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Nerve injury of the central nervous system and the peripheral nervous system still poses a major challenge in modern clinics. Understanding the roles of neurotrophic factors and their molecular mechanisms on neuro-regeneration will not only benefit patients with neural damage but could potentially treat neurodegenerative disorders, such as amyotrophic lateral sclerosis. In this study, we showed that human IL12 p40-p40 homodimer (hIL12p80) within PLA and PLGA conduits improved sciatic nerve regeneration in mice. As such, the group of conduits with NSCs and hIL12p80 (CNI) showed the best recovery among the groups in the sciatic functional index (SFI), compound muscle action potential (CMAP), and Rotarod performance analyses. In addition, the CNI group had a faster recovery and outperformed the other groups in SFI and Rotarod performance tests beginning in the fourth week post-surgery. Immunohistochemistry showed that the CNI group increased the diameter of the newly regenerated nerve by two-fold (p < 0.01). In vitro studies showed that hIL12p80 stimulated differentiation of mouse NSCs to oligodendrocyte lineages through phosphorylation of Stat3 at Y705 and S727. Furthermore, implantation using PLGA conduits (C2.0 and C2.1) showed better recovery in the Rotarod test and CMAP than using PLA conduits in FVB mice. In B6 mice, the group with C2.1 + NSCs + hIL12p80 (C2.1NI) not only promoted sciatic functional recovery but also reduced the rate of experimental autotomy. These results suggested that hIL12p80, combined with NSCs, enhanced the functional recovery and accelerated the regeneration of damaged nerves in the sciatic nerve injury mice. Our findings could further shed light on IL12′s application not only in damaged nerves but also in rectifying the oligodendrocytes’ defects in neurodegenerative diseases, such as amyotrophic lateral sclerosis and multiple sclerosis.

This study explored the perspectives of mathematics teacher educator-researchers (MTE-Rs) on the use of theory in facilitating teacher growth. We adopted the framework of the theory-centered scholarship triangle (Silver & Herbst, 2007) to probe the underlying meanings of perspectives on theory use expressed by MTE-Rs. Qualitative analysis revealed three distinct types of perspectives: a perspective focusing on research, a perspective focusing on practice, and a perspective on the connection between research and practice. For the perspective on the connection between research and practice, two sub-categories were identified: connection with consideration of context and that without consideration of context. Different perspectives that MTE-Rs possess may influence their actions taken in professional development and consequently influence teachers’ learning of theory. Specifically, the cyclic process of decontextualizing and recontextualizing theory between research and practice domains is the key to the development of MTE-Rs’ educative power so that they can better facilitate teachers in learning theory.

Nasopharyngeal carcinoma (NPC) is a malignancy derived from the epithelial cells of the nasopharynx. Although a combination of radiotherapy with chemotherapy is effective for therapy, relapse and metastasis after remission remain major causes of mortality. Epstein-Barr virus (EBV) is believed to be one of causes of NPC development. We demonstrated previously that EBV reactivation is important for the carcinogenesis of NPC. We sought, therefore, to determine whether EBV reactivation can be a target for retardation of relapse of NPC. After screening, we found luteolin is able to inhibit EBV reactivation. It inhibited EBV lytic protein expression and repressed the promoter activities of two major immediate-early genes, Zta and Rta. Furthermore, luteolin was shown to reduce genomic instability induced by recurrent EBV reactivation in NPC cells. EBV reactivation-induced NPC cell proliferation and migration, as well as matrigel invasiveness, were also repressed by luteolin treatment. Tumorigenicity in mice, induced by EBV reactivation, was decreased profoundly following luteolin administration. Together, these results suggest that inhibition of EBV reactivation is a novel approach to prevent the relapse of NPC.

