• Title/Summary/Keyword: Non small cell lung cancer

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Subsequent Treatment Choices for Patients with Acquired Resistance to EGFR-TKIs in Non-small Cell Lung Cancer: Restore after a Drug Holiday or Switch to another EGFR-TKI?

  • Song, Tao;Yu, Wei;Wu, Shi-Xiu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.205-213
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    • 2014
  • The outcomes of first-generation EGFR-TKIs (Gefitnib and Erlotinib) have shown great advantages over traditional treatment strategies in patients with non-small cell lung cancer (NSCLC), but unfortunately we have to face the situation that most patients still fail to respond in the long term despite initially good control. Up to now, the mechanism of acquired resistance to EGFR-TKIs has not been fully clarified. Herein, we sought to compile the available clinical reports in the hope to better understanding the subsequent treatment choices, particularly on whether restoring after a drug holiday or switching to another EGFR-TKI is the better option after failure of one kind of EGFR-TKI.

Postoperative Radiation Therapy in Resected N2 Stage Non-Small Cell Lung Cancer (N2 병기 비소세포 폐암의 수술후 방사선치료)

  • Lee, Chang-Geol
    • Radiation Oncology Journal
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    • v.11 no.2
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    • pp.285-294
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    • 1993
  • A total of forty patients with resected N2 stage non-small cell lung cancer treated with postoperative adjuvant radiation therapy between Jan. 1975 and Dec. 1990 at the Department of Radiation Oncology, Yonsei University College of Medicine, Yonsei Cancer Center were retrospectively analysed to evaluate whether postoperative radiation therapy improves survival. Patterns of failure and prognostic factors affecting survival were also analysed. The 5 year overall and disease free survival rate were $26.3\%,\;27.3\%$ and median survival 23.5 months. The 5 year survival rates by T-stage were $T1\;66.7\%,\;T2\;25.6\%\;and\;T3\;12.5\%.$ Loco-regional failure rate was $14.3\%$ and distant metastasis rate was $42.9\%$ and both $2.9\%.$ Statistically significant factor affecting distant failure rate was number of postitive lymph nodes(>=4). This retrospective study suggests that postoperative radiation therapy in resected N2 stage non-small cell lung cancer can reduce loco-regional recurrence and may improve survival rate as compared with other studies which were treated by surgery alone. Further study of systemic control is also needed due to high rate of distant metastasis.

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Improved Antitumor Efficacy of Hyaluronic Acid-Complexed Paclitaxel Nanoemulsions in Treating Non-Small Cell Lung Cancer

  • Kim, Joo-Eun;Park, Young-Joon
    • Biomolecules & Therapeutics
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    • v.25 no.4
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    • pp.411-416
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    • 2017
  • Paclitaxel (PTX) is a effectively chemotherapeutic agent which is extensively able to treat the non-small cell lung, pancreatic, breast and other cancers. But it is a practically insoluble drug with water solubility less than $1{\mu}g/mL$, which restricts its therapeutic application. To overcome the problem, hyaluronic acid-complexed paclitaxel nanoemulsions (HPNs) were prepared by ionic complexation of paclitaxel (PTX) nanoemulsions and hyaluronic acid (HA) to specifically target non-small cell lung cancer. HPNs were composed of ${\small{DL}}-{\alpha}$-tocopheryl acetate, soybean oil, polysorbate 80, ferric chloride, and HA and fabricated by high-pressure homogenization. The HPNs were $85.2{\pm}7.55nm$ in diameter and had a zeta potential of $-35.7{\pm}0.25mV$. The encapsulation efficiency was almost 100%, and the PTX content was 3.0 mg/mL. We assessed the in vivo antitumor efficacy of the HPNs by measuring changes in tumor volume and body weight in nude mice transplanted with CD44-overexpressing NCI-H460 xenografts and treated with a bolus dose of saline, $Taxol^{(R)}$, PTX nanoemulsions (PNs), or HPNs at a dose of 25 mg/kg. Suppression of cancer cell growth was higher in the PN- and HPN-treated groups than in the $Taxol^{(R)}$ group. In particular, HPN treatment dramatically inhibited tumor growth, likely because of the specific tumor-targeting affinity of HA for CD44-overexpressed cancer cells. The loss of body weight and organ weight did not vary significantly between the groups. It is suggest that HPNs should be used to effective nanocarrier system for targeting delivery of non-small cell lung cancer overexpressing CD44 and high solubilization of poorly soluble drug.

