bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective inhibition by monosaccharides of tumor cell cytotoxicity mediated by mouse macrophages, macrophage‐like cell lines, and natural killer cells
Authors: Brunda Michael J. , Wiltrout Robert H. , Holden Howard T. , Varesio Luigi
Published: February 2007

A series of monosaccharides were tested for their ability to inhibit the effector phase of macrophage‐mediated cytolysis against two susceptible murine tumor target cells, L5I78Y and RL♂I. Two monosaccharides, D‐mannose and N‐acetyl‐D‐galactosamine, were found to decrease cytotoxicity consistently in a dose‐dependent manner. However, D‐mannose preferentially inhibited lysis of RL♂I target cells with little effect on lysis of L5I78Y target cells, while the reverse was found with N‐acetyl‐D‐galactosamine. Neither monosaccharide interfered with the activation of macrophages by polyinosinic:polycytidylic acid. Natural killer cell activity was decreased by a 25 mM concentration of D‐mannose but not by N‐acetyl‐D‐galactosamine, although increasing concentrations of N‐acetyl‐D‐galactosamine were inhibitory. Neither monosaccharide affected cytotoxicity by alloimmune T cells. Cytotoxicity of macrophage‐like cell lines against tumor target cells was also decreased by monosaccharides but the pattern of inhibition was different from that seen with activated macrophage effector cells. Both D‐mannose and N‐acetyl‐D‐galactosamine inhibited glucose oxidation by activated macrophages but only D‐mannose significantly decreased protein synthesis of activated macrophages. These results indicate that monosaccharides can inhibit macrophage‐mediated cytotoxicity in a selective manner with the pattern dependent on the tumor target cell used in the assay.
Dietary habits and lung cancer risk
Authors: Kvåle Gunnar , Bjelke Erik , Gart John J.
Published: February 2007

A previously reported negative association between a high index of dietary vitamin A and lung cancer incidence was confirmed in an extended follow‐up, covering 11 1/2 years, of 13,785 men and 2,928 women. Responses to a postal questionnaire provided the dietary information. Relationships between the major dietary items and lung cancer were explored for various diagnostic subsets of the 168 lung cancer cases diagnosed among the study subjects. Analyses were stratified for sex, age, residence characteristics, cigarette smoking and, at times, socioeconomic group. Although the data do not permit a firm interpretation in terms of risk enhancement by a marginal retinoid deficiency, we found that the apparent protection afforded by higher intakes of vitamin A or its provitamins was particularly strong for lung cancer appearing as squamous‐cell carcinoma and among those with higher alcohol intakes. The individual food items which showed the strongest negative association with lung cancer were carrots and milk. These two items made a major contribution to the vitamin A index and its variation among the respondents.
Mortality patterns among embalmers
Authors: Walrath Judy , Fraumeni Joseph F.
Published: February 2007

In view of recent findings of nasal cancer in rats exposed to formaldehyde vapors, we investigated the proportionate mortality experience of embalmers licensed to practice in New York State. Mortality was significantly elevated for cancers of the skin and colon and for arterio‐sclerotic heart disease, whereas significant deficits were seen in mortality from respiratory diseases and accidents. Respiratory cancer mortality was not excessive and no deaths were attributed to nasal cancer. Mortality was significantly elevated for cancers of the skin, kidney, and brain among those licensed only as embalmers, whereas mortality patterns were unremarkable among those licensed also as funeral directors (and presumably less exposed to formaldehyde). These preliminary results indicate the need for occupational cohort studies to clarify the carcinogenic potential of formaldehyde.
Prospective study of “early” gastric cancer
Authors: Tsukuma Hideaki , Mishima Takashi , Oshima Akira
Published: February 2007

In order to elucidate the natural history of early gastric cancer, we followed up non‐concurrently certain patients who had been diagnosed endoscopically as having “early” gastric cancer and who had histological evidence of cancer by biopsy, but on whom surgical resection had been delayed or had not been conducted. At the Center for Adult Diseases, Osaka, 56 cases were eligible for this study. Out of these, 27 cases progressed to advanced cancer and 16 remained at the early stage during the follow‐up period (6‐88 months, mean: 29 months). The remaining 13 cases had had neither surgical resection nor examinations. The survivorship function for the duration of “early” gastric cancer was estimated by the life‐table method of Kaplan and Meier. The median of the duration was estimated as 37 months. The 5‐year survival rate of the 34 cases on whom surgical resection had not been conducted was estimated as 64.5%. These results suggest that early diagnosis and early treatment may lead to a reduction of mortality from stomach cancer.
A new mechanism for tumor‐induced platelet aggregation. Comparison with mechanisms shared by other tumors with possible pharmacologic strategy toward prevention of metastases
Authors: Lerner William A. , Pearlstein Edward , Ambrogio Cynthia , Karpatkin Simon
Published: February 2007

