bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiosensitivity of small‐cell lung cancer xenografts compared with activity of c‐myc, N‐myc, L‐myc, c‐raf‐1 and K‐ras proto‐oncogenes
Authors: Rygaard Kåre , Slebos Robert J. C. , Spang‐Thomsen Mogens 
Published: February 2007

AbstractOncogenes of the myc family c‐raf‐I and K‐ras have been reported to modulate radiosensitivity. We examined the possible relationship between in vivo radiosensitivity to single‐dose irradiation with 3‐10 Gy, and activity of these proto‐oncogenes in 2 sets of small‐cell lung cancer (SCLC) xenografts, the CPH and the GLC series. CPH‐54A and CPH‐54B are in vitro‐derived subclones of a SCLC cell line, while the GLC tumours were established as cell lines from a patient during longitudinal follow‐up. Both tumours were later transferred into nude mice. CPH‐54A was more sensitive to single‐dose irradiation than CPH‐54B, while, with respect to the 3 GLC tumours examined, GLC‐16 was most sensitive, followed by GLC‐14 and GLC‐19. The CPH tumours expressed similar amounts of c‐myc and c‐raf‐I mRNA, and neither expressed N‐myc or L‐myc. GLC‐14 expressed N‐myc and c‐raf‐I mRNA but no c‐myc. GLC‐16 and GLC‐19 expressed identical amounts of c‐raf‐I and high levels of c‐myc mRNA, but neither expressed N‐myc or L‐myc. None of the tumours was mutated at codon 12 of K‐ras. Our results show that SCLC xenografts with different radiosensitivity may express identical amounts of some of the proto‐oncogenes reported to modulate radiosensitivity. Thus, factors other than activation of the examined proto‐oncogenes must be involved in causing the differences in radiosensitivity found in the SCLC xenografts. Possible long‐term effects of irradiation on proto‐oncogene expression was examined in xenografts of GLC‐16, following regrowth after single‐dose irradiation. No long‐term difference in expression of c‐raf‐I or c‐myc mRNA was detected between control tumours and tumours irradiated with 5 or 10 Gy.
Incidence of histologic types of uterine sarcoma in relation to menstrual and reproductive history
Authors: Schwartz Stephen M. , Weiss Noel S. , Daling Janet R. , Newcomb Polly A. , Liff Jonathan M. , Gammon Marilee D. , Douglas Thompson W. , Watt Janice D. , Armstrong Bruce K. , Weyer Peter , Isaacson Peter , Ek Marit 
Published: February 2007

AbstractTo determine whether the occurrence of one or more histologic types of uterine sarcoma is related to events in a woman's reproductive life, a population‐based case‐control study was conducted. One‐hundred sixty‐seven women newly diagnosed with uterine sarcoma among residents of 6 geographic regions were compared to 208 women selected at random from the same populations with regard to histories of menstruation, pregnancy and childbearing, and breast feeding, as reported during a telephone interview. Compared to women whose menstrual periods began at age 13, women whose menses began earlier were at increased risk of leiomyosarcoma (OR = 2.0, 95% CI 0.9, 4.3); other histologic types were less strongly associated with early age at menarche. Women with leiomyosarcoma and endometrial stromal sarcoma, but not malignant mixed Müllerian tumors, tended to have ceased menstruating 2‐3 years later than controls. None of the histologic types was clearly related to parity or to age at first live birth, but each was inversely related to age at last live birth. Associations were observed between leiomyosarcoma and histories of an induced abortion (OR = 4.2, 95% CI 1.2, 14.2) and of breast feeding after a live birth (OR = 0.5, 95% CI 0.3, 1.0); these relationships were not observed for other morphologic variants. These results suggest possible similarities and differences in menstrual and reproductive risk factors among histologic types of uterine sarcoma, and between these malignancies and the more common breast, endometrial and ovarian carcinomas.
Re‐transformation of non‐transformed hybrids between c‐myc‐activating mouse plasmacytoma cells and normal fibroblasts by transfection with activated c‐Ha‐ras but not c‐myc
Authors: Satoh Chiharu , Oikawa Tsuneyuki , Kondoh Nobuo , Kuzumaki Noboru 
Published: February 2007

