• IMMUNE NETWORK
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• v.21 no.4
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• pp.31.1-31.16
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• 2021

Gastric cancer (GC) is the fourth most common cause of cancer-related death globally. The classification of advanced GC (AGC) according to molecular features has recently led to effective personalized cancer therapy for some patients. Specifically, AGC patients whose tumor cells express high levels of human epidermal growth factor receptor 2 (HER2) can now benefit from trastuzumab, a humanized monoclonal Ab that targets HER2. However, patients with HER2^negative AGC receive limited clinical benefit from this treatment. To identify potential immune therapeutic targets in HER2^negative AGC, we obtained 40 fresh AGC specimens immediately after surgical resections and subjected the CD45⁺ immune cells in the tumor microenvironment to multi-channel/multi-panel flow cytometry analysis. Here, we report that HER2 negativity associated with reduced overall survival (OS) and greater tumor infiltration with neutrophils and non-classical monocytes. The potential pro-tumoral activities of these cell types were confirmed by the fact that high expression of neutrophil or non-classical monocyte signature genes in the gastrointestinal tumors in The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases associated with worse OS on Kaplan-Meir plots relative to tumors with low expression of these signature genes. Moreover, advanced stage disease in the AGCs of our patients associated with greater tumor frequencies of neutrophils and non-classical monocytes than early stage disease. Thus, our study suggests that these 2 myeloid populations may serve as novel therapeutic targets for HER2^negative AGC.

• International Journal of Stem Cells
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• v.16 no.2
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• pp.244-249
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• 2023

Background and Objectives: To examine whether ischemic retinal ganglion cells (RGCs) will be salvaged from cell death by human adipose-derived mesenchymal stem cells (ADSCs) in an organotypic retina model. Methods and Results: Deprived of arterial oxygen supply, whole mice retinas were cultured as an ex vivo organotypic cultures on an insert membrane in a 24-well plate. The therapeutic potential of ADSCs was examined by co-culture with organotypic retinas. ADSCs were seeded on top of the RGCs allowing direct contact, or at the bottom of the well, sharing the same culture media and allowing a paracrine activity. The number of surviving RGCs was assessed using Brn3a staining and confocal microscopy. Cytokine secretion of ADSCs to medium was analyzed by cytokine array. When co-cultured with ADSCs, the number of surviving RGCs was similarly significantly higher in both treatment groups compared to controls. Analysis of ADSCs cytokines secretion profile, showed secretion of anti-apoptotic and pro-proliferative cytokines (threshold>1.4). Transplantation of ADSCs in a co-culture system with organotypic ischemic retinas resulted in RGCs recovery. Since there was no advantage to direct contact of ADSCs with RGCs, the beneficial effect seen may be related to paracrine activity of ADSCs. Conclusions: These data correlated with secretion profile of ADSCs' anti-apoptotic and pro-proliferative cytokines.

• The Korean Society of Law and Medicine
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• v.19 no.1
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• pp.113-142
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• 2018

In recent years, there have been opinions in which physicians are liable to the revocation of their medical license if they are sentenced to above a certain level for criminal charges regardless of the types of offenses. Accordingly, a revised bill of law was submitted in the National Assembly, and related discussions are thus expected to commence. Considering the morality and ethics or the level of the rule of law that the general public expects of physicians, as well as the license revocation system in other professional sectors, it is assessed that medical license revocation due to criminal convictions of physicians is appropriate to some degree. However, if a poorly devised system is established based on unrefined inferences or emotional judgements, unexpected side-effects are likely to arise. With regard to serious criminal acts that society generally perceives as unacceptable, it can be assessed that the revocation of physicians' licenses would appropriately protect the general public from threats. However, given the life-saving characteristics of high-risk medical practices, higher malpractice exposures, and social values, it is difficult to assess charges of professional negligence resulting in death(or in injury) and minor offences in the same manner as anti-social criminal offences are handled. Physicians need to be treated the same as any other professions. At the same time, they are engaged in administering medical treatment to patients in the face of great risks as professionals. Under the circumstances, a discussion on the introduction of a more specific and empirical system is needed by considering the intrinsic characteristics of medical treatment and the need for an equitable health and medical policy. Accordingly, based on the above judgment and perception, this study explores the code of ethics for physicians and medical license revocation related to criminal offences at home and abroad, and examines various legislative alternatives appropriate for the Republic of Korea. In doing so, the purpose of the study is to contribute to the development of a reasonable system for handling criminal offences by physicians.

