Characterisation of the anti-bladder-cancer monoclonal antibody BLCA-8: Identification of its antigen as a neutral glycolipid

A monoclonal antibody, BLCA-8, was raised against the human bladder cancer cell line, UCRU-BL-17CL. By flow cytometry and immunoperoxidase staining, this antibody was found to possess high specificity for bladder tumours, some reactivity with fetal tissues, and no reactivity with normal bladder, or any normal or malignant tissue. This high specificity and the stability of the antigen to the urinary environment suggest that BLCA-8 may have potential for use as an anti-bladder-cancer therapeutic agent. By thin-layer chromatography and autoradiography, BLCA-8 was found to bind four components within the neutral lipid fraction of a bladder cancer cell line, UCRU-BL-17/23. These components hadR _F values of 0.22, 0.16/0.15 (doublet), 0.12 and 0.08, and migrated below globoside, indicating the presence of more than four sugars. By enzyme-linked immunosorbant assay and thin-layer chromatography it was found that the binding of BLCA-8 to the lipid extract was increased by both mild alkaline hydrolysis and enzymatic treatments, indicating that adjacent phospholipids and glycolipids interfere with the accessibility of the antibody-binding site. Full biochemical characterisation of the BLCA-8 antigen is currently underway.     

大肠癌中p53基因突变的研究

应用聚合酶链反应(PCR)──单链构型多态性(SSCP)结合银染法对14例大肠癌p53基因的第4、第5─6和第7外显子进行了点突变的研究,结果共检测出6例点突变,而且发现各外显子的突变频率存在差异。另外,利用购自ATCC的两个探针 (p53cDNA探针和pYNZ22探针)对大肠癌中p53基因的杂合性失去进行了研究,在14例大肠癌中共检出6例杂合性丢失。将点突变检测结果同杂合性丢失结果进行比较分析, 并着重探讨了大肠癌中p53基因失活导致肿瘤的作用方式。 Abstract:The exons 4-7 of p53 gene were examined in 14 colorectal Cancer patients by using PCR-SSCP-silver staining method.The results showed 6 cases of point mutation and the mutation frequencies of exons were different from each other.p53 cDNA and pYNZ22 VNTR were used as probes to examine LOH(Loss of heterozygosity)of 14 colorectal cancers.6 cases with LOH were found.The results of present research suggest that mutation and LOH of p53 gene are critical events in the progress and development of Cancer.There were different kinds of inactivation model of p53 gene in the process of development of cancer and transformation of cells.     

Cell-cell interactions influence oligosaccharide modifications on mucins and other large glycoproteins

Intratumoral phenotypic diversity is well documented with regard to tumor associated carbohydrate antigens (TACA). The factors which control the expression of these cell-surface oligosaccharides on different cells of the same tumor are not understood. We investigated the expression of a panel of mucin associated oligosaccharides in cell lines growing at different surface densities (number of cells per cm² of growth flask). Results show that the apparent expression of extended Le^a-Le^x, Le^a and Le^x, sialyl Le^a, Tn and sialyl Tn varies with density of growth by an invasive human squamous cell lung carcinoma cell line (NU6-1), a benign variant (NE-18) and the human lung epithelial cell line BEAS-2B. The results indicate that one of the factors influencing the apparent expression of mucin-associated oligosaccharides is cell-cell interactions.Abbreviations Mab monoclonal antibody - FIT fluorescein isothiocyanate - TACA tumor associated carbohydrate antigen     

A high resolution PIXE measurement for blood plasma ultrafiltrate

A new technique for investigation of elemental concentrations in subfractions of blood plasma is presented. The method is composed of the ultrafiltration of plasma in the presence of ethylenediaminetetraacetic acid (EDTA) and the measurement of the elemental composition by proton-induced X-ray emission (PIXE). The blood samples were collected from both healthy persons and patients suffering from breast cancer. The main emphasis in this study was on the determination of loosely bound copper (Cu) in plasma subfractions containing substances with molecular mass under 10,000, but zinc (Zn) and iron (Fe) contents of these fractions were also determined. The detection limits obtained with this method for Cu, Zn and Fe were ≈10 ppb (wet wt).     

