Effect of a Cyclooxygenase-2 Inhibitor in Combination with (-)-Epigallocatechin Gallate or Polyphenon E on Cisplatin-Induced Lung Tumorigenesis in A/J Mice.

We investigated the effects of celecoxib combined with (-)-epigallocatechin-3-gallate (EGCG) or polyphenon E in a cisplatin-induced lung tumorigenesis model. Four-week-old female A/J mice were divided into seven groups: (i) Control, (ii) 150 mg/kg celecoxib (150Cel), (iii) 1,500 mg/kg celecoxib (1500Cel), (iv) EGCG+150 mg/kg celecoxib (EGCG+150Cel), (v) EGCG+1,500 mg/kg celecoxib (EGCG+1500Cel), (vi) polyphenon E+150 mg/kg celecoxib (PolyE+150Cel), and (vii) polyphenon E+1,500 mg/kg celecoxib (PolyE+1500Cel). All mice were administered cisplatin (1.62 mg/kg of body weight, i.p.) 1×/week for 10 weeks and sacrificed at week 30; the numbers of tumors on the lung surface were then determined. The tumor incidence and multiplicity (no. of tumors/mouse, mean±SD) were respectively 95% and 2.15±1.50 in Control, 95% and 2.10±1.29 in 150Cel, 86% and 1.67±1.20 in 1500Cel, 71% and 1.38±1.24 in EGCG+150Cel, 67% and 1.29±1.38 in EGCG+1500Cel, 80% and 1.95±1.36 in PolyE+150Cel, and 65% and 1.05±0.10 in PolyE+1500Cel. The combination of high-dose celecoxib with EGCG or polyphenon E significantly reduced multiplicity in cisplatin-induced lung tumors.

Prognostic nutrition index affects the prognosis of patients undergoing trimodality therapy for locally advanced non-small cell lung cancer.

PURPOSE: Trimodality therapy, comprised of induction chemoradiotherapy (iCRT) followed by surgery, is a highly invasive treatment option for locally advanced non-small cell lung cancers (LA-NSCLCs; defined as a heterogenous disease). We conducted this study to investigate the prognostic nutritional index (PNI) of LA-NSCLC patients undergoing trimodality therapy, which has not been studied in detail before. METHODS: The subjects of this retrospective study were 127 patients who underwent trimodality therapy between 1999 and 2016. We measured the PNI at three points: before iCRT (pre-iCRT), before the operation, and after the operation. RESULTS: PNIs decreased significantly as treatment progressed. Patients with clinical T3/4 (cT3/4) disease had a significantly lower PNI than those with cT1/2 disease, but the extent of lymph-node metastasis did not affect the PNI at any point. Using the cut-off values of receiver-operating curve analyses, multivariable analyses revealed that a high PNI pre-iCRT correlated significantly with a better survival of LA-NSCLC patients, especially those with cT3/4 disease (hazard ratio 3.84; 95% confidential interval 1.34-12.5, P = 0.012). CONCLUSIONS: Measuring the PNI before trimodality therapy is important for predicting the clinical outcome of patients with LA-NSCLC, with differing predictive ability according to the disease extent. Perioperative intensive nutritional intervention must be considered for patients who undergo trimodality therapy for LA-NSCLC.

Basal segmental auto-transplantation after pneumonectomy for advanced central lung cancer.

In patients with central lung cancer that extensively involves the bronchus/pulmonary artery, a double-sleeve lobectomy is often difficult to perform. We describe a case of post-pneumonectomy basal segmental auto-transplantation using a lung preservation technique that uses cold low-potassium dextran glucose solution to protect the lung graft from ischaemia-reperfusion injury during the ex situ division of the segmental graft and the pathological investigations for the clearance of the surgical margins. A right basal segmental auto-transplantation procedure was performed in a patient with stage-IIIA squamous cell lung cancer. This technique could allow extensive pulmonary resection while minimizing the loss of pulmonary reserve.

Epidermal growth factor receptor mutation status and adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung.

PURPOSE: Adjuvant chemotherapy with uracil-tegafur has been demonstrated to prolong survival among patients with resected lung adenocarcinomas. Epidermal growth factor receptor (EGFR) mutations have been reported to be present in lung adenocarcinomas. The present study evaluated whether the EGFR status could be used as a biologic predictor of the outcome of adjuvant chemotherapy with uracil-tegafur. PATIENTS AND METHODS: The EGFR mutational status of 187 patients with resected lung adenocarcinomas was determined using a polymerase chain reaction-based assay for EGFR exons 19 and 21; the results were then correlated with the effect of adjuvant uracil-tegafur chemotherapy on survival. The antiproliferative effect of fluorouracil (FU) on adenocarcinoma cell lines with EGFR wild-type or mutant type status was examined by measuring the inhibitory concentrations at 50% (IC(50)s). RESULTS: Among the 187 patients, 68 received uracil-tegafur as adjuvant chemotherapy, and 119 were not treated with any chemotherapeutic agents. EGFR mutations were present in 79 patients (43%). Overall, the adjuvant chemotherapy with uracil-tegafur significantly prolonged survival compared with the control group (hazard ratio = 0.38; P = .005). The survival benefit of adjuvant chemotherapy with uracil-tegafur was also examined after stratifying the patients according to EGFR mutation status. Adjuvant chemotherapy significantly prolonged survival among patients with EGFR wild-type tumors (hazard ratio = 0.34; P = .013) but not among patients with EGFR mutant tumors. In an in vitro experiment, the IC(50)s of EGFR mutant cells to FU were higher than those of wild-type cells, indicating that EGFR wild-type cells are more sensitive to FU than mutant cells. CONCLUSION: EGFR status influenced the effect of adjuvant chemotherapy with uracil-tegafur. Adjuvant chemotherapy could be customized based on EGFR status.

[A successful case of lower gingival cancer with pulmonary metastases by adjuvant chemotherapy including paclitaxel, cisplatin and 5-fluorouracil following a surgical procedure].

We report a successful case with pulmonary metastases from lower gingival cancer by a surgical procedure and four cycles of adjuvant chemotherapy including paclitaxel (PTX), cisplatin (CDDP) and 5-fluorouracil (5-FU). A 47-year-old woman underwent chemotherapy with CDDP and 5-FU after an operation for lower gingival squamous cell carcinoma and its neck lymph node metastases. At 4 months from the initial treatment, pulmonary metastatic lesion was resected by video-assisted thoracoscopic surgery (VATS). Fourteen months later, pulmonary metastatic lesion was found and dissected again using VATS. Furthermore, the patient was treated by adjuvant chemotherapy with PTX 135 mg/m(2) over 3 hours on day 1, CDDP 75 mg/m(2)on day 2 and 5-FU 350 mg/m(2)/day by continuous intravenous infusion on day 2 through 5. After that, there is no evidence of pulmonary recurrence for more than six years.