Open Access Articles | Antitumor Activity of Cyclodextrin-based Supramolecular Platinum Prodrug In vitro and In vivo

Journal Name: Letters in Drug Design & Discovery

Author(s): Yu-Hui Zhang, Jie Wang, Siqintana Xin, Li-Juan Wang, Xianliang Sheng*.

 

 

 

 

Graphical Abstract:

 

Abstract:

Background: Considering the limitations of cisplatin in clinical application, there is ongoing research to fabricate new platinum-containing prodrug which are highly effective to tumor cells and have low toxicity to normal cells.

Methods: In this study, a cyclodextrin-based supramolecular platinum prodrug that is 6,6’-ophenylenediseleno- bridged bis (β-cyclodextrin)s (CD) and its potassium tetrachloroplatinate(II) complex was reported. The cytotoxicity experiments were performed to evaluate the anticancer activities of supramolecular prodrug in vitro by means of MTT assay. The practical application of supramolecular prodrug in tumor treatment in vivo were evaluated using BALB/c nude mice model bearing Hela cancer cells.

Results: Compared with commercial anticancer drug cisplatin, the resultant cyclodextrin-based platinum prodrug exhibited comparative anticancer effect but with much lower toxicity side effects in vitro and in vivo.

Conclusion: The cyclodextrin-based supramolecular platinum prodrug displayed antitumor activity comparable to the commercial antitumor drug cisplatin but with lower side effects both in vitro and in vivo, implying that the two adjacent cyclodextrin cavities not merely act as desired solubilizer, but also endowed the prodrug with cell permeability through the interaction of cyclodextrin with phospholipids and cholesterol on cell membrane. To read out more, please visit: http://www.eurekaselect.com/172707/article

Press Release | Frontiers in clinical drug research — Anti-cancer agents, now in its 5th edition

9789811405150-1

This eBook is authored by Dr. Ata-ur-Rahman, published on June 12, 2019.

For Further Details, Please visit https://ebooks.benthamscience.com/book/9789811405150/

 

Frontiers in Clinical Drug Research – Anti-Cancer Agents brings updated and critical information about developing clinical trials and research in anti-cancer research. Reviews in each volume are written by experts in medical oncology and clinical trials research and compile the latest information available on special topics of interest to oncology researchers.

The fifth volume of the series features reviews on biochemical inhibitors (second-generation protein kinase Inhibitors, histone deacetylase inhibitors, immune checkpoint inhibitors, EGFR Tyrosine Kinase inhibitors, non-coding RNAs), apoptosis, and physical exercise therapy for cancer patients undergoing chemotherapy. The treatment strategies in this volume cover neoplasms such as acute myeloid leukemia, gastrointestinal cancer, breast cancer and lung cancer. Read full press release to find out more at: https://www.eurekalert.org/pub_releases/2019-06/bsp-fic062019.php

eBook Highlights| Topics in Anti-Cancer Research -Volume 7

The seventh volume of the series covers topics such as drug delivery, new avenues for treatment of esophageal cancer and the role of nutrigenomics in finding new therapies.

Topics in Anti-Cancer Research covers important advances on both experimental (preclinical) and clinical cancer research in drug development. The book series offers readers an insight into current and future therapeutic approaches for the prevention of different types of cancers, synthesizing new anti-cancer agents, new patented compounds, targets and agents for cancer therapy as well as recent molecular and gene therapy research.

The comprehensive range of themes covered in each volume will be beneficial to clinicians, immunologists, and R&D experts looking for new anti-cancer targets and patents for the treatment of neoplasms, as well as varied approaches for cancer therapy.

The latest volume of the series starts with a review on non-coding RNAs and associated patents. These patents help researchers to identify various cancer biomarkers and oncogenic regulatory mechanisms. 3 chapters cover nanocarrier patents for enhanced drug delivery of chemotherapeutic agents. Nanocarriers allow drug manufacturers to encapsulate chemotherapeutic agents within thin membranes which allows the molecules to reach the targeted cellular location in the body. The specific topics refer to Nanotaxol which is a nanotechnology enhanced version of Taxol® – a chemotherapeutic agent derived from chemicals in the bark of Taxus brevifolia, stimuli responsive nanocarriers which change behavior according to temperature and pH and smart nanoformulations which rely on different chemical formulations to reach molecular targets. Other topics covered in this volume include the role of autophagy in esophageal cancer, and nutrigenomics (the science of how biological nutrients affect gene expression) in cancer research. In terms of patents, the reader will find a list of compounds which modulate autophagy, and nutrigenomic methods that allow researchers to understand nutritional biomarkers of disease and customize nutraceutical formulations based on genetic and metabolic factors, respectively. To read out more, please visit: https://ebooks.benthamscience.com/book-highlights/190102001/

 

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MOST ACCESSED ARTICLE – Role of Mitochondrial Mechanism in Chemotherapy-Induced Peripheral Neuropathy

Journal Name: Current Drug Metabolism

Author(s): Mohammad Waseem, Pooja Kaushik, Heena Tabassum*, Suhel Parvez.

