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The Gaoligong Mountains are characterized by large variations in elevation and topography, which support high levels of biodiversity and endemism that remain largely understudied. Herein, based on the integration of morphological comparisons and phylogenetic reconstruction, we describe a new species of Rhacophorus from the northern Gaoligong Mountains, Yunnan Province, China. The new species, Rhacophorus dulongensis sp. nov., is morphologically distinguishable from its congeners based on the differences in body size, head length, tibia length, snout and tongue shape, toe webbing formula and coloration, ventral skin texture and coloration, dorsal pattern and coloration, body macroglands, iris coloration, and pattern of markings on flanks. Phylogenetically, it differs from its congeners by uncorrected p-distances of >4.8% for the 16S rRNA gene fragment. Rhacophorus dulongensis sp. nov. is likely to be found in Myanmar, considering its type locality lies close to the China-Myanmar border. The phylogenetic analysis revealed that the “widespread” species, R. rhodopus, is a species complex and a composite of five distinct lineages. The results revealed that R. napoensis is also found in Vietnam, making it a new country record for Vietnam. Interestingly, R. dulongensis sp. nov. likely breeds in bamboo, a hidden behavioral characteristic that makes them easy to overlook. Given the ongoing habitat loss and degradation in the region, further biological exploration is urgently needed in the Gaoligong Mountains as a biodiversity reservoir.

Abstract The torrent frogs of the genus Amolops represent a great anuran diversification in southern China and Southeast Asia. Previous studies have shown that, the diversity of this genus still remains underestimated. During herpetological surveys from 2021 to 2022, several Amolops specimens were collected from the international border regions of southwestern Yunnan Province, China. Herein, we utilized molecular phylogenetic and morphological data to identify these specimens. Our findings indicate the presence of a separate and previously unknown lineage in the A. viridimaculatus group, which we formally describe as a new species. Furthermore, the specimen from Xishuangbanna National Nature Reserve clustered with A. vitreus from the paratype, supporting the morphological diagnosis. Therefore, we describe a new species and a new species record for China. Our study contributes to the species richness of the genus Amolops as well as the diversity of amphibians in China. Notably, our discovery brings the total number of Amolops species to 85 and the total number of torrent frog species known to occur in China to 53. In addition, our study further confirmed that Yunnan and Indochina Peninsula have similar faunal composition, implying that more studies are needed to achieve a complete understanding of the species diversity and distribution pattern.

To date, 10 species of the genus Microhyla have been recorded in China, of which six were distributed in Yunnan Province. Microhyla hmongorum Hoang, Nguyen, Phan, Pham, Ninh, Wang, Jiang, Ziegler, and Nguyen, 2022 was also speculated to be distributed in Xishuangbana, Yunnan Province, China. However, there is no evidence of documentation of M. hmongorum.We report the first country record of Microhyla hmongorum, based on specimens collected from Yunnan border region. Morphologically, the specimen was consistent with the original descriptions of M. hmongorum. Phylogenetically, the sequences of the specimens from China clustered with the sequence of type specimens of M. hmongorum from Vietnam, with uncorrected pairwise distances of 0.9% at the 16S gene fragment analysed. Therefore, we report M. hmongorum as a new record species in China.

Abstract Objective Standard medical treatment for early non‐small cell lung cancer (NSCLC) is surgery; however, stereotactic body radiotherapy (SBRT) can be a viable substitute for elderly patients who can no longer tolerate or refuse surgery. The unsurpassed care for elderly patients with early NSCLC remains inconclusive. We conducted a propensity‐score matching analysis to compare the efficacy and side‐effects of SBRT and video‐assisted thoracic surgery (VATS) in elderly patients with pathologically‐proven early NSCLC. Methods This single‐institution retrospective study included 310 elderly patients who underwent VATS (n = 180) or SBRT (n = 130) from January 2011 to November 2018 at the Tianjin Medical University Cancer Institute and Hospital. Sex, performance status, pathology type, Charlson Comorbidity Index, and T‐stage according to the eighth tumor node metastasis classification were considered when performing propensity‐score matching. Results After propensity‐score matching, 71 patients were included in each group for analysis. A median follow‐up period of 53.5 months was observed for all patients; 72 and 53 months for patients undergoing VATS and SBRT, respectively. Overall survival (p = 0.492), progression‐free survival (p = 0.294), locoregional recurrence‐free survival (p = 0.866), and distant metastasis‐free survival (p = 0.452) did not differ significantly between the VATS and SBRT groups. Multivariate analysis showed a significant correlation between the T‐stage and overall survival. However, treatment‐related toxicity was lower in the SBRT group than in the VATS group. Conclusions SBRT is an option comparable with surgery for elderly patients with pathologically‐proven early‐stage NSCLC.

