bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody‐induced growth inhibition is mediated through immunochemically and functionally distinct epitopes on the extracellular domain of the c‐erbb‐2 (her‐2/neu) gene product p185
Authors: Xu Fengji , Lupu Ruth , Rodriguez Gustavo C. , Whitaker Regina S. , Boente Matthew P. , Berchuck Andrew , Yu Yinhua , Desombre Karen A. , Boyer Cinda M. , Bast Robert C. 
Published: February 2007

AbstractOver‐expression of the c‐erbB‐2 (HER‐2/neu) gene product p185 occurs in 30% of breast and ovarian cancers. The p185 protein might serve as a target for serotherapy in that antibodies against different epitopes on the extracellular domain of p185 can inhibit growth of tumor cells in the absence of cellular or humoral effector mechanisms. To define epitopes of functional relevance, II monoclonal antibodies (MAbs) were evaluated for their ability to bind to the extracellular domain of p185. Results of competition studies with 1251‐labeled and non‐labeled antibodies indicated that 10 of 11 epitopes were grouped in a linear array. Antibodies against 7 epitopes inhibited anchorageindependent growth and antibodies against 2 of these epitopes also inhibited anchorage‐dependent growth of SKBr3 breast‐cancer cells that over‐expressed p185. Treatment with antibodies exerted cytotoxic rather than cytostatic effects. When antibodies were used in combination, additive or supra‐additive inhibition of anchorage‐independent and anchorage‐dependent growth was observed between pairs of antibodies. Growth inhibition did not relate to the affinity of the antibody or its isotype. Two antibodies that inhibited both anchorage‐dependent and anchorage‐independent growth also blocked binding of the HER‐2/neu ligand, whereas 5 antibodies that inhibited only anchorage‐independent growth had no effect on ligand binding. Inhibition of cell growth did not correlate with internalization of p185 or down‐regulation of p185 on the cell surface. Fab fragments of active antibodies could also inhibit anchorage‐independent growth of SKBr3. Thus, murine MAbs and their fragments recognized both immunochemically distinct and functionally distinct epitopes on the p185 molecule. Whereas inhibition of anchorage‐dependent growth correlated with the ability of antibodies to block ligand binding, inhibition of anchorage‐independent growth did not correlate with effects on ligand binding, internalization, cell‐surface expression or cross‐linking of pl85.
Immortalization of normal human fibroblasts by treatment with 4‐nitroquinoline 1‐oxide
Authors: Bai L. , Mihara K. , Kondo Y. , Honma M. , Namba M. 
Published: February 2007

AbstractNormal human fibroblasts (the OUMS‐24 strain), derived from a 6‐week‐old human embryo, were transformed (into the OUMS‐24F line) and immortalized by repeated treatments (59 times) with 4‐nitroquinoline 1‐oxide (4NQO). Treatment began during primary culture and ended at the 51st population doubling level (PDL). At the 57th PDL (146 days after the last treatment), morphologically altered, epithelial‐type cells appeared, began to grow and became immortal (now past the 100th PDL). However, the control fibroblasts, which were not treated with 4NQO, senesced at the 62nd PDL. The finding that extensive, repeated treatments with 4NQO are required for the immortalization of normal human cells, indicates that multiple mutational events are involved in the immortalization of human cells in general. In other words, immortalization itself seems to be a multi‐step process. Karyotypic analysis showed that many cells were hypodiploid before immortalization, but that afterwards chromosomes were distributed broadly in the diploid to tetraploid regions. The immortalized cells showed amplification and enhanced expression of c‐myc. Two‐dimensional electrophoretic analysis showed that the number of disappearing cellular proteins was greater than the number of the newly appearing ones after the cells became immortalized. Since the immortalized cells showed neither anchorage‐independent growth nor tumorigenicity, they are useful for studying factors that can contribute to multi‐step carcinogenesis in human cells. In addition, genetically matched normal (OUMS‐24) and immortalized (OUMS‐24F) cells will be useful for analyzing the genes related to cellular mortality and immortalization.
Phenotypic and molecular analysis of ph1‐chromosome‐positive acute lymphoblastic leukemia cell lines
Authors: Miyagi T. , Ohyashiki J. , Yamato K. , Koeffler H. P. , Miyoshi I. 
Published: February 2007

