bluuebunny/crossref_metadata_2025 huggingface dataset:
67‐kDa laminin‐receptor expression adds prognostic information to intra‐tumoral microvessel density in node‐negative breast cancer
Authors: Gasparini Giampietro , Barbareschi Mattia , Boracchi Patrizia , Bevilacoua Picrantonio , Verderio Paolo , Palma Paolo Dalla , Ménard Sylvie
Published: February 2007

Experimental studies have shown that the 67‐kDa laminin receptor (LRec) is an important molecule for the interaction of tumour cells with the extracellular matrix, and that it plays a role in the early steps of angiogenesis and in tumour invasion and metastasis. We performed a multi‐parametric study in 171 node‐negative breast cancers, followed for a median time of 6 years, to verify whether determination of the LRec provides prognostic information in addition to intra‐tumoral microvessel density (IMD), a measure of tumour angiogenesis, and to other biological and conventional indicators. A positive association between LRec expression and high neovascularization was found, although it did not reach significance. LRec was not associated either with other biological markers (oestrogen receptor, progesterone receptor and p53 expression) or to the conventional prognostic features [menopausal status, tumour size, histological types, grading and peri‐tumoral lymphatic vessel invasion (PLVI)]. In univariate analysis, IMD, p53, PgR, PLVI, grading and tumour size were significant prognostic indicators of relapse‐free survival (RFS). LRec expression approached significance when considered as a dichotomous variable, after having selected the optimum cutoff of 10% to distinguish high‐risk from low‐risk patients. For overall survival (OS), tumour size and IMD (continuous variable) were significant prognostic factors, and p53 approached significance. In multivariate analysis for RFS, the joint variable LRec and vascularization was the strongest independent prognostic factor, followed by PgR, PLVI and p53. For OS, tumour size was the only independent prognostic indicator in this series.
Diet, alcohol, smoking and cancer of the upper aerodigestive tract: A prospective study among Hawaii Japanese men
Authors: Chyou Po‐Huang , Nomura Abraham M. Y. , Stemmermann Grant N.
Published: February 2007

A cohort study of upper aerodigestive tract cancer was conducted among 7,995 Japanese—American men who were interviewed and examined from 1965 to 1968. Information was collected about smoking history and alcohol and dietary intake. After 24 years, 92 incident cases with histological confirmation of diagnosis were identified. Current cigarette smokers at time of examination had a 3‐fold risk for upper aerodigestive tract cancer compared with never‐smokers. A dose‐response relationship was present with increasing amount and duration of cigarette use. Consumption of beer, wine, spirits and total alcohol was strongly associated with increased risk. Of 23 food and beverage categories, only candy/jelly/soda pop consumption had a statistically significant inverse trend. Frequent consumption of fruit was also inversely associated with this cancer. In contrast, the risk tended to be positively associated with consumption of rice, seaweed, tofu or tsukudani (a mixed dish of fish, sugar, soy sauce and seaweed), but the dose—response relationship was not statistically significant. For nutrient intake, increased calcium and fat intake decreased the risk for this cancer.
Karyotypic features of malignant tumors of the nasal cavity and paranasal sinuses
Authors: Jin Yucsheng , Mertens Fredrik , Arheden Kristina , Mandahl Nils , Wennerberg Johan , Dictor Michael , Heim Sverre , Mitelman Felix
Published: February 2007

Cytogenetic analysis of short‐term cultures from 6 tumors of the nasal cavity and paranasal sinuses—one esthesioneuroblas‐toma, 2 adenocarcinomas and 3 squamous‐cell carcinomas (SCC)—revealed clonal chromosome aberrations in all cases. The esthesioneuroblastoma had a complex hyperdiploid karyotype. None of the aberrations was similar to those previously described in short‐term cultures or established cell lines from esthesioneuroblastomas. The 2 adenocarcinomas had complex karyotypic changes, which in both cases included rearrangements of bands 9p22 and 14q11. One SCC had 5 unrelated pseudodiploid clones, I displayed a highly complex karyotype, including rearrangement of band 11 q 13, and I had simple karyotypic changes with loss of 6q material and gain of 3q. These findings are similar to those described in head‐and‐neck SCC at other sites.
Elevated antibody titers to Epstein‐Barr virus prior to the diagnosis of Epstein‐Barr‐virus‐associated gastric adenocarcinoma
Authors: Levine Paul H. , Stemmermann Grant , Lennette Evelyne T. , Hildesheim Allan , Shibata Darryl , Nomura Abraham
Published: February 2007

Epstein‐Barr virus (EBV) has recently been identified in the tumor cells of patients with gastric carcinoma. We tested pre‐morbid serum samples from a carefully monitored cohort of Japanese men in order to investigate the possibility that patients with EBV‐associated gastric cancer represent a sub‐set of individuals with long‐standing difficulties in appropriately managing EBV infection. From a serum bank, we obtained 108 samples derived from 54 patients destined to develop gastric adenocarcinoma and 54 controls. Samples were tested under code for antibodies to EBV‐capsid antigen, early antigen and nuclear antigen. Individuals who were positive for IgA antibodies against EBV viral‐capsid antigen (VCA) and IgG antibodies against the R component of EBV early antigen were at a 3.9‐fold and 1.9‐fold excess risk of disease, respectively. Antibody titers to EBV VCA were significantly higher in those destined to get EBV‐associated gastric cancer than those subsequently developing non‐EBV‐associated gastric cancer or age‐and‐gender‐matched controls. These findings suggest that the inability to control EBV infection on a long‐term basis exists many years prior to the development of EBV‐associated gastric cancer, and that EBV may play an etiologic role in this sub‐set of malignancies.
Over‐expression of hsp70 confers tumorigenicity to mouse fibrosarcoma cells
Authors: Jäättelä Marja
Published: February 2007

