• Tuberculosis and Respiratory Diseases
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• v.46 no.1
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• pp.36-43
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• 1999

Background : Tumor growth is the net result of intrinsic proliferation and escape from active cell death. bcl-2 is a member of a new category of oncogenes that is not involved in influencing cell proliferation but is involved in regulating cell death(apoptosis). Based on this information, it seems to be reasonable to expect that there may be clinical prognostic significance of bcl-2 expression in non-small cell lung cancer. But its prognostic significance is not established. Methods: To investigate the role of bcl-2 in lung cancer, we performed immunohistochemical stain of bcl-2 on 57 biopsy specimens from resected primary non-small cell lung cancer. Thereafter, flow cytometric cell cycle analysis was done. And we analyzed the correlation between bcl-2 expression, clinical parameters, S-, $G_1$-phase fraction and survival. Results: bcl-2 were detected in 43.8% of total 57 patients(according to histology, squamous cancer 47%, adenocarcinoma 32%, according to TNM stage, I 28.6%, II 52.3%, III 45.5%. both differences were insignificant). By using the flow cytometric analysis, mean S-phase fraction of bcl-2(+) and (-) group were 14.1($\pm7.8$)%, 24.7($\pm10.5$)% (p<0.005), mean $G_1$-phase fraction of bcl-2(+) and bcl-2(-) group were 75.5($\pm10.8$)%, 65.5($\pm11.4$)%(p<0.05). 2yr, 3yr and 5yr survival and median survival time of bcl-2(+) group were 65%, 54%, 41%, 53 months, and those of bcl-2(-) group were 71%, 52%, 46%, 37 months. (p>0.05, Kaplan-Meier, log rank) Conclusion: bcl-2 was detected in 43.8% of primary non-small cell lung cancer. The S-phase fraction of bcl-2(+) group was less than bcl-2(-) group, and G1-phase fraction of bcl-2(+) group was more than bcl-2(-) group. But, expression of bcl-2 could not be a prognostic factor.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.290-297
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• 2000

Background : Current non-invasive methods for evaluating the mediastinum by computed tomographic (CT) scan have limited sensitivity and specificity. The recently introduced PET was reported to be a more sensitive and specific method for the mediastinal staging of NSCLC (sensitivity : 76-100 %, specificity : 81-100%) than CT or MRI. We assessed the usefulness of PET in the mediastinal staging of NSCLC. Methods : We reviewed the medical records of NSCLC patients that had undertaken staging work-up by both CT and PET before thoracotomy between January 1997 and December 1998. A total of 23 patients were enrolled in the study (14 males and 7 females) with a mean age of 61$\pm$9 years. By comparing the clinical(CT and PET) and pathologic stagings, we evaluated the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of PET in thoracic nodal staging. Results : Sensitivity, specificity, positive predicted value and negative predicted value were 38%, 40%, 25% and 50% respectively for computed tomography, and 50%, 60%, 30% and 69% for PET. The accuracy of FDG-PET in our study was lower than that reported by previous other studies. Conclusion : The addition of FDG-PET to CT scanning has limited benefit for the thoracic nodal staging of NSCLC, but its value in our study was lower than that observed by others.

• The Korean Journal of Nuclear Medicine
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• v.28 no.2
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• pp.186-191
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• 1994

Tc-99m MIBI, a lipophilic cation, was reported as a useful agent for localization of lung cancer. The effect of radiation therapy on the uptake of Tc-99m MIBI in lung cancer, however, was not well evaluated. The aim of the present study was to elucidate the usefulness of Tc-99m MIBI SPECT in the localization and the assessment of radiotherapy in non-small cell lung cancer. Twenty patients(19 males and 1 female, mean age 59, 16 squamous cell ca and 4 adenoca) were studied with Tc-99m MIBI SPECT before radiation therapy. Eleven patients(10 males and 1 female, mean age 59, 8 squamous cell ca and 3 adenoca) were repeated the study 1 month after the completion of radiation therapy(mean dose 6453cGy). All patients showed positive uptakes of Tc-99m MIBI in their tumors. One patient showed a hot uptake in atelectatic area. There was no difference of Tc-99m MIBI uptakes between squamous cell ca and adenoca either on planar or tomographic images. Tc-99m MIBI uptake ratios of squamous cell ca and adenoca were $1.50{\pm}0.16$ and $1.45{\pm}0.15$ on planar images, and $2.73{\pm}0.46$ and $2.54{\pm}0.37$ on tomographic images, respectively. The concordance between radiological change(chest x-ray and CT) and change of Tc-99m MIBI uptakes was 9/11 (81.8% ). In conclusion, Tc-99m MIBI SPECT was useful in the localization of tumor and the assessment of radiation therapy in non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.54-62
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• 1996