• Tuberculosis and Respiratory Diseases
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• v.65 no.1
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• pp.15-22
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• 2008

Background: Lung cancer is the leading cause of cancer death in South Korea since the year 2000 and it is more common in elderly patients, with a peak incidence at around 70~80 years of age. However, these elderly patients receive treatment less often than do the younger patients because of organ dysfunction related to their age and their comorbidities, and they show poor tolerance to chemotherapy. The aims of this study were to analyze the clinical characteristics and treatment-related survival of elderly patients with lung cancer. Methods: In this retrospective study, we analyzed the clinical data of 706 lung cancer patients who were diagnosed at hospitals in Daegu and Gyeongsangbukdo from January 2005 to December 2005. We compared the clinical characteristics and outcomes of the patients who were aged 70 years and older (elderly patients) with those clinical characteristics and outcomes of the younger individuals. Results: The median age of the patients was 68 years (from 29 to 93) and the elderly patients were 38.7% (n=273) of all the study's patients. Squamous cell carcinoma was the most common type of lung cancer in both the elderly and younger patient groups. Elderly patients had more symptoms of dyspnea and chronic obstructive pulmonary disease (COPD) than the younger patients (p<0.001 and p<0.001, respectively). A good performance status (ECOG 0-1) was less common for the elderly patients (p<0.001). The median survival of the non-small cell lung cancer (NSCLC) patients was significantly higher in the younger patient group than in the elderly patient group (962 days vs 298 days, respectively, p=0.001). However, the median survival of the NSCLC patients who received any treatment showed no significant difference between the younger patient group and the elderly patient group (1,109 days vs 708 days, respectively, p=0.14). Conclusion: Our data showed that appropriate treatment for selected elderly patients improved the survival of patients with NSCLC. Therefore, elderly NSCLC patients with a good performance status should be encouraged to receive appropriate treatment.

• Journal of Acupuncture Research
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• v.22 no.3
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• pp.169-183
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• 2005

Objective : The purpose of this study was to investigate the anti-caner effect of cobrotoxin on the prostatic cancer cell line (PC-3).The goal of study is to ascertain whether cobrotoxin inhibits tile cell growth and cell cycle of PC-3, or the expression of relative genes and whether the regression of PC-3 cell growth is due to cell death or the expression of gene related to apoptosis. Methods : After the treatment of Pc-3 cells with cobrotoxin, we performed 형광현미경, MTT assay, Western blotting, Flow cytometry, PAGE electrophoresis and Surface plasmon resonance analysis to identify the cell viability, cell death, apoptosis, the changes of cell cycle and the related protein, Adk, MAP kinase. Results : 1. Compared with normal cell, the inhibition of cell growth reduced in proportion with the dose of cobrotoxin(0-16nM) in PC-3. 2. Cell viabilities of 0.1, 1, 4nM cobrotoxin treatment were decreased and those of 8, 16nM were decreased significantly. 3. S phase of cell cycle was decreased at the group of 1, 2, 4, 8, 16nM cobrotoxin, but M phase was increased at 0.1, 1, 2, 4, 8, 16nM cobrotoxin. 4. Cox-2 expression after cobrotoxin was peaked at 12hours and was decreased significantly after 6, 12, 24 hours. 5. The expression of Cdk4 was decreased dose-dependently at 1, 2, 4, 8nM cobrotoxin and was decreased siginificantly at 4, 8nM Cyclin D1 was decreased at 1, 2, 4, 8nM and Cycline E was not changed. Cycline B was decreased at 1, 2, 4, 8nM dose-dependently and was decreased siginificanlty at 2, 4, 8nM. 6. The expression of Akt was decreased at 1, 2, 4, 8nM dose-dependently and was decreased significantly at 2, 4, 8nM. 7. ERK was increased at 1, 2nM and decreased at 4, 8nM, p-ERK was increased at 1, 2, 4 nM, but decreased at 8nM. JNK and p-JNK were increased at 1, 4, 8 nM. p38 was increased at 2nM p-p38 was increased at lnM but decreased significantly at 2, 4, 8nM. 8. The nucli of normal cells were stained round and homogenous in DAPI staining, but those of PC-3 were stained condense and splitted. Apoptosis was increased dose-dependently at 2, 4, 8, 16nM and increased significantly at 2, 4, 8, 16nM. 9. Bax wasn`t changed at 1, 2, 4, 8nM and Bcl-2 was decreased significantly at 1, 2, 4, 8nM. Caspase 3 and 9 weren`t changed at 1, 2, 4nM but were decreased significantly at 8nM. Conclusions : These results indicate that cobrotoxin inhibits the growth of prostate Cancer cells, has anti-cancer effects by inducing apoptosis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.29 no.5
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• pp.272-281
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• 2003