Over‐expression of the major heat‐shock protein hsp70 in WEHI‐S tumor cells renders them resistant to the cytotoxic effects of tumor necrosis factor (TNF). To study the significance of this resistance in vivo, the tumorigenic potential of WEHI‐S cells transfected with human hsp70 in sense and anti‐sense orientation was investigated in athymic and in normal syngenic mice. A striking correlation was observed between the level of hsp70 expression and tumorigenicity in athymic mice. Hsp70 expression rendered WEHI cells tumorigenic also in normal mice, but higher numbers of cells were required for tumor formation than in athymic mice. Over‐expression of hsp70 in WEHI‐S cells did not enhance their anchorage‐dependent growth in vitro or their ability to form colonies in soft agar. The hsp70‐transfected cells exhibited greatly increased resistance against killing by murine natural cytotoxic cells and macrophages in vitro. A similar tumorigenic phenotype could also be induced independently of hsp70 by prolonged culture of WEHI‐S cells with TNF. These results suggest that over‐expression of hsp70 increases the tumorigenic potential of WEHI‐S cells in mice, by allowing these cells to escape from the early TNF‐mediated anti‐tumor immune surveillance.
Clustering and clinical diversity of adult T‐cell leukemia/lymphoma associated with HTLV‐I in a remote black population of French Guiana
Authors: Gérard Yann , Lepere Jean‐François , Pradinaud Roger , Joly Frank , Lepelletier Louis , Joubert Michel , Marie Dominique Sainte , Mahieux Renaud , Vidal Abel Ureta , Larregain‐Fournier Dominique , Valensi Francoise , Moynet Daniel , De Thé Guy , Guillemain Bernard , Moreau Jean‐Paul , Gessain Antoine
Published: February 2007

An epidemiological study was performed in French Guiana (population 115,000) to determine the prevalence and incidence of adult T‐cell leukemia/lymphoma (ATL) associated with human T‐cell leukemia/lymphoma virus type I (HTLV‐I). From January 1990 to December 1993, all suspected cases of ATL were enrolled in this study, and their clinical, epidemiological and immunovirological features were analyzed. Out of the 19 suspected cases, 18 were considered as ATL associated with HTLV‐I (8 acute forms, 8 lymphoma types and 2 smoldering cases). Before this study, only 2 ATL cases had been reported in French Guiana over a 10‐year period. This demonstrates that the number of ATL cases is greatly underestimated in most tropical HTLV‐I endemic areas unless a specific disease search is performed. The mean age of the patients was 41 years. While HTLV‐I antibodies were present in all cases, molecular studies demonstrated a clonal integration of HTLV‐I in the tumoral cells in 7 cases out of the 9 tested. Fifteen patients died within a year of diagnosis. The crude incidence rate of ATL in French Guiana is around 3.5/100,000/year, a situation similar to that found in the Caribbean and in HTLV‐I‐endemic regions of Japan. However it reaches around 30/100,000/year (highest incidence ever described) in a small remote ethnic group of African origin (around 6200 inhabitants). Possible causes of ATL clustering in this ethnic group are presented. © 1995 Wiley‐Liss, Inc.
Effect on breast cancer mortality of biennial mammographic screening of women under age 50
Authors: Peer Petronclla G. M. , Werre Jan M. , Mravunac Marcel , Hendriks Jan H. C. L. , Holland Roland , Verbeek Andre L. M.
Published: February 2007

The effects on breast cancer mortality seen after 16 years of biennial screening of younger women are assessed in this prospective cohort study. Since 1975 some 13,500 women, aged 35—49 in 1975, were invited to participate in the Nijmegen screening programme comprising a mammographic examination every 2 years. By the end of 1990, 75 women had died of breast cancer out of the 332 cases diagnosed after the start of the screening project. Women from the same birth cohort, living in Arnhem, a neighbouring city with a comparable population and without a screening project, were used as controls. In this city, 74 breast cancer deaths out of 284 cases occurred during the same period. In Nijmegen, after 16 years of follow‐up, breast cancer mortality showed a non‐significant reduction of 6% (95% confidence interval: 32% reduction, 29% excess). In the relevant period, after a time lag of 10 years from the start of the programme, this reduction rose to 20% (95% confidence interval: 48% reduction, 23% excess). No reduction in breast cancer mortality was observed in the first decade of screening. For a later period, a shift towards a reduction emerges, but the data are as yet inconclusive. © 1995 Wiley‐Liss. Inc.
T‐cell malignancies in Brazil. Clinico‐pathological and molecular studies of HTLV‐I‐positive and ‐negative cases
Authors: De Oliveira Maria S. Pombo , Matutes Estella , Schulz Thomas , Carvalho Silvia M. , Noronha Helio , Reaves Jacqueline D. , Loureiro Paula , Machado Cintia , Catovsky Daniel
Published: February 2007

T‐cell malignancies in Brazil have a high seroprevalence rate of HTLV‐I antibodies. We have analyzed the disease features in 188 Brazilian patients with a T‐cell disorder. These included 40 with T‐lymphoblastic leukaemia or lymphoma (T‐ALL/T‐LbLy) and 148 with mature T‐cell diseases: 5 T‐prolymphocytic leukaemia, 53 adult T‐cell leukaemia/lymphoma (ATLL), 54 cutaneous T‐cell lymphomas, 29 pleomorphic T‐cell lymphomas and 7 large granular lymphocyte leukaemia. The diagnosis was based on clinical, morphological and immunological features and HTLV‐I serology. ATLL in Brazil has the same disease features as in other endemic regions, the only apparent differences being: age, Brazilian patients being younger than Japanese, and ethnic grouping, one third of Brazilians being white Caucasians of European descent. We applied a scoring system based on the presence or absence of typical features associated with ATLL: hypercalcaemia, cell morphology, immunophenotype, histopathology and HTLV‐I status, to see whether it may help in diagnosing cases of ATLL. All had high scores, whereas all other T‐cell diseases scored low. Only 5 ATLL cases were HTLV‐Inegative by serology, but they had otherwise typical features of ATLL, and their cells did not have HTLV‐I proviral sequences by DNA analysis. Such cases suggest that ATLL may develop in a minority of individuals living in regions where it is endemic, without evidence of HTLV‐I infection, and that other factors may contribute to the pathogenesis of the disease.
Characterization of factors regulating successful immunotherapy using a tumor‐specific cytotoxic T lymphocyte clone: Role of interleukin‐2, cycling pattern of lytic activity and adhesion molecules
Authors: Hammond‐Mckibben Dcnisc M. , Seth Aruna , Nagarkatti Prakash S. , Nagarkatti Mitzi
Published: February 2007

