bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction and characterization of cytotoxic T‐lymphocytes recognizing a mutated p21ras peptide presented by HLA‐A*0201
Authors: Van Elsas Andrea , Nijman Hans W. , Van Der Minne Caroline E. , Mourer Jacqueline S. , Kast W. Martin , Melief Cornelis J. M. , Schrier Peter I. 
Published: February 2007

AbstractThe ras oncogene is frequently found to be activated in human cancer through point mutations at codons 12, 13 or 61. We explored whether these altered p21 ras protein sequences contain peptide sequences that can activate naive CD8+ cytotoxic T lymphocytes (CTL). Several wild‐type and mutated p21 ras peptides were identified that carry a binding motif for human leukocyte antigen (HLA)‐A*0201. Two peptides were found to bind strongly to this allele. CD8* CTL bulk cultures specifically reacting with one of these peptides could be induced, using processing‐defective T2 cells loaded with peptide CLLDILDTAGL as stimulators. The peptide is derived from p21ras, position 51–61, and carries a 61 Gln → Leu mutation. In contrast, a 9‐mer peptide CLLDILDTA corresponding to amino acid sequence 51–59 of wild‐type p21ras did not yield reactive CTL cultures. T‐cell clones with low affinity for the 11‐mer peptide were isolated from CLLDILDTAGL‐reactive bulk cultures. These T cells did not lyse melanoma cells transfected with 61‐Leu N‐ras, although lysis was found when these transfectants were pulsed with the 11‐mer peptide. Possibly, T cells of higher affinity may be required to demonstrate processed peptide on the cell surface. The combined experiments suggest that a peptide derived from mutated p21ras can be recognized by HLA class 1‐restricted CTL, whereas an analogous wild‐type p21ras peptide may not be immunogenic. © 1995 Wiley‐Liss, Inc.
Interleukin‐3: A putative protective factor against breast cancer which is secreted by male but not female breast fibroblasts
Authors: Speirs Valerie , Birch Mark A. , Boyle‐Walsh Eilis , Green Andrew R. , Gallagher James A. , White Michael C. 
Published: February 2007

AbstractThe enzyme 17β‐hydroxysteroid dehydrogenase (17‐HSD) is a key regulator of intracellular 17β‐estradiol (E2), which is associated with breast cancer and is influenced by paracrine factors released by breast‐cancer fibroblasts. Since the incidence of breast cancer is much higher in females than in males, we have used an in vitro ceil culture system to investigate whether male fibroblasts may inhibit breast‐cancer genesis by restricting the intracellular accumulation of E2. Fibroblasts were obtained from normal males and females undergoing reduction mammoplasty, and from females with benign or malignant breast lesions. Fibroblast‐conditioned medium (CM) was incubated with the established breast‐cancer cell line, MCF‐7, and its effects on 17‐HSD activity were assessed. CM (25% v/v) from male breast fibroblasts had a significant inhibitory effect on reductive i 7‐HSD, decreasing E2 production. This was in direct contrast to the effects of CM from female breast fibroblasts, which had a powerful stimulatory effect on reductive 17‐HSD. RT‐PCR allowing simultaneous detection of a range of cytokines was performed on each type of fibroblast. IL‐3 mRNA was consistently detected in fibroblasts from male but not female breast tissue. Addition of rhIL‐3 to cultures of MCF‐7 caused a reduction in 17‐HSD activity and addition of a polyclonal antibody directed against IL‐3 to male CM completely reversed the inhibitory effects of CM. Thus, male breast fibroblasts may be responsible for secreting IL‐3‐like factors which, given the considerably lower incidence rates of breast cancer in men, may have a protective effect against breast cancer. © 1995 Wiley‐Less, Inc.
Increased LDL receptor mRNA expression in colon cancer is correlated with a rise in plasma cholesterol levels after curative surgery
Authors: Niendorf Axel , Nägele Herbert , Gerding Daisy , Meyer‐Pannwitt Udo , Gebhardt Angelika 
Published: February 2007