AbstractIn a mouse plasmacytoma S194, c‐myc oncogene is rearranged with Ig gene by chromosomal translocation and consequently activated. We previously reported that transformation of phenotype and expression of rearranged c‐myc were repressed in independently isolated hybrid clones, I‐1 and IV‐10, between S194 and normal fibroblasts. In order to investigate the relationship between transformation of phenotype and oncogene expression, transcriptionally enhanced c‐myc or activated c‐Ha‐ras was transfected into I‐1 or IV‐101, a subclone IV‐10. Transfectants expressing high levels of c‐myc were found to retain the non‐transformed phenotypes. On the other hand, transfectants expressing activated c‐Ha‐ras showed the transformed phenotypes. These results suggest that enhanced expression of c‐myc is not sufficient for re‐transformation of the non‐transformed hybrid clones between c‐myc‐activating plasmacytoma cells and normal fibroblasts, but expression of activated c‐Ha‐ras could diminish or overcome the tumor‐suppressive activity of normal fibroblasts.
Immunomodulation in an apparently non‐immunogenic murine tumor
Authors: Bursuker Isia , Petty Barbara A. , Neddermann Kim M. , Keller Lynn S. 
Published: February 2007

AbstractMadison lung carcinoma (M 109), a murine tumor of spontaneous origin, appears to be non‐immunogenic, according to commonly employed tests for tumor immunogenicity. However, C.parvum‐induced immunopotentiation during the growth of M109 tumor results in post‐excision anti‐tumor immunity to M109 tumor implants. The C.parvum‐potentiated post‐excision immunity to M109 is tumor‐specific and T‐cell‐dependent. T cells from mice whose progressive M109 tumors have been excised are capable, on passive transfer, of inhibiting adoptive immunotherapy of T‐cell‐deficient recipients by spleen cells from mice immunized with an admixture of M109 cells and C.parvum. The data are interpreted as evidence supporting the hypothesis that the apparent lack of anti‐tumor immunity in this tumor model is not due to the absence of tumor‐associated antigens. We suggest that, instead, in this model the balance between the effector and suppressor arms of the immune response favors tumor‐induced immunosuppression, resulting in a magnitude of anti‐tumor immunity insufficient for detection by commonly employed tests for tumor immunogenicity. Our study shows that shifting the balance in favor of the effector arm by means of immunopotentiation results in a measurable immune response to an apparently non‐immunogenic tumor.
Macrophage infiltration and growth of sarcoma clones expressing different amounts of monocyte chemotactic protein/JE
Authors: Walter Sabine , Bottazzi Barbara , Govoni Deanna , Colotta Francesco , Mantovani Alberto 
Published: February 2007

AbstractTumor‐derived chemotactic factors (TDCF) have been identified and thought to play a role in the regulation of macrophage infiltration in neoplastic tissues. The present study was designed to assess the in vivo relevance of the TDCF molecularly identified as monocyte chemotactic protein/JE, by investigating murine sarcoma clones expressing diffevent levels of MCP/JE. The ID3 clone derived from the 677 RSV‐induced sarcoma expressed appreciable levels of MCP/JE mRNA and, concomitantly, chemotactic activity for mononuclear phagocytes. In contrast, the 5BII clone from the same tumor had undetectable levels of MCP/JE transcripts and little or no chemotactic activity. The chemotactic activity of ID3 cells was blocked by an appropriate specific antiserum. The in vitro growth rate of the 2 sarcoma lines was identical. Upon in vivo transplantation, the ID3 clone showed a substantially higher level of tumor‐associated macrophages (28.9%; range 21%‐34%) than the 5BII clone (16.6%; range 13%‐20%). 5BII‐induced tumors appeared earlier and grew faster than those induced by ID3. The difference in growth rate and in macrophage infiltration between ID3 and 5BII clones was also evident upon transplantation into nude mice. These results are consistent with the hypothesis that TDCF, identified as MCP/JE, is one important determinant of macrophage infiltration in tumors.
Human tumor spontaneous metastasis in immunosuppressed newborn rats. I. Characterization of the bioassay
Authors: Bailly Maryse , Bertrand Suzanne , Doré Jean‐François 
Published: February 2007

