Efficacy of sorafenib on metastatic renal cell carcinoma in Asian patients: Results from a multicenter study

<p>Abstract</p> <p>Background</p> <p>The effects of sorafenib in the treatment of advanced renal cell carcinoma (RCC) have been confirmed in an international collaborative phase III trial. This study aims to confirm similar efficacy and treatment-induced toxicities of sorafenib in the treatment of metastatic RCC in ethnic Chinese patients.</p> <p>Methods</p> <p>Ninety-eight consecutive and non-selected patients with pathologically confirmed metastatic RCC were treated according to an institutional treatment protocol. All patients were treated with 400 mg of sorafenib orally twice daily on a continuous basis until disease progression or intolerance to treatment occurred. Dose reduction to 400 mg once daily was required if grade 3 or 4 toxicities occurred. All patients except for 7 received nephrectomy in the course of their disease. All patients were assessed for tumor response, progression-free survival (PFS), overall survival (OS), and treatment-induced toxicities.</p> <p>Results</p> <p>The median follow-up time was 76 weeks (range 2–296 weeks) for the entire group of patients. Radiologically confirmed complete response (CR), partial response (PR), stable disease (SD) of more than 4 months, and disease progression as best objective responses were observed in 1 (1%), 23 (23.5%), 62 (63.3%), and 12 (12.2%) patients, respectively. The tumor control rate (CR+PR+SD of >4 months) was 87.8%. The 1-year estimated PFS and OS were 58.4% and 64.6%, respectively. The median progression-free survival (PFS) time was 60 weeks (95% CI 41–79); and the median overall survival (OS) time was not reached with a follow-up of 76 weeks. Reduction of sorafenib dose was required in 26 patients who developed grade 3 or 4 treatment-cause adverse-effects. An additional 9 patients discontinued sorafenib treatment due to severe adverse-effects. No grade 5 toxicity occurred.</p> <p>Multivariate analysis revealed that independent predictive factors for tumor response to sorafenib treatment included ECOG status, presence of lymph node metastasis, and nephrectomy prior to the development of metastasis.</p> <p>Conclusion</p> <p>Sorafenib produced an 87.8% disease control rate for metastatic renal cell carcinoma in Chinese patients, with acceptable rates of toxicity. The medication dosed at 400 mg twice daily is both efficacious and safe in the treatment of metastatic renal cell carcinoma in Chinese patients.</p

Nitroxoline suppresses metastasis in bladder cancer via EGR1/circNDRG1/miR-520h/smad7/EMT signaling pathway

Bladder cancer is one of the most common and deadly cancer worldwide. Current chemotherapy has shown limited efficacy in improving outcomes for patients. Nitroxoline, an old and widely used oral antibiotic, which was known to treat for urinary tract infection for decades. Recent studies suggested that nitroxoline suppressed the tumor progression and metastasis, especially in bladder cancer. However, the underlying mechanism for anti-tumor activity of nitroxoline remains unclear. Methods: CircRNA microarray was used to explore the nitroxoline-mediated circRNA expression profile of bladder cancer lines. Transwell and wound-healing assay were applied to evaluate the capacity of metastasis. ChIP assay was chosen to prove the binding of promotor and transcription factor. RNA-pulldown assay was performed to explore the sponge of circRNA and microRNA. Results: We first identified the circNDRG1 (has_circ_0085656) as a novel candidate circRNA. Transwell and wound-healing assay demonstrated that circNDRG1 inhibited the metastasis of bladder cancer. ChIP assay showed that circNDRG1 was regulated by the transcription factor EGR1 by binding the promotor of host gene NDRG1. RNA-pulldown assay proved that circNDRG1 sponged miR-520h leading to the overexpression of smad7, which was a negative regulatory protein of EMT. Conclusions: Our research revealed that nitroxoline may suppress metastasis in bladder cancer via EGR1/circNDRG1/miR-520h/smad7/EMT signaling pathway

Five Inhibitory Receptors Display Distinct Vesicular Distributions in Murine T Cells.

T cells can express multiple inhibitory receptors. Upon induction of T cell exhaustion in response to a persistent antigen, prominently in the anti-tumor immune response, many are expressed simultaneously. Key inhibitory receptors are CTLA-4, PD-1, LAG3, TIM3, and TIGIT, as investigated here. These receptors are important as central therapeutic targets in cancer immunotherapy. Inhibitory receptors are not constitutively expressed on the cell surface, but substantial fractions reside in intracellular vesicular structures. It remains unresolved to which extent the subcellular localization of different inhibitory receptors is distinct. Using quantitative imaging of subcellular distributions and plasma membrane insertion as complemented by proximity proteomics and biochemical analysis of the association of the inhibitory receptors with trafficking adaptors, the subcellular distributions of the five inhibitory receptors were discrete. The distribution of CTLA-4 was most distinct, with preferential association with lysosomal-derived vesicles and the sorting nexin 1/2/5/6 transport machinery. With a lack of evidence for the existence of specific vesicle subtypes to explain divergent inhibitory receptor distributions, we suggest that such distributions are driven by divergent trafficking through an overlapping joint set of vesicular structures. This extensive characterization of the subcellular localization of five inhibitory receptors in relation to each other lays the foundation for the molecular investigation of their trafficking and its therapeutic exploitation

The Effects of Venture Capital Investment on P2P Lending: Evidence from Users™ Responses in Social Media

Using panel-structured data from a leading P2P lending portal in China, we investigate the effects of VC investment on the performance of Chinese peer-to-peer (P2P) lending platforms. We find that VCs prefer to the platforms having larger transaction vol

Exfiltrating data from an air-gapped system through a screen-camera covert channel

In recent years, many methods of exfiltrating information from air-gapped systems, including electromagnetic, thermal, acoustic and optical covert channels, have been proposed. However, as a typical optical channel, the screen-camera method has rarely been considered; it is less covert because it is visible to humans. In this paper, inspired by the rapid upgrades of cameras and monitors, we propose an air-gapped screen-camera covert channel with decreased perceptibility that is suitable for complex content. Our method exploits the characteristics of the human vision system (HVS) and embeds quick response (QR) codes containing sensitive data in the displayed frames. This slight modification of the frames cannot be sensed by the HVS but can be recorded by the cameras. Then, using certain image processing techniques, we reconstruct the QR codes to some degree and extract the secret data with a certain level of robustness due to the error correction capacity of QR codes. In the scenario to which our method applies, we assume that a program has been installed in the target system and has the authority to modify the frames without affecting the normal operations of valid users. Cameras, such as web cameras, surveillance cameras and smartphone cameras, can be receivers in our method. We illustrate the applicability of our method to frames with complex content using several different cover images. Experiments involving different angles between the screen and the camera were conducted to highlight the feasibility of our method with angles of 0°,15° and 30°