bluuebunny/crossref_metadata_2025 huggingface dataset:
Karyotype evolution in a transformed rat cerebral endothelial cell line
Authors: Tyrkus Michael , Diglio Clement A. , Gohle Norma
Published: February 2007

Primary cultures of rat microvascular endothelial cells were transformed, in vitro, by exposure to Rous sarcoma virus. Transformed cells were followed and evaluated cytogenetically through numerous passages. Highly specific karyotypic changes in karyotype (both structural and numerical) were documented. These changes became established and intimately involved in further “karyotypic evolution”. The findings were reproducible, and when considered in the light of the literature suggest regular patterns of karyotypic change in rat tumors. The in vitro methodology utilized promises to be of practical value in the study of the early stages of malignancy.
A Rauscher‐virus‐induced T‐lymphocyte cell line. Induction of differentiation under influence of dimethylsulfoxide and phorbolesters
Authors: De Both N. J. , Rhijnsburger E. H. , Van Ewijk W.
Published: February 2007

DBA/2 mice which are neonatally infected with Rauscher helper virus (R‐MuLV) develop predominantly lymphatic leukemias. From one of these lymphatic leukemias we established a permanent cell line which we named RLD (Rauscher Lymphoid DBA/2). Phenotyping of this cell line with a panel of monoclonal antibodies directed to cell‐surface determinants shows that RLD cells have T‐cell characteristics: they bind monoclonal antibodies directed to the antigens Thy‐1, T‐200 and Lyt‐1; they do not react with anti‐Lyt‐2 antibodies, nor do they react with antibodies directed to determinants on B cells or myelomonocytic cells. RLD cells show a high activity of the nuclear enzyme terminal deoxyribonucleotidyl transferase (TdT). RLD cells are able to differentiate after in vitro stimulation with 1% DMSO or with 30 nM tetra‐decanoylphorbol‐1.3‐acetate (TPA). This differentiation process is reflected by (I) changes in the 2D gel electro‐phoresis pattern of metabolically labelled proteins, (2) a decrease in TdT activity and (3) changes in the expression of cell‐surface markers. Flow cytometric analysis of stimulated RLD cells shows a strong increase in the Lyt‐1 expression. Together these data indicate that RLD cells are immature T lymphocytes which upon appropriate stimulation differentiate along the line of T helper cells.
Stable heat‐resistant clones selected from wild‐type and surface variants of B‐16 melanoma
Authors: Tao Tien‐Wen , Calderwood Stuart , Hahn George M.
Published: February 2007

Stable heat‐resistant clones were selected from wild‐type B‐16 melanoma cells and from three of their surface variants resistant to the lectins wheat‐germ agglutinin, ricin and concanavalin A. The selection procedure included three or four cycles of heating the cells in culture at 43°C for 2‐1/2 to 3‐1/2 h interspersed with growth at 37°C. The survivability of the heat‐resistant (HR) variant cells at elevated temperatures of 43°C for 160 min and 45°C for 40 min was 2–4 logs greater than that of their respective parents. This acquired property of heat resistance appeared to be a stable phenomenon, persisting in these cell lines for more than 80 generations. One HR variant line carried in tissue culture for 250 generations showed no change in the heat‐resistance characteristic. Acquisition of resistance appeared to be a gradual process with intermediate stages preceding the more pronounced degree of resistance. These newly selected HR variants join the existing surface variants of B‐16 melanoma to result in a large family of variants from the same cell lineage to make this system a powerful tool for studying the relationship between heat sensitivity, metastasis and hyperthermia treatment of cancer.
Presence of EBV‐DNA sequences in nasopharyngeal cells of individuals without IgA‐VCA antibodies
Authors: Desgranges C. , Pi G. H. , Bornkamm G. W. , Legrand C. , Zeng Y. , De‐Thé G.
Published: February 2007

Exfoliated nasopharyngeal (NP) cells from 62 normal Cantonese Chinese having IgA/VCA antibodies for more than a year and from 39 similar persons without IgA/VCA antibodies, were tested for the presence of EBV/DNA sequences by spot followed by blot hybridization tests, using the cloned internal repeat of B95‐8 viral DNA as probe. Thirteen out of 62 specimens from IgA/VCA‐positive (21%) and six out of 39 specimens (15.4%) from IgA/VCA‐negative individuals were found to contain EBV/DNA sequences. Forty‐six cases (20 IgA/VCA‐positive and 26 IgA/VCA‐negative) were followed a year later for EBV/DNA sequences and EBV serology. Half of the individuals having EBV/DNA sequences in their exfoliated NP cells in 1981 did not have detectable EBV sequences a year later, and to out of 15 negative individuals became EBV/DNA‐positive. There was no obvious correlation between EBV/DNA detectability and EBV serology. (We conclude that the best marker for NPC risk remains the increasing IgA/VCA and/or EA antibody titers.)
Expression of major histocompatibility antigens and nature of inflammatory cellular infiltrate in ovarian neoplasms
Authors: Kabawat Salim E. , Bast Robert C. , Welch William R. , Knapp Robert C. , Bhan Atul K.
Published: February 2007

