ASPP2, a New Regulator of the Mevalonate Pathway in Cancer
DOI: 10.29245/2578-2967/2022/1.1198 View / Download PdfBeibei Liang1,2, Yangyang Xie1, Lisha Zhang1,3, Jian Zhao1,3*
1Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine & Health Sciences, Shanghai, 201318, China
2Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai 201318, China
3Shanghai University of Traditional Medicine, Shanghai 201203, China
Potential Transdermal Cancer Treatment Through Blood Brain Barrier with a Crystalline Neratinib Salt
Thomas E. Beesley1* and Mark V. Beesley2
1TEB Chiral View LLC, Consulting, Towaco, NJ 07082, USA
2MB Manufacturing, Blairstown, NJ 07825, USA
The tyrosine kinase inhibitor Neratinib has demonstrated its efficacy against HER2+ breast cancer metastases as the maleate salt. It has, however, had only a limited success as the maleate acid salt to cross the blood-brain barrier (BBB) due in part to its low oral absorption rate. At high oral doses severe diarrhea occurs. The potential to treat metastasized HER2+ cancer in the cerebellum and spinal cord that effects 30-50% of patients with this condition with a new crystalline salt and a topical application of a dimethyl sulfoxide (DMSO) solution has been investigated. This work proposes to use different Neratinib salts to improve solubility and BBB transport by a transdermal rather than an oral administration protocol. The preparation of the salts is described, and analytical methods developed for LC and LC/MS. The log P coefficient utilizing octanol/buffered water, shake flask method, will be used as a predictor of potential improvement in BBB transfer due to increased lipophilicity. Solubility data is supplied. An extensive review of DMSO and BBB experiments was undertaken leading to the establishment of rules to make this methodology work. First, a log P in the range of 2-4 is essential. Second, amine functions have to be blocked with suitable salts. If an amine function is present, it will be trapped by the endothelial membrane. DMSO has a well-documented favorable toxicological profile and can be sterilized making it safe for oral and parenteral routes. A transdermal protocol using Neratinib succinate in 20/20/60: H2O/EtOH/DMSO is described with all the safety measures presented.
DOI: 10.29245/2578-2967/2022/1.1197 View / Download Pdf Recent Advances in Development of New Technology in Pre and Intra Operative Breast Cancer Diagnoses
Justina A Ugwah1,4, Martin O’Sullivan2, Brian O’Donnell3, Eric J. Moore1,4*
1Life Sciences Interface, Tynadall National Institute, University College Cork, Ireland
2Department of Surgery, Cork University Hospital, Cork
3Department of Anaesthesia, Cork University Hospital, Cork
4School of Chemistry, University College Cork
Breast cancer is the second most occurring malignant disease in women. 1 in 9 women will be affected by this disease in their lifetime. The gold standard for breast cancer screening is the mammographic technique, which has its limitations especially for women aged below 40 as a result of breast density. Ongoing research are exploring techniques that can improve detection accuracy as well as reduce time and money spent in advanced stage treatment options. This review paper highlights the different technologies that have been developed for breast cancer diagnoses.
DOI: 10.29245/2578-2967/2021/2.1194 View / Download Pdf