• Journal of Life Science
• /
• v.29 no.1
• /
• pp.9-17
• /
• 2019

As tumors develop, they encounter microenvironmental stress, such as hypoxia and glucose depletion, due to poor vascular function, thereby leading to necrosis, which is observed in solid tumors. Necrotic cells are known to release cellular cytoplasmic contents, such as high mobility group box 1 (HMGB1), into the extracellular space. The release of HMGB1, a proinflammatory and tumor-promoting cytokine, plays an important role in promoting inflammation and metabolism during tumor development. Recently, HMGB1 was shown to induce the epithelial-mesenchymal transition (EMT) and metastasis. However, the underlying mechanism of the HMGB1-induced EMT, invasion, and metastasis is unclear. In this study, we showed that noninvasive breast cancer cells MCF-7 formed tightly packed, rounded spheroids and that the cells in the inner regions of a multicellular tumor spheroid (MTS), an in vitro model of a solid tumor, led to necrosis due to an insufficient supply of O2 and glucose. In addition, after 7 d of MTS culture, the EMT was induced via the transcription factor Snail. We also showed that HMGB1 receptors, including RAGE, TLR2, and TLR4, were induced by MTS culture. RAGE, TLR2, and TLR4 shRNA inhibited MTS growth, supporting the idea that RAGE/TLR2/TLR4 play critical roles in MTS growth. They also prevented MTS culture-induced Snail expression, pointing to RAGE/TLR2/TLR4-dependent Snail expression. RAGE, TLR2, and TLR4 shRNA suppressed the MTS-induced EMT. In human cancer tissues, high levels of RAGE, TLR2, and TLR4 were detected. These findings demonstrated that the HMGB-RAGE/TLR2/TLR4-Snail axis played a crucial role in the growth of the MTS and MTS culture-induced EMT.

• Tuberculosis and Respiratory Diseases
• /
• v.48 no.5
• /
• pp.757-765
• /
• 2000

Background : Angiogenesis plays a critical role in human tumor growth and metastasis. Microvessel count as a measure of tumor angiogenesis, has been significantly correlated with invasive and metastatic patterns in breast. prostate and cutaneous carcinomas. Materials and Methods : Fifty patients with curatively resected non-small cell lung cancer were evaluated. Tumor tissues embedded in paraffin block were stained by anti CD 31 (PECAM, platelet endothelial cellular adhesion molecule) using immunohistochemical method to assess microvessel count. Microvessels were counted in the most active areas of neovascularization(microscopy, 200$\times$). Results: 1) Mean microvessel count was 47.1$\pm$17.7(per 200$\times$field) in total 50 cases. 2) Mean microvessel count of adenocarcinoma (54.4$\pm$19.9) was significantly higher than that of squamous cancer (43.9$\pm$16.2) (p<0.05), but there were no relationship between microvessel count and TNM stages. 3) Median survival time, 2-year and 5-year survival rates of the low microvascular group (microvessel count<45, 22 cases) were 61 months, 80% and 40%, respectively, and those of the high microvascular group(microvessel count$\geq$45, 28 cases) were 46 months, 75% and 12%, respectively. As results, prognosis of low microvascular group is statistically significantly superior to that of the high microvascular group (p=0.0162, Kaplan-Meier, log-rank). Conclusion : Angiogenesis assessed by microvessel count can be used as one of the significant prognostic factors in non-small cell lung cancer.

• Physical Therapy Korea
• /
• v.10 no.1
• /
• pp.15-27
• /
• 2003

Therapeutic ultrasound is commonly applied for deep heating in physical therapy setting. However, it is difficult to determine the exact application dosage and to confirm the immediate heating effect. Microwave Radio-Thermometer (MRT) can measure the temperature by the electromagnetic energy in the microwave region of the object that emits above absolute zero temperature. MRT was used for early diagnosis of breast cancer since it was not harmful, non-invasive, and non-ionizing to the human body. The purposes of this study were to investigate how accurately 1.1 GHz RTM (RES Ltd. Russia) measures the change of average temperature in the tissue, and to determine the depth of temperature change measurement. Therapeutic ultrasound was applied (continuous wave for 5 minutes, 1 MHz, intensity of 1.5 $W/cm^2$ [in vitro] and 1.0 $W/cm^2$ [in vivo]) in four different conditions: (1) 30 cases of in vitro specimen of pork, (2) 30 cases of in vitro specimen of pork ankle joint, (3) 10 cases of in vivo canine thigh, and (4) 30 cases of in vivo human body. Intraclass Correlation Coeffients (ICC[3,1]) between average needle probe thermometer below surface and MRT temperature was revealed as followed: (1) Before ultrasound application ICCs ranges above .8 in specimen of pork (15 mm underneath the skin) and above .82 in specimen of pork ankle joint (10~30 mm underneath the skin). (2) After ultrasound application ICCs ranges above .7 in both specimens of pork and pork ankle joint. (3) Before ultrasound application ICCs ranges above .8 in canine thigh (20 mm underneath the skin). (4) After ultrasound application ICCs ranges above .82 in canine thigh. The temperature of the human body increased significantly with the mean of $15^{\circ}C$ in muscle tissue and with the mean of $3.5^{\circ}C$ in joint (p<.00). It was revealed that the average depth of temperature measurement of the tissue by MRT was in between 10 and 35 mm, and determined that the proper temperature measurement band was $36.5{\sim}37.0^{\circ}C$.

• Journal of Hospice and Palliative Care
• /
• v.12 no.1
• /
• pp.27-31
• /
• 2009

Purpose: Lymphedemas are tissue fluid swellings, usually on the arms or legs, and occur as a result of impaired lymphatic drainage. Presently, the most effective treatment available is complete decongestive physiotherapy (CDP). However, this therapy is ineffective in some patients and surgery may be indicated. Herein, we examined the efficacy of minimally invasive needle aspiration of the most enlarged areas in hypodermic adipose tissues, of patients who had failed CDP. Methods: We included 21 patients who were diagnosed with lymphedema stage II-III in the upper or lower extremities and visited the lymphedema clinic at a university hospital from September 1, 2003 to February 28, 2004. All patients had been treated with CDP at least once, but had failed to respond to the therapy for more than one year. Nine patients had breast cancer and 12 had cervical cancer. We identified the area with the most severe edema by using MRI and performed a 16-gauge angio-needle aspiration on the area. The patients were followed up for 3 months. Effectiveness of the treatment was evaluated by comparing the volume of edema before and after the treatment using Wilcoxon signed rank-test. Results: The mean reduction ratio of the volume of edema comparison normal volume was 41.1${\pm}$35.3% (P=0.001). There were no major or minor operative complications except localized hemorrhage. Conclusion: We conclude that a needle aspiration prior to other surgical treatments is relatively safe and effective for those patients who are unresponsive to CDP.