bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of buthionine sulfoximine on PtII and PtIV drug accumulation and the formation of glutathione conjugates in human ovarian‐carcinoma cell lines
Authors: Mistry Prakash , Loh Swee Y. , Kelland Lloyd R. , Harrap Ken R. 
Published: February 2007

AbstractGlutathione (GSH) has often been implicated in the mechanism of resistance to platinum anti‐cancer drugs. It has been suggested that GSH may reduce the cytotoxicity of these drugs by forming inactive conjugates and by enhancing the repair of DNA‐platinum crosslinks. In the present study we have examined the effect of D, L‐buthionine‐S, R‐sulfoximine (BSO) pretreatment on the accumulation of platinum in a sensitive (CH I) and 2 relatively resistant (SKOV‐3, HX/62) human ovarian‐carcinoma cell lines following exposure to PtII‐ (cisplatin, carboplatin) and PtIV‐drugs (tetraplatin). The metabolism of cisplatin and tetraplatin (particularly the extent of platinum‐GSH conjugate formation) in the presence and absence of BSO pre‐treatment was also examined in these cell lines. BSO pretreatment reduced the accumulation of PtII but not that of PtIV drugs in the relatively resistant SKOV‐3 and HX/62 cell lines. It had no effect on the accumulation of either class of drugs in the sensitive CHI cells. Metabolism studies with cisplatin showed that the SKOV‐3 and HX/62 cells, which contained 2‐ to 3‐fold higher levels of GSH, were able to inactivate a greater proportion of cellular cisplatin, by the formation of platinum‐GSH conjugates, than the CH I cells. A significant inhibition in formation of these conjugates, by BSO‐induced depletion of cellular GSH (over 80%), did not, however, increase cisplatin concentration in the resistant cells. In contrast, a small increase in cisplatin concentration was observed in the sensitive cells following BSO pre‐treatment. Comparison of cisplatin and tetraplatin metabolism in the SKOV‐3 cells indicated that a greater proportion of the latter drug was inactivated by formation of GSH conjugates. BSO‐induced depletion of cellular GSH in this cell line significantly reduced the formation of such conjugates from both drugs. However, concomitant increases in intracellular levels of reactive species were observed only after tetraplatin exposure. Our data suggest that the greater potentiation of PtIV‐ compared with PtII‐drug cytotoxicity in the relatively resistant cell lines following 24 hr BSO pre‐treatment may be caused by a differential effect of BSO on the metabolism and cellular distribution of these drugs. A BSO‐induced reduction in PtII‐ but not PtIV‐drug accumulation in these cells may also partially contribute to the differential potentiation of cytotoxicity of these drugs.
Immunization with interleukin‐2‐secreting allogeneic mouse fibroblasts expressing melanoma‐associated antigens prolongs the survival of mice with melanoma
Authors: Kim Tae Sung , Russell Stephen J. , Collins Mary K. L. , Cohen Edward P. 
Published: February 2007

AbstractThe survival of C57BL/6 mice (H‐2b) bearing B16 melanoma (H‐2b) was prolonged if the animals were treated solely by immunization with an interleukin‐2 (IL‐2)‐secreting allogeneic cell construct that expressed melanoma‐associated antigens (MAA) along with major histocompatibility complex (MHC) class‐l determinants (H‐2k; RLBA‐IL‐2 cells). This was the case if the mice were immunized simultaneously with, or 6 days following, the injection of viable B16 cells. Under similar conditions, the survival of tumor‐bearing mice immunized with an allogeneic cell construct (H‐2k) that expressed MAA but did not secrete IL‐2 (RLBA‐ZipNeo cells), or with an allogeneic construct (H‐2k) that secreted IL‐2 but did not form MAA (LM‐IL‐2 cells), was also prolonged. However, in these instances, the period of survival was significantly shorter than that of mice immunized with the cell construct that combined IL‐2 secretion with the expression of MAA. Tumor‐bearing mice immunized with non‐transfected LM(TK‐) cells (H‐2k), or irradiated B16 cells (H‐2b) failed to survive longer than untreated mice. Although the survival of the treated animals was prolonged, in most instances tumor growth recurred. The recurrent tumors in mice treated with the allogeneic cell constructs formed melanin and were histologically indistinguishable from tumors in untreated mice. Cells from the recurrent tumors were resistant to further immunotherapy and to cytotoxic effector cells obtained from the spleens of mice immunized with the same cellular immunogen used initially. The injection of IL‐2‐secreting syngeneic B16 cells into C57BL/6 mice invariably resulted in the appearance of non‐IL‐2‐secreting melanomas. Under similar circumstances, tumors failed to develop in C57BL/6 mice injected with IL‐2‐secreting, or non‐secreting, allogeneic cell constructs. Thus, the expression of allogeneic antigens protected the mice from growth of the cellular immunogens.
Estimates of the worldwide mortality from eighteen major cancers in 1985. Implications for prevention and projections of future burden
Authors: Pisani P. , Parkin D. M. , Ferlay J. 
Published: February 2007

