Tanshinone-1 induces tumor cell killing, enhanced by inhibition of secondary activation of signaling networks.

Tumor multidrug resistance (MDR) can result from overexpression of drug transporters and deregulation of cellular signaling transduction. New agents and strategies are required for overcoming MDR. Here, we report that tanshinone-1, a bioactive ingredient in traditional Chinese medicine, directly killed MDR tumor cells and their corresponding parental cells, which was potentiated by inhibition of secondary activation of signaling networks. Tanshinone-1 was slightly more potent at inducing cytotoxicity and apoptosis in MDR cells than in corresponding parental cells. Tanshinone-1-induced MDR cell killing was independent of the function and expression of drug transporters but was partially correlated with the phosphatase-dependent reduction of phospho-705-Stat3, which secondarily activated p38-, AKT-, and ERK-involved signaling networks. Cotreatments with p38, AKT, and ERK inhibitors potentiated the anti-MDR effects of tanshinone-1. Our study presents a model for MDR cell killing using a compound of natural origin. This model could lead to new therapeutic strategies for targeting signaling network(s) in MDR cancers as well as new strategies for multitarget design.

Short-term hazards of low-dose radioiodine ablation therapy in postsurgical thyroid cancer patients.

During the last two decades, there has been a trend to use low-dose I-131 ablation therapy in patients with thyroid carcinoma without metastases. However, information regarding the incidence of acute adverse reactions in patients after low-dose radioiodine therapy has not been reported. In this study, the acute radiation effects after low-dose radioiodine ablation therapy in postsurgical differentiated thyroid cancer patients was evaluated. Fifty-six patients with differentiated thyroid cancer were prospectively evaluated. None of these patients had evidence of a distant metastasis. All patients received 40 mCi (1480 MBq) I-131 MIBG orally and were evaluated for symptoms and signs by a physician on the second and seventh days after therapy. Xerostomia and nausea were the most common complaints with the same incidence rate of 5.35%. Gastralgia occurred at a frequency of 3.57%. Pain in the thyroid bed, tenderness over a parotid gland, submandibular glands, change in taste, and vomiting all were found at a frequency of 1.78%. Maximum reactions generally occurred 24-48 hours after therapy. All the symptoms except for xerostomia resolved completely in most patients within a week. In comparison with high-dose ablation therapy published in the literature, the incidence of radiation reactions in low-dose radioiodine therapy was much lower. It was concluded that in patients without lymph node or distant metastases, low-dose I-131 MIBG therapy may be recommended to avoid the high incidence of local complications after high-dose treatment.

CPEO and carnitine deficiency overlapping in MELAS syndrome.

Mitochondrial myopathy, encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is one of the mitochondrial encephalomyopathies that has distinct clinical features including stroke-like episodes with migraine-like headache, nausea, vomiting, encephalopathy and lactic acidosis. We report a 27-year-old woman who presented with partial seizure, stroke-like episodes including hemiparesis, hemianopia and hemihypethesia, sensorineural hearing loss, migraine-like headache, and lactic acidosis. Brain computed tomographic scan showed encephalomalacia in the right parieto-occipital area and recent hypodensity in the left temporoparieto-occipital area with cortical atrophy. Muscle biopsy revealed ragged-red fibers and paracrystaline inclusions in the mitochondria. Genetic study revealed an A to G point mutation at nucleotide position (np) 3243 of mitochondrial DNA. External ophthalmoplegia and ptosis were also found during two exaggerated episodes in this patient. Therefore, the overlapping syndrome of chronic progressive external ophthalmoplegia in the MELAS syndrome is considered in this case. Furthermore, we also found carnitine deficiency in this patient and she was responsive well to steroid therapy. Muscle biopsy also revealed excessive lipid droplets deposits. Therefore, the carnitine deficiency may occur in MELAS syndrome with the A to G point mutation at np 3243. We recommend the steroid or carnitine supplement therapy be applied to the MELAS syndrome with carnitine deficiency.

[Effect of shenmai injection on sIL-2R NK and LAK cells in patients with advanced carcinoma].

Serum interleukin-2 receptor (sIL-2R) level activities of natural killer cell (NK) and lymphokine activated killer cell (LAK) cells were determined in 60 patients with advanced carcinoma (AC) before and after treatment with Shenmai injection (SMI), 40 healthy persons were taken as non-carcinoma control (NC). The results showed that: Serum sIL-2R level in AC were much higher than those in NC (P < 0.05) and activities of NK and LAK cells in AC were much lower than those in NC (P < 0.05) before treatment. There was no significant difference among gastric cancer, colonic carcinoma and lung cancer (P < 0.05). After treatment with SMI we also found that the level of sIL-2R in all patients were obviously lower (P < 0.05) while the activity of NK and LAK cells were significantly higher than that prior treatment (P < 0.05). Linear correlation was not found between sIL-2R and NK, LAK cells. These data suggested that the immune function was compromised in AC. The mechanism of the inhibitory effect of SMI on carcinoma might be related to the activity of biological response modifier.