bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancement of in vitro tumor—cell transcellular migration by tumor—cell—secreted endothelial—cell—retraction factor
Authors: Kusama Toshiyuki , Nakamori Shoji , Ohigashi Hiroaki , Mukai Mutsuko , Shinkai Kiyoko , Ishikawa Osamu , Imaoka Shingi , Matsumoto Yoshirou , Akedo Hitoshi 
Published: February 2007

AbstractTo investigate the factors affecting endothelial‐cell retraction, we have studied the interaction of tumor cells with endothelial cells in 2 human pancreatic cancer cell lines, PSN‐1 and MiaPaca‐2. The extent of endothelial‐cell retraction measured by the amount of intercellular junctional transport of F1TC‐dextran through an endothelial monolayer was increased by the addition of a conditioned medium (CM) from both cell lines, while CM from PSN‐I cells was 2 to 3 times more potent than that from MiaPaca‐2 cells. After the treatment of endothelial monolayer with CM of PSN‐1 cells, the ability of both PSN‐1 cells and MiaPaca cells to adhere to or invade the monolayer increased. The addition of CM from PSN‐1 cells did not affect the growth rate of either the endothelial or the tumor cells. The activity in the CM was heat‐stable and bound to heparin‐Sepharose, but was inactivated when treated by 0.5% trypsin. Protease inhibitors did not influence the activity. Pre‐treatment of PSN‐I cells by an inhibitor of protein synthesis, cyclohexi‐mide, or of protein processing, benzyl‐N‐acetyl‐a‐D‐galactos‐aminide, reduced endothelial‐cell‐retraction activity in the CM. The active substance in the CM fractionated in the molecular‐weight range of 10,000 to 50,000. These results suggest that PSN‐1 cells produce and secrete (a) soluble factor(s) that can induce endothelial‐cell retraction, thus facilitating tumor‐cell invasion.
Increased susceptibility of ras‐transformed cells to phenylacetate is associated with inhibition of p21ras isoprenylation and phenotypic reversion
Authors: Shack Sonsoles , Chen Li‐Chuan , Miller Alexandra C. , Danesi Romano , Samid Dvorit 
Published: February 2007

AbstractAlterations in the expression of ras oncogenes are characteristic of a wide variety of human neoplasms. Accumulating evidence has linked elevated ras expression with disease progression and with failure of tumors to respond to conventional therapies, including radiotherapy and certain chemotherapies. These observations led us to investigate the response of ras‐transformed cells to the differentiation‐inducer phenylacetate (PA). Using gene transfer models, we show that PA caused cytostasis in ras‐transformed mesenchymal cells, associated with increased expression of 2′,5′‐oligoadenylate synthetase, an enzyme implicated in negative growth control. PA also induced phenotypic reversion characterized by loss of anchorage‐independent growth, reduced invasiveness and increased expression of collagen a type 1, a marker of cell differentiation. The anti‐tumor activity of PA was observed in cases involving either Ha‐ or Ki‐ras and was independent of the mode of oncogene activation. Interestingly, in contrast to their relative resistance to radiation and doxorubicin, ras‐transformed cells were significantly more sensitive to PA than their parental cells. The profound changes in tumor cell and molecular biology were associated with reduced isoprenylation of the ras‐encoded p21. Our results indicate that PA can suppress the growth of ras‐transformed cells, resistant otherwise to free‐radical based therapies, through interference with p21ras isoprenylation, critical to signal transduction and maintenance of the malignant phenotype.
Efficacy of tnf‐α gene‐transduced tumor cells in treatment of established in vivo tumor
Authors: Koshita Yoshikazu , Lu Yue , Fujii Shigeyuki , Neda Hiroshi , Matsuyama Tomohiko , Satoh Yasushi , Itoh Yoshinori , Takahashi Minoru , Kato Junji , Sakamaki Sumio , Watanabe Naoki , Kohgo Yutaka , Niitsu Yoshiro 
Published: February 2007

