• Journal of Veterinary Science
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• v.25 no.2
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• pp.31.1-31.8
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• 2024

Background: Recently, there has been a growing interest in stem cells for human medicine. Limited feline endometrial mesenchymal stem cell (fEM-MSC) research in veterinary medicine necessitates reporting for future feline disease research and therapy. Objectives: This study aimed to isolate fEM-MSCs from feline endometrial tissues and evaluate their morphology, proliferative ability, differentiation ability, and immunophenotype. Methods: Feline endometrial tissues were obtained from the ovariohysterectomies of healthy cats and isolated using an enzymatic method. The morphology and proliferative ability of the isolated cells were assessed using a doubling time (DT) assay from passages 3 to 6 (P3 - P6). We measured pluripotency gene expressions of cells in P2 using quantitative real-time polymerase chain reaction (qRT-PCR). To investigate MSC characteristics, a trilineage differentiation assay was conducted in P4, and cells in P4 were immunophenotyped using flow cytometry. Results: fEM-MSCs showed a typical spindle-shaped morphology under a microscope, and the DT was maintained from P3 to P6. fEM-MSCs could differentiate into adipocytes, osteoblasts, and chondrocytes, and expressed three pluripotency markers (OCT4, SOX2, and NANOG) by qRT-PCR. Immunophenotypic analysis showed that the fEM-MSCs were CD14 ^-, CD34 ^-, CD45 ^-, CD9⁺, and CD44⁺. Conclusions: In this study, the feline endometrium was a novel source of MSCs, and to the best of our knowledge, this is the first report on the isolation method and characteristics of fEM-MSCs.

• The Korean Journal of Cytopathology
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• v.7 no.1
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• pp.1-11
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• 1996

From the concepts of cellular pathology and of exfoliative cytology, as elucidated by Virchow and Papanicolaou respectively in the late 19th and early 20th century, have evolved the primary methods for the diagnosis of cancer today. From Papanicolaou's concept of exfoliative cytology developed fine needle aspiration biopsy in the early 1960's, this has become a major diagnostic procedure and has contributed to a significant reduction in open biopsies and, therefore, to medical cost-effectiveness immunobiochemical techniques provided us with a supplement to cancer diagnosis in the 1980's. The immunoperoxidase method, using monoclonal antibodies, is applied primarily as an ancillary measure to elucidate the nature of cancers The availability of specific monoclonal antibodies has greatly facilitated the identification of cell products or surface markers. For example, antibodies directed against intermediate filaments have proved to be of value in determining the histogenesis oi poorly differentiated neoplasms. Tumor markers may serve as biochemical indicators of the presence of a neoplasm. They can be detected In plasma and other body fluids. Their concentration can be applied as a diagnostic test, for monitoring the clinical course of known cancer, and as a screening measure to detect certain cancers in a population at risk. Flow cytometry is a useful tool for distinguishing several cell characteristics, such as the immunophenotype of leukemia-lymphoma cells, the DNA content of neoplastic cells, and cell proliferation rate. Molecular biologic techniques provided a giant step for the management of cancer patients encompassing diagnosis, prognostic evaluation, and therapy. Nucleic acid hybridization techniques are utilized as Southern, Northern, and dot blots and in situ hybridization. Molecular biology and its techniques may bring a blight new horizon for understanding cancer biology and in designing therapy on the basis of gene manipulation.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.1073-1081
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• 1998

Primary pulmonary lymphoma (PPL) is an uncommon tumor, which constitutes 3-4% of all extranodal lymphomas and 0.3-0.5 % of all primary pulmonary malignant tumors. Low-grade B-cell lymphomas of bronchus-associated lymphoid tissue (BALT) accounted for the majority of PPL. This BALT lymphomas are frequently asymptomatic and have an excellent prognosis and an indolent clinical course by contrast with T-cell type. Therefore, determination of the B- or T-immunophenotype of the tumor cells is known to be very important from a clinical aspect. Recent advances in immunohistochemical techniques, cytogenetics, and molecular biology have allowed better definition of type, maturation, and clonality of lymphoma cells and have made it possible to better understand the PPL. We experienced an asymptomatic 43-year-old man who was evaluated for infiltrates on both sides discovered incidentallly after a routine chest roentgenogram. He was eventually diagnosed as low-grade B-cell lymphoma of BALT by immunohistochemical staining from specimens obtained by open lung biopsy. He was treated with combination chemotherapy. At follow up 12 mons following initial diagnosis, he remains in stable. We report this case, who showed a relatively favorable prognosis and indolent clinical course compatible with low-grade B-cell lymphoma.