Amolops putaoensis is a recently described torrent frog species from A. monticola group that is known only from its type locality, northern Myanmar. We compared morphology and mitochondrial DNA sequence data from ten recently collected adult male specimens from the upper Dulong River System in Gongshan County, Yunnan Province, China, to the original description of A. putaoensis. Both datasets strongly supported referring the Chinese specimens to A. putaoensis, extending the known range of this species by approximately 133.7 km distance into China. Molecular phylogenetic analyses recovered A. putaoensis to be closely related to A. aniqiaoensis, A. kohimaensis, A. monticola, and A. adicola. We use the newly collected Chinese specimens to expand the morphological description of the species.

Asian leaf-litter toads of the genus Leptobrachella represent charismatic anuran diversification with 80 species, of which 25 are from China. Recent new discoveries suggest that the diversity of this genus is underestimated. Here, we describe a new species of Leptobrachella, Leptobrachella bashaensis sp. nov. from the Basha Nature Reserve, Congjiang County, Guizhou Province, China. The new species is distinguished from its congeners by the following suite of morphological traits: small body size (SVL 22.9–25.6 mm in six adult males and 27.1 mm in one adult female); head longer than wide; dorsal skin slightly shagreened with small tubercles; creamy-white chest and belly with irregular black spots; distinct ventrolateral glands forming a white line; finger webbing and fringes absent; toe webbing rudimentary and lateral fringes narrow; iris bicolored with bright orange in upper half and silver in lower half; dorsal surface of tadpole head dark brown with small, brown, irregular spot, air sac-shaped bulges on both sides of body. The new species differs from all known congeners by an uncorrected p-distance of >5.3% of the 16S rRNA gene fragment examined, and the phylogenetic analysis clusters the new species with L. maoershanensis and L. laui. At present, the new species is only known from a small range of montane evergreen secondary forests in Basha Nature Reserve approximately 900 m elevation. Its natural history and conservation status are discussed.

Abstract There has been no previous study on the efficacy of the thoracic radiotherapy (TRT) in oligometastatic or polymetastatic extensive stage small-cell lung cancer (ES-SCLC) to the overall survival (OS). In a group of 270 ES-SCLC cases retrospective study, 78 patients (28.9%) had oligometastases and 192 (71.1%) had polymetastases, among which 51 oligometastatic patients (65.4%) and 93 polymetastatic patients (51.6%) received TRT. Propensity score matching (PSM) was utilized. The 2-year OS, progression free survival (PFS) and local control (LC) in oligometastatic and polymetastatic patients were 22.8% and 4.5% (p

OBJECTIVE To investigate an initial approach of radiotherapy, which produces cellular radiation injury by high dose in one fraction. METHODS Human pancreatic carcinoma cell line MIA PaCa-2, was cultivated and divided into 5 groups: 0, 2, 5, 10, 17 Gy. Cultivated cells were irradiated by 6MV-X ray in one fraction. Analysis were done as follows: comet assay, which assessed the level of DNA damage in the treated cells right a er the cell was irradiated, fl ow cytometry, which was performed at 0, 6, 12, 24, 36 h a er the cell line treated to asses changes of its cell cycle, DNA ladder, which quantitatively assessed the degree of DNA injury after 6 and 12 h, and histological examination, which analyzed cellular morphology a er 24 h. RESULTS (1) A er X-ray irradiated, the morphological change of human pancreatic carcinoma cell line (MIA PaCa-2) was mainly swelling. (2) When the dose of radiation was lower than 10 Gy, increasing the dose could greatly improve cell necrosis, apoptosis and blockage of cell cycle in G2/M phase, which was consistent with the theory of radiation biology. (3) When radiation dose was more than the 10 Gy, the peak of apoptotic necrosis appeared strong and early. (4) The degree of DNA injury was also related to the dose of radiation therapy and most obvious in the 10 Gy group and not so obvious in the 17 Gy group. (5) When dose was less than 10 Gy, DNA ladder was a single electrophoretic band; in the 10 Gy group, the electrophoresis showed a multiple ladder band; when dose was more than 10 Gy, a vague and irregular band appeared on the electrophoresis. CONCLUSION Oncotic necrosis may be the main cell death style when dose per fraction is high, which differs from conventional dose fraction radiation therapy.