AbstractThe therapeutic effect of TNF gene‐transduced mouse fibro‐sarcoma cells (Meth‐A: C5) on pre‐inoculated parental cells (Meth‐A: MO) was studied. Subcutaneous (s.c.) transplantation of MO cells into one flank of syngeneic BALB/c mice was followed by s.c. injection of irradiated MO or C5 into the opposite flank I week later. The initial MO tumor (T‐MO) completely regressed in C5‐vaccinated mice, whereas in Mo‐vaccinated mice continuous growth of T‐MO was observed. When a similar experiment was carried out in SCID mice, no regression of T‐MO was observed, suggesting that the tumor regression in BALB/c mice was not due to direct anti‐tumor activity of TNF secreted from C5, but to systemic immunity. Regression of the rechallenged MO tumor was observed in mice which had shown T‐MO regression by C5 vaccination, but rechallenged Colon 26 cells (syngeneic to BALB/c mice) continued to grow, indicating a specific immunity to Meth‐A cells. The systemic immunity evoked in C5‐vaccinated mice was directly demonstrated by enhanced killer activities of LAK and CTL with a proliferation of T‐cell population in their splenocytes. Abrogation of the therapeutic effect of C5 vaccination with anti‐Thy I and anti‐Lyt 2 also demonstrates the involvement of cellular immunity in tumor regression.
Differential inactivation of O6‐methylguanine‐dna methyltransferase activity by O6‐arylmethylguanines
Authors: Mineura Katsuyoshi , Fukuchi Masahito , Kowada Masayoshi , Terashima Isamu , Kohda Kohfuku 
Published: February 2007

AbstractActivity of O6‐methylguanine‐DNA methyltransferase (MGMT) is well related with drug resistance of tumor cells to chloroethylnitrosoureas (CENUs), because MGMT removes CENU‐induced O6‐alkylguanines in DNA by accepting the alkyl group at a cysteine moiety. Inactivation of MGMT is a feasible way to overcome MGMT‐related resistance of tumor cells to CENUs. O6‐Benzylguanine is known to be a strong depleter of MGMT. We previously reported the potentiation effect of O6‐arylmethylguanine derivatives on cytotoxicity of 1 ‐(4‐amino‐2‐methyl‐5‐pyrimidinyl)methyl‐3‐(2‐chloroethyl)‐3‐nitrosourea hydrochloride (ACNU), a CENU, for HeLa S3 cells. In this study, we tested the activity of these O6‐arylmethylguanine derivatives as depleters of MGMT using HeLa S3 cell‐free extract. The O6‐arylmethylguanine derivatives tested were O6‐benzylguanine (I), O6‐(4‐, 3‐, and 2‐fluorobenzyl)guanines (2–4), O6‐(4, 3‐, and 2‐trifluoromethylbenzyl)guanines (5–7), O6‐(4‐, 3‐, and 2‐pyridylmethyl)guanines (8–10), and O6‐(2‐ and 1 ‐naphtylmethyl)guanines (11, 12). Among these, compounds 1–3, 5, 8, 9 and 11 showed a strong MGMT depletion activity, whereas compounds 4, 6, 7, 10 and 12 were inactive. These inactive compounds, except for 6, have a substituent at the a position of the benzyl group (4, 7, 12) or are an α nitrogen analogue of 1 (10). There was a good relation (r = ‐0.856, p 0.001) between the MGMT depletion activity of O6‐arylmethylguanine derivatives and their potentiation activity of ACNU cytotoxicity. These results suggest that the a position of the benzyl group plays an important role in the interaction of O6‐arylmethylguanine derivatives with MGMT to result in the inactivation of MGMT. Potent MGMT inactivators (1–3, 5, 8, 9, 11) sensitize tumor cells to CENU chemotherapy.
Novel muteins of human tumor necrosis factor with potent antitumor activity and less lethal toxicity in mice
Authors: Kuroda Kensei , Miyata Keizo , Shikama Hiroshi , Kawagoe Tomoko , Nishimura Koji , Takeda Ken , Sakae Nahoko , Kato Masanari 
Published: February 2007

