bluuebunny/crossref_metadata_2025_split huggingface dataset:
Production of monoclonal antibodies to human estrogen‐receptor protein (ER) using recombinant ER (RER)
Authors: Saati Talal Al , Cohen‐Knafo Edith , Caverivière Paul , Delsol Georges , Clamens Simone , Faye Jean Charles , Prats Hervé , Bayard Francis , Coindre Jean Michel , Wafflart Jean 
Published: February 2007

AbstractTwo monoclonal antibodies (MAbs), IC5 and ID5, were produced using spleen cells from BALB/c mice immunized with recombinant estrogen‐receptor protein (RER). On immunoblotting, both MAbs reacted with the 67‐kDa polypeptide chain obtained by transformation of E. coli and transaction of COS cells with plasmid vectors expressing ER. The epitopes of both MAbs were in the N‐terminal domain (A/B region) of the receptor. In normal human tissues, IC5 and ID5 reacted with cells known to contain large amount of ER, such as cells of the mammary gland and the uterus. Staining was localized predominantly in nuclei with little or no cytoplasmic reactivity. IC5 and ID5 were unreactive with tissues usually considered to be negative for ER. The reactions of these 2 MAbs were further tested on different tumor types, using immunohistochemical (IHC) method on frozen sections. In breast cancer, a good correlation was found between the results obtained on frozen sections and those using the conventional radioligand dextran‐coated charcoal (DCC) assay. Immunostaining with IC5 and ID5 MAbs was also assessed on routinely processed paraffin sections using the antigen‐retrieval method. Staining was comparable to that obtained on frozen sections in virtually all the breast carcinomas. Negative reactions were consistently obtained with both antibodies on human neoplasms derived from other non‐estrogen‐dependent organs. IC5 and ID5 MAbs may thus be of value in routine diagnostic histopathology for assessment of the estrogen‐receptor content in human carcinomas.
A sub‐set of immediate early mRNAs induced by tumor necrosis factor‐α during cellular cytotoxic and non‐cytotoxic responses
Authors: Klefstrom Juha , Saksela Eero , Alitalo Kari , Koskinen Päivi J. , Jäättelä Marja , Bravo Rodrigo 
Published: February 2007

AbstractTNF‐α is a multifunctional cytokine which is cytotoxic for some cell lines. In order to characterize the early genomic response to TNF‐α, we have analyzed the induction of a sub‐set of serum‐inducible immediate early genes in WEHI‐S and L929 fibrosarcoma cell lines, which are sensitive to TNF‐α, and in the 3T3‐L1 pre‐adipocytic cell line, which is resistant to TNF‐α cytotoxicity. Among 77 immediate early mRNAs screened by dot blot and/or Northern blot analyses, the expression of 23 mRNAs was found to be induced by TNF‐α. Ten of these mRNAs encode proteins known to function as pro‐inflammatory cytokines or transcription factors, while 13 others have as yet uncharacterized activities. The magnitude of c‐fos induction by TNF‐α inversely correlated with cell‐type‐specific cytotoxicity. Rapid and transient mRNA responses were observed in the TNF‐α‐resistant cells, whereas a slower and more persistent response was characteristic for TNF‐α‐sensitive cells. The prolonged induction of immediate early mRNAs may contribute to TNF‐α‐induced cellular cytotoxic responses.
Anti‐angiogenic activity of arachidonic acid metabolism inhibitors in angiogenesis model systems involving human microvascular endothelial cells and neovascularization in mice
Authors: Ito Ken‐Ichi , Ono Mayumi , Abe Tatsuya , Kuwano Michihiko , Morimoto Akio , Kohno Kimitoshi , Mori Teruaki , Tomita Mika , Sugenoya Akira , Nishihira Tetsuro 
Published: February 2007

