bluuebunny/crossref_metadata_2025_split huggingface dataset:
DOK, a cell line established from human dysplastic oral mucosa, shows a partially transformed non‐malignant phenotype
Authors: Chang Sidney E. , Foster Sharon , Betts David , Marnock Wendy E. 
Published: February 2007

AbstractThere are many reports of cell lines being established from human oral squamous‐cell carcinomas but apparently none of cell lines from dysplastic or “pre‐malignant” oral mucosa. We describe here the isolation and characterization of a cell line, DOK (dysplastic oral keratinocyte), from a piece of dorsal tongue showing epithelial dysplasia. The tissue was obtained from a 57‐year‐old man who was a heavy smoker prior to the appearance of a white patch on his tongue. Eleven years later a squamous‐cell carcinoma developed at the site and was excised. Subsequently the remaining dysplasia was removed, and it was from a piece of this that the primary cell cultures which eventually gave rise to DOK were initiated. The DOK line has been single‐cell cloned and is apparently immortal. It grows in the absence of 3T3 feeder cells, is anchorage‐dependent for growth and is non‐tumorigenic in nude mice. The keratin profile of the cells shows a striking similarity to that of the original tongue dysplasia. The karyotype of DOK is aneuploid and complex. By PCR and oligonucleotide hybridization on dot blots, codons 12, 13 and 61 of Ha‐ras, Ki‐ras and N‐ras in DNA extracted from DOK cells were shown to be normal. Immunohistochemistry showed no abnormal, i.e., elevated expression of the onco‐suppressor protein p53. Because of its origin and partially transformed phenotype, DOK presents an opportunity to study whether specific carcinogens associated with tobacco and areca nut can cause malignant transformation of oral keratinocytes in vitro. © 1992 Wiley‐Liss, Inc.
Des‐(1–3)‐IGF‐I, an insulin‐like growth factor analog used to mimic a potential IGF‐II autocrine loop, promotes the differentiation of human colon‐carcinoma cells
Authors: Remacle‐Bonnet Maryse , Garrouste Francoise , Atiq Fatima El , Roccabianca Monique , Marvaldi Jacques , Pommier Gilbert 
Published: February 2007

AbstractHT29‐D4 human colon‐carcinoma cells have been shown to secrete insulin‐like growth factor (IGF)‐II and to simultaneously express type‐I IGF receptors. However, the sequestration of IGF‐II by several molecular forms of IGF‐binding proteins (IGFBP) in the culture medium prevents the establishment of an operative IGF‐II autocrine loop. IGFBPs secreted by HT29‐D4 cells (HT29‐D4 IGFBP) comprise isoforms of IGFBP‐4 (25, 27 and 30 kDa) and 2 unidentified forms (34.5 and 32‐34 kDa). This latter does not bind 125I‐IGF‐I. The net affinity of HT29‐D4 IGFBP is about 12 times stronger for IGF‐II (KD approx. 10−10 M) than for IGF‐I. All the HT29‐D4 IGFBP molecular forms are unable to bind the N‐terminally truncated IGF‐I analog, des‐(1–3)‐IGF‐1. In contrast, HT29‐D4 cell‐surface type‐l IGF receptors bind IGF‐I and des‐(1–3)‐IGF‐l identically (KD approx. 5 × 10−10M). We have taken advantage of these particular binding properties to use des‐(1–3)‐IGF‐1 to mimic a potential IGF autocrine loop and to observe its biological consequences. Nanomolar concentrations of des‐(1–3)‐IGF‐1 induce HT29‐D4 cells to develop into a differentiated phenotype, as judged by a substantial carcinoembryonic antigen release and the induction of numerous intercellular cysts with well‐organized microvilli. In the same way, des‐(1–3)‐IGF‐1 early induces a slight inhibition of HT29‐D4 cell proliferation. Based on these findings, we conclude that the type‐l IGF receptor primarily controls the differentiation of these colonic cells, and that HT29‐D4 cancer cells remain in an undifferentiated state because of their inability to use endogenous IGF‐II as an autocrine regulatory factor. © 1992 Wiley‐Liss, Inc.
Human prolactin regulates transfected MMTV LTR‐directed gene expression in a human breast‐carcinoma cell line through synergistic interaction with steroid hormones
Authors: Haraguchi Soichi , Good Robert A. , Engelman Robert W. , Day Noorbibi K. 
Published: February 2007

