• Journal of Veterinary Clinics
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• v.41 no.4
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• pp.215-222
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• 2024

An adult female dog was presented for evaluation of rapid growth of mammary gland masses. Complete blood count, serum biochemistry, and diagnostic imaging results were unremarkable. Fine needle aspirates of the mammary masses indicated mammary carcinoma characterized by large globoid cells with finely granular eosinophilic globules or Melamed-Wolinska-like bodies. A regional mastectomy was performed on the masses. Subsequent histopathologic examination of the surgically resected masses resulted in a diagnosis of mammary comedocarcinoma with nodal metastasis and distinct perivascular immune infiltrates, which were subject to immunohistochemical and flow cytometric immunophenotyping. Immunohistochemical examination confirmed the infiltration of CD3⁺ T and PAX5⁺ B lymphocytes. Flow cytometric analysis demonstrated tumor-infiltrating CD4⁺CD25⁺FOXP3⁺ regulatory T, CD8⁺ T, CD11b⁺ myeloid, and CD21⁺ B cells. Of note, paired flow cytometric analysis of peripheral blood and tumor tissues showed a preferential tumor infiltration of regulatory T and B cells. Approximately two months after the mastectomy, the tumor reoccurred at the surgery site. The dog died due to deteriorating conditions. We report a rare case of canine mammary comedocarcinoma, providing clinical, clinicopathologic, histologic, and immunophenotypic characteristics. Our case is valuable in providing a rationale for basic research that maps the immune landscape of mammary comedocarcinoma to identify key immune subsets for cancer progression.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.691-701
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• 2004

Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.

• Radiation Oncology Journal
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• v.23 no.2
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• pp.71-77
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• 2005

Purpose: This retrospective study was conduced to analyze the treatment results and to evaluate the prognostic factors affecting the survival of nasopharyngeal carcinoma patients. Materials and Methods: From 1987 to 2002, we analyzed 43 patients who had nasopharyngeal carcinomas that were histologically confirmed and who had also completed the planned radiation therapy course at Keimyung University Dongsan Medical Center According to the 6th edition of American Joint Committee on Cancer staging system, 12 patients ($27.9\%$) were at Stage 11, 13 ($30.2\%$) were at Stage III and 18 ($41.9\%$) were at Stage IV Histopathologically, there were 15 ($34.9\%$) squamous cell carcinomas, 8 ($18.5\%$) nonkeratinizing carcinomas, 17 ($39.5\%$) undifferentiated carcinomas, and 3 ($7.0\%$) lymphoepitheliomas. Among the total 43 patients, 31 patients ($72.1\%$) were treated with only radiation therapy. Neoadjuvant chemotherapy was peformed on 7 patients ($16.3\%$) and concurrent chemoradiotherapy was performed on S patients ($11.6\%$). Cisplatin and 5-Fluorouracil were administered to 11 patients for 4 cycles, and Cisplatin and Taxotere were administered to 1 patient for 6 cycles. The range of the total radiation dose delivered to the primary tumor was from 61.2 to 84 Gy (median 70.4 Gy), The follow-up period ranged from 2 to 197 months with median follow-up of 84 months. Results: The local control rate at 6 months after radiation therapy was $90.7\%$. The five year overall survival and disease free survival rates were $50.7\%$ and $48.9\%$, respectively. On the multivariate analysis, the age, T-stage ($T_{1-3}\;vs\;T_4$), N-stage and AJCC stage were the statistically significant prognostic factors affecting survival (p<0.05). The patterns of failure were as follows: local failure only in 3 patients ($7.0\%$), local and systemic failure in 1 patient ($2.3\%$), and distant metastasis only in 11 patients ($25.6\%$). Conclusion: The prognostic factors affecting the outcome of nasopharyngeal carcinoma were age, T-stage (7$T_{1-3}\;vs\;T_4$), N-stage and stage. Because systemic metastasis was the main failure pattern noted for nasopharyngeal carcinoma, systemic chemotherapy is needed to decrease the rate of distant metastasis for nasopharyngeal carcinoma. In audition, research for more effective chemotherapeutical regimens and schedules is also needed.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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• pp.880-886
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• 2004

Phellinus igniarius has been clinically used for the treatment of hemorrhoidal fistula, dysmenorrhea and the prevention of cancer in traditional oriental medicine. Recent studies showed that Phellinus igniarius produced anti-cancer, anti-metastasis and immuno-modulatory effects, There is lack of studies regarding the effects of Phellinus igniarius on the immunological activities. The present study was conducted to evaluate the effect of Phellinus igniarius on the regulatory mechanism of cytokines and nitric oxide (NO) for the immunological activities in Raw 264,7 cells. After the treatment of Phellinus igniarius water extract, cell viability was measured by MTT assay, NO production was monitored by measuring the nitrite content in culture medium. COX-2 and iNOS were determined by Immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. Results provided evidence that Phellinus igniarius inhibited the production of nitrite and nitrate (NO), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and the activation of phospholylation of inhibitor κBα (p-IκBα) in Raw 264.7 cells activated with lipopolysaccharide (LPS). These findings suggest that Phellinus igniarius can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections.