A case-control study on selenium,zinc, and copper in plasma and hair of subjects affected by breast and lung cancer

The purpose of our study was to investigate the relationship between plasma and hair levels of Se, Zn, and Cu, and cancer. We selected a total of 66 patients affected by either breast (38) or lung (28) cancer. They entered into the study at the onset of disease, and before any chemical or radiotherapy. Controls were randomly selected among healthy people and were matched for sex, age, smoking habits, and residence. In the group of breast cancer, a significant decrease in hair Se was found compared to controls (p<0.01), whereas plasma Se was only slightly decreased. No difference between cases and controls was detected in both hair and plasma levels of Zn and Cu. Subjects who developed lung cancer were significantly lower in hair Zn (p<0.05) and Cu (p<0.01) than controls, whereas there was no difference with regard to Se. In addition, plasma Cu of these patients was increased as compared to controls.     

Ichnology and sedimentology of the early Permian deep-water deposits from the Lercara-Roccapalumba area (Western Sicily,Italy)

Summary Diverse and abundant trace fossils of the deep-waterNereites ichnofacies have been found in well-dated Early Permian deep-water turbidites (Lercara Formation) of western Sicily (Italy). Conodonts indicate a latest Artinskian to Cathedralian (late Early Permian) age. Microfossils (pelagic conodonts, albaillellid Radiolaria, paleopsychrospheric ostracods, foraminiferal associations dominated byBathysiphon), trace fossils (deep-bathyal to abyssalNereites ichnofacies) and sedimentologic data collectively indicate a deep-water environment for the Early Permian turbidites of the Lercara Formation. The dominance ofAgrichnium and of thePaleodictyon subichnogeneraSquamodictyon andMegadictyon suggests that this icnofauna is closely related in ichnotaxonomic composition to other late Paleozoic deep-water ichnofaunas. The occurrence ofAcanthorhaphe. Dendrotichnium andHelicoraphe, to date only reported from Cretaceous or Tertiary flysch deposits, suggests that the entire ichnofauna corresponds well to previously documented Silurian-Tertiary flysch ichnofaunas. Eight new ichnospecies and a new ichnosubgenus,Megadictyon, are described.     

Early Permian facies and paleogeography of the Southeastern Russian craton

Summary During the Early Permian deep-water basins existed in the southeastern part of the Russian craton. North and west of the Cis-Ural foredeep and the Precaspian depression (micro-ocean) carbonate platforms were formed on a shallow-marine shelf during the Asselian, Sakmarian and Early Artinskian. Reefs developed on the margin of these platforms along the slopes of the Cis-Ural foredeep and the Precaspian depression. The reefs shifted platform ward in the eastern areas, due to the tectonic subsidence of the platform margin and at the same time, prograded basinward in the south. Movements of continental blocks from the south during the Late Artinskian and Kungurian caused the separation of the Early Permian basin of the Russian craton from the Palaeo-Tethys, followed by evaporite sedimentation in the restricted basins. The existence of source rocks (bituminous deep-water sediments), thick reservoir rocks (limestones and dolostones), evaporitic seals and structural as well as stratigraphic traps are responsible for large productive gas and oil fields (e.g., Orenburg field), some of which are distinctly associated with reef carbonates.     

Early ordovician reefs from Argentina: Stromatoporoid vs stromatolite origin

Summary Late Arenigian biohermal reef mounds and biostromes within the shallow-marine platform facies of the upper San Juan Formation of the Precordillera (Western Argentina) represent a new Early Ordovician reef type. The meter-sized reefs are dominated byZondarella communis n.g. n. sp. The new taxon is characterized by domical, bulbous and laminar morphotypes exhibiting growth layers and thin horizontal and vertical as well as intermingled skeletal elements included within different sets. The fossil maybe compared with stromatolites and stromatoporoids but an interpretation as primitive stromatoporoids is favoured.     

