bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular detection of pre‐atl state among healthy HTLV‐1 carriers in an endemic area of Japan
Authors: Ghen Yun‐Xian , Jkeda Shuichi , Mori Hiroyuki , Hata Tomoko , Tsukasaki Kunihiro , Momita Saburo , Yamada Yasuaki , Kamihira Shimeru , Mine Mariko , Tomonaga Masao 
Published: February 2007

AbstractAdult T‐cell leukemia/lymphoma (ATL) usually develops after age 40 in Japan, suggesting a long latency since HTLV‐I is considered to be transmitted mainly from mothers to babies via breast milk. Our previous studies had suggested that HTLV‐I carriers who have a monoclonal integration of HTLV‐I proviral DNA in the peripheral blood cells, designated pre‐ATL, account for about 2% of healthy carriers and are at high risk of developing ATL Their ages ranged from 32 to 80 (median 57). Nevertheless, many cases of pre‐ATL showed a long‐lasting carrier state (10‐year probability around 90%). In the present investigation we conducted a large‐scale molecular detection of monoclonal integration in a population (481 cases) of healthy carriers with ages ranging from 16 to 82 (median 49) for the purpose of clarifying the earliest onset of this pre‐ATL state. Southern‐blot analysis of DNA extracted from peripheral blood mononuclear cells revealed 6 cases (1.2%) with a monoclonal band. All of these 6 were older than 40; no single positive case was found in 220 carriers under age 40. These results indicate that the molecularly detectable pre‐ATL state also develops after a long latency. Thus the pre‐ATL state seems to be a subtype of ATL showing an extremely indolent course of disease development, but not merely an early phase of all subtypes of ATL. We propose that, in order to reveal a promoter(s) responsible for the development of ATL from the pre‐ATL state, intensive epidemiological investigation of life style, eating habits, occupation and exposure to carcinogens must be conducted on this unique group prone to ATL. It is also important to perform such an epidemiological study on the general population of carriers by paying special attention to the first 3‐4 decades of each carrier's life in Japan and by comparing the data with those from carriers in different geographical areas of the world.
Inhibition of invasion, gelatinase activity, tumor take and metastasis of malignant cells by N‐acetylcysteine
Authors: Albini Adriana , D'Agostini Francesco , Giunciuglio Daniela , Paglieri Isabella , Balansky Roumen , De Flora Silvio 
Published: February 2007

AbstractThe thiol N‐acetylcysteine (NAC) is currently considered one of the most promising cancer chemopreventive agents by virtue of its multiple and coordinated mechanisms affecting the process of chemical carcinogenesis. Recent studies have shown that an unpaired cysteine residue in the propeptide plays a key role in inactivation of latent metastasis‐associated metalloproteinases: the present study was designed to assess whether NAC could also affect tumor take, invasion and metastasis of malignant cells. As assessed by zymographic analysis, NAC completely inhibited the gelatinolytic activity of type‐IV collagenases in the cells tested (gelatinases A and B). Moreover, NAC was efficient in inhibiting the chemotactic and invasive activities of tumor cells of human (A2058 melanoma) and murine origin (K1735 and B16‐F10 melanoma cells as well as C87 Lewis lung carcinoma cells) in Boyden‐chamber assays, which are predictive of the invasive and metastatic properties. Reduced glutathione (GSH) had a similar, although less effective activity. The number of lung metastases decreased sharply when B16‐F10 murine melanoma cells, injected i.v. into nude mice, were pre‐treated with NAC and resuspended in medium supplemented with 10 mM NAC. In other experiments NAC was given in drinking water, starting 48‐72 hr before subcutaneous inoculation of either B16‐F10 cells or of their highly metastatic variant B16‐BL6, or intramuscular injection of LLC cells. In all experiments NAC treatment decreased the weight of the locally formed primary tumor and produced a dose‐related delay in tumor formation. Spontaneous metastasis formation by B16‐F10 and B16‐BL6 tumors was slightly yet significantly reduced by oral administration of NAC. However, this was not observed for Lewis lung tumors. These data indicate that NAC affects the process of tumor‐cell invasion and metastasis, probably due to inhibition of gelatinases by its sulfhydryl group, with the possible contribution of other mechanisms, including the potent antioxidant activity of this thiol. © 1995 Wiley‐Liss, Inc.
Suppression of pulmonary metastasis by angiogenesis inhibitor TNP‐470 in murine osteosarcoma
Authors: Mori Shigeki , Ueda Takafumi , Kuratsu Shigeyuki , Hosono Noboru , Izawa Kazutaka , Uchida Atsumasa 
Published: February 2007

