The possible role of TNF-α and IL-2 in inducing tumor-associated metabolic alterations

This study was conducted to investigate the role of tumor necrosis factor- (TNF-) and interleukin-2 (IL-2) in inducing cancer cachexia, and the results were compared with those obtained from our previous study on Fisher 344 rats with methylcholanthrene-induced sarcoma. Three groups of male Fisher 344 rats received one of the following regimens: 4×10⁴ IU of human recombinant TNF- per rat per day subcutaneously (sc) for 5 consecutive days (n=5), 3.5×10⁵ U human recombinant IL-2 per rat per day sc for 14 consecutive days (n=5), or normal saline (n=5). The activities of both phosphoenolpyruvate carboxykinase (PEPCK) and malic enzyme (ME) were increased slightly in the IL-2 group. Furthermore, LPL activity was significantly increased in the adipose tissue of the TNF group and in the cardiac muscle of the IL-2 group, but not in that of the TNF group. These results show that there is a significant difference between the metabolic alterations seen in the tumor-bearing state and those induced by either TNF- or IL-2 alone. Thus, it is unlikely that IL-2 or TNF- is the sole mediator of cancer cachexia in this tumor and rat model.     

Phyllodes tumor of the breast with a grossly malignant appearance: A case report

A huge phyllodes tumor of the breast that appeared grossly malignant in a 43-year-old woman is described. The patient suffered from a large breast tumor that suddenly increased in size over 5 months to occupy the entire breast. The tumor was hard, ulcerated and 20 cm in greatest diameter. Diagnostic imaging (US, CT and MRI) demonstrated a circumscribed mass with a large cystic cavity. She underwent total mastectomy under a diagnosis of malignant breast tumor. Grossly, the cut surface of the tumor showed a large cystic cavity surrounding a fleshy, hemorrhagic and necrotic mass with a lobulared or trabeculared appearance. Unexpectedly, benign phyllodes tumor (PT) without any stromal overgrowth was diagnosed histologically. She has been doing well since total mastectomy. In our case and in many other reported cases, PT does not show any distinctive correlation between pathologic findings and tumor behavior. Thus wide local excision is the preferred initial treatment for PT.     

Primary pleomorphic adenoma in posterior cranial fossa

A 35-year-old woman had an intradural tumor in the posterior fossa adjacent to the posterior wall of the left pyramidal bone, which was totally removed and histologically diagnosed as a pleomorphic adenoma. Follow-up examination for 2 years showed no recurrence of the tumor. There was no primary lesion in any other gland of the body, and therefore there is no alternative but to conclude a “migration” of some gland cells. The pathogenesis of this tumor remains unclassified.     

Preclinical and clinical strategies for development of telomerase and telomere inhibitors

Background: Telomerase is an important enzyme whose activity has been convincingly demonstrated in humans recently. It is required for maintenance of ends of chromosomes (telomeres) during cell division. Since its presence has been selectively demonstrated in dividing cells including tumor cells, it has generated considerable excitement as a potential anti-cancer strategy.Design: In this article, we review the current relevant biology of the enzyme, the challenges encountered in the preclinical phase of target development and the current efforts that focus on telomeres and telomerase as therapeutic targets. We also speculate on the potential toxicities and mechanisms of resistance that may be encountered during use of such therapies.     

Discrepancy between E-cadherin protein expression and morphology in human gastric carcinoma cells

BACKGROUND/AIMS: The E-cadherin-mediated cell adhesion system is now considered to be an "invasion suppressor system" in cancer cells. The purpose of this study is to examine the effect of E-cadherin on morphogenesis of MKN28 human gastric carcinoma cell line in the course of E-cadherin antisense S-oligodeoxynucleotide (ODN) treatment. METHODOLOGY: The effect of E-cadherin antisense or random S-ODN treatment on cell growth, morphology in monolayer culture, and E-cadherin protein expression of MKN28 cells were evaluated. Further, immunohistochemical examination was performed. RESULTS: Cell growth under 3-microM and 6-microM E-cadherin antisense S-ODN treatment did not differ from that under random S-ODN treatment. Although the expression of E-cadherin was decreased assuredly at the time of 6 days after 3-microM E-cadherin antisense S-ODN treatment by immunohistochemical examination, cell-cell adhesion was still observed until Day 10 after the treatment. On Day 15, the cells lost the cell-cell adhesion and showed the detachment and intercellular slits at least. Expression of the insoluble fraction of E-cadherin protein decreased in E-cadherin antisense S-ODN treatment cells at 6 days. CONCLUSIONS: In this study, we demonstrated that discrepancy between E-cadherin protein expression and morphology exists in MKN28 cells treated with E-cadherin antisense S-ODN treatment.     

Metalloselenonein, the selenium analogue of metallothionein: synthesis and characterization of its complex with copper ions.

We used an automated peptide synthesizer to produce a peptide, metalloselenonein, that contains selenocysteine residues substituted for all cysteine residues in Neurospora crassa copper metallothionein. Metalloselenonein binds 3 mol of Cu(I) per mol. This adduct shows a broad absorption band between 230 and 400 nm and a fluorescence band at 395 nm, which can be attributed to copper-selenolate coordination. The circular dichroism spectrum of the copper-metalloselenonein complex shows a positive band around 245 nm attributable to asymmetry in metal coordination.     

p53 point mutations in primary human gastric carcinomas

Summary p53 point mutations in primary gastric carcinomas were analyzed by performing cDNA deoxynucleotide sequencing of the gene. Out of 16,9 (56.3%) primary gastric carcinoma cases, including early cancer, showed one or more p53 point mutations in their open-reading frame, and 4 out of 9 cases had a p53 point mutation within highly conserved domains. The characteristics of the p53 mutation spectrum observed in primary tumors were (a) frequent mutation at an A:T pair (50%, 7 out of 14 mutations), (b) high transversion incidence (29%, 4 out of 14 mutations), (c) no transition at CpG, and (d) no G:C to T:A transversion. Our results suggest that p53 mutation is a common event in gastric carcinoma occurring from the early stage of progression with its specific mutation spectrum.Abbreviation PCR-SSCP polymerase chain reaction single-strand conformation polymorphism     

Lymphoid crisis with T-cell phenotypes in a patient with Philadelphia chromosome negative chronic myeloid leukaemia

A case of Philadelphia (Ph1) chromosome negative chronic myeloid leukaemia (CML) developed lymphoid crisis. Immunological marker studies disclosed that the lymphoid cells were sheep erythrocyte-rosetting-, Leu-1+, Leu-5+, OKT-4+, OKT-8+, common ALL antigen-, HLA-DR-, cytoplasmic and surface immunoglobulin-, MAS 036C(antithymocyte)+ (after in vitro culture) and terminal deoxynucleotidyl transferase-, indicating T-cell phenotypes, probably of common thymocytes. Cytochemical staining also demonstrated immature T-cell characters: dot-positivity for acid phosphatase and beta-glucuronidase, and negative for acid alpha-naphthyl acetate esterase. All bone marrow metaphases exhibited normal karyotypes. Our observation suggests that the neoplastic features of a common stem cell for myeloid and lymphoid cell lines are very similar in Ph1 positive and negative CMLs, and that the stem cell can differentiate towards T-lineage.