Product innovation, Process innovation, Internal capability, External partnership, Biotechnology industry,

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Purpose Innovation ecosystem is an emerging and popular concept in both academic and industrial circles. It offers a new perspective for enterprise strategy positioning. A business can create more value through a healthy innovation ecosystem. The paper aims to discuss these issues. Design/methodology/approach In this paper, the authors utilize a new triple-layer core-periphery framework to analyze Insigma Group’s multi-platform collaboration innovation ecosystem, in order to explore the architecture and heterogeneous functions inside an innovation ecosystem. Findings The authors illustrate the components and working mechanisms of the four platforms, which function as ideation, entrepreneurship, financing and investment, and innovation, inside Insigma’s innovation ecosystem in detail, and explain how they interact and collaborate toward a shared aim of the whole innovation ecosystem. Research limitations/implications The innovation ecosystem is an emerging concept. In this study, the authors combined two existing analytical frameworks of innovation ecosystem, and proposed a triple-layer core-periphery framework, which enable us to analyze the heterogeneity inside an innovation ecosystem. Practical implications The authors discussed the role of government and its policies in shaping the innovation ecosystem at the enterprise level. Originality/value The authors believe that this paper provides a holistic study of Insigma’s innovation ecosystem. The triple-layer core-periphery framework can be used to study other enterprise innovation ecosystem in the future.

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Background: The tumor microenvironment (TME) plays a crucial role in virtually every aspect of tumorigenesis of glioblastoma multiforme (GBM). A dysfunctional TME promotes drug resistance, disease recurrence, and distant metastasis. Recent evidence indicates that exosomes released by stromal cells within the TME may promote oncogenic phenotypes via transferring signaling molecules such as cytokines, proteins, and microRNAs. Results: In this study, clinical GBM samples were collected and analyzed. We found that GBM-associated macrophages (GAMs) secreted exosomes which were enriched with oncomiR-21. Coculture of GAMs (and GAM-derived exosomes) and GBM cell lines increased GBM cells’ resistance against temozolomide (TMZ) by upregulating the prosurvival gene programmed cell death protein 4 (PDCD4) and stemness markers SRY (sex determining region y)-box 2 (Sox2), signal transducer and activator of transcription 3 (STAT3), Nestin, and miR-21-5p and increasing the M2 cytokines interleukin 6 (IL-6) and transforming growth factor beta 1(TGF-β1) secreted by GBM cells, promoting the M2 polarization of GAMs. Subsequently, pacritinib treatment suppressed GBM tumorigenesis and stemness; more importantly, pacritinib-treated GBM cells showed a markedly reduced ability to secret M2 cytokines and reduced miR-21-enriched exosomes secreted by GAMs. Pacritinib-mediated effects were accompanied by a reduction of oncomiR miR-21-5p, by which the tumor suppressor PDCD4 was targeted. We subsequently established patient-derived xenograft (PDX) models where mice bore patient GBM and GAMs. Treatment with pacritinib and the combination of pacritinib and TMZ appeared to significantly reduce the tumorigenesis of GBM/GAM PDX mice as well as overcome TMZ resistance and M2 polarization of GAMs. Conclusion: In summation, we showed the potential of pacritinib alone or in combination with TMZ to suppress GBM tumorigenesis via modulating STAT3/miR-21/PDCD4 signaling. Further investigations are warranted for adopting pacritinib for the treatment of TMZ-resistant GBM in clinical settings.

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Standard interventions for glioma include surgery, radiation and chemotherapies but the prognosis for malignant cases such as glioblastoma multiforme remain grim. Even with targeted therapeutic agent, bevacitumab, malignant glioma often develops resistance and recurrence. Thus, developing alternative interventions (therapeutic targets, biomarkers) is urgently required. Bruton's tyrosine kinase (Btk) has been long implicated in B cell malignancies but surprisingly it has recently been shown to also play a tumorigenic role in solid tumors such as ovarian and prostate cancer. Bioinformatics data indicates that Btk is significantly higher in clinical glioma samples as compared to normal brain cells and Btk expression level is associated with stage progression. This prompts us to investigate the potential role of Btk as a therapeutic target for glioma. Here, we demonstrate Btk expression is associated with GBM tumorigenesis. Down-regulation of Btk in GBM cell lines showed a significantly reduced abilities in colony formation, migration and GBM sphere-forming potential. Mechanistically, Btk-silenced cells showed a concomitant reduction in the expression of CD133 and Akt/mTOR signaling. In parallel, Ibrutinib (a Btk inhibitor) treatment led to a similar anti-tumorigenic response. Using xenograft mouse model, tumorigenesis was significantly reduced in Btk-silenced or ibrutinib-treated mice as compared to control counterparts. Finally, our glioma tissue microarray analysis indicated a higher Btk staining in the malignant tumors than less malignant and normal brain tissues. Collectively, Btk may represent a novel therapeutic target for glioma and ibrunitib may be used as an adjuvant treatment for malignant GBM.

Purpose: To analyze the use of optical coherence tomography angiography (OCTA) in order to observe the changes in chronic central serous chorioretinopathy (CCSC) after half-dose photodynamic therapy (PDT). Methods: This is a retrospective study evaluating an imaging technique in a cohort of patients. Fundus photography, fluorescein angiography (FA), indocyanine green angiography (ICGA) (Heidelberg Spectralis, Heidelberg, Germany), OCT, and OCTA with the split-spectrum amplitude-decorrelation angiography algorithm (XR Optovue, Fremont, CA, USA) were performed prior to half-dose PDT. OCT and OCTA were conducted at week 1, month 1, month 2, and month 3 after half-dose PDT. Results: A total of 33 eyes of 28 patients were enrolled in the study. At the baseline assessment, the patient pool had a mean best-correct visual acuity of logMAR 0.29 ± 0.34 and the mean choroidal thickness was 407.45 ± 77.98 µm. At month 3 after PDT, the patient pool had a mean best-correct visual acuity of logMAR 0.1 ± 0.17 and the mean choroidal thickness was 355.48 ± 67.90 µm. Abnormal flow in the choriocapillary, which corresponded to the initial examinations using OCTA, was observed in all 33 eyes (100%). The images show an irregular high pixel values interval from low pixel values. At week 1 after half-dose PDT, 25 eyes (75.8%) resembled the baseline images of the choriocapillary layer of OCTA. Areas of nonperfusion in the choriocapillary were observed in 5 eyes (15.2%), and vessel-like material in the choriocapillary was observed in 3 eyes (9.0%). At month 3 after PDT, the choriocapillary layer of OCTA was shown to return to normal in 32 eyes (97%). Conclusions: We have detected choriocapillary changes in patients diagnosed with CCSC following half-dose PDT by using noninvasive OCTA. These findings provide new evidence in support of the previously proposed hypothesis on the effect of PDT and suggest that OCTA may become a useful tool in the follow-up of CCSC.