AbstractWe treated a murine osteosarcoma cell line, LM8, which preferentially metastasizes to the lungs, with a new angiogenesis inhibitor, TNP‐470, to evaluate the efficacy of this compound in the suppression of pulmonary metastasis of osteosarcoma. In an in vivo experiment, tumor cells were inoculated i.v. into C3H mice, and TNP‐470 or vehicle alone (control group) was administered s.c. every day for 3 weeks. In the TNP‐470‐treated groups, both the number of pulmonary metastatic nodules and the lung wet weight were significantly reduced in a dose‐dependent manner. Similarly, vascular density in the metastatic tumors estimated by immunohistochemical staining with anti‐von‐Willebrand factor antibody as an endothelial marker were significantly reduced. No severe side‐effects were found. In an in vitro experiment, viable tumor cells were counted after 3 days' treatment with TNP‐470. The 50% inhibitory concentration was 0.6 ng/ml for LM8, which was more sensitive than other tumor cells previously reported. Our results show that TNP‐470 suppresses the pulmonary metastasis of LM8 and suggest that both its anti‐angiogenic activity and cytostatic activity towards LM8 are responsible for the anti‐tumor effect. © 1995 Wiley‐Liss, Inc.
Perinatal characteristics and adult mammographic patterns
Authors: Ekbom Anders , Thurfjell Erik , Hsieh Chung‐Cheng , Trichopoulos Dimitrios , Adami Hans‐Olov 
Published: February 2007

AbstractWe retrieved breast mammograms for 370 women 40 to 74 years old with no history of breast cancer, for whom birth weight, birth length, placental weight and other birth characteristics were indicated in their standard birth records at the Uppsala University Hospital. Blind evaluation of the mammograms allowed these to be classified according to Wolfe's pattern. Logistic regression analysis was applied using as independent variables the recorded birth characteristics and as outcome variable, high risk (P2 and DY) versus low risk (N1 and P1) mammographic parenchymal pattern. After controlling for all the recorded variables, the odds ratio for a high‐risk pattern (P2 or DY) increased consistently and significantly (P for trend 0.02) with the weight of the placenta, i.e. the main estrogen‐producing organ during pregnancy. There were weak and non‐significant positive associations with increasing birth weight (P for trend 0.53) and birth length (P for trend 0.52). These results are compatible with hypotheses suggesting that pregnancy estrogens or other perinatal characteristics may play a risk‐modulating role influencing breast cancer in the offspring. © 1995 Wiley‐Liss, Inc.
Decreased cytotoxic effects of doxorubicin in a human ovarian cancer‐cell line expressing wild‐type p53 and WAF1/CIP1 genes
Authors: Vikhanskaya Faina , Broggini Maurizio D'Incalcimassimo 
Published: February 2007

