Renal cell carcinoma (RCC) occurs in 2-4% of patients with tuberous sclerosis complex (TSC). Previous reports have noted a variety of histologic appearances in these cancers, but the full spectrum of morphologic and molecular features has not been fully elucidated. We encountered 46 renal epithelial neoplasms from 19 TSC patients and analyzed their clinical, pathological and molecular features, enabling separation of these 46 tumors into three groups. The largest subset of tumors (n=24) had a distinct morphological, immunological and molecular profile, including prominent papillary architecture and uniformly deficient SDHB expression prompting the novel term “TSC-associated papillary RCC.” The second group (n=15) was morphologically similar to a hybrid oncocytic/chromophobe tumor (HOCT) while the last 7 renal epithelial neoplasms of group 3 remained unclassifiable. The TSC-associated papillary RCCs (PRCC) had prominent papillary architecture lined by clear cells with delicate eosinophilic cytoplasmic thread-like strands that occasionally appeared more prominent and aggregated to form eosinophilic globules. All 24 (100%) of these tumors were the International Society of Urological Pathology (ISUP) nucleolar grade 2 or 3 with mostly basally located nuclei. Tumor cells from 17 of 24 TSC-associated PRCC showed strong, diffuse labeling for CA-IX (100%), CK7 (94%), vimentin (88%), CD10 (83%), and were uniformly negative for succinate dehydrogenase subunit B (SDHB), TFE3 and AMACR. Gains of chromosomes 7 and 17 were found in 2 tumors, whereas chromosome 3p deletion and TFE3 translocations were not detected. In this study, we reported a sizable cohort of renal tumors seen in TSC and were able to identify them as different morphotypes which may help to expand the morphologic spectrum of TSC-associated RCC.

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Prostate cancer (PCa) is one of the major men malignancies worldwide. Long noncoding RNAs (lncRNAs) have been reported as essential regulators in human cancers, including PCa. In the present study, lncRNA forkhead box P4 antisense RNA 1 (FOXP4-AS1) was found to be highly expressed in TCGA PCa samples. Upregulation of FOXP4-AS1 was further validated in 64 PCa tissues and predicted poor prognosis in patients with PCa. Functionally, high FOXP4-AS1 level was associated with increased cell proliferation and decreased cell apoptosis, indicating that FOXP4-AS1 exerted oncogenic functions in the tumorigenesis of PCa. Furthermore, FOXP4-AS1 was located in the cytoplasm of PCa cell lines and positively regulated FOXP4. LncRNAs can exert their functions by cooperating with their nearby genes. Mechanistically, FOXP4-AS1 post-transcriptionally regulated FOXP4 by acting as a competing endogenous RNA (ceRNA) in PCa to sponge miR-3184-5p. Considering the upregulation of both FOXP4-AS1 and its nearby gene FOXP4, we further detected the coactivator of FOXP4-AS1 and FOXP4. Mechanism analysis indicated that paired box 5 (PAX5) transcriptionally activated FOXP4-AS1 and FOXP4 in PCa. Collectively, we determined that PAX5-induced upregulation of FOXP4-AS1/FOXP4 axis promoted tumorigenesis of PCa.

Early aggressive metastasis of osteosarcoma (OS) leads to rapid progression and poor prognosis. Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) could serve as crucial regulators to modulate tumour metastasis. In this study, we reported the critical role of lncRNA TUG1 in determining OS metastasis. TUG1 was significantly upregulated in OS tissues and associated with tumour size, distant metastasis, TNM stage, and overall and recurrence-free survival, which further indicated poor prognosis. Furthermore, CAFs-derived TGF-β could upregulate TUG1 expression, and the crosstalk between CAFs and OS cells induced TUG1 to promote OS cell metastasis. Dysregulated TUG1 expression could act as an miRNA “sponge” to competitively protect the HIF-1α mRNA 3′UTR from miR-143-5p. Our study emphasised the effects of TUG1 in OS and demonstrated a novel axis by which TUG1 regulated OS cell metastasis, angiogenesis, and proliferation in vivo and in vitro. Collectively, TUG1 might be a prognostic indicator for OS and could be a therapeutic target for OS.

MiR‐329 has been proved to be a tumor suppressor gene in various malignancies, however, its role in osteosarcoma remains elusive. We found that miR‐329 is remarkably downregulated in osteosarcoma tissues and relates to advanced stages. MiR‐329 is able to inhibit osteosarcoma cell proliferation, promote apoptosis, and induce G0/G1 cell cycle arrest. In addition, miR‐329 also suppresses wound‐healing and migration ability of osteosarcoma cells and inhibits tumorigenicity in vivo. Rab10 was identified as a target of miR‐329 in osteosarcoma and mediates its biofunction. These findings may shed light to the understanding of tumor development in osteosarcoma.