AbstractWe have established an in vitro angiogenesis model using human omental microvascular endothelial (HOME) cells, in which epidermal growth factor (EGF) or transforming growth factor‐alpha (TGF‐α) stimulated cell migration and tube formation. In this study, we examined whether α‐guaiaconic acid (GR‐12) and its synthetic 20 derivatives showed inhibition of cell migration and tubular formation of HOME cells. We found that GR‐12 inhibits arachidonic acid metabolism, while GR‐12 and one derivative, GS‐01, inhibit tubular formation of endothelial cells in our model system. Confluent monolayers of HOME cells were damaged with a razor blade and incubated with or without TGF‐α; HOME cell migration was stimulated about 1.5‐fold over control values in the presence of TGF‐α. Treatment of HOME cells with GR‐12 or GS‐01 inhibited both spontaneous and TGF‐α‐stimulated migration. GR‐12 or GS‐01 inhibited TGF‐α‐induced HOME‐cell tube formation in type‐1 collagen gels. We examined whether these compounds could modulate tubular formation of HOME cells induced by human cancer cells. Enhanced tube formation of HOME cells by co‐cultured esophageal cancer cells was almost completely inhibited by co‐administration of GR‐12 or GS‐01. Both compounds also inhibited formation of tubular networks of HOME cells on Matrigels. We also examined anti‐angiogenic activity of these compounds in an in vivo model system of tumor angiogenesis in mice. In this system, GS‐01 inhibited development of capillary networks at a rate comparable to that of a well‐known anti‐angiogenic compound, fumagillin, but GR‐12 did not. The inhibitor of arachidonic acid metabolism is thus expected to modulate tumor angiogenesis.
Parvovirus H‐1 inhibits growth of short‐term tumor‐derived but not normal mammary tissue cultures
Authors: Van Pachterbeke C. , Tuynder M. , Rommelaere J. , Cosyn J. P. , Lespagnard L. , Larsimont D. 
Published: February 2007

AbstractInfection with parvovirus H‐1 strongly interfered with the proliferation of non‐established tissue cultures derived from human breast tumors, but had little effect on the growth of corresponding normal human mammary cells. Even though tumor cells were always more sensitive to the virus than normal tissue from the same patient, appreciable quantitative differences were observed among tumor specimens. With time and sub‐cultures, the killing effect of the virus on tumor cells became amplified. The impaired growth of infected tumor cells was due both to cytotoxic and to cytostatic action of H‐1 virus and was associated with their greater capacity for virus‐DNA amplification as compared with normal cells.
Increased accumulation of p53 protein in cisplatin‐resistant ovarian cell lines
Authors: Brown Robert , Clugston Carol , Edlin Angela , Vasey Paul , Kaye Stanley B. , Burns Philip , Vojtěšek Borek 
Published: February 2007

AbstractWe have examined p53 protein levels in cell lines selected for resistance to the chemotherapeutic drug cis‐diamminedichloroplatinum (II), cisplatin. The majority of the independent cisplatin‐resistant clones isolated by a single selection with cisplatin from the ovarian tumour cell line A2780 showed increased levels of p53 protein compared to the parental cell line. Elevated p53 protein levels were also observed in cisplatin‐resistant ovarian human tumour lines isolated after multiple exposures to cisplatin (A2780/cp70 and OVIP/DDP). Direct PCR sequencing of p53 cDNAs showed that both the A2780/cp70 and the parental A2780 cell lines had a wild‐type p53 gene sequence. The OVI P and OVI P/DDP lines both had a heterozygous mutation at codon 126. Cell‐cycle analysis after gamma‐irradiation or cisplatin treatment showed evidence of a G1/S and G2/M cell‐cycle checkpoint in both A2780/cp70 and the sensitive parental cell lines. However, the resistant cell line A2780/cp70 showed less inhibition of DNA synthesis after gamma‐irradiation than the sensitive cell line. Transfection of a mutant p53 gene construct (containing a mutation at codon 143, val to ala) into the A2780/cp70 resistant cells conferred a significantly increased sensitivity to cisplatin, suggesting that p53 is a direct determinant of cisplatin resistance in these cells. However, expression of this mutant p53 in the A2780 cells did not affect sensitivity.
Mitotic activity, apoptosis and TRPM‐2 mRNA expression in dmba‐induced rat mammary carcinoma treated with anti‐estrogen toremifene
Authors: Huovinen Riikka , Wärri Anni , Collan Yrjö 
Published: February 2007

