bluuebunny/crossref_metadata_2025 huggingface dataset:
D‐verapamil and L‐verapamil are equally effective in increasing vincristine accumulation in leukemic cells in vitro
Authors: Gruber Astrid , Peterson Curt , Reizenstein Peter
Published: February 2007

Leukemic cells isolated from peripheral blood from 6 patients with chronic lymphocytic leukemia, immunocytoma and prolymphocytic leukemia were incubated with vincristine (10nM) with and without racemic verapamil and its L‐ and D‐ isomers (6.6 μM). Verapamil increased vincristine accumulation in all cells, the increase varying between 100 and 700%. Racemic verapamil and the L‐ and D‐isomer increased cellular vincristine accumulation to the same extent. The verapamil effect could not be reversed by increasing the calcium concentration in the incubation medium (final concentration 2.5–5.0mm). The results indicate that the mechanism behind the effect of verapamil on cellular accumulation of vincristine does not depend upon changes in calcium transport.
Macrophages associated with murine tumours express plasminogen activator activity
Authors: Mussoni Luciana , Riganti Monica , Acero Raffaella , Erroi Annalaura , Conforti Grazia , Mantovani Alberto , Donati Maria Benedetta
Published: February 2007

The fibrinolytic activity of cancer cells has been repeatedly implicated in mechanisms of local spread and tumour invasiveness. Mononuclear phagocytes associated with solid tumours might also contribute to fibrin dissolution at the tumour/host interface through the expression of plasminogen activator (PA) activity. We have investigated the PA activity of tumour‐associated macrophages (TAM) from 4 transplanted murine tumours in syngeneic hosts; peritoneal macrophages (native and thioglycolate‐elicited) from both tumour‐bearing and control animals were studied as reference cells. TAM from 3 tumours (MSV, mFS6, MN/MCA1) had basal levels of PA activity (20% plasminogen‐independent) comparable to or higher than those of thioglycolate‐elicited peritoneal macrophages from the same tumour‐bearing animals. TAM isolated from I tumour (MS2) had a PA which was very low (60% plasminogen‐independent), but higher than the activity of unstimulated peritoneal macrophages. Molecular analysis of PA by SDS‐PAGE electrophoresis and fibrin autography revealed in all macrophages a single species having an apparent MW of 48 kDA. It thus appears that, in some experimental neoplasms, tumour cell vicinity may represent an in vivo stimulus for macrophage PA expression.
Species‐dependent antigenicity of the 34‐kDa glycoprotein found on the membrane of various primate lymphocytes transformed by human t‐cell leukemia virus type‐I (HTLV‐I) and simian T‐cell leukemia virus (STLV‐I)
Authors: Tozawa Hideki , Andoh Satoshi , Takayama Yoshinaga , Tanaka Yuetsu , Lee Bunsho , Nakamura Hideo , Hayami Masanori , Hinuma Yorio
Published: February 2007

Sixteen monoclonal antibodies (MAbs) against TA34 antigen found on the surface of human T‐cell leukemia virus type‐I (HTLV‐I) infected cells were prepared. These MAbs and one previously prepared anti‐TA34 MAb (TAG34) recognized 34‐kDa peptide not only in HTLV‐I‐infected cells, but also in cells infected with simian T‐cell leukemia virus (STLV‐I), which is analogous in antigenicity and gene structure to HTLV‐I. Radioimmuno‐precipitation (RIP) tests with the MAbs showed that TA34 antigen had at least 3 overlapping epitope groups. The antigenicities of the TA34 antigens of HTLV‐I‐infected cells derived from various primates were investigated by immunofluorescence staining using 9 anti‐TA34 MAbs. Cells from humans, apes and Old World monkeys reacted with all these antibodies, whereas cells from New World monkeys were stained by most of the antibodies, but little if at all by the remaining 2 (5A8 and TAG34). Similar results were obtained with various primate cells infected with STLV‐I. All 17 MAbs used recognized a 22‐kDa peptide in HTLV‐I‐infected cells cultured in the presence of tunicamycin. When incubated with 1% 2‐mercaptoethanol at ph 7.2 at 37°C, TA34 antigen lost its reactivity with TAG34, suggesting that the antigen has an intramolecular S‐S bond. Twenty sera of adult T‐cell leukemia (ATL) patients did not react with TA34 antigen in RIP tests.
Inhibition by tetragastrin of experimental carcinogenesis in rat colon: Effect of wheat bran consumption
Authors: Tatsuta Masaharu , Iishi Hiroyasu , Yamamura Hisako , Taniguchi Haruo
Published: February 2007

The effect of dietary wheat bran consumption on the anticarcinogenic action of tetragastrin upon colon carcinogenesis induced by azoxymethane was investigated in 122 inbred Wistar rats. Rats were given a control fiber‐free diet or the same basal diet plus 20% wheat bran. From week 5, they were given 250 μg per kg body weight of tetragastrin in depot form every other day until the end of the experiment at week 45. Prolonged administration of tetragastrin resulted in a significant reduction of the incidence and number of colonic tumors per rat in the group given the fiber‐free diet. The adenocarcinomas that did develop in this group had high mucin‐producing activity, unlike the cancers produced in controls without tetragastrin. However, administration of tetragastrin had little or no influence on the incidence, number or histology of colonic tumors in the group given basal diet plus wheat bran. Dietary supplementation with wheat bran alone had little or no effect on the development or histology of colonic tumors. Before and during the administration of carcinogens, addition of fiber to the diet resulted in a significant fall in the colonic ph and a significant increase in the crypt column length, but administration of tetragastrin did not have an additive effect on the crypt column length in rats fed diet supplemented with fiber.
Mouse monoclonal antibodies detecting disialogangliosides on mouse and human t lymphomas
Authors: Kawashima Ikuo , Tada Nobuhiko , Ikegami Shuji , Nakamura Shuji , Ueda Ryuzo , Tai Tadashi
Published: February 2007

