bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mouse model for studying epidermodysplasia‐verruciformis‐associated carcinogenesis
Authors: Majewski Slawomir , Breitburd Francoise , Skopinska Magdalena , Croissant Odile , Jablonska Stefania , Orth Gerard 
Published: February 2007

AbstractEpidermodysplasia verruciformis (EV) is considered as a model of genetic cancer due to unusual susceptibility to EV‐specific human papillomaviruses (HPVs). We established an in vivo experimental system for long‐term propagation of EV tissue which should facilitate the study of tumor progression in EV. Skin fragments from benign and early pre‐malignant lesions of 6 EV patients were grafted under the kidney capsule of athymic mice. After several months the grafted tissue formed epidermal cysts. These cysts, showed typical EV cytopathic effect, in situ hybridization revealed the presence of HPV 5, 8, 9, 12 and 36 DMA, and immunoperoxidase staining detected papillomavirus‐group‐specific antigens in the permissive cells of the cysts. In some cysts, there were numerous mitoses and downward proliferation of the epidermis with slight dyskeratotic changes. The experimental system described constitutes a model for studies on the role of HPV and other co‐factors in human cutaneous carcinogenesis.
Fibroblast‐mediated differentiation in human breast carcinoma cells (MCF‐7) grown as nodules IN VITRO
Authors: Brouty‐Boyé Danièle , Mainguené Claire , Magnien Véronique , Israel Lucien , Beaupain Rene 
Published: February 2007

AbstractThe growth of cells in 3‐dimensional form as nodules in vitro facilitates studies of in vivo cellular interactions. Taking advantage of this technique, human breast carcinoma cells (MCF‐7) were co‐cultured with stromal fibroblasts isolated from either normal or tumorous breast tissue to study the influence of such fibroblasts on tumor‐cell growth and differentiation. Ten days after co‐culture of carcinoma cells with fibroblasts from normal tissue at a 1:10 ratio, the size of nodules began to increase and stabilize by day 30 while the fibroblast number decreased and finally disappeared. Concurrently, the carcinoma cells underwent a progressive redifferentiation process which histologically resulted in the appearance of highly developed papillar and tubular structures after 2 months in culture. The production of mucins was further evidence that these cells had undergone differentiation. By contrast, when MCF‐7 cells were grown alone or with fibroblasts isolated from a breast carcinoma, the nodules continued to exhibit their characteristic histodedifferentiation properties and did not grow. The re‐establishment of a normal epithelial state of differentiation in MCF‐7 carcinoma nodules indicates that the phenotypic characteristics of tumor cells are reversible and are influenced or controlled by the stromal environment by which these tumor cells are surrounded or in contact with. Overall, our results open the possibility of exploiting the effects that connective tissue cells have on tumor‐cell differentiation for use in prevention and treatment of cancer.
Response of four human ovarian carcinoma cell lines to ALL‐TRANS retinoic acid: Relationship with induction of differentiation and retinoic acid receptor expression
Authors: Caliaro M. J. , Marmouget C. , Guichard S. , Mazars Ph. , Valette A. , Moisand A. , Bugat R. , Jozan S. 
Published: February 2007

AbstractThe response of 4 human ovarian carcinoma cell lines to retinoic acid was found to be related to the histological type and degree of differentiation of these tumor cells. The 2 serous cell lines NIHOVCAR3 and OVCCR1 were the most sensitive to the antiproliferative effect of RA. This inhibition was associated with morphological and biological changes that were indicative of differentiation. The undifferentiated IGROV1 cell line was not affected by RA. Since the effects of RA are thought to be mediated by nuclear retinoic acid receptors (RARs), the expression of RARs in human ovarian cancer cells was studied. RARα was detected as mRNA species of 3.1 and 2.6 kb in all 4 cell lines. RARβ was not detected in any of the cell lines, while RARγ (3 kb) was expressed in all of the ovarian cancer cells but at a very low level in the RA‐resistant IGROV1 cells.
Radiation leukemogenesis: Quantitative relationship between pre‐leukemic cells in the thymus and lymphoma induction
Authors: Kotler M. , Ruchlemer R. , Avni O. , Yefenof E. 
Published: February 2007