AbstractAnti‐estrogen toremifene inhibits growth of the 7,12‐dimethylbenz(a)anthracene(DMBA)‐induced rat mammary carcinoma. The changes in proliferation and cell death were studied in detail. Proliferation was measured by counting mitotic figures in histologic sections, expressed by volume‐corrected mitotic index (M/V INDEX). Respective volume corrected apoptotic index (A/V INDEX) was measured by counting apoptotic nuclei in the same sections. The presence of apoptotic cells was confirmed by transmission electron microscopy. In the untreated tumors, both mitosis and apoptosis were frequent. In the toremifene‐treated tumors, the mean M/V INDEX was about half of the mean M/V INDEX in the untreated control tumors. The mean A/V INDEX in the toremifene‐treated tumors was about % of the mean A/V INDEX in the controls. In toremifene‐treated tumors, A/V INDEX was strongly correlated with TRPM‐2‐gene expression, which was also enhanced when compared with the controls. TRPM‐2 gene has been associated with programmed cell death induced by hormonal ablation in prostate‐ and breast‐cancer cells. No such correlation was seen in control tumors. These findings suggest that, in the DMBA‐tumor model, toremifene affects the cell turnover by inhibiting mitotic activity and modifying abundant spontaneous apoptosis. In this model, the inhibition of tumor growth results mostly from reduction of mitotic activity.
Nerve growth factor effects on human and mouse melanoma cell invasion and heparanase production
Authors: Marchetti Dario , Menter Dave , Jin Li , Nicolson Garth L. , Nakajima Motowo 
Published: February 2007

AbstractThe role of growth factor networks in regulating the progression of human melanocytes towards tumorigenicity and ultimately the malignant phenotype is poorly understood. In particular, the autocrine and paracrine influences that modulate cellular invasion and extracellular matrix degradative enzymes of melanoma cells remain undefined at the molecular level. We report here that nerve growth factor (NGF) can modify some metastasis‐associated cellular properties of human and mouse melanoma cells. Treatment of early‐passage human metastatic melanoma cells (MeWo) or their variants (3S5, 70W) with biologically active 2.5S NGF resulted in (a) delayed density‐dependent inhibition of melanoma cell growth; (b) increased in vitro invasion through a reconstituted basement membrane; and (c) time‐ and dose‐dependent induction of heparanase, a heparan‐sulfate‐specific endo‐β‐D‐glucuronidase associated with human melanoma metastasis. These effects of NGF were most marked in the 70W brain‐colonizing cells (70W > MeWo > 3S5). The NGF enhancement of heparanase secretion was not species‐specific, since it was also observed in murine B16 melanoma cells; the highest NGF stimulation of heparanase was found in brain‐colonizing murine B16‐B15b variant (B16‐B15b > B16‐BL6, B16‐F10, B16‐F1). NGF also increased the invasive capacity of the human 70W and murine B16‐B15b sublines in a chemoinvasion assay performed with filters coated with purified heparan sulfate proteoglycan (HSPG). The enhancement of chemotactic response and heparanase production was detected at NGF concentrations sufficient to fully saturate both low‐ and high‐affinity NGF receptors (NGFR), the neurotrophin receptor (p75) and the trkA gene product, respectively. The results suggest that, in addition to the effects of NGF on cellular development and differentiation within the peripheral and central nervous systems, NGF can exert changes in the invasive properties of neuroectoderm‐derived melanoma cells.
Working group report on hepatitis viruses
Authors: Vainio H. , Heseltine E. , Møller H. 
Published: February 2007

AbstractViruses play a major role in the etiology of a number of malignancies, including hepatocellular carcinoma (HCC) and cervical cancer, which are common in many parts of the world. In 1991, an ad hoc advisory group was convened by the International Agency for Research on Cancer (IARC) to consider whether viruses and other biological agents should be included in the IARC Programme for the preparation of Monographs on the Evaluation of Carcinogenic Risks to Humans. The group agreed unanimously that the carcinogenic risks of biological agents should be evaluated by expert groups such as those that have been convened by IARC over the past 20 years to discuss chemicals, physical agents, industries and cultural habits. A list of biological agents to be evaluated was drawn up, and the priority of each was designated by consensus on the basis of considerations regarding both their importance to public health and the status of the available epidemiological and biological evidence.On 8‐15 June 1993, IARC convened a Working Group consisting of experts in epidemiology, experimental carcinogenicity, internal medicine, pathology, communicable diseases and molecular biology (see list of participants) to discuss 3 viruses given high priority by the ad hoc advisory group, i.e., hepatitis B virus (HBV), hepatitis C virus (HBC) and hepatitis D virus (HDV, or the delta agent).These 3 viruses all cause a similar acute illness involving the liver, but they are very different in structure and biology. Their common feature is that the liver disease they cause may have a chronic course; they differ in that way from hepatitis A and hepatitis E viruses, for which no association with chronic liver infection has been recognized. Furthermore, no indication is available to suggest that hepatitis A virus leads to HCC or any other cancer, and no studies have been reported on hepatitis E virus. The considerations of the Working Group were thus limited to HBV, HCV and HDV.
Characterization of a monoclonal antibody against human prolactin receptors
Authors: Banerjee Rina , Ginsburg Erika , Vonderhaar Barbara K. 
Published: February 2007

