bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathological characteristics of p53 overexpression in endometrial cancers
Authors: Inoue Masaki , Okayama Akira , Fujita Masami , Enomoto Takayuki , Sakata Masahiro , Tanizawa Osamu , Ueshima Hirotsugu 
Published: February 2007

AbstractUsing immunohistochemical methods, we analyzed the association between nuclear p53 overexpression and various clinico‐pathological parameters in patients with endometrial cancers. Formalin‐fined and paraffin‐embedded tissue sections from 139 cases of endometrial cancer (endometrioid type, 126; serous papillary type, 12; and clear‐cell type, 1) were stained with anti‐p53 monoclonal antibody (MAb) DO7. Overexpression of p53 was associated with high malignant potential, including extensive muscular invasion, advanced surgical stage, high histological grade, serous papillary type and a personal history of cancer. Lymph‐node metastasis was also related to p53 overexpression with marginal significance. Survival curves determined by the Kaplan‐Meier method and univariate analysis showed p53 overexpression to be associated with a poor outcome in endometrial cancer patients. However, multivariate analysis using the stepwise Cox proportional‐hazard model showed that whereas lymph‐node metastasis, a personal history of cancer and muscular invasion were related to poor survival rates, p53 overexpression was not. Consequently, p53 overexpression itself does not appear to be an independent prognostic factor in endometrial cancer, although a still larger sample of patient material would be required to assess this issue definitively. © 1994 Wiley‐Liss, Inc.
Intratumoral heterogeneity for amplified genes in human breast carcinoma
Authors: Lönn Ulf , Lönn Sigrid , Nilsson Bo , Stenkvist Björn 
Published: February 2007

AbstractIntratumoral heterogeneity was studied in human breast cancer by examining separate tumor lesions of individual patients. Tumor samples were obtained from each patient by fine‐needle biopsies from 2 to 4 separate tumor lesions. We used a semi‐quantitative PCR to distinguish between samples with gene amplification and single gene copy samples. Five genes were analyzed in each biopsy: MDR‐1, dihydrofolate reductase, thymidylate synthase, c‐erb‐B2 and int‐2. Three groups of patients were examined: those awaiting initiation of treatment; those receiving first‐line endocrine therapy; and those receiving second‐line endocrine treatment. A pattern of intratumoral heterogeneity for gene amplification was clearly apparent. The frequency of amplification was lowest before initiating therapy and highest in patients receiving second‐line treatment (p = 0.023).
A prospective study of pancreatic cancer in the elderly
Authors: Shibata Atsuko , Mack Thomas M. , Paganini‐Hill Annlia , Ross Ronald K. , Henderson Brian E. 
Published: February 2007

AbstractRisk factors for pancreatic cancer were examined in a cohort study of 13,979 residents of a retirement community. After 9 years of follow‐up, 65 incident cases of pancreatic cancer were identified. An increased risk of pancreatic cancer was associated with a history of diabetes and cholecystectomy. Higher intake of vegetables, fruits, dietary beta‐carotene, and vitamin C were each associated with a reduced risk of pancreatic cancer, although none of these associations was statistically significant. Risk of pancreatic cancer decreased with increasing tea consumption but was unrelated to coffee consumption. No strong or consistent association was seen between either smoking or alcohol consumption and risk of pancreatic cancer, but a consistent and significant increase in risk followed cholecystectomy. © 1994 Wiley‐Liss, Inc.
Expression and activity of MMPS and their regulators in ovarian cancer
Authors: Naylor M. S. , Stamp G. W. , Davies B. D. , Balkwill F. R. 
Published: February 2007

