bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CD16/CD30 bispecific monoclonal antibody induces lysis of hodgkin's cells by unstimulated natural killer cells In AND In vivo
Authors: Hombach Andreas , Jung Wolfram , Pohl Christoph , Renner Christoph , Sahin Ugur , Schmits Rudolf , Wolf JÜRgen , Kapp Ursula , Diehl Volker , Pfreundschuh Michael 
Published: February 2007

AbstractIn order to target NK cells against the Hodgkin's‐derived cell line L540, we developed bispecific monoclonal antibodies (Bi‐MAbs) by somatic hybridization of the 2 mouse hybridoma cell lines HRS‐3 and A9 which produce monoclonal antibodies (MAbs) with reactivity against the Hodgkin and Reed‐Sternberg cell‐associated CD30 antigen and the CD 16 antigen (FcγIII receptor), respectively. The CD 16 MAb‐producing cell line A9 was selected as a partner for HRS‐3 because of its efficiency in inducing lysis of the A9 hybridoma cells by resting NK cells. The hybrid hybridoma cell line HRS‐3/A9 produced the supernatant with the strongest bispecific reactivity and was repeatedly subcloned and used for ascites production. Crude supernatant and purified HRS‐3/A9 Bi‐MAb triggered specific lysis of the CD30+ Hodgkin's‐derived cell line L540, but not of the CD30− cell line HPB‐ALL by unstimulated peripheral‐blood lymphocytes and NK‐cell‐enriched populations. Moreover, treatment of SCID mice bearing heterotransplanted human Hodgkin's tumors with HRS‐3/A9 and human peripheral blood lymphocytes induced specific complete tumor regression in 10/10 animals. We thus report successful tumor treatment in an in vivo model using NK‐cell‐associated Bi‐MAbs and show that the Bi‐MAb HRS‐3/A9 is an efficient promoter of the anti‐tumor effects of NK cells in vitro and in vivo.
Quantitative and/or qualitative changes in the P21‐H‐ras post‐translational products in regenerating liver and during hepatocarcinogenesis
Authors: Gulbis Beatrice , Alexandre Kathy , Galand Paul 
Published: February 2007

AbstractUsing Western immunoblot analysis with the Ras‐10 monoclonal antibody (MAb), we characterized 4 post‐translational products of the c‐H‐ras gene in rat tissues, and showed that they were readily distinguished from the normal p2l‐N‐ras or Val12 mutant p21‐ras products. In the present study, we used this approach to compare the electrophoretic pattern of p21 ‐H‐ras during chemically induced hepatocarcinogenesis in rats with that in control liver samples. Three types of pattern were defined in the liver samples taken at various stages of malignant progression. The first type, like all the 18 normal samples analyzed, was characterized by a predominant intensity of spot a (corresponding to the palmitoylated p21 ‐H‐ras product). This was observed in all the samples at the stage of foci and only in a proportion of nodular or tumoral tissues. The second type of pattern deviates from this normal basal pattern by a higher relative level in one or more of the precursors of the fully processed p21‐H‐ras product. It was observed in all liver samples at the stage of nodules and in a proportion of tumors, but also in all samples from fetal or regenerative liver, thus suggesting an association with high proliferative activity of the hepatocytes. The third type of pattern was characterized by the presence of spots never detected in any of the normal rat tissue or cells that we investigated. Abnormal spots were observed in nodular liver samples and in hepatocarcinomas, indicating that they probably correspond to mutant p21 ‐H‐ras products. The fact that the 2 types of abnormal products were not constantly associated with neoplasms indicates that if they play a role in their induction or maintenance this may also be achieved in an independent way, perhaps, but not necessarily, involving another mutation of the ras gene.
α galnac is essential for recognition of EXO‐1 epithelial antigen by mouse monoclonal antibody Pa‐G‐14
Authors: Schröder Helmut , Francí Clara , Egea Gustavo , Oriol Rafael , Klingel Reinhard , Dippold Wolfgang G. , Real Francisco X. 
Published: February 2007

