bluuebunny/crossref_metadata_2025 huggingface dataset:
An analysis of autologous T‐cell anti‐tumour responses in colon‐carcinoma patients following active specific immunization (ASI)
Authors: Patel B. T. , Lutz M. B. , Schlag P. , Schirrmacher V.
Published: February 2007

As part of a phase‐II clinical trial of post‐operative active specific immunization (ASI) with virus‐modified autologous tumour cells (AuTu) in colorectal carcinoma patients, we have analyzed in vitro anti‐AuTu immune responses with lymphocytes isolated from the peripheral blood (PBL) of 5 treated patients. The PBL of 3 “responder patients”, those who developed a positive DTH reaction to AuTu, when stimulated in standard in vitro autologous lymphocyte tumour‐cell cultures (ALTC), showed cytotoxic anti‐AuTu reactivity only in association with natural‐kilIer‐cell(NK)‐like activity. We removed nonspecific cytotoxic cells (CD56‐positive) from PBL of colon carcinoma or melanoma patients and positively selected T cells with strong CD8 staining (CD8hi) using FACS. Following in vitro stimulation, specific cytotoxic T cells (CTL) directed against either autologous EBV‐transformed B cells (AuEBV‐B) or autologous melanoma cells were identified in the CD8hi T‐cell population. However, even using this novel technique, no specific CTL against autologous colon carcinoma cell lines were detected in PBL from ASI‐treated patients (2 DTH responders and 2 DTH non‐responders). If AuTu‐specrfic CTL precursors existed in these blood samples, their frequency must have been very low (less than 1 in 8 × 104 CD8 positive T cells). Sorted CD4 T cells from these patients, in the presence of autologous antigen‐presenting cells, showed no specific anti‐tumour proliferative response, and in one instance we observed inhibition of proliferation in the presence of tumour cells.
A prospective study of transmission by transfusion of HTLV‐I and risk factors associated with seroconversion
Authors: Manns Angela , Wilks Rainford J. , Murphy Edward L. , Haynes Grace , Figueroa J. Peter , Barnett Marge , Hanchard Barrie , Blattner William A.
Published: February 2007

To evaluate the risk of transfusion‐related transmission of HTLV‐I in Jamaica, a prospective study was initiated, prior to availability of a licensed HTLV‐I serological screening assay. This information would prove useful in formulating strategies for blood‐donor screening. We followed 118 pre‐transfusion HTLV‐l‐negative transfusion recipients at monthly intervals posttransfusion for I year. Laboratory and questionnaire data were obtained at each visit to evaluate the clinical and immunological status of recipients. Cumulative incidence of HTLV‐I seroconversion was estimated and risk‐factor data associated with seroconversion among 66 HTLV‐l‐exposed transfusion recipients were analyzed. Seroconversion occurred in 24/54 (44%) of recipients of HTLV‐l‐positive cellular blood components, 0/12 recipients of positive non‐cellular donor units and 0/52 recipients of HTLV‐l‐negative donor units. Significant risk factors associated with recipient seroconversion were receipt of a seropositive cellular blood component stored for less than one week [odds ratio (OR) = 6.34, 95% confidence interval (CI) = 1.83 to 21.92], male sex (OR = 4.79, 95% CI = 1.15 to 20.0) or use of immunosuppressive therapy at time of transfusion (OR = 12.20, 95% CI = 0.95 to 156). Risk of blood‐borne infection per person per year in Jamaica was estimated to be 0.009%. Our results confirm that blood transfusion carries a significant risk of HTLV‐I transmission and that screening of donor blood effectively prevents HTLV‐I seroconversion. Recipients at greatest risk for seroconversion were those who required multiple transfusions or who were receiving immunosuppressive therapy at the time of transfusion. These patients should be given priority in receiving selectively screened blood components, if universal blood‐donor screening for HTLV‐I is not possible.
Inhibitory effects of human interferons on the immortalization of HUMAN, but not rabbit, T lymphocytes by human T‐lymphotropic virus type‐I (HTLV‐I)
Authors: Oka Takashi , Iwata Jun , Furihata Mutsuo , Sonobe Hiroshi , Miyoshi Isao , Ohtsuki Yuji
Published: February 2007

The effects of human interferon (IFN)‐α, ‐β, and ‐γ on the immortalization of human and rabbit lymphocytes by human T‐lymphotropic virus type‐l (HTLV‐I) have been investigated. The immortalization of human peripheral‐blood lymphocytes co‐cultured with lethally X‐ray‐irradiated HTLV‐l‐producer cells, MT‐2, was blocked in the presence of more than 40 u/ml human recombinant IFN‐α or more than 200 u/ml human natural type IFN‐fi. However, rhlFN‐γ did not block immortalization by HTLV‐I even at higher doses. On the other hand, the presence of high doses of hlFN‐α, ‐β, or ‐γ did not exhibit any biological effect on the immortalization of rabbit peripheral‐blood lymphocytes co‐cultured with lethally X‐ray‐irradiated MT‐2 cells. Integration of the full length of HTLV‐I genome was detected in every transformant by Southern blot analysis. All cell lines established were CD4+/CD8÷ T‐lymphocytes, except for one cell line of CD4+/CD8+. Morphologically intact HTLV‐I production was observed by electron microscopy in these cells. Our results indicate that HTLV‐I released under the strongly suppressed condition in the presence of IFNs remains active and able to immortalize T lymphocytes. It is also suggested that immortalization of human T lymphocytes by HTLV‐I can be inhibited by the antiviral state induced by the treatment with low doses of hlFN‐α and ‐β, whereas immortalization of rabbit T lymphocytes is not inhibited because of the species specificity of hlFNs.
Modifications of an immunodominant peptide antigen induce different anti‐polyoma tumor responses in two separate mouse strains
Authors: Reinholdsson‐Ljunggren Git , Dalianis Tina
Published: February 2007