AbstractIn order to understand the ability of human ovarian cancers to degrade the basement membrane, we have studied the localization and activity of matrix metalloproteases (MMPs) 2 and 9, using in situ hybridization and quantificative zymography on sequential sections of tumor biopsies. We have related these data to expression of some of the controlling elements of the enzymes, namely tissue inhibitors of metastasis (TIMPs) and tumor necrosis factor (TNF). mRNA for MMP‐2 was found in the majority of cases and localized to stromal areas with maximal expression adjacent to neoplastic areas. MMP‐9 expression was associated with cells in epithelial and stromal areas, consistent with distribution of macrophages. Zymography revealed higher levels of MMP‐9 activity in the ovarian cancer biopsy samples than in other cancers studied, but in contrast to our previous observations in breast and bladder cancer, there was no correlation between MMP levels and tumor grade. Nor was there any association between amount of TNF mRNA and levels of MMP enzymes. TIMP‐I expression was localized to stromal areas adjacent to tumor epithelial cells as well as, in some cases, to epithelial cells. The pattern of TIMP‐2 expression wax similar to that of MMP‐2. We conclude that the stromal elements of ovarian tumors express MMP‐2 and 9 and their specific inhibitors, but these do not seem to be controlled by endogenous TNF in the tumor microenvironment. © 1994 Wiley‐Liss, Inc.
Target cells are sensitized for cytotoxic T‐lymphocyte‐mediated destruction by estradiol and tamoxifen
Authors: Baral Edward , And Eva Nagy , Berczi Istvan 
Published: February 2007

AbstractThe effect of estradiol (E2) and tamoxifen (TX) on cytotoxic T‐tymphocyte (CTL)‐mediated target‐cell lysis was studied. CTL was generated in mixed cultures of rat spleen cells, using female Fischer 344 rat cells as responders and female Wistar rat cells or Nb2 rat lymphoma cells as stimulators. Concanavalin‐A‐stimulated Wistar lymphoblasts or Nb2 cells were used as targets. CTL harvested on day 5 exerted 16‐25% cytotoxicity when used at 1:12‐1:50 target:effector cell ratios. Day‐6 CTL had no cytotoxic activity. Treatment of target cells with either TX or E2, or both, at I‐μM concentrations for 4 hr prior to cytotoxicity testing raised the target‐cell killing to 100%. Highly significant enhancement of cytotoxicity was also observed when the drugs were used at I00‐, 10‐, or 1‐nM concentrations. Treatment of effector cells under similar conditions led to inhibition of cytotoxicity at I‐μM concentration, some enhancement at 100 nM and no effect at 10 and I nM. When treated target and effector cells were combined, the amplification of target‐cell lysis was similar in magnitude to that seen in tests with treated targets only. Drug treatment of target cells had no influence on their resistance to lysis in hypotonic solutions or on total and spontaneous 51Cr release. The inhibition of DNA and protein synthesis in target cells interfered with both basal cytolysis and drug‐induced enhancement. The release of the nuclear label, [3H]‐thymidine, from Nb2 targets by CTL, was also enhanced by target treatment with TX. These results illustrate that CTL‐mediated cytotoxicity is amplified by physiological concentrations (1 and 10 nM) of E2 and equimolar concentrations of TX. © 1994 Wiley‐Liss, Inc.
Melanoma‐specific CD4+ T lymphocytes recognize human melanoma antigens processed and presented by epstein‐barr virus‐transformed B cells
Authors: Topalian Suzanne L. , Rivoltini Licia , Mancini Marie , Ng Jennifer , Hartzman Robert J. , Rosenberg Steven A. 
Published: February 2007

