DEVELOPMENT OF AN EXTENDED-RANGE BONNER SPHERE SPECTROMETER FOR CHINA INITIATIVE ACCELERATOR-DRIVEN SYSTEM.

To measure the extended-range neutron spectra and calibrate the extended-range neutron dosemeters of the China initiative Accelerator-Driven System (CiADS), an Extended-range Bonner Sphere Spectrometer (EBSS) has been developed. The EBSS was designed based on the PHITS codes, investigating various combinations of materials and diameters of the neutron moderators and the neutron multipliers for extended-range neutrons. Finally, seven polyethylene-only spheres and seven extended-range spheres were selected and subsequently built. The neutron multipliers of the extended-range spheres embedded concentric shells of lead, copper and tungsten. The response functions of the EBSS were analyzed and experimentally validated. It was subsequently tested with 252Cf neutron source and cosmic ray neutron source. The results demonstrate that the EBSS is capable of accurately measuring neutron spectra.

[The prognostic impact of number-indexes of lymph nodes in stage N1c colorectal cancer patients].

Objective: To evaluate the impact of number-indexes of lymph nodes for prognostic stratification in stage N1c colorectal cancer (CRC) patients. Methods: The clinicopathologic data of CRC patients with stage pTxN1cM0 who initially underwent radical surgery in Cancer Hospital, Chinese Academy of Medical Sciences and the Surveillance, Epidemiology and End Results (SEER) database from January 2010 to December 2015 were retrospectively analyzed. A total of 1 165 patients with stage N1c were included in this study. Among them, 85 patients (including 54 males and 31 females) were from Cancer Hospital, Chinese Academy of Medical Sciences and their median age was 58 (range: 32-80) years; 1 080 patients (including 566 males and 514 females) were from the SEER database and their median age was 66 (range: 24-98) years. The prognostic significance of total number of lymph node (TLN), number of negative lymph node (NLN), and log odds of positive lymph nodes (LODDS) in stage N1c CRC patients were explored. Results: The optimal cut-off value of TLN or NLN was 13, and the optimal cut-off value of LODDS was -1.43. Among the 85 patients of Cancer Hospital, Chinese Academy of Medical Sciences, the 5-year overall survival (OS) rates of stage N1c1 (TLN or NLN≥13, 69 cases) and group LODDS1 patients (LODDS≤-1.43, 69 cases) were both 80.9%, which higher than that of stage N1c2 (TLN or NLN<13, 16 cases) and group LODDS2 (LODDS>-1.43, 16 cases) patients (both 53.3%, P=0.002); In the SEER cohort, the 5-year OS rates of stage N1c1 (837 cases) and group LODDS1 patients (LODDS≤-1.43, 837 cases) were both 64.7%, which higher than that of stage N1c2 (243 cases) and group LODDS2 (LODDS>-1.43, 243 cases) patients (both 52.2%, P<0.001). Both in the NCC cohort and SEER cohort, the results of Cox multivariate analysis all demonstrated that TLN or NLN<13 was the risk factor of OS of CRC patients with stage N1c (HR=3.794, 95%CI: 1.539-9.349, P=0.004; and HR=1.588, 95%CI:1.232-2.048, P<0.001; respectively); LODDS≤-1.43 was the independent protective factor of OS of stage N1c CRC patients (HR=0.264, 95%CI: 0.107-0.650; and HR=0.630, 95%CI: 0.488-0.812; respectively). Conclusions: TLN or NLN and LODDS were all independent prognostic factors of CRC patients with stage N1c. The clinicians could use TLN or NLN and LODDS for prognostic stratification and make the different adjuvant therapeutic schemes for CRC patients with stage N1c.

Targeted therapies and checkpoint inhibitors in sarcoma.