An immunodominant polyoma peptide antigen MT162‐176 was modified with regard to amino acid (aa) composition in an attempt to analyze its immunogenicity in detail. Twelve modifications of peptide MT 162‐176, 3 overlapping peptides and 9 peptides with point mutations, were synthesized and used for immunizations of (A.CA x C57BL/6)F1 and CBA mice against the syngeneic polyoma tumors SECA and SEBA All 3 overlapping peptides MT 162‐176, MT165‐174 and MT 170‐176, were immunogenic in (A.CA x CS7BL/6)F1 mice against SECA, indicating that possibly more than one immunogenic epitope may be recognized within the MT 162‐176 sequence. In CBA mice, the 2 peptides covering the C‐terminal half were immunogenic against SEBA, while the N‐terminal peptide was possibly somewhat less efficient. The peptides with aa point mutations induced different anti‐tumor responses in the 2 mouse strains. In CBA mice, only one mutant, MT162‐176.28, was immunogenic. For (A.CA x C57BI)F1 3 different mutants, MTI62176.29, MTI62‐I76.35 and MTI62‐I76.36 were immunogenic against SECA, while the remaining 6 had lost their activity. These results suggest that a different emphasis of recognition of peptide MT 162‐176 exists with regard to the 2 mouse strains examined. Furthermore, different immunization procedures were tested. We found that repeated immunizations with peptide without Freund's adjuvant was the most efficient. © 1992 Wiley‐Liss, Inc.
K‐ras point mutations in human colorectal carcinomas: Relation to aneuploidy and metastasis
Authors: Suchy Bernhard , Zietz Christian , Rabes Hartmut M.
Published: February 2007

Material from paraffin sections of 109 human colorectal carcinomas, mostly obtained at autopsy, was analyzed for the presence of K‐ras point mutations at codon 12, position 2. Mutations at this position were found in 23 cases (21.1%). Aneuploid colorectal carcinomas showed a significantly higher prevalence of K‐ras point mutations than diploid tumors, suggesting an involvement of ras mutations in the development of aneuploidy. No differences in the prevalence of K‐ras mutations were observed with respect to the patients' age, sex and tumor type. In metastases, the type of ras gene mutation was always identical to that of the respective primary tumor. Mutations were not found in metastases from primary tumors devoid of ras mutations. This renders a clonal selection of K‐ras mutated cells from a wild‐type primary tumor during the metastatic process unlikely. However, nearly twice as many ras gene mutations were seen in metastatic than in non‐metastatic primary tumors. © 1992 Wiley‐Liss, Inc.
Detection of distinct Epstein‐Barr virus genotypes in NPC biopsies from Southern Chinese and Caucasians
Authors: Lung Maria Li , Chang Garrick C.
Published: February 2007

Using the polymerase chain reaction (PCR) to analyze paraffin sections from 12 Caucasian patients, we detected only the prototype F Epstein‐Barr virus (EBV) in 10 specimens from patients with nasopharyngeal carcinoma (NPC). This is in contrast to the higher frequency of association of “f” variants in NPC biopsies from Southern Chinese. The results of EBV genotyping support evidence that the EBV strains associated with NPC in the Southern Chinese population differ from those found in Caucasians. DNA sequencing confirmed that a simple point mutation is responsible for the restriction‐fragment‐ length polymorphism which distinguishes the prototype F virus from the “f” variant. © 1992 Wiley‐Liss, Inc.
Micronuclei in bronchial biopsy specimens from heavy smokers: Characterization of an intermediate marker of lung carcinogenesis
Authors: Benner Steven E. , Lippman Scott M. , Wargovich Michael J. , Velasco Marco , Peters Edward J. , Morice Rodolfo C. , Hong Waun K.
Published: February 2007

Bronchial micronuclei, small fragments of extra‐nuclear DNA formed during cell division, provide a non‐specific but quantifiable marker of DNA damage. Micronuclei have been used to assess carcinogen exposure and as an intermediate endpoint in chemoprevention trials. As part of an ongoing chemoprevention trial, heavy smokers underwent screening bronchoscopy, with biopsies taken at 6 standardized sites. Micronuclei counts were obtained for each site in each of the 40 volunteers found to have squamous metaplasia. Unlike squamous metaplasia, the average micronuclei counts among these heavy smokers were not associated with smoking history. Micronuclei counts were also not associated with the presence or extent of metaplasia. A striking degree of intra‐individual variability was observed by comparing the micronuclei counts from different biopsy sites within individuals. The findings suggest that use of micronuclei from single sites may be misleading as a marker of carcinogen exposure or as an estimate of cancer risk. Serial measurements in individuals may provide the most useful information concerning carcinogenic exposure and the impact of chemopreventive agents. © 1992 Wiley‐Liss, Inc.
Distribution of autologous tumor‐specific cytotoxic T lymphocytes in human metastatic melanoma
Authors: Itoh K. , Salmeron M. A. , Morita T. , Seito D. , Mansfield P. P. , Ross M. I. , Balch C. M. , Augustus L. B.
Published: February 2007

