bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiosensitization of human tumor cells by alpha‐difluoromethylornithine
Authors: Courdi A. , Milano G. , Bouclier M. , Lalanne C. M. 
Published: February 2007

AbstractThe effect of polyamine depletion on the radiosensitivity of a human tumor cell line was investigated. CAL 18 A cells, derived from a breast carcinoma, were incubated with alpha‐difluoromethylornithine (DFMO)—a specific and irreversible inhibitor of ornithine decarboxylase (ODC)—at a 1 mM or 10‐mw concentration for either 1 hr or 24 hr and irradiated thereafter. Survival curves of exponentially growing cells revealed a moderate but significant enhancement of radiosensitivity as compared to untreated irradiated cells. Maximum radiosensitization was observed at a concentration of 10 mw after I hr incubation. Plateauphase cells were used to study the effect of polyamine inhibition on repair of radiation‐induced potentially lethal damage (PLD). DFMO enhanced the radiation response and significantly inhibited PLD repair in these cells. Measurement of ODC indicated that this enzyme was markedly inactivated upon brief incubation of CAL 18 A cells with DFMO, reflecting a depletion of polyamine synthesis. These results extend findings that have demonstrated enhancement of drug‐induced cytotoxicity, and raise the possibility of clinical use of this substance for potentiation of radiation response.
Low frequency of NK‐cell progenitors and development of suppressor cells in IL‐2‐dependent cultures of spleen cells from low NK‐reactive SJL/J mice
Authors: Migliorati Graziella , Herberman Ronald B. , Riccardi Carlo 
Published: February 2007

AbstractStudies were performed to determine the basis for low NK activity in the spleens of SJL/J mice. In contrast to substantial boosting by IL‐2 or IFN of NK activity of spleen cells from high NK‐reactive strains of mice, no detectable effect of these citokines on SJL spleen cells was seen. When SJL spleen cells were cultured for 7 days in the presence of IL‐2, the frequency of proliferating cells was comparable to that of other strains of mice. However, the SJL spleen cells showed a frequency of NK‐cell progenitors which was at least 50 times lower than that of the CBA/J spleen cells. In addition to having no detectable effector‐cell activity, the cultures of SJL spleen cells contained suppressor cells which were able to inhibit the NK activity of spleen cells from other strains of mice. These suppressor cells did not adhere to plastic or nylon wool and were found in low‐density fractions after Percoll density gradient centrifugation. The cultured SJL spleen cells had a high percentage of cells capable of binding to NK‐susceptible target cells, which was similar to that seen in lytic cultures from other strains of mice. Thus, the suppressor activity may be attributable to competitive inhibition of the interaction of effector cells with target cells. Although several of the characteristics of suppressor cells were similar to those of cultured effector cells; they may not represent inactive or pre‐NK cells since their progenitors were Thyl+ and Asialo GM whereas the progenitors of cultured effector cells in high NK strains were Thy I−. and GM. The ability to eliminate the progenitors of the suppressor cells by pretreatment of spleen cells with anti‐Thyl plus C' also suggested that the low or undetectable NK activity of the cultured SJL cells is not attributable to suppression but may be due to an inherent deficit of NK cells.
Chromosomal study demonstrating the clonal evolution and metastatic origin of a metachronous colorectal carcinoma
Authors: Muleris Martine , Salmon Rémy Jacques , Dutrillaux Bernard 
Published: February 2007

AbstractDetailed cytogenetic studies were performed on 3 samples of a metachronous rectal carcinoma. Two samples were obtained from the primary tumor, and one from a secondary growth which arose 10 months after surgical removal of the primary. All 149 R‐banded metaphases analysed were abnormal and most likely derived from the same modified karyotype: 45, XY,−1, −18, +20, der(6) t(l;6) (q21.100; q22.3), i(17q). These data are consistent with our previous findings that the loss of chromosome 18 and of the short arm of chromosome 17 may be the primary chromosomal changes associated with carcinoma of the large bowel. From all the karyotypes observed, a typical clonal evolution could be reconstructed, indicating that the second tumor was indeed metastatic from the first one, based on similar chromosome markers. An identical secondary chromosomal anomaly, i.e. gain of chromosome 8 or X, occurred independently twice in two different cell populations during the evolution of this tumor.
Effect of tunicamycin on synthesis and secretion of carcinoembryonic antigen by human colonic adenocarcinoma cells
Authors: Miura Soichiro , Kim Young S. 
Published: February 2007

