bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD30‐specific AB1‐AB2‐AB3 internal image antibody network: Potential use as anti‐idiotype vaccine against Hodgkin's lymphoma
Authors: Pohl C. , Renner C. , Schwonzen M. , Schobert I. , Liebenberg V. , Wolf J. , Diehl V. , Jung W. , Pfreundschuh M. 
Published: February 2007

AbstractThe tumor‐associated CD30 antigen is presently under study as a target for active specific immunotherapy of Hodgkin's lymphoma with anti‐idiotypic antibodies. Internal image antibodies (Ab2(i) 9G10 and 14G9 against the CD30‐specific antibody HRS‐4 (Abl) have been described, which induce a CD30‐specific T‐ and B‐cell response in BALB/c mice and New Zealand white rabbits. In extension of this work, murine monoclonal anti‐idiotypic Ab2β 9G10, mimicking structures of the nominal CD30 antigen, was used to generate monoclonal Ab3 in mice and polyclonal Ab3 in rabbits with specificity for CD30. The Ab2p 9G10‐specific murine monoclonal Ab3 4A4 bound specifically to the 120‐kDa band of CD30 present on Hodgkin cell lines and Hodgkin tumor tissue, and effectively inhibited binding of Ab1 HRS‐4 to Ab2 9G10 as well as to CD30+ cells. Monoclonal Ab3 4A4 was cytotoxic for CD30+ cell lines in vitro and effectively prevented the s.c. growth of L540 cell tumors after passive i.v. administration in a SCID mouse tumor model. While this cytotoxic effect of the IgM subclass monoclonal Ab3 4A4 was due to complement activation, the murine monoclonal Abl HRS‐4 and a polyclonal Ab3 preparation of 1gG‐subclass from New Zealand white rabbits were cytotoxic by an antibody‐dependent cell‐mediated mechanism in vitro. In conclusion, Ab2p 9G10 is able to induce a CD30‐specific cytotoxic 1gG and 1gM response. Cytotoxicity was shown to be mediated by complement activation and antibody‐dependent cell‐mediated cytotoxicity in vitro and in vivo and across species barriers. Thus, the CD30‐like Ab2β 9G10 may hold promise for effective active specific immunotherapy of human Hodgkin's lymphoma.
Intracellular glutathione heterogeneity in L1210 murine leukemia sublines made resistant to dna‐interacting anti‐neoplastic agents
Authors: Tagliabue Giovanna , Ubezio Paolo , Balconi Giovanna , Mascellani Enrico , D'Incalci Maurizio , Pifferi Antonio , Geroni Cristina 
Published: February 2007

AbstractIntracellular glutathione (GSH) content was measured by flow cytometry using monochlorobimane (mBCI) and by the enzymatic assay in a set of 6 sublines of murine L1210 leukemia cells made resistant to DNA‐interacting agents having distinct mechanisms of action: L‐phenylalanine mustard (L‐PAM), 1,3‐bis(2‐chloroethyl)‐1‐nitrosourea (BCNU), cisplatin (DDP), N‐de‐formyl‐N‐(4‐N, N‐bis(2‐chloroethylamino) benzoyl) distamycin A (FCE 24517), doxorubicin (DX) and 3′ ‐deamino‐3′ (2‐methoxy‐4‐morpholinyl)‐doxorubicin (FCE 23762). A significant correlation was demonstrated between the mean intracellular mBCI fluorescence values measured by flow cytometry and levels of GSH measured by the classical enzymatic assay, despite the possible influence of glutathione‐S‐transferases and of other thiols on the mBCI fluorescence. Although less specific, the flow cytometric method is more informative than the enzymatic assay, allowing detection of fluorescence distributions, which we proved to be characteristic of each subline. In order to assess a procedure enabling a quantitative analysis to be made of intercellular GSH heterogeneity, we propose the use of appropriate thresholds and parameters of the mBCI flow cytometric distribution. By use of this analysis procedure, distinct types of alterations, with respect to the heterogeneity distribution of the parental L1210 cell line, have been evidenced in resistant cells. A uniform increase in mBCI fluorescence was observed among cells of the sublines resistant to L‐PAM and FCE‐24517. The mean mBCI fluorescence increase in sublines resistant to DX and DDp was due to a higher number of cells with fairly high mBCI fluorescence, but still within the range spanned by the parental cell line. A less heterogeneous mBCI fluorescence distribution was found in the L1210 subline resistant to FCE 23762, which was, however, similar to a cloned sensitive line. Though GSH was linked to the principal cause of drug resistance only in the L‐PAM‐resistant cell line, alterations in heterogeneity, as detected by mBCI fluorescence distributions, were found in 5 out of 6 resistant lines.
Inhibition of glycolysis and mitochondrial respiration of ehrlich ascites carcinoma cells by methylglyoxal
Authors: Halder Jyotsnabaran , Ray Manju , Ray Subhankar 
Published: February 2007