AbstractThis report presents worldwide estimates of annual mortality from all cancers and for 18 specific cancer sites around 1985. Crude and age‐standardized mortality rates and numbers of deaths were computed for 24 geographical areas. Of the estimated 5 million deaths from cancer (excluding non‐melanoma skin cancer), 56% occurred in developing countries. The most frequent neoplasm is lung cancer, accounting for 22% of cancer deaths in men. Among women breast cancer is the leading malignancy, accounting for 16% and 11% of all cancer deaths in developed and developing countries, respectively. In developing countries, cancer of the cervix uteri ranks first, breast cancer second. The second most frequent cause of death from cancer in both sexes is cancer of the stomach, followed by liver cancer in men and by colon/rectum cancer in women. Cancers of the colon/rectum and prostate maintain a high rank in men living in developed countries, while cancers of the lung, ovary and pancreas occupy similar ranks among women. In developing countries, cancers of the oesophagus and mouth/pharynx follow those previously mentioned in both sexes. If the estimated rates continue to prevail, increases in the numbers of deaths of 20.4% in developed and 18.1 % in developing countries are expected by the year 2000, simply as a consequence of demographic trends towards ageing and population growth. Our results provide an indication of the potential impact of preventive practices. It is estimated that 20% of all cancer deaths (1 million) could be prevented by eliminating tobacco smoking. Mortality from cancers of the liver and uterine cervix, both major problems in developing countries, could be substantially reduced by immunization against hepatitis B virus infection and early detection through Pap smears, respectively.
Targeting of T lymphocytes against egf‐receptor+ tumor cells by bispecific monoclonal antibodies: Requirement of CD3 molecule cross‐linking for t‐cell activation
Authors: Ferrini Silvano , Cambiaggi Anna , Sforzini Sabrina , Marciano Sabrina , Canevari Silvana , Mezzanzanica Delia , Colnaghi Maria Ines , Grossi Carlo Enrico , Moretta Lorenzo 
Published: February 2007

AbstractTargeting of T lymphocytes against epidermal growth‐factor‐receptor (EGF‐R)+ tumor cells was achieved by constructing a hybrid hybridoma which secretes an anti‐EGF‐R/anti‐CD3 bispecific monoclonal antibody (biMAb) of hybrid isotype (IgG1/ IgG2a). Purification of biMAb molecules from parental anti‐EGF‐R and anti‐CD3 MAbs was performed by protein‐A chromatography. The purified biMAb was able to trigger the lysis of EGF‐R+ tumor cell lines (A431, IGROV‐1, MDA‐468 and U‐87) and of NIH‐3T3 transfectants expressing human EGF‐R by cytolytic T lymphocytes, but it was ineffective in the case of EGF‐R‐negative tumor targets. Normal EGF‐R+ (keratinocytes and endometrial cells) were also susceptible to biMAb‐targeted cytolysis. However, the amount of biMAb required to induce half‐maximal cytolysis of tumor cells over‐expressing the EGF‐R molecule (A43I) was considerably lower than that required to induce lysis of EGF‐R+ tumor or normal cells which express EGF‐R at considerably lower density. The ability of such biMAbs to deliver activation signals to T cells was evaluated by Ca++ mobilization and lymphokine production experiments. The soluble anti‐EGF‐R/anti‐CD3 biMAb failed to induce intracellular Ca++ increases, which occurred only after cross‐linking induced by an anti‐mouse IgG antibody. Secretion of lymphokines (IFN‐γ, TNF‐α and GM‐CSF) was induced by contact of the biMAb‐coated effector cells with the relevant tumor target, whereas the soluble biMAb was virtually ineffective. In addition, biMAb‐coated effector cells retained the ability to recognize and to lyse EGF‐R+ tumor cells for a prolonged period of time. Our data indicate that activation of effector cells targeted by biMAbs can only occur at the tumor site, where cross‐linking of surface CD3 molecules is induced by contact with the tumor cells.
TPA‐enhanced invasion of matrigel associated with augmentation of cell motility but not metalloproteinase activity in a highly metastatic variant (L‐10) of human rectal adenocarcinoma cell line RCM‐1
Authors: Nabeshima Kazuki , Komada Naoto , Kishi Jun‐Ichi , Koita Hiroyuki , Inoue Teruhiko , Hayakawa Taro , Koono Masashi 
Published: February 2007