AbstractThe effect of the glycosylation inhibitor, tunicamycin, on synthesis and secretion of the membrane‐associated glycoprotein carcinoembryonic antigen (CEA), was studied in the LSI74T human colon cancer cell line. Tunicamycin treatment inhibited total cellular glycoprotein synthesis but did not affect CEA levels of cellular homogenate, membrane or cytosol fractions as determined by enzyme immunoassay. Control cells metabolically labelled with 3H‐glucosamine, 3H‐leucine or 35S‐cysteine exhibited membranous and extracellular (i.e. secreted) CEA with an MW of 200 kDa as judged by SDS‐gel electrophoresis following immuno‐precipitation. However, in the tunicamycin‐treated cells several forms of CEA with lower MWs and representing molecules with decreased glycosylation could be detected in addition to the original CEA molecule of 200 kDa present in control cells. The rates of synthesis, secretion and turnover of the lower‐molecular‐weight forms of poorly glycosylated CEA that appear after tunicamycin treatment are similar to those of CEA in control cells. These data suggest that the carbohydrate portion of the CEA molecule is not essential in synthesis, incorporation into the membrane, and secretion of CEA by colon cancer cells in vitro.
Induction of thymic lymphosarcomas in C57BL/6 mice after inoculation of weakly oncògenic viruses associated with a sub‐leukemogenic radiation exposure (1.75 GY × 2)
Authors: Galiay M. , Leorand E. , Aster‐Gin T. , Rollet C. , Guillemain B. , Duplan J. F. 
Published: February 2007

AbstractB‐ecotropic retroviruses arise frequently in old or irradiated C57BL/6 mice as a consequence of a genetic recombination between endogenous eco‐ and xenotropic retroviruses. They are weakly oncogenic and express a very low tropism for thymic cells. However, their activation by X‐rays and the subsequent insertion of new proviral sequences in the cell genome of in vivo‐ and in vitro‐passaged tumors suggest that they might play a role in radioleukemogenesis. To study this possibility, a cloned B‐ecotropic virus (1223) was injected into C57BL/6 mice subjected to a subleuke‐mogenenic irradiation which induses only 7% of thymic lymphosarcomas (TL). When it was injected prior to or after irradiation, 1223 induced respectively 31 % and 19% of TL. The incidence of TL in the different groups closely correlated with virus expression in hemato‐poietic tissues during the preleukemic period. Thus, irradiation seems to amplify bone marrow (BM) and thymic cell populations) which play a decisive role in viral expression. A recombinant provirus (presumably the injected 1223) was detected in the genomic DNA of all tumors tested irrespective of the inductive protocol. BM restoration, which does not inhibit TL produced by highly oncogenic passaged viruses, but prevents the development of TL induced by 4 doses of 1.75 Gy, also provided strong protection in the present experiments. The present data support the hypothesis whereby weakly oncogenic B‐ecotropic viruses similar to those activated by radiation might be involved in the development of TL.
Effect of some proliferative and environmental factors on the toxicity of mitomycin C to tumor cells in vitro
Authors: Rockwell Sara 
Published: February 2007

AbstractMitomycin C (MC) was more toxic to EMT6 mouse mammary tumor cells in vitro under hypoxia than under aerobic conditions. This was evidenced both in survival curves defining the toxicity of treatment with a constant dose of MC given for different periods of time and in survival curves defining the effect of a 1‐hr treatment with different concentrations of MC. Cultures preincubated for different periods from 1 to 6 hr in hypoxia all had similar MC sensitivities. In contrast, cultures preincubated in hypoxia for 4 hr then “reoxygenated” before MC treatment had the same sensitivities as cultures which had never been hypoxic. This shows that the oxygenation at the time of MC exposure, rather than the preincubation protocol, was the parameter determing cell sensitivity. Exponentially‐growing (proliferating) and plateau‐phase (quiescent) cultures had similar MC survival curves; neither type of culture repaired potentially lethal damage when held for up to 24 hr in HBSS after MC treatment. The sensitivity of the cells increased as the pH of the culture medium was decreased to low values (pH 7.0–6.0), but extracellular pH had no significant effect on the cytotoxicity of MC over the physiologic range (7.0–7.4). These data suggest that differences in the metabolic characteristics of cells that are hypoxic and aerobic during MC treatment, rather than perturbations of the cell proliferation patterns, the PLDR capacity of the cells, or the extracellular pH during the hypoxic incubation, are responsible for the different sensitivities of aerobic and hypoxic cells to MC in vitro.
Red blood cell polyamine levels and host toxicity during continuous alpha‐difluoromethylornithine infusion
Authors: Ota David M. , Grossie V. Bruce , Ajani Jaffer A. , Stephens L. Clifton , Nishioka Kenji 
Published: February 2007

