Inhibition of STAT3 enhances sensitivity to tamoxifen in tamoxifen-resistant breast cancer cells.

BACKGROUND: The mechanisms of endocrine resistance are complex, and deregulation of several oncogenic signalling pathways has been proposed. We aimed to investigate the role of the EGFR and Src-mediated STAT3 signalling pathway in tamoxifen-resistant breast cancer cells. METHODS: The ER-positive luminal breast cancer cell lines, MCF-7 and T47D, were used. We have established an MCF-7-derived tamoxifen-resistant cell line (TamR) by long-term culture of MCF-7 cells with 4-hydroxytamoxifen. Cell viability was determined using an MTT assay, and protein expression levels were determined using western blot. Cell cycle and annexin V staining were analysed using flow cytometry. RESULTS: TamR cells showed decreased expression of estrogen receptor and increased expression of EGFR. TamR cells showed an acceleration of the G1 to S phase transition. The protein expression levels of phosphorylated Src, EGFR (Y845), and STAT3 was increased in TamR cells, while phosphorylated Akt was decreased. The expression of p-STAT3 was enhanced according to exposure time of tamoxifen in T47D cells, suggesting that activation of STAT3 can cause tamoxifen resistance in ER-positive breast cancer cells. Both dasatinib (Src inhibitor) and stattic (STAT3 inhibitor) inhibited cell proliferation and induced apoptosis in TamR cells. However, stattic showed a much stronger effect than dasatinib. Knockdown of STAT3 expression by siRNA had no effect on sensitivity to tamoxifen in MCF-7 cells, while that enhanced sensitivity to tamoxifen in TamR cells. There was not a significant synergistic effect of dasatinib and stattic on cell survival. TamR cells have low nuclear p21(Cip1) expression compared to MCF-7 cells and inhibition of STAT3 increased the expression of nuclear p21(Cip1) in TamR cells. CONCLUSIONS: The EGFR and Src-mediated STAT3 signalling pathway is activated in TamR cells, and inhibition of STAT3 may be a potential target in tamoxifen-resistant breast cancer. An increase in nuclear p21(Cip1) may be a key step in STAT3 inhibitor-induced cell death in TamR cells.

Efficacy of concurrent chemoradiotherapy for patients with limited-disease small-cell lung cancer: a retrospective, nationwide, population-based cohort study.

BACKGROUND: Small-cell lung cancer (SCLC) is a highly proliferative, rapidly growing tumor with a poor prognosis, even in cases of limited disease (LD). Timely and accurate high-intensity therapy is necessary. For concurrent chemoradiotherapy (CCRT), etoposide/platinum (EP)-based regimens are recommended, although irinotecan/platinum (IP)-based regimens are also effective with radiotherapy. This large-scale, retrospective, nationwide cohort study aimed to analyze the efficacy of CCRT in patients with LD-SCLC. METHODS: Population data registered between January 2008 and December 2018 was extracted from the Health Insurance Review and Assessment Service of Korea database. Survival outcomes of 4446 LD-SCLC patients who received CCRT were analyzed. RESULTS: Patients who received EP-CCRT (n = 4187) showed better time to first subsequent therapy (TFST: 11.2 months) and overall survival (OS: 22.2 months) than those who received IP-CCRT (n = 259; TFST: 9.6 months, P = 0.0477; OS: 16.4 months, P <  0.0001). When CCRT failed, dual-agent chemotherapy (n = 925; OS: 9.1 months) provided a better survival benefit than single-agent chemotherapy (n = 815; OS: 7.5 months). IP-based chemotherapy resulted in better OS (9.6 months) than EP-based chemotherapy (7.1 months, P = 0.017) in platinum-resistant relapsed patients; the opposite was observed for platinum-sensitive relapsed patients (OS: EP, 17.2 months; IP, 6.6 months; P <  0.0001). Poisson regression analysis demonstrated that age, EP-CCRT, and hypercholesterolemia retained significant associations with OS after adjustment for all variables. CONCLUSION: In the Korean population, the effects of EP-CCRT on OS and TFST are significantly more favorable than those of IP-CCRT.