Six monoclonal antibodies (MAbs) (4 IgG3 and 2 IgM) were produced by hybridomas obtained from A/J mice immunized with EL4(C57BL/6 derived‐T lymphoma). They were found to react with antigens expressed on both mouse and human T‐lymphomas but not on B lymphomas or normal cells. All of these antibodies reacted with the disialoganglioside GD2, GalNAcβI→4(NeuAcα2→8NeuAcα2→3)GalβI→4Glc‐Cer, by 3 different assay systems including the immune adherence inhibition test, enzyme‐linked immunosorbent assay, and enzyme immunostaining on thin‐layer chromatography. The binding specificities of these MAbs to disialogangliosides differed. Four MAbs (AI‐201, AI‐287, AI‐410. and AI‐425) showed restricted specificities, detecting only GD2, whereas the other 2 (AI‐245 and AI‐267) had a broader specificity, recognizing GD2, GD3, and GDlb. No evidence was obtained for the presence of the antigenic epitope in glycoproteins of mouse and human tumor cells. The ganglioside content of EL4 was low in comparison with that of M14 (a human melanoma cell line).
Stability of cytogenetic alterations in a human melanoma cell line and five clonal derivatives
Authors: de Lucca Edmundo Jose , Pathak Sen , Cheung Mei‐Chi Peng
Published: February 2007

A cytogenetic study was done on a human malignant melanoma cell line and its 5 clones. Chromosome banding analysis indicated the presence of 7 “shared” markers (M) and 9 unique markers (m) that were present only in the clones. Chromosomes 1, 5, 9, 12, 17 and 21 were involved in M‐markers and chromosomes 1, 2, 4, 6, 8, 9, 11, 16, 17, 18 and 21 were involved in m‐marker formation. Both parental and clonal lines had near‐triploid chromosome numbers. A number of M‐markers were isochromosomes of the short (p) and long (q) arms of chromosome I. Our cytogenetic data indicate that the parental line contained subpopulations of cells that were in different stages of karyotypic evolution.
Conjugates of elliptinium acetate with mouse monoclonal anti‐α‐fetoprotein antibodies or fab fragments: In vitro cytotoxic effects upon human hepatoma cell lines
Authors: Alberici Gilles F. , Pallardy Marc , Manil Luc , Dessaux Jean‐Jacques , Fournier Jacqueline , Mondesir Jean‐Marc , Bohuon Claude , Gros Pierre
Published: February 2007

Elliptinium acetate (EA) is a new anti‐cancer compound displaying cytostatic activity against various malignancies including hepatoma. Using 3 hepatoma cell lines, we compared the in vitro activity of doxorubicin (reference drug), of EA and of conjugates made up with this latter drug and monoclonal antibodies (MAbs). The linkage was performed by a direct oxidation method. Specific immunoconjugates were prepared with an anti‐alphafetoprotein (AFP) MAb (AF01) or its Fab fragment (Fab AF01). Non‐specific conjugates were obtained with an anti‐thyroglobulin MAb (TG01) or its Fab (Fab TG01). Direct membrane injury (51Cr‐release), DNA and protein synthesis as well as AFP release were investigated for all compounds. Free EA displayed only weak activity on DNA and protein synthesis, at 10‐fold higher molar concentration than doxorubicin. Conjugation of EA with whole AF01 allowed significant potentiation of protein synthesis inhibition without affecting the 3 other tests. In contrast, Fab AF01 × EA conjugates displayed a marked effect in the 4 tests; in particular, this conjugate was at least 100 times more efficient than any other compound when tested in the 51Cr‐release test. Neither Fab AF01 nor free EA alone or in combination exhibited such an effect. Fab TG01 × EA conjugate was not directly cytotoxic but potentiated inhibition of DNA and protein synthesis between 2‐ and 10‐fold. The mechanism of the direct cytotoxic effect of anti‐AFP Fab × EA conjugate, which has never been described in any other immunodrug model, was investigated.
Eradication of mouse melanoma by combined treatment with recombinant human interleukin 2 and recombinant murine interferon‐gamma
Authors: Silagi Selma , Dutkowski Regina , Schaefer Annette
Published: February 2007

Successful immunotherapy of early s.c. or i.p. (B16) melanoma in syngeneic C57BL/6 (B6) mice was achieved with s.c. perilesional injections (for s.c. tumors) or i.p. injections (for i.p. tumors) of recombinant human interleukin 2 (rIL‐2) and recombinant murine interferon‐gamma (rIFN‐γ). Over a 28‐day period, rIL‐2 and rIFN‐γ were injected 14 times. Results with this combination were additive with s.c. tumors and synergistic with i.p. tumors. Treatment with 6,250 U‐25,000 U of rIL‐2 and 2 μg of rIFN‐γ began 1‐3 days after s.c. inoculation of melanoma. On day 50, 87% (72/83) of mice thus treated were completely free of tumor. None of the 78 control mice (tumor + buffer) survived. Of mice receiving either rIL‐2 or rIFN‐γ alone, 59% (47/79) and 53% (44/83), respectively, were tumor‐free. I.p. tumors were also eradicated by i.p. injections of rIL‐2 (50,000 U) with rIFN‐γ (5, 10, and 15 μg) as judged by absence of tumor in 81% (21/26) of mice autopsied between days 45 and 65. No control mice survived, and only 17% (2/12) and 20% (6/30) given either rIL‐2 or rIFN‐γ separately (i.p.) were tumor‐free. Doses of rIFN‐γ from 1‐4 μg were more beneficial in eliminating 1‐day s.c. melanomas than were higher doses, and local s.c. treatment was far superior to distant or systemic treatment. Non‐adherent peritoneal or splenic cells from mice bearing 6‐day‐old i.p. melanomas and treated with one or both lymphokines on days 3 and 4 were used in cytotoxicity assays in vitro. Significant cytotoxicity against cultured melanoma cells was displayed by cells harvested from lymphokine‐treated mice, but there was no evidence of the synergism observed with combination treatment of i.p. tumors in vivo. rIFN‐γ inhibited proliferation of melanoma cells in vitro, whereas rIL‐2 stimulated proliferation at 1,000 U/ml. Plating efficiency was increased by at least 30% by culture with 100 U or 1,000 U of rIL‐2/ml and both concentrations neutralized the inhibitory effect of 0.05 ng/ml of IFN‐γ but not of 0.5 or 5.0 ng/ml.
Expression of the gangliosides GM3, GD3 and GD2 in tissue sections of normal skin, naevi, primary and metastatic melanoma
Authors: Hersey P. , Jamal O. , Henderson C. , Zardawi I. , D'Alessandro G.
Published: February 2007

