bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunohistochemical detection of c‐Ha‐ras oncogene p21 product in pre‐neoplastic and neoplastic lesions during hepatocarcinogenesis in rats
Authors: Galand P. , Jacobovitz D. , Alexandre K.
Published: February 2007

An immunohistochemical study of c‐Ha‐ras expression was performed on preneoplastic and neoplastic stages of diethl nitrosamine (DENA)‐induced hepatocarcinogenesis in rats, using an antibody raised against a peptide sequence of the Ha‐ras p21 product. Moderate to high immunostaining intensity was observed in the following hepatocytic lesions: (I) hepato‐cellular carcinomas (14/14) and associated neoplastic nodules (S/S) and foci of phenotypic alterations (35/40) (after 13–20 months of treatment); (2) neoplastic nodules (6/6) and associated foci (42/50) (after 5–9 months); (3) foci (10/10) (after 2 months); and (4) small, slowly growing foci (26/40) found 9 months after treatment with DENA without prior partial hepatectomy, resulting in low number of nodules and no tumor even after IS months. No c‐Ha‐ras p21 was detected immunohistochemically in normal nor in regenerating rat liver. Our result indicate that increased Ha‐ras expression is an early and stable event in liver lesions associated with he‐patocarcinogenesis. They also imply that increased Ha‐ras expression is insufficient (if at all implicated) for inducing fully malignant hepatocyte transformation. It might be indicative of cell populations at an increased transformation risk.
Place of birth and incidence of ocular melanoma in the United States
Authors: Schwartz Stephen M. , Weiss Noel S.
Published: February 2007

To examine whether or not being born in the southern United States is associated with an increased risk of ocular melanoma, the distribution of State of birth of 763 patients (White, not of Spanish origin) with ocular melanoma diagnosed between 1973 and 1984 and identified by 9 population‐based cancer registries participating in the Surveillance, Epidemiology, and End Results program, was compared to the distribution of State of birth of the underlying population of the regions served by these registries. The incidence of ocular melanoma among persons born in the southern United States was nearly the same as that among persons born in the north, after adjustment for age, sex, and residence at diagnosis (Incidence Ratio = 1.1, 95% C.I. 0.8, 1.5). Comparisons of the risk of ocular melanoma between persons born in States with high and low levels of solar radiation yielded similar results, and a trend with increasing solar radiation was observed only among females. These findings do not support the hypothesis that exposure to the sun early in life is a major risk factor for ocular melanoma.
Soft‐tissue sarcomas of the head and neck in adults and children: Experience at a single institution with a review of literature
Authors: Figueiredo Marco T. A. , Marques Lourdes A. , Campos‐Filho Nelson
Published: February 2007

Ninety‐four soft‐tissue sarcomas of head and neck occurring among 10,700 malignancies, seen during the period 1953–1980 in the head‐and‐neck surgical department, were studied with reference to age, sex, ethnic origin, site, histological type and survival. The objective was to review our own experience with sarcomas in these sites seen in the Department of Pathology, A.C. Camargo Hospital. The predominant site was the head. Fibrosarcoma was the most frequent type in adults and rhabdomyosarcoma, located exclusively in the head, was the most frequent in children.
Generation of monoclonal antibodies reactive with nuclear proteins of human primary breast tumors
Authors: Dinh Bao‐Linh , Tremblay Monique , Paradis Diane , Roy Paul‐Emile , Tetu Bernard
Published: February 2007

Nuclear proteins were extracted from purified nuclei of human primary breast tumors (BrT) and bladder tumors and of human normal breast, kidney and lymphocytes by enzymatic treatment. SDS‐Polyacrylamide gel electrophoresis of nuclear proteins from breast tumors showed different bands in the molecular weight zones from 25 to 220 kDa which were absent or present only as traces in normal breast tissue. Murine monoclonal antibodies (MAbs) have been produced using nuclear extracts of human primary breast tumors as immunogens. Approximately 2,000 hybridomas were generated from 5 hybridizations. According to their reactivity to BrT nuclear extracts and mammary carcinoma cell line MCF‐7, seven hybridomas were selected and cloned. They were further characterized with histological immunoperoxidase assays of formaldehyde‐fixed BrT paraffin tissue sections. MAb 6A3 particularly gave strong nuclear staining with all BrT specimens while MAb ID8 showed both nuclear and cytoplasmic staining with only some of them. Specimens from mammoplasty did not react with these MAbs. Immunoblotting of BrT nuclear extracts as developed with MAbs 6A3 and ID8 revealed major protein bands with molecular weight of 120 and 130 kDa. The potential use of these MAb‐defined BrT‐related nuclear proteins as markers for human breast cancer was suggested.
Recombinant human tumor necrosis factor‐α: Thrombus formation is a cause of anti‐tumor activity
Authors: Shimomura Kyoichi , Manda Toshitaka , Mukumoto Sueo , Kobayashi Katsumasa , Nakano Kazuo , Mori Jo
Published: February 2007

In a previous study we showed that recombinant human tumor necrosis factor‐α (rTNF‐α) has no cytolytic effect on Meth A fibrosarcoma cells in vitro but that it has a strong anti‐tumor activity in vivo. In the present work, we define the in vivo mode of action of rTNF‐α on solid‐form Meth A fibrosarcoma implanted intradermally (i.d.) in mice. rTNF‐α exhibited strong anti‐tumor activity when given intravenously (i.v.) 7 or 10 days after tumor implantation, but not when given 3 days after implantation. Light and electron microscopy showed that rTNF‐α impaired microcirculation by producing fibrin‐like substances in newly formed microcapillaries in 7‐day‐old tumor tissue. An anti‐coagulant, dicoumarol, abrogated the effect of rTNF‐α. Injection of carbon particles showed that the development of capillaries in 7‐day‐old tumors was more extensive than in 3‐day‐old tumors, and suggested that the anti‐tumor activity of rTNF‐α depends upon a fully developed fine network of induced capillaries in the tumor. Electron microscopy showed that rTNF‐α increases the number of primary and secondary lysosomes in the cytoplasm of 7‐day‐old tumor cells. The results suggest that rTNF‐α selectively stems the blood flow in newly formed microcapillaries, eventually leading to autolysis of the tumor cells.
JB/MS murine melanoma: A new model for studies on the modulation of differentiation and of tumorigenic and metastatic potential
Authors: Hearing Vincent J. , Cannon Grace B. , Vieira Wilfred D. , Jiménez‐Atiénzar Mercedes , Kameyama Koichiro , Law Lloyd W.
Published: February 2007