Background: $^{99m}Tc$ MIBI(Methoxyisobutylisonitrile complex), a member of the isonitrile class of coordination compounds, is a lipophilic cation presently under investigation for clinical use as myocardial perfusion imaging agent and is widely used to detect myocardial infarction. Preliminary reports indicate that $T_1$-201 accumulate in human neoplasm and several authors reported $^{99m}Tc$ MIBI may also localized in primary malignant tumor and metastatic deposits from lung cancer. We evaluated the uptake of $^{99m}Tc$ MIBI in lung cancer and localization of mediastinal and other site metastasis, and compared the benign lesion of the lung. Method: Thirty four patients of lung cancer and ten patients of benign lung lesion were studied with chest CT and $^{99m}Tc$ MIBI Lung SPECT. $^{99m}Tc$ MIBI uptake ratio was assessed by TR/NL(Lung lesion/ Normal area), HT/NL (Heart/Normal area) and HT/TR(Heart/Lung lesion). Results: 1) All lung cancer patients showed increased uptakes of $^{99m}Tc$ MIBI in malignant lung lesion and Tc-99m MIBI uptake was also increased in mediastinal and lymph node metastasis except two cases. 2) There was significant different ratio of TR/NL between malignant and benign lesion, $3.79{\pm}1.82$ and $1.67{\pm}0.63$ on planar images, respectively(p<0.001). 3) There was no significant difference of $^{99m}Tc$ MIBI uptake ratio between squamous cell carcinoma, small cell carcinoma and adeno carcinoma($3.64{\pm}1.66$, $3.57{\pm}0.72$, $4.31{\pm}2.28$ respectively). Conclusion: $^{99m}Tc$ MIBI lung SPECT was useful in the localization of tumor and mediastinal or other site metastatic lesion in lung cancer and also in the differential diagnosis between benign and malignant lesion.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.290-300
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• 1998

Background: CYFRA 21-1 is a tumor marker which measures a fragment of cytokeratin 19 expressed by epithelial cells in bronchus. It is known that cytokeratin 19 is abundant in squamous epithelial cell cancer of the lung. However, if the incidence of elevated serum CYFRA 21-1 level in patients with benign lung diseases or pulmonary tuberculosis with severe parenchymal damage is high the specificity of CYFRA 21-1 could be decreased. The purpose of this study is to investigate the changes of serum CYFRA 21-1 according to the degree of parenchymal damage and the usefulness of CYFRA 21-1 for diagnosing possibly combined lung cancer in patients with pulmonary tuberculosis. Method: We studied the changes of serum CYFRA 21-1 according to the sputum AFB stain, radiologic manifestation and history of treatment in 81 patients with pulmonary tuberculosis, and 20 healthy persons, 25 patients with lung cancer, as a control group. CYFRA 21-1 concentration in serum was quantified by the immunoradiometry assay(Centocor$^{(R)}$). Result: The results were as follow; Serum CYFRA 21-1 level was significantly lower in patients with pulmonary tuberculosis($1.54{\pm}1.19ng/mL$, p<0.01) as compared to patients with lung cancer($12.25{\pm}15.97ng/mL$), and was slightly higher than the level in heathy persons($0.90{\pm}0.49ng/mL$) but there was no significant difference. Serum CYFRA 21-1 level was below the cut-off value of 3.3ng/mL in 95 percent of patients with pulmonary tuberculosis but it was above the cut-off value in 64 percent of patients with lung cancer. Serum CYFRA 21-1 level was significantly higher in the initial treatment group($1.91{\pm}1.55ng/mL$, p<0.05) as compared to the treatment. failure group ($0.92{\pm}0.30ng/mL$). According to the sputum AFB smear, serum CYFRA 21-1 level in patients with negative result was slightly higher than the level in patients with positive result but there was no significant difference. According to the radiologic manifestation, serum CYFRA 21-1 level was significantly higher in patients with infiltrative lesion ($2.15{\pm}1.63ng/mL$, p<0.01) as compared to patients with destructive lesion ($l.04{\pm}0.54ng/mL$). As the size of cavity or destructive lesion was larger, the level was significantly lower(p<0.05). Conclusion: As serum CYFRA 21-1 level was significantly higher in the initial treatment group and patients with infiltrative lesion, it suppose to be closely related with the degree of parenchymal damage of the lung of the pulmonary tuberculosis. However CYFRA 21-1 could be useful method for diagnosing lung cancer even in patients with pulmonary tuberculosis combined with lung cancer because of the fact that it was below the cutoff value of 3.3ng/mL in 95 percent of patients with pulmonary tuberculosis.