Nontraditional or alternative medicine is becoming an increasingly attractive approach for the treatment of various inflammatory disorders and cancers. Curcumin is the major constitute of turmoric powder extracted from the rhizomes of the plant Curcuma longa. Resveratrol is a phytoalexin present in grapes and a variety of medicinal plants. In this report, We investigated the effect of curcumin and resveratrol on regulatory protein of cell cycle, induction of apoptosis and MMP activity. Treatment with 75 M curcumin for 24 hrs produced morphological changing in HN-4 cells. Curcumin and resveratrol inhibited the cellular growth in HN-4 cells. Inhibition of cell growth was associated with down-regulation of cell cycle regulatory proteins. Curcumin-induced caspase-3 activation and Bax degradation were dose-dependent with a maximal effect at a concentration of 100 M. The elevated caspase-3 activity in curcumin treated HN-4 cells are correlated with down-regulation of survivin and cIAP1, but not cIAP2. Curcumin induced a dose-dependent increase of cytochrome c in the cytosol. Curcumin induced-apoptosis was mediated through the release of cytochrome c. In addition, curcumin-induced apoptosis was caused by the generation of reactive oxygen species, which was prevented by antioxidant N-acetyl-cysteine (NAC). Cotreatment with NAC markedly prevented cytochrome c release, Bax cleavage and cell death. Also resveratrol-induced apoptosis was preceded by down-regulation of the anti-apoptotic Bcl-2, cIAP1, and caspase-3 activity. However, resveratrol-induced apoptosis was not prevented by antioxidant NAC. In addition, HN-4 cells release basal levels of MMP2 when cultured in serum-free medium. Treatment of the cells with various concentrations of PMA for 24 hr induced the expression and secretion of latent MMP9 as determined by gelatin zymography. HN-4 cells were treated with various concentrations of curcumin and resveratrol in the presence of 75 nM PMA, and MMP2 and 9 activities were inhibited by curcumin and resveratrol. These findings have implications for developing curcumin-based anticancer and anti-inflammation therapies.

• Journal of Hospice and Palliative Care
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• v.5 no.2
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• pp.146-154
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• 2002

Purpose : Death due to cancer has been continuously increasing, therefore cancer is the first in the cause of death now. A national policy for the elevation of medical costs in cancer patients is necessary, therefore, we searched for the medical costs and its related factors in terminal cancer patients for the effective reduction of the medical costs. Methods : We reviewed the medical records of 259 hospitalized terminal cancer patients who had died during the period of July 1, 2000 to June 30, 2002. History of cancer included type of cancer, type of past treatment, existence of metastasis. Clinical manifestation was examined and medical costs on last admission was categorized based on the account of charges of the department of patient affair on the last hospitalization. For analysis of factors related with medical costs, ANOVA was used. Results : Of the 259 patients, the number of male was 135 cases (52.1%), and the female, 124 cases (47.9%). The most frequent type of cancer was stomach (21.9%) cancer. Of the clinical manifestation, anorexia (87.6%) was the most frequent manifestation. Total medical costs was 740,628,045won, the mean costs was $285,968{\pm}3,070,272won$. The frequent category of medical costs was injection (32.0%), medical accommodation (27.9%), examination (14.0%), in order. The only factor related with mean medical costs was pain (P<0.05). Conclusion : If unnecessary injection of opioid analgesics is reduced, hospice care at home is activated and excessive examination is reduced In terminal cancer inpatients, it will be possible to reduce the medical costs in terminal cancer patients more effectively.

• Journal of Chest Surgery
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• v.37 no.1
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• pp.27-34
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• 2004

