• Tuberculosis and Respiratory Diseases
• /
• v.40 no.2
• /
• pp.177-184
• /
• 1993

Background: Accurate staging of bronchogenic carcinoma is important in determining resectability and metastasis of tumor to the subcarinal nodes is generally believed to indicate poor prognosis. The technique of Transbronchial needle aspiration (TBNA) has offered a safe & effective way to asscess mediastinal lymph node involvement in the staging of lung cancer. We performed TBNA in patients who were suspected lung cancer to evaluate the clinical usefulness of the TBNA. Method: TBNA of the subcarinal lymph node was performed at the time of initial diagnostic bronchoscopy in 60 patients with suspected lung cancer, and 42 cases of histologically proved bronchogenic cancer were analized. Results: The frequency of adequate samples by transbronchial needle aspiration (TBNA) was 81% and the positive rate of malignant cells by TBNA was 14.7%. There were no differences in positive rates by tumor cell types. In patients with thickened carina on bronchoscopy, the TBNA was positive in 33.3% as compared to 5.3% of normal carina on bronchoscopy, and the difference was statistically significant (p<0.05). In patients with enlarged subcarinal lymph node on chest CT, the positive rate of malignant cells (50.0%) was higher than that of normal sized subcarinal lymph node on chest CT (4.8%) (p<0.01). There were no specific complications in the TBNA procedure. Conclusion: TBNA is a relatively safe procedure and it offers the possibility of avoiding the cost and morbidity of surgical staging in patients especially whose carina is thickened on bronchoscopy and whose subcarinal LN was enlarged on chest CT.

• Journal of Life Science
• /
• v.26 no.3
• /
• pp.376-386
• /
• 2016

Apoptosis induction has been proposed as an efficient mechanism by which malignant tumor cells can be removed following chemotherapy. The intrinsic mitochondria-dependent apoptotic pathway is frequently implicated in chemotherapy-induced tumor cell apoptosis. Since DNA-damaging agent (DDA)-induced apoptosis is mainly regulated by the tumor suppressor protein p53, and since more than half of clinical cancers possess inactive p53 mutants, microtubule-damaging agents (MDAs), of which apoptotic effect is mainly exerted via p53-independent routes, can be promising choice for cancer chemotherapy. Recently, we found that the apoptotic signaling pathway induced by MDAs (nocodazole, 17α-estradiol, or 2-methoxyestradiol) commonly proceeded through mitotic spindle defect-mediated prometaphase arrest, prolonged Cdk1 activation, and subsequent phosphorylation of Bcl-2, Mcl-1, and Bim in human acute leukemia Jurkat T cells. These microtubule damage-mediated alterations could render the cellular context susceptible to the onset of mitochondria-dependent apoptosis by triggering Bak activation, Δψm loss, and resultant caspase cascade activation. In contrast, when the MDA-induced Bak activation was inhibited by overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2 or Bcl-xL), the cells in prometaphase arrest failed to induce apoptosis, and instead underwent mitotic slippage and endoreduplication cycle, leading to formation of populations with 8N and 16N DNA content. These data indicate that cellular apoptogenic mechanism is critical for preventing polyploid formation following MDA treatment. Since the formation of polyploid cells, which are genetically unstable, may cause acquisition of therapy resistance and disease relapse, there is a growing interest in developing new combination chemotherapies to prevent polyploidization in tumors after MDA treatment.

• Journal of Life Science
• /
• v.26 no.11
• /
• pp.1289-1297
• /
• 2016

Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the oral cavity, comprising up to 90% of oral cancer. Oral cancer is characterized by a marked tendency of local invasiveness and is good for early detection and treatment; therefore, it is recognized as a good model for cancer prevention. The present study investigated the antioxidant, thrombin inhibitory, and anti-invasive activities of the solvent fractions of Zingiber officinale Roscoe. Samples were fractionated into hexane, chloroform, ethyl acetate, butanol, and water fractions, and each of these was assayed individually. The water fraction showed the highest extraction yield at 9.79%(w/w). Anti-oxidative activity was analyzed by DPPH assay. Thrombin inhibitory activity was used to analyze thrombin inhibitor assay. Cell viability was detected by the MTS assay. The activity and mRNA expression of MMP-2 and MMP-9 in human oral squamous carcinoma YD-10B cells were examined by zymography and RT-PCR. The antioxidative activities of hexane and water fractions were 92.38% and 92.96%, respectively. In the thrombin inhibitory activity test, water fraction was the highest, with a value of 65.86%. MMP-2/-9 activation was increased in phorbol 12-myristate 13-acetate (PMA)-induced YD-10B cells. MMP-9 activation was increased in thrombin-treated YD-10B cells. In PMA- or thrombin-treated YD-10B cells, the increased mRNA expression and protein activation of MMP-2/-9 were significantly inhibited in the hexane fraction. Therefore, the hexane fraction obtained from a Zingiber officinale Roscoe water extract is a promising therapeutic anti-invasive agent in oral cancer.

