[Comparison of the predictive value of Padua and the IMPEDE assessment scores for venous thromboembolism in patients with newly diagnosed multiple myeloma: A single institution experience].

Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.

Peri-prostatic adipose tissue measurements using MRI predict prostate cancer aggressiveness in men undergoing radical prostatectomy.

OBJECTIVES: To evaluate the effect of peri-prostatic adipose tissue (PPAT) measurements using preoperative MRI on the prediction of prostate cancer (PCa) aggressiveness in men undergoing radical prostatectomy (RP). METHODS: We performed a retrospective study on 179 consecutive patients receiving RP from June 2016 to October 2018. Clinical characteristics were collected. PPAT measurements including peri-prostatic fat area (PPFA) and peri-prostatic fat area to prostate area (PA) ratio (PPFA/PA) were calculated by MRI. Multivariable logistic regression analysis was performed to identify independent predictors of PCa lymph node metastasis (LNM). The predictive performance was estimated through ROC curves. Nomograms were created based on the predictors. RESULTS: Pathologic Gleason score positively correlated with digital rectal examination (DRE), PSA, PPFA/PA, P504S, and Ki-67 (all P < 0.05). ROC curves revealed that high PPFA and high PPFA/PA were associated with LNM (both P < 0.05). Multivariate analysis revealed that high PPFA/PA, pathologic Gleason score, pT stage, and Ki-67 were independently predictive of LNM. The nomograms were created and the C-index was 0.945. CONCLUSIONS: PPFA/PA is an independent predictor for LNM along with Gleason score, pT stage, and Ki-67. PPFA/PA may help predict LNM in men undergoing RP, thus providing adjunctive information for therapeutic strategy and prognosis.

Decreased REG1α expression suppresses growth, invasion and angiogenesis of bladder cancer.

BACKGROUND: Previous study has indicated association between REG1α and bladder cancer. The aim of this study was to investigate the role of Regenerating gene I alpha (REG1α) in bladder cancer. METHODS: The role of REG1α in bladder cancer cell proliferation, migration and VEGF-induced angiogenesis was explored in vitro and in vivo. Immunohistochemistry (IHC) analysis was assessed to determine the expression of REG1α in ten paired bladder cancer and adjacent non-cancerous tissues, and in 296 bladder cancer samples. RESULTS: Down-regulation of REG1α expression significantly reduced the proliferation, migration, invasion and VEGF-induced angiogenesis in vitro and the growth of xenograft tumors in vivo. VEGF expression in bladder cancer is associated with REG1α expression and recurrence. REG1α was overexpressed in bladder cancer tissues compared with adjacent normal samples. Patients with elevated REG1α exhibited shorter recurrence times and poor survival. CONCLUSION: Downregulation of REG1α expression can reduce tumor growth, migration, invasion and angiogenesis. Our study demonstrates that REG1α can be used as a marker of recurrence and prognosis in bladder cancer. Therefore, REG1α targeting in bladder cancer patients represents a promising therapeutic strategy.

Novel chimpanzee adenovirus-vectored respiratory mucosal tuberculosis vaccine: overcoming local anti-human adenovirus immunity for potent TB protection.

Pulmonary tuberculosis (TB) remains to be a major global health problem despite many decades of parenteral use of Bacillus Calmette-Guérin (BCG) vaccine. Developing safe and effective respiratory mucosal TB vaccines represents a unique challenge. Over the past decade or so, the human serotype 5 adenovirus (AdHu5)-based TB vaccine has emerged as one of the most promising candidates based on a plethora of preclinical and early clinical studies. However, anti-AdHu5 immunity widely present in the lung of humans poses a serious gap and limitation to its real-world applications. In this study we have developed a novel chimpanzee adenovirus 68 (AdCh68)-vectored TB vaccine amenable to the respiratory route of vaccination. We have evaluated AdCh68-based TB vaccine for its safety, T-cell immunogenicity, and protective efficacy in relevant animal models of human pulmonary TB with or without parenteral BCG priming. We have also compared AdCh68-based TB vaccine with its AdHu5 counterpart in both naive animals and those with preexisting anti-AdHu5 immunity in the lung. We provide compelling evidence that AdCh68-based TB vaccine is not only safe when delivered to the respiratory tract but, importantly, is also superior to its AdHu5 counterpart in induction of T-cell responses and immune protection, and limiting lung immunopathology in the presence of preexisting anti-AdHu5 immunity in the lung. Our findings thus suggest AdCh68-based TB vaccine to be an ideal candidate for respiratory mucosal immunization, endorsing its further clinical development in humans.

