Abstracts Ahead of Print | Safety Profiles and Pharmacovigilance Considerations for Recently Patented Anticancer Drugs: Lung Cancer

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Author(s): Alessandra Bearz, Sara Cecco, Sara Francescon, Francesco Lo Re, Giuseppe Corona, Paolo Baldo*.

 

 

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Background: Lung cancer is the most frequent cause of cancer-related death. In the last decades, the introduction of targeted therapies and more recently, of immunotherapy, has led to significant improvements in different outcomes of this malignant neoplasm.

Objective: The present review provides a balanced overview of most recent targeted therapies and immunotherapies patented for the treatment of lung cancer.

Method: An extensive scientific literature and patent databases search were performed to identify peer-reviewed studies containing information on recently patented drugs for the treatment of lung cancer, with a particular focus on their safety data and recently patented combinations.

Results: The development of therapies directed to different pathways involved in the tumor angiogenesis, proliferation, and metastasis has transformed the clinical practice of lung malignancies. Several clinical trials have shown an improvement in terms of progression-free survival and overall survival in patients with advanced/metastatic lung cancer. Safety data, extracted from clinical trials and from the WHO global database of adverse drug reactions (VigiAccessTM database), show that recently patented drugs for the treatment of lung cancer are well- tolerated and most of the adverse events reported are mild to moderate.

Conclusion: Currently, a consistent number of new drugs and combinations have been introduced for the treatment of patients with advanced-stage lung cancer. Safety data remain essential to better assess the long-term risk/benefit ratio of these valuable emerging therapies. The new patents’ development could provide further significant improvements for lung cancer treatment. To read full abstract, please visit: http://www.eurekaselect.com/173895/article

Press Release | Dosimetry and toxicity studies of a sulfonamide derivative of Sulforhodamine 101

 

The article by Dr. E Savio et al. is published in Current Radiopharmaceuticals, 2018

BACKGROUND

The SR101 N-(3-[18F]Fluoropropyl) sulfonamide ([18F]SRF101) is a Sulforhodamine 101 (SR101) derivative that was previously synthesised by our group. The fluorescent dye SR101 has been reported as a specific marker of astroglia in the neocortex of rodents in vivo. Some limitations of SR101 with respect to cell specificity have been identified. This derivative was labelled to study its biological in vivo behaviour through PET imaging.

As some recent investigations have shown, astroglia is affected in the early stages of different neurologic diseases, and reactive astrocytes contribute to neuroinflammation at later stages. This investigation focused on reactive astrocytosis in Alzheimer’s disease (AD). It is postulated that [18F]SRF101 is a potential PET radiotracer for astrocytosis detection. A biological characterisation of the novel tracer in a triple-transgenic mice model of AD (3xTg) was performed, and the results were compared with those of healthy Black C57BL6J mice. The biodistribution studies showed a hepatobiliary metabolisation of the compound. PET imaging with [18F]SRF101 revealed that the novel tracer could be a marker of astrocytosis in this animal model. These results suggested that [18F]SRF101 is a promising candidate for a more extensive evaluation as a PET astrocyte tracer.

To conclude the preclinical characterisation of [18F]SRF101 and to allow for drafting a pilot clinical evaluation in patients, radiation dosimetry studies of [18F]SRF101 injections were conducted on mice considering the following issues: i) the absorbed dose assessment can be based on biokinetic data obtained in small animals and ii) to develop new radiotracers for brain imaging, studies have been carried out on time-activity curves in different sections of the brain and in other organs.

A single-dose toxicity study was also carried out considering the guidelines on toxicology studies applicable to radiopharmaceuticals. The toxicological limit chosen in this case was <100 μg based on the concept of microdosing. The study was carried out with a dose set by allometric scaling with a safety factor of 100. Because [18F]SRF101 is a radiopharmaceutical prepared by a not-quantitative radiolabelling reaction and its synthetic procedure involves a purification step to separate the desired radioactive compound from the reaction mixture, toxicity studies were performed for unlabelled SRF101.

In summary, the aim of this study was to perform a toxicological evaluation of [18F]SRF101 and to estimate the human radiation dosimetry of this tracer based on preclinical studies. Obtaining this data will allow for moving forward to assess its potential as a PET imaging radiopharmaceutical for clinical use.

RESULTS

All animals survived until the end of the study with no systemic signs of toxicity throughout the entire observation period. No drug related changes were noted in the parameters examined during the 14-day study, including body weight, food consumption, eyes changes, clinical pathology parameters, gross necropsy findings, absolute and relative organ weights, histopathology findings, or microscopic lesions.

The absorbed and effective doses were estimated by OLINDA/EXM V2.0. Both dosimetric models–male and female–presented the same tendency. The highest total absorbed dose values were for the different sections of the intestines (left colon, small intestine, right colon and rectum). For the male dosimetric model, other organs exhibiting a high total absorbed dose included the liver, kidneys, gallbladder wall and pancreas. For the female dosimetric model, the uterus was added in addition to the mentioned organs.

The effective dose for male and female dosimetric models was 4.03E-03mSv/MBq and 5.08E-03mSv/MBq, respectively. For an administrated activity of 350MBq this would correspond to 1.41mSv and 1.78mSv for the same dosimetric models.

CONCLUSIONS

A toxicological evaluation of SRF101 was performed, which verified the biosafety of the new compound for single-intravenous injections in humans. The dosimetry calculations from the animal data revealed that the radiation-associated risk of [18F]SRF101 would be of the same order as other 18F radiopharmaceuticals used in clinical applications. In summary, the data generated through these studies confirm that the novel radiotracer would be safe for use in human PET imaging. This would allow for drafting a pilot clinical evaluation of patients.

