• Journal of Korean Neurosurgical Society
• /
• 제56권5호
• /
• pp.431-435
• /
• 2014

A fifty-year-old female non-smoker with no other specific medical history visited our institute. She complained of axial back pain with no other neurological deficit. Chest X-ray, chest computed tomography (CT) scan, CT-guided needle aspiration biopsy, whole-body positron emission tomography, spine CT and spine magnetic resonance image findings suggested NSCLC with epidermal growth factor receptor (EGFR) mutation, multiple brain metastases, and two isolated metastases to the T3 and L3 vertebral bodies. She underwent chemotherapy with gefitinib ($Iressa^{TM}$) for NSCLC and gamma knife surgery for multiple brain metastases. We performed a two-staged, total en bloc spondylectomy of the T3 and L3 vertebral bodies based on several good prognostic characteristics, such as the lack of metastases to the appendicular bone, good preoperative performance status, and being an excellent responder (Asian, never-smoker and adenocarcinoma histology) to EGFR inhibitors. Improved axial back pain after the surgery enabled her to walk with the aid of a thoracolumbosacral orthosis brace on the third postoperative day. Her Karnofsky performance status score (KPS) was 90 at the time of discharge and has been maintained to date 3 years after surgery. In selected NSCLC patients with good prognostic characteristics, we suggest that locally curative treatment such as total en bloc spondylectomy or radiosurgery should be emphasized to achieve longer term survival for the selected cases.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권3호
• /
• pp.1787-1790
• /
• 2013

This study evaluated the effects of ZD1839, an orally active, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, on nasopharyngeal carcinoma (NPC) both in vitro and in vivo. Influence of ZD1839 alone or combined with cisplatin on the NPC cell line CNE2 was detected by MTT assay with flow cytometry assessment of cell cycle distribution and apoptosis rates. Nude mice NPC xenografts were also used to evaluate the effects of ZD1839 alone or combined with cisplatin. The Student's t test evaluated statistical significance. ZD1839 alone or combined with cisplatin inhibited CNE2 cell line proliferation. ZD1839 induced CNE2 cell cycle arrest in the G1 phase, and higher concentrations induced apoptosis. Xenograft tumors were significantly smaller when treated with 200 mg/kg ZD1839, cisplatin, or cisplatin combined with 100 mg/kg ZD1839 than untreated controls. ZD1839 (200 mg/kg) alone showed good tumor inhibition effects, reduction of tumor weights, and smaller tumor volume without loss of body weight. ZD1839 (200 mg/kg) might provide a good and effective therapeutic reagent for NPC.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권7호
• /
• pp.3471-3476
• /
• 2012

Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of ${\alpha}$-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.

• Tuberculosis and Respiratory Diseases
• /
• 제74권1호
• /
• pp.37-40
• /
• 2013

Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been widely used for non-small-cell lung cancer patients. Its untoward cutaneous effects are largely well known and developed in many patients treated with EGFR TKIs. However trichomegaly of eyelash is rarely reported. Although trichomegaly is not a drug-limiting side effect, it could be troublesome of continuing the treatment because of cosmetic issue or eyeball irritation by long eyelashes. Therefore clinicians are needed to pay attention to this uncommon effect. We herein describe erlotinib induced trichomegaly of eyelashes in a woman with adenocarcinoma of the lung.