Adoptive immunotherapy against cancer has met with varying degrees of success, the reasons for which remain unclear. The present study characterizes factors that regulate successful immunotherapy of mice bearing a syngeneic T‐cell lymphoma, designated LSA, using a tumor‐specific cytotoxic T lymphocyte (CTL) clone, PE‐9. Adoptive transfer of PE‐9 cells afforded significant protection in normal but not in nude mice against LSA tumor. However, the PE‐9 cells could protect the nude mice when injected along with normal CD4+ T cells. Administration of IL‐2 along with PE‐9 cells failed to enhance tumor immunotherapy. IL‐2 therapy was toxic inasmuch as injection of the CTL clone PE‐9 + IL‐2, but not PE‐9 or IL‐2 alone, for 5 days into irradiated mice caused vascular leak syndrome (VLS). PE‐9 cells cultured with high doses of rIL‐2 in vitro also caused TCR‐independent and MHC‐unrestricted lysis of SV40‐transformed endothelial cells. Furthermore, PE‐9 cells cultured in vitro for 24‐96 hr with IL‐2 exhibited cycling pattern of tumorspecific cytotoxicity with maximum cytotoxicity demonstrable at 48 hr and virtually no cytolytic activity at 96 hr of culture or thereafter. The loss of cytotoxicity correlated with downregulation of several adhesion molecule expressions on PE‐9 cells, particularly the αβ‐TCR, as well as the mRNA for TNF‐α, IFN‐γ and perforin, although the levels of granzyme A were not altered. Interestingly, the outcome of immunotherapy by PE‐9 cells depended on the cycling pattern of cytotoxicity. Our data suggest that successful immunotherapy against cancer using a CTL clone depends on several factors, such as the cycling pattern of lytic activity, density of adhesion molecules, levels of cytokines expressed and the ability of IL‐2 and CTL to trigger VLS.
Human T‐Cell lymphotropic virus type I and severe neoplasia of the cervix in jamaica
Authors: Strickler Howard D. , Rattray Carole , Escoffery Carlos , Manns Angela , Schiffman Mark H. , Brown Claudette , Cranston Beverly , Hanchard Barrie , Palefsky Joel M. , Blattner William A.
Published: February 2007

Human T‐cell lymphotropic virus type 1 (HTLV‐1) was associated with carcinoma of the cervix in Japan in a recent study that compared hospital cases with healthy population‐based controls. To test this relationship in women more alike for cervical neoplasia risk factors (including sexual behavior and human papilloma virus; HPV), we enrolled consecutive patients from a colposcopy clinic in Kingston, Jamaica (an HTLV‐1 endemic area). Patients underwent Pap smear, colposcopy, biopsy and cervical swab for detection of HPV by polymerase chain reaction. Cases were defined as women with CIN‐3 or invasive cancer (CIN‐3/CA). Controls included all patients with either CIN‐1 or koilocytotic atypia, atypical squamous cells of undetermined significance or benign cervical pathology (all but one had at least inflammatory changes). Patients with CIN‐2 were excluded to minimize risk of case‐control misclassification. Cases were much more likely to be HTLV‐1 seropositive than controls. Although mean age differed significantly between cases (mean age = 39 years) and controls (mean age = 33 years), control for age did not explain the relation of CIN‐3/CA with HTLV‐1. Among HPV DNA positive subjects the age‐adjusted association was not diminished but lost statistical significance. HTLV‐1 seroprevalence may be independently associated with progression to severe neoplasia of the cervix. © 1995 Wiley‐Liss, Inc.
Induction of cellular immune responses by a murine monoclonal anti‐idiotypic antibody recognizing the 791tgp72 antigen expressed on colorectal, gastric and ovarian human tumours
Authors: Durrant Lindy G. , Doran Mark , Austin Eric B. , Robins R. Adrian
Published: February 2007

There is accumulating evidence that cellular rather than antibody responses are more effective for tumour rejection. It is therefore important to screen anti‐idiotypic (anti‐id) antibodies for their ability to stimulate anti‐tumour T‐cell responses. The human anti‐id monoclonal antibody (MAb) 105AD7 stimulated both delayed‐type hypersensitivity (DTH) responses in animals and antigen‐specific blastogenesis and IL‐2 induction in advanced cancer patients. It may not be necessary to use human anti‐id antibodies as murine anti‐id antibodies, which elicit DTH responses against immunodominant human T‐cell epitopes and may be just as useful in the clinic. We have therefore produced a murine anti‐id antibody to the same MAb as was used to generate the human anti‐id antibody and screened it for its ability to generate cellular anti‐tumour immune responses. Low‐dose immunization with the murine anti‐id MAb NCRC60, which recognises the paratope of the anti‐79ITgp72 MAb 79IT/36, induced DTH responses to 79ITgp72‐expressing tumour cells but not to antigen‐negative cells. DTH responses with no detectable antibody responses were induced with 5 μg of anti‐id NCRC60 without adjuvant. Addition of either complete Freund's adjuvant or Quil A did not enhance DTH responses. However, when the anti‐id NCRC60 was linked to KLH and injected in the presence of Freund's adjuvant anti‐anti‐id antibodies and anti‐79ITgp72 antibodies were induced. NCRC60 anti‐id was also capable in vitro of priming human T cells from cancer patients to proliferate in response to secondary stimulation with 79ITgp72‐expressing tumour cells, suggesting that it may have therapeutic potential in cancer patients. © 1995 Wiley‐Liss, Inc.
Tyrosine phosphorylation as a marker for aberrantly regulated growth‐promoting pathways in cell lines derived from head and neck malignancies
Authors: Cardinali Massimo , Pietraszkiewicz Halina , Ensley John F. , Robbins Keith C.
Published: February 2007