AbstractWhile much emphasis has been placed on the role of MHC class I‐restricted CDS+ T cells in the recognition of tumor‐specific antigens (Ag), evidence has accumulated that CD4+ T cells also play a critical role in the anti‐tumor immune response. However, little information exists on the nature of MHC class II‐restricted human tumor Ag. In an attempt to develop in vitro systems to characterize such Ag, we examined the ability of Epstein‐Barr virus(EBV) transformed B cells to present melanoma‐associated Ag to melanoma‐specific CD4+ cells. CD4+ T cells cultured from lymphocytes infiltrating a s.c. melanoma metastasis secreted TNF‐α and GM‐CSF specifically in response to autologous cultured melanoma cells expressing MHC class II molecules. These CD4+ cells also recognized MHC class II‐compatible EBV‐B cells pulsed with extracts of autologous melanoma cells, but failed to recognize EBV‐B cells pulsed with autologous non‐transformed cells or a variety of allogeneic tumors or normal cells. B cells pre‐fixed with paraformaldehyde were incapable of Ag presentation, suggesting that intracellular processing events were occurring. Antibody‐blocking studies defined HLA‐DR as the dominant if not exclusive restriction locus in this T‐B interaction, and HLA‐DR genocyping revealed DRBI 0404 to be the probable restriction element. In a second patient, a CD4+ T‐cell clone cultured from a melanoma lesion recognized autologous tumor Ag presented by autologous EBV‐B; no cross‐reactivity was observed with the other tumor system investigated, nor with autologous CD4+ T cells specific for tetanus toxoid. These findings demonstrate that tumor Ag can be processed and presented by EBV‐transformed B cells to MHC class II‐restricted tumor‐specific CD4+ T cells. They also provide a model system for direct identification of these tumor‐derived antigens. © 1994 Wiley‐Liss, Inc.
Hydroxyrubicin, a deaminated derivative of doxorubicin, inhibits mammalian DNA topoisomerase II and partially circumvents multidrug resistance
Authors: Solary Eric , Ling Vi‐He , Perez‐Soler Roman , Priebe Waldemar , Pommier Yves 
Published: February 2007

AbstractIn vivo effectiveness of doxorubicin remains restricted due to toxicity and drug resistance. Hydroxyrubicin is a synthetic analog of doxorubicin in which the basic amino group at the C‐3′ has been replaced by a hydroxyl group in order to overcome recognition by the multidrug resistant (MDR) P‐ghlcoprotein and limit cardiotoxicity. The present study shows that hydroxyribicin is a less potent intercalator than doxorubicin. Induction of topoisomerase II‐mediated DNA cleavage in the human C‐myc origin by the two drugs was similar, reaching a maximum at 0.5 μM. Results from the NCI Cell Screening program indicate a relatively good correlation between the cytotoxicity of the 2 drugs on 55 cell lines of various origins (r = 0.723). Using a donogenic assay, we observed that hydroxyrubicin was 20‐fold more cytotoxic against the MDR KB‐VI cell line than doxorubicin and was slightly more cytotoxic than doxorubicin in the sensitive KB3.1 cell line. Uptake studies showed that doxorubicin was retained up to I hr in KB3.1 cells and rapidly eliminated from resistant KB‐VI cells. In contrast, hydroxyrubicin was rapidly eliminated from both sensitive KB3.1 and MDR‐positive KB‐VI cells. Both drugs induced protein‐linked DNA single‐strand breaks (SSBs) in both KB3.I and KB‐VI cells, which is consistent with topoisomerase inhibition. However, the kinetics of DNA SSBs induced by both drugs was very different. DNA breaks disappeared quickly in both KB3.1 and KB‐VI cell lines after hydroxyrubicin removal while DNA breaks induced by doxorubicin disappeared very slowly in KB3.1 cells and rapidly in KB‐VI cells. We conclude that removal of the basic amino group at the C‐3′ of doxorubicin modifies drug transport and partially circumvents MDR without changing topoisomerase II inhibition when compared with doxorubicin. © 1994 Wiley‐Liss, Inc.
Non‐proteolytic release of carcinoembryonic antigen from normal human colonic epithelial cells cultured in collagen gel
Authors: Kinugasa Tetsushi , Kuroki Motomu , Yamanaka Takahiko , Matsuo Yoshino , Oikawa Shinzo , Nakazato Hiroshi , Matsuota Yuji 
Published: February 2007