Because tumor‐induced platelet aggregation appears to play a role in the development of certain experimental tumor metastases, we examined the mechanism(s) of tumor‐induced platelet aggregation as well as the effect of various anti‐platelets agents. Two mechanisms for tumor‐induced platelet aggregation have been previously described: (1) a mechanism which requires complement, a stable plasma factor, divalent cation and a sialo‐lipo‐pro‐tein vesicular component of the tumor membrane for platelet aggregation; and (2) a mechanism which operates via the generation of thrombin and requires a phos‐pholipid component of the tumor membrane. We now report a new mechanism of tumor‐induced platelet aggregation which is shared by three different tumors: a spontaneously metastatic human melanoma, HM29, a murine melanoma, B16F10, and a carcinogen‐induced metastatic murine colon carcinoma, CT26. These tumors do not require cell‐surface sialic acid or serum complement as does the first mechanism. They do not require cell‐surface phospholipid, as do the tumors representing the other two mechanism. They do not aggregate platelets via the generation of thrombin as do tumors representing the second mechanism. These tumors are unique in that they require a trypsin‐sensitive surface protein for activity. The ability of the thrombin‐generating tumors to aggregate platelets is uniquely sensitive to two highly specific, synthetic thrombin‐competitive inhibitors: DAPA and No. 805. The other two groups of tumors are at least 10 times more sensitive to inhibition of platelet aggregation by elevation of cyclic AMP levels (prostacy‐clin, 6‐keto‐PGE1, dibutyryl cyclic AMP) and at least 10 times more sensitive to inhibition of prostaglandin synthesis (indomethacin, ibuprofen). Thus, tumor‐induced platelet aggregation is heterogeneous with respect to mechanism of action as well as inhibition by anti‐platelet pharmacologic agents. Sensitivity to anti‐platelet agents correlates with the mechanism by which tumor cells aggregate platelets.
The mutational origin of serum independence in Chinese hamster cells in vitro
Authors: Varshaver Nina B. , Marshak Marina I. , Shapiro N. I.
Published: February 2007

The genetic mechanisms determining the ability of transformed cells to grow in a medium with a low serum content (ser+) were studied in a clone of Chinese hamster cells with normal serum requirements. The fluctuation test has shwon that serum independence occurs as a random spontaneous event. Its rate of occurrence is about 10−5. The concomitant study of a gene mutation (resistance to 6‐mercaptopurine ‐ 6MP) revealed similar characteristics with respect to the distribution of the number of mutants in replicate cultures. N‐methyl‐N1‐nitro‐N‐nitrosoguanidine (MNNG) and SV40 significantly increased the frequency of ser+ colonies. Induction was detected after an expression time of 3‐4 days, which is typical of gene mutations. In 16 out of 18 ser+ clones of independent origin the ser+ character remained stable. The results suggest that the ser+ character originates in most cases from a mutation event.
Systemic adoptive immunotherapy of a highly immunogenic murine lymphoma growing in the brain
Authors: Romani L. , Blanchi R. , Puccetti P. , Floretti M. C.
Published: February 2007

Systemic adoptive immunotherapy with specifically immune lymphocytes was successfully performed in immunodepressed mice challenged intracerebrally with L5178Y/DTIC lymphoma cells, a tumor subline rendered highly immunogenic through In vivo exposure to 5‐(3,3‐dimethyl‐1‐triazenyl)‐1H‐imidazole‐4‐carboxamide (DTIC)1. The systemic immunotherapy relied on the infusion of in vitro‐generated primary cytotoxic T‐lympho‐cytes (CTL), the anti‐tumor activity of which was evaluated by measuring tumor‐cell proliferation In the brain in terms of radiolabel uptake and by recording survival times of recipient leukemic mice. The protection afforded by CTL appeared to be specific and was largely conditioned by dose and time of CTL administration. The levels of protection correlated well with the in vitro killing of L5178Y/DTIC tumor cells.
In vitro detection of cell‐mediated immunity to individual tumor‐specific antigens of chemically induced BALB/c fibrosarcomas
Authors: Carbone Giusi , Colombo Mario P. , Sensi M. Luisa , Cernuschi Antonio , Parmiani Giorgio
Published: February 2007

In this study we have analyzed the in vitro cell‐mediated cytotoxicity of immune peritoneal exudate cells (PEC), elicited in syngeneic mice against the MCA‐induced, TSTA‐bearing BALB/c fibrosarcomas CA‐2, GI‐17 and C‐3. The 4 h 51Cr‐release assay showed the immune PEC effectors to be specifically cytotoxic to fibrosarcoma used for the immunization, but not to other syngeneic MCA‐induced tumors or normal fibroblasts. Cold target inhibition experiments on CA‐2 cells confirmed the specificity of the reaction. When PEC, lymph‐node and spleen cells from BALB/c anti‐CA‐2 mice were compared for anti‐tumor activity, only PEC were found to kill tumor cells significantly. PEC effectors did not have a significant level of NK or NC activities since they were unable to destroy YAC‐1 target and the PEC‐mediated anti‐tumor activity was not inhibited by unlabelted YAC‐1 or WEHI‐164 tumor cells. PEC anti‐CA‐2 were analyzed for the expression of T‐cell markers by anti‐Thy 1.2, anti‐Ly 1.2 and Ly 2.2 monoclonal antibodies. Anti‐tumor specific effector cells were identified as mature T cells since they were not adherent to plastic and showed Thy l.2+, Ly 1.2− and Ly 2.2+ phenotypes. In addition, anti‐H‐2Kd but not anti‐H‐2Dd alloantiserum added to target cells, blocked CA‐2 tumor lysis, thus supporting the conclusion that the T‐cell response against TSTA is H‐2 restricted.
Formation and growth of multicellular spheroids of human origin
Authors: Carlsson J. , Nilsson K. , Westermark B. , Pontén J. , Sundström C. , Larsson E. , Bergh J. , Påhlman S. , Busch C. , Collins V. P.
Published: February 2007

