Exosomes-Promising Carriers for Regulatory Therapy in Oncology.

Extracellular vesicles (EVs), including exosomes and microvesicles, together with apoptotic bodies form a diverse group of nanoparticles that play a crucial role in intercellular communication, participate in numerous physiological and pathological processes. In the context of cancer, they can allow the transfer of bioactive molecules and genetic material between cancer cells and the surrounding stromal cells, thus promoting such processes as angiogenesis, metastasis, and immune evasion. In this article, we review recent advances in understanding how EVs, especially exosomes, influence tumor progression and modulation of the microenvironment. The key mechanisms include exosomes inducing the epithelial-mesenchymal transition, polarizing macrophages toward protumoral phenotypes, and suppressing antitumor immunity. The therapeutic potential of engineered exosomes is highlighted, including their loading with drugs, RNA therapeutics, or tumor antigens to alter the tumor microenvironment. Current techniques for their isolation, characterization, and engineering are discussed. Ongoing challenges include improving exosome loading efficiency, optimizing biodistribution, and enhancing selective cell targeting. Overall, exosomes present promising opportunities to understand tumorigenesis and develop more targeted diagnostic and therapeutic strategies by exploiting the natural intercellular communication networks in tumors. In the context of oncology, regulatory therapy provides the possibility of reproducing the original conditions that are unfavorable for the existence of the cancer process and may thus be a feasible alternative to population treatments. We also review current access to the technology enabling regulatory intervention in the cancer process using exosomes.

Biochemical Parameters in Cognitive Functions.

Cognitive impairment is a common disease. Many studies attempt to explain the mechanisms of these dysfunctions formation, including correlations between cognitive functions and biochemical parameters. Scientists search for substances that would be indicators of cognitive functions and which could be determined in the cerebrospinal fluid or blood of the subjects. To date, they have isolated a few of such substances; however, research on their specificity, validity and the possibility of their use in diagnostics and prognostic assessment is still ongoing. However, there have been only few reports in the literature systematizing the existing knowledge on this subject, and they are mostly related to Alzheimer's disease, not cognition in general, or referring only to a specific group of substances. This article discusses the most important biochemical exponents of cognitive functions.

Cognitive function, depression, and anxiety in patients undergoing radical prostatectomy with and without adjuvant treatment.

BACKGROUND: Prostate cancer (PC) is one of the most common malignant tumors in developed countries. Both PC and treatment for PC have an adverse impact on physical and mental well-being, and are associated with decreased quality of life. The aim of the present study was to examine the relationship between neuropsychological symptoms and clinical course in PC patients undergoing radical prostatectomy with or without adjunct therapy. METHODS: The cohort comprised 100 patients aged 50-77 years who underwent radical, laparoscopic prostatectomy for PC. Twenty-three patients with a more advanced clinical stage also received adjuvant therapy (radiotherapy and hormonotherapy). Clinical evaluation included self-report assessment, physical examination, and biochemical tests (testosterone and prostate-specific antigen). In addition, the presence and intensity of sexual dysfunction, urinary dysfunction, anxiety-depressive symptoms, and cognitive dysfunction were assessed. RESULTS: The group of patients undergoing complex therapy was characterized by a significantly worse result of deferred memory (p=0.04). A significant correlation was found between post-surgery erectile function and scores for the visual working memory test (correct answers; VWMT-C; p=0.006) and Hospital Anxiety and Depression Scale depression (p=0.045) and anxiety scores (p=0.02). A trend toward significance was also observed for simple reaction time (correct answers; p=0.09). A significant correlation was found between results for the delayed verbal memory test and all physical symptoms (International Consultation on Incontinence Questionnaire-total, p=0.02; International Index of Erectile Function-5, p=0.006). Similarly, a significant correlation was found between the VWMT-C and score for sexual dysfunction (p=0.003). CONCLUSION: Patients undergoing both surgical and adjunct therapy for PC are at risk for psychological burden and cognitive disorders. In the present cohort, physical complications of therapy were associated with depression, anxiety, and delayed memory dysfunction. Furthermore, this study has proven that fewer complications after surgery are associated with better psychological and cognitive functioning. Appropriate neuropsychological and psychiatric care can improve compliance and quality of life among patients after prostatectomy.

LC/MS/MS analysis of α-tocopherol and coenzyme Q10 content in lyophilized royal jelly, beebread and drone homogenate.

