bluuebunny/crossref_metadata_2025 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

We 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

Scaling 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

Serial 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

Isopentenyladenosine (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

This 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

Resistance 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

By 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

Ultrastructural 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

Cell 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

Growth 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

The 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

Cells 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

In 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

Submandibular 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

Ascitic 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

Sous 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.
Burkitt's tumour in england a comparison with childhood lymphosarcoma
Authors: Wright D. H.
Published: February 2007

The histological sections of 63 English cases of non‐leukaemic lymphosarcoma of childhood have been reviewed. On histological criteria 50 cases were classified as non‐leukaemic lymphosarcoma, 9 as Burkitt's tumour and in 4 cases an equivocal diagnosis was made. The 9 children diagnosed as having Burkitt's tumour showed a similar clinical and anatomical tumour distribution to cases of Burkitt's tumour described from Africa, with a high incidence of jaw involvement and multiple visceral tumours. In contrast, most of the 50 cases diagnosed as lymphosarcoma presented with superficial lymphadenopathy, tumours of the lymphoid tissue of Waldeyer's ring, mediastinal masses or intussusception.

Burkitt's tumour is composed of cells that closely resemble lymphocytes transformed by phytohaemagglutinin. It is suggested that the tumour should be defined and classified on the basis of this cell type.

The hypothesis that Burkitt's tumour may be induced by an insect‐vectored virus is based mainly on the distribution of the tumour in tropical Africa. The implication of the English cases of Burkitt's tumour, reported here, is discussed in relation to this hypothesis.
Biological characteristics of primary tumors induced by polyoma virus in hamsters
Authors: Defendi V. , Lehman J. M.
Published: February 2007

Eleven primary subcutaneous tumors induced by polyoma virus in hamsters were analyzed for morphology, growth capacity in vitro, transplantability and karyology. In most cases, cultures prepared from these tumors grew for a few generations and then degenerated with loss of a majority of cells; from the few surviving cells, a population emerged that was able to grow indefinitely in vitro.

The initial explanted population differed from that which emerged from the degenerative phase in its susceptibility to the toxic activity of 3,4‐benzo (a)pyrene and in its high MTD (median tumor dose) values (105–106 cells) when transplanted in adult hamsters. The MTD decreased to 102–103 cells with prolonged growth in vitro. Cultures derived from the transplanted tumors grew permanently in vitro and had low MTD values. All the tumors were aneuploid with a prevalent near‐diploid mode and remained so even after prolonged growth in vitro. No common karyotypic changes were observed, but in 4/8 tumors there was a chromosome marker longer than the X. The long chromosome of the various lines differed in the arm ratios. The occurrence of monosomy and trisomy of pairs ≠1 and ≠21 was not random in 4/8 primary tumors.

A comparison with previous studies of hamster embryo cells infected in vitro with polyoma virus indicates that there is a strong parallelism in the biological properties and progression toward neoplasia between cell populations infected in vivoor in vitro by the virus.
Covalent binding of 4‐dimethylaminophenylazo‐3H‐benzene (butter yellow) metabolites with liver ribosomal RNA: The dissociation of the binding mechanism from the orotic acid incorporating system
Authors: Roberts J. J. , Warwick G. P.
Published: February 2007

No overall correlation between the binding of 3H‐labelled metabolites of 4‐dimethylaminophenylazobenzene (DAB) to the r‐RNA of liver, spleen and kidney and the incorporation of orotic acid‐14C into the same fractions after the same time was observed.

While actinomycin D inhibited the incorporation of orotic acid‐14C into liver r‐RNA it did not cause a similar depression in the binding of 3H‐labelled metabolites of DAB to r‐RNA.

Actinomycin D did not affect the overall metabolism of DAB as judged by the binding of 3H‐labelled metabolites to liver cytoplasmic and nuclear protein fractions.