AbstractWe have established 2 Philadelphia chromosome (Ph1)‐positive acute lymphoblastic leukemia (ALL) cell lines, designated PALL‐1 and PALL‐2, from distinct adult Ph1‐positive ALL patients. PALL‐1 was established in nude mice, and PALL‐2 was established in culture. Both retained the Ph1 chromosome and expressed the ALL type bcr/abl chimeric mRNA containing the junction of the first exon of BCR gene (eI) and second exon of c‐abl gene (a2). PALL‐1 and PALL‐2 expressed CD34 surface antigen which is characteristic of early hematopoietic progenitor cells. PALL‐2 expressed antigens for both pre‐B and early myeloid cells and had rearrangements of both the heavy chain of immunoglobulin gene and the β chain of T‐cell‐receptor gene. Both PALL‐1 and PALL‐2 expressed detectable levels of p53 gene RNA. Polymerase‐chain‐reaction‐single‐strand conformation polymorphism (PCR‐SSCP) analysis of the p53 gene showed a normal pattern of mobility in both cell lines. Taken together, the 2 cell lines had features of Ph1‐positive ALL (i) hematopoietic progenitor cells with pre‐B‐cell phenotype and, (ii) activation of el‐a2 type bcr/abl oncogene without alterations of p53 gene. These unique lines should provide a valuable tool for studying the pathogenesis of Ph1‐positive ALL.
Activators of coagulation in cultured human lung‐tumor cells
Authors: Seitz R. , Heidtmann H.‐H. , Maasberg M. , Immel A. , Egbring R. , Havemann K. 
Published: February 2007

AbstractTumor matrix generation and tumor cell growth are supported by coagulation processes within the tumor tissue. Activators of coagulation were searched for in suspensions of 9 permanent human squamous‐cell lung‐cancer (EPLC 32MI, U1752), large‐cell lung‐cancer (LCLC 97TMI, LCLC 103H, U 1810), and small‐cell lung‐cancer (N‐592, H‐526, DMS79, 86MI) cell lines. Incubation with these cells shortened the recalcification time in normal plasma (also in the presence of antibodies against tissue factor) or coagulation‐factor‐VII‐, VIII‐,IX‐or X‐deficient plasmas. The activators of coagulation in the 2 most active cell lines (U1752 and LCLC 103H) were further characterized in purified systems: the cleavage of chromogenic substrates, and the generation of markers of pro‐thrombin activation were assessed. Three activators of coagulation were found in intact or sonicated cell suspensions and culture supernatants: (i) a tissue factor (TF)‐like activity; (ii) an activity activating factor X, which in contrast to “cancer pro‐coagulant” was not inhibited by iodoacetamide; and (iii) an activity‐ activating pro‐thrombin, which was inhibited by the serine protease inhibitor PMSF and appeared to require plasmatic co‐factor(s). The heterogeneous expression of coagulation activators by lung‐tumor cell lines might be of significance for tumor biology and response to therapy.
Review article: Epidemiology of male breast cancer. A meta‐analysis of published case‐control studies and discussion of selected aetiological factors
Authors: Sasco Annie J. , Lowenfels Albert B. , Jong Pieternel Pasker‐De 
Published: February 2007

AbstractMale breast cancer is a rare tumour in all parts of the world. About 1% of all breast cancers occur in men, but the male/female ratio is higher among black than among white populations. This effect can be seen in US cancer registries and even more markedly in African data. A positive correlation exists on a population scale between male breast cancer and prostate cancer. Seven case‐control studies of male breast cancer are available, and a pooled analysis was conducted of the most commonly suspected risk factors. Male breast cancer appears to be associated with marital status: Mantel‐Haenszel exposure odds ratio (EOR) for never married = 1.6; 95% confidence limits (CL) = 1.1, 2.3, religion (EOR for being Jewish = 2.1; 95% CL = 1.4, 3.2), previous breast pathology (EOR for positive history of benign breast disease = 2.7; 95% CL = 1.7, 4.2), gynaecomastia (EOR for positive history = 6.2, 95% CL = 3.4, 11.4), previous testicular pathology (EOR for positive history = 2.2; 95% CL = 1.5, 3.3), previous liver diseases (EOR for positive history = 1.6; 95% CL = 1.0, 2.4) and family history of breast cancer (EOR for first‐degree relative with breast cancer = 2.5; 95% CL = 1.7, 3.7). No association is found with smoking history. Other potential risk factors such as reproductive history, education, occupation, anthropometric variables, association with various diseases, and specific exposures such as drug use, were not systematically evaluated in all studies and provide sometimes contradictory results, possibly due to small numbers of exposed subjects. Overall, the analytical epidemiology of male breast cancer presents similarities with the epidemiology of female breast cancer, with a potential role of factors related to hormonal status, relative hyperoestrogeny in men being potentially linked to increased risk of disease. Genetics may also play a role, with high risk linked to a familial history of breast cancer, and with a major risk in patients with Klinefelter's syndrome.
Prognostic significance of the proliferative potential of intracranial gliomas measured by bromodeoxyuridine labeling
Authors: Hoshino Takao , Ahn David , Prados Michael D. , Lamborn Kathleen , Wilson Charles B. 
Published: February 2007