Expression of histocompatibility antigens and the intensity of inflammatory cellular infiltrate were evaluated in frozen tissue sections from 70 human ovarian tumors and six normal ovaries using monoclonal antibodies and an avidin‐biotin immunoperoxidase technique. In the normal human ovary, surface epithelial cells, mature granulosa cells and lutein cells reacted with anti‐HLA‐A, B, C (HLA) and beta2‐microglobulin antibodies but not with anti‐la (la‐like, HLA‐DR). Stromal cells and granulosa cells of the primordial follicles did not react with any of the antibodies. Among the neoplasms examined, all benign epithelial tumors, 86% of borderline an 81% of malignant epithelial tumors reacted with anti‐HLA and/or beta2‐microglobulin antibodies. HLA‐negative epithelial tumors were of serous or endometrioid types. Although la was not found in normal ovarian surface epithelium, the antigen could be detected in 44% of benign, and 43% of borderline and malignant epithelial ovarian tumors. Mono‐nuclear cellular infiltrate was generally scarce in ovarian tumors and consisted mainly of T cells. Malignant epithelial tumors contained significantly more T cells than did benign tumors. More T cells were observed in HLA‐positive ovarian tumors than in HLA‐negative neoplasms, but the difference did not achieve statistical significance. No correlation could be found between la expression and the intensity of T‐cell infiltrate. Significantly more T8 and Leu‐3a‐positive cells were found in the tumor stroma than amongst neoplastic cells. HNK‐I‐positive natural killer cells, OK‐MI‐positive macrophages and BI‐positive B lymphocytes were rarely encountered either in the tumor stroma or between adjacent tumor cells.
Karyotype evolution in B‐cell lymphoid malignancy with AN 8;14 translocation
Authors: Fukuhara Shirou , Kita Kenkichi , Nasu Kaori , Kannagi Mari , Kamezaki Tadashi , Ohno Hitoshi , Yamazowa Michihiko , Nishigori Masaru , Uchino Haruto , Yagita Masato , Matsuo Naomitsu , Yamabe Hirohiko , Tanaka Satoru
Published: February 2007

To evaluate the significance of karyotypic evolution of tumor cells with an 8;14 translocation [t(8;14)(q24;q32)], we examined the clinicopathologic features and immunologic phenotypes of nine Japanese patients with various types of B‐cell malignancy with the translocation. All these patients had structural rearrangements of the long arm of chromosome No. I (Iq) in a stem line or the sub‐line of tumor cells with a t(8;14). The rearrangements were composed of a translocation involving Iq with other chromosomes and a tandem duplication of Iq, and they were exclusively associated with a partial trisomy for Iq. Two patients with diffuse large‐cell lymphoma, whose tumor cells did not express surface immunoglobulins (s‐Ig), had the Iq translocation in their highly complex karyo‐types. Tumor cells from the other seven patients expressed s‐Ig and the karyotypes were relatively simple. Among these patients, the Iq translocation was found in two patients with Burkitt's lymphoma, and the Iq duplication were observed in a stem line or the sublines from four patients with Burkitt's lymphoma‐leukemia and one each with small non‐cleaved‐cell or diffuse large‐cell lymphoma. Except for one patient in the stage of IE, these patients had a poor prognosis because of the clinical conversion of extranodal metastases in the earlier disease phase. These findings are compatible with those of Western patients with a t(8;14). Therefore, tumor cells marked primarily with a t(8;14) could have “major routes” in the karyotypic evolution, for which potentials should be recognized as clinical risk factors, and the morphologic presentation and the expression of surface immunoglobulins may be associated with the process of karyotypic evolution.
Decreased natural killer activity in patients with liver cirrhosis
Authors: Nakamura Tatsuya , Morizane Toshio , Watanabe Tetsu , Tsuchimoto Kanji , Inagaki Yasutaka , Kumagai Naoki , Tsuchiya Masaharu
Published: February 2007

Natural killer (NK) activity of peripheral blood mono‐nuclear cells from patients with non‐alcoholic liver cirrhosis (LC) (30 cases), patients with other, non‐malignant diseases (41 cases), and healthy subjects (36 cases) were investigated using 51Cr‐labelled CCRF‐CEM and K562 target cells. NK activity in patients with LC was lower than that in healthy subjects and that in patients with other, non‐malignant diseases. The differences were statistically significant by Student's t‐test and the Wilcoxon rank test. There was no difference of NK activity between serologically hepatitis B surface antigen (HBsAg)‐positive and ‐negative patients.
Antibodies against three purified structural proteins of the human type‐C retrovirus, HTLV, in Japanese adult T‐cell leukemia patients, healthy family members, and unrelated normals
Authors: Schüpbach Jörg , Kalyanaraman V. S. , Sarngadharan M. G. , Nakao Y. , Ito Y. , Gallo Robert C.
Published: February 2007

The immunological relationship of human T‐cell leukemia/lymphoma virus (HTLV) and the virus found in Japanese adult T‐cell leukemia/lymphoma (ATL) was investigated in detail by testing the specific binding of serum antibodies from Japanese ATL patients and normal Japanese donors to the purified HTLV proteins p24, p19, and p15. Sera were prescreened for antibodies to p24. Of those positive, 67% of the ATL sera and 78% of the normal sera were further shown to have antibodies against p19. In both groups 17% had antibodies to p15. Generally, the average antibody titers were twice as high in ATL as in normal sera. Competition radioimmunoprecipitation assays done with various sera and involving HTLV‐producing cells, virus‐positive cells from a Japanese ATL patient, and virus‐positive cultured T cells of one of his healthy family members as competing materials demonstrated no differences between the p24, p19, and p15 found in these cells. These results provide strong and detailed immunological evidence that the human retrovirus isolates first made from US patients with cutaneous T‐cell malignancies, and those made later in Japanese ATL are either identical or very closely related strains of the same virus, HTLV, a finding verified in other detailed analyses of the HTLV genomes of the respective isolates. To date only HTLV‐II, isolated from a US case of hairy‐cell leukemia of a T‐cell type, is a distinct additional human retrovirus class.
Inhibition of initiator‐induced SV40 gene amplification in SV40‐transformed Chinese hamster cells by infection with a defective parvovirus
Authors: Schlehofer Jörg R. , Heilbronn Regine , Georg‐Fries Brigitte , Hausen Harald Zur
Published: February 2007

