bluuebunny/crossref_metadata_2025_split huggingface dataset:
Administration of disulfide‐stabilized Fv‐immunotoxins B1(dsFv)‐PE38 and B3(dsFv)‐PE38 by continuous infusion increases their efficacy in curing large tumor xenografts in nude mice
Authors: Benhar Itai , Reiter Yoram , Pai Lee H. , Pastan Ira 
Published: February 2007

AbstractB1 (dsFv)‐PE38 and B3(dsFv)‐PE38 are recombinant immunotoxins in which the Fv fragments of MAbs B1 and B3, respectively, are stabilized by an engineered interchain disulfide bond and are fused at their C‐termini to a modified Pseudomonas exotoxin from which the cell‐binding domain has been deleted (PE38). Both immunotoxins have been shown to be specifically cytotoxic toward human cancer cell lines which express LeY‐related carbohydrates on their surface, and when given i.v., eradicated 30‐to 50‐mm3 s.c. A431 tumors growing in nude mice. A major advantage of dsFv‐immunotoxins is their stability at 37°C compared with the relatively unstable single‐chain Fvs. This allows them to be given continuously by osmotic pumps placed in the peritoneal cavity. In an attempt to increase the therapeutic index of the immunotoxins, we have now delivered them continuously for 6 days through mini‐osmotic pumps placed in the peritoneal cavity of tumor‐bearing nude mice. Using this mode of administration, we were able to maintain a constant level of immunotoxin in the serum which was non‐toxic to the mice, but caused complete regressions of large 150‐to 200‐mm3 tumors which lasted for over a month at 1/11 of the LD50 with B1(dsFv)‐PE38 and 1/6 of the LD50 with B3(dsFv)‐PE38. Complete regression of tumors of similar size could also be achieved by i.v. bolus injections of these immunotoxins at 1/7 of the LD, o with B1 (dsFv)‐PE38) and 1/3 of the LD50 with B3(dsFv)‐PE38. These results suggest that in patients it may be advantageous to administer dsFv‐immunotoxins by continuous infusion, since a larger therapeutic index is achieved. © 1995 Wiley‐Liss Inc.
Enhanced expression of transforming growth factor‐β and its type‐I and type‐II receptors in human glioblastoma
Authors: Yamada Naoshi , Kato Mitsuyasu , Yamashita Hidetoshi , Nistér Monica , Miyazono Kohei , Heldin Carl‐Henrik , Funa Keiko 
Published: February 2007

AbstractImmunohistochemical studies of transforming growth factor‐p (TGF‐P) and its receptors have been carried out on 16 glioma tissues and compared with 5 cases of gliosis. Significantly higher expressions of TGF‐βI, as well as type‐I and type‐II TGF‐β receptors (TβR‐I and TβR‐II, respectively), were observed in advanced‐malignant‐glioma tissues when compared with non‐tumorous gliosis. Immunoreactivities of TGF‐β and TβR‐I were localized in the cytoplasm of spindle‐shaped tumor cells surrounding proliferating vessels or around areas of necrosis. The advancing edge of the tumor clusters frequently stained positive. Similar expression patterns were found for TGF‐β2 and TGF‐β3, whereas only weak or no expression was found for endoglin. In low‐grade astrocytomas and in gliosis cases, the expression was moderate for TβR‐I and weak for TGF‐β and TβR‐II. In 3 examined human malignant glioma cell lines, clear immunostainings were detected for TGF‐β and its receptors. Ligand‐induced heteromeric complexes of the receptors were formed in these cell lines, but the amount of the receptors was less than that of mink lung epithelial cells, which are sensitive target cells for TGF‐β. TGF‐β I showed no growth‐inhibitory activity on any of these glioma cell lines. These results suggest that malignant gliomas produce TGF‐β and receptors, but are refractory to TGF‐β, implying dysregulation in the signalling pathway in the tumor cells. It is possible that the released TGF‐β acts on neighboring cells and affects stromal growth, angiogenesis, metastasis or immune surveillance in human glioma. © 1995 Wiley‐Liss, Inc.
Comparison of protein kinase C activity and isoform expression in cisplatin‐sensitive and ‐resistant ovarian carcinoma cells
Authors: Basu Alakananda , Weixel Kelly M. 
Published: February 2007

