• CELLMED
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• v.3 no.1
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• pp.9.1-9.10
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• 2013

In traditional systems of medicine including homeopathy, the Condurango extract (Con) is often used to cure stomach cancer mainly, without having any scientific validation of its anti-cancer ability. Con has therefore been tested against non-small-cell lung cancer cells (NSCLC) A549 and NCI-H522 (H522) known to contain the KRAS mutation, making them resistant to most chemotherapeutic agents. As cancer cells generally defy cytotoxicity developed by chemopreventive agents and escape cell death, any drug showing the capability of preferentially killing cancer cells through apoptosis is worth consideration for judicious application. A549 and H522 cells were exposed to $0.35{\mu}g/{\mu}l$ and $0.25{\mu}g/{\mu}l$ of Con, respectively, for 48 h and analysed based on various protocols associated with apoptosis and DNA damage, such as MTT assay to determine cell viability, LDH assay, DNA fragmentation assay, comet assay, and microscopical examinations of DNA binding fluorescence stains like DAPI, Hoechst 33258 and acridine orange/ethidium bromide to determine the extent of DNA damage made in drug-treated and untreated cells and the results compared. Changes in mitochondrial membrane potential and the generation of reactive oxygen species were also documented through standard techniques. Con killed almost 50% of the cancer cells but spared normal cells significantly. Fluorescence studies revealed increased DNA nick formation and depolarized membrane potentials after drug treatment in both cell types. Caspase-3 expression levels confirmed the apoptosis-inducing potential of Con in both the NSCLC lines. Thus, overall results suggest considerable anticancer potential of Con against NSCLC in vitro, validating its use against lung cancer by practitioners of traditional medicine including homeopathy.

• Radiation Oncology Journal
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• v.13 no.4
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• pp.303-309
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• 1995

Purpose : The effect of dose escalation of up to 6500 cGy on local control and survial was investigated in locally advanced non-small cell lung cancer. Materials and Methods: Ninety eight patients with biopsy-proven unresec-table non-small cell lung cancer without distant metastases or medically inoperable patients with lower-stage were treated with definitive radio-therapy alone. Group A was treated by thoracic irradiation, 6000 cGy or less in total tumor dose with daily fractions of 180 to 200 cGy; and group B was treated with 6500 cGy of same daily fractions. Results : The actuarial overall survival rate for the entire group was 54% at 1 year, 26.6% at 2 years and 16.4% at 3 years with a median survival time of 13 months. Statistically significant prognostic factors that affect survival rate were stage and N-stage. However, no improvement in local control and survival has been seen with higher dose radiotherapy(group B). Conclusion : Dose escalation of up to 6500 cGy was no effect on local control and survival rate. To increase the survival rate of non-small cell lung cancer hyperfractionated radiotherapy or concurrent chemoradiotherapy should be considered.

• Journal of Chest Surgery
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• v.33 no.8
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• pp.662-668
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• 2000

Background: Many recent results of clinical trials show that pre-operative concurrent chemoradiotherapy and surgical resection could increase the survival of N2 positive stage IIIA non-small cell lung cancer. This study was performed to assess the feasibility, toxicity, and affect rates of concurrent chemoradiotherapy and surgical resection in N2 positive stage IIIA non-small cell lung cancer. Material and Method: Thirty-one patients who underwent preoperative concurrent chemoradiotherapy for N2 positive stage IIIA non-small-cell lung cancer from May 1997 to April 1999 were entered into the study. Mean age was 61 yrs(43∼70 yrs), There were 24 men and 7 women. The confirmation of N2 disease were achieved through mediastinoscopic biopsy(24) and CT scans(7). Induction was achieved by two cycles of cisplatin and etoposide(EP) plus concurrent chest radiotherapy to 45 Gy. Resections were done at 3 weeks after the complection of preoperative concurrent chemoradiotherapy. Resections were performed in 23 patients, excluding 5 refusals and 3 distant metastasis. Result: All patients were compled the thoracic radiotherapy except one who had distant metastasis. Twenty three patients were completed the planned 2 cycles of EP chemotherapy, and 8 patients were received only 1 cycle for severe side effects(6), refusal(1), and distant metastasis(1). There was one postoperative mortality, and the cause of death was ARDS. Three patients who had neutropenic fever and one patient who had radiation pneumonitis were required admission and treatment. Esophagitis was the most common acute side effect, but relatively well-tolerated in most patients. The complection rate of concurrent chemoradiotherapy was 74%, resection rate was 71%, pathologic complete remission rate was 13.6%, and pathologic down-staging rate was 68%. Conclusion: Morbidity related to each treatment was acceptable and many of the patients have benefited down staging of its disease. Further prospective, preferably randomized, clinical trials of larger scale may be warranted to confirm the actual benefit of preoperative concurrent chemoradiotherapy and surgical resection in N2-positive stage IIIA non-small cell lung cancer.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.283-289
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• 1998