The recently obtained JB/MS melanoma (induced by DMBA in C57BI/6 mice) has been successfully established in culture, and characterization of various parameters of these cells, as they have been serially passaged in vivo and in vitro, has begun. The culture lines were initially highly dendritic and melanotic, growing slowly in vitro and extremely slowly in vivo. During serial passage in vivo and in vitro the cell lines have gradually evolved into less melanotic, but more proliferative, tumorigenic and metastatic cells. We have been able to demonstrate that the JB/MS melanoma shares the common melanoma TSTA previously reported for B16, K1735 and JB/RH melanomas, but does not cross‐react with the S91 melanoma or with other non‐melanoma cell lines used as specificity controls. The JB/MS cells can be induced to differentiate in vitro by α‐melanocyte stimulating hormone, a physiologically relevant agent, and studies have been initiated to detail the level at which this induction occurs. These sublines should prove to be excellent models for study of the progression of transformed cells from non‐tumorigenic to tumorigenic phenotypes, and for progression through stages of varying metastatic potential, immunogenicity and differentiation.
The reversal of doxorubicin resistance by verapamil is not due to an effect on calcium channels
Authors: Huet S. , Robert J.
Published: February 2007

Using a model of doxorubicin‐resistant rat glioblastoma cells, we have studied the relationship between the reversal of multi‐drug resistance by verapamil and calcium fluxes into the cells. Although it is known to be a voltage‐dependent calcium channel blocker, verapamil exerted no effect on calcium entry into the cells. In the absence of calcium in the medium, drug resistance was not affected and verapamil was still active. It was possible to modify calcium fluxes into the cells by using manganese ions (decreasing calcium uptake) or the calcium ionophore A23187 (increasing calcium uptake). These agents had only a marginal effect on the expression of drug resistance by the cells and did not prevent the action of verapamil on its reversal.
Fucosylated type‐2 chain polylactosamine antigens in human lung cancer
Authors: Zenita Koichi , Kirihata Yoshiko , Kitahara Aiko , Shigeta Katsuyoshi , Higuchi Kayoko , Hirashima Kunimi , Murachi Takshi , Miyake Masayuki , Takeda Toshio , Kannagi Reiji
Published: February 2007

Four specific monoclonal antibodies (MAbs) have been used to study distributions of fucosylated type‐2 chain polylactosamine antigens, Lex, poly Lex, Ley and sialylated Lex‐i antigens, in human lung cancer tissues and in the serum of patients with lung cancers. Radioimmunoassay frequently showed abnormally high antigen levels in the sera of 66 lung cancer patients tested. When histological typing was performed, high serum levels of the above 4 antigens were most frequently observed in patients with adenocarcinoma of the lung; i.e., after combining the results from the 4 antigens, 75% of the sera from patients with lung adenocardnoma were positive (50% in the case of large‐cell carcinoma, 30% in the case of squamous‐cell carcinoma and 27% for small‐cell carcinoma). Among the 4 antigens, the sialylated Lex‐i antigen had the highest positive incidence, 58%, in the sera of patients with adenocarcinoma of the lung, compared to 33% for Ley 29% for poly Lex, and 8% for Lex antigen. On the other hand, when the distributions of these antigens in the lung cancer tissues of 42 patients were studied by immunohistological techniques, the Lex antigen had the highest positive incidence, 100%, in lung adenocarcinoma tissues, poly Lex antigen had 86%, sialylated Lex‐i antigen had 71%, and Lex antigen had 29%. In cancer tissues, the incidence of non‐sialylated antigens, such as Ley, poly Lex and Lex antigens, often exceeds the positive incidence of the sialylated antigen, but the sialylated form of the antigen, such as sialylated Lex‐i antigen, appears more often than the non‐sialylated form in patients' sera.
Sister chromatid exchanges and chromosomal aberrations in lymphocytes of nurses handling cytostatic agents
Authors: Benhamou Simone , Pot‐Deprun Jacques , Sancho‐Garnier Hélène , Chouroulinkov Ivan
Published: February 2007

A cohort study of 29 nurses who constantly handled cyto‐static drugs, and 29 controls matched according to sex and age, was carried out between 1983 and 1986. Cytogenetic damage was assessed by sister chromatid exchanges (SCE) and chromosomal aberrations. No significant increase in mean number of SCE was found for nurses (7.37) as compared to matched controls (7.00), whereas a significant excess of SCE (p < 0.001) was observed for smokers (8.23) as compared to non‐smokers (6.75). The number of SCE was studied in relation to the amount and nature of cytostatics handled as well as to the duration of exposure. A significant association (p < 0.05) was found between individual mean number of SCE and the total number of drugs handled after adjustment for confounding factors. In contrast, the number of SCE was not significantly related to the nature of drugs handled or to the duration of exposure. With regard to chromosomal damage, no significant difference was observed between nurses and controls in gap, break, dicentric and translocation frequencies.
Tumor‐associated alpha‐2‐macroglobulin in human melanomas
Authors: Matoska J. , Wahlstrom T. , Vaheri A. , Bizik J. , Grofova M.
Published: February 2007