AbstractWe characterize a new model of spontaneous metastasis of human tumor cells using anti‐thymocyte serum (ATS) immunosuppressed newborn rats. We analyzed the intrinsic value of the bioassay of measurement of tumorigenicity and metastatic capacity using 17 human tumor cell lines, of which were 9 human malignant melanomas. Most of these cell lines revealed as tumorigenic and metastatic in lungs and/or lymph nodes 3 weeks after s.c. injection in the ventral flank of newborn rats, irrespective of their origin. All the melanoma cell lines that we injected were tumorigenic and 77% were metastatic, whereas the same cell lines grafted in nude mice showed no evidence of metastases after 6 weeks′ examination. We were not able to show any relationship between tumorigenicity in nude mice and the malignant behavior of these cells in ATS‐treated newborn rats. Likewise, neither chromosome abnormalities, nor anti‐genic marker expression were found to be related to tumor growth in nude mice or newborn rats. Two intrinsic parameters of the model were studied: number of cells injected vs. dose of ATS injected for one melanoma cell line; and role of the 3rd and 4th injections of ATS in the establishment and development of pulmonary metastases. Moreover, we show that s.c. injection in the ATS‐treated newborn rat may represent a suitable method for studying melanoma cell tumor growth and spontaneous dissemination.
Effects of the ras‐related rap2 protein on cellular proliferation
Authors: Jimenez Benilde , Pizon Véronique , Lerosey Isabelle , Béranger Florence , Tavitian Armand , De Gunzburg Jean 
Published: February 2007

AbstractRas oncogenes encode 21‐kDa (p21s) GTP binding proteins that are capable of transforming immortalized cells in culture. The ras‐related rap 1A/Krev‐1/smgp21A protein, that exhibits a similar structural organization and contains the same effector domain as ras proteins, antagonizes ras‐transformation. In order to investigate whether the closely related (61% identical) rap2 protein had similar capacities, the corresponding cDNA was inserted into constitutive as well as inducible mammalian expression vectors. Neither the wild‐type, nor an „activated”︁ mutant carrying a glycine‐to‐valine substitution at position 12, had any transforming activity. Several independent lines of evidence demonstrate that the rap2 protein exhibits neither growth‐promoting nor growth‐inhibitory effects, and that its over‐expression does not interfere with ras‐induced transformation. Thus, in spite of their great similarities, the rap 1A/Krev‐1/smgp21A and rap2 proteins have distinct physiological properties.
Univariate and multivariate analyses of the relationship between adenocarcinoma and solitary and multiple adenomas in colorectal adenoma patients
Authors: Gatteschi B. , Costantini M. , Bruzzi P. , Merlo F. , Torcoli R. , Nicolo G. 
Published: February 2007

AbstractIn 584 consecutive patients with no previous history of cancer or polypectomy, 769 adenomas were excised endoscopically and classified retrospectively according to the following parameters: macroscopic growth pattern, size, histological type, grade of dysplasia, anatomical site, presence of adenocarcinoma (ADK), number of adenomas and sex and age of the patient. A multivariate logistic analysis confirmed that size and histological type are the 2 most important predictors of ADK, both solitary and in multiple adenomas. Adenomas located in the sigmoid portion and in the rectum have an increased probability of ADK, independent of size and histology. Multiple polyps, when compared to solitary polyps, were more frequent in males (p < 0.01) and were more often larger than 2 cm. Significant similarities in histology, morphology and degree of dysplasia were observed among multiple adenomas from the same patient.
Breast cancer screening and cost‐effectiveness; Policy alternatives, quality of life considerations and the possible impact of uncertain factors
Authors: de Koning Harry J. , Martin van Ineveld B. , van Oortmarssen Gerrit J. , de Haes J. C. J. M. , Collette Hubertine J. A. , Hendriks Jan H. C. L. , van der Maas Paul J. 
Published: February 2007

AbstractMammographic screening for women aged 50‐70 is effective in reducing breast cancer mortality, but the impact on quality of life and the attainable mortality reduction remain t o be discussed. The consequences of expanding screening programmes to include women in other age groups are uncertain. We have predicted the effects and costs for 5 popular screening variants, differing in age group and screening interval, on the basis of our analysis of the Dutch screening trials and of the reported mortality reductions in other trials. We have also investigated the influence of a large number of uncertain factors. Screening for women aged 50 and over with a 2‐ or 3‐year interval is very cost‐effective and will result in reductions of respectively 16% or 10% in breast cancer mortality in a real population. Variation of most variables keeps the cost‐effectiveness (CE) ratio limited to the range of US $3,000 to 5,000 per life‐year gained. A 2‐ to 3‐fold change in CE ratio would only occur if the extreme estimates of mortality reduction in the Swedish screening trials were applied. The impact on quality of life (QoL) is limited: for the 2‐yearly screening policy for women aged 50‐70, the cost per Quality‐Adjusted Life‐Year (QALY) gained is 4,050, whereas the cost per life‐year gained is US $3,825. The CE ratio for 2‐yearly screening of women aged 40‐70 is 5,400, but the additional cost per additional life‐year gained is US $35,000. It would be preferable by far to extend the screening programme to women over the age of 70 or to shorten the screening interval for women aged 50‐70. Screening performances, the demand for mammograms outside screening and the possibility of a survival improvement irrespective of screening have a strong impact on QoL and CE.
An analysis of T‐cell‐receptor variable‐region genes in tumor‐infiltrating lymphocytes within malignant tumors
Authors: Nitta Taizo , Sato Kiyoshi , Okumura Ko , Steinman Lawrence 
Published: February 2007