AbstractTamoxifen is the first line of therapy for most human breast cancers. It not only works through the estrogen receptor but also can directly affect the binding of prolactin to its receptor. To define this latter mechanism, the nature of the prolactin receptor needs to be clearly defined. Monoclonal antibody (MAb) B6.2, an IgG1 raised against a membrane‐enriched fraction from metastatic human breast cancer cells, was as effective as polyclonal anti‐prolactin receptor antibody in inhibiting the binding of prolactin to membranes from human tissue and to T47D human breast cancer cells. Control MAbs, MOPC‐21 and the anti‐NCA B1.1 MAb, had no effect on binding. Epidermal growth‐factor receptors on these same cells were unaffected by B6.2. Prolactin‐induced growth of the T47D cells was blocked by addition of B6.2 to the media while the control antibodies were without effect. Specific binding of B6.2 to the cells was completely inhibited by prolactin. Binding of both prolactin and B6.2 was inhibited by growing the T47D cells in the presence of tunicamycin A, under conditions where protein synthesis was not affected but glycosylation of proteins was. An affinity column of B6.2 was used to purify its antigen from T47D cells. The primary purification product, a Mr 90,000 protein, specifically bound the lactogenic hormones human prolactin, human growth hormone and ovine prolactin but not the somatogenic hormone, bovine growth hormone and was precipitated by the polyclonal anti‐prolactin receptor antibody but not by control MAbs. When tryptic and V8 digests of the B6.2 antigen and purified prolactin receptors were compared, identical electrophoretic profiles were obtained. Mouse 3T3 cells, when stably transfected with the gene for the long form of the human prolactin receptor, reacted with B6.2 and polyclonal anti‐prolactin receptor antibody. Parental 3T3 cells, devoid of prolactin receptors, were negative for all antibodies tested. Thus, MAb B6.2 provides a useful tool for further studies on purification and characterization of these receptors from human tissues and may provide new insights into treatment for breast cancer.
Non‐viral risk factors for nasopharyngeal carcinoma in the philippines: Results from a case‐control study
Authors: West Sheila , Hildesheim Allan , Dosemeci Mustafa 
Published: February 2007

AbstractIn a case‐control study of NPC conducted in the Philippines, 104 predominantly non‐Chinese (<10% ethnically Chinese) cases of nasopharyngeal carcinoma (NPC) and 205 hospital and community controls were recruited. Risk factor information was obtained through personal interview. The occupational history of each subject was reviewed “blind” by an industrial hygienist to determine estimates of exposure to formaldehyde, solvents, dusts, exhaust and pesticides. After control for confounding, subjects who were first exposed to formaldehyde 25 or more years prior to diagnosis/interview or who were first exposed before the age of 25 were found, in relation to those never exposed, to be at a 4.0‐fold excess risk of disease. Similarly, those first exposed to dust and/or exhaust 35 or more years prior to diagnosis/ interview were at a 4.4‐fold excess risk of disease and those first exposed before the age of 20 were at a 3.5‐fold excess risk of disease. Salted fish consumption was not associated with risk, while consumption of processed meats protected against NPC. Smoking was positively associated with NPC, but only when cases were compared to community controls. Relative to non‐smokers, subjects reporting more than 30 years of smoking were at an adjusted 7.2‐fold excess risk of disease. Herbal medicine use and burning of anti‐mosquito coils were both independently associated with risk of NPC, with ever‐users of herbal medicines being at a 2.5‐fold excess risk of disease and those reporting daily use of anti‐mosquito coils being at a 5.9‐fold excess risk of disease relative to never users. Exposure to solvents, pesticides, or use of betel nuts were not associated with NPC risk.
Chemotherapy‐induced differential changes in lymphocyte subsets and natural‐killer‐cell function in patients with advanced breast cancer
Authors: Sewell Herb F. , Halbert Cyril F. , Robins R. Adrian , Galvin Alison , Chan Stephen , Blamey Roger W. 
Published: February 2007