AbstractEight muteins of recombinant human tumor necrosis factor‐α (rhTNF; SSSRTP … 29RR … 155L), in which 29Arg was replaced by another amino acid, were prepared and their anti‐tumor effects in BALB/c mice bearing Meth A fibrosarcoma were evaluated. The therapeutic indices, which mark the extent of the therapeutically effective dose, of V29 (29Arg ± Val) and D29 (± Asp) were 3.5 and 3.2, respectively, whereas that of rhTNF was 1.4. Clearly, the therapeutically effective range of these muteins was extended along with a decrease in lethal toxicity. V29 did not produce hypotension in the rat system, but D29 did. In addition, V29 showed potent anti‐tumor activity (Tumor Volume Inhibition Rate = 81% on day 15 after implantation) in 3 consecutive injection schedules despite the decreases in toxicity compared with rhTNF. The relative receptor binding constant was determined using HEp‐2 cells (expressing mainly 55‐kDa‐TNF receptor; p55R) and HL60 cells (expressing mainly 75‐kDa‐TNF receptor; p75R), and revealed that the reduced toxicity of V29 in mice was due to the reduced binding to p55R (34% of rhTNF). On the other hand, the ratio of the constants HEp‐2/HL60 of V29 was 11 in comparison with the value of 1.0 for rhTNF, suggesting that this mutein binds preferentially to p55R. The biological activities in human cell lines (HEp‐2 and HL60 cells) correlated well with the binding activities to each receptor in vitro. Therefore, the much lower toxicity and the potent anti‐tumor activity of this mutein suggest that V29 merits further investigation in pre‐clinical and clinical trials.
Membrane fatty acids of breast carcinoma: Contribution of host fatty acids and tumor properties
Authors: Chajès Véronique , Lanson Monique , Fetissof Frank , Lhuillery Claude , Bougnoux Philippe 
Published: February 2007

AbstractTo assess the part that host fatty‐acid supply and tumor‐specific fatty‐acid utilization contribute to the membrane lipid composition of tumor tissue, intra‐individual comparisons of membrane fatty acids were carried out between breast‐carcinoma tissue and non‐tumorous breast tissue adjacent to the tumor and taken as reference. Phospholipids were purified by thin‐layer chromatography from tumor biopsies obtained from 59 patients with a localized presentation of breast cancer, and fatty acids analyzed by capillary gas chromatography. Elevated levels of palmitic, palmitoleic and arachidonic acids, along with a low level of linoleic acid, were observed in membrane phospholipids of tumors with poor histoprognostic grade. The level of mono‐unsaturated fatty acids was higher, and the level of essential fatty acids was lower in the tumor than in the reference breast tissue. Fatty‐acid‐desaturating activity was not detectable in tumors. A positive relationship was observed among patients for most of the fatty acids between carcinoma and non‐tumorous breast tissue, except for mono‐unsaturated and essential fatty‐acid levels, which were not correlated between both tissues. These data suggest that mechanisms specifically related to malignant transformation and tumor progression influence the membrane fatty‐acid profile of breast carcinoma. Fatty acid supply to the tumor, possibly modified by metabolic conditions related to the host, also seems to play a decisive role in this composition.
Expression of resistance‐related proteins in nephroblastoma after chemotherapy
Authors: Volm Manfred , Mattern Jürgen , Stammler Gerd , Royer‐Pokora Brigitte , Schneider Susanne , Weirich Angela , Ludwig Rolf 
Published: February 2007