AbstractRecent studies have shown that, even with a minimal content of carcinoembryonic antigen (CEA), normal human colonic epithelial cells express substantial amounts of CEA mRNA and colonic mucosal fragments cultured in vitro produce CEA quite actively, indicating that CEA should no longer be considered to be of an oncofetal nature. To understand the basis of the usefulness of CEA as a tumor marker, we analyzed the release of CEA, a glycosyl‐phosphatidylinositol (GPI)‐anchored protein, from colonic epithelial cells, by culturing isolated colonic crypts in collagen gel. The crypts appeared to preserve their morphological and biochemical integrity in the gel for at least 16 hr, and released CEA spontaneously. Three forms of CEA—spontaneously released CEA, CEA liberated with phosphatidylinositol‐specific phospholipase C (PI‐PLC) and CEA in cell lysates—were indistinguishable on SDS‐PAGE. This is in contrast to recombinant CEA spontaneously released from CHO transfectants, which showed a smaller molecular mass than that of PI‐PLC‐cleaved recombinant CEA. By phase separation using Triton X‐114, CEA in the cell lysates of crypts was separated mostly into the detergent phase, while the spontaneously released and the PI‐PLC‐cleaved CEA were separated into the aqueous phase. When the cells were metabolically labeled with the precursors of the GPI‐anchor, 3H‐ethanolamine but not JH‐palmitic acid was found in the spontaneously released CEA. These findings suggest that, in contrast to the proteolysis‐like release of the recombinant CEA from CHO cells, CEA in normal colonic epithelial cells is released by a non‐proteolytic cleavage, which probably occurs through the action of some endogenous phospholipase. © 1994 Wiley‐Liss, Inc.
Transfection of glioma cells with the neural‐cell adhesion molecule NCAM: Effect on glioma‐cell invasion and growth in vivo
Authors: Edvardsen Klaus , Pedersen Paal‐Henning , Bjerkvig Rolf , Hermann Gregers G. , Zeuthen Jesper , Laerum Ole Didrik , Waish Frank S. , Bock Elisabeth 
Published: February 2007

AbstractThe tumor growth and the invasive capacity of a rat glioma cell line (BT4Cn) were studied after transfection with the human transmembrane 140‐kDa isoform of the neural‐cell adhesion molecule, NCAM. After s.c. injection, the NCAM‐transfected cells showed a slower growth rate than the parent cell line (BT4Cn). Upon intracerebral implantation with BT4Cn cells and different clones of NCAM‐transfected cells, all animals developed neurological symptoms within 13‐16 days. However, the tumors showed different growth characteristics. The NCAM‐transfected BT4Cn cells were localized in the region of the injection site, with a sharply demarcated border between the tumor and brain tissue. In contrast, the parental cell line showed single‐cell infiltration and more pronounced destruction of normal brain tissue. Using a 51Cr‐release assay, spleen cells from rats transplanted with BT4Cn tumor cells generally showed a lower cytotoxic response than the spleen cells from rats transplanted with the transfected variants of BT4Cn cells, indicating that the transfection procedure in itself mediated an activation of the immune system. The present data suggest that NCAM may influence the malignant behavior of rat glioma cells in vivo. © 1994 Wiley‐Liss, Inc.
Molecular requirements for rapid plasmacytoma and Pre‐B lymphoma induction by abelson murine leukemia virus in myc‐transgenic mice
Authors: Sugiyama Hiroyuki , Wang Yisong , Jackson Peter , Sawyers Charles L. , Klein George 
Published: February 2007

