Apatinib Monotherapy or Combination Therapy for Non-Small Cell Lung Cancer Patients With Brain Metastases

Apatinib, an oral small molecular receptor tyrosine kinase inhibitor (TKI) developed first in China, exerts antiangiogenic and antineoplastic function through selectively binding and inhibiting vascular endothelial growth factor receptor 2 (VEGFR-2). In this study, we aimed to explore the efficacy and safety profile of apatinib monotherapy, or combined with chemotherapy or endothelial growth factor receptor (EGFR)-TKI in heavily pretreated non-small cell lung cancer (NSCLC) patients with brain metastases. We performed a retrospective analysis for relapsed NSCLC patients with brain metastases from our institute, who received apatinib (250 mg or 500 mg p.o. qd) monotherapy, or combination with EGFR-TKI or chemotherapy as second or more line systemic therapy until disease progression or unacceptable toxicity occurred. The objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and safety were analyzed. A total of 26 eligible patients were included: 24 patients diagnosed with adenocarcinoma, 2 with squamous carcinoma, and 14 patients harboring EGFR sensitizing mutations. The mPFS and mOS were 4.93 (range, 0.27−32.91; 95% CI 3.64−6.22) and 14.70 (range, 0.27−32.91; 95% CI 0.27−43.60) months for the whole group. The ORR and DCR were 7.7% (2/26) and 69.2% (18/26) for the entire lesions, and 7.7% (2/26) and 79.6% (20/26) for brain metastases, respectively. Compared with patients who received apatinib monotherapy, patients who received apatinib combination treatment had more favorable mPFS (11.77 vs. 2.27 months, p<0.05) and mOS (24.03 vs. 6.07 months, p<0.05). Treatment-related toxicities were tolerable including grade 1/2 hypertension, hand-and-foot syndrome, fatigue, nausea, liver dysfunction, myelosuppression, skin rash, and palpitation. In conclusion, apatinib exhibited high activity and good tolerance for NSCLC patients with brain metastasis, and it might become a potential choice for metastatic brain tumors in NSCLC patients.     

miR-122 Inhibits Hepatocarcinoma Cell Progression by Targeting LMNB2

In the present study, we investigated the role of miR-122 in hepatocarcinoma progression and explored the mechanism. In hepatocarcinoma tissues and cells, we used qRT-PCR to validate the miR-122 expression level. Next, we used colony formation by crystal violet staining assay to compare cell proliferation ability, and we used scratch test or Transwell assay to compare cell migration or invasion ability. We then conducted bioinformatics or luciferase reporter gene assay to prove the regulation effect of miR-122 on lamin B2 (LMNB2), and the biological function of LMNB2 was analyzed. We used nude mouse tumorigenicity assay to test the inhibition effect of miR-122 ASO therapy against hepatocarcinoma. miR-122 was reduced in hepatocarcinoma tissues compared to the paracarcinoma tissues, which was relatively low or high in hepatocarcinoma cell line SMMC7721 or Hep3B, and overexpressed miR-122 inhibited proliferation, migration, and invasion in hepatocarcinoma cells. Additionally, some reports showed that LMNB2 was regulated by miR-122, which inhibited the expression of LMNB2. Moreover, LMNB2 functioned to promote cell proliferation, migration, and invasion. We could achieve the inhibition of hepatocarcinoma using miR-122 therapy through decreasing LMNB2 expression in vivo. Our data indicated that miR-122 could inhibit hepatocellular carcinoma cell progression by targeting LMNB2 and as a therapeutic target for hepatocarcinoma treatment.     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.     

