Novel Palliative Chemotherapy for Cholangiocarcinoma / 대한췌담도학회지

The term cholangiocarcinoma (CC) refers to all tumors arising from bile duct epithelium. CCs are characterized by their rarity, difficulty in diagnosis, and overall poor prognosis. This leads to a paucity of data from which to define the natural history and optimal treatment regimens. Currently, surgical resection remains the only potentially curative treatment, but many patients develop recurrence. In addition, a limited number of patients can be candidates for curative resection at diagnosis. Therefore, chemotherapy is inevitable choice for the treatment of advanced CC. Gemcitabine plus cisplatin (GP) is considered a standard option for advanced biliary cancer. A randomized phase III trial (ABC-02 trial) showed the superiority of gemcitabine plus cisplatin over gemcitabine alone. Treatment with nab-paclitaxel plus gemcitabine-cisplatin prolonged median progression-free survival and overall survival vs. those reported for historical controls treated with gemcitabine-cisplatin alone in a phase II study of 60 patients with locally advanced unresectable or metastatic biliary tract cancer. Recent data of the ABC-06 trial has provided slight evidence for the use of second-line chemotherapy after progression on cisplatin plus gemcitabine combination. Other active regimens, that could be considered in patients who include have disease progression while receiving GP and who retain an adequate performance status, includes capecitabine plus cisplatin, liposomal irinotecan plus leucovorin-modulated fluorouracil and a fluoropyrimidine alone. We herein review recent published data regarding the use of palliative chemotherapies in CC patients, with a particular focus on novel cytotoxic agents.

An Analysis on Distribution of Handgrip Strength and Associated Factors in Korean Adults

Background@#Sarcopenia is a skeletal muscle disorder that involves the loss of muscle mass and function. Handgrip strength (HGS) is the most commonly used tool to assess muscle strength to diagnose sarcopenia. HGS is also associated with various diseases and health outcomes. Thus, we aimed this study to examine the HGS status in Korean adults and relevant factors of HGS. @*Methods@#Data was obtained from the 7th Korea National Health and Nutrition Examination Survey (KNHANES), a population-based nationwide survey. The estimated mean value of HGS was calculated in each age group. The mean HGS in men and women aged over 40 was compared according to the household income level, lifestyle factors, and comorbidities. @*Results@#A total of 16,708 participants were included in this study. The mean HGS showed a maximum value in the 30s for both men and women, and then tended to decrease with increasing age. When analyzed for people aged 40 or older, the mean HGS was significantly higher in the current or past smoker, drinker, and aerobic exercise groups in both men and women. The mean HGS was lower in the group with comorbidities such as hypertension, dyslipidemia, type 2 diabetes, and bone diseases. @*Conclusion@#Our study found that the mean HGS was significantly different between those with and without underlying chronic diseases. In groups with relevant comorbidities, close monitoring for the development of sarcopenia and taking preventive measures such as exercise and nutritional support may be recommended.

An Analysis on Distribution of Handgrip Strength and Associated Factors in Korean Adults

Background@#Sarcopenia is a skeletal muscle disorder that involves the loss of muscle mass and function. Handgrip strength (HGS) is the most commonly used tool to assess muscle strength to diagnose sarcopenia. HGS is also associated with various diseases and health outcomes. Thus, we aimed this study to examine the HGS status in Korean adults and relevant factors of HGS. @*Methods@#Data was obtained from the 7th Korea National Health and Nutrition Examination Survey (KNHANES), a population-based nationwide survey. The estimated mean value of HGS was calculated in each age group. The mean HGS in men and women aged over 40 was compared according to the household income level, lifestyle factors, and comorbidities. @*Results@#A total of 16,708 participants were included in this study. The mean HGS showed a maximum value in the 30s for both men and women, and then tended to decrease with increasing age. When analyzed for people aged 40 or older, the mean HGS was significantly higher in the current or past smoker, drinker, and aerobic exercise groups in both men and women. The mean HGS was lower in the group with comorbidities such as hypertension, dyslipidemia, type 2 diabetes, and bone diseases. @*Conclusion@#Our study found that the mean HGS was significantly different between those with and without underlying chronic diseases. In groups with relevant comorbidities, close monitoring for the development of sarcopenia and taking preventive measures such as exercise and nutritional support may be recommended.

Neuroprotective effects of α-iso-cubebene against glutamate-induced damage in the HT22 hippocampal neuronal cell line.

Since oxidative stress is critically involved in excitotoxic damage, we sought to determine whether the activation of the transcription factors, cAMP-responsive element binding protein (CREB) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2, also known as NFE2L2), by α-iso-cubebene is involved in its protective effects against glutamate-induced neuronal cell death. Pre-treatment with α-iso-cubebene significantly attenuated glutamate-induced cytotoxicity in mouse hippocampus-derived neuronal cells. α-iso-cubebene also reduced the glutamate-induced generation of reactive oxygen species and calcium influx, thus preventing apoptotic cell death. α-iso-cubebene inhibited glutamate-induced mitochondrial membrane depolarization and, consequently, inhibited the release of the apoptosis-inducing factor from the mitochondria. Immunoblot anlaysis revealed that the phosphorylation of extracellular signal-regulated kinase (ERK) by glutamate was reduced in the presence of α-iso-cubebene. α-iso-cubebene activated protein kinase A (PKA), CREB and Nrf2, which mediate the expression of the antioxidant enzymes, heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO1), involved in neuroprotection. In addition, α-iso-cubebene induced the expression of antioxidant responsive element and CRE transcriptional activity, thus conferring neuroprotection against glutamate-induced oxidative injury. α-iso-cubebene also induced the expression of Nrf2-dependent genes encoding HO-1 and NQO1. Furthermore, the knockdown of CREB and Nrf2 by small interfering RNA attenuated the neuroprotective effects of α-iso-cubebene. Taken together, our results indicate that α-iso-cubebene protects HT22 cells from glutamate-induced oxidative damage through the activation of Nrf2/HO-1/NQO-1, as well as through the PKA and CREB signaling pathways.

Therapeutic effects of α-iso-cubebenol, a natural compound isolated from the Schisandra chinensis fruit, against sepsis.

α-Iso-cubebenol, a natural compound isolated from the Schisandra chinensis fruit, strongly enhances survival rate in cecal ligation and puncture (CLP) challenge-induced sepsis. Mechanistically, α-iso-cubebenol markedly reduces viable bacteria in the peritoneal fluid and peripheral blood, by increasing production of superoxide anion. α-Iso-cubebenol also significantly attenuates widespread immune cell apoptosis in a mouse CLP sepsis model, and inhibits the production of proinflammatory cytokines including interleukin-1ß (IL-1ß) and IL-6 in CLP mice and lipopolysaccharide-stimulated splenocytes. Taken together, the results indicate that α-iso-cubebenol can reverse the progression of septic shock by triggering multiple protective downstream signaling pathways to enhance microbial killing and maintain organ function and leukocyte survival.