AbstractWe previously found that the enhanced activity to invade Matrigel upon stimulation with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) was one of the major properties of a highly metastatic variant (L‐10) of a human rectal adenocarcinoma cell line RCM‐1. To clarify the mechanism of this enhancement, we examined the effect of TPA on 2 major biological factors involved in tumor cell invasion: cell motility and matrix‐degrading metalloproteinase activity. The enhanced invasiveness was inhibited by protein‐kinase‐C inhibitors. TPA markedly enhanced both haptotactic response to type‐IV collagen and motility on tissue‐culture glass substrate of L‐10 cells in a dose‐response manner quite similar to that of TPA‐enhanced invasion of Matrigel. On the other hand, TPA showed little enhancement of metalloproteinase production, which was assessed by gelatin‐ and casein‐zymography, and of type‐IV collagenolytic activity. Addition of TIMP (tissue inhibitors of metalloproteinase)‐1 inhibited TPA‐enhanced invasion of Matrigel by only up to 13%. Thus, TPA treatment of L‐10 cells enhanced invasion of Matrigel in association with augmentation of cell motility but did not enhance metalloproteinase activity.
Biochemical and immunological characterization of the human carcinoma‐associated antigen MH 99/KS 1/4
Authors: Schön Michael P. , Schön Margarete , Mattes M. Jules , Stein Rhona , Weber Lutz , Alberti Saverio , Klein C. Eberhard 
Published: February 2007

AbstractWe have characterized the 38‐kDa transformation‐associated membrane glycoprotein MH 99, whose expression is highly elevated in many epithelial malignancies. A spontaneous cleavage of MH 99 into a 32‐ and a 6‐kDa chain in some carcinoma cell lines was recently shown. Sequence homologies to nidogen, a matrix‐adhesion molecule, support the suggestion of a receptor‐like function. In this study, we characterized biochemical and immunogenic aspects of MH 99. Transformed epithelial cell lines which do not spontaneously cleave MH 99 were exposed to 8 proteases with distinct specificities. Each of the enzymes produced similar specific fragmentation into chains of about 30 to 32 and 6 kDa, indicating a characteristic cleavage site of MH 99. The fragments were not distinguishable from those in carcinoma cells showing spontaneous cleavage of MH 99. The specific fragmentation depends on the localization in intact membranes and is not shared by other membrane proteins. N‐glycosylation of MH 99 of about 4 kDa was exclusively found on the 32‐kDa fragment. Characterization of antigenic epitopes was performed using 16 different monoclonal antibodies (MAbs). Only 2 independent determinants were found. One is located on the 32‐kDa chain and is recognized only by the MM 104 MAb. The other 15 antibodies bind to a dominant epitope on the 6‐kDa fragment which can be divided into 3 overlapping sub‐epitopes. The unique features of MH 99 indicate that its immunogenic epitopes are mainly located at its 6‐kDa chain, and support the suggestion of a transformation‐associated cell‐surface receptor which might be proteolytically regulated.
Regulation of melanoma‐cell motility by the lipoxygenase metabolite 12‐(S)‐hete
Authors: Timar Jozsef , Silletti Steve , Bazaz Rajesh , Raz Avraham , Honn Kenneth V. 
Published: February 2007

AbstractCellular motility, a prerequisite for metastasis of tumor cells, is affected by a 55‐kDa tumor‐cell‐secreted cytokine which influences the migration of the producing cells and is called autocrine motility factor (AMF). Previous studies indicated that AMF stimulates motility by binding to its receptor, a cell‐surface glycoprotein of 78 kDa (gp78), inducing its phosphorylation, activating a pertussis toxin (PT)‐sensitive G‐protein, and stimulating inositol metabolism. However, the intracellular signaling mechanisms which transduce and regulate the AMF motility response remain largely unknown. 12‐(S)‐HETE, a lipoxygenase metabolite of arachidonic acid which affects the cytoskeletal architecture of murine melanoma cells, also stimulates cell motility independently of PT‐sensitive G‐proteins and up‐regulates gp78 surface expression. 12‐(S)‐HETE induces the phosphorylation of gp78 in a manner analogous to AMF and the motility response of these murine melanoma cells to both AMF and 12‐(S)‐HETE is inhibited by protein kinase C inhibitors. Furthermore, perturbation of the AMF receptor stimulated endogenous biosynthesis of 12(S)HETE. These results suggest the existence of an “autocrine motility cycle” which influences melanoma cell motility by gp78 activation, and production of second messengers which affect the cytoskeletal architecture and expression of the AMF receptor itself.
Ability of the non‐phorbol ester‐type tumor‐promoter thapsigargin to mimic the stimulatory effects of 12‐0‐tetradecanoylphorbol‐13‐acetate on ornithine decarboxylase activity, hydroperoxide production, and macromolecule synthesis in mouse epidermis In vivo
Authors: Perchellet Elisabeth M. , Gali Hala U. , Gao Xiao Mei , Perchellet Jean‐Pierre 
Published: February 2007