• Radiation Oncology Journal
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• v.9 no.1
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• pp.59-63
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• 1991

Thirty-one patients with previously untreated and locally advanced nasopharyngeal cancer were retrospectively reviewed for comparing the effects of radical radiotherapy alone with that of combining chemotherapy and radiotherapy from 1983 to 1989 at Kangnam 51. Mavy's hospital.23/31 were evaluable for recurrence and suwival. There were 8 patients for stage III, and 15 patients for stage IV. Eleven patients were treated with radical radiation therapy done (arm I). Twelve patients were given 1~3 courses of cisplatin-5FU or cisplatin-bleomycin-vincristine prior to radiation therapy (arm II). The two arms were comparable in patient characteristics Of 11 radiotherapy Patients, complete response was 55%(6/11) and Partial response 45%(5/11). Among 12 patients after induction chemotherapy, complete response was 25%(3/12) and partial response 75%(9/12). After subsequent radiotherapy, complete response was increased to 83%(10/12) and partial response was 17%(2/12). Treatment failure was 30%(local recurrence; 3/11, and regional recurrence; 1/11) in arm 1 and 33% (local recurrence; 1/12, regional recurrence; 2/12 and distant metastasis; 1/12) in arm ll . There was no significant difference in survival between arm I and arm II (p> 0.05). The toxicities of treatment were acceptable. More controlled clinical trials must be completed before acceptance of chemotherapy as part of a standard radical treatment for locally advanced nasopharyngeal cancer.

• Radiation Oncology Journal
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• v.13 no.1
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• pp.55-61
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• 1995

Purpose : Despite a development of therapeutic machines and advance in modern radiation therapy techniques, locally advanced cervical carcinoma has shown high rate of local failure and poor survival rate, Combination of chemotherapy and radiotherapy demonstrated benefit in improving local control and possibly the overall survival. Our study was performed to evaluate effect of concurrent chemoradiation on locally advanced uterine cervical cancer. Methods and Materials : Twenty six patients with locally advanced stage(FIGO stage IIB with ${\geq}5cm$ in diameter, III, IVA) were treated with combination of radiation therapy and concurrent cisplatinum between May of 1988 and September of 1993 at our hospital. Radiation therapy consisted of external irradiaton and 1-2 sessions of intracavitary irradiation. Cisplatinum was administered in bolus injection of 25mg/$m^2$ at weekly intervals during the course of external radiation therapy. Results : Of the 26 Patients, twenty-five patients were evaluable for estimation of response. Median follow-up period was 25 months with ranges from 3 to 73 months. Stage IIB, III, and IVA were 16, 5, 4 patients, respectively, Twenty patients were squamous cell carcinoma. Response was noted in all 25 patients: complete response(CR) in 17/25($68\%$), Partial response(PR) in 8/25($32\%$). Of the 24 patients except one who died of sepsis at 3 months follow-up, seventeen patients($70.8\%$) maintained local control in the pelvis: 16/17($94.1\%$) in CR, 1/17($14.3\%$) in PR. Fourteen of the 17 patients with CR are alive disease free on the completion of follow-up. Median survival is 28 months for CR and 15 months for PR. Analysis of 5-year survival by stage shows 11/16($59.8\%$) in IIB, 3/5($60.0\%$) in III, and 1/4($25.0\%$) in IVA. Overall 5-year survival rate was $55.2\%$. Ten patients recurred: 4 at locoregional, 3 in distant metastasis and 3 with locoregional and distant site. Toxicity by addition of cisplatinum was not excessive. Conclusion : Although the result of this study was obtained from small number of patients, it is rather encouraging in view of markedly improved response rate compared with the results of historical group.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.4
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• pp.298-305
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• 2015

Stem cell-like tumor cells are reported to be the main reason for tumor recurrence and metastasis. As one of the new approaches to overcome cancer, studies are emerging to inhibit the expressions of stem cell transcriptional factors (Oct4, Sox2, Klf-4, and Lin28) in cancer cells. MicroRNAs are master genetic regulators that can control development and differentiation of stem cells. In this study using various ovarian tumors (Skov3, Ovcar3, Tov112D, Tov21G, PA-1 and Hsc832(c)T), we examined the expressions of stem cell-related transcription factors, and the biological changes in cell survival and growth by miR-126 that targets stem cell transcriptional factors. We observed that treatment of miR-126 induced the morphological changes and cell suspension in most cells. In addition, miR-126 induced gradual regression of cell division except Skov3 cells, especially significant time-dependent reduction in Tov112D, Tov21G and PA-1. When we examined the expression of stem cell transcriptional factors, Sox2 was shown to be down-regulated after miR-126. Our results demonstrate that miR-126 treatment can provide the reversible environment to regulate cell division and to induce cell death of ovarian tumors, suggesting the molecular biological clues for clinical usage.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.4
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• pp.314-320
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• 2001