We and others have previously shown that human melanoma cell lines in culture synthesize alpha‐2‐macroglobulin (α2M). We have now studied melanomas from 30 patients for the presence of α2M using the peroxidase anti‐peroxidase technique on histologic sections from paraffin‐embedded tissues and primary antibody raised against tumor‐associated α2M in rabbits. α2M was detected in 10 of the 30 melanomas studied. In all but 2 cases the presence of α2M was restricted to solitary tumor cells or to solitary foci of tumor tissue. In one case of melanoma almost all tumor cells were positive for α2M, while in the others between 20% and 50% of tumor cells were positive. In all but one of the melanomas, the positivity was characteristic of epithelioid or large‐cell type or was confined to this component in melanomas with more than one cell type. In 4 positive cases, differences in the extent of α2M‐containing tumor tissue were observed between primary tumor and metastases or metastases from different localizations, with equivocal trend. Clinical follow‐up of the melanoma patients suggested that α2M‐positivity tends to correlate with an unfavorable prognosis.
Absence of expression of a human endogenous retrovirus is correlated with choriocarcinoma
Authors: Kato Nobuyuki , Larsson Erik , Cohen Maurice
Published: February 2007

We examined the RNA expression of a human endogenous provirus, termed ERV3, in 170 human tissue and cell specimens. The highest expression was found in normal placental chorionic villi as mRNAs of 9, 7.3, and 3.5 kb. The 7.3‐kb RNA species was found only in the placenta. ERV3 mRNA was expressed in most other normal and malignant tissues at a level which was 2‐10% of that seen in placenta. However, several tissues and tumor cell lines had higher transcnptional levels, equal to 10–60% of the placental level. In contrast, an almost complete abrogation of ERV3 mRNA expression was noted in choriocarcinoma cell lines and in an invasive hydatidiform mole tissue biopsy. This abrogation was not linked to deletions or rearrangements of the ERV3 genome. It appeared to be unassociated with methylation because the ERV3 provirus was similarly methylated in the DNA of placental chorionic villi and choriocarcinoma cells, and ERV3 transcription in choriocarcinoma cells was not induced by 5‐azacytidine. These results suggest that the loss of ERV3 mRNA expression is associated with susceptibility to choriocarcinoma.
Tamm‐horsfall protein is a marker of renal and extra‐renal rhabdoid tumours
Authors: Kumar S. , Jakatte S. M. , Marsden H. B. , Kumar P. , Jasani B.
Published: February 2007

A monoclonal antibody (MAb) to Tamm‐Horsfall protein (THP) was used to stain 6 renal rhabdoid tumours (RRT) and 2 primary extra‐renal rhabdoid tumours (E‐RRT). One of the E‐RRT was a tumour from the posterior fossa of a 3‐year‐old child and the other was a lump from the right side of the neck in an 18‐month‐old girl. Five of 6 RRT and both cases of E‐RRT were positive for THP. Both cases of E‐RRT also reacted with vimentin and cytokeratin MAbs. On electron microscopy, cells from both E‐RRT were seen to contain concentric whorls of intermediate filaments characteristic of rhabdoid tumours. Viable tissues from one RRT and one E‐RRT (the posterior fossa tumour) were available for tissue culture. Ninety‐five percent of the cells growing out of both tumours were polygonal and approximately 5% of these cells were THP‐positive.
Methylxanthines and breast cancer
Authors: Rohan Thomas E. , McMichael Anthony J.
Published: February 2007

The association between intake of methylaxnthines and risk of breast cancer was examined in this population‐based case‐control study conducted in Adelaide, South Australia. The study included 451 cases, and one control was matched to each case for age (to the nearest year). Overall, and within the post‐menopausal stratum, there was relatively little variation in the risk of breast cancer in association with total caffeine and total methylxanthine intake. In pre‐menopausal women, risk was increased at the higher levels of intake, but the increase in risk was not dose‐dependent. There was no evidence for an effect of methylxanthines at high levels of fat intake. Prior epidemiological and experimental studies have not provided strong support for a positive association between intake of methylxanthines and risk of breast cancer. However, the possibility that they are linked through an association between methylxanthines and those histological subcategories of benign breast disease which are strongly associated with risk of breast cancer is discussed.
Elevated antibody titers against cytomegalovirus among patients with testicular cancer
Authors: Mueller Nancy , Hinkula Jorma , Wahren Britta
Published: February 2007

The epidemiology of testicular cancer (TC) has 2 distinguishing features. First, it has an unusual unimodal age‐incidence curve which peaks about age 30, and decreases with increasing age. Second, risk of the disease has been consistently associated with a high standard of living inasmuch as it is a disease of young white men of generally higher social class in economically developed populations. These features suggest that risk may be related to relatively late age of exposure to common infectious agents resulting in damage to the developing testis. We evaluated this hypothesis in a serologic case‐control study in which subjects were compared for both prevalence and level of antibody to the following agents: measles, mumps, rubella, varicella (VZV), herpes simplex {HSV), cytomegalovirus (CMV), toxoplasmosis, Chlamydia, and Mycoplasma hominis. The TC cases included 50 with seminoma, 50 with embryonal carcinoma, and 17 with other sub‐classification. There were 100 male controls of comparable age. No consistent differences were found for any of the non‐herpes viruses. For VZV, cases generally had elevated titers, significantly so for the seminoma patients, relative risk (RR) = 6.3 (95% confidence interval, 3.0–13.3) adjusted for the titer distributions of HSV and CMV. For HSV, seminoma patients also had elevated titers, RR = 2.6 (1.0–6.4). The strongest association was with CMV. Patients had a higher prevalence rate than controls, RR = 2.0 (1.1–3.6), and a gradient of risk with titer level. Overall, those in the highest titer quartile had an RR of 4.9 compared to those with no antibody, with a significant trend (p = 0.0002). Since age at CMV infection is directly related to social class, these findings suggest that delayed exposure to CMV, resulting in a more severe infection, may be related to risk of TC. However, confounding by immune status of the cases or by other risk factors of TC could not be evaluated and may account for this observation.
Role of concomitant resistance in the development of murine lung metastases
Authors: Bonfil R. Daniel , Ruggiero Raul A. , Bustuoabad Oscar D. , Meiss Roberto P. , Pasqualini Christiane Dosne
Published: February 2007