Expression of the gangliosides GM3, GD3 and GD2 was studied in tissue sections from 19 naevi, 29 primary and 83 metastatic melanoma using the ABC immunoperoxidase technique. GM3 was not detected in normal skin whereas GD2 was detected on the basal and stratum spinosum of the epidermis and on peripheral nerves in the dermis. GD3 was expressed on melanocytes but not on most other components of normal skin. However, GD3 was strongly expressed on epidermis adjacent to naevi and primary melanoma whereas GD2, in contrast to that in normal skin, was not expressed on the epidermis adjacent to 26/29 primary melanoma. All naevi were positive for GM3 and GD3 except that GM3 was not detected on junctional components of naevi. GD2 was not expressed on naevi except in areas showing neuroid differentiation. Studies on melanoma revealed that approximately 60% of primary and 75% of metastatic melanoma expressed GM3 to a varying extent. With 2 exceptions, all primary and metastatic melanomas expressed GD3 although there was variable expression within most of the individual tumours. GD2 was detected in only approximately 25% of primary and 50% of metastatic melanomas. Both GD2 and GD3 were detected on lymphocytes surrounding melanoma. The higher expression of GD2 on metastases compared to primary melanomas was consistent with the view that GD2 expression was associated with increased metastatic potential. However, the low proportion of metastases expressing GD2 and the absence of any correlation with thickness of the primary tumour suggested that GD2 expression was not a reliable marker of metastatic potential. No differences could be detected in ganglioside expression on metastases in skin or lymph nodes. These results appear to have implications for the use of MAbs against gangliosides in therapy of melanoma and in the study of melanocytic differentiation.
A prospective study of circulating immune complexes in patients with breast cancer
Authors: Bukh A. , Aguado M. T. , Krarup N. , Poulsen H. S. , Nordentoft A. M. , Moller N. P. H.
Published: February 2007

Levels of circulating immune complex (cIC) and complement split product C3d were studied in 86 patients with breast cancer (BC), 22 patients with benign breast disease (BD), and 72 age‐ and sex‐matched blood‐bank donors (NC), using solid‐phase CIq‐protein A RIA, CIq‐anti‐IgG RIA, anti‐C3d anti‐IgG RIA, and polyclonal IgM‐rheumatoid factor ELISA for cIC detection. No significant differences in cIC and C3d levels were found between the groups. The incidence of raised cIC levels varied from 4.9 to 8.2% in the BC group and from 4.5 to 22.7% in the BD group in comparison with 2.9 to 3.0% in the NC group. Using the solid‐phase polyclonal IgM‐rheumatoid factor ELISA we found that the cIC levels of patients with stage‐III cancer were significantly higher than those of patients with stage‐I or stage‐II cancer. However, the other tests showed no relationship to tumor burden. Likewise, an effect of mastectomy on the cIC levels was also only detectable by one of the assays, i.e., the post‐mastectomy levels of cIC as measured by the solid‐phase anti‐C3d anti‐IgG RIA were significantly lower than the pre‐mastectomy levels. Serial analyses of cIC and C3d levels were performed pre‐operatively, one month post‐operatively and every 3 months during the first year after mastectomy in 46 of the patients. During a I‐year observation period, 7 patients developed metastatic disease. The occurrence of metastatic disease was not, however, preceded by characteristic changes in serially determined cIC and C3d levels.
Increased frequency of sister chromatid exchanges in lymphocytes of breast cancer patients
Authors: Adhvaryu Sidharth G. , Rawal Urwashi M. , Patel Jayesh V. , Patel Devendra D. , Balar Damodar B.
Published: February 2007

Spontaneous and mitomycin‐C (MMC)‐induced rates of sister chromatid exchanges (SCEs) were studied in peripheral blood lymphocytes (PBLs) of 40 patients with cancer of the breast and 40 healthy female volunteers as controls. Spontaneous SCE per cell value in PBL cultures was 7.72 for the breast cancer patients, which was significantly higher (p < 0.001) than the 6.28 SCEs per cell scored for the controls. Eight of the patients were studied a second time, 3 to 6 months following surgical removal of the tumour. A significant (p < 0.05) reduction in SCE per cell value was observed following mastectomy. MMC‐induced frequencies of SCE remained comparable in patients and controls. Cellular kinetics, calculated as average generation time (AGT) from the frequency of cells in Ml, M2 and M3 cycles, were comparable in patients and controls.
Aminoterminal propeptide of type III procollagen in serum—an indicator of clinical behavior of advanced ovarian carcinoma?
Authors: Risteli Leila , Kauppila Antti , Mäkila Ulla‐Maija , Risteli Juha
Published: February 2007

