• Molecules and Cells
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• v.42 no.9
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• pp.628-636
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• 2019

Altered genetic features in cancer cells lead to a high rate of aerobic glycolysis and metabolic reprogramming that is essential for increased cancer cell viability and rapid proliferation. Pyruvate kinase muscle (PKM) is a rate-limiting enzyme in the final step of glycolysis. Herein, we report that PKM is a potential therapeutic target in triple-negative breast cancer (TNBC) cells. We found that PKM1 or PKM2 is highly expressed in TNBC tissues or cells. Knockdown of PKM significantly suppressed cell proliferation and migration, and strongly reduced S phase and induced G2 phase cell cycle arrest by reducing phosphorylation of the CDC2 protein in TNBC cells. Additionally, knockdown of PKM significantly suppressed $NF-{\kappa}B$ (nuclear factor kappa-light-chain-enhancer of activated B cells) activity by reducing the phosphorylation of p65 at serine 536, and also decreased the expression of $NF-{\kappa}B$ target genes. Taken together, PKM is a potential target that may have therapeutic implications for TNBC cells.

• Radiation Oncology Journal
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• v.33 no.2
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• pp.126-133
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• 2015

Purpose: To evaluate the outcomes of adjuvant radiotherapy (RT) and to analyze prognostic factors of survival in the International Federation of Gynecology and Obstetrics (FIGO) IB-IIA uterine cervical cancer. Materials and Methods: We retrospectively reviewed the medical records of 148 patients with FIGO IB-IIA uterine cervical cancer who underwent surgery followed by adjuvant RT at the Yonsei Cancer Center between June 1997 and December 2011. Adjuvant radiotherapy was delivered to the whole pelvis or an extended field with or without brachytherapy. Among all patients, 57 (38.5%) received adjuvant chemotherapy either concurrently or sequentially. To analyze prognostic factors, we assessed clinicopathologic variables and metabolic parameters measured on preoperative 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). To evaluate the predictive performance of metabolic parameters, receiver operating characteristic curve analysis was used. Overall survival (OS) and disease-free survival (DFS) were analyzed by the Kaplan-Meier method. Results: The median follow-up period was 63.2 months (range, 2.7 to 206.8 months). Locoregional recurrence alone occurred in 6 patients, while distant metastasis was present in 16 patients, including 2 patients with simultaneous regional failure. The 5-year and 10-year OSs were 87.0% and 85.4%, respectively. The 5-year and 10-year DFSs were 83.8% and 82.5%, respectively. In multivariate analysis, pathologic type and tumor size were shown to be significant prognostic factors associated with both DFS and OS. In subset analysis of 40 patients who underwent preoperative PET/CT, total lesion glycolysis was shown to be the most significant prognostic factor among the clinicopathologic variables and metabolic parameters for DFS. Conclusion: Our results demonstrated that adjuvant RT following hysterectomy effectively improves local control. From the subset analysis of preoperative PET/CT, we can consider that metabolic parameters may hold prognostic significance in early uterine cervical cancer patients. More effective systemic treatments might be needed to reduce distant metastasis in these patients.

• Journal of Korean Neurosurgical Society
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• v.62 no.5
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• pp.519-525
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• 2019

Objective : The circadian pattern of the onset time of aneurysmal subarachnoid hemorrhage (aSAH) has been reported by various authors. However, the effect of the degree of physical exertion on the circadian pattern has not been studied in detail. Therefore, we conducted this study to investigate the effect of physical exertion on the circadian pattern of aSAH. Methods : Of the 335 patients presenting with aSAH from January 2012 to December 2017, 234 patients with identifiable onset time and metabolic equivalent (MET) values were enrolled. The onset time of aSAH was divided into 4-hour intervals. The patient's physical exertion was then assessed on a scale between 1 and 8 METs using generally accepted MET values, and categorized into two groups-light exertion (1 to 4 METs) and moderate to heavy exertion (5 to 8 METs)-to determine the effect of the degree of physical exertion on the onset time distribution of aSAH. Multivariate analysis was used to calculate the odds ratio (OR) between the two groups to determine the effect of the degree of physical exertion on each set of time periods. Results : There was a definite bimodal onset pattern that peaked at 08:00-12:00 hours followed by 16:00-20:00 hours (p<0.001). MET values at all time intervals were found to be significantly higher than the night time (00:00-04:00 hours) values (p<0.031). The MET value distribution showed a unimodal pattern that slightly differed from the bimodal distribution of the onset time of aSAH. There were no significant differences in the ORs of each time interval according to the degree of the MET value. Conclusion : This study reaffirmed that aSAH occurs in a bimodal pattern, especially showing the highest prevalence in the morning. Although aSAH could be related to daily activity, there were no significant changes in diurnal variations affected by the degree of physical exertion.