AbstractIt is currently under debate whether the low serum cholesterol levels that are frequently observed in cancer patients represent a risk factor for/or, rather, are a consequence of the tumour. We postulate that malignant tumours are directly involved in an increased catabolism of cholesterol‐rich low‐density lipoprotein (LDL) particles. In a prospective study of 25 patients with colorectal carcinoma, we measured intra‐individual shifts in serum cholesterol levels after surgery, and the expression of LDL‐receptor mRNA in surgically removed specimens. A significant rise in plasma cholesterol levels was observed in patients 3 and 12 months after curative surgery, but not after non‐curative surgery. In human colon carcinoma tissues LDL receptor mRNA expression, as determined by competitive reverse‐transcriptase‐polymerase‐chain reaction, was found to be significantly increased when compared to tissues from the tumour‐free margin (median values, 1.2 x 106 vs. 2.0 x 105 molecules/μg total cellular RNA, respectively, n = 17). The extent of LDL‐receptor mRNA expression positively correlated to the percentage rise of plasma cholesterol levels 3 months (n = 7, r = 0.8763) and 12 months (n = 6, r = 0.9181) after curative surgery. This finding provides in vivo evidence that the tumour tissue itself contributes to decreased plasma cholesterol levels in patients suffering from colorectal carcinomas. It supports the hypothesis that low cholesterol levels in cancer patients are a consequence, and not the cause, of the malignancy. © 1995 Wiley‐Loss, Inc.
CD69+ and HLA‐DR+ activation antigens on peripheral blood lymphocyte populations in metastatic breast and ovarian cancer patients: Correlations with survival following active specific immunotherapy
Authors: Yacyshyn Mary Beth Bowen , Poppema Sibrand , Berg Ann , Maclean Grant D. , Reddish Mark A. , Meikle Alison , Longenecker B. Michael 
Published: February 2007

AbstractLymphocyte activation markers CD69 and HLA‐DR were studied in metastatic breast and ovarian cancer patients who received active specific immunotherapy (ASI) using cancer vaccines containing the synthetic tumor‐associated antigen sialyl‐Tn or the Thomsen‐Friedenreich antigen conjugated to KLH plus DETOX adjuvant. Breast cancer patients who showed prolonged survival following ASI had lower numbers of total CD69+ and CD4+CD69+ cells prior to ASI compared to patients who died. However, following ASI, the surviving patients showed an increase in CD69+ and CD4+CD69+ cells and the deceased patients showed a decrease. A greater than 50% increase in the percentage of cells bearing the activation marker CD69 is associated with an increase in survival in both ovarian and breast cancer patients. In the surviving breast cancer patients there was a significant decrease in the percentage of non‐B lymphocyte HLA‐DR+ (CD20−HLA‐DR+) cells following cyclophosphamide treatment. A strong positive correlation was found between lymphocyte populations CD20− HLA‐DR+ and CD8+CD57+, a putative suppressor cell population. Breast cancer patients who showed a greater than median decrease in CD20−HLA‐DR+ lymphocytes following cyclophosphamide treatment had a survival advantage over patients who had less than the median decrease in the percent CD20−HLA‐DR+ lymphocytes. © 1995 Wiley‐Liss, Inc.
Average intake of anti‐oxidant (PRO)vitamins and subsequent cancer mortality in the 16 cohorts of the seven countries study
Authors: Ocké Marga C. , Kromhout Daan , Menotti Alessandro , Aravanis Christ , Blackburn Henry , Buzina Ratko , Fidanza Flaminio , Jansen Annemarie , Nedeukovic Srecko , Nissinen Aulikki , Pekkarinen Maija , Toshima Hironori 
Published: February 2007