These results suggest that the association of radioactivity with liver r‐RNA following injection of DAB‐3H is mediated by reactions independent of the orotic acid incorporation mechanism. They also confirm the earlier findings that reaction with liver r‐RNA is particularly favoured compared to that with r‐RNA from other sites.
Absence of specific chromosome alterations in bovine lung fibroblasts exposed to rous sarcoma virus
Authors: Pontén Jan , Lithner Folke
Published: February 2007

Bovine lung fibroblasts from individual embryos were exposed to three different strains of Rous sarcoma virus (Bryan, Engelbreth‐Holm, Schmidt‐Ruppin) in vitro. Chromosomal analysis early as well as late after infection, including cultures with advanced morphologic cell transformation, failed to disclose any aberrations exceeding the findings in control cultures grown in parallel under identical conditions. Simian virus 40, on the other hand, caused pronounced changes with widely scattered heteroploid counts and various rearrangements.
Essai de classification clinique tnm dans le cancer du sein
Authors: Lalanne C. M. , Juret P. , Hourtoule F. , Sarrazin D. , Rouquette C.
Published: February 2007

TNM classification in cancer of the breast

The TNM classification for breast cancer has been used at the Institut Gustave Roussy (I.G.R.) since 1960 following the recommendations of the International Union Against Cancer. It has been possible to stage nearly all cases (93%) and on preliminary experience the classification has been satisfactory. It is essential that the staging be carried out when the patient is first seen and not made retrospectively. The groups obtained are quite homogeneous but vary in size. The signs which appear to have been most important in determining the stage of a tumor are size, adherence to skin or pectoral muscle. If patients presenting with distant metastases and those retrospectively staged are excluded, the number of T1 cases is small (2%) in comparison with T2 (33%) and T3 (37%).

The 3‐year survival rate assessed on 199 patients staged according to the TNM classification underlines the advantages of the classification: T1, 100%, T2, 81%; T3, 68%; T4, 58%; N0 + N1, 78%; N2 + N3, 46%; M0, 70%; M1, 19%.

Means of improving distribution between the various groups and homogeneity within each group are reviewed. Additional information is needed in certain cases, for example, the method of measuring the tumour, assessment of pectoral adherence, whether or not it was provoked by muscle contraction. The definition of adenopathy “fixed en bloc” and its eventual replacement by other criteria, the classification of multiple tumours in one breast or cases apparently bilateral at onset and finally details of extension “beyond the tumour” or “beyond the mammary region”. Thus in spite of its deficiences we have found the TNM classification of breast cancer to be a useful tool and will continue to use it. We feel however that it should be periodically reviewed and adjusted in the light of fresh experience.
A colony inhibition (CI) technique for demonstration of tumor cell destruction by lymphoid cells in vitro
Authors: Hellström Ingegerd
Published: February 2007

A colony inhibition technique is described which was used to demonstrate that immune lymphocytes have a destructive effect on cultivated tumor target cells, if the target cells contain H‐2 isoantigens or tumor‐specific antigens foreign to the lymphocytes. Untreated allogeneic lymphocytes and lymphoma cells, added to the target cells together with phytohemagglutinin, were also effective in reducing the number of colonies formed.
Spermidine, spermine and glutathione in Rd/3 sarcoma rats
Authors: Neish W. J. P. , Key Linda
Published: February 2007

Concentrations of the polyamines spermidine and spermine and of glutathione have been studied in livers of normal rats and in livers and tumours of rats bearing Rd/3 sarcoma transplants. In livers of tumour‐bearing rats it was found that the spermidine content increased and glutathione content diminished with increasing tumour size.
Ètude du mècanisme de l'induction chez des cellules de hamster syrien transformèes par le virus SV40 I. Propriètès d'une lignèe cellulaire clonale
Authors: Tournier P. , Cassingena R. , Wicker R. , Coppey J. , Suarez H.
Published: February 2007

A clonal cell line (clone 2 TSV‐5) has been derived from a primary SV40 Syrian hamster turmor.

Association of clone 2 TSV‐5 cells to kidney cells of some animal species (Cercopithecus monkey, Rhesus monkey, Man) allows to recover infectious SV40 virus from the mixed cultures. This phenomenon can be considered an induction phenomenon.

The clone 2 TSV‐5 is characterized by a mean frequency of induction by association of 6%, but the SV40 genome is entirely present in all these clonal cells. The induced SV40 virus is similar to the SV40 virus by which the clone 2 TSV‐5 cells have been originally converted. The clone 2 TSV‐5 is not inducible by rabbit kidney cells, by mouse embryo cells or by human KB cells. It is neither inducible by × or ultraviolet irradiations, nor by several chemical agents, such as mitomycin C, proflavine and hydrogen peroxide.

