• Title/Summary/Keyword: survival model

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Pulmonary passage of canine adipose tissue-derived mesenchymal stem cells through intravenous transplantation in mouse model

  • Jaeyeon Kwon;Mu-Young Kim;Soojung Lee;Jeongik Lee;Hun-Young Yoon
    • Journal of Veterinary Science
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    • v.25 no.3
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    • pp.36.1-36.15
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    • 2024
  • Importance: The intravenous administration of adipose tissue-derived mesenchymal stem cells (AdMSCs) in veterinary medicine is an attractive treatment option. On the other hand, it can result in severe complications, including pulmonary thromboembolism (PTE). Objective: The present study assessed the occurrence of PTE after the intravenous infusion of canine AdMSCs (cAdMSCs) into experimental animals. Methods: Five-week-old male BALB/c hairless mice were categorized into groups labeled A to G. In the control group (A), fluorescently stained 2×106 cAdMSCs were diluted in 200 µL of suspension and injected into the tail vein as a single bolus. The remaining groups included the following: group B with 5×106 cells, group C with 3×106 cells, group D with 1×106 cells, group E with 1×106 cells injected twice with a one-day interval, group F with 2×106 cells in 100 µL of suspension, and group G with 2×106 cells in 300 µL of suspension. Results: Group D achieved a 100% survival rate, while none of the subjects in groups B and C survived (p = 0.002). Blood tests revealed a tendency for the D-dimer levels to increase as the cell dose increased (p = 0.006). The platelet count was higher in the low cell concentration groups and lower in the high cell concentration groups (p = 0.028). A histological examination revealed PTE in most deceased subjects (96.30%). Conclusions and Relevance: PTE was verified, and various variables were identified as potential contributing factors, including the cell dose, injection frequency, and suspension volume.

Enriching CCL3 in the Tumor Microenvironment Facilitates T cell Responses and Improves the Efficacy of Anti-PD-1 Therapy

  • Tae Gun Kang;Hyo Jin Park;Jihyun Moon;June Hyung Lee;Sang-Jun Ha
    • IMMUNE NETWORK
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    • v.21 no.3
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    • pp.23.1-23.16
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    • 2021
  • Chemokines are key factors that influence the migration and maintenance of relevant immune cells into an infected tissue or a tumor microenvironment. Therefore, it is believed that the controlled administration of chemokines in the tumor microenvironment may be an effective immunotherapy against cancer. Previous studies have shown that CCL3, also known as macrophage inflammatory protein 1-alpha, facilitates the recruitment of dendritic cells (DCs) for the presentation of tumor Ags and promotes T cell activation. Here, we investigated the role of CCL3 in regulating the tumor microenvironment using a syngeneic mouse tumor model. We observed that MC38 tumors overexpressing CCL3 (CCL3-OE) showed rapid regression compared with the wild type MC38 tumors. Additionally, these CCL3-OE tumors showed an increase in the proliferative and functional tumor-infiltrating T cells. Furthermore, PD-1 immune checkpoint blockade accelerated tumor regression in the CCL3-OE tumor microenvironment. Next, we generated a modified CCL3 protein for pre-clinical use by fusing recombinant CCL3 (rCCL3) with a non-cytolytic hybrid Fc (HyFc). Administering a controlled dose of rCCL3-HyFc via subcutaneous injections near tumors was effective in tumor regression and improved survival along with activated myeloid cells and augmented T cell responses. Furthermore, combination therapy of rCCL3-HyFc with PD-1 blockade exhibited prominent effect to tumor regression. Collectively, our findings demonstrate that appropriate concentrations of CCL3 in the tumor microenvironment would be an effective adjuvant to promote anti-tumor immune responses, and suggest that administering a long-lasting form of CCL3 in combination with PD-1 blockers can have clinical applications in cancer immunotherapy.

