Tubulin colchicine site binding agent LL01 displays potent antitumor efficiency both in vitro and in vivo with suitable drug-like properties

In this study, we further demonstrated that LL01 was not a P-gp substrate. It potently inhibited the growth of a variety of tumor cells, including those with multidrug resistance, with GI50 values in the low nanomole ranges. In vitro liver microsome stability assay, LL01 was modest stable in the liver microsomes of human, mouse and rat, but was fast metabolized in dog. After single oral administration of LL01 at a dose of 10  mg/kg in SD male rats, LL01 showed acceptable PK properties with a mean bioavailability of 41%. In human HepG2 hepatoma xenograft, at the oral doses of 25 mg/kg/day and 12.5 mg/kg/day, LL01 inhibited the tumor growth by 61.27%, and 43.74%, respectively, which is much better than the positive dru g sorafenib (29.45%; 30 mg/kg/day). Therefore, LL01 might be a potential drug candidate for further investigation for hepatocellular carcinoma therapy.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research

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Conclusion: The incidence of penile and anal high-grade intraepithelial neoplasia and SCC in men with diabetes was increased compared with men without diabetes. For penile and anal SCCs, this was primarily due to an increased risk in men with T2D.
Source: Epidemiology - Category: Epidemiology Tags: Infectious Diseases Source Type: research
Tigecycline has been used as one of the therapeutic choices for the treatment of infections caused by multidrug-resistant Klebsiella pneumoniae. However, the emergence of tigecycline heteroresistance has led to great challenges in treating these infections. The purpose of this study was to investigate whether tigecycline-heteroresistant K. pneumoniae (TGCHR-Kp) exists in clinical isolates, and to further characterize the underlying molecular mechanisms involved in the development of tigecycline-resistant subpopulations. Of the 268 tigecycline-susceptible clinical K. pneumoniae isolates, 69 isolates were selected as tigecyc...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Condition:   Cutaneous Squamous Cell Carcinoma Intervention:   Drug: Imgatuzumab Sponsors:   Pega-One S.A.S.;   ICON plc Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Abstract Over the past decades, studies of phytochemicals as modifiers of radiotherapeutic efficacy have become increasingly popular to improve the treatment outcome of human malignancies. In the current comprehensive review article, radiosensitizing effects of curcumin, a yellow-colored polyphenolic constituent of turmeric, in various preclinical cancer models, both In Vitro and In Vivo, are presented. Attenuation of radioadaptation and augmentation of irradiation-induced cancer cell killing are achieved through multifaceted action of curcumin on suppression of prosurvival and antiapoptotic factors. Mos...
Source: Nutrition and Cancer - Category: Cancer & Oncology Authors: Tags: Nutr Cancer Source Type: research
In conclusion, e-As4S4 holds great potential for an alternative therapeutics in the treatment of breast cancer, due to its unique function of correcting the aggressive microenvironment. Introduction Metastasis is the leading cause of breast cancer mortality, which has been one major challenge in clinical treatment (1). In particular, triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptors (ER), progesterone receptors (PR) and HER2 receptors, which is one of the most aggressive types of breast cancers, marked by high rates of relapse, visceral metastases and early death (2, 3). The...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Qingbin Cui1,2, Chao-Yun Cai2, Hai-Ling Gao2,3, Liang Ren1, Ning Ji2,4, Pranav Gupta2, Yuqi Yang2, Suneet Shukla5, Suresh V. Ambudkar5, Dong-Hua Yang2 and Zhe-Sheng Chen2* 1School of Public Health, Guangzhou Medical University, Guangdong, China 2Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, United States 3Department of Histology and Embryology, Clinical Medical College, Weifang Medical University, Weifang, China 4Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tian...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppres...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Discussion Suppressor of cytokine signaling 1 is an essential molecule for maintaining immune homeostasis and subverting inflammation. Disorders arising from excess inflammation or SOCS1 deficiency can be potentially treated with SOCS1 mimetics (Ahmed et al., 2015). While SOCS1 has promising potential in many disorders, it should be noted that new targets and actions of SOCS1 are still being discovered and not all the effects of this protein are beneficial in autoimmune diseases and cancer. For instance, SOCS1 degrades IRS1 and IRS2, required for insulin signaling, via the SOCS Box domain, thus, limiting its potential in ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In conclusion, NC-LAP demonstrate antitumoral effect in HER-positive bladder cells by inducing cell cycle arrest and apoptosis exhibiting better effects compared to the non-encapsulated lapatinib. Our work suggests that the LAP loaded in nanoformulations could be a promising approach to treat tumors that presents EGFR overexpression phenotype. Introduction Bladder cancer (BC) is a heterogeneous disease which presents several molecular characteristics associated with different clinical outcomes (1). Urothelial or transitional cell carcinoma (TCC) represent the most frequent type of bladder cancer (2) and are classifie...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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