Phosphatidylinositol-4,5-bisphosphate 3-kinases (PI3Ks) regulate several important cellular and subcellular processes including cell proliferation and differentiation. LY294002 was originally reported to be a selective inhibitor of PI3K-Akt. Later, it showed that this compound also inhibits several other molecules. In this study, we investigated the effect of LY294002 on the growth of suspension (MV4-11 and TF-1a) and tissue (Hep-G2) cells. In exponential phase, MV4-11 cells, but not TF-1a and Hep-G2 cells, expressed a low level of PI3Kp85 and addition of LY294002 inhibited the phosphorylation of PI3Kp85. LY294002 also significantly inhibited the proliferation of MV4-11, TF-1a and Hep-G2 cell and caused formation of cell clusters/aggregates measured by MTT and BrdU assays, and observed under an inverted microscope, respectively. Surprisingly, we found that LY294002 markedly repressed the activation of mitogen-activated protein kinase (MAPK) signal molecules, MEK and ERK, in all these cells. The inhibition of MEK and ERK was confirmed by using MEK stimulators, GM-CSF and phorbol 12-myristate 13-acetate, and MEK-specific inhibitor, PD98059. Although transforming growth factor beta (TGFβ) also inhibited the growth of Hep-G2 cells, it had no effect on the activity of MEK and ERK. see more The clusters/aggregates found in LY294002-treated cells were not detectable in TGFβ-treated cells. Our data suggest that LY294002 may directly inhibit the activation of MEK and ERK by its ability to bind to the ATP-binding site of the MAPK molecules.Renal cell carcinoma (RCC) scenario has radically changed with the advent of immunotherapy; in this setting, the identification of predictive and prognostic factors represents an urgent clinical need to evaluate which patients are the best candidate for an immunotherapy approach. The aim of our study was to analyze the association between nivolumab in pretreated patients with metastatic RCC and clinicopathological features, metastatic sites, and clinical outcomes. A total of 37 patients treated between January 2017 and April 2020 in our institution were retrospectively evaluated. All patients received nivolumab as second- or later-line of therapy after progression on previous tyrosine kinase inhibitors. The primary outcomes were overall survival (OS) from immunotherapy start and OS from first-line start. Univariate analysis was performed through the log-rank test and a Cox regression proportional hazards model was employed in multivariable analysis. Of the 12 variables analyzed, 4 were significantly associated with prognoses at multivariate analysis. Cox proportional hazard ratio models confirmed that International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) risk group, liver metastases at diagnosis, and central nervous system (CNS) metastases at diagnosis were associated with worse OS with an estimated hazard ratio of 4.76 [95% confidence interval (CI), 2.05-19.8] for liver metastases and 2.27 (95% CI, 1.13-28.9) for CNS metastases. Pancreatic metastases at diagnosis were correlated to a better prognosis with an estimated hazard ratio of 0.15 (95% CI, 0.02-0.38). IMDC risk group, liver metastases at diagnosis, and CNS metastases at diagnosis may identify a population of patients treated with immunotherapy in second- or later-line associated with worse prognosis.Treatment options for unresectable local recurrence or metastatic well-differentiated/dedifferentiated liposarcoma (WDLS/DDLS) remain limited. Different liposarcoma subtypes have varying clinical features and sensitivities to treatment regimens. The multitarget tyrosine kinase inhibitors (TKIs), such as pazopanib and regorafenib, have been approved for use in nonadipocytic soft tissue sarcomas (STS). Anlotinib, another TKI, has been approved in China for treating metastatic STS that has progressed after the use of anthracycline-based regimens. In this study, we aimed to evaluate the role of anlotinib in the treatment of local recurrence or metastatic WDLS/DDLS. From August 2018 to June 2020, 17 patients with unresectable local recurrence or metastatic WDLS/DDLS treated with anlotinib in our center were included. The follow-up cutoff time was set as 20 October 2020. Baseline and observation indicators were collected and analyzed. Estimated median progression-free survival (PFS) was 27.9 weeks, the PFS rate at 24 weeks was 58.8%, overall survival (OS) was 56.6 weeks, the disease control rate was 64.7% and no complete response or partial response was detected. Grade 3/4 adverse events occurred in four cases and could be managed. Anlotinib is a potential treatment option for unresectable local recurrence or metastatic WDLS/DDLS.A 71-year-old female was diagnosed with localized renal cell carcinoma in July 2008 with subsequent metastasis in 2012 to the right adrenal gland, lungs, and brain. Due to disease progression, she was started on pazopanib 800 mg daily in October 2012. In November 2016, the patient developed an ill-defined, red, 10 × 15 cm indurated plaque on the left lateral upper thigh with a discrete 3 cm firm tender tumor without ulceration. An incisional biopsy was performed and showed panniculitis with features resembling sclerosing lipogranuloma. Alternative causes including rheumatologic disease and trauma were ruled out. We report the first case of pazopanib-induced panniculitis. Key clinical and histopathological features include tender subcutaneous nodules, exclusion of other causes, and fatty microcysts within a densely sclerotic background on pathology. As targeted therapies are becoming increasingly common in the field of oncology, prompt identification and reporting of adverse reactions is critical for proper management.Lung cancer is one of the most common human cancers. Long noncoding RNA AFAP1-AS1 (LncRNA AFAP1-AS1) and microRNA-545-3p (miR-545-3p) were reported to play important roles in lung cancer development. This study aimed to elucidate the functional mechanisms of AFAP1-AS1 and miR-545-3p in lung cancer. Quantitative real time polymerase chain reaction was carried out to determine the levels of AFAP1-AS1, miR-545-3p and hepatoma-derived growth factor (HDGF). Cell proliferation, apoptosis, migration and invasion were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay, flow cytometry, and transwell migration and invasion assays, respectively. Furthermore, the interaction between miR-545-3p and AFAP1-AS1 or HDGF was predicted by bioinformatics analysis software starbase and confirmed by the dual luciferase reporter assay. Western blot assay was used to detect the protein level of HDGF. Besides, murine xenograft model was conducted through injecting A549 cells transfected with sh-AFAP1-AS1.