Three other Syrian hamster cell lines converted by SV40 virus are not inducible by Cercopithecus monkey kidney cells. It is assumed that these malignant cells contain only a portion of the viral genome.
Further studies on mammary tumours induced in rats by 7,12‐dimethylbenz(a)anthracene (DMBA)
Authors: Daniel Peter M. , Prichard Marjorie M. L.
Published: February 2007

Mammary tumours were induced in female Sprague‐Dawley rats by a single oral dose of 20 mg of 7,12‐dimethylbenz(a)anthracene (DMBA) given when the rats were 50 days old. The tumours were of three main types: non‐secreting adenomata, milk‐secreting adenomata and fibro‐adenomata. The histological appearance of the nonsecreting adenomata was similar to that of tumours induced by 3‐methylcholanthrene. The appearance of the milk‐secreting adenomata, with prominent vacuoles in the epithelial cells and milk filling the lumen of the acini, resembled the picture of the normal mammary gland of the rat in late pregnancy. The tumours which appeared earliest were the non‐secreting adenomata, and most of these tumours developed during the first 6 months after administration of DMBA. In the first 5 months milk‐secreting adenomata and fibro‐adenomata were rare, but after this time nearly all the tumours which developed were either milk‐secreting adenomata or fibro‐adenomata. The milk‐secreting adenomata, though late in appearing, were the most numerous of all the tumours induced. The reasons for describing the tumours as adenomata rather than carcinomata are given.

Hypophysectomy was very effective in causing regression of the non‐secreting adenomata. Less successful results were obtained by removal of the ovaries and adrenal glands.
Aspects ultrastructuraux des tumeurs de souris induites par l'adénovirus 12
Authors: Salomon J.‐Ci.
Published: February 2007

In a study of the ultrastructure of tumors induced in mice by adenovirus 12, no intranuclear adenovirus particles could be found. In some nuclei, however, there were inclusions resembling those observed during the lytic cycles of adenovirus 12. There was an abundance of intracytoplasmic particles of type A and type C. Deposits of a very dense substance were found along the external surface of the cell membranes and also in the neighborhood of the C particles.
Neutralization kinetics of friend and rauscher leukemia viruses studied with the spleen focus assay method
Authors: Steeves R. A. , Axelrad A. A.
Published: February 2007

The rates of neutralization of Friend and Rauscher viruses in vitro by specific antisera were measured with the spleen focus assay method in order to obtain quantitative information on the antigenic relationship between these viruses. Sera were obtained from C3H mice pretreated with formalinized cell suspensions from leukemias induced in the same strain by Friend, Rauscher, Moloney, Gross and Graffi viruses; the Friend and Rauscher virus preparations used were harvested from the plasma of infected C3H mice, and the titrations of residual virus were also carried out in mice of the C3H strain.

Both Friend and Rauscher viruses were neutralized by sera from mice pretreated with Friend, Rauscher and Moloney leukemias, but no neutralizing activity was detected in sera from mice pretreated with either Gross or Graffi leukemias. Friend and Rauscher viruses behaved identically to one another with regard to the kinetics of their neutralization, whether antisera prepared against Friend or Rauscher or Moloney leukemias were used, and despite marked differences in the potency and quality of these antisera. The data are considered to provide strong evidence that the antigenic sites on Friend and Rauscher viruses which participate in these neutralization reactions are identical.
Studies on allogeneic inhibition III. Inhibition of mouse tumor cell colony formation in vitro by contact with lymphoid cells containing foreign H‐2 antigens
Authors: Hellström K. E. , Hellström I. , Bergheden C.
Published: February 2007

A colony inhibition (CI) technique was used to demonstrate that lymphocytes and lymphoma cells derived from allogeneic or “semi‐syngeneic” F1 hybrid hosts decreased the plating efficiency ofhomozygous mouse tumor cells in comparison to lymphoid cells of the syngeneic type. Phytohemagglutinin was present in all experiments. Syngeneic lymphocytes and lymphoma cells also reduced plating efficiencies compared to untreated controls, if they were added in high ratios, but this effect was significantly smaller than with allogeneic and F1 hybrid cells.

The data strongly indicate that allogeneic inhibition of mouse tumor cells is due to their exposure to foreign H‐2 isoantigens or to cellular material closely associated with these antigens. They also support the postulate that cellbound immunity reactions, as studied with mouse cells in vitro, are partly due to exposure of the target cells to foreign H‐2 isoantigens of the added lymphoid cells.
Spontaneous lymphoblastoid transformation of long‐term cell cultures from human malignant lymphoma
Authors: Pontén Jan
Published: February 2007