Bilateral Ovarian Metastases from ALK Rearranged Non-Small Cell Lung Cancer

  • Lee, Kyung Ann;Lee, Jong Sik;Min, Jae Ki;Kim, Hee Joung;Kim, Wan Seop;Lee, Kye Young
    • Tuberculosis and Respiratory Diseases
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    • v.77 no.6
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    • pp.258-261
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    • 2014
  • Anaplastic lymphoma kinase (ALK) rearrangement, is a kind of driver mutation, accounts for 3%-5% of non-small cell lung cancer (NSCLC). NSCLC patients harboring ALK fusion genes have distinct clinical features and good response to ALK inhibitors. Metastasis from lung cancer to the ovary has rarely been known. We report a case of a 54-year-old woman with bilateral ovarian metastases from ALK rearranged NSCLC. She underwent bilateral salpingo-oophorectomy for ovary masses, which were progressed after cytotoxic chemotherapy although primary lung mass was decreased. Histopathological examination of the ovary tumor showed characteristic adenocarcinoma patterns of the lung and ALK rearrangement.

Involvement of FoxM1 in Non-Small Cell Lung Cancer Recurrence

  • Xu, Nuo;Wu, Sheng-Di;Wang, Hao;Wang, Qun;Bai, Chun-Xue
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4739-4743
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    • 2012
  • Background: Predictive biomarkers for lung cancer recurrence after curative tumor resection remain unclear. This study set out to assess the role of FoxM1 in the recurrence of non-small cell lung cancer. Methods: Immunohistochemistry for FoxM1 expression was performed on paraffin-embedded tumor tissues from 165 NSCLC patients. Association of FoxM1 expression with clinicopathological parameters and disease free survival were evaluated. Results: Our results indicated FoxM1 expression to be significantly associated with poorer tissue differentiation (P =0.03), higher TNM stage (P <0.01), lymph node metastasis (P <0.01), advanced tumor stage (P <0.01), and poorer disease free survival (P <0.01). Multivariable analysis showed that FoxM1 expression increased the hazard of recurrence (hazard ratio= 1.96, 95% CI, 1.04-3.17, P <0.05), indicating that FoxM1 is an independent and significant predictor of lung cancer recurrence. Conclusion: Therefore, FoxM1 is an independent risk factor for recurrence of NSCLC. Elevated FoxM1 expression could be used as an indicator of poor disease free survival.

PD-L1 Targeted Immunoliposomes with PD-L1 siRNA and HDAC Inhibitor for Anti-Lung Cancer Immunotherapy

  • Se-Yun Hong;Seong-Min Lee;Pyung-Hwan Kim;Keun-Sik Kim
    • Biomedical Science Letters
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    • v.28 no.4
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    • pp.247-259
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    • 2022
  • Immunotherapy, which uses an immune mechanism in the body, has received considerable attention for cancer treatment. Suberoylanilide hydroxamic acid (SAHA), also known as a histone deacetylase inhibitor (HDACi), is used as a cancer treatment to induce active immunity by increasing the expression of T cell-induced chemokines. However, this SAHA treatment has the disadvantage of causing PD-L1 overexpression in tumor cells. In this study, we prevented PD-L1 overexpression by blocking the PD-1/PD-L1 pathway using PD-L1 siRNA. We designed two types of liposomes, the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC) for SAHA, and 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) for siRNA. To effectively target PD-L1 in cancer cells, we conjugated PD-L1 antibody with liposomes containing SAHA or PD-L1 siRNA. These immunoliposomes were also evaluated for cytotoxicity, gene silencing, and T-cell-induced chemokine expression in human non-small cell lung cancer A549 cells. It was confirmed that the combination of the two immunoliposomes increased the cancer cell suppression efficacy through Jurkat T cell induction more than twice compared to SAHA alone treatment. In conclusion, this combination of immunoliposomes containing a drug and nucleic acid has promising therapeutic potential for non-small-cell lung carcinoma (NSCLC).

Pharmacophore Based Screening and Molecular Docking Study of PI3K Inhibitors

  • Rupa, Mottadi;Madhavan, Thirumurthy
    • Journal of Integrative Natural Science
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    • v.9 no.1
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    • pp.41-61
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    • 2016
  • Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Phosphoinositide 3-kinases (PI3Ks) play important role in Non-Small Cell Lung Cancer. PI3Ks constitute a lipid kinase family which modulates the function of numerous substrates involved in the regulation of cell survival, cell cycle progression and cellular growth. Herein, we describe the ligand based pharmacophore combined with molecular docking studies methods to identify new potent PI3K inhibitors. Several pharmacophore models were generated and validated by Guner-Henry scoring Method. The best models were utilized as 3D pharmacophore query to screen against ZINC database (Chemical and Natural) and the retrieved hits were further validated by fitness score, Lipinski's rule of five. Finally four compounds were found to have good potential and they may act as novel lead compounds for PI3K inhibitor designing.