AbstractCellular sensitivity to cis‐diamminedichloroplatinum(II) (cDDP) can be regulated by protein kinase C (PKC) signal transduction pathway. Activators of PKC were shown to en‐ hance the sensitivity of human ovarian carcinoma 2008 cells to cDDP. We have examined whether or not the PKC signal transduction pathway is affected during‐development of resistance by tumor cells to cDDP. A 2‐fold decrease in PKC activity was observed in cDDP‐resistant ovarian carcinoma 2008 J. C13*5.25 cells compared with the drug‐sensitive 2008 cells. Subceflular distribution studies revealed a reduction in both cytosolic and paniculate PKC activities in 2008/C13*5.25 cells. The pattern of PKC isoform expression was compared in cDDP‐sensitive and ‐resistant cell lines by Western blot analysis with isoform‐specific antibodies to PKC. The parental cells expressed PKCα, ‐ε, and ‐ζ isoforms. The abundance of PKCα decreased significantly in 2008/C 13*5.25 cells, whereas the amount of PKCe increased moderately in the resistant variant, with no alteration in PKCε content. Therefore, a reduction in PKCa and/or an increase in PKCε expression may be associated with the drug‐resistant phenotype. © 1995 Wiley‐Liss, Inc.
Determinants of plasma pepsinogen levels in a population at high risk for stomach cancer in venezuela
Authors: Kato Ikuko , Miki Kazumasa , Muñoz Nubia , Vivas Jorge H. , Lopez Gladys , Peraza Simon , Carillo Elsa , Castro Denis , Andrade Olga , Sanchez Victor , Cano Elsa , Ramirez Hernan , Muggli Reto , Benz Maja , Oliver Walter 
Published: February 2007

AbstractDeterminants of plasma pepsinogens (PG) levels were studied in 1365 participants in a chemoprevention trial for gastric pre‐cancerous lesions being conducted in Venezuela. Gastric biopsies, plasma samples and information on smoking and dietary habits were obtained at baseline examination. Both PG‐I and PG‐II levels increased progressively with the level of Helicobacter pylori infection in gastric biopsies, resulting in no clear trend in the I/II ratio. Instead, there was a progressive decrease in the I/II ratio with increasing degrees of infiltration of polynuclear cells and monocytes, atrophy, intestinal metaplasia and the stage of pre‐cancerous lesions. The mean I/II ratios for atrophic gastritis or more advanced lesions were less than 4.0. When subjects with the I/II ratio 4 or higher were used as controls, severe reduction in the I/II ratio (<2.0) was inversely associated with tobacco consumption. This may be due to a pharmacological effect of nicotine. The severe reduction of I/II ratio was also inversely associated with fresh fruit consumption. In addition, a decreased I/II ratio was positively associated with rice/pasta and arepas (tortilla made from corn) consumption and inversely associated with plantain consumption. Possible effects of vitamins and starchy food on the development of atrophic gastritis need to be studied further. © 1995 Wiley‐Liss, Inc.
Induction of platelet‐derived growth factor A and B chains and over‐expression of their receptors in human pancreatic cancer
Authors: Ebert Matthias , Yokoyama Munehiro , Friess Helmut , Kobrin Michael S. , Büchler Markus W. , Korc Murray 
Published: February 2007