AbstractThis ecologic study aimed to investigate whether differences in population mortality from lung, stomach and colorectal cancer among the 16 cohorts of the Seven Countries Study could be explained by differences in the average intake of anti‐oxidant (pro)vitamins. In the 1960s, detailed dietary information was collected in small sub‐samples of the cohorts by the dietary record method. In 1987, food‐equivalent composites representing the average food intake of each cohort at baseline were collected locally and analyzed in a central laboratory. The vital status of all participants was verified after 25 years of follow‐up. The average intake of vitamin C was strongly inversely related to the 25‐year stomach‐cancer mortality (r = –0.66, p = 0.01), also after adjustment for smoking and intake of salt or nitrate. The average intake of α‐carotene, β‐carotene, and α‐tocopherol were not independently related to mortality from lung, stomach or colorectal cancer, nor was vitamin C related to lung and colorectal cancer. © 1995 Wiley‐Liss, Inc.
IGF‐2 autocrine stimulation in tumorigenic clones of a human colon‐carcinoma cell line
Authors: Lamonerie Thomas , Lavialle Christian , Haddada Hedi , Brison Olivier 
Published: February 2007

AbstractClonal analysis has shown that the SW613‐S human colon‐carcinoma cell line is heterogeneous; some cell clones display a high level of amplification of the c‐myc gene and are tumorigenic in nude mice, whereas others have a small number of copies of this gene and are non‐tumorigenic. Tumorigenic clones can proliferate in a chemically defined serum‐free medium, whereas non‐tumorigenic clones cannot. Suramin, like anti‐insulin‐like growth factor (IGF) or anti‐IGF‐1 receptor antibodies, efficiently inhibits the growth of tumorigenic clones in defined medium. Inhibition by suramin or by anti‐IGF antibodies can be reversed by pure IGF‐1 or IGF‐2. Pure IGF‐1 or IGF‐2 or culture medium conditioned by tumorigenic clones can stimulate DNA synthesis in cells of non‐tumorigenic clones. Co‐culture with cells of tumorigenic clones sustains the growth of non‐tumorigenic clones in defined medium. Cells of both tumorigenic and non‐tumorigenic clones express high‐affinity IGF‐1 receptors at their surface but tumorigenic clones produce on average 5 times more IGF‐1 and 25 times more IGF‐2 than non‐tumorigenic ones. These results indicate that autocrine growth stimulation of tumorigenic clones by IGFs through the IGF‐I receptor is essential for their ability to grow in defined medium. Since cells of tumorigenic clones produce IGF‐2 at levels 80 times higher than IGF‐1 and since an antibody strictly specific for IGF‐1 has no effect on DNA synthesis in cells of tumorigenic clones grown in defined medium, IGF‐2 is very likely the main effector in the autocrine loop. © 1995 Wiley‐Liss, Inc.
Cancer incidence and mortality in young adults in vaud, Switzerland, 1974‐1992
Authors: Levi Fabio , La Vecchia Carlo , Randimbison Lalao , Te Van‐Cong 
Published: February 2007

AbstractTrends in cancer incidence and mortality in young adults (aged 20 to 44 years) over the period 1974‐1992 were analyzed using data from the Vaud Cancer Registry, Switzerland. A total of 1,497 cancers were registered in males, after excluding non melanomatous skin cancers. The most common neoplasms were testis, lymphomas, lung, skin melanoma and oral cavity and pharynx. The overall age‐standardized (world population) incidence was 750 per million males, and increased from 676 in 1974‐1979 to 808 in 1986‐1992. These upward trends were due mainly to cancers of the oral cavity and pharynx, lung, skin melanoma and colorectum, while testicular cancer rates remained stable. For females, a total of 1,899 malignant neoplasms was notified, corresponding to an overall age‐standardized incidence of 914 per million. The overall rate increased from 818 in 1974‐1979 to 1,003 in 1986‐1992. The most frequent neoplasms were breast, skin melanoma, ovary, thyroid and lymphomas. The major types of cancer responsible for these upward trends were breast cancer, skin melanoma and lung cancer. In the period studied there were 458 cancer deaths in males and 408 in females, corresponding to an overall age‐standardized rate of 227 per million males and 193 per million females. Death rates in males tended to decline, to reach 194 per million in 1986‐1992, but no consistent trend was observed in females. The decline in males was essentially due to the fall in rates for testicular cancer and Hodgkin's disease. In females, falls in death rates were observed for cancer of the cervix uteri, ovary and Hodgkin's disease. Death rates were upwards for lung cancer in both sexes, and for skin melanoma and breast cancer in females. © 1995 Wiley‐Liss, Inc.
Up‐regulation of intercellular adhesion molecule 1 (ICAM‐1) on human renal cell carcinoma cells by interleukin‐4
Authors: Obiri Nicholas I. , Tandon Nandita , Puri Raj K. 
Published: February 2007