OBJECTIVE To reveal the biological effects and effective dosage in radiotherapy model which applies high single-dose irradiation by animal experiment.METHODS We inoculated subcutaneouly human pancreatic carcinoma cell line (MIA PaCa-2) in the lateral of the right lower extremity of the athymic mouse to grow transplantation tumor. While the median diameter of transplantation tumor reached 10 mm approximately, the animals were randomly divided into 7 groups (6 animals per group) and fixed with consciousness for irradiation by different dose in one fraction (0, 2, 5, 10, 17, 25, 35 Gy). All were kept on to be bred for observation of the change in gross tumor volume, calculation of delayed growth time and delayed growth curve. RESULTS With increased dose per fraction, cutaneous reaction on the neoplasma surface of the animal, which was mainly moist yellow effusion was more and more severe. When dosage is less than 10 Gy, all animals showed similar effects, that’s the delayed tumor growth was not obvious. Tumors receiving more than 10 Gy in one fraction showed very good biological effect and the delayed tumor growth was obviously related to dosage. The difference in delayed tumor growth between the 2 groups was statistically significant. The delayed tumor growth time in 10, 17, 25 Gy group was respectively 3 weeks, 6 weeks and more.CONCLUSION The biological effect of the model which applies high single-dose irradiation (more than 10 Gy in one fraction) was very good. The effect of delayed tumor growth was obviously related to the dosage after transplantation tumor was radiated. Because of its higher dose per fraction and biological effects, the model of high single-dose irradiation can get better clinical effects.

Evolutionary biologists are always interested in deciphering the geographic context of diversification, therefore they introduced the concept of comparative phylogeography, which helps to identify common mechanisms that contribute to shared genetic structures among organisms from the same region. Here, we used multi-locus genetic data along with environmental data to investigate shared phylogeographic patterns among three Asianendemic newt genera, Cynops, Paramesotriton and Pachytriton, which occurred in montane/submontane streams or ponds in southern China. Our 222 samples from 78 localities covered the entire range of the three genera and represented the largest dataset of this group to date. We reconstructed matrilineal genealogies from two protein-coding, mitochondrial genes, and gene network from two nuclear genes. We also estimated divergence times of major cladogenetic events and used occurrence data to evaluate niche difference and similarity between lineages. Our results revealed a common basal split in all three genera that corresponds to the separation of two geographic terrains of southern China. Those ancient divergence occurred during middle to late Miocene and likely correlate with paleoclimatic fluctuations caused by the uplift of the Qinghai-Xizang (Tibet) Plateau (QTP). Particularly, the strengthening and weakening of Asian summer monsoons during the Miocene may have profoundly impacted southern China and led to repeatedly vicariance in those newts. However, despite differences in realized niches between lineages, there is no evidence for divergence of fundamental niches. Preservation of old newt matriline lineages in mountains of southern China suggests that the region acts as both museums and cradles of speciation. Based on those results, we advocate a multi-pronged protection strategy for newts in the three genera. [ABSTRACT FROM AUTHOR]

Asian leaf-litter toads of the genus Leptobrachella represent a great anuran diversification in Asia. Previous studies have suggested that the diversity of this genus is still underestimated. During herpetological surveys from 2013 to 2018, a series of Leptobrachella specimens were collected from the international border areas in the southern and western parts of Yunnan Province, China. Subsequent analyses based on morphological and molecular data revealed three distinct and previously unknown lineages, which we formally describe as three new species herein. Among them, we describe a new species that occurs at the highest known elevation for Leptobrachella in China. Four species of Leptobrachella, including two new species, are found in the same reserve. Furthermore, our results suggest that the population from Longchuan County, Yunnan, may represent an additional new species of Leptobrachella, although we tentatively assigned it to Leptobrachella cf. yingjiangensis due to the small sample size examined. Lastly, we provide the first description of females of L. yingjiangensis. Our results further highlight that both micro-endemism and sympatric distributions of species are common patterns in Leptobrachella, that contribute to taxonomic and conservation challenges in these frogs. We provide an identification key for Leptobrachella known to occur in Yunnan. Given the lack of knowledge on species diversity of Leptobrachella along international border areas, we recommend that future studies include transboundary collaborative surveys. [ABSTRACT FROM AUTHOR]