AbstractTo elaborate a rational approach to chemoimmunotherapy in humans, information is required as to how current cytotoxic chemotherapy regimens modulate patients' endogenous immune cells. We have studied a group of 16 advanced breast cancer patients who received cyclical cytotoxic chemotherapy (CMF‐cyclophosphamide, methotrexate and 5‐fluorouracil) and have documented the progressive differential effects of chemotherapy on endogenous immune cells as judged by changes in immunophenotype and absolute numbers of lymphocyte subsets, together with analysis of natural‐killer‐cell function. Cells with the immunophenotype of natural killer cells and lympho‐kine‐activated killer cells (NK/LAK cells) were well retained, but their function was suboptimal. Additionally, CD8 T cells were well preserved, but the numbers of CD4 T cells decreased with succeeding cycles of chemotherapy; B‐cell numbers decreased rapidly from the first cycle of chemotherapy. These cellular changes in humans indicate defined and precisely timed windows of opportunity for introducing in vivo, simple and direct immune stimulation of the cells modulated by chemotherapy, with the possibility of improving therapy and survival in this disease.
Detection of circulating intercellular adhesion molecule‐1 in hepatocellular carcinoma
Authors: Hyodo Ichinosuke , Jinno Kenji , Tanimizu Masahito , Hosokawa Yasushi , Nishikawa Yoshiyuki , Akiyama Masanori , Mandai Koichi , Moriwaki Shousuke 
Published: February 2007

AbstractSerum levels of circulating intercellular adhesion molecule‐1 (cICAM‐1) were measured in 23 patients with chronic hepatitis (CH), 22 with liver cirrhosis (LC) and 45 with hepatocellular carcinoma (HCC) using an ELISA. Serum samples from all patients showed significantly higher cICAM‐1 levels than serum from 50 normal controls. The cICAM‐l level was significantly increased in LC or HCC when compared with CH, but no differences were noted between LC and HCC. Levels of cICAM‐1 correlated well with serum bilirubin, retention rate of indocyanine green, hyaluronic acid, type IV collagen 7‐S and type III procollagen peptide levels but not with tumor size or circulating tumor markers (α‐fetoprotein and des‐γ‐carboxyprothrombin). Our findings indicate that the measurement of cICAM‐l is useful for the determination of the severity of liver disease and hepatic fibrosis. HCC tissues obtained from 10 patients were immunohistochemically stained for ICAM‐I. Enhanced ICAM‐I expression was found on the tumor cell membranes. Sequential measurements of cICAM‐1 levels showed that they changed in a similar manner to those of a‐fetoprotein during the course of treatment of HCC in a patient with very high pretreatment levels of both markers. These results suggest that HCC cells shed ICAM‐1 into the circulation. We conclude that cICAM‐1 is not a diagnostic marker for HCC, but may be useful for monitoring the response to treatment.
Screening of human bladder tumors and urine sediments for the presence of H‐ras mutations
Authors: Levesque Peter , Ramchurren Nirasha , Saini Kulvinder , Joyce Adrian , Libertino John , Summerhayes Ian C. 
Published: February 2007

AbstractA series of 111 human bladder tumors were screened using oligonucleotide mutant specific probes, restriction enzyme analysis and single‐stranded confirmation polymorphism (SSCP) for the presence of H‐ras activation events. Thirty‐three tumors were found to harbor H‐ras mutations where a glycine to valine (G→ T) change in codon 12 was the most common point mutation recorded (26 tumors). Additional mutations involved glycine to cysteine at codon 13 (2 tumors) and glutamine to arginine/lysine/leucine at codon 61 (3/1/1 tumors, respectively). Ambiguous signals recorded with oligonucleotide probes were further analyzed using SSCP analysis revealing the presence of H‐ras mutations in restricted regions of some tumors. The apparent sensitivity of SSCP enabled us to extend this study to DNA isolated from urine sediments where 4 of the 9 patients studied showed representation of mutant H‐ras. Our study demonstrates a sensitive, non‐invasive assay for the screening of urine‐borne cells, with no requirement for prior knowledge of the mutational change at the H‐ras locus.
Characterization of cell lines established from merkel‐cell (“small‐cell”) carcinoma of the skin
Authors: Leonard J. Helen , Bell John R. , Kearsley John H. 
Published: February 2007

AbstractSix cell lines have been established from different biopsies of the rare small‐cell skin cancer of neuro‐endocrine origin known as Merkel‐cell carcinoma (MCC). These were established from metastatic lesions and have now been in culture for periods varying from 1 to 3 years. All lines grow as suspension cultures and exhibit typical MCC cytological features of small round cells with little cytoplasm, round nuclei and tight junctions. There was variation in the number and size of nucleoli and dense‐core granules. We present details of their immunohistochemistry and growth characteristics in culture. The latter were similar to small‐cell lung‐cancer (SCLC) lines and can be subdivided, by their appearance, into type I, type II and type III in the same way as SCLC lines. This classification may be of significance for the prognosis and management of MCC.