AbstractFractionated irradiation of C57BL/6 mice induces a population of pre‐leukemic (PL) cells that progress into mature thymic lymphomas after a latency of 4 to 6 months. Transfer of graded numbers of thymocytes from an irradiated mouse into recipient mice indicated that PL cells first appear in the thymus 6 weeks after irradiation. The initial proportion of the thymic PL cells is ≥10−5 and their frequency continuously increases with time, reaching ≥ 10−3 10 weeks after irradiation. The PL cell population that emerges early during the pre‐malignant latency consists of pleioclonal T lymphocytes. However, within 4 weeks a dominant PL clone can be detected which becomes the progenitor of a clonal fymphoma 9 to 15 weeks later. These results suggest that radiation leukemogenesis involves continuous accumulation of pleioclonal PL cells in the thymus, one of which is then selected for further maturation into frank lymphoma.
Effect of dibutyryl cyclic amp on morphologic features and marker production of human cervical argyrophil small‐cell carcinoma cell line
Authors: Shimizu Hiromu , Sawada Masumi , Tohyama Masaya , Takemura Koichi , Akedo Hitoshi , Ichimura Hiroshi , Ueda Gaiko , Tanizawa Osamu 
Published: February 2007

AbstractThe effect of dibutyryl cyclic AMP (dB‐cAMP) on the morphologic features and marker production of a human cervical argyrophil small‐cell carcinoma (ASCC) cell line was examined. Following 1–5 days' exposure to 5 mM dB‐cAMP, morphologic differentiation as defined by the expression of cytoplasmic processes (stellate cells) was observed. The number of stellate cells depended on the dose of dB‐cAMP and incubation time. Shortly after removal of dB‐cAMP from the culture medium, the treated cells returned to their original spherical shape. dB‐cAMP caused a reduction in the growth rate of cells which recovered after removal of the agent. The morphological changes appeared not to be the result of growth inhibition by dB‐cAMP, because the cells maintained in a serum‐free medium did not show any change in shape. Electron microscopic study revealed the development of intracytoplasmic microtubules, microfilaments, and an increase in the number of neurosecretory granules in the treated cells. The levels of neuron‐specific enolase, serotonin and gastrin in treated cells were significantly higher than those in untreated controls. These findings indicate that a reversible differentiation of cultured ASCC cells into neuroendocrine cells occurs in a growth medium containing dB‐cAMP.
Expression of tumour necrosis factor (TNFα) and its receptors in benign and malignant breast tissue
Authors: Miles D. W. , Happerfield L. C. , Naylor M. S. , Bobrow L. G. , Rubens R. D. , Balkwwill F. R. 
Published: February 2007

AbstractAs well as having anti‐tumour activity in animal models, TNFα has been implicated in the promotion of tumour invasion and metastasis. Expression and localization of TNFα mRNA and protein has been investigated in a series of benign and malignant breast tissues. TNFα mRNA was expressed in a minority of cells (≤0.5%) in 4/11 cases of benign breast tissue and in a higher proportion of invasive carcinomas (43/49 cases). Expression of TNFα mRNA was focal and confined to the tumour stroma. The presence of TNFα protein was confirmed by immunohistochemistry and again was predominantly stromal. Expression of mRNA and protein localized to infiltrating macrophages defined by the antibody EBM/11 in adjacent sections and using 2‐colour immunofluoresence. Although the average number of macrophages per high‐power field did not vary among invasive carcinomas of different histological type or grade, the number of cells expressing TNFα increased with increasing tumour grade. Immunodetectabfe p75 TNF receptor and to a lesser extent p55 receptor was present on cells of the mononuclear infiltrate and on the endothelium of invasive carcinomas, but not on the tumour cells themselves.
Analysis of cytomorphologically abnormal cervical scrapes for the presence of 27 mucosotropic human papillomavirus genotypes, using polymerase chain reaction
Authors: Husman Ana‐Maria De Roda , Walboomers Jan M. M. , Meijer Chris J. L. M. , Risse Ellen K. J. , Schipper Marguérite E. I. , Helmerhorst Theo M. , Bleker Otto P. , Delius Hajo , Van Den Brule Adriaan J. C. , Snijders Peter J. F. 
Published: February 2007