Background: Infective endocarditis shows higher operative morbidity and mortality rates than other cardiac diseases. The vast majority of studies on infective endocarditis have been made on aortic endocarditis, with little attention having been paid to infective endocarditis on the mitral valve. This study attempts to investigate the clinical aspects and operative results of infective endocarditis on the mitral valve. Meterial and Method: The subjects of this study consist of 23 patients who underwent operations for infective endocariditis on the mitral valve from June 1995 to May 2003. Among them, 2 patients suffered from prosthetic valvular endocarditis and the other 21 from native valvular endocarditis. The subjects were evenly distributed age-wise with an average age of 44.8$\pm$15.7 (11∼66) years. Emergency operations were performed on seventeen patients (73.9%) due to large vegetation or instable hemodynamic status. In preoperative examinations, twelve patients exhibited congestive heart failure, four patients renal failure, two patients spleen and renal infarction, and two patients temporary neurological defects, while one patient had a brain abscess. Based on the NYHA functional classification, seven patients were determined to be at Grade II, 9 patients at Grade III, and 6 patients at Grade IV. Vegetations were detected in 20 patients while mitral regurgitation was dominant in 19 patients with 4 patients showing up as mitral stenosis dominant on the preoperative echocardiogram. Blood cultures for causative organisms were performed on all patients, and positive results were obtained from ten patients, with five cases of Streptococcus viridance, two cases of methicillin-sensitive Staphylococcus aureus, and one case each of Corynebacteriurn, Haemophillis, and Gernella. Operations were decided according to the AA/AHA guidelines (1988). The mean follow-up period was 27.6 $\pm$23.3 (1 ∼ 97) months. Result: Mitral valve replacements were performed on 43 patients, with mechanical valves being used on 9 patients and tissue valves on the other 4. Several kinds of mitral valve repair or mitral valvuloplasty were carried out on the remaining 10 patients. Associated procedures included six aortic valve replacements, two tricuspid annuloplasty, one modified Maze operation, and one direct closure of a ventricular septal defect. Postoperative complications included two cases of bleeding and one case each of mediastinitis, low cardiac output syndrome, and pneumonia. There were no cases of early deaths, or death within 30 days following the operation. No patient died in the hospital or experienced valve related complications. One patient, however, underwent mitral valvuloplasty 3 months after the operation. Another patient died from intra-cranial hemorrhage in the 31st month after the operation. Therefore, the valve-related death rate was 4.3%, and the valve-related complication rate 8.6% on mid-term follow-up. 1, 3-, and 5-year valve- related event free rates were 90.8%, 79.5%, and 79.5%, respectively, while 1, follow-up. 1, 3-, and 5-year valve- related event free rates were 90.8%, 79.5%, and 79.5%, respectively, while 1, 3-, and 5-year survival rates were 100%, 88.8%, and 88.8%, respectively. Conclusion: The findings suggest that a complete removal of infected tissues is essential in the operative treatment of infectious endocarditis of the mitral valve. It is also suggested that when infected tissues are completely removed, neither type of material nor method of operation has a significant effect on the operation result. The postoperative results also suggest the need for a close follow-up observation of the patients suspected of having brain damage, which is caused by preoperative blood contamination or emboli from vegetation, for a possible cerebral vascular injury such as mycotic aneurysm.

• Radiation Oncology Journal
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• v.28 no.3
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• pp.133-140
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• 2010

Purpose: We retrospectively investigated the effect of irradiation using helical tomotherapy in recurrent pelvic tumors that underwent prior irradiation. Materials and Methods: Fourteen patients with recurrent pelvic tumors consisting of rectal cancer (57.1%), cervical cancer (35.7%) and cancer with an unknown origin (7.1%) were treated with tomotherapy. At the time of irradiation, median tumor size was 3.5 cm and 7 patients complained of pain originating from a recurrent tumor. The median radiation dose delivered to the gross tumor volume, clinical target volume, and planning target volume was 50 Gy, 47.8 Gy and 45 Gy, respectively and delivered at 5 fractions per week over the course of 4 to 5 weeks. Treatment response and duration of local disease control were evaluated using the Response Evaluation Criteria in Solid Tumors (ver. 1.0) and the Kaplan-Meyer method. Treatment-related toxicities were assessed through Common Terminology Criteria for Adverse Events (ver. 3.0). Results: The median follow-up time was 17.3 months, while the response rate was 64.3%. Symptomatic improvement appeared in 6 patients (85.7%). The median duration time of local disease control was 25.8 months. The rates of local failure, distant failure, and synchronous local and distant failure were 57.1%, 21.4%, and 7.1%, respectively. Acute toxicities were limited in grade I or II toxicities, except for one patient. No treatment related death or late toxicity was observed. Conclusion: Helical tomotherapy could be suggested as a feasible palliative option in recurrent pelvic tumors with prior radiotherapy. However, to increase treatment effect and overcome the limitation of this outcome, a large clinical study should be performed.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8495-8497
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• 2014

Purpose: To investigate whether it is safe to use leucogen tablets 60 mg three times per day (180 mg for a day) and whether this regimen could reduce the incidence of febrile neutropenia caused by chemotherapy. Methods: This prospectively designed study focused on the safety and effectiveness of leucogen tablets 60mg three times per day for a group of cancer patients during chemotherapy for mainly lung or gastric cancers. The tablets were administered from 5 days before until the termination of chemotherapy. Neutropenia and other healthcare encounters were defined as events and occurrence was estimated for comparison. Results: We identified 39 patients receiving leucogen tablets 60mg three times per day, including 11 with gastric, 12 with lung and 16 with other sites of cancer. The mean age was 65 (29-75) years and there were 27 male and 12 female patients. The mean duration of leucogen tablets intake was 59 days. Eighteen patients were treated with taxane-based, 4 with irinotecan-based and 17 with other chemotherapy. The incidence of febrile neutropenia was 0%. Twelve patients were found severe neutropenia (grade III/IV), and the duration of severe neutropenia (grade III/IV) was 5 days. Treatment-emergent adverse events were attributable to complications of myelosuppressive chemotherapy or the primary disease (i.e., alopecia, nausea, asthenia, neutropenia, and severe hepatic renal dysfunction). No chemotherapy was delayed and no treatment related death was observed. Conclusions: This study suggested that leucogen tablets 60mg three times per day (180mg for a day) are safe and could be effective for preventing febrile neutropenia in patients with chemotherapy.