Prospective aspects in the oncological treatment of prostate cancer

Prostate cancer (PC) is the second most common malignancy worldwide; the incidence is growing in every industrial country. Depending on the stage, surgical therapy, radiotherapy, and hormonal therapy are the potential therapeutic options. The elevation of radiation dose significantly improves biochemical control and disease-free survival independently of the type of radiotherapy (RT). The short-term and long-term side-effects of therapy are very important as PC patients usually have long survival. Although RT is getting more targeted, tolerance of normal tissues limits dose escalation and increases acute and chronic gastrointestinal (GI) and urogenital (UG) morbidity, exacerbating the pre-existing urological, sexual, and psychological problems. Symptoms depend on the degree and extent of the tissue damage and have a significant adverse effect on the patient’s quality of life (QOL). In clinical practice, toxicity can be reduced by the use of modern radiotherapy techniques by decreasing the safety margins (e.g. intensity-modulated radiotherapy (IMRT), image-guided radiotherapy (IGRT)), by advantageous patient positioning and with almost constant fullness of the rectum and the urinary bladder. During radiotherapy the supine position is the most frequently used laying method. Patients can be treated also in a prone position (with the use of belly board - BB). The use of BB is associated with lower dose burden of intestines in several clinical trials of pelvic cancers formerly in the 3DCRT and nowadays in the IMRT-IGRT era. Despite advances in loco-regional medical treatment, advanced or metastatic PC is still very serious problem. Systematic treatment of metastatic prostate cancer can be divided into hormone-sensitive (HS) and castration-resistant (CR) pathophysiological phases. For metastatic hormone-sensitive prostate cancer (mHSPC) until recently, androgen deprivation therapy (ADT) alone by surgical or medical castration was the standard-of-care. Although the histological classification of PC is well-known, the different molecular subtypes and variants may respond differently to certain therapies. In recent years, many retrospective studies have focused on identifying potential predictive factors for optimizing treatment decisions

Angiomyolipoma of the kidney—Clinicopathological analysis of 52 cases

The renal angiomyolipoma (AML) is a benign tumor characteristically composed of fat, smooth muscle tissue, and vessels. We collected AMLs from our nephrectomy database, reclassified them according to their histological appearance, recorded the demographic, clinical, and pathological parameters, and compared them with oncocytoma (RO) and renal cell carcinoma (RCC). Immunohistochemistry was ordered in 41 cases. In 2224 nephrectomies, we found 52 AMLs with a 53 mm median size. The mean age was 52.76. Forty-eight tumors were sporadic, while four were hereditary. The revision resulted in 31 classic, 13 leiomyoma-like, five lipoma-like, two epithelioid, and one AML with epithelial cysts. SMA was diffusely positive, except for the epithelioid type, while MelanA harbored stronger expression than HMB45. AML was more frequent in females and appeared ten and 7 years earlier than RO and RCC, respectively. The follow-up time was 7.42 years, and neither tumor-related death nor relapse occurred. AML is rare in nephrectomies and develops primarily in females in their 50s with an average size of 50–60 mm at the surgery. The histological appearance in order of frequency is classic, leiomyoma-like, lipoma-like, epithelioid, and cystic. The MelanA, HMB45, and SMA immunohistochemistry can support the light-microscopic findings

Regulation of type I interferon responses by mitochondria-derived reactive oxygen species in plasmacytoid dendritic cells

Mitochondrial reactive oxygen species (mtROS) generated continuously under physiological conditions have recently emerged as critical players in the regulation of immune signaling pathways. In this study we have investigated the regulation of antiviral signaling by increased mtROS production in plasmacytoid dendritic cells (pDCs), which, as major producers of type I interferons (IFN), are the key coordinators of antiviral immunity. The early phase of type I IFN production in pDCs is mediated by endosomal Toll-like receptors (TLRs), whereas the late phase of IFN response can also be triggered by cytosolic retinoic acid-inducible gene-I (RIG-I), expression of which is induced upon TLR stimulation. Therefore, pDCs provide an ideal model to study the impact of elevated mtROS on the antiviral signaling pathways initiated by receptors with distinct subcellular localization. We found that elevated level of mtROS alone did not change the phenotype and the baseline cytokine profile of resting pDCs. Nevertheless increased mtROS levels in pDCs lowered the TLR9-induced secretion of pro-inflammatory mediators slightly, whereas reduced type I IFN production markedly via blocking phosphorylation of interferon regulatory factor 7 (IRF7), the key transcription factor of the TLR9 signaling pathway. The TLR9-induced expression of RIG-I in pDCs was also negatively regulated by enhanced mtROS production. On the contrary, elevated mtROS significantly augmented the RIG-I-stimulated expression of type I IFNs, as well as the expression of mitochondrial antiviral-signaling (MAVS) protein and the phosphorylation of Akt and IRF3 that are essential components of RIG-I signaling. Collectively, our data suggest that increased mtROS exert diverse immunoregulatory functions in pDCs both in the early and late phase of type I IFN responses depending on which type of viral sensing pathway is stimulated