AbstractThe cytotoxicity of Doxorubicin and cis‐dichloro‐diammine‐platinum (DDP) was evaluated in clones, obtained from a human ovarian cancer cell line transfected with a temperature‐sensitive p53 mutant, which express mutant p53 at 37°C and wild‐type‐like p53 at 32°C. DDP was equally active in cells not expressing p53 (SKN) or cells expressing a mutated form of p53 (SK23a kept at 37°C) or a wild‐type‐like form of p53 (SK23a cells kept at 32°C). In contrast, Doxorubicin was less cytotoxic in cells expressing wild‐type p53 than in cells expressing no p53 or mutated p53. This reduction was not due to a decreased intracellular accumulation or to a faster efflux of Doxorubicin. Topoisomerase II was found to be present in the same amount in all the systems utilized and to be functionally active, thus not accounting for the observed effect of Doxorubicin. A clear induction of WAF1 / CIP1 and GADD45 genes in cells expressing wild‐type p53 after Doxorubicin treatment was found. DDP, which was equally active in the cells utilized, caused an increase in the transcription only of GADD45 gene but not of WAF1 / CIP1 gene. Doxorubicin was also able to induce the transcription of WAF1 / CIP1 gene in SKN cells (not expressing p53) or in SK23a cells at 37°C (expressing mutated p53), indicating that the expression of this gene also, in some tumor‐cell lines, is not necessarily or uniquely induced by wild‐type p53. © 1995 Wiley‐Liss, Inc.
Escape mechanisms of human leukemic cells to long‐term immunotoxin treatment in an in vitro experimental model
Authors: Chignola Roberto , Pasti Marcella , Candiani Carola , Franceschi Antonia , Anselmi Cristina , Tridente Giuseppe , Colombatti Marco 
Published: February 2007

AbstractIn kinetic assays, an anti‐CD5‐ricin A chain (ST.1 ‐RTA) immunoconjugate (immunotoxins, IT) specifically inhibited up to 40% the protein synthesis of Jurkat target cells within the first 40 hr. Longer exposures of leukemia cells to ST.I‐RTA resulted in a progressively higher number of target cells escaping IT treatment and becoming resistant to further treatment with ST.I‐RTA even in the presence of the RTA‐IT enhancer monensin. Resistant Jurkat cells proliferated at the same rate as control untreated cells, and were as sensitive as control cells to a transferrin‐RTA IT, indicating that the ST.I‐RTA‐resistant tumor‐cell population did not become insensitive to the enzymatic activity of RTA. Binding studies revealed that the anti‐CD5 IT treatment induced a transient modulation of CD5 antigens but not of the functionally related CD3 antigens. The CD5 antigens were re‐expressed at the cell surface following removal of the IT molecules from the culture medium with 1.1% of the total CD5 Ag being re‐expressed per hr. When our experimental data on the kinetics of cell intoxication by the IT were corrected for the proliferative potential of the resistant and of the sensitive tumor‐cell populations, it appeared that the effect of ST.I‐RTA treatment on Jurkat cells was only to delay cell growth for a limited time period (20 hr) without reducing effectively the tumor‐cell burden. Our results may have implications for the long‐term treatment of target tumor cells with IT. © 1995 Wiley‐Liss, Inc.
Adoptive transfer of ex vivo‐activated memory T‐cell subsets with cyclophosphamide provides effective tumor‐specific chemoimmunotherapy of advanced metastatic murine melanoma and carcinoma
Authors: Gold Jay E. , Zachary David T. , Osband Michael E. 
Published: February 2007