BACKGROUND: Radiosensitivity by blocking the epidermal growth factor receptor and cyclooxygenase-2 pathways with erlotinib and celecoxib in A549 human lung cancer cell was investigated. METHODS: MTT assays were used to detect the antitumor effects of erlotinib and celecoxib in A549 cells. Colony formation assays were used to evaluate the antitumor effects. Flow cytometry analysis was used to assess the cell cycle and cell apoptosis, and western blotting analysis was performed to evaluate the expression of AKT and phosphorylated AKT. RESULTS: Either erlotinib or celecoxib inhibited the A549 cell proliferation in a dose-dependent manner. Combining Erlotinib or celecoxib with radiation can suppress the cell colony formation and the Dq, D0, SF2 of the combining erlotinib or celecoxib with radiation was lower than in the combinations either erlotinib or celecoxib with radiation (t = 6.62,P <0.05). The SER of radiation with celecoxib or erlotinib and celecoxib and erlotinib were 1.299, 1.503 and 2.217, respectively. The Flow cytometry analysis results showed that either celecoxib or erlotinib could induce G0/G1 arrest, and reduction of S phase cell proportion, especially when combinations erlotinib-celecoxib with radiation. Either celecoxib or erlotinib could enhance radiation-induced apoptosis, especially significant when combinations erlotinib-celecoxib with radiation. Moreover, radiation can promote the expression of pAKT, and the pAKT was remarkably lowest in the combinations erlotinib-celecoxib with radiation group (t = 4.89, P <0.05). CONCLUSIONS: Blocking both EGFR- and COX-2-related pathways could enhance the antitumor effect of radiation. The underlying mechanisms including the enhancement of apoptosis and radiation-induced G0/G1 arrest, possibly via inhibiting the PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

South China and Indochina host striking species diversity and endemism. Complex tectonic and climatic evolutions appear to be the main drivers of the biogeographic patterns. In this study, based on the geologic history of this region, we test 2 hypotheses using the evolutionary history of Microhyla fissipes species complex. Using DNA sequence data from both mitochondrial and nuclear genes, we first test the hypothesis that the Red River is a barrier to gene flow and dispersal. Second, we test the hypothesis that Pleistocene climatic cycling affected the genetic structure and population history of these frogs. We detect 2 major genetic splits that associate with the Red River. Time estimation suggests that late Miocene tectonic movement associated with the Red River drove their diversification. Species distribution modeling (SDM) resolves significant ecological differences between sides of the Red River. Thus, ecological divergence also probably promoted and maintained the diversification. Genogeography, historical demography, and SDM associate patterns in southern China with climate changes of the last glacial maximum (LGM), but not Indochina. Differences in geography and climate between the 2 areas best explain the discovery. Responses to the Pleistocene glacial-interglacial cycling vary among species and regions. [ABSTRACT FROM AUTHOR]

True frogs of the genus Rana are widely used as model organisms in studies of development, genetics, physiology, ecology, behavior, and evolution. Comparative studies among the more than 100 species of Rana rely on an understanding of the evolutionary history and patterns of diversification of the group. We estimate a well-resolved, time-calibrated phylogeny from sequences of six nuclear and three mitochondrial loci sampled from most species of Rana, and use that phylogeny to clarify the group's diversification and global biogeography. Our analyses consistently support an "Out of Asia" pattern with two independent dispersals of Rana from East Asia to North America via Beringian land bridges. The more species-rich lineage of New World Rana appears to have experienced a rapid radiation following its colonization of the New World, especially with its expansion into montane and tropical areas of Mexico, Central America, and South America. In contrast, OldWorld Rana exhibit different trajectories of diversification; diversification in the OldWorld began very slowly and later underwent a distinct increase in speciation rate around 29-18 Ma. Net diversification is associated with environmental changes and especially intensive tectonic movements along the Asian margin from the Oligocene to early Miocene. Our phylogeny further suggests that previous classificationswere misled by morphological homoplasy and plesiomorphic color patterns, as well as a reliance primarily on mitochondrial genes.We provide a phylogenetic taxonomy based on analyses of multiple nuclear and mitochondrial gene loci. [ABSTRACT FROM AUTHOR]