Changes in electroencephalographic power and bicoherence spectra according to depth of dexmedetomidine sedation in patients undergoing spinal anesthesia.

Background: Assessment the depth of dexmedetomidine sedation using electroencephalographic (EEG) features can improve the quality of procedural sedation. Previous volunteer studies of dexmedetomidine-induced EEG changes need to be validated, and changes in bicoherence spectra during dexmedetomidine sedation has not been revealed yet. We aimed to investigate the dexmedetomidine-induced EEG change using power spectral and bicoherence analyses in the clinical setting. Patients and Methods: Thirty-six patients undergoing orthopedic surgery under spinal anesthesia were enrolled in this study. Dexmedetomidine sedation was conducted by the stepwise increase in target effect site concentration (Ce) while assessing sedation levels. Bispectral index (BIS) and frontal electroencephalography were recorded continuously, and the performance of BIS and changes in power and bicoherence spectra were analyzed with the data from the F3 electrode. Results: The prediction probability values for detecting different sedation levels were 0.847, 0.841, and 0.844 in BIS, 95% spectral edge frequency, and dexmedetomidine Ce, respectively. As the depth of sedation increased, δ power increased, but high ß and γ power decreased significantly (P <0.001). α and spindle power increased significantly under light and moderate sedation (P <0.001 in light vs baseline and deep sedation; P = 0.002 and P <0.001 in moderate sedation vs baseline and deep sedation, respectively). The bicoherence peaks of the δ and α-spindle regions along the diagonal line of the bicoherence matrix emerged during moderate and deep sedation. Peak bicoherence in the δ area showed sedation-dependent increases (29.93%±7.38%, 36.72%±9.70%, 44.88%±12.90%; light, moderate, and deep sedation; P = 0.008 and P <0.001 in light sedation vs moderate and deep sedation, respectively; P = 0.007 in moderate sedation vs deep sedation), whereas peak bicoherence in the α-spindle area did not change (22.92%±4.90%, 24.72%±4.96%, and 26.96%±8.42%, respectively; P=0.053). Conclusions: The increase of δ power and the decrease of high-frequency power were associated with the gradual deepening of dexmedetomidine sedation. The δ bicoherence peak increased with increasing sedation level and can serve as an indicator reflecting dexmedetomidine sedation levels.

QKI, a miR-200 target gene, suppresses epithelial-to-mesenchymal transition and tumor growth.

The microRNA-200 (miR-200) family plays a major role in specifying epithelial phenotype by preventing expression of the transcription repressors ZEB1 and ZEB2, which are well-known regulators of the epithelial-to-mesenchymal transition (EMT) in epithelial tumors including oral squamous cell carcinoma (OSCC). Here, we elucidated whether miR-200 family members control RNA-binding protein quaking (QKI), a newly identified tumor suppressor that is regulated during EMT. We predicted that miR-200a and miR-200b could recognize QKI 3'-UTR by analyzing TargetScan and The Cancer Genome Atlas head and neck squamous cell carcinoma (HNSCC) dataset. Forced expression of miR-200b/a/429 inhibited expression of ZEB1/2 and decreased cell migration in OSCC cell lines CAL27 and HSC3. QKI expression was also suppressed by miR-200 overexpression, and the 3'-UTR of QKI mRNA was directly targeted by miR-200 in luciferase reporter assays. Interestingly, shRNA-mediated knockdown of QKI led to pronounced EMT and protumor effects in both in vitro and in vivo studies of OSCC. Furthermore, high expression of QKI protein is associated with favorable prognosis in surgically resected HNSCC and lung adenocarcinoma. In conclusion, QKI increases during EMT and is targeted by miR-200; while, it suppresses EMT and tumorigenesis. We suggest that QKI and miR-200 form a negative feedback loop to maintain homeostatic responses to EMT-inducing signals.

OH reactivity in urban and suburban regions in Seoul, South Korea - an East Asian megacity in a rapid transition.