• Journal of Life Science
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• v.29 no.4
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• pp.499-508
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• 2019

Cancer stem cells (CSCs), which are primarily responsible for metastasis and recurrence, have self-renewal, differentiation, therapeutic resistance, and tumor formation abilities. Numerous studies have demonstrated the signaling pathways essential for the acquisition and maintenance of CSC characteristics, such as WNT/${\beta}$-catenin, Hedgehog, Notch, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Bone morphogenetic protein (BMP), and TGF-${\beta}$ signals. However, few therapeutic strategies have been developed that can selectively eliminate CSCs. Recently, neutralizing antibodies against Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs), have shown promising outcomes in clinical trials of melanoma, lung cancer, and pancreatic cancer, as well as in hematologic malignancies. ICIs are considered to outperform conventional anticancer drugs by maintaining long-lasting anti-cancer effects, with less severe side effects. Several studies reported that ICIs successfully blocked CSC properties in head and neck squamous carcinomas, melanomas, and breast cancer. Together, these findings suggest that novel and effective anticancer therapeutic modalities using ICIs for selective elimination of CSCs may be developed in the near future. In this review, we highlight the origin and characteristics of CSCs, together with critical signaling pathways. We also describe progress in ICI-mediated anticancer treatment to date and present perspectives on the development of CSC-targeting ICIs.

• Tuberculosis and Respiratory Diseases
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• v.55 no.1
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• pp.98-106
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• 2003

Background : To evaluate the efficacy and safety of gemcitabine and cisplatin chemotherapy in advanced non-small cell lung cancer (NSCLC). Materials and Methods : Forty patients (21 men, 19 women ; age range, 37 to 73 years; median, 63 years) with unresectable stage IIIB to IV NSCLC were evaluated. Patients received cisplatin $60mg/m^2$ (Day 1), gemcitabine $1200mg/m^2$ (Day 1 and 8) every 21 days. Eighteen patients had stage IIIB disease and 22 had stage IV. There were 28 patients of adenocarcinoma (70.0%), 11 of squamous cell carcinoma (27.5%), and one of large cell carcinoma (2.5%). Results : Of 40 patients, no patients showed complete response while 15(37.5%) showed partial response, 7(17.5%) had stable diseases, 18(45%) had progressive diseases. During a total of 195 courses of chemotherapy, grade 3 or more granulocytopenia and thrombocytopenia occured in 12.5% and 2.5% of patients respectively. Non-hematologic toxicity was mild and easily controlled. There was one case of treatment-related death by pneumomia. The median survival was 55 weeks (95% CI, 34~75weeks), and the time to progression was 19 weeks (95% CI, 16~23weeks). One year survival rate was 55% and 2 year survival rate was 10%. Conclusion : The efficacy of cisplatin and gemcitabine combination chemotherapy was acceptable in the treatment of advanced NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.257-264
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• 2004

Background : There are many combinations of treatment for locally advanced non-small cell lung cancer (NSCLC). Recent studies have showed the efficacy of concurrent chemoradiotherapy (CCRT) in NSCLC. At present, however, there is no consensus about the optimal dosages and timing of radiation and chemotherapeutic agents. The aims of study were to determine the feasibility, toxicity, response rate, and survival rate in locally advanced NSCLC patients treated with doxetaxel and cisplatin based CCRT. Method : Sixteen patients with unresectable stage III NSCLC were evaluated from May 2000 until September 2001. Induction chemoradiotherapy consisted of 3 cycles of docetaxel (75 $mg/m^2/IV$ on day 1) and cisplatin (60 $mg/m^2/IV$ on day 1) chemotherapy every 3 weeks and concomitant hyperfractionated chest irradiation (1.15 Gy/BID, total dose of 69 Gy) in 6 weeks. Patient who had complete or partial response, and stable disease were applied consolidation chemotherapy of docetaxel and cisplatin. Results : All patients showed response to CCRT. Four patients achieved complete response (25%), partial responses in 12 patients (75%). The major common toxicities were grade III or more of neutropenia (87.3%), grade III esophagitis (68.8%), pneumonia (18.8%) and grade III radiation pneumonitis (12.5%). Thirteen patients were ceased during follow-up period. Median survival time was 19.9 months (95% CI; 4.3-39.7 months). The survival rates in one, two, and three years are 68.7%, 43.7%, and 29.1%, respectively. Local recurrence was found in 11 patients (66.8%), bone metastasis in 2, and brain metastasis in 1 patient. Conclusion : The response rate and survival time of CCRT with docetaxel/cisplatin in locally advanced NSCLC were encouraging, but treatment related toxicities were high. Further modification of therapy seems to be warranted.

