Sesquiterpene lactones, secondary metabolites of plants, present in a large number of species mostly from the Asteracea family, are used in the traditional medicine of many countries for the ...treatment of various pathological conditions. They exert a broad range of activities, including antiinflammatory, anti-bacterial and anti-cancer properties. The best-known sesquiterpene lactones which are already used as drugs or are used in clinical trials are artemisinin, thapsigargin and parthenolide. Yet another sesquiterpene lactone, helenalin, an active component of Arnica montana, known for its strong anti-inflammatory activity, has been used for centuries in folk medicine to treat minor injuries. Unfortunately, helenalin's ability to cause allergic reactions and its toxicity to healthy tissues prevented so far the development of this sesquiterpene lactone as an anticancer or anti-inflammatory drug. Recently, the new interest in the biological properties, as well as in the synthesis of helenalin analogs has been observed. This review describes helenalin's major biological activities, molecular mechanisms of action, its toxicity and potential for further research.
Cancer is one of the leading causes of mortality in the developed countries. The search for novel drug candidates is a priority goal for cancer therapy. However, the emergence of drug resistance ...reduces the effectiveness of new medications. The ATP binding cassette (ABC) family of proteins are efflux pumps that transport various structurally unrelated and potentially dangerous substances out of the cells. These transporters have evolved as a complex cellular defense system, for the recognition and removal of toxic agents entering the cells from their environment. Several of the ABC transporters are related to chemoresistance in cancer therapy, as the rapidly dividing malignant cells use them to protect themselves from medical interventions. Here we review the members of the ABC transporter families responsible for the multidrug resistance in anticancer therapy.
Purpose
HPV is involved in the development of some head and neck squamous-cell carcinomas (HNSCC). It was suggested that only transcriptionally active virus can induce carcinogenesis, therefore, the ...aim of our study was to analyze the frequency of active HPV infection, virus type, and its prognostic role in HNSCC patients.
Methods
Status of active HPV infection was assessed for 155 HNSCC patients based on p16 expression and HPV DNA presence. Univariate and multivariate analyses with Cox proportional regression model were performed to select independent prognostic factors.
Results
Active HPV infection was detected in 20.65% of patients. We identified 16.0, 40.9 and 1.7% of HPV positive oral cavity, oropharyngeal, and laryngeal cancer cases, respectively. HPV16 was dominant (81.25%) followed by HPV35 (9.38%) and double infections with HPV16 and 35 (6.25%) or HPV35 and 18 (3.12%). Patients with active HPV infection demonstrated significantly higher survival than HPV negative ones (OS 80.89% vs. 37.08%,
p
= 0.000; DFS 93.0% vs. 53.35%,
p
= 0.000, respectively). Longer OS and DFS were maintained for infected patients when oropharyngeal and non-oropharyngeal cases were analyzed separately. Interestingly, all patients infected with other than HPV16 types survived 5 years without cancer progression. In the analyzed group of 155 patients the strongest independent favourable prognostic factor for both OS and DFS was HPV presence.
Conclusions
High prevalence of HPV-driven HNSCC (mostly within oropharynx) was detected, with HPV16 type the most frequent, followed by HPV35 and HPV18. The presence of active HPV infection improved survival of both oropharyngeal and non-oropharyngeal cancer patients and should be taken into account in treatment planning.
A proper diet is one of major factors contributing to good health and is directly related to general condition of the organism. Phenolic compounds are abundant in foods and beverages (fresh and ...processed fruits and vegetables, leguminous plants, cereals, herbs, spices, tea, coffee, wine, beer) and their pleiotropic biological activities result in numerous health beneficial effects. On the other hand, high reactivity and very large diversity in terms of structure and molecular weight renders polyphenols one of the most difficult groups of compounds to investigate, as evidenced by ambiguous and sometimes contradictory results of many studies. Furthermore, phenolics undergo metabolic transformations, which significantly change their biological activities. Here, we discuss some aspects of metabolism and absorption of phenolic compounds. On the basis of information reported in the literature as well as in summaries of clinical trials and patent applications, we also give an overview of strategies for enhancing their bioavailability.
A sesquiterpene lactone, thapsigargin, is a phytochemical found in the roots and fruits of Mediterranean plants from
L. species that have been used for centuries in folk medicine to treat rheumatic ...pain, lung diseases, and female infertility. More recently thapsigargin was found to be a potent cytotoxin that induces apoptosis by inhibiting the sarcoplasmic/endoplasmic reticulum Ca
ATPase (SERCA) pump, which is necessary for cellular viability. This biological activity encouraged studies on the use of thapsigargin as a novel antineoplastic agent, which were, however, hampered due to high toxicity of this compound to normal cells. In this review, we summarized the recent knowledge on the biological activity and molecular mechanisms of thapsigargin action and advances in the synthesis of less-toxic thapsigargin derivatives that are being developed as novel anticancer drugs.