The study of specific immunity in human cancers has been hampered by the elusive distribution and heterogeneity of effector cells. In this study, we have investigated the distribution of autologous melanoma‐specific cytotoxic T lymphocytes (CTLs) in 18 different distant metastases from melanomas (9 non‐ visceral and 9 visceral metastases). Uncultured cells from tumors were provided directly for the establishment of T‐cell clones using limiting dilution analysis to avoid any possible effects of in vitro sensitization of T cells to coexisting tumor cells. Autologous tumor‐specific CTL, clones were detected in 6 of 18 tumors (33%, 4 non‐visceral and 2 visceral metastases). The majority of GTL clones (35 of 46 and 17 of 19) in 2 patients with HLA class‐1 A2 haplotype failed to lyse either A2+ or A2− allogeneic melanoma cells, although anti‐class‐1 (monomorphic) MAb inhibited their cytotoxicity. The remaining 11 of 46 and 2 of 19 CTL clones showed A2‐restricted cytotoxicity. Autologous tumor‐specific cytotoxicity was also detected after polyclonal culture of these tumor‐infiltrating lymphocytes (TILs) in 8 of 16 tumors (50%, 5 non‐visceral and 3 visceral metastases). These results suggest that tumor‐specific T cells exist at tumor sites in at least one‐third of distant metastases of melanomas and could be induced by the addition of IL‐2 in at least half of the tumors. Tumor‐specific T cells were detectable more often in non‐ visceral than in visceral metastases. © 1992 Wiley‐Liss, Inc.
Single‐step transformation of human breast epithelial cells by SV40 large T oncogene
Authors: Berthon Philippe , Goubin Gérard , Dutrillaux Bernard , Degeorges Armelle , Faille Annick , Gespach Christian , Calvo Fabien
Published: February 2007

Normal human mammary epithelial cell (HMEC) cultures originating from 2 mammoplasty reduction surgical samples were transfected with replication‐defective SV 40 DMA. Two independent cell lines designated as S2T2 and S1T3, selected for their increased proliferation potential and lifespan, were propagated for >22 months in culture. They maintained a near‐diploid karyotype with few chromosomal markers such as trisomy 1q (SITS) and trisonny 8q (S2T2), which are most common in breast cancer in vivo. Immortalized S1T3 cells were not tumorigenic, whereas S2T2 cells produced slowly growing tumors in nude mice. One tumor was propagated in vitro and the transformed NS2T2 cell line subsequently raised 100% large tumors in the nude mouse. Rearrangement of the SV40 genome was observed in NS2T2 cells, which was not associated with increased expression of large T antigen. S1T3, S2T2 and transformed NS2T2 cell lines expressed cytokeratins CK18, CK19, the mammary‐specific antigen DF3, and functional EGF receptors. Single‐step immortalization and malignant transformation of human breast epithelial cells can thus occur upon transfection with SV40 large T oncogene. The chromosomal abnormalities observed in these cell lines suggest that they could offer a model for the study of breast‐tumor progression in vitro. © 1992 Wiley‐Liss, Inc.
Effects of light exposure on the uptake of photofrin II in tumors and normal tissues
Authors: Ma L. W. , Moan J. , Peng Q.
Published: February 2007

DBA mice bearing CaD2mammary carcinomas were used to determine the effect of giving small doses of light to the tumor area 1.5 hr after injecting Photofrin II (PII). The smallest light dose applied (12.5 J/cm2) had no effect on the uptake of Pll in the tumor and its surrounding tissues, as measured 24 hr after the i.p. injection. However, several higher light doses increased the uptake of PII in the tumor significantly, the uptake in skin slightly, while the uptake in muscle tissue was decreased rather than increased. Thus, the PII concentration ratio between the tumor and the surrounding normal tissues was significantly improved. The rates of clearance of PII from irradiated tissues and non‐irradiated tissues were not significantly different. Most likely, the present observations are due to transient pH lowering in the tumor resulting from vascular damage. © 1992 Wiley‐Liss, Inc.
Enhancement of hepatitis‐B surface‐antigen expression by 5‐azacytidine in a hepatitis‐B‐virus‐transfected cell line
Authors: Miyoshi Eiji , Fujii Junichi , Hayashi Norio , Ueda Keiji , Towata Takahiro , Fusamoto Hideyuki , Kamada Takenobu , Taniguchi Naoyuki
Published: February 2007

The human hepatoblastoma‐derived cell line HB611 secretes hepatitis‐B surface antigen (HBsAg) and hepatitis‐B e antigen (HBeAg) into the medium. Hepatitis‐B‐virus(HBV) DNA integrated into the cellular genome was found to be hypermethylated. When the cells were treated with 5‐azacytidine for 3 days, the level of HBsAg in the medium increased, while the level of HBeAg remained constant. The level of alphafetoprotein (AFP) decreased with the 5‐azacytidine treatment. Southern blot analysis of DNA digested with Hpall or Mspl showed that 5‐azacytidine treatment resulted in hypomethylation of the integrated HBV DNA, suggesting that 5‐azacytidine increased HBsAg production in the cells through hypomethylation of the HBV genomic DNA. © 1992 Wiley‐Liss, Inc.
P‐glycoprotein transports corticosterone and is photoaffinity‐labeled by the steroid
Authors: Wolf David C. , Horwitz Susan Band
Published: February 2007

Multi‐drug‐resistant cells overproduce a 130–180‐kDa integral membrane phosphoglycoprotein known as P‐glycoprotein which acts as an energy‐dependent drug efflux pump. While P‐glycoprotein has been shown to transport hydrophobic anti tumor drugs out of multi‐drug‐resistant cells in tissue culture, its endogenous substrates remain unknown. This report shows that 3H‐corticosterone can specifically photoaffinity label P‐glycoprotein. Furthermore, corticosterone is effluxed from multidrug‐resistant cells by P‐glycoprotein. These data suggest that corticosterone may be an endogenous substrate for P‐glycoprotein. © 1992 Wiley‐Liss, Inc.
Direct detection of Epstein‐Barr virus in peripheral blood and comparison of Epstein‐Barr virus genotypes present in direct specimens and lymphoblastoid cell lines established from nasopharyngeal carcinoma patients and healthy carriers in Hong Kong
Authors: Lung Maria Li , Lam Wai Pang , Chan Kwok Hung , Li Shaobing , Sham Jonathan , Choy Damon
Published: February 2007