Sarcomas are defined as a group of mesenchymal malignancies with over 100 heterogeneous subtypes. As a rare and difficult to diagnose entity, micrometastasis is already present at the time of diagnosis in many cases. Current treatment practice of sarcomas consists mainly of surgery, (neo)adjuvant chemo- and/or radiotherapy. Although the past decade has shown that particular genetic abnormalities can promote the development of sarcomas, such as translocations, gain-of-function mutations, amplifications or tumor suppressor gene losses, these insights have not led to established alternative treatment strategies so far. Novel therapeutic concepts with immunotherapy at its forefront have experienced some remarkable success in different solid tumors while their impact in sarcoma remains limited. In this review, the most common immunotherapy strategies in sarcomas, such as immune checkpoint inhibitors, targeted therapy and cytokine therapy are concisely discussed. The programmed cell death (PD)-1/PD-1L axis and apoptosis-inducing cytokines, such as TNF-related apoptosis-inducing ligand (TRAIL), have not yielded the same success like in other solid tumors. However, in certain sarcoma subtypes, e.g. liposarcoma or undifferentiated pleomorphic sarcoma, encouraging results in some cases when employing immune checkpoint inhibitors in combination with other treatment options were found. Moreover, newer strategies such as the targeted therapy against the ancient cytokine macrophage migration inhibitory factor (MIF) may represent an interesting approach worth investigation in the future.

[Lengths of the fixed loop and the adjustable loop in the coarse bone tunnel were compared to influence the widening of the femoral bone tunnel and the function of the knee joint].

OBJECTIVE: To evaluate the effects of two different femoral cortical suspension devices (fixation loop and adjustable loop) on tunnel widening and knee function in patients following anterior cruciate ligament reconstruction for 12 months. METHODS: A total of 60 patients who had undergone anterior cruciate ligament reconstruction were included in this study. According to the length of the loop(n)[n= total length of loop-(total length of femoral tunnel-total length of coarse tunnel)] in the rough bone tunnel, the patients were divided into A (adjustable loop was 0 mm in the coarse bone tunnel), B (fixation loop was greater than 0 mm and less than or equal to 10 mm in the coarse bone tunnel) and C (fixation loop was greater than 10 mm in the coarse bone tunnel) groups, of which 11 cases were in group A, 27 cases in group B and 22 cases in group C. In the three-dimensional reconstruction of the knee joint with multi-slice spiral CT, the widening of the bone tunnel in the three groups was compared. At the same time, IKDC, Lysholm and Tegner scores of the patients in the three groups were compared. RESULTS: There were differences in the widening degree of the femoral canal among groups A, B and C, and the median difference of the widening degree of the femoral tunnel 12 months and immediately after the surgery was A < B < C. The difference of femoral canal widening in group A was significantly different from that in groups B and C (P < 0.05).According to the linear regression the relationship between the difference of the width of the femoral canal and the change of the length (n) of the loop in the coarse canal, it was found that there was a linear relationship between the value of n and the difference of the width of the bone canal. With the increase of the value of n, the difference of the width of the bone canal gradually became larger. The median difference of the width of the middle and superior tunnel was negative, while the median difference of the width of the middle and inferior tunnel was positive. During the follow-up, we found that there were no statistical differences in IKDC, Lysholm and Tegner scores among the three groups one year after surgery (P > 0.05). CONCLUSION: Twelve months after surgery, compared with group B (fixed loop group) and group C (fixed loop group), group A (adjustable loop group) had less bone tunnel widening.In groups A, B and C, as the length of the loop in coarse bone tunnel gradually increased, the width of bone tunnel became more significant. At the end of 12 months follow-up after anterior cruciate ligament reconstruction, the medial and inferior femoral tunnel was significantly wider than immediately after surgery, and the medial and superior femoral tunnel had gradually begun to undergo tendon-bone healing. There was no significant difference in knee function scores among groups A, B, and C in the follow-up 12 months after surgery.

[MUC4 Silencing Inhibits TGF-ß1-induced Epithelial-mesenchymal Transition VIA the ERK1/2 Pathway in Human Airway Epithelial NCI-H292 Cells].

