The primary focal area of carcinoma of unknown primary (CUP) can not be determined by clinical examination.It is difficult to find the primary site and its prognosis is poor.The traditional diagnostic approaches mainly include pathological examination,endoscopy,imaging technology and so on.However,positron emission tomography is the preferred approach.In recent years,gene expression profiling has become a new diagnostic approach to find the source of CUP.The detection rate by gene expression profiling is high,and the approach can accurately identify the primary site.The recommended therapies include classic platinum-or paclitaxel-based chemotherapy,radiotherapy or surgery,and site-directed therapy by gene expression profiling for patients with CUP improves their survival rate.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) preferentially induces apoptosis in tumor cells but not in normal cells. It induces apoptosis in its target cells by interacting with surface death receptors DR4 and DR5,which contain a cytoplasmic region designated as thedeath domain. Clinical use of rhTRAIL and its agonistic antibodies is limited due to partial or completetolerance to TRAIL in human tumor cell lines. As TRAIL binding to its death receptors is the initial and crucial step in initiating apoptosis, the mechanisms of TRAIL-tolerance in tumor cells is closely related to the expression,location,distribution and function of TRAIL receptors . Personalized care combined with other therapies targeting TRAIL receptors may be expected to overcome the TRAIL-tolerance of tumor cells eventually.

Ubiquitin specific peptidases play important roles in controlling proteasome activity,organogenesis,tumorigenesis and transcriptional regulation.Ubiquitin specific peptidase 9X is able to remove ubiquitin from substrate proteins,so it may effectively regulate the proliferation,adhesion and signal transduction of tumor cells.It is a one of the most important factors in tumor progression.

Small cell lung cancer (SCLC) is a highly malignant tumor, which is very sensitive to first-line chemotherapy, but easy to recurrence and metastasis early.So it always has poor prognosis.Second-line therapy for SCLC develops slowly.Topotecan is the only drug approved by US Food and Drug Administration as a second-line chemoradiotherapy.Numerous studies on molecular targeted therapy and immunotherapy are being carried out, but most of them have no or little benefit.Rovalpituzumab tesirine (Rova-T) targeted antibody-drug conjugate (ADC) which is published at the 2016 American Society of Clinical Oncology Annual Meeting shows a good anti-tumor activity, which seems to bring a new dawn of molecular targeted therapy.

Myocardial fibrosis is a predominant pathological change of radiation-induced heart disease (RIHD) in late stage.It often occurs several or more than ten years after radiotherapy and can lead to myocardial remodeling, impaired cardiac function, and heart failure.At present there is no effective method to prevent or reverse the development of radiation-induced myocardial fibrosis.Many cells, cytokines, and other factors are involved in the development and progression of myocardial fibrosis in RIHD and some of them have been validated.But most investigators focused on the pathological changes and related mechanisms in early stage, and myocardial fibrosis was just regarded as an endpoint event.The definitive mechanisms of myocardial fibrosis in late stage remain unclear.This paper reveiws the studies about general mechanisms of myocardial fibrosis in RIHD and summarizes the roles of microcirculation dysfunction, mast cells, several cytokines, hypoxia, oxidative stress, and renin-angiotensin system, and points out the future research direction of the pathogenesis of myocardial fibrosis in RIHD.It provides new ideas for discovering the potential targets for clinical intervention of myocardial fibrosis in RIHD.

Objective To analyze the incidence and risk factors of pelvic insufficiency fractures (PIF) in patients with cervical cancer who received pelvic intensity-modulated radiotherapy.Methods This study a retrospective review of all patients was performed with cervical cancer who received pelvic intensity-modulated radiotherapy at our institution from November 2013 to December 2015,and the incidence and risk factors of insufficiency fractures were analyzed.Results Among the 104 patients,16 (with a total of 31 lesions) were diagnosed with pelvic insufficiency fracture.The occurrence rate of pelvic insufficiency was 15.4％.Ten patients (62.5％) had multiple fractures and five patients (31％) complained of pain.All patients' pain was relieved by rest or analgesic drugs.Insufficiency fractures were detected at a median of 6.5 months (range 1-16) from radiotherapy completion.The distribution of PIFs was followed:sacral had 16 cases (51.6％),sacroiliac joint had 7 cases (22.6％),iliac had 6 cases (19.4％),femoral head had 1 case (3.2％) and pubis had 1 case (3.2％).Univariate analysis and multiple analysis showed that postmenopausal status and low body weight (≤55 kg) were thought to be risk factors for PIF(P ＜ 0.05).Subgroup analysis also confirmed that postmenopausal status was a risk factor for PIF (P ＜ 0.05) in postoperative cervical cancer patients after pelvic intensity-modulated radiation therapy.Conclusions Cervical cancer patients with menopausal status and low body weight (≤55 kg) are at some risk for the development of PIF after pelvic intensity-modulated radiotherapy.