AbstractThe aim of this study was to investigate the distribution of 27 mucosotropic human papillomavirus (HPV) genotypes (HPV 6, 11, 13, 16, 18, 30, 31, 32, 33, 35, 39,4 0, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 57, 58, 59, 61 and 66) in cytomorphologically abnormal cervical scrapes (Pap IIIa‐Pap IV; n = 1, 373) using the polymerase chain reaction (PCR) method on crude cell suspensions. The scrapes were analyzed for the presence of HPV DNA by HPV general‐primer‐mediated PCR (GP‐PCR), which allows the detection of a broad spectrum of HPV types at the subpicogram level. Subsequently, 2 HPV typing procedures based on either type‐specific PCR (for HPV 6, 11, 16, 18, 31 and 33) or characterization of GP‐PCR products by hybridization (for HPV 13, 30, 32, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 57, 58, 59, 61 and 66) were applied. Increasing total HPV prevalence was found with increasing severity of dysplasia from 71% in Pap IIIa to 100% in Pap IV scrapes (carcinoma in situ). The scrapes which were positive by type‐specific PCR included 47% cases of Pap IIIa, 71% cases of Pap IIIb and 90% cases of Pap IV. Moreover, 12% of Pap IIIa scrapes, 6% of Pap IIIb scrapes and 8% of Pap IV scrapes revealed positivity for one or more of the remaining HPV types, as determined by successive hybridizations of the GP‐PCR products. Taking the typing data together, we noted that the level of HPV heterogeneity decreased from 22 different HPV types (HPV 6, 11, 16, 18, 31, 33, 35, 39, 40, 42, 43, 44, 45, 51, 52, 54, 55, 56, 58, 59, 61 and 66) detected in the group of Pap IIIa scrapes to 13 (HPV 6, 11, 16, 18, 31, 33, 35, 45, 51, 52, 58, 59 and 61) and 10 HPV genotypes (HPV 6, 16, 18, 31, 33,45, 51, 52, 54 and 58) in the Pap IIIb and Pap IV classes, respectively. An increasing prevalence rate from Pap IIIa to Pap IV was found for HPV 16, 18, 31, 33, 45 and 54. The prevalence rate of identified HPV genotypes increased from 59% in Pap IIIa to 98% in Pap IV, indicating that almost all high‐risk HPV genotypes related to cervical cancer in The Netherlands have been characterized.
Reproductive history and gastric cancer among post‐menopausal women
Authors: Palli Domenico , Cipriani Francesco , Decarli Adriano , Galli Monica , Saieva Calogero , Fraumeni Joseph F. , Blot William J. , Buiatti Eva 
Published: February 2007

AbstractA total of 339 post‐menopausal women with gastric cancer (GC) and 515 population controls were interviewed in a multi‐center study in Italy for information on reproductive history, dietary habits and other socio‐demographic variables. After adjusting for these factors, GC risk was significantly higher among women reporting menopause below age 45, while no effect was shown for age at menarche, parity, age at first livebirth, and number of abortions. When age at menopause was considered together with age at menarche for an index of fertility years, GC risk showed a significant inverse relation to duration of fertility. These results suggest a protective role for endocrine or other factors related to late age at menopause or to length of fertility. These findings may be relevant to explain the fact that rates of GC reported among females are lower than among males around the world, and suggest the need for further research into hormonal and other related risk factors.
Increased mutagen sensitivity in head‐and‐neck squamous‐cell carcinoma patients, particularly those with multiple primary tumors
Authors: Cloos Jacqueline , Braakhuis Boudewijn J. M. , Steen Ivar , Copper Marcel P. , De Vries Nico , Nauta Jos J. P. , Snow Gordon B. 
Published: February 2007

AbstractMutagen sensitivity is a constitutional factor which may be used to identify head‐and‐neck squamous‐cell carcinoma (HNSCC) patients at high risk for the development of multiple primary tumors (MPT). In this retrospective study, mutagen sensitivity was measured in HNSCC patients with a single primary tumor (SPT), HNSCC patients who have already developed MPT and control subjects with no tumor history. In vitro, lymphocytes were challenged with bleomycin and chromosomal damage was quantified by scoring chromatid breaks of 100 cells. A significant difference in the mean number of breaks per cell (b/c) was found between SPT patients and controls. Patients with MPT showed a significantly higher mean b/c value than SPT patients. This increase in mutagen sensitivity in HNSCC patients was not related to well‐known cancer risk factors such as age, or life‐style factors such as smoking and alcohol drinking habits. In addition, tumor site but not tumor stage was found to be related to mutagen sensitivity. On the basis of our findings, we propose that mutagen sensitivity is not an independent risk factor but a constitutional factor which reflects the way in which genotoxic compounds are dealt with and is thereby directly related to cancer risk.
Expression of cytokine/growth factors and their receptors in human melanoma and melanocytes
Authors: Mattei Stefano , Colombo Mario P. , Melani Cecilia , Silvani Anna , Parmiani Giorgio , Herlyn Meenhard 
Published: February 2007