We have utilized a broad approach to address whether tyrosine kinases and the growth pathways they regulate might be functionally aberrant in squamous cell carcinomas (SCC) of the upper aerodigestive tract. This strategy involved assaying for evidence of tyrosine kinase action in lysates of cell lines representing SCC. Our findings revealed a spectrum of elevated tyrosine phosphorylation in SCC lines ranging from less than 2‐fold to more than 10‐fold above that of control human epidermal keratinocytes. Thus the ability to regulate growth and other pathways controlled by tyrosine phosphorylation was impaired in all the 19 lines examined. Assessment of the receptor for epidermal growth factor (EGF) revealed that its activity was elevated above normal in 14 of the 19 cell lines examined, suggesting that at least a portion of the increased tyrosine phosphorylation observed could be attributed to excessive EGF receptor activity. Our findings provide functional evidence that growth pathways are aberrantly regulated in cell lines representing SCC of the upper aerodigestive tract. © 1995 Wiley‐Liss, Inc.
Induction of apoptotic cell death in non‐melanoma skin cancer by interferon‐α
Authors: Rodríguez‐Villanueva Julio , McDonnell Timothy J.
Published: February 2007

Interferon‐α (IFN‐α) is a cytokine that is effective in the treatment of a variety of cancers, including non‐melanoma skin cancers. The biologic responses of cells to IFN‐α are pleiotropic and include growth suppression and immunomodulation. The potential direct effects of IFN‐α on tumor cell populations are incompletely characterized. Our findings indicate that IFN‐α can directly induce apoptosis (programmed cell death) in sensitive squamous cell skin cancer cell lines. Cell lines resistant to the cytotoxic effects of IFN‐α showed no evidence of apoptosis induction. Transfection of IFN‐α‐sensitive cell lines with a bcl‐2 expression vector conferred partial resistance to cell death induction by IFN‐α Our results indicate that the clinical efficacy of IFN‐α may, in part, be related to the ability of this cytokine to induce apoptosis. © 1995 Wiley‐Liss, Inc.
P‐glycoprotein epitope mapping. II. The murine monoclonal antibody MM6.15 to human multidrug‐resistant cells binds with three distinct loops in the MDR1‐P‐glycoprotein extracellular domain
Authors: Cianfriglia Maurizio , Romagnoli Giulia , Tombesi Marina , Poloni Francesca , Falasca Giuliana , Modugno Francesca Di , Castagna Maura , Chersi Alberto
Published: February 2007

A new murine monoclonal antibody (MAb), MM6.15, to human MDR1 P‐glycoprotein was found to be reactive in ELISA with synthetic peptides selected from the predicted sequences of the first, fourth and sixth extracellular loop of MDRI‐P‐glycoprotein. In order to precisely define the MM6.15‐binding site, a peptide library of overlapping 5‐ to 9‐mer residues covering the entire sixth extracellular loop of both human and rodent class‐1 P‐glycoproteins was synthesized on polyethylene pins and tested for MAb binding. The results of this ELISA demonstrated that the MAb MM6.15 reacts only with human synthetic peptides and that the critical component of the MAb recognition is made up of the amino‐acid sequence LVAHKL (residues 963–968 of the MDRI‐P‐glycoprotein) with histidine (H), lysine (K) and possibly leucine (L), key residues of this immunogenic domain. © 1995 Wiley‐Liss, Inc.
Expression of fgf and fgf receptor genes in human breast cancer
Authors: Penault‐Llorca Frédérique , Bertucci François , Adélaïde José , Parc Patricia , Coulier François , Jacquemier Jocelyne , Birnbaum Daniel , Delapeyrière Odile
Published: February 2007

The family of FGF growth factors is involved in several biological processes and might play an important role in tumori‐genesis. We have studied the respective expression of 8 of the 9 characterized FGF genes, and of the 4 known FGF receptor genes, in a panel of 10 tumor‐cell lines and 103 breast‐tumor samples, using RT‐PCR and Northern‐blot analyses. FGF1 and FGF2 were expressed in almost all samples, while expression of FGF5, FGF6, FGF7 and FGF9 was more restricted. FGFR1, FGFR2 and FGFR4 were expressed at high levels in respectively 22%, 4% and 32% of tumors. FGFR3 expression was not detected. The transcript encoding an FGFR1 isoform with 2 immunoglobulin‐like domains was the most prevalent. © 1995 Wiley‐Liss, Inc.
International renal‐cell cancer study. V. Reproductive factors, gynecologic operations and exogenous hormones
Authors: Lindblad Per , Mellemgaard Anders , Schlehofer Brigitte , Adami Hans‐Olov , McCredie Margaret , McLaughlin Joseph K. , Mandel Jack S.
Published: February 2007

The relationships between reproductive factors, exogenous hormones and renal‐cell cancer were examined in an international, multicenter, population‐based, case‐control study undertaken in 1989‐1991. Data from 5 centers situated in Australia, Denmark, Germany, Sweden and the United States included for analysis 608 women with renal‐cell cancer and 766 female controls. A significant trend in risk (p = 0.002) was associated with number of births, with an 80% excess risk for 6 or more births [RR = 1.8, 95% confidence interval (CI) = 1.1 to 2.9] compared with one birth. A decreasing risk was seen for increasing age at first birth, although this was confounded by body‐mass index and number of births. A suggestive reduction of risk was also seen for increasing age at menarche. Age at menopause was unrelated to risk of renal‐cell cancer. An increased risk was observed for women having had both a hysterectomy and an oophorectomy. Use of oral contraceptives in non‐smoking women reduced the risk of renal‐cell cancer (RR = 0.5, 95% CI = 0.4 to 0.8); this reduction increased with longer duration of use. No association was observed for estrogen replacement therapy. Our results indicate that certain hormonal and reproductive variables may be related to risk of renal‐cell cancer and deserve further investigation, both epidemiologically and experimentally. © 1995 Wiley‐Liss, Inc.
Sv40‐induced immortalization and ras‐transformation of human bronchial epithelial cells
Authors: Reedel Roger R. , De Silva Ruwani , Duncan Emma L. , Rogan Eileen M. , Whitaker Noel J. , Zahra David G. , Ke Yang , McMenamin Mary G. , Gerwin Brenda I. , Harris Curtis C.
Published: February 2007

