Biological Activities of Essential Oils: From Plant Chemoecology to Traditional Healing Systems

Essential oils are complex mixtures of hydrocarbons and their oxygenated derivatives arising from two different isoprenoid pathways. Essential oils are produced by glandular trichomes and other secretory structures, specialized secretory tissues mainly diffused onto the surface of plant organs, particularly flowers and leaves, thus exerting a pivotal ecological role in plant. In addition, essential oils have been used, since ancient times, in many different traditional healing systems all over the world, because of their biological activities. Many preclinical studies have documented antimicrobial, antioxidant, anti-inflammatory and anticancer activities of essential oils in a number of cell and animal models, also elucidating their mechanism of action and pharmacological targets, though the paucity of in human studies limits the potential of essential oils as effective and safe phytotherapeutic agents. More well-designed clinical trials are needed in order to ascertain the real efficacy and safety of these plant products

Phytochemicals in Cancer Prevention and Therapy: Truth or Dare?

A voluminous literature suggests that an increase in consumption of fruit and vegetables is a relatively easy and practical strategy to reduce significantly the incidence of cancer. The beneficial effect is mostly associated with the presence of phytochemicals in the diet. This review focuses on a group of them, namely isothiocyanate, curcumin, genistein, epigallocatechin gallate, lycopene and resveratrol, largely studied as chemopreventive agents and with potential clinical applications. Cellular and animal studies suggest that these molecules induce apoptosis and arrest cell growth by pleiotropic mechanisms. The anticancer efficacy of these compounds may result from their use in monotherapy or in association with chemotherapeutic drugs. This latter approach may represent a new pharmacological strategy against several types of cancers. However, despite the promising results from experimental studies, only a limited number of clinical trials are ongoing to assess the therapeutic efficacy of these molecules. Nevertheless, the preliminary results are promising and raise solid foundations for future investigations

Stranger Things: New Roles and Opportunities for Androgen Receptor in Oncology Beyond Prostate Cancer

The androgen receptor (AR) is one of the oldest therapeutic targets in oncology and continues to dominate the treatment landscape for advanced prostate cancer, where nearly all treatment regimens include some form of AR modulation. In this regard, AR remains the central driver of prostate cancer cell biology. Emerging preclinical and clinical data implicate key roles for AR in additional cancer types, thereby expanding the importance of this drug target beyond prostate cancer. In this mini-review, new roles for AR in other cancer types are discussed as well as their potential for treatment with AR-targeted agents. Our understanding of these additional functions for AR in oncology expand this receptor\u27s potential as a therapeutic target and will help guide the development of new treatment approaches

Skin Tissue Models

Skin Tissue Models provides a translational link for biomedical researchers on the interdisciplinary approaches to skin regeneration. As the skin is the largest organ in the body, engineered substitutes have critical medical application to patients with disease and injury - from burn wounds and surgical scars, to vitiligo, psoriasis and even plastic surgery. This volume offers readers preliminary description of the normal structure and function of mammalian skin, exposure to clinical problems and disease, coverage of potential therapeutic molecules and testing, skin substitutes, models as study platforms of skin biology and emerging technologies. The editors have created a table of contents which frames the relevance of skin tissue models for researchers as platforms to study skin biology and therapeutic approaches for different skin diseases, for clinicians as tissue substitutes, and for cosmetic and pharmaceutical industries as alternative test substrates that can replace animal models. Offers descriptions of the normal structure/function of mammalian skin, exposure to clinical problems, and more Presents coverage of skin diseases (cancer, genodermatoses, vitiligo and psoriasis) that extends to clinical requirements and skin diseases in vitro models Addresses legal requirements and ethical concerns in drugs and cosmetics in vitro testing Edited and authored by internationally renowned group of researchers, presenting the broadest coverage possible. © 2018 Elsevier Inc. All rights reserved.(undefined)info:eu-repo/semantics/publishedVersio

FDG-PET in Cervical Cancer - Translational Studies

Cervical cancer is the second most common cancer in females. The treatment, based on clinical FIGO stage, carries a significant risk of side effects. FDG-PET enables non-invasive studies of glucose metabolism. Cancer cells show an increased glucose uptake and metabolism that can be visualised and further analysed. The aims of this thesis were to evaluate FDG-PET in the clinical management of cervical cancer and to experimentally investigate the metabolic changes in a tumour following cytotoxic treatment. In a prospective study we found that FDG-PET provided important information about the extent of the disease in primary staging of locally advanced cases and in re-staging of recurrent disease. The treatment plans were altered as a result of the FDG-PET findings for one fourth of the patients. Surveillance FDG-PET 6 months after surgery for early-stage disease showed no clinical value. With a predictive FDG-PET early during radiotherapy for locally advanced disease we could identify a group of patients with an excellent prognosis. However, for the majority of the patients early prediction of outcome was not possible. Persisting hypermetabolism on FDG-PET 3 months after completed radiotherapy was associated with relapse. Experimentally, we found a transient metabolic flare in xenografted tumours on day 1 following cisplatin exposure. A metabolic flare in squamous cell carcinoma cells in vitro was found to be an early sign of response to cisplatin treatment. No increase in metabolism was detected in fibroblasts in vitro or in reactive cells in vivo. In conclusion, we have demonstrated a clinical value of FDG-PET in the management of cervical cancer, and in an experimental setting we have increased the understanding of tumour metabolism

Antibody engineering & therapeutics, the annual meeting of the antibody society December 7-10, 2015, San Diego, CA, USA