Different types of human cells which normally grow as monolayers or suspension cultures were tested for their capacity to form and grow as spheroids. Sixteen out of the 27 tested tumour cell lines formed spheroids. Nearly all of these spheroids also grew. With only two exceptions the doubling times were longer when the tumour cells grew as spheroids than when they grew in conventional mass culture. Eleven out of 13 tested human non‐tumour cells formed small spheroids but of these only the spheroids of lymphoid origin could grow. These lymphoid cells grew faster when aggregated to spheroids than when in single‐cell suspension culture. None of the other non‐tumour cells, which normally grew as monolayers, could grow as spheroids. The normally monolayer‐cultured tumour cells formed symmetrical spheroids with smooth surfaces while the normally suspension‐cultured cells formed irregular spheroids with rough surfaces. All large spheroids had a necrotic centre surrounded by a shell of viable cells. The thickness of the viable cell layer varied depending on cell type. The shape and organization of cells within the spheroids also varied largely. The results show that many types of human cells can be cultured as spheroids and that a wide spectrum of morphological appearances and growth rates can be obtained.
Differential reactivity of monoclonal antibodies with human colon adenocarcinomas and adenomas
Authors: Stramignoni Daniela , Bowen Robert , Atkinson Barbara F. , Schlom Jeffrey
Published: February 2007

Monoclonal antibodies have been generated using membrane‐enriched extracts of human metastatic mammary carcinoma lesions (Colcher et at., 1981), some of which demonstrated binding to the surface of human colon carcinoma cell lines. We report here an analysis of the reactivity of three of these monoclonal antibodies with formalin fixed tissue sections of human colon adenocar‐cinomas and adenomas. The three monoclonals employed were B72.3, which is reactive with a 220‐400 kdal high molecular weight glycoprotein complex; B6.2, reactive with a 90 kdal glycoprotein, and B1.1, which is reactive with the 180 kdal glycoprotein CEA. B1.1 was least selective in its reactivity to colon carcinoma versus adenoma lesions. When 10 μg/ml of purified B1.1 IgG were used per slide, 94% (15 of 16) of carcinomas and 83% (15 of 18) adenomas showed reactivity. Monoclonal B72.3 demonstrated the most selective reactivity for carcinomas. Eighty‐two percent (14 of 17) of carcinomas were positive while none of 18 adenomas examined showed reactivity with more than a few percent of adenoma cells positive. When a low concentration of purified B72.3 immunoglobulin was used per slide, 8 of 16 carcinomas and none of 46 adenomas or normal colon epithelium samples scored positive. Monoclonal B72.3 also reacted with cells in areas of “atypia” within adenomas. The reactivity of monoclonal B6.2 was intermediate as compared to B1.1 and B72.3 in its selectivity of reactivity for carcinoma cells. A heterogeneity in the populations of tumor cells showing reactivity with the three monoclonals was observed within many of the tumor masses. Both colon adenocar‐cinomas and adenomas can now be placed in several distinct groups based on their expression of antigens reactive with the three monoclonal antibodies employed.
Quantitative fluorescence measurements of ao‐stained normal and malignant bladder cells
Authors: Hemstreet George P. , West Seymour S. , Weems W. Lamar , Echols Candace K. , McFarland Sandra , Lewin Jack , Lindseth Gunnbjorg
Published: February 2007

Quantitative, corrected fluorescence emission spectra from the nuclei of acridine orange‐stained bladder epithelial cells were obtained with a corrected spectrum microspectrofluorophotometer (MSF)5 which is calibrated with a phosphor particle fluorescence standard. The spectra demonstrated that the green fluorescence band (λmax≅530 nm) is stoichiometrically related to the amount of nucleic acids (NA) present in a given nucleus, provided this spectroscopic species has reached saturation. The shape of this spectral band is constant. On the basis of this information, we used a simple microfluorometer, (SFM), calibrated with the phosphor particle standard, to routinely measure the amount of green fluorescence emission from the nuclei of AO‐stained bladder epithelial cells. The amount of green fluorescence per normal nucleus never exceeded 0.5 phosphor particle units (ppu). In contrast, in every sample containing malignant or cancerrelated cells, one or more cells contained nuclei that exhibited more than 0.5 ppu total green nuclear fluorescence. Results obtained with the SFM on 794 AO‐stained cells from 80 samples taken from 40 patients are reported here. Samples consisted of urine specimens, bladder washings, and biopsies. One or more malignant cells from every grade 3 or 4 tumor and 17 of 17 grade 1 or 2 tumors showed markedly elevated levels of total (integrated) green nuclear fluorescence indicating the presence of DNA aneuploidy, strongly, suggestive of the presence of malignant or potentially malignant cells. Comparison with diagnoses based on H and E‐stained biopsy material and Papanicolaou‐stained cytological preparations show excellent correlation. The quantitative fluorescence measurements demonstrate a clear difference between negatives and positives with linear ordering up through Grade 4 and CIS. Grades 1 and 2 were clearly different from 3 and 4 (p<0.001). The results indicate that the quantitative fluorescence methodology reveals the presence and extent of DNA aneuploidy which may prove to be a more sensitive cytologic method for detection of low grade tumors and may also provide an objective biochemical basis for tumor grade classification. Detecting the presence of DNA aneuploidy may even serve to provide earlier detection than is possible with conventional means, but this remains to be confirmed by longitudinal studies.
Biological characterization and clinical applications of a monoclonal antibody recognizing an antigen restricted to neuroectodermal tissues
Authors: Allan Patricia M. , Garson J. A. , Harper Edna I. , Asser Ushi , Coakham H. B. , Brownell Betty , Kemshead J. T.
Published: February 2007

