bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soy isoflavones enhance radiotherapy in a metastatic prostate cancer model
Authors: Raffoul Julian J. , Banerjee Sanjeev , Che Mingxin , Knoll Zvi E. , Doerge Daniel R. , Abrams Judith , Kucuk Omer , Sarkar Fazlul H. , Hillman Gilda G. 
Published: February 2007

AbstractWe previously reported that genistein, the bioactive isoflavone of soybeans, acts as a radiosensitizer for prostate cancer. Pretreatment of tumor cells with genistein potentiated radiation‐induced killing in vitro and in orthotopic models in vivo. However, pure genistein promoted increased lymph node metastasis, when administered alone in vivo. We investigated in vitro and in vivo the effects of soy isoflavones (genistein, daidzein and glycitein) as soy pills of similar composition are used in human interventions but not pure genistein. Soy isoflavones inhibited cell survival and potentiated radiation cell killing in PC‐3 tumor cells, in vitro. Increased cell killing correlated with inhibition of antiapoptotic molecules Bcl‐xL and survivin, upregulation of proapoptotic Bax molecule and PARP cleavage, suggesting activation of apoptotic pathways. In vivo, using the PC‐3 orthotopic metastatic mouse model, soy isoflavones and prostate tumor irradiation led to enhanced control of primary tumor growth and metastasis, as observed with pure genistein and radiation. Interestingly, treatment with soy isoflavones did not increase metastasis to para‐aortic lymph nodes in contrast to the consistent increase caused by pure genistein. Histologically prostate tumors, treated with soy isoflavones and radiation, showed tumor destruction and in situ tissue alterations, comparable with genistein and radiation effects. However, genistein, but not soy isoflavones, caused induction of HIF1‐α in prostate tumors, suggesting that induction of hypoxia by pure genistein could contribute to increased metastasis. Our studies demonstrate the safety and potential role of soy isoflavones for enhancing the therapeutic effect of radiotherapy in prostate cancer. © 2007 Wiley‐Liss, Inc.
Immunogenicity and safety of a DNA prime/adenovirus boost vaccine against rhesus CEA in nonhuman primates
Authors: Aurisicchio Luigi , Mennuni Carmela , Giannetti Patrizia , Calvaruso Francesco , Nuzzo Maurizio , Cipriani Barbara , Palombo Fabio , Monaci Paolo , Ciliberto Gennaro , Monica Nicola La 
Published: February 2007

AbstractScaling up experimental protocols from rodents to humans is often not a straightforward procedure, and this particularly applies to cancer vaccines, where vaccination technology must be especially effective to overcome a variety of immune suppressive mechanisms. DNA electroporation (DNA‐EP) and adenoviral vectors (Ad) have shown high potency and therapeutic efficacy for different antigens in several pre‐clinical models. To evaluate the ability of DNA‐EP and Ad to break tolerance to a self‐antigen in large animals, we have cloned the CEA homologue (rhCEA) from rhesus monkeys (Macaca mulatta) colon tissue samples. rhCEA is a 705 aa protein and shares 78.9% homology to human CEA protein. Immunogenicity of rhCEA expressing vectors was tested in mice and subsequently in rhesus monkeys. To further increase the immunogenic potency of these vectors, a synthetic codon optimized rhCEA cDNA (rhCEAopt) was constructed. Genetic vaccination of rhesus monkeys was effective in breaking immune tolerance to rhCEA in all immunized animals, maintaining over time the elicited immune response, and most importantly, neither autoimmunity nor other side‐effects were observed upon treatment. Our data confirm the efficacy of genetic cancer vaccines in large animals such as nonhuman primates and show that development of modified expression cassettes that result in increased potency of plasmid DNA and adenovirus may have a significant impact on vaccine development against malignancies expressing tumor associated antigens in patients. © 2007 Wiley‐Liss, Inc.
Inactivation of LLC1 gene in nonsmall cell lung cancer
Authors: Hong Kyeong‐Man , Yang Sei‐Hoon , Chowdhuri Sinchita Roy , Player Audrey , Hames Megan , Fukuoka Junya , Meerzaman Daoud , Dracheva Tatiana , Sun Zhifu , Yang Ping , Jen Jin 
Published: February 2007