Long‐term tissue cultures of human malignant lymphomas have been compared to cultures of lymphadenitis and normal skin. A modified Trowell grid type of culture was used. Six out of six cases of malignant lymphoma differed from the control cultures by exhibiting patches of irregular, apparently random growth of fibroblastoid cells. Three of these six cultures underwent a lymphoblastoid transformation morphologically similar to the alteration described by Benyesh‐Melnick et al. (1963) in a small fraction of bone marrow cultures obtained from leukemic children. The process involved growth of fibroblastoid cells during a preliminary stage lasting 9–18 weeks after explantation. After this the cultures changed into a system consisting of reticulum‐like cells with apparent differentiation to lymphoblast‐ and lymphocyte‐like elements. The reticulolymphoid cells could only be grown and maintained in the presence of fibroblastic cells. Heterologous and homologous fibroblastic cells could be used, but the best survival and multiplication of the reticulo‐lymphoid cells was obtained in mixtures with autologous fibroblastic elements. Lymphoblastoid transformation seemed to require that the original explants be kept as intact grid cultures for a minimum time of about 6–12 weeks corresponding to at least three grid transfers.

No lymphoblastoid transformation was observed in five non‐malignant lymphnodes.

The only transformed culture analyzed showed a chromosome number of 47. The extra chromosome was a large metacentric which resembled a normal chromosome No. 3. All dividing cells apparently had the same chromosome change.

Fibroblastic cells from non‐neoplastic skin or lymph‐nodes had a finite life span in vitro of about the same length regardless of whether they were trypsinized and subcultivated or transferred as undisturbed grid cultures.
Malignancies at the hospital of Doctor Albert Schweitzer, Lambaréné, Gabon, 1950–1965
Authors: Denues A. R. T. , Munz Walter
Published: February 2007

Records from 1950 through 1965 for 64,297 persons seen at the Hospital of Dr. Albert Schweitzer, Lambaréné, Gabon (equatorial West Africa) disclose 196 histologically‐proven malignancies. Dominated by carcinomas, chiefly of the genitourinary and alimentary tracts, these malignancies also include substantial numbers of lymphomas and sarcomas. Although primary cancers of the liver were found, no evidence was found at Lambaréné of certain other tumors prevalent elsewhere in Africa. No nasopharyngeal or esophageal cancers were recorded; further, few malignancies were recorded for young persons, and for children no evidence was found of leukemias or the malignant lymphoma of Burkitt. A near‐constant proportion of numbers of malignancies to total numbers of histopathological reports was found throughout the 16‐year period 1950–1965; this result does not support the suggestion of an increased general prevalence of malignancies during recent years. Collectively, the data extend the published information for malignancies in equatorial West Africa, and suggest several directions—both clinical and endemiologic—for studies at Lambaréné.
RNA with high template activity from leukaemic myeloblasts (Bai strain a virus‐induced avian myeloblastosis) I. Optimal conditions for its isolation and activity in the subcellular protein‐synthesizing system
Authors: Trávníč M. , Veprek L. , Ríman J.
Published: February 2007

Three methods of phenol fractionation of metabolically active RNA of leukaemic myeloblasts were compared on the basis of the template activity of the isolated fractions. It was shown that the method of phenol fractionation based on increasing the extraction temperature is most suitable for obtaining a fraction substantially enriched in template active RNA.

Standardization of the extraction conditions employed (the use of acetate buffer pH6) led to the separation of RNA of high template activity (65°‐RNA) not contaminated with DNA and highly purified with respect to the presence of other cellular RNAs.

The template activity of isolated RNA fractions was tested in the subcellular protein‐synthesizing system from E. coli under the optimal conditions described here with respect to the function of the RNA fraction with the highest template activity (65°‐ RNA).

It was found that the 65°‐RNA fraction has characteristic sedimentation properties, a nucleotide composition resembling the DNA of leukaemic myeloblasts and, by its high template activity, meets the requirements of a highly purified preparation of m RNA. Its template activity, tested by incorporation of two amino acids (2160 pmol leucine, 578 pmol phenylalanine/mg RNA) exceeds several‐fold the highest values of template activity so far published for ribonucleic acids isolated from the cells of higher organisms.

It was found that the same results can be achieved by applying the method to other types of tissue, such as normal chick liver tissue.
Étude chromosomique de tumeurs provoquées chez le hamster Syrien par le 20‐méthylcholanthrène
Authors: Horacio Suarez Rolando Cassingena Et
Published: February 2007

Primary tumors induced in the Syrian hamster by 20‐methylcholanthrene exhibit a diploid stemline.

After several passages in vitro or in vivo, some of these tumors still show a diploid stemline.