• Journal of Chest Surgery
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• v.34 no.11
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• pp.831-842
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• 2001

Background: Patients with cardiac diseases who have structural defects in their heart bring about metabolic insult such as preoperative acid-base imbalance. Cardiac operation requires many nonphysiologic procedures such as extracorporeal circulation, hypothermia, and hemodilution. We studied the acid-base status of surgical heart diseases pre-operatively, during extracorporeal circulation, and post-operatively and researched the treatment indications of acid-base disturbances. Material and Method: From January 1997 to May 1999, fifty two cases of open heart surgery were carried out under extracorporeal circulation, which divided into a set of pediatric and adult groups, congenital and acquired groups, non-cyanotic and cyanotic groups, The $\alpha$ -stat arterial blood gas analysis was done in each group during the preoperative period, during the operation with extracorporeal circulation, and during the postoperative period. Result: Before surgery, all patients present metabolic acidosis, PaO2 was low in adult group and acquired group and compensatory respiratory alkalosis was noted in cyanotic group. During extracorporeal circulation, adult group revealed alkalosis and normal in acquired group. Pediatric group presents low Pa$CO_2$, metabolic acidosis and respiratory alkalosis. Congenital group and non-cyanotic group showed non-compensatory alkalosis trend and non-compensatory respiratory acidosis were observed in cyanotic group during extracorporeal circulation. Postoperative acid-base status of adult group was recovered to normal and the standard bicarbonate was increased in the acquired group. All of the pediatric, congenital non-cyanotic, and cyanotic groups revealed the lack of buffer base.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.19 no.11
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• pp.370-379
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• 2018

This study was conducted 1) to investigate the effects of treatment and other factors on the quality of life of thyroid cancer surgical patients and 2) to provide fundamental data for development of an intervention and symptom management program to improve the quality of life of those patients. A total of 76 patients who were diagnosed with thyroid cancer and underwent thyroidectomy from July 2013 to December 2014 participated in this study. To investigate the factors affecting quality of life, a t-test and ANOVA analyses were conducted, after which multiple regression analysis was performed. The results were statistically significant between preoperative and one month after surgery of sex, cancer history, fatigue, and quality of life until 3 months after surgery of stage, cancer history, anxiety, and pain. Multiple regression analysis showed that the most influential factors affecting the quality of life were depression and fatigue at one month prior to and after surgery and anxiety at three months after surgery, while no factors were found to be influential at six months after surgery. Overall, the results of this study suggested that it is imperative to manage depression and fatigue one month prior to and after surgery to reduce the physical and psychological pain experienced by thyroid cancer patients. Moreover, three months after the surgery, anxiety should be closely monitored and controlled to improve the quality of life of the patients. This approach is expected to reduce the burden on the health care system and social costs, which will positively affect public health.

• Journal of Gastric Cancer
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• v.18 no.3
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• pp.218-229
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• 2018

Purpose: This study investigated whether the metabolic avidity of primary tumors and/or metastatic lymph nodes (LNs) measured by $^{18}F$-fluorodeoxyglucose ($^{18}F-FDG$) positron emission tomography/computed tomography (PET/CT) was related to survival after surgery in patients with advanced gastric cancer (AGC). Materials and Methods: One hundred sixty-eight patients with AGC who underwent preoperative $^{18}F-FDG$ PET/CT and curative resection were included. The $^{18}F-FDG$ avidity of the primary gastric tumor and LNs was determined quantitatively and qualitatively. The diagnostic performance of $^{18}F-FDG$ PET/CT was calculated, and the prognostic significance of $^{18}F-FDG$ avidity for recurrence-free survival (RFS) and overall survival (OS) was assessed. Results: In all, 51 (30.4%) patients experienced recurrence, and 32 (19.0%) died during follow-up (median follow-up duration, 35 months; range, 3-81 months); 119 (70.8%) and 33 (19.6%) patients showed $^{18}F-FDG$-avid primary tumors and LNs, respectively. $^{18}F-FDG$ PET/CT showed high sensitivity (73.8%) for the detection of advanced pathologic T ($pT{\geq}3$) stage and high specificity (92.2%) for the detection of advanced pN (${\geq}2$) stage. $^{18}F-FDG$ avidity of LNs was significantly associated with RFS (P=0.012), whereas that of primary tumors did not show significance (P=0.532). Univariate and multivariate analyses revealed that $^{18}F-FDG$ avidity of LNs was an independent prognostic factor for RFS (hazard ratio=2.068; P=0.029). Conclusions: $^{18}F-FDG$ avidity of LNs is an independent prognostic factor for predicting RFS. Preoperative $^{18}F-FDG$ PET/CT can be used to determine the risk and prognosis of patients with AGC after curative resection.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.1
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• pp.1-6
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• 2009

DNA double-strand breaks (DSBs) occur commonly in the all living and in cycling cells. They constitute one of the most severe form of DNA damage, because they affect both strand of DNA. DSBs result in cell death or a genetic alterations including deletion, loss of heterozygosity, translocation, and chromosome loss. DSBs arise from endogenous sources like metabolic products and reactive oxygen, and also exogenous factors like ionizing radiation. Defective DNA DSBs can lead to toxicity and large scale sequence rearrangement that can cause cancer and promote premature aging. There are two major pathways for their repair: homologous recombination(HR) and non-homologous end-joining(NHEJ). The HR pathway is a known "error-free" repair mechanism, in which a homologous sister chromatid serves as a template. NHEJ, on the other hand, is a "error-prone" pathway, in which the two termini of the broken DNA molecule are used to form compatible ends that are directly ligated. This review aims to provide a fundamental understanding of how HR and NHEJ pathways operate, cause genome instability, and what kind of genes during the pathways are associated with head and neck cancer.