AbstractWe have previously demonstrated that human renal cell carcinoma (RCC) cells express high‐affinity IL‐4 receptors (IL‐4R). To study the functions of these receptors, we have examined the effect of IL‐4 on the expression of intercellular adhesion molecule‐1 (ICAM‐1 or CD54) on human RCC cells. Following incubation with various concentrations of IL‐4, RCC cells were examined for ICAM‐1 expression by flow cytometric analysis. The 2 primary RCC cell cultures and the 2 cell lines examined expressed varying basal levels of ICAM‐1 on the cell surface. IL‐4 treatment increased ICAM‐1 expression in a time‐dependent manner and maximum augmentation of ICAM‐1 expression was observed after a 48 hr incubation. The increase in ICAM‐1 expression was specific because anti‐hIL‐4 antibody blocked this effect. No enhancement of ICAM‐1 expression was observed when RCC cells were incubated with IL‐4 in the presence of cycloheximide, indicating that the IL‐4 effect requires new protein synthesis. Up‐regulation of ICAM‐1 expression was also observed at the mRNA level and maximum increase in message occurred 8 hr post‐IL‐4 treatment. Both IL‐4 and IFN‐γ also increased soluble ICAM‐1 levels in WS‐RCC culture supernatant. The significance of enhanced soluble and surface ICAM‐1 expression was investigated by examining the lymphokine activated killer (LAK) cell‐mediated lysis of IL‐4‐treated WS‐RCC cells. LAK cells lysed WS‐RCC cells very effectively, but lysis observed in target cells pre‐treated with IL‐4 did not correlate with the increased expression of ICAM‐1 antigen. Our results indicate a previously unknown function of IL‐4 on RCC and further demonstrate that IL‐4R on RCC are functional. © 1995 Wiley‐Liss, Inc.
Retinoic acid induced death of ovarian carcinoma cells correlates with c‐myc stimulation
Authors: Krupitza Georg , Hulla Wolfgang , Harant Hanna , Dittrich Evelyn , Kallay Enikö , Huber Heinz , Grunt Thomas , Dittrich Christian 
Published: February 2007

AbstractIn the ovarian adenocarcinoma subline N.1, all‐trans retinoic acid (ATRA) induced substantial cell death. This response was elicited only at decreased serum levels. Exposure of N.I cells to increasing concentrations of ATRA was accompanied by a considerable up‐regulation of c‐myc transcript levels that correlated with the rate of cell killing, which itself was an active process as judged by sustained transcriptional expression. ATRA‐triggered rounding and detaching of single cells from the substratum was accompanied by degradation of genomic DNA. We show that the N.I model cell line, which is otherwise highly ATRA‐resistant, can undergo an ATRA‐triggered suicide program when serum is limited. The accompanying c‐myc up‐regulation seems to be mediated by retinoic‐acid‐receptor‐independent pathways involving membrane‐associated phospholipases instead, because manoalide partly suppressed c‐myc induction by ATRA but left constitutive c‐myc expression unaffected. © 1995 Wiley‐Liss, Inc.
Effect of vesicle size and lipid composition on the in vivo tumor selectivity and toxicity of the non‐cross‐resistant anthracycline annamycin incorporated in liposomes
Authors: Zou Yiyu , Ling Yi‐He , Reddy Sara , Priebe Waldemar , Perez‐Soler Roman 
Published: February 2007