• Journal of Breast Cancer
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• v.21 no.4
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• pp.406-414
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• 2018

Purpose: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is an emerging immune response molecule related to T-cell anergy. There has been tremendous interest in breast cancer targeting immune checkpoint molecules, especially in the triple-negative breast cancer (TNBC). This study was designed to investigate TIM-3 expression on tumor infiltrating lymphocytes (TILs), its relationships with clinicopathological parameters and expression of programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), and its prognostic role. Methods: Immunohistochemistry on tissue microarray blocks produced from 109 samples of invasive ductal carcinoma type TNBC was performed with antibodies toward TIM-3, PD-1, PD-L1 and breast cancer-related molecular markers. Associations between their expression and clinicopathological parameters as well as survival analyses were performed. Results: TIM-3 was expressed in TILs from all 109 TNBCs, consisting of 17 cases (<5%), 31 cases (6%-25%), 48 cases (26%-50%), and 13 cases (>51%). High TIM-3 was significantly correlated with younger patients (p=0.0101), high TILs (p=0.0029), high tumor stage (p=0.0018), high PD-1 (p=0.0001) and high PD-L1 (p=0.0019), and tended to be associated with higher histologic grade, absence of extensive in situ components and microcalcification. High TIM-3 expression was significantly associated with a combinational immunophenotype group of high PD-L1 and high PD-1 (p<0.0001). High TIM-3 demonstrated a significantly better disease-free survival (DFS) (p<0.0001) and longer overall survival (OS) (p=0.0001), together with high TILs and high PD-1. In univariate survival analysis, high TIM-3 showed reduced relapse risk (p<0.0001) and longer OS (p=0.0003), together with high PD-1 expression. In multivariate analysis, high TIM-3 was statistically significant in predicting prognosis, showing better DFS (hazard ratio [HR], 0.0994; 95% confidence interval [CI], 0.0296-0.3337; p=0.0002) and longer OS (HR, 0.1109; 95% CI, 0.0314-0.3912; p=0.0006). Conclusion: In this study, we demonstrate that TIM-3 expression is an independent positive prognostic factor in TNBC, despite its association with poor clinical and pathologic features.

• International Journal of Stem Cells
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• v.16 no.4
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• pp.425-437
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• 2023

Obesity, which continues to increase worldwide, was shown to irreversibly impair the differentiation potential and angiogenic properties of adipose tissue mesenchymal stromal cells (ADSCs). Because these cells are intended for regenerative medicine, especially for the treatment of inflammatory conditions, and the effects of obesity on the immunomodulatory properties of ADSCs are not yet clear, here we investigated how ADSCs isolated from former obese subjects (Ex-Ob) would influence macrophage differentiation and polarization, since these cells are the main instructors of inflammatory responses. Analysis of the subcutaneous adipose tissue (SAT) of overweight (OW) and Ex-Ob subjects showed the maintenance of approximately twice as many macrophages in Ex-Ob SAT, contained within the CD68⁺/FXIII-A^- inflammatory pool. Despite it, in vitro, coculture experiments revealed that Ex-Ob ADSCs instructed monocyte differentiation into a M2-like profile, and under inflammatory conditions induced by LPS treatment, inhibited HLA-DR upregulation by resting M0 macrophages, originated a similar percentage of TNF-α⁺ cells, and inhibited IL-10 secretion, similar to OW-ADSCs and BMSCs, which were used for comparison, as these are the main alternative cell types available for therapeutic purposes. Our results showed that Ex-Ob ADSCs mirrored OW-ADSCs in macrophage education, favoring the M2 immunophenotype and a mixed (M1/M2) secretory response. These results have translational potential, since they provide evidence that ADSCs from both Ex-Ob and OW subjects can be used in regenerative medicine in eligible therapies. Further in vivo studies will be fundamental to validate these observations.