South Korea has recently achieved developed country status with the second largest megacity in the world, the Seoul Metropolitan Area (SMA). This study provides insights into future changes in air quality for rapidly emerging megacities in the East Asian region. We present total OH reactivity observations in the SMA conducted at an urban Seoul site (May-June, 2015) and a suburban forest site (Sep, 2015). The total OH reactivity in an urban site during the daytime was observed at similar levels (∼15 s(-1)) to those previously reported from other East Asian megacity studies. Trace gas observations indicate that OH reactivity is largely accounted for by NOX (∼50%) followed by volatile organic compounds (VOCs) (∼35%). Isoprene accounts for a substantial fraction of OH reactivity among the comprehensive VOC observational dataset (25-47%). In general, observed total OH reactivity can be accounted for by the observed trace gas dataset. However, observed total OH reactivity in the suburban forest area cannot be largely accounted for (∼70%) by the trace gas measurements. The importance of biogenic VOC (BVOCs) emissions and oxidations used to evaluate the impacts of East Asian megacity outflows for the regional air quality and climate contexts are highlighted in this study.

Total Lesion Glycolysis Using ¹8F-FDG PET/CT as a Prognostic Factor for Locally Advanced Esophageal Cancer.

Standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) have been considered prognostic factors for survival in many cancers. However, their prognostic value for radiotherapy-treated squamous esophageal cancer has not been evaluated. In this study, SUV, MTV, and TLG were measured to predict their prognostic role in overall survival (OS) in 38 esophageal cancer patients who had undergone (18)F-FDG PET/CT before radiotherapy. TLG demonstrated higher sensitivity and specificity for predicting OS than MTV and SUV; and a better OS was observed in patients with low TLG compared to those with high TLG in locally advanced disease (OS, 46.9 months; 95% confidence interval [CI], 33.50-60.26 vs. 25.3 months; 95% CI, 8.37-42.28; P=0.003). Multivariate analyses in these patients determined that TLG and the use of combination chemotherapy were the independent prognostic factors for OS (hazard ratio [HR], 7.12; 95% CI, 2.038-24.857; P=0.002 and HR, 6.76; 95% CI, 2.149-21.248; P=0.001, respectively). These results suggest that TLG is an independent prognostic factor for OS and a better predictor of survival than MTV and SUV in patients with locally advanced esophageal cancer treated with radiotherapy.

The expression of microRNA-34a is inversely correlated with c-MET and CDK6 and has a prognostic significance in lung adenocarcinoma patients.

We aimed to establish whether the expression of microRNA-34a (miR-34a) is correlated with that of c-MET and G1 phase regulators such as cyclin dependent kinase (CDK) 4, CDK6, and cyclin D (CCND) 1 in non-small cell lung cancer (NSCLC), and whether a relationship exists between miR-34a expression and both clinicopathologic factors and recurrence-free survival (RFS). For 58 samples archived from NSCLC patients, we measured the expression of miR-34a and c-MET, CDK4/6, and CCND1 by quantitative RT-PCR and assessed the relationship between miR-34a expression, clinicopathological factors, and RFS. The expression of miR-34a was significantly lower in squamous cell tumors (P < 0.001) and in tumors associated with lymphatic invasion (P = 0.001). We found significant inverse correlations between miR-34a and c-MET (R = -0.316, P = 0.028) and CDK6 expression (R = -0.4582, P = 0.004). RFS were longer in adenocarcinoma patients with high miR-34a expression than in those with low miR-34a expression (55.6 vs. 21.6 months; P = 0.020). With univariate analysis, statistically significant prognostic factors for RFS in adenocarcinoma patients were miR-34a expression (Relative risk (RR), 8.14; P = 0.049), TNM stage (RR, 13.55; P = 0.001), LN metastasis (RR, 4.19; P = 0.043), and the presence of lymphatic invasion (RR, 7.05; P = 0.015). In multivariate analysis, only miR-34a was prognostic for RFS (RR, 11.5; P = 0.027). miR-34a expression was inversely correlated with that of c-MET and CDK6 in NSCLC, and had prognostic significance for RFS, especially in adenocarcinoma patients.

Correction: Sung et al. Linear Tumor Regression of Rectal Cancer in Daily MRI during Preoperative Chemoradiotherapy: An Insight of Tumor Regression Velocity for Personalized Cancer Therapy. Cancers 2022, 14, 3749.

