Determination of serum glycosylated proteins in normoglycemic patients with cancer

The nitroblue tetrazolium "fructosamine" test was elaborated by Johnson et al. in 1982. It gives an easy evaluation of the degree of non enzymatic glycosylation of serum proteins. This degree, like the percentage of HbA1C, is a biochemical test of the average level of glycemia and so is useful in diabetic patient management. The authors test "fructosamine" with a Kone-Progress automated analyzer on blood collected without anticoagulant or antiglycolytic substances; if iodoacetate is added to the blood sample, they observed a partial inhibition of chemical reaction. The results of the tests carried on two groups of normoglycemic patients with localized and metastatic cancers don't show significant statistical difference with healthy subjects. The nitroblue tetrazolium test can be used to manage diabetics patients suffering from cancers; however for metastatic and cachectic patients, an accelerated turn-over of proteins might decrease the non enzymatic glycosylation degree.     

Estrogen receptor and alpha-fetoprotein in human breast cancer: brief communication.

Concentrations of estrogen receptor (ER) and alpha-fetoprotein were determined by dextran-coated charcoal assay and analyzed with Scatchard plots and radioimmunoassay, respectively, in cytosols of 72 human breast cancers. The values for ER ranged from 0 to 340 fmoles/mg cytosol protein. The concentrations of alpha-fetoprotein, which were low in all tumor cytosols examined, ranged from less than 0.1 to 1.1 ng/mg cytosol protein. No positive relationship was found between ER and alpha-fetoprotein concentrations. These results show that ER, but not alpha-fetoprotein, usually accounts for most of the high estrogen-binding capacity in cytosols of human breast cancers.     

Detection of nuclear matrix proteins in serum from cancer patients.

Morphological characteristics of the cell nucleus have long been used by pathologists in the clinical diagnosis of cancer. The nuclear matrix of the cell, the structure that serves to organize the chromatin within the nucleus, is known to reflect these morphological characteristics with regard to cell and cancer type. Monoclonal antibodies were developed to extracted nuclear matrix proteins. These antibodies were used in two-site immunometric assays to detect soluble nuclear matrix proteins in the supernatants of two dying cell lines and 15 tumor tissues. Furthermore, nuclear matrix proteins were detected at elevated levels in the sera of cancer patients compared with normal patient sera. In one assay, 63.2% of cancer sera read above 95% of normal sera, and in another assay, 73.7% of cancer sera read above 95% of the normal sera. With the development of monoclonal antibodies with greater cancer specificity, the detection of circulating nuclear matrix proteins may become an important clinical tool in the diagnosis and monitoring of cancer.     

Interactions between "fever" proteins and normal serum proteins in febrile cancer patients.

When analyzed by cationic discontinuous electrophoresis in urea-containing polyacrylamide gels, plasma or serum from febrile individuals contains trace quanitites of five protein bands that are not recognizable in the blood of normal individuals. These proteins appear and disappear in parallel in sequential samples. Cerebrospinal fluid from febrile and nonfebrile individuals contains a protein band that is electrophoretically identical with only one of these proteins. Since the trace proteins migrate, in urea-containing polyacrylamide gel electrophoresis, as if they has molecular size of less than or equal to30,000 daltons, their absence from cerebrospinal fluid implies the existence, in vivo, of interactions between them and other serum proteins. Under nondissociating conditions, four of the bands appear to circulate in physical interaction with one another. In molecular sieve chromatography at neutral pH in lipid-free sera, the trace proteins have an approximate molecular size of 165,000 daltons; in lipemic sera they have a molecular weight of larger than or equal to200,000 daltons. Their behavior in gel filtration and in ion-exchange chromatography excludes extensive interaction with any of the following: immunoglobulin M, immunoglobulin G, alpha2-macroglobulin, haptoglobin, and albumin. Interactions between these and other serum proteins are reduced by high concentrations of urea and by low PH. The mechanisms responsible for the observed protein-protein associations would appear to include electrostatic attraction, hydrogen bonding, and weak hydrophobic interaction.     

