알레젠 제거 옻나무 추출물 투여로 생존기간이 연장된 편평세포폐암 환자 1례

김은희,박소정,최원철,이수경,Kim, Eun-Hee,Park, So-Jeong,Choi, Won-Cheol,Lee, Soo-Kyung 대한암한의학회 2011 大韓癌韓醫學會誌 Vol.16 No.2

Background : Lung cancer is one of the most common malignancy in the world. Types of lung cancer are Non small cell lung cancer and small cell lung cancer. Subtypes of Non small cell lung cancer are adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Knowing the type of lung cancer is important in determining both treatment and prognosis. Recently, due to newly developed anti-cancer drugs, squamous cell carcinoma has relatively poor prognosis than non-squamous cell carcinoma. Case : We report a squamous cell lung cancer case treated with allergen removed Rhus verniciflua Stokes (aRVS) extract. The patients initially diagnosed stage squamous cell lung carcinoma, but she refused recommended operation. She initiated aRVS extract monotherapy in October. 2006. The follow up Computed tomography in March. 2007, she diagnosed stable disease of tumor response on aRVS treatment. However, this case was lost to follow up for 6 months while she was treated with tomotherapy. In October 2007, she came back to our cancer center after diagnosed stage IV metastasized lung to lung, and aRVS monotherapy was restarted. She had survived 2 years after metastasis of squamous cell lung carcinoma. Conclusion : Allergen removed Rhus verniciflua Stokes(aRVS) sucessfully prolonged overall survival of a squamous cell lung cancer patient.

비소세포성 폐암의 예후인자로서 Flow Cytometric Nuclear DNA Content 와 S - phase Fraction 의 의의

강석민(Suck Min Kang),김주항(Joo Hang Kim),김성규(Sung Kyu Kim),이원영(Won Young Lee),정경영(Kyong Young Jung),이이형(Yi Hyeong Lee) 대한내과학회 1997 대한내과학회지 Vol.52 No.4

N/A Objectives: In surgically treated non-small cell lung cancer, patients have a wide difference in prognosis even though they may be in the same stage. Therefore it is difficult to establish the prognosis for individual lung cancer patients. In this study, by using flow cytometric analysis of nuclear DNA content and S-phase fraction(SPF) of surgically treated non-small cell lung cancer patients, we proposed to establish other prognostic factors and their validity in comparison with the existing ones. Methods: Paraffin-embedded tissue specimens from 81 surgically treated patients, diagnosed with non-small cell lung cancer ranging from stage I to stage IIIa, were analyzed by flow cytometrically determined nulear DNA content and S-phase fraction. Cellular DNA content stained with propidium iodide was analyzed by flow cytometry: histograms with a coefficient of variation exceeding 8% were not used. Results: 1) DNA content analysis was carried out for 59 of 81 patients. Of the 59 patients who were investigated by flow cytometry, 45 (76.3%) of the tumors were DNA aneuploidy and 14 (23.7%) were DNA diploidy. The proportion of DNA aneuploidy tumors showed no significant difference between cell types or stage. 2) S-phase fraction was evaluated for 36 of 81 patients. Mean value of SPF was 19.2% (±12.62)%. The value of SPF had nothing to do with stage. 3) The proportion of the high SPF group (more than 10% of cell proliferation cycle) was 75% With advance staging, the proportion of the high SPF group increased. 4) Significant difference in the median survival time was observed between the low SPF group and the high SPF group (32 months in low SPF, 12 months in high SPF) (p<0.05). No significant difference in the median survival time was observed between the aneuploidy group and the diploidy group (19 months in aneuploidy, 34 months in diploidy). 5) Significant difference in the disease free median survival time was observed between the low SPF group and the high SPF group (5 months in low SPF, 19 months in high SPF) (p<0.05). No significant difference in the disease free median survival time was observed between the aneuploidy group and the diploidy group (12 months in aneuploidy, 34 months in diploidy). 6) Upon multivariate analysis, stage and high SPF (more than 10% of cell proliferation cycle) were significant prognostic factors in surgically treated non-small cell lung cancer patients. Conclusion: The TNM stage and high SPF were significant as prognostic factors in surgically treated non-small cell lung cancer patients. There- fore new treatment plan should be needed in the patients who have high SPF.