AbstractProlactin plays a key role in the regulation and growth of mammary cells, and influences tumor promotion. We have shown that chronic energy restriction intake depresses prolactin levels, inhibits production of MMTV proviral DNA and proto‐oncogene expression in mammary glands and prevents development of mammary tumors. Since the expression and proto‐oncogene activation of MMTV are regulated by promoter/enhancer elements within its long terminal repeat (LTR), in the present study we used a chloramphenicol acetyl transferase (CAT) reporter gene system and gene transfection methods to study the effect of prolactin on MMTV LTR using a human ductal carcinoma cell line T47D stably or transiently transfected with a plasmid consisting of the LTR upstream of CAT gene. Human prolactin or dexamethasone induced, respectively, a 2‐fold or 6‐fold increase in CAT activity compared with background CAT activity in the absence of hormones. However, the combination of human prolactin and dexamethasone strongly enhanced (20‐fold) induction of the LTR compared with the control. Human prolactin also showed a synergistic effect with progesterone on LTR induction. Both LTR and CAT genes needed to be linked for induction of CAT activity by prolactin and dexamethasone. Our results indicate that human prolactin can act synergistically with steroid hormones to regulate MMTV LTR‐directed gene expression in transfected T47D cells. © 1992 Wiley‐Liss, Inc.
Functions of estrogens and anti‐estrogens in the rat endometrial adenocarcinoma cell lines RUCA‐I and RUCA‐II
Authors: Schütze Norbert , Kraft Volker , Deerberg Friedrich , Winking Heinz , Meitinger Daniela , Ebert Kirsten , Knuppen Rudolf , Vollmer Günter 
Published: February 2007

AbstractInbred rats of the DA/Han and BDII/Han strains have been proposed as suitable model systems for studying hormonal carcinogenesis, because they die mainly from hormone‐dependent endometrial adenocarcinoma. Here we characterize the RUCA‐I cell line derived from an endometrial adenocarcinoma of an inbred DA/ Han rat and the RUCA‐II cell line derived from an endometrial adenocarcinoma of an inbred BDII/Han rat. The RUCA‐I cell line, if transplanted to the neck of female DA/ Han rats, gives rise to endometrial adenocarcinomas at the ectopic site. The morphology of these ectopically grown tumors is predominantly of the moderately differentiated sub‐class. In contrast, ectopic tumor growth of the RUCA‐II cell line can be observed only if cells are transplanted to athymic nude mice. Biochemically, both cell lines are characterized by the stable expression of estrogen receptors. However, no statistically significant mitotic response of RUCA‐I and RUCA‐II cells to estradiol was measurable, and no induction of expression of the progesterone receptor by estradiol was detectable, although estradiol transformed the estrogen receptor into its stable DNA‐binding state. In contrast, the rate of proliferation of RUCA‐I but not of RUCA‐II cells was reduced in the presence of 10−6 M tamoxifen. From these results we conclude that (i) both cell lines, RUCA‐I and RUCA‐II, represent a new and promising endometrial tumor model; (ii) the mechanism of the hormone‐ dependent growth regulation of RUCA‐I and RUCA‐II cells is obviously impaired; (iii) the RUCA‐I cell line appears to be a suitable model system for the study of molecular aspects of estrogen‐ and tamoxifen‐dependent gene expression. © 1992 Wiley‐Liss, Inc.
Analysis of two human monoclonal antibodies against melanoma
Authors: Yeilding Newman M. , Gerstner Carolyn , Kirkwood John M. 
Published: February 2007