In the original publication [...].

Practice guidelines for managing extrahepatic biliary tract cancers.

Backgrounds/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions: The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Metronomic chemotherapy as a potential partner of immune checkpoint inhibitors for metastatic colorectal cancer treatment.

The use of immune checkpoint inhibitors (ICIs) in clinical practice for the treatment of metastatic colorectal cancer (mCRC) is currently limited to patients with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H), which comprise less than 5% of all mCRC cases. Combining ICIs with anti-angiogenic inhibitors, which modulate the tumor microenvironment, may reinforce and synergize the anti-tumor immune responses of ICIs. In mCRCs, combinations of pembrolizumab and lenvatinib have shown good efficacy in early phase trials. These results suggest the potential utility of immune modulators as partners in combination treatment with ICIs in immunologically cold microsatellite stable, as well as hot dMMR/MSI-H tumors. Unlike conventional pulsatile maximum tolerated dose chemotherapy, low-dose metronomic (LDM) chemotherapy recruits immune cells and normalizes vascular-immune crosstalk, similar to anti-angiogenic drugs. LDM chemotherapy mostly modulates the tumor stroma rather than directly killing tumor cells. Here, we review the mechanism of LDM chemotherapy in terms of immune modulation and its potential as a combination partner with ICIs for the treatment of patients with mCRC tumors, most of which are immunologically cold.

Effect of total intravenous versus inhalation anesthesia on long-term oncological outcomes in patients undergoing curative resection for early-stage non-small cell lung cancer: a retrospective cohort study.

BACKGROUND: Propofol-based total intravenous anesthesia (TIVA) improves long-term outcomes after cancer surgery compared with inhalation anesthesia. However, its effect on patients undergoing non-small cell lung cancer (NSCLC) surgery remains unclear. We aimed to compare the oncological outcomes of TIVA and inhalation anesthesia after curative resection of early-stage NSCLC. METHODS: We analyzed the medical records of patients diagnosed with stage I or II NSCLC who underwent curative resection at a tertiary university hospital between January 2010 and December 2017. The primary outcomes were recurrence-free survival (RFS) and overall survival (OS) according to anesthesia type. RESULTS: We included 1,508 patients with stage I/II NSCLC. The patients were divided into the TIVA (n = 980) and Inhalation (n = 528) groups. The two groups were well-balanced in terms of baseline clinical characteristics. The TIVA group demonstrated significantly improved RFS (7.7 years, 95% CI [7.37, 8.02]) compared with the Inhalation group (6.8 years, 95% CI [6.30, 7.22], P = 0.003). Similarly, TIVA was superior to inhalation agents with respect to OS (median OS; 8.4 years, 95% CI [8.08, 8.69] vs. 7.3 years, 95% CI [6.81, 7.71]; P < 0.001). Multivariable Cox regression analysis revealed that TIVA was an independent prognostic factor related to recurrence (hazard ratio [HR]: 1.24, 95% CI [1.04, 1.47], P = 0.014) and OS (HR: 1.39, 95% CI [1.12, 1.72], P = 0.002). CONCLUSIONS: Propofol-based TIVA was associated with better RFS and OS than inhalation anesthesia in patients with stage I/II NSCLC who underwent curative resection.

Prognostic impact of 18F-FDG PET/CT in pathologic stage II invasive ductal carcinoma of the breast: re-illuminating the value of PET/CT in intermediate-risk breast cancer.

