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LKT Labs is happy to announce its annual AACR iPad drawing winner for 2017 – Dr. Haiyan Xiao of Augusta University in Augusta, Georgia.

Dr. Xiao’s primary research focus is based on developing novel and effective vaccines to prevent or treat cancers. Her doctoral dissertation topic was, “Preventive and Therapeutic Roles of Lentiviral Vector Prime and Vaccinia Virus Boost in Mouse Melanoma.” Her dissertation research was published in several well-received articles in the Journal of Immunology. Dr. Xiao’s postdoctoral research is focused on examining how circulating leukocytes interact with the vascular endothelium during chronic inflammatory conditions such as cancer and sickle cell disease.