Triptolide induces S phase arrest via the inhibition of cyclin E and CDC25A and triggers apoptosis via caspase- and mitochondrial-dependent signaling pathways in A375.S2 human melanoma cells.

Triptolide (TPL), a diterpene triepoxide compound, extracted from Tripterygium wilfordii Hook F. [a traditional Chinese medicinal herb (TCM)], has demonstrated great chemotherapeutic potential for the treatment of tumors. However, the anticancer mechanisms of action of TPL in human skin cancer remain to be further investigated. In this study, we used A375.S2 human melanoma skin cancer cells as a model to investigate the effect of TPL on cell death. A375.S2 cells were treated with various concentrations of TPL for different periods of time and investigated the effects on cell cycle distribution and apoptosis were investigated. The data showed that TPL induced cell morphological changes, decreased the percentage of viable cells, and induced S phase arrest and apoptosis in A375.S2 cells in a concentration- and time-dependent manner. Furthermore, we used flow cytometry analysis and the data showed that TPL promoted reactive oxygen species, NO and Ca2+ production, decreased the mitochondrial membrane potential (ΔΨm) and increased the activity of caspase-3, -8 and -9 in the A375.S2 cells. Western blot analysis showed that TPL promoted the expression of p21 and p27 but inhibited that of cyclin A and CDC25A, leading to S phase arrest. Furthermore, the data also showed that TPL promoted the expression of Fas and FasL and increased the activity of caspase-3, -8 and -9, cytochrome c, Bax, apoptosis-inducing factor (AIF) and endonuclease G (Endo G); however, the expression of Bax was decreased, leading to apoptosis. Based on these observations, TPL induces apoptosis in A375.S2 cells through Fas-, caspase- and mitochondrial-mediated pathways.

Evaluation of genotoxicity and subclinical toxicity of Agaricus blazei Murrill in the Ames test and in histopathological and biochemical analysis.

This study was conducted in order to assess the safety and tolerability of Agaricus blazei Murrill (ABM) in general toxicological studies by Ames tests in vitro and in 28-day feeding toxicity experiments. There were no dose-dependent increases or decreases in the number of revertant colonies both with and without metabolic activation in Ames tests. Doses of 10, 5 and 0.1 mg/per mouse of ABM daily were administered by oral gavage to mice (n=10) for 28 days. The effects on clinical observations, clinical pathology, and histopathology were evaluated. There were no significant changes in the brain, heart, kidney, liver, spleen, adrenal gland, testes or ovaries visually. With increasing doses, male and female treated mice did not show any gradual elevation of serum concentration in any of the nine items we examined, except for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in females. The AST levels of the treatment by medium or high dose and the ALT levels of the treatment by high dose in females were abnormal in comparison to those of the baseline control group, with significant differences. On studying the histological changes in mice, tissue sections of negative control and experimental groups exhibited no apparent pathological alterations. In summary, the Ames test, pathology determinations, biochemical analysis and routine blood parameters were all normal, except for AST and ALT in females. Results showed that the statistical differences observed in one sex were not observed in the other and were not dose dependent.

Primary cardiac lymphoma.

Primary cardiac lymphoma (PCL) has rarely been reported in Chinese populations. PCL mostly occurs in the right atrium. The clinical manifestations may be variable and are attributed to its location, the presence of congestive heart failure, pericardial effusion, arrhythmia, and cardiomegaly. The prognosis is usually poor because it is usually found too late and therefore, clinicians should be aware of PCL. Imaging examinations are the best methods for initial diagnosis and include echocardiography, computed tomography (CT) scan, magnetic resonance imaging (MRI), and radioisotope scan. However, the final diagnosis is made by pathology, such as cytologic examination of the effusive fluid and tissue biopsy. Because the tumors are difficult to resect, the main treatment for the disease is chemotherapy, which can be successful. Here, we report a 58-year-old man who had a tumor measuring 8 x 5 cm in the right atrium. By clinical staging, including chest X-ray, echocardiography, CT scan of the abdomen, MRI of the heart, whole body tumor Gallium scan, and gastrointestinal series, no metastatic lesion or involvement was found in other parts of the body. Pathologic findings including cytology of pericardial effusion and heart tumor biopsy revealed the case as a diffuse large B-cell lymphoma. After chemotherapy with COP (cyclophosphamide + vincristine + prednisone) and CHOPBE (COP + doxorubicin + bleomycin + etoposide) regimens, the intracardiac tumor had disappeared, but the patient survived for 12 months in total, despite additional radiotherapy over the pericardial lesions. It was presumed that because the tumor was very large and involved all 3 layers of the heart, it did not respond as well to the therapy as expected.