MicroRNA as a Novel Biomarker in the Diagnosis of Head and Neck Cancer

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide, with 890,000 new cases and 450,000 deaths in 2018, and although the survival statistics for some patient groups are improving, there is still an urgent need to find a fast and reliable biomarker that allows early diagnosis. This niche can be filled by microRNA, small single-stranded non-coding RNA molecules, which are expressed in response to specific events in the body. This article presents the potential use of microRNAs in the diagnosis of HNSCC, compares the advances in this field to other diseases, especially other cancers, and discusses the detailed use of miRNA as a biomarker in profiling and predicting the treatment outcome with radiotherapy and immunotherapy. Potential problems and difficulties related to the development of this promising technology, and areas on which future research should be focused in order to overcome these difficulties, were also indicated

Impact of the Ser326Cys polymorphism of the OGG1 gene on the level of oxidative DNA damage in patients with colorectal cancer

As a result of reactive oxygen species operation, cell damage occurs in both cellular organelles and molecules, including DNA. Oxidative damage within the genetic material can lead to accumulation of mutations and consequently to cancer transformation. OGG1 glycosylase, a component of the Base Excision Repair (BER) system, is one of the enzymes that prevents excessive accumulation of 8-oxoguanine (8-oxG), the most common compound formed by oxidative DNA damage. In case of structural changes of OGG1 resulting from polymorphic variants, we can observe a significant increase in the concentration of 8-oxG. Linking individual polymorphisms to DNA repair systems with increased risk of colorectal cancer will allow patients to be classified as high risk and included in a prophylactic program. The aim of the study was to determine the level of oxidative DNA damage and to analyze the distribution of Ser326Cys polymorphism of the OGG1 gene in a group of patients with colorectal cancer and in a control group in the Polish population. Material and methodology. DNA was isolated from the blood of 174 patients with colorectal cancer. The control group consisted of 176 healthy individuals. The level of oxidative damage was determined by analyzing the amount of 8-oxguanine using the HT 8-oxo-dG ELISA II Kit. Genotyping was performed via the TaqMan method. Results. The obtained results indicate that Ser326Cys polymorphism of the OGG1 gene increases the risk of RJG and is associated with significantly increased levels of 8-oxoguanine. Conclusions. Based on the results obtained, we conclude that Ser326Cys polymorphism of the OGG1 gene may modulate the risk of colorectal cancer by increasing the level of oxidative DNA damage

Wpływ polimorfizmu Ser326Cys genu OGG1 na poziom uszkodzeń oksydacyjnych DNA u pacjentów z rakiem jelita grubego

W wyniku działania reaktywnych form tlenu na komórki dochodzi do szerokiego zakresu uszkodzeń zarówno organelli komórkowych, jak i cząsteczek, w tym DNA. Uszkodzenia oksydacyjne w obrębie materiału genetycznego prowadzić mogą do akumulacji mutacji i w konsekwencji do transformacji nowotworowej. Glikozylaza OGG1 – składowa systemu naprawy Base Excision Repair (BER) – to jeden z enzymów zapobiegających nadmiernej akumulacji 8-oksoguaniny (8-oxG), która jest najczęstszym związkiem powstającym w wyniku oksydacyjnego uszkodzenia DNA. W przypadku zmian strukturalnych OGG1 wynikających z wariantów polimorficznych obserwować możemy znaczący wzrost stężenia 8-oxG. Powiązanie poszczególnych polimorfizmów systemów naprawy DNA ze zwiększonym ryzykiem raka jelita grubego pozwoli na kwalifikację pacjentów do grup podwyższonego ryzyka i objęcie ich programem profilaktycznym. Cele pracy: Określenie poziomu uszkodzeń oksydacyjnych DNA oraz analiza rozkładu polimorfizmu Ser326Cys genu OGG1 w grupie pacjentów z rakiem jelita grubego i w grupie kontrolnej w populacji polskiej. Materiał i metody: Jako materiał wykorzystano DNA wyizolowane z krwi pobranej od 174 pacjentów ze zdiagnozowanym rakiem jelita grubego. Grupę kontrolną stanowiło 176 zdrowych osób. Poziom uszkodzeń oksydacyjnych określono na podstawie analizy ilości 8-oksguaniny, używając HT 8-oxo-dG ELISA II Kit. Genotypowanie przeprowadzono metodą TaqMan. Wyniki: Uzyskane wyniki wskazują, iż polimorfizm Ser326Cys genu OGG1 zwiększa ryzyko występowania RJG oraz jest powiązany ze znacząco zwiększonym poziomem 8-oksoguaniny. Wnioski: Na podstawie uzyskanych wyników wnioskujemy, że polimorfizm Ser326Cys genu OGG1 może modulować ryzyko występowania raka jelita grubego poprzez zwiększony poziom uszkodzeń oksydacyjnych DNA

The Role of the ER-Induced UPR Pathway and the Efficacy of Its Inhibitors and Inducers in the Inhibition of Tumor Progression

Cancer is the second most frequent cause of death worldwide. It is considered to be one of the most dangerous diseases, and there is still no effective treatment for many types of cancer. Since cancerous cells have a high proliferation rate, it is pivotal for their proper functioning to have the well-functioning protein machinery. Correct protein processing and folding are crucial to maintain tumor homeostasis. Endoplasmic reticulum (ER) stress is one of the leading factors that cause disturbances in these processes. It is induced by impaired function of the ER and accumulation of unfolded proteins. Induction of ER stress affects many molecular pathways that cause the unfolded protein response (UPR). This is the way in which cells can adapt to the new conditions, but when ER stress cannot be resolved, the UPR induces cell death. The molecular mechanisms of this double-edged sword process are involved in the transition of the UPR either in a cell protection mechanism or in apoptosis. However, this process remains poorly understood but seems to be crucial in the treatment of many diseases that are related to ER stress. Hence, understanding the ER stress response, especially in the aspect of pathological consequences of UPR, has the potential to allow us to develop novel therapies and new diagnostic and prognostic markers for cancer

New cyclopentaquinoline and 3,5-dichlorobenzoic acid hybrids with neuroprotection against oxidative stress for the treatment of Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative brain disease. Thus, drugs including donepezil, rivastigmine, and galantamine are not entirely effective in the treatment of this multifactorial disease. The present study evaluates eight derivatives (3a-3h) as candidates with stronger anti-AD potential but with less side effects. Reactive oxygen species (ROS) assays were used to assess oxidative stress which involve in the neurodegeneration. The neuroprotective properties of 3e against oxidative stress were done in three experiments using MTT test. The anti-AD potential was determined based on their anticholinesterase inhibition ability, determined using Ellman's method, Aβ aggregation potential according to thioflavin (Th) fluorescence assay, and their antioxidative and anti-inflammatory activities. Compound 3e exhibited moderate cholinesterase inhibition activity (AChE, IC50 = 0.131 µM; BuChE, IC50 = 0.116 µM; SI = 1.13), significant inhibition of Aβ(1-42) aggregation (55.7%, at 5 µM) and acceptable neuroprotective activity. Extensive analysis of in vitro and in vivo assays indicates that new cyclopentaquinoline derivatives offer promise as candidates for new anti-AD drugs