BACKGROUND: The aim of this study is to investigate the impact of 18F-FDG PET/CT on prognosis of stage II invasive ductal carcinoma (IDC) of the breast primarily treated with surgery. METHODS: The clinical records of 297 consecutive IDC with preoperative PET/CT and pathologically staged II in surgery from 2013 to 2017 were retrospectively reviewed. The maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), tumor-to-liver ratio (TLR), and metabolic tumor volume (MTV) were measured. Association of clinicopathologic factors (age, T stage, N stage, AJCC pathologic stage of IIA or IIB, pathologic prognostic stage, grade, hormonal receptor status, HER2 status, Ki-67, and adjuvant therapy) and PET parameters with DFS was assessed using the Cox proportional hazards model. RESULTS: There were 35 recurrences and 10 deaths at a median follow-up of 49 months (range 0.8 ~ 87.3). All PET parameters were significantly associated with DFS in univariate analysis but in multivariate analysis, SUVpeak was the only factor significantly associated with DFS (hazard ratio 2.58, 95% confidence interval 1.29-5.15, P = 0.007). In cohorts with higher values of SUVpeak or TLR, patients who received adjuvant chemotherapy had significantly superior DFS. CONCLUSION: Metabolic parameters derived from preoperative PET/CT was significantly associated with recurrence in stage II IDC primarily treated with surgery. PET/CT can be a powerful prognostic tool in conjunction with novel staging systems and current biomarkers for patients undergoing contemporary therapy. Our results urge to reconsider the currently underestimated value of PET/CT confined to diagnostic aspect and to newly recognize its prognostic impact in these intermediate-risk breast cancer.

A Randomized Phase III Study of Patients With Advanced Gastric Adenocarcinoma Without Progression After Six Cycles of XELOX (Capecitabine Plus Oxaliplatin) Followed by Capecitabine Maintenance or Clinical Observation.

PURPOSE: Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy. MATERIALS AND METHODS: Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level. RESULTS: Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250-0.890; P=0.020). CONCLUSIONS: After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02289547.

Linear Tumor Regression of Rectal Cancer in Daily MRI during Preoperative Chemoradiotherapy: An Insight of Tumor Regression Velocity for Personalized Cancer Therapy.

Objective: Neoadjuvant chemoradiotherapy (CCRT) is current standards of care for locally advanced rectal cancer. The precise and thorough investigation of a tumor during the full course of CCRT by means of daily MRI can provide an idea on real-time treatment sensitivity in addition to tumor biology. Tumor volumetry from daily MRI during CCRT may allow patient-driven treatment decisions. Material and Methods: Patients diagnosed with cT3-4 and/or cN+ rectal adenocarcinoma undergoing preoperative CCRT with capecitabine on the pelvis up to 50 Gy in 25 daily fractions from November 2018 to June 2019 were consecutively included. Rectal tumor volume was uniformly measured by a single physician (YKK) in daily 0.35T MRI obtained with MR-guided linear accelerator. Primary endpoint was to assess the pattern of tumor volume regression throughout the full course of CCRT using daily registration MRI. Secondary endpoint was to assess the effect of tumor regression velocity on disease-free survival (DFS). Tumor regression velocity (cc) per fraction of each patient was calculated using the simple regression analysis of tumor volumes from fraction 1 to fraction 25. Results: Twenty patients were included. Daily tumor volumetry demonstrated linear tumor regression during CCRT. The tumor regression velocity of all 20 patients was 2.40 cc per fraction (R2 = 0.93; p < 0.001). The median tumor regression velocity was 1.52 cc per fraction. Patients with tumor regression velocity ≥ 1.52 cc per fraction were grouped as rapid regressors (N = 9), and those with tumor regression velocity < 1.52 cc per fraction were grouped as slow regressors (N = 11). Rapid regressors had greater tumor regression velocity (4.58 cc per fraction) compared to that of slow regressors (0.78 cc per fraction) with statistical significance (p < 0.001). The mean DFS of rapid regressors was 36.8 months, numerically longer than the 31.9 months of slow regressors (p = 0.400) without statistical significance. Rapid regressors had numerically superior DFS rate compared to slow regressors without statistical significance. The 2-year DFS was 88.9% for rapid regressors and 72.7% for slow regressors, respectively (p = 0.400). Conclusion: This study is the first observation of linear tumor regression in daily MRI during the preoperative CCRT of locally advanced rectal cancer. Daily tumor regression velocity discriminated DFS, although without statistical significance. This study with a phenomenal approach is hypothesis-generating. Nevertheless, the potential of CCRT from therapeutics to a newer level, the "theranostics", has been inceptively suggested. Further validation studies for the value of daily tumor volumetry on treatment decisions are warranted.

Prognostic Impact of Total Lesion Glycolysis (TLG) from Preoperative 18F-FDG PET/CT in Stage II/III Colorectal Adenocarcinoma: Extending the Value of PET/CT for Resectable Disease.