Amplification of SV40 genes in SV40‐transformed Chinese hamster embryo cells (CO631) by chemical carcinogens as well as by herpes simplex virus infection can be inhibited by infection with the defective parvovirus, AAV‐5. This is shown by in situ hybridization with SV40 DNA of AAV‐5‐infected CO631 cells after treatment with herpes simplex virus type I or with chemical carcinogens: the initiator‐induced selective amplification of SV40 sequences is prevented in the presence of the parvovirus. During HSV‐infection and also in the presence of carcinogens, in CO631 cells parvovirus DNA is synthesized and AAV‐5‐specific antigens are expressed as revealed by hybridization with cloned AAV‐5 DNA or by immuno‐fluorescence with monoclonal antibodies, respectively. The inhibition of initiator‐induced gene amplification could point to the mechanism of parvovirus‐mediated inhibition of tumor development and may indicate an important role of selective gene amplification in oncogenesis.
Immunoaffinity chromatography of a cellular tumor antigen from mouse neuroblastoma cells
Authors: Levitsky Kenneth , Chandrasekaran Krish , Mora Peter T. , Simmons Daniel T.
Published: February 2007

The cellular tumor antigen p53 was isolated from mouse neuroblastoma cells and was found in a form not complexed to another protein. The p53 in these cells was stable, turning over about every 10 h. Its methionine‐labelled tryptic peptides were very similar to those of the p53 isolated from SV40‐transformed mouse cells. The labelled protein was purified from neuroblastoma cells by immunoaffinity using specific monoclonal antibodies and was about 80% radiochemically pure. Furthermore, the purified p53 sedimented in sucrose gradients with a sedimentation coefficient of approximately 8S. This correlated with the sedimentation coefficient of p53 prior to purification, showing that the purified protein retained its native size.
Increase in homotypic aggregation of metastatic morris hepatoma cells after fusion with membranes from non‐metastatic cells
Authors: Hausman R. E.
Published: February 2007

Three types of Morris hepatoma: 7288C, 5123tc, and 9618A were assessed for their ability to grow and produce metastases in the lungs of male buffalo rats. Hepatoma 7288 formed metastatic growths more rapidly than 5123, while 9618 did not form metastatic growths in the lung at all. Cells from the same three hepatomas were then assessed for their ability to aggregate homotypically in vitro. This was used as a measure of potential for detachment from the site of primary growth in vivo, one of the critical steps in metastasis. The results were that 9618 aggregated more effectively than 5123 and 7288 did not aggregate homotypically. Thus, the ability to metastasize and the ability to aggregate homotypically were inversely related in these three tumors, with the most metastatic tumor, 7288, hardly aggregating at all. Was the ability of hepatoma 9618 to aggregate homotypically and the inability of hepatoma 7288 to do so a characteristic of the plasma membrane? Plasma membranes either from the tumor which aggregated best, 9618, or from the liver of non‐tumorous neonatal buffalo rats were fused into the surface of the 7288 cells. Either fusion conferred the ability to aggregate on the previously non‐aggregating metastatic hepatoma cells. In contrast, fusion of plasma membranes from hepatoma 7288 into 9618 cells failed to affect their ability to aggregate homotypically. The aggregation‐conferring effect required actual fusion of the donor membrane, was dependent on the amount of membrane fused and was sensitive to treatment of the donor plasma membranes with trypsin. The results are interpreted as suggesting the presence of homotypic aggregation materials, probably proteins, in the plasma membranes of non‐metastatic cells. These may be reduced or absent in the membrane of the highly metastatic hepatomas.
Gamma‐interferon (IFN‐γ) produced during effector and target interactions renders target cells less susceptible to NK‐cell‐mediated lysis
Authors: Grönberg Alvar , Kiessling Rolf , Masucci Giuseppe , Guevara Luis A. , Eriksson Eréne , Klein George
Published: February 2007

Human mitomycin C‐treated PBL were mixed with cells of an NK sensitive hybrid cell line (PUTKO‐I). A fraction of tumor cells survived this treatment and could be recovered from the cultures. These surviving cells were completely NK‐resistant and this property persisted for 2–3 weeks after cultivation in fresh medium. Treatment of a clone (C13) of PUTKO‐I with PBL‐PUTKO mixed lymphocyte‐tumor‐cell culture (MLTC) supernatants resulted in a marked reduction in NK sensitivity after 8–12 h of treatment. The kinetics of induction of NK resistance by MLTC supernatants was similar to that of purified IFN‐γ and was faster than for IFN‐α. The active component in the supernatants was characterized as a mixture of IFN‐γ and IFN‐α based on neutralization of activity with specific antisera. The role of mycoplasma contamination was investigated and it was found that cell lines free of detectable mycoplasma stimulated production of NK‐protective activity by PBL and this activity was neutralized by anti‐IFN‐γ serum. Separation of PBL on discontinuous Percoll gradients demonstrated a correlation between the NK activity of cell fractions and their ability to produce IFN in response to tumor cells. Taken together, the selection‐dependent variations in NK sensitivity, the kinetics of IFN production and induction of resistance suggest that tumor cells may be able to escape elimination by NK cells due to protection by IFN produced by the effector‐cell‐containing population.
A 3q+ marker chromosome in EBV‐carrying nasopharyngeal carcinomas
Authors: Mitelman F. , Mark‐Vendel E. , Mineur A. , Giovanella B. , Klein G.
Published: February 2007

The malignant epithelial cells of two anaplastic EBV‐carrying nasopharyngeal carcinomas (NPC) were investigated cytogenetically by Giemsa banding technique. Both tumors had a similar 3q+ marker chromosome with an involvement of band q25, either a dupliction of the region q25–q27, or insertion of an unidentified segment at band q25.
Characterization of malignant and non‐neoplastic cell phenotypes in highly malignant non‐Hodgkin lymphomas
Authors: Porwit‐Ksiazek Anna , Christensson Birger , Lindemalm Christina , Mellstedt Håkan , Tribukait Bernhard , Biberfeld Gunnel , Biberfeld Peter
Published: February 2007