By means of a PCR assay, EBV was demonstrated directly in peripheral blood of previously infected individuals. The virus was detected in approximately 80% of specimens from EBV‐seropositive individuals, but not in cord‐blood lymphocytes by this method. When virus present in peripheral blood was compared to that observed directly in NPC biopsies or throat washings, it was distinct from that seen in biopsies in 4/15 cases (17%) and from that seen in throat washes in 1/22 cases (5%). The throat‐wash virus differed from the biopsy virus in 3/20 cases (15%). The prototype F virus was found in 7/10 LCLs (70%) established from NPC patients' peripheral blood, but was only detected in 2/9 specimens (22%) directly analyzed by the PCR assay. This finding suggests selective isolation of prototype F EBV in spontaneous LCLs established from NPC patients. © 1992 Wiley‐Liss, Inc.
The study of markers of biological effect in cancer prevention research trials
Authors: Greenwald Peter , Witkin Karen M. , Malone Winfred F. , Byar David P. , Freedman Laurence S. , Stern Harriet R.
Published: February 2007

Biological markers may provide a valuable tool for the development of cancer prevention agents, for monitoring patient compliance to a selected intervention, or for further defining the carcinogenic process. This discussion focuses on markers of biological effect and the rationale for their use in cancer prevention trials. Recent studies with biological markers are investigating their incorporation into phase‐I, ‐II, and ‐III chemoprevention clinical trial designs. Their use in clinical studies is expected to increase the number of agents that may be evaluated and to provide valuable information on the biological effectiveness of agents, doses, and schedules. Markers may also provide information to help in selecting high‐risk groups for prevention research, and to indicate the pathways inhibited and the stage of carcinogenesis affected. Such information may prove of crucial importance in strengthening the rationale for long‐term trials and other ancillary research. Biomarker research for colon carcinogenesis is discussed, including examples of a number of recent trials that may influence future progress in this area of prevention research. A crucial step in this process is marker validation as an aspect of major prospective observational and intervention studies where cancer incidence is the endpoint. We cannot be fully confident of markers as intermediate endpoints until the evidence from clinical trials is sufficiently strong to support major public health initiatives for prevention. © 1992 Wiley‐Liss, Inc.
The effect of endocrine therapy with medroxyprogesterone acetate, 4‐hydroxyandrostenedione or tamoxifen on plasma concentrations of insulin‐like growth factor (IGF)‐I, IGF‐II and IGFBP‐1 in women with advanced breast cancer
Authors: Reed M. J. , Christodoulides A. , Koistinen R. , Seppälä M. , Teale J. D. , Ghilchik M. W.
Published: February 2007

Tamoxifen treatment of women with advanced breast cancer has previously been reported to reduce plasma insulin‐like growth factor‐type I (IGF‐I) concentrations. In this study we have examined the effect of treatment with Tamoxifen, medroxyprogesterone acetate (MPA) or 4‐hydroxyandrostenedione (4‐OHA) on plasma IGF‐I and IGF‐II concentrations. As IGF‐binding proteins (IGFBPs) can modulate the biological effects of IGF‐I, plasma IGFBP‐I levels were also measured. Treatment with Tamoxifen for 2 weeks resulted in a small, but significant, decrease in IGF‐I levels, but increase in the plasma concentration of IGFBP‐I. In contrast, treatment with MPA increased levels of IGF‐I, but significantly reduced plasma IGFBP‐I concentrations. Treatment with 4‐OHA had no significant overall effect on plasma IGF‐I or IGFBP‐I levels, although changes were detected for some subjects. Plasma IGF‐II concentrations were not altered by treatment with Tamoxifen, MPA or 4‐OHA. It is concluded that although treatment with Tamoxifen or MPA produced significant changes in plasma IGF‐I concentrations, any physiological effects of such changes are likely to be modulated by the corresponding alterations in plasma IGFBP‐I concentrations. © 1992 Wiley‐Liss, Inc.
Effects of short‐chain fatty acids on growth and differentiation of the human colon‐cancer cell line HT29
Authors: Gamet Laurence , Daviaud Danièle , Denis‐Pouxviel Colette , Remesy Christian , Murat Jean‐Claude
Published: February 2007

Short‐chain fatty acids (SCFAs), namely butyrate, acetate and propionate, originate from the bacterial fermentation of dietaiy fibers and are the predominant anions present in the large bowel. Our study was carried out to investigate the effects of SCFAs on growth of the human adenocarcinoma cell line, HT29. The results show that, under our culture conditions, both propionate and butyrate inhibit growth of HT29 cells, whereas acetate has no significant effect. The antiproliferative effect of propionate or butyrate is associated with an inhibition of FCS‐induced activation of ornithine decarboxylase (ODC), a key enzyme of polyamine metabolism. Inhibition of growth induced by either propionate or butyrate is not reversed by the addition of putrescine, which reveals that these SCFAs are not acting solely on the ODC/polyamine system. Our data show that propionate and butyrate, unlike acetate, induce an increase in alkaline phosphatase activity, which reflects a more differentiated phenotype than that of untreated control cells. Taken together, our results suggest that propionate, like butyrate, may play an important role in the physiology of the colon and could partially account for the protective effect of dietary fibers with respect to colon carcinogenesis. © 1992 Wiley‐Liss, Inc.
Clonal variation of expression of the genes coding for plasminogen activators, their inhibitors and the urokinase receptor in HT1080 sarcoma cells
Authors: Laug Walter E. , Wang Kai , Mundi Rita , Rideout William , Kruithof Egbert K. O. , Bogenmann Emil
Published: February 2007