• Tuberculosis and Respiratory Diseases
• /
• 제66권4호
• /
• pp.280-287
• /
• 2009

연구배경: 표피성장인자수용체(epidermal growth factor receptor, EGFR) 티로신 활성효소 억제제(tyrosine kinase inhibitor, TKI)는 진행성 비소세포폐암의 새로운 치료제이다. 몇몇 연구 결과 gefitinib와 erlotinib에 대한 반응률과 반응 예측인자에 차이가 있을 가능성을 제시하였다. 저자들은 한국인 진행성 비소세포폐암에서 gefitinib와 erlotinib의 효과 및 독성을 비교하고 각 약제에 대해 서로 다른 반응 예측인자가 있는지 평가하였다. 방 법: 2003년 7월부터 2009년 2월까지 이화여자대학 교부속병원에서 진행성 비소세포폐암으로 gefitinib 또는 erlotinib로 치료 받은 환자들의 임상정보를 수집하였다. 중앙 생존기간은 Kaplan-Meier법으로 계산하였다. 결 과: 대상 환자는 총 86명이었다(gefitinib군 52명 대 erlotinib군 34명). 나이의 중앙값은 64세였고 53명(62%)이 남자였다. 86명 중 83명에서 반응평가가 가능했으며, 83명 중 35명이 반응을 보였고 12명이 안정성 질환이었으며 36명이 진행성 질환으로, 치료 반응률이 42%였고 질병 조절률이 57%였다. 중앙 추적관찰기간 502일 동안, 진행까지의 중앙기간은 129일이었으며 중앙 생존기간은 259일이었다. 치료 반응률(gefitinib 44% 대 erlotinib 39%, p=0.678), 중앙 생존기간(gefitinib 301일 대 erlotinib 202일, p=0.151) 및 병의 진행까지 기간의 중앙값(gefitinib 136일 대 erlotinib 92일, p=0.672)은 두 군 사이에 차이가 없었다. 두 약제는 비슷한 독성을 보였다. Cox 회귀모형을 이용한 다변수분석에서 선암이 생존과 관련된 독립적인 예후인자였다(상대위험도: 0.487, 95% 신뢰구간: 0.292~0.811, p=0.006). 아집단 분석 결과 두 약제에 대한 서로 다른 반응 예측인자는 없었다. 결 론: Gefitinib와 erlotinib 사이에 반응률, 생존기간, 진행까지의 기간 및 독성에 차이는 없었다. 각 약제에 대한 특이적인 반응 예측인자도 없었다.

• 대한암한의학회지
• /
• 제16권1호
• /
• pp.55-61
• /
• 2011

Objectives : Epidermal growth factor receptor-inhibitors have demonstrated improved overall survival in patients with non-small cell lung cancer, but their use is associated with dermatologic adverse reactions that often require symptomatic treatment. Methods : A 44-year-old woman, who started the chemotherapy of Iressa$^{(R)}$ on August 2010, developed cutaneous symptoms such as papulopustular rash, dry skin, and pruritus on her face and scalp after taking Iressa$^{(R)}$ for four weeks. The patient visited our clinic with such symptoms on March 2011 and underwent herebal remedy targeted to alleviate the skin reactions. The severity of dermatologic symptoms was evaluated with the numeric rating scale and the Common Terminology Criteria for Adverse Events version 4.0. Results : Noticeable changes on the skin lesion were observed after the two months of treatment, without any dose modification of the Iressa$^{(R)}$. The cutaneous symptoms as papulopustular rash, dry skin and pruritus were improved and there was no adverse event induced by the treatment with herbal medicine. Conclusions : This case report suggests that the treatment with a herbal medicine, Samultang-gagambang be considered as a useful treatment to relieve EGFR-inhibitor induced dermatologic adverse reactions.

• 대한물리치료과학회지
• /
• 제13권2호
• /
• pp.137-145
• /
• 2006

We investigated whether increased contractile responsiveness to epidermal growth factor (EGF) is associated with altered activation of mitogen-activated protein kinase (MAPK) in the aortic smooth muscle of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. EGF induced contraction and MAPK activity in aortic smooth muscle strips, which were significantly increased in tissues from the DOCA-salt hypertensive rats compared with those from sham-operated rats. AG1478, PD98059, and LY294002, inhibitors of EGF receptor (EGFR) tyrosine kinase, MAPK/extracellular signal-regulated kinase (ERK) kinase, and phosphatidylinositol 3-kinase (PI3K), respectively, inhibited the contraction and the activity of ERK1/2 that were elevated by EGF. Y27632 and GF109203X, inhibitors of Rho kinase and protein kinase C, respectively, attenuated EGF-induced contraction, with no diminution of ERK1/2 activity. Although EGF also elevated the activity of EGFR tyrosine kinase in both sham-operated and DOCA-salt hypertensive rats, the expression and the magnitude of activation did not differ between strips. These results strongly suggest that EGF induces contraction by the activation of ERK1/2, which is regulated by the PI3K pathway in the aortic smooth muscle of DOCA-salt hypertensive rats.