Season of Diagnosis and Survival of Advanced Lung Cancer Cases - Any Correlation?

Oguz, Arzu,Unal, Dilek,Kurtul, Neslihan,Aykas, Fatma,Mutlu, Hasan,Karagoz, Hatice,Cetinkaya, Ali Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Introduction: The influence of season at diagnosis on cancer survival has been an intriguing issue for many years. Most studies have shown a possible correlation in between the seasonality and some cancer type survival. With short expected survival, lung cancer is an arena that still is in need of new prognostic factors and models. We aimed to investigate the effect of season of diagnosis on 3 months, 1 and 2 years survival rates and overall survival of non small cell lung cancer patients. Materials and Methods: The files of non small cell lung cancer patients that were stages IIIB and IV at diagnosis were reviewed retrospectively. According to diagnosis date, the patients were grouped into 4 season groups, autumn, winter, spring and summer. Results: A total of 279 advanced non small cell lung cancer patients' files were reviewed. Median overall survival was 15 months in the entire population. Overall 3 months, 1 and 2 years survival rates were 91.0%, 58.2% and 31.2% respectively. The season of diagnosis was significantly correlated with 3 months survival rates, being diagnosed in spring being associated with better survival. Also the season was significantly correlated with T stage of the disease. For 1 and 2 years survival rates and overall survival, the season of diagnosis was not significantly correlated. There was no correlation detected between season and overall survivals according to histological subtypes of non small cell lung cancer. Conclusion: As a new finding in advanced non small cell lung cancer patients, it can be concluded that being diagnosed in spring can be a favorable prognostic factor for short term survival.

항암화학요법과 병행한 한의기반 통합암치료를 통한 전이성 비소세포폐암 환자의 암성 통증 호전 증례보고

조영민,양재호,주한음,박소정,박지혜,유화승,Young-min Cho,Jae-ho Yang,Han-eum Joo,So-jeong Park,Ji-hye Park,Hwa-seung Yoo 대한한방내과학회 2023 大韓韓方內科學會誌 Vol.44 No.3

Objective: To demonstrate an improvement in metastatic cancer pain and a decrease in tumor size in a patient with non-small cell lung cancer. Method: A 53-year-old female patient diagnosed with metastatic non-small cell lung cancer in August 2022 underwent integrative cancer treatment (ICT) for two months to decrease the tumor size and improve back pain from bone metastasis. The patient underwent chemotherapy with ICT. Radiologic outcomes were assessed by chest, abdomen, and pelvis computed tomography based on the Response Evaluation Criteria in Solid Tumors (RECIST) protocol. Clinical outcomes were assessed using National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), Eastern Cooperative Oncology Group (ECOG), and a numeric rating scale (NRS). Result: During the two months of treatment, the NRS scores for back pain were improved, and the ECOG score improved from grade 2 to 1. The size and metabolic activity of the primary lung tumor decreased and underwent partial remission based on RECIST. No serious side effects of grade 3 or higher were noted on the NCI-CTCAE test. Conclusion: This case suggests that ICT may have a therapeutic effect for cancer pain and a synergetic effect with chemotherapy for metastatic non-small cell lung cancer.

