A Comparative Analysis of Tumors and Plasma Circulating Tumor DNA in 145 Advanced Cancer Patients Annotated by 3 Core Cellular Processes.

Matched-targeted and immune checkpoint therapies have improved survival in cancer patients, but tumor heterogeneity contributes to drug resistance. Our study categorized gene mutations from next generation sequencing (NGS) into three core processes. This annotation helps decipher complex biologic interactions to guide therapy.

A comprehensive review of protein kinase inhibitors for cancer therapy.

Protein kinases are involved in various cellular functions. About 2% of the human genome encodes for protein kinases. Dysregulation of protein kinases is implicated in various processes of carcinogenesis.

Celastrol Attenuates the Invasion and Migration and Augments the Anticancer Effects of Bortezomib in a Xenograft Mouse Model of Multiple Myeloma.

Several lines of evidence have demonstrated that deregulated activation of NF-κB plays a pivotal role in the initiation and progression of a variety of cancers including multiple myeloma (MM). Therefore, novel molecules that can effectively suppress deregulated NF-κB upregulation can potentially reduce MM growth. In this study, the effect of celastrol (CSL) on patient derived CD138+ MM cell proliferation, apoptosis, cell invasion, and migration was investigated.

Thymoquinone overcomes chemoresistance and enhances the anticancer effects of bortezomib through abrogation of NF-κB regulated gene products in multiple myeloma xenograft mouse model.

Multiple myeloma (MM) is a B cell malignancy characterized by clonal proliferation of plasma cells in the bone marrow. With the advent of novel targeted agents, the median survival rate has increased to 5 -7 years. However, majority of patients with myeloma suffer relapse or develop chemoresistance to existing therapeutic agents.

Celastrol suppresses growth and induces apoptosis of human hepatocellular carcinoma through the modulation of STAT3/JAK2 signaling cascade in vitro and in vivo.

Cumulative evidences(s) have established that the constitutive activation of STAT3 plays a pivotal role in the proliferation, survival, metastasis, and angiogenesis and thus can contribute directly to the pathogenesis of hepatocellular carcinoma (HCC). Thus, novel agents that can inhibit STAT3 activation have potential for both prevention and treatment of HCCs. The effect of celastrol on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was investigated.

Plumbagin inhibits invasion and migration of breast and gastric cancer cells by downregulating the expression of chemokine receptor CXCR4.

Background: Increasing evidence indicates that the interaction between the CXC chemokine receptor-4 (CXCR4) and its ligand CXCL12 is critical in the process of metastasis that accounts for more than 90% of cancer-related deaths. Thus, novel agents that can downregulate the CXCR4/CXCL12 axis have therapeutic potential in inhibiting cancer metastasis.

Methods: In this report, we investigated the potential of an agent, plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), for its ability to modulate CXCR4 expression and function in various tumor cells using Western blot analysis, DNA binding assay, transient transfection, real time PCR analysis, chromatin immunoprecipitation, and cellular migration and invasion assays.

Celastrol inhibits tumor cell proliferation and promotes apoptosis through the activation of c-Jun N-terminal kinase and suppression of PI3 K/Akt signaling pathways.

Celastrol, a plant triterpene has attracted great interest recently, especially for its potential anti-inflammatory and anti-cancer activities. In the present report, we investigated the effect of celastrol on proliferation of various cancer cell lines. The mechanism, by which this triterpene exerts its apoptotic effects, was also examined in detail.

Celastrol inhibits proliferation and induces chemosensitization through down-regulation of NF-κB and STAT3 regulated gene products in multiple myeloma cells.

Background And Purpose: Activation of pro-inflammatory transcription factors NF-κB and signal transducer and activator of transcription 3 (STAT3) is one of the major contributors to both pathogenesis and chemoresistance in multiple myeloma (MM), which results in high mortality rate. Thus, in the present study, we investigated whether celastrol could suppress the proliferation and induce chemosensitization of MM cells by interfering with NF-κB and STAT3 activation pathways.

Experimental Approach: The effects of celastrol were investigated using both a virtual predictive tumour cell system and different MM cell lines resistant to doxorubicin, melphalan and bortezomib.

Targeting cell signaling and apoptotic pathways by dietary agents: role in the prevention and treatment of cancer.

Cancer is one of the leading causes of death in the United States and around the world. Most modern drug-targeted therapies, besides being enormously expensive, are associated with serious side effects and morbidity. Still, the search continues for an ideal treatment that has minimal side effects and is cost-effective.

Molecular targets of celastrol derived from Thunder of God Vine: potential role in the treatment of inflammatory disorders and cancer.

Identification of active constituents and their molecular targets from traditional medicine is an enormous opportunity for modern pharmacology. Celastrol is one such compound that was originally identified from traditional Chinese medicine (Thunder of God Vine) almost three decades ago and generally used for the treatment of inflammatory and auto-immune diseases. Celastrol has attracted great interest recently, especially for its potential anti-inflammatory and anti-cancer activities.