Improving communication with cancer patients

If doctors and nurses involved in cancer care are to help patients and their families achieve an optimal level of quality of life and psychological adjustment they must be able to carry out key communication tasks successfully. Yet, objective scrutiny of their consultations confirms that deficiencies in their ability to conduct these tasks remain. The reasons for this are dicussed before important innovations in training and their impact are described.     

Improving communication with cancer patients

If doctors and nurses involved in cancer care are to help patients and their families achieve an optimal level of quality of life and psychological adjustment they must be able to carry out key communication tasks successfully. Yet, objective scrutiny of their consultations confirms that deficiencies in their ability to conduct these tasks remain. The reasons for this are discussed before important innovations in training and their impact are described.     

A surface antigen associated with Hodgkin's disease: brief communication.

We used an indirect immunofluorescence technique to detect a surface antigen that may be associated with Hodgkin's disease (HD). A heteroantiserum raised in a rabbit given an injection of cells obtained from an HD lymph node (Stage I, classification of Lukes and Butler) allowed us to detect an antigen on the surfaces of HD-derived cells in 25 of 27 instances. Benign and malignant non-HD-type lesions (both lymph node and spleen) did not have this antigen. The nature of this antigen and the type of cells bearing it are unknown.     

Evaluation of AFP glycosylation heterogeneity in cancer patients with AFP-producing tumors

It has been postulated that analysis of alpha-fetoprotein (AFP) glycosylation heterogeneity in cancer patients whose AFP levels are elevated (e.g., non-seminomatous germ cell tumors, ovarian germ cell tumors and primary hepatocellular carcinoma) might provide useful clinical information. We undertook a study to determine whether scrutiny of AFP glycosylation heterogeneity in patients with non-seminomatous germ cell tumors would provide information useful in diagnosis, staging, prognosis, or monitoring for recurrence of disease following therapy. While an analysis of AFP glycosylation heterogeneity using Concanavalin A lectin chromatography did not provide useful information in regard to staging or prognosis, it does supply unique information useful in discriminating between benign liver dysfunction (e.g. alcoholic hepatitis, chemotherapy-related liver damage) and that due to nonsemininomatous germ cell tumors. It was also concluded that an analysis of Concanavalin A binding patterns is not sufficient to discriminate between recurrent non-seminomatous germ cell tumor and primary hepatocellular carcinoma in patients with elevated serum AFP.     

Detection of metastatic tumors in nude mice: brief communication.

Homozygous nude (nu/nu) mice were inoculated ip with either highly malignant human bladder transitional cell carcinoma or human prostate adenocarcinoma. These animals were subsequently given injections of normal human T-lymphocytes to restore the known T-lymphocyte deficiency present in homozygous nude mice. Metastatic spread of the prostate and bladder carcinomas was evident in mice given human T-lymphocytes. Although tumor growth was observed at the sites of tumor inoculation, no tumor spread was observed in mice not receiving T-lymphocytes.     

宫颈癌广泛子宫全切及盆腔淋巴结清除术后血清蛋白质变化

目的比较宫颈癌患者在广泛子宫切除和盆腔淋巴结清除手术前后血清中蛋白质的变化,寻找评价治疗效果的可能性指标。方法采用铜离子结合芯片、表面增强激光解吸离子化飞行时间质谱仪以及配套软件,检测49例宫颈癌及71例年龄相配的健康女性血清,筛选出一组有分类意义的差异蛋白质。用同样的方法检测35例宫颈癌广泛子宫切除和盆腔淋巴结清除手术后10d及术后3个月的血清,比较这一组差异蛋白质的变化。结果宫颈癌与正常对照组比较,共有47种蛋白质质谱峰差异有统计学意义(P<0.05),有分类意义的蛋白质有6种,质荷比(M/Z)为M8929.31、M7930.52、M9127.31、M8141.01、M7963.06和M9280.63,在宫颈癌患者中低表达,含量明显低于正常对照,用质荷比为M8929.31的蛋白质建立决策树分类模型,敏感性为97.96%(48/49),特异性为98.59%(70/71)。经手术治疗后,除M/Z为M9280.63的蛋白质较手术前略有下降外(P>0.05),其余5种则明显回升(P<0.05),术后3个月时复查,这6种蛋白质继续回升(P<0.05)。结论质荷比为M8929.31、M7930.52、M9127.31、M8141.01、M7963.06及M9280.63的一组蛋白质与宫颈癌密切相关,有可能成为评价宫颈癌治疗效果以及判断预后的一组指标。     