Non‐tumorigenic SV40‐immortalized human cells may be transformed to tumorigenicity by activated oncogenes, but the molecular genetics of this process are still poorly understood. We describe here 4 SV40‐transformed bronchial epithelial (BE) cell lines that became immortalized after a period of crisis, and then transfection of 6 BE lines or sub‐lines with an activated c‐Ha‐ras (EJ‐ras) oncogene. pSV2neo‐transfected cells did not form any tumors in athymic nude mice. Even though each of the EJ‐ras‐transfected lines was shown to be expressing the mutant ras gene, only one cell line, BEAS‐2B, and 2 of its sub‐lines were tumorigenic after transfection. We conclude that immortalization is not sufficient for BE cells to be transformed by the EJ‐ras oncogene. Thus there are at least 2 unknown genetic events in this in vitro model of carcinogenesis: escape from crisis (immortalization), and development of ability to cooperate with activated ras in tumorigenic transformation. We found no evidence that either immortalization or ability to complement ras is related to abnormalities of the SV40 T antigens, of p110RB or of p53. © 1995 Wiley‐Liss, Inc.
Molecular analysis of tumours from feline immunodeficiency virus (FIV)‐infected cats: An indirect role for FIV?
Authors: Terry Anne , Callanan John J. , Fulton Ruth , Jarrett Oswald , Neil James C.
Published: February 2007

Five tumours, which arose in cats naturally or experimentally infected with feline immunodeficiency virus (FIV), were examined with molecular probes to establish tumour cell lineage and to screen for integrated viral sequences. Three of the tumours were classed as B‐cell lymphomas on the basis of morphology, immunocytochemistry, rearrangement of immunoglobulin heavy chain genes and lack of rearrangement of T‐cell receptor (TCR) β‐chain genes. Two of these B‐cell tumours arose in specific pathogen‐free (SPF) cats experimentally infected with FIV. One case of multi‐centric lymphosarcoma came from a cat naturally infected with both FIV and feline leukaemia virus (FeLV). This tumour contained integrated FeLV proviral sequences and was judged to be of T‐cell origin on the basis of TCR gene rearrangement. The fifth case was a mast cell tumour. Rearrangement of the c‐myclocus was not found in any of the FIV‐associated tumours but was shown to be present in a rare immunoblastic B‐cell lymphoma which arose in an uninfected SPF cat. None of the FIV‐associated tumours showed evidence of integrated FIV sequences by Southern biot hybridisation, despite isolation of infectious virus from in vitro cultures of tumour cells in I case. These results confirm that FIV‐associated tumours can occur in the absence of FeLV and suggest that the role of FIV in lymphomagenesis is generally indirect. ©1995 Wiley‐Liss, Inc.
Multi‐generational carcinogenesis from diethylstilbestrol investigated by blastocyst transfers in mice
Authors: Walker Bruce E. , Kurth Lori A.
Published: February 2007

Previous studies have shown that a carcinogenic effect can be transmitted from female mice exposed prenatally to diethylstil‐bestrol (DES) to their female offspring. Furthermore, male mice exposed pre‐natally to DES can transmit a carcinogenic effect to their offspring through their germ cells. To study how multi‐generational carcinogenesis is transmitted through females exposed pre‐natally to DES. the technique of blastocyst transfer was utilized. Blastocysts from strain CD‐1 mice exposed pre‐natally to vehicle were transferred to mice exposed pre‐natally to DES. Among 143 offspring from these transfers, there were 10 ovarian adenomas and 10 uterine adenocarcino‐mas. Among 92 offspring from blastocyst transfers between mice exposed pre‐natally to vehicle only, there was 1 ovarian adenoma and 1 uterine adenocarcinoma. Thus the pre‐natal exposure of the host to DES produced a maternal environment which increased the incidence of ovarian and uterine tumors. The reverse type of transfer was also performed, in which blastocysts from female mice exposed pre‐natally to DES were transferered into mice exposed to vehicle only pre‐natally. Among 99 offspring derived from DES‐exposed germ cells, 6 developed ovarian adenomas and 16 developed uterine adeno‐carcinomas. Thus DES also has a multi‐generational effect transmitted through the blastocyst, which is consistent with fetal germ cell mutation from DES. © 1995 Wiley‐Liss, Inc.
Comparison of the inhibitory effect of the angiogenesis inhibitor, TNP‐470, and mitomycin c on the growth and liver metastasis of human colon cancer
Authors: Konno Hiroyuki , Tanaka Tatsuo , Matsuda Iwao , Kanai Toshikazu , Maruo Yuji , Nishino Nobuhiko , Nakamura Satoshi , Baba Shozo
Published: February 2007