This study shows the results of application liquid chromatography-tandem mass spectrometry (LC/MS/MS) for assay of the content of α-tocopherol and coenzyme Q10 in bee products of animal origin, i.e. royal jelly, beebread and drone homogenate. The biological matrix was removed using extraction with n-hexane. It was found that drone homogenate is a rich source of coenzyme Q10 . It contains only 8 ± 1 µg/g of α-tocopherol and 20 ± 2 µg/g of coenzyme Q10 . The contents of assayed compounds in royal jelly were 16 ± 3 and 8 ± 0.2 µg/g of α-tocopherol and coenzyme Q10 , respectively. Beebread appeared to be the richest of α-tocopherol. Its level was 80 ± 30 µg/g, while the level of coenzyme Q10 was only 11.5 ± 0.3 µg/g. Copyright © 2016 John Wiley & Sons, Ltd.

The Influence Of Obesity On Results Of AT (Doxorubicin Plus Docetaxel) Neoadjuvant Chemotherapy In Locally Advanced Breast Cancer Patients.

UNLABELLED: The achieve pathologic complete response is proven to be the most important parameter of prognosis. Thereports evaluating the impact of obesity on the obtained pathologic response to chemotherapy are unequal. The aim of the study was to evaluate in locally advanced breast cancer patients, treated with AT(doxorubicin plus docetaxel) neoadjuvant chemotherapy: 1. The relationship of obesity with obtaining pathological response. 2. The relationship of obesity and free of disease recurrence survival (DFS) and overall survival (OS) associated with the tumour. MATERIAL AND METHODS: A retrospective study was carried out in a group of 105 patients with locally advanced breast cancer, treated with AT neoadjuvant chemotherapy and then treated with radical surgery. Two variants of pathological response have been adopted: a pCR (T0N0) and pCR1 (TisN0, TxN1, T1N0, T1N1, T0N1). The relationship of obesity with pathological response and survival was investigated. RESULTS: In univariate analysis the pCR1 was obtained with its arising from the borderline of statistical significance with lower incidence of obesity. In pCR1 multivariate analysis, negative pCR1 relationship with obesity was on the borderline of the statistical significance. The multivariate analysis showed a significant negative association OS with obesity (p=0.047) and positive with the occurrence of menopause (p = 0.029). CONCLUSIONS: In patients with locally advanced breast cancer treated with AT neoadjuvant chemotherapy. 1. Obesity seems to be an independent and unfavourable predictor of the lack of obtaining pCR1 pathological response 2. In the multivariate analysis, the obesity was a significant independent factor related to shorter OS.

Studies on the kinetics of carbamazepine degradation in aqueous matrix in the course of modified Fenton's reactions.

The present article describes a study into the kinetics of carbamazepine degradation under influence of the standard Fenton's reagent, light-enhanced Fenton's reagent, as well as modified Fenton's systems in which iron(II) ion is replaced by Cu(I), Cu(II), Ni(II), Mn(II), Cr(III) and V(V) ions. In the course of the study it was established that V(V) ion modified Fenton's reagent was equally effective in relation to carbamazepine as the standard reagent. Parameters of both standard and modified Fenton's reagents were optimized. It was observed that an increased concentration of inorganic ions and acidic pH levels precipitated the decomposition of carbamazepine.

Are synchronous and metachronous bilateral breast cancers different? An immunohistochemical analysis aimed at intrinsic tumor phenotype.

UNLABELLED: The biology and pathomechanism of bilateral breast cancers is not fully understood. We compared the morphological and immunohistochemical characteristics of primary tumors in patients with synchronous bilateral breast cancers and metachronous bilateral breast cancers, with special focus on intrinsic tumor phenotype. METHODS: Tumor morphology and expression of 8 immunohistochemical markers were assessed in tissue microarrays containing primary breast tumor cores from 113 metachronous bilateral breast cancers and 61 synchronous bilateral breast cancers. Analyzed markers included hormone receptors (estrogen receptor, progesterone receptor), HER2, Ki67, cytokeratin 5/6, E-cadherin, vimentin and epidermal growth factor receptor. Cutoff levels are provided in the table. RESULTS: Metachronous bilateral breast cancers tumors had lower estrogen receptor expression (p=0.047) and higher expression of cytokeratin 5/6 (p=0.017) and of vimentin (p=0.008); in multivariate analysis only vimentin retained the significance (p=0.01). Ten (13%) and 11 (26%) of metachronous bilateral breast cancers and synchronous bilateral breast cancers had luminal A phenotype, 39 (50%) and 15 (36%) were luminal B HER2-negative, 13 (17%) and 12 (28%) - luminal B HER2-positive, 3 (4%) and 2 (5%) - HER2-positive (not luminal), and 12 (16%) and 2 (5%) had triple negative phenotype (p=0.07). CONCLUSION: Metachronous bilateral breast cancers, compared to synchronous bilateral breast cancers, are characterized by more aggressive phenotype, expressed by lower expression of estrogen receptor and stronger expression of cytokeratin 5/6 and vimentin; this does not, however, translate into differences in the distribution of intrinsic tumor phenotypes.