Kanahia Laniflora Methanolic Extract Suppressed Proliferation of Human Non-Small Cell Lung Cancer A549 Cells

  • Alfaif, Mohammad Yahya
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.10
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    • pp.4755-4759
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    • 2016
  • Introduction: Lung cancer is one of the most common cancers worldwide. In certain countries such as United States of America, it is the leading cause of related cancer mortality among both men and women. Natural products play an important role in overcoming the limitations of chemotherapy and radiotherapy. Objectives: In this study, we investigated the antiproliferative and apoptotic activities of Kanahia laniflora methanolic extract against human non-small cell lung cancer cells (A549). Methods: Sulforhodamine B colorimetric assays were used to determine the inhibitory effects of a leaf methanolic extract against A549 cells. Results: The extract showed strong cytotoxic activity against A549 cells with an $IC_{50}$ value of $0.13{\mu}g/ml$ compared to $0.21{\mu}g/ml$ for doxorubicin. The extract also significantly increased the percentage of apoptotic cells to 49.7% as compared to 1.4% and 47.4% for control and doxorubicin respectively. Conclusion: These results showed, for the first time, that a methanolic extract of Kanahia laniflora leaves can inhibit the proliferation of human non-small cell lung cancer cells (A549). Further attention to its potential as a new effective anticancer agent is warranted.

Radiation Therapy in Non-Small Cell LUNG Cancer (비소세포성 폐암의 방사선 치료)

  • Han, Hae-Gyeong;Lee, Myung-Za
    • Radiation Oncology Journal
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    • v.6 no.1
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    • pp.35-39
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    • 1988
  • From Jan.1984 to Dec. 1986, 90 patients with lung cancer were treated at the Department of Radiation Therapy in Hanyang University Hospital. Histopathologically, 67 cases of them were the squamous cell carcinoma,7 cases were the adenocarcinoma, 4 cases were the large cell undiffe rentiated carcinoma and 12 cases were the small cell carcinoma. Among the 78 patients with non small cell carcinoma, 50 patients had received radiation dosage above 4000 cGy.40 patient had follow up from 17 months to 53 months. The complete response rate was $7.3\%$ and partial response rate was $68.3\%$. Overall survival at 1, 2 and 3 years were $47.5\%,\;23.5\%\;and\;6.3\%$ respectively. None was survived longer than 38 months. Median survival was 12.2 month for 40 patient and 9 month for stage III, M1 group and 9.5 month for stage III, MO group. In M1 patient no survival was seen after 2 years while in M0 patient $23.3\%$ survival was seen.

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Immunohistochemical Staining of Insulin-like Growth Factor-1 in Human Lung Cancer Cells (폐암의 조직학적 형태에 따른 인슐린양 성장인자-1의 면역조직학적 염색의 비교)

  • Park, Ji-Hyun;Kang, Myoung-Jae;Lee, Heung-Bum;Lee, Yong-Chul;Rhee, Yang-Kuen
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.3
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    • pp.324-330
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    • 2000
  • Objective : Lung cancer arises after a series of morphological changes, which take several years to progress from normal epithelium to invasive cancer. Multiple molecular changes and growth factor production have been documented in lung cancers, both small cell and non-small cell types. Insulin-like growth factors(IGFs) are important mitogenic and anabolic peptides, both in vivo and in vitro, and are thought to be significant autocrine-paracrine factors involved in normal and malignant cell proliferation. In this study, the degree of expression of IGF-1 on the immunohistochemical staining in human non-small cell lung cancer(NSCLC) cells and small cell lung cancer (SCLC) cells were investigated. Methods : Immunohistochemical staining for IGF-1 was performed in 15 cases of small cell carcinoma, 15 cases of squamous cell carcinoma, 15 cases of adenocarcinoma, and 12 cases of bronchoalveolar carcinoma. Results : The expression of IGF-1 on the immunohistochemical staining significantly increased in NSCLC cells than in SCLC cells. Conclusion : These results suggest the expression of IGF-1 in human lung cancer cells. The immunohistochemical staining of IGF-1 in lung cancer cell lines may assist in the differentiation of NSCLC and SCLC.

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