AbstractMouse monoclonal antibody Pa‐G‐14 detects Exo‐1, an antigen whose expression is regulated in the processes of epithelial‐cell differentiation and transformation. The epitope recognized by Pa‐G‐14 is present both in glycosphingolipids and in mucin glycoproteins. To characterize the specificity of Pa‐G‐14, immuno‐thin‐layer chromatography, biochemical, and enzymatic treatment of glycosphingolipid extracts from human pancreas were used. The antibody bound to all blood‐group‐A substances; αGaINAc, but not fucose, was essential for reactivity. In ELISA, Pa‐G‐14 also reacted with ovine and bovine submaxillary mucins but not with porcine submaxillary mucin. Binding to ovine submaxillary mucin was resistant to neuraminidase treatment. In solid‐phase absorption assays on synthetic carbohydrate structures, Pa‐G‐14 recognized broadly blood group A, Tn and sialyl‐Tn. Using immuno‐electron‐microscopic techniques, reactivity with all Golgi cisternae and mucin droplets of mucous cells in ovine submaxillary gland was demonstrated. All these assays indicate that Pa‐G‐14 shows a novel specificity, since it binds blood group A, Tn and sialyl‐Tn, the common structural feature of these epitopes being the presence of a terminal αGalNAc sugar unit.
Immunohistochemical survey of pS2 expression in intraductal lesions associated with invasive ductal carcinoma of the breast
Authors: Inaji Hideo , Koyama Hiroki , Motomura Kazuyoshi , Noguchi Shinzaburo , Tsuji Naoko , Wada Akira 
Published: February 2007

AbstractWe examined the expression of pS2 protein in 48 invasive ductal breast carcinomas with an extensive intraductal component, using immunohistochemical staining of paraffin‐embedded sections. The patients selected for this study would have met the criteria for breast‐conserving surgery applied at our institute at present. The rate of pS2 expression in the intraductal lesion was significantly higher than that in the main invasive lesion. The incidence of pS2 protein expression in the latter lesions was very similar to that in invasive carcinoma without intraductal lesions. The pS2 positivity of the intraductal lesion was equal to or higher than that of the invasive lesion. Of intraductal lesions, those classified as non‐comedo carcinomas frequently contained more pS2 protein than did comedo carcinomas.
Low incidence of C‐Ha‐ras gene mutations in benign and malignant cutaneous lesions from transplant recipients
Authors: Pélisson I. , Chardonnet Y. , Euvrard S. , Schmitt D. 
Published: February 2007

AbstractTransplant recipients successively develop benign, pre‐malignant and malignant skin lesions on sun‐exposed areas. It has been suggested that UV radiations might induce mutations in ras oncogenes and p53 tumour‐suppressor gene, responsible for skin cancers. With PCR and oligoprobe hybridization, we investigated c‐Ha‐ras gene mutations at codons 12 and 61 in 120 cutaneous lesions from grafted patients, since they could represent a marker of the evolution of benign skin lesions towards malignancy in this population; 29 similar skin biopsies from non‐immunosuppressed patients were also analyzed. In transplant recipients, we detected mutations at codon 12 only in 1/42 non‐melanoma skin cancers and 2/29 pre‐cancerous keratoses. No mutation was detected in 11 cases of cutaneous Bowen's disease from grafted patients and in pre‐malignant and malignant skin samples from control patients. Benign warts exhibited an overall incidence of 18% and 15% of mutations at codon 12 of c‐Ha‐ras gene in grafted and control patients respectively. We detected only one mutation at codon 61 in a plantar wart. Human papillomaviruses (HPV) are thought to be involved in the malignant evolution of cutaneous disorders in transplant recipients and cooperate with a ras oncogene to induce malignancy in vitro. The presence of HPV ONA in our series of skin samples from grafted patients showed no correlation with the occurrence of c‐Ha‐ras mutations. Our findings indicate that c‐Ha‐ras‐gene activation by mutations is rare in cutaneous lesions from transplant recipients, and is unlikely to play a crucial role in transformation towards malignancy in skin carcinogenesis among grafted patients.
Expression and shedding of ICAM‐1 in bladder cancer and its immunotherapy
Authors: Jackson Andrew M. , Alexandrov Anton B. , Gribben Shona C. , Esuvarnathan K. , James Keith 
Published: February 2007