MUC4 is a predominant membrane-tethered mucin lubricating and protecting the epithelial surface and playing various biological roles in the renewal and differentiation of epithelial cells, cell signaling, cell adhesion, and carcinogenesis. Interestingly, recent studies have demonstrated that MUC4 expression regulates the epithelial-mesenchymal transition (EMT) of cancer cells in ovarian, pancreatic, and lung cancer. However, the effects of MUC4 expression on EMT in human airway epithelial cells are not yet well known. Here, we describe the effects of transforming growth factor beta 1 (TGF-ß1)-induced MUC4 expression on EMT and evaluate its downstream signaling pathway in human airway epithelial cells. In human airway epithelial NCI-H292 cells, exposure to TGF-ß1 induced expression of MUC4, CDH2, VIM and SNAI1 genes and encoded by them proteins, MUC4, N-cadherin, vimentin and Snail, and reduced the level of CDH1 and its product, E-cadherin. In MUC4-knockdown cells, TGF-ß1-induced expression levels of MUC4, CDH2, VIM and SNAI1 and corresponding proteins were suppressed, but CDH1 and E-cadherin levels were not. In addition, TGF-ß1-induced phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2) was suppressed, but that of Smad2/3, Akt, and p38 was not. The results of this study suggest that MUC4 silencing inhibits TGF-ß1 -induced EMT via the ERK1/2 pathway, and a possible role of MUC4 in the induction of EMT in human airway epithelial cells.

Comparison of a covered metallic ureteral stent and a double-J stent for malignant ureteral obstruction in advanced gastric cancer.

AIM: To compare the patency and safety of covered metallic stents (CMS) and the double-J stent (DJS) for treating malignant ureteral obstruction (MUO) in advanced gastric cancer (AGC). MATERIALS AND METHODS: Between 2016 and 2018, the medical records of 61 patients (84 ureters; CMS, 39 patients, 54 ureters; DJS, 22 patients, 30 ureters) with MUO caused by AGC were reviewed retrospectively. The Kaplan-Meier method and log-rank test were used to evaluate differences of primary or assisted primary patency between groups. Cox regression was conducted separately for early (within 7 days) and late (after 7 days) primary patency. RESULTS: Technical success of CMS placement was 100% (54/54) and 96.8% (29/30) for DJS (p=0.357). The cumulative stent patency rates at 1, 3, 6, and 12 months were 77%, 74%, 70%, and 70%, in the CMS group and 72%, 60%, 53%, and 26%, in the DJS group. Apart from the period within 7 days (p=0.784), primary patency was consistently higher in the CMS group when compared to the DJS group over the entire follow-up period (p=0.034). Assisted primary patency was consistently higher in the CMS group than in the DJS group over the entire follow-up period (p=0.001). The CMS group was more likely to have complications than the DJS group (48.1% versus 16.7%, p=0.004). Complications were minor, self-limiting events such as haematuria/haematoma. CONCLUSION: CMS had better late patency and assisted primary patency than DJS. Procedure-related minor complications more frequently occurred with CMS.

Fipronil upregulates inflammatory cytokines and MUC5AC expression in human nasal epithelial cells.

BACKGROUND: Airway inflammation and excessive mucin production are pathophysiological characteristics of airway diseases. Fipronil, a pesticide, is being extensively used in agriculture and veterinary medicine worldwide. However, this compound impairs immune function in non-target organisms. The present study aimed to evaluate the effect of fipronil on pro-inflammatory cytokine and mucus production and signalling pathways in human primary nasal METHODOLOGY: The effect of fipronil on pro-inflammatory cytokine and MUC5AC expression and the signalling pathway of fipronil were investigated using real-time PCR, enzyme immunoassays, immunofluorescence, and immunoblot analysis with specific inhibitors and small interfering RNA. RESULTS: Fipronil treatment increased pro-inflammatory cytokine interleukin (IL)-1beta, IL-6, IL-8, and MUC5AC expression in human primary nasal epithelial cells. It also induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) mitogenactivated protein kinase (MAPK), p38 MAPK, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). MAPK and NF-kB inhibitor treatment significantly inhibited increases in IL-1beta, IL-6, IL-8, and MUC5AC expression. Ex vivo data confirmed that fipronil-induced MUC5AC expression occurs through ERK1/2, p38, and NF-kB signalling pathways in nasal inferior turbinate tissue. CONCLUSIONS: Fipronil induced pro-inflammatory cytokine IL-1beta, IL-6, IL-8, and MUC5AC expression via ERK1/2 MAPK, p38 MAPK, and NF-kB in human primary nasal epithelial cells.

Prediction of local control in early glottic carcinoma using the maximum standardised uptake value.