A novel anti-cancer role of β-apopicropodophyllin against non-small cell lung cancer cells

Kim, Ju Yeon,Cho, Jeong Hyun,Choi, Jong-Ryoo,Shin, Hyun-Jin,Song, Jie-Young,Hwang, Sang-Gu,Um, Hong-Duck,Yoo, Young Do,Kim, Joon,Park, Jong Kuk Elsevier 2018 Toxicology and applied pharmacology Vol.357 No.-

<P><B>Abstract</B></P> <P>We previously reported that podophyllotoxin acetate (PA) inhibits the growth and proliferation of non-small cell lung cancer (NSCLC) cells and also makes them more sensitive to radiation and chemotherapeutic agents. In an attempt to enhance PA activity, we synthesized 34 derivatives based on podophyllotoxin (PPT). Screening of the derivative compounds for anti-cancer activity against NSCLC led to the identification of β-apopicropodophyllin (APP) as a strong anti-cancer agent. In addition to its role as an immunosuppressive regulator of the T-cell mediated immune response, the compound additionally showed anti-cancer activity against A549, NCI-H1299 and NCI-460 cell lines with IC<SUB>50</SUB> values of 16.9, 13.1 and 17.1 nM, respectively. The intracellular mechanisms underlying the effects of APP were additionally examined. APP treatment caused disruption of microtubule polymerization and DNA damage, which led to cell cycle arrest, as evident from accumulation of phospho-CHK2, p21, and phospho-Cdc2. Moreover, APP stimulated the pro-apoptotic ER stress signaling pathway, indicated by elevated levels of BiP, phospho-PERK, phospho-eIF2α, CHOP and ATF4. We further observed activation of caspase-3, -8 and -9, providing evidence that both intrinsic and extrinsic apoptotic pathways were triggered. In vivo, APP inhibited tumor growth of NSCLC xenografts in nude mice by promoting apoptosis. Our results collectively support a novel role of APP as an anticancer agent that evokes apoptosis by inducing microtubule disruption, DNA damage, cell cycle arrest and ER stress.</P> <P><B>Highlights</B></P> <P> <UL> <LI> β-apopicropodophyllin (APP) is one of derivatives of podophyllotoxin. </LI> <LI> APP retards growth of non-small cell lung cancer cells. </LI> <LI> APP could cause disruption of microtubule polymerization and DNA damage. </LI> <LI> APP stimulated the pro-apoptotic G2/M cell cycle arrest ER stress signaling. </LI> <LI> Final effect of APP on non-small cell lung cancer cells is in vitro/in vivo apoptosis. </LI> </UL> </P>

Effect of 5-aza-2'-deoxycytidine on Cell Proliferation of Non-small Cell Lung Cancer Cell Line A549 Cells and Expression of the TFPI-2 Gene

Dong, Yong-Qiang,Liang, Jiang-Shui,Zhu, Shui-Bo,Zhang, Xiao-Ming,Ji, Tao,Xu, Jia-Hang,Yin, Gui-Lin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Objective: The present study employed 5-aza-2'-deoxycytidine (5-Aza-CdR) to treat non-small cell lung cancer (NSCLC) cell line A549 to investigate the effects on proliferation and expression of the TFPI-2 gene. Methods: Proliferation was assessed by MTT assay after A549 cells were treated with 0, 1, 5, 10 ${\mu}mol/L$ 5-Aza-CdR, a specific demethylating agent, for 24, 48 and 72h. At the last time point cells were also analyzed by flow cytometry (FCM) to identify any change in their cell cycle profiles. Methylation-specific polymerase chain reaction (MSPCR), real time polymerase chain reaction(real-time PCR) and western blotting were carried out to determine TFPI-2 gene methylation status, mRNA expression and protein expression. Results: MTT assay showed that the growth of A549 cells which were treated with 5-Aza-CdR was significantly suppressed as compared with the control group (0 ${\mu}mol/L$ 5-Aza-CdR). After treatment with 0, 1, 5, 10 ${\mu}mol/L$ 5-Aza-CdR for 72h, FCM showed their proportion in G0/G1 was $69.7{\pm}0.99%$, $76.1{\pm}0.83%$, $83.8{\pm}0.35%$, $95.5{\pm}0.55%$ respectively (P<0.05), and the proportion in S was $29.8{\pm}0.43%$, $23.7{\pm}0.96%$, $15.7{\pm}0.75%$, $1.73{\pm}0.45%$, respectively (P<0.05), suggesting 5-Aza-CdR treatment induced G0/G1 phase arrest. MSPCR showed that hypermethylation in the promoter region of TFPI-2 gene was detected in control group (0 ${\mu}mol/L$ 5-Aza-CdR), and demethylation appeared after treatment with 1, 5, 10 ${\mu}mol/L$ 5-Aza-CdR for 72h. Real-time PCR showed that the expression levels of TFPI-2 gene mRNA were $1{\pm}0$, $1.49{\pm}0.14$, $1.86{\pm}0.09$ and $5.80{\pm}0.15$ (P<0.05) respectively. Western blotting analysis showed the relative expression levels of TFPI-2 protein were $0.12{\pm}0.01$, $0.23{\pm}0.02$, $0.31{\pm}0.02$, $0.62{\pm}0.03$ (P<0.05). TFPI-2 protein expression in A549 cells was gradually increased significantly with increase in the 5-Aza-CdR concentration. Conclusions: TFPI-2 gene promoter methylation results in the loss of TFPI-2 mRNA and protein expression in the non-small cell lung cancer cell line A549, and 5-Aza-CdR treatment could induce the demethylation of TFPI-2 gene promoter and restore TFPI-2 gene expression. These findings provide theoretic evidence for clinical treatment of advanced non-small cell lung cancer with the demethylation agent 5-Aza-CdR. TFPI-2 may be one molecular marker for effective treatment of advanced non-small cell lung cancer with 5-Aza-CdR.