 

 

 

Graphical Abstract:

 

Abstract:

Background: Even though chemotherapeutic regimens show considerable importance, it may cause progressive, continuing and sometimes irreversible peripheral neuropathy. Chemotherapy induced peripheral neuropathy (CIPN) is comprised of sensory abnormalities that are most distressing issues. The mechanism associated with CIPN pathogenesis is not completely revealed and its treatment is still questionable. The purpose of this review was to investigate the role of mitochondria in CIPN.

Methods: This review is literature based that describes the mitochondrial mechanism underlying CIPN and the neuropathic complications associated with different antineoplastic agents.

Results: For severe pain, a modification towards less efficient chemotherapeutic drugs could possibly be needed and/or patients perhaps prefer to withdrawal therapeutic regimen. The epidemiology of CIPN is still debatable. The major recurrent molecules causing CIPN are platinum based drugs including cisplatin and oxaliplatin, thalidomide, bortezomib, vinka alkaloids and taxanes. Neuropathic pain is one of the symptoms of CIPN. Various neuropathic disorders as well as CIPN are due to mitochondrial impairment, relevant impairment of Ca2+ signalling pathways and reactive oxygen species (ROS) that ultimately leads to apoptosis.

Conclusion: The pathophysiology of CIPN is complicated as chemotherapeutic medications often involve combination of drugs. With these combinatorial therapies cancer survivors develop continuing effects of CIPN which require rehabilitation strategies for the recovery of patient’s condition and quality of life.

 

READ MORE HERE: http://www.eurekaselect.com/158146

MOST ACCESSED ARTICLE – C-type Lectin Receptor: Old Friend and New Player – Medicinal Chemistry

Journal: Medicinal Chemistry

Author(s): Hai Hou*, Yahui Guo, Qing Chang, Tianming Luo, Xin Wu, Xueqiang Zhao

Graphical Abstract:

 

Abstract:

During the last two decades, C-type lectin receptors (CLRs) have been demonstrated to play key roles in initiating the host immune response against fungal infection. It is well established that CLRs, such as Dectin-1, Dectin-2, Dectin-3 and Mincle recognize the cell wall component from the infected microorganisms by using their carbohydrate recognition domain (CRD). Upon stimulation, CLRs induce multiple signal transduction cascades through their own immunereceptor tyrosine-based activation motifs (ITAMs) or interacting with ITAM-containing adaptor proteins such as FcRγ, which then lead to the activation of nuclear factor kappa B (NF-κB) through Syk- and CARD9-dependent pathway. Dissecting CLR signal cascades and their effects on host immune cells is essential to understand the molecular mechanisms in regulating host antifungal immunity. Recently, the activated CLRs including Dectin-1 and Dectin-2 are reported to undergo lysome-mediated degradation by an E3 ubiquitin ligase CBL-b. Moreover, structural analysis will help understand the molecular mechanism of these CLRs and provide clues to rational design for effective anti-fungal drugs. Overall, we summarize the current knowledge on activating and inhibitory CLRs and discuss how to boost host immune system to fight against invasive fungal infection.

 

To access the article, please visit: http://www.eurekaselect.com/152316/article

Highlighted Article – Glioblastoma Multiforme, Diagnosis and Treatment– Current Medicinal Chemistry

CMC-Articles_24-42-Noam Asna

http://www.eurekaselect.com/152454/article

Most Accessed Article – Neoadjuvant Therapy for HER2-positive Breast Cancer – Reviews on Recent Clinical Trials

Journal: Reviews on Recent Clinical Trials

Author(s): Rachel Wuerstlein, Nadia Harbeck.

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Abstract:

In HER2-positive early breast cancer, neoadjuvant treatment with a combination of sequential chemotherapy and HER2-targeted therapy is currently the standard of care. This is followed by breast surgery, radiotherapy (if indicated), completion of 12 months of HER2-directed therapy, and – depending on the tumor biology – endocrine adjuvant therapy, and ultimately follow up.

10-year survival rates in the HER2-positive subgroup of breast cancer do reach now more than 75% with the introduction of first adjvuant and later neoadjuvant HER2-targeted therapies over the last 15 years. The neoadjvuant setting helps to downstage locally advanced tumors, to provide early information of tumor response, to assess the efficacy of new therapies in vivo, to reduce treatment duration, and to introduce new targeted therapies into the clinical routine. It also allows enrolling fewer patients into clinical trials in order to reach adequate effects in clinical outcome.