原肌球蛋白4在胃癌细胞迁移、侵袭和转移中的作用

目的:探索原肌球蛋白4（Tropomyosin4,TPM4）在胃癌细胞的迁移、侵袭和转移中的作用。方法:利用Real-time PCR、Western Blot及免疫荧光，检测原肌球蛋白4在不同胃癌细胞系及正常胃上皮细胞中的表达情况；利用免疫组化，检测原肌球蛋白4在胃癌组织及癌旁正常组织中的表达情况；利用慢病毒技术，在GC9811-P细胞中，分别转染LV-TPM4、shRNA-TPM4及对照空载体；通过Transwell和体内实验，检测胃癌细胞迁移、侵袭和转移。结果:Real-time PCR、Western Blot及免疫组化结果显示，原肌球蛋白4在胃癌细胞系及胃癌组织中的表达降低；上调原肌球蛋白4的表达后，抑制胃癌细胞的迁移、侵袭和转移；下调原肌球蛋白4的表达后，促进胃癌细胞的迁移、侵袭和转移（P<0.05）。结论:原肌球蛋白4抑制胃癌细胞的迁移、侵袭和转移。     

Multiple pipeline embolization devices improves aneurysm occlusion without increasing morbidity: A single center experience of 140 cases

IntroductionRates of aneurysm occlusion with the pipeline embolization device (PED) has varied widely in the literature from 55.7% to 93.3% at 6 months, which may reflect a difference in technique including sizing and number of devices used.Methods140 cases at our institution were retrospectively reviewed, and aneurysms treated with a single PED vs. multiple were compared.ResultsComplete aneurysm occlusion was achieved in 86.9% at 6 months, 91.8% at 1 year, and 97.6% at longest follow-up. Retreatment with an additional device was required in 7 (5.1%). Major and minor complication rate within 30 days was 1.4% and 5.0%, and at greater than 30 days was 0.8% and 3.1%.Patients treated with multiple PEDs had significantly higher rates of aneurysm occlusion at 6 months (92.9% vs. 75.6%, p = 0.017) and 12 months (98.4% vs. 81.1%, p = 0.014), with no difference in complications. The two groups were similar aside from a higher number of ophthalmic and paraophthalmic aneurysms treated with multiple PEDs (23.4% vs. 6.5%, p = 0.004; and 35.1% vs. 17.4%, p = 0.020), and more posterior communicating artery and recurrent aneurysms treated with a single PED (28.3% vs. 3.2%, p = 0.001; 23.9% vs. 8.5%, p = 0.031). The use of multiple PEDs was found to be an independent predictor of aneurysm occlusion in a multivariate analysis (p = 0.015).ConclusionsThe use of multiple PEDs for intracranial aneurysms leads to significantly higher occlusion rates without added morbidity. This benefit is particularly appropriate for ophthalmic segment aneurysms, while more distal segments with eloquent perforating branches should be managed with caution.     

Participatory research in Northwest Atlanta's Proctor Creek Watershed: Using photovoice to explore environmental health risks at the water's edge

In this study we used a participatory research method, photovoice, to explore community perceptions about environmental health risks, community assets, and strengths in and around an urban, degraded watershed in Northwest Atlanta, Georgia. This watershed, formed by Proctor Creek, is a focal point for redevelopment and infrastructure investments for years to come. Using a community-based participatory research approach, 10 Proctor Creek residents (watershed researchers), and a university partner, engaged in data collection; participatory data analysis; internal discussions; translation of research findings into watershed restoration, community revitalization, remedial action, and policy solutions; and dissemination of results to fellow watershed residents, stakeholders, and decision makers. We present a conceptual model linking the watershed researchers' understanding of urban policies and practice in the Proctor Creek Watershed to environmental, neighborhood and housing conditions and their influence on health outcomes and quality of life. Engaging community members in defining their own community environmental health challenges and assets yielded the following primary themes: 1) threats to the natural environment, 2) built environment stressors that influence health, 3) blight and divestment of public resources, and 4) hope for the future. Residents’ vision for the future of the watershed - a restored creek, revitalized neighborhoods, and restored people - is fueled by a strong connection to history, memory, and sense of place. We demonstrate the value of local knowledge in identifying previously unaddressed environmental health risks in the Proctor Creek Watershed as well as solutions to reduce or eliminate them.