• Journal of Life Science
• /
• v.24 no.12
• /
• pp.1378-1382
• /
• 2014

Phospholipase D (PLD) catalyzes the hydrolysis of phospholipid to phosphatidic acid (PA), a lipid secondary messenger. Two forms of PLD isozymes, phosphatidylcholine-specific PLD1 and PLD2, have been identified. PLD has emerged as a critical regulator of cell proliferation and survival signaling, and dysregulation of PLD occurs in a various illnesses, including cancer. PLD activity is essential for cell survival and protection from apoptosis. Overexpression of PLD isozymes or PLD-generated PA attenuates the expression of apoptotic genes and confers resistance to apoptosis. The apoptosis-related molecular mechanisms of PLD remain largely unknown. Recently, the dynamics of PLD turnover during apoptosis have been reported. The cleavage of PLD isozymes as specific substrates of caspase differentially regulates apoptosis. PLD1 is cleaved at one internal site, and PLD2 is cleaved two sites at the front of the N-terminus. The cleavage of PLD1 reduces its enzymatic activity, probably via the dissociation of two catalytic motifs, whereas the cleavage of PLD2 does not affect the catalytic motifs and its activity. Thus, PLD2 maintains antiapoptotic capacity, despite its cleavage. Therefore, the differential cleavage pattern of PLD isozymes by caspase affects its enzymatic activity and antiapoptotic function. Thus, PLD is considered a potential target for cancer therapy. We summarize recent studies regarding the functional role of PLD in apoptosis.

• IMMUNE NETWORK
• /
• v.14 no.6
• /
• pp.296-306
• /
• 2014

There is growing evidence that crosstalk between mantle cell lymphoma (MCL) cells and stromal microenvironments, such as bone marrow and secondary lymphoid tissues, promotes tumor progression by enhancing survival and growth as well as drug resistance of MCL cells. Recent advances in the understanding of lymphoma microenvironment have led to the identification of crucial factors involved in the crosstalk and subsequent generation of their targeted agents. In the present study, we evaluated the combinatory effect of blocking antibodies (Ab) targeting CXCR4 and VLA-4, both of which were known to play significant roles in the induction of environment-mediated drug resistance (EMDR) in MCL cell line, Jeko-1. Simultaneous treatment with anti-CXCR4 and anti-VLA-4 Ab not only reduced the migration of Jeko-1 cells into the protective stromal cells, but also enhanced sensitivity of Jeko-1 to a chemotherapeutic agent to a greater degree than with either Ab alone. These combinatorial effects were associated with decreased phosphorylation of ERK1/2, AKT and NF-${\kappa}B$. Importantly, drug resistance could not be overcome once the adhesion of Jeko-1 to the stromal occurred despite the combined use of Abs, suggesting that the efforts to mitigate migration of MCLs should be attempted as much as possible. Our results provide a basis for a future development of therapeutic strategies targeting both CXCR4 and VLA-4, such as Ab combinations or bispecific antibodies, to improve treatment outcomes of MCL with grave prognosis.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.6
• /
• pp.2833-2839
• /
• 2016

Background: Tobacco use among youth is a major public health problem. Youth outside of formal school settings are often understudied but may be at increased risk. Materials and Methods: A descriptive cross-sectional study was carried out among 326 young people aged 15-24 years in four randomly selected motor parks in Lagos state. Interviewer-administered questionnaires were used to collect data. Results: The mean age of the respondents was $21.0{\pm}2.3yrs$. Many 252 (77.3%) dropped out before the end of the third year of secondary schooling. The majority were aware that active (78.2%), and passive smoking (77.3%) are harmful to health. Nearly two-thirds of the respondents disagreed with an outright ban of cigarettes (63.2%) and restriction of cigarette sales to persons below 18 years (67.9%) while 254 (66.8%) supported a ban on tobacco smoking in enclosed public places. One hundred and fifty (46.0%) respondents had experimented with smoking of which 106 (32.5%) had progressed to become current smokers. Half of the current smokers, 54 (50.9%), felt the need for a cigarette first thing in the morning. A multivariate analysis for smoking initiation, showed that for every increasing year of age, respondents were 1.08 times more likely to have initiated cigarette smoking; males and respondents who lived alone or with peers were 2.34 times and 1.77 times more likely to have initiated smoking respectively; those who consume alcohol and marijuana were 7.27 and 1.89 times respectively more likely to have initiated smoking while those who consumed alcohol were 6.17 times more likely to be current smokers.