In ovarian carcinoma, elevated serum concentrations of the aminoterminal propeptide of type‐Ill procollagen are related to the clinical stage of the disease and to the presence of ascites, which contains very high concentrations of the pro‐peptide. In a follow‐up of patients with advanced disease, favorable clinical course was associated with normalizing pro‐pep tide values, whereas in progressing disease the values increased several weeks before clinical progression. In stable disease the concentrations were constantly above the reference range. Laminin and type‐IV‐collagen‐related serum antigens were mostly within the reference range.
Inhibitory effect of prolonged administration of cysteamine on experimental carcinogenesis in rat stomach induced by N‐methyl‐N′‐nitro‐N‐nitrosoguanidine
Authors: Tatsuta Masaharu , Iishi Hiroyasu , Yamamura Hisako , Baba Miyako , Mikuni Tomiko , Taniguchi Haruo
Published: February 2007

The effect of cysteamine (2‐aminoethanethiol hydrochloride) on the incidence and histology of gastric adenocarcinomas induced by N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) was investigated in inbred Wistar rats. Prolonged administration of 25 or 50 mg per kg body weight of cysteamine after treatment with MNNG for 25 weeks significantly reduced the incidence and number of adenocarcinomas of the glandular stomach. Histological examination showed that the adenocarcinomas that did develop in rats treated with these 2 doses of cysteamine had high mucin‐producing activity. Furthermore, treatment with cysteamine caused significant increases in serum gastrin level and gastric acid secretion, together with significant decreases in the antral mucosal pH and the labelling indices of pyloric and oxyntic gland mucosae and gastric cancer. These findings indicate that cysteamine inhibits the development of gastric adenocarcinomas and that its effect may be related to decreasing proliferation of cells in the gastric mucosae.
Thromboplastin release, but not content, correlates with spontaneous metastasis of cancer cells
Authors: Girimstad Ivar Amund , Prydz Hans
Published: February 2007

No previous studies on the possible contribution of cancer‐cell procoagulants to metastasis have fulfilled all the criteria for attaining biologically relevant and readily interpretable data (Grimstad et al., 1986), viz: (I) Spontaneous metastasis from primary tumors should be assessed in syngeneic animals; (2) cloned cell lines should be used to correlate cell properties, because heterogeneity within the cell lines employed is a source of serious error; (3) enough clones, derived from the same original tumor, should be used to identify only non‐random correlations. Observing these criteria, we examined the procoagulant activities of 19 murine fibrosarcoma cell clones and 4 uncloned cell lines with high to moderate or low potential for lung metastases formation. The procoagulant activity found was exclusively of the thromboplastin (tissue factor, factor III) type. It occurred in all cell homogenates, but the quantities did not correlate with metastatic potential. In contrast, all highly to moderately metastatic cell clones and lines from 2 different fibrosarcomas shed thromboplastin activity into the culture medium, whereas no weakly metastatic cells did. Histological examination further supported these indications that release of thromboplastin from cancer cells can promote metastasis by initiating blood clotting and thereby facilitating arrest of the cancer cells in target organ vessels. Examination of a third fibrosarcoma showed that release of thromboplastin activity is not necessary for metastasis in all tumors.
A new experimental metastasis model in athymic nude mice, the human malignant melanoma lox
Authors: Fodstad ØYstein , Aamdal Steinar , McMenamin Mary , Nesland Jahn M. , Pihl Alexander
Published: February 2007

The human tumor line LOX was established as an s.c. xenograft in nude mice from a lymph‐node metastasis of a patient with malignant melanoma, I.v. injection into adult nude mice of single‐cell suspensions prepared from xenografts resulted in progressively growing lung tumor colonies that killed the animals. No difference in colony formation was seen between cells taken from lung colonies and s.c. xenografts. An in vitro cell line, LOX‐L, was established from lung colonies, and the mono layer cells, detached with EDTA, retained the same ability to form experimental lung metastases. In a total of 14 experiments, 82 of 89 mice receiving I × 106 viable tumor cells died with a mean survival time of 34.1 ± 4.8 days. Long‐term passaging in vivo and in vitro did not result in any alteration of the lung‐colonizing potential of the LOX cells, whereas trypsinization of the cells before i.v. injection reduced lung colony formation. The life span was inversely related to the number of LOX cells injected, permitting estimation of the cell kill caused by chemotherapy. Mice injected i.v. with the LOX cells showed the same relative response to cis‐diamminedichloroplatinum (CDDP) and mitozolomide (MZA) as did animals carrying s.c. xenografts. The LOX cells have shown a remarkable stability and similarity to the cells of the patient's tumor with respect to morphology, karyotype and chemosensitivity. The LOX model may be useful for testing effects of therapy on lung micro‐ and macrometastases, and the activity of antimetastatic agents, as well as for studying mechanisms involved in the metastatic process.
Establishment of a human cell line (mono mac 6) with characteristics of mature monocytes
Authors: Ziegler‐Heitbroc H. W. Löms , Thiel Eckhard , Futterer Agnes , Herzog Volker , Wirtz Antje , Riethmüller Gert
Published: February 2007