Purpose:To study the expression and clinical significance of nm23 protein in human breast carcinoma.Methods:The expression of nm23 were detected by immunohistochemical S P methods in tissue samples from 65 cases of breast carcinoma with full follow up .Their prognostic value was analyzed by Cox regression model.Results:Positive expression of nm23 was 55.4% in the 65 breast carcinoma specimens. In the total number of patients, the 5 year overall survival rate(OS) and disease free survival rate(DFS) were 63.1% and 52.3%,respectively. Expression of nm23 was negatively associated with distant metastasis( P =0.0003) and positively with DFS and OS( P =0.0034, P =0.0001). In both monovariate Kaplan Meier plot and multivariate Cox regression analysis, the axillary lymph node status and expression of nm23 were two important prognostic factors of breast carcinoma. The hazard ratios of axillary lymph node status and expression of nm23 were 3.1046 and 0.3704, respectively. Conclusions:In breast carcinoma, secondary to the axillary lymph node status, the expression of nm23 could be an independent prognosticator, which would be helpful in selecting the high risk cases for further treatment.

Normal lung tissues are inevitably exposed to X-ray in thoracic radiotherapy,causing radiation-induced lung injury (RILI).The main pathological manifestations include the accumulation of inflammatory cells,release of cytokines,accumulation and proliferation of fibroblasts,and excessive deposition of alveolar interstitial collagen in the irradiated region.RILI severely affects the treatment compliance and quality of life and even threatens the life in the patients receiving radiotherapy.In recent years,numerous studies have found that Th1/Th2 imbalance is closely associated with the development and progression of RILI,and the cytokine network plays an executive role in the progression of RILI.Therefore,restoring the Th1/Th2 balance in vivo may provide a new way to prevent and treat RILI.

Objective To observe the expression of GATA-3 and IL-13 in mice with radiationinduced lung fibrosis,and to study the function of GATA-3.Methods A total of 63 C57BL/6 female mice were randomly into 2 groups,including 21 mice in control group and 42 mice in irradiated group.The thoraces of mice in irradiated group were exposed with 12 Gy of X-rays.All the mice were sacrificed at 1 h,and 1,2,4,8,16 and 24 weeks post-irradiation.The lung issues were stained by using HE and Masson methods to determine the histological changes.The expression of IL-13 in serum,and the expression of hydroxyproline and the mRNA and protein of GATA-3 in lung tissue were assayed.Results Compared with control group,there was a significant histological and pathologic change in irradiated group.The content of hydroxyproline in irradiated group was significantly higher than that in control group( Z =3.14,P ＜0.05).The expressions of GATA-3 and IL-13 were found in mice post-irradiation.Without causing conspicuous fibrotic pathological changes,there was a significantly elevated expression of Th2-specific transcription factor GATA-3 mRNA at 1 and 2 weeks post-irradiation ( t =6.50,6.33,P ＜ 0.01 ),while the expression of IL-13 reached the maximal value in serum at 16 weeks post-irradiation( t =32.21,P ＜0.01 ).Conclusions GATA-3 might play a role in promoting radiation-induced pulmonary fibrosis by upregulation of expression of Th2 cytokine IL-13.

Objective To investigate the effects of 5-azacytidine on radiation-induced epithelialmesenchymal transition in rat alveolar type Ⅱ epithelial cell line (RLE-6TN) and explore their working mechanisms,and to provide experimental evidence for the potential drug-based treatment of radiationinduced pulmonary fibrosis.Methods RLE-6TN cells were cultured in vitro and divided into four groups according to the experimental purposes:control group (C),radiation group (R),5-azacytidine group (A),and radiation followed by 5-azacytidine group (R + A).The microstructural changes in cells were determined by transmission electron microscopy.Inverted phase-contrast microscopy revealed the morphological changes in cells.The mRNA expression levels of E-cadherin and α-SMA were measured by quantitative real-time polymerase chain reaction (qRT-PCR).The protein expression levels of E-cadherin,GSK3 β,and p-GSK3 β (Ser9) were measured by Western blot.The one-way analysis of variance was used for pairwise comparison.Results The cells in group R became spindle-like.Similar morphological changes were not observed in cells in group R + A.Osmiophilic lamellar bodies disappeared at last in cells in group R.RT-PCR results showed that compared with group C,group R had a significantly lower mRNA expression level of E-cadherin ((0.23 ± 0.06) vs.(1.00 ± 0.00),P =0.002)) and a significantly higher mRNA expression level of α-SMA ((2.91 ± 0.01) vs.(1.00 ± 0.00),P =0.000)).However,compared with group R,group R + A had a significantly higher mRNA expression level of E-cadherin ((0.47 ± 0.05) vs.(1.00 ± 0.00),P =0.024)) but a significantly lower mRNA expression level of α-SMA ((2.50 ± 0.02) vs.(1.00 ±0.00),P =0.037)).The results of Western blot showed that the protein expression level of Ecadherin was significantly reduced ((0.07 ± 0.01) vs.(0.48 ± 0.02),P =0.028)),while the protein expression level of p-GSK3β was significantly increased in Group R than in Group C ((0.85 ± 0.04) vs.(0.23 ± 0.03),P =0.031)).However,compared with group R,group R + A had a significantly lower protein expression level of E-cadherin ((0.25 ± 0.00) vs.(0.07 ± 0.01),P =0.024)) and significantly less up-regulation of the protein expression level of p-GSK3β ((0.39 ± 0.03) vs.(0.85 ± 0.04),P =0.014)).Conclusions X-ray radiation can induce the epithelial-mesenchymal transition in epithelial cells.5-azacytidine suppresses radiation-induced epithelial-mesenchymal transition by inhibition of the activity of p-GSK3β in RLE-6TN cells.