• Gut and Liver
• /
• v.12 no.6
• /
• pp.655-663
• /
• 2018

Background/Aims: The association between metabolic syndrome and colorectal cancer (CRC) has been suggested as one of causes for the increasing incidence of CRC, particularly in younger age groups. The present study examined whether the current age threshold (50 years) for CRC screening in Korea requires modification when considering increased metabolic syndrome. Methods: We analyzed data from the National Health Insurance Corporation database, which covers ~97% of the population in Korea. CRC risk was evaluated with stratification based on age and the presence/absence of relevant metabolic syndrome components (diabetes, dyslipidemia, and hypertension). Results: A total of 51,612,316 subjects enrolled during 2014 to 2015 were analyzed. Among them, 19.3% had diabetes, hypertension, dyslipidemia, or some combination thereof. This population had a higher incidence of CRC than did those without these conditions, and this was more prominent in subjects <40 years of age. The optimal cutoff age for detecting CRC, based on the highest Youden index, was 45 years among individuals without diabetes, dyslipidemia, and hypertension. Individuals with at least one of these components of metabolic syndrome had the highest Youden index at 62 years old, but the value was only 0.2. Resetting the cutoff age from 50 years to 45 years achieved a 6% increase in sensitivity for CRC detection among the total population. Conclusions: Starting CRC screening earlier, namely, at 45 rather than at 50 years of age, may improve secondary prevention of CRC in Korea.

• Journal of Gastric Cancer
• /
• v.20 no.4
• /
• pp.376-384
• /
• 2020

Purpose: The role of prophylactic abdominal drainage in total gastrectomy is not well-established. This study aimed to evaluate the efficacy of abdominal drainage in the prevention and management of major intra-abdominal complications after total gastrectomy for gastric carcinoma. Materials and Methods: We retrospectively reviewed the data of 499 patients who underwent total gastrectomy for gastric carcinoma in a high-volume institution. The patients were divided into drainage and non-drainage groups and compared for the development and management of major intra-abdominal complications, including anastomotic leak, abdominal bleeding, abdominal infection, and pancreatic fistulas. Results: The drainage group included 388 patients and the non-drainage group included 111 patients. The 2 groups showed no significant differences in clinicopathological characteristics or operative procedures, except for more frequent D2 lymphadenectomies in the drainage group. After surgery, the overall morbidity (drainage group vs. non-drainage group: 24.7% vs. 28.8%, P=0.385) and incidence of major intra-abdominal complications (6.4% vs. 6.3%, P=0.959) did not significantly differ between the two groups. The non-drainage group showed no significant increase in the incidence rate of major intra-abdominal complications in the subgroups divided by age, sex, comorbidity, operative approach, body mass index, extent of lymphadenectomy, and pathological stage. Abdominal drainage had no significant impact on early diagnosis, secondary intervention or reoperation, or recovery from major intra-abdominal complications. Conclusions: Prophylactic abdominal drainage showed little demonstrable benefit in the prevention and management of major intra-abdominal complications of total gastrectomy for gastric carcinoma.

• Journal of Ginseng Research
• /
• v.45 no.1
• /
• pp.41-47
• /
• 2021

A wide range of studies have steadily pointed out the relation of oxidative stress to the primary and secondary causes of human disease and aging. As such, there have been multiple misconceptions about oxidative stress. Most of reactive oxygen species (ROS) generated from chronic diseases cause oxidative damage to cell membrane lipids and proteins. ROS production is increased by abnormal stimulation inside and outside in the body, and even though ROS are generated in cells in response to abnormal metabolic processes such as disease, it does not mean that they directly contribute to the pathogenesis of a disease. Therefore, the focus of treatment should not be on ROS production itself but on the prevention and treatment of diseases linked to ROS production, including types 1 and 2 diabetes, cancer, heart disease, schizophrenia, Parkinson's disease, and Alzheimer's disease. In this regard, Korean Red Ginseng (KRG) has been traditionally utilized to help prevent and treat diseases such as diabetes, cancer, inflammation, nervous system diseases, cardiovascular disease, and hyperlipidemia. Therefore, this review was intended to summarize in vivo animal and human clinical studies on the antioxidant activities of KRG and its components, ginsenosides.