A monocytic cell line, termed Mono Mac, was established from peripheral blood of a patient with monoblastic leukemia. Two clones, designated Mono Mac I and Mono Mac 6, were isolated and both were assigned to the monocyte lineage on the basis of morphological, cytochemical and immunological criteria. Most importantly, the clones express NaF‐sensitive non‐specific‐esterase, produce reactive oxygen and stain with MAb My4. Mono Mac 6, in addition, constitutively exhibits phagocytosis of antibody‐coated erythrocytes in 80% of the cells and reacts with a panel of MAbs that are specific for mature monocytes, i.e., M42, LeuM3, 63D3, Mo2 and UCHMI. By contrast, the monoblastic cell lines U937 and THP‐I are negative for all these markers. Only expression of My4 could be detected after differentiation induced by interferon‐γ (IFN‐γ). Similar treatment of Mono Mac I, however, resulted in staining with all the monocyte‐specific MAbs mentioned above, while IFN‐γ treatment of Mono Mac 6 enhanced antigen expression. In addition, the cells showed an increased frequency of multinucleated cells with a rise from 4.8% to 21.9%. Mono Mac 6 appears to be the only one of the cell lines studied to constitutively express phenotypic and functional features of mature monocytes.
Cancer of the larynx/hypopharynx, tobacco and alcohol: Iarc international case‐control study in Turin and Varese (Italy), Zaragoza and Navarra (Spain), Geneva (Switzerland) and Calvados (France)
Authors: Tuyns A‐J. , Esteve J. , Raymond L. , Berrino F. , Benhamou E. , Blanchet F. , Boffetta P. , Crosignani P. , Moral A. Del , Lehmann W. , Merletti F. , Pequignot G. , Rreou E. , Sancho‐Garnier H. , Terracini B. , Zubiri A. , Zubiri L.
Published: February 2007

A case‐control study on larynx and hypopharynx cancer was carried out in 6 populations including the city of Turin and the province of Varese (Italy), the provinces of Navarra and Zara‐goia (Spain), the canton of Geneva (Switzerland), and the departement of Calvados (France). This report presents an analysis of the risk associated with alcohol and tobacco consumption based on 1,147 male cases and 3,057 male population controls. Special attention was given to the study of the risk at various sites of larynx and hypopharynx. The effect of tobacco is similar for all sites and the risk associated with ever smoking is on the order of 10. The risks from alcohol drinking depend on site. They are similar for epilarynx and hypopharynx (RR = 4.3, for more than 80 g/day) and lower for endolarynx (RR = 2.1, For more than 80 g/day). For all sites the risk decreases after quitting (RR = 0.3 after 10 years); exclusive use of filter cigarettes is protective (RR = 0.5 relative to smokers of plain cigarettes only) as is exclusive use of blond tobacco (RR = 0.5 relative to smokers of black tobacco only). Inhalation increases the risk of endolaryngeal cancer but not that of hypopharynx or epilarynx. The relative risks for joint exposure to alcohol and tobacco are consistent with a multiplicative model.
A case‐control study of diet and colo‐rectal cancer in Northern Italy
Authors: La Vecchia Carlo , Negri Eva , Decarli Adriano , D'Avanzo Barbara , Gallotti Liliana , Gentile Antonella , Fkanceschi Silvia
Published: February 2007

The relation between dietary factors and the risk of colo‐rectal cancer was investigated in a case‐control study conducted in Northern Italy on 339 cases of colon cancer, 236 cases of rectal cancer and 778 controls admitted to hospital for acute, non‐neoplastic or digestive disorders. Consistent positive associations were observed with more frequent consumption of starchy foods (pasta or rice) (relative risk, RR = 3.0 for colon and I.S for rectum (or highest vs. lowest fertile) and beef/veal meats (RR = 2.1 for colon, 2.1 for rectum), whereas reduced relative risks were observed in subjects reporting more frequent green vegetable consumption (RR = 0.5 for highest vs. lowest tertile), a few specific vegetable or fruit items, and coffee (RR = 0.6 for highest vs. lowest tertile). Various fats in seasonings were positively, but inconsistently, related to intestinal cancer risk, whereas no association was evident with measures of whole grain foods or alcohol intake. For both intestinal sites, a 4‐ to 5‐fold difference in risk was evident between the extreme quintiles of a simple score obtained by algebraic sum of the A major groups of foods. These findings could not be explained in terms of confounding by socio‐economic status or other major potential distorting factors, are in agreement with the results from previous studies of colo‐rectal cancer in Southern Europe, and are consistent with various aspects of the descriptive epidemiology of intestinal cancer in Italy.
Human papillomavirus, herpes simplex virus and cervical cancer incidence in greenland and denmark. A population‐based cross‐sectional study
Authors: Kjaer S. K. , de Villiers E.‐M , Haugaard B. J. , Christensen R. B. , Teisen C. , Møller K. A. , Poll P. , Jensen H. , Vestergaard B. F. , Lynge E. , Jensen O. M.
Published: February 2007

In Greenland, the incidence of cervical cancer is 5.7 times higher than in Denmark among women aged 20‐39. From Nuuk (Greenland) and Nykftbing Falster (Denmark) a sample of 800 women aged 20‐39 years was drawn at random. A total of 586 and 661 women were investigated in Greenland and Denmark respectively. All women had a gynecological examination including a PAP‐smear and cervical scrape for HPV‐anafysis (filter in situ hybridization). A blood sample was taken for analysis of HSV type‐specific antibodies (ELISA). The percentage of normal smears was identical in the 2 areas (95%). The total HPV 16/18 infection rate was 13% in Denmark and 8.8% in Greenland, and the age‐adjusted prevalence rate in Greenland was only 67% of that in Denmark (95% Cl: 0.05‐0.89). The proportion of HPV 6711 positivity was the same in Greenland and in Denmark (6.7% vs. 7.5%). A significantly higher proportion of the Greenlandic women had HSV‐2 antibodies (68.2%) in comparison with Danish women (30.9%) (p < 0.01). The prevalence of HSV‐I was also higher in Greenland, especially in women aged 20 to 24. Our finding of a higher HPV infection rate in Denmark than in Greenland, opposed to cervical cancer rates, does not support a role for these viruses as determinants of cervical cancer incidence. In contrast, the rate of HSV‐2 infection co‐varies with the observed incidence of cervical cancer. This is in line with the notion that differences in cervical cancer incidence between Denmark and Greenland are determined by aspects of sexual behavior.
A colposcopical lesion of the uterine cervix frequently associated with papillomavirus type 16 as detected by in situ and southern blot hybridization: A cytohistological correlation study
Authors: Morin Carol , Bouchard Celine , Fortier Michel , Levesque Roger , Meisels Alexandra
Published: February 2007

