The efficacy of HDAC inhibitors in neoplasm treatment

Introduction and purpose: Histone Deacetylases (HDACs) are associated with epigenetic regulation of gene expression. They are responsible of adequate action of not only histone proteins, but also crucial cell cycle proteins, such as p53, NF‐κB or alpha tubulin. Recent studies have shown the connection between expression of HDAC and carcinogenesis and impact of HDAC inhibitors on cancer therapy. The aim of the study was to review the recent studies on HDAC inhibitors efficiency in the treatment of hematologic neoplasms and solid tumors. It is a study review from 2010 to 2020 using the PubMed database and ClinicalTrials.gov. Description of state of knowledge: Most studies related to HDAC inhibitors impact in hematological neoplasms, such as multiple myeloma, Hodgkin lymphoma, T-cell lymphomas and acute myeloid leukemia. Among studied agents panobinostat, vorinostat and showed efficacy. Moreover, some HDACi demonstrated effectiveness in solid tumors treatment, foremost vorinostat in breast cancer and entinostat in non-small cell lung lymphoma. Summary: Including HDAC inhibitors in tumor treatment could be beneficial for patients, especially those with advanced, relapsed or refractory hematologic neoplasm. However, further studies are necessary to confirm their efficacy and to reveal side effects

Resveratrol impacts health in patients with diabetes mellitus and other metabolic conditions

Background Resveratrol is a polyphenol with many properties, including activity against glycation, oxidative stress, inflammation, neurodegeneration, carcinogenesis and aging. It appears to be a promising compound for the prevention and treatment of metabolic diseases. The aim of this review is to summarize the results of the latest clinical trials that concern effects of resveratrol in diabetes mellitus type 1 and 2 and its complications - diabetic foot ulcers, diabetic nephropathy and non-alcoholic fatty liver disease.   Aim of the study Based on in vitro studies and animal models, it has been observed that resveratrol reverses the factors causing premature death: obesity, hypertension, and hyperlipidemia. Because of its anti-inflammatory, antioxidant, cardioprotective and blood lowering glucose effects, it appears to be a promising compound for the treatment of metabolic conditions. The review presents different clinical trials concerning the efficiency of resveratrol supplementation in patients with diabetes mellitus and metabolic syndrome and their complications. Most studies focused on assessing the effect of resveratrol supplementation as an adjunctive treatment of diabetes mellitus type 2 and in this group of patients it gave the best results causing reduction of fasting glucose levels, fasting insulin concentration, insulin resistance and improvement of insulin sensitivity and lipid profiles.   Conclusions Resveratrol remains a potential drug in the treatment of metabolic diseases like diabetes mellitus. However, the results of the conducted trials are inconscient. More research is needed to confirm the effectiveness of resveratrol supplementation in treating diabetes, its complications and other metabolic conditions

Does SSRI have a neuroprotective effect in patent after ischemic stroke?

Introduction and purpose:Ischemic stroke accounts for the majority of all stroke cases, with recurrence rates of around 12% within the first year, rising to around 30% within five years.Thrombolytic therapy based on the intravenous administration of rtPA (recombinant plasminogen activator) is the only treatment that has been proven to improve treatment outcomes after ischemic stroke. New methods that would increase the number of motor function returns are still being sought.A brief description of the state of knowledge: SSRIs, selective serotonin reuptake inhibitors are used primarily in the treatment of depression and emotional lability after stroke. Many clinical and preclinical studies have suggested that SSRIs have a beneficial effect on the outcomes of stroke patients.Our work is a brief overview of the current knowledge and clinical trials conducted. Review of the available literature using the PubMed database. Search criteria for scientific articles published from 2010 to 2020, search term: "SSRI ischaemic stroke". Ultimately, 12 randomized clinical trials were analyzed (3 articles apply for one study). One of the studies does not have unequivocal results. Conclusions: The safety of SSRIs in stroke patients has been confirmed. Further multi-center studies are required to investigate the neuroprotective role of SSRIs

Passing across the blood-brain barrier in glioblastoma multiforme (GBM)