Lung cancer in coastal Georgia: a death certificate analysis of occupation: brief communication

A comparison of death certificate statements on occupation for 858 white males who lived in coastal Georgia counties and who died of lung cancer during 1961--74, and for 858 controls who were of the same age and county of residence revealed a twofold excess risk of lung cancer associated with the construction industry. No elevated risk of lung cancer was found for workers in the wood and paper industries in the urban areas of Savannah, Brunswick, or Waycross, but a threefold increase was uncovered for the remaining coastal counties where the wood and paper industry was the largest employer.     

Heat shock proteins: stress proteins with Janus-like properties in cancer.

Heat shock proteins (HSPs) were first identified as stress proteins that confer resistance to physical stresses such as elevated temperatures in all cellular organisms. HSPs are rapidly elevated after stress and confer a temperature resistant phenotype. Temperature resistance is dependent on the ability of HSPs to function as molecular chaperones and prevent aggregation and on the capacity of Hsp27 and Hsp70 to act as wide spectrum inhibitors of the cell death pathways. HSP expression becomes deregulated in cancer leading to elevated expression. Elevated HSP expression promotes cancer by inhibiting programmed cell death (Hsp27, Hsp70) and by promoting autonomous growth (Hsp90) and leads to resistance to chemotherapy and hyperthermia. Tumor HSPs have another property that can be exploited in therapy. They are immunogenic and can be used to form the basis of anticancer vaccines. Elevation in HSP levels may thus have competing effects in tumor growth, being required for tumor cell survival but conferring a hazard for cancer cells due to their immunogenic properties. This dichotomy is also reflected by the approaches used to target HSP in therapy. Pharmacological approaches are being employed to inhibit activity or expression of tumor HSP. Immunological approaches aim at increasing HSP levels in cells and tissues with the aim of increasing tumor antigen presentation to the immune system.     

Alterations in serum levels of insulin-like growth factors and insulin-like growth-factor-binding proteins in patients with colorectal cancer

It has been reported that insulin-like growth factor (IGF) II is associated with human primary colorectal tumors and colon-carcinoma cell lines. Here, we examine alterations in circulating levels of IGFs and IGF binding proteins (IGFBPs) in patients with colorectal carcinoma, and compare them to age- and nutrition-adjusted references. We report (i) an increase in serum IGF-11 concentrations (about 2-fold), whereas IGF-1 concentrations are regarded as normal when aging is taken into account; (ii) an apparent increase in serum IGFBP-3 levels when compared to those of healthy elderly subjects, IGFBP-3 only being detected in the 150-kDa IGFBP ternary complex as in normal serum; (iii) abnormally elevated serum IGFBP 2 levels taking into account the apparent concentrations of IGFBP-3. This simultaneous elevation of IGFBP-3 and IGFBP-2 in the serum of patients with colorectal tumors appears to be unique in that it reflects a break in the inverse relationship between the serum IGFBP-3 and IGFBP-2 levels that is observed in normal and in several physiopathotogical conditions. Moreover, it enables a distinction to be made between 76.5% (13/17) of patients with colorectal carcinoma and normal adults, age-related healthy aged and malnourished patients. We propose that the disturbed serum IGFBP profile observed in the patients with colorectal cancer may be a consequence of oversecretion of IGF-11 by the tumor cells. The usefulness of IGFs and IGFBPs as potential colorectal tumor-associated metabolic markers should be further investigated. © 1994 Wiley-Liss, Inc.     

Prognostic relevance of serum hyaluronan levels in patients with breast cancer.

The serum hyaluronan (HA) level of 238 women with breast cancer was measured by means of a specific radiometric assay. The results show no significant increase in serum HA when compared to levels in 120 control sera. A number of prognostic factors were evaluated including stage of disease, lymph-node involvement, tumour size, histology and presence of oestrogen and progesterone receptors in the tumour. No correlation was found with serum HA concentration and we conclude that serum HA level is of no prognostic significance in breast cancer.