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Chemotherapeutic drugs can cause cardiac toxicities such as cardiomyopathy, arrhythmia, and cardiovascular disease. The well-known side effects of cisplatin are nephrotoxicity, nausea, vomiting, and electrolyte imbalance. Cardiotoxicity induced by cisplatin is rare, and its pathophysiology is unknown. Here, we present two cases of complete and high-degree atrioventricular (AV) block that occurred during cisplatin-based chemotherapy and required pacemaker placement. A 64-year-old woman and a 75-year-old man, who had no underlying heart disease, developed dyspnea without chest pain and bradycardia during cisplatin-based chemotherapy. However, there were no significant differences in their serum electrolyte levels, cardiac enzyme levels, and echocardiography results before and after drug administration. The ECGs were confirmed with complete AV block and high-degree AV block, which requiring pacemaker placement. We assume that cisplatin directly caused the complete, high-degree AV block, which required a pacemaker placement in our cases. In such cases, a cumulative dose of cisplatin over 240 mg/m2 is a risk factor for early symptoms of AV block. If patients complain of dyspnea without chest pain during cisplatin-based chemotherapy, arrhythmic complications should be considered. This information may be helpful for clinicians treating patients with cisplatin chemotherapy.

Extra-pulmonary neuroendocrine carcinoma is a rare and aggressive cancer. Although several biological and histological markers have been suggested as prognostic factors for this cancer, the prognostic importance of systemic inflammatory markers, including the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, is unclear. This study aimed to evaluate the association between systemic inflammatory markers and the prognosis of extra-pulmonary neuroendocrine carcinoma. We retrospectively analyzed the clinical data of 85 patients with unresectable or metastatic extra-pulmonary neuroendocrine carcinoma who received platinum-based chemotherapy as first-line chemotherapy from August 2007 to November 2019. We used time-dependent receiver operating characteristic curve analysis to determine the cut-off values. The cut-off values for the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were 3.0 and 158.5, respectively. There was no significant difference in the Eastern Cooperative Oncology Group performance status score, Ki-67 index, or response to chemotherapy between groups. The high neutrophil-lymphocyte ratio group showed significantly worse overall survival (high vs. low, median 11.1 vs. 21.0 months, log-rank p=0.004) and shorter median progression-free survival, but the latter was not statistically significant. The high platelet-lymphocyte ratio group also showed significantly worse progression-free survival and overall survival than the low platelet-lymphocyte ratio group (high vs. low: median 5.6 vs. 9.8 months, log-rank p=0.047 and median 13.8 vs. 21.0 months, log-rank p=0.013, respectively). In multivariable analysis, a high neutrophil-lymphocyte ratio was an independent prognostic factor for overall survival. The neutrophil-lymphocyte ratio is a potent and readily available prognostic factor for extra-pulmonary neuroendocrine carcinoma.

Adjuvant chemotherapy for gastric cancer, particularly stage III, improves survival after curative D2 gastrectomy. We investigated the clinical value of the lymph-node ratio (LNR; number of metastatic lymph nodes/number of lymph nodes examined) for selecting the appropriate adjuvant chemotherapy regimen in patients with D2-resected stage II/III gastric cancer.We reviewed the data of 819 patients who underwent curative D2 gastrectomy followed by adjuvant chemotherapy. Of them, 353 patients received platinum-based chemotherapy and 466 received TS-1. The patients were categorized into three groups according to their LNR (LNR 1, 0-0.1; LNR 2, 0.1-0.25; and LNR 3, 0.25), and their disease-free survival (DFS) was evaluated.The DFS curves of the patients were well separated according to stage and LNR. In multivariate analyses, an LNR 0.1 was strongly associated with the 3-year DFS (hazard ratio 2.402, 95% confidence interval 1.607-3.590, P 0.001). Platinum-based chemotherapy improved the 3-year DFS compared to TS-1 in patients with LNR 3 group in stage III gastric cancer (platinum vs. TS-1, median DFS 26.87 vs. 16.27 months, P = 0.028). An LNR 0.1 was associated with benefiting from platinum-based adjuvant chemotherapy in stage III gastric cancer patients with lymphovascular invasion (platinum vs. TS-1, median DFS 47.57 vs. 21.77 months, P = 0.011).The LNR can be used to select the appropriate adjuvant chemotherapy regimen for patients with D2-resected gastric cancer, particularly in stage III.