AbstractThe effect of methylglyoxal (MG) on the aerobic glycolysis of Ehrlich ascites carcinoma (EAC) cells has been tested. Methylglyoxal inhibited glucose utilization and glucose 6‐phosphate (G6P) and L‐lactate formation in whole EAC cells. Methylglyoxal strongly inactivated glyceraldehyde 3‐phosphate dehydrogenase (GA3PD) of the malignant cells, whereas MG has little inactivating effect on this enzyme from several normal sources. Methylglyoxal also inactivated only the participate hexominase of the EAC cells, but this inactivation was less pronounced than the effect on GA3PD. Methylglyoxal has little inactivating effect on glucose 6‐phosphate dehydrogenase (G6PD), and no effect on L‐lactate dehydrogenase (LDH) of the malignant cells. Glucose‐dependent L‐lactic acid formation of EAC‐cell‐free homogenate was strongly inhibited by MG, but when GA3PD of normal cells was added to this homogenate, significant lactate formation was observed even in the presence of MG. Methylglyoxal also inhibited the respiration of EAC‐cell mitochondria. Respiration of mitochondria isolated from liver and kidney of normal mice, however, remained unaffected. As a consequence of the inhibition of glycolysis and mitochondrial respiration, the ATp level of the EAC cells was drastically reduced. Studies reported herein strongly suggest that the tumoricidal effect of MG is mediated at least in part through the inhibition of mitochondrial respiration and inactivation of GA3PD, and this enzyme may play an important role in the high glycolytic capacity of the malignant cells.
Transformation of mouse fibroblasts with the oncogenes H‐ras or trk is associated with pronounced changes in drug sensitivity and metabolism
Authors: Peters G. J. , Wets M. , Keepers Y. P. A. M. , Oskam R. , Van Ark‐Otte J. , Noordhuis P. , Smid K. , Pinedo H. M. 
Published: February 2007

AbstractMalignant activation of oncogenes ras or trk is implicated in a number of solid tumors and leukemias. We determined the chemosensitivity profile of wild‐type mouse NIH‐3T3 fibro‐blasts, and that of NIH‐3T3 lines transformed by the H‐ras (S2‐721) and trk (106–632) oncogenes, against 11 different drugs from various classes. Differences in sensitivity were related to drug accumulation and metabolism. Both ras‐ and trk‐trans‐formed cell lines were less sensitive to cisplatin (CDDp) and doxorubicin (DXR) than the wild type. NIH‐3T3 transformants expressing H‐ras were less sensitive than those expressing trk or the wild type to the indoloquinone EO9, methotrexate and arabino‐furanosylcytosine. No clear difference in sensitivity was observed for vincristine, Vp‐16, or the new cytidine analog 2′, 2′ ‐difluoro‐deoxycytidine. In both ras‐ and trk‐transformed cell lines sensitivity to 5FU was increased moderately, but sensitivity to 5′ deoxy‐5‐fluorouridine (5′dFUR) was increased markedly. Only the trk‐transformed line NIH‐3T3 was more sensitive to 2′ deoxy‐5‐fluorouridine. Expression of P‐glycoprotein was not different between the 3 cell lines but DXR accumulation in both mutants was decreased, indicating a non‐P‐glycoprotein‐associated difference in sensitivity. Conversion of 5′ dFUR to 5FU (catalyzed by pyrimidine nucleoside phosphorylases) was 5–10 times higher in both mutants than in the wild type. The activity of the phosphoribosyl‐transferase (direct conversion of 5FU to FUMP) was comparable, but the rate of conversion of 5FU to fluorouridine (FUR) was lower in the wild type, as well as that of 5FU to FUMP via FUR. In contrast, the activity of thymidylate synthase, the target enzyme for fluoropyrimidines, was higher in the wild‐type cells. The concentrations of both purine and pyrimidine nucleotides were lower in cells expressing trk. In conclusion, transformation of cells with the H‐ras or trk oncogenes can markedly influence sensitivity to several drugs and affect normal metabolism and that of several anti‐cancer agents.
The effect of ion channel blockers, immunosuppressive agents, and other drugs on the activity of the multi‐drug transporter
Authors: Weaver James L. , Pine P. Scott , Aszalos Adorjan , Szabo Gabor , Gottesman Michael M. , Goldenberg Sarah 
Published: February 2007