Angiogenesis inhibitors have attracted considerable interest. The anti‐tumor and anti‐metastatic effects of TNP‐470, an angiogenesis inhibitor, and mitomycin C (MMC), a representative anti‐neoplastic agent, were investigated using a xenotrans‐planted human colon cancer, TK‐4. Suturing of small pieces of TK‐4 tumors to the cecal wall in nude mice (orthotopic transplantation) induced liver metastasis. Mice were randomly divided into 3 groups; a control group given saline solution, a group receiving TNP‐470 and a group receiving MMC. TNP‐470 was given s.c. on alternate days for 5 weeks from day 10 after cecal transplantation and MMC was administered intraperitoneally (i.p.) once a week from day 10 after cecal transplantation. MMC significantly inhibited cecal tumor growth. In the control group, liver metastases developed in 9 out of 10 mice, including 3 with more than 20 metastatic foci. Liver metastasis also developed in 8 out of 10 mice receiving MMC, 2 of which had many metastases. In contrast, liver metastasis developed in only 2 out of 8 mice in the TNP‐470 group and neither of these animals had numerous metastases. © 1995 Wiley‐Liss, Inc.
An epidemiological study of posterior uveal melanoma in israel, 1961–1989
Authors: Iscovich Jose , Ackerman Calvin , Andreev Helen , Pe'er Jacob , Steinitz Ruth
Published: February 2007

Trends in the incidence rate of uveal melanoma in Israel during the period 1961–1989 among Jews of various geographical origins and among non‐Jews were examined, and found to be stable over time. Based on data of the Israel Cancer Registry, 515 cases were included in the final study population after an independent case‐finding ascertainment survey. The average annual incidence rate per million for all Jews was 5.7 for both males and females; the rates for non‐Jews were: males 1.6, females 1.3. Incidence rates within the Jewish sub‐populations show significant differences. The highest rates by sub‐population were for Jews born in Europe or America (7.5 for males and for females), followed by Jews born in Israel (males 6.8, females 6.7); and lowest in Jews born in Africa (males 2.1, females 2.3) and Asia (males 1.6, females 2.8). Jews born in Israel had rates lower than Jews born in Europe and America during the 1960s, but in the 1980s the situation was reversed. Results suggest that rate differences between population groups and over time stem from constitutional factors or from the direct or indirect effect of sunlight radiation, whether early in life or from cumulative exposure. © 1995 Wiley‐Liss, Inc.
α‐interferon potentiates epidermal growth factor receptor‐mediated effects on human epidermoid carcinoma KB cells
Authors: Caraglia Michele , Leardi Annalisa , Corradino Stefania , Ciardiello Fortunato , Budillon Alfredo , Guarrasi Rosario , Bianco Angelo R. , Tagliaferri Pierosandro
Published: February 2007

The molecular mechanisms underlying the growth inhibition of human tumor cells induced by recombinant interferon‐α (IFNα) are mostly unknown. It has been proposed that this effect could be related to down‐regulation and/or impaired function of peptide growth factor receptors (PGF‐Rs) in tumor cells exposed to IFNα. However, we have previously described that IFNα‐induced growth inhibition of human epidermoid carcinoma cells is paralleled by up‐regulation of epidermal growth factor receptor (EGF‐R). Here we report that an increase in EGF‐R synthesis is detectable after 3 hr of exposure to cytostatic concentration of IFNα in epidermoid KB tumor cells. In these experimental conditions IFNα does not depress and even potentiates EGF‐R function. IFNα‐treated KB cells retain sensitivity to the cytotoxic activity of the anti‐EGF‐R 225 monoclonal antibody (MAb), which acts through receptor blockade, and are sensitized to the growth‐promoting effect of EGF. EGF‐induced tyrosine (tyr) phosphorylation both of total cellular protein extracts and of the immunoprecipitated EGF‐R is increased in IFNα‐treated cells. We conclude that a cross‐talk between IFNα and EGF occurs in KB cells since IFNα, at cytostatic concentration, potentiates the effects mediated by the EGF‐R. © 1995 Wiley‐Liss, Inc.
Role of anti‐LFA‐1 and anti‐ICAM‐1 combined mab treatment in the rejection of tumors induced by moloney murine sarcoma virus (M‐MSV)
Authors: Rosato Antonio , Mandruzzato Susanna , Bronte Vincenzo , Zambon Annalisa , Macino Beatrice , Calderazzo Francesca , Zanovello Paola , Collavo Dino
Published: February 2007

We investigated the effect of combined treatment with anti‐LFA‐1 and anti‐ICAM‐1 monoclonal antibodies (MAbs) in the immune reaction to Moloney‐murine‐sarcoma‐virus (M‐MSV)‐induced tumors, which spontaneously regress due to the generation of a strong virus‐specific cytotoxic‐T‐lymphocyte(CTL) response. Repeated systemic administration of both MAbs to M‐MSV‐injected mice enhanced tumor growth and delayed regression, while treatment with a single MAb had a similar, though less pronounced, effect. The immune depression achieved could not be attributed to lymphocyte depletion, because no reduction in the total number of leukocytes was detected in the peripheral blood or spleen of these mice. However, anti‐LFA‐1 MAb, alone or in combination with anti‐ICAM‐1 MAb, prevented lymphocyte homing in tumor‐draining lymph nodes. Cytofluorimetric analysis disclosed a profound down‐modulation of LFA‐1 and ICAM‐1 molecule expression on T cells following in vivo MAb treatment. Moreover, in anti‐LFA‐1 MAb‐treated mice, the receptor was coated to saturation, while anti‐ICAM‐1 MAb treatment brought about ICAM‐1‐molecule‐coating levels below saturation. Evaluation of M‐MSV‐specific CTL precursor (p) frequency in lymphoid organs of mice receiving combined MAb treatment showed that CTL generation was greatly reduced 10 days after M‐MSV injection, and returned to control levels by day 15. Our findings indicate that systemic administration of MAbs to LFA‐1 and ICAM‐1 molecules brings about a strong immune suppressive effect which is mainly due to a block in T‐lymphocyte re‐circulation, and activation by tumor cells. However, this immune‐depressive effect is only temporary, and strictly dependent on continuous MAb administration. Thus, our data suggest that treatment with anti‐LFA‐1 and anti‐ICAM‐1 MAbs combined is unable to induce T‐cell tolerance in a highly immunogenic system. © 1995 Wiley‐Liss, Inc.
Partial circumvention of multi‐drug resistance by annamycin is associated with comparable inhibition of DNA synthesis in the nuclear matrix of sensitive and resistant cells
Authors: Ling Yi‐He , Zou Yiyu , Priebe Waldemar , Perez‐Soler Roman
Published: February 2007