Background and aim: The aim of this study is to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) using CyberKnife in the treatment of patients with recurrent pancreatic adenocarcinoma at the abdominal lymph node or stump after surgery. Patients and methods: Between October 1, 2006 and May 1, 2015, patients with recurrent pancreatic adenocarcinoma at the abdominal lymph node or stump after surgery were enrolled and treated with SBRT at our hospital. The primary end point was local control rate after SBRT. Secondary end points were overall survival, time to symptom alleviation, and toxicity, assessed using the Common Terminology Criteria for Adverse Events version 4.0. Results: Twenty-four patients with 24 lesions (17 abdominal lymph nodes and seven stumps) were treated with SBRT, of which five patients presented with abdominal lymph nodes and synchronous metastases in the liver and lung. The 6-, 12-, and 24-month actuarial local control rates were 95.2%, 83.8%, and 62.1%, respectively. For the entire cohort, the median overall survival from diagnosis and SBRT was 28.9 and 12.2 months, respectively. Symptom alleviation was observed in eleven of 14 patients (78.6%) within a median of 8 days (range, 1-14 days) after SBRT. Nine patients (37.5%) experienced Common Terminology Criteria for Adverse Events version 4.0 grade 1-2 acute toxicities; one patient experienced grade 3 acute toxicity due to thrombocytopenia. Conclusion: SBRT is a safe and effective treatment for patients with recurrent pancreatic adenocarcinoma at the abdominal lymph node or stump after surgery. Further studies are needed before SBRT can be recommended routinely. [ABSTRACT FROM AUTHOR]

Background: The breast is a rare site of extranodal involvement of diffuse large B-cell lymphoma (DLBCL). We aimed to assess the clinical characteristics, prognostic factors, and treatment outcomes of breast DLBCL. Patients and methods: We retrospectively analyzed 113 patients (from our institution and the literature) between 1973 and 2014. The primary end point was overall survival (OS). Kaplan-Meier OS curves were compared with the log-rank test. Cox regression analysis was applied to determine the prognostic factors for OS, progression-free survival (PFS), local control (LC), and cause-specific survival (CSS). Results: A total of 113 patients were included in the study: 42 cases from our hospital and 71 cases from 12 publications. The median age at diagnosis was 58 years. With a median follow-up time of 39.2 months, the estimated 5-year OS, PFS, LC, and CSS were 71.4%, 58.8%, 75.6%, and 74.9%, respectively. In multivariate analysis, more than four cycles of chemotherapy, having localized cancer, lumpectomy with or without axillary lymph node (ALN) dissection, and low to low-to-intermediate International Prognostic Index were favorable factors for OS. For PFS, significant prognostic factors were rituximab use, B symptoms, and tumor size. As for the local group, lumpectomy with or without ALN dissection and more than four cycles of chemotherapy were favorable factors for OS. Tumor size .4 cm andnonuse of rituximab were adverse factors for PFS. Twenty-one patients (18.6%) developed local relapse and 33 (29.2%) developed systemic relapse. Eight patients had central nervous system relapse (7.3%). Conclusion: Our results reveal that local and extended staging criteria can reflect the different prognosis and treatment outcomes of breast DLBCL. Rituximab use, lumpectomy, and more than four cycles of chemotherapy are recommended as a treatment regimen. However, further study is warranted to validate our data. [ABSTRACT FROM AUTHOR]