AbstractIntercellular adhesion molecule‐1 (ICAM‐1) is one of 3 major ligands for the β2 integrin leucocyte function‐associated antigen‐ I (LFA‐1). Several reports have emerged describing soluble forms of ICAM‐1 in association with normal and pathological states (e.g., malignancy). In this study we have identified the secretion of soluble ICAM‐1 in tissue culture supernatants from bladder tumour monolayers and in the urine of patients receiving intravesical BCG immunotherapy for superficial bladder cancer. In vitro, small amounts of sICAM‐1 were detected in the tissue culture supernatants of bladder cancer cells, known to constitutively express ICAM‐1. Following stimulation with interferon γ, the levels of sICAM‐1 increased inversely to the levels of cell surface ICAM‐1, suggesting shedding. Induction and augmentation of cell surface ICAM‐1 required de novo mRNA and protein synthesis. However, treatment with cycloheximide, after stimulation with IFN‐γ, resulted in increased levels of membrane associated ICAM‐1. Correspondingly, the level of sICAM‐1 in the supernatant was low in comparison with controls, suggesting that cycloheximide acted via stabilization of membrane ICAM‐1 or via prevention of some enzymatic cleavage event. In vivo, sICAM‐1 can be detected at high levels in patients' urine following immunotherapy of bladder cancer with intravesically administered BCG organisms. Production of sICAM‐1 is transient and occurs only in the first 12 hr following instillation. Furthermore, production of sICAM‐1 is heterogeneous as some patients fail to produce any at all. If the source of sICAM‐1 is the bladder tumour per se, then its detection in urine could indicate a response of the tumour to immunotherapy and indeed may prove a useful indicator of clinical response.
Normal breast epithelial cells produce interleukins 6 and 8 together with tumor‐necrosis factor: Defective il6 expression in mammary carcinoma
Authors: Basolo Fulvio , Conaldi Pier Giulio , Fiore Lisa , Calvo Simonetta , Toniolo Antonio 
Published: February 2007

AbstractVirtually pure primary cultures of normal mammary epithelial cells (MEC) obtained from healthy women were shown to release interleukin 6 and 8 (IL6, IL8) and to produce a non‐secreted form of tumor‐necrosis factor (TNF). No interferon (IFN), whether α, β or γ, or ILI‐α or ‐β could be detected. Analysis of cellular RNA confirmed these findings and showed that MEC also express IL6 receptor and TNF‐α‐related mRNAs. Epithelial cells were selectively stained by antibodies to IL6, IL8 and TNF‐α both in primary cultures and in the normal mammary gland. Samples of human milk contained sizable amounts of IL6, IL8 and IFN‐γ; yet the liquid phase was consistently negative for other cytokines (i.e., TNF‐α, IFN‐α/‐β, ILI‐α/‐β). Expression of IL6 (but not of IL8 and TNF‐α) was abolished in ductal infiltrating carcinomas and greatly reduced in cultures of oncogene‐transfected mammary cells, suggesting that alterations of IL6 expression are associated with pathogenesis in breast cancer.
Specificity and properties of MAb RS7‐3G11 and the antigen defined by this pancarcinoma monoclonal antibody
Authors: Stein Rhona , Basu Amartya , Chen Susan , Shih Lisa B. , Goldenberg David M. 
Published: February 2007

AbstractThe murine monoclonal antibody (MAb) RS7‐3G11 is an IgG1 with pancarcinoma reactivity, which has been raised against human squamous‐cell carcinoma of the lung. Immunoperoxi‐dase staining of frozen tissue sections demonstrated that the antigen defined by RS7‐3G11 is present in tumors of the lung, stomach, bladder, breast, ovary, uterus and prostate. The rate and extent of internalization of RS7‐3G11 into Calu‐3, an adenocarcinoma of the lung cell line, was investigated using unconjugated MAb, followed by fluorescence labeling, and by binding 125l‐RS7‐3G 11 followed by acid removal of surface‐bound antibody. Rapid internalization of MAb RS7‐3G11 into target cells was observed. Antibody internalization was noted at 30 min, and by 2 hr virtually all MAb RS7‐3GII was internal. Although MAb RS7‐3G11 was raised against non‐small‐cell carcinoma of the lung, ME‐180, a cervical‐carcinoma cell line, expresses higher quantities of the antigen than the lung carcinoma cell lines. Due to the higher antigen density in ME‐180 cells, this line was used for immunoprecipitation studies and antigen purification. Immunoprecipitation studies using the ME‐180 cervical‐carcinoma cell line metabolically labeled with [3H] leucine or [3H]glucosamine demonstrated that the antigen defined by RS7‐3G11 is a glycoprotein of Mr 46 kDa. Deglycosylation by treatment with endoglycosidase‐F resulted in a protein with a Mr of 35 kDa. RS7‐3G11 ‐antigen was purified from ME‐180 tissue‐culture cells using affinity‐column chromatography. By SDS‐PAGE it was seen that the antigen was highly purified. The major band appeared at Mr of 45 to 48 kDa. This result is in agreement with the immunoprecipitation studies. The broad band observed in the SDS‐PAGE is typical of many glycoproteins, and suggests heterogeneity of glycosylation. Chemical and enzymatic treatments of the antigen, followed by Western blot analyses, suggest that the RS7‐3G11 antigenic determinant is composed of a conformation‐dependent peptide.
Alterations of the p53 tumor‐suppressor gene in transformed mouse liver cells
Authors: Sun Yi , Hegamyer Glenn , Nakamura Kazuki , Kim Hyungtae , Oberley Larry W. , Colburn Nancy H. 
Published: February 2007