The neoadjuvant approach and our interest in this setting are based on pCR (pathological complete response) and its translation into better long-term outcome. In recent trials, we have reached more than 60% pCR with a subsequent improvement of DFS and hopefully OS. Therefore, chemotherapy schedules and new HER2-targeted agents such as lapatinib, pertuzumab, and T-DM1 have been introduced into the neoadjuvant setting. To balance over- and undertreatment, current trials include personalized concepts and assess new biomarkers and tumorbiological factors. We have learned for example to differentiate between HR (hormone receptor)-positive and -negative tumors in the HER2-positive population. Depending on pCR or non-pCR after neoadjuvant treatment, the adjuvant therapy may be adjusted. This concept of post-neo-adjuvant trials is now entering the field of strategies in the neoadjuvant setting for HER2-positive non-metastatic primary breast cancer.
The 2017 standard of care in the neoadjuvant setting according to national and international guidelines combines a taxane-containing chemotherapy with a dual blockade of trastuzumab and pertuzumab.
This review will point out current trials and their strategies to continue improving outcome and reduce morbidity as well as mortality in HER2-positive early breast cancer.

Article by Disease – “Understanding Unmet Needs in the Older Acute Myeloid Leukemia (AML) Patient”

Article by Disease on “Oncology

Graphical Abstract:

 

Abstract:

Introduction: Acute Myeloid Leukemia (AML) is a rare form of cancer characterized by the infiltration of abnormal white blood cells that accumulate in the bone marrow at a rapid rate. AML has an overall incidence of 4 per 100,000 persons and accounted for over 10,000 deaths within the United States in 2015 [1]. Indeed, AML also represents a disease typically associated with the elderly, as the median age of diagnosis for AML is around 72 years old [2].

Advances: Over the past decades we have seen major advances in terms of understanding AML’s biology and prognosis, but some questions still remain unanswered, particularly for the elderly population. This gap in our understanding of AML translates into unmet needs for this population.

Conclusion: The current paper seeks to describe these specific needs and their associated barriers related to treatment, prognostic factors and relapse, health-related quality of life, disease costs, and palliative care support. Acquiring a better understanding of AML for elderly patients can lead to improved therapy options and quality-of-life for this population.

Editor’s Choice – “Hitting a Moving Target: Glioma Stem Cells Demand New Approaches in Glioblastoma Therapy”

Journal: Current Cancer Drug Targets

Author(s): Drew A. Spencer, Brenda M. Auffinger, Jason P. Murphy, Megan E. Muroski, Jian Qiao, Yureve Gorind, Maciej S. Lesniak

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Abstract:

Background: Glioblastoma multiforme (GBM) continues to devastate patients and outfox investigators and clinicians despite the preponderance of research directed at its biology, pathogenesis and therapeutic advances. GBM routinely outlasts multidisciplinary treatment protocols, almost inevitably recurring in a yet more aggressive and resistant form with distinct genetic differences from the original tumor. Attempts to glean further insight into GBM point increasingly toward a subpopulation of cells with a stem-like phenotype. These cancer stem cells, similar to those now described in a variety of malignancies, are capable of tumorigenesis from a population of susceptible cells.

Conclusions: Glioma stem cells have thus become a prevalent focus in GBM research for their presumed role in development, maintenance and recurrence of tumors. Glioma stem cells infiltrate the white matter surrounding tumors and often evade resection. They are uniquely suited both biochemically and environmentally to resist the best therapy currently available, intrinsically and efficiently resistant to standard chemo- and radiotherapy. These stem cells create an extremely heterogenous tumor that to date has had an answer for every therapeutic question, with continued dismal patient survival. Targeting this population of glioma stem cells may hold the long-awaited key to durable therapeutic efficacy in GBM.

Read more here: http://www.eurekaselect.com/148386

 

New Chemotherapy and Immunotherapy for Tuberculosis!

On World Tuberculosis Day 2016, read our research article on tuberculosis from the journal Current Respiratory Medicine Reviews

Abstract: Tuberculosis (TB) has been a widespread infectious disease since ancient times and remains a worldwide major health problem. TB morbidity with 8 to 9 million active cases per year and 1.3 deaths annually represent the largest number of incidences and of human deaths attributable to a single bacterial agent. Its causal agent Mycobacterium tuberculosis is able to survive in a latent state in infected individuals, thereby serving as a reservoir, waiting for the reactivation that usually occurs in immune-suppressed individuals, such as HIV patients. According to World Health Organization estimation, 2 billion people, almost one-third of the world’s population, are believed to be latently infected. An additional significant factor is the continued emergence of new multidrug resistant strains often associated to poor compliance due to the long, complex, toxic and expensive treatment. Thus, new anti-TB drugs and better therapeutic strategies are urgently needed. New drug candidates should short the standard regimens and being effective against drug resistant strains. In recent years, an emphasized research activity in the development of new TB drugs has being produced. Some compounds are presently in clinical development, while others are being investigated pre-clinically. The immune system is a critical factor for containment and cure of mycobacterial infection. Augmentation of protective immunity or decreasing the immune modulatory responses during late disease can be of value in the TB treatment. Thus, the use of immunotherapy with cytokines or bacterial derivatives as an adjunct to drug treatment may improve success rates for treatment of MDR-TB and shorten treatment time for drug-sensitive TB.

The present review concentrates to describe the most promising new drugs against TB which are now in clinical trials, as well as the immunotherapeutic assays performed in humans.

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