The monoclonal antibody UJ13A was raised following immunization of mice with human foetal brain and subsequent somatic cell hyridization of spleen cells with the mouse myeloma cell line P3‐X63‐AG8‐653. The antibody is of the IgG1 subclass and has been shown by indirect immunofluorescence studies on normal foetal, paediatric and adult tissues to selectively bind to most tissues of neuroectodermal origin. Many tumours of neural origin also express the UJI3A antigen and the reagent can be used to distinguish primary intracranial neural tumours from secondary carcinomas and lymphomas. UJI3A is also useful as one of a panel of reagents employed for the identification of metastatic spread of neuroblastoma cells to bone marrow and cerebrospinal fluid. Knowledge of the full spectrum of normal and malignant tissues binding UJ13A suggests that the antibody may have a role in the radioimmunolocalization of neuronal tumours such as neuroblastoma.
Preparation and properties of a drug‐carrier‐antibody conjugate showing selective antibody‐directed cytotoxicity in vitro
Authors: Garnett M. C. , Embleton M. J. , Jacobs E. , Baldwin R. W.
Published: February 2007

The preparation and properties of a drug‐carrier‐antibody preparation are reported. The antifolate chemotherapeutic agent methotrexate was covalently coupled to human serum albumin as a carrier. The carrier‐drug preparation was then chemically linked to a monoclonal antibody, raised originally against a human osteogenic sarcoma cell line, 79IT, in a manner permitting retention of antibody‐binding activity. The cytotoxic properties of the conjugate were tested in vitro in comparison with carrier‐methotrexate and free methotrexate against a panel of tumour cell lines containing both antigenically cross‐reactive cell lines and cell lines having low antigenic cross‐reactivity with the monoclonal antibody. The cytotoxicity tests demonstrated that coupling of methotrexate to carrier caused a loss of some drug activity but that coupling of the antibody to the carrier‐drug preparation permitted full expression of drug cytotoxicity against antibody‐reactive cell lines. It was further demonstrated that the conjugate was selective in its action and was preferentially cytotoxic towards antibody‐reactive cell types. The cytotoxicity against antibody‐reactive cell lines was shown by competitive inhibition by free antibody to be entirely dependent on antibody binding. A clonogenic assay showed that the conjugate was capable of killing >99% of 79IT target cells. These results indicate that a drug‐carrier antibody conjugate can be synthesized which has all the in vitro properties theoretically necessary for a successful antibody‐targeted cytotoxic agent.
Phenotypic diversity within clones of human normal t cells
Authors: Zagury D. , Bernard J. , Morgan D. A. , Fouchard M. , Feldman M.
Published: February 2007

Human normal T cells were selected for in vittro cloning according to the expression of T4, T8 or T10 antigens on individual cells. Clones were produced from each of these cells irrespective of the antigenic phenotype of the parental cell. The cloned progeny manifested, in many cases, shifts in antigen expression. Thus, T4+T8− cells gave clones expressing predominantly T4−T8+ and vice versa. The clonal expression of T4 and T8 seemed to be mutually exclusive. Antigenic shifts were recorded also in clones derived from T4−T8−T10− cells, resulting in T10+ clones which were also either T4+ or T8+ and from T4+T8−T10+ cloned cells yielding clones of either T4+ or T8+ cells. Testing functional properties we found that NK activity was mediated not only by T10+ cells but also, in some cases, by T4+ and T8+ cells. Moreover, TCGF production, which may reflect helper activity, was mediated not only by T4+ cells. Only the cytotoxic (CTL) activity seems to be confined to the T8 phenotype. Thus, it appears that T antigens, which seemed to be molecular markers of differentiation, are not markers for terminal differentiation and do not always reflect defined functional properties. These conclusions are drawn from cloning of normal T cells which manifest properties different from those of T‐cell lines or T hybridomas.
Trends in malignant melanoma of skin in New Zealand
Authors: Cooke K. R. , Skegg D. C. G. , Eraser J.
Published: February 2007

Incidence and mortality rates for malignant melanoma of skin in the New Zealand non‐Maori population over the past 30 years were analysed in relation to sex, age, birth cohort and time. In both sexes, the age‐standardized incidence rates increased approximately exponentially with time, with an annual increment of 7.5%. The age‐standardized mortality rates increased approximately linearly with time, resulting in a two‐ to three‐fold increase over 30 years, as compared with an eight‐ to nine‐fold increase in the incidence rates. Descriptive birth cohort analysis shows different patterns of increase for incidence and mortality rates. The main difference is that, whereas incidence rates have continued to increase in recent birth cohorts, mortality rates have stabilized. The explanation for this difference is uncertain.
Alterations of the basement membrane and connective tissue antigens in human metastatic lymph nodes
Authors: Burtin P. , Chavanel G. , Foidart J. M. , Andrfi J.
Published: February 2007

Antigens of the basement membrane (type‐IV collagen and laminin) and the connective tissue (type‐Ill collagen and fibronectin) were studied by immunofluorescence in 16 lymph nodes draining colorectal carcinomas and 6 lymph nodes draining breast carcinomas. A comparison was also made between 7 primary colorectal carcinomas and 9 lymph nodes draining these tumors. Anti‐type‐IV collagen and anti‐laminin rarely stained the basement membrane of metastatic tumors. In contrast, we detected type‐IV collagen in the peritumoral stroma, although similar images were rarely seen in primary tumors. When tumoral cells were in the vicinity of lymphoid cells, they were occasionaly separated by a barrier stained by the four antisera, or only by antifibronectin and anti‐type‐lll collagen. In other cases no barrier was observed between both types of cells which were in close contact. On the whole the above alterations were more marked in the lymph nodes draining breast carcinomas, in comparison to those draining colorectal carcinomas. Tumor cells were never stained by antitype‐IV collagen or antilaminin serum. Some cells found either in the lymphoid or in the tumor area of metastatic lymph nodes were stained not only by these antisera, but also by a monoclonal antibody against Willebrand Factor, which is a marker of endothelial cells. Thus the labelled cells were characterized as being derived from the capillary wall.
A comparison of epstein‐barr virus‐specific T‐cell immunity in malaria‐endemic and ‐nonendemic regions of Papua New Guinea
Authors: Moss D. J. , Burrows S. R. , Castelino D. J. , Kane R. G. , Pope J. H. , Rickinson A. B. , Alpers M. P. , Heywood P. P.
Published: February 2007