Background and aim: Limited-stage combined small cell esophageal carcinoma (LS-CSCEC) is a rare, poorly understood, underdiagnosed disease, with components of both small cell esophageal cancer and non–small cell esophageal cancer. We investigated the optimal treatment strategy and prognostic factors in patients with LS-C-SCEC. Patients and methods: LS-C-SCEC patients included in the analysis (from our hospital and the literature) were treated between January 1966 and December 2013. Patient treatment strategies included surgery (S), chemotherapy (CT), and radiation therapy (RT). The primary end point was overall survival (OS); the secondary end points included tumor complete response rates, patterns of failure, and toxicity. Kaplan–Meier curves were compared with the log-rank test. Univariate and multivariate analyses were used to determine prognosticators for OS. Results: A total of 72 patients were included in the analysis: 24 (33%) from our hospital and 48 (67%) from the literature. The median OS of all patients was 15.0 months. Patients who received CT had a significantly longer median OS than did those who did not (OS 22.8 months vs 10.0 months) (P=0.03). Patients treated with multimodality therapy (including RT+CT [18%], S+CT [40%], or S+RT+CT [17%]) vs monotherapy (typically, S [18%]) had significantly improved OS (15.5 months vs 9.3 months) (P=0.02) and complete response rates. On multivariate analysis, tumor location (upper third of the esophagus) and type of treatment (monotherapy) were the only factors predictive of poor OS. Conclusion: Multimodality therapy (including RT+CT, S+CT, or S+RT+CT) improves OS for patients with LS-C-SCEC compared with monotherapy (typically, S). Additional studies are necessary to personalize multimodal treatment approaches to individual patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) in the treatment of patients with liver metastases. Between August 2006 and July 2011, patients with 1-4 liver metastases were enrolled and treated with SBRT using the CyberKnife® system at Tianjin Medical University Cancer Institute and Hospital. The metastases were from different primary tumors, with a maximum tumor diameter of less than 6 cm. The primary endpoint was local control. Secondary endpoints were overall survival, progression-free survival, distant progression-free survival, and adverse events. Fifty-seven patients with 80 lesions were treated with SBRT. The 1-year and 2-year local control rates were 94.4% and 89.7%, respectively. The difference in local control between patients who received adjuvant treatment before SBRT and those who did not reached statistical significance (P=0.049). The median overall survival for the entire cohort was 37.5 months. According to the primary tumor sites, the median overall survival was not reached. The 2-year overall survival rate was 72.2% in the favorable group (primary tumors originating from the colon, breast, or stomach, as well as sarcomas); however, in the unfavorable group (primary tumors originating from the pancreas, lung, ovary, gallbladder, uterus, hepatocellular carcinoma, as well as olfactory neuroblastoma), the median overall survival and 2-year overall survival rates were 37.5 months and 55.9%, respectively (P=0.0001). Grade 1-2 fatigue, nausea, and vomiting were the most common adverse events, and no grade 3 and higher adverse events were observed. With excellent local control in the absence of severe toxicity, SBRT provides an alternative for patients with 1-4 liver metastases who cannot undergo surgery or other treatments. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this paper was to investigate the efficacy and activity variation associated with phosphoinositide 3-kinase (PI3K) signal transduction when combining erlotinib with radiation, using different administration schedules. Materials and methods: Erlotinib was delivered to A973 cancer cells in the following three ways: (1) irradiation after administration, (2) irradiation upon administration, and, (3) irradiation before administration. The cell-survival rates were detected using colony-forming assays, while cell apoptosis was detected with flow cytometry. The expression levels of C-MET, p-C-MET, AKT, and p-AKT were determined via Western blotting analysis, under 6 Gy irradiation with/without erlotinib. Results: The sensitizer enhancement ratios (SERs) of erlotinib irradiation after administration, irradiation upon administration, and irradiation before administration groups were 2.19, 1.53, and 1.38, respectively. A higher apoptosis rate was observed when irradiation was delivered after erlotinib. In addition, changes in cell apoptosis were found to be related to concurrent changes in C-MET, p-C-MET, AKT, and p-AKT expression. Protein expression increased in the combination groups, with trends showing a negative relationship with cell apoptosis. Conclusion: The radiosensitive effect of erlotinib varied because of the different administration schedules; this variation may be related to PI3K signal transduction and its associated regulating effect. [ABSTRACT FROM AUTHOR]

The clinical success of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) as therapeutic agents has prompted great interest in their further development and clinical testing for a wide variety of malignancies. However, most studies have focused on the efficacy of TKI, and few studies have been done on the criteria for their discontinuation. The current standard for drug discontinuation is "until progression", based on change in tumor size. However, tumor size is not related to the gene expression which determines the efficacy of TKI in the final analysis, and it is also difficult to make a thorough and correct prediction based on tumor size when the TKI is discontinued. Nevertheless, clinical evaluation of the criteria for TKI discontinuation is still in its early days. Some promising findings have started to emerge. With the improving knowledge of EGFR and its inhibitors, it is expected that the criteria for discontinuation of EGFR inhibitor therapy will become clearer. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of cyberknife (CK) and neurosurgery (NS) in patients newly diagnosed as solitary brain metastasis (SBM) from non-small cell lung cancer (NSCLC). Methods and materials: We retrospectively analyzed 76 patients between 1990 and 2012 from our institution, including 38 patients performing CK and the other half performing NS. The observation end point was overall survival time (OS), local control of treated metastasis (LC) and intracranial control (IC). Kaplan-Meier OS curves were compared with the log-rank test. Cox regression analysis was used to determine prognosticators for OS, LC and IC. Results: The baseline characteristic between the two groups was not significantly different. The 1-year OS rates were 53.5% and 30.5% in the CK group and NS group, respectively, (p = 0.121). The 1-year LC rates were 50.8% and 31.3%, respectively, (p = 0.078). The 1-year IC rates were 50.8% and 27.7%, respectively, (p = 0.066). In multivariate analysis, improved OS was significantly associated with younger age (p = 0.016), better ECOG performance status (p = 0.000) and graded prognostic assessment (GPA, 3.5-4.0, p = 0.006). The LC was also associated with better ECOG performance status (p = 0.000). The IC was associated with both better ECOG performance status (p = 0.000) and GPA (3.5-4.0, p = 0.005). Conclusions: There was no statistical difference between CK and NS for SBM from NSCLC in OS, LC and IC. However, CK is less invasive and may be more acceptable for patients. The result needs randomized trials to confirm and further study. [ABSTRACT FROM AUTHOR]

