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

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

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.

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

The awareness of Polish society about bee pollen and its health-promoting properties - preliminary assessment of factors determined bee pollen supplementation in survey-based study

Introduction: The apiculture is an old and long-established craft. Bee pollen is a flower pollen packed by bees and used as a food source for a hive. Mainly, it consists of simple sugars, protein, fatty acid but also minerals and vitamins. Bee pollen has multiple properties: antioxidative, antineoplastic, antibacterial and much more. It is commonly used by herbalists in treatment of certain medical conditions. Nevertheless, it is unsure whether bee pollen has any health benefits.Purpose: The aim of our study was to assess initially a knowledge of respondents about bee pollen and find out which factors can determine bee pollen supplementation.Materials and methods:  The study was based on an on-line questionnaire, which was created by using Google Forms tool. It consisted of 27 both open and closed questions. Anonymity and resignation opportunity were warranted. The statistical analysis based on questionnaires were elaborated by using R custom script.The Pearson Chi-square test was applied to investigate the relationship between bee pollen usage and: (a) gender, (b) body mass index (BMI) and (c) living area.Results: The study was based on questionnaires given to 511 respondents, 153 of them were represented by men, whereas 358 by women. The 403 respondents gathered what was bee pollen. Bee pollen has been used by 123 persons (24% of respondents). Majority of respondents knew what bee pollen is. However, only one third of this group already used this product in their diet. People who took bee pollen had awareness about the advantages of this dietary supplement. Interestingly, Chi-square test analysis showed that the relationship between bee pollen usage and gender, as well as bee pollen usage and BMI is statistically significant. Contrary, there is no relationship between bee pollen and living area. Conclusions:  Our study has highlighted the issue of this problem area among polish society. Quarter of respondents have ever used bee pollen as a part of their diet. Current results show that polish society has been able to have the knowledge about its beneficial properties, because of their declaration submitted to our survey.</p

Changes in Histological Structure, Interleukin 12, Smooth Muscle Actin and Nitric Oxide Synthase 1. and 3. Expression in the Liver of Running and Non-Running Wistar Rats Supplemented with Bee Pollen or Whey Protein

Introduction: Bee pollen is a natural substance obtained from flowers by bees. It is a rich source of protein, vitamins and minerals. It can be used as a dietary supplement. Bee pollen has been investigated for the treatment of some diseases with promising potential. It can be helpful in supportive therapy for dyslipidemia, metabolic syndrome, diabetes type 2, as well the prevention and control of coronary heart disease and myocardial infarction. Whey protein is a rich source of amino acids. It is a basic dietary supplement for many athletes, both professional and amateur. It stimulates muscle growth and provides nutrition for cachectic patients. Aim of the study: The objective of the study was to assess the impact of dietary supplementation of bee pollen or whey protein on the Wistar rat liver histological structure and expression of interleukin 12, smooth muscle actin and nitric oxide synthases among running and non-running rats. Material and methods: Thirty male Wistar rats were divided into six equal groups, three running and three non-running. Among both there was one control, one supplemented with bee pollen and one receiving whey proteins. After 8 weeks, all animals were decapitated and their livers were collected. Five micrometer thick slides were prepared and used for classical histological staining and immuno-histochemistry. ImageJ image analysis software was used to measure optical density and immunohistochemistry profile coverage. Results: Among all groups, morphology of liver was similar. In the running control group, expression of interleukin-12 (IL-12) was decreased as well as expression of endothelial nitric oxide synthase (eNOS) in a group of bee pollen supplemented rats. No significant changes in α- smooth muscle actin (α-SMA) expression was observed. Conclusions: Bee pollen is proving to be a questionable choice for athletes as an alternative to whey protein. Bee pollen supplementation affects hepatocyte cellular activity and has hepatoprotective effects. Whey protein performs worse in this regard. Lower antioxidant properties were found in groups supplemented with bee pollen than with whey protein

Ocena rearanżacji genu ROS1 za pomocą fluorescencyjnej hybrydyzacji in situ w niedrobnokomórkowym raku płuca