Epstein‐barr virus genome‐positive Burkitt's lymphoma is endemic in Africa and Papua New Guinea and in both countries the tumour is restricted to regions with holoendemic malaria. The present work has compared groups of healthy indigenous individuals living in malarious and non‐malarious regions of Papua New Guinea for Epstein‐Barr virus‐specific T‐cell‐mediated immunity using the in vitro regression assay. Residents of the malarious region (55 tested), when compared with either residents of the non‐malarious area (35 tested) or Caucasian controls (27 tested) showed a significant (p < 0.0001) impairment of virus‐specific T‐cell immunity but no obvious disturbance (p > 0.05) of anti‐viral antibody titres. These results may be important in explaining the postulated role of malarial infection as a co‐factor in the patho‐genesis of Burkitt's lymphoma.
Diet and colorectal cancer: A case‐control study in Greece
Authors: Manousos O. , Day N. E. , Trichopoulos D. , Gerovassilis F. , Tzonou A. , Polychronopoulou A.
Published: February 2007

A case‐control study probing the role of diet on the incidence of colorectal cancer was undertaken in Athens, Greece, in a population characterized by ethnic homogeneity but substantial heterogeneity with respect to dietary habits. The case series consisted of 100 consecutive patients with histologically confirmed colorectal cancer admitted to two large hospitals of Athens during a 16‐month period; the control series consisted of orthopaedic patients, admitted to the same hospitals during the same time period, individually matched to the index cases by age and sex. Dietary histories concerning the frequency of consumption (per month or per week) of about 80 food items were obtained by the same interviewer. Cases reported significantly less frequent consumption of vegetables (particularly beets, spinach, lettuce and cabbage) and, independently, significantly more frequent consumption of meat (notably lamb and beef). Between the two extremes (high‐vegetable, low‐meat diet versus high‐meat, low‐vegetable diet) a risk ratio of about 8 appears to exist, sufficient (in size and direction) to explain a substantial part of the international variation in the incidence of colorectal cancer. Significant associations were not found with beer or other alcoholic beverages, and significant interactions were not noted with respect to age, sex and anatomic localization (colon vs. rectum).
Lysis of fresh human tumor cells by autologous large granular lymphocytes from peripheral blood and pleural effusions
Authors: Uchida Atsushi , Micksche Michael
Published: February 2007

Human lymphocytes and their subpopulations from the peripheral blood and pleural effusions of cancer patients were tested for cytotoxicity against fresh tumor cells isolated from carcinomatous pleural effusions of the same patients. Fresh tumor cells were relatively resistant to lysis by autologous unseparated lymphocytes in a 4 h Cr‐release assay. Positive reactions were recorded in 10 of 38 blood samples and 10 of 37 effusion specimens. Purification of large granular lymphocytes (LGL) by discontinuous Percoll gradient centrifugation resulted in enhancement of cytotoxic activity against autologous tumor cells and K562 cells, with no reactivity in LGL‐depleted small T‐lymphocyte populations. Significant lysis of effusion tumor cells by autologous LGL was observed in 15 of 22 blood specimens and 15 of 21 effusion samples. Further depletion of high‐affinity sheep erythrocyte resetting cells from Percoll‐purified LGL populations gave an increase in autologous tumor‐killing activity. Depletion of LGL/K562 conjugates from LGL populations decreased lysis of autologous tumor cells and K562 cells. Effusion tumor cells that were susceptible to lysis by allogeneic normal LGL were also killed by autologous LGL, and effusion tumor cells resistant to lysis by allogeneic NK cells were not lysed by autologous LGL. In a single‐cell cytotoxicity assay in agarose, 4–26% LGL bound autologous tumor cells and 0.2–5% LGL killed these target cells, while 12–45% LGL bound K562 cells and 2–20% LGL lysed them. These results indicate that cytotoxic potential for autologous effusion tumor cells is present in the peripheral blood and pleural effusions of cancer patients; it is strongly associated with a minor proportion of LGL and restricted to the cell population that can lyse NK‐sensitive K562 cells.
Herpes simplex virus‐induced amplification of SV40 sequences in transformed Chinese hamster embryo cells
Authors: Schlehofer Jörg R. , Gissmann Lutz , Matz Bertfried , Hausen Harald Zur
Published: February 2007

Infection with Herpes simplex viruses (HSV) induces amplification of SV40 sequences in SV40‐transformed Chinese hamster embryo cells (CO631). This is shown by in situ hybridization of the infected cells with cloned 32P‐labelled SV40 DNA. The HSV‐mediated synthesis of SV40 DNA is more pronounced than after treatment with chemical carcinogens. This initiator‐like effect of HSV may, in concert with the previously reported mutagenic activity of this virus (Schlehofer and zur Hausen, 1982), point to a possible mechanism of HSV infection in human genital cancer.
Food items and food groups as risk factors in a case‐control study of diet and colo‐rectal cancer
Authors: Miller A. B. , Howe G. R. , Jain M. , Craib K. J. P. , Harrison L.
Published: February 2007

