Pentraxin-3 (PTX3) belongs to the pentraxine family, innate immune regulators involved in angiogenesis, proliferation and immune escape in cancer. Here, we evaluated PTX3 tissue expression and serum levels as biomarkers of clear cell renal cell carcinoma (ccRCC) and analyzed the possible role of complement system activation on tumor site. A 10-year retrospective cohort study including patients undergoing nephrectomy for ccRCC was also performed. PTX3 expression was elevated in both neoplastic renal cell lines and tissues, while it was absent in both normal renal proximal tubular cells (HK2) and normal renal tissues. Analysis of complement system activation on tumor tissues showed the co-expression of PTX3 with C1q, C3aR, C5R1 and CD59, but not with C5b-9 terminal complex. RCC patients showed higher serum PTX3 levels as compared to non-neoplastic patients (p<0.0001). Higher PTX3 serum levels were observed in patients with higher Fuhrman grade (p<0.01), lymph node (p<0.0001), and visceral metastases (p<0.001). Patients with higher PTX3 levels also showed significantly lower survival rates (p=0.002). Our results suggest that expression of PTX3 can affect the immunoflogosis in the ccRCC microenvironment, by activating the classical pathway of CS (C1q) and releasing pro-angiogenic factors (C3a, C5a). The up-regulation of CD59 also inhibits the complementmediated cellular lysis.

The effects of obstruction on renal function are the consequence of many factors that profoundly alter all components of glomerular function. Besides the acute effects on glomerular filtration rate and tubule function, a chronic obstruction induces tubular and interstitial injury that results from the activation of different pathways. The progression of tubulointerstitial injury leads to chronic renal damage characterized by tubular atrophy, inflammatory cell infiltration, and interstitial fibrosis. Obstructive nephropathy is an evolving disease in which the renal damage continues even after relief of the obstruction. In particular, it has been demonstrated that the time of relief is the most important factor in predicting long-term renal function deterioration. In this setting, the EGF/MCP-1 ratio, urinary NGAL, and urinary KIM-1 are useful early biomarkers of progressive renal damage and could have a potential role in predicting the long-term renal outcome. This minireview summarizes the role of these emerging urinary biomarkers of obstructive nephropathy based on the current understanding of the pathophysiology of renal injury.

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Dendritic cells (DCs) are potent antigen-presenting cells responsible for the activation and functional polarization of specific T cells. In patients with renal cell carcinoma (RCC) and other cancers, coordinate DC and T cell defects have been reported. In particular, DC and T cell functional subsets that are not conducive to tumor clearance are hypothesized to predominate in patients with advanced-stage disease. Two major peripheral blood DC subsets have been identified in humans: myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) that are believed to mediate contrasting effects on cancer immunity. Given the lack of information regarding DC subsets in patients with RCC, in the present study we have investigated the comparative frequencies and activation states of mDC and pDC in peripheral blood, cancer tissues and lymph nodes of patients with RCC using flow cytometry and immunohistochemistry. Three monoclonal antibodies (mAbs) reactive against specific DC subsets (BDCA-2 or BDCA-4 for pDC and BDCA-1 and BDCA-3 which represent two distinct subsets of mDC, mDC1 and mDC2, respectively) were employed. We observed a significant reduction of both DC subsets in the peripheral blood of patients as compared to normal donors. Similarly, both mDC and pDC were recruited in large numbers into RCC tumor tissues, where they displayed an immature phenotype (DC-LAMP−) and appeared unable to differentiate into mature DC (CD83+) that were competent to migrate to draining lymph nodes. However, we were readily able to generate ex vivo mDC from RCC patients. These DC stimulated robust anti-tumor CTL in vitro and would be envisioned for use in DC-based vaccines applied in patients with RCC whose existing immune system is judged dysfunctional, anergic or prone to undergo apoptosis.

Aims Lower urinary tract symptoms (LUTS) can be classified into symptom syndromes based on which symptoms are predominant. Overactive bladder (OAB) syndrome, a storage dysfunction, and underactive bladder (UAB) syndrome, a voiding dysfunction, are common syndromes, which urodynamic tests may show to be caused by detrusor overactivity (DO) and detrusor underactivity (DU), but can also be associated with other urethro‐vesical dysfunctions. Sometimes OAB and UAB can coexist in the same patient and, if so, need a specific approach beyond treatment of the single and apparently opposing syndromes. Methods During its 2019 meeting in Bristol, the International Consultation on Incontinence Research Society held a literature review and expert consensus discussion focused on the emerging awareness of the coexisting overactive–underactive bladder (COUB). Results The consensus considered whether COUB is the combination of OAB and UAB syndromes, or a real unique clinical syndrome in the same patient, possibly with a common etiology. Definitions, pathophysiology, diagnosis, and treatment were discussed, and high‐priority research questions were identified. Conclusions COUB (with or without urodynamic evidence of DO and DU) may be considered a real clinical syndrome, because it differs from single OAB and UAB, and may not be the combination of both syndromes. Urodynamic tests may be necessary in unclear cases or in cases not responding to initial treatment of the most troublesome symptoms. It is pivotal to define the evolution of the syndrome and the characteristic population, and to recognize predictive or phenotyping factors to develop a specific approach and adequate outcome measures.