AbstractExpression of T‐cell‐receptor (TCR) Vα and Vβ genes in tumor‐infiltrating lymphocytes (TILs) of 29 patients, 15 melanomas and 14 malignant glial tumors (glioma and medulloblastoma), was investigated. The identification and propagation of T cells with anti‐tumor reactivity is crucial to the understanding of the human immune response to tumors, which may possibly be useful in the successful implementation of adoptive immunotherapy against cancer. Despite clinical evidence that a more favorable prognosis is associated with the degree of lymphocyte infiltration within a tumor, the actual role of TIL remains uncertain. In order to address this question, we examined the diversity of the RNA transcripts of TCR genes in TlLs within 29 specimens obtained at surgery. Using the polymerase‐chain‐reaction (PCR) method and primers for 18 different human TCR Vα and 21 Vβ families to analyze TCR V‐(D)‐J‐C gene rearrangements, we detected a limited expression of TCR variable‐region Vα genes of TILs. TCR Vβ gene rearrangements were more diverse than those for Vα. In addition to restricted usage of TCR Vα genes, preferential expression of Vα 7 genes was found in 20 out of 29 cases (69%). Predominant usage of Vα 7 genes was more remarkable in melanoma TlLs (14/15) than in glial tumor TILs (6/14). These findings were also confirmed by Southern blot analysis with oligonucleotide probes for the constant (C) region of TCR α and β chains. We suspect that some specific T‐cell populations may be directed to antigenic determinants in melanoma cells.
Sero‐epidemiological investigations on human herpesvirus 6 (HHV‐6) infections using a newly developed early antigen assay
Authors: Iyengar Sujatha , Levine Paul H. , Ablashi Dharam , Neequaye Janet , Pearson Gary R. 
Published: February 2007

AbstractMonoclonal antibodies (MAbs) were developed against immunodominant HHV‐6 (GS isolate) late and early proteins. The major late protein was identified as a probable glycoprotein with a molecular weight of approximately 110 kDa (gp 110). Immunoblotting of the early antigen yielded proteins of 41 and 38 kDa (p41/38). The MAb to the early protein reacted with cells infected with 14 different HHV‐6 isolates. In contrast, the MAb against the late protein reacted with only 10 of these isolates, indicating that there was strain variation in this glycoprotein. The percentage of antibody‐positive sera reactive with gp110 in the ELISA ranged from 56% to 96% among the different serum donor categories. In contrast, only 10‐30% of the sera were positive for antibodies to p41/38 with the exception of sera from patients with African Burkitt's lymphoma (ABL) and Hodgkin's disease (HD). These antibody patterns denote the presence of active HHV‐6 replication in patients with ABL and HD.
Efficacy and selectivity of monoclonal‐antibody‐targeted drugs and free methotrexate in fluorescence‐labelled mixed tumour‐cell monolayer cultures and multicellular spheroids
Authors: Embleton M. J. , Charleston Angela , Affleck Karen 
Published: February 2007

AbstractFree methotrexate (MTX) and 2 monoclonal antibody (MAb)‐MTX conjugates were tested against mixed human tumour‐cell cultures, in which 2 cell lines of differing antigenicity or drug sensitivity, pre‐labelled with fluorescent dyes, were added together in microtitre wells. Conjugates were selectively cytotoxic for cells bearing high concentrations of the relevant antigen, and MTX was preferentially cytotoxic for wild‐type cells rather than MTX‐resistant variants when tested on separate cultures. In mixed cultures these selectivities were substantially retained, although there was a varying tendency towards intermediate cytotoxicity for each cell line of the pair. MTX was cytotoxic for cell line 791T grown as multicellular spheroids, but MAb‐MTX conjugate and a MAb‐RTA immunotoxin showed little cytotoxicity against spheroids at the highest concentrations tested, although they were highly effective against monolayer cells. Mixed spheroids could be formed efficiently from most cell lines, although in some cases cell distribution was non‐random. In mixed spheroids prepared between wild‐type and MTX‐resistant 791T variants, relative MTX sensitivities conformed broadly to those seen in separate monolayer cultures. Fluorescence‐labelling was a reliable method for determining cell behaviour under the above conditions. We conclude that selectivity of therapeutic agents in mixed cultures was partially, but not completely, impaired compared to that observed in separate cultures, and (b) that low Mr drugs are effective against 3‐dimensional tumour‐cell structures but antibody‐targeted conjugates are not.
Kinetics of biochemical, electrophysiological and morphological events (including lysosomal disorder) during the course of suramin‐induced differentiation of the human colon‐cancer cell clone HT29‐D4
Authors: Baghdiguian Stephen , Verrier Bernard , Marvaldi Jacques , Fantini Jacques 
Published: February 2007