Critical Adjuvant Influences on Preventive Anti-Metastasis Vaccine Using a Structural Epitope Derived from Membrane Type Protease PRSS14

  • Ki Yeon Kim;Eun Hye Cho;Minsang Yoon;Moon Gyo Kim
    • IMMUNE NETWORK
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    • v.20 no.4
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    • pp.33.1-33.19
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    • 2020
  • We tested how adjuvants effect in a cancer vaccine model using an epitope derived from an autoactivation loop of membrane-type protease serine protease 14 (PRSS14; loop metavaccine) in mouse mammary tumor virus (MMTV)-polyoma middle tumor-antigen (PyMT) system and in 2 other orthotopic mouse systems. Earlier, we reported that loop metavaccine effectively prevented progression and metastasis regardless of adjuvant types and TH types of hosts in tail-vein injection systems. However, the loop metavaccine with Freund's complete adjuvant (CFA) reduced cancer progression and metastasis while that with alum, to our surprise, were adversely affected in 3 tumor bearing mouse models. The amounts of loop peptide specific antibodies inversely correlated with tumor burden and metastasis, meanwhile both TH1 and TH2 isotypes were present regardless of host type and adjuvant. Tumor infiltrating myeloid cells such as eosinophil, monocyte, and neutrophil were asymmetrically distributed among 2 adjuvant groups with loop metavaccine. Systemic expression profiling using the lymph nodes of the differentially immunized MMTV-PyMT mouse revealed that adjuvant types, as well as loop metavaccine can change the immune signatures. Specifically, loop metavaccine itself induces TH2 and TH17 responses but reduces TH1 and Treg responses regardless of adjuvant type, whereas CFA but not alum increased follicular TH response. Among the myeloid signatures, eosinophil was most distinct between CFA and alum. Survival analysis of breast cancer patients showed that eosinophil chemokines can be useful prognostic factors in PRSS14 positive patients. Based on these observations, we concluded that multiple immune parameters are to be considered when applying a vaccine strategy to cancer patients.

The pattern of metachronous recurrence after endoscopic submucosal dissection for gastric adenocarcinoma and dysplasias

  • Sunah Suk;Yeon Joo Seo;Dae Young Cheung;Han Hee Lee;Jin Il Kim;Soo-Heon Park
    • Clinical Endoscopy
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    • v.56 no.4
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    • pp.470-478
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    • 2023
  • Background/Aims: Metachronous recurrence incidences and risk factors following endoscopic submucosal dissection (ESD) for gastric adenocarcinoma and dysplasias were investigated. Methods: Retrospective review of electronic medical records of patients who underwent gastric ESD at The Catholic University of Korea, Yeouido St. Mary's Hospital. Results: A total of 190 subjects were enrolled for analysis during the study period. The mean age was 64.4 years and the male sex occupied 73.7%. The mean observation period following ESD was 3.45 years. The annual incidence rate of metachronous gastric neoplasms (MGN) was about 3.96%. The annual incidence rate was 5.36% for the low-grade dysplasia group, 6.47% for the high-grade dysplasia group, and 2.74% for the EGC group. MGN was more frequent in the dysplasia group than in the EGC group (p<0.05). For those with MGN development, the mean time interval from ESD to MGN was 4.1 (±1.8) years. By using the Kaplan-Meier model, the estimated mean MGN free survival time was 9.97 years (95% confidence interval, 8.53-11.40) The histological types of MGN were not related to the primary histology types. Conclusions: MGN following ESD developed in 3.96% annually and MGN was more frequent in the dysplasia group. The histological types of MGN did not correlate with those of primary neoplasm.

Parathyroid Hormone-Related Protein Promotes the Proliferation of Patient-Derived Glioblastoma Stem Cells via Activating cAMP/PKA Signaling Pathway

  • Zhenyu Guo;Tingqin Huang;Yingfei Liu;Chongxiao Liu
    • International Journal of Stem Cells
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    • v.16 no.3
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    • pp.315-325
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    • 2023
  • Background and Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its heterogeneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM. Methods and Results: Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP. Conclusions: Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.