A convoluted aceto‐white lesion was observed by colpos‐copy on the uterine cervix of 19 patients. A search for specific types of papillomavirus was undertaken in these lesions which proved histologically to be a vertical association of CIN in the lower strata of the squamous epithelium and typical condy‐loina in the uppermost layers. Previous cell samples correlated with histology in only (I out of the 19 cases, and were not therefore an accurate predictor of his to logic findings. However 16 out of our (9 cases had sufficient cellular changes to warrant colposcopy and biopsy. Papillomavirus caps id antigen was detected by peroxidase‐antiperoxidase staining technique in 12 out of the 19 cases (63.1%). In situ hybridization using biotinylated HPV‐16 DNA probes was positive in 13 out of 18 cases (72.2%). Southern blot hybridization gave the typical Pstl pattern of HPV‐ONA in 8 out of 9 cases examined. The detection of HPV‐DNA and HPV capsid antigen was particularly high in this “convoluted”cervical lesion, suggesting that the virus remains biologically active. It may therefore be assumed that this lesion represents a particular phase of the disease process in which early gene function and late gene expression of the viral genome are markedly manifested. Furthermore, this lesion may well represent a link between the early manifestation of HPV infection (condyloma) and CIN, which constitute a morphologic continuum initiated by papillomviruses.
Glycoprotein P3.58, associated with tumor progression in malignant melanoma, is a novel leukocyte activation antigen
Authors: Hulzmann Bcrnhard , Lkhmann Jiirgen M. , Ziegler‐Heitbrock H. W. Löms , Funke Ilona , Riethülier Gert , Johnson Judith P.
Published: February 2007

The P3.58 antigen is defined by monoclonal antibodies (MAbs) selected to discriminate between benign and malignant melanocytk cells. Its expression in malignant cells has been shown to correlate with an increased risk of metastasis. A survey of a wide range of tissues revealed that, on normal tissue, expression of P3.58 antigen is restricted to a subset of cells involved in the immune response. The antigen was found not only on certain endothelia, but also on activated macro‐phages in vivo and in vitro and as well as on activated B lymphocytes. A comparison with known B‐lymphocyte and leukocyte activation antigens indicated that P3.5B is a novel leukocyte activation antigen. Biochemical analysis of the P3.58 antigen isolated from cells of different histogenic origin indicated that different molecular forms of the antigen exist, apparently depending on the cell type of origin. P3.58 molecules precipitated from tunicamycin‐treated cells were identical in all cell types, suggesting that the variation observed is due to variable N‐glycosylation.
Lymphoma‐specific T‐ and B‐cell responses suggest the involvement of HTLV‐I in virus‐non‐productive lymphomas of a married couple
Authors: Schneider E. Marion , Saal Johannes G. , Mann Dean L. , Pawelec Graham , Schneider Josef , Schlote Wolfgang , Wernet Peter
Published: February 2007

The occurrence of aberrant cellular progeny is not an infrequent event in vivo. Viral infections (Hanto et al., 1981; Gallo, 1984) and/or failures in genetic programming during cell proliferarion may facilitate the manifestation of malignancy in states of incomplete immune surveillance. This is suggested by a high incidence of lymphoid malignancies in immunode‐pressed individuals, as for example after organ transplantation (Penn, 1981). Efficient cellular defense mechanisms which control malignant growth have been postulated. So far, MHC‐restricted, tumor‐specific cytotoxic T cells have not been identified in vivo. Moreover, effector cells with natural killer activity have not consistently been shown to function as general or specific anti‐tumor agents in vivo. Nevertheless, LAK cells are presently under investigation in adoptive immuno‐therapy for tumors. The concept of LAK‐cell treatment is based on the observation that high concentrations of interleu‐kin 2 (IL‐2) induce activation and proliferation of autologous, tumor‐specific cytotoxic cells (Hersey et al., 1981; Lotze et al., 1981). The most promising results have been obtained in mouse tumor models, whereas treatment of human diseases has rarely been successful (Rosenberg et al., 1986).

In the present report, high percentages of CD25‐positive T lymphocytes were detected in PB and LN cell suspensions of a patient with a B‐cell NHL. These T cells were successfully enriched in cultures containing low doses of IL‐2. The CTX mediated by these T‐cell lines and a single T‐cell clone derived from them was specific for autologous lymphoma cells as well as for the lymphoma cells from a different individual. Interestingly, an HTLV‐I‐infected tumor‐cell line was recognized also. The specific cellular as well as the humoral immune response. however, was drastically reduced following chemo‐ and radiotherapy. In contrast, non‐specific CTX mediated by aclivated NK‐like cells persisted.
The effects of human recombinant tumor necrosis factor on glioma‐derived cell lines: Cellular proliferation, cytotoxicity, morphological and radioreceptor studies
Authors: Rutka James T. , Giblin Jane R. , Berens M. E. , Bar‐Shiv Enav , Tokuda Kouichi , McCulloch John R. , Rosenblum Mark L. , Eessalu Thomas E. , Aogarwal Bharat B. , Bodell William J.
Published: February 2007