An attempt was made to explain the distinct lung metastatic patterns of 2 mammary adenocarcinomas with a common BALB/c origin: M3, which does not induce spontaneous metastases, and MM3 with an almost 100% incidence. No difference between the 2 tumors was detected with respect to host mononuclear cell content, degree of immunogenicity or lung‐colony‐forming ability. Conversely, there was a marked difference in the capacity to induce concomitant resistance: M3‐bearing mice induced stronger and earlier resistance against i.v. challenge of both M3 and MM3 tumor cells than MM3‐bearing mice; this resistance was expressed as lower number of lung metastases and lower tumor‐cell proliferation in metastatic nodules. M3 was also able to control the development of spontaneous metastases: metastases developed in all M3‐excised mice, compared with none in M3‐bearing mice, while MM3‐bearing mice also bearing a secondary M3 tumor developed fewer metastases than mice bearing MM3 only. This anti‐metastatic effect does not appear to depend on classical immunological mechanisms since no difference could be detected between the 2 tumors in response to T cells, NK, macrophages or antibodies.
Effects of metastatic cascades on metastatic patterns: Studies on colon‐26 carcinomas in mice
Authors: Weiss Leonard , Ward Pamela M.
Published: February 2007

The present studies are based on autopsy data showing that in upper esophageal and lower rectal carcinomas, hematogenous metastasis occurs mainly first to the lungs, and cancer cells from pulmonary metastases generate arterial metastases. In lower esophageal and upper rectal carcinomas, he‐matogenous metastases occur first in the liver, then in the lungs, and are further disseminated by the arterial route. The arterial metastatic patterns are different in the 2 groups. One possible explanation for these differences in pattern is that liver “residence” is associated with different metastatic behavior; this has been tested in a model system. Experiments with the transplantable colon‐26 carcinoma in mice reveal that, when cancer cells from common s.c. transplant sites are grown in the liver, lungs or liver‐and‐lungs, and then injected into the bloodstream of fresh recipients via the left ventricle, the portal vein or the tail vein, different patterns and degrees of colonization of 11 different target sites are observed. These results are consistent with the hypothesis that growth of cancers in different anatomic sites may modify the subsequent arterial metastatic patterns, due to site‐induced changes occurring in cancer cell populations, which influence metastasis from metastases or so‐called “cascade” processes.
Establishment and characterization of cisplatin‐resistant sublines of human lung cancer cell lines
Authors: Hong Weon‐Seon , Saijo Nagahiro , Sasaki Yasutsuna , Minato Koichi , Nakano Hidehiko , Nakagawa Kazuhiko , Fujiwaka Yasuhiro , Nomura Kazuhiro , Twentyman Peter R.
Published: February 2007

Human lung cancer sublines resistant to cisplatin (CDDP) have been developed by continuously exposing cells to gradually increasing doses of CDDP and use of the limiting dilution technique. The cell lines used were PC‐7, PC‐9 and PC‐14 (pulmonary adenocarcinoma) and H69 and N23I (small‐cell lung cancer). The resistant phenotype of the resistant sublines was stable for more than 2 months in the absence of drug. PC‐7/1.2 (i.e., PC‐7 cells growing stably in medium containing 1.2 μg/ml of CDDP), PC‐9/0.5, PC‐14/1.5, H69/0.4, and N23I/ 0.2 have been developed, which are 22.9, 7.1, 3.1, 25.6, and 8.4 times more resistant to CDDP than the respective parent cell line in terms of IC50 in the soft agar colony assay with continuous drug exposure. Cloning efficiency decreased significantly in N23I/0.2. The doubling times increased significantly in most of the resistant sublines. Cellular DNA contents increased in all resistant sublines, but statistical significance was observed only in H69/0.4 (p<.0.05). Cells of the resistant sublines of PC‐7, PC‐9, PC‐14 and H69 were larger than cells of the parent lines, but the differences were not significant. The growth morphologies of all resistant sublines in the drug‐free medium were similar to those of parent cell lines. All resistant sublines tested were significantly cross‐resistant to carboplatin. The patterns of cross‐resistance, cross‐sensitivity and collateral sensitivity to adriamycin, mitomycin‐C, 5‐fluorouradl, vindesine, etoposide, aclacinomycin and vincristine were different in each resistant subline. Verapamil (1.3 μg/ml) showed little modifying effect on CDDP resistance in 5 CDDP‐resistant sublines tested except N231/0.2 (Modification Index: 0.49). Cy‐closporin A (5.0 μg/ml) modified CDDP resistance in CDDP‐resistant small‐cell lung cancer sublines (H69/0.4 and N23I/0.2) (Modification Index: 0.45 and 0.07, respectively), while in CDDP‐resistant NSCLC sublines (PC‐7/1.0 and PC‐9/0.5). cyclosporin A reduced the sensitivity to CDDP.
Development of an enzyme‐linked immunosorbent assay (ELISA) for detecting IgA antibodies to the epstein‐barr virus
Authors: Uen Wu‐Ching , Luka Janos , Pearson Gary R.
Published: February 2007