Catechin hydrate prevents cisplatin-induced spermatogonia GC-1 spg cellular damage

  • Hyeon Woo Shim;Won-Yong Lee;Youn-Kyung Ham;Sung Don Lim;Sun-Goo Hwang;Hyun-Jung Park
    • Journal of Animal Reproduction and Biotechnology
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    • v.39 no.2
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    • pp.145-152
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    • 2024
  • Background: Despite its anticancer activity, cisplatin exhibits severe testicular toxicity when used in chemotherapy. Owing to its wide application in cancer therapy, the reduction of damage to normal tissue is of imminent clinical need. In this study, we evaluated the effects of catechin hydrate, a natural flavon-3-ol phytochemical, on cisplatin-induced testicular injury. Methods: Type 2 mouse spermatogonia (GC-1 spg cells) were treated with 0-100 μM catechin and cisplatin. Cell survival was estimated using a cell proliferation assay and Ki-67 immunostaining. Apoptosis was assessed via flow cytometry with the Dead Cell Apoptosis assay. To determine the antioxidant effects of catechin hydrate, Nrf2 expression was measured using qPCR and CellROX staining. The anti-inflammatory effects were evaluated by analyzing the gene and protein expression levels of iNOS and COX2 using qPCR and immunoblotting. Results: The 100 μM catechin hydrate treatment did not affect healthy GC-1 spg cells but, prevented cisplatin-induced GC-1 spg cell death via the regulation of anti-oxidants and inflammation-related molecules. In addition, the number of apoptotic cells, cleaved-caspase 3 level, and BAX gene expression levels were significantly reduced by catechin hydrate treatment in a cisplatin-induced GC-1 spg cell death model. In addition, antioxidant and anti-inflammatory marker genes, including Nrf2, iNOS, and COX2 were significantly downregulated by catechin hydrate treatment in cisplatintreated GC-1 cells. Conclusions: Our study contributes to the opportunity to reintroduce cisplatin into systemic anticancer treatment, with reduced testicular toxicity and restored fertility.

Evaluation of Seakeeping Performance of an Light Aircraft Carrier (경항모 내항성능 평가 연구)

  • Dong-Min Park;Min-Guk Seo;Hyungdo Song;Seok-Kyu Cho;Sa Young Hong
    • Journal of the Society of Naval Architects of Korea
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    • v.61 no.5
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    • pp.297-311
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    • 2024
  • In this study, a combined seakeeping performance evaluation method has been developed for the design purpose of the light aircraft carrier CVX of Korean Navy. A frequency domain analysis method was developed for evaluation of safe operating envelope up to sea state 6, while a time domain analysis method was developed for survival condition of sea state 7 and higher. The frequency-domain solver AdFLOW-Navy was developed by adding empirical formula of roll damping and fin-stabilizer to the existing AdFLOW by KRISO, which was based on the three-dimensional higher order boundary element method (HOBEM). For the estimation of the roll damping coefficient, a two-dimensional cross-section was automatically extracted from the three-dimensional panel, and the roll damping coefficient was analyzed for the two-dimensional cross-section. As for the time domain analysis method, KIMAPS-Navy was developed by improving and expanding the KIMAPS series developed by KRISO which is based on the impulse response function by utilizing the hydrodynamic coefficients obtained from the AdFLOW-Navy. In addition, a weakly nonlinear analysis approach was applied to analyze highly nonlinear motion under heavy sea states. Finally numeraical analysis results were compared with model tests, which showed practical usefulness of the present combined seakeeping analysis approach.