AbstractThe MDRI protein is an energy‐dependent transport protein responsible for the multi‐drug resistance seen in many tumors. A variety of drugs have been shown to inhibit the function of this pump, including compounds known to block various ion channels. The mouse lymphoma cell line L5178Y has been transduced with the human mdr 1 gene. Using this cell line, we have tested a number of compounds to determine whether there is a correlation between the ability to block a specific type of ion channel, or shift membrane potential, and the ability to act as an MDR‐reversing agent using the fluorescent substrates Rhodamine 123 and daunorubicin as test compounds. Our results show no apparent correlation between the ability to block a specific ion channel and reversal of MDR transport ability. We have found active MDR inhibitors in compounds that affect K+, Na+, Ca+ +, H+, but not Cl− channels. Our data suggest that Cl−channel activity may be distinct from MDR activity. Several immunosuppressive compounds and analogs were also tested and found to be active reversing agents. Measurements suggest a significant difference in resting membrane potential between the L5178YvMDR line and the L5178Y parental cell line used in these experiments. No correlation was found between the ability of drugs to alter membrane potential and to inhibit MDR transport activity. Our results suggest that MDR transport function may be independent of the physiological movement of ions and show that a wide variety of compounds can inhibit MDR transport.
Monoclonal antibody directed against colon cancer mucin has high specificity for malignancy
Authors: Siddiki Badcr , Ho Jenny J. L. , Huang Jian , Byrd James C. , Lau Eva , Yuan Mei , Kim Young S. 
Published: February 2007

AbstractExposure of core carbohydrate structures such as NeuAc alpha2–6GalNAc‐Ser/Thr (sialosyl‐Tn) in mucus glycoproteins is often associated with malignant transformation in a number of different tissues. Reagents that specifically identify such structures would be useful in the diagnosis of cancer. Monoclonal antibody JT10e has been produced against mucins from xeno‐grafts of LS174T colon cancer cells but also reacts with mucins of pancreatic cancer xenografts. The following data suggest that JTlOe reacts with sialosyl‐Tn: (I) reactivity with bovine and ovine submaxillary mucins; (2) reactivity sensitive to neuramini‐dase or mild acid; (3) inhibition of reactivity by NeuAc and NeuAc alpha2–6 lactose; and (4) lack of reactivity with other glycoproteins with related carbohydrate structures but no sialosyl‐Tn. JTlOe is distinguishable from 2 other antibodies which react with sialosyl‐Tn, B72.3 and TKH2 because JT10e: (a) did not react with normal gastric tissue while B72.3 and TKH2 did; (b) was only partially inhibited by TKH2 and not at all by B72.3; (c) did not react with Tn antigen while B72.3 did; and (d) bound more strongly to pancreatic cancer mucins than did either B72.3 or TKH2. JT10e reacted with a high percentage of malignant colonic, pancreatic, gastric and mammary tissues but not with the corresponding normal tissues. A high percentage of patients with colonic, pancreatic, gastric, mammary and lung cancers had elevated blood levels of JT10e antigen. A number of colonic cancer patients had elevated JT10e antigen levels without corresponding elevations in CA19–9 levels. These results suggest that JT10e antibody could be used in conjunction with other mucin markers to improve the identification of malignancy in colon, and to study the structure of oligosaccha‐rides in cancer mucins.
Sensitized T lymphocytes render DBA/2 beige mice responsive to IFN α/β therapy of friend erythroleukemia visceral metastases
Authors: Kaido Thomas , Gresser Ion , Maury Chantal , Vignaux Françoise , Maunoury Maric‐Thérèse , Belardelli Filippo 
Published: February 2007