We studied the subcellular and subnuclear distributions of the partially cross‐resistant anthracycline Annamycin (Ann) in KB‐3‐1 and multi‐drug resistant KB‐V1 cells. Subcellular drug localization was assessed qualitatively by fluorescence microscopy and quantitatively by cell fractionation and fluorescence measurements. Doxorubicin (Dox) localized predominantly in the nucleus in KB‐3‐1 cells and in the membranes in KB‐V1 cells. In contrast, the subcellular distribution of Ann was identical in both cell lines, with preferential drug localization in the perinuclear region, Golgi apparatus, endoplasmic reticulum and endosomes. Dox rate of efflux from the nucleus was negligible in KB‐3‐1 cells but markedly enhanced in KB‐V1 cells, whereas Ann was lost at a similar rate from the nucleus in both cell lines. In KB‐3‐1 cells Dox levels in the nuclear non‐matrix were about 2‐fold higher than those of Ann, while in the matrix the inverse relationship was observed. In spite of these differences, Dox and Ann had a similar inhibitory effect on new DNA synthesis in the nuclear matrix and non‐matrix of KB‐3‐1 cells. Dox levels were reduced by 10‐fold in the nuclear non‐matrix and 2‐fold in the matrix in KB‐V1 cells compared with KB‐3‐1 cells, whereas Ann levels were reduced by about 2‐ to 3‐fold in the non‐matrix and were unchanged in the matrix. In correlation with these findings, Dox did not cause inhibition of new DNA synthesis in either nuclear fraction in KB‐V1 cells, whereas inhibition of new DNA synthesis in the matrix by Ann was similar in both cell lines. Our results indicate that Ann's partial circumvention of multi‐drug resistance is associated with its ability to cause comparable new DNA synthesis inhibition in the nuclear matrix of sensitive and resistant cells. © 1995 Wiley‐Liss, Inc.
Mechanism of cross‐resistance to cisplatin in a mitomycin C‐resistant human bladder cancer cell line
Authors: Singh Shivendra V. , Xu Bing H. , Jani Jitesh P. , Emerson Erling O. , Backes Mary G. , Rihn Christopher , Scalamogna Domenic , Stemmler Nancy , Specht Susan , Blanock Kurt , Katoh Arthur , Gupta Vicram
Published: February 2007

This study was undertaken to elucidate the mechanism(s) of cross‐resistance to cisplatin (CDDP) in a mitomycin C (MMC)‐resistant human bladder cancer cell line, J82/MMC. The J82/MMC celi line displayed 2‐ to 3‐fold cross‐resistance to CDDP and carboplatin when compared to the parental J82/WT cells. Drug uptake studies revealed that cross‐resistance to CDDP in the J82/MMC cell line was independent of reduced platinum accumulation. The J82/MMC cetl line exhibited approximately a 1.5‐fold resistance to cadmium chloride, an indicator for increased metallothionein (MT) content, when compared to the J82/WT cells. Northern blot analysis showed a 2.7‐fold higher level of MT‐IIA mRNA in the J82/MMC ceil line compared with J82/WT. We have reported previously that, whereas glutathi‐one (GSH) level is comparable in these cells, GSH transferase (GST) activity is significantly higher in the J82/MMC eell line compared with J82/WT. Results of the present study showed that the elevated GST activity in the J82/MMC cell line was due to an over‐expression of π‐type GST protein. Although buthio‐nine‐S,R‐sulfoximine (BSO)‐induced GSH depletion significantly enhanced CDDP cytotoxicrty in both cell lines, the magnitude of potentiation was markedly higher in J82/MMC cells (about 2.1‐fold) relative to J82/WT (about 1.6‐fold). Our results suggest that cross‐resistance to CDDP in the J82/MMC cell tine may be due to alterations in cellular thiols. © 1995 Wiley‐Liss, Inc.
Expression of E‐selectin on endothelial cells of small veins in human colorectal cancer
Authors: Ye Chunlin , Kiriyama Kozo , Mistuoka Chikako , Kannagi Reiji , Ito Katsuki , Watanabe Tadashi , Kondo Ken , Akiyama Seiji , Takagi Hiroshi
Published: February 2007

E‐selectin is an adhesion molecule of endothelial cells that binds to cancer cells mediated by sialyl Lewis A (sLea) or sialyl Lewis X (sLex). It is suspected to be involved in hematogenous metastasis of tumors. Therefore, it is worth examining E‐selectin expression in human colorectal cancer and its hepatic metastasis. In the present study, E‐selectin was clearly revealed on the endothelial cells of small vessels adjacent to cancer nests both in primary and in metastatic nests in immunohistochemistry. In these tissues, E‐selectin was observed on the endothelial cells lining the lumen of small vessels. Its expression adjacent to cancer nests appears to be induced through some stimuli by cancer cells, since its degree of expression is inversely correlated to the distance of the blood vessels from the cancer nests (p < 0.001). Endothelial cells adjacent to the metastatic lesion expressed E‐selectin more extensively than those adjacent to the primary foci. This is also in line with the finding on serum E‐selectin levels which were significantly elevated in the metastatic group as compared with the non‐metastatic group. The serum E‐selectin level may provide useful information in the diagnosis for hepatic metastasis of colorectal cancer, although the results are still tentative. © 1995 Wiley‐Liss, Inc.
Reduction in risk of mortality from colorectal cancer by fecal occult blood screening with immunochemical hemagglutination test. A case‐control study
Authors: Saito Hiroshi , Soma Yasushi , Koeda Junichi , Wada Toyohito , Kawaguchi Hitoshi , Sobue Tomotaka , Aisawa Tadashi , Yoshida Yutaka
Published: February 2007