AbstractExpression of platelet‐derived growth factor (PDGF) and PDGF receptors was examined in cultured human pancreatic cancer cells, in the normal human pancreas and in pancreatic adenocarcinomas. mRNA transcripts encoding PDGF A and B chains, and PDGF receptor 0 (PDGFR3) were present in PANC‐I and HPAF human pancreatic cancer cells. Transforming growth factor β I (TGF‐βl), but not PDGF‐AA or ‐BB, enhanced PDGF A and B chain mRNA levels in both cell lines. In the normal human pancreas PDGF A chain mRNA levels were relatively abundant, whereas PDGF B chain mRNA levels were not detected and PDGF receptor a (PDGFRa) and p mRNA transcripts were present at low levels. PDGF immunoreactivity was present in islet cells, and PDGFRa was present in acinar cells, whereas PDGFRβ was present in acinar cells and in the connective tissue. In the pancreatic cancers, PDGF A chain mRNA transcripts were also abundant, and 6 of 13 samples exhibited the PDGF B chain mRNA transcript. In addition, there was a 7‐fold increase in the levels of PDGFRa and PDGFRp in the cancer samples by comparison with the normal pancreas. By immunohistochemistry, PDGF and both PDGF receptors were present in the cancer cells, and PDGFR3 was abundant in fibroblasts and endothelial cells within the connective tissue. © 1995 Wiley‐Liss, Inc.
Tumor‐infiltrating T lymphocytes from renal‐cell carcinoma express B7‐1 (CD80): T‐Cell expansion by T‐T cell co‐stimulation
Authors: Thurnher Martin , Radmayr Christian , Hobisch Alfred , Böck Günther , Romani Nikolaus , Bartcch Georg , Klocker Helmut 
Published: February 2007

AbstractB7‐I (CD80) provides co‐stimulation for T‐cell activation by interacting with CD28 or CTLA4. Here we demonstrate the expression of B7‐I in freshly isolated and cultured lymphocytes from renal‐cell carcinoma. In fresh preparations of lymphocytes infiltrating renal‐cell‐carcinoma tissue, B7‐1 mRNA could readily be detected by reverse transcription PCR, and 2‐color flow‐ cytometry analysis revealed substantial B7‐1 expression on T cells from these isolates. As expected, tumor‐derived T cells also expressed CD28, the B7 receptor. While B7‐1 expression of tumor‐derived T cells was maintained during culture in interleukin‐2‐supplemented medium, CD28 expression was further enhanced. We also show that B7‐I is functionally involved in T‐cell expansion: anti‐B7‐1 MAb inhibited the PHA‐induced proliferation of tumor‐derived B7‐1+ T cells (35%) in the absence of exogenous antigen‐presenting cells, indicating that B7‐1 mediates T‐T cell co‐stimulation (self‐co‐stimulation). Our data demonstrate that T cells infiltrating renal‐cell carcinoma express B7‐I, and that mutual co‐stimulation via the B7‐I/ CD28 pathway contributes to the interleukin‐2‐driven expansion of tumor‐derived T cells in vitro. The frequency of B7‐1+ T cells in tumor lesions and the level of B7‐I on these cells may determine the time course of T‐cell expansion in vivo. Self‐co‐stimulation, however, might also represent one mechanism leading to the state of suppression or anergy characteristic of tumor‐infiltrating lymphocytes. © 1995 Wiley‐Liss, Inc.
Progression toward metastatic phenotype with loss of growth‐inhibiting tumor‐cell/cell interactions in vivo
Authors: Takeda Yasutaka , Sayama Kazutoshi , Saegusa Yoshiyuki , Matsuzawa Akio 
Published: February 2007