We investigated the prognostic role of metabolic parameters from preoperative 18F-FDG PET/CT in stage II/III colorectal adenocarcinoma. A total of 327 stage II/III colorectal adenocarcinoma patients who underwent curative resection were included. The maximal standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were analyzed for optimal cut-offs and their effect on DFS. Differences in DFS rates and hazard ratios for DFS between cut-offs were statistically significant in SUVmax, MTV2.5, MTV3, TLG 2.5, TLG3, and TLG30%. Factors significantly related to DFS in univariate Cox regression were age, sex, stage, preoperative CEA, SUVmax, MTV2.5, MTV3, TLG2.5, TLG3, and TLG30%. Age, sex, preoperative CEA, and TLG2.5 (p = 0.009) sustained statistically significant difference in multivariate analysis. The 1-, 3-, and 5-year DFS rates for TLG2.5 ≤ 448.5 were 98.1%, 79.6%, and 74.8%, significantly higher than 78.4%, 68.5%, and 61.1% of TLG2.5 > 448.5, respectively (p = 0.012). TLG, a parameter indicating both the metabolic activity and metabolic volume, was the strongest predictor independently associated with DFS, among several PET parameters with statistical significance. These results suggest the potential prognostic value of preoperative 18F-FDG PET/CT in stage II/III resectable colorectal cancer.

MicroRNA-769-3p Acts as a Prognostic Factor in Oral Squamous Cell Cancer by Modulating Stromal Genes.

miR-769-3p expression is suppressed in the stromal subtype of head and neck squamous cell carcinoma (HNSCC); however, its role in stromal HNSCC has not been fully elucidated. To investigate the biological relevance of miR-769-3p in the stromal phenotype, we established oral squamous cell cancer (OSCC) cell lines, namely CAL27, HSC3, and YD8, overexpressing miR-769-3p. miR-769-3p expression was positively and negatively correlated with interferon-gamma-related genes and MYC target gene sets, respectively. miR-769-3p decreased OSCC cell migration and invasion as well as mesenchymal marker expression and increased epithelial marker expression. Moreover, miR-769-3p enhanced OSCC cell sensitivity to 5-fluorouracil. High miR-769-3p expression was associated with good prognosis of HNSCC patients. Collectively, these results suggest that miR-769-3p suppression enhances stromal gene expression and promotes the epithelial-to-mesenchymal transition. Therefore, miR-769-3p may be a potential biomarker of the miRNA phenotype in OSCC patients.

Comparison of analytical methods and residue patterns of pymetrozine in Aster scaber.

Residues of the polar pesticide pymetrozine were compared using two methods: hydromatrix and liquid-liquid extraction (LLE). The biological half-life and the final residue level were investigated using Aster scaber over a 10-days cultivation period. The respective biological half-lives of the pesticide were 4.2 and 3.5 days at the recommended and double dose. The final residue levels were 1.28 and 1.98 mg kg(-1), respectively, at the same application rate of pymetrozine according to the GAP standard of the United Kingdom. Average recovery was higher with LLE than with the hydromatrix method. Dissipation curves of pymetrozine were influenced by the application amount and growth rate of A. scaber. The final residue level of pymetrozine could be predicted to be lower than the UK maximum residue limit for lettuce applying the GAP standard.

Serum conversion pattern of SCC-Ag levels between pre- and post-chemoradiotherapy predicts recurrence and metastasis in cervical cancer: a multi-institutional analysis.