AbstractAnnamycin (Ann) is a non‐cross‐resistant lipophilic anthracy‐cline antibiotic optimally suited for liposome delivery. We studied how vesicle size and presence of phospholipids with a high phase transition temperature and monosialoganglioside (GM1) in the liposome bilayers affect the pharmacokinetics, tumor selectivity and toxicity of Ann. Entrapment of Ann in multilamellar vesicles (L‐Ann) resulted in a 20% lower heart AUC and a 30–40% higher tumor and liver AUC. Reduction of the liposome size from 1.6 to 0.03 μm increased Ann plasma circulation time and tumor AUC by 2‐fold, enhanced Ann tumor selectivity and decreased Ann subacute toxicity by 2‐fold. The presence of phospholipids with a high phase transition temperature and GM1 in the liposome bilayers further prolonged Ann plasma circulation time by 2‐ to 4‐fold, did not increase Ann tumor AUC and moderately increased Ann subacute toxicity. The anti‐tumor activity of Ann correlated with the tumor AUC achieved with each particular formulation. Our results strongly suggest that vesicle size may be an important determinant of the therapeutic index of liposomal Ann, but they fail to demonstrate a beneficial tumor‐targeting effect of liposomes composed of GM1 and phospholipids with a high phase transition temperature, as has been reported for the hydrophilic parent compound doxorubicin. © 1995 Wiley‐Liss, Inc.
Identification of a highly specific surface marker of T‐cell acute lymphoblastic leukemia and neuroblastoma as a new member of the transmembrane 4 superfamily
Authors: Takagi Shin , Fujikawa Kiyomi , Imai Toshio , Fukuhara Norio , Fukudome Kenji , Minegishi Masayoshi , Tsuchiya Shigeru , Konno Tasuke , Hinuma Yorio , Yoshie Osamu 
Published: February 2007

AbstractFive monoclonal antibodies detected a surface antigen expressed exclusively on T‐cell acute lymphoblastic leukemia (T‐ALL) in a panel of 45 human hematopoietic cell lines, including T‐cell lines derived from adult T‐cell leukemia and those established by immortalization with human T‐cell leukemia virus type 1 or Herpesvirus saimiri. Peripheral blood mono‐nuclear cells, including fresh and activated T cells, were also completely devoid of this antigen. We designated this antigen as TALLA‐1 (from T‐ALL‐associated antigen 1). By expression cloning, a cDNA clone encoding TALLA‐1 was isolated from T‐ALL cell line Molt‐4. TALLA‐1 was found to be a member of the transmembrane 4 superfamily (TM4SF). The cDNA was also essentially identical to A15, which was isolated from another T‐ALL cell line, HPB‐ALL, by differential hybridization with normal peripheral blood lymphocytes, and to CCG‐B7, which was isolated from a brain cDNA library using CCG repeat as a probe. The gene product was now characterized in detail at the protein level. Northern blot analysis showed that the gene was expressed most strongly in brain, skeletal muscle and spleen. In a panel of 52 non‐hematopoietic human cell lines, the majority of neuroblastoma cell lines were found to be positive for TALLA‐1. Like ME491, CO‐029 and L6, TALLA‐1 may be another TM4SF member behaving as a potential tumor‐associated antigen. © 1995 Wiley‐Liss, Inc.
Liposomal doxorubicin‐induced toxicity: Depletion and impairment of phagocytic activity of liver macrophages
Authors: Daemen Toos , Hofstede Gert , Ten Kate Marian T. , Bakker‐Woudenberg Irma A. J. M. , Scherphof Gerrit L. 
Published: February 2007