A 3‐step enzyme‐linked immunosorbent assay (ELISA) was developed for detecting IgA antibodies Co purified Epstein‐Barr virus (EBV) polypeptides. The 3‐step procedure included the use of a mouse anti‐human IgA monoclonal antibody (MAb) to amplify the IgA reaction. The 2 major EBV proteins used in this assay were the 125‐kDa component (gpl25) associated with the viral capsid antigen (VCA) complex and a major glycoprotein (gp 250/200) associated with the membrane antigen (MA) complex. Eighty‐two sera were tested on ELISA plates containing either both of the glycoproteins or each one separately. These included 45 IgA antibody‐positive sera from patients with nasopharyngeal carcinoma {NPC). With these sera, there was a good correlation, both qualitatively and quantitatively, between results with the immuno‐fluorescence (IF) and ELISA procedures. Although most IgA antibody‐positive sera contained antibodies reactive with both gpl2S and gp250/200, a number of sera contained antibodies reactive with one of the glycoproteins but not with both. The data indicated that both of these glycoproteins should be used in assays for detecting IgA antibodies to EBV, to avoid false‐negative results. This assay should be useful for screening large populations for IgA antibodies to EBV and also possibly for monitoring disease course in patients with NPC.
Non‐ocular cancer in patients with hereditary retinoblastoma and their relatives
Authors: Derkinderen D. J. , Koten J. W. , Nagelkerke N. J. D. , Tan K. E. W. P. , Beemer F. A. , Otter W. Den
Published: February 2007

In The Netherlands, retinoblastoma patients have been registered in the Utrecht national retinoblastoma registry since 1862. This register is virtually complete from 1945 onwards. We describe a unique epidemiological survey of the occurrence of non‐ocular cancer in all patients registered during the period 1945‐1970. The occurrence of non‐ocular cancer in relatives of patients with hereditary retmoblastoma is also reported. One hundred and forty‐one patients with hereditary retinoblastoma were studied for non‐ocular second primary cancer. Nineteen patients died of retrnoblastoma. The median follow‐up of the surviving 122 patients was 25 years. Seventeen of these patients developed a second primary cancer, most frequently soft‐tissue sarcoma. The cumulative incidence of non‐ocular cancer was I at the age of 35, i.e., a 14‐fold increase as compared to the general population. Twelve patients with hereditary retinoblastoma died of non‐ocular cancer whereas none of 252 patients with non‐hereditary retinoblastoma died of non‐ocular cancer. Furthermore, among the parents of our hereditary retinoblastoma patients, 24 (born before 1945) had also been affected by retinoblastoma or had affected sibs. In the parents, 4 tumors occurred, of which 2 were rhabdomyosarcomas and 2 were urinary bladder cancers. Both types of non‐ocular cancer were also encountered among the 122 patients with hereditary retinoblastoma. In 103 fathers and 103 mothers of patients with hereditary retinoblastoma who did not have retinoblastoma themselves, there was no previous family history of retinoblastoma. The fathers had a relative risk of 8.3 for pancreatic cancer compared to the general population. There was no significant increase in the number of non‐ocular tumors in 332 sibs of patients with hereditary retinoblastoma.
The third nation‐wide study on adult T‐cell leukemia/lymphoma (ATL) in Japan: Characteristic patterns of hla antigen and HTLV‐I infection in atl patients and their relatives
Authors:   The T‐ and B‐cell Malignancy Study Group
Published: February 2007

To clarify the intrinsic factors involved in the manifestation of adult T‐cell leukemia/lymphoma (ATL) in Japan, a third nation‐wide study on ATL was conducted by the T‐ and B‐cell Malignancy Study Group. General clinico‐epidemiological findings on ATL and infectious modes of transmission of human T‐lymp ho tropic virus type I (HTLV‐I) from 181 ATL patients and their relatives were analyzed and the frequency of HLA antigens in 64 ATL patients was compared with that of 48 relatives of ATL pro bands, 340 controls from all Japan and 236 controls from Kyushu (Tanaka et al., 1984). General findings on ATL were mostly the same as those in the 2 previous nation‐wide studies. The age‐specific positivity rate of anti‐HTLV‐I antibody in siblings of ATL patients was markedly higher than that in children of ATL patients. This suggests that there is a high risk of mothers of ATL patients transmitting HTLV‐I to their children who may develop clinical ATL after reaching ATL risk age. Frequencies of HLA antigens A26 and B39, among patients with ATL in ATL‐endemic areas (Kyushu and South Shikoku), were higher (RR>2.0 and p<0.05) than those of controls in Kyushu, and lower (RR<0.5 and p < 0.05) with respect to A24, Bw46, BwSI, Bw61 and DR7. The frequency of BwS2 was also lower in relatives positive for anti‐HTLV‐1 antibody than in relatives without antibody. However, these differences were not statistically significant after correction for the 45 antigens typed. These results can neither support nor refute the possibility of genetic susceptibility to HTLV‐1 infection and manifestation of ATL.
Prevalence of antibodies to 3 retroviruses in a captive colony of macaque monkeys
Authors: Daniel Muthiah D. , Letvin Norman L. , Sehgal Prabhat K. , Schmidt Diane K. , Silva Daniel P. , Solomon Keith R. , Hodi F. Stephen , Ringler Douglas J. , Hunt Ronald D. , King Norval W. , Desrosiers Ronald C.
Published: February 2007