The human sarcoma cell line HT1080 was found, by in situ hybridization, to consist of cells expressing various levels of urokinase (uPA) and tissue type (tPA) plasminogen activator (PA) suggesting clonal variation of expression of these genes. Colonies originating from single HT1080 cells were, therefore, established and screened for PA activity using a fibrin agarose overlay. Colonies inducing lysis (clone C+ and H+) or no lysis (clones B− and M−) were isolated and tested for mRNA levels of uPA, tPA, uPA receptor (uPAR) and the 3 PA inhibitors (PAI), PAI‐1, PAI‐2 and protease‐nexin I. The different clones revealed considerable variation of expression of the different PA and PAI genes, with lysis‐inducing clones expressing mainly the PA genes, whereas non‐lysing clones demonstrated higher expression of the PAI genes. Amplification or loss of specific genes was excluded by Southern blotting. The protein levels of cellular and secreted PA and PAI determined by ELISA and Western blots demonstrated a pattern similar to that observed for PA and PAI mRNA concentrations, suggesting clonal differences either on the level of transcription or in RNA processing and/or stability. Due to complex interactions between PA and PAI, neither mRNA nor protein levels of the different genes were predictive for the amount of functional PA activity present in the supernatant or on the cell surface of the different clones. Receptor‐bound uPA activity was found to be considerably higher in lysis‐inducing than in non‐lysing clones and the activity was dependent on neutralization by PAI‐1 rather than on the level of uPAR mRNA. © 1992 Wiley‐Liss, Inc.
Effects of areca nut on growth, differentiation and formation of DNA damage in cultured human buccal epithelial cells
Authors: Sundqvist Kristina , Grafström Roland C.
Published: February 2007

Because the high incidence of oral cancers in South‐East Asia is causally linked to the common habit of betel quid chewing, the effects of an aqueous extract of areca nut, one of the main ingredients of the quid, on growth, differentiation, morphology and DNA damage were studied in cultured human buccal epithelial cells. An acute exposure (3 hr) of the cells to the extract altered their morphology and induced ridges in the plasma membrane, with indications of internalization of extract particles. Such exposure also caused formation of DNA single‐strand breaks which accumulated during post‐treatment culture, indicating continuous exposure to residual particles and/or the possibility of inhibited DNA repair. The extract accelerated terminal differentiation of the cells, measured as involucrin expression at relatively non‐toxic levels. The extract caused similar loss of colony‐forming efficiency in normal cells and in a buccal carcinoma cell line (SqCC/YI) which was defective in its ability to undergo differentiation, indicating that extract toxicity could occur independently from this response. Finally, the genotoxicity of the salivary areca‐nut‐specific carcinogen 3‐(N‐nitrosomethyl‐amino)propionaldehyde, was demonstrated by the formation of DNA protein cross‐links and DNA single‐strand breaks in normal buccal epithelial cells. These findings in vitro suggest that betel quid carcinogenesis in the human oral cavity may involve cytopathic alterations of normal cell morphology, growth and differentiation, as well as formation of DNA damage by areca‐nut‐related agents extracted or formed in saliva. © 1992 Wiley‐Liss, Inc.
Schedule‐dependent effects of two consecutive, divided, low doses of actinomycin D on translocation of protein B23, inhibition of cell growth and RNA synthesis in hela cells
Authors: Yung Benjamin Yat‐Ming , Chang Fu‐Jung , Bor Amy Meei‐Shuu , Lee Edith Siew‐Teh
Published: February 2007

The effects of 2 consecutive, divided, low doses of actinomycin‐D (Act‐D) on cellular localization of protein B23, inhibition of cell growth, RNA synthesis and colony formation were studied in HeLa cells. The second dose of Act‐D was administered at various times after removal of the first dose. One short exposure of HeLa cells to Act‐D had previously been shown to induce “resversible” translocation of protein B23, inhibition of cell growth, and RNA synthesis. Relocalization of protein B23 from the nucleoplasm to nucleoli as well as “reversible” inhibition of cell growth and RNA synthesis were still observed in cells that had been treated with a second dose of Act‐D administered as early as 0–2 hr or as late as 30 hr after removal of the first dose of Act‐D. In contrast, no relocalization of protein B23 from the nucleoplasm to nucleoli was observed in cells that had been treated with a second dose of Act‐D administered 9 hr after removal of the first dose. A second exposure to Act‐D, administered 9 hr after removal of the first dose, caused irreversible inhibition of cell growth and RNA synthesis; a significant inhibitory effect on colony formation was also observed. RNA synthesis in HeLa cells after 2 sequential exposures to Act‐D was further analyzed by 1 % agarose gel electrophoresis. There were higher‐molecular‐weight bands above 28S RNA, which may be the 45S and 32S RNA, observed in the controls and in the cells that had been exposed to Act‐D treatment once or in the cells that underwent Act‐D exposure twice, in which the second dose was administered as early as 0–2 hr or as late as 30 hr after removal of the first dose. These high‐molecular‐weight bands were not observed in the cells that underwent Act‐D exposure twice, in which the second dose was administered 9 hr after removal of the first. These results indicated that cells at different stages of inhibition or that have recovered from the first exposure to Act‐D respond differently to the second short Act‐D exposure. © 1992 Wiley‐Liss, Inc.
Reproductive factors and the risk of hepatocellular carcinoma in women
Authors: La Vecchia Carlo , Negri Eva , Franceschi Silvia , D'Avanzo Barbara
Published: February 2007