• Genomics & Informatics
• /
• v.19 no.4
• /
• pp.39.1-39.8
• /
• 2021

Tamoxifen (TAM) is an anticancer drug used to treat estrogen receptor (ER)-positive breast cancer. However, its ER-independent cytotoxic and antifungal activities have prompted debates on its mechanism of action. To achieve a better understanding of the ER-independent antifungal action mechanisms of TAM, we systematically identified TAM-sensitive genes through microarray screening of the heterozygous gene deletion library in fission yeast (Schizosaccharomyces pombe). Secondary confirmation was followed by a spotting assay, finally yielding 13 TAM-sensitive genes under the drug-induced haploinsufficient condition. For these 13 TAM-sensitive genes, we conducted a comparative analysis of their Gene Ontology (GO) 'biological process' terms identified from other genome-wide screenings of the budding yeast deletion library and the MCF7 breast cancer cell line. Several TAM-sensitive genes overlapped between the yeast strains and MCF7 in GO terms including 'cell cycle' (cdc2, rik1, pas1, and leo1), 'signaling' (sck2, oga1, and cki3), and 'vesicle-mediated transport' (SPCC126.08c, vps54, sec72, and tvp15), suggesting their roles in the ER-independent cytotoxic effects of TAM. We recently reported that the cki3 gene with the 'signaling' GO term was related to the ER-independent antifungal action mechanisms of TAM in yeast. In this study, we report that haploinsufficiency of the essential vps54 gene, which encodes the GARP complex subunit, significantly aggravated TAM sensitivity and led to an enlarged vesicle structure in comparison with the SP286 control strain. These results strongly suggest that the vesicle-mediated transport process might be another action mechanism of the ER-independent antifungal or cytotoxic effects of TAM.

• Journal of Yeungnam Medical Science
• /
• v.39 no.1
• /
• pp.77-80
• /
• 2022

Fistulas between the arteries and the gastrointestinal tract are rare but can be fatal. We present a case of an ilioenteric fistula between the left external iliac artery and sigmoid colon caused by radiotherapy for cervical cancer, which was treated with endovascular management using a stent graft. A 38-year-old woman underwent concurrent chemoradiotherapy for cervical cancer recurrence. Approximately 9 months later, the patient suddenly developed hematochezia. On her first visit to the emergency room of our hospital, computed tomography (CT) images did not reveal extravasation of contrast media. However, 8 hours later, she revisited the emergency room because of massive hematochezia with a blood pressure of 40/20 mmHg and a heart rate of 150 beats per minute. At that time, CT images showed the presence of contrast media in almost the entire colon. The patient was referred to the angiography room at our hospital for emergency angiography. Inferior mesenteric arteriography did not reveal any source of bleeding. Pelvic arteriography showed contrast media extravasation from the left external iliac artery to the sigmoid colon; this was diagnosed as an ilioenteric fistula and treated with a stent graft. When the bleeding focus is not detected on visceral angiography despite massive arterial bleeding, pelvic arteriography is recommended, especially in patients with a history of pelvic surgery or radiotherapy.

• Journal of Korean Academy of Nursing
• /
• v.53 no.3
• /
• pp.359-369
• /
• 2023

Purpose: This study evaluated the internal structure (structural validity, internal consistency, and measurement invariance) of the Health-Related Quality of Life Instrument with Eight Items (HINT-8), developed to measure Korean people's health-related quality of life. Methods: A secondary analysis was conducted using data from the Korea National Health and Nutrition Examination Survey, involving 6,167 adults aged over 18 years. The structural validity of the HINT-8 was assessed using exploratory graph analysis and confirmatory factor analysis. Internal consistency and measurement invariance were analyzed using McDonald's omega (ω) and multigroup confirmatory factor analysis, respectively. Results: The HINT-8 had a single dimension and good internal consistency (ω =.804). The one-dimension HINT-8 exhibited matric invariance but not scalar invariance across sociodemographic groups (sex, age, education, and marital status). Further, it exhibited scalar or partial scalar invariance across medical condition groups (hypertension, diabetes, depressive symptoms, and cancer). Conclusion: The study finds that the HINT-8 demonstrated satisfactory structural validity and internal consistency, indicating its suitability for practice and research. However, the HINT-8 scores cannot be compared across different groups regarding sex, age, education, and marital status, as the interpretation varies within each sociodemographic category. Conversely, interpretation of the HINT-8 is consistent for individuals with and without hypertension, diabetes, depressive symptom, and cancer.

• International Journal of Stem Cells
• /
• v.16 no.1
• /
• pp.108-116
• /
• 2023

γδ T cells are a rare and unique prototype of T cells that share properties with natural killer cells in secondary lymphoid organs. Although many studies have revealed the function and importance of adult-derived γδ T cells in cancer biology and regenerative medicine, the low numbers of these cells hamper their application as therapeutic cell sources in the clinic. To solve this problem, pluripotent stem cell-derived γδ T cells are considered alternative cell sources; however, few studies have reported the generation of human pluripotent stem cell-derived γδ T cells. In the present study, we investigated whether lymphoid lineage γδ T cells were successfully generated from human pluripotent stem cells via hemogenic endothelium under defined culture conditions. Our results revealed that pluripotent stem cells successfully generated γδ T cells with an overall increase in transcriptional activity of lymphoid lineage genes and cytolytic factors, indicating the importance of the optimization of culture conditions in generating lymphoid lineage γδ T cells. We uncovered an initial step in differentiating γδ T cells that could be applied to basic and translational investigations in the field of cancer biology. Based on our result, we will develop an appropriate method to purify γδ T cells with functionality and it helpful for the study of basic mechanism of γδ T cells in pathophysiologic condition as well as clinic application.