AbstractThe biochemical effects of the non‐12‐0‐tetradecanoylphorbol‐13‐acetate (TPA)‐type tumor promoter thapsigargin (TG), which does not bind to the phorbol‐ester receptor, or activate protein kinase C (PKC) or increase inositol polyphosphates, were characterized in mouse epidermis in vivo. The cold scraping method is required to detect the induction of ornithine decarboxylase (ODC) activity by TG, a response much smaller than that caused by TPA and with a different time course, TG pre‐treatments do not alter or cause a refractory state against ODC induction by TPA. But TG stimulates hydroperoxide (HPx) production and RNA, protein, and DNA synthesis almost as much as TPA. Moreover, the sequential effects of TG and TPA on DNA synthesis are identical: early inhibition at 8 hr followed by maximal stimulation at 16‐32 hr. TG‐stimulated HPx production requires protein synthesis and xanthine oxidase, phospholipase A2, and lipoxygenase activities but not RNA and DNA synthesis, and cyclooxygenase and protease activities. The HPx response to TG is not mimicked by the PKC activator prostratin or inhibited by pre‐treatments with prostratin or specific PKC inhibitors. However, the Ca2+‐ATPase inhibitor cyclopiazonic acid and the Ca2+ ionophore and weak ODC inducer A23187 mimic remarkably the HPx responses to TG and TPA. Since TG and A23187 are known to be, respectively, weak and incomplete tumor promoters as compared with TPA, the present results suggest that the HPx responses common to Ca2+‐mobilizing and TPA‐ or non‐TPA‐type agents are insufficient to achieve tumor promotion in the absence of major ODC induction.
High‐fiber diets and reduced risk of breast cancer
Authors: Baghurst Peter A. , Rohan Thomas E. 
Published: February 2007

AbstractIn a case‐control study of 451 women with breast cancer and 451 population‐based controls from metropolitan Adelaide, Australia, the risk of breast cancer was studied in relation to intake of dietary fiber and various fiber components. Intakes were estimated by means of a self‐administered quantitative food‐frequency questionnaire, and risks of breast cancer were estimated for each quintile of fiber density (intake/megajoule of total energy intake) relative to an arbitrarily assigned risk of unity for women in the lowest quintile of fiber density. There were highly significant reductions in relative risk associated with increasing intake of a number of components of total dietary fiber. In women with the highest 20% estimated dietary densities of total non‐starch polysaccharides (NSP), the relative risk of breast cancer was 0.46, and a test for trend across the quintiles was significant at p < 0.001. Separate risk estimations for various fiber components defined by the Enlists method of analysis revealed highest risk reductions associated with high densities of mannose from insoluble NSP and of glucose from soluble NSP. For many fiber components the point estimates of relative risk were quite similar both for pre‐and for postmenopausal women, although results for the latter (who comprised over two thirds of all cases) were statistically more significant. The study provides strong support for recent conjecture that foods rich in dietary fiber may be protective against breast cancer.
Identification of integrated epstein‐barr virus in nasopharyngeal carcinoma using pulse field gel electrophoresis
Authors: Kripalani‐Joshi S. , Law H. Y. 
Published: February 2007

AbstractIntegrated Epstein‐Barr virus (EBV) was found in 4 of 17 pathologically diagnosed, EBV‐positive nasopharyngeal carcinoma (NPC) biopsy samples using pulse field gel electrophoresis (PFGE). The analyses were carried out after digestion of biopsy DNA with rare restriction enzymes such as Pacl, which does not cleave EBV due to the absence of the recognition sequence, and Clal. Employing this technique, EBV integration in IB4, through Ecol, and Namalwa through the terminal repeats, was confirmed. We also established that integration of EBV in AW Ramos was through the terminal repeats. The Raji cell line was also found to harbour integrated virus in addition to episomal DNA. However, the site of integration could not be confirmed, since as the Raji DNA appeared to be heavily methylated and could not be cleaved with CPG rare cutters. As in the Raji cell line, the DNA of EBV in nasopharyngeal‐carcinoma (NPC) biopsies also appeared to be methylated.
Genetic alteration of the hepatitis C virus hypervariable region obtained from an asymptomatic carrier
Authors: Nakazawa Takahide , Kato Nobuyuki , Ootsuyama Yuko , Sekiya Hitomi , Fujioka Takahiro , Shibuya Akitaka , Shimotohno Kunitada 
Published: February 2007