The relationship between reproductive factors and the risk of primary liver cancer was analyzed using data of a case‐control study conducted in Northern Italy between 1984 and 1991 on 79 women with histologically or serologically confirmed hepatocellular carcinoma and 344 controls in hospital for a wide spectrum of acute, non‐neoplastic diseases. The multivariate relative risk (RR) for parous vs. nulliparous women was 2.6 (95% confidence interval (CI) 1.2 to 5.8), and the risk increased with parity from 2.1 for 1, to 2.6 for 2, to 3.2 for 3, to 3.5 for 4 or more births (x trend = 6.49, p = 0.01). The relative risks were above unity, though not significantly, in women reporting spontaneous (RR = 1.3) and induced (RR = 1.6) abortions, and there was a significant trend in risk with total number of abortions. An apparent inverse trend in risk with age and first birth was accounted for by parity. No relationship emerged with age at menarche, at menopause or other menstrual factors. The association between parity and hepatocellular carcinoma was, if anything, more marked at older ages, since the RR was 1.6 (95% CI 0.5 to 4.6) below age 60, and 4.8 (95% CI 1.3 to 18.1) at age 60 or over. This observation has relevant public‐health implications, since in developed countries primary liver cancer is extremely rare among young women, but not at older ages. The association between parity and hepatocellular carcinoma is similar to that described for combined oral contraceptives, again confirming that the impact of contraceptives on the risk of several neoplasms is similar to that of pregnancy. © 1992 Wiley‐Liss, Inc.
Presence and physical state of HPV DNA in prostate and urinary‐tract tissues
Authors: Rotola A. , Monini P. , di Luca D. , Savioli A. , Simone R. , Secchiero P. , Reggiani A. , Cassai E.
Published: February 2007

Neoplastic and non‐neoplastic tissues from the urinary tract and the prostate were analyzed for the presence of human papillomavirus (HPV) DNA. The analysis was performed by PCR using primers specific for HPV 6/11 and 16. HPV DNA was present in bladder, ureter, kidney and prostate, with percentages ranging between 46% and 87%. Benign and oncogenic HPV types were detected with similar frequencies both in non‐neoplastic and in neoplastic biopsies, and HPV 16 was not preferentially associated with malignant lesions. In all instances, small amounts of HPV DNA were present in the tissues, suggesting the absence of productive infection. Analysis of the physical state of HPV DNA performed by 2‐dimensional gel electrophoresis and Southern blot hybridization revealed that HPV 16 DNA harbored in the urinary tract can be integrated also in non‐neoplastic tissues. The results indicate that HPV 16 does not seem to be associated with urinary‐tract and prostate oncogenesis, but that these tissues may represent an important reservoir for the transmission of HPV types normally infecting the genital tract. © 1992 Wiley‐Liss, Inc.
Immunogenic tumor variants induced by drug treatment of the L5178Y lymphoma: Search for serologically defined antigens at the clonal level
Authors: Grohmann U. , Puccetti P. , Romani L. , Binaglia L. , Bianchi R. , Belladonna M. L. , Ullrich S. J. , Appella E. , Fioretti M. C.
Published: February 2007

Highly immunogenic tumor variants are generated by in vitro or in vivo treatment of the murine L5178Y lymphoma line with triazene derivatives. Most of these variants express new transplantation‐ and antibody‐defined antigens that previous studies have shown to be closely related. One such 80‐kDa protein on the surface of clone‐D cells was found to be related to xenotropic MuLV gp70 molecules. To investigate the possible relevance of clone‐D data to general properties of immunogenic variants in this tumor model system, polyclonal syngeneic antisera raised to a panel of immunogenic clones (including clone D) of the drug‐treated L5178Y lymphoma line were employed in the immunoprecipitation of cell‐surface and intrinsically labeled variant cells. In all clones, 1‐ and 2‐dimensional electrophoretic analysis of the immunoprecipitates detected an antigen of approximately 80 kDa, and 35S‐labeled 80‐kDa molecules could be cross‐precipitated from all clones by the panel of clone‐ specific antisera. In addition, 45‐ and 30‐kDa components were also found in metabolically labeled variant cells. While the surface 80‐kDa component was reactive with anti‐xenotropic gp70 antibodies, the 30‐kDa molecule was removed by anti‐gag p30 antibody in sequential immunoprecipitation experiments. These data suggest that expression of aberrant, retrovirus‐related proteins is a common finding in immunogenic cells of the drug‐treated L5178Y lymphoma line. © 1992 Wiley‐Liss, Inc.
Enhanced epidermal growth factor receptor synthesis in human squamous carcinoma cells exposed to low levels of oxygen
Authors: Laderoute Keith R. , Grant Tandora D. , Murphy Brian J. , Sutherland R. M.
Published: February 2007

Exposure of human A431 squamous carcinoma cells to levels of hypoxia found in some solid tumors causes 2‐fold increases in epidermal growth‐factor receptor (EGF‐R) mRNA levels and rate of receptor protein synthesis compared with aerobic cells. Similar results are shown for receptor message from other squamous carcinoma cells, human keratinocytes, and human W138 fibroblasts. Less basal tyrosine phosphorylation of the receptor occurs in hypoxic compared with aerobic A431 cells. Scatchard analysis also shows that reoxygenated A431 cells display enhanced surface expression of the EGF‐R compared with aerobic control cells. Possible mechanisms and implications for tumor therapy are discussed. © 1992 Wiley‐Liss, Inc.
Distribution and photosensitizing efficiency of porphyrins induced by application of exogenous 5‐aminolevulinic acid in mice bearing mammary carcinoma
Authors: Peng Q. , Moan J. , Warloe T. , Nesland J. M. , Rimington C.
Published: February 2007