PURPOSE: This retrospective study aimed to determine whether the maximum standardised uptake value (SUVmax) can predict local tumour control in early glottic cancer (Tis, T1, and T2). PATIENTS AND METHODS: Fifty-nine patients treated with definitive radiotherapy for early glottic cancer between 2003 and 2011 were enrolled. We evaluated the SUVmax in the region of interest around the original tumour site. Local tumour control and survival were estimated using Kaplan-Meier curves. Receiver operating characteristic curves were used to assess the optimal SUVmax cut-off for predicting local control. RESULTS: As determined by laryngoscopy, all patients achieved a complete response. Eleven patients experienced local recurrence, while no distant metastasis occurred. One patient died due to local recurrence, while five lost their larynxes. The median follow-up was 61.5 (range: 6.2-123.4) months. The five-year local progression-free survival was 84.7%, and larynx preservation was possible in 89.6% of cases. The median SUVmax was 2.2. The optimal SUVmax for predicting local tumour control was identified as 3.4. Patients with glottic cancers with an SUVmax>3.4 showed a significantly lower local progression-free survival rate than those with tumours with an SUVmax<3.4 (five-year local progression-free survival rate: 53.4% vs. 95.4%, P<0.01). Multivariate analysis confirmed that a high SUVmax was an independent predictive factor for local progression-free survival (P=0.006). CONCLUSION: The use of (18F)-fluorodeoxyglucose-positron emission tomography for evaluation of the SUVmax is useful to predict local progression-free survival in patients with early glottic cancer treated by radiation. Early glottic cancer with a high SUVmax may require aggressive local treatment and careful surveillance.

Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas).

OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. TRIAL REGISTRATION NUMBER: IRB 00006477.

Retinoic acid prevents mesenteric lymph node dendritic cells from inducing IL-13-producing inflammatory Th2 cells.

The vitamin A (VA) metabolite retinoic acid (RA) affects the properties of T cells and dendritic cells (DCs). In VA-deficient mice, we observed that mesenteric lymph node (MLN)-DCs induce a distinct inflammatory T helper type 2 (Th2)-cell subset that particularly produces high levels of interleukin (IL)-13 and tumor necrosis factor-α (TNF-α). This subset expressed homing receptors for skin and inflammatory sites, and was mainly induced by B220(-)CD8α(-)CD11b(+)CD103(-) MLN-DCs in an IL-6- and OX40 ligand-dependent manner, whereas RA inhibited this induction. The corresponding MLN-DC subset of VA-sufficient mice induced a similar T-cell subset in the presence of RA receptor antagonists. IL-6 induced this subset differentiation from naive CD4(+) T cells upon activation with antibodies against CD3 and CD28. Transforming growth factor-ß inhibited this induction, and reciprocally enhanced Th17 induction. Treatment with an agonistic anti-OX40 antibody and normal MLN-DCs enhanced the induction of general inflammatory Th2 cells. In VA-deficient mice, proximal colon epithelial cells produced TNF-α that may have enhanced OX40 ligand expression in MLN-DCs. The repeated oral administrations of a T cell-dependent antigen primed VA-deficient mice for IL-13-dependent strong immunoglobulin G1 (IgG1) responses and IgE responses that caused skin allergy. These results suggest that RA inhibits allergic responses to oral antigens by preventing MLN-DCs from inducing IL-13-producing inflammatory Th2 cells.

Comparison of the HINTEGRA and Mobility total ankle replacements. Short- to intermediate-term outcomes.

In a retrospective study we compared 32 HINTEGRA total ankle replacements (TARs) and 35 Mobility TARs performed between July 2005 and May 2010, with a minimum follow-up of two years. The mean follow-up for the HINTEGRA group was 53 months (24 to 76) and for the Mobility group was 34 months (24 to 45). All procedures were performed by a single surgeon. There was no significant difference between the two groups with regard to the mean AOFAS score, visual analogue score for pain or range of movement of the ankle at the latest follow-up. Most radiological measurements did not differ significantly between the two groups. However, the most common grade of heterotopic ossification (HO) was grade 3 in the HINTEGRA group (10 of 13 TARs, 76.9%) and grade 2 in the Mobility group (four of seven TARs, 57.1%) (p = 0.025). Although HO was more frequent in the HINTEGRA group (40.6%) than in the Mobility group (20.0%), this was not statistically significant (p = 0.065).The difference in peri-operative complications between the two groups was not significant, but intra-operative medial malleolar fractures occurred in four (11.4%) in the Mobility group; four (12.5%) in the HINTEGRA group and one TAR (2.9%) in the Mobility group failed (p = 0.185).