Morphine and related drugs that act through activating opioid receptors are the most effective analgesics for the relief of severe pain. They have been used for decades, despite the range of unwanted ...side effects that they produce, as no alternative has been found so far. The major goal of opioid research is to understand the mechanism of action of opioid receptor agonists and to improve the therapeutic utility of opioid drugs. In the search for safer and more potent analgesics, analogs with mixed opioid receptor profile gained a lot of interest. However, recently the concept of biased agonism, that highlights the fact that some ligands are able to differentially activate receptor downstream pathways, became a new approach in the design of novel drug candidates for clinical application. In this review, we summarize current knowledge on the development of opioid ligands of peptide and nonpeptide structure, showing how much opioid pharmacology evolved in recent years.
The aminocoumarin antibiotic, novobiocin, is a natural product that inhibits DNA gyrase, a bacterial enzyme involved in cell division.
More recently, novobiocin was found to act also on eukaryotic ...cells by blocking the 90 kDa heat shock protein (Hsp90). Hsp90 is a molecular chaperone, critical for folding, stabilization and activation of many proteins, in particular oncoproteins responsible for cancer progression. As opposed to the geldanamycin and radicicol, the known inhibitors of Hsp90 that bind to the N-terminal region, the binding domain of novobiocin is localized in the C-terminal part of this protein. While the N-terminal inhibition also leads to the induction of some pro-survival signals, C-terminal inhibitors in which prosurvival responses are avoided and client degradation is maintained can be developed as a new class of potential anticancer chemotherapeutics. Numerous novobiocin analogs have been designed in the search for more potent compounds and some of them exhibit significantly enhanced anti-proliferative activity versus the natural product, as evaluated by cellular efficacies against several cancer cell lines.
This review describes structure-activity-relationships of novobiocin analogs and some biological data reported so far on the anticancer activity of these modified compounds.
A proper extraction method from formalin-fixed paraffin-embedded (FFPE) blocks is essential to obtain DNA of satisfactory quality/quantity. We compared the effectiveness of eight commercially ...available kits for DNA extraction based on 10 FFPE tissues. Kits differed significantly in terms of DNA yield, purity, and quality. Using the QIAamp DNA FFPE Tissue Kit (Qiagen) and the ReliaPrep FFPE gDNA Miniprep System (Promega), we obtained DNA of the highest quality and acceptable quantity. We also demonstrated that overnight digestion of samples usually improved DNA yield and/or purity. For precious or limited material, double elution is recommended for obtaining up to 42% higher amount of DNA.
Rubiscolins are two naturally occurring, linear peptides, isolated from the pepsin digests of D-ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCo) from spinach leaves. Their sequences are as ...follows: Tyr-Pro-Leu-Asp-Leu (YPLDL, rubiscolin-5) and Tyr-Pro-Leu-Asp-Leu-Phe (YPLDLF, rubiscolin-6, also known as rubixyl). Though their structure does not resemble typical opioid peptides, rubiscolins were found to exhibit high affinity and selectivity for the delta opioid receptor and an antinociceptive effect in mice after oral administration. Moreover, orally administered rubiscolin-6 was shown to possess orexigenic, anxiolytic-like, and memory-enhancing activities in mice. This review summarizes various biological activities of rubiscolins in mammalian organism and recent developments on the structure-activity relationship of rubiscolin analogs, aimed at improving their pharmacological properties. Naturally occurring substances, such as rubiscolins, may provide a rational and powerful approach in the design of new therapeutics or functional foods.
Morphine and the other alkaloids found in the opium poppy plant still represent the preferred therapeutic tools to treat severe pain in first aid protocols, as well as chronic pain. The use of the ...opiate alkaloids is accompanied by several unwanted side effects; additionally, some forms of pain are resistant to standard treatments (e.g. neuropathic pain from cancer). For these reasons, there is currently renewed interest in the design and assay of modified versions of the potent endogenous opioid peptides endomorphin-1 and endomorphin-2. This review presents a selection of the strategies directed at preparing highly stable peptidomimetics of the endomorphins, and of the strategies aimed at improving central nervous system bioavailability, for which increased in vivo antinociceptive efficacy was clearly demonstrated.
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