By means of a chemical extraction procedure and confocal laser scanning microscopy, we investigated the kinetic patterns of uptake and biolocalization of 5‐aminolevulinic acid (ALA)‐induced porphyrins in s.c. transplanted tumors, adjacent normal skin and muscle, and liver of mice bearing mammary carcinoma, after i.p. injection of 250 mg/kg ALA or topical application of ALA (20% in an oil‐in‐water emulsion). Furthermore, we evaluated the tumor responses after either i.p. injection or topical application of 5‐ALA followed by laser irradiation (632 nm, 150 mW/cm2, 25 min) by measuring the treated tumor regression/regrowth time and by light and electron microscopy. Strong fluorescence of ALA‐induced porphyrins was detected in the tumor, skin and liver tissues, while little fluorescence was seen in the adjacent muscle tissue. Moreover, the highest amounts of ALA‐induced porphyrins in the tumor and skin tissues were found 1 hr after i.p. injection, whereas the amounts of the porphyrins in both tissues increased with increasing time after topical application of ALA. The fluorescence of the porphyrins was localized in several components of the skin tissue (epidermis, hair follicles and their associated sebaceous glands). Furthermore, the fluorescence was diffusely distributed in the s.c. transplanted tumor tissue. Little could be observed under a confocal laser scan microscope (CLSM) in the muscle tissue. The uptake and biolocalization data correlate well with the results of PCT efficiency of the same tumor model with ALA‐induced porphyrins. Light and electron microscopy showed that the mitochondria of the tumor cells and of the endothelial cells and the basal lamina of vascular walls beneath the endothelium in the tumor tissue were initially extensively destroyed after PCT with ALA‐induced porphyrins. Thereafter, diffuse degeneration followed by local and/or diffuse severe necrosis of the tumor cells was found. This may be due mainly to the initial damage to mitochondria in the cancerous and endothelial cells and also to the destruction of the vascular wall in the tumor tissue. © 1992 Wiley‐Liss, Inc.
Spontaneously transformed rat‐liver epithelial‐cell line producing autocrine and paracrine growth factors
Authors: Narita Takeo
Published: February 2007

A spontaneously transformed rat‐liver epithelial‐cell line that could proliferate in unsupplemented, serum‐free medium and be passaged with trypsinization has been established. At the time of writing, the line has undergone more than 100 passages in serum‐free culture. This cell line produced an autocrine growth‐stimulatory factor (AGSF) and a paracrine growth‐stimulatory factor (PGSF). AGSF had a remarkable growth‐stimulatory effect on transformed rat‐liver epithelial‐cells, but had no such effect on non‐transformed rat‐liver epithelial‐cells that could not proliferate in serum‐free medium. AGSF did not show a growth‐inhibitory or stimulatory effect on normal rat kidney (NRK) cells in monolayer culture, and did not induce anchorage‐independent growth in soft‐agar culture even with epidermal growth factor (EGF) or transforming growth factor (TGF)‐p. AGSF was protease‐sensitive, but heat‐ and acid‐stable. The molecular weight was about 700 Dalton (Da) on size‐exclusion chromatography. PGSF showed a growth‐stimulatory effect on NRK cells and induced anchorage‐independent growth in soft‐agar culture without EGF or TGF‐β. On the other hand, PGSF slightly inhibited the growth of the spontaneously transformed rat‐liver epithelial cells. PGSF was heat‐, protease‐ and acid‐sensitive. The molecular weight was 30 kDa on size‐exclusion chromatography. © 1992 Wiley‐Liss, Inc.
Specific growth stimulation in the absence of specific cellular adhesion in lung colonization by retinoic‐acid‐treated F9 teratocarcinoma cells
Authors: Rusciano Dario , Lorenzoni Patrizia , Burger Max M.
Published: February 2007

In most studies concerning organ‐specific metastasis, different or selected lines are compared with one another. Here we report results with the same cell line (the F9 murine teratocarcinoma) which can be directed towards liver or lung, depending on whether or not it is treated with retinoic acid and cyclic AMP. Thus, organ‐specific colonization by tail‐vein‐injected murine F9 teratocarcinoma cells shows a particular pattern: unselected, undifferentiated F9 cells preferentially colonize the liver of the syngeneic animal. The lungs, the first capillary bed encountered by cells thus injected, are only very rarely colonized. By contrast, the lungs become the main target organ of F9 cells induced to differentiate by treatment with retinoic acid and cyclic AMP. We have recently shown that liver colonization by undifferentiated F9 cells correlated with the adhesiveness of the cells (higher to fibronectin and liver‐derived extracellular matrix than to laminin and lung‐derived extracellular matrix) as well as with their growth response to organ‐derived extracts (no response with lung extracts and good response with liver extracts). The data reported below indicate that induction of differentiation causes at most a decreased adhesiveness of F9 cells to all the substrata tested (laminin, fibronectin, type‐IV collagen, organ‐derived extracellular matrix), suggesting that the shift in organ colonization observed with differentiated F9 cells is not due to an enhancement of the specific adhesion to the lung matrix. On the other hand, differentiated cells, but not undifferentiated ones, were able to respond to growth stimulation mediated by lung‐derived extracts, thereby implying a relevant role for organ‐specific growth stimulation in lung colonization by differentiated F9 cells. © 1992 Wiley‐Liss, Inc.
Activation of c‐fos and c‐fes in metastatic lympho‐macrophage hybrids
Authors: Fumagalli Stefano , Volpi Ludovica , Rossi Daniela , Larizza Lidia
Published: February 2007

The expression of proto‐oncogenes involved in myelomonocytic differentiation was studied in 3 metastatic murine lympho‐macrophage hybrids (ESb, EbF1, EbF2‐C4) which display several antigenic and functional macrophage properties. Constitutive expressions of fos and fesmRNA, which were not detectable in the weakly metastatic parent lymphoma (Eb), was shown in all the proliferating hybrid lines. By contrast, c‐myc and c‐myb expressions were shared by the tumor parent and the hybrids. The c‐fos transcripts observed in the hybrids were atypical in size, 2.3 kb, but standard 2.2‐kb transcripts could be detected in serum‐induced cells, even in the non‐expressing Eb lymphoma. The kinetics of the induced fos mRNA was found to conform to the features reported in the literature for a large variety of cells. No structural alteration of the c‐fos gene was detected by Southern analysis. PCR amplification of the 2.3‐ and 2.2‐kb fos mRNA showed that they are identical in size in both the coding and the 3′ untranscribed region. A longer poly A tail is thought to account for the additional 100 bp in the 2.3‐kb fos mRNA, as both the 2.3‐ and 2.2‐kb transcripts attain the same size following de‐adenylation. © 1992 Wiley‐Liss, Inc.
Human melanoma cell‐derived factor(S) stimulate fibroblast glycosaminoglycan synthesis
Authors: Edward Michael , Grant Allison W. , Mackie Rona M.
Published: February 2007