Purpose : This study was performed to analyze the efficacy of induction chemotherapy fellowed by radiation therapy in locally advanced non-small cell lung cancer Materials and Methods : Eighty patients with locally advanced non-small cell lung cancer treated from 1989 to 1995 at Pusan Paik hospital were analyzed retrospectively. Twenty-one patients were treated with induction chemotherapy followed by radiation therapy and Fifty-nine Patients were treated with radiation therapy alone. Chemotherapy regimen consisted of cisplatin-based combination (2 or 3 drugs). All patients were treated by Co-60 or 6 MV linear accelerators. Radiation dose ranged from 50 Gy to 80 Gy (median 64.8 Gy). We evaluated response rate, survival rate, and pattern of failure in both treatment groups. Results : Overall response rate in induction chemotherapy group and radiotherapy alone group were 48% and 45%, respectively. Of the 80 patients, 46 patients were evaluable for pattern of failure. Initial failure pattern in induction chemotherapy group was as follows: 8 (67%) at locoregional, 4 (33) in distant metastasis. Radiation alone group was 21 (71%) and 5 (29%), respectively. Results showed no difference of distant failure between induction chemotherapy group and radiation alone group. The 1 and 2 year survival rate in induction chemotherapy group were 43% and 14%, respectively and in radiotherapy alone group, 31% and 7%, respectively (p=0.135). Conclusion : In stage III non-small cell lung cancer, induction chemotherapy and radiation therapy showed increased tendency in survival with no statistical significance Induction chemotherapy seems to have no effect of decreasing distant failure and no survival advantage compared with radiotherapy alone.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.221-225
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• 1991

Twenty five patients with unresectable non-small cell carcinoma of the lung have been treated with hyperfractionated radiotherapy with concomitant boost technique since September, 1989. Those patients with history of previous surgery or chemotherapy, pleural effusion or significant weight loss (greater than $10\%$ of body weight) were excluded from the study. Initially, 27 Gy were delivered in 15 fractions in 3 weeks to the large field. Thereafter, large field received 1.8 Gy and cone down boost field received 1.4 Gy with twice a day fractinations up to 49.4 Gy. After 49.4Gy, only boost field was treated twice a day with 1.8 and 1.4 Gy. Total tumor doses were 62.2 Gy for 12 patients and 65.4 Gy for remaining 13 patients. Follow up period was ranged from 6 to 24 month. Actuarial survival rates at 6, 12, and 18 month were $88\%,\;62\%,\;and\;38\%$, respectively. Corresponding disease free suwival rates were $88\%,\;41\%,\;and\;21\%$, respectively. Actuarial cumulative local failure rates at 9, 12 and 15 month were $36\%,\;43\%,\;and\;59\%$, respectively. No significant increase of acute or late complications including radiation pneumonitis was noted with maximum follow up of 24 month. Although the longer follow up is needed, it is worthwhile to try the prospective randomized study to evaluate the efficacy of hyperfractionated radiotherapy with concomitant boost technique for unresectable non-small cell lung cancers in view of excellent tolerance of this treatment. In the future, further increase of total radiation dose might be necessary to improve local control for non-small cell lung cancer.

• Journal of Microbiology and Biotechnology
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• v.31 no.11
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• pp.1508-1518
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• 2021

Hsa_circ_0001947 is associated with multiple cancers, but its function in non-small cell lung cancer (NSCLC) is ambiguous and needs further research. The targeting relationship among circ_0001947, miR-661, and downstream of tyrosine kinase 7 (DOK7) was predicted by database and further verified by dual-luciferase reporter assay, while their expressions in cancer tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). After transfection, cell biological behaviors and expressions of miRNAs, miR-661 and DOK7 were determined by cell function experiments and qRT-PCR, respectively. Circ_0001947 was low-expressed in NSCLC tissues and cells. Circ_0001947 knockdown intensified cell viability and proliferation, induced cell cycle arrest at S phase, suppressed apoptosis and evidently enhanced miR-510, miR-587, miR-661 and miR-942 levels, while circ_0001947 overexpression did the opposite. MiR-661 was a target gene of circ_0001947 that participated in the regulation of circ_0001947 on cell biological behaviors. Furthermore, DOK7, the target gene of miR-661, partly participated in the regulation of miR-661 on cell viability. Hsa_circ_0001947 acts as a sponge of miR-661 to repress NSCLC development by elevating the expression of DOK7.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.536-546
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• 1996

