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

• BMB Reports
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• 제33권6호
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• pp.525-530
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• 2000

The nerve growth factor (NGF) induces neuronal differentiation and neurite outgrowth of PC12 cells, whereas epidermal growth factors (EGF) stimulate growth and proliferation of the cells. In spite of this difference, NGF-or EGF-treated PC12 cells share various properties in cellular-signaling pathways. These include the activation of the phosphoinositide (PI)-3 kinase, 70 kDa S6 kinase, and in the mitogen-activated protein (MAP) kinase pathway, following the binding of these growth factors to intrinsic receptor tyrosine kinases (RTKs). Therefore, many studies have been attempted to access the critical signaling events in determining the differentiation and proliferation of PC12 cells. In this study, we investigated the cytosolic phospholipase $A_2$ ($cPLA_2$) in neurite behavior in order to identify the differences of signaling pathways between the NGF-induced differentiation and the EGF-induced proliferation of PC12 cells. We have showed here that the $cPLA_2$ was translocated from cytosol to membrane only in NGF-treated cells. We also demonstrated that this translocation is associated with NGF-induced activation of phospholipase $C-{\gamma}(PLC-{\gamma})$, which elevates intracellular $Ca^{2+}$ concentration. These results reveal that the translocation of $cPLA_2$ may be a requisite event in the neuronal differentiation of PC12 cells. Various phospholipase inhibitors were used to confirm the importance of these enzymes in the differentiation of PC12 cells. Neomycin B, a PLC inhibitor, dramatically inhibited the neurite outgrowth, and two distinct $PLA_2$ inhibitors, 4-bromophenacyl bromide (BPB) and arachidonyltrifluoro-methyl ketone ($AACOCF_3$) also suppressed the neurite outgrowth of the cells, as well Taken together, these data indicated that $cPLA_2$ is involved in NGF-induced neuronal differentiation and neurite outgrowth of PC12 cells.

• 대한임상검사과학회지
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• 제55권4호
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• pp.298-305
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• 2023

버킷 림프종(Burkitt's lymphoma)은 B-세포에서 발생하는 비호지킨 림프종의 한 형태로, 빠른 성장과 면역계 장애와 관련된 특성으로 인해 약물이 투여되지 않으면 생존율이 감소하거나 나쁜 예후로 이어질 수 있다. Food and Drug Administration (FDA) 승인된 약물의 최적 활용, 안전한 약물을 병용하는 방법은 시간과 비용 절감을 가능하게 한다. 이 접근법은 새로운 치료법 개발을 하기 보다는 기존에 FDA 승인된 약물을 적응증이 다른 환자에게 빠르게 접근할 수 있는 가능성을 제공한다. 이 연구는 BTK를 표적으로 하는 이브루티닙(Ibrutinib)과 EGFR/HER2를 표적으로 하는 라파티닙(Lapatinib) 병용 치료 전략의 잠재력을 확인하였다. 버킷 림프종의 잘 알려진 Ramos 및 Daudi 세포주가 이 연구에 활용되어 이 병합 치료의 영향을 밝히는 역할을 하였다. 이브루티닙과 라파티닙의 병용치료가 단일 약물 대비 세포 증식을 상당히 억제하는 것을 보여주었다. 또한 병용 치료가 세포 사멸을 유도하고 S 및 G2/M 단계에서 세포주기 중단을 유발하는 것을 관찰하였다. 이 접근법은 약물 개발 일정을 간소화하는 데 그치지 않고 이미 존재하는 자원의 활용을 극대화하는 것을 의미한다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.551-557
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• 2015

Background: Differentiating morphologic features based on hematoxylin-eosin (HE) staining is the most common method to classify pathological subtypes of non-small-cell lung cancer (NSCLC). However, its accuracy and inter-observer reproducibility in pathological diagnosis of poorly differentiated NSCLC remained to be improved. Materials and Methods: We attempted to explore the role of immunohistochemistry (IHC) staining in diagnosing pulmonary squamous cell carcinoma (SQCC) with poorly differentiated features by HE staining or with elevated serum adenocarcinoma-specific tumor markers (AD-TMs). We also compared the difference of epidermal growth factor receptor (EGFR) mutation rate between patients with confirmed SQCC and those with revised pathological subtype. Logistic regression analyses were used to test the association between different factors and diagnostic accuracy. Results: A total of 132 patients who met the eligible criteria and had adequate specimens for IHC confirmation were included. Pathological revised cases in poor differentiated subgroup, biopsy samples and high-level AD-TMs cases were more than those with high/moderate differentiation, surgical specimens and normal-level AD-TMs. Moreover, biopsy sample was a significant factor decreasing diagnostic accuracy of pathological subtype (OR, 4.037; 95% CI 1.446-11.267, p=0.008). Additionally, EGFR mutation rate was higher in patients with pathological diagnostic changes than those with confirmed SQCC (16.7% vs 4.4%, p=0.157). Conclusions: Diagnosis based on HE staining only might cause pathological misinterpretation in NSCLC patients with poor differentiation or high-level AD-TMs, especially those with biopsy samples. HE staining and IHC should be combined as pathological diagnostic standard. The occurrence of EGFR mutations in pulmonary SQCC might be overestimated.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5915-5916
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• 2012