A Study on Qulity Perceptions and Satisfaction for Medical Service Marketing (의료서비스 마케팅을 위한 품질지각과 만족에 관한 연구)

  • Yoo, Dong-Keun
    • Journal of Korean Academy of Nursing Administration
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    • v.2 no.1
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    • pp.97-114
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    • 1996
  • INSTRODUCTION Service quality is, unlike goods quality, an abstract and elusive constuct. Service quality and its requirements are not easily understood by consumers, and also present some critical research problems. However, quality is very important to marketers and consumers in that it has many strategic benefits in contributing to profitability of marketing activities and consumers' problem-solving activities. Moreover, despite the phenomenal growth of medical service sector, few researchers have attempted to define and model medical service quality. Especially, little research has focused on the evaluation of medical service quality and patient satisfaction from the perspectives of both the provider and the patient. As competition intensifies and patients are demanding higher quality of medical service, medical service quality and patient satisfaction has emerged as a critical research topic. The major purpose of this article is to explore the concept of medical service quality and its evaluation from both nurse and patient perspectives. This article attempts to achieve its purpose by (1)classfying critical service attibutes into threecategories(satisfiers, hygiene factors, and performance factors). (2)measuring the relative importance of need criteria, (3)evaluating SERVPERF model and SERVQUAL model in medical service sector, and (4)identifying the relationship between perceived quality and overall patient satisfaction. METHOD Data were gathered from a sample of 217 patients and 179 nurses in Seoul-area general hospitals. From the review of previous literature, 50 survey items representing various facets of the medical service quality were developed to form a questionnaire. A five-point scale ranging from "Strongly Agree"(5) to "Strongly Disagree"(1) accompanied each statement(expectation statements, perception statements, and importance statements). To measure overall satisfaction, a seven-point scale was used, ranging from "Very Satisfied"(7) to "Very Dissatisfied"(1) with no verbal labels for scale points 2 through 6 RESULTS In explaining the relationship between perceived performance and overall satisfaction, only 31 variables out of original 50 survey items were proven to be statistically significant. Hence, a penalty-reward analysis was performed on theses 31 critical attributes to find out 17 satisfiers, 8 hygiene factors, and 4 performance factors in patient perspective. The role(category) of each service quality attribute in relation to patient satisfaction was com pared across two groups, that is, patients and nurses. They were little overlapped, suggesting that two groups had different sets of 'perceived quality' attributes. Principal components factor analyses of the patients' and nurses' responses were performed to identify the underlying dimensions for the set of performance(experience) statements. 28 variables were analyzed by using a varimax rotation after deleting three obscure variables. The number of factors to be extracted was determined by evaluating the eigenvalue scores. Six factors wereextracted, accounting for 57.1% of the total variance. Reliability analysis was performed to refine the factors further. Using coefficient alpha, scores of .84 to .65 were obtained. Individual-item analysis indicated that all statements in each of the factors should remain. On 26 attributes of 31 critical service quality attributes, there were gaps between actual patient's importance of need criteria and nurse perceptions of them. Those critical attributes could be classified into four categories based on the relative importance of need criteria and perceived performance from the perspective of patient. This analysis is useful in developing strategic plans for performance improvement. (1) top priorities(high importance and low performance) (in this study)- more health-related information -accuracy in billing - quality of food - appointments at my convenience - information about tests and treatments - prompt service of business office -adequacy of accommodations(elevators, etc) (2) current strengths(high importance and high performance) (3)unnecessary strengths(low importance and high performance) (4) low priorities(low importance and low performance) While 26 service quality attributes of SERPERF model were significantly related to patient satisfation, only 13 attributes of SERVQUAL model were significantly related. This result suggested that only experience-based norms(SERVPERF model) were more appropriate than expectations to serve as a benchmark against which service experiences were compared(SERVQUAL model). However, it must be noted that the degree of association to overall satisfaction was not consistent. There were some gaps between nurse percetions and patient perception of medical service performance. From the patient's viewpoint, "personal likability", "technical skill/trust", and "cares about me" were most significant positioning factors that contributed patient satisfaction. DISCUSSION This study shows that there are inconsistencies between nurse perceptions and patient perceptions of medical service attributes. Also, for service quality improvement, it is most important for nurses to understand what satisfiers, hygiene factors, and performance factors are through two-way communications. Patient satisfaction should be measured, and problems identified should be resolved for survival in intense competitive market conditions. Hence, patient satisfaction monitoring is now becoming a standard marketing tool for healthcare providers and its role is expected to increase.

