Development and validation of prognostic models for small cell lung cancer patients with liver metastasis: a SEER population-based study.

BACKGROUND: This study was to establish and validate prediction models to predict the cancer-specific survival (CSS) and overall survival (OS) of small-cell lung cancer (SCLC) patients with liver metastasis. METHODS: In the retrospective cohort study, SCLC patients with liver metastasis between 2010 and 2015 were retrospectively retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly divided into the training group and testing group (3: 1 ratio). The Cox proportional hazards model was used to determine the predictive factors for CSS and OS in SCLC with liver metastasis. The prediction models were conducted based on the predictive factors. The performances of the prediction models were evaluated by concordance indexes (C-index), and calibration plots. The clinical value of the models was evaluated by decision curve analysis (DCA). RESULTS: In total, 8,587 patients were included, with 154 patients experiencing CSS and 154 patients experiencing OS. The median follow-up was 3 months. Age, gender, marital status, N stage, lung metastases, multiple metastases surgery of metastatic site, chemotherapy, and radiotherapy were independent predictive factors for the CSS and OS of SCLC patients with liver metastasis. The prediction models presented good performances of CSS and OS among patients with liver metastasis, with the C-index for CSS being 0.724, whereas the C-index for OS was 0.732, in the training set. The calibration curve showed a high degree of consistency between the actual and predicted CSS and OS. DCA suggested that the prediction models provided greater net clinical benefit to these patients. CONCLUSION: Our prediction models showed good predictive performance for the CSS and OS among SCLC patients with liver metastasis. Our developed nomograms may help clinicians predict CSS and OS in SCLC patients with liver metastasis.

Growth-inhibitory and apoptosis-inducing effects of tanshinones on hematological malignancy cells and their structure-activity relationship.

This study has investigated the growth-inhibitory and apoptosis-inducing effects of dihydrotanshinone, tanshinone I, tanshinone IIA, and cryptotanshinone on hematological malignancy cell lines, aiming to explore their structure-activity relationship. The growth-inhibitory effects of the tanshinones on K562 and Raji cells were assessed using a modified MTT assay; the apoptosis-inducing effects were assessed by fluorescence microscopy and flow cytometry analysis. The changes in cellular morphology were observed using an inverted phase-contrast microscope. MTT results revealed that these tanshinones inhibited cell proliferation in a concentration-dependent and time-dependent manner. The IC50 values of dihydrotanshinone, tanshinone I, tanshinone IIA, and cryptotanshinone for K562 cells were 3.50, 13.52, 19.32, and 47.52 µmol/l at 24 h; 1.36, 4.70, 5.67, and 22.72 µmol/l at 48 h; and 1.15, 1.59, 2.82, and 19.53 µmol/l at 72 h, and the values for Raji cells were 3.30, 4.37, 12.92, and 52.36 µmol/l at 24 h; 1.55, 1.71, 6.54, and 25.45 µmol/l at 48 h; and 1.07, 1.38, 1.89, and 18.47 µmol/l at 72 h. The flow cytometry analysis demonstrated that these tanshinones induced apoptosis of K562 cells in a concentration-dependent manner, and dihydrotanshinone as well as tanshinone I were more potent than tanshinone IIA and cryptotanshinone. Some noticeable apoptotic morphologies could be observed by fluorescence microscopy on tanshinones-treated Raji cells. Collectively, these tanshinones caused growth inhibition and apoptosis in hematological malignancy cell lines, with dihydrotanshinone being the most potent, followed by tanshinone I, tanshinone IIA, and cryptotanshinone. These results suggested that the structure of aromatic ring A enhanced the cytotoxicity and the structure of ring C may have contributed to the cytotoxicity, but the mechanisms need to be further investigated.

[Growth inhibition of tanshinones on SPC-A-1 cell line and their structure-activity relationship].

BACKGROUND AND OBJECTIVE: Numerous studies have shown that Tanshinones have anti-tumor effects in vitro, but few studies were focusing on the anti-tumor activity of Tanshinones against one special cancer cell line. The aim of this study is to investigate the growth inhibition effect of four Tanshinones on SPC-A-1 cell line and the relationship between their structures and cytotoxicity. METHODS: The modified MTT assay was adopted to measure the inhibition effect of Tanshinones on SPC-A-1 cells at different concentrations at 24 h, 48 h and 72 h, and the changes of cell morphology were observed by inverted phase contrast microscope. RESULTS: Tanshinones could inhibit the proliferation of SPC-A-1 cells effectively, and their cytotoxicities on SPC-A-1 cells are all in concentration-dependent and time-dependent manners. The IC50 of dihydro-Tanshinone I, Tanshinone I, Tanshinone IIA and Cryptotanshinone at 24 h were 2.77 µg/mL, 6.01 µg/mL, over 10 µg/mL and over 10 µg/mL, at 48 h were 1.80 µg/mL, 4.04 µg/mL, 8.12 µg/mL, 8.71 µg/mL, at 72 h were 1.36 µg/mL, 1.69 µg/mL, 3.81 µg/mL, 7.35 µg/mL, respectively. CONCLUSIONS: All of the four Tanshinones have proliferation inhibitory effects on SPC-A-1 cell line, among which the Dihydrotanshinone I is the most active one, followed by Tanshinone I, Tanshinone IIA and Cryptotanshinone subsequently. The results showed that the structure of aromatic ring A could enhance the cytotoxicity and the structure of furan ring C would influence the cytotoxicity, but the mechanism is still remained to be further investigated.

[Inhibitory effect of tanshinones on proliferation of K562 cell line and its structure-activity relationship].

The study was purposed to investigate the growth inhibitory effect of tanshinones on K562 cell line and the relationship between their structures and cytotoxicity. The modified MTT assay was adopted to measure the inhibitory effect of tanshinones at different concentrations and chemical structures on K562 cells, and the changes of cell morphology were observed by inverted phase contrast microscopy. The results indicated that the tanshinones could inhibit the proliferation of K562 cells effectively, and their cytotoxicities on K562 cells showed concentration- and time-dependent manners. The IC(50) of dihydrotanshinone I, tanshinone I, tanshinone IIA and cryptotanshinone at 24 hours were 0.91, 4.04, 5.95, 13.85 µg/ml at 48 hours were 0.37, 1.35, 1.71, 6.71 µg/ml; at 72 hours were 0.33, 0.46, 0.82, 6.02 µg/ml, respectively. It is concluded that all of the four tanshinones have proliferation inhibitory effect on K562 cell line, among them the dihydrotanshinone I is the most active one, followed by tanshinone I, tanshinone IIA and cryptotanshinone subsequently, indicating that the chemical structure of aromatic ring A of tanshinones can enhance their cytotoxicity and the structure of furan ring C may influence the cytotoxicity, but their mechanism is still remained to be further investigated.