Blocking circ_0014130 suppressed drug resistance and malignant behaviors of docetaxel resistance-acquired NSCLC cells via regulating miR-545-3p-YAP1 axis.

Recent evidences have claimed that circular RNAs are deregulated in docetaxel (DTX) resistance in malignant tumors, including non-small-cell lung cancer (NSCLC). Hsa_circ_0014130 (circ_0014130) is a new biomarker in NSCLC. However, its role in DTX-resistant NSCLC remained to be annotated. In this study, real-time PCR was used to measure expression of circ_0014130, and circ_0014130 was upregulated in NSCLC tumors and DTX-resistant NSCLC cells (NCI-H1299/DTX and A549/DTX). MTT assay analyzed the half inhibitory concentration (IC50) of DTX, and it was lowered by circ_0014130 interference in DTX-resistant NSCLC cells. Moreover, colony formation assay, flow cytometry, transwell assays, and xenograft tumor model revealed that silencing circ_0014130 facilitated apoptosis rate of DTX-resistant NSCLC cells, suppressed the colony formation, migration and invasion, and retarded xenograft tumor growth in nude mice. Dual-luciferase reporter assay and RNA immunoprecipitation confirmed that circ_0014130 was one competing endogenous RNA (ceRNA) for miRNA (miR)-545-3p, and circ_0014130 modulated expression of yes-associated protein 1 (YAP1), a target gene for miR-545-3p. YAP1 upregulation and miR-545-3p downregulation were allied with circ_0014130 upregulation in NSCLC tumors and DTX-resistant NSCLC cells. Functionally, downregulating miR-545-3p could abate the effects of circ_0014130 knockdown in DTX-resistant NSCLC cells in vitro, whereas its overexpression exerted similar effects of circ_0014130 knockdown. Either, restoring YAP1 partially reversed miR-545-3p effects in DTX-resistant NSCLC cells. Collectively, there might be a novel circ_0014130-miR-545-3p-YAP1 ceRNA pathway in regulation of chemoresistance and malignant behaviors of DTX-resistant NSCLC cells, suggesting a potential therapeutic approach for DTX resistance.

Cerebral Arterial Bifurcations Harboring D Type Aneurysm are more Asymmetrical than those with C Type Aneurysm.

OBJECTIVES: This study was designed to determine aneurysm deviation and to compare anatomical differences of bifurcations harboring C and D-type aneurysms. MATERIALS AND METHODS: A total of 198 arterial bifurcations harboring aneurysms were enrolled in this study, including 58 anterior cerebral arteries (ACAs), 64 middle cerebral arteries (MCAs), 19 basilar arteries (BAs), and 57 internal carotid artery-posterior communicating arteries (ICA-PComAs). Aneurysms were defined as C type if the neck was located on the extension of the parent artery midline and D type if it was not, then, aneurysm deviation was examined. The angles forming between bilateral branching arteries and the main artery were lateral angles, and smaller one named φ2, larger one termed φ3, respectively, D2, S2, C2 and T2 representing the diameter, cross-sectional area, circumference, and tortuosity of the branch forming angle φ2 with the parent vessel, respectively, and D3, S3, C3 and T3 representing the corresponding values of the contralateral branch. The lateral angle ratio (LA ratio; larger lateral angle/smaller lateral angle), daughter artery ratio (DA ratio; the diameter of branch forming larger lateral angle with parent artery/ the diameter of contralateral branch), SA (S3/S2), CA (C3/C2) and TA (T3/T2) ratios were used to describe bifurcation symmetry. RESULTS: The angle φ2 of the main cerebral bifurcations was significantly smaller than the angle φ3, whereas T2 was significantly larger than T3. Most of the C-type and 100% of the D-type aneurysms deviated toward the angle φ2. The LA, DA, SA and CA ratios of ACA, MCA bifurcations and ICA-PComAs harboring D-type aneurysms were all significantly larger than those harboring C-type aneurysms; moreover, the LA, DA and SA ratios demonstrated significant differences between the bifurcations with C and D-type aneurysms, as determined by ROC analysis. CONCLUSIONS: The majority of C-type and all of the D-type aneurysms deviated toward the smaller lateral angle, and bifurcations harboring D-type aneurysms were more asymmetrical than those harboring C-type aneurysms.

Multidisciplinary treatment of primary intracranial yolk sac tumor: A case report and literature review.