AbstractTumor tissues of untreated and cytostatic‐agent‐treated patients with nephroblastomas were investigated for expression of resistance‐related proteins (P‐glycoprotein, glutathione S‐transferase‐π, glutathione peroxidase and topoisomerase II) to ascertain whether resistance proteins are changed after treatment. Tumor tissue was analyzed by means of mRNA. Twenty‐three children were treated with actinomycin D and vincristine for 4 to 8 weeks. Eight children received no pre‐operative chemotherapy. In untreated patients, no expression of P‐glycoprotein was seen, whereas, in the patients who were treated with actinomycin D and vincristine, 12 out of 23 tumors showed increased P‐glycoprotein expression (> mean value). Although we found no difference between treated and untreated tumors for glutathione S‐transferase‐π, we found significant differences in the expression of glutathione peroxidase. In the 8 untreated patients, 7 tumors showed low glutathione peroxidase (< mean value) and one high (> mean value) glutathione‐peroxidase‐mRNA content. With treatment, 11 tumors expressed low levels and 12 tumors high levels of mRNA. A significant positive correlation between P‐glycoprotein and glutathione peroxidase was found. In addition, of the 8 untreated patients, 2 had low topoisomerase‐ll expression, and 6 high expression. With treatment, the expression was reduced in 18 tumors, and only 5 tumors had high levels of this protein. These results were confirmed by PCR and immunohistochemistry.
Clinical pharmacokinetic studies of tetra(meta‐hydroxyphenyl)chlorin in squamous cell carcinoma by fluorescence spectroscopy at 2 wavelengths
Authors: Braichotte Daniel , Savary Jean‐François , Glanzmann Thomas , Westermann Patrick , Folli Silvio , Wagnieres Georges , Monnier Philippe , Van Den Bergh Hubert 
Published: February 2007

AbstractTo optimize photodynamic therapy (PDT) and photodetection of cancer with second‐generation photosensitizers, knowledge of important variables such as the uptake of the dye and the dye contrast between normal and tumoral tissue after injection is necessary. The pharmacokinetics of a second‐generation photosensitizer, tetra(meta‐hydroxyphenyl)chlorin (mTHPC), is presented. To study this in a clinical context, an apparatus based on fluorescence spectroscopy and a non‐invasive optical fiber probe has been used. The mTHPC fluorescence is induced at 2 excitation wavelengths (420 and 520 nm) with different penetration depth. The pharmacokinetics of mTHPC in patients with a squamous‐cell carcinoma in the oral cavity show a signal selectivity as high as 16 about 3 hr after i.v. injection for the more advanced carcinomas. The magnitude of this selectivity appears to correlate with the staging of the cancer, the more invasive tumors showing the highest selectivity. Results obtained at 420 and 520 nm show little difference. These pharmacokinetics can be used directly for optimizing photodetection with mTHPC. However, complementary information on the localization of the drug by fluorescence microscopy, and a correlation of this data with tumor necrosis efficacy, are needed to optimize PDT timing.
International renal‐cell cancer study. VIII. Role of diuretics, other anti‐hypertensive medications and hypertension
Authors: McLaughlin Joseph K. , Chow Wong Ho , Mandel Jack S. , Mellemgaard Anders , McCredie Margaret , Lindblad Per , Schlehofer Brigitte , Pommer Wolfgang , Niwa Shelley , Adami Hans‐Olov 
Published: February 2007

AbstractRisk of renal‐cell cancer in relation to use of diuretics, other anti‐hypertensive medications and hypertension was assessed in a multi‐center, population‐based, case‐control study conducted in Australia, Denmark, Germany, Sweden and the United States, using a shared protocol and questionnaire. A total of 1,732 histologically confirmed cases and 2,309 controls, frequency‐matched to cases by age and sex, were interviewed. The association between renal‐cell cancer and the drugs was estimated by relative risks (RRs) and 95% confidence intervals (CIs). Risks were increased among users of diuretics and other anti‐hypertensive medications. After adjustment for hypertension, risk for diuretics was reduced to unity, except among long‐term (15+ years) users. Risk for use of non‐diuretic anti‐hypertensive drugs remained significantly elevated and increased further with duration of use. Overall risk was not enhanced when both classes of medications were used. Excess risk was not restricted to any specific type of diuretic or anti‐hypertensive drug and no trend was observed with estimated lifetime consumption of any particular type of product. The RR for hypertension after adjustment for diuretics and other anti‐hypertensive medications was 1.4 (95% Cl = 1.2–1.7), although among non‐users of any anti‐hypertensive medications, there was little excess risk associated with a history of hypertension. Exclusion of drug use that first occurred within 5 years of cancer diagnosis or interview did not alter the associations. Our findings suggest small effects on renal‐cell cancer risk associated with hypertension and use of diuretics and other anti‐hypertensive medications. However, because of potential misclassifications of these highly correlated variables, it is difficult to distinguish the effect of treatment from its indication, hypertension.
Intracellular uptake and catabolism of anti‐IgM antibodies and BI‐specific antibody‐targeted hapten by B‐lymphoma cells
Authors: Manetti Corine , Doussal Jean Marc Le , Rouvier Eric , Gruaz‐Guyon Anne , Barbet Jacques 
Published: February 2007