AbstractFive autonomous sub lines, T4‐O1320, T4‐O1320CY, T4‐O1165, T4‐O1145 and T4‐O196, were established from the transplantable hormone‐dependent mouse mammary tumor, TPDMT‐4, by pass aging under different conditions. These autonomous tumors were characterized by rapid growth in DDD virgin mice and the parental TPDMT‐4 by no growth in these mice. Thus, 105 T4‐O1320, 2 × 104 T4‐O1320CY, 2 × 103 T4‐O1165, 2 × 103 T4‐O1145 and 103 T4‐O196 cells were co‐injected with 5 × 102 TPDMT‐4 cells into virgin mice to determine whether or not hormone‐dependent tumor cells influence the growth of autonomous tumor cells. TPDMT‐4 cells retarded the growth of T4‐O1320 and T4‐O1320CY tumors but accelerated that of T4‐O1165, T4‐O1145 and T4‐O196. Irradiated TPDMT‐4 cells stimulated the growth of all the sub lines except T4‐O1320. In 3‐dimensional collagen‐gel culture, T4‐O1320 and T4‐O1320CY cells formed branched or stellate structures similar to normal mammary glands, as did TPDMT‐4, but T4‐O1165, T4‐O1145 and T4‐O196 cells grew as rounded masses with knobs and showed a completely different morphology. T4‐O1165, T4‐ O1145 and T4‐O196 cells, but not the others, had lung‐colonizing ability. Chromosomal aberration was found in T4‐O1320CY and T4‐O196 but not in the others. Thus, the susceptibility of autonomous sub line tumor cells to growth‐inhibitory regulation from the parental hormone‐dependent tumor cells correlated well with growth morphology within collagen gels and meta‐static ability, but not with chromosomal aberration. The results suggest that meta‐statically‐competent tumor‐cell variants, once they appear, may have a growth advantage in hormone‐ dependent mammary tumors. © 1995 Wiley‐Liss, Inc.
Effect of hyperthermia on the cytotoxicity of 2′,2′‐difluorodeoxycytidine (gemcitabine) in cultured SW1573 cells
Authors: Haveman J. , Rietbroek R. C. , Geerdink A. , van Rijn J. , Barker P. J. M. 
Published: February 2007

AbstractDifluorodeoxycitidine (dFdCyd, gemcitabine) was tested for cytotoxicity in cultured human lung‐cancer cells SW1573 in combination with 1 hr hyperthermia at 43°C. The results show that the timing is extremely important. Simultaneous application led to decreased cytotoxicity, whereas an interval of 20 or 24 hr between exposure to dFdCyd and hyperthermia led to enhanced cell killing. The decrease in cytotoxicity after simultaneous hyperthermia and dFdCyd probably results from inhibition of activation of dFdCyd to the triphosphate metabolite. The enhanced cytotoxicity in sequential application of dFdCyd and hyperthermia is not caused by accumulation of cells in a sensitive cell‐cycle phase. Our results show that the G1 phase becomes relatively abundant 20 hr after exposure to 0.1 μM dFdCyd, approximately 48% versus 31% in control cultures. Presumably,. inhibition by hyperthermia of repair of DNA damage plays a role. Our results confirm earlier data with regard to reutilization of activated dFdCyd at high cell density. dFdCyd was clearly more toxic to SW1573 cells at 4 × 105 cells per dish than at 400 cells per dish. This reutilization of activated drug is evidently not a restricted property of a particular cell fine and may add to the value of the drug in cancer treatment. © 1995 Wiley‐Liss, Inc.
Familial aggregation of tumors and detection of hereditary non‐polyposis colorectal cancer in 3‐year experience of 2 population‐based colorectal‐cancer registries
Authors: Modica Salvatore , Roncucci Luca , Benatti Piero , Gafà Lorenzo , Tamassia M. Grazia , Dardanoni Luigi , de Leon Maurizio Ponz 
Published: February 2007