• Clinical and Experimental Pediatrics
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• v.50 no.12
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• pp.1217-1224
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• 2007

Purpose : Due to its high potency against leukemic blasts, our institution has opted for the use of dexamethasone during acute lymphoblastic leukemia (ALL) remission induction, but in our most recent treatment protocol, CMCPL-2005, we shortened the length of steroid treatment from 4 to 3 weeks. We compared both the rates of remission induction and significant complications observed during induction with CMCPL-2005, with those noted for our previous protocol, CMCPL-2001. Methods : We retrospectively reviewed the records of patients diagnosed with ALL from January, 2001 to December, 2006 at the Department of Pediatrics, St. Mary's Hospital, the Catholic University of Korea. Data concerning age, sex, WBC count at diagnosis, immunophenotype, cytogenetic traits, and risk group were collected for each patient. Results of remission induction treatment were compared between the two patient groups. Infection and other major complications resulting from treatment were investigated according to NCI toxicity criteria. Results : A total of 141 and 88 patients received remission induction under CMCPL-2001 and CMCPL-2005 respectively. In the CMCPL-2001 group, 136 (96%) achieved complete remission while 82 (93%) achieved CR in the CMCPL-2005 group. Patients in the CMCPL-2005 group were more likely to undergo remission induction without experiencing major complications. However, with regards to steroid related toxicities such as infection, no significant differences were noted. Conclusion : We shortened the length of steroid administration from four to three weeks, yet found the remission induction rate to be comparable to that of our previous regimen. However, rates of steroid related toxicities such as infectious complications remain unchanged despite shortened exposure to dexamethasone.

• Korean Journal of Head & Neck Oncology
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• v.15 no.2
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• pp.149-155
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• 1999

Objectives: To study the clinical features of the primary nasal/nasopharyngeal non-Hodgkin's lymphomas and to evaluate the implication of immunophenotyping as a prognostic factor. Patients and Methods: From January 1990 to December 1997,41 patients(median age, 41 years) of primary nasal/nasopharyngeal non-Hodgkin's lymphoma were studied. The clinical records and paraffin-embedded tissue blocks were reviewed retrospectively. The histologic features, immunophenotypic findings(pan-T, pan-B, CD3, CD56) and Epstein-Barr virus in situ hybridizatios were examined. The prognostic factors for clinical outcome were evaluated in these patients. According to Ann-Arbor system, there were 30 patiets(73%) with stage IE, 4(10%) with stage IIE, 3(7%) with stage IIIE, 4(10%) with stage IVE lymphoma. Among the patients with stage IE/IIE, 4 patients received local radiation alone, 4 received chemotherapy alone, 25 received combination chemotherapy and radiotherapy and 1 refused treatment. The patients with stage IIIE/IVE were given combination chemotherapy and radiotherapy. Results: Immunophenotyping were performed in 40 patients and staining results were as follows: 3(7%) patients with B cell, 17(42%) with T cell, 18(44%) with NK/T cell(CD56 positive), and two patients with unclassifiable result. Epstein-Barr(EB) virus in situ hybridization were performed in 28 patients and 23(82%) patients had positive EBV-encoded RNAs(EBERs). 21(55%) patients achieved a complete remission. There was no difference in complete remission between radiation alone and combination therapy. With median follow-up of 30 months, 5-years disease free survival of complete responders was 60% and 5-years overall survival rate was 36%. Multivariate analysis showed that better overall survival was related with absence of B symptoms, ECOG performance${\leq}1$ and non-NK cells. Conclusion: Most of all cases were positive for EBER. Since NK/T phenotype carried the worst prognosis, analysis for CD56 expression should be done. Further prospective studies were warranted to evaluate the role of chemotherapy in stage IE/IIE.

• Radiation Oncology Journal
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• v.23 no.2
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• pp.98-105
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• 2005

Purpose : The objective of our study was to evaluate the immunohistochemical expression of p53 and bax proteins as prognostic markers in FIGO stage IIb invasive squamous cell carcinoma of the uterine cervix. Materials and Methods : Sixty-five cases of squamous cell carcinoma of the cervix (stage IIb) that were diagnosed from October 1995 to December 2003 were analyzed retrospectively for the bax and p53 expression. These expressions were determined immunohistochemically and they were correlated to the patients' overall survival and disease-free survival. Results : The overall 5-year survival (OS) rate and the disease-free survival (DFS) rate were $65.1\%$ and $62.9\%$, respectively. p53 and bax immunoreactivity was seen in $26.2\%$ and $52.3\%$ of cases, respectively, with variable levels of expression. On the univariate analysis, only p53 positivity correlated with poor survival in DFS (log-rank test p=0.027), but this significance was not maintained on multivariated analysis by Cox's regression. The nine cases with the immunophenotype ps3+/bax- had the poorest survival. Conclusion : Neither p53 nor bax expression are Independent predictors of the prognosis for stage IIb cervical squamous cancers. Evaluation of p53 and bax co-expression may affect the clinical outcome and further investigation is needed.