Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD.Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC.

Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD.Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC.

Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD.Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC.

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.

Pedicle ossification is a rare but significant complication following mandibular reconstruction using a fibular free flap (FFF), a technique widely employed in maxillofacial surgery due to its reliable vascularized bone supply and low donor site morbidity. The FFF supports dental implantation and prosthetic rehabilitation, with its vascularized periosteum enhancing osteogenic potential. Despite these advantages, unexpected ossification of the flap’s vascular pedicle may occur, potentially mimicking tumor recurrence and causing diagnostic uncertainty. This case report describes a 38-year-old male with left buccal squamous cell carcinoma treated by wide excision, modified radical neck dissection, and reconstruction using a radial forearm free flap. Postoperative radiotherapy led to complications including trismus and alveolar bone exposure, culminating in a pathological mandibular fracture. Mandibular reconstruction was performed using an FFF. Over 4 years of follow-up, computed tomography revealed ossification within the vascular pedicle. Notably, the patient remained asymptomatic, maintaining normal speech and swallowing without functional impairment. Pedicle ossification may present radiographically as a suspicious bony change misinterpreted as tumor recurrence. Routine follow-up imaging such as computed tomography is essential for differentiation. Although trismus, bony swelling, or pain may occur, surgical intervention is typically deferred unless symptoms develop. Therefore, careful clinical assessment and monitoring remain crucial.

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.

Pedicle ossification is a rare but significant complication following mandibular reconstruction using a fibular free flap (FFF), a technique widely employed in maxillofacial surgery due to its reliable vascularized bone supply and low donor site morbidity. The FFF supports dental implantation and prosthetic rehabilitation, with its vascularized periosteum enhancing osteogenic potential. Despite these advantages, unexpected ossification of the flap’s vascular pedicle may occur, potentially mimicking tumor recurrence and causing diagnostic uncertainty. This case report describes a 38-year-old male with left buccal squamous cell carcinoma treated by wide excision, modified radical neck dissection, and reconstruction using a radial forearm free flap. Postoperative radiotherapy led to complications including trismus and alveolar bone exposure, culminating in a pathological mandibular fracture. Mandibular reconstruction was performed using an FFF. Over 4 years of follow-up, computed tomography revealed ossification within the vascular pedicle. Notably, the patient remained asymptomatic, maintaining normal speech and swallowing without functional impairment. Pedicle ossification may present radiographically as a suspicious bony change misinterpreted as tumor recurrence. Routine follow-up imaging such as computed tomography is essential for differentiation. Although trismus, bony swelling, or pain may occur, surgical intervention is typically deferred unless symptoms develop. Therefore, careful clinical assessment and monitoring remain crucial.

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.

Pedicle ossification is a rare but significant complication following mandibular reconstruction using a fibular free flap (FFF), a technique widely employed in maxillofacial surgery due to its reliable vascularized bone supply and low donor site morbidity. The FFF supports dental implantation and prosthetic rehabilitation, with its vascularized periosteum enhancing osteogenic potential. Despite these advantages, unexpected ossification of the flap’s vascular pedicle may occur, potentially mimicking tumor recurrence and causing diagnostic uncertainty. This case report describes a 38-year-old male with left buccal squamous cell carcinoma treated by wide excision, modified radical neck dissection, and reconstruction using a radial forearm free flap. Postoperative radiotherapy led to complications including trismus and alveolar bone exposure, culminating in a pathological mandibular fracture. Mandibular reconstruction was performed using an FFF. Over 4 years of follow-up, computed tomography revealed ossification within the vascular pedicle. Notably, the patient remained asymptomatic, maintaining normal speech and swallowing without functional impairment. Pedicle ossification may present radiographically as a suspicious bony change misinterpreted as tumor recurrence. Routine follow-up imaging such as computed tomography is essential for differentiation. Although trismus, bony swelling, or pain may occur, surgical intervention is typically deferred unless symptoms develop. Therefore, careful clinical assessment and monitoring remain crucial.

People with obesity maintain low levels of inflammation; therefore, their exposure to foreign antigens can trigger an excessive immune response. In people with obesity or allergic contact dermatitis (ACD), symptoms are exacerbated by a reduction in the number of regulatory T cells (Tregs) and IL-10/TGF-β–modified macrophages (M2 macrophages) at the inflammatory site. Benefits of intermittent fasting (IF) have been demonstrated for many diseases; however, the immune responses regulated by macrophages and CD4+ T cells in obese ACD animal models are poorly understood. Therefore, we investigated whether IF suppresses inflammatory responses and upregulates the generation of Tregs and M2 macrophages in experimental ACD animal models of obese mice. The IF regimen relieved various ACD symptoms in inflamed and adipose tissues. We showed that the IF regimen upregulates Treg generation in a TGF-β-dependent manner and induces CD4+ T cell hypo-responsiveness. IF-M2 macrophages, which strongly express TGF-β and inhibit CD4+ T cell proliferation, directly regulated Treg differentiation from CD4+ T cells. These results indicate that the IF regimen enhances the TGF-β-producing ability of M2 macrophages and that the development of Tregs keeps mice healthy against ACD exacerbated by obesity. Therefore, the IF regimen may ameliorate inflammatory immune disorders caused by obesity.