Downregulated miR-646 in clear cell renal carcinoma correlated with tumour metastasis by targeting the nin one binding protein (NOB1).

BACKGROUND: Nin one binding protein (NOB1) was identified as a potential oncogene in human glioma and miR-646 plays an important role in human growth and development. However, the underlying molecular mechanisms of NOB1 in tumorigenicity and its correlation with miR-646 in renal cell carcinoma (RCC) have not been investigated. METHODS: We performed bioinformatic analysis to explore miRNA targeting NOB1. The expression of NOB1 and miR-646 from 100 cases of clear cell RCC (ccRCC) and 30 cases of adjacent non-tumour tissues were detected by quantitative real-time PCR. The expression of miR-646 was correlated with NOB1 expression, tumour features and patient metastasis-free survival. The effect of overexpression of mir-646 on renal cancer cell proliferation was detected by colony formation in soft agar. Using a xenograft tumour model, we observed the in vivo tumorigenesis effect of miR-646 and NOB1. RESULTS: miR-646 negatively regulated NOB1 and inhibited the proliferation and migration of renal cancer cells. There was a significant upregulation of NOB1 in ccRCC and it was further increased in metastatic cases, while miR-646 was downregulated in tumour tissues and further decreased in metastatic ccRCC. Additionally, expression of miR-646 was inversely correlated with the expression of NOB1. The downregulation of miR-646 also indicated a higher probability of developing metastasis. Most importantly, miR-646 expression was an independent predictor of ccRCC metastasis by the univariate analysis and binary logistic regression model (both P<0.05). Colony formation in soft agar and xenograft tumour model suggested that miR-646 and NOB1 are required for tumorigenesis in vitro and in vivo. Furthermore, suppression of NOB1 increased the phosphorylation of several proteins in MAPK pathway. CONCLUSIONS: Downregulated miR-646 in ccRCC was associated with tumour metastasis through MAPK pathway by targeting NOB1. miR-646 and NOB1 may play an important role in the development of ccRCC.

Transcriptome profiling of prostate tumor and matched normal samples by RNA-Seq.

BACKGROUND: RNA-Sequencing (RNA-Seq) has greatly influenced cancer researches, and it provides an unprecedented resolution in estimating gene expression and has less signal noises compared to cDNA microarray. AIM: We aimed to identify a list of protein-coding genes and lincRNAs that are expressed differentially between tumor and normal tissues. MATERIALS AND METHODS: In this study, we analyzed including 10 human prostate tumor tissues and their matched normal tissues transcriptome dataset generated by recently developed RNA-Seq technology. RESULTS: By aligning short reads to human RefSeq genes and lincRNAs, we identified 10 RefSeq genes that were differentially expressed between tumor and normal samples with a p-value < 0.05, which were sufficiently enough to distinguish these two groups. Further loosing the p-value cutoff to 0.1 identified an lincRNA which is antisense to Cullin-associated and neddulation-dissociated 1 (CAND1), whose expression is repressed in prostate tumor cells. By examining the expression of CAND1 and its antisense lincRNA in the transcriptome dataset, we found an interaction between them as high expression of CAND1 and low expression of lincRNA is normal samples, and verse visa in tumor samples. CONCLUSIONS: These findings suggest the important usage of RNA-Seq in cancer studies for biomarker development and functional investigation.

Acting locally: innate mucosal immunity in resistance to HIV-1 infection in Kenyan commercial sex workers.