The optimal combination and sequence of radiotherapy (RT) and chemotherapy (CT) for extranodal nasal-type natural killer/T-cell lymphoma (NKTCL) are not well-defined. The aim of this study was to create a risk-adapted therapeutic strategy for early-stage NKTCL. A total of 1273 early-stage patients from 10 institutions were reviewed. Patients received CT alone (n =170), RT alone (n = 253), RT followed by CT (n = 209), or CT followed by RT (n = 641). A comprehensive comparative study was performed using multivariable and propensity score-matched analyses. Early-stageNKTCLwasclassified as low risk or high risk based on 5 independent prognostic factors (stage, age, performance status, lactate dehydrogenase, primary tumor invasion). RT alone and RT with or without CT were more effective than CT alone (5-year overall survival [OS], 69.6% and 67.7% vs 33.9%, P < .001). For low-risk patients, RT alone achieved a favorable OS (88.8%); incorporation of induction or consolidation CT did not provide additional benefit (86.9% and 86.3%). For highrisk patients, RT followed by CT resulted in superior OS (72.2%) compared with induction CT and RT (58.3%, P = .004) or RT alone (59.6%, P = .017). After adjustment, similar significant differences in OS were still observed between treatment groups. New CT regimens provided limited benefit in early-stage NKTCL. Risk-adapted therapy involving RT alone for low-risk patients and RT consolidated by CT for high-risk patients is a viable, effective strategy for early-stage NKTCL. [ABSTRACT FROM AUTHOR]

Aim: To investigate the mechanism of chaperone-mediated autophagy (CMA)-induced resistance to irradiation-triggered apoptosis through regulation of the p53 protein in hepatocellular carcinoma (HCC)., Methods: Firstly, we detected expression of lysosome-associated membrane protein 2a (Lamp-2a), which is the key protein of CMA, by western blot in HepG2 and SMMC7721 cells after irradiation. We further used shRNA Lamp-2a HCC cells to verify the radioresistance induced by CMA. Next, we detected the HMGB1 and p53 expression after irradiation by western blot, and we further used RNA interference and ethyl pyruvate (EP), as a HMGB1 inhibitor, to observe changes of p53 expression. Finally, an immunoprecipitation assay was conducted to explore the interaction between Lamp-2a and HMGB1, and the data were analyzed., Results: We found the expression of Lamp-2a was increased on irradiation while apoptosis decreased in HepG2 and SMMC7721 cells. The apoptosis was increased markedly in the shRNA Lamp-2a HepG2 and SMMC7721 cells as detected by western blot and colony formation assay. Next, we found p53 expression was gradually reduced on irradiation but obviously increased in shRNA Lamp-2a cells. Furthermore, p53 increased the cell apoptosis on irradiation in Hep3B (p53-/-) cells. Finally, p53 levels were regulated by HMGB1 as measured through RNA interference and the EP treatment. HMGB1 was able to combine with Lamp-2a as seen by immunoprecipitation assay and was degraded via the CMA pathway. The decreased HMGB1 inhibited p53 expression induced by irradiation and further reduced the apoptosis in HCC cells., Conclusion: CMA pathway activation appears to down-regulate the susceptibility of HCC to irradiation by degrading HMGB1 with further impact on p53 expression. These findings have clinical relevance for radiotherapy of HCC., Competing Interests: Conflict-of-interest statement: All authors in this paper declared that there is no conflicts of interest to this work.