AbstractThe growth potential of 174 intracranial gliomas was estimated by calculating the bromodeoxyuridine labeling index (BUdR LI). Each patient received a 30‐min infusion of BUdR, 200 mg/m2, before tumor removal. Excised tumor specimens were stained immunohistochemically to determine the BUdR LI, or percentage of S‐phase cells. A Cox proportional‐hazards stepwise model was used to determine the correlation between the BUdR LI and survival. Among patients with glioblastomas, the BUdR LI did not improve the prediction once age was entered in the model. Among patients with malignant or low‐grade astrocytomas, the BUdR LI was the best single predictor of survival. The relative predictive abilities of BUdR LI and histopathology were determined by analyzing malignant astrocytoma and glioblastomas together. Distinguishing between malignant astrocytomas and glioblastomas did not significantly improve the prediction of survival once the BUdR LI and age were entered into the model. Equations derived from the model indicate that the probability of survival is a function of age and BUdR LI in patients with glioblastoma or malignant astrocytoma, but is a function of BUdR LI alone in patients with low‐grade astrocytoma. The equations also show a substantial difference in the impact of increased BUdR LI on survival among patients with glioblastoma or malignant astrocytoma and those with low‐grade astrocytoma. Without highly effective treatments for specific tumor phenotypes, the survival of a patient with an intracranial glioma appears to depend strongly on the proliferative potential of the tumor. Thus, accurate estimates of the proliferative potential are important in predicting the survival of individual patients with gliomas as well as in evaluating the effectiveness of various types of treatment.
Trends in non‐melanocytic skin cancer treated in Australia: The second national survey
Authors: Marks R. , Staples M. , Giles G. G. 
Published: February 2007

AbstractAn Australia‐wide survey in 1985 recorded the highest rates of medically treated non‐melanocytic skin cancer (NMSC) ever reported. We report the findings of a repeat survey conducted in 1990. This second survey confirmed the differences, by age, sex, body site, latitude, country of birth and skin reaction to strong sunlight, that were observed in 1985. Over the 5‐year period certain changes were noted: the incidence of NMSCs increased by 19%, of basal‐cell carcinomas (BCC) by 11% and of squamous‐cell carcinomas (SCC) by 5%. With advancing age, men and women differed in their incidence, and this difference was greater for SCC than for BCC. Log‐linear modelling, however, failed to detect either a cohort or a survey effect between the 2 surveys. The proportional distribution of BCCs and SCCs by body site indicated an increase in BCCs on the trunk in both men and women, and half the proportion of SCCs on the head and neck in women as compared with men. The latitudinal gradients observed in 1985 were even stronger in 1990; the population living north of 37°s experienced a 30% increase in the incidence of treated NMSC between 1985 and 1990, while the population living south of 37s had a 25% decrease. The implications of these findings for cancer‐control initiatives are discussed.
Serological responses to HPV 16 in cervical dysplasia and neoplasia: Correlation of antibodies to E6 with cervical cancer
Authors: Ghosh Anna K. , Smith Nigel K. , Stacey Simon N. , Glew Susan S. , Connor Mary E. , Arrand John R. , Stern Peter L. 
Published: February 2007