Cohort studies of female commercial sex workers (CSWs) in Kenya were among the first to identify highly HIV-1-exposed seronegative (HESN) individuals. As natural resistance is usually mediated by innate immune mechanisms, we focused on determining whether expression and function of innate signaling pathways were altered locally in the genital mucosa of HESN CSWs. Our results demonstrated that selected pattern-recognition receptors (PRRs) were significantly reduced in expression in cervical mononuclear cells (CMCs) from HESN compared with the new HIV-negative (HIV-N) and HIV-positive (HIV-P) groups. Although baseline levels of secreted cytokines were reduced in CMCs of HESN, they were highly stimulated following exposure to ssRNA40 in vitro. Importantly, cervical epithelial cells from HESN also expressed reduced levels of PRRs, but Toll-like receptor 3 (TLR3) and TLR7 as well as nuclear factor-κB and activator protein 1 were highly expressed and activated. Lastly, inflammatory cytokines interleukin (IL)-1ß, IL-8, and RANTES (regulated and normal T cell expressed and secreted) were detected at lower levels in cervicovaginal lavage of HESN compared with the HIV-N and HIV-P groups. Overall, our study reveals a local microenvironment of HIV resistance in the genital mucosa consisting of a finely controlled balance of basal immune quiescence with a focused and potent innate anti-viral response critical to resistance to sexual transmission of HIV-1.

Molecular changes of mesenchymal stromal cells in response to dexamethasone treatment.

BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into a variety of cell types. The MSCs can be activated and mobilized if needed. AIM: This study aimed to investigate the response mechanism of MSCs under Dexamethasone (Dex) treatment by combining MSCs microarray and bioinformatics methods. MATERIALS AND METHODS: We downloaded the gene expression profile of rat's MSCs challenge with or without Dex (GSE3339) from Gene Expression Omnibus database, including 2 Dex treated samples and 3 untreated samples. The differentially expressed genes (DEGs) were identified by packages in R language. Then, Gestalt (Genomic Sequence Total Analysis and Lookup Tool) and EASE (Expression Analysis Systematic Explorer) to were employed to obtain the molecular events of MSCs under Dex treatment. RESULTS: A total of 17 genes were identified as DEGs between untreated and treated samples, and they were significant enriched in immune response and cell differentiation. The C3 gene was the common candidate gene selected from two different algorithms, and 24 conserved sites were identified in the 3'UTR of C3 gene. CONCLUSIONS: Genes associated with immune response and cell differentiation were dysregulated in MSCs under Dex.

Conditional survival in patients treated with vascular endothelial growth factor-targeted therapy for advanced renal cell carcinoma.

PURPOSE: Conditional survival (CS) offers more relevant prognostic information for patients once they have survived for some time. The objective of this study was to determine the CS for advanced renal cell carcinoma (RCC) patients treated with vascular endothelial growth factor-targeted therapy. METHODS: A total of 345 patients treated between 2006 and 2011 fulfilled the inclusion criteria and were reviewed for analyses. The 1-year conditional and actual survival rates were calculated for survivors from treatment to month 24. Subgroup-specific CS rates were generated after adjustment of the covariate influence. The Cox proportional hazard models were used to assess the prognostic factors at baseline and 1-year landmark. RESULTS: The probabilities of surviving an additional year given survival to 6, 12, 18, and 24 months were 72.2, 76.3, 78.2, and 78.6 %, respectively. Remarkable increase in CS was observed in patients initially classified as intermediate or poor risk according to Heng risk groups. For patients survived 24 months after treatment, the adjusted CS for the following year was over 80 % regardless of initial risk attribution. Compared to baseline analysis, Heng risk groups were less predictive of survivorship after surviving 1 year. The addition of disease control status to multifactorial model significantly improved survival estimation for 1-year survivors (p < 0.01). CONCLUSIONS: CS provides useful information regarding life expectancy for survivors of advanced RCC treated with targeted therapy. Furthermore, disease control status within a specific period of time is critical to the prediction of subsequent survival.

Efforts to resolve the contradictions in early diagnosis of prostate cancer: a comparison of different algorithms of sarcosine in urine.