The prevalence of antibodies to 3 retroviruses in the macaque colony of the New England Regional Primate Research Center (NERPRC) was determined using enzyme‐linked immunosorbent assay procedures as well as radioimmunoprecipitation‐SDS polyacrylamide gel electrophoresis and indirect immunofluorescence tests. Out of 848 macaques, 3 (0.35%) had antibodies to simian immunodeficiency virus (SIV), 27 (3.2%) had antibodies to simian T‐lymphotropic virus type I (STLV‐I) and approximately 285 (34%) had antibodies to type D retrovirus. Of 3 macaques infected with SIV, 2 were rhesus monkeys (Macaca mulatta) and I was a cynomolgus monkey (Macaca fascicularis). STLV‐I and D retrovirus infection occurred in all 4 macaque species examined. SIV, STLV‐I and D retroviruses were isolated from sero‐positive macaques. The low prevalence of SIV infection suggests that SIV is not being readily transmitted among macaques at NERPRC; this contrasts markedly with the high SIV prevalence in some captive mangabey colonies. In contrast to African green monkeys from eastern Africa, 160 Caribbean green monkeys examined showed no sign of SIV infection. These results provide a framework for monitoring spontaneous disease associated with infection by these 3 retroviruses and will help in further definition of STLV‐I and SIV infection of non‐human primates as animal models for human disease.
Human ovarian carcinoma lysis by cytotoxic t cells targeted by bispecific monoclonal antibodies: Analysis of the antibody components
Authors: Mezzanzanica D. , Canevari S. , Ménard S. , Pupa S. M. , Tagliabue E. , Lanzavecchia A. , Colnaghi M. I.
Published: February 2007

In the perspective of in vivo therapeutic applications, the monoclonal antibody (MAb) MOv18 was selected for its restricted reactivity with human ovarian carcinoma. Using the pH 2.8 desorption assay, we found that the antigen recognized by MOv18 had a high stability on the cell membrane and poor internalization. Therefore, a therapeutic approach which does not require internalization, i.e., the re‐targeting of cytotoxic T lymphocytes (CTL) by bispecific MAbs, was investigated. MOv18 and anti‐CD3 MAbs were used to produce bispecific reagents, obtained either by chemical cross‐linkage (heteroconjugates) or by somatic hybridization techniques (hybrid MAbs). The maintenance of the binding reactivity and specificity of the bispecific MAbs was analyzed by solid‐phase radioimmunoassay, immunofluorescence and cross‐competition tests on the relevant target cells (ovarian carcinoma cell line OVCA 432 for MOv18 and PHA‐stimulated peripheral blood mononuclear cells for anti‐CD3 MAbs), and on 2 irrelevant tumor cell lines. Bv a 51Cr‐release assay the bispecific MAbs were found to efficiently promote, at picomolar concentration, cell lysis by CTL clones, but the specificity pattern was wider than that predicated by the binding studies. The F(ab')2 fragment of one hybrid MAb mediated a lysis which was just as efficient as the entire MAb on the relevant target cells and allowed specific lysis to be distinguished from Fc‐receptor‐mediated lysis. Human immunoglobulins were unable to compete with the Fc receptor binding of the hybrid MAbs and therefore, in the perspective of in vivo applications, Fc fragment removal seems to be an essential step. Analysis of the bispecific reagents indicated that hybrid MAbs are superior to the heteroconjugate as far as storage stability is concerned.
Characterization of plasma membrane shedding from murine melanoma cells
Authors: Taylor Douglas D. , Taylor Cicek Gercel , Jiang Cheng‐Gan , Black Paul H.
Published: February 2007

Tumor cells release intact portions of their plasma membranes in the process of membrane fragment shedding. This released material has been shown to inhibit various synthetic functions of normal cells, which may play an important role in certain patho‐physiological events occurring in advancedstage cancer patients. Our studies on metastatic variants of the murine B16 melanoma, B16‐F1 (low incidence of lung colonization) and B16‐F10 (high incidence of lung colonization) indicate that the shed membrane fragment material is composed predominantly of vesicles, ranging in size from 20 to 100nm in diameter. The release of membrane fragments represents a small percentage (approximately 16%) of the total shedding of plasma membrane components. Membrane fragments were shed at a higher rate from the highly “metastatic”(colonizing) B16‐F10 cells than from poorly metastatic B16‐F1 cells, resulting in a 2‐fold greater accumulation of membrane fragment material by cultures of B16‐F10 cells than by B16‐F1 cultures during the 48‐hr assay period. The study of various intracellular metabolic processes (protein and RNA synthesis, glycosylation, and generation of ATP) required for the shedding of membrane fragments indicated that the shedding event is only dependent on energy when inhibitors of the above processes are present for 2 hr. Treatment of cells with these inhibitors for 8 hr results in cessation of the shedding process, indicating both a limited pool of components to be shed and the requirement for further synthesis of the shed material. Glycoprotein components of the shed membrane fragments were analyzed by SDS‐polyacrylamide gel electrophoresis. In addition to quantitative differences, 2 additional bands were present in fluorographs from SDS‐PAGE gels from the B16‐F10 membrane fragment material which were not present in fluorographs from B16‐F1 fragments. The glycoprotein components of shed membrane fragments were shown to represent selected domains of the cell's plasma membranes, in that only certain plasma membrane glycoproteins are shed as part of membrane fragments. The glycoproteins released as non‐particulate molecules into the extracellular environment failed to exhibit these quantitative and qualitative differences.
Differential expression of platelet‐derived growth factor and transforming growth factor genes in small‐ and non‐small‐cell human lung carcinoma lines
Authors: Söderdahl G. , Betsholtz C. , Johanson A. , Nilsson K. , Bergh J.
Published: February 2007