AbstractSerial analysis of gene expression studies led us to identify a previously unknown gene, c20orf85, that is present in the normal lung epithelium but absent or downregulated in most primary nonsmall cell lung cancers and lung cancer cell lines. We named this gene LLC1 for Low in Lung Cancer 1. LLC1 is located on chromosome 20q13.3 and has a 70% GC content in the promoter region. It has 4 exons and encodes a protein containing 137 amino acids. By in situ hybridization, we observed that LLC1 message is localized in normal lung bronchial epithelial cells but absent in 13 of 14 lung adenocarcinoma and 9 out of 10 lung squamous carcinoma samples. Methylation at CpG sites of the LLC1 promoter was frequently observed in lung cancer cell lines and in a fraction of primary lung cancer tissues. Treatment with 5‐aza deoxycytidine resulted in a reduced methylation of the LLC1 promoter concomitant with the increase of LLC1 expression. These results suggest that inactivation of LLC1 by means of promoter methylation is a frequent event in nonsmall cell lung cancer and may play a role in lung tumorigenesis. © 2007 Wiley‐Liss, Inc.
N6‐isopentenyladenosine: A potential therapeutic agent for a variety of epithelial cancers
Authors: Spinola Monica , Colombo Francesca , Falvella F. Stefania , Dragani Tommaso A. 
Published: February 2007

AbstractIsopentenyladenosine (i6A) is a product of isopentenyltransferases and, in mammals, occurs either bound to tRNA or as a free nucleoside. Sporadic reports have suggested an anticancer effect of i6A, mostly on leukemia cells. The present analysis of 9 human epithelial cancer cell lines derived from different types of malignant tissue revealed complete suppression of clonogenic activity in 8 of the lines after exposure to i6A at a concentration of 10 μM. Mechanistic studies showed that i6A tumor suppressor activity is associated with inhibition of cell proliferation, a block in DNA synthesis and morphological changes. These results point to i6A and to its possible derivatives as a new potential class of wide‐spectrum anticancer agents. © 2007 Wiley‐Liss, Inc.
Validation of clinical AJCC/UICC TNM staging system for hepatocellular carcinoma: Analysis of 5,613 cases from a medical center in southern Taiwan
Authors: Kee Kwong‐Ming , Wang Jing‐Houng , Lee Chuan‐Mo , Chen Chao‐Long , Changchien Chi‐Sin , Hu Tsung‐Hui , Cheng Yu‐Fan , Hsu Hsuan‐Chih , Wang Chih‐Chi , Chen Tai‐Yi , Lin Chih‐Yun , Lu Sheng‐Nan 
Published: February 2007

AbstractThis study was aimed to validate the 5th and 6th editions of tumor‐node‐metastasis (TNM) system for patients with hepatocellular carcinoma (HCC), and attempted to improve prognostic stratification by modifying the 6th edition according to vascular invasion and tumor size. From 1986 to 2002, a total of 5,613 HCC cases from Kaohsiung Chang Gung Memorial Hospital in southern Taiwan were enrolled. The 6th edition was modified by dividing stage I into stages IA (single tumor, ≤2cm) and IB (single tumor, >2cm), and by dividing stage II into IIA (multiple tumors, none >5cm) and IIB (tumor with segmental macro vascular invasion). The Akaike information criteria (AIC), within a Cox proportional hazard regression model were used; lower AIC value indicated a better discriminatory ability for staging system. The 1‐, 3‐, 5‐, and 7‐year overall survival rates were 45.6, 25.9, 17.9, and 13.4%, respectively. Significant differences in survival curve existed in the 5th, 6th, and modified 6th edition TNM systems. For the modified 6th edition TNM, survival differed significantly between stages IA and IB, and between stage IIA and IIB. The AIC values of 5th (72,328), 6th (72,188), modified 6th (71,991) edition TNM system were decreasing. This investigation demonstrated better prognostic stratifications for the 6th edition than the 5th edition TNM staging system. Moreover, the modified 6th edition staging system demonstrated better prognostic prediction than the former two. Pretreatment staging and simple classification of current modified 6th edition TNM staging can be applied to all HCC patients and are clinically useful. © 2007 Wiley‐Liss, Inc.
Biochemical changes associated with the development of resistance to 5‐azacytidine in AKR leukemic mice
Authors: Veselý J. , Seifert J. , Čihák A. , Šorm F. 
Published: February 2007