AbstractMutants and fusion products of the c‐abl gene were used to define some of the molecular requirements for rapid plasmacytoma (PC) and pre‐B‐lymphoma induction in pri5tane‐treated N‐myc transgenic BALB/c mice. A‐MuLV induced PCs in 21 of 25 mice with a mean post‐pristane latency period of 46 ± 9 days, compared to 134 ± 25 days in controls exposed to pristane alone. ΔXB, a mutant of type IV c‐abi with a deletion of the SH3 domain, was equally effective in inducing PCs in 7 of 7 mice with a latency period of 49 ± 7 days, indicating that gag sequences are not required for rapid PC induction. The ΔXBΔNar mutant that carried a large C‐terminal deletion in addition showed only a negligible activity, if any, suggesting that PC acceleration requires the C‐terminal domain in the same way as lymphoid transformation and in contrast to fibroblast transformation. BCR‐ABL fusion constructs encoding an 185‐kDa protein as in acute leukemia, or a 210‐kDa protein as in chronic myelocytic leukemia (CML), did not accelerate pristane‐induced PC development in the N‐mye transgenic mice, in contrast to their known ability to immortalize lymphoid cells in vitro. Only one of 14 non‐transgenic littermates developed a pre‐B lymphoma after A‐MuLV infection, and none of 10 normal littermates infected with ΔXB virus developed a construct‐carrying tumor. This result suggests that PC acceleration is due to co‐operative interaction of the N‐myc transgene and activated abl. Infection of N‐myc transgenic bone marrow or spleen cells with A‐MuLV in vitro led to the outgrowth of pre‐B lymphonias after transplantation to pristine‐treated BALB/c recipients. The rymphoma‐inducing activity of A‐MuLV depends on its high titer, since diluted A‐MuLV or the lower‐titered ΔXB induced only PCs under the same conditions. The v‐abl, ΔXB and BCR‐ABL‐carrying viruses generated immortalized lymphoblastoid lines in vitro, regardless of the presence of the N‐myc transgene, suggesting that lymphoid transformation is a direct function of appropriate abl sequences in contrast to PC acceleration.
Characterization of autologous tumor‐specific T‐helper 2 cells in tumor‐infiltrating lymphocytes from a patient with metastatic melanoma
Authors: Kharkevitch Dmitri D. , Seito Dai , Balch Glen C. , Maeda Tomoyuki , Balch Charles M. , Itoh Kyogo 
Published: February 2007

AbstractHuman autologous tumor‐specific T‐helper 2 (Th2) cells were investigated in melanoma tumor‐infiltrating lymphocytes (TILs). Both a CD4+ T‐cell line and its 5 potential T‐cell clones established from TILs of a patient with metastatic melanoma produced significant levels of IL‐4, IL‐6, IL‐10 and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in response to autologous, but not any of 12 allogeneic, melanoma cell lines. They also produced IL‐3 and IL‐8 but not IL‐2, IFN‐γ, TNF‐α or TNF‐β in response to autologous tumor cells. Furthermore, they showed autologous melanoma‐specific cytotoxicity only in an 18‐hr 51Cr‐release assay. Specific IL‐4, IL‐6 or IL‐10 production by the CD4+ M73 T‐cell line and its clone was inhibited by anti‐class 11 DR (but not anti‐class 1) MAb, whereas their specific cytotoxicity was inhibited by anti‐class 1 (but not anti‐class 11) MAb. Anti‐CD3 and ‐CD4 MAb (but not anti‐CD8) abrogated both IL‐4, IL6 and IL‐10 production and cytotoxicity, while anti‐IL‐4 antibody did not inhibit cytotoxicity. CD4+ potential T‐cell clones, but not CD8+ clones, that were established from freshly isolated TILs without in vitro sensitization by autologous tumor cells also produced IL‐4, IL‐6 and IL‐10 but not IFN‐γ or tumor necrosis factor (TNF)α in an autologous tumor‐specific fashion. These Th2 cells were neither reactive to EBV‐B cells nor suppressive against CD8+ T‐cell clones. PMA and PHA stimulated these potential T‐cell clones, regardless of their specific lymphokine production, to produce IL‐3, IL‐4, IL‐6, IL‐8, IL‐10, GM‐CSF, TNFα and IFN‐γ. Our results demonstrate the presence of autologous tumor‐specific Th2 cells at the melanoma sites.
DNA ploidy in primary fallopian‐tube carcinoma using image cytometry
Authors: Rosen Alexander C. , Graf Anton H. , Klein Matthias , Lahousen Michael , Vavra Norbert , Reiner Angelika , Hacker Gerhard W. 
Published: February 2007