We have investigated a panel of human lung cancer cell lines representing the major groups of lung cancer, i.e., small‐cell carcinoma (SCC) and the group of non‐SCC, consisting of squamous‐cell carcinoma (SQC), adenocarcinoma (ADC) and large‐cell carcinoma (LCC), for their expression of certain growth factor genes. Messenger RNA from each cell line was hybridized with probes for platelet‐derived growth factor (PDGF) A‐ and B‐chains, insulin‐like growth factor (IGF)‐I and ‐II, transforming growth factor (TGF)‐α and β, epidermal growth factor (EGF) as well as a probe for the EGF receptor. All non‐SCC cell lines examined showed expression of the PDGF A‐chain gene. The PDGF B‐chain and TGF‐β gene were expressed in all non‐SCC cell lines but one, H‐125 (ADC). TGF‐α gene expression was demonstrated in the SQC cell line U‐1752, in both ADC cell lines (H‐23 and H‐125) and in one of the 3 LCC cell lines, U‐1810. IGF‐II was only transcribed in the LCC cell line U‐1810. The EGF‐receptor was detected in all non‐SCC cell lines but one, H‐661 (LCC). Neither IGF‐I nor EGF transcripts could be seen in any of the 10 cell lines examined. In contrast to the non‐SCC cell lines, the 4 SCC lines were constantly negative for the probes employed in this study. The frequent and heterogeneous expression of growth factor transcripts in all non‐SCC studied, but not SCC‐cell lines, may contribute to the difference in biological behaviour observed in vivo and in vitro between the 2 major lung cancer entities.
Comparative histopathology of resected bronchial cancers of women in Hong Kong and Japan
Authors: Tsuchiya Eiju , Chan John K. C. , Chan Suk‐Hung , Saw Daisy , Ho John H. C. , Tominaga Suketami
Published: February 2007

Pathological findings relating to lung cancers removed surgically from women at the Kowloon Hospital (KH), Hong Kong, and the Cancer Institute Hospital (CIH), Japan (77 and 54 cases respectively), were examined in order to clarify possible differences between Hong Kong Chinese and Tokyo Japanese women. Adenocarcinoma was the most frequent subtype encountered in both hospitals, but the rate was higher in CIH (90.9% in CIH and 68.8% in KH); that of large‐cell carcinoma was second in KH where the rate was higher (14.3% in KH and 0%, in CIH). A remarkable difference was observed in the location of adenocarcinomas; the percentages of central and peripheral types were 60.4% and 24.5% respectively in KH, but 4% and 96% respectively in CIH. The proportion of the central type (45.5%) was higher than that of the peripheral type (27.3%) in large‐cell carcinomas of KH. The number of adenocarcinomas having a bronchiolo‐alveolar pattern (which is observed more frequently in peripheral‐type adenocarcinomas) was higher in CIH (50%) than in KH (17%). Tall columnar cells were observed more often in KH (43.1 % in KH and 20.8% in CIH), and hobnail and cuboidal cells more often in CIH (31.4 and 80.4% respectively in KH, and 54.2 and 95.8% respectively in CIH). The difference may be explained by the frequent presence of tall columnar cells in the glands of central carcinomas, and hobnail and cuboidal cells in peripheral adenocarcinomas. The frequent occurrence of the central type of adenocarcinoma and large‐cell carcinoma appears characteristic of the lung carcinomas removed from women in Hong Kong. This suggests the existence of exogenous causative agents for lung cancer in Hong Kong females.
A unifying concept of the aetiology of breast cancer
Authors: de Waard F. , Trichopoulos D.
Published: February 2007

A number of risk factors for breast cancer are considered jointly in one pathogenetic framework which relates to the formation of pre‐cancerous lesions. Energy‐rich diet during puberty and adolescence enhances the occurrence of pre‐cancerous lesions in the breast. This process is counteracted by full‐term pregnancies, and the earlier they come the fewer the number of such lesions. Energy‐rich diet later in life contributes to the occurrence of obesity which, after menopause, enhances the growth of existing subclinical and clinical breast cancer. In both periods of life the nutritional factor exerts its effect through endocrine mechanisms in which oestrogens play a major part.
Cancer mortality in illinois Mexican and Puerto Rican immigrants, 1979‐1984
Authors: Mallin Katherine , Anderson Karen
Published: February 2007

The site‐specific cancer mortality in Illinois immigrant His‐panics for 1979‐1984 was compared to that of US‐born, non‐Hispanic whites (Anglos). Using indirect methods of standardization, 22 site‐specific cancer SMR & (Standard Mortality Ratios) were calculated for Mexican and Puerto Rican immigrants, using standard rates for Illinois Anglos. SMRs were also calculated for Puerto Rican immigrants using 1979‐1982 mortality rates from Puerto Rico. Cancer mortality for all sites was lower in both immigrant groups than in Anglos. Colon cancer mortality risk was lower in immigrants, but had increased from home country rates in Puerto Rican male immigrants. In addition, immigrants retained their lower home country risks for cancer of the lung, prostate and female breast. Significantly higher risks were found in immigrant females only, for cancer of the stomach, cervix and gall‐bladder (Mexican females). The cancer rates for immigrant Puerto Rican males were closer to those of Anglos than the rates for females and Mexicans, suggesting differences in the rates of transition to the Anglo cancer experience.
Alcohol consumption and risk op breast cancer
Authors: Rohan Thomas E. , McMichael Anthony J.
Published: February 2007

In a population‐based case‐control study conducted in Adelaide, South Australia, and involving 451 case‐control pairs aged 20‐74 years, the risk of breast cancer for women consuming more than 9.3 g of alcohol per day was 50% higher than for non‐drinkers (unadjusted RR 1.46, 95% Cl 1.00‐2.13). The increase in risk persisted upon control for potential confounding variables including dietary or diet‐related factors, and was not restricted to any particular type of beverage. Lower levels of alcohol consumption were not associated with substantial alterations in risk of breast cancer. When examined within menopausal strata, the effect of alcohol was more pronounced in pre‐menopausal women, although none of the estimates of effect within menopausal strata were statistically significant. Although positive associations between alcohol consumption and risk of breast cancer have been observed in previous studies, support for a causal association is, at most, qualified. However, given the widespread nature of this exposure, at least in developed countries, further and more detailed investigations of this association are required.
In vivo activation of lymphocytes in melanoma patients receiving escalating doses of recombinant interleukin 2
Authors: Gambacorti‐Passerini Carlo , Radrizzani Marina , Marolda Raffaele , Belli Filiberto , Sciorelli Gianalfredo , Galazka Andrew R. , Schindler John D. , Cascinelli Natale , Parmiani Giorgio
Published: February 2007