AbstractHepatitis C virus (HCV) genome shows extensive sequence diversity at 2 hypervariable regions (HVR1 and HVR2) of the putative envelope glycoprotein (gp70). We recently reported that the amino‐acid sequence of HVR1, but not of HVR2, underwent a striking mutation or mutated sequentially over a period of several months in patients with chronic hepatitis (CH). Here, we examined whether these genetic alterations in HVR1 occurred in an asymptomatic HCV carrier. The level of HCV RNA in serum was almost the same throughout the 4 time points sampled over 16 months. However, we found that the amino‐acid sequence of the HCV HVR1 from this asymptomatic carrier altered with time, as seen in patients with CH. Alterations of amino acids in the HVR1 were correlated with persistent HCV infection rather than with clinical symptoms. Sequence heterogeneity of HVR1 was not correlated with alanine aminotransferase (ALT) values or liver histological findings. The necessity of clinical follow‐up of HCV asymptomatic carriers is discussed.
Induction of tissue‐type plasminogen activator and 72‐kDa type‐IV collagenase by ionizing radiation in rat astrocytes
Authors: Sawaya Raymond , Tofion Philip J. , Mohanam Sanjeeva , Ali‐Oosman Francis , Liotta Lance A. , Stetler‐Stevenson William G. , Rao Jasti S. 
Published: February 2007

AbstractRadiation‐induced damage in the central nervous system (CNS) is believed to be targeted to glial or endothelial cells or both, although the pathophysiology of the process is still poorly understood. In this study, we irradiated rat astrocytes with single doses of X‐rays and then estimated the levels of tissue plasminogen activator (tPA) and collagenase in serum‐free medium and cell extracts at different times. Fibrin zymography revealed increased levels of intracellular tPA activity at 12 hr after irradiation. Gelatin zymography showed continuously increasing levels of extracellular 72‐kDa type‐IV collagenase after irradiation. Quantitative enzymatic activities by densitometry showed a 3‐to 4‐fold elevation in the level of the intracellular tPA activity at 12 hr and a 5‐to 6‐fold increase in the level of the extracellular 72‐kDa type‐IV collagenase activity at 48 hr. An ELISA with specific antibodies for tPA and 72‐kDa type‐IV collagenase indicated a 5‐fold increase in the level of tPA at 12 hr and a more‐than‐7‐fold increase in the level of 72‐kDa type‐IV collagenase at 48 hr. This study adds considerable credibility to the proposed role of plasminogen activators and type‐IV collagenase in the development of CNS damage after radiotherapy for brain tumors.
Growth inhibition of human melanoma‐derived cells by 12‐O‐tetradecanoyl phorbol 13‐acetate
Authors: Arita Yuko , O'Driscoll Kevin R. , Weinstein I. Bernard 
Published: February 2007

AbstractIn vitro growth of 6 human melanoma‐derived cell lines was inhibited markedly by the phorbol‐ester tumor promoter 12‐O‐tetradecanoyl phorbol 13‐acetate (TPA), a potent activator of several isoforms of protein kinase C (PKC). Utilizing PKC isoform‐specific antibodies in immunoblotting experiments, we found that the PKCα and PKC isoforms were expressed in all of the 6 melanoma cell lines tested, whereas the PKCβ isoform was expressed at detectable levels in only 2 of the 6 cell lines. The SK‐Mel‐173 melanoma cell line, which had relatively high levels of PKCβ mRNA and protein expression, and which was also the most sensitive to cell growth inhibition by TPA, was used to isolate clones whose growth was less inhibited by TPA. Immunoblotting experiments revealed that in parental SK‐Mel 173 cells PKCβ was rapidly down‐regulated to below detectable levels after treatment for 48 hr with TPA, but that in TPA‐resistant variant clones there was negligible down‐regulation of PKCβ by TPA. On the other hand, treatment of parental and TPA‐resistant SK‐Mel 173 cells with TPA led to partial down‐regulation of PKCα in both cell lines. Total PKC enzyme activity was also greater in TPA‐resistant cells than in parental SK‐Mel 173 cells. Our results show that TPA might inhibit the growth of melanoma cells by causing down‐regulation of specific isoforms of PKC that are required to maintain the growth of these cells.