Early Growth Response Protein-1 Involves in Transforming Growth factor-β1 Induced Epithelial-Mesenchymal Transition and Inhibits Migration of Non-Small-Cell Lung Cancer Cells

Shan, Li-Na,Song, Yong-Gui,Su, Dan,Liu, Ya-Li,Shi, Xian-Bao,Lu, Si-Jing Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

The zinc finger transcription factor EGR 1 has a role in controlling synaptic plasticity, wound repair, female reproductive capacity, inflammation, growth control, apoptosis and tumor progression. Recent studies mainly focused on its role in growth control and apoptosis, however, little is known about its role in epithelial-mesenchymal transition (EMT). Here, we aim to explore whether EGR 1 is involved in TGF-${\beta}1$-induced EMT in non-smallcell lung cancer cells. Transforming growth factor (TGF)-${\beta}1$ was utilized to induce EMT in this study. Western blotting, RT-PCR, and transwell chambers were used to identify phenotype changes. Western blotting was also used to observe changes of the expression of EGR 1. The lentivirus-mediated EGR 1 vector was used to increase EGR 1 expression. We investigated the change of migration to evaluate the effect of EGR 1 on non-small-cell lung cancer cells migration by transwell chambers. After stimulating with TGF-${\beta}1$, almost all A549 cells and Luca 1 cells (Non-small-cell lung cancer primary cells) changed to mesenchymal phenotype and acquired more migration capabilities. These cells also had lower EGR 1 protein expression. Overexpression of EGR 1 gene with EGR 1 vector could decrease tumor cell migration capabilities significantly after adding TGF-${\beta}1$. These data s howed an important role of EGR 1 in the EMT of non-small-cell lung cancer cells, as well as migration.

Circular RNA PIP5K1A promotes glycolysis and malignancy of non-small cell lung cancer via miR-656-3p/GBE1 axis under hypoxia

Sun Zhiguang,Han Jinsheng,Wang Jindong 대한독성 유전단백체 학회 2024 Molecular & cellular toxicology Vol.20 No.2

