Search results for "Alter"

Diabetes and Metabolism Disorders Medicinal Plants: A Glance at the Past and a Look to the Future 2018

2018

Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology.

2018

Abstract Introduction Adaptogens are natural compounds or plant extracts that increase adaptability and survival of organisms under stress. Adaptogens stimulate cellular and organismal defense systems by activating intracellular and extracellular signaling pathways and expression of stress-activated proteins and neuropeptides. The effects adaptogens on mediators of adaptive stress response and longevity signaling pathways have been reported, but their stress-protective mechanisms are still not fully understood. Aim of the study The aim of this study was to identify key molecular mechanisms of adaptogenic plants traditionally used to treat stress and aging-related disorders, i.e., Rhodiola r…

In silico RNA-seq and experimental analyses reveal the differential expression and splicing of EPDR1 and ZNF518B genes in relation to KRAS mutations …

2016

Several drugs used for the treatment of colorectal cancer (CRC) are targeted at the epidermal growth factor receptor, but mutations in genes of the RAS family cause resistance to these drugs. Thus, extensive research is being carried out to counterbalance this resistance. The G13D mutation of KRAS is common in humans, and we previously reported that this mutation results in the epigenetic modification of hnRNP proteins, involved in RNA splicing. As aberrant splicing often results in oncogenicity, the present study aimed to identify the genes which show altered splicing patterns in connection with the G13D KRAS mutation. To accomplish this, we first carried out an in silico analysis of RNA-s…

Frequency and prognostic impact of ALK amplifications and mutations in the European Neuroblastoma Study Group (SIOPEN) high-risk neuroblastoma trial …

2021

Purpose: In neuroblastoma (NB), the ALK receptor tyrosine kinase can be constitutively activated through activating point mutations or genomic amplification. We studied ALK genetic alterations in high-risk (HR) patients on the HR-NBL1/SIOPEN trial to determine their frequency, correlation with clinical parameters, and prognostic impact. Materials and methods: Diagnostic tumor samples were available from 1,092 HR-NBL1/SIOPEN patients to determine ALK amplification status (n = 330), ALK mutational profile (n = 191), or both (n = 571). Results: Genomic ALK amplification (ALKa) was detected in 4.5% of cases (41 out of 901), all except one with MYCN amplification (MNA). ALKa was associated with …

Aberrant splicing of the tumor suppressor CYLD promotes the development of chronic lymphocytic leukemia via sustained NF-κB signaling

2017

The pathogenesis of chronic lymphocytic leukemia (CLL) has been linked to constitutive NF-κB activation but the underlying mechanisms are poorly understood. Here we show that alternative splicing of the negative regulator of NF-κB and tumor suppressor gene CYLD regulates the pool of CD5+ B cells through sustained canonical NF-κB signaling. Reinforced canonical NF-κB activity leads to the development of B1 cell-associated tumor formation in aging mice by promoting survival and proliferation of CD5+ B cells, highly reminiscent of human B-CLL. We show that a substantial number of CLL patient samples express sCYLD, strongly implicating a role for it in human B-CLL. We propose that our new CLL-l…

Fatal Liver and Bone Marrow Toxicity by Combination Treatment of Dichloroacetate and Artesunate in a Glioblastoma Multiforme Patient: Case Report and…

2016

A 52-year-old male patient was treated with standard radiochemotherapy with temozolomide for glioblastoma multiforme (GBM). After worsening of his clinical condition, further tumor-specific treatment was unlikely to be successful, and the patient seeked help from an alternative practitioner, who administered a combination of dichloroacetate (DCA) and artesunate (ART). A few days later, the patient showed clinical and laboratory signs of liver damage and bone marrow toxicity (leukopenia, thrombocytopenia). Despite successful restoration of laboratory parameters upon symptomatic treatment, the patient died 10 days after the infusion. DCA bears a well-documented hepatotoxic risk, while ART can…

Anti-Inflammatory Activity of Citrus bergamia Derivatives: Where Do We Stand?

2016

Inflammatory diseases affect a large portion of the worldwide population, and chronic inflammation is a major risk factor for several dangerous pathologies. To limit the side effects of both synthetic and biological anti-inflammatory drugs, the use of herbal medicines, nutraceuticals and food supplements has increased tremendously as alternative and/or complementary medicine to treat several pathologies, including inflammation. During the last decades, the biological properties of Citrus bergamia (bergamot) derivatives have obtained important scientific achievements, and it has been suggested their use in a context of a multitarget pharmacological strategy. Here, we present an overview of t…

Introduction: Novel hybrid combinations containing synthetic or antibiotic drugs with plant-derived phenolic or terpenoid compounds

2017

Abstract Background There is a paradigm shift in chemotherapy from mono-drug therapy towards multidrug combination regimens. Natural products from medicinal plants may play an important role for the design of novel combination therapy protocols. Hypothesis We introduce the novel term “hybrid combination” for the therapeutic combination of chemically defined plant-derived constituents (e.g. phenolic or terpenoid compounds with synthetic or antibiotic drugs to increase pharmacological activity and simultaneously toxic side effects. Study design Several literature databases were screened on the combination of phenolic/terpenoid compounds with synthetic/antibiotic drugs. Results Phenolic compou…

Cancer combination therapy of the sesquiterpenoid artesunate and the selective EGFR-tyrosine kinase inhibitor erlotinib.

2017

Abstract Background The shift from cytotoxic to targeted chemotherapy led to improved treatment outcomes in oncology. Nevertheless, many cancer patients cannot be cured from their disease because of the development of drug resistance and side effects. Purpose There is an ongoing quest for novel compounds, which raised not only the interest in natural products but also in novel combination therapy regimens. Study design In this review, we report on the inhibition epidermal growth factor receptor (EGFR) by targeted small molecules and their combination with natural products from medicinal plants. Results The combination of erlotinib with artesunate leads to synergistic inhibition of cell grow…

Prevention from radiation damage by natural products

2018

Abstract Background Radiotherapy is a mainstay of cancer treatment since decades. Ionizing radiation (IR) is used for destruction of cancer cells and shrinkage of tumors. However, the increase of radioresistance in cancer cells and radiation toxicity to normal tissues are severe concerns. The exposure to radiation generates intracellular reactive oxygen species (ROS), which leads to DNA damage by lipid peroxidation, removal of thiol groups from cellular and membrane proteins, strand breaks and base alterations. Hypothesis Plants have to deal with radiation-induced damage (UV-light of sun, other natural radiation sources). Therefore, it is worth speculating that radioprotective mechanisms ha…