Hematopoietic pre-B cell leukemia transcription factor interacting protein (HPIP) has been shown to play an important role in the development and progression of some cancers. However, the role of HPIP in gastric cancer (GC) is unclear. Here, we show that HPIP is upregulated in most GC patients and promotes GC cell proliferation, migration, and invasion. In GC patients, HPIP positively associates with tumor size and nodal metastasis, and negatively associates with tumor differentiation. Hematopoietic pre-B cell leukemia transcription factor interacting protein increases GC cell proliferation through activation of G1/S and G2/M cell cycle transitions, accompanied by a marked increase of the positive cell cycle regulators, including cyclin D1, cyclin A, and cyclin B1. Hematopoietic pre-B cell leukemia transcription factor interacting protein enhances GC cell migration and invasion, and modulates epithelial–mesenchymal transition, which plays a key role in cancer cell migration and invasion. These data underscore the critical role of HPIP in GC cell proliferation and progression and suggest that HPIP inhibition may be a useful therapeutic strategy for GC treatment.

Hematopoietic pre-B cell leukemia transcription factor (PBX)-interacting protein (HPIP) was shown to be crucial during the development and progression of a variety of tumors. However, the role of HPIP in renal cell carcinoma (RCC) is unknown. Here we report that HPIP is upregulated in most RCC patients, positively correlates with tumor size, high Fuhrman grade and preoperative metastasis, and predicts poor clinical outcomes. Mechanistically, we identified casein kinase 1α (CK1α), a critical regulator of tumorigenesis and metastasis, as a novel HPIP-interacting protein. HPIP facilitates RCC cell growth, migration, invasion and epithelial–mesenchymal transition depending on its interaction with CK1α. Activation of mammalian target of rapamycin pathways by HPIP is partly dependent on CK1α and is required for HPIP modulation of RCC cell proliferation and migration. HPIP knockdown suppresses renal tumor growth and metastasis in nude mice through CK1α. Moreover, expression of CK1α is positively correlated with HPIP in RCC samples, and also predicts poor clinical outcome-like expression of HPIP. Taken together, our data demonstrate the critical regulatory role of the HPIP–CK1α interaction in RCC, and suggest that HPIP and CK1α may be potential targets for RCC therapy.

This single-center, observational study analyzed the association between plasma concentration of sorafenib and its safety and efficacy in Chinese patients with metastatic renal cell carcinoma (mRCC). Adult patients with RCC (n = 94), treated with sorafenib were enrolled between January 2014 and January 2015. Sorafenib plasma concentrations were measured by liquid chromatography-tandem mass spectrometry. Safety and efficacy variables were evaluated using National Cancer Institute-Common Toxicity Criteria for Adverse Events and Response Evaluation Criteria in Solid Tumors criteria. Association of plasma concentration with safety and efficacy was analyzed. The steady state plasma concentration of sorafenib after 2 weeks of treatment ranged from 881 to 12,526 ng/mL. Major adverse reactions (ADRs) included diarrhea (76.5%), hand-foot syndrome (HFS; 68.99%) and fatigue (55.32%). Significant association was reported between plasma concentration and all the ADRs except rash. At 6 weeks, complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) was reported in 3.1%, 13.82%, 52.2% and 13.82% patients, respectively. Objective response and disease control rates were 17.02% and 69.14%. Plasma concentration of sorafenib was >10,000 ng/mL in patients with severe ADRs, which decreased with reduction in dose or discontinuation of treatment. After 21.2 weeks follow-up, median progression free survival was 12.3 months. CR, PR, SD and PD were reported in 1%, 46%, 33% and 19% patients. In conclusion, plasma concentration of sorafenib was associated with its safety and efficacy in Chinese patients with mRCC.

Background: The incidence of gastric cardia cancer (GCC) patients has been increasing, while the survival trends of GCC patients over time remains unclear. Thus, the aim of our study was to determine the survival trends of GCC patients over time using a population-based data in the United States. Methods: A total of 9044 surgically resected GCC patients during 1988 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were identified. The survival probabilities were calculated by Kaplan-Meier method and the different survival probabilities between groups were examined by log-rank test. Results: The median overall survival time was 27 (interquartile range, 12 to 99) months, and the median disease-specific survival time was 32 (interquartile range, 13 to 320) months for GCC patients. There was a statistically significant increase in median overall survival time (17 to 46 mo; P<0.001) and disease-specific survival time (19 to 67 mo; P<0.001) from 1988 to 1997 to 2008 to 2015. More GCC patients were diagnosed at an early stage in recent years. Meanwhile, adequate lymph nodes examined (eLNs) were obtained in more GCC patients during surgery. Also, the proportion of GCC patients who received chemoradiotherapy increased significantly. Moreover, early diagnosis, adequate eLNs, and chemoradiotherapy were associated with mortality. Conclusions: The survival rates of surgically resected GCC patients had a significant improvement from 1988 to 1997 to 2008 to 2015 in the United States, which might relate to the early discovery of GCC, greater utilization of adequate eLNs, and chemoradiotherapy.

No abstract