Background: We previously identified mouse interleukin-12p80 (mIL12p80, a homodimer of IL12p40) in the cell extracts of implanted poly(L-lactic acid) (PLA) nerve conduit combined with neural stem cells (NSCs) and showed that mIL12p80 enhances the functional recovery and nerve regeneration in mice. Here, we showed that human IL12p80 (hIL12p80) improves the sciatic nerve regeneration in mice. Methods: Implantation of hIL12p80 and NSCs into nerve conduit promotes repair of the sciatic nerve injury in mouse model. Findings: NSCs transplanted with hIL12p80 showed the best recovery than the other groups in sciatic functional index (SFI), compound muscle action potential (CMAP) and Rotarod analyses. In addition, the group with Conduit+NSC+hIL12p80 (CNI) outperformed the other groups in SFI and Rotarod tests beginning at the fourth-week post-surgery. Immunohistochemistry showed that the CNI group increases the diameter of newly regenerated nerve 98%. In vitro studies showed that hIL12p80 stimulates differentiation of mouse NSCs to oligodendrocyte lineages through phosphorylation of Stat3 at Y705. Further, implantation using poly(L-lactic-co-glycolic acid) (PLGA) nerve conduits (C 2.0 and C 2.1) showed better recovery in Rotarod test and CMAP than using PLA conduits (C 1.0) in FVB/NJ (FVB) mice. In C57BL/6J (B6) mice, the group with C 2.1+NSC+hIL12p80 (C 2.1NI) not only promotes sciatic functional recovery but also reduces experimental autotomy. Interpretation: These results suggest that hIL12p80 together with NSCs enhance the functional recovery and accelerate the regeneration of damaged nerves in mice. These findings could be used in devising potential strategies for nerve injury treatment. Funding Statement: This research is supported by National Health Research Institutes, Taiwan (CS-107-PP-02), and Ministry of Science and Technology, Taiwan (107-1901-01-19-03; 107-0324-01-19-03). Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: In this study, all animal experimental procedures followed ethical guidelines and were approved by the Institutional Animal Care and Use Committee (IACUC) of the National Health Research Institutes (Protocol No. NHRI-IACUC-101067A).

This paper aims to explore the educative power of an experienced mathematics teacher educator-researcher (MTE-R) who displayed his insights and strategies in teacher professional development (TPD) programs. To this end, we propose a framework by first conceptualizing educative power based on three constructs—communication, reasoning, and connection—and then we extend the conceptualization with another two dimensions: the reciprocal facilitator-learner relationships involving educators, teachers, and students, as well as a bridge between research and practice. Based on both self-study and case-study approaches, we further elaborate features specific to the MTE-R’s educative power which includes communication using an approach of creating educative phenomenology, reasoning by mapping teachers’ ideas onto emergent models to solve problems in educative challenges, and connection between research and practice by coordination. In particular, the core of the educative power that supported the MTE-R to initiate at-the-moment actions was his insights into the essence of mathematics, and the learning of students and teachers. We believe that the conceptual framework in this study offers a powerful tool that could guide the analyses of educative power, especially for those studies related to the initiation of at-the-moment actions and the implementation of TPD programs.

(−)-Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, has been shown to inhibit the proliferation of a variety of tumor cells. Epidemiological studies have shown that drinking green tea can reduce the incidence of nasopharyngeal carcinoma (NPC), yet the underlying mechanism is not well understood. In this study, the inhibitory effect of EGCG was tested on a set of Epstein Barr virus-negative and -positive NPC cell lines. Treatment with EGCG inhibited the proliferation of NPC cells but did not affect the growth of a non-malignant nasopharyngeal cell line, NP460hTert. Moreover, EGCG treated cells had reduced migration and invasive properties. The expression of the cell adhesion molecules E-cadherin and β-catenin was found to be up-regulated by EGCG treatment, while the down-regulation of matrix metalloproteinases (MMP)-2 and MMP-9 were found to be mediated by suppression of extracellular signal-regulated kinase (ERK) phosphorylation and AP-1 and Sp1 transactivation. Spheroid formation by NPC cells in suspension was significantly inhibited by EGCG. Oral administration of EGCG was capable of suppressing tumor growth in xenografted mice bearing NPC tumors. Treatment with EGCG was found to elevate the expression of p53 and p21, and eventually led to apoptosis of NPC cells via caspase 3 activation. The nuclear translocation of NF-κB and β-catenin was also suppressed by EGCG treatment. These results indicate that EGCG can inhibit the proliferation and invasiveness, and induce apoptosis, of NPC cells, making it a promising agent for chemoprevention or adjuvant therapy of NPC.