Wstęp. Rearanżację genu kodującego protoonkogen ROS (ROS1) obserwuje się u bardzo niewielkiego odsetka (1–2%) chorych na niedrobnokomórkowego raka płuca (NDRP). Charakterystyka kliniczna chorych z omawianym zaburzeniem genu ROS1 jest podobna jak w grupie chorych z rearanżacją genu ALK. Wykrycie nieprawidłowości w genie ROS1 stanowi niezmiernie ważny czynnik predykcyjny, umożliwiający zastosowanie kryzotynibu w pierwszej linii leczenia u chorych na NDRP w stopniu IIIB (chorzy poza możliwością leczenia radykalnego) lub IV. W związku z dodaniem kryzotynibu do listy leków refundowanych od stycznia 2019 roku analiza tej zmiany genetycznej powinna być częścią panelu badań molekularnych wykonywanych u chorych na miejscowo zaawansowanego i zaawansowanego NDRP w ramach kwalifikacji do leczenia ukierunkowanego molekularnie. Cel badania. Celem badania była analiza częstości występowania rearanżacji genu ROS1 wśród chorych na NDRP w stadium IIIB lub IV, kwalifikowanych do terapii ukierunkowanych molekularnie. Przedstawiono także trudności metodologiczne badania fluorescencyjnej hybrydyzacji in situ (FISH), wykonywanego w celu wykrycia tej nieprawidłowości genetycznej. Materiał i metody. Analiza rearanżacji genu ROS1 została przeprowadzona za pomocą metody fluorescencyjnej hybrydyzacji in situ w próbkach materiału pobranego od 573 chorych na NDRP o typie innym niż płaskonabłonkowy w trakcie rutynowej diagnostyki patomorfologicznej. Wyniki. Analizie poddano materiał uzyskany z guza nowotworowego, utrwalony w formalinie i zarchiwizowany w parafinie. U 408 chorych uzyskano materiał histologiczny, a u 165 — cytologiczny (cytoblok). U 439 chorych otrzymano wiarygodny (diagnostyczny) wynik badania rearanżacji genu ROS1 (76,61%). Głównymi przeszkodami w dokonaniu analizy w pozostałych przypadkach były mała liczba komórek nowotworowych oraz wysokie zakłócenia fluorescencyjne tła i fragmentacja jąder komórkowych. Rearanżację genu ROS1 wykryto u 9 chorych na raka gruczołowego (1,57% wszystkich chorych), w tym u 5 mężczyzn i 4 kobiet. U 19 chorych zaobserwowano inne nieprawidłowości dotyczące genu ROS1, przede wszystkim polisomię badanego fragmentu genu ROS1 (3,32%). Polisomia nie współistniała z rearanżacją genu ROS1. Wnioski. Fluorescencyjna hybrydyzacja in situ stanowi użyteczne narzędzie w wykrywaniu rearanżacji genu ROS1. Badanie może być przeprowadzone w materiale zarówno histologicznym, jak i cytologicznym (cytoblok). Niezmiernie istotne dla uzyskania wiarygodnego wyniku są jednak prawidłowe utrwalenie materiału oraz odpowiednia liczba komórek nowotworowych w badanym preparacie

Ocena rearanżacji genu ROS1 przy pomocy fluorescencyjnej hybrydyzacji in situ w niedrobnokomórkowym raku płuca