In the different tumors studied, the idiogram analysis reveals the presence of pseudo‐diploid mitoses but does not indicate any specific karyotype modification.
Effects of freund's adjuvant on adenovirus oncogenesis and antibody production in hamsters
Authors: Berman L. D. , Allison A. C. , Pereira H. G.
Published: February 2007

Hamsters were inoculated with varied regimens of adenovirus type 12 and complete Freund's adjuvant neonatally, and/or during the latent period preceding appearance of tumors. Virus and/or adjuvant were administered either separately or together as emulsions. In all instances adjuvant treatment up to one week of age reduced the incidence of tumors as compared to that in animals receiving a single dose of virus. Complement‐fixing antibodies to virion or “T” antigens were not demonstrable in animals failing to develop tumors following neonatal inoculation of virus with or without adjuvant. However, subsequent administration of virus with or without adjuvant led to production of high liter antibodies, so that the first injection of virus had not made the animals tolerant to virion or “T” antigens. Administration of virus/adjuvant emulsions after the 5th or 6th day of life produced high tilers of anti‐virion antibodies regardless of tumor production. Only animals with tumors produced measurable quantities of anti‐ T antibody. These results suggest that oncogenesis by adenovirus can be impeded by non‐specific immunological stimuli during the latent period.
Embryonal serum α‐globulin in cancer patients: Diagnostic value
Authors: Abelev G. I. , Assecritova I. V. , Kraevsky N. A. , Perova S. D. , Perevodchikova N. I.
Published: February 2007

Sera of 308 patients, of whom 242 were suffering from various types of tumours and 66 from non‐cancerous diseases, were tested for the presence of αf‐globulin. The reaction was positive in 17 out of 28 patients with primary cancer of the liver. Among these there were 18 cases with tumours of the hepatocellular type, and 14 of these gave a positive αf‐globulin reaction. The test was negative in 67 patients with metastatic liver tumours.

This confirms Tatarinov's (1964) findings indicating that αf‐globulin is detected in sera of patients with primary hepatocellular carcinoma. In addition, αf‐globulin was found in some patients with mixed hepatocellular and cholangiocellular carcinoma.

The fact that the αf‐globulin test is usually positive in hepatocellular and mixed liver carcinomas and negative in metastatic liver tumours makes it potentially useful for the differential diagnosis of liver tumours.

αf‐globulin was found also in the blood of patients with testicular teratoblastoma, which exhibited some elements of embryonal carcinoma. This novel finding cannot be interpreted as yet. The test was negative in other types of testicular tumours.
Burkitt's lymphoma outside the known endemic areas of Africa and New Guinea
Authors: Burkitt Denis
Published: February 2007

Burkitt's lymphoma (African lymphoma) was first thought to be limited to tropical and subtropical areas of Africa and New Guinea. The histological criteria described by Wright in 1963 and 1964 made it possible to distinguish the tumour from other forms of malignant lymphoma in children and led to the discovery of a number of undoubted cases of Burkitt's lymphoma in many countries. Retrospective surveys of histological sections have in fact brought to light 65 cases in territories outside tropical Africa. Prior to recognition of the disease as a separate entity, references to probable cases were made in 22 papers from the United States, France, India, and Vietnam. African lymphoma has actually been diagnosed in 23 cases in 10 countries outside Central Africa. The study of fresh imprint preparations, together with new techniques in tissue culture and electron microscopy, will in future render any prospective search for cases of this tumour simpler and more accurate than retrospective studies.
Lymphoma of the Burkitt type in Singapore
Authors: Shanmugaratnam K. , Tan K. K. , Lee K. W.
Published: February 2007

Fourteen cases of lymphoma of the Burkitt type were found in a retrospective review of histopathological material in Singapore over a 15‐year period (1950–1964). The cases ranged from 4–14 years of age; there were 13 Chinese and 1 Indian and 12 male and 2 female patients in this series. The age‐specific incidence rates were 0.05 per 100,000 children per annum for the 0–4 year age group, 0.18 for the 5–9 year age group and 0.29 for the 10–14 year age group; there were no cases in the 15–19 year age group. The incidence rates for the 0–14 year age group were 0.25 per 100,000 children per annum for males, 0.04 for females and 0.15 for both sexes. The neoplasm comprised 3.6% of all histologically diagnosed cancers in the 0–14 year age group. The relative rarity of lymphoma of the Burkitt type in Singapore is of interest as the climatic conditions here conform to the observed requirements for endemicity of the disease in Africa.