AbstractMutational inactivation of p53, a potential tumor‐suppressor gene, has been found in many tumors of humans as well as rodents. The p53 status in normal and transformed mouse liver cell lines has, however, not been investigated. We examined possible point mutations and compared mRNA and protein expression of the p53 gene in normal vs. transformed mouse liver cells. The transformed cells studied included lines spontaneously transformed by sub‐culture, virally transformed by simian virus 40 (SV40), and chemically transformed by N‐methyl‐N‐nitro‐N‐nitrosoguanidine (MNNG) or methylcholanthrene epoxide (MC). A heterozygous G → A point mutation at codon 241, position I, of p53 was detected in MNNG‐transformed cells after screening of 5 evolutionarily conserved regions where mutation hot‐spots are clustered. The mutation causes a glyarg substitution. No mutations were found in normal or other transformed cells. The steady‐state levels of p53 mRNA were decreased in chemically transformed (both MNNG‐ and MC‐transformed) cells. Elevated levels of p53 protein were found in spontaneously transformed and SV40‐transformed cells, an observation that may reflect a longer half‐life of the protein, as has been shown in other transformed lines. The low level of the p53 protein in MC‐transformed cells may result from transcriptional depression of the p53 gene. We conclude from these data that abnormal p53 status, such as point mutation or altered expression, may play a role during the malignant transformation of mouse liver cells.
Effect of serum and cell density on transmembrane distribution of cAMP and cGMP in transformed (C4‐i) and non‐transformed (WI‐38) human cells
Authors: Ørbo A. , Jaeger R. , Sager G. 
Published: February 2007

AbstractThe ratio between cGMP and cAMP in plasma/urine is elevated in several types of malignancies. The present in vitro study showed that the ratio between extracellular cGMP and cAMP increased during the proliferation of C4‐1 cells (derived from a carcinoma of the uterine cervix), whereas this ratio decreased in W1‐38 cells (normal lung fibroblasts). These results can be explained by differences between the transformed and non‐transformed cells in the cell‐density‐dependent transmembrane distribution and intracellular levels of cyclic nucleotides. In the serum‐deprived cultures, no profound effects were seen on the cell‐density‐dependent biokinetics of cAMP and cGMP. In the absence of serum, growth of C4‐1 cells was markedly retarded, whereas W1‐38 cells were unable to expand at all.
Effect of epidermal growth factor and transforming growth factor β1 on growth and invasive potentials of newly established rat bladder carcinoma cell lines
Authors: Kawamata Hitoshi , Kameyama Shuji , Nan Li , Kawai Koji , Oyasu Ryoichi 
Published: February 2007

AbstractWe established 5 rat bladder cell lines (MYU3L, MYU4, MYU6s, MYKUIL and MYP3). EGF stimulated DNA synthesis of all the cells in monolayer culture, regardless of the number of EGF receptors. In soft agar, only MYU3L formed colonies, and EGF enhanced their growth. However, EGF did not induce the other cells to grow in soft agar. In contrast, TGF‐β1 inhibited the growth of the cells, but a tumorigenic cell and the cells which were established from large in vivo tumors were more resistant than the others to TGF‐β1. We tested the effect of growth factors on the invasive potential of MYP3 cells (non‐tumorigenic), MYU3L cells (tumorigenic/highly invasive but not metastatic) from newly established cell lines, and another metastatic cell line, LMC 19. MYP3 expressed only a trace amount of 92‐kDa gelatinase (MMP‐9), whereas MYU3L expressed interstitial collagenase (MMP‐1) and MMP‐9, and LMC19 expressed 72‐kDa gelatinase (MMP‐2) and MMP‐9. The release of MMP‐2 in LMC 19 was stimulated by TGF‐β1, but EGF had no effect on the release of any MMPs in either type of cells. These observations suggest that EGF acted as a mitogen on all the cells tested, but did not enhance the malignant phenotype. Further, the loss of responsiveness to the suppressive effect of TGF‐β1 may be an important step toward a malignant phenotype. Some of malignant tumors may utilize TGF‐β1 for enhancing their invasive and metastatic potential.
Chemoprevention by indomethacin of tumor promotion in a rat urinary bladder carcinogenesis model
Authors: Shibata Masa‐Aki , Hasegawa Ryohei , Shirai Tomoyuki , Takesada Yasuko , Fukushima Shoji 
Published: February 2007

