PAD4 inhibitor promotes DNA damage and radiosensitivity of nasopharyngeal carcinoma cells.

Peptidylarginine deiminases 4 (PAD4), a kind of enzyme capable of converting protein arginine or mono-methylarginine into citrulline, has been identified to display a key role in diverse diseases. Radiotherapy is frequently used in nasopharyngeal carcinoma (NPC) treatment and induces DNA double strand breaks. In this study, whether PAD4 inhibitor YW3-56 affects the radiosensitivity of NPC cells was explored. RT-qPCR, immunofluorescence, western blot, clonogenic survival, and flow cytometry assays were used to assess the function of PAD4 and YW3-56 in NPC. We found the upregulation of PAD4 expression in NPC cells. PAD4 overexpression suppressed NPC cell apoptosis and promoted cell cycle, while PAD4 depletion had an opposite result. Moreover, the survival of NPC cells after irradiation was increased by overexpression of PAD4. PAD4 overexpression inhibited DNA damage and sensitivity of NPC cells to irradiation. Functional assays showed that YW3-56 treatment promoted DNA damage, apoptosis, and radiosensitivity of NPC cells. Importantly, YW3-56 treatment inhibited tumor growth in vivo. Overall, this study revealed the efficacy of PAD4 inhibitor YW3-56 in promoting sensitivity of NPC cells to irradiation.

Prognostic implications of survivin and lung resistance protein in advanced non-small cell lung cancer treated with platinum-based chemotherapy.

Platinum-based chemotherapy is the first-line treatment for non-small cell lung cancer (NSCLC), but the chemotherapy often results in the development of chemoresistance. The present study aimed to explore the prognostic implications of survivin and lung resistance protein (LRP) in advanced NSCLC treated with platinum-based chemotherapy. Tumor samples were collected from 61 hospitalized patients with stage IIIB-IV NSCLC that underwent platinum-based chemotherapy. All patient samples were collected in the Oncology Department of the Third Affiliated Hospital of Guangxi Medical University between January 2006 and January 2011. Cytoplasmic survivin and LRP expression were evaluated using immunohistochemistry. The expression of LRP and survivin reached 77% (47/61) and 76% (45/61), respectively. Positive expression of survivin was associated with a lower median progression-free survival (PFS) time (4 vs. 9 months; P=0.038) and a lower median overall survival (OS) time compared with the absence of survivin expression (9 vs. 16 months; P=0.039). Patients with LRP and survivin expression (n=41) demonstrated a median PFS time of 4 months. However, patients with either LRP or survivin expression (n=10) demonstrated a median PFS time of 8 months, which is similar to the median PFS time of the 10 patients with no expression of LRP and survivin (9 months; P=0.022). Either the expression of survivin or the combined expression of LRP and survivin is associated with a poor prognosis in advanced NSCLC treated with platinum-based chemotherapy.

[Combination of gemcitabine and carboplatin in the treatment of advanced non-small cell lung cancer].

BACKGROUND: To evaluate the efficacy and toxicity of the combination of gemcitabine and carboplatin in the treatment of patients with advanced non-small cell lung cancer (NSCLC). METHODS: Forty-one patients with locally advanced (stage IIIB) or metastatic (stage IV) NSCLC were enrolled into the study. The patients received gemcitabine 1 000 mg/m² on days l, 8 and 15, and carboplatin AUC 5 on day 1, with 28 days as a cycle. Each patient received at least two cycles. RESULTS: Of the 41 patients, 2 cases got complete response, 18 got partial response, 15 had stable disease, and 6 had progressive disease, with an overall response rate of 48.8%. The response rate was 55.6% (10/18) in the initial patients, and 43.5% (10/23) in the retreated patients (P > 0.05). The median survival duration was 11.8 months. The 1-year survival rate was 49%. There were 29 patients whose KPS score increased. The main toxicities were leukopenia (incidence of 34.1% for grade III+IV) and thrombocytopenia (incidence of 29.3% for grade III+IV). CONCLUSIONS: The combination of gemcitabine and carboplatin is a feasible, well-tolerated and active scheme in either first-line or second-line treatment of advanced NSCLC.

[Clinical application of lung biopsy through CT-guided percutaneous paracentesis].

BACKGROUND: To explore the significance of lung biopsy through CT-guided percutaneous paracentesis in the diagnosis of space-occupying lesions of the lung. METHODS: Thirty-five patients with space occupying lesions of the lung underwent lung biopsy through CT-guided percutaneous paracentesis and DLTRA-CUT 16G, 18G or 20G soft-tissue-cutting biopsy needles and PICKER IQ computerized tomograph were used. RESULTS: Of the 35 patients, 26 were confirmed by pathological examination to suffer from primary malignant tumor, 1 from metastatic carcinoma, 3 from tuberculosis and 3 from inflammatory pseudotumor. No definite diagnosis was made in two patients. The diagnostic rate was 94.3%. After operation, minor pneumothorax occurred in 5 cases and traces of blood in sputum in 2 cases, however, they didn't need any treatment. CONCLUSIONS: Lung biopsy through CT-guided percutaneous paracentesis is a safe and practical technique and may be widely used in hospitals if conditions permit.