bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractAdoptive 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

AbstractHuman 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

AbstractThere 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

AbstractWe 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

AbstractInterferon‐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

AbstractA 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

AbstractThe 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

AbstractThe 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

AbstractNon‐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

AbstractFive 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

AbstractPrevious 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

AbstractAngiogenesis 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

AbstractTrends 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

AbstractThe 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

AbstractWe 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.