Malignant and non‐neoplastic cells in 38 cases of highly malignant non‐Hodgkin lymphomas: 3 centrocytic anaplastic, 18 centroblastic, 13 immunoblastic and 4 lymphoblastic (according to the Kiel classification) were immunophenotyped in cryosections and cell suspensions by means of monoclonal antibodies. Additionally, cell cycle analysis on cell suspensions was performed by DNA flow cytofluorometry. In 33 (87%) lymphomas the malignant cells expressed monoclonal surface immunoglobulin (Ig), which indicated B‐cell origin of tumors. In 7 of the 19 B‐cell lymphomas tested by the peroxidase‐antiperoxidase method, cytoplasmic Ig was found. Four lymphomas were of T‐cell and one of non‐B/non‐T‐cell origin. In 11 B‐cell and 2 lymphoblastic non‐B‐cell tumors, common acute lymphobiastk leukemia antigen (CALLA) was found. In 25 of 30 studied NHL the mafignant cells expressed receptor for transferrin and in 19 of 28 cases a high percentage of cells in S‐phase (> 10.85%) was found. Number and distribution as well as type of non‐B‐cell infiltrating B‐cell‐derived lymphomas varied considerably from case to case. Among these cells Leu 3+ (T heloer/inducer) cells predominated. Leu 2+ (T suppressor/cytotoxk) and Leu 7+ (natural killer and killer) cells constituted less numerous groups. Correlation of cytodiagnostic analyses with clinical observations indicates that high content of infiltrating T cells may be a favorable prognostic feature in highly malignant B‐cell lymphomas.
Prognostic implications of karyotype and morphology in patients with non‐Hodgkin's lymphoma
Authors: Kaneko Yasuhiko , Rowley Janet D. , Variakojis Daina , Haren J. Marie , Ueshima Yoshimi , Daly Karen , Kluskens Larry F.
Published: February 2007

Clonal chromosome abnormalities were observed in 30 patients with non‐Hodgkin's lymphoma; the type of lymphoma was characterized on the basis of the International Working Formulation. The 30 patients were classified into five groups according to the chromosome abnormality. There were 8 patients with t(14;18), 3 with t(8;14), 7 with a translocation to the long arm of chromosome 3 (a 3q+ chromosome), 5 with near‐tetraptoidy, and 7 with other abnormalities. Among the 8 patients with t(14;18), 5 had follicular small cleaved‐cell lymphoma (FSC), I had follicular mixed cell lymphoma (FM), and 2 had diffuse large‐cell lymphoma (DL); the diagnosis in these 2 patients was based on extranodal tissue. All 3 patients with t(8;14) had DL and B‐cell markers. Except for I patient, all those with a 3q+ chromosome had DL; 4 of those who were tested had B‐cell or pre‐B‐cell markers. Four of the 5 patients with near‐tetraploidy had follicular mixed‐cell lymphoma, and 2 of the 7 patients with other abnormalities had T‐cell lymphoma. Thus, patients with a t(8;14), a 14q+ chromosome, or a 3q+ chromosome all tend to have diffuse large‐cell lymphoma, usually of the non‐cleaved type. On the other hand, our data suggest that patients with FSC generally have a t(14;18) whereas those with follicular and diffuse mixed small cleaved cells and large non‐cleaved cells have a different pattern with modal chromosome numbers in the tetraploid range. We added 17 previously reported patients to the 30 presented here and correlated the karyotype with survival. The 6 patients with near‐tetraploidy had the longest median survival, 69 months, the 15 patients with t(14;18) had the next longest, 48 months. The 4 patients with (8;14) had Che shortest urvival, 12 months, and the 9 with other abnormalities had the next shortest, 17 months. Intermediate survivals of 27 and 30 months were observed in patients with a 14q+ or a 3q+ chromosome, respectively. The median survival of thaw various categories differs and our data, thus, indicate that the karyotypic pattern of the malignant cell may be a significant independent prognostic feature influencing the survival of patients with non‐Hodgkin's lymphoma.
Establishment and characterization of a human colon carcinoma cell line (KMS‐4) from a patient with hereditary adenomatosis of the colon and rectum
Authors: Namba Masayoshi , Miyamoto Kanji , Hyodoh Fuminori , Iwama Takeo , Utsunomiya Joji , Fukushima Fujiko , Kimoto Tetsuo
Published: February 2007

A human colon carcinoma cell line was established from a metastatic lymph node of a patient with hereditary adenomatosis of the colon and rectum (ACR). Cells of this line, designated KMS‐4, have been continuously propagated in culture during the past 24 months. The cells growing on the surface of culture dishes showed epithelial features, and, when inoculated into athymic nude mice, produced adenocarcinomas with a morphology similar to that of the original tumor. Electron micrographs showed that the cultured cells have desmosomes and numerous surface microvilli typical of colon epithelium. Chromosomal analysis revealed the cell line to be of human origin with a diptoid mode of chromosome number, but the karyotypes examined were all abnormal. Most of the metaphases Commonly had such abnormalities as 7p+, 12p+, +13, +16 and 17p+, accompanied by loss of chromosome No. 19 and/or 20, and, interestingly, all the metaphases contained 7p+ and +13. The cells had a log phase doubling time of 48 to 72 h. The cloning efficiency of the cells was 0.06% in the soft agar medium. Neither 12‐0‐tetradecanoytphorbol‐13‐acetate nor bile acids enhanced cell proliferation. The cells abundantly secreted CEA protein into the culture medium (700 ng/ml/106 cells during a 48 h period). The present colon carcinoma cell line derived from a genetically defined individual with ACR should prove useful for research in human oncology or genetics.
A pigmentation‐associated, differentiation antigen of human melanoma defined by a precipitating antibody in human serum
Authors: Mattes M. Jules , Thomson Timothy M. , Old Lloyd J. , Lloyd Kenneth O.
Published: February 2007