Matrix metalloproteinases have long been viewed as ideal candidates for proteinases that enables tumor cells to permeated basement membrane defenses and invade surrounding tissue. There is growing evidence that the MMPs have an expanded role, as they are important for the creation and maintenance of a microenvironment that facilitates growth and angiogenesis of tumors at primary and metastatic sites. MT-MMPs are not secreted but instead remaining attached to cell surfaces. Although not all of the MT-MMPs are fully characterized, MT-MMPs have important role in localizing and activating secreted MMPs. The MMP genes are transcriptionally responsive to a wide variety of oncogene, growth factors, cytokine, and hormones. Currently, a number of MMP inhibitors are being developed and some have reached clinical trials as anti-metastatic or anti-cancer therapies. MT1-MMP is involved in the activation of proMMP-2. MT1-MMP is significant not only as a tumor marker but as a new target for chemotherapy against cancer. The purpose of this study was to evaluate the effects of protein kinase C inhibitor(genistein) on the proliferation of HT1080 and expression of MT1-MMP mRNA. Human fibrosarcoma cell line HT1080 was cultured and divided 2 groups. The experimental group was treated with $100{\mu}M$ genistein and incubated 12h, 24h for $[3^H]-thymidine$ uptake assay and northern hybridization individually. And the control group was treated with same amount of PBS for the above procedures. $[3^H]-thymidine$ incorporation was measured with ${\beta}$ ray detector. And RT-PCR and northern blotting for MT1-MMP mRNA was performed. The results were as follows 1. $[3^H]-thymidine$ uptake was reduced in experimental group with statistical significance. 2. MT1-MMP mRNA expression was significantly reduced in experimental group. These results showed that protein kinase C inhibitor (genistein) inhibited proliferation of HT1080 and almost completely blocked transcription of MT1-MMP mRNA. So, it is possible to use the protein kinase inhibitor (genistein) as anti-metastatic and anti-proliferative agent.

• Journal of radiological science and technology
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• v.36 no.4
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• pp.299-304
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• 2013

Whole body bone scan has been used to confirm bone metastasis and follow-up study with radio isotope. However, if the factors related to $^{99m}Tc$ uptake and waiting time for study are inappropriate, it would be image of low quality. The purpose of present study was to investigate correlation between the evaluation index of renal function and uptake of radiopharmaceuticals. The population for this retrospective study consisted of 387 patients who underwent whole body bone scan between June 2012 and December 2012. As a result of quantitative and qualitative analysis, we were able to confirm that GFR of less than normal range and creatinine levels in blood of more than average are more likely to be under the mean uptake rate. As a result of analysis on the indicator affecting soft-tissue and bone uptake, the correlation of all elements was somewhat low. Also there are no statistically significances due to the other parameters we did not deal with. Therefore, further research on additional factors is needed for exact study and improvement of the image quality.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.6
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• pp.782-788
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• 2013

Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae), colloquially known "Gujulcho" in Korea, has been used in traditional medicine for the treatment of various diseases, including cough, common cold, bladder-related disorders, gastroenteric disorders, hypertension, and inflammatory diseases, such as pneumonia, bronchitis, pharyngitis, and rheumatoid arthritis (RA) However, the effect of Chrysanthemum zawadskii var. latilobum on breast cancer invasion is unknown. In this study, we investigated the inhibitory effect of Chrysanthemum zawadskii var. latilobum extract (CZE) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-9 (MMP-9) expression and cell invasion, as well as the molecular mechanisms involved in MCF-7 cells. CZE were not cytotoxic up to 100 ${\mu}g/ml$ concentration in the MCF-7 cell line. CZE decreased MMP-9 expression. TPA substantially increased NF-${\kappa}B$ DNA binding activity. Pre-treatment with CZE inhibited TPA-stimulated NF-${\kappa}B$ binding activity and NF-${\kappa}B$ related protein expression. To identify invasion ability of MCF-7 cells decreased by CZE, we used martrigel invasion assay. As a result, it is significantly decreased cell invasion. These results indicate that CZE-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the NF-${\kappa}B$ pathway in MCF-7 cells. Chrysanthemum zawadskii var. latilobum may have potential value in restricting breast cancer metastasis.