The contributions of food items and food groups as risk factors in a previously reported case‐control study of diet and colo‐rectal cancer have been analyzed. The study included 348 patients with colon cancer, 194 with rectal cancer, 542 neighbourhood controls individually matched to the cases on the basis of age and sex and a second control series of 535 surgical hospital controls frequency matched to the cases. For colon cancer, as in the previous analysis, the major risk factor was saturated fat, individual food items or groups failing to make a significant contribution to the risk. In particular there was no protective effect of dietary fibre and, for cruciferous vegetables, only a minor protective effect in females. No individual cruciferous vegetable made an important contribution to this effect. For rectal cancer, on the other hand, a significant effect of saturated fat, independent of other food items or groups, was only found for females in the highest consumption category. For males, consumption of eggs, beef and veal significantly increased risk but not consumption of pork, while for females, there was a non‐significant increase in risk with consumption of eggs, no increased risk with consumption of beef or veal and a significantly increased risk with consumption of pork. There was no protective effect of dietary fibre or of cruciferous vegetables for rectal cancer, but in females, there was a significantly increased risk for consumption of beer, though this was somewhat reduced when controlled for consumption of saturated fat. There was no indication of an effect of alcohol in either sex or of beer in males. Thus, these results confirm the previous report in showing a significant effect of saturated fat in increasing risk of colon cancer but suggest a contribution of meats to risk of rectal cancer.
The organization of intermediate filaments in normal human colonic epithelium and colonic carcinoma cells
Authors: Brown D. T. , Anderton B. H. , Wylie C. C.
Published: February 2007

A comparative ultrastructural study of the organization of intermediate filaments (tonofilaments) within normal colonic epithelium and colonic carcinoma cells was carried out. The pattern of development of the specialized intermediate filament (IF) network, occurring during the differentiation of normal colonic epithelial cells, was examined to allow a more complete comparison with tumour cells of different degrees of differentiation. Essentially the IF system becomes more organized as the cells differentiate, resulting in the formation of a three‐dimensional network loosely surrounding the nucleus, extending through the sub‐terminal web and basal cytoplasm, and inserting into lateral desmosomes. Another system of IFs also runs directly between lateral desmosomes, lying parallel to the plasma‐membrane and desmosomal plaque, without inserting directly into the junction. Alterations in the organization of the IF system were seen in tumour cells with the type and extent being dependent upon their location and degree of differentiation. Cells within areas of the tumour where some degree of glandular structure was retained exhibited major alterations in their microfilament‐containing structures. However, their IF system was essentially intact and lateral desmosomes were still present in similar numbers to those seen in normal, partially differentiated mid‐crypt cells. Apolar tumour cells within areas of the tumour where a gross loss of cryptal architecture had occurred exhibited a striking disorganization of their IF system. No parallel bundles of interdesmosomal tonofilaments were present beneath the cell surface and the majority of the three‐dimensional network appeared to have collapsed around the nucleus, although some extensions to randomly distributed surface desmosomes still occurred. It appears that this disorganization of the IF system is associated with a loss of cell polarity and may involve alterations in putative IF‐associated proteins important in the interaction of IFs with surface desmosomes or other cytoskeletal elements. A study of this phenomenon may shed light on both the means of IF organization and assembly and their role in normal cells as well as the possible role of alterations in cytoskeletal elements in the expression or maintenance of the malignant phenotype.
Association of some supraglottic laryngeal carcinomas with EB virus
Authors: Břicháček B. , Hirsch I. , Šíbl O. , Vilikusova E. , Vonka V.
Published: February 2007

Thin sections of biopsies from five patients with supraglottic laryngeal carcinoma who possessed antibody to early antigen of EB virus were examined for the presence of EB virus nuclear antigen (EBNA) and EB virus DNA by cytological hybridization in situ. Both EBNA and EB virus DNA were found in the tumour cells of three of the patients. The present findings suggest an association between EB virus and supraglottic carcinoma of the larynx.
Natural antibodies in human sera directed against blood‐group‐related determinants expressed on colon cancer cells
Authors: Knuth A. , Lloyd K. O. , Lipkin M. , Oettgen H. F. , Old L. J.
Published: February 2007

Sera from 136 normal males and 33 members of families at high risk for colon cancer were tested for reactivity with six colon cancer cell lines by the protein A‐mixed hemadsorption assay. Ninety‐one sera had antibodies to colon cancer cell line HT‐29. In 89 cases the antibodies were absorbed by human A and B erythrocytes or sheep erythrocytes. Antibodies in the remaining two sera, which were from sisters in the high‐risk group, were not absorbed by red cells but could be absorbed by tumor cells expressing A or B blood‐group determinants. Their reactivity was inhibited by some soluble blood‐group glycoproteins. One serum (No. 4) was inhibited by A‐active glycoproteins from human saliva and ovarian cyst fluids and from porcine mucosa, as well as by a polysaccharide derived from gastric cancer; it has an anti‐A‐like specificity. The other serum (No. 6) was inhibited by A and B glycoproteins, by a blood group precursor glycoprotein and by the same gastric cancer polysaccharide; it seems to have a wider specificity directed towards both A‐ and B‐like structures. It is not known what caused production of these antibodies but it may be significant that they occurred in members of a family at high risk for developing colon cancer.
Fibronectin and anchorage‐independent and anchorage‐dependent growth of benign and malignant cell lines
Authors: Dodson Melvin G. , Gelder Frank B. , Slota John , Lange Charles
Published: February 2007