Involvement of brain oxidation in the cognitive impairment in a triple transgenic mouse model of Alzheimer's disease: noninvasive measurement of the brain redox state by magnetic resonance imaging.

Oxidative stress is considered to be related to the onset and/or progression of Alzheimer's disease (AD), but there is insufficient evidence of its role(s). In this study, we evaluated the relationships between the brain redox state and cognitive function using a triple transgenic mouse model of AD (3 × Tg-AD mouse). One group of 3 × Tg-AD mice started to receive an α-tocopherol-supplemented diet at 2 months of age and another group of 3 × Tg-AD mice was fed a normal diet. The levels of α-tocopherol, reduced glutathione, oxidized glutathione, and lipid peroxidation were decreased in the cerebral cortex and hippocampus at 4 months of age in the 3 × Tg-AD mice fed a normal diet. These reductions were abrogated by the supplementation of α-tocopherol in the diet. During Morris water maze testing, the 3 × Tg-AD mice did not exhibit cognitive impairment at 4 months of age, but started to show cognitive dysfunction at 6 months of age, and α-tocopherol supplementation suppressed this dysfunction. Magnetic resonance imaging (MRI) using 3-hydroxymethyl-proxyl as a probe showed decreases in the signal intensity in the brains of 3 × Tg-AD mice at 4 months of age, and this reduction was clearly attenuated by α-tocopherol supplementation. Taken together, these findings suggest that oxidative stress can be associated with the cognitive impairment in 3 × Tg-AD mice. Furthermore, MRI might be a powerful tool to noninvasively evaluate the increases in reactive radicals, especially those occurring during the early stages of AD.

Reactive oxygen species-responsive miR-210 regulates proliferation and migration of adipose-derived stem cells via PTPN2.

Hypoxia enhances the proliferation and migration of adipose-derived stem cells (ASCs) via the generation of reactive oxygen species (ROS). Therefore, this study primarily investigated whether or not ROS generation could regulate microRNA-210 (miR-210) expression, and increase proliferation/migration of ASCs. In addition, we tried to identify the signaling pathways involved in miR-210 upregulation and the direct target genes of miR-210 that mediate these functions. Various sources of ROS generation such as hypoxia, antimycin, rotenone, and platelet-derived growth factor (PDGF)-BB upregulated miR-210 expression, and increased the proliferation/migration of ASCs. There is a positive feed-forward loop between ROS generation and miR-210, and miR-210 itself increases ROS generation by downregulation of iron-sulfur cluster scaffold homolog 2 (ISCU2). Although hypoxia-inducible factor-1α was not involved in miR-210 expression, pharmacological or small interfering RNA (siRNA)-driven inhibition of Akt and ERK1/2 molecules reduced miR-210 expression. Transfection of siRNAs of NF-κB and Elk1 also reduced miR-210 expression, indicating that these signaling pathways mediate miR-210 upregulation. Protein tyrosine phosphatase, non-receptor type 2 (PTPN2) was selected for miR-210 target gene, and it was downregulated by ROS generators or miR-210 mimic treatment. PTPN2 was first proven to be a direct miR-210 target in luciferase activity assay, and pharmacological inhibition or overexpression of PTPN2 regulated the proliferation and migration of ASC. In conclusion, ROS generation from diverse sources induces miR-210 expression in ASCs via PDGFR-ß, Akt and ERK pathways. Transcription of miR-210 expression is regulated by NF-κB and Elk1, and miR-210 increases the proliferation and migration of ASCs via ISCU2 and PTPN2 downregulation.

Phase III trial of concurrent thoracic radiotherapy with either first- or third-cycle chemotherapy for limited-disease small-cell lung cancer.