AbstractSera from patients with cervical cancer, cervical intraepithelial neoplasia (CIN) and non‐genital cancers, and from healthy individuals, were investigated for antibodies to human papilloma virus (HPV) early proteins E4, E6 and E7 and the major capsid protein LI by Western blot analysis of recombinant HPV proteins. There was a significantly higher prevalence of sera with antibodies to E6 in cervical cancer patients than in healthy individuals or in CIN or non‐genital‐cancer patients. Antibodies to E7 were detected in 25% of cervical‐cancer patients, which is significantly higher than in HPV‐associated cervical lesions or in control populations, but not significantly different from the incidence in patients with non‐genital cancers. Antibodies to L I were found more frequently in CIN, while antibodies to E4 had a similar prevalence in cervical‐cancer, cervical‐dysplasia and non‐genital‐cancer groups, with 24% in the controls. The inability to detect antibodies to E6 and E7 in the majority of cervical‐cancer patients limits the application of this methodology to the monitoring of HPV infection and the development of cervical cancer. However, the latter approach may be useful in combination with other assay systems which allow detection of different, including conformational, epitopes of HPV E6 and/or E7 recombinant proteins.
Orthotopic transplantation of histologically intact clinical specimens of stomach cancer to nude mice: Correlation of metastatic sites in mouse and individual patient donors
Authors: Furukawa Toshiharu , Kubota Tetsuro , Watanabe Masahiko , Kitajima Masaki , Hoffman Robert M. 
Published: February 2007

AbstractFresh surgical specimens derived from 36 patients with advanced stomach cancer were orthotopically transplanted in nude mice using histologically intact tissue. Twenty of 36 patient tumors gave rise to locally growing tumors in the mice. All 20 patients whose stomach tumors resulted in local growth in the nude mice had clinical lymph‐node involvement, whereas 8 of the other 16 patients whose tumors were rejected had lymph‐node involvement. There was a statistical correlation(p <0.01) between local tumor growth in nude mice and clinical lymph‐node involvement. Of the 20 cases resulting in local growth in the nude mice, 5 had clinical liver metastases and all 5 cases resulted in liver metastases in the nude mice. Of the 20 cases, 6 had clinical peritoneal involvement of their tumor, and of these 5 resulted in peritoneal metastasis in the nude mice. There were statistical correlations (p < 0.01) for both liver metastases and peritoneal involvement between patients and mice. These results indicate that, after orthotopic transplantation of histologically intact stomach cancers from patients to nude mice, the subsequent metastatic behavior of the tumors in the mice closely correlated with the course of the tumors in the patients.
Correlation between the lung distribution patterns of Lu‐Ecam‐1 and melanoma experimental metastases
Authors: And Duzhang Zhu , Pauli Bendicht U. 
Published: February 2007

AbstractLu‐ECAM‐1 is a 90‐kDa lectin‐like, melanoma‐cell‐binding endothelial‐cell adhesion molecule that mediates colonization of the lungs by B16‐FIO melanoma cells. The well‐known formation of pleural and sub‐pleural B 16‐F10 melanoma colonies is correlated quantitatively with prominent histochemical staining of endothelia of pleural capillaries and sub‐pleural venules with anti‐Lu‐ECAM‐I MAb 6D3. The less frequent endothelial staining of perivenous and peribronchial venules is associated with fewer B16‐F10 colonies in these locations, and the occasional segmental staining of pulmonary veins coincides with rare tumor nodules which usually expand in an asymmetric fashion around these veins. Lu‐ECAM‐I is also expressed on endothelia of some tumor vessels, indicating that these vessels are recruited from the same host blood vessels that originally caused the arrest of blood‐borne B16‐F10 melanoma cells. The close association between the lung distribution patterns of Lu‐ECAM‐I‐positive blood vessels and experimental melanoma metastases is further evidence of the importance of endothelial‐ cell adhesion molecules in the formation of metastases.
Detection of a progression‐linked DNA restriction fragment in rat hepatoma cells probed with a hexokinase CDNA
Authors: Wigley W. Christian , Corson Gary E. , Nakashima Richard A. 
Published: February 2007

AbstractWe have compared genomic DNA isolated from a series of rat hepatomas and from normal rat liver tissue by restriction fragment analysis. Our objective was to identify a tumor‐specific restriction fragment that would be present in rapidly growing tumors and missing in normal tissues. Using a cDNA probe specific for the C‐terminal half of rat brain hexokinase, we have identified several changes in DNA restriction fragment lengths in rat hepatoma vs. normal rat liver. Most of these involved restriction fragments that were present in normal rat DNA and missing in tumor DNA. However, one Hinfl fragment of Mr = 13.4 kilobase pairs (kb) was found to be present in rapidly growing rat hepatomas, but missing in normal rat tissue and in hepatomas of slow or intermediate growth rate.
The development and characterization of vinca alkaloid‐resistant Caco‐2 human colorectal cell lines expressing mdr‐1
Authors: Hoskins Joann , Deherdt Sonja V. , Moore Robert E. , Bumol Thomas F. 
Published: February 2007