Background The clinical features and therapeutic strategies for gastric cancer with positive peritoneal washing cytology but without visible gross peritoneal metastasis have not been defined. The aim of this study was to evaluate the effect and clinical prognostic value of postoperative chemotherapy in gastric cancer patients with positive peritoneal washing cytology without gross peritoneal metastasis who underwent radical D2 gastrectomy in terms of disease-free survival (DFS) and overall survival (OS). Materials and Methods Intraoperative peritoneal washing cytology was performed in 285 patients who underwent radical D2 gastrectomy between April 2004 and May 2016. Of them, 88 patients with positive cytology but without gross peritoneal metastasis were included in the study. In total, 64 patients received postoperative chemotherapy, whereas 24 patients underwent surgery only. Results Most gastric cancer patients with positive cytology without gross peritoneal metastasis demonstrated pT4 and/or pN3 disease. Postoperative chemotherapy improved DFS and OS compared to surgery only in gastric cancer patients with positive cytology without gross peritoneal metastasis (median DFS 11.63 vs. 6.98 months, p p p p

Background Extrapulmonary neuroendocrine carcinoma (EP-NEC) is an aggressive type of cancer with poor prognosis. Although several biological and histological markers are prognostic factors in NEC, the correlation between prognosis and systemic inflammation markers, such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), is unclear. This study evaluated the association between NLR or PLR and median overall survival (OS) or progression-free survival (PFS) in EP-NEC. Methods We retrospectively analyzed the clinical data from patients with unresectable or metastatic EP-NECs who received platinum-based chemotherapy at Chonnam National University Hwasun Hospital from August 2007 to March 2019. The cut-off values for NLR and PLR were 3 and 160, respectively. Results In total, 38 patients were analyzed. Both NLR and PLR at diagnosis had no significant associations with the response to initial chemotherapy. However, in the high-PLR group, median overall survival (OS) and progression-free survival (PFS) were poorer than those in the low-PLR group (high vs. low: 10.6 vs. 17.1 months, log-rank p = 0.007 and 4.1 vs. 9.3 months, log-rank p = 0.032, respectively). However, the high-NLR group had insignificantly poorer median OS and PFS than the low-NLR group. In the multivariate analysis, high PLR and LDH were independent prognostic factors for median OS and PFS. Conclusions High PLR was associated with shorter survival of EP-NEC patients receiving platinum-based chemotherapy. Therefore, PLR may be an independent prognostic factor in EP-NEC.

BubR1 acetylation is essential in spindle assembly checkpoint (SAC) signaling. Here we show that BubR1 deacetylation is a signal that initiates mitotic exit. Sustained BubR1 acetylation arrests the cells in metaphase, although chromosome congression is achieved. BubR1 deacetylation was coordinated with dephosphorylation in mitotic exit, suggesting the presence of a coordinated acetylation-phosphorylation code in mitotic signaling. Histone deacetylase (HDAC) 2 and 3 bound to acetylated BubR1 exclusively in mitosis and led to the polyubiquitination of BubR1. Subsequent degradation of BubR1 resulted in the disassembly of the mitotic checkpoint complex. Importantly, BRCA2 was required for HDAC2/3 association with acetylated BubR1 in nocodazole (Noc)-arrested cells. Plk1, PP2A, P300/CBP-associated factor (PCAF) and BubR1 were found in the mitotic BRCA2 complex, suggesting that BRCA2 acts as a signaling scaffold for BubR1 modification. Furthermore, we show that Plk1 is required for BRCA2 to localize at the prometaphase kinetochore (KT). Inhibition of Plk1 resulted in the loss of BRCA2 from the KT, and so did PCAF, consistent with the loss of BubR1 acetylation. Concordantly, BRCA2-dysfunctional cells exhibited resistance to trichostatin A, which was restored when BRCA2 was introduced. That loss of Brca2 conferred resistance to various HDAC inhibitors was corroborated by the experiments in mouse pancreatic organoids. These results suggest that the BRCA2-BubR1 acetylation-deacetylation pathway is an important decision-making point for the HDAC inhibitor response. Taken together, BRCA2 is a signaling platform for BubR1, and BubR1 deacetylation is a cue for SAC silencing.

Substitution effect of sea tangle (ST) with tunic of sea squirt (SS) in diet on growth and carcass composition of juvenile abalone was determined. One thousand four hundred and seventy abalones were distributed into 21 containers. Six formulated diets in triplicate were prepared. A 200 g/kg ST was included into the ST0 diet. The 200, 400, 600, 800 and 1000 g/kg of ST were substituted with the same amount of tunic of SS, referred to as the ST200, ST400, ST600, ST800 and ST1000 diets, respectively. Finally, Undaria was prepared to compare effect of the formulated diets on performance of abalone. The experimental diets were fed to abalone for 16 weeks. Weight gain of abalone fed the ST400 diet was higher than that of abalone fed the ST0, ST600, ST800 and ST1000 diets and Undaria. Weight gain of abalone fed the formulated diets was higher than that of abalone fed the Undaria. The chemical composition of the carcass of abalone was affected by dietary substitution of ST with tunic of SS. In conclusion, ST could be completely substituted with tunic of SS without retardation in performance of abalone. Abalone fed the ST400 diet substituting 400 g/kg ST with tunic of SS achieved the best growth.

A 16-wk feeding trial was conducted to assess the effects of different types of dietary carbohydrate on growth and body composition of juvenile abalone (Haliotis discus). A total of 1,680 abalone were randomly distributed among 24 containers (70 per container) and fed one of eight diets, including seven experimental diets containing different types of carbohydrates, including dextrin (DT), glucose (GC), corn starch (CS), α-cellulose (CL), maltose (MT), sucrose (SC), and wheat flour (WF), and Undaria to compare effect of experimental diets. Water stability of the diets was measured 12, 24, and 48 h after seawater immersion. Water stability of the diets was different over all periods of time and their significant interaction was also observed. Survival was not significantly affected by diet. Weight gain and specific growth rate were greatest in abalone fed on the CL diet. Shell length, width, height, and soft body weight were greatest in abalone fed the CL diet, followed by the WF, DT, SC, CS, GC, ...