We used mathematics-pedagogy tasks (MPTs) to design content and methods (pedagogy) courses to facilitate the professional growth of pre-service elementary teachers, especially those who did not study in mathematics-related areas. MPTs, together with the use of relevant theories, enable pre-service elementary teachers to coordinate the learning of mathematics, student cognition, the sequence of mathematics content arranged in the curriculum, and teaching activities designed in textbooks. For those pre-service teachers studying in non-mathematics areas, the learning of mathematics should be the starting point, as it enables them not only to understand the mathematics but also to build personal learning theories that can subsequently be applied to realize student cognition. The integration of mathematics and student cognition becomes the foundation for pre-service elementary teachers to comprehend curriculum arrangement and textbook design. In this chapter, we discuss and exemplify the notion of MPTs using examples implemented in two teacher education courses (one content course and one methods course).

Nasopharyngeal carcinoma (NPC) is a head and neck cancer prevalent throughout Southern China and Southeast Asia. Patient death following relapse after primary treatment remains all too common but the cause of NPC relapse is unclear. Clinical and epidemiological studies have revealed the high correlation among NPC development, Epstein-Barr virus (EBV) reactivation and host genomic instability. Previously, recurrent EBV reactivation was shown to cause massive genetic alterations and enhancement of tumor progression in NPC cells and these may be required for NPC relapse. Here, EBV BALF3 has the ability to induce micronuclei and DNA strand breaks. After recurrent expression of BALF3 in NPC cells, genomic copy number aberrations, determined by array-based comparative genomic hybridization, had accumulated to a significant extent and tumorigenic features, such as cell migration, cell invasion and spheroid formation, increased with the rounds of induction. In parallel experiments, cells after highly recurrent induction developed into larger tumor nodules than control cells when inoculated into NOD/SCID mice. Furthermore, RNA microarrays showed that differential expression of multiple cancer capability-related genes and oncogenes increased with recurrent BALF3 expression and these changes correlated with genetic aberrations. Therefore, EBV BALF3 is a potential factor that mediates the impact of EBV on NPC relapse.

We examined geometric calculation with number tasks used within a unit of geometry instruction in a Taiwanese classroom, identifying the source of each task used in classroom instruction and analyzing the cognitive complexity of each task with respect to 2 distinct features: diagram complexity and problem-solving complexity. We found that instructional tasks were drawn from multiple sources, including textbooks, tests, supplemental materials, and the teacher. Our analysis of cognitive complexity indicated that the instructional tasks frequently involved both diagram complexity and problem-solving complexity. Moreover, the geometric calculation with number tasks from nontextbook sources tended to be more cognitively demanding than those found in the textbooks. Implications of task analysis on geometry domain and textbook analysis studies are discussed.

Background Lytic reactivation of EBV has been reported to play an important role in human diseases, including NPC carcinogenesis. Inhibition of EBV reactivation is considered to be of great benefit in the treatment of virus-associated diseases. For this purpose, we screened for inhibitory compounds and found that apigenin, a flavonoid, seemed to have the ability to inhibit EBV reactivation. Methods We performed western blotting, immunofluorescence and luciferase analyses to determine whether apigenin has anti-EBV activity. Results Apigenin inhibited expression of the EBV lytic proteins, Zta, Rta, EAD and DNase in epithelial and B cells. It also reduced the number of EBV-reactivating cells detectable by immunofluorescence analysis. In addition, apigenin has been found to reduce dramatically the production of EBV virions. Luciferase reporter analysis was performed to determine the mechanism by which apigenin inhibits EBV reactivation: apigenin suppressed the activity of the immediate-early (IE) gene Zta and Rta promoters, suggesting it can block initiation of the EBV lytic cycle. Conclusion Taken together, apigenin inhibits EBV reactivation by suppressing the promoter activities of two viral IE genes, suggesting apigenin is a potential dietary compound for prevention of EBV reactivation. Electronic supplementary material The online version of this article (doi:10.1186/s12929-016-0313-9) contains supplementary material, which is available to authorized users.