The presence of fibronectin in three “malignant” (AU‐471, AU‐436, LT‐2) and two “benign” (BHK‐21, WI‐38) cell lines was demonstrated with a fluorescent antibody technique; two malignant (AU‐471, AU‐436) cell lines were fibronectin‐negative and one (LT‐2) retained fibronectin expression. One “benign” cell line (WI‐38) expressed fibronectin, the other (BHK‐21) did not. Anchorage‐independent soft agar (AISA) growth correlated better with loss of fibronectin than with malignant potential. All three fibronectin‐negative cell lines (benign and malignant) grew anchorage‐independently (AU‐471, AU‐436, BHK‐21), and both fibronectin‐positive cell lines were anchorage‐dependent (LT‐2, WI‐38). Surprisingly, the addition of Clg to anchorage‐independent cells increased their anchorage‐independent soft‐agar cloning efficiency, but had no effect on anchorage‐dependent cell lines. Anti‐Clg antibodies decreased AISA growth. The effect of Clg on anchorage‐independent growth varied with the concentration, and also between cell lines, and a variation in effect was noted between anchorage‐independent (AISA) and anchorage‐dependent (in flasks) growth even in the same cell line.
Human T‐cell leukemia virus type I: Induction of syncytia and inhibition by patients' sera
Authors: Nagy Károly , Clapham Paul , Cheingsong‐Popov Rachanee , Weiss Robin A.
Published: February 2007

HTLV‐producing T‐cell lines induce cell fusion when cocultivated with a wide variety of indicator cells, suggesting that HTLV envelope antigens interact with the membranes of many cell types. Serum antibodies from adult T‐cell lymphoma‐leukemia (ATL) patients inhibited the formation of syncytia, and sera from British, American and Japanese ATL patients inhibited cell fusion induced by American and Japanese HTLV isolates equally well. No serological cross‐inhibition of syncytium induction was found between HTLV and bovine leukosis virus, Moloney murine leukemia virus and simian sarcoma‐associated virus. A simple syncytium inhibition test in microtiter plates has been developed to provide a rapid screen for antibodies presumed to be specific to HTLV envelope glycoproteins.
Antibodies against human T‐cell leukemia/lymphoma virus (HTLV) and expression of HTLV p19 antigen in relatives of a T‐cell leukemia patient originating from Surinam
Authors: Vyth‐Dreese Florry A. , Rümke Philip , Robert‐Guroff Marjorie , De Lange Gerda , Gallo Robert C.
Published: February 2007

Serum and peripheral blood cell samples from eleven relatives of a T‐cell leukemia patient with human T‐cell leukemia/lymphoma virus (HTLV)‐associated disease, were investigated for the presence of HTLV antibody and antigen expression. In addition to the patient, three family members were seropositive and a wide range in HTLV antibody titer was observed. The father of the patient showed the highest titer (173,000) and carried HTLV p19+ cells in his peripheral blood. Upon induction of proliferation of these cells by short‐term culture in the presence of phytohemagglutinin (PHA) and 12‐O‐tetradecanoyl phorbol‐13‐acetate (TPA), an increase from 1% to 28% HTLV p19+ cells was observed confirming previous findings that HTLV p19 expression was correlated with proliferative activity of the host cells. In none of the other seronegative or seropositive relatives of the patient HTLV p19 expression was revealed when tested in freshly isolated mononuclear cells, upon short‐term incubation in PHA + TPA or after prolonged culture for 2 or 3 passages in medium containing T‐cell growth factor. The results from HLA typing studies did not provide any evidence for HTLV related abnormalities in haplotype expression. Our data confirmed the earlier notion of a prevalence of HTLV infection within families of patients with HTLV‐associated disease. It is furthermore obvious from our results that a normal individual may possess high titer HTLV antibody and circulating HTLV p19+ cells without showing signs of disease.
Yolk‐sac carcinoma of extra‐embryonic origin in the 129 Sv/Sl mouse
Authors: Sobis Halina , Van Hove Luc , Vandeputte Michel
Published: February 2007

Displacement of the visceral yolk‐sac in fetectomized rats and hamsters does not only induce benign teratomas but may also lead to the development of malignant yolksac carcinoma. In the mouse, displacement of this extraembryonic membrane readily induces teratoma but until now yolk‐sac carcinoma has never been observed in this species. In the present study we report the development of yolk‐sac carcinoma in 129 Sv/Sl mice after a long latent period (8 months). The tumor is composed of visceral and parietal patterns in the primary neoplasm and in its metastases. It develops from the extra‐embryonal part belonging to normal (+/+), heterozygous (SI/+) or sterile (SI/SI) embryos, which proves that these yolk‐sac carcinomas are not of germ‐cell origin.
Expression of gamma‐glutamyltranspeptidase in cultures of spontaneously and chemically transformed rat liver cells
Authors: Miyazaki Masahiro , Wahid Syarifuddin , Miyano Keiko , Yabe Tamae , Sato Jiro
Published: February 2007