AbstractThe dose effects of continuous alpha‐difluoromethylornithine (DFMO) infusion on red blood cell (RBC) polyamine levels, host toxicity and tumor growth were determined. Male rats with and without a transplantable methylcholanthrene‐induced sarcoma received intravenously either 0.45% NaCI or DFMO at 500 mg, 1,000 mg, or 2,000 mg/kg body wt/day for 6 or 12 days. Dose‐related inhibition of tumor growth was noted after the 12‐day treatment. There were no changes in host carcass weight, food intake, plasma albumin, hematocrit or white blood cell counts. Platelet supression was associated with the 1,000‐ and 2,000‐mg doses with the 12‐day treatment. Morphometry of the small intestine revealed mild but significant shortening of villi in the duodenum and jejunum at the 2,000‐mg dose, but none of the animals developed diarrhea. The 500‐mg DFMO dose reduced the rate of tumor growth without inducing platelet suppression or altering intestinal morphology. A decrease in RBC putrescine levels was noted at all doses. RBC spermidine levels increased with the 500‐mg dose. RBC spermine levels were higher at all doses compared with controls. These results suggest that thrombocytopenia is the major dose‐limiting side‐effect of continuous DFMO infusion but does not occur at a dose of 500 mg/kg body wt/day.
IL‐2‐ and IL‐2‐R‐ independent proliferation of T‐cell lines from adult T‐cell leukemia/lymphoma patients
Authors: Katoh Taiji , Harada Takayuki , Morkawa Shigeru , Wakutani Tadao 
Published: February 2007

AbstractHuman T‐cell leukemia/lymphoma virus 1 (HTLV‐1) is known to be associated with adult T‐cell leukemia/lymphoma (ATL) as an etiological agent. The mechanism of leukemogenesis by HTLV, however, is still obscure. Two hypotheses have been proposed concerning abnormalities in 1L‐2 production and its receptor (Tac antigen) expression based on the experimental observations of 1L‐2‐dependent ATL cell lines. In this study, we examine these hypotheses by using 3 leukemic T‐cell lines from 3 Japanese patients with ATL. These cell lines were cultivated and established without addition of 1L‐2 to the culture medium. Cell‐surface phenotype analysis by immunofluorescence with monoclonal antibodies (MAbs) and 1L‐2 binding assays revealed that one of the ATL cell lines, HPB‐ATL‐2, expresses only a minimal amount of 1L‐2 receptor (1L‐2‐R) on the cell surface and binds less radiolabelled human recombinant 1L‐2 than the other highly Tac‐positive cell lines. Expression of Tac antigen in all ATL cell lines was not affected by 1L‐2, anti‐Tac MAb or the tumor‐promoter phorbol ester in the culture medium. The culture supernatant from these cell lines showed no 1L‐2 activity toward Con‐A‐stimulated human peripheral blood lymphocytes, and their growth was not affected by additional 1L‐2 in cultures. 1L‐2‐independent growth and constitutive expression of its receptors on the cell surface were evident in our ATL cell lines. However, dense expression of 1L‐2 receptors was not essential for stimulation of leukemic proliferation of T cells by HTLV‐I. Trans‐activation of the PX″ gene product of HTLV‐I for activation of 1L‐2‐R gene might not be coincidentally associated with stimulation for cell proliferation.
Organ specificity of metastatic tumor colonization is related to organ‐selective growth properties of malignant cells
Authors: Nicolson Garth L. , Dulski Kim M. 
Published: February 2007