To fully empower sensor networks with cognitive Internet of Things (IoT) technology, efficient medium access control protocols that enable the coexistence of cognitive sensor networks with current wireless infrastructure are as essential as the cognitive power in data fusion and processing due to shared wireless spectrum. Cognitive radio (CR) is introduced to increase spectrum efficiency and support such an endeavor, which thereby becomes a promising building block toward facilitating cognitive IoT. In this paper, primary users (PUs) refer to devices in existing wireless infrastructure, and secondary users (SUs) refer to cognitive sensors. For interference control between PUs and SUs, SUs adopt dynamic spectrum access and power adjustment to ensure sufficient operation of PUs, which inevitably leads to increasing latency and poses new challenges on the reliability of IoT communications. To guarantee operations of primary systems while simultaneously optimizing system performance in cognitive radio ad hoc networks (CRAHNs), this paper proposes interference-aware flooding schemes exploiting global timeout and vaccine recovery schemes to control the heavy buffer occupancy induced by packet replications. The information delivery dynamics of SUs under the proposed interference-aware recovery-assisted flooding schemes is analyzed via epidemic models and stochastic geometry from a macroscopic view of the entire system. The simulation results show that our model can efficiently capture the complicated data delivery dynamics in CRAHNs in terms of end-to-end transmission reliability and buffer occupancy. This paper sheds new light on analysis of recovery-assisted flooding schemes in CRAHNs and provides performance evaluation of cognitive IoT services built upon CRAHNs., Comment: 10 pages

The chapter begins with the present challenges that mathematics educators in Taiwan are facing. It outlines the hierarchical structure of in-service teacher development and highlights how the top-down approach often adopted may not address the needs of classroom teachers. The authors of the chapter next describe an innovative school-based program, Lighten-up School-Based Program (LUSBP), they initiated for facilitating professional growth of mathematics teachers in Taiwan. The core for LUSBP is that all tiers of educators, teachers, and students learn through active participation whilst interacting with each other. The project employs a design-based approach with teachers as designers who learn from the process of creating tasks, enacting tasks with classroom students, and revising tasks based on students’ learning. The school-based model enables the creation of a friendly learning environment where teachers take it for granted to make changes and are willing to share their experiences with one another. The outcomes of LUSBP are positive and hold promise for the future.

The role of ionic currents on procaine-elicited action potential bursts was studied in an identifiable RP1 neuron of the African snail, Achatina fulica Ferussac, using the two-electrode voltage clamp method. The RP1 neuron generated spontaneous action potentials and bath application of procaine at 10 mM reversibly elicited action potential bursts in a concentration-dependent manner. Voltage clamp studies revealed that procaine at 10 mM decreased [1] the Ca2+ current, [2] the Na+ current, [3] the delayed rectifying K+ current I(KD), and [4] the fast-inactivating K+ current (I(A)). Action potential bursts were not elicited by 4-aminopyridine (4-AP), an inhibitor of I(A), whereas they were seen after application of tetraethylammonium chloride (TEA), a blocker of the I(K)(Ca) and I(KD) currents, and tacrine, an inhibitor of I(KD). Pretreatment with U73122, a phospholipase C inhibitor, blocked the action potential bursts elicited by procaine. U73122 did not affect the I(KD) of the RP1 neuron; however, U73122 decreased the inhibitory effect of procaine on the I(KD). Tacrine decreased the TEA-sensitive I(KD) of RP1 neuron but did not significantly affect the I(A). Tacrine also successfully induced action potential bursts in the RP1 neuron. It is concluded that the inhibition on the I(KD) is responsible for the generation of action potential bursts in the central snail RP1 neuron. Further, phospholipase C activity is involved in the procaine-elicited I(KD) inhibition and action potential bursts.

Pemphigus vulgaris is a life-threatening autoimmune bullous dermatosis and its management represents a major challenge to medical teams. The primary treatments for pemphigus vulgaris are oral steroids and immunosuppressants, but topical approaches also play a role in disease management. Here, we report a patient with pemphigus vulgaris involving 62% of the total body surface area, with initial poor clinical response to systemic steroids and topical silver sulfadiazine therapy. However, a marked improvement in wound healing and decreased patient discomfort were observed after application of silver-containing hydrofiber dressings (Aquacel-Ag®). Therefore, silver-containing hydrofiber dressings may offer an effective adjunct in the treatment of patients with pemphigus vulgaris with extensive skin involvement. Our encouraging experience with these dressing patches may be extended to manage other large exudation wounds.