AbstractB cells derived from peripheral‐blood lymphocytes (PBL) and tumor‐infiltrating lymphocytes (TIL) from a patient with a high serum antibody titer to autologous melanoma were transformed with Epstein‐Barr virus (EBV) and evaluated for reactivity against autologous tumor. B cells producing antibody reactive with autologous tumor and unreactive with normal fibroblasts were detected both in TIL and in PBL. One cell line derived from PBL and another derived from TIL sustained production of tumor‐reactive antibody for 10 weeks and over 15 months respectively. The cell line derived from PBL, 2D11, produced an antibody reactive with a trypsin‐resistant antigen expressed on the cell membrane of autologous and allogeneic melanoma cell lines. The cell line derived from TIL, IF6, produced an antibody reactive with a cell‐surface glycoprotein expressed by 5 autologous melanoma cell lines derived from 5 different metastases and 16/19 allogeneic melanoma cell lines. IF6 also showed reactivity with cell lines derived from a blue nevus, a congenital nevus, an astrocytoma, and 1/4 renal‐cell carcinomas; but it was not reactive with 5 foreskin melanocyte cell lines, 2 normal fibroblast lines, 5 leukemia/lymphoma lines, 8 lung‐cancer lines, 8 glioblastoma lines, or lines derived from 1 ovarian carcinoma, f colon carcinoma, 1 vulvar carcinoma, 1 fibrosarcoma, 1 murine melanoma, or 4 murine leukemia/lymphomas. We describe here an antibody that detects a new melanoma specificity obtained by EBV transformation of tumor‐infiltrating B cells. © 1992 Wiley‐Liss, Inc.
Proliferation of human colon cancer cells: Role of epidermal growth factor and transforming growth factorα
Authors: Huang Shuang , Trujillo Jose M. , Chakrabarty Subhas 
Published: February 2007

AbstractHuman colon cancer cells produce and secrete a variety of polypeptide growth factors. The functional role of these growth factors, however, is poorly understood. Though the secretion of epidermal growth factor (EGF)‐like activity and EGF‐related molecules by human colon cancer cells in culture has been reported, it is not known whether colon cancer cells produce and secrete EGF, and the functional role of EGF in the growth control of these cells is also unknown. We have shown that EGF acts as a potent growth stimulator on the moderately differentiated Moser colon cancer cell line and as an inhibitor on the highly metastatic KM12SM cell line. In the present study, we show that EGF is produced by human colon cancer cells and characterize the levels of EGF mRNA expression and EGF protein secretion from 8 human colon cancer cell lines. The cell‐surface EGF receptors on these cell lines were also characterized by radiolabeled ligand binding and Scatchard analyses. All the cell lines expressed EGF mRNA and secreted EGF. Both high‐ and low‐affinity subtypes of EGF receptor were detected on 7 of the cell lines. These lines also secreted transforming growth factor (TGF)α. Some cell lines exhibited a proliferative response to treatment with either exogenous EGF or TGFα, while others did not respond to treatment with these growth factors. Antibody‐blocking experiments, using anti‐EGF or anti‐EGF receptor antibody, suggested that these cell lines could be broadly classified into 2 groups in terms of their autocrine or paracrine growth regulation via the cell‐surface EGF receptor: (1) cells that utilized EGF and/or TGFα; and (2) cells that did not utilize EGF or TGFα (via the cell‐surface receptor), even though they secreted abundant amounts of these growth factors. © 1992 Wiley‐Liss, Inc.
Loss of heterozygosity at chromosome 17p is associated with HER‐2 amplification and lack of nodal involvement in breast cancer
Authors: Imyanitov Evgeny N. , Chernitsa Oleg I. , Nikiforova Irina F. 
Published: February 2007