AbstractSeveral novel cell lines with variable resistance to Vinca alkaloids have been derived from the Caco‐2 human colorectal carcinoma cell line. Parental Caco‐2 cells were found by PCR analysis and immunofluorescence studies to produce a low amount of the mdr‐1 gene product (P‐glycoprotein) that may well be clinically significant. These cells, which were initially highly sensitive to desacetylvinblastine sulfate (DAVLB sulfate) were selected, without mutagenesis, through continuous culture with increasing concentrations of DAVLB sulfate over a 335‐day period. This selection resulted in cell lines that displayed an mdr (multiple‐drug‐resistance) cross‐resistance profile that could be reversed with agents such as verapamil and vindoline. During the selection process the amount of mdr‐I mRNA present, the extent of gene amplification and the amount of gp 170 expressed all correlated well with the level of drug resistance. However, this correlation does not hold in the absence of selective pressure for the more resistant cell lines where gene amplification and the amount of P‐glycoprotein present remained constant while the level of drug resistance and the amount of mdr‐l mRNA present declined. These cell lines are potential models for studying mdr‐1 gene expression and drug resistance in human epithelial malignancies.
Expression of autocrine motility factor receptor in serum‐ and protein‐independent fibrosarcoma cells: Implications for autonomy in tumor‐cell motility and metastasis
Authors: Watanabe Hideomi , Shinozaki Tetsuya , Raz Avraham , Chigira Masaki 
Published: February 2007

AbstractThe motile response of serum‐dependent (Gc‐4 SD) and protein‐independent (Gc‐4 PF) murine fibrosarcoma cells to monoclonal antibody (MAb) that binds to gp78 a cell‐surface receptor (M, 78,000) for an autocrine motility factor (AMF) was analyzed. The Gc‐4 PF cells responded to the anti‐gp78 by increased motility in vitro (3‐fold) and increased lung colonization in vivo (8‐to 20‐fold), while the serum‐dependent counter‐part failed to respond to motile stimulation both in vitro and in vivo. Immuno‐analysis of cell‐surface expression and cell extracts revealed a smaller amount of gp78 in Gc‐4 SD cells than in Gc‐4 PF cells. Both cell lines secrete an equal amount of AMF to the culture media. Our results suggest that protein‐free culture of Gc‐4 PF cells is associated with high response to AMF and with high expression of its receptor, and that autonomous motile regulation may play a role in tumor dissemination.
Effect of monoclonal antibody 17‐1A and gm‐CSF in patients with advanced colorectal carcinoma—long‐lasting, complete remissions can be induced
Authors: Ragnhammar Peter , Fagerberg Jan , Frödin Jan‐Erik , Hjelm Anna‐Lena , Lindemalm Christina , Magnusson Inger , Masucci Giuseppe , Mellstedt Håkan 
Published: February 2007

AbstractAntibody‐dependent cellular cytotoxicity (ADCC) is considered to be one of the effector functions of unconjugated monoclonal antibodies (MAbs) in tumor therapy. The antitumor activity of MAbs might therefore be augmented if the cytotoxic capability of the effector cells could be increased. In an in vitro system, the killing capacity of MAb was significantly enhanced by pre‐treatment of the effector cells with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Based on these findings, the therapeutic effect of the combination of mouse MAb 17‐IA (IgG2a) and GM‐CSF was evaluated in 20 patients with metastatic colorectal carcinoma (CRC). The patients received GM‐CSF for 10 days and a single i.v. infusion of MAb 17‐IA on day 3 of the cycle. Four cycles were given at 1‐monthly intervals. There was a continuous increase in blood monocytes and lymphocytes during all 4 GM‐CSF cycles. Neutrophils and eosinophils were also significantly augmented but in a biphasic manner and the cell counts on day 10 of cycle IV were significantly lower than in cycles I and II. GM‐CSF‐related side‐effects were of no major clinical importance. During the third cycle, an immediate‐type allergic reaction (ITAR) against MAb 17‐ IA occurred in most patients, necessitating reduction of the MAb dose as well as of the infusion rate. Two patients achieved complete remission. One patient had a minor response, and 3 other patients were considered to have stable disease >3 months.