BACKGROUND. In western countries, the Kirsten ras oncogene homolog gene (KRAS) mutation rate is high in patients with nonsmall cell lung cancer (NSCLC), especially in those with adenocarcinoma (30%-50%), but the epidermal growth factor receptor gene (EGFR) mutation rate is very low (3%-8%). In addition, KRAS mutations reportedly were associated with EGFR tyrosine kinase inhibitor (EGFR-TKI) resistance. In Taiwan, high EGFR mutation rates associated with high EGFR-TKI response rates in patients with NSCLC have been reported; however, KRAS mutation data are limited and have not been correlated with TKI response. METHODS. KRAS mutation analysis was performed on 237 NSCLC specimens, and the results were correlated with clinicopathologic features. All but 2 tumors also underwent EGFR mutation analysis. RESULTS. KRAS mutations were identified in only 9 of 237 patients (3.80%). Five patients were women who were nonsmokers, and 4 patients were men who were ever-smokers. The mutation rate was 5.03% in patients with adenocarcinoma (8 of 159 patients) and 1.56% in patients with squamous cell carcinoma (1 of 64 patients). Four mutations were G12V, 3 mutations were G12D, 1 mutation was L19F, and 1 was the duplication insertion mutation dupT50_M72. In contrast, EGFR mutations were detected in 96 of 235 patients (40.8%) and in 90 of 157 adenocarcinomas (57.3%). None of the KRAS mutations coexisted with EGFR mutations. KRAS mutations were not associated significantly with any clinicopathologic characteristics, including smoking status. Among the 53 patients who had received TKI monotreatment, only 1 patient had a KRAS mutation and had progressive disease. CONCLUSIONS. The KRAS mutation rate was too low to play a significant role in TKI resistance or tumorigenesis among Taiwanese patients with NSCLC, which was the complete reverse of the results reported in western countries. Cancer 2008. © 2008 American Cancer Society.

The lytic reactivation of Epstein-Barr virus (EBV) has been reported to be strongly associated with several human diseases, including nasopharyngeal carcinoma (NPC). Inhibition of the EBV lytic cycle has been shown to be of great benefit in the treatment of EBV-associated diseases. The administration of dietary compounds is safer and more convenient than other approaches to preventing EBV reactivation. We screened several dietary compounds for their ability to inhibit EBV reactivation in NPC cells. Among them, the flavonoid luteolin showed significant inhibition of EBV reactivation. Luteolin inhibited protein expression from EBV lytic genes in EBV-positive epithelial and B cell lines. It also reduced the numbers of EBV-reactivating cells detected by immunofluorescence analysis and reduced the production of virion. Furthermore, luteolin reduced the activities of the promoters of the immediate-early genes Zta (Zp) and Rta (Rp) and also inhibited Sp1-luc activity, suggesting that disruption of Sp1 binding is involved in the inhibitory mechanism. CHIP analysis revealed that luteolin suppressed the activities of Zp and Rp by deregulating Sp1 binding. Taken together, luteolin inhibits EBV reactivation by repressing the promoter activities of Zp and Rp, suggesting luteolin is a potential dietary compound for prevention of virus infection.

to investigate the effects of 2'-hydroxy-4'-methoxyacetophenone (paeonol) on the electrophysiological behavior of a central neuron (right parietal 4; RP4) of the giant African snail (Achatina fulica Ferussac).intracellular recordings and the two-electrode voltage clamp method were used to study the effects of paeonol on the RP4 neuron.the RP4 neuron generated spontaneous action potentials. Bath application of paeonol at a concentration of ≥ 500 micromol/L reversibly elicited action potential bursts in a concentration-dependent manner. Immersing the neurons in Co(2+)-substituted Ca(2+)-free solution did not block paeonol-elicited bursting. Pretreatment with the protein kinase A (PKA) inhibitor KT-5720 or the protein kinase C (PKC) inhibitor Ro 31-8220 did not affect the action potential bursts. Voltage-clamp studies revealed that paeonol at a concentration of 500 micromol/L had no remarkable effects on the total inward currents, whereas paeonol decreased the delayed rectifying K(+) current (I(KD)) and the fast-inactivating K(+) current (I(A)). Application of 4-aminopyridine (4-AP 5 mmol/L), an inhibitor of I(A), or charybdotoxin 250 nmol/L, an inhibitor of the Ca(2+)-activated K(+) current (I(K(Ca))), failed to elicit action potential bursts, whereas tetraethylammonium chloride (TEA 50 mmol/L), an I(KD) blocker, successfully elicited action potential bursts. At a lower concentration of 5 mmol/L, TEA facilitated the induction of action potential bursts elicited by paeonol.paeonol elicited a bursting firing pattern of action potentials in the RP4 neuron and this activity relates closely to the inhibitory effects of paeonol on the I(KD).

