Thalidomide suppresses melanoma growth by activating natural killer cells in mice.

Although thalidomide (Thd) is being extensively investigated for its effects on cytokine production and T cell costimulation, it is poorly understood whether it is capable of modulating the activities of natural killer (NK) cells. In this study, Thd effects on NK cell activity were examined with a murine model of melanoma, which is mostly rejected by NK cell-dependent mechanism. Administration of Thd significantly (p<0.01 on Day 21) suppressed the growth of subcutaneous B16F1 melanoma. In Thd-treated mice, marked splenomegaly and augmented splenocyte count were observed. Additionally, the percentage of splenic NK1.1+ cells was elevated to approximately 2.5-fold within 10 days after Thd treatment. The expression of interferon inducible protein (IP)-10, interferon (IFN)-gamma, interleukin (IL)-12 and IL-18 was remarkably upregulated. Production of the cytotoxic molecule perforin was also augmented. These data suggest that Thd strongly activates NK cell activity in mice, possibly resulting in enhanced tumor surveillance defense.

Gene expression profiles of oral leukoplakia and carcinoma: genome-wide comparison analysis using oligonucleotide microarray technology.

Although leukoplakia is the most common precancerous lesion of the oral cavity, its molecular biological properties are largely unknown. The aim of this study was to identify the genes responsible for its pathogenesis and malignant transformation using oligonucleotide microarray technology. The expression profiles of 8,800 genes in human oral leukoplakia (n=4) and oral squamous cell carcinoma (OSCC) (n=2) were analyzed using the Affymetrix GeneChip system and the results were confirmed with RT-PCR. Eight genes were up-regulated (>2.0-fold) and ten were down-regulated (<0.5-fold) in all leukoplakias analyzed with the GeneChip. In particular, loricrin and keratins displayed greater differences between normal tissue and leukoplakia. Some of the 18 alternatively expressed genes were markedly down-regulated in squamous cell carcinoma compared with leukoplakia. Our data suggested that gene abnormalities in cytoskeleton network components might be responsible for the development and progression of oral leukoplakia.

Effect of 5-fluorouracil on G1 phase cell cycle regulation in oral cancer cell lines.

5-fluorouracil (5-FU) has been widely used for chemotherapy of head and neck cancer, and is known to affect the cell cycle and induce apoptotic death of cancer cells. However, the molecular actions of 5-FU on the cell cycle regulatory mechanism have not been fully explained. Herein we analyzed the effects of 5-FU on the expression of G1/S-related cell cycle regulators in oral cancer cell lines. In vitro 5-FU treatment of oral cancer cells resulted in an increase in G1/S phase cells. p21 expression was augmented by 5-FU without any notable changes in p53 expression. A remarkable up-regulation of cyclin E and a concomitant down-regulation of cyclin D were observed after 24 h 5-FU treatment. Our results suggest that 5-FU-induced changes in cell cycle regulation of oral cancer cells might associate with an alteration of G1 cyclins expression. p21 was remarkably up-regulated, but it was speculated that its activity might be cancelled by an increased binding to CDK4.

[Studies on the prognostic factors of idiopathic acute sensorineural deafness].

Acute sensorineural deafness(ASD) presents with various hearing types, and dizziness and tinnitus are accompanied in some cases. The purpose of this study was to estimate the influence of risk factors, including dizziness and tinnitus, on the recovery of hearing acuity. Eighty-three patients who visited our hospital within 1 month from its onset and who were diagnosed with ASD between October 1998 and September 1999 were retrospectively reviewed. The patients whose etiology was defined, or whose symptoms shifted to inconsistent deafness were excluded. There were 35 males(ages ranged from 22 to 71 years; average 49 years) and 48 females(ages ranged from 17 to 79 years; average 46 years). The improvement rates were analysed using the following factors such as levels and hearing types at initial examination, interval between its onset and treatment, and presence or absence of dizziness and tinnitus. Concerning hearing types at initial examination, tan type or low sound disturbance type resulted in favorable prognosis. The patients whose treatment was started by the 7th day from its onset had significantly better prognosis than those whose treatment begun after 15 days. The patients who were complicated with tinnitus, especially accompanied with dizziness, indicated a significantly worse prognosis than those without tinnitus. Tan type or low sound disturbance type is a favorable factor, and tinnitus is an unfavorable factor for ASD prognosis. Though tinnitus generally is a significant factor for poor prognosis, this study remains to suggest that it alone causes the poor prognosis. The sooner treatment is provided indicates the better outcome.