[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.

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.

[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.

[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.

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.

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.

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.

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.

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.

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.

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.

Recombinant human epidermal growth factor treatment of radiation-induced severe oral mucositis in patients with head and neck malignancies.

Mucositis of the oral cavity and pharynx is a major dose-limiting factor in the application of radiotherapy (RT) to patients with head and neck cancer. Therefore, we evaluated the wound healing effect of human recombinant epidermal growth factor (rhEGF) in head and neck cancer and lymphoma patients with irradiation (with or without combined chemotherapy-induced oral mucositis). Patients at Asan Medical Center who had undergone definitive RT of the head and neck region with or without combined chemotherapy and who had developed severe oral mucositis (higher than the Radiation Therapy Oncology Group grade 3) were treated with topical rhEGF twice daily for 7 days. The evaluation of response with regard to oral mucositis was performed 1 week later. Of the 11 treated patients, three had nasopharyngeal carcinoma, three had carcinoma of the oropharynx, two had carcinoma of the oral cavity, one had carcinoma of the hypopharynx and two had lymphoma of the head and neck. Six patients received RT only, and five patients received concurrent chemoradiotherapy. All patients showed improvements in their oral mucositis after topical treatment with rhEGF in that the Radiation Therapy Oncology Group grade was significantly decreased (P = 0.0000). This finding suggests that rhEGF is effective and safe for the treatment of radiation-induced mucositis. Further studies are needed to determine the optimal dosage and fractionation schedule.

Prognostic factors in FIGO stage IB-IIA small cell neuroendocrine carcinoma of the uterine cervix treated surgically: results of a multi-center retrospective Korean study.

BACKGROUND: To determine the clinical and pathologic prognostic factors in surgically treated patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIA small cell neuroendocrine carcinoma of the uterine cervix (SCNEC). PATIENTS AND METHODS: We retrospectively reviewed a total of 68 patients with FIGO stage IB-IIA SCNEC surgically treated from January 1997 to December 2003 in Korea. RESULTS: Of the 68 patients, 43 had FIGO stage IB1 SCNEC, 15 had stage IB2, and 10 had stage IIA. Seven were treated with radical surgery alone; 11 with neoadjuvant chemotherapy (NACT) followed by radical surgery; 24 with radical surgery followed by adjuvant chemotherapy; and 26 with radical surgery followed by adjuvant radiation or chemoradiation. After a median follow-up of 44 months (range, 6-113 months), the 2-year and 5-year survival rates for all patients were 64.6% and 46.6%, respectively. Univariate and multivariate analysis showed that FIGO stage was predictive of poor prognosis. Patients who received NACT showed poorer prognosis than those who did not receive NACT. Adjuvant chemoradiation did not improve survival compared with adjuvant chemotherapy alone. CONCLUSIONS: FIGO stage may act as a surrogate for factors prognostic of survival. Primary radical surgery followed by adjuvant chemotherapy is the preferred treatment modality for patients with early stage SCNEC.

Expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) inversely correlates with tumor progression in gastric adenomas and carcinomas.

PURPOSE: The expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), one of TGF-beta superfamily gene, is reported to be responsible for NSAID-induced apoptosis. We analyzed NAG-1 expression in gastric cancer and adenoma to find out its clinical implication. METHODS: Immunostaining was performed using standard procedures with antibody to NAG-1 on gastric tissue microarrays of tissue specimens obtained by gastrectomy. The immunoreactivity of normal and tumor tissues was graded as no, weak, moderate, and strong expression. RESULTS: The NAG-1 expression was stronger in intestinal metaplasia and adenoma than normal gastric epithelium. 47 (74.6%) of 63 normal gastric epithelium showed no or weak expression, but 33 (56.9%) of 58 and 13 (86.7%) of 15 intestinal metaplsia and adenoma showed moderate or strong expression. Only NAG-1 expression in diffuse type gastric cancer was weaker than in normal gastric tissue. Compared to intestinal metaplasia, both intestinal and diffuse type gastric cancer showed weaker expression. The intensity of NAG-1 expression inversely correlated with tumor differentiation and T and N stage status. While only 1 (2.2%) of 45 T1 stage cases lacked NAG-1 expression, 27 (45.8%) of 59 T3 stage cases lacked NAG-1 expression. Likewise, in N0 stage tumors only 10 (15.4%) of 65 cases lacked NAG-1 expression, but 17 (63.0%) of 27 N3 cases lacked NAG-1 expression. CONCLUSIONS: The NAG-1 was expressed strongly in intestinal metaplasia and adenoma, and inversely correlated to tumor stages. This interesting finding may provide new targets for chemoprevention and future development of drugs.