AbstractResistance to 5‐azacytidine, a potent inhibitor of the growth of mouse lympaoid leukemia cells in vivo, was achieved in an inbred strain of AKR mice in the third transplant period. The incorporation of orotic acid into the livers of such resistant mice was more than six times lower than in animals carrying the 5‐azacytidine‐sensitive parent strain of leukemia. The incorporation of orotic acid by 5‐azacytidine‐sensitive mice was inhibited by 5‐azacytidine twice as much as in 5‐azacytidine‐resistant animals. The incorporation of uridine, cytidine, thymidine, deoxycytidine, and of guanosine into nucleic acids was also significantly depressed in 5‐azacytidine‐resistant leukemic cells. Uridine kinase activity was decreased by 20%, while uridine phosphorylase activity was diminished by 31–50%. The resistant leukemic mice were cross‐resistant to 5‐fluorouracil; in contrast, however, their sensitivity to aminopterin was increased significantly.
Demonstration of a tumor‐specific antigen in spontaneously developing AKR lymphomas
Authors: Wahren Britta 
Published: February 2007

AbstractBy using the cytotoxic technique, a tumor‐specific antigen was detected in six out of ten spontaneously developing AKR lymphomas investigated. With more sensitive methods such as induction of cytotoxic antibodies in allogeneic hosts and quantitative absorptions, a tumor antigen could be detected in all the AKR lymphomas studied. Cross‐reaction was demonstrated between the AKR tumor antigen and a tumor antigen previously reported for Gross passage A virus‐induced lymphomas. The cross‐reactivity supports the theory that Gross virus acts as one etiological agent of the AKR lymphomas.
Ultrastructural cytochemistry of enzymes associated with murine leukemia viruses. I. Adenosine triphosphatase
Authors: De‐Thé Guy 
Published: February 2007

AbstractUltrastructural cytochemistry of plasma‐virus pellets from mice injected with Rauscher or Moloney virus showed a phosphatase activity specific for adenosine triphosphate and diphosphate, and for inosine triphosphate and diphosphate.This enzymatic activity was localized at the viral envelope and was associated with only part of the virus population. Moloney virus showed a smaller proportion of active virions than Rauscher virus. The adenosine triphosphatase activity associated with the murine leukemia viruses was far less pronounced than that associated with avian myeloblastosis virus.The origin of this enzymatic activity has not been clarified. Since the envelope of the budding viruses reflects some of the properties of the budding cell membrane, the adenosine triphosphatase of the blood‐forming organs was extensively investigated. Most of the virus‐replicating cells were adenosine triphosphatase‐negative in these organs. The viral enzyme might be adsorbed at the surface of the virus by electrostatic forces.
Transformation of rat and guinea‐pig cells in vitro by SV40, and the transplantability of the transformed cells
Authors: Diderholm Hans , Berg Rebekka , Wesslén Tore 
Published: February 2007

AbstractCell cultures of rat and guinea‐pig kidneys inoculated with simian virus 40 (SV40) were found to undergo morphological changes characteristic for SV40 transformation.Cell lines of rapidly‐growing transformed rat cells were obtained and found to be free from infectious SV40. They contained a specific antigen which was demonstrated in complement fixation tests with serum from hamsters bearing SV40 tumors.When the transformed rat cells were injected subcutaneously into the autologous hosts, tumors histologically classified as sarcomas developed in animals which had been pretreated by X‐ray irradiation. Tumor cells from one of the rats were passaged in vivo and gave rise to sarcomas of high malignancy also in non‐treated animals. A tumor line was thus established in rats. It contained the specific complement‐fixing “tumor” antigen but no infectious SV40.Transformed guinea‐pig cells autotransplanted into the irradiated host caused a small tumor which regressed within a few weeks.The results indicate that autotransplantation of in vitro‐ transformed cells into irradiated animals is a more promising way of obtaining SV40 tumors in different animals than the inoculation of newborns with virus.
Growth patterns in vitro of invasive squamous carcinomas of the cervix—a correlation of cultural, histologic, cytogenetic and clinical features
Authors: Auersperg Nelly , Worth Ann 
Published: February 2007

AbstractGrowth patterns of primary cultures of human cervical invasive squamous carcinomas were analysed with regard to cell cohesion, differentiation, cell shape, stratification and migration. On the basis of these criteria, the tumor cultures were divided into several distinct morphologic groups. Collagen gel proved superior to glass as a growth surface for cancer cells, but did not influence the morphologic classification of the cultures. In addition to the initial tissue‐specific epithelial outgrowths, secondary non‐specific epithelioid cells appeared in many of the cultures.The in vitro growth patterns of the tumors were correlated to histologic, cytogenetic and clinical characteristics. Cell cohesion in culture was associated with carcinomas that were histologically cohesive, poorly differentiated or of the basal cell type and had small nuclei with near‐diploid chromosome stemlines. Lack of cohesion in culture was related histologically to dispersed cell infiltration, squamous differentiation, large, differentiating nuclei and to higher chromosome modes. Some tumor cultures underwent characteristic changes, similar to changes in benign epithelial cultures. These features were interpreted as evidence of differentiation of squamous carcinoma cells in vitro, and were related to differentiation in vivo. There was a tendency for differentiating cultures to originate from exophytic tumors in early clinical stages and to be associated with a satisfactory short‐term radiation response.These results suggest that some characteristics of squamous carcinomas in primary culture are expressions of tumor cell properties present in vivo.
Tumour‐specific immunity against spontneous rat tumours
Authors: Baldwin R. W. 
Published: February 2007