Fecal occult blood testing by immunochemical hemagglutination has been shown to be superior to the Hemoccult test, both in sensitivity and in specificity. The test has been widely used as a tool for population screening in Japan, but there has been no study to evaluate the efficacy of screening using this test. A case‐control study to evaluate the screening was conducted in study areas where no previous and no other concomitant colorectal cancer screening had been performed. Case series in the study were 193 cases who died of colorectal cancer. Three controls were selected randomly from the list of individuals who were alive at the time of diagnosis of the corresponding case and had been living in the same area as the case, matched by gender and by age. Odds ratios (OR) of dying of colorectal cancer for those screened within 1, 2 and 3 years of case diagnosis vs. those not screened were 0.40 [95% confidence interval (CI) 0.17‐0.92], 0.41 (95% CI 0.20‐0.82), and 0.48 (95% CI 0.25‐0.92), respectively. OR increased towards 1.0 as the duration during which screening histories were compared was extended, and showed similar tendencies when analyzed by number of years since the most recent screening history. These results suggest that colorectal cancer screening by the immunochemical fecal occult blood test would reduce mortality from colorectal cancer.
Variations in the expression of cell‐adhesion molecules on liver‐associated lymphocytes and peripheral‐blood lymphocytes in patients with and without liver metastasis
Authors: García‐Barcina María , Bidaurrazaga Ioseba , Neaud Véronique , Bioulac‐Sage Paulette , Balabaud Charles , Vidal‐Vanaclocha Fernando , Winnock María
Published: February 2007

We evaluated the expression of the cell‐adhesion molecules (CAM) that might be involved in liver‐associated lymphocyte (LAL) contacts with other sinusoidal cells and/or be responsible for natural‐killer(NK)‐ and lymphokine‐activated killer(LAK) activity in patients with liver metastasis. The LAL population was isolated by sinusoidal high‐pressure lavage from partial hepatectomies obtained from patients operated for metastases (n = 13) and benign liver tumors (n = 9). Surface expression of the beta‐2‐integrin chains (CD11a, CD11b, CD11c and CD 18), and the beta‐1‐integrin chains (CD49b, CD49d, CD49f and CD29), as well as that of members of the immunoglobulin superfamily (CD2, CD54, CD56 and CD58), were analyzed by one‐ or two‐color flow cytometry. Quantitative and qualitative differences were observed in both groups of patients in the expression of CAM between LAL and peripheral blood lymphocytes (PBL). LAL were characterized by an increase in the percentage of CD11b‐, CD49b‐, CD49d‐, CD54‐, CD56‐ and CD58‐positive cells in comparison with PBL. Fluorescence values for CD2, CD11a, CD18 and CD56 were higher in LAL than in PBL. Moreover, the population expressing these antigens of differentiation presented a bimodal distribution (dim and bright): in LAL, as opposed to PBL, the percentage of cells with a bright phenotype was greater than of those with a dim one. The increase in CAM expression on LAL could be due to the influence of the liver sinusoidal micro‐environment. Results were more unexpected for the comparison between benign and malignant tumors. No difference was found in CAM expression on LAL between these 2 categories. Consequently, it cannot be this factor that explains the decrease in LAK activity of LAL in patients with metastasis. © 1995 Wiley‐Liss, Inc.
Establishment and characterization of cachexia‐inducing and ‐non‐inducing clones of murine colon 26 carcinoma
Authors: Fujimoto‐Ouchi Kaori , Tamura Sumie , Mori Kazushige , Tanaka Yutaka , Ishitsuka Hideo
Published: February 2007

To investigate the mechanism causing cachexia and its association with shorter patient survival, we cloned weight‐loss‐inducing and ‐non‐inducing sublines of murine colon 26 carcinoma (colon 26). One clone, clone 20, induced substantial weight loss, wasting of adipose tissue and muscle, and hypogly‐cemia in mice with a minimum tumor burden of 0.3 g (2 g per 100 g body weight). Clone‐20‐bearing mice had a median survival of 24.5 days with average tumor weight of 0.4 g. In contrast, clone 5 induced neither severe weight loss, wasting of adipose tissue and muscle, nor hypoglycemia; clone‐5‐bearing mice survived for a median of 70 days with average tumor weight of 12 g. These results clearly indicate that shorter survival is associated with the degree of cachexia and is independent of tumor size. Using this pair of colon 26 clones, we examined mediators of cachexia. Neither TNFα, IL‐1α nor IFNγ was detected in the serum of mice bearing either clone, while IL‐6 was detected in mice bearing both clones by ELISA and a bioassay. Administration of anti‐IL‐6 monoclonal antibody (MAb) partially but significantly suppressed cachexia induction in clone‐20‐bearing mice. These results point to the involvement of IL‐6 in experimental cachexia. However, our finding of the presence of IL‐6 in the serum of mice bearing clone 5, which does not induce weight loss, clearly indicates that IL‐6 is not solely responsible for the induction of cachexia. © 1995 Wiley‐Liss, Inc.
Urokinase plasminogen activator and urokinase plasminogen activator receptor in breast cancer
Authors: Duggan C. , Maguire T. , McDermott E. , O'Higgins N. , Fennelly J. J. , Duffy M. J.
Published: February 2007

Urokinase plasminogen activator (uPA) is a serine protease involved in cancer invasion and metastasis. uPA mediates its action while attached to a membrane‐bound receptor (uPAR). In this investigation we show that uPAR levels correlate with uPA levels in human breast cancers. uPAR levels, however, do not correlate with other components of the plasminogen activator system such as tissue‐type plasminogen activator (t‐PA), PAI‐1 or PAI‐2. In addition, uPAR levels showed no correlation with tumor size, axillary‐node status or estrogen‐receptor status. On the basis of an optimum cut‐off point, patients with breast cancers containing high levels of uPAR had a worse prognosis than patients with low levels of the receptor. However, as a prognostic marker in breast cancer, uPAR was not as strong as uPA. Our results are consistent with data from model systems suggesting that both uPA and uPAR are necessary for metastasis. © 1995 Wiley‐Liss, Inc.