The 26th Antibody Engineering & Therapeutics meeting, the annual meeting of The Antibody Society united over 800 participants from all over the world in San Diego from 6-10 December 2015. The latest innovations and advances in antibody research and development were discussed, covering a myriad of antibody-related topics by more than 100 speakers, who were carefully selected by The Antibody Society. As a prelude, attendees could join the pre-conference training course focusing, among others, on the engineering and enhancement of antibodies and antibody-like scaffolds, bispecific antibody engineering and adaptation to generate chimeric antigen receptor constructs. The main event covered 4 d of scientific sessions that included antibody effector functions, reproducibility of research and diagnostic antibodies, new developments in antibody-drug conjugates (ADCs), preclinical and clinical ADC data, new technologies and applications for bispecific antibodies, antibody therapeutics for non-cancer and orphan indications, antibodies to harness the cellular immune system, building comprehensive IgVH-gene repertoires through discovering, confirming and cataloging new germline IgVH genes, and overcoming resistance to clinical immunotherapy. The Antibody Society's special session focused on "Antibodies to watch" in 2016. Another special session put the spotlight on the limitations of the new definitions for the assignment of antibody international nonproprietary names introduced by the World Health Organization. The convention concluded with workshops on computational antibody design and on the promise and challenges of using next-generation sequencing for antibody discovery and engineering from synthetic and in vivo libraries

Bevacizumab Effect on Topotecan Pharmacokinetics in a Murine Orthotopic Rhabdomyosarcoma Xenograft Model

Increasing evidence suggests that inhibition of vascular endothelial growth factor (VEGF) can transiently normalize tumor vasculature, thereby improving delivery of systemic chemotherapy. Bevacizumab (BEV), an anti-VEGF antibody, has been shown to transiently normalize tumor vasculature by increasing tumor vessel maturity, decreasing tumor vessel permeability, and increasing tumor oxygenation in an Rh30 orthotopic rhabdomyosarcoma xenograft model. However, the effects of BEV on the pharmacokinetics of TPT and the antitumor activity of TPT have not been evaluated. This study aimed to investigate the effect of BEV on TPT systemic and tumoral pharmacokinetics and to determine how these changes affect the efficacy of TPT in the Rh30 mouse model. Mice bearing Rh30 orthotopic xenografts were treated with BEV alone (5 mg/kg), TPT alone (2 mg/kg) or a combination of the two administered intravenously with different schedules. The pharmacokinetics of TPT, including TPT intratumoral penetration, as well as the efficacy of the monotherapy and combination therapy were evaluated. Population pharmacokinetic modeling and covariate analysis of TPT pharmacokinetics were performed using the maximal likelihood expectation maximization (MLEM) method in ADAPT 5 to predict the plasma and tumor concentration-time profile, to estimate the pharmacokinetic parameters of individual mouse and mice population, and to evaluate the effect of BEV on TPT systemic and tumoral pharmacokinetics. Tumor penetration was assessed by the tumor-to-plasma ratio of area under concentration-time curve (AUC). Tumor volume before and after the treatment were measured to evaluate the antitumor activity of the treatment regimen, and to assess the effect of BEV on the antitumor activity of TPT in Rh30 xenografts. Covariate analysis showed a single dose of BEV was associated with the increased systemic elimination rate and clearance of TPT. Furthermore, a single dose BEV had a time-dependent effect on the tumor elimination rate of TPT. The elimination rate of TPT from tumor compartment increased when it was given 1 day after a single dose of BEV and gradually decreased to control level when TPT was given 3 days and 7 days after a single dose of BEV. Multiple doses of BEV had no effect on TPT pharmacokinetics. TPT penetration was not altered after administering multiple doses of BEV, but a single dose of BEV produced a trend in changes of TPT penetration. Tumor efficacy was not dependent on the schedule of BEV and TPT. TPT significantly enhanced the antitumor activity of combination therapy while pre-treatment of BEV did not alter the antitumor activity of TPT. Tumor efficacy in MDBT groups was mainly due to the multiple doses of BEV and the antitumor activity of TPT was diminished. The present work provides crucial insights into the effect of coadministration of BEV on the pharmacokinetic changes and antitumor activity of TPT. The increased TPT systemic elimination and clearance after single dose of BEV treatment may be due to the altered renal clearance by VEGF. The increased TPT elimination from tumor tissue after 1 day pre-treatment of BEV may be caused by a normalization of tumor vasculature. The overall effect of BEV on TPT pharmacokinetics as well as TPT penetration is determined by the net balance of the pharmacologic changes of tumor microenvironment by BEV. And the antitumor activity of combination is determined by the balance between angiogenesis inhibition-induced tumor cell starvation and the tumor cytotoxicity due to the exposure to cytotoxic drugs. This study highlights the complexity of pharmacokinetic (PK) and pharmacodynamic (PD) interaction that may take place when antiangiogenic agent and cytotoxic drug are combined and cautions that more consideration and mechanistic investigation should be made before using a combination of anti-angiogenic agents with cytotoxic drugs for cancer treatment

Oncogenic Tyrosine Phosphatases: Novel Therapeutic Targets for Melanoma Treatment

Despite a large number of therapeutic options available, malignant melanoma remains a highly fatal disease, especially in its metastatic forms. The oncogenic role of protein tyrosine phosphatases (PTPs) is becoming increasingly clear, paving the way for novel antitumor treatments based on their inhibition. In this review, we present the oncogenic PTPs contributing to melanoma progression and we provide, where available, a description of new inhibitory strategies designed against these enzymes and possibly useful in melanoma treatment. Considering the relevance of the immune infiltrate in supporting melanoma progression, we also focus on the role of PTPs in modulating immune cell activity, identifying interesting therapeutic options that may support the currently applied immunomodulating approaches. Collectively, this information highlights the value of going further in the development of new strategies targeting oncogenic PTPs to improve the efficacy of melanoma treatment

The HBP1 tumor suppressor is a negative epigenetic regulator of MYCN driven neuroblastoma through interaction with the PRC2 complex

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