• Journal of Ginseng Research
• /
• 제43권4호
• /
• pp.527-538
• /
• 2019

Background: Ginsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor (ER) via mitogen-activated protein kinase-mediated pathway. Our study aimed to delineate the mechanisms by which Rg1 activates the rapid ER signaling pathways. Methods: ER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidney HEK293 cells were treated with Rg1 ($10^{-12}M$, $10^{-8}M$), $17{\beta}$-estradiol ($10^{-8}M$), or vehicle. Immunoprecipitation was conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or their inhibitors were applied. Results: Rg1 rapidly induced $ER{\alpha}$ translocation to plasma membrane via caveolin-1 and the formation of signaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator of nongenomic activity of ER (MNAR), $ER{\alpha}$, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase (MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interfering RNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in these cells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor (EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). The increase in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could be abolished by G15. Conclusion: Ginsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.

• Tuberculosis and Respiratory Diseases
• /
• 제85권2호
• /
• pp.155-164
• /
• 2022

Background: The remarkable efficacy of osimertinib in non-small cell lung cancer (NSCLC) with acquired T790M mutation has been widely documented in clinical trials and real-world practice. However, some patients show primary resistance to this drug. Even patients who initially show a favorable response have inconsistent clinical outcomes later. Therefore, the aim of this study was to identify additional clinical predictive factors for osimertinib efficacy. Methods: A prospective cohort of patients with acquired T790M positive stage IV lung adenocarcinoma treated with osimertinib salvage therapy in Hallym University Medical Center were analyzed. Results: Sixty-one eligible patients were analyzed, including 38 (62%) women and 39 (64%) who never smoked. Their mean age was 63.3 years. The median follow-up after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) was 36.0 months (interquartile range, 24.7-50.2 months). The majority (n=45, 74%) of patients were deceased. Based on univariate analysis, low baseline neutrophil-to-lymphocyte ratios (NLR), age ≥50 years, never-smoking history, stage IVA at osimertinib initiation, and prolonged response to previous TKIs (≥10 months) were associated with a significantly longer progression-free survival (PFS). Multivariate analysis showed that never-smoking status (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.30-0.98; p=0.041) and a baseline NLR less than or equal to 3.5 (HR, 0.23; 95% CI, 0.12-0.45; p<0.001) were independently associated with a prolonged PFS with osimertinib. Conclusion: Smoking history and high NLR were independent negative predictors of osimertinib PFS in patients with advanced NSCLC developing EGFR T790M resistance after the initial EGFR-TKI treatment.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권7호
• /
• pp.3053-3060
• /
• 2016

Gastric cancer is generally associated with poor survival rates and accounts for a remarkable proportion of global cancer mortality. The prevalence of gastric carcinoma varies in different regions of world and across teh various ethnic groups. On the basis of pathological assessment, gastric cancer can be categorized as intestinal and diffuse carcinomas. The etiology is diverse, including chemical carcinogen exposure, and high salt intake Helicobacter pylori also plays a vital role in the pathogenesis of certain gastric carcinomas. The development of gastric cancer involves various alterations in mRNAs, genes (GOLPH3, MTA2) and proteins (Coronins). miRNAs, Hsa-mir-135b, MiR-21, miR-106b, miR-17, miR-18a, MiR-21, miR-106b, miR-17, miR-18a and MiRNA-375, miRNA-195-5p are the latest diagnostic biomarkers which can facilitate the early diagnosis of gastric carcinomas. Recent development in the treatment strategies for gastric carcinoma include the introduction of monoclonal antibodies, TKI inhibitors, inhibitors of PDGFR ${\beta}$, VEGFR-1, VEGFR-2, Anti-EGFR and anti-HER2 agents which can be applied along with conventional therapies.