AbstractThe clinical data of 2 population‐based registries, located in areas with different incidence rates of colorectal cancer, were used in order to assess the role of familial factors in the pathogenesis of these tumors. The occurrence of tumors in family members was investigated in 389 subjects with colorectal cancer registered in Modena (Northern Italy, an area characterized by a high incidence of colorectal malignancies) between 1984 and 1986; similar information was obtained in 213 patients with tumors of the large bowel registered in Ragusa (Sicily, Southern Italy, an area of similar magnitude and with low incidence rates for these tumors) in the 3‐year period 1988 to 1990. In both series, colorectal cancer occurred significantly more often among relatives of patients. Controls were patients of the same sex and age (±5 years) hospitalized during the study periods, but not for gastrointestinal or neoplastic diseases. There were 89 cancer cases (3.1%) among 2,851 relatives of patients in Modena, vs. 17 cases among 1,744 relatives (1.0%) in Ragusa (p < 0.01). Apart from colorectal cancer, there was no excess of other types of tumors in patients' families (in both series). During the 3 years of registration, 17 cases of hereditary non‐polyposis colorectal cancer (HNPCC, or Lynch syndrome) were diagnosed in Modena; in contrast, this syndrome was more rare in Ragusa (one case only during 3 years of observation). Similarly, many more families with clinical suspicion of HNPCC were recorded in Northern regions (44 vs. 10). Although incidence rates of colorectal cancer are appreciably higher in Northern than in Southern Italian regions, the excess of this cancer type among close relatives is similar. However, fullblown HNPCC or suspected Lynch syndrome were significantly more frequent in Northern Italy. © 1995 Wiley‐Liss, Inc.
Among 17 inducers of differentiation only sodium butyrate causes a permanent down‐regulation of c‐myc in Burkitt's lymphoma
Authors: Rottleb Christoph , Bornkamm Georg W. , Polack Axel 
Published: February 2007

AbstractDe‐regulation of c‐myc by chromosomal translocation is one crucial step for the development of Burkitt's lymphoma. The de‐regulation is caused through juxtaposition of c‐myc with one of the 3 immunoglobulin loci. We have reported earlier that treatment of Burkitt's lymphoma cells with n‐butyrate causes transcriptional down‐regulation of c‐myc expression. Because of the possible therapeutic implication of this result, we looked for other compounds which, on the one hand, might be applicable in vivo and, on the other hand, might cause down‐regulation of c‐myc expression in Burkitt's lymphoma cells. Since n‐butyrate is known to induce differentiation, we have examined other differentiation inducers of different chemical nature for their ability to reduce c‐myc expression in Burkitt's lymphoma cells. Many of the substances tested caused down‐regulation of c‐myc expression, which, however, was transient except for n‐butyrate. Three types of compounds proved to be particularly active: polar planar compounds (e.g., dimethylsulfoxide), heterocyclic compounds (e.g., hypoxanthine), and short‐chain fatty acids (e.g., n‐butyric acid). The action of n‐butyrate on c‐myc supression was exceptional not only in not being transient, but also in being allele‐specific: it down‐regulated the translocated allele without affecting the normal one. Medium transfer experiments revealed that neither degradation of the active compound nor an intracellular resistance mechanism can fully account for the reversibility of c‐myc down‐regulation after treatment with the transiently acting polar planar compounds. © 1995 Wiley‐Liss, Inc.
Involvement of a transforming‐growth‐factor‐β‐like molecule in tumor‐cell‐derived inhibition of nitric‐oxide synthesis in cerebral endothelial cells
Authors: Murata Jun‐Ichi , Corradin Sally Betz , Felley‐bosco Emanuela , Juillerat‐Jeanneret Lucienne 
Published: February 2007

AbstractNitric oxide (NO) has been shown to exert cytotoxic effects on tumor cells. We have reported that EC219 cells, a rat‐brain‐microvessel‐derived endothelial cell line, produced NO through cytokine‐inducible NO synthase (iNOS), the induction of which was significantly decreased by (a) soluble factor(s) secreted by DHD/PROb, an invasive sub‐clone of a rat colon‐carcinoma cell line. In this study, the DHD/PROb cell‐derived NO‐inhibitory factor was characterized. Northern‐blot analysis demonstrated that the induction of iNOS mRNA in cytokine‐activated EC219 cells was decreased by PROb‐cell‐conditioned medium. When DHD/PROb cell supernatant was fractionated by affinity chromatography using Con A‐Sepharose or heparin‐Sepharose, the NO‐inhibitory activity was found only in Con A‐unbound or heparin‐unbound fractions, respectively, indicating that the PROb‐derived inhibitory factor was likely to be a non‐glycosylated and non‐heparin‐binding molecule. Pre‐incubation of DHD/PROb‐cell supernatant with anti‐TGF‐β neutralizing antibody completely blocked the DHD/PROb‐derived inhibition of NO production by EC219 cells. Addition of exogenous TGF‐β, dose‐dependently inhibited NO release by EC219 cells. The presence of active TGF‐β in the DHD/PROb cell supernatant was demonstrated using a growth‐inhibition assay. Moreover, heat treatment of medium conditioned by the less invasive DHD/REGb cells, which constitutively secreted very low levels of active TGF‐β, increased both TGF‐β activity and the ability to inhibit NO production in EC219 cells. Thus, DHD/PROb colon‐carcinoma cells inhibited NO production in EC219 cells by secreting a factor identical or very similar to TGF‐β. © 1995 Wiley‐Liss, Inc.
Estrogen‐induced anchorage‐independence in human endometrial stromal cells
Authors: Xu Li‐Hui , Rinehart Clifford A. , Kaufman David G. 
Published: February 2007