Antibodies in the serum of melanoma patient AU precipitate an antigen from 125I‐labelled extracts of cultured autologous melanoma cells. The antigen, which is probably not a cell surface component, is present in other pigmented melanomas but not in non‐pigmented melanomas or other tumor cell types, and the amount of antigen is correlated with the degree of pigmentation. These conclusions are based on absorption experiments with 11 pigmented melanomas, 8 non‐pigmented melanomas, 3 astrocytomas, 12 carcinomas of various histological types, 1 leukemia, 2 EB‐virus‐transformed B lymphocyte lines, and human erythrocytes. The antigen was also detected in cultured human melanocytes. It has a molecular weight of 70,000, an isoelectric point of pH 5.3, and it binds to concanavalin A‐Sepharose. Ninety‐six sera from other melanoma patients were examined and none of them precipitated this antigen. As described previously, the serum from patient AU also has antibodies to a unique (Class 1) tumor antigen found only on AU melanoma cells. The pigmentation‐associated, differentiation antigen and the unique antigen are clearly different in their distribution, but some relationship between these unusual antibody responses is possible.
A prospective study of urinary androgen levels and ovarian cancer
Authors: Cuzick Jack , Bulstrode J. C. , Stratton I. , Thomas B. S. , Bulbrook R. D. , Hayward J. L.
Published: February 2007

The three major urinary androgen metabolites, dehydroepiandrosterone (DHEA), androsterone (ANDRO), and aetiocholanolone (AETIO) were measured in 1,484 volunteer women between 29 and 60 years of age on the island of Guernsey from 1962–1967. Twelve of these women subsequently developed ovarian cancer after a median interval of 130 months and a minimum interval of 19 months. All three androgen levels in these women were lower than those in controls matched for age and menopausal status. The results were most striking for DHEA, where half of the cases were below the 27th percentile of their matched controls (p = 0.007, two‐sided). The results for ANDRO were of marginal significance (p = 0.06), and those for AETIO were not significant (p= 0.033).
Dietary cholesterol and lung cancer risk in a multiethnic population in Hawaii
Authors: Hinds M. Ward , Kolonel Laurence N. , Hankin Jean H. , Lee James
Published: February 2007

We interviewed 364 subjects with lung cancer and 627 age‐ and sex‐matched controls among the multiethnic population of Hawaii. Quantitative estimates of dietary cholesterol and vitamin A intakes were obtained, as well as smoking and occupational histories. Using multiple logistic regression analysis to control for potential confounding variables, we found a monotonic positive dose‐response relationship between dietary cholesterol and lung cancer risk in all subjects, in smoking subjects, and in men. In each of these groups, subjects in the highest quartile of dietary cholesterol were at significantly increased risk of lung cancer (lower 95% confidence limit >1.0). Among females, however, no clear association of dietary cholesterol with lung cancer risk was apparent.
Protein a treatment of cancer: Activation of a serum component with trans‐species anti‐B16 melanoma activity
Authors: Cooper Peter D. , Masinello Gillian R.
Published: February 2007

Mice (C57BL) succumbed to cultured B16 melanoma cells i.p. with reproducible kinetics and an MST2 of about 26 days. Serum from tumour‐bearing or normal mice was treated at 0°C with fixed SAC cells and injected i.p. into fresh tumour‐bearing mice. If serum was given 7 days or less after B16 inoculation, the MST of the mice was highly significantly increased by up to 32%. Similar activity has been generated in normal human, rabbit and guinea‐pig serum, while untreated sera were ineffective. Apparently the sera contained an inactive native precursor that was activated by the SAC to produce an anti‐tumour agent. Precursor and product were both relatively labile at 0°C. Anti‐tumour activity was eluted at pH 2.5 from SAC or Sepharose‐protein‐A pretreated with serum, thus implicating the protein A component of SAC. The eluates contained haemolytically active Cl, the first component of complement, and five crude Cl preparations made by standard methods showed good anti‐tumour activity. However, seven other highly haemolytic Cl preparations had no anti‐tumour effect. Similarly, two crude preparations of the subcomponent Clq had good anti‐tumour activity, but eight other, more pure and highly haemolytic Clq preparations were inactive in mice. Thus the antitumour principle was not Cl or Clq alone, although it had some chemical properties in common with these substances. It remains unidentified, but has potential interest for cancer therapy.
Enhancement or inhibition of tumor growth by interferon: Dependence on treatment protocol
Authors: Murasko Donna M. , Fresa Kerin , Mark Raymond
Published: February 2007

MSC cells are tumor cells originally induced in BALB/c mice by Moloney sarcoma virus. In these studies we demonstrated that, although these tumor cells are sensitive in vitro both to lysis by NK or NK‐like cells and to the growth‐inhibitory effect of murine L‐cell interferon (IFN), the growth of the tumor in vivo could be either inhibited or enhanced by IFN. The outcome of in vivo IFN treatment was dependent on the timing and route of IFN administration relative to tumor challenge. IFN given systemically at the same time as tumor challenge resulted in enhancement of primary tumor formation, rate of tumor growth and subsequent progressive tumor growth. In contrast, IFN administered at the site of tumor inoculation on days 1–3 after tumor challenge inhibited tumor formation and growth. Histopathology of tissue sections obtained from the site of tumor challenge confirmed these results. Similar studies performed in mice given 450 rads of X‐irradiation showed that IFN could still inhibit tumor growth when administered at the site of tumor inoculation on days 1‐3 after tumor challenge. IFN administered simultaneously with tumor challenge, however, did not enhance tumor growth in irradiated mice. These results are consistent with the interpretation that 1) inhibition of MSC‐induced tumor growth by IFN has a radioresistant component and 2) the enhancement of MSC‐induced tumor formation by IFN is dependent on interaction with a radiosensitive population of cells, possibly lymphoid cells.
Association between susceptibility to dibenzanthracene‐induced fibrosarcoma formation and the Ah locus
Authors: Kour Richard E. , Connolly Geralynn M. , Nebert Daniel W. , Lubet Ronald A.
Published: February 2007