• The Journal of the Korean bone and joint tumor society
• /
• v.15 no.2
• /
• pp.111-121
• /
• 2009

Background: Osteosarcoma is one of the most common primary malignant tumors of bone occurring mainly in children and adolescents. Although surgery combined with chemotherapy has markedly improved patient survival during the last years, the use of anticancer drugs is still associated with serious problem, such as the frequent acquisition of drug-resistant phenotypes and occurrence of "secondary malignancies". Several solid tumors display enhanced expression of matrix metalloproteinases (MMPs), and recently clinical trials have been initiated on MMP-inhibitors. On the other hand, bisphosphonates (BPs) are inhibitors of bone resorption, and widely used to treat osteoclast-mediated bone diseases. Also they appear to possess direct antitumor activity. Methods: One osteosarcoma cell line (U2OS) was treated with ibandronate (0, 0.1, 1, $10{\mu}M$) for 48 hours. Cell viabilities were determined using MTT assay, the mRNA levels of MMP-2 and MT1-MMP were detected by reverse-transcription polymerase chain reaction, the amount of MMP-2 and MT1-MMP protein were measured by Westernblot, the activities of MMP-2 were observed by Gelatin zymography, and Matrigel invasion assays were used to investigate the invasive potential of osteosarcoma cell lines before and after ibandronate treatment. Results: The invasiveness of U2OS cell line was reduced dose-dependently following 48 hour treatment of up to $10{\mu}M$ of the ibandronate at which concentration no cytotoxicity occurred. Furthermore, the gelatinolytic activities and protein and mRNA levels of MMP-2 and MT1-MMP were also suppressed by increasing ibandronate concentrations. Conclusion: Given that MMP-2 is instrumental in tumor cell invasion, it is very likely that the reduction in osteosarcoma cell invasion by ibandronate is a consequence, at least in part, of suppressed expression of both MMP-2 and MT1-MMP. Isolation of a molecule (s) responsible for the bisphosphonate inhibition of tumor cell invasion would pave the way for the development of a new generation of metastasis inhibitors.

• Journal of Life Science
• /
• v.20 no.10
• /
• pp.1519-1524
• /
• 2010

Apigenin (4', 5, 7-trihydroxyflavone), a common dietary flavonoid abundantly present in fruits and vegetables, has shown remarkable anti-proliferative effects against various malignant cell lines. To observe the anti-proliferative effects, oral cavity cancer cell lines, $6{\times}10^3$ cells/well (96 well plate) of KB oral cavity tumor cells were plated and 24 hr later treated with apigenin for one day, after which MTT assay was performed. Apigenin induced cell death in a dose-dependent manner after incubation. Cell viability was significantly decreased in the group treated with 100 ${\mu}M$ apigenin for 24 hr (p<0.05) compared to the control group. To assess apoptosis, the nuclei of KB cells were stained with DAPI. The presence of chromatin condensation in the apigenin treated cells was detected on a fluorescent microscope (${\times}200$). We investigated the in vivo growth inhibitory effects of apigenin on oral cavity cancer KB tumor xenograft subcutaneously implanted in male nude mice. Apigenin was administered to mice by gavage at doses of 25 and 50 mg/kg/day in 0.2ml of PBS. Tumor volume was significantly decreased in 25 and 50 mg/kg apigenin-administration groups compared to the control group. For apoptosis analysis, TUNEL staining was performed. A significant increase in TUNEL positive cells was found in the 25 mg/kg apigenin administration group compared to the non- apigenin administration group. Histopathological changes were not observed. These results indicate that apigenin inhibits oral cavity cancer cell growth through the induction of apoptosis.

• Progress in Medical Physics
• /
• v.21 no.2
• /
• pp.153-164
• /
• 2010

To determine the clinical target volumes considering vascularity and cellularity of tumors, the software was developed for mapping of the analyzed biological clinical target volumes on anatomical images using regional cerebral blood volume (rCBV) maps and apparent diffusion coefficient (ADC) maps. The program provides the functions for integrated registrations using mutual information, affine transform and non-rigid registration. The registration accuracy is evaluated by the calculation of the overlapped ratio of segmented bone regions and average distance difference of contours between reference and registered images. The performance of the developed software was tested using multimodal images of a patient who has the residual tumor of high grade gliomas. Registration accuracy of about 74% and average 2.3 mm distance difference were calculated by the evaluation method of bone segmentation and contour extraction. The registration accuracy can be improved as higher as 4% by the manual adjustment functions. Advanced MR images are analyzed using color maps for rCBV maps and quantitative calculation based on region of interest (ROI) for ADC maps. Then, multi-parameters on the same voxels are plotted on plane and constitute the multi-functional parametric maps of which x and y axis representing rCBV and ADC values. According to the distributions of functional parameters, tumor regions showing the higher vascularity and cellularity are categorized according to the criteria corresponding malignant gliomas. Determined volumes reflecting pathological and physiological characteristics of tumors are marked on anatomical images. By applying the multi-functional images, errors arising from using one type of image would be reduced and local regions representing higher probability as tumor cells would be determined for radiation treatment plan. Biological tumor characteristics can be expressed using image registration and multi-functional parametric maps in the developed software. The software can be considered to delineate clinical target volumes using advanced MR images with anatomical images.