AbstractHuman tumors can constitutively express cytokines and growth factors, but the extent of this expression has not been investigated. Using 44 different probes to cytokines, growth factors, and their receptors, we tested 21 melanoma and 5 melanocyte cultures for RNA transcript expression by reverse transcriptase‐polymerase chain reaction. With 30 amplification cycles, expression of the cytokines interleukin (IL)‐1β, IL‐6, leukemia inhibitory factor (LIF), IL‐7, groα, IL‐8 and the p35 chain of IL‐12 was detected in more than 60% of melanomas. Concomitant receptors for IL‐6 and IL‐7 were also detected. IL‐1α, IL‐5, Rantes, IL‐10, interferon (IFN)‐β, tumor‐necrosis factor (TNF)‐α, G‐colony‐stimulating factor (CSF) and GM‐CSF were expressed at lower levels. Melanocytes showed greatly reduced cytokine RNA transcripts, and only groα was consistently detected. No expression of IL‐2, IL‐3, IL‐4, IL‐9, the p40 chain of IL‐12, IFN‐α or IFN‐γ RNA transcripts was detected in melanomas or melanocytes. The growth factors expressed by melanomas and, after further signal amplification, by melanocytes were transforming growth factor (TGF)‐α, epidermal growth factor (EGF), TGF‐β, endothelial‐cell growth factor (ECGF), basic‐fibroblast growth factor (bFGF), nerve growth factor (NGF) and steel. The receptors EGFR, FGFR, NGFRp70 and c‐kit were also expressed by melanomas and melanocytes. These results point to new possible autocrine and paracrine pathways in melanoma biology.
Expression and function of the insulin‐like growth factor I system in human non‐small‐cell lung cancer and normal lung cell lines
Authors: Favoni Roberto E. , De Cupis Alessandra , Ravera Federica , Cantoni Claudia , Pirani Paolo , Ardizzoni Andrea , Noonan Douglas , Biassoni Roberto 
Published: February 2007

AbstractIn order to analyze the presence and the function of the “insulin‐like growth factor 1 (IGF‐1) system” in human non‐small‐cell lung cancer (N‐SCLC) we tested 5 cell lines of different histological sub‐types: A549, Ca‐Lu‐6, SK‐Lu‐1 (adenocarcinoma); Ca‐Lu‐1, SK‐Mes‐1 (squamous carcinoma) and one normal fibroblast‐like fetal lung cell line (IMR‐90) for expression of the IGF‐1 peptide and its RNA transcribed from the IGF‐1 gene; IGF‐binding proteins (IGF‐BP); IGF‐1 receptor (IGF‐1‐R) and its mRNA. In addition, we examined the capacity of exogenous human recombinant IGF‐1 to enhance the in vitro cell proliferation. In medium conditioned from cell cultures, we detected immunoreactive IGF‐1 material by radioimmunoassay. Western ligand blot and affinity labelling demonstrated the presence of several molecular species of IGF‐BPs (IGF‐BP‐4, −1, −2, −3) as well. Northern blot analysis of polyA+ RNA from all cell lines examined revealed the presence of IGF‐1 and IGF‐1‐R mRNA. Moreover, binding studies on cultured cell lines showed one class of high‐affinity, operative type‐1 IGF cell‐surface binding sites. Finally, by thymidine uptake and colorimetric metabolic MTT assays, we found that most neoplastic cell lines react mitogenically to IGF‐1 and that its physiological effect is abolished by an anti‐IGF‐1‐receptor antibody. These data indicate the importance of the IGF‐1 system in N‐SCLC growth. Furthermore, they suggest that this mitogenic complex should be appraised as a possible target for anti‐neoplastic drugs, antibodies or growth‐factor analogues offering potential new approaches to therapy.
Influence of fibroblasts on the invasion and migration of highly or weakly metastatic b16 melanoma cells
Authors: Saiki Ikuo , Murataxd Jun , Yoneda Junya , Kobayashi Hideo , Azuma Ichiro 
Published: February 2007