Background : The survival benefit of combination chemotherapy comparing supportive care to patients with advanced non-small cell lung cancel, especially stage IV non-small cell lung cancer patients with metastatic disease, is controversial. The main goal of this study was to evaluate the difference in survival between patients treated with chemotherapy and those who were not and to identify prognostic factors in the patients with stage IV non-small cell lung cancer. Methods : From January 1989 to December 1994, total 67 patients including 20 patients treated with combination chemotherapy and 47 patients treated with only supportive care in stage IV non-small cell lung cancer patients with metastatic disease were enrolled in this study. Combination chemotherapy consisted of etoposide $120mg/m^2$ iv for 3 days and cis-platin iv day 1 every 4 weeks. The treatment groups were retrospectively analyzed by age, sex, histologic cell type, weight loss, serum LDH level, ECOG performance status and major organ metastasis. Results : The significant prognostic factors influencing survival on this study were ECOG performance status and histologic subtype. Overall response rate by combination chemotherapy was 30%(complete response 0%, partial response 30%). Median survival of overall patients was 13.6 weeks and median survival of Chemotherapy group, 20 weeks, was significantly longer than that of supportive care group, 11.7 week(p<0.01). Median survival of responded in patients receiving chemotherapy, 45.5 weeks, was significantly longer than that of non-responder, 17.3 weeks(p<0.05). 1 year-survival rate of chemotherapy group and supportive care group was 15N and 8%, respectively. Nausea or vomiting, alopecia and anemia were seen in nearly most cases after this combination chemotherapy. Toxicities above grade 3 included neutropenia, anemia, thrombocytopenia, infection, fever, nausea, vomiting and alopecia. But this combination chemotherapy was relatively well tolerated except one treatment-related death from sepsis associated with severe granulocytopenia. Conclusion : These results suggest that systemic chemotherapy might be helpful to the stage IV non-small cell lung cancer patients with good performance status and large scale randomized prospective trials should be performed.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6267-6271
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• 2013

Objective: To determine clinical efficacy, safety and prognostic factors of pemetrexed plus platinum as first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: Clinical characteristics, short-term efficacy, survival and adverse reactions of 47 advanced non-squamous NSCLC patients who had received pemetrexed plus platinum as first-line treatment in Shanghai Pulmonary Hospital from January 2009 to June 2011 were retrospectively analyzed. The Chi-squared test was applied to statistically analyze the overall response rate (ORR), disease control rate (DCR) and toxicity reactions in both groups, while survival data wereanalyzed by Kaplan-Meier and logrank methods, and the COX proportional hazards model was adopted for a series of multi-factor analyses. Results: Only two patients were lost to follow-up. The ORR, DCR, medium progression-free survival time (PFS) and medium overall survival (OS) were 31.9%, 74.5%, 5 months and 15.2 months, while 1- and 2-year survival rates were 63.8% (30/47) and 19.2% (9/47), respectively. Single-factor analysis showed that tumor pathological patterns and efficacy were in association with medium PFS (P<0.05), whereas tumor pathological patterns, smoking history and efficacy were closely connected with medium OS (P<0.05). Multi-factor analyses demonstrated that pathological patterns and efficacy were independent factors influencing OS (P<0.05). The rate of toxicity reactions in degree III/IV was low, including hematologic toxicity marked by decline in white blood cell count and decrease in the platelet count (PLT), and non-hematologic toxicity manifested by gastrointestinal reactions, such as nausea and vomiting. Conclusions: Pemetrexed plus platinum as first-line treatment has excellent efficacy and slight adverse reactions with favorable drug-tolerance in patients with advanced non-squamous NSCLC.

• The Journal of the Korean life insurance medical association
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• v.31 no.1
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• pp.34-36
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• 2012

Lung cancer such as small cell lung cancer(SCLC) and non small cell lung cancer(NSCLC) have high mortality rate, so, we insurance doctors have little interest in their risk. But nowadays there's a lot of development in targeted therapy of NSCLC. Screening by CT scanning and early resection strategy also shows better prognosis. It is helpful for underwriters and insurance doctors to review the current development of targeted therapy of NSCLC and estimation of extra-risk of early lung cancer. The preferred treatment option for patients whose tumors contain EGFR-activating mutations are one of the EGFR-directed tyrosine kinase inhibitors, such as gefitinib or erlotinib. In patients with NSCLC whose tumors harboured an ALK rearrangement, there was 61% objective response rate to crizotinib in the phase 1 study. The median survival progression-free survival was 10 months. Mortality analysis of early lung cancer who were detected by CT screening, MR of 105% and EDR of 1‰ were calculated.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1391-1396
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• 2014

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the most common cause of lung cancer death. Currently, the epidermal growth factor receptor inhibitor gefitinib is used for its treatment; however, drug resistance is a major obstacle. Expression of Met has been associated with both primary and acquired resistance to gefitinib, but the mechanisms regulating its expression are not fully understood. Recently, miRNAs such as miR-130a have been shown to play a role in gefitinib resistance, but importance in NSCLC and relationships with Met have not been fully explored. Here we show that miR-130a is over-expressed in gefitinibsensitive NSCLC cell lines, but is low in gefitinib-resistant NSCLC cell lines. Moreover, miR-130a expression was negatively correlated with that of Met. Further analysis revealed that over-expression of miR-130a increased cell apoptosis and inhibited proliferation of NSCLC cells treated with gefitinib, whereas lowering the expression of miR-130a decreased cell apoptosis and promoted cell proliferation after treatment with gefitinib in both gefitinib-sensitive and -resistant NSCLC cell lines, suggesting that miR-130a overcomes gefitinib resistance. We also demonstrated that miR-130a binds to the 3'-UTR of Met and significantly suppresses its expression. Finally, our results showed that over-expressing Met could "rescue" the functions of miR-130a regarding cell apoptosis and proliferation after cells are treated with gefitinib. These findings indicate that the miR-130a/Met axis plays an important role in gefitinib resistance in NSCLC. Thus, the miR-130a/Met axis may be an effective therapeutic target in gefitinib-resistant lung cancer patients.