• Journal of Chest Surgery
• /
• v.39 no.11 s.268
• /
• pp.828-837
• /
• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, 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 increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

• Tuberculosis and Respiratory Diseases
• /
• v.59 no.5
• /
• pp.504-509
• /
• 2005

Background : Endobronchial tumors cause life-threatening dyspnea and can lower the quality of life due to central airway obstruction. In those cases with an intraluminal tumor, various bronchoscopic techniques are available for tumor debulking. The therapeutic effect of bronchoscopic electrocautery for palliation in patients with a symptomatic tumor obstruction was studied. Method : Nineteen patients with bronchogenic carcinomas (n=15) and metastatic tumors affecting the bronchi (n=4), between March 2002 and March 2005, were enrolled in this study. Electrocautery was performed under local anesthesia using an electroprobe and diathermic snare. Using flexible bronchoscopy, a follow-up bronchoscopic examination was performed 3-4 days later. Symptom improvement was evaluated by $FEV_1$, FVC and dyspnea score (Modified Borg Category Scale (0~10)), both before and after the electrocautery. Results : The success rate of electrocautery on the follow up examination was 84%. Patients with endoluminal airway lesions had a mean overall decrease in the size of the obstruction to $47.8{\pm}15.7%$. The mean Improvement in the dyspnea score immediately after the endobronchial tumor debulking was $2.78{\pm}1.42$. The average improvements in the $FEV_1$ and FVC after electrocautery were $0.32{\pm}0.19L$ and $0.5{\pm}0.22L$, respectively. There were 2 cases of complications related with electrocautery (one each of pneumothorax and pneumonia). Conclusion : Electrocautery using an electroprobe and diathermic snare was an effective and safe palliative treatment for a symptomatic endoluminal airway obstruction in lung cancer.

• The Journal of the Korean bone and joint tumor society
• /
• v.8 no.1
• /
• pp.1-11
• /
• 2002

Purpose : We evaluated the radiological and functional results of prosthetic reconstruction for locally aggressive benign and malignant tumor in the lower extremity. Materials and Methods : Eighty eight patients were followed up for an average 76 months(22~174). We examined the survival rate of prosthesis, and evaluated the final result by MSTS functional score and ISOLS radiological implants evaluation system. They were statistically analyzed according to the age(<20 year vs. ${\geq}$20 year), fixation methods, amount of bony resection, chemotherapy, local recurrence, and presence of metastasis. Results : The 5 year prosthetic survival rates were 100% in the proximal femur, 83.3% in the distal femur, 81.9% in the proximal tibia. Mean total functional scores were 73.3%, 72%, 68.7%, respectively. In distal femur, the non-chemotherapeutic group was superior in the prosthetic survival rate. Recurrence or metastasis affected the functions in the distal femur and proximal tibia. In the radiological evaluation of the distal femur, older patients over 20 years of age and with cement fixation were superior in bone remodeling(p<0.05). Postoperative infection and radiological loosening were the main causes of the prosthetic failure. Conclusion : The prosthetic reconstruction in the lower extremity led to good clinical and radiological results. Amount of bony resection, chemotherapy, recurrence and metastasis seemed to influence the prosthetic survival, and long-term follow-up will be necessary to investigate more significant prognostic factors.

• The Korean Journal of Nuclear Medicine
• /
• v.33 no.4
• /
• pp.422-429
• /
• 1999

Purpose: The measurement of radiation absorbed dose is useful to predict the response after I-131 labeled metaiodobenzylguanidine (MIBG) therapy and determine therapy dose in patients with unresectable or malignant pheochromocytoma. We estimated the absorbed dose in tumor tissue after high dose I-131 MIBG in a patient with pheochromocytoma using a gamma camera and Medical Internal Radiation Dose (MIRD) formula. Materials and Methods: A 64-year old female patient with pheochromocytoma who had multiple metastases of mediastinum, right kidney and periaortic lymph nodes, received 74 GBq (200 mCi) of I-131 MIBG. We obtained anterior and posterior images at 0.5, 16, 24, 64 and 145 hours after treatment. Two standard sources of 37 and 74 MBq of I-131 were imaged simultaneously. Cummulated I-131 MIBG uptake in tumor tissue was calculated after the correction of background activity, attenuation, system sensitivity and count loss at a high count rate. Results: The calculated absorbed radiation dose was 32-63 Gy/ 74 GBq, which was lower than the known dose for tumor remission (150-200 Gy). follow-up studies at 1 month showed minimally reduced tumor size on computed tomography, and mildly reduced I-131 MIBG uptake. Conclusion: We estimated radiation absorbed dose after therapeutic I-131 MIBG using a gamma camera and MIRD formula, which can be peformed in a clinical nuclear medicine laboratory. Our results suggest that the measurement of radiation absorbed dose in I-131 MIBG therapy is feasible as a routine clinical practice that can guide further treatment plan. The accuracy of dose measurement and correlation with clinical outcome should be evaluated further.