DNMT3A governs tyrosine kinase inhibitors responses through IAPs and in a cell senescence-dependent manner in non-small cell lung cancer.

Patients with non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs) inevitably exhibit drug resistance, which diminishes therapeutic effects. Nonetheless, the molecular mechanisms of TKI resistance in NSCLC remain obscure. In this study, data from clinical and TCGA databases revealed an increase in DNMT3A expression, which was correlated with a poor prognosis. Using NSCLC organoid models, we observed that high DNMT3A levels reduced TKI susceptibility of NSCLC cells via upregulating inhibitor of apoptosis proteins (IAPs). Simultaneously, the DNMT3Ahigh subset, which escaped apoptosis, underwent an early senescent-like state in a CDKN1A-dependent manner. Furthermore, the cellular senescence induced by TKIs was observed to be reversible, whereas DNMT3Ahigh cells reacquired their proliferative characteristics in the absence of TKIs, resulting in subsequent tumour recurrence and growth. Notably, the blockade of DNMT3A/IAPs signals enhanced the efficacy of TKIs in DNMT3Ahigh tumour-bearing mice, which represented a promising strategy for the effective treatment of NSCLC.

[Cytokine responses after lobectomy for early non-small cell lung cancer: a prospective randomized comparison of video-assisted thoracic surgery and open thoracotomy].

OBJECTIVE: To compare video-assisted thoracic surgery (VATS) and open thoracotomy (OT) on acute inflammatory responses and immunosuppression after lobectomy for early non-small cell lung cancer (NSCLC). METHODS: Present prospective randomized study. OT or VATS lobectomy was performed in patients who met enter criteria and clinical data was collected. Plasma concentration of IL-6, IL-8 and IL-10 were measured before surgery and at postoperative day (POD) 1 and POD 3. There were 271 patients underwent lobectomy for early NSCLC, including of 133 patients in group VATS and 138 patients in group OT from January 2007 to June 2008. There were 132 males and 139 females, aging from 19 ∼ 70 years with a mean of (56 ± 8) years. RESULTS: Compared with OT group, shorter postoperative hospital stay [(8.2 ± 2.5) d vs. (9.8 ± 6.2) d, P = 0.03], lower morbidity rate (11.3% vs. 21.7%, P = 0.02) and lower increase of plasma concentration of IL-6 at POD 1 [(35 ± 25)% vs. (65 ± 43)%, P = 0.00], IL-6 at POD 3 [(14 ± 22)% vs. (55 ± 44)%, P = 0.00] and IL-10 at POD 1 [(25 ± 20)% vs. (43 ± 35)%, P = 0.00] were observed in patients of VATS group. CONCLUSION: VATS lobectomy for early NSCLC is associated with less acute inflammatory responses and less immunosuppression when compared with OT.

Bronchial angiolipoma.

Angiolipoma occurs preferentially in the extremities and trunk. We present a patient with involvement of the bronchus and describe successful localized resection of the lesion.

[The early outcome of video-assisted thoracic surgery lobectomy for primary lung carcinoma].

OBJECTIVE: To evaluate the early outcome of patients who underwent video-assisted thoracic surgery (VATS) lobectomy for primary lung carcinoma. METHODS: The records of 121 patients with lung cancer undergoing VATS lung resection from 1997 to 2004 were reviewed retrospectively, I stage: 101 cases, 34 cases underwent right upper lobectomy, 13 cases underwent right middle lobectomy, 17 cases underwent right down lobectomy, 21 cases underwent left upper lobectomy, 16 cases underwent left down lobectomy. Thirty-eight cases underwent VATS lobectomy without assisted mini-incision. RESULTS: There were 18 cases of morbidities (15%) and no surgical mortality. The 1-year, 2-year and 3-year survival rates of primary non-small cell lung cancer with I stage is: 99% (76/77), 96% (49/51) and 79% (15/19), respectively. There are statistic difference (P < 0.01) between adenocarcinoma and the others. There are no statistic difference (P > 0.05) between the VATS lobectomy with assisted mini-incision (n = 38) and without (n = 63), also no statistic difference (P > 0.05) between the VATS lobectomy and the standard procedure. CONCLUSION: Our findings suggest that VATS lobectomy is superior regarding its ability to achieve the same survival rates and little morbidities in comparison with the standard procedure.

[Surgical management for pulmonary metastasis].

OBJECTIVE: To investigate the indications of resection for lung metastasis, the surgical procedure and factors affecting the survival based on our experience accumulated for 37 years. METHODS: A total of 108 patients with pulmonary metastasis was treated by surgery. Pathology showed 93 carcinoma (86.1%) and 15 (13.9%) sarcoma. Totally 122 operations were performed: partial lung resection 51, segmental lobectomy 7, lobectomy 40, pneumonectomy 15. RESULTS: After surgery, the cumulative 1-, 3-, 5-, 7- and 10-year post-thoracotomy survivals were 87.9%, 47.3%, 31.7%, 23.7% and 13.9%, with an overall median survival of 34.8 months. Solitary lesions, disease-free interval (DFI) > 36 months, absence of extrathoracic disease and "open" thoracotomy were predictors of a longer survival whereas age, gender, symptom and pathology of the primary tumor were found statistically insignificant prognostic factors. CONCLUSION: Surgery should be undertaken for patients who do fulfill these criteria, and "open" thoracotomy is a better choice. Surgical treatment for patients with short DFI and multiple lesions should be attempted with prudence.

[Cooccurrence of pulmonary tuberculosis and carcinoma: diagnosis and the prognostic factors for surgical effects].

OBJECTIVE: To study the association, clinical diagnosis and treatment of the coexistence of lung cancer and tuberculosis. METHODS: Sixty-five patients with coexistence of lung cancer and tuberculosis underwent surgical treatment in our hospital between 1954.1 and 2004.3. Twelve factors possibly influencing the survival were selected. A multivariate analysis of these individual variables was performed using the cumulative survival rate by the computer' COX proportional hazard model. RESULTS: Histologically, there were 41 cases of squamous cell carcinoma, 15 adenocarcinoma, 3 small cell carcinoma and 6 mixed carcinoma. Chest radiological study showed infiltrative tuberculosis in 41, military tuberculosis in 2, and chronic fibrocavitary tuberculosis in 22 cases. Of these, wedge excision was performed in 4, lobectomy in 38, bilobectomy in 4, pneumonectomy in 17 and palliative resection in 2 patients. There was no operative mortality. Follow-up showed that 1-, 3- and 5-year survival was 67.7% (44/65), 35.4% (23/65), and 23.1% (15/65) respectively. Clinical analysis showed that the major significant prognostic factors influencing survival were malignancy occurred in local tuberculosis, the operation procedures for lung cancer, and the stage of lung cancer (P < 0.01). CONCLUSIONS: The occurrence of lung cancer is highly correlated to the site of tuberculosis. The recognize of this can facilitate the early diagnosis and resection of malignancy as well as the initiation of regular medical therapy.