BackgroundWhether men with a prostate‐specific antigen (PSA) level of 4–10 ng/mL should be recommended for a biopsy is clinically challenging.PurposeTo develop and validate a radiomics model based on multiparametric MRI (mp‐MRI) in patients with PSA levels of 4–10 ng/mL to predict prostate cancer (PCa) preoperatively and reduce unnecessary biopsies.Study TypeRetrospective.SubjectsIn all, 199 patients with PSA levels of 4–10 ng/mL.Field Strength/Sequence3T, T2‐weighted, diffusion‐weighted, and dynamic contrast‐enhanced MRI.AssessmentLesion regions of interest (ROIs) from T2‐weighted, diffusion‐weighted, and dynamic contrast‐enhanced MRI were annotated by two radiologists. A total of 2104 radiomic features were extracted from the ROI of each patient. A random forest classifier was used to build the radiomics model for PCa in the primary cohort. A combined model was constructed using multivariate logistic regression by incorporating the radiomics signature and clinical‐radiological risk factors.Statistical TestsFor continuous variables, variance equality was assessed by Levene's test and Student's t‐test, and Welch's t‐test was used to assess between‐group differences. For categorical variables, Pearson's chi‐square test, Fisher's exact test, or the approximate chi‐square test was used to assess between‐group differences. P < 0.05 was considered statistically significant.ResultsThe combined model incorporating the multi‐imaging fusion model, age, PSA density (PSAD), and the PI‐RADS v2 score yielded area under the curve (AUC) values of 0.956 and 0.933 on the primary (n = 133) and validation (n = 66) cohorts, respectively. Compared with the clinical‐radiological model, the combined model performed better on both the primary and validation cohorts (P < 0.05). Furthermore, the use of the combined model to predict PCa could identify more negative PCa patients than the use of the clinical‐radiological model by 18.4%.Data ConclusionThe combined model was developed and validated to provide potential preoperative prediction of PCa in men with PSA levels of 4–10 ng/mL and might aid in treatment decision‐making and reduce unnecessary biopsies.Level of Evidence: 3Technical Efficacy Stage: 3J. Magn. Reson. Imaging 2020;51:1890–1899.

BackgroundMetabolites of arachidonic acid such as prostacyclin (PGI2) have been shown to participate in the pathogenesis of pulmonary fibrosis by inhibiting the expression of pro-inflammatory and pro-fibrotic mediators. In this investigation, we examined whether iloprost, a stable PGI2 analogue, could prevent bleomycin-induced pulmonary inflammation and fibrosis in a mouse model.MethodsMice received a single intratracheal injection of bleomycin with or without intraperitoneal iloprost. Pulmonary inflammation and fibrosis were analysed by histological evaluation, cellular composition of bronchoalveolar lavage (BAL) fluid, and hydroxyproline content. Lung mechanics were measured. We also analysed the expression of inflammatory mediators in BAL fluid and lung tissue.ResultsAdministration of iloprost significantly improved survival rate and reduced weight loss in the mice induced by bleomycin. The severe inflammatory response and fibrotic changes were significantly attenuated in the mice treated with iloprost as shown by reduction in infiltration of inflammatory cells into the airways and pulmonary parenchyma, diminution in interstitial collagen deposition, and lung hydroxyproline content. Iloprost significantly improved lung static compliance and tissue elastance. It increased the expression of IFNγ and CXCL10 in lung tissue measured by RT-PCR and their levels in BAL fluid as measured by ELISA. Levels of TNFα, IL-6 and TGFβ1 were lowered by iloprost.ConclusionsIloprost prevents bleomycin-induced pulmonary fibrosis, possibly by upregulating antifibrotic mediators (IFNγ and CXCL10) and downregulating pro-inflammatory and pro-fibrotic cytokines (TNFα, IL-6, and TGFβ1). Prostacyclin may represent a novel pharmacological agent for treating pulmonary fibrotic diseases.

PurposeTo compare the diagnostic accuracy of biparametric MRI (bpMRI) and multiparametric MRI (mpMRI) for prostate cancer (PCa) and clinically significant prostate cancer (csPCa) and to explore the application value of dynamic contrast-enhanced (DCE) MRI in prostate imaging.Methods and materialsThis study retrospectively enrolled 235 patients with suspected PCa in our hospital from January 2016 to December 2017, and all lesions were histopathologically confirmed. The lesions were scored according to the Prostate Imaging Reporting and Data System version 2 (PI-RADS V2). The bpMRI (T2-weighted imaging [T2WI], diffusion-weighted imaging [DWI]/apparent diffusion coefficient [ADC]) and mpMRI (T2WI, DWI/ADC and DCE) scores were recorded to plot the receiver operating characteristic (ROC) curves. The area under the curve (AUC), accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for each method were calculated and compared. The patients were further stratified according to bpMRI scores (bpMRI ≥3, and bpMRI = 3, 4, 5) to analyse the difference in DCE MRI between PCa and non-PCa lesions (as well as between csPCa and non-csPCa).ResultsThe AUC values for the bpMRI and mpMRI protocols for PCa were comparable (0.790 [0.732–0.840] and 0.791 [0.733–0.841], respectively). The accuracy, sensitivity, specificity, PPV and NPV of bpMRI for PCa were 76.2, 79.5, 72.6, 75.8, and 76.6%, respectively, and the values for mpMRI were 77.4, 84.4, 69.9, 75.2, and 80.6%, respectively. The AUC values for the bpMRI and mpMRI protocols for the diagnosis of csPCa were similar (0.781 [0.722–0.832] and 0.779 [0.721–0.831], respectively). The accuracy, sensitivity, specificity, PPV and NPV of bpMRI for csPCa were 74.0, 83.8, 66.9, 64.8, and 85.0%, respectively; and 73.6, 87.9, 63.2, 63.2, and 87.8%, respectively, for mpMRI. For patients with bpMRI scores ≥3, positive DCE results were more common in PCa and csPCa lesions (both P = 0.001). Further stratification analysis showed that for patients with a bpMRI score = 4, PCa and csPCa lesions were more likely to have positive DCE results (P = 0.003 and P < 0.001, respectively).ConclusionThe diagnostic accuracy of bpMRI is comparable with that of mpMRI in the detection of PCa and the identification of csPCa. DCE MRI is helpful in further identifying PCa and csPCa lesions in patients with bpMRI ≥3, especially bpMRI = 4, which may be conducive to achieving a more accurate PCa risk stratification. Rather than omitting DCE, we think further comprehensive studies are required for prostate MRI.