Introduction and purpose: Blood-brain barrier (BBB) consists of  capillary endothelium, in which there are three types of intercellular junctions - adherent, tight and gap junctions.Efficient therapy involves delivering a therapeutic dose of drug into a specific site in the body, and maintaining this dose for adequate time afterwards. The aim of this study is to review current knowledge of new strategies in drug delivery to CNS and the effectiveness of these methods in glioblastoma multiforme (GBM) treatment. This review was performed using the PubMed database. A brief description of the state of knowledge:  Methods for delivering drugs to the brain are divided into invasive and non-invasive. Invasive methods involve temporary disrupting tight intercellular junctions of the vascular endothelial cells and delivering drugs intracerebrally or intraventricularly during neurosurgical procedures. In recent years, there has been a growing interest in the use of nanoparticles as drug carriers to the central nervous system via blood-brain barrier. The usage of nanoparticles implies many advantages, such as non-invasive, low cost, good biodegradability, stability, ability to carry various types of agents, selectivity and ability to control drug release. Conclusions: Limited options in treating brain located tumors, including glioblastoma multiforme, due to difficulties in drug penetration through the BBB engages scientists to search for new treatments. Crossing the BBB using invasive methods based on interruption of cell junctions show promising results, but they are associated with i.a. a high risk of uncontrolled influx of toxins to the CNS or  ion-electrolyte imbalance, which may lead to neuronal dysfunction. Invasive methods can be effective only in tumors, while treatment of diseases such as Alzheimer’s disease is impossible. Recent studies show that nanoparticles would be a great, non-invasive alternative, but they are difficult to use with relatively low permeability through undamaged BBB. In some studies using nanoparticles as nanocarriers  (EDVDox) or SYMPHONY method (combining photothermal therapy with GNS and immunotherapy of checkpoints in a mouse model) against GBM shows positive results. More research is required to confirm the effectiveness and safety of these treatments

Increase in IL-15 levels in patients with alopecia areata

Introduction and purpose: Alopecia areata (AA) is a condition that causes non-scarring hair loss (often with acute onset). Alopecia areata in the population occurs in 0.1-0.2% of people, with a similar frequency in men and women. Alopecia areata is an example of an autoimmune disease of the hair follicle. Hair loss in alopecia areata is caused by lymphocytic infiltration around the hair follicle and IFN-γ. IgG antibodies against hair follicle cells are also found in people suffering from alopecia areata.  Recent studies have shown a significant increase in IL-15 in AA. The aim of the study was to review the current knowledge on the use of IL-15 in the treatment of alopecia areata.A brief description of the state of knowledge: Interleukin-15 (IL-15) is a pleiotropic cytokine that exhibits multidirectional biological effects on various cell types. It affects the functions of the immune system, both innate and acquired, and therefore plays an important role in inflammation and during the immune response to infections and infestations. In the AA mouse model, antibody-mediated blockade of IFN-γ, interleukin-2 (IL-2), or interleukin-15 receptor β (IL-15Rβ) prevented disease progression by minimizing the accumulation of CD8 (+) NKG2D (+) T cells in the skin and reducing the cutaneous IFN response. The concentration of IL-15 in patients with alopecia areata was significantly higher than in the control group. Moreover, the concentration of IL-15 increased in direct proportion to the area of alopecia, the highest value in patients with total alopecia.For this reason, it is important to search for new medical treatments that will enable patients to stay physically healthy, and what is equally important, to remain mental health. Conclusions: In addition, studies have shown an increase in IL-15 levels in patients with alopecia areata, which correlated with the duration of the disease. However, too few studies conducted so far do not allow conclusions to be drawn regarding the use of IL-15 as a therapeutic point

Targeted therapy in age-related macular degeneration (AMD)

Introduction and purpose: Age-related macular degeneration (AMD) is a major cause of blindness in highly developed countries, with blindness frequency of 8.7%. This article is a review of the latest therapeutic options for AMD.A brief description of the state of knowledge: AMD is a multifactorial disease which etiology is not completely understood. Its development is affected by disorders at the cellular level, environmental and genetic factors. Intraocular injections of anti-VEGF agents are currently considered as the basis of AMD neovascular treatment. In the search for better and better therapeutic agents, the effects of administration of bevacizumab and ranizumab were tested. Many clinical studies confirm long-term and effective improvement in patients' vision after using the above-mentioned drugs, indicating that the initial response to treatment and the persistence of the therapeutic effect is individually variable and may be associated with genotypic difference. Another promising alternative to AMD treatment is the use of specific viral vectors that transfer substances slowing down the disease into the vitreous. Another method of gene therapy is the use of HIF transcription factors (hypoxia-induced factors), for now, the research is performed on animal models. Patients with dry AMD also have a chance for successful treatment. Examined gene therapy in dry form of AMD, including retinal surgery combined with viral vector injection, is in I/II phase study in Great Britain.  Conclusions: Looking at the number of blindness cases in highly developed countries caused by AMD, every effort should be made to introduce effective treatment that at least inhibits disease progression. Undoubtedly, more research is needed to confirm the efficacy and long-term safety of AMD.

Targeted therapy with Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of solid tumours

Introduction: According to the National Cancer Register in Poland, the number of cancers including breast cancers has more than doubled in the past three decades. Poly(ADP-ribose) polymerase (PARP) inhibitors lead to the death of cells with a BRCA1/2 mutation. The use of PARP inhibitors has increased significantly over the last 5 years.Objective: This article summarizes the current knowledge about the safety and clinical  efficacy of PARP inhibitors in the treatment of solid tumors.Abbreviated description of the state of knowledge: PARP inhibitors have been used in the standard treatment of ovarian cancer. Three of them: Olaparyb, Rucaparyb and Niraparyb have indications for maintenance treatment in recurrent platinum-sensitive ovarian cancer. Olaparib and Weliparib are used to treat breast cancer patients. Research shows that the use of Olaparib in breast cancer patients has reduced tumours size as much as around 60% of women with BRCA mutation. The combination of veloparin with carbolatin and paclitaxel was associated with a longer mean survival period than chemotherapy alone in treatment of non-small cell lung cancer(NSCLC).In addition, there are studies showing the benefits of PARP inhibitor therapy in prostate cancer. Olaparyb in combination with abiraterone shows greater clinical efficacy in patients with castration-resistant prostate cancer compared alone abiraterone.Conclusions: FDA approval of new PARP inhibitors is a promising method for more effective treatment of the most common cancers in the world. In the future further research may lead to a better definition of the patient group benefiting most from PARP inhibitor therapy.