AbstractSixty DNA samples from breast carcinoma (BC) patients were analyzed by Southern blot to examine certain oncogene and anti‐oncogene alterations. Amplification of the HER‐2 oncogene was detected in 15 tumours (25%), c‐myc in 2 (3%) only and HER‐1 in none. Distribution of Hras‐1 oncogene alleles in BC did not significantly differ from that seen in healthy donors. Not a single case of RB‐1 anti‐oncogene alteration and only one of p53 suppressor gene abnormality was found when appropriate cDNA copies were used as probes. With the use of DNA polymorphic markers, loss of heterozygosity (LOH) was revealed at chromosome 17p (probe YNZ‐22) in 18 of 39 (46%) informative cases, at 17q (probe THH‐59) in 10 of 34 (29%) and at 11p (probe Hras‐1) in 8 of 30 (27%). The only significant correlation between these genetic alterations and the clinical characteristics of the tumours studied was the association of LOH at 17p with node‐negative BC (p < 0.02). Also, the tendency for correlation (p < 0.2) between HER‐2 amplification and loss of 17p sequences was revealed: 7 of 10 amplification‐positive, but only 11 of 29 amplification‐negative BC possessed o LOH of YNZ‐22 IOCUS.
Visualization of the plasmin receptor on sections of human mammary carcinoma cells
Authors: Burtin P. , Zhang S. , Schauffler J. , Komano O. , Sastre X. , Mathieu M. C. 
Published: February 2007

AbstractIn previous studies we observed the presence of an antigen reacting with anti‐plasminogen serum on tumor cells found in sections of human colorectal and mammary carcinomas, using immunofluorescence. This antigen could be plasminogen, or plasmin or both. These results led us to surmise that carcinoma cells, and not normal epithelial cells, had a receptor for plasmin and plasminogen. We demonstrated the existence of such a receptor on cells of established tumor cell lines of colonic and mammary origin. We observed that binding of plasmin(ogen) to its receptor was inhibited by lysin and its analogs. We undertook to characterize the plasmin receptor on sections of human mammary Carcinomas (18 series of sections, originating from 15 infiltrating ductal carcinomas). In our immunofluorescence studies, we observed that the fluorescence induced by anti‐plasminogen serum was suppressed by pre‐treatment of the sections with tranexamic acid, a lysin analog. Furthermore, when parallel sections were incubated with tranexamic acid, then with solutions of plasminogen, tumor cells were made fluorescent again. Another important finding was the strong increase of labelling observed when sections were incubated with plasminogen or plasmin before reaction with antiplasminogen serum. This labelling disappeared when tranexamic was added to plasminogen. As a whole, these results confirm the existence of plasmin receptors on tumor cells in mammary carcinoma sections. They also show that these receptors are not saturated in vivo and may bind,in vitro, additional amounts of ligand.
Increased expression of p34cdc2 and its kinase activity in human gastric and colonic carcinomas
Authors: Yasui Wataru , Ayhan Ayse , Kitadai Yasuhiko , Nishimura Kenji , Yokozaki Hiroshi , And Hisao Ito , Tahara Eiichi 
Published: February 2007

AbstractWe examined the expression of p34cdc2 and its kinase activity in human gastric and colonic carcinoma cell lines and carcinoma tissues and studied its relation with a tumor‐suppressor gene product, p53. All the gastric and colonic cancer cell lines expressed p34cdC2 and showed its kinase activity at various levels. When the cells were arrested in mitotic metaphase by the use of nocodazole, p34cdC2 kinase activity was induced and p53 was apparently phosphorylated. Of 12 gastric carcinoma cases, 11 (91.7%) showed higher p34cdC2 kinase activity in tumor tissues than in corresponding non‐neoplastic mucosa. The protein kinase activities in the individual cases were well correlated with the levels of p34cdc2 protein expression. A good correlation was also found between the expression of p34cdc2 and proliferating cell nuclear antigen (PCNA). Almost all the colonic carcinomas showed higher cdc2 kinase activity and increased p34 expression when compared with non‐neoplastic mucosa. Interestingly, most of the gastric and colonic carcinomas having high cdc2 kinase activity expressed high levels of p53. These findings suggest that the increased p34cdc2 kinase activity might cause the development and proliferation of gastric and colonic carcinomas, partly through abnormal p53 accumulation.
Non‐hodgkin lymphoma in gabon and its relation to HTLV‐I
Authors: Delaporte Eric , Klotz Francis , Peeters Martine , Martin‐Prevel Yves , Bedjabaga Léonard , Larouzé Bernard , Nguembi‐Mbina Celestin , Walter Andpaul , Piot Peter 
Published: February 2007