AbstractDoxorubicin entrapped within conventional liposomes (200 nm in diameter; lip‐Dox) has major toxic effects on liver macrophages of the rat for a considerable period of time following i.v. administration, with respect to both specific phagocytic capacity and cell numbers. At different time‐points after injection of lip‐Dox or free doxorubicin, radiolabeled, negatively charged, “empty” test liposomes were injected. Phagocytic capacity was determined by isolating the liver macrophages and measuring the amount of macrophage‐associated radioactivity. Four subfractions of liver macrophages of different cell‐size and with intrinsically different phagocytic capacity were isolated. Twenty‐four hours after injection of lip‐Dox, the phagocytic capacity of the larger‐sized liver macrophages was strongly decreased. The relatively low intrinsic phagocytic capacity of the smaller‐sized macrophages was only slightly impaired. Phagocytic capacity after injection of lip‐Dox was nearly restored to control values after 14 days. Blood clearance of Klebsiella pneumoniae bacteria after pre‐treatment with lip‐Dox was strongly decreased. Pre‐treatment with the free drug and/or placebo liposomes had no effect on phagocytic and bacterial blood‐clearance capacity. A major depletion of the liver macrophage population was observed, as revealed by both macrophage isolation and histology. Only 2 weeks after injection of lip‐Dox, the number of cells had returned to that seen in control animals. In view of the important host‐defense functions of the liver macrophages, especially in the control of tumor growth and infection, the findings reported here should be taken into consideration when lip‐Dox is to be administered in anti‐tumor therapy. © 1995 Wiley‐Liss, Inc.
Sensitization to cisplatin action by step‐down heating in cddp‐sensitive and ‐resistant cells
Authors: Hettinga Judith V. E. , Lemstra Willy , De Vries Elisabeth G. E. , Konings Antonius W. T. , Kampinga Harm H. 
Published: February 2007

AbstractHyperthermia treatment (≥ 43°C) has been shown to be able to (partially) reverse acquired cDDP resistance. However, such heat treatment is difficult to achieve in the clinic. Short pre‐treatment at a high temperature (>42°C), immediately before a treatment at a lower temperature (<42°C) can enhance the heat toxicity of the lower temperatures. This “step‐down heating schedule” was explored for its possible drug‐sensitizing potential in in vitro‐cultured cDDP‐sensitive and ‐resistant murine and human tumour cells. A 10‐min pre‐treatment at 44°C enhanced the cytotoxicity of 41°C hyperthermia alone. It also enhanced sensitivity to cDDP when given at 37°C. However, it did not increase the 41°C‐induced cDDP sensitization. Thus, no correlation was found between heat kill and cDDP sensitization for step‐down heating schedules. The observed effects of step‐down heating were comparable in sensitive and in resistant cells, so the step‐down heating schedule, unlike the 43°C treatment, did not lead to a decrease of the cDDP‐resistance factor. Yet the total cytotoxicity caused by this treatment protocol was 10‐fold more than for cDDP with 41°C alone, due to the extra hyperthermic cell killing and the cDDP‐sensitizing effect of the pre‐treatment. This treatment could have a substantial impact on cDDP efficacy in the clinic even when cDDP resistance has developed. © 1995 Wiley‐Liss, Inc.
Isolation of antigenic mimics of MDR1‐P‐glycoprotein by phage‐displayed peptide libraries
Authors: Poloni Francesca , Romagnoli Giulia , Cianfriglia Maurizio , Felici Franco 
Published: February 2007

AbstractTo identify an MC57 epitope which is more efficiently expressed on inactivated forms of P‐glycoprotein we utilized peptide libraries displayed on filamentous phage. Using this technology, we selected specific phage clones blocking the binding of the murine monoclonal (MAb) MC57 with live human multi‐drug‐resistant (MDR) cells, and sequenced and analyzed their DNA. The results we obtained indicate that MAb MC57 epitope could be formed by 2 regions localized on the predicted fourth and sixth extracellular loops of the current 12‐transmembrane‐domain model predicted for MDR1‐P‐glycoprotein. Surprisingly, a third region, defined by residues 800–807 of the MDR1‐P‐glycoprotein sequence and postulated to be intracellular, was also identified as a putative part of the MC57 epitope. This finding adds weight to the interesting hypothesis that a P‐glycoprotein structure different from the current model may exist. © 1995 Wiley‐Liss, Inc.