A phase‐1 study of the recombinant, non‐mutagenized interleukin 2 (rIL2, BioleukinTM) was performed in 12 melanoma patients (Pts). From 100 to 800 μg/m2 of rIL2 were administered by i.v. bolus injection, TID for 4‐8 days. Side‐effects included fever, malaise, low serum K+ and Ca++ values, electrocardiographic abnormalities, leukopenia and thrombocytopenia. No major organ toxicity and no significant fluid retention were observed at the administered doses. Treatment induced a rapid depletion of peripheral blood lymphocytes (PBL) with a rebound (2‐6 times the pre‐treatment values), 24‐48 hr after rIL2 discontinuation. PBL obtained between the 5th treatment day and the 2nd post‐treatment day showed: (a) enhanced proliferation (11/12 Pts) with stimulation indexes of 6‐52; (b) increased cytotoxicity against autologous tumor cells (2/2 Pts), allogeneic melanomas (5/7 Pts), the Daudi (5/6 Pts) and K562 cell lines (7/12 Pts); and (c) increased expression of IL2 receptors (8/12 Pts) and of DR antigens (6/12 Pts). Lymphocytes collected 1‐2 days after treatment and activated in vitro with rIL2 showed a more rapid development of tumor cytotoxicity, with an earlier loss of activity. Spontaneous proliferation, autologous or allogeneic tumor cytotoxicity and expression of IL2 receptors obtained after in vivo treatment with rIL2 were significantly weaker than those induced during in vitro stimulation. No major objective responses were detected in these patients.
Further studies on chromosome 15 trisomy in murine T‐cell lymphomas: Mapping of the relevant chromosome segment
Authors: Silva Santiago , Babonits Magda , Wiener Francis , Klein George
Published: February 2007

Trisomy 15 is the most common chromosomal aberration in murine T‐cell lymphomas. The relevant chromosomal region responsible for the growth advantage of the 15‐trisomic cell has not been defined. In order to map this region, we have induced thymic lymphomas by chemical carcinogens (DMBA or MNU) in mice with 2 different constitutional translocations, T(7;15)9H homozygotes and [T(7;15)9H x T(5;15)4Ad] F1 hybrids. Twenty‐two tumors developed in 90 carcinogen‐treated mice. Among the 14 cytogenetically analyzed thymic lymphomas, 4 were diploid and 5 were aneu‐ploid, with no chromosome‐15‐associated changes. Five lymphomas showed partial duplication of chromosome 15. Four of them have duplicated the segment distal to the C/DI breakpoint of T9H, while the 5th carried an interstitial duplication of the D2 sub‐band of the T(7;15) translocation chromosome. These findings suggest that the duplication of the D 2/3 region, known to contain the c‐myc and the pvt‐1 genes (Banerjee et al., 1985), rather than other regions of chromosome 15, contributes to the development and/or progression of murine T‐cell leukemias.
Uptake of glutamine antimetabolites 6‐diazo‐5‐oxo‐L‐norleucine (DON) and acivicin in sensitive and resistant tumor cell lines
Authors: Huber Klaus R. , Rosenfeld Henry , Roberts Joseph
Published: February 2007

The uptake system for 6‐diazo‐5‐oxo‐L‐norleucine (DON) was studied in mouse P388 leukemia cells. The DON transport system was found to resemble that of another glutamine antimetabolite, Acivicin, in its strong temperature dependence, utilization of the “L” transport system, inhibition by glutamine but not by glutamate, potent inhibition by p‐chlo‐romercuribenzene sulfonate, Na+, and only minimal inhibition by various energy poisons. A Km of approximately 70 μm and a Vmax0, of 3.4 nmoles/106 cells/min was calculated for this cell line. The accumulated DON was not metabolized by P388 cells and moderate efflux occurred at 37°C. The DON transport characteristics of a DON‐resistant P388 cell line (100 times ID50 of parent line) were similar to those of the DON‐sensitive parent line, indicating that altered drug transport may not be involved in development of resistance to this antimetabolite. The finding that an Acivicin‐resistant subline of P388 cells which exhibited good transport of DON showed negligible transport of Acivicin suggests different modes of resistance towards the two glutamine and metabolites.
Quantitation and localization of cellular retionol‐binding protein in squamous‐cell carcinomas of the cervix uteri and of the oral cavity
Authors: Wahlberg Peter , Fex Göran , Biörklund Anders , Tropé Claes , Willén Roger
Published: February 2007

The concentration of cellular retinal‐binding protein (CRBP) was determined by radioimmunoassay in biopsies of normal muscoa and squamous‐cell carcinomas of cervix uteri form 30 women. The tumour tissues contained significantly higher concentrations of CRBP (median = 120 μg/g protein) than normal mucosa (median = 32 μg/g protein). The distribution of CRBP in normal mucosa and squamous‐cell carcinomas from cervix uteri and from oral cavity was evaluated by immunohistochemical techniques. In tissue sections of normal epithlium from the cervix uteri and the oral cavity, the maturing kerationocytes in the prickle‐cell layer were moderately or strongly stained when antiserum against CRBP was used, while the proliferating cells in the basal‐cell layer were stained only lightly if at all. Squamous‐cell carcinomas of the cervix uteri and the oral cavity presented much the same picture. The observed difference in CRBP concentration between squamous‐cell carcinomas and normal squamous‐cell mucosa may therefore be more quantitative than qualitative.