AbstractA case‐control study was performed in Libreville, Gabon, to determine whether a relationship can be established between the relatively high proportion of non‐Hodgkin lymphoma (NHL) among all cancer cases and the high seroprevalence rate of HTLV‐I observed, and to discover whether cases of adult T‐leukemia/lymphoma (ATLL) related to HTLV‐I exist in Gabon. From November 1987 to April 1989, a total of 32 patients with NHL were recruited; 6 were infants with Burkitt's lymphoma and 26 were adults with NHL. Each patient was matched with 2 asymptomatic controls for age, sex and ethnic group. HTLV‐I serology was done by ELISA and Western blot. Comparison of the groups was done by chi‐square analysis. None of the 6 infants with Burkitt's lymphoma and none of their controls had antibodies to HTLV‐I. Of the 26 patients with NHL, 7 (26.9%) had HTLV‐I antibodies. Among the 52 controls, the HTLV‐I rate was 13.4% (n = 7). There was no difference between cases and controls (Fisher's exact test, p = 0.16). Among the 26 NHL, 4 cases fitted the criteria of ATLL and were HTLV‐I‐positive; 3 others who were positive for HTLV‐I were a woman with lymphoblastic gastric NHL and 2 old men with an unclassified lymphoma. From the results of this limited series it is not possible to state that there is an association between NHL and HTLV‐I infection. Nevertheless, cases of ATLL related to HTLV‐I are reported from this area. Based on the HTLV‐I seroprevalence rates reported in Gabon, the estimated incidence rate of ATL among seropositive people in Gabon appears much lower than in Japan. Different explanations can be proposed, but under‐diagnosis of ATLL is probably one of the main factors.
Desmoplasia and its relevance to colorectal tumour invasion
Authors: Hewitt Robert E. , Powe Desmond G. , Ian Carter G. , Turner David R. 
Published: February 2007

AbstractSome invasive tumours characteristically have an abundant stroma rich in collagen, the production of which is termed the desmoplastic response. It has been suggested that this response may have a protective effect, and act to limit the process of tumour invasion. To investigate this possibility, we have examined various colorectal tumours for inter‐ and intra‐tumoural variations in the desmoplastic response. As markers of this response, the distributions of collagen‐I protein and myofibroblasts have been demonstrated by immunocytochemistry, while collagen‐I messenger RNA has been demonstrated by in situ hybridization (ISH). Evidence of a desmoplastic response was obvious in carcinomas, but not in non‐invasive adenomas. In carcinomas, we found that the response was marked in the tumour centre, where morphological features of active invasion have been reported to be absent. By contrast, we found little evidence of a desmoplastic response at the invasive edge of these carcinomas, where features suggestive of active invasion are prominent: in this location, collagen‐I immunostaining was limited and myofibroblasts were sparsely distributed or absent. While our ISH results suggested active collagen‐I synthesis in the tumour centre, there was little evidence of collagen‐I synthesis in host tissues ahead of the invasion front. On the basis of these and other reported findings, we suggest that, while the desmoplastic response may reduce the invasive activity of neoplastic cells in the tumour centre, it fails to prevent the spread of colorectal cancer because of its deficiency at the invasive edge.
An immunohistochemical study of c‐erbb‐2 protein in gastric carcinomas and lymph‐node metastases: Is the c‐erbB‐2 protein really a prognostic indicator?
Authors: Ohguri Takehiko , Sato Yuichi , Koizumi Wasaburo , Saigenji Katsunori , Kameya Toru 
Published: February 2007