AbstractIn cancers such as malignant melanoma, tumor spread or metastasis occurs preferentially to certain organ sites. Mouse B16 melanoma cell sublines that have been selected sequentially in vivo for enhanced blood‐borne colonization of lung, brain, or ovary were tested for their survival and growth stimulation in vitro by soluble factors released from suspensions of mouse lung, brain, liver, ovary or kidney tissues. In general, the growth rate of lung‐colonizing B16 cells was stimulated by high concentrations of lung‐tissue‐derived factors significantly more than by factors from the other tissues, whereas the growth rate of ovary‐colonizing B16 cells was stimulated by ovary or lung‐tissue‐derived factors significantly more than by factors from the other tissues. In contrast, the growth of brain‐colonizing B16 cells was not stimulated by factors released from brain tissue. When it occurred, stimulation of B16 cell growth by factors released from mouse organ tissues was dose‐dependent. Liver tissue factors, and at high concentrations kidney tissue factors, inhibited cell growth of the B16 sublines, an inhibition correlating with the low potential of B16 cells to colonize liver and kidney in vivo. In addition to preferential target‐organ cell adhesion found previously with B16 sublines (Nicolson et al., 1985a), the present results suggest that metastasis to specific organ sites is also dependent on the survival and growth of B16 cells affected by soluble organ‐derived factors.
Molecular and immunological evidence of B‐cell commitment in “null” acute lymphoblastic leukaemia
Authors: Foa R. , Migone N. , Basso G. , Cattoretti G. , Pizzolo G. , Lauria F. , Casorati G. , Giubellino M. C. , Capuzzo F. , Cantu‐Rajnqldi A. , Lusso P. , Carbonara A. O. , Gavosto F. 
Published: February 2007

AbstractThe DMA configuration of the immunoglobulin (Ig) heavy and light chain genes and the expression of B‐ cell‐related markers were evaluated in 13 cases of non‐ T, non‐B, non‐common (“null”) acute lymphoblastic leukaemia (ALL). A rearrangement of the Ig heavy‐ chain gene was found in all cases studied; in 5 of these a structural reorganization of the K or Λ light chain gene was also demonstrated. Leukaemic cells from 10 of the 13 cases analysed showed one or more B‐cell antigens, the expression of which followed a sequential order of presentation (OKB2, B4, BA‐1, B1). The B‐cell commitment was confirmed by means of a sensitive immunoperoxidase assay which revealed a weak expression of the common ALL (cALL) antigen in 7/10 cases tested, which were all cALL‐negative by conventional immunofluorescence techniques. These findings suggest that in “null” ALL the neoplastic cells show molecular and immunological evidence of B‐cell differentiation and that most cases may indeed be characterized by “early” cALL with a very low density expression of the cALL antigen. This was further documented in one case in which the expression of the cALL antigen (and of other B‐cell markers) could be induced after exposure to 12‐O‐tetradecanoylphorbol‐ 13‐acetate (TPA). The presence in a few cases of myeloid features, particularly when the cALL antigen could not be demonstrated by the immunoperoxidase assay, suggests that the leukaemic process may sometimes involve a very early progenitor cell capable of both lymphoid and myeloid phenotypic differentiation. The heterogeneity of “null” ALL documented by this study may help to explain the variable clinical course and prognosis of these patients.
Thyroid function and the incidence of breast cancer in Hawaiian, British and Japanese women
Authors: Thomas B. S. , Bulbrook R. D. , Goodman Madeleine J. , Russell M. J. , Quinlan Michelle , Hayward J. L. , Takatani O. 
Published: February 2007

AbstractSerum‐free thyroxine (FT4) concentrations are lower in Hawaiian and Hawaiian Caucasian women than in Hawaiian Japanese, Hawaiian Filipino, Hawaiian Chinese, and English and Japanese mainland women. There is a high inverse correlation between FT4 and risk of breast cancer in these ethnic groups. Thyroid‐ stimulating hormone (TSH) concentrations, which are inversely correlated with FT4, generally show the same relationship.
Long‐term use of oral contraceptives and risk of invasive cervical cancer
Authors: Brinton Louise A. , Huggins George R. , Lehman Herman F. , Mallin Katherine , Savitz David A. , Trapido Edward , Rosenthal Jeanne , Hoover Robert 
Published: February 2007

AbstractTo evaluate the relationship between use of oral contraceptives and risk of invasive cervical cancer, a case‐control study involving 479 patients and 789 population controls was undertaken in 5 geographic regions of the US. Initially, the relationship was obscured by confounding variables, particularly the interval since last Pap smear. Control for this variable as well as for sexual and sociodemographic factors revealed an RR of 1.5 overall, with long‐term users (5 or more years) being at a 2‐fold higher risk than non‐users. Pill associations prevailed for both adenocarcinomas and squamous‐cell tumors, and risks were highest for those using pills containing high estrogen potencies. In addition, there was some evidence that pill associations were most pronounced among women who had never used barrier methods of contraception or who had histories of genital infections, suggesting that oral contraceptives may act as co‐carcinogens with transmisible agents. Our findings provide further evidence that long‐term use of oral contraceptives may have a carcinogenic effect on cervical epithelium, but emphasize the need for careful evaluation of confounding influences.
Growth of human mammary carcinoma cells from biopsy specimens in serum‐free medium on extracellular matrix
Authors: Biran S. , Vlodavsky I. , Fuks Z. , Lijovetzky G. , Horowitz A. T. 
Published: February 2007