AbstractWe have examined the influence of fibroblasts on the invasive and migratory potential of highly metastatic melanoma B16‐BL6 and weakly metastatic B16‐FI cells in vitro. Co‐culture of B16‐BL6 cells with a fibroblast monolayer without cellular contact in a Transwell chamber more effectively induced tumor‐cell invasion into Matrigel basement membrane than co‐culture of B16‐FI cells with a fibroblast monolayer. The activity was closely correlated with the chemotactic migration of tumor cells toward the fibroblast monolayer. We also found that the conditioned medium (CM) from the co‐culture of fibroblasts with B16‐BL6 cells without cellular contact, i.e., CM (B16‐BL6/fibroblast), rather than from co‐culture with B16‐FI cells, could potentially promote the migration of tumor cells of both types. Tumor cells did not chemotactically migrate to the CM (B16‐BL6), CM (B16‐FI) or CM (fibroblast). Antibodies against TGF‐β1 or FN almost completely abolished the chemotactic migration of B16‐BL6 cells to the CM (B16‐BL6/fibroblast) or CM (TGF‐β1 ‐treated fibroblast) when these antibodies were c‐incubated with fibroblasts and either B16‐BL6 or TGF‐β1. In contrast, the anti‐EGF antibody did not show any inhibitory effects. Analysis of amounts of TGF‐β1 or FN in various CM using ELISA plates, and using their specific antibodies, revealed that the concentration of TGF‐β1 in the CM (B16‐BL6) was slightly higher than in the CM (B16‐FI), and the amount of FN in the CM (B16‐BL6/fibroblast) was twice as high as in the CM (B16‐FI /fibroblast). These results suggest that TGF‐β1 released from B16‐BL6 cells can stimulate fibroblasts to produce FN; consequently, the tumor cells were able to chemotactically migrate toward the released FN, and the differences in invasive and migratory activities towards fibroblasts in B16‐BL6 and B16‐FI cells may in part be due to the amounts of TGF‐β1 from tumor cells and of FN from TGF‐β1 ‐stimulated fibroblasts.
γ‐glutamyltranspeptidase expression regulates the growth‐inhibitory activity of the anti‐tumor prodrug γ‐L‐glutaminyl‐4‐hydroxy‐3‐iodobenzene
Authors: Prezioso Joseph A. , Hughey Rebecca P. , Wang Nu , Damodaran Kalyani M. , Bloomer William D. 
Published: February 2007

Abstractγ‐L‐glutaminyl‐4‐hydroxy‐3‐iodobenzene (I‐GHB), a novel iodinated analog of γ‐L‐glutaminyl‐4‐hydrpxybenzene (GHB), demonstrates greater anti‐tumor activity in human and in murine melanoma cell lines. These phenolic amides are substrates for γ‐glutamyltranspeptidase (GGTP; E.G. 2.3.2.2), a cell‐membrane‐associated ecto‐enzyme which is elevated in a number of tumor systems. We now present data to show that the growth‐inhibitory activity of I‐GHB and GHB may be mediated via GGTP‐catalyzed reactions. The growth‐inhibitory activity of I‐GHB and GHB in pigmented B16‐BL6 melanoma cells was blocked significantly by rabbit anti‐rat GGTP polyclonal antibodies. The combination of L‐serine and sodium borate, a specific transition‐state inhibitor of GGTP, as well as acivicin, a glutamine antagonist and irreversible GGTP inhibitor, inhibited the killing of BL6 cells by GHB and I‐GHB. To further define the role of GGTP expression in the regulation of phenolic amide cytotoxicity, GGTP‐negative Chinese hamster ovary cells (CHO‐KI) were transfected with a functional rat renal cDNA representing the full‐length GGTP transcript. I‐GHB and GHB were significantly more cytotoxic in GGTP cDNA transfected Chinese hamster ovary (CHO‐KI‐GGTP) cells than in non‐transfected CHO‐KI cells. The combination of L‐serine and sodium borate blocked the cytotoxic activity of these pro‐drugs and also inhibited GGTP‐catalyzed formation of polymerized products from these phenolic amides in intact BL6 melanoma and CHO‐KI‐GGTP cells. Furthermore, melanin formation from GHB was not observed in non‐transfected CHO‐KI cells lacking GGTP expression. The combined data strongly suggest that GGTP‐catalyzed hydrolysis of the anti‐tumor pro‐drugs I‐GHB and GHB to 4‐aminophenols mediates the expression of antitumor activity.
Enhancement of interstitial photodynamic therapy by mitomycin C and EO9 in a mouse tumour model
Authors: Baas P. , Michielsen C. , Oppelaar H. , Van Zandwijk N. , Stewart F. A. 
Published: February 2007

AbstractThe tumoricidal effect of interstitial photodynamic therapy (IPDT) using Photofrin was found to increase when combined with the bioreductive alkylating agent mitomycin C (MMC) and, to a lesser extent, with the indoloquinone EO9. When MMC was given prior to IPDT of RIFI tumours, the light dose required for a given regrowth time or for 50% cure was reduced by a factor of 2 compared with IPDT alone. MMC given immediately after illumination did not increase the effects of IPDT, although MMC plus illumination without photosensitizer produced a significant increase in regrowth time compared with MMC or light alone. Combination of IPDT with EO9, given directly before illumination, only marginally increased the tumour regrowth times at non‐toxic doses. These results demonstrate that combining IPDT with MMC greatly improves the tumour response. Factors such as PDT‐induced hypoxia, pH changes, temperature in‐creases and production of toxic reactive oxygen species by both drugs may play a role in the enhanced MMC cvtotoxicity.