The relationship between the Ah locus and the induction of subcutaneous fibrosarcomas by dibenz[a,h]anthracene and dibenz[a,c]anthracene was investigated in C57BL/6J (Ahb/Ahb), (C57BL/6J)(DBA/2J)F1 (Ahb/Ahd) and (Ahd/Ahd) mice. Ahb/Ahb and Ahb/Ahd mice have the high‐affinity Ah receptor and therefore the polycyclic hydrocarbon induction of aryl hydrocarbon hydroxylase activity (cytochrome P1‐450) proceeds with ease; Ahd/Ahd mice have the poor‐affinity Ah receptor and this induction process proceeds more poorly, by a factor of at least 10‐fold. Dibenz[a,c]anthracene proved to be a relatively weak carcinogen, producing less than 3% tumor incidence at doses up to 300 μg per mouse. In contrast, dibenz‐[a,h]anthracene caused an almost 50% tumor incidence in Ahb/Ahb and Ahb/Ahd mice, while causing ∼2% tumor incidence in Ahd/Ahd mice. Both isomers bind avidly to the cytosolic Ah receptor, and both chemicals induce aryl hydrocarbon hydroxylase activity in Ahb/Ahb and Ahd/Ahd animals. Among progeny of the (C57BL/6J) (DBA/2J) F1 × DBA/2J backcross, 63 of 100 Ahb/Ahd mice and none of 75 Ahd/Ahd mice developed tumors. These data demonstrate a strict correlation between susceptibility to dibenz[a,h]anthracene‐induced subcutaneous tumors and expression of the Ahb allele, i.e. presence of the high‐affinity Ah receptor and therefore readily inducible P1‐450.
Cell surface properties of high‐ and low‐metastatic cell lines selected from a spontaneous mouse lung carcinoma
Authors: Steele John G. , Rowlatt Charles , Sandall Jane K. , Franks L. M.
Published: February 2007

The surface oligosaccharide residues, glycoproteins and sialyl components of CMT64 lung carcinoma cells and high‐metastatic sublines CMT167 and CMT181 have been studied in culture. (I) The total cellular sialic acid content did not differ appreciably between the three lines. However, the accessibility of surface sialyl groups, measured by metabolic incorporation of [3H]NAcmannosamine followed by neuraminidase hydrolysis, was decreased from 42% in CMT64 to 25% hydrolyzed in CMT181. (2) The major plasma membrane glycoproteins of the lines were radiolabelled by lactoperoxidase iodination, metabolic incorporation of [3H]fucose or labelling in the terminal sialyl residues by the NalO4‐NaB[3H]4 method and the labelled glycoproteins were analyzed by two‐dimensional gel electrophoresis. Each labelling technique identified a complex pattern of glycoproteins including a prominently labelled group of high‐molecular‐weight acidic sialoglycoproteins: GP200/4.9–5.1 (apparent molecular weight ×10−3/pI of iodoprotein); GP150/5.1–5.6; GP130/5.0–5.6; GP110/5.0; GP100/4.8 and GP100/5.0–5.4. (3) The neuraminidase‐susceptible glycoproteins on CMT64 and CMT181 were identified in the isoelectric focusing separation of the two‐dimensional gel separation by the charge difference caused by desialylation. The glycoproteins most susceptible to neuraminidase were the high‐molecular‐weight acidic glycoproteins which showed marked charge heterogeneity: GP150/5.1–5.6, GP130/5.0–5.6; GP100/5.0–5.4 and GP100/4.8. (4) Using these procedures we did not detect modifications between CMT181 and CMT64 and we conclude that the cultured cells of the sublines do not display marked surface glycoprotein alterations that reflect their enhanced spontaneous metastatic potential.
Cross‐linking of cell surface immunoglobulins induces epstein‐barr virus in burkitt lymphoma lines
Authors: Takada Kenzo
Published: February 2007

Anti‐human immunoglobulin (Ig) antibodies with single‐chain specificities induced Epstein‐Barr virus (EBV) in various Burkitt lymphoma lines when the corresponding Ig chain was expressed on the cell surface. The F(ab')2 fragments of IgG antibody were as potent as intact Ig, while the Fab and Fc fragments gave no induction, indicating that cross‐linking of surface Ig was required for the induction. Simultaneously with EBV induction, anti‐Ig inhibited the uptake of 3H‐thymidine. This inhibition was also seen in EBV‐genome‐negative Burkitt lymphoma lines. In contrast, no effect on virus induction and cell growth was noted in lymphoblastoid lines of non‐neoplastic origin. The possible relationship between cell differentiation and latency of EBV‐carrier state is discussed.
Prospective study on the relationship between cervical neoplasia and herpes simplex type‐2 virus. I. Epidemiological characteristics
Authors: Vonka V. , Kaňka J. , Jelínek J. , Šubrt I. , Suchánek A. , Havránková A. , Váchal M. , Hirsch I. , Domorázková E. , Závadová H. , Richterová V. , Náprstková J. , Dvořáková V. , Svoboda B.
Published: February 2007