RATIONALE: Intracranial yolk sac tumors (YSTs) are rare malignancies with limited treatment options and a dismal prognosis. They are usually managed with surgical resection and chemoradiotherapy. PATIENT CONCERNS: Here, we report a patient with primary YST in the pineal region who achieved long term survival. Despite undergoing treatment, he experienced several recurrences over a 15-year period. DIAGNOSIS: Brain magnetic resonance imaging (MRI) demonstrated the presence of space-occupying lesions in the pineal region and the medial tail of the left lateral ventricle. The tumors were excised, and the histological diagnosis suggested an intracranial YST. INTERVENTIONS: The patient achieved long term survival after combined modality therapy including surgery, stereotactic radiosurgery (SRS)/intensity modulated radiation therapy (IMRT), chemotherapy, and targeted therapy. OUTCOMES: The disease remained stable. However, the patient gave up treatment and passed away in October 2020, with a total survival of about 15 years. LESSONS: To the best of our knowledge, this patient with intracranial YST had received a longer survival compared with other published reports. We summarize previously published reports of intracranial YST and discuss the importance of multidisciplinary treatment. SRS may have a role, as a focal boost to residual tumor after resection or in case of recurrence after conventional radiotherapy, in the multimodality management of intracranial YSTs.

MicroRNA expression profile and TNM staging system predict survival in patients with lung adenocarcinoma.

ObjectThe current study was performed to construct a model with microRNA (miRNA/miR) expression profile and TNM staging system for prognosis predicting in patients with lung adenocarcinoma (LUAD). MethodsDifferentially expressed miRNAs were identified from miRNA data of LUAD in The Cancer Genome Atlas (TCGA) database. Potential prognostic miRNAs and TNM classification parameters, screened out by Cox proportional hazards regression analysis, were included in the prognostic model. The prognostic model was visualized with a nomogram, and tested by calculating the C-index and drawing the calibration curve in the training set and validating set, respectively. Finally, the prognostic miRNAs were analyzed with bioinformatics tools. ResultsA total of 194 differentially expressed miRNAs were identified between LUAD tissues and matched normal tissues, including 99 up-regulated and 95 down-regulated miRNAs. miRNA index (miR.index), constructed with nine miRNAs (hsa-let-7i, hsa-mir-1976, hsa-mir-199a-1, hsa-mir-31, hsa-mir-3940, hsa-mir-450a-2, hsa-mir-4677, hsa-mir-548v and hsa-mir-6803), was an independent prognostic indicator for the survival of patients with LUAD. Bioinformatics analysis suggests that the selected miRNAs are involved in the development and progress of LUAD. ConclusionThe prognostic model constructed with nine miRNA expression profile and TNM classification parameters can predict the survival in patients with LUAD, and the predictive power of the model are warranted for further validations.

A meta-analysis of treatment effects of imiquimod for basal cell carcinoma.

OBJECTIVE: We conducted this meta-analysis to assess the efficacy and safety of imiquimod in comparison with other treatments in patients with BCC. METHODS: A comprehensive literature search was performed in the database of PubMed, Embase, and Web of Science. Outcomes of interest included histological/composite clearance rate, success rate, complete response rate, tumor free survival, and adverse events. Pooled risk ratio (RR) with 95% confidence intervals (CIs) using a fixed-effects or random-effects model were determined for each outcome. RESULTS: A total of 13 studies involving 4256 patients were identified. Imiquimod was associated with significantly higher histological clearance rate (RR = 9.28, 95%CI: 5.56, 15.49; P < .001) and composite clearance rate (RR = 34.24, 95%CI: 21.29, 55.06; P = .001). Moreover, imiquimod also significantly increased complete response rate (RR = 3.15, 95%CI: 1.55, 6.38; P = .001) but had no effect in the success rate (RR = 0.98, 95%CI: 0.89, 1.08; P = .727) and probability of tumor-free survival (RR = 1.15, 95%CI: 0.98, 1.35; P = .088), as compared with other treatments. There were more patients in imiquimod group who developed adverse events than in other treatment group (RR = 2.00, 95%CI: 1.39, 2.88; P < .001). CONCLUSION: This study indicated the effects of imiquimod in improving the histological/composite clearance rates as compared with other treatments. However, its treatment-related adverse events also should be noticed. Our findings supported that, imiquimod could be used as the first-choice treatment for BCC.

Concurrent apatinib and local radiation therapy for advanced gastric cancer: A case report and review of the literature.

RATIONALE: Apatinib is a novel anti-angiogenic agent targeting vascular endothelial growth factor receptor-2, which is effective in patients with chemotherapy-refractory gastric cancer. There are no reports of concurrent apatinib with local radiation therapy in elderly patients with advanced gastric cancer. PATIENT CONCERNS AND DIAGNOSES:: we present the first published report of a 70-year-old male patient with advanced gastric cancer who received concurrent apatinib and local radiation therapy after failure of oxaliplatin and S-1 chemotherapy. INTERVENTIONS AND OUTCOMES: The patient received concurrent apatinib and local radiation therapy and was followed up 7 months after therapy without disease progress, 14 months later indicated extensive metastasis and this patient died of pulmonary infection. LESSONS: Elderly patients with advanced gastric cancer may benefit from concurrent apatinib with local radiation therapy when chemotherapy is not tolerated or successful. Further studies are needed to investigate the clinical outcomes and toxicities associated with concurrent apatinib and radiation therapy in gastric cancer.