Browse the Article at: http://www.eurekaselect.com/165008

MOST ACCESSED ARTICLE – Opioids in the Frame of New Psychoactive Substances Network: A Complex Pharmacological and Toxicological Issue

Journal Name: Current Molecular Pharmacology

Author(s): Ludovic Ventura, Felix Carvalho, Ricardo Jorge Dinis-Oliveira*.

 

 

Graphical Abstract:

 

Abstract:

Background: New psychoactive substances (NPS), often referred to as “legal highs” or “designer drugs”, are derivatives and analogues of existing psychoactive drugs that are introduced in the recreational market to circumvent existing legislation on drugs of abuse.

Objective: This systematic review aims to gather the state of the art regarding chemical, molecular pharmacology and toxicological information of opioid class of NPS.

Methods: Chemical, pharmacological, toxicological and clinical effects of opioid class of NPS were searched in books and in PubMed (U.S. National Library of Medicine) without a limiting period.

Results: Within this class, fentanyl analogues are among the most frequently abused and pose several clinical concerns and therefore will be thoroughly discussed. Other opioid sub-categories of NPS frequently misused include AH-7921, MT-45, U-47700, U-50488, desomorphine, mitragynine, tramadol, tapentadol, salvinorin A and its analogue herkinorin.

Conclusion: Due to inefficient monitoring techniques, as well as limited knowledge regarding the acute and long-term effects of opioids NPS, further clinical and forensic toxicological studies are required.

 

 

READ MORE HERE: http://www.eurekaselect.com/153703

EDITOR’S CHOICE – Stereotactic Body Radiation Therapy in Head and Neck Squamous Cell Carcinoma – Current Cancer Therapy Reviews

Journal: Current Cancer Therapy Reviews

Author(s): Rashi Garg, Omar Mahmoud

Abstract:

Background: Stereotactic body radiotherapy (SBRT) or radiosurgery has emerged as a viable highly precise technique that delivers a hypofractionated radiotherapy regimen with a high biologic effective dose. In addition to patient convenience, this dose is thought to provide acceptable local control while keeping toxicity to a minimum due to the typical small target size. The aims of this paper are to review recent outcomes with the application of SBRT in the management of head and neck cancer.

Methods: Research and online content related to head and neck cancer SBRT were reviewed focusing on dose fractionation schedules, incorporation of systemic therapy and long term toxicity.

Results: SBRT technique provided convenient precise approach in the management of primary as well as recurrent head and neck cancer with adequate local control rates and tolerable long term toxicity profile.

Conclusion: The use of stereotactic body radiotherapy is still evolving and multiple studies are needed to optimize the dose fractionation of SBRT and its integration with systemic therapy.

Read more here: http://www.eurekaselect.com/159256/article

Press Release for EurekAlert! Zebrafish as an animal model to study the effects of endocrine disruptors

zebra-fish

Water is vital for our survival. However, water quality is always a concern for public health authorities as it may contain diverse environmental pollutants, including endocrine disrupting chemicals (EDCs). Endocrine disrupting chemicals are one group of potentially hazardous substances that comprise natural and synthetic chemicals, with the ability to mimic endogenous hormones or interfere with their biosynthesis, metabolism, and normal functions. Common examples are bisphenol A, triclosan, phthalates, lead, mercury, nickel and polychlorinated biphenyls, among others.

Fish are known to be quite sensitive to the effects of EDCs and therefore, are employed as research models to study the possible impacts of these chemicals in humans. In a review led by Purdue University (USA) and the University of Cartagena (Colombia), a team of researchers has proposed the zebrafish as a model to predict the effects of EDCs on humans using toxicogenomic tools, such as microarrays or whole-genome sequencing. This is possible due to the fact that zebrafish genes that have significantly altered expression after exposure to EDCs are very similar to those found in humans. In addition, many of the glandular system found in zebrafish have similarities with those in humans, making this fish model suitable to study alterations on the endocrine system.

According to the authors, vitellogenin and aromatase cytochrome P450 are key genes that can be monitored in zebrafish to detect the presence of EDCs in water samples, especially at environmentally relevant concentrations.

Toxicogenomic tools also offer the possibility to find new mechanisms by which EDCs alter the reproductive status of zebrafish, allowing its use to test the safety of new products entering the market. The possibilities are immense and the goal is to continue finding new markers of toxicity, and therefore alternative bridges to link EDC exposure to common diseases in humans.

Co-authors of the paper include Karina Caballero-Gallardo, Jesus Olivero-Verbel (University of Cartagena, Cartagena, Colombia) and Jennifer L. Freeman (Purdue University, USA).

Reference: Caballero-Gallardo, K.; et al (2016). Toxicogenomics to Evaluate Endocrine Disrupting Effects of Environmental Chemicals Using the Zebrafish Model., DOI: 10.2174/1389202917666160513105959

For more information about the article, please visithttp://benthamscience.com/journals/current-genomics/volume/17/issue/6/page/515/

New Issue Published!!

Current Drug Safety – 9 Issue 2

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Aims & Scope

Current Drug Safety publishes frontier articles on all the latest advances on drug safety. The journal aims to publish the highest quality research articles, reviews and case reports in the field. Topics covered include: adverse effects of individual drugs and drug classes, management of adverse effects, pharmacovigilance and pharmacoepidemiology of new and existing drugs, post-marketing surveillance. The journal is essential reading for all researchers and clinicians involved in drug safety.

 www.eurekaselect.com

Abstracted & Indexed in:

Chemical Abstracts, PubMed/MEDLINE, Scopus, EMBASE, Genamics JournalSeek, PubsHub, J-Gate, EMCare.

 http://www.eurekaselect.com/123007/issue/2

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