AbstractAutolymphocyte therapy (ALT) is adoptive cellular therapy of neoplastic disease using ex vivo activation of autologous (human) or syngeneic (murine) lymphocytes from tumor‐bearing hosts (TBH) by low doses of anti‐CD3 monoclonal antibody (MAb) and a mixture of previously prepared autologous cytokines (T3CS). Ex vivo activation by T3CS without tumor antigen results in expansion of CD44+ (memory) T cells. These memory T cells (ALT cells) mediate in vivo anti‐tumor specificity and with cyclophosphamide (CY) are capable of curing metastatic disease in murine TBH. To determine whether CY could enhance the effectiveness of CD4+ or CD8+ subsets of ALT cells, C57BL/6J TBH with B16 melanoma or Lewis lung (3LL) carcinoma were treated with adoptive chemoimmunotherapy (ACIT) using CD4‐depleted or CD8‐depleted ALT cells and CY. ALT cells were derived from splenocytes of B16 or 3LL‐TBH and activated ex vivo with T3CS. Depletion of CD4+ or CD8+ T cells was performed before or after activation with T3CS. B16‐TBH or 3LL‐TBH that received ACIT using CY with B16‐derived or 3LL‐derived CD8‐depleted ALT cells, respectively, demonstrated cure of metastatic disease regardless of whether CD8+ T cells were depleted before or after T3CS activation. B16 or 3LL‐TBH that received ACIT using CY with B16 or 3LL‐derived CD4‐depleted ALT cells also cured metastatic disease but only if CD4+ T cells were depleted after T3CS activation. Interleukin (IL)‐2 added to pre‐T3CS CD4‐depleted ALT cells cultured with T3CS restored anti‐tumor activity when combined with CY. TBH cured by ACIT using CY and ALT‐cell subsets derived from syngeneic TBH with the identical tumor displayed tumor‐specific immunity in rejecting a lethal challenge of identical but not reciprocal tumor. TBH given ACIT using CY and ALT‐cell subsets derived from splenocytes of syngeneic TBH with reciprocal tumors rejected lethal challenges of both tumors. Tumor specificity measured by interferon (IFN)‐γ and 51Cr‐release assays was demonstrated in pre‐ or post‐T3CS/CD8‐depleted, post‐T3CS/CD4‐depleted and pre‐T3CS + IL‐2/CD4‐depleted ALT‐cell subsets. Our data demonstrate that ACIT using CY combined with ex vivo T3CS‐activated CD44+ memory T‐cell subsets conveys long‐term tumor‐specific immunity. © 1995 Wiley‐Liss, Inc.
Quantitative variation of proto‐oncogene and cytokine gene expression in isolated breast fibroblasts
Authors: Spanakis Emmanuel , Brouty‐Boyé Danièle 
Published: February 2007

AbstractTranscripts coding for transcription factors (RB, P53, FOS, MYC, MYB, ERBA, REL), growth factors (FGFI, FGF2, INT2, TGFA, TGFB, PDGF, IGF1, IGF2), interleukins, (IL1, IL2, IL3, IL4, IL6, TNF), growth‐factor receptors or cytosolic protein kinases (RAF, PIM, FES, MET, SRC, ROS, TRK, KIT, CSFR, IGFR, PDGFR, EGFR, NEU) were quantified in cultured human mammary fibroblasts from normal tissues, benign tumours, carcinomas and post‐radiation fibrosis lesions by slot‐blot auto‐radiography and image analysis. The effects of a differentiating agent (cholera toxin) and of a tumour promoter (12‐O‐tetradecanoyl‐phorbol‐13‐acetate) were also examined. The drugs modulated the levels of the anti‐oncogene transcripts (RB, P53) and of ERBA, REL, RAF, MET, ROS, TRK, CSFR, EGFR, NEU, FGF1, INT2, IGF1, IL1, IL2, IL4 and IL6. Apart from this variation, there were multiple differences in gene expression among normal and pathological cells (concerning all but P53, TGFB and interleukin transcripts) and between sub‐types defined by the presence of α‐sm‐actin (myofibroblasts) or EDB‐fibronectin (RAF, ROS, FES, KIT, IGFR, NEU, INT2, TGFB, PDGF, IGFs, ILs). It appears, therefore, that mammary stroma progress irreversibly along with the epithelium during tumoral development, and that breast cancer is not only a multi‐gene but also a multi‐tissue phenotype. © 1995 Wiley‐Liss, Inc.
High incidence of bk virus large‐T‐antigen‐coding sequences in normal human tissues and tumors of different histotypes
Authors: De Mattei Monica , Martini Fernanda , Corallini Alfredo , Gerosa Massimo , Scotlandi Katia , Carinci Paolo , Barbanti‐Brodano Giuseppe , Tognon Mauro 
Published: February 2007