Background Non-small cell lung cancer (NSCLC) is a common malignant tumor with a poor 5-year survival rate. Hypoxia is a common phenomenon that occurs in solid tumors, especially after tumor growth. Circular RNA (circRNA) is aberrantly expressed in NSCLC cells under hypoxia. However, the underlying mechanism of biological function has remained unclear. Objective The purpose of this study is to explore the underlying mechanism of the biological function of Circular RNA PIP5K1A in non-small cell lung cancer. Results The levels of circ-PIP5K1A and 1, 4-alpha-glucan branching enzyme 1 GBE1 (GBE1) were upregulated in NSCLC tissues and NSCLC cells under hypoxia, whereas miR-656-3p was downregulated. Knockdown of circ-PIP5K1A or GBE1 inhibited cell glycolysis, proliferation, and motility while promoting cell apoptosis under hypoxia. Besides, miR-656-3p was a direct target of circ-PIP5K1A, and miR-656-3p could specially bind to GBE1. Moreover, circ-PIP5K1A sponged miR-656-3p to upregulate GBE1 expression. In addition, GBE1 overexpression reversed the inhibitory effect of circ-PIP5K1A knockdown on NSCLC cell malignant phenotype under hypoxia. Conclusion Circ-PIP5K1A could be a tumor promoter in NSCLC and regulated NSCLC cell malignant phenotype under hypoxia through miR-656-3p/GBE1 axis. Background Non-small cell lung cancer (NSCLC) is a common malignant tumor with a poor 5-year survival rate. Hypoxia is a common phenomenon that occurs in solid tumors, especially after tumor growth. Circular RNA (circRNA) is aberrantly expressed in NSCLC cells under hypoxia. However, the underlying mechanism of biological function has remained unclear. Objective The purpose of this study is to explore the underlying mechanism of the biological function of Circular RNA PIP5K1A in non-small cell lung cancer. Results The levels of circ-PIP5K1A and 1, 4-alpha-glucan branching enzyme 1 GBE1 (GBE1) were upregulated in NSCLC tissues and NSCLC cells under hypoxia, whereas miR-656-3p was downregulated. Knockdown of circ-PIP5K1A or GBE1 inhibited cell glycolysis, proliferation, and motility while promoting cell apoptosis under hypoxia. Besides, miR-656-3p was a direct target of circ-PIP5K1A, and miR-656-3p could specially bind to GBE1. Moreover, circ-PIP5K1A sponged miR-656-3p to upregulate GBE1 expression. In addition, GBE1 overexpression reversed the inhibitory effect of circ-PIP5K1A knockdown on NSCLC cell malignant phenotype under hypoxia. Conclusion Circ-PIP5K1A could be a tumor promoter in NSCLC and regulated NSCLC cell malignant phenotype under hypoxia through miR-656-3p/GBE1 axis.

Identification of a Cancer Stem-like Population in the Lewis Lung Cancer Cell Line

Zhang, An-Mei,Fan, Ye,Yao, Quan,Ma, Hu,Lin, Sheng,Zhu, Cong-Hui,Wang, Xin-Xin,Liu, Jia,Zhu, Bo,Sun, Jian-Guo,Chen, Zheng-Tang Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.3

Objective: Although various human cancer stem cells (CSCs) have been defined, their applications are restricted to immunocompromised models. Developing a novel CSC model which could be used in immunocompetent or transgenic mice is essential for further understanding of the biomolecular characteristics of tumor stem cells. Therefore, in this study, we analyzed murine lung cancer cells for the presence of CSCs. Methods: Side population (SP) cells were isolated by fluorescence activated cell sorting, followed by serum-free medium (SFM) culture, using Lewis lung carcinoma cell (LLC) line. The self-renewal, differentiated progeny, chemosensitivity, and tumorigenic properties in SP and non-SP cells were investigated through in vitro culture and in vivo serial transplantation. Differential expression profiles of stem cell markers were examined by RT-PCR. Results: The SP cell fraction comprised 1.1% of the total LLC population. SP cells were available to grow in SFM, and had significantly enhanced capacity for cell proliferation and colony formation. They were also more resistant to cisplatin in comparison to non-SP cells, and displayed increased tumorigenic ability. Moreover, SP cells showed higher mRNA expression of Oct-4, ABCG2, and CD44. Conclusion: We identified SP cells from a murine lung carcinoma, which possess well-known characteristics of CSCs. Our study established a useful model that should allow investigation of the biological features and pharmacosensitivity of lung CSCs, both in vitro and in syngeneic immunocompetent or transgenic/knockout mice.