To determine whether tumor necrosis factor is of potential value for the treatment of human malignant gliomas, we studied the effects of human recombinant tumor necrosis factor (rTNF‐α) on the morphology, incorporation of tritiated thymidine, and proliferation of 5 established cell lines derived from human malignant gliomas and 3 normal human brain cell cultures. A radioreceptor analysis for rTNF‐n was performed on all cell fines and cultures. Two of the 5 human glioma cell lines (SF‐188 and U 343 MG‐A) demonstrated a marked decrease (60% or less of untreated controls) in the uptake of tritiated thymidine when treated with rTNF‐α at a concentration of 40 U/ml; rTNF‐α at 100 U/ml had antiprolif‐erative and cytotoxic effects on both cell lines. The growth and proliferation of cell tines SF‐126 and U 251 MG were not affected by rTNF‐α even at high concentrations (5,000 U/ml). The growth and proliferation of SF‐S39 were affected to an intermediate degree. A colony‐forming efficiency assay corroborated the results of the proliferation studies: SF‐126 was relatively resistant (surviving fraction of 0.9 at 500 U/ml) and SF‐188 was relatively sensitive (surviving fraction of 0.08 at 500 U/ml) to the cytotoxic effects of rTNF‐α. Time‐sequence electron microscopy showed that rTNF‐α at a concentration of 500 U/ml caused ultrastructural changes in SF‐ 188, including increased intracytoplasmic vesiculation, swelling and degeneration of mitochondria, loss of cell:cell junctions! complexes, and fragmentation of the plasma membrane. Studies with 125I‐rTNF‐α showed a variable degree of binding in all cell lines and cultures. SF‐188, a highly sensitive cell line, demonstrated the strongest binding of 125I‐rTNF‐α (3,400 receptors/ cell with high affinity; kd = 0.27 nm), while SF‐126, a highly resistant cell line, had the weakest binding (809 receptors/cell; kd = 0.25 nm). We conclude that there is a spectrum of anti‐proliferative and cytotoxic activity among glioma‐derived tumor cell lines exposed to rTNF‐α. An increased number of rTNF‐α receptors appears to be a necessary but insufficient condition to explain the antiproliferative effects observed in some glioma‐derived cell lines.
Expression of a hepatocyte membrane antigen during hepatocarcinogenesis and in the developing liver of the rat
Authors: Matsumoto Masahiro , Tamakoshi Katsutoshi , Kanai Koichi , Kako Makoto , Fukumoto Tetsuo
Published: February 2007

Changes in the expression of a cell membrane antigen during hepatocarcinogenesis and in the developing liver were analyzed by HAM.4, a monoclonal antibody (MAb) against a membrane glycoprotein of normal rat hepatocyte. Of the precancerous lesions observed during hepatocarcinogenesis induced by diethylnitrosamine, 2‐acetylaminofluorene and partial hepatectomy, early neoplastic foci were uniformly stained by HAM.4. In contrast, some cells in the neoplastic nodules at the late stage did not express HAM.4 antigen on the cell surface. Of the cancer tissues, well‐differentiated hepatocellular carcinomas were stained by HAM.4 whereas poorly differentiated carcinomas did not bind HAM.4. In developing rat liver, HAM.4 antigen was first expressed on fetal hepatocytes at the 18th day of gestation. It gradually increased until 4 weeks after birth when the intensity of the stain was almost the same as in adult rat liver. These results suggest that the expression of a membrane antigen defined by HAM.4 is closely associated with the differentiation of bile canalicular face and that HAM.4 might be useful in characterizing differentiation of cells during malignant transformation of hepatocytes.
Development of in vivo models for studies of brain metastasis
Authors: Schackert G. , Fidler I. J.
Published: February 2007

To develop an in vivo model for studies of brain metastasis, varying doses of K‐1735 tumor cells with differing metastatic potentials were injected into the carotid arteries of anesthetized mice. Direct intracerebral administration of cells produced tumors in the brain parenchyma, and all tumor cells produced melanotic lesions at these sites. Studies with radio‐actively‐labelled tumor cells confirmed that tumor cells reached the meninges and extracerebral organs. Distant metastases were found in the lungs and hearts of mice which received K‐1735 cells into the carotid artery, but not in animals which received tumorigenic non‐metastatic cells. Regardless of the type of cells injected, no growths were found in the meninges. The high degree of reproducibility recommends this model for studies designed to investigate the biology and therapy of cancer metastasis to the brain.
An atypical t(12;15) translocation of chromosomes found in murine plasmacytomas and activation of the c‐myc oncogene
Authors: Ohno Shinsuke , Takahashi Rei , Mihara Koh‐Ichiro , Chen Hui‐Ling , Migita Shunsuke , Sugiyama Taketoshi
Published: February 2007

Cells from murine plasmacytomas (MPC) consistently exhibit either the 12;15 or the 6;15 translocation. Recently, we found that cells from 2 MPC (ABPC 45 and ABPC 26) did not exhibit any known translocation. However, these MPC contained one chromosome 15 (15q‐) that was shorter than its normal homologue and one 12 (12q+) that was longer than its normal 12 counterpart. Chromosome 15q‐ contained only one thin D band, corresponding in size to either D1 or D3 band. A minor light band D2 was apparently deleted. Chromosome 12q+ contained a light F1 band that was longer than the normal 12F1. In ABPC 45, the c‐myc gene was assigned by in situ hybridization to the F1 region of 12q+ as well as to its original site of 15D2. Moreover, the in situ hybridization experiment assigned the Sα gene to the F1 regions of both chromosomes 12 and 12q+. These findings indicate that a minor light band D2 of chromosome 15 carrying the c‐myc gene was translocated into the major light band F1 of 12, resulting in a longer chromosome 12q+ and a correspondingly shorter chromosome 15q‐. This type of chromosomal translocation suggests that ABPC 45 developed through a cytogenetic mechanism different from that of MPC with the typical t(12;15) translocation.
Target‐cell specificity of hematopoietic regulatory proteins for different clones of myeloid leukemic cells: Two regulators secreted by krebs carcinoma cells
Authors: Shabo Yosef , Lotem Joseph , Sachs Leo
Published: February 2007

