Long-term primary culture of mammalian cells has been always difficult due to unavoidable senescence. Conventional methods for generating immortalized cell lines usually require manipulation of genome which leads to change of important biological and genetic characteristics. Recently, conditional reprogramming (CR) emerges as a novel next generation tool for long-term culture of primary epithelium cells derived from almost all origins without alteration of genetic background of primary cells. CR co-cultures primary cells with inactivated mouse 3T3-J2 fibroblasts in the presence of RHO-related protein kinase (ROCK) inhibitor Y-27632, enabling primary cells to acquire stem-like characteristics while retain their ability to fully differentiate. With only a few years’ development, CR shows broad prospects in applications in varied areas including disease modeling, regenerative medicine, drug evaluation, drug discovery as well as precision medicine. This review is thus to comprehensively summarize and assess current progress in understanding mechanism of CR and its wide applications, highlighting the value of CR in both basic and translational researches and discussing the challenges faced with CR.

ObjectiveCurrently, concurrent chemoradiotherapy has become the standard treatment for locally advanced non‐small cell lung cancer, but it is often difficult for elderly patients to tolerate. In this study, we evaluated the curative effect, acute radiation reaction, and clinical application of stereotactic radiotherapy with whole‐body gamma‐knife combined with pemetrexed treatment in elderly patients with locally advanced lung adenocarcinoma.MethodsA total of 37 elderly patients with lung adenocarcinoma from Hubei Provincial Armed Police Corps Hospital from 2 January 2013 to 30 December 2015, who were treated with stereotactic radiotherapy with super‐gamma‐knife, were included in the study. The radiotherapy plan was made according to the patient's physical condition, tumor location and size, and therapeutic purpose. A dose of 3.5–5 Gy was administered by 50–70% isodose curve, with a total dose range of peripheral irradiation 35–45 Gy. In the same period, pemetrexed was administered at 500 mg/m2, the first day of chemotherapy (d1), intravenous drip, with 21 days as one cycle, and the number of cycles was more than two.ResultsThe median follow‐up duration was 18 months, and the 1‐, 2‐, and 3‐year follow‐up rates were 86.49% (32/37), 59.46% (33/37), and 21.62% (8/37), respectively. There were no missing cases. After 2–3 months of treatment, computed tomography showed that 13 patients (35.14%) had complete remission, 22 patients (59.46%) had partial remission, one patient (2.70%) achieved a stable status, and one patient (2.70%) still had progression, and the total response rate was 94.59%. The 1‐year local control rate was 67.57%. The 1‐, 2‐, and 3‐year overall survival rates were 86.49%, 45.45%, and 25.00%, respectively. The median overall survival time was 17.0 months (95% CI 14.5–21.3 months); the progression‐free survival time was 12.0 months (95% CI 11.6–12.8 months). Multivariate analysis showed that lymph node stage N ≥2 and radiotherapy biological effective dose <60 Gy were the adverse prognostic indicators of overall survival (P = 0.016 and P = 0.032, respectively). The 1‐year local control rate and median survival time were 62.50% and 71.43%, and 19 and 17 months in the gross tumor volume ≥120 cm3 subgroup and gross tumor volume <120 cm3 subgroup, respectively. There was no significant statistical difference (P = 0.061 and P = 0.400, respectively). The incidence rates of grade 3–4 neutropenia and thrombocytopenia were 10.81% (4/37) and 5.41% (2/37), respectively, during the period of concurrent chemoradiotherapy. The incidence of grade 2 radiation‐induced pneumonitis and esophagitis was 13.51% and 16.22%, respectively. No grade >2 acute or late lung and esophagus toxicity was observed.ConclusionsIn elderly patients with lung adenocarcinoma, stereotactic body radiotherapy with super‐gamma‐knife combined with pemetrexed treatment is safe and definitive, with mild adverse effects.

Objective With the development of interventional therapy and precise radiotherapy, such as 3‐D conformal intensity‐modulated radiation therapy and stereotactic body radiotherapy (SBRT), transarterial chemoembolization (TACE) combined with radiotherapy has become an important method of comprehensive treatment for advanced liver cancer. However, few studies focus on the treatment of massive hepatocellular carcinoma (HCC) with SBRT. In this study, we investigated the effects and prognostic factors of whole‐body gamma‐knife SBRT combined with TACE in the treatment of massive HCC. Methods A retrospective analysis was carried out in 81 patients with massive, who received super gamma‐knife (type SGS‐I) SBRT after TACE treatment between 2 January 2011 and 30 June 2016. The curative effects were evaluated using the Modified Response Evaluation Criteria in Solid Tumors criteria. The alpha‐fetoprotein and alanine aminotransferase levels were measured before and after treatment. Patients were followed up for overall survival and 1‐, 3‐, and 5‐year survival rates. Adverse reactions were evaluated using the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer criteria. Results A total of 81 patients were evaluated, including 29 patients with complete response, 48 patients with partial response, two patients with stable disease, and two patients with progressive disease; the total response rate was 95.06%. The 1‐year local control rate was 71.60%. The overall survival rates at 1, 3, and 5 years were 81.48%, 40.74%, and 16.67%, respectively. The median survival time was 15.0 months (95% CI 10.1–19.8 months). Progression‐free time was 11.0 months (95% CI 9.5–14.4 months). The alpha‐fetoprotein level after treatment was (85.53 ± 21.36) μg/L and was significantly lower than that before treatment (635.62 ± 125.83 μg/L; t = 8.189, P = 0.002). The alanine aminotransferase levels were 70.34 ± 16.60 and (54.95 ± 12.02) U/L before and after treatment, respectively, and were not significantly different (t = 1.348, P = 0.624). Multivariate analysis showed that a portal vein tumor thrombus (χ2 = 4.727, P = 0.016) and the Child–Pugh grade of liver function (χ2 = 4.893, P = 0.013) were adverse prognostic factors of overall survival. The 1‐year local control rates and the median survival times were 72.03% and 71.17%, and 16 and14 months, respectively, for the clinical target volumes ≥120 cm3 and <120 cm3 subgroups; there were no statistical differences in these parameters (P = 0.923 and P = 0.845, respectively). The main adverse reactions during treatment were gastrointestinal effects, fatigue, and radioactive liver injury, mainly grades 1–2. The adverse reactions could be relieved by symptomatic treatment. Conclusions SBRT with a super gamma‐knife combined with TACE for the treatment of massive HCC had a significant clinical effect and mild side‐effects. Therefore, this approach is worthy of clinical promotion and application.