To determine the risk associated with previous herpes simplex type‐2 (HSV‐2) infection and possibly other virus infections, a prospective study of cervical neoplasia in more than 10,000 women was performed in the 1975–1983 period. The subjects were selected at random from an alphabetical listing of eligible women living in one district of Prague. At enrolment colposcopy and cervical cytology were performed, a blood sample was taken and data regarding education, socio‐economic status, personal habits and sexual and reproduction‐associated attributes were otained from each woman. A total of 10,683 women were enrolled; a complete set of data was obtained in 10,389 were invited for further colposcopical and cytological investigations after 2 years and 4 years, the other women were followed at 3‐to 6‐monthly intervals. In women with highly significant findings, histological investigation was performed. The total of 150 cases of moderate to severe dysplasia (i.e. cervical intraepithelial neoplasia, grade II, CIN II), 83 cases of carcinoma in situ(CIN III) and 21 cases of invasive carcinoma (INCA) were detected. More than 60% of the patients were ill at enrolment, the other cases developed in subjects with originally slightly suspicious (27 CIN II, 17 CIN III, 3 INCA) or negative findings (30 CIN II, 12 CIN III, 3 INCA). Analysis of the data indicated significantly positive correlation of one or more of these clinical conditions with a number of sexual and reproduction‐related attributes of which early age at first intercourse was most consistent. Among the other attributes, the smoking habit was associated with the highest risk of developing the disease. A negative correlation of cervical neoplasia with several attributes was demonstrated; of these diathermoelectrocoagulation of the ectopic epithelium and transformation zone of cervix was the most important single protective factor. On the basis of these findings, control subjects were selected for serological studies.
Prospective study on the relationship between cervical neoplasia and herpes simplex type‐2 virus. II. Herpes simplex type‐2 antibody presence in sera taken at enrolment
Authors: Vonka V. , Kanaka J. , Hirsch I. , Závadová H. , Krčmář M. , Suchánková A. , Řezácová D. , Brouček J. , Press M. , Domorázková E. , Svoboda B. , Havránková A. , Jelinek J.
Published: February 2007

Sera obtained at enrolment in the study from patients suffering from moderate to severe dysplasia (cervical intraepithelial neoplasia grade II), carcinoma in situ (cervical intraepithelial neoplasia grade III) and invasive carcinoma, or developing any of these conditions in the course of the prospective study, and from control subjects, were examined for herpes simplex type‐2 (HSV‐2) antibody presence. The controls were matched with the patients by age, age at first intercourse, number of sexual partners, smoking habits and history of diathermoelectrocoagulation of the ectopic epithelium and transformation zone of cervix. Only those subjects were selected as controls who remained free of pathological colposcopical and cytological findings throughout the observation period, i.e. for at least 4 years after their serum sample was obtained. The microneutralization test (MNT) and type‐2‐specific solid‐phase radioimmunoassay (SPIRA) were used as serological tests. No difference in the prevalence of HSV‐2 antibody between the patients and controls was revealed by either test. Various combinations of the results from the two tests also failed to show any difference between patients and controls. Moreover, no significant differences were observed in the prevalence of HSV‐2 antibody between patients suffering from the various pathological conditions and those diagnosed at enrolment and later in the course of the study. These results do not provide any support for the hypothesis of the involvement of HSV‐2 in cervical neoplasia.
Immunological responses to a murine mammary adenocarcinoma. outgrowth of pulmonary occult metastases induced by immunosuppressive perturbations
Authors: Yamamura Yasuhiro , Braunschweiger Paul G. , Ramananda Madyastha K. , Proctor Julian W.
Published: February 2007

Intravenously (i.v.) or subcutaneously (s.c.) injected T1699 tumor cell subpopulations (Ts, and TL1–1) were destroyed more rapidly in BALB/c nu/nu athymic mice than in syngeneic DBA/2J mice. The number of artificial pulmonary metastases of TL1–1 tumors was significantly lower, and the growth rate of s.c. Ts, and TL1–1 tumors was correspondingly slower in the nude mice. No macroscopic outgrowth of pulmonary metastases of Ts tumors was detected in either group of s.c. tumor‐bearers, even though the s.c. tumors progressed and killed the hosts. Unexpectedly, however, s.c. implantation in normal DBA/2J mice of lung homogenates not only from DBA/2J but also from s.c. Ts tumor‐bearing BALB/c nu/nu mice produced tumors, suggesting that significant numbers of clonogenic Ts cells were present in the lungs of animals without spontaneous outgrowth of pulmonary metastases. Perturbations of s.c. Ts tumor‐bearing DBA/2J or BALB/c nu/nu mice with immunosuppressive drugs or with anti‐mouse thymocyte serum, respectively, induced rapid outgrowth of pulmonary metastases.
Lymphoreticular cells isolated by centrifugal elutriation from a mammary adenocaricinoma. i. characterization of an in situ lymphocyte suppressor population by surface markers and functional reactivity
Authors: Buessow Scott C. , Paul Ronald D. , Miller Alan M. , Lopez Diana M.
Published: February 2007

The procedure of centrifugal elutriation was evaluated as a means of purifying large numbers of in situ lymphocytes from enzymatically disaggregated mouse mammary tumors. The eluate obtained at a flow rate of 3.0 ml/min was optimal for high levels of lymphocyte recovery with low levels of contaminating tumor cells, polymorphonuclear leukocytes, and macrophages. The majority of the tumor infiltrating lymphocytes (90%) expressed the Thy 1.2 antigen, while less than 5% possessed surface immunoglobulin. Further analysis of the T lymphocyte population was accomplished by flow cytometric analysis of in situ lymphocytes stained with fluorescein‐conjugated monoclonal anti‐Lyt 2 antibodies. The results of such studies reveal an increase in the levels of Lyt 2+ lymphocytes within the in situ population. To determine whether these Lyt 2+ cells were functionally active as suppressor cells, the ISL1 were mixed with spleen cells from tumor bearers and then tested for their ability to respond to mitogen and TAA‐induced blast transformation of tumor‐bearer spleen cells. Removal of macrophages from ISL by Sephadex G‐10 columns did not alter the suppression. Treatment with monoclonal anti‐Lyt 1 antibody and complement did not affect the inhibition observed. However, treatment of ISL with anti‐Lyt 2+ monoclonal antibody and complement resulted in the elimination of the suppressor cell activity. We concluded that within the tumor‐infiltrating lymphoreticular cells there is a population of Thy 1.2+ Lyt 2.2+ lymphocytes responsible for the suppression of mitogen and tumor‐antigen‐induced blastogenesis.
Effect of hydrocortisone on the macrophage content, growth and metastasis of transplanted murine tumors
Authors: Acero Raffaella , Polentarutti Nadia , Bottazzi Barbara , Alberti Saverio , Ricci Maria Rosaria , Bizzi Adalgisa , Mantovani Alberto
Published: February 2007