This study was conducted to evaluate the long term complications and their risk factors including of survival outcomes in patients with locally advanced nasopharyngeal cancer (NPC) treated with docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy (CCRT).Among the patients who were diagnosed as NPC, we consecutively evaluated the late complications in 104 patients who completed 3 cycles of TPF induction chemotherapy followed by CCRT and received regular follow-up by otolaryngologist and oncologist. The prognostic factors for overall survival, relapse free survival and each complication were analyzed based on clinical characteristics.Over a median follow-up of 54 months (range, 7.9-152.9 months), 5-year overall survival rate was 87% for stage II, 89% for stage III, 87% for stage IV patients. The significant prognostic factor for survival is complete response rate after CCRT in multivariate analysis. The most frequent toxicity was ear complication (29.8%) including of hearing loss requiring hearing aid (6.7%) and bone necrosis (3.8%). Decreased renal function over grade 2 was occurred in only 4 patients (3.8%) regardless of the cumulative dose of cisplatin. The long term complications did not affect the survival outcome. Patients who received radiation therapy more than 5400 cGy had better survival outcome than those who did not. However, ear complication was significantly related to radiation dose (≥ 6,600 cGy) and type of radiation therapy (conventional). Age over 65 years was a significant risk factor for both ear and renal toxicity. In conclusion, close follow-up to monitor long-term complications should be performed in patients treated with TPF induction chemotherapy followed by CCRT treatment, especially in elderly patients. Reestablishing the optimal chemotherapeutic agent during CCRT and adjustment of radiation dose after induction chemotherapy could be helpful to reduce the toxicity associated with the subsequent treatment strategy for locally advance NPC patients.

Performance and stress resistance of juvenile abalone (Haliotis discus) fed formulated diets substituting fish meal (FM) and macroalgae (MA) with soybean meal and rice bran, respectively, was compared with the MA under various stress conditions. Four experimental diets (Standard, FM50, FM50 + MA50, and FM50 + MA100 diets) were prepared in duplicate. The dry MA (Undaria pinnatifida and Laminaria japonica)were also prepared to compare with the effects of formulated diets on the performance of abalone to achieve the industry standard. About 84,000 juvenile abalone were distributed into twelve 5-ton tanks (7,000 abalone per tank). The diets were fed to abalone once a day to satiation. At the end of the 16-wk feeding trial, abalone were subjected to various stress (air exposure, sudden salinity, and temperature changes) conditions and cumulative mortality was monitored. Weight gain and specific growth rate of abalone fed the all formulated diets were higher than the dry MA. The cumulative mortality of...

Mist chemical vapor deposition (mist-CVD)-processed, lithium (Li)-doped ZnO thin film transistors (TFTs) are investigated. Li doping significantly increases the field-effect mobility in TFTs up to ∼100 times greater than that of undoped ZnO. The addition of Li into mist-CVD-grown ZnO semiconductors leads to improved film quality, which results from the enhanced crystallinity and reduced defect states, including oxygen vacancies. Our results suggest that Li doping of ZnO-based oxide semiconductors could serve as an effective strategy for high-performance, mist-CVD-processed oxide TFTs with low-cost and low-temperature fabrication.

【This study was performed to determine effects of the supplementation of Kimchi lactic acid bacterial culture in extruded pellets (EP) on the growth, body composition, blood chemistry and immune response of olive flounder Paralichthys olivaceus. Four hundred eighty individuals averaging 16.1 g were randomly distributed into 12, 180 L flow-through tanks (forty fish per tank). Four concentrations of Kimchi lactic acid bacterial culture (KL) were prepared: Control (0%), 0.1%, 0.2% and 0.5%. Three concentrations (0.1%, 0.2% and 0.5%) of Kimchi lactic acid bacterial culture were each diluted to 10% of EP weight and then fully absorbed by EP for 10 minutes. Each diet was fed to triplicate groups of fish. Fish were hand-fed to apparent satiation twice a day for 8 weeks. At the end of the 8-week feeding trial, the plasma lysozyme and bacterial activities of fish were determined. In addition, the cumulative mortality of fish was monitored for 8 days after their artificial infection with Edwardsiella tarda. The weight gain, specific growth rate, feed efficiency ratio, protein efficiency ratio, protein retention, hepatosomatic index and condition factor of fish were not affected by dietary supplementation with KL. None of the proximate composition, plasma parameters, lysozyme or bactericidal activities of fish was affected by dietary supplementation with KL. However, the cumulative mortalities of fish fed EP containing 0.1% and 0.5% Kimchi lactic acid bacterial culture were relatively low compared to that of fish fed the control diet. In conclusion, dietary supplementation with KL did not effectively improve growth, feed utilization, body composition, plasma chemistry, lysozyme, bactericidal activities or immune response of olive flounder after E. tarda infection under these experimental conditions.】