The expression of gamma‐glutamyltranspeptidase (gamma‐GTP) and the relationship between this enzyme activity and tumorigenicity were studied in 38 tumorigenic and non‐tumorigenic epithelial cell lines derived from livers of normal and aminoazo‐dye‐fed rats. Nine of 22 non‐tumorigenic epithelial cell lines exhibited gamma‐GTP‐positive cells, whereas 9 of 16 tumorigenic epithelial cell lines did not exhibit gamma‐GTP‐positive cells. This finding revealed that no correlation existed between the acquisition of gamma‐GTP activity and tumorigenicity. None of 10 spontaneously transformed epithelial cell lines, which consisted of 8 tumorigenic and 2 nontumorigenic cell lines, exhibited gamma‐GTP‐positive cells. On the other hand, 16 of 28 transformed epithelial cell lines, which were derived from aminoazo‐dye‐fed rat livers and aminoazo‐dye‐treated cultures of normal rat liver cells, included gamma‐GTP‐positive cells in various percentages. As described above, in contrast to in vitro spontaneous transformation of rat liver cells, it is obvious that the carcinogen‐induced transformation of rat liver cells in vitro as well as in vivo was frequently accompanied by the acquisition of gamma‐GTP‐activity. Therefore, it is concluded that the expression of gamma‐GTP in liver cells may be mainly associated with exposure to chemical carcinogens.
Precipitable immune complexes in Hodgkin's disease
Authors: Euler Hans‐Hartwig , Béress Rosemarie , Moldenhauer Imme , Löffler Helmut
Published: February 2007

Sera from 28 untreated patients with Hodgkin's disease and from 120 healthy controls were investigated for the presence of circulating immune complexes using a modified 3% polyethylene glycol precipitation method with subsequent quantification of the precipitated protein. Elevated levels of precipitable protein were found in 79% (p <0. 005) of Hodgkin's disease sera. The degree of elevation was associated with disease activity including the presence of B‐symptoms. Constant and pronounced increase of precipitable protein was found in six patients with stage‐III B nodular sclerosis subtype, thus exceeding the average amount of precipitable protein in healthy controls by a factor of 3–4. The erythrocyte sedimentation rate in 20 patients correlated with the amount of precipitable protein (r = 0. 79). Additionally, partial component analysis of the precipitates was carried out by laser nephelometry. Immunoglobulins and complement components were identified as being major components of the precipitated material in sera both from patients and healthy controls, thus confirming the probability of the immune complex nature of the precipitates. Significant differences between patients and healthy controls concerned the amount of precipitable components. Elevation of precipitable IgM was found to be the most sensitive parameter (86% above X̄ + 2 sd of normal controls, p <0. 005). Increased amounts of precipitable IgG, C4, and Clq were found in 57‐46% of patients' sera. Elevation of precipitable IgA and C3c were identified less often. The results suggest the quantification of precipitable immune complexes and their components to be of value as adjuncts in determining disease activity in Hodgkin's dis‐ease.
Oesophageal cancer in non‐smoking drinkers and in non‐drinking smokers
Authors: Tuyns Albert J.
Published: February 2007

Alcohol and tobacco are the two major risk factors for cancer of the oesophagus; they usually combine their action. The action of each factor is studied here in non‐users of the other. Among non‐drinking male smokers the relative risk is higher than 5; among non‐smoking drinkers, risks are much higher and increase with average daily intake; this effect is also observed in females, with risk values of the same order of magnitude as for males. Thus the high sex ratio of oesophageal cancer in France can be entirely ascribed to different drinking levels in females and in males.
Preliminary identification of a tumor‐associated glycoprotein in bilharzial bladder cancer urine
Authors: Higashi Gene I. , El‐Asfahani Adel M. A.
Published: February 2007

A tumor‐associated antigen was preliminarily identified in urine from bilharzial (squamous‐cell carcinoma) bladder cancer patients. Monospecific rabbit antisera were made by immunization with concentrated bladder cancer urine and exhaustive absorption with insoluble normal human serum and urine. The urine tumor‐associated antigen was identical to an antigen from 3M KCl bladder tumor extract by immunodiffusion. The antigen in urine was found in nine of 10 bladder cancer patients and was absent from normal urine and serum by immunodiffusion and immunoelectrophoresis. The antigen was a concanavalin‐A‐binding glycoprotein which was anodal on immunoelectrophoresis. It was stable up to 2 years at‐20°C and did not cross‐react with carcinoembryonik antigen or with Schistosoma haematobium antigens.
Analysis of spontaneous, carcinogen‐induced and promoter‐induced chromosomal instability in patients with hereditary retinoblastoma
Authors: Gainer H. St. C. , Kinsella A. R.
Published: February 2007

Skin fibroblasts from patients with hereditary retino‐blastoma (RB cells) were examined since predisposition to the tumour might be expected to involve some degree of chromosomal instability, as has been noted for several cancer‐prone conditions. Spontaneous and N‐Methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG)‐induced aberration frequencies were measured, the cytogenetic effects of long‐term treatment with 12‐O‐tetradecanoyl‐phorbol‐13acetate (TPA) were examined and also the spontaneous and TPA‐induced sister chromatid exchange (SCE) frequencies. In all the studies the RB cells behaved in a similar fashion to normal human skin fibroblasts.
Double minutes in acute myeloid leukemia
Authors: Li You‐Sheng
Published: February 2007

Five out of 110 patients with acute myeloid leukemia (AML) showed double minutes (DM) in cytogenetic preparations. DM were found to occur predominantly in elderly patients, and in erythroleukemia or acute myelomonocytic leukemia. The five patients were apparently divided into two groups according to the number of DM per cell. Patients with few sets of DM had exclusively complex karyotypes and a poor prognosis while patients with numerous DM had otherwise normal or nearly normal karyotypes and a good prognosis. Data on II previously reported cases of AML with DM were collected from the literature and consistent results were revealed except that several of the II patients were diagnosed as having acute myeloblastic leukemia (Ml and M2 in the FAB classification), which is apparently due to differences in diagnostic criteria. Therefore, numerous or few DM in a cell might relate to different entities. When the number of DM was small they might have resulted from breakdown of existing chromosomes.