부산, 경남지역 폐암 환자의 방사선치료 이용에 대한 임상 결정 모델 연구

손종기,김윤진,조덕영 한국방사선학회 2015 한국방사선학회 논문지 Vol.9 No.6

Radiation therapy for lung cancer is an effective treatment during monotherapy or combination therapy. Studies have reported that the optimum utilization rate of radiation therapy is estimated at 61% to 74%. Radiation therapy in Korea has been investigated to be low; further studies are needed.This study was intended to assess the appropriateness of the use of radiation and to reveal the use of radiation therapy-related factors by examining radiation therapy in lung cancer patients of Busan and South Gyeongnam Province. This study was aimed at the population diagnosed with lung cancer in Busan and South Gyeongnam Province. To conduct the study, 1036 patients enrolled in two hospitals were collected and 897 appropriate as subjects were selected.We compared the optimum utilization rate and actual rate of radiation therapy, and revealed the adequacy and related factors for use of radiotherapy. Of 897 patients, 503 (56%) were treated with medical therapy and 394 (44%) weregiven radiotherapy.The radiotherapy utilization rate of all lung cancer patients was 42%. The proportion of non-small cell lung cancer by histologic type was 33% and that of small cell lung cancer was 90%. Factors related to radiation therapy used in cancer were age, histological type, clinical stage, doctor refereed to, and clinical examination. Compared to radiation utilization by region (site), curative chest therapy was 42%; palliative treatment was 26%. In the comparison of histologic types, utilization of small-cell lung cancer is lower; the lowest especially in the stage Ⅲ. Utilization of radiation therapy in Busan and South Gyeongnam Province was lower than the reasonable one. Utilization difference could be explained by patient factors, tumor factors, and health service factors. To improve utilization,development ofoutreach service programs and activation of the multidisciplinary team are required. 폐암에 대한 방사선치료는 단독치료 또는 병용치료 시에 효과적인 치료이다. 연구에 의하면 최적의 방사선치료 이용률은 61%에서 74% 범위로 추정되고 있으나, 우리나라의 방사선치료 이용률은 낮은 것으로 조사되어 이에 대한 연구가 필요하다. 본 연구는 부산, 경남 지역에서 폐암환자의 방사선치료 이용률을 조사하여 방사선 이용의 적절성을 평가하고 방사선치료 이용관련 인자를 밝히고자 하는 것이다. 본 연구는 폐암으로 진단된 부산, 경남 지역 인구를 대상으로 하였다. 연구를 위하여 2개의 병원에 등록된 환자 1,036명의 환자 자료를 수집하여 최종적으로 연구에 적합한 897명을 대상으로 연구를 수행하였다. 연구는 적정 이용비율과 실제 방사선치료 비율을 비교하였고, 방사선치료 이용의 적정성과 관련인자를 확인하고자 하였다. 연구대상자 897명 중에서 503명(56%)은 내과적 치료가 시행되었고, 394명(44%)는 방사선치료가 시행되었다. 전체 폐암환자의 방사선치료 이용률은 42%이었다. 조직학적 분류에 의한 비소세포 폐암의 비율은 33%이었고, 소세포 폐암은 90%이었다. 폐암의 방사선치료 이용과 관련 인자는 연령, 조직학적 유형, 임상병기, 의뢰의사, 임상검사이었다. 부위(site)별 방사선치료 이용률을 비교했을 때 근치적 흉부치료는 42%이었고, 완화적 치료는 26%이었다. 조직학적 유형의 비교에서 소세포 폐암의 이용률은 낮았고 특히 병기 Ⅲ기에서 이용률은 가장 낮았다. 부산, 경남지역에서 방사선치료의 이용률은 적정한 이용률 보다 낮게 나타났다.이용률 차이는 환자요인, 종양요인, 의료 서비스 요인으로 설명할 수 있었다. 이용률 개선을 위해서는 아웃리치 서비스(outreach service) 프로그램의 개발과 다 학제적 팀의 활성화가 필요하다.