AbstractAn immunohistochemical study of the c‐erbB‐2 protein was conducted on formalin‐fixed paraffin‐embedded tissue sections from 136 primary gastric carcinomas and 50 metastatic lymph node tumors obtained at gastrectomy. Expression of the protein was detected in 35 of 136 primary gastric carcinomas (25.7%) and 22 of 50 metastatic lymph nodes (44%). The staining pattern of tumor cells was classified as membranous or cytoplasmic. An immunohistochemical study using serially diluted antibody demonstrated that 82.6% of positive cases in metastatic lymph nodes showed c‐erbB‐2 immunoreactivity stronger than that in the primary tumors. Membranous staining was stronger than cytoplasmic staining. c‐erbB‐2 protein of the cytoplasmic as well as membranous types was confirmed to be a 185‐kDa whole molecule by immunoblotting. Correlation between the expression of c‐erbB‐2 protein and clinical and histological parameters was investigated. No significant correlation between 5‐year survival rate of patients and expression of c‐erbB‐2 protein was found. In the poorly differentiated carcinoma group possessing c‐erbB‐2 protein, overall survival was significantly shorter than in cases without protein expression ( p < 0.01). We conclude that c‐erbB‐2 protein is not a useful prognostic indicator in gastric carcinomas.
Altered glycosylation of β1 integrins associated with reduced adhesiveness to fibronectin and laminin
Authors: Kawano Takehiro , Takasaki Seiichi , Tao Tien‐Wen , Kobata Akira 
Published: February 2007

AbstractThe carbohydrate structures of the β1 integrins obtained from a mouse metastatic melanoma 816 FI and its weakly metastatic wheat‐germ agglutinin‐resistant mutant Wa4‐bI were studied comparatively. The results indicated that the integrins from both cells contain high mannose‐type and bi‐, tri‐ and tetra‐antennary complex‐type sugar chains. No significant difference was found in the outer chain branching between both integrins, but sialylation of the sugar chains of the mutant's integrin was markedly decreased and almost all the outer chain moieties of tri‐ and tetra‐antennary oligosaccharides of the mutant's integrin were fucosylated, resulting in the formation of X‐antigenic determinants, GalβI → 4 (Fucα → 3) GlcNAc. In contrast, the integrin from parental cell contained no X‐antigenic determinant. These structural differences found in the integrin are thought to account for the reduction in the metastatic potential of the mutant which also shows reduced adhesion to fibronectin and laminin as compared with the parental cell.
Biologic properties of a Ch2 domain‐deleted recombinant immunoglobulin
Authors: Slavin‐Chiorini Dale C. , Hand Patricia Horan , Kashmiri S. V. S. , Calvo Benjamin , Zaremba Sam , Schlom Jeffrey 
Published: February 2007

AbstractMonoclonal antibody (MAb) B72.3 reacts with TAG‐72, a high‐molecular‐weight mucin expressed on several types of human carcinoma, and is currently being used in clinical trials for the diagnosis and therapy of human carcinoma. An expression construct containing cDNA encoding an immunoglobulin (Ig) heavy chain, with the variable region of murine MAb B72.3 and a human Ig constant region with a deletion of the CH2 domain, was generated. Immunoglobulin from the transfectoma with the highest expression of the TAG‐72 immunoreactive antibody was designated MAb chimeric (c) B72.3°CH2. The pharmacokinetics of serum clearance of iodine‐labeled MAbs cB72.3°CH2 and the intact cB72.3 were compared in athymic mice. By 24 hr, less than 1% of the cB72.3°CH2 was left in the plasma, while 36% of the cB72.3 still remained. The T1/2β values of the cB72.3°CH2 and cB72.3 MAbs were 1.7 and 2.4 hr, respectively. The T1/2β values were 7.8 hr for the domain‐deleted cMAb and 48.9 hr for cB72.3. Biodistribution studies in athymic mice bearing LS‐174T xenografts showed a reduction in the percentage of injected dose per gram in tumor with 1311‐cB72.3°CH2; however, the 1311‐cB72.3ΔCH2 both localized to tumors faster and cleared from the blood faster than the 1251‐cB72.3 MAb. Only trace amounts of the 1311‐CB72.3°CH2 were detected in normal tissues, including kidney. The faster clearance rate, more rapid tumor targeting and lack of metabolic uptake in normal tissues demonstrated with the iodine‐labeled CH2 domain‐deleted cMAb may be an advantage for certain clinical protocols.