Alternating bolus and continuous infusion 5-fluorouracil: a strategy to overcome resistance to this fluoropyrimidine in advanced colorectal cancer patients

Focusing our effort on the importance of FUra scheduling we have tested the hypothesis that pulse and continuous infusion (CI) of the fluoropyrimidine have different mechanisms of cytotoxicity. Our initial approach was to compare the mechanism of resistance of a cell line resistant to a short term exposure to FUra (HCT-8/FU4hR) to that of a cell line resistant to a prolonged exposure to the fluoropyrimidine (HCT-8/FU7dR). Cytotoxicity studies showed that HCT-8/FU4hR cells were still sensitive to FUra given as a 7-d exposure, suggesting different mechanisms of resistance. Indeed, rapid recovery of TS activity after drug removal was evident in the HTC-8/FU7dR cell line while HCT-8/FU4hR cells were similar to the parental cell line with regard to both the degree of in situ TS inhibition by FUra and duration of inhibition after FUra removal. In contrast, labelling studies with [³H-6] FUra (4 h exposure, 100 M) showed that the incorporation of the fluoropyrimidine into RNA is significantly decreased in HCT-8/FU4hR cells as compared to parental HCT-8 cells.Given the lack of cross resistance between the two schedulesin vitro, a pilot trial was done on patients with colorectal cancer refractory to bolus FUra. On 15 patients failing after FUra+LV or FUra alone 1 PR, 3 MR, 3 SD and 8 P were observed, confirmng a certain degree of activity of CI FUra in patients clinically resistant to bolus FUra.Based on this rationale, a phase II trial of schedule-oriented biochemical modulation of FUra in advanced colorectal cancer patients was conducted, employing a hybrid regimen of 2 biweekly cycles of FUra bolus (600 mg/sqm), preceeded by (24 h interval) methotrexate, 200 mg/sqm (in order to maximize the RNA effect of the drug) alternating with FUra continuous infusion, 200 mg/sqm daily for 3 weeks, modulated by leucovorin, 20 mg/sqm weekly bolus (in order to maximize the DNA effect).Thirty-three consecutive patients (median ECOG PS 1) with advanced measurable colorectal cancer and no prior therapy for metastatic disease entered the study, from February 1992 to August 1993. Three complete and 13 partial responses were obtained among these 33 patients (RR=48%, 95% confidence limis, 31–66%). After a median follow-up time of 23 months, 16 patients are still alive. The median progression free survival and overall survival were 9.6 and 20.8 months, respectively. No toxic deaths or grade 4 toxicity occurred. The incidence of grade 3 toxicity per patient in any cycle was: mucositis 6%, diarrhea 3% and vomiting 3% for the bolus part and 21%, 3% and 6% respectively, for the continuous infusion part of the regimen. Hand-foot syndrome occurred in 27% of the patients treated with the continuous infusion regimen.In conclusion, this experimental and clinical project has generated a novel regimen of schedule oriented biochemical modulation that is twice as active and half as toxic compared to bolus FU+LV given with either the daily x 5 or the weekly schedule. This high clinical activity is very encouraging, especially considering that 1) consecutive patients were entered, 2) the responses were independently reviewed, 3) the progression free survival and survival were much longer than those actually reported for this disease, 4) the toxicity of the program, in particular the bolus regimen, was relatively low allowing further intensification.     

Effect of sizofiran on regional lymph nodes in patients with head and neck cancer

The immunomodulating effects of preoperative sizofiran (SPG) administration on regional lymph nodes were studied in patients with stage III or IV head and neck cancer, by comparing the immunofunction of peripheral blood. The regional lymph nodes were dissected surgically, and freshly obtained mononuclear cells were studied to investigate the interleukin-2 (IL-2) production, the LAK and NK activities, and the quantitative analysis of the surface phenotype of the mononuclear cells. The results indicated that SPG enhanced immunological activities in the regional lymph nodes, as shown by increased IL-2 production and cytotoxic activities of the effector cells (NK, LAK), and increased helper T lymphocytes (CD4⁺) in the tumor-uninvolved lymph nodes. The immunofunction following SPG administration was attenuated, but was still augmented in the regional lymph nodes with metastases. Therefore, SPG was found to be a biologic response modifier to enhance the immunofunctions of the regional lymph node in patients with head and neck cancer.