AbstractInterferon α/β (IFN α/β) is highly effective in inhibiting the development of Friend erythroleukemia cell (FLC) visceral metastases in DBA/2 mice injected intravenously (i.v.) with FLC, but does not protect FLC‐injected DBA/2 beige (bg/bg) mice. Use of IFN α/β‐resistant FLC indicated that IFN was acting through host mechanisms in DBA/2 mice and thus pointed to a defect in some host mechanism in bg/bg mice essential for IFN's anti‐metastatic action. We undertook experiments to restore in bg/bg mice the marked anti‐FLC meta‐static effect of IFN a/p observed in DBA/2 and +/bg mice. Adoptive transfer of spleen cells from normal syngeneic mice to IFN‐treated bg/bg mice was ineffective, but the transfer of splenic T lymphocytes from FLC‐immunized DBA/2 or +/bg mice markedly increased the survival time of FLC‐injected bg/bg mice provided that these mice were also treated with IFN a/p. Neither treatment alone resulted in an increase in survival time. As few as 1 × 107 immune spleen cells were effective in IFN‐treated FLC‐injected bg/bg mice. The T‐cell immune response to FLC of bg/bg mice was diminished compared with that of +/bg mice. Likewise, only combination therapy of immune spleen cells and IFN α/β resulted in an increased survival time of ESb‐lymphoma‐injected bg/bg mice. Our results indicate the essential participation both of T‐cell‐mediated immune mechanisms and of IFN α/βin the inhibition of FLC visceral metastases.
Differential expression and release of LFA‐3 and ICAM‐1 in human melanoma cell lines
Authors: Scheibenbogen Carmen , Keilholz Ulrich , Hunstein Werner , Meuer Stefan , Dengler Thomas , Tilgen Wolfgang 
Published: February 2007

AbstractWe examined 10 different melanoma cell lines for cellular expression and release of I CAM‐1 (CD54) and LFA‐3 (CD58) and the influence of cytokines, including IFNa, IFNγ and TNFa. Cellular ICAM‐I expression and density varies considerably between the melanoma cell lines. While IFNα has no effect on cellular ICAM‐I (cICAM‐l) expression, IFNγ and to a lesser extent TNFα can effectively up‐regulate cICAM‐l. Soluble I CAM‐1 (sICAM‐1) is detected in the supernatants of all lines tested, release of sICAM‐1 correlates with cellular expression. LFA‐3 does not much differ in its expression level on melanoma lines, and cytokines have little or no effect on its expression. Soluble LFA‐3 is released by only 6 out of 10 lines. Its release can effectively be inhibited by IFNγ in all lines and by TNFa in one, while IFNa has no effect. These data show that expression and release of LFA‐3 and ICAM‐I differ between melanoma cell lines. This may be of importance for the interaction of melanoma cells with immune effector cells in vivo.
Disialoganglioside GD2 anti‐idiotypic monoclonal antibodies
Authors: Cheung Nai‐Kong V. , Canete Adela , Cheung Irene Y. , Ye Jian‐Nan , Liu Chongyuan 
Published: February 2007

