• Journal of Chest Surgery
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• v.30 no.6
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• pp.566-572
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• 1997

A major obstacles to evaluation of newly-developed treatment strategy for human lung cancer has been the lack of appropriate experimental animal models. We describe a new experimental model of orthotopically-developed non-small cell lung cancer in nude rat, involving inoculation of tumor cell suspension by thoracotomy. Over 40 direct implantation to the periphery of the lung has been performed to date, each requiring less than'1 hour for completion. This model has been used to perform a series of experiments to investigate whether the rat lung and surrounding structures trapped tumor cells with 2 different non-small cell lung cancer cell lines(NCI-H46O and NCI-H1299). Every animal showed development of tumor masses, which were loculated at the periphery of the lung karenchyma and identified also by radiography. After 3 weetu of the inoculation, tumor develop meat at the mediastinal strutures were identified. The life expectancies of the victims were different between the cell lines, but were approximately 5 weeks when NCI-H46O cell line was used. This new orthotopic lung cancer model may be facilitate future studies of the new therapeutics of localized non-small cell lung cancer .

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.4137-4142
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• 2015

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.

• Tuberculosis and Respiratory Diseases
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• v.85 no.2
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• pp.147-154
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• 2022

Background: The expression of calcium signaling pathway molecules is altered in various carcinomas, which are related to the proliferation and altered characteristics of cancer cells. However, changes in calcium signaling in anti-cancer drug-resistant cells (bearing a T790M mutation in epidermal growth factor receptor [EGFR]) remain unclear. Methods: Afatinib-mediated changes in the level of store-operated Ca²⁺ entry (SOCE)-related proteins and intracellular Ca²⁺ level in non-small cell lung cancer cells with T790M mutation in the EGFR gene were analyzed using western blot and ratiometric assays, respectively. Afatinib-mediated autophagic flux was evaluated by measuring the cleavage of LC3B-II. Flow cytometry and cell proliferation assays were conducted to assess cell apoptosis and proliferation. Results: The levels of SOCE-mediating proteins (ORAI calcium release-activated calcium modulator 1 [ORAI1], stromal interaction molecule 1 [STIM1], and sarco/endoplasmic reticulum Ca²⁺ ATPase [SERCA2]) decreased after afatinib treatment in non-small cell lung cancer cells, whereas the levels of SOCE-related proteins did not change in gefitinib-resistant non-small cell lung cancer cells (PC-9/GR; bearing a T790M mutation in EGFR). Notably, the expression level of SOCE-related proteins in PC-9/GR cells was reduced also responding to afatinib in the absence of extracellular Ca²⁺. Moreover, extracellular Ca²⁺ influx through the SOCE was significantly reduced in PC-9 cells pre-treated with afatinib than in the control group. Additionally, afatinib was found to decrease the level of SOCE-related proteins through autophagic degradation, and the proliferation of PC-9GR cells was significantly inhibited by a lack of extracellular Ca²⁺. Conclusion: Extracellular Ca²⁺ plays important role in afatinib-mediated autophagic degradation of SOCE-related proteins in cells with T790M mutation in the EGFR gene and extracellular Ca²⁺ is essential for determining anti-cancer drug efficacy.

• Journal of Korean Traditional Oncology
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• v.16 no.2
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• pp.35-41
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• 2011

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.

• 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.

• Journal of Chest Surgery
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• v.31 no.10
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• pp.973-981
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• 1998

Background: About 30% to 40% of the patients with pathologic stage I non-small cell lung cancer (NSCLC) die within 5 years after complete resection. The identification of poor prognostic factors and the application of additional treatment are very important to improve the survival rate in resected stage I NSCLC. Materials and methods: Sixty-eight(68) patients who had been diagnosed postoperatively between Janury 1989 and December 1995 as having stage I non-small cell lung cancer according to the TNM classification were studied. The postoperative 5-year survival rate was calculated with the Kaplan-Meier method, and clinico- histopathologic factors including age, sex, operative method, type of tumor cell, T factor, grade of the differentiation in a squamous cell carcinoma, invasion of blood vessel and expression of the nm23-H1 protein were investigated and analyzed. Results: The median survival of the entire group of patients was 58$\pm$3 months, with a 5-year survival of 58.9%. In univariate analysis, invasion of blood vessel and poor differentiation of the tumor cell in a squamous cell carcinoma significantly worsened the survival. In multivariate analysis, invasion of blood vessel and grade of the differentiation of the tumor cells in a squamous cell carcinoma remained independent prognostic factors. High expression of the nm23-H1 protein was related to a high postoperative 5-year survival in comparision with low expression of the nm23-H1 pretein (73.0% vs 50.7%), but there was no statistical significance. Conclusions: These results highlight the negative prognostic value of poor differentiation of tumor cells in a squamous cell carcinoma and invasion of blood vessel in stage I non-small cell lung cancer. Also, further studies are necessary to be determined prognostic value of the T factor and expression of the nm23 protein in non-small cell lung cancer.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.52 no.6
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• pp.627-632
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• 2002

Intramedullary spinal cord metastasis (ISCM) has rarely been reported in patients with carcinomas. In about half the ISCM reported the primary origins are lung cancer, with small cell lung cancer responsible for almost all reported cases. Thus, ISCM from small cell lung cancer is relatively well documented, but ISCM from non-small cell lung cancer is rarely diagnosed prior to the patients' demise, so very little data about such patients is available. Spine MRI is the most sensitive technique for diagnosing ISCM. ISCM are now being encountered with increasing frequency due to the increasing survival rates of lung cancer patients, and the development of new imaging technique. We reported a case of an ISCM from non-small cell lung cancer with a brief review of the literature.

• Tuberculosis and Respiratory Diseases
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• v.75 no.5
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• pp.181-187
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• 2013

The emergence of new therapeutic agents for non-small cell lung cancer (NSCLC) implies that histologic subtyping and molecular predictive testing are now essential for therapeutic decisions. Histologic subtype predicts the efficacy and toxicity of some treatment agents, as do genetic alterations, which can be important predictive factors in treatment selection. Molecular markers, such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement, are the best predictors of response to specific tyrosine kinase inhibitor treatment agents. As the majority of patients with NSCLC present with unresectable disease, it is therefore crucial to optimize the use of tissue samples for diagnostic and predictive examinations, particularly for small biopsy and cytology specimens. Therefore, each institution needs to develop a diagnostic approach requiring close communication between the pulmonologist, radiologist, pathologist, and oncologist in order to preserve sufficient biopsy materials for molecular analysis as well as to ensure rapid diagnosis. Currently, personalized medicine in NSCLC is based on the histologic subtype and molecular status. This review summarizes strategies for tissue acquisition, histologic subtyping and molecular analysis for predictive testing in NSCLC.