AbstractT‐antigen (TAg) coding sequences specific for BK virus (BKV) were detected, by PCR amplification followed by Southern‐blot hybridization, in a high percentage of human tumors and tumor‐cell lines, as well as in normal tissues, by analysis of 189 specimens. Specifically, the BKV early region was detected in 85% of brain tumors and in all normal brain tissues, in 78% of osteosarcomas, in 38% of Ewing's tumors, in 40% of normal bone specimens and in 71% of normal peripheral blood cell samples. Wilms' tumor tissues used as a control were all negative for BKV sequences. RT‐PCR analysis indicated that TAg coding sequences were expressed in specimens carrying BKV early region, ranging from 64% of the osteosarcomas to 100% of glioblastomas, Ewing's tumors, peripheral blood cells and normal bone. Moreover, DNA sequencing performed in 12 different positive samples revealed that the amplified PCR products are identical to the early‐region sequence of wild‐type BKV. The role of BKV TAg and its possible mechanism of action in human tumorigenesis are discussed. © 1995 Wiley‐Liss, Inc.
Gene transfer of human TNFα into glioblastoma cells permits modulation of mdr1 expression and potentiation of chemosensitivity
Authors: Walther Wolfgang , Stein Ulrike , Pfeil Dagmar 
Published: February 2007

AbstractDespite substantial advances in the surgery, radiotherapy and chemotherapy of gliomas, the prognosis of patients with glioblastomas has still not improved. Disappointing results in chemotherapy of glioblastomas resulting from multi‐drug resistance (MDR) prompted us to investigate the influence of cytokine gene transfer in glioblastoma cells on the expression of P‐glycoprotein and on chemosensitivity of transduced cells. Several investigations have shown that malignant gliomas express P‐glycoprotein at high levels. The P‐glycoprotein is a product of the multi‐drug resistance gene (mdr 1) and functions as an energy‐dependent efflux pump which decreases drug accumulation and cytotoxicity. Since tumour necrosis factor alpha (TNFα) is a powerful anti‐cancer agent used in clinical trials and gene therapy protocols, this cytokine gene was chosen for the present investigations. Transduction of the human TNFα (hTNF) gene carrying retrovtral vector pN2tk‐hTNF into U373MG human glioblastoma cells resulted in expression and secretion of biologically active hTNF. Release of transduced hTNF reduces P‐glycoprotein expression and is associated with enhanced rhodamine‐123 uptake and potentiation of cytotoxicity of the MDR‐relevant drugs vincristine and doxorubicin. Furthermore, the transfected cell clones showed a reduced growth rate compared to the parental cells. © 1995 Wiley‐Liss, Inc.
Cellular death in neuroblastoma: in situ correlation of apoptosis and bcl‐2 expression
Authors: Hoehner Jeff C. , Hedborg Fredrik , Wiklund Helena Jernberg , Olsen Leif , Påhlman Sven 
Published: February 2007

AbstractApoptosis is the selective physiologic deletion of cells that are no longer required. Over‐expression of the bcl‐2 protooncogene extends survival of neurons otherwise destined for apoptosis. The unique capacity of neuroblastoma (NB) to undergo spontaneous regression and the prognostic dichotomy of children with this malignancy led us to evaluate bcl‐2 expression and apoptosis in NB. An in situ DNA nick‐labeling technique to detect apoptotic cells, as well as immunohistochemistry and morphology, were utilized in a selection of NB tumor specimens and in the human fetal sympathetic nervous system. bcl‐2 expression was present in all 28 NB tumors examined and in sympathetic ganglia of the human fetus. Measurement of overall bcl‐2 expression and of extent of apoptosis correlated with favorable prognosis. In low‐stage tumors, bcl‐2 expression was most intense in poorly differentiated tumor cells adjacent to fibroyascular stroma. Cells distant from the stroma exhibited increasing degrees of chromaffin differentiation, with apoptosis most evident in bcl‐2‐negative neuroblasts adjacent to well‐differentiated NB cells. The spatial distribution of bcl‐2 expression, apoptosis and chromaffin differentiation in favorable‐prognosis NB may provide insight into mechanisms of persistent tumor existence or regression. © 1995 Wiley‐Liss Inc.
Molecular events underlying schistosomiasis‐related bladder cancer
Authors: Ramchurren Nirasha , Cooper Kum , Summerhayes Ian C. 
Published: February 2007