AbstractDetermination of DNA ploidy in 61 samples of primary Fallopian‐tube carcinoma (FTC) by use of image cytometry is presented. Of these samples, 48 showed an aneuploid DNA content. Patients with euploid DNA content showed a median survival time of 33.8 months compared to 24.5 months for aneuploid cases. A high incidence of aneuploid tumors was consistently observed among all FIGO stages and in all groups of histologic grading. However, no correlation between ploidy and FIGO stage or histologic garding could be demonstrated. This observation could be regarded as a marker for the high aggressiveness of FTC which has been repeatedly described in the past.
T lymphocytes infiltrating renal cell carcinoma have a reduced expression of transferrin receptor
Authors: Kudoh Seiji , Stanley Jill , Edinger Mark G. , Tubbs Raymond R. , Klein Eric , Bukowski Ronald M. , Finke James H. 
Published: February 2007

AbstractT‐cell responses have been reported to be impaired in cancer patients, and lymphocytes infiltrating human tumors (T‐TIL) appear to be more affected than those in the peripheral blood. T‐TIL display a poor proliferative response when compared to peripheral blood T (T‐PBL) cells that show a strong response to all stimuli. Here we report that T‐TIL from patients with renal cell carcinoma (RCC) also have a defect in transferrin receptor (TfR) expression that is not present in T‐PBL cells. Immunocy‐tometry studies (dual staining for CD3s and TfR) demonstrated that autologous T cells from the peripheral blood but not from the tumor expressed TfR following stimulation with IL2, anti‐CD3 or PHA. Expression of TfR correlated with the capacity of T cells from the blood and tumor to proliferate. Gene expression studies using reverse transcriptase‐polymerase chain reaction (RT‐PCR) demonstrated that TfR mRNA levels in T‐TIL were undetectable or low relative to T‐PBL following stimulation. The failure to detect TfR mRNA in T‐TIL after stimulation was not due to a shift in kinetics of mRNA accumulation since TfR mRNA was not detectable at any of the times tested (4, 12, 24 and 36 hr). The defect in TfR gene expression is selective since IL2Rα gene expression was induced in T‐TIL Because IL2 binding to its receptor results in TfR expression, the defect in TfR induction in T‐TIL appears to be distal to IL2Rα expression. Our studies illustrate another alteration in T‐TIL that is not observed in T cells from the peripheral blood. The absence of TfR gene expression may contribute to the poor proliferative response of T cells from the tumor.
Expression of transforming growth factor‐beta (TGF‐β) receptors, TGF‐β1 and TGF‐β2 production and autocrine growth control in osteosarcoma cells
Authors: Kloen Peter , Jennings Candace L. , Gebhardt Mark C. , Springfield Dempsey S. , Mankin Henry J. 
Published: February 2007

AbstractTransforming growth factor‐beta (TGF‐β) is a polypeptide with multiple physiological functions. Isoforms of this growth factor have important roles in control of the cell cycle, in regulation of cell‐cell interactions and in growth and development. Malignant transformation has been shown to be associated with increased expression of TGF‐β. Since bone is the largest storage site and producer of TGF‐β, we speculated on the existence of an autocrine mechanism in osteosarcoma, a malignant bone tumor. Expression of TGF‐β cell surface receptors, effects on growth of TGF‐p and TGF‐β antibodies and production of 2 TGF‐β isoforms were studied in a panel of 7 osteosarcoma cell lines. In contrast to most previous reports on the effects of TGF‐β on osteosarcoma cell growth, we found a mitogenic effect of TGF‐β 1 in 4 of 7 osteosarcoma cell lines. Receptor profiles for TGF‐β were aberrant in 5 of the 7 cell lines tested, and production of TGF‐β1 and TGF‐β2 varied among cell lines. Addition of anti‐TGF‐β antagonized the effects of endogenous TGF‐β. Our results suggest a potential role of TGF‐β in autocrine growth control of osteosarcoma cells.