AbstractDisialoganglioside GD2 is widely expressed among neuroblas‐tomas, melanomas, small‐cell lung carcinoma, sarcomas and brain tumors. Immunity directed against this antigen may have anti‐tumor utility. Since GD2 is poorly immunogenic, anti‐idiotypic antibodies may serve as alternative tumor vaccines. Monoclonal antibody 3F8, a murine lgG3 specific for GD2, has shown excellent tumor‐targeting ability in vitro and in vivo. LOU/CN rats were immunized with 3F8 and their spleens were used in somatic‐cell hybridization, using Sp2/0, p3 and Y3 as fusion partners. Six anti‐idiotypic (anti‐id) MAbs (C2D8, ldio‐2, AIG4, C2H7, C4E4, A2A6) were selected based on their reactivity with 3F8 and non‐reactivity with murine lgG3 myelomas. Specificity of each anti‐id was demonstrated by using various ELISA: (i) lack of direct binding to solid phase myelomas and serum proteins; (ii) inability of other myelomas to inhibit anti‐id binding to 3F8; (iii) absence of cross‐reactivity of other myelomas to solid‐phase anti‐id; (iv) lack of inhibition by anti‐id of binding of other ganglioside antibodies to their antigens. Antigen specificity was further examined by inhibition of binding of 3F8 to GD2 on immuno‐thin‐layer chromatography, and by inhibition of 3F8 immunostaining of neuroblastoma cell lines. These 6 antibodies were demonstrated to be distinct, in view of their cross‐reactivity, fusion partners and relative strength of binding to 3F8. Anti‐GD2 antibodies were induced after immunization with these anti‐id antibodies in C57BI/6 mice. These rat anti‐3F8‐idiotypic antibodies with exquisite specificity for anti‐GD2 antibodies may be useful in vaccine construction.
Dualistic effects of cis‐diammine‐dichloro‐platinum on the anti‐tumor efficacy of subsequently applied recombinant interleukin‐2 therapy: A tumor‐dependent phenomenon
Authors: Bernsen Moniquc R. , Heintz A. Peter M. , Van Barungen Harrold J. J. , Van Der Velden Alike W. , Dullens Hub F. J. , Otter Willem Den 
Published: February 2007

AbstractThe efficacy with which disseminated SL2 and P815 tumors, in syngeneic DBA/2 mice, can be eradicated with low‐dose recombinant interleukin‐2 (rlL‐2) therapy is about equal. Treatment (i.p.) of DBA/2 mice, injected i.p. with SL2 or P8I5 cells on day 0, with rlL‐2 (Proleukin) on days 10 to 14 results in a cure rate of 50 to 60% in each case. The in vitro sensitivity of SL2 and P8I5 cells to cis‐diammine‐dichloro‐platinum [II] (cisplatin) is also comparable, although P8I5 appears to be slightly more sensitive. In vivo, however, therapy with cisplatin is far less effective against P8I5 than against SL2. In the DBA/2‐SL2 model, at all doses tested, combination therapy with cisplatin (administered on day 2) and rlL‐2 (administered on days 10–14) resulted in anti‐tumor efficacy greater than that of either drug separately. In contrast, in the DBA/2‐P8I5 model, cisplatin decreased the anti‐tumor efficacy of subsequently applied rlL‐2 therapy. As the only difference between the 2 tumor models is the tumor itself, the success of combination therapy with cisplatin and rlL‐2 was dependent on tumor characteristics. We suggest that in these 2 tumor models, neither the sensitivity of these tumors to cisplatin nor their growth and dissemination patterns were responsible for the contrasting results of combination therapy in these models. Instead, tumor‐dependent immune‐modulating effects of cisplatin may be the cause of these effects. These immune‐modulating effects may comprise (a) effects of cisplatin on the tumor cells, resulting in changes in their susceptibility to immune effector cells, or changes in their immunogenicity; (b) activating or suppressive effects of cisplatin on immune effector cells; or (c) a combination of these effects. These effects could then either synergize or antagonize with the immune activating properties of rlL‐2.
Increased risk of nasopharyngeal carcinoma among males of french origin born in maghreb (north africa)
Authors: Jeannel D. , Ghnassia M. , Hubert A. , Sancho‐Garnier H. , Eschwège F. , Crognier E. , De‐Thé G. 
Published: February 2007