BACKGROUND: We compared late thoracic radiotherapy (TRT) with early TRT in the treatment of limited-disease small-cell lung cancer (LD-SCLC). PATIENTS AND METHODS: Patients with LD-SCLC received four cycles of etoposide plus cisplatin every 21 days. Patients were randomly assigned to receive either TRT administered concurrently with the first cycle (early TRT) or the third cycle (late TRT) of chemotherapy. The primary end point was complete response rate. RESULTS: Two hundred twenty-two patients were randomly assigned.Late TRT was not inferior to early TRT in terms of the complete response rate (early v late; 36.0% v 38.0%). Other efficacy measures including overall survival [median, 24.1 v 26.8 months;hazard ratio (HR) 0.93; 95% CI = 0.67­1.29] and progression free survival (median, 12.4 v 11.2 months; HR 1.09; 95%CI = 0.80­1.48) were not different between two arms. No statistical difference was noted in the pattern of treatment failures.However, neutropenic fever occurred more commonly in the early TRT arm than the late TRT arm (21.6% v 10.2%; P = 0.02) [corrected]. CONCLUSION: In LD-SCLC treatment, TRT starting in the third cycle of chemotherapy seemed to be noninferior to early TRT, and had a more favorable profile with regard to neutropenic fever.

Stage IE/IIE extranodal NK/T-cell lymphoma arising in the nasal cavity: analysis of CT findings and their prognostic value.

AIM: To investigate the computed tomography (CT) findings in patients with stage IE/IIE extranodal natural killer/T-cell lymphoma (ENKTL) arising in the nasal cavity and to evaluate whether imaging findings revealed by CT have prognostic value. MATERIALS AND METHODS: The CT findings of 62 patients diagnosed with IE/IIE ENKTL arising in the nasal cavity were retrospectively reviewed. Imaging findings were investigated, and evaluated imaging findings were analysed for the prognostic value of overall survival (OS) and disease-free survival (DFS). RESULTS: Of the 62 patients, 21 (34%) presented with a superficial infiltrative, 38 (61%) with a mass forming, and three (5%) with a combined pattern. Of all imaging findings, local invasiveness (n = 26, 42%), including bony destruction, erosion, or soft-tissue involvement, was the only independent prognostic factor for OS [p = 0.008; hazard ratio (HR): 3.85; 95% confidence intervals (CI): 1.42-10.44] and DFS (p = 0.001; HR: 4.25; 95% CI: 1.72-10.47). In a subgroup analysis of 36 cases with no local invasiveness, a superficial infiltrative pattern in one nasal cavity was a positive prognostic factor for OS (p = 0.028) and DFS (p = 0.008). CONCLUSION: Imaging findings at CT provided clinically useful predictions for treatment outcomes. Local invasiveness revealed by CT findings was a strong prognostic factor for poor OS and DFS. In addition, in patients with no local invasiveness, a superficial infiltrative pattern in one nasal cavity predicted favourable OS and DFS.

Identification of differentially expressed genes according to chemosensitivity in advanced ovarian serous adenocarcinomas: expression of GRIA2 predicts better survival.

BACKGROUND: The purpose of this study was to identify genes that are differentially expressed in chemosensitive serous papillary ovarian carcinomas relative to those expressed in chemoresistant tumours. METHODS: To identify novel candidate biomarkers, differences in gene expression were analysed in 26 stage IIIC/IV serous ovarian adenocarcinomas (12 chemosensitive tumours and 14 chemoresistant tumours). We subsequently investigated the immunohistochemical expression of GRIA2 in 48 independent sets of advanced ovarian serous carcinomas. RESULTS: Microarray analysis revealed a total of 57 genes that were differentially expressed in chemoresistant and chemosensitive tumours. Of the 57 genes, 39 genes were upregulated and 18 genes were downregulated in chemosensitive tumours. Five differentially expressed genes (CD36, LIFR, CHL1, GRIA2, and FCGBP) were validated by quantitative real-time PCR. The expression of GRIA2 was validated at the protein level by immunohistochemistry, and patients with GRIA2 expression showed a longer progression-free and overall survival (P=0.051 and P=0.031 respectively). CONCLUSIONS: We found 57 differentially expressed genes to distinguish between chemosensitive and chemoresistant tumours. We also demonstrated that the expression of GRIA2 among the differentially expressed genes provides better prognosis of patients with advanced serous papillary ovarian adenocarcinoma.

Treatment results of post-operative radiotherapy in patients with salivary duct carcinoma of the major salivary glands.