AbstractA method developed for the initiation and maintenance in primary culture of human normal mammary epithelial cells was adopted for the growth of epithelial cells from 45 primary human breast tumors. The cells were grown on a naturally produced extracellular matrix (ECM) or on regular tissue culture plastic in a serum‐free medium containing growth supplements and high‐density lipoprotein (HDL). Successful enzymatic dissociation of the tumor biopsy into organoid structures and cell aggregates was crucial for subsequent cell attachment and growth. Fifty‐five percent of the biopsy specimens were successfully dissociated and 87% of these gave rise to actively dividing epithelial cells forming monolayer cultures. In contrast, only 21% of the biopsies which were not optimally dissociated yielded growing cultures. Variations in sample size, duration of enzymatic digestion, and tumor composition affected the outcome of tumor dissociation. Omission of serum from the culture medium prevented the growth of fibroblasts, while plating on ECM greatly improved and in some cases was essential for cell attachment and subsequent outgrowth. The epithelial nature of the cells was verified by their cuboidal and closely apposed morphology and positive staining with antikeratin antibodies. The growth and subculture requirements and the expression of the B38.1 tumor marker were compared in human mammary epithelial cells derived from solid tumors, pleural effusion and normal breast tissue.
Identification and localization of urokinase‐type plasminogen activator in human NK‐cells
Authors: Carpén O. , Saksela O. , Saksela E. 
Published: February 2007

AbstractWe have studied the presence of plasminogen activators in large granular lymphocytes and other peripheral blood cells. After immunofluorescence staining with polyclonal antiserum against urokinase‐ type plasminogen activator, the majority of LGLs showed granular staining which was located in Golgi‐ derived vesicles. LGLs were negative for tissue‐type activator. The presence of only urokinase‐type PA in LGLs was also confirmed by determining the molecular weight of the intracellular activator and by immunoblotting the antigen from solubilized cell preparations. Monocytes and granulocytes were more intensely stained with anti‐u‐PA than LGLs. In LGL/ K562 cell conjugates the fluorescence was often located close to the contact area and the vesicular fluorescence polarized during conjugate formation. Inhibitors of PA and other serine proteinases are known to abolish NK‐cell activity. We now show that they affect a later stage than programming for lysis in the cytotoxic action, suggesting a role for u‐PA or other serine proteases in the lethal‐hit stage of NK activity.
Cytomorphologic evaluation of the neoplastic potential of 28 cell culture lines by a panel of diagnostic cytopathologists
Authors: Boone Charles W. , Sanford Katherine K. , Frost John K. , Mantel Nathan , Gill Gary W. , Jones Gary M. 
Published: February 2007

AbstractA panel of 7 diagnostic cytopathologists, i.e., physicians trained to diagnose the malignant potential of human cells in Papanicolaou‐stained smears, was asked to evaluate two sets of microscope slides of stained coverslip preparations of 28 cell culture lines, 15 of which were neoplastic. Slide Set I consisted of 13 pairs of cell lines, one member of each pair being non‐ tumorigenic and the other tumorigenic; the lines were of mouse (9 pairs), rat (3 pairs), and human (1 pair) origin. Slide Set II contained 4 human lines: one lung cancer, one melanoma, and two fibroblast lines. Of a total of 114 diagnostic decisions by the panel, 88 were correct (66/86, 77%) in choosing which member of a pair was neoplastic and 22 were correct (22/28, 79%) in choosing whether a given individual human line was or was not neoplastic. Two members of the panel were correct more frequently, with 16/17 (94%) correct diagnoses, each. Five nuclear morphologic criteria of malignancy used by cytopathologists were prominent in the tumorigenic lines: altered chromatin pattern characterized by increasing size of chromatin granules and chromatin clumping, sharp angularity of large nucleolar and/or chromocenter borders with spicule formation (pointed projection), irregular parachromatin clearing (increase in the clarity of the clear spaces between chromatin threads, granules, and clumps), uneven thickness of chromatin at the nuclear border, and variability in nuclear size and shape from cell to cell. These markers of neoplastic transformation, when added to those previously reported, should increase overall accuracy in the diagnosis of neoplastic transformation of mammalian cells in culture.