AbstractThe efficiency of radioimmunotherapy with iodine‐labelled antibodies is often limited by intracellular internalisation and catabolism after initial binding to the cellular targets. We have developed a technique called affinity enhancement system (AES) which uses bi‐specific antibodies to target radiolabelled bivalent haptens to cells. This targeting method has been applied successfully to tumour imaging in colorectal cancer patients and is now considered for therapy. We have investigated the potential of this technique to target iodine radioisotopes by comparing it to targeting with covalently iodine‐labelled antibodies in a rapidly internalising antigenic system, the surface IgM of a B‐lymphoma cell line. A 5‐fold increase in the intracellular retention time of activity as compared to l25l‐labelled F(ab')2 or IgG was observed. The radiolabelled hapten did not undergo any catabolism after internalisation. Resistance to cellular proteases and failure of recognition of the hapten by amino acid transporter systems may be potential explanations for these observations. This should make non‐covalent targeting, particularly the AES, a method of choice to target modulating antigens for the therapy of malignant hemopathies.
Antagonists of bombesin/gastrin‐releasing peptide inhibit growth of SW‐1990 human pancreatic adenocarcinoma and production of cyclic AMP
Authors: Qin Yunfeng , Ertl Tibor , Cai Ren‐Zhi , Horváth Judit E. , Groot Kate , Schally Andrew V. 
Published: February 2007

AbstractWe investigated the effects of bombesin/GRP antagonists RC‐3095 and RC‐3940‐II on the growth of SW‐1990 human pancreatic adenocarcinoma cells xenografted into nude mice or cultured in vitro. Nude mice implanted with SW‐1990 tumors received s.c. injections of RC‐3095 and RC‐3940‐II or the vehicle (control) for 28 days. Chronic administration of RC‐3940‐II inhibited the growth of SW‐1990 tumors, as shown by a reduction in tumor volume during the treatment and a significant increase in tumor doubling time. RC‐3940‐II decreased final tumor volume by 57.7% and tumor growth rate by 65%. Final tumor weights in mice treated with RC‐3940‐II were 75% lower than in controls. Treatment with RC‐3095 induced smaller, and not significant, decreases in tumor volume and weight. In cell cultures, both RC‐3095 and RC‐3940‐II effectively inhibited the proliferation of SW‐1990 cells, inducing a dose‐ and time‐dependent decrease in the number of cells. RC‐3940‐II again suppressed in vitro growth of SW‐1990 cells more effectively than RC‐3095. After 72 hr of culture, RC‐3940‐II and RC‐3095 at I μM concentrations decreased cell numbers by 45.7% and 27.7%, respectively. The estimated EC50 value for RC‐3940‐II was I nM. When SW‐1990 cells were cultured in the presence of I nM and 10 nM RC‐3095 for 72 hr, cAMP levels in the incubation medium were decreased to 77.3% and 26.9% of the control value. Our results indicate that bombesin/GRP antagonist RC‐3940‐II can inhibit the proliferation of SW‐1990 human pancreatic adenocarcinoma cells in vivo and in vitro. Our findings also suggest that this effect may involve the intracellular cAMP pathway.
Decreased biotolerability for ivermectin and cyclosporin a in mice exposed to potent P‐glycoprotein inhibitors
Authors: Didier Agnès D. , Loor Francis 
Published: February 2007