OBJECTIVE: Salivary duct carcinoma (SDC) is a rare malignancy of high-grade pathological type. We evaluated clinical outcomes and prognostic factors in 35 patients with SDC treated post-operatively with adjuvant radiation. METHODS: We retrospectively assessed overall survival, locoregional control and disease-free survival in 35 patients with SDC of the major salivary glands who underwent surgery and were subsequently treated with radiotherapy. The evaluated prognostic factors included gender, age, symptom duration, tumour site, tumour size, TNM classification, and the following pathological features: perineural invasion, lymphovascular invasion, extraparenchymal invasion and resection-margin status. RESULTS: Of the 35 patients, 30 (85.7%) were male. Median age at initial diagnosis was 62 years (range 38-75 years). The parotid gland was the main site affected in 22 patients (62.9%). 18 patients (51.5%) had pathological T3/T4 tumours, and 26 (74.3%) showed pathological nodal involvement. Actuarial 5-year locoregional control, disease-free survival and overall survival rates were 63.3%, 47.4% and 55.1%, respectively. The cause-specific death rate was 31.4% (n=11). Pathological nodal involvement was correlated with distant metastasis (p=0.011). Lymphovascular invasion was significantly prognostic for distant metastasis-free survival (p=0.049), locoregional control (p=0.012) and overall survival (p=0.003) in a Cox proportional hazard model, whereas perineural invasion was only significantly prognostic for overall survival (p=0.005). CONCLUSIONS: Surgery and post-operative radiotherapy were effective for locoregional control. Lymphovascular invasion and perineural invasion were significant prognostic factors in patients with SDC.

Proteins involved in DNA damage response pathways and survival of stage I non-small-cell lung cancer patients.

BACKGROUND: Biological complexity leads to significant variation in the survival of patients with stage I non-small-cell lung cancer (NSCLC). DNA damage response (DDR) pathways play a critical role in maintaining genomic stability and in the progression of NSCLC. Therefore, the development of a prognostic biomarker focusing on DDR pathways is an intriguing issue. PATIENTS AND METHODS: Expression of several proteins (ATM, ATMpS1981, γH2AX, 53BP1, 53BP1pS25, Chk2, Chk2pT68, MDC1, MDC1pS964, BRCA1pS1423, and ERCC1) and overall survival were investigated in 889 pathological stage I NSCLC patients. RESULTS: Low expression of BRCA1pS1423 or ERCC1 was significantly associated with worse survival in the whole cohort of patients. Analysis performed based on histology revealed that low expression of γH2AX, Chk2pT68, or ERCC1 was a poor prognostic factor in squamous cell carcinoma patients [adjusted hazard ratio (aHR), Cox P: 1.544, 0.012 for γH2AX; 1.624, 0.010 for Chk2pT68; 1.569, 0.011 for ERCC1]. The analysis of the interaction between two proteins showed that this effect was more pronounced in squamous cell carcinoma patients. However, these effects were not detected in adenocarcinoma patients. CONCLUSIONS: The proteins involved in DDR pathways exhibited differential expression between squamous cell carcinoma and adenocarcinoma and were important determinants of survival in stage I squamous cell carcinoma patients.

A novel disposable, transnasal esophagoscope: a pilot trial of feasibility, safety, and tolerance.

A novel disposable transnasal esophagoscope, the E.G. Scan (IntroMedic Co. Ltd., Seoul, Korea), was developed for the evaluation of esophageal diseases while eliminating the inconvenience associated with sterilization, portability, patient monitoring, complications, and the economic burden of sedation. The feasibility, safety, and tolerability of the first version of the E.G. Scan was evaluated in this pilot study. Nasal esophagoscopy was performed successfully in 46 patients with known or suspected esophageal diseases. At least 50% of the Z-line was visualized by the E.G. Scan in 38 (82.6%) of 46 patients. Abnormalities were identified in 27 patients: erosive esophagitis (n=18), Barrett's esophagus (n=1), esophageal varices (n=7), and esophageal candidiasis (n=1). Nasal pain was absent or mild in most patients, and adverse events were not observed. Further technical improvement of the E.G. Scan would increase the diagnostic usefulness in future clinical practice.