AbstractA study on the incidence of nasopharyngeal carcinoma (NPC) has been performed in the Provence—Alpes—Cote d'Azur (PACA) region, South of France, where Maghrebian migrants represent 10% of the population. During the years 1986–1990, 76 cases of NPC were diagnosed, of which 44 were French by birth, 25 were Maghrebian migrants and 7 were other migrants. We found that 36% of the French patients were either born in endemic areas or had lived there for more than 15 years. Standardized annual incidence rates of NPC among Maghrebian migrants remained close to those observed in North Africa, while, standardized annual incidence rates for French by birth in the PACA region were similar to those observed in cancer registries in other regions of France and countries of low incidence. However, for males of French origin born in Maghrebian countries, the incidence of NPC (all cases being of undiffer‐entiated type) was 5.7 times higher than that of males of French origin born in France (p = 0.00001). These results favor a critical role of environmental factors in the risk of NPC.
Allelic loss in ovarian cancer
Authors: Yang‐Feng Teresa L. , Han Hong , Chen Kuang‐Chao , Li Shi‐Bo , Claus Elizabeth B. , Carcangiu Maria L. , Chambers Setsuko K. , Chambers Joseph T. , Schwartz Peter E. 
Published: February 2007

AbstractLoss of heterozygosity (LOH) was examined at 86 loci distributed on every chromosomal arm in 50 human ovarian tumors. Frequent allele losses were observed on chromosomes 13q (42%), 17p (42%), 17q (45%), and Xp (41%). Deletion mapping on chromosome 17 revealed a candidate gene on the long arm distal to D17S41/S74 for ovarian cancer which is distant from the locus for early onset breast cancer. LOH on chromosome 17q was found to be concordant with LOH on chromosomes 3p, 13q, 17p and Xp suggesting that it may be an early event in neoplastic development. These findings indicate that multiple tumor‐suppressor genes for ovarian cancer possibly exist on chromosomes 13q, 17, and/or Xp and provide the basis for the identification of candidate gene(s) associated with ovarian cancer. The chromosomal mechanisms resulting in allele losses in ovarian cancer include deletion, deletion/duplication, mitotic recombination and monosomy, in concordance with the developed genetic model.
Estimates of the worldwide incidence of eighteen major cancers in 1985
Authors: Parkin D. M. , Pisani P. , Ferlay J. 
Published: February 2007

AbstractThe annual incidence rates (crude and age‐standardized) and numbers of new cases of 18 different cancers have been estimated for the year 1985 in 24 areas of the world. The total number of new cancer cases (excluding non‐melanoma skin cancer) was 7.6 million, 52% of which occur in developing countries. The most common cancer in the world today is lung cancer, accounting for 17.6% of cancers of men worldwide, and 22% of cancers in men in the developed countries. Stomach cancer is now second in frequency (it was slightly more common than lung cancer in 1980) and breast cancer—by far the most important cancer of women (19.1% of the total)—is third. There are very large differences in the relative importance of the different cancers by world area. The major cancers of developed countries (other than the 3 already named) are cancers of the colon‐rectum and prostate, and, in developing countries, cancers of the cervix uteri, mouth and pharynx, liver and oesophagus. The implications of these patterns for cancer control, and specifically prevention, are discussed. Tobacco smoking and chewing are almost certainly the major prevent able causes of cancer today.
Expression of MMP‐7(pump‐1) mRNA in human colorectal cancers
Authors: Yoshimoto Mitsuru , Itoh Fumio , Yamamoto Hiroyuki , Hinoda Yuji , Imai Kohzoh , Yachi Akira 
Published: February 2007

AbstractThe expression of MMP‐7 (pump‐1) gene was examined in 10 cases of colorectal cancer by utilizing RT‐PCR. In 9 out of 10 cases, MMP‐7 mRNA was detected in cancerous tissue, whereas none was detected in adjacent normal colon tissue. However, this message was detected in only I out of 6 colon‐cancer cell lines. In colonic mucosa from 3 patients with ulcerative colitis it was not detected. The expression of MMP‐2 (72‐kDa type‐IV collagenase) mRNA was also investigated in the same tissue samples, and was detected in all samples, including cancerous and non‐cancerous tissue. Our data suggest that MMP‐7 is expressed in a tumor‐associated manner in colorectal cancers and may play a role in tumor progression.