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Microarray Analysis of Gene Expression by Rhei Rhizoma Water Extracts in a Hypoxia Model of Cultured Neurons (배양신경세포의 저산소증모델에서 대황 물추출물에 의한 유전자 표현 변화의 microarray 분석)

  • Lee, Hyun-Sook;Song, Jin-Young;Moon, Il-Soo
    • Journal of Life Science
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    • v.19 no.1
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    • pp.21-33
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    • 2009
  • In this study, we investigated the effect of Rhei Rhizoma (RR; 大黃) water extract on gene expression in a hypoxia model of cultured rat hippocampal neurons. RR water extract $(2.5{\mu}g/ml)$ was added to the culture media on day 10 in vitro (DIV10), and a hypoxic shock (2% $O_2$/5% $CO_2$, $37^{\circ}C$, 3 h) was given on DIV13. After maintaining the cultures in normoxia for 24 hr, total RNA was isolated and used for microarray analysis. The MA-plot indicated that most genes were up- or downregulated within 2-fold. There were more downregulated genes (725 ea) than upregulated ones (472 ea) when larger than Global M value 0.2 (i.e., >15% increase) or smaller than Global M value -0.2 (i.e., >15% decrease) were considered. Antiapoptosis genes such as Tegt (2.4-fold), Nfkb1 (2.4-fold) Veg (1.8-fold), Ngfr (1.6-fold) were upregulated, while pro-apoptosis genes such as Bad (-64%), Cstb (-66%) were downregulated. Genes for combating environmental stress (stress response genes) such as Defb3 (2.7-fold), Cygb (2.2-fold), Ahsg (2.18-fold), Alox5 (2-fold) were upregulated. Genes for cell proliferation (cell cycle-related genes) such as Erbb2 (1.84-fold), Mapk12 gene (1.8-fold) was upregulated. Therefore, RR water extracts upregulate many pro-survival genes while downregulating many pro-death genes. It is interpreted that these genes, in combination with other regulated genes, can promote neuronal survival in a stress such as hypoxia.

Effect of Subtotal Pancreatectomy of Female Mice on the Embryo and Offspring (암컷 생쥐의 췌장 부분절제가 배아와 신생자에 미치는 영향)

  • Cho, Young-Jae;Lee, Jung-Sun;Gu, Sun-Kyung;Park, Moon-Nyeo;Lee, Ha-Kye;Cho, Byung-Nam
    • Development and Reproduction
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    • v.10 no.3
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    • pp.185-192
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    • 2006
  • It is known that maternal diabetes induces a premature delivery and a congenital malformation. Although it was suggested that hyperglycemia is a main cause, little has been known. The effects of subtotal pancreactomized animal as a diabetic model on the embryo and the offspring were investigated. 1) Although survival rate of offsprings from the 90% pancreactomized female was lower than that of control, body weight of the survived offsprings was similar to that of control until 6 weeks after birth. When the liver was investigated, abnormal tissue was observed in both female and male offsprings from the pancreactomized mother. The level of major urinary protein(MUP) that is synthesized in the liver and secrets into urine was decreased in both female and male, supporting the liver abnormality. 2) In the pancreactomized female, size of the Langhan's island was increased and the liver also was observed abnormal. However, blood glucose level of the pancreactomized mother was not different from that of control. The low body weight and survival rate of offsprings from the $inhibin-{\alpha}$ overexpressed mice was very similar to those of the offsprings from diabetic mother. Thus when the mother itself was investigated after DNA injection, blood glucose level in the $inhibin-{\alpha}$ overexpressed mice was not different from that of control although size of the Langhan's island was decreased. Taken together, subtotal pancreactomy affected the offspring and embryo and influenced deeply the mother itself. However glucose level of the mother was not changed during investigation. It suggested that the relationship between the diabetic mother and embryo through offspring is very complex.

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