AbstractThe antigenicities of two spontaneously developing rat tumours, a reticulum cell sarcoma and a squamous cell carcinoma, have been studied. With the reticulum cell sarcoma, no immunity could be demonstrated following either destruction of tumour grafts or implantation of heavitly irradiated (14,500 R) tumour into isogeneic hosts. Destruction of subcutaneous grafts by ligation oftheir blood supply proved to be effective for inducing immunity to the squamous cell carcinoma. In contrast, implantation of heavily irradiated tumour was completely inefective in producing resistance.The level of immunity imduced following destruction of subcutaneous grafts fo the squamous cell varcinoma varied markedly and this was ascribed to the tendency of the tumour to metastasize. Moreover, in some instances, rats immune to subcutaneous challenges with this tumour eventually developed lung metastases.Whils the prsent studies demonstrate the antigenicity of a spontaneously arising tumour, th level of resistance which can be produced is much lower than that detected with carcinogen‐induced tumours. Furthermore, immunological control of tumour metastases appears to be a problem not previously encountered with carcinogen‐induced tumours and this may also reflect differences in the antigenicities of the two tumour types.
Changes in the biological and biochemical properties of mouse hepatoma during long‐term cultivation in vitro
Authors: Irlin I. S. , Perova S. D. , Abelev G. I. 
Published: February 2007

AbstractCells of transplantable ascitic hepatoma originally induced in C3HA mice by orthoaminoazotoluene were explanted in tissue culture. Several established cell‐lines of ascitic hepatoma (AH‐2, AH‐3, AH‐4) and clonal lines from AH‐2 (clones N1, N2, N3) were obtained. During the early stages of cultivation, embryonal serum αf‐globulin, serum albumin and β2–1‐globulin were demonstrated in the culture medium. In the course of subsequent cultivation the production of embryonal αf‐globulin ceased while albumin and β2–1‐globulin were present in the medium during the whole period of cultivation. One culture, AH‐4, lost the ability to produce not only the embryonal αf‐globulin but serum albumin as well. However, when grafting of AH‐2, AH‐3 and clones N1, N2, and N3 was successful, it was possible to demonstrate the appearance of embryonal αf‐globulin in the sera of tumor‐bearing mice.The tumors induced by injection of AH‐4 cells did not produce αf‐globulin in vivo. In all tumors one organospecific liver antigen could be detected.Transplantability of cultures in isologous mice decreased during cultivation. This was demonstrated both by increase of minimum tumorigenic cell dose and increase of latent period of tumor appearance in comparison with original ascitic tumor.The possible correlation between the synthesis of αf‐globulin and the ability of tissue culture cells to induce tumor is discussed.
Decreased susceptibility to the mammary tumour agent in mice with advancing age
Authors: Dux Anna , Mühlbock O. 
Published: February 2007

AbstractIn mice, susceptibility to the mammary tumour agent (Bittner virus) decreases with advancing age. With the newly developed technique of transplantation of the mammary gland and of complete extirpation of all mammary glands, the role of the host and of the mammary gland with regard to the decreased susceptibility towards the mammary tumour agent was investigated. The experiments were done with female hybrids (♀ O20 × ♂ DBAf) F1. The susceptibility to the mammary tumour agent was determined by the percentage of mammary tumours which appeared in the transplanted glands. Comparison was made between the tumour incidence in young mammary glands transplanted into both young and old hosts and in old mammary glands transplanted into young and old hosts. Both the age of the host and the age of the mammary gland are determining factors in the development of mammary tumours. With advancing age of the host and advancing age of the mammary gland, tumour incidence in the mammary gland decreases and the induction time is longer under otherwise equal conditions.
Influence of epithelio‐mesenchymal interactions on tumor induction by polyoma virus
Authors: Dawe Clyde J. , Morgan Willie D. , Slatick Marilyn S. 
Published: February 2007