AbstractThe chemopreventive effects of indomethacin (IM) on the enhancement of bladder carcinogenesis and transitional‐epithelial‐cell proliferation by butylated hydroxyanisole (BHA) or sodium L‐ascorbate (Na‐AsA) were investigated. All animals were given 0.05% N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine (BBN) in their drinking water for 4 weeks. They then received 2% BHA or 5% Na‐AsA for 20 weeks, followed by 20 ppm IM in the drinking water or normal tap water without supplement for a further 20 weeks, or BHA or Na‐AsA alone or concomitantly with IM for 40 weeks. No differences in bladder‐tumor development were found when IM was administered after cessation of BHA or Na‐AsA exposure. However, IM in combination with either BHA or Na‐AsA significantly reduced both the incidence and the multiplicity of papillomas and carcinomas as compared with the values of groups receiving BHA or Na‐AsA alone. This was associated with decreased DNA synthesis and prostaglandin (PG) E2 levels in the existing bladder tumors. Combined treatment with IM did not exert any effects on BHA forestom‐ach carcinogenesis. A separate 8‐week combination study demonstrated that IM diminished the increase in expression of proliferation nuclear‐cell antigen (PCNA) induced by BHA or Na‐AsA alone. The present results suggest that PGE2 may be involved in promotion of rat bladder carcinogenesis and that the PG synthesis blocker IM might exert preventive effects on the development of bladder cancer in humans.
Tamoxifen modulation of cisplatin cytotoxicity in human malignancies
Authors: McClay Edward F. , Albright Kathleen D. , Jones Jeffrey A. , Christen Randolph D. , Howell Stephen B. 
Published: February 2007

AbstractRecent clinical trials have indicated that addition of tamoxifen (TAM) to a combination of cisplatin (DDP), carmustine and dacarbazine markedly increases the overall objective response rate of patients with metastatic malignant melanoma. Previous studies have determined that there is remarkable synergy between TAM and DDP in a human melanoma cell line T‐289. Using the technique of median effect analysis, in clonogenic assay, we observed a highly synergistic interaction between TAM and DDP. To determine whether or not this synergistic interaction was unique to human melanomas, or is generally observed in other types of malignancy, we examined the nature of this interaction using a human ovarian carcinoma and small cell lung cancer cell line. Synergy was observed in both cell lines. In the case of all 3 types of malignancy, synergy was observed at concentrations of both TAM and DDP that can be achieved in patients. Our results demonstrate that cytotoxic synergy between the DDP and TAM is observed in cell lines established from multiple types of human malignancies. It is important to note that the synergy between TAM and DDP is not dependent on the presence of estrogen or progesterone receptors. Since TAM is well tolerated by patients, it is particularly attractive as a potential agent with which to sensitize human tumors to DDP.
Inhibition of metastatic cell colonization in murine lungs and tumor‐induced morbidity by non‐peptidic Arg‐Gly‐Asp mimetics
Authors: Hardan I. , Weiss L. , Hershkoviz R. , Greenspoon N. , Alon R. , Cahalon L. , Reich S. , Slavin S. , Lider O. 
Published: February 2007

AbstractThe spreading and colonization of tumor cells require their migration to metastatic sites via blood vessels. To penetrate blood‐vessel walls, cells, including malignant ones, must recognize and associate with the sub‐endothelium extracellular matrix (ECM) and its glycoproteins. Recognition of ECM‐glycoproteins, such as fibronectin (FN) and vitronectin (VN), is mediated by integrin receptors expressed on various cell types, including platelets, leukocytes and tumor cells. The Arg‐Gly‐Asp (RGD)‐containing peptide, a major adhesive ligand of ECM, is present in various plasma and matrix glycoproteins, such as FN and VN. Non‐peptidic mimetics of RGD, consisting of carboxylate and guanidinium groups of Asp and Arg divided by a linear atom spacer, express a high affinity for the α11b ‐β3 integrin and inhibit platelet aggregation. Herein, the ability of RGD mimetics to inhibit adhesive interactions between tumor cells and RGD, and tumor progression in vivo, was examined. RGD‐containing peptides and the RGD mimetic, compound SF‐6,5, but not the Arg‐Gly‐Glu (RGE) peptide or the corresponding mimetic, specifically inhibited B16‐F10 melanoma cell adhesion to immobilized VN and FN. Daily administration in vivo of SF‐6,5 to mice inhibited the formation of B16‐F10 colonies in experimental and spontaneous models of metastases. Moreover, SF‐6,5 could prevent mouse death caused by massive colonization of tumor cells in the lungs. The therapeutic effect of RGD‐containing peptides on tumor metastasis formation was marginal, probably due to the small amounts used, and its susceptibility to proteolysis in situ. Thus, non‐peptidic mimetics of small adhesive epitopes may provide a novel therapeutic tool to prevent an adverse pathological event involving integrindependent cell‐cell and cell‐ECM interactions.