AbstractEstrogens are important etiologic agents for most gynecologic malignancies, and chronic exposure to estrogen that is unopposed by progestins conveys the greatest risk. Treatments with estrogen facilitate the process of malignant transformation in rodents, but relatively few studies of estrogen‐induced carcinogenesis have been performed using human cells. Most malignancies in estrogen‐responsive tissues arise from epithelial cells, but an increasing body of evidence emphasizes the role of stromal cells as mediators of the effects of estrogens on epithelial cells. Our studies were designed to assess estrogens as carcinogens for human endometrial stromal cells and to provide a basis for studies of the role of stroma in estrogen‐induced carcinogenesis in humans. Acute treatments with the estrogens diethylstilbestrol (DES), 17β‐estradiol E2 and β‐dienestrol enhance anchorage‐independent proliferation (AIP) of SV40‐immortalized human endometrial stromal cells in the rank order of DES > E2 > β‐dienestrol. The anti‐estrogenic compound tamoxifen inhibits DES‐induced AIP. The magnitude of DES‐induced AIP increases with prolonged duration of treatment. After 11 months of chronic treatment with 0.1 nM DES, AIP was 20‐fold higher than in vehicle‐treated control cultures. Expression of the estrogen receptor was altered by treatments with DES in parallel with increased capacity for AIP. These conditionally immortal human endometrial stromal cells appear to be a good model for estrogen‐induced transformation of human cells. © 1995 Wiley‐Liss, Inc.
Cell‐cell and cell‐collagen interactions influence gelatinase production by human breast‐carcinoma cell line 8701‐BC
Authors: Minafra Salvatore , Giambelluca Carola , Andriolo Maria , Pucci‐Minafra Ida 
Published: February 2007

AbstractWe previously produced evidence that the human mammary‐carcinoma cell line 8701‐BC expresses several metalloproteinases (MMP‐1, ‐2, ‐9, and ‐10) and their tissue inhibitors. In order to obtain a better understanding of the environmental control over gelatinolytic activities, we have tested the enzyme production of 8701‐BC cells, at time intervals after plating on different collagen substrates, i.e., types I, III, IV, V and OF/LB, used as films in culture dishes. Proteinase activities, released in the conditioned culture media, were tested by zymography on SDS‐PAGE, and by quantificative analyses, using 14C carboxy‐methylated transferrin as substrate in a liquid incubation medium. Enzymatic activities varied with time and were inversely related to cell densities, with minimum values at cell confluence. The enzymatic activity was positively supported by collagen substrates, with a maximal increase in activity when OF/LB collagen was used. In addition to the known MMPs, we found a proteinase with an Mr of about 20 kDa, which displayed higher activity at 48 hr after cell plating and gradually decreased with cell increment. In contrast to the other MMPs, this proteinase is inhibited by soybean trypsin inhibitor, but it does not display a complete identity with trypsin, since it does not digest casein and is not inhibited by other serine proteinase inhibitors. © 1995 Wiley‐Liss, Inc.