The value of squamous-cell carcinoma antigen (SCC-Ag) as a tumor marker for cervical cancer is controversial because it is not elevated (> 2 ng/mL) in a quarter of patients at diagnosis. Two hundred ninety one IB-IVA cervical squamous cell-carcinoma patients who underwent definitive chemoradiotherapy (CRT) were included in four tertiary institutions. Serum conversion pattern between pre- and post-treatment SCC-Ag levels was categorized into the following three arms: (1) Consistent Seronegative arm (both ≤ 2 ng/mL); (2) Negative Conversion arm (from > 2 ng/mL to ≤ 2 ng/mL); and (3) Consistent Seropositive arm (both > 2 ng/mL). Median follow-up time was 40.3 months. For Consistent Seronegative (N = 67), Negative Conversion (N = 165), and Consistent Seropositive (N = 59) arms, the 3-year recurrence-free survival (RFS) rates were 79.4%, 62.0%, and 48.4% (P < 0.001) and the 3-year overall survival (OS) rates were 86.3%, 80.6%, and 58.7% (P = 0.001), respectively. The serum conversion pattern of SCC-Ag between pre- and post-treatment was the most significant and potent prognostic factor of RFS (P = 0.001) and OS (P = 0.007) on the multivariate analysis. Simply checking whether SCC-Ag level is above or below 2 ng/mL before and after definitive CRT can provide clinicians with a simple rule-of-thumb for prediction of disease outcome in cervical cancer patients.

Treatment Outcomes of 9,994 Patients With Extensive-Disease Small-Cell Lung Cancer From a Retrospective Nationwide Population-Based Cohort in the Korean HIRA Database.

To investigate the efficacy of irinotecan-based (IP) and etoposide-based (EP) platinum combinations, and of single-agent chemotherapy, for treatment of extensive-disease small cell lung cancer (ED-SCLC), we performed a large-scale, retrospective, nationwide, cohort study. The population data were extracted from the Health Insurance Review and Assessment Service of Korea database from January 1, 2008, to November 30, 2016. A total of 9,994 patients were allocated to ED-SCLC and analyzed in this study. The primary objectives were to evaluate the survival outcomes of systemic first-line treatments for ED-SCLC. For first-line treatment, patients who received IP showed a better time to first subsequent therapy (TFST) of 8.9 months (95% confidence interval [CI], 8.50-9.40) than those who received EP, who had a TFST of 6.8 months (95% CI, 6.77-6.97, P < 0.0001). In terms of overall survival (OS), IP was superior to EP (median OS, 10.8 months; 95% CI, 10.13-11.33 vs. 9.5 months; 95% CI, 9.33-9.73; P < 0.0001). Taken together, in the Korean population, first-line IP combination chemotherapy had significantly favorable effects on OS and TFST.

The effect of adjuvant chemotherapy and early tumor regression on the outcome of nasopharyngeal cancer patients treated with concurrent chemoradiotherapy.

OBJECTIVES: We assessed the role of adjuvant chemotherapy (ACT) in patients with advanced nasopharyngeal carcinoma treated with concurrent chemoradiotherapy (CCRT) and investigated the prognostic factors for recurrence and survival. MATERIALS AND METHODS: Between January 2008 and January 2018, 88 non-metastatic nasopharyngeal carcinoma patients treated with CCRT and with or without ACT in two institutions were retrospectively reviewed. The initial tumor response evaluation was performed 1 month after CCRT completion. Survival analysis was performed for factors such as initial tumor regression, ACT and other clinical factors. Subgroup analysis was performed for the four-group categorized according to tumor regression and ACT (CR with/without ACT, non-CR with/without ACT). RESULTS: Complete response (CR) 1 month after CCRT was a favorable prognosticator for progression-free survival (PFS) (hazard ratio [HR] 3.16, 95% confidence interval [CI] 1.02-9.85, p = 0.046) and overall survival (OS) (HR 3.19, 95% CI 1.14-8.93, p = 0.027). Also, ACT was an independent factor for PFS (HR 0.38, 95% CI 0.15-0.98, p = 0.047) and OS (HR 0.37, 95% CI 0.13-0.99, p = 0.047). In subgroup analysis, the CR after CCRT followed by ACT group showed significantly higher locoregional recurrence-free survival (p = 0.02), OS (p = 0.003), distant-metastasis free survival (p = 0.07), and PFS (p = 0.01) than the other three groups. CONCLUSION: Tumor regression 1 month after CCRT, and administration of ACT identified as an independent prognosticator for PFS and OS in this study. Even patients who show early tumor regression after CCRT may benefit from ACT. Further randomized trials should define the role of ACT in patients with nasopharyngeal cancer who achieved CR after CCRT.