Hydrocortisone (HC) reduced the macrophage content of four murine tumors to less than half of control values. Since HC causes monocytopenia and inhibits the recruitment of mononuclear phagocytes at sites of inflammation but does not affect the viability and proliferative capacity of macrophages, this finding suggests that the maintenance of macrophage levels in growing tumors is in part dependent upon the entry into the neoplasm of circulating monocytes. HC inhibited the growth of these tumors. The effect of HC was most marked on the mFS6 and MN/MCA1 sarcomas and 3LL carcinoma, with only marginal inhibition in the M109 carcinoma. HC augmented spontaneous and/or artificial (i.v.) metastasis in these tumor models. Cells from metastatic foci of the mFS6 sarcoma and M109 carcinoma inoculated i.m. were as susceptible to HC as cells from primary tumors. The effects of HC on macrophage content, growth and metastasis of the M109 carcinoma and mFS6 sarcoma were similar in mice with defective T‐cell function (nude or thymectomized) or defective NK activity (beige or antiasialo GM1‐treated) and in controls. The in vitro growth of the mFS6 and MN/MCA1 sarcomas was not modified by HC. Some inhibition of tumor‐cell proliferative capacity was observed with the 3LL and M109 tumors. Tumor cell had high‐affinity binding sites for glucocorticoid hormones, but these were not correlated to susceptibility in vivo. Thus it is unlikely that a direct interaction of HC with tumor cells accounts for the inhibition of tumor growth observed in vivo. To evaluate whether HC affected tumor growth by reducing the macrophage content of tumors, mFS6 sarcoma cells were transplanted, mixed with peritoneal macrophages into normal or HC‐treated mice. Macrophages did not affect the growth of tumor cells in normal mice, whereas in HC‐created animals lesions from mixtures of macrophages and sarcoma cells appeared earlier and weighed more than those from tumor cells alone or tumor cells and thymocytes. However, macrophages did not reconstitute growth of the other sarcoma (MN/MCA1) in HC‐treated mice. These results are consistent with the hypothesis that HC inhibited growth of some poorly immunogenic transplanted murine tumors, at least in part, by interfering with the macrophage levels in neoplastic tissues, tumor‐associated macrophages providing the conditions for optimal tumor‐cell proliferation at least in some neoplasms.
Induction of plasma membrane alterations in AKR‐2B mouse embryo fibroblasts by endogenous growth factors from malignant human cells
Authors: Marks Michael E. , Brattain Michael G.
Published: February 2007

AKR‐2B mouse fibroblasts were treated with 50 μg/ml of crude transforming growth factor (TGF) of human origin. Cell surface proteins of treated cells were radioiodinated and compared to untreated cells at various times after the addition of TGF. Treated cells showed a several‐fold increase (0˜6‐fold) in cell surface 125I incorporation relative to normal cells at 24 h. Electrophoretic comparisons of treated and untreated cells showed large increases in the labelling of cell surface proteins of mol. wt. 50,000–90,000 from TGF‐exposed cells between 10 and 24 h post treatment. By 48 h post treatment, the electrophoretic profiles of TGF‐exposed cells had returned to a pattern similar to that of untreated cells. However, even after a 48 h exposure to TGF, the cells retained a transformed morphology indicating that the electrophoretic alterations were not simply due to the morphological transformation induced by TGF. The electrophoretic pattern of TGF‐treated cells at 24 h post treatment was similar to that of AKR‐2B cells permanently transformed by treatment with methylcholanthrene, but was clearly distinct from that induced by treatment of normal AKR‐2B cells with epidermal growth factor (EGF). EGF induced an increase in a protein of mol. wt. 60,000 in the electrophoretic profile taken 24 h post treatment. As with TGF, the appearance of electrophoretic profiles of EGF‐treated cells returned to ‚normal’︁ by 48 h. Again, these alterations did not appear to be dependent upon morphological changes since EGF‐treated cells showed a morphological transformation similar to that of cells treated with TGF, and this was maintained throughout the 48 h experimental period.
In vitro antibody‐dependent cellular cytotoxicity against human T‐cell leukemia/lymphoma virus (HTLV)‐producing cells
Authors: Miyakoshi Hideo , Koide Hiroko , Aoki Tadao
Published: February 2007

Human T‐cell leukemia/lymphoma virus (HTLV)‐producing cells were lysed by peripheral mononuclear cells (PMNC) from both anti‐HTLV antibody‐positive and ‐negative healthy persons in the presence of natural humoral antibodies against HTLV‐related antigens (antibody‐dependent cellular cytotoxicity, ADCC). PMNC from patients with T‐cell leukemia, however, did not possess the positive reaction even in the presence of natural antibodies. In contrast, when the antibodies were absent, no cytotoxicity was caused by PMNC from any donors. Additionally, the complement present in the antibody‐positive plasma did not contribute to humoral antibody‐dependent cytotoxicity in the presence of plasma without PMNC. Therefore, ADCC against HTLV‐producing cells may correlate with the prophylaxis of HTLV‐induced malignancy in vivo.