The normal myeloid hematopoietic regulatory proteins include one class of proteins that induces viability and multiplication of normal myeloid precursor cells to form colonies (called MGI‐1=CSF or IL‐3) and another class (called MGI‐2=DF) that induces differentiation of normal myeloid precursors without inducing cell multiplication. Different clones of myeloid leukemia cells can differ in their response to these regulatory proteins. The present experiments characterize proteins secreted by Krebs ascites carcinoma cells that induce differentiation of 2 different types of myeloid leukemic cell clones (clones II and 7‐M12). The results indicate the following: (1) Krebs cells produce 2 distinct and separable proteins, each inducing differentiation in one of the leukemic clones. (2) One protein induced differentiation of clone‐II myeloid leukemic cells and of normal myeloid precursor cells was free of any colony‐inducing (MGI‐1=CSF or IL‐3) activity, bound to double‐stranded mammalian DNA, and was thus a differentiation‐inducing protein MGI‐2, This MGI‐2 protein (MGI‐2A) was purified to a single silver‐stained band on an SDS polyacrylamide gel. (3) The other protein induced differentiation of clone 7‐M12 myeloid leukemic cells, did not bind to doublestranded DNA and could not be separated from the myeloid growth‐inducing protein MGI‐IGM (GM‐CSF) after 6 steps of purification including high‐pressure liquid chromatography. The use of specific antisera confirmed that the protein which induced differentiation of clone 7‐M12 leukemic cells was MGI‐IGM. The results show that Krebs ascites tumor cells produce 2 different myeloid hematopoietic regulatory proteins that differ in their target specificity for different clones of myeloid leukemic cells.
Autologous mixed lymphocyte‐tumor reaction and autologous mixed lymphocyte reaction. II. Generation of specific and non‐specific killer T cells capable of lysing autologous tumor
Authors: Uchida Atsushi , Moore Michael , Klein Eva
Published: February 2007

The specific and non‐specific nature of autotumor cytotoxicity induced in autologous mixed lymphocyte‐tumor culture (AMLTC) and autologous mixed lymphocyte culture (AMLC) was studied in patients with carcinomatous pleural effusions. Small‐ and medium‐sized blood lymphocytes that were isolated by centrifugation on discontinuous Percoll gradients did not lyse autologous, freshly isolated effusion tumor cells. In vitro activation of the small lymphocytes, but not of the medium lymphocytes, with autologous tumor cells generated cytotoxic potential restricted to autologous tumor. When stimulated with autologous non‐malignant non‐T cells, the medium lymphocytes, but not small lymphocytes, were triggered to cytotoxicity that acted not only on autologous tumor cells but also on allogenek tumor cells, T blasts, and tumor cell lines. Experiments using monoclonal antibodies (MAb) and complement (C) showed that both types of killer cells were CD2+CD3+CD16‐ T cells. Autotumor cytotoxicity developed in AMLTC was mediated by the CD4+CD8+ T cell subset in 6 of 9 cases and the CD4+ CD8‐ subset in the other 3 cases. In contrast, cytotoxicity induced in AMLC was exerted exclusively by the CD8+ subset. The enrichment of blasts from cultured T cells on discontinuous density gradients enhanced autotumor killing activity, with no reactivity recorded for blast depleted, resting T cells. Addition of mito‐mycin‐C‐treated large granular lymphocytes (LGL) to AMLTC abolished the induction of autotumor killer cells, whereas non‐specific killer cells were generated in AMLC irrespective of the pretence of LGL. These results indicate that stimulation of autoreactive T cells in AMLTC and in AMLC could induce 2 distinct types of autotumor killer cells.
Frequency of gallbladder cancer in chile, A high‐risk area
Authors: Nervi Flavio , Duarte Ignacio , Gómez Guillermo , Rodríguez Germán , Pino Guido Del , Ferrerio Osvaldo , Covarrubias Carmen , Valdivieso Vicente , Torres María Isabel , Urzúa Alejandro
Published: February 2007

We report an autopsy study of gallbladder cancer prevalence in Chile, where the risk of this disease is among the highest reported world‐wide. In 14,768 autopsy protocols obtained from 3 university hospitals, 45% of women and 20% of men older than 20 years had gallstone disease (the major known risk factor for gallbladder cancer). The prevalence of gallbladder cancer in Chileans was compared to that found in a Swedish‐Chechoslovakian autopsy study previously published. These countries were chosen because of their high frequency of gallstone disease. The comparison was performed by using logistic regression models adjusting for possible differences in the age‐sex structure or the true incidence of gallstones in both populations. We found that the most important single risk factor for gallbladder cancer in Chile was gallstone disease, with an estimated effect on the logistic scale meaning that the cancer risk for subjects with gallstones is seven times higher than for those without the disease. Second in importance was the risk for sex, women being 2.8 times higher than for men. The estimated difference in the sex composition and the incidence of gallstones resulted in 17.9% higher odds of cancer in Chile than in Sweden and Czechoslovakia. However, this difference was not significant. This study suggests that the major etiologic factors of gallbladder cancer in Chileans, Swedes and Czechoslovakians are primarily related to gallstone disease.