AbstractSubmandibular salivary glands (strain C3H/Bi mice), at stages of development ranging from prerudimentary condition through full development, were tested for their capacity to give rise to tumors after infection with polyoma virus (PV). Responsiveness was judged on the basis of (1) morphologic transformation in organotypic culture, and (2) the development of tumors within PV‐infected transplants to syngeneic newborn hosts.By the tumor‐in‐transplant criterion, the salivary gland was susceptible to the oncogenic action of PV from rudiment Stages 2 and 3 (11% incidence) through higher stages including complete development. With rudiments or glands beyond Stage 4, tumors developed in 60 to 78% of the infected transplants. No tumors developed from Stage 1 or from prerudimentary tissues. It is evident that in this organ, capacity of neoplastic response to PV develops concurrently with morphogenesis and does not diminish with advanced organ development.Morphologic transformation was seen in organotypic cultures of infected glands and rudiments of all stages, including Stage 1. However, the precise origin and the biologic capacities of the transformed epithelium in Stage 1 cultures remain in question.When Stage 2 to 5 rudiments were separated into epithelial and mesenchymal components by trypsinization, neither component alone gave rise to tumors after PV infection and transplantation to newborn recipients. Recombination of the infected components before transplantation restored the capacity to develop neoplasia (23% incidence).These results suggest that, in mouse salivary glands, the unit responding neoplastically to PV is an epithelio‐mesenchymal complex. It is postulated that the integrity of this complex is a critical factor in: (1) conditioning salivary gland epithelium to the initiating action of PV; (2) promoting the emergence of tumor; and (3) directing the pattern of tumor growth.
Interrelationships of contacting cells in the cell complexes of mouse ascites hepatoma
Authors: Vasiliev Ju. M. , Gelfand I. M. , Guelstein V. I. , Malenkov A. G. 
Published: February 2007

AbstractAscitic fluid formed after intraperitoneal implantation of mouse ascites hepatoma 22a contains single cells (I‐cells) and complexes consisting of two, three or more cells (II, III, IV‐complexes). Relative numbers of I‐cells and of the complexes of various types were the same in all samples of ascitic fluid taken from various generations of tumour transplantation. Non‐separation of sister cells after mitosis seems to play a leading role in the formation of the complexes. There are two stages in the mitotic cycle at which the complex may be broken: a) prophase, beginning synchronously in several contacting cells of the complex and, b) beginning of G1 phase in cells formed after mitoses of a I‐cell or after asynchronous mitosis in the complex.There are two discrete types of the II‐complexes in the ascitic fluid: complexes with synchronous mitotic cycles of contacting cells and those with considerable asynchrony of the cycle. Both cells of “synchronous” complexes start and finish S phase and G2 phase simultaneously.The mean generation time of the cells forming II‐complexes is shorter than that of I‐cells; this shortening is due to differing mean duration of the G1 phase which is 10–11 hours for the cells in II‐complexes as compared with 17–18 hours for I‐cells.
Le phénomène de la ségrégation nucléolaire: Spécificité d'action de certains antimétabolites
Authors: Simard R. , Bernhard W. 
Published: February 2007

AbstractSous l'effet de certains composés, le nucléole présente des lésions morphologiques distinctes et caractéristiques. Ces lésions consistent en une ségrégation des composants nucléolaires en trois zones: granulaire, fibrillaire et amorphe, avec parfois apparition d'une quatrième zone, plus contrastée, de nature inconnue. Dans le but de déterminer la spécificité de la lésion et d'en établir si possible la signification biochimique, des cellules d'embryons de rat sont traitées par différents antimétabolites agissant au niveau I) des précurseurs du DNA et du RNA, II) des polynucléotides, III) du système de transcription DNA‐RNA et IV) de la synthèse des protéines. Les substances qui donnent la ségrégation nucléolaire agissent toutes par liaison au DNA et action au niveau de la transcription du RNA (Groupe III). Ce sont: la Nogalamycine, la Daunomycine, l'Echinomycine, la Chromomycine A3, la Proflavine, le bromure d'éthidium, ainsi que l'Azasérine à fortes doses. La séquence de l'apparition des lésions de ségrégation causées par ces inhibiteurs métaboliques se retrouve de façon constante si on choisit bien les doses et le temps de traitement. L'action de ces inhibiteurs ainsi que leur mode de liaison au DNA sont étudiés. Une hypothèse de travail est proposée qui tient également compte de l'action nucléolaire sélective déjà connue de certaines substances, telles que l'Actinomycine D, la nitroquinoline N‐oxyde, la Mitomycine et l'Aflatoxine.