Controversial data on sarcosine as a promising biomarker for prostate cancer (PCa) detection are present. The objective was to clarify these discrepancies and reevaluate the potential value of sarcosine in PCa. Sarcosine algorithms (supernatant and sediment sarcosine/creatinine, supernatant and sediment log2 (sarcosine/alanine)) in urine samples from 71 untreated patients with PCa, 39 patients with no evidence of malignancy (NEM) and 20 healthy women and men were quantified by liquid chromatography/tandem mass spectrometry. Although any sarcosine algorithms were significantly higher in PCa patients than in NEM patients (all P<0.05), comparable sarcosine values were measured in healthy women and men. Additionally, neither biopsy Gleason score nor clinical T-stage were correlated with sarcosine algorithms (all P>0.05), and receiver operating characteristic curve analysis indicated that the diagnostic power of any of sarcosine algorithms was nonsignificantly higher than that of serum and urine PSA, but nonsignificantly lower than prostate cancer antigen 3 (PCA3) and the percent-free PSA (%fPSA). Improved diagnostic performances were observed when any of sarcosine algorithms was combined with PCA3 or %fPSA. In conclusion, the predictive power of sarcosine in PCa is modest compared with PCA3 and %fPSA. Sarcosine, which awaits more validation before it reaches the clinic, could be included into the list of candidate PCa biomarkers.

Clinicopathological characteristics, management and outcome of metastatic penoscrotal extramammary Paget's disease.

BACKGROUND: Metastatic penoscrotal extramammary Paget's disease (EMPD) has seldom been reported in the literature. OBJECTIVES: To improve the knowledge of the clinicopathological characteristics, management and outcome in patients with this disease. METHODS: The medical records and pathological slides of 10 patients with metastatic EMPD and 33 patients with nonmetastatic disease were reviewed. Immunohistochemical staining for epithelial cadherin (E-cadherin) was performed in the primary skin disease. All the 10 patients received 5-fluorouracil- or docetaxel-based chemotherapy. RESULTS: The most common sites of metastases were lymph nodes followed by bone. Patients with metastatic EMPD were more likely to be young and had elevated carcinoembryonic antigen (CEA) levels. Dermal or deeper invasion, lymphovascular embolization and negative expression of E-cadherin were important pathological predictors of metastatic potential. In invasive EMPD, lymphovascular embolization but not expression of E-cadherin was significantly associated with the risk of metastases. In three patients, (18)F-fluorodeoxyglucose positron emission tomography (PET)-computed tomography (CT) scans revealed occult lymph node metastases which were overlooked at conventional CT examinations. Two patients had complete response to the chemotherapy, three had partial response and five had progressive disease. The 2-year overall survival rate was 48% in patients with metastatic EMPD. In those patients with significantly elevated CEA level, the value of CEA paralleled the disease course. CONCLUSIONS: Metastatic EMPD tended to have dermal invasion and lymphovascular embolization. PET-CT scans were helpful in detecting distant metastases. 5-Fluorouracil- or docetaxel based-chemotherapy was effective in some patients. Serum CEA level can be a useful biomarker for monitoring disease course.

A new approach to the treatment of malignant effusion.

Lymphocytes isolated from malignant effusion were induced to become LAK cells after in vitro culture with rIL-2. 28 patients with malignant effusion were treated by i.p. or intrapleural administration of autologous LAK cells combined with rIL-2 or by rIL-2 alone. The effusion disappeared in 13 patients and significantly decreased in another 13. Two patients did not respond to the treatment. Tumor cells in effusion disappeared or significantly decreased and lymphocytes significantly increased in all responses. Except for transient fever in 9 patients, no serious side effects were found.

[Antimetastasis effect of lymphokine-activated killer (LAK) cells on fibrosarcoma in WKA rats].

Treating WKA rats with fibrosarcoma with LAK cells, antimetastasis effect was studied. The results indicated that splenocytes incubated by IL-2 could produce lytic activity to WKA rats with fibrosarcoma in vitro. Passive infusion of LAK cells lead to a marked reduction in the number of metastatic nodules in the lung. After intravenous injection of LAK cells, cancer cells in the lung speedily disappeared. LAK cell administration for 3 times gave better result than once only (P less than 0.01). In this paper, the possibility of LAK cells used as an adoptive immunotherapy for human neoplasms is briefly discussed.