Increased expression of Toll-like receptor 5 during progression of cervical neoplasia.

The purpose of this study was to determine whether Toll-like receptor 5 (TLR5) expression was associated with disease progression in cervical neoplasia. TLR5 expression was evaluated by immunohistochemistry (IHC) in 55 formalin-fixed paraffin-embedded cervical tissues; 10 normal cervical specimens, 9 low-grade cervical intraepithelial neoplasias (CINs), 12 high-grade CINs, and 24 invasive squamous cell carcinomas (ISCCs). TLR5 expression was also evaluated at the RNA level, in fresh, frozen cervical carcinoma tissues by real-time quantitative RT-PCR. TLR5 expression, which was mainly observed as cytoplasmic staining, gradually increased in accordance with the histopathologic grade in the following order: low-grade CIN less than high-grade CIN less than ISCC (P < 0.001). Immunohistochemical staining showed that TLR5 expression was undetectable (80%) or weak (20%) in normal cervical squamous epithelial tissues. However, moderate expression was detected in 33.3% of low-grade CIN (3/9), 41.7% of high-grade CIN (5/12), and 45.8% of ISCC (11/24). Strong expression was detected in as much as 33.3% of high-grade CIN (4/12) and 50% of ISCC (12/24). Contrary to IHC results, real-time quantitative RT-PCR revealed that TLR5 expression in tumors was not statistically different compared to normal cervical tissues (P = 0.1452). The IHC result suggests that TLR5 may play a significant role in tumor progression of cervical neoplasia and may represent a useful marker for malignant transformation of cervical squamous cells.

Characteristics of early colorectal carcinoma with lymph node metastatic disease.

BACKGROUND/AIMS: Endoscopic resection may safely and effectively remove early colorectal cancers. However, additional surgical treatment is needed in cases with metastatic lymph nodes for curative treatment. The purpose of this study was to investigate the correlation between lymph node metastasis and various pathological parameters in early colorectal cancers. METHODOLOGY: The clinicopathological records of 3,557 colorectal adenocarcinoma patients who underwent surgical resection at the Samsung Medical Center from August 1995 to June 2005 were reviewed. One hundred forty seven tissue samples with early colorectal cancer were used in this study. Various parameters were studied including gender, location, macroscopic appearance, differentiation, lymphatic tumor emboli, and the depth of tumor invasion. RESULTS: Twenty five patients (17.0%) had lymph node metastasis. Male gender, left colon, macroscopically depressed lesions, moderately or poorly differentiated carcinoma, depth of tumor invasion (Sm2 or Sm3), and presence of lymphatic tumor emboli were the risk factors for lymph node metastasis. CONCLUSIONS: Early colorectal cancers with male gender, location in the left colon, macroscopically depressed lesion, moderate or poor differentiation, depth in Sm2 or Sm3, and the presence of lymphatic tumor emboli have higher risk of lymph node metastasis than those without. The early colorectal cancers with these risk factors should have surgical resection.

Environmental risk assessment of genetically engineered herbicide-tolerant Zoysia japonica.

Herbicide-tolerant Zoysia grass (Zoysia japonica Steud.) has been generated previously through Agrobacterium tumefaciens-mediated transformation. The genetically modified (GM) Zoysia grass survived Basta spraying and grew to maturity normally while the wild-type (WT) grass stopped growing and died. GM Zoysia grass will permit more efficient weed control for various turf grass plantings such as home lawns, golf courses, and parks. We examined the environmental/biodiversity risks of herbicide-tolerant GM Zoysia before applying to regulatory agencies for approval for commercial release. The GM and WT Zoysia grass' substantial trait equivalence, ability to cross-pollinate, and gene flow in confined and unconfined test fields were selectively analyzed for environmental/biodiversity effects. No difference between GM and WT Zoysia grass in substantial traits was found. To assess the potential for cross-pollination and gene flow, a non-selective herbicide, Basta, was used. Results showed that unintended cross-pollination with and gene flow from GM Zoysia grass were not detected in neighboring weed species examined, but were observed in WT Zoysia grass (on average, 6% at proximity, 1.2% at a distance of 0.5 m and 0.12% at a radius of 3 m, and 0% at distances over 3 m). On the basis of these initial studies, we conclude that the GM Zoysia grass generated in our laboratory and tested in the Nam Jeju County field does not appear to pose a significant risk when cultivated outside of test fields.