AbstractSuramin, a polysulfonated naphtylurea, has been shown to bind to a wide variety of tumor growth factors, and to exhibit anti‐proliferative effects on several cell lines. We have followed the suramin‐induced (100 μg/ml) evolution of morphological, biochemical and electrophysiological changes in HT29‐D4 human colonic adenocarcinoma cell clone as a function of culture time. After 5 days of culture in the presence of the drug the cells were polarized and exhibited apical brush border and tight junctions. The polarization process of carcino‐embryonic antigen (CEA) in the apical membrane domain was achieved after 8 days of treatment, while the correct localization of HLA class‐I molecules in the basolateral membrane domain occurred after 14 days of culture in the presence of suramin. Spontaneous potential difference (PD) and transepithelial resistance (Rt) were recorded from the 9th day of treatment and reached maximum values at day 15 (PD = 3 mV; RT = 450 Ωcm2), giving evidence that the differentiation process triggered by suramin concerned virtually all cells in the monolayer. Untreated cells were consistently found to be electrically inactive. Finally, from day 10 of suramin treatment, the lysosomal system was perturbed including accumulation of large autophagic vacuoles and, later, typical lamellar inclusion bodies. These structures were never seen when cells were induced to differentiate in suramin‐containing serum‐free medium. Moreover, similar perturbations of the lysosomal system could be obtained by adding BSA in the suramin‐containing defined medium, suggesting that the lysosomal storage disorder occurring upon suramin treatment was due to endocytosis of suramin‐BSA complexes. We conclude that lysosomal impairment due to the presence of BSA in the culture medium did not prevent HT29‐D4 cells from differentiating and that it was not an early event which could be involved in the mechanism of action of suramin. However, this perturbation might account for some of the toxic effects occurring during chronic suramin treatment in humans.
Estrogen suppression of erbB2 expression is associated with increased growth rate of ZR‐75‐1 human breast cancer cells in vitro and in nude mice
Authors: Wärri Anni M. , Laine Aire M. , Majasuo Karin E. , Alitalo Kari K. , Härkönen Pirkko L. 
Published: February 2007

AbstractAmplification and enhanced expression of the erbB2/HER‐2/neu gene has been associated with an increased growth rate and poor prognosis of human breast cancer. We have studied the relationship between erbB2 expression and the regulation of cell growth by estrogen and anti‐estrogens in the human breast cancer cell line ZR‐75‐1 in vitro and in athymic nude mice, pS2 being used as a marker gene for estrogen‐stimulated gene expression. Only low amounts of erbB2 mRNA were seen in the cells grown in vitro in the presence of estrogen which stimulated the cells to proliferate rapidly and induced the expression of pS2 mRNA. Upon hormone withdrawal, erbB2 mRNA and protein increased, while pS2 mRNA declined to an undetectable level and cell proliferation slowed down. Opposite but more rapid changes were observed upon estrogen addition. The anti‐estrogens toremifene and tamoxifen inhibited estrogen induction of pS2 expression, down‐regulation of erbB2 expression and proliferation of the ZR‐75‐1 cells in a concentration‐ dependent manner. Similar results were obtained in nude mice. ZR‐75‐1 cells formed tumors only in mice carrying estrogen pellets. In these tumors little erbB2 mRNA was seen. Concomitant administration of toremifene or tamoxifen increased erbB2 mRNA and abolished pS2 mRNA. Our results show that enhanced expression of erbB2 is associated with hormone deprivation and growth arrest of the estrogen‐dependent breast cancer cell line ZR‐75‐1. Thus, in mammary epithelial cells, erbB2 may have important estrogen‐regulated functions which are not related to cell proliferation.