Conditioned media from cultures of human metastatic Hs294T melanoma cells contain a factor/factors that promote(s) fibro‐blast‐mediated contraction of collagen lattices, and stimulate(s) fibroblast glycosaminoglycan (GAG) synthesis. Complete medium from melanoma cell cultures stimulated fibroblast hyaluronate synthesis 9.3‐fold, and sulphated GAG synthesis 2.6‐fold, as measured by 3H‐glucosamine incorporation. 35SO4 incorporation into sulphated GAGS was essentially unaltered, the net result being a decrease in the degree of sulphation. Fibroblasts synthesized hyaluronate with an increased molecular weight when grown in the presence of the melanoma‐cell culture medium, while the molecular weights of heparan and chondroitin sulphates remained essentially unaltered.

Our results indicate that the tumour‐cell‐derived factor(s) stimulate(s) changes in fibroblast glycosaminoglycan synthesis, and that these changes may facilitate tumour cell invasion in vivo. © 1992 Wiley‐Liss, Inc.
Prevalence of the rhesus‐negative phenotype in caucasian patients with small‐cell lung cancer (SCLC)
Authors: Cerny T. , Fey M. F. , Oppliger R. , Castiglione M. , Nachbur B. , Gertsch M. , Gasser A. , Joss R. A. , Thatcher N. , Lind M. , von Rohr A. , Nydegger U. E.
Published: February 2007

We report that the Rhesus (Rh)‐negative phenotype is more prevalent in patients with small‐cell lung cancer (SCLC) than in the normal Caucasian population (SCLC: 25% Rh‐negative vs. 15% expected, p < 0.0001). This finding has been validated for a Central and a Northern European population (Switzerland and UK). In contrast, the Rh‐negative phenotype is no more frequent in non‐small‐cell lung cancer patients or in heavy smokers with coronary heart disease than in the general population. There was a normal distribution of the ABO blood group phenotype in all patients studied. Whilst the significance of this observation is unclear, we hypothesize that a genetic predisposition to the development of SCLC may be linked to a hitherto unidentified gene on chromosome 1 p near the Rh locus. Our observation may perhaps allow further progress to be made in understanding genetic mechanisms of SCLC carcinogenesis. © 1992 Wiley‐Liss, Inc.
Insulin resistance and breast‐cancer risk
Authors: Bruning Peter F. , Bonfrèr Johannes M. G. , van Noord Paul A. H. , Hart Augustinus A. M. , de Jong‐Bakker Maartje , Nooijen Wim J.
Published: February 2007

Life‐style has a major influence on the incidence of breast cancer. To evaluate the effects of life‐style related metabolic‐endocrine factors on breast cancer risk we conducted a case‐control study comparing 223 women aged 38 to 75 years presenting with operable (stage I or II) breast cancer and 441 women of the same age having no breast cancer, who participated in a population‐based breast cancer screening program. Women reporting diabetes mellitus were excluded. Sera from 110 women of the same age group presenting with early stage melanoma, lymphoma or cervical cancer were used as a second ‘other‐cancer control group’.

Serum levels of C‐peptide were significantly higher in early breast cancer cases compared to controls. The same was found for the ratios C‐peptide to glucose or C‐peptide to fructosamine, indicating insulin resistance. Sex hormone binding globulin was inversely, triglycerides and available estradiol were positively related to C‐peptide. Serum C‐peptide levels were related to body mass index (BMI), and to waist/hip ratio (WHR), in particular in controls. However, the relative increase of C‐peptide, C‐peptide to glucose or C‐peptide to fructosamine in cases was independent of BMI or WHR. The log relative risk was linearly related to the log C‐peptide levels. Relative risk according to quintiles, and adjusted for age, family history, BMI and WHR, for women at the 80% level was 2.9 as compared with those at the 20% level for C‐peptide. Elevated C‐peptide or C‐peptide to fructosamine values were not observed in the sera from women belonging to the ‘other‐cancer control group’.

This study suggests that hyperinsulinemia with insulin resistance is a significant risk factor for breast cancer independent of general adiposity or body fat distribution. © 1992 Wiley‐Liss, Inc.
Descriptive epidemiology and survival analysis of nasopharyngeal carcinoma in the united states
Authors: Burt Richard D. , Vaughan Thomas L. , McKnight Barbara
Published: February 2007

Population‐based incidence data on nasopharyngeal carcinomas (NPC) from the Surveillance, Epidemiology and End Results program in the United States were examined for the years 1973–1986. The 1,645 cases showed incidence rates varying according to ethnic origin, with Chinese having the highest, followed by Filipinos, Blacks and Whites. In females the incidence was about half of that seen in males, in each of these groups. There was no evidence of changes in incidence rates during the study period. An analysis of survival with NPC was undertaken using hazard function regression models to allow for control of multiple variables. Survival was found to be independently influenced by age and stage at diagnosis, histologic type, grade and sex. Significant ethnic differences in survival remained after adjustment for these factors, with Chinese surviving longest followed by Filipinos, Whites and Blacks. These differences in survival remained after control for the variation in population‐wide mortality rates associated with age, ethnicity, sex and calendar year. We present evidence that survival has improved for this disease over time. © 1992 Wiley‐Liss, Inc.