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.709-719
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• 1996

Background: Surgical resection is the only way to cure non-small cell lung cancer(NSCLC) and the prognosis of NSCLC in patients who undergo a complete resection is largely influenced by the pathologic stage. After surgical resection, recurrences in distant sites is more common than local recurrences. An effective postoperative adjuvant therapy which can prevent recurrences is necessary to improve long tenn survival Although chemotherapy and radiotherapy are still the mainstay in adjuvant therapy, the benefits of such therapies are still controversial. We initiated this retrospective study to evaluate the effects of adjuvant therapies and analyze the prognostic factors for survival after curative resection. Method: From 1990 to 1995, curative resection was perfomled in 282 NSCLC patients with stage I, II, IIIa, Survival analysis of 282 patients was perfonned by Kaplan-Meier method. The prognostic factors, affecting survival of patients were analyzed by Cox regression model. Results: Squamous cell carcinoma was present in 166 patients(59%) ; adenocarcinoma in 86 pmients(30%) ; adenosquamous carcinoma in II parients(3.9%); and large cell undifferentiated carcinoma in 19 patients(7.1%). By TNM staging system, 93 patients were in stage I; 58 patients in stage II ; and 131 patients in stage rna. There were 139 postoperative recurrences which include 28 local and 111 distant failures(20.1% vs 79.9%). The five year survival rate was 50.1% in stage I ; 31.3% in stage II ; and 24.1% in stage IIIa(p <0.0001). The median survival duration was 55 months in stage I ; 27 months in stage II ; and 16 months in stage rna. Among 131 patients with stage rna, the median survival duration was 19 months for 81 patients who received postoperative adjuvant chemotherapy only or cherne-radiotherapy and 14 months for the other 50 patients who received surgery only or surgery with adjuvant radiotherapy(p=0.2982). Among 131 patients with stage IIIa, the median disease free survival duration was 16 months for 21 patients who received postop. adjuvant chemotherapy only and 4 months for 11 patients who received surgery only(p=0.0494). In 131 patients with stage IIIa, 92 cases were in N2 stage. The five year survival rate of the 92 patients with N2 was 25% and their median survival duration was 15 months. The median survival duration in patients with N2 stage was 18 months for those 62 patients who received adjuvant chemotherapy and 14 months for the other 30 patients who did not(p=0.3988). The median survival duration was 16 months for those 66 patients who received irradiation and 14 months for the other 26 patients who did not(p=0.6588). We performed multivariate analysis to identify the factors affecting prognosis after complete surgical resection, using the Cox multiple regression model. Only age(p=0.0093) and the pathologic stage(p<0.0001) were significam prognostic indicators. Conclusion: The age and pathologic stage of the NSCLC parients are the significant prognostic factors in our study. Disease free survival duration was prolonged with statistical significance in patients who received postoperative adjuvant chemotherapy but overall survival duration was not affected according to adjuvant therapy after surgical resection.

• The Journal of Internal Korean Medicine
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• v.42 no.6
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• pp.1341-1348
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• 2021

The purpose of this study is to report the effect of Korean medicine on a squamous cell lung cancer patient with chemotherapy induction peripheral neuropathy (CIPN). A 61-year old male patient, who had received 4 cycles of chemotherapy after lung surgery from squamous cell lung cancer, was treated with acupuncture and herbal medicines, including Uchasingi-hwan and Samchilchoongcho-capsule, to control CIPN and dyspnea on exertion. The degree of pain was assessed by a numeric rating scale (NRS). After receiving acupuncture and herbal medicines, the NRS score for CIPN symptoms was reduced from 4 to 1 and the NRS score for dyspnea on exertion decreased from 3 to less than 1. Korean medicine could therefore be useful in reducing peripheral neuropathy occurring after chemotherapy and dyspnea after lobectomy.