Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes. Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals. Conclusions UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.

Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes. Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals. Conclusions UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.

Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes. Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals. Conclusions UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.

Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes. Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals. Conclusions UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes. Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals. Conclusions UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Purpose: In men with metastatic castration-resistant prostate cancer (mCRPC), new bone lesions are sometimes not properly categorized through a confirmatory bone scan, and clinical significance of the test itself remains unclear. This study aimed to demonstrate the performance rate of confirmatory bone scans in a real-world setting and their prognostic impact in enzalutamide-treated mCRPC. Materials and Methods: Patients who received oral enzalutamide for mCRPC during 2014-2017 at 14 tertiary centers in Korea were included. Patients lacking imaging assessment data or insufficient drug exposure were excluded. The primary outcome was overall survival (OS). Secondary outcomes included performance rate of confirmatory bone scans in a real-world setting. Kaplan-Meier analysis and multivariate Cox regression analysis were performed. Results: Overall, 520 patients with mCRPC were enrolled (240 [26.2%] chemotherapy-naïve and 280 [53.2%] after chemotherapy). Among 352 responders, 92 patients (26.1%) showed new bone lesions in their early bone scan. Confirmatory bone scan was performed in 41 patients (44.6%), and it was associated with prolonged OS in the entire population (median, 30.9 vs. 19.7 months; p < 0.001), as well as in the chemotherapy-naïve (median, 47.2 vs. 20.5 months; p=0.011) and post-chemotherapy sub-groups (median, 25.5 vs. 18.0 months; p=0.006). Multivariate Cox regression showed that confirmatory bone scan performance was an independent prognostic factor for OS (hazard ratio 0.35, 95% confidence interval, 0.18 to 0.69; p=0.002). Conclusion Confirmatory bone scan performance was associated with prolonged OS. Thus, the premature discontinuation of enzalutamide without confirmatory bone scans should be discouraged.

Background/Aims: Synchronous multiple gastric cancer (SMGC) accounts for approximately 6% to 14% of gastric cancer (GC) cases. This study aimed to identify risk factors for SMGC. Methods: A total of 14,603 patients diagnosed with GC were prospectively enrolled. Data including age, sex, body mass index, smoking, alcohol consumption, family history, p53 expression, microsatellite instability, cancer classification, lymph node metastasis, and treatment were collected. Risk factors were analyzed using logistic regression analysis between a single GC and SMGC. Results: The incidence of SMGC was 4.04%, and that of early GC (EGC) and advanced GC (AGC) was 5.43% and 3.11%, respectively. Patients with SMGC were older (65.33 years vs 61.75 years, p<0.001) and more likely to be male. Lymph node metastasis was found in 27% of patients with SMGC and 32% of patients with single GC. Multivariate analysis showed that SMGC was associated with sex (male odds ratio [OR], 1.669; 95% confidence interval [CI], 1.223 to 2.278; p=0.001), age (≥65 years OR, 1.532; 95% CI, 1.169 to 2.008; p=0.002), and EGC (OR, 1.929; 95% CI, 1.432 to 2.600; p<0.001). Survival rates were affected by Lauren classification, sex, tumor size, cancer type, distant metastasis, and venous invasion but were not related to the number of GCs. However, the survival rate of AGC with SMGC was very high. Conclusions SMGC had unique characteristics such as male sex, older age, and EGC, and the survival rate of AGC, in which the intestinal type was much more frequent, was very good (Trial registration number: NCT04973631).