0.88, 95% confidence interval = 0.36–2.11). These data argue that in North America there is little difference between blacks and whites in the incidence of plantar melanoma, and that the well known proportional difference appears to be due instead to the decreased incidence in blacks of melanoma on skin surfaces other than the soles of the feet.
Hormone and cytotoxic drug responsiveness of cultured human breast cancer cells resistant to specific hormones
Authors: Coldham N. G. , Patel K. , Braunsberg H. 
Published: February 2007

AbstractAttempts have been made to develop sublines of MCF‐7 cells resistant to the growth‐inhibitory actions of medroxyprogesterone acetate (MPA), dexamethazone (DEX), antioestrogens or high‐dose oestradiol (E2) by prolonged exposure to high hormone concentrations. While high degrees of resistance to MPA, DEX and E2 were achieved, cells remained anti‐oestrogen‐sensitive after prolonged treatment with 4 μM tamoxifen (TAM) or the anti‐oestrogen LY 117018 (LY), Cells resistant to DEX were also resistant to MPA, while cells resistant to high‐dose E2 remained sensitive to TAM. Cells resistant to MPA and E2 appeared to be less responsive to cytotoxic drugs than wild‐type cells, while resistance to DEX was associated with increased sensitivity. The responses of tumours to cytotoxic drugs may be affected by prior endocrine therapy.
Exacerbation of doxorubicin cardiotoxicity by digoxin administration in an experimental rabbit model
Authors: Reeves William C. , Griffith James W. , Wood Mary Ann , Whitesell Lawrence 
Published: February 2007

AbstractThe relationship between digoxin administration and the development of doxorubicin cardiomyopathy was evaluated in a chronic experimental rabbit model. We graded the myocardial pathology by conventional light microscopic histologic techniques. Additionally, myocardial fibrosis was quantified by hydroxyproline determinations and myocardial cellular damage by technetium‐99m pyrophosphate uptake. Twenty‐four rabbits were studied: 6 control, 6 doxorubicin‐treated, and 12 digoxin‐doxorubicin‐treated. Mortality in the digoxin‐doxorubicin group was 50%. All other rabbits lived throughout the entire experiment. The severest grades of histologic lesions were seen only in the digoxin‐doxorubicin group. Myocardial hydroxyproline content was greater (p < 0.05) in the digoxin‐doxorubicin group than in the doxorubicin or control groups. Myocardial technetium‐99m pyro‐phosphate content was also significantly greater (p < 0.05) in the digoxin‐doxorubicin group than in controls. In conclusion, the pretreatment and continued administration of digoxin, together with doxorubicin, increased the severity of myocardial damage and reduced longevity in this experimental model of doxorubicin cardiotoxicity.
Immune surveillance: Both CD3+ CD4+ and CD3+ CD8+ T cells control in vivo growth of P815 mastocytoma
Authors: Flamand Véronique , Biernaux Cécile , Van Mechelen Marcelle , Sornasse Thierry , Urbain Jacques , Leo Oberdan , Moser Muriel 
Published: February 2007

AbstractThe aim of this study was to examine whether a spontaneous immune response controls neoplastic growth in P815‐bearing DBA/2 mice, and to characterize the cells involved in tumor resistance in vivo. Several cell lineages such as T‐cell‐receptor (TcR)‐bearing T cells, NK cells and macrophages mediate some anti‐tumor activity in vitro. P815 was chosen as a model because it is weakly immunogenic and is a good target both for tumor‐specific, MHC‐restricted CTL‐mediated lysis and for MHC‐unrestricted lysis exerted by long‐term cultured lymphocytes or activated macrophages. Since most “NK‐like activity” in freshly isolated populations appears to be associated with CD3− cells, whereas antigen‐specific, MHC‐restricted T cells mostly express CD3 determinants, CD3 was a good marker for evaluating the role of T cells and “NK” cells in tumor resistance in vivo. The survival of anti‐CD3‐treated animals that were inoculated with tumor cells was strongly reduced (mean survival time: 17 days vs. 40 days for the control group) and was associated with increased tumor growth rate. We followed the same approach to define the T‐cell subset(s) that mediate(s) this immune response. Both CD4+ and CD8+ T cells were required for induction of immune control on neoplastic growth. The approach used has revealed the important role of CD4+ T cells in immune responses that control in vivo growth of a class‐1‐positive, class‐II‐negative tumor and suggests that these cells may play a central role in tumor resistance. Since CD4+ cells are activated by soluble, exogenous proteins, this finding may have important implications for immunotherapy.