The association between PSA density, prostate cancer (PCa) and BPH is well established. The aim of the present study was to establish whether PSA density can be used as a reliable parameter to predict csPCa and to determine its optimal cutoff to exclude increased PSA levels due to intraprostatic inflammation. This is a large prospective single-center, observational study evaluating the role of PSA density in the discrimination between intraprostatic inflammation and clinically significant PCa (csPCa). Patients with PSA ≥ 4 ng/ml and/or positive digito-rectal examination (DRE) and scheduled for prostate biopsy were enrolled. Prostatic inflammation (PI) was assessed and graded using the Irani Scores. Multivariable binary logistic regression analysis was used to assess if PSA density was associated with clinically significant PCa (csPCa) rather than prostatic inflammation. A total of 1988 patients met the inclusion criteria. Any PCa and csPCa rates were 47% and 24% respectively. In the group without csPCa, patients with prostatic inflammation had a higher PSA (6.0 vs 5.0 ng/ml; p=0.0003), higher prostate volume (58 vs 52 cc; p&lt;0.0001), were more likely to have a previous negative biopsy (29% vs 21%; p=0.0005) and a negative DRE (70% vs 65%; p=0.023) but no difference in PSA density (0.1 vs 0.11; p=0.2). Conversely in the group with csPCa, patients with prostatic inflammation had a higher prostate volume (43 vs 40 cc; p=0.007) but no difference in the other clinical parameters. At multivariable analysis adjusting for age, biopsy history, DRE and prostate volume, PSA density emerged as a strong predictor of csPCA but was not associated with prostatic inflammation. The optimal cutoffs of PSA density to diagnose csPCa and rule out the presence of prostatic inflammation in patients with an elevated PSA (&gt;4 ng/ml) were 0.10 ng/ml2 in biopsy naïve patients and 0.15 ng/ml2 in patients with a previous negative biopsy. PSA density rather than PSA, should be used to evaluate patients at risk of prostate cancer who may need additional testing or prostate biopsy. This readily available parameter can potentially identify men who do not have PCa but have an elevated PSA secondary to benign conditions.

Micropapillary carcinoma of the bladder (MPBC) is a variant type of infiltrating urothelial carcinoma, which portends a poor biological behavior in terms of disease stage at first diagnosis and clinical outcome; its peculiar morphology raises issues concerning the ability of tumor detection by imaging techniques and proper biopsy procedure, and the appropriate treatment for non-muscle infiltrating and muscle-infiltrating MPBC remains a matter of debate. On the basis of its established prognostic and therapeutic role in breast and gastro-esophageal cancer in the first instance, the human epidermal growth factor receptor-2 (HER2) has been investigated in selected case series of MPBC over the last 10 years. The aim of the present review was to summarize the existing evidence on HER2 status in MPBC, and to discuss its present and future utility in risk assessment and treatment choice of this uncommon, yet aggressive, disease.

Dendritic cells (DCs) are potent antigen presenting cells and represent attractive candidates for use in novel immunotherapies for patients with renal cell carcinoma (RCC), a disease that has proven refractory to conventional treatment modalities, such as chemotherapy and radiotherapy. Given the perceived need to augment antitumor type-1 immunity (TC1 and Th1) as a therapeutic end point, and the known functional plasticity of DC populations that may display heterogeneous capacity to promote T-cell responses, we sought to identify a preferred DC preparation with this capacity. We compared 2 different preparations of monocyte-derived DC using interferon-alpha (IFN-alpha) (IFN-DC and alphaDC1) with classic DCs "matured" (mDCs) using interleukin-1beta/interleukin-6/tumor necrosis factor-alpha/prostaglandin E2, for their ability to promote autologous TC1 antitumor responses from RCC patients in vitro. IFN-alpha-conditioned DC promoted significantly higher numbers of RCC-specific CD8+ T cells exhibiting a cytotoxic phenotype after in vitro stimulation (IVS) than cytokine cocktail-mDCs. Furthermore, IVS using IFN-DCs was able to diminish regulatory-type T cells among CD4+ T-cell responder populations versus IVS using conventional mDC-based vaccines. These data emphasize an important role for IFN-alpha in modulating the immunologic functions of DCs toward a polarized DC1-type capable of coordinately promoting TH1-type and TC1-type T-cell mediated immunity and supports the translational development of patient-derived IFN-alpha-conditioned DC for use in novel immunotherapies for patients with RCC, and in whom, endogenous tumor-specific TC1 effector cells may be dysfunctional, anergic, or prone to undergo apoptosis.