Background Atopic dermatitis (AD) is a chronic, relapsing dermatosis. Previous studies have focused mostly on pediatric patients, and investigations emphasizing adult AD have been limited. Objective We set out to determine the 1-year prevalence and evaluate the validity of the International Study of Asthma and Allergies in Childhood (ISAAC) and United Kingdom Working Party (UKWP) AD questionnaires of adult AD in Taiwan. Methods We conducted a cross-sectional study among nursing staff at a university hospital. The 1-year prevalence of AD was assessed by ISAAC and UKWP questionnaires. Subsequently, the dermatologists' diagnosis based on Hanifin and Rajka criteria was used as a reference for validation. Results The overall response rate was 92.9%, equivalent to 1131 complete questionnaires. Ninety adult patients with AD (8%) were identified by dermatologists' diagnosis whereas ISAAC identified 107 (9.5%); sensitivity and specificity were 36.7% and 92.9%, respectively. UKWP identified 42 (3.7%) patients with AD; sensitivity and specificity were 42.2% and 99.6%, respectively. Using the receiver operating characteristic curve analysis, the UKWP criteria performed significantly better than its ISAAC counterpart. Further analysis indicated that modification of these criteria resulted in significant improvement in their diagnostic efficacy. More specifically, modified ISAAC showed 90.0% and 55.2% sensitivity and specificity, respectively, whereas modified UKWP demonstrated 82.2% and 94.2% sensitivity and specificity, respectively. Limitation Most of the study subjects were female with a high educational background. Conclusion Currently available questionnaire instruments do not perform well in the identification of adult patients with AD. Modification of the original questionnaires may allow for future large-scale epidemiologic studies.

Background: Hand eczema is a commonly encountered occupational disease and has a negative impact on life quality. Objective: This study aimed to identify the specific conditions that may pose a higher risk for occurrence of hand eczema and evaluate the impact of hand eczema on life quality. Method: Nursing staff from a university hospital were invited to participate in a cross-sectional study. Validated questionnaires for hand eczema and life quality were used to evaluate the point prevalence and determine the impacts of hand eczema, respectively. Results: The overall response rate was 93%, equivalent to 1132 completed questionnaires. Two hundred and forty-eight (22%) reported occurrence of hand eczema. Occurrence of hand eczema was significantly associated with nursing for >10 years and working in a special care unit, with prevalences of 27% and 26%, respectively. In addition, hand eczema was associated with suboptimal life quality; pruritus or burning sensations were associated with a lower quality of life among those with hand eczema. Conclusion: Hand eczema is a work-related problem for nursing staff; proper preventive programmes should be implemented for those nursing staff working in high-risk areas to avoid further lowering of their quality of life.

To evaluate the association of epidermal growth factor receptor (EGFR) gene copy number with EGFR and k-ras mutation status and tyrosine kinase inhibitor (TKI) sensitivity in non-small cell lung cancer (NSCLC), EGFR gene copy number of 182 NSCLC tumor specimens were analyzed by chromogenic in situ hybridization (CISH). EGFR and k-ras mutation analyses were also performed for, respectively, 176 and 157 of the 182 patients. Additionally, 36 patients in this study had received TKI monotherapy. The tumor was considered to be CISH positive if the gene copy number wasor=5 signals per nucleus inor=40% of tumor cells. CISH-positive tumors were strongly associated with adenocarcinoma (56.8%) compared with squamous cell carcinoma (15.9%) (p0.0001). The CISH-positive tumors were also strongly associated with EGFR mutations (78%) compared with wild type (20.2%) (p0.0001). Only six tumors had k-ras mutations. None had EGFR mutation and only one was CISH positive. In the patients treated with TKI, EGFR mutation was strongly associated with TKI responsiveness (22/25 responders) (p0.0001), but the CISH-positive tumors were only marginally significant (18/25 responders) (p=0.0665). Patients with EGFR mutations or CISH-positive tumors were all associated with longer median survival, although not statistically significant. Our results suggest Increased EGFR copy number was highly correlated with EGFR mutation in adenocarcinoma. Although it is less correlated with TKI responsiveness when compared with EGFR mutations, it still could be a good alternative molecular predictive marker for TKI responsiveness, since CISH can be done on paraffin section and is much quicker than DNA sequencing.