Available markers in the diagnosis and prognosis of kidney cancer

Introduction and purpose:Renal cell carcinoma (RCC) is the most common kidney cancer that has no symptoms for a long time. It is most often diagnosed accidentally during abdominal ultrasound or abdominal computed tomography, performed primarily due to non-specific clinical symptoms. Despite progress in treatment, late detection is associated with poor prognosis. The aim of the study is to analyze literature (database PubMed) for potential prognostic markers and those used in RCC diagnostics.A brief description of the state of knowledge: The most common RCC subtype is clear cell renal cell carcinoma(ccRCC). Metastatic ccRCC is associated with poor prognosis. The pathogenesis of ccRCC includes, among others, disorders of miRNA change. These molecules are described as a promising marker of both diagnostic and prognostic. Detection of CD163 + antigen on cancer cells may be useful in assessing the clinical course of ccRCC patients. In clinical diagnosis of RCC, the presence of mutations and epigenetic inactivation of the von Hippel-Lindau (VHL) gene, vascular endothelial growth factor (VEGF) and carbonic anhydrase IX (CIAX) genes are particularly important. Plasma CIAX levels are described as not only a diagnostic and prognostic marker, but also lymph node involvement. There are studies on molecular markers that can also be a therapeutic target, including Caveolin-1 (CAV1), CCL5. Recent research results show a link between PDL1 expression and high-grade tumors. PDL-1 may also be an important prognostic factor.Conclusions:Research on molecular markers is a promising personalized diagnostic and prognostic route. The limitation is the nonspecificity of molecular markers, so research on new and current markers is needed

The use of the PD-1/PD-L1 pathway as an immunotherapy in oncological diseases, autoimmune diseases and infectious diseases

Introduction: PD-1 is programmed death receptor 1 belonging to the CD28 family of receptors. Immune cells have this receptor on their surface. PD-L1 allows cancer cells to avoid the host's response. Connection to the PD-1 receptor leads to the death of the immune cell.Objective: The use of PD-1 receptors in the treatment of oncological, autoimmune and infectious diseases.Abbreviated description of the state of knowledge: The development and progression of immunotherapy in recent years has resulted in the approval of five immunotherapy pathways targeting PD-1 (pembrolizumab and durvalumab) or PD-L1 (atezolizumab, nivolumab and avelumab) in patients with progression during or after cisplatin based chemotherapy. The latest updates show that in some types of cancer, positive PD-L1 expression has an effect on treatment effect and qualification. These therapies are used, among others in melanoma, lymphomas, kidney cancer or breast cancer. PD-1 is also used to treat autoimmune and infectious diseases.Conclusions: Understanding the mechanism of the PD-1/PD-L1 pathway allows to design targeted therapy for individuals. It has been already used in NSCLC treatment program, whether bladder cancer or melanoma. Immunotherapy increases the survival time of patients with advanced stages of cancer. The therapies targeting the PD-1/PD-L1 pathway in autoimmune and infectious diseases are in clinical trials

Deep brain stimulation in Parkinson's disease - the review

Introduction: Parkinson’s disease (PD) is a common neurodegenerative disorder and is the second most common neurodegenerative disease after Alzheimer’s disease. The clinical features are associated with motor symptoms: tremor, rigidity, and bradykinesia with postural instability. PD is also associated with many non-motor symptoms, and these often precede the motor symptoms by years or even decades. In general, treatment is based on usage of medicaments which increase a level of dopamine. Surgical therapy is reserved for more advanced cases. Objective: To review currently available data on PubMed about a surgical treatment of Parkinson’s disease and future prospects. Abbreviated description of the state of knowledge: Surgical therapy is typically reserved for bradykinesia, rigidity and tremor in patients who no longer respond to medication in a predictable manner or who suffer medication-induced dyskinesias. Currently, the most common surgical treatment for Parkinson's disease is deep brain stimulation (DBS). Ablative procedures like radiofrequency, radiosurgery and focused ultrasound are also utilized for select tremor symptoms. We also analyzed future prospects including cells transplantation. DBS decreases a level of disability, depression and increases quality of life. It should to take under consideration in early as well as advanced PD. Conclusions: PD is still incurable, however both pharmacological and surgical treatment can stifle the progression of disease for years and increase quality of life. New methods of treatment are promising. However, the further research about possible therapy is required