AbstractTwenty‐one invasive squamous‐cell carcinomas (SCC) of the bladder from Schistosoma‐hematobium‐infected patients were examined immunohistochemically for the expression of p53, Rb, EGFR and c‐erbB‐2 protiens; and screened by single‐strand conformation polymorphism and sequencing for mutations in the ras (H, N, K) codon hotspots (12, 13, 61) and p53 (exons 4‐9) genes. Positive staining for p53, EGFR and c‐erbB‐2 was reported in 39, 67 and 28% of tumors respectively. Only one of the tumors, the oly one that was poorly differentiated, displayed an absence of nuclear Rb staining. Ras alterations were detected in the H‐ras gene in 3 tumors, 2 of which harbored a condon‐13 (Gly → Arg) and one condon‐12 (Gly → Ser) point mutation. p53 mutations were recorded in 12 tumors (57%), 6 of which stained positively for p53. Four tumors had exon‐7 mutations (codons 235, 241 and 249; one tumor had 2 exon‐7 mutations). Eight tumors were mutated in exon 8 (codons 264, 271, 273, 285, 286, 288 and 294), 5 of which harbored miltiple mutations. One tumor had an insertion/deletion event in exon 9. The frequency of detection of over‐expression of EGFR and c‐erbB‐2 in bilharzial‐bladder lesions is comparable to that reported in TCC, contrasting with the infrequent loss of Rb expression found in invasive lesions associated with schistosomiasis infection. However, the detection of multiple p53 mutations in these lesions is suggestive of the involvement of a carcinogenic agent with maintenance of preferential activation of the H‐ras gene. © 1995 Wiley‐Liss Inc.
In situ expression of B7 and CD28 receptor families in human malignant melanoma: Relevance for T‐cell‐mediated anti‐tumor immunity
Authors: Denfeld Ralf W. , Dietrich Andrea , Wuttig Christiane , Tanczos Eszter , Weiss Johannes M. , Vanscheidt Wolfgang , Schöpf Erwin , Simon Jan C. 
Published: February 2007

AbstractWork in animal models has suggested that interactions of members of the B7 receptor family (e.g., B7–1, B7–2) on tumor cells with their ligands CD28 and CTLA‐4 on cytotoxic T cells (CTL) are important for the induction of anti‐tumor immunity against malignant melanoma (MM). To determine whether these molecules are of relevance for CTL responses against human MM, we studied the expression of B7–1, B7–2, CD28 and CTLA‐4 in primary tumors of MM (PMM), MM metastases (MMM) and benign melanocytic nevi (BMN) by immunohisto‐chemistry (IH) and by reverse transcription polymerase chain reaction (RT‐PCR). By RT‐PCR, B7–1 and B7–2‐specific mRNAs were detected in most PMM, MMM and BMN. These PCR‐signals were derived from CD45+‐infiltrating leukocytes and not from tumor cells since (1) MMM depleted of CD45+ cells contained no B7–1 or B7–2 mRNA; and (2) by IH, B7–1 and B7–2 were found on infiltrating dendritic cells, macrophages and a variable proportion of tumor‐infiltrating lymphocytes (TIL) but not on melanoma cells or nevus cells. The important exceptions were 5/5 spontaneously regressing PMM, in which B7–1 and B7–2 were expressed by melanoma cells, that were surrounded by TIL expressing CD28 but not CTLA‐4. We conclude that, in PMM, MMM and BMN, the majority of TIL are CD28+ and that B7–1 and B7–2 are expressed by CD45+‐infiltrating antigen‐presenting cells (APC) and TIL, but not by the tumor cells. However, in spontaneously regressing PMM, melanoma cells express B7–1, B7–2 and MHC class‐I and‐II antigens, particularly in areas with clinical and histological signs of an ongoing anti‐tumor response. These data suggest that the absence of B7–1 and B7–2 favors the escape of MM from immunosurveillance, while B7–1, B7–2 expression enhances T‐cell‐mediated anti‐tumor immunity. © 1995 Wiley‐Liss Inc.