AbstractSDZ PSC 833 or SDZ 280‐446 are strong blockers of the function of class 1 mdr gene‐encoded P‐glycoprotein molecules, which were developed for the reversal of multi‐drug‐resistance of tumor cells. When treated with such drugs, normal mice may display hypersensitivity to cyclosporin A and ivermectin. The recorded signs of acute toxicity are compatible with alterations of the murine central nervous system functions and with earlier data suggesting that P‐glycoprotein expressed at the murine blood‐brain barrier might be involved in the exclusion of cyclosporin A or ivermectin from brain tissue.
Cellular pharmacology of azatoxins (topoisomerase‐II and tubulin inhibitors) in P‐glycoprotein‐positive and ‐negative cell lines
Authors: Eymin Beatrice , Solary Eric , Chevillard Sylvie , Dubrez Laurence , Goldwasser François , Duchamp Olivier , Genne Philippe , Leteurtre François , Pommier Yves 
Published: February 2007

AbstractAzatoxin (NSC 640737), a synthetic molecule, was rationally designed as a topoisomerase‐ll inhibitor and was shown to be a potent cytotoxic agent that inhibits both tubulin and topoisom‐erase II. A structure‐activity relationship study allowed to select 3 derivatives that inhibit either tubulin (methylazatoxin) only or topoisomerase II (fluoroanilinoazatoxin and nitroanilino‐azatoxin) in MTT assays performed on K562 and K562/ADM cells; the latter, expressing P‐glycoprotein, indicated cross‐resistance of K562/ADM cells to all 4 compounds. DNA double‐strand breaks induced by the 3 azatoxins that inhibit topoisomerase II in vitro were decreased in K562/ADM as compared with K562 cells. Nitroanilino‐azatoxin was the only compound for which resistance and reduced DNA damage observed in K562/ADM cells was partially reversed by verapamil, suggesting that nitroanilinoazatoxin was a substrate for P‐glycoprotein. These results were confirmed by testing the cytotoxic activity of azatoxins on P‐glycoprotein‐expressing rat colon‐carcinoma DHDKI2/TRb cells in the absence and the presence of verapamil. Cell‐cycle and mitotic‐index studies indicated that azatoxin‐ and methylazatoxin‐induced M‐phase arrest was less in K562/ADM than in KS62 cells. The G2 block induced by fluoro‐ and nitroanilino‐azatoxins was delayed in K562/ADM cells. Verapamil increased cell‐cycle inhibition induced by nitroanilinoazatoxin in K562/ ADM cells without modifying cell‐cycle effects of fluoroanilinoazatoxin. These results (i) are consistent with the specific inhibition of topoisomerase II or tubulin by azatoxin derivatives in cells; (ii) indicate that the nitro group of nitroanilinoazatoxin allows recognition and efflux by the P‐glycoprotein; and (iii) suggest that cross‐resistance of K562/ADM cells to other azatoxin derivatives is not mediated by P‐glycoprotein.
Prior immunity‐related medical conditions and pancreatic‐cancer risk in Shanghai
Authors: Dai Qi , Zheng Wei , Ji Bu‐Tian , Shu Xiao‐Ou , Jin Fan , Zhu Jin‐Liang , Gao Yu‐Tang 
Published: February 2007

AbstractTo investigate the role of immunity‐related medical conditions in the etiology of pancreatic cancer, we analyzed data from a population‐based case‐control study of pancreatic cancer conducted in Shanghai during 1992 and 1993. Information on prior histories of selected auto‐immune diseases and allergic conditions was obtained from 108 incident pancreatic‐cancer cases and 275 age‐ and gender‐frequency matched controls by face‐to‐face interviews using a structured questionnaire. A prior history of auto‐immune diseases was associated with a 2‐fold elevated risk of pancreatic cancer (95% C1 = 1.0–4.2), with an indication of a dose‐response relation for the number of reported diseases. In contrast, a prior history of allergic condition was related to reduced risk (OR = 0.6,95% C1 = 0.4–1.1). With the possible exception of drug allergy, such an inverse association was seen for virtually all allergic conditions, although none of the OR was statistically significant. This study suggests that host immune function may be involved in the etiology of pancreatic cancer. Further investigations into the mechanism of these observed associations are warranted.