• The Korean Journal of Pain
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• v.10 no.2
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• pp.170-178
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• 1997

Background: The analgesic efficacy and safety of propacetamol, an injectable prodrug of acetoaminophen, in combination with intravenous morphine PCA were studied in 40 patients after gynecological surgery requiring lower abdominal incision. Methods: Using a double-blind, randomized, parallel-group design, the effects of four(every 6 hr) intravenous injections of 2 g propacetamol(=1 g acetoaminophen) were compared with four injections of placebo(PL) immediately after surgery. Efficacy of cumulative dose of morphine and number of boluses requested was assessed over 24 hours by automated recording on the PCA device. It was assessed on pain scores rated on a ten-point verbal scale along with vital signs, $K^+$, glucose, BUN, creatinine, PT and PTT were measured along with stress hormones(epinephrine, norepinephrine and cortisol). Results: There were no differences in demographic data between two groups. Propacetamol group demonstrated approximately 21% morphine sparing effect compared to placebo group($33.1{\pm}10.4$ mg vs $41.4{\pm}8.0$ mg). No significant differences noted in $K^+$, glucose, BUN, Creatinine, PT and PTT levels. There were significant increases in norepinephrine and cortisol in placebo group postoperatively, compared to preoperative values. At the same time, propacetamol group also showed significant changes in these hormones. Both group revealed high degree of patient satisfaction. Conclusion: Propacetamol showed significant morphine sparing effect to some degree. Side effects were much less in propacetamol group with subsequently high patient satisfaction. The secretion of stress hormone were not blocked by postoperative propacetamol injections. Authors concluded that propacetamol should be considered as an excellent adjuvant analgesics in postoperative pain control in opioid patient controlled analgesia.

• Radiation Oncology Journal
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• v.36 no.2
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• pp.95-102
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• 2018

Purpose: To evaluate the prognostic value of $^{18}F$-fluorodeoxyglucose positron-emission tomography (FDG PET) with computed tomography (CT) before and during radiotherapy (RT) in patients with head and neck cancer. Methods: Twenty patients with primary head and neck squamous cell carcinoma were enrolled in this study, of whom 6 had oropharyngeal cancer, 10 had hypopharyngeal cancer, and 4 had laryngeal cancer. Fifteen patients received concurrent cisplatin and 2 received concurrent cetuximab chemotherapy. FDG PET/CT was performed before RT and in the 4th week of RT. The parameters of maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis (TLG) of the primary tumor were measured, and the prognostic significance of each was analyzed with the Cox proportional hazards model. Results: Higher TLG (>19.0) on FDG PET/CT during RT was a poor prognostic factor for overall survival (OS) (p = 0.001) and progression-free survival (PFS) (p = 0.007). In the multivariate analysis, TLG during RT as a continuous variable was significantly associated with OS and PFS rate (p = 0.023 and p = 0.016, respectively). Tumor response worse than partial remission at 1 month after RT was another independent prognostic factor for PFS (p = 0.024). Conclusions: Higher TLG of the primary tumor on FDG PET/CT during RT was a poor prognostic factor for OS and PFS in patients with head and neck cancer.

• Archives of Plastic Surgery
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• v.34 no.4
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• pp.528-530
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• 2007

Purpose: Holoprosencephaly(HPE) is a rare developmental defect due to incomplete cleavages of the prosencephalon during the third week of fetal development. Chromosomal anomalies, genetic syndrome, teratogen, or genetic disorder of non-syndromic HPE are usually accepted as etiology. The consequences of prechordal mesoderm defect are varying degrees of deficit of midline facial development, especially the median nasal process(premaxilla), and incomplete morphogenesis of the forebrain. We experienced a case of lobar HPE with complete cleft lip and palate. Methods: A female newborn infant was born at $38^{+6}$ weeks' gestational age via NSVD. The infant's birth weight was 3.6 kg, height 52 cm, and head circumference 32.5 cm, showing microcephaly, flat nose, median complete cleft lip & palate, and hypotelorism, along with defects of midfacial development including losses of premaxilla, philtrum, nasal septum, and columella. Results: There were no specific findings noted from the head and neck X-ray and tests for endocrine and metabolic disorders, but clinical characteristics of midface and dysgenesis corpus callosum on brain MRI were seen, so that this case was diagnosed with HPE. Conclusion: HPE is divided into three categories of alobar, semilobar, and lobar prosencephaly according to the degree of cerebral hemisphere separation. Assesment of patient's brain abnormality and malformation is essential in determining the extent and benefit of surgical intervention. This case was included in the lobar type HPE which shows relatively good prognosis compared with other types and reconstruction of median complete cleft lip & palate and midfacial defects will be performed.