The Wnt and the extracellular signal regulated-kinase (ERK) pathways are both involved in the pathogenesis of various kinds of cancers. Recently, the existence of crosstalk between Wnt and ERK pathways was reported. Gathering all reported results, we have discovered a positive feedback loop embedded in the crosstalk between the Wnt and ERK pathways. We have developed a plausible model that represents the role of this hidden positive feedback loop in the Wnt/ERK pathway crosstalk based on the integration of experimental reports and employing established basic mathematical models of each pathway. Our analysis shows that the positive feedback loop can generate bistability in both the Wnt and ERK signaling pathways, and this prediction was further validated by experiments. In particular, using the commonly accepted assumption that mutations in signaling proteins contribute to cancerogenesis, we have found two conditions through which mutations could evoke an irreversible response leading to a sustained activation of both pathways. One condition is enhanced production of beta-catenin, the other is a reduction of the velocity of MAP kinase phosphatase(s). This enables that high activities of Wnt and ERK pathways are maintained even without a persistent extracellular signal. Thus, our study adds a novel aspect to the molecular mechanisms of carcinogenesis by showing that mutational changes in individual proteins can cause fundamental functional changes well beyond the pathway they function in by a positive feedback loop embedded in crosstalk. Thus, crosstalk between signaling pathways provides a vehicle through which mutations of individual components can affect properties of the system at a larger scale.

Three different clinical courses were found in six patients with an HV-like eruption associated with chronic EBV infection: (i) spontaneous remission; (ii) clearing after photoprotection; and (iii) continuous recurrence irrespective of sun exposure. It is possible that there are two patterns of HV-like eruption associated with chronic EBV infection. One is characterized by recurrent necrotic papulovesicles of the face and the other by nodules and facial swelling. It was demonstrated that the skin lesions could be triggered by repeated UVA exposure in the patients showing recurrent necrotic papulovesicles of the face.

OBJECTIVE:To investigate an association between the metabolic syndrome (MS) and alanine aminotransferase (ALT) of normal ranges. DESIGN: A population-based cross-sectional survey in three rural communities, South Korea. SUBJECTS: A total of 1248 men and 2157 women aged 30 y and older. MEASUREMENTS: Body mass index (BMI), waist circumference, fasting blood lipid and glucose, resting blood pressure, and ALT. RESULTS: ALT and BMI increased with an addition of the MS components. A consistent association between ALT more than 15 IU/l and the MS was found in both sexes, independently of age, education, BMI, smoking, alcohol drinking, and sedentary life style. The odds ratios for the MS in the highest quintiles of ALT were 7.1-fold higher than the reference quintile in men and 2.1-fold higher in women. The likelihood ratio tests for trend were also significant with ALT increments (Po0.001 for trend). CONCLUSION: The MS is significantly associated with the higher quintiles of normal ALT in both genders. ALT could be a sensitive marker of hepatic dysfunction associated with the MS, even in the range below the current limit.

Bowenoid papulosis (BP) of the genitalia, characterized by the histological findings of a squamous cell carcinoma, follows a largely benign clinical course. The detection of oncogenic human papilloma viruses (HPV) from BP points to an aetiological role of these viral infections. A 47-year-old man with multiple genital skin lesions was seen over a 10-year period with the diagnosis of BP. Recently, he attended again with a recurrent genital tumour that was diagnosed as squamous cell carcinoma. His genital lesions progressed and became polymorphic in appearance, from a wart-like tumour to a reddish invasive plaque. To screen for the presence of different HPV sequences from different skin lesions and to correlate each HPV type with distinct clinical manifestations, polymerase chain reaction and single-strand conformational polymorphism (PCR-SSCP) were performed. PCR-SSCP revealed the presence of several types of HPV from different genital lesions. Sequencing results disclosed that he had a mixed infection of HPV6b, HPV16, HPV18 and HPV33, respectively. Interestingly, the clinical findings were fairly well correlated with the oncogenic potential of HPV found from each lesion.

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