Risk factors for brain relapse in HER2-positive metastatic breast cancer patients.

Brain relapse is a common occurrence in HER2-positive breast cancer patients. However, the factors determining the risk of brain metastasis in these patients remain to be established. The aim of this study was to assess the impact of particular clinical and pathological factors on the risk of brain relapse in HER2-positive advanced breast cancer patients. The study group included 264 consecutive HER-2 positive metastatic breast cancer patients, most of whom (210; 80%) were administered trastuzumab, usually in combination with chemotherapy. Time from the diagnosis to distant relapse ranged from 0 to 142 months (median 16 months). The most common dominant site of metastatic disease was viscera (80%), followed by soft tissue (11%) and bones (10%). After a median follow-up of 3.1 years, the symptomatic brain relapse occurred in 103 patients (39%). Median time from treatment dissemination to brain relapse was 15 months (range, 0-81 months), and the cumulative 1-year, 3-year and 5-year risk of brain relapse was 17, 42 and 55%, respectively. The average annual risk of brain relapse for surviving patients during consecutive 7 years of follow-up was 10.0% (95% CI, 6.6-13.5%). In the univariate analysis the only variable significantly related to the increased risk of brain relapse was time from initial diagnosis to distant relapse shorter than 2 years (HR = 1.55, 95% CI, 1.03-2.33, P = 0.034). Patients with dominant site of disease in soft tissue or bones tended to have lower risk of relapse (HR = 0.54 and 0.62; P = 0.098 and 0.203, respectively) compared to patients with visceral metastases. Treatment with trastuzumab was not associated with reduced risk of brain relapse (HR = 0.91, 95% CI, 0.47-1.77, P = 0.78). In the multivariate analysis, time from initial diagnosis to distant relapse shorter than 2 years remained the only significant variable related to increased risk of brain relapse (adjusted HR = 1.62, 95% CI, 1.07-2.44; P = 0.022). HER2-positive breast cancer patients remain at high and continuous risk of brain relapse for a prolonged period of time after diagnosis of disease dissemination. Short time from initial diagnosis to distant relapse is related to increased risk of brain relapse. Molecular predictors are sorely needed to better characterize patients with high probability of early brain relapse.

The influence of interferon alpha on the rat liver injured by chronic administration of carbon tetrachloride.

Due to their complex and not fully known etiopathogenesis as well as difficulties in treatment, chronic hepatitis and cirrhosis still remain one of the main problems of hepatologists. Nowadays, the use of IFN alpha is considered the most effective method of treatment in chronic hepatitis. Recently, a new property of IFN, i.e. its effects on the reduction of fibrosis, has been discovered. The aim of the paper was to examine the effects of IFN alpha on biochemical parameters (AlAt and AspAt activities), on the metabolic function of the liver and its morphologic picture observed under the light and electron microscope after the 3- and 6-week CCl4-induced damage. The experiments were carried out in Wistar male rats. To evaluate the liver function, the test of aminophenazone elimination in the isolated perfused rat livers was used according to Miller modified by Hafte. Additionally, AspAt and AlAt activities were determined. The liver specimens were analysed under the light and electron microscope and using immunohistochemical methods. The findings show that after the 3-week CCl4-induced liver damage, IFN alpha does not significantly affect AlAt and AspAt activities, irrespective of the dose used. IFN alpha administered after the 6-week damage significantly changes those activities when the doses used are high. It was found that carbon tetrachloride does not result in evident cirrhotic changes, however it activates Ito cells, causes focal retraction of the stroma and fibrosis. The increased number of Ito cells in Disse's space observed in immunohistochemical and ultrastructural examinations is indicative of the activation of liver fibrotic processes following CCl4 administration in both variants used. IFN alpha substantially weakens fibrogenesis of the CCl4-damaged liver which is visible in the decreased number of Ito cells and weaker expression of the stroma retraction. Moreover, IFN alpha administered to the experimental animals after the CCl4-induced injury of the liver increases aminophenazone clearance, especially when used in higher doses. Positive effects of IFN confirmed in the studies suggest that the drug may be used in patients with chronic hepatitis and early cirrhosis since it is likely not only to eliminate the virus but also to improve the liver function and reduce fibrosis.