Human epidermal growth factor receptor (HER) 2 overexpression, observed in 20-25 percent of invasive breast cancers, is well known to be associated with a more aggressive phenotype and poor prognosis, with resistance to certain chemotherapeutic agents. The majority of patients with metastatic breast cancer who initially respond to trastuzumab, demonstrate disease progression within 1 year of treatment initiation. Furthermore, lack of response in some patients and relapse during the course of therapy, continue to challenge researchers and clinicians. A better understanding of the fundamental mechanisms of trastuzumab action is required so that new therapies directed at HER2 can be developed. We present here findings for mechanisms, both of Trastuzumab action and clinical resistance or escape.

• Tuberculosis and Respiratory Diseases
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• 제77권6호
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• pp.271-273
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• 2014

Disease flare-up after discontinuing epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has been considered as a critical issue in lung cancer patients who have experienced radiologic progression after showing initial durable response. This is a case of systemic nocardiosis that occurred after chronic steroid use for radionecrosis from stereotactic radiosurgery. It was initially thought as a disease flare-up after stopping EGFR-TKI.

• Tuberculosis and Respiratory Diseases
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• 제83권1호
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• pp.14-19
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• 2020

Lung cancer remains the most common cause of cancer-related deaths worldwide. Although there are many possible treatments, including targeted therapies such as epidermal growth factor receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase inhibitors, new therapeutic strategies are needed to improve clinical outcomes. Immunotherapy through the use of immune checkpoint inhibitors has provided one of the most important breakthroughs in the management of solid tumors, including lung cancers, and has shown promising results in numerous clinical trials. This review will present the current status of immunotherapy for lung cancer and future perspectives on these treatments.

• BMB Reports
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• 제45권12호
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• pp.719-723
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• 2012

A close association between the obesity hormone leptin and breast cancer progression has been suggested. The present study investigated the molecular mechanism for enhanced leptin expression in breast cancer cells and its functional significance in breast cancer aggressiveness. We examined whether leptin expression level is affected by the oncoprotein human epidermal growth factor receptor2 (HER2), which is overexpressed in ~30% of breast tumors. Here, we report, for the first time, that HER2 induces transcriptional activation of leptin in MCF10A human breast epithelial cells. We also showed that p38 mitogen-activated protein kinase signaling was involved in leptin expression induced by HER2. We showed a crucial role of leptin in the invasiveness of HER2-MCF10A cells using an siRNA molecule targeting leptin. Taken together, the results indicate a molecular link between HER2 and leptin, providing supporting evidence that leptin represents a target for breast cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1885-1887
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• 2014

Skin metastases of breast cancer are usually late events in the course of tumor progression and signify a poor prognosis. They may remain as a therapeutic challenge especially after failure of standard treatments. Topical interventions, together with or without radiotherapy, may only palliate the symptoms temporarily. However, there may be alternative treatment modalities for unresectable breast cancer skin metastases resistant to chemotherapy and radiotherapy. There are various genetic alterations in tumors and therapeutic potential of expression patterns for factors like epidermal growth factor receptor may have important clinical implications in case of disease refractory to the conventional treatments. Here, we clarified the therapeutic options and genetic alterations in skin metastatic breast cancer patients refractory to standard chemotherapeutics.

• BMB Reports
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• 제50권3호
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• pp.132-137
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• 2017

Elevated glucose levels in cancer cells can be attributed to increased levels of glucose transporter (GLUT) proteins. Glut1 expression is increased in human malignant cells. To investigate alternative roles of Glut1 in breast cancer, we silenced Glut1 in triple-negative breast-cancer cell lines using a short hairpin RNA (shRNA) system. Glut1 silencing was verified by Western blotting and qRT-PCR. Knockdown of Glut1 resulted in decreased cell proliferation, glucose uptake, migration, and invasion through modulation of the EGFR/MAPK signaling pathway and integrin ${\beta}1$/Src/FAK signaling pathways. These results suggest that Glut1 not only plays a role as a glucose transporter, but also acts as a regulator of signaling cascades in the tumorigenesis of breast cancer.