Introduction. The rearrangement of the gene encoding ROS protooncogene (ROS1) is observed in a very small percentage (1–2%) of patients with non-small cell lung cancer (NSCLC). The clinical characteristics of ROS1-positive patients are similar to those observed in the group of patients with ALK gene rearrangement. Detection of ROS1 gene rearrangement is an extremely important predictive factor enabling the use of crizotinib in the 1st line of NSCLC patients with stage IIIB or IV. Due to the addition of crizotinib to the list of reimbursed drugs from January 2019, the analysis of this genetic change should be part of a molecular tests panel performed in patients with locally advanced and advanced NSCLC in the qualification for molecularly targeted treatment. Aim of the study. Analysis of ROS1 gene rearrangement incidence among NSCLC patients in stage IIIB or IV qualified for molecularly targeted therapies. Presentation of methodological difficulties with fluorescent in situ hybridization (FISH) technique which is used to detect ROS1 genetic abnormality. Materials and methods. The analysis of ROS1 gene rearrangement was carried out using fluorescent in situ hybridization technique in tissue samples taken from 573 NSCLC patients of non-squamous cell type during routine pathomorphological diagnostics. Results. The material obtained from the tumor was fixed in formalin and archived in paraffin. Histological material was obtained from 408 patients, and 165 — cytological (cytoblock). A reliable (diagnostic) result of the ROS1 gene rearrangement was obtained in 439 patients (76.61%). The main difficulties for ROS1 gene analysis were low number of cancer cells, as well as high background fluorescence interference and fragmentation of cell nuclei. ROS1 gene rearrangement was detected in 9 patients with adenocarcinoma (1.57% among all patients), including 5 men and 4 women. In 19 patients, other abnormalities regarding the ROS1 gene were observed, primarily the polysomy of the examined ROS1 gene fragment (3.32%). Polysomy did not coexist with the ROS1 rearrangement. Conclusion. Fluorescent in situ hybridization is a useful tool in detecting ROS1 gene rearrangement. The test can be performed in both histological and cytological material (cytoblock). However, the correct fixation of the material and the appropriate number of tumor cells in the tested samples is extremely important for obtaining a reliable result.Wprowadzenie Rearanżacja genu kodującego protoonkogen ROS (ROS1) jest obserwowana u bardzo niewielkiego odsetka (1-2%) chorych na niedrobnokomórkowego raka płuca (NDRP). Charakterystyka kliniczna chorych z omawianym zaburzeniem genu ROS1 jest podobna do obserwowanej w grupie chorych z rearanżacją genu ALK. Obecność nieprawidłowości w genie ROS1 jest niezmiernie ważnym czynnikiem predykcyjnym, ponieważ umożliwia zastosowanie kryzotynibu w 1. linii leczenia u chorych na NDRP w stopniu IIIB (chorzy poza możliwością leczenia radykalnego) lub IV. W związku z dodaniem kryzotynibu do listy leków refundowanych od stycznia 2019 roku, analiza tej zmiany genetycznej powinna być częścią panelu badań molekularnych wykonywanych u chorych na miejscowo zaawansowanego i zaawansowanego NDRP w kwalifikacji do leczenia ukierunkowanego molekularnie. Cel badania Celem badania była analiza częstości występowania rearanżacji genu ROS1 wśród chorych na NDRP w stopniu zawansowania IIIB lub IV kwalifikowanych do leczenia ukierunkowanego molekularnie oraz przedstawienie trudności metodologicznych badania fluorescencyjnej hybrydyzacji in situ (FISH) stosowanej w celu wykrycia wspomnianej nieprawidłowości genetycznej. Materiały i metody Rearanżację genu ROS1 przeprowadzono metodą FISH – podczas rutynowej diagnostyki patomorfologicznej – w materiale uzyskanym od 573 chorych na NDRP o typie innym niż rak płaskonabłonkowy. Wyniki Analizie poddano materiał pochodzący z nowotworu i utrwalony w formalinie oraz zabezpieczony w parafinie. U 408 chorych uzyskano materiał histologiczny, a u 165 dostępny był materiał cytologiczny (cytoblok). U 439 chorych uzyskano wiarygodny (diagnostyczny) wynik badania rearanżacji genu ROS1 (76,61%). Główną przeszkodą w dokonaniu analizy w pozostałych przypadkach była mała liczba komórek nowotworowych oraz wysokie zakłócenia fluorescencyjne tła i fragmentacja jąder komórkowych. Rearanżacja genu ROS1 została wykryta u 9 chorych na raka gruczołowego (1,57% wśród wszystkich chorych), w tym u 5 mężczyzn i 4 kobiet. U 19 chorych zaobserwowano inne nieprawidłowości dotyczące genu ROS1, przed wszystkim polisomię badanego fragmentu genu ROS1 (3,32%). Polisomia nie współistniała z rearanżacją genu ROS1. Wnioski Badanie FISH jest użytecznym narzędziem w wykrywaniu rearanżacji genu ROS1 i może być przeprowadzone w materiale histologicznym lub cytologicznym (cytoblok). Niezmiernie istotne dla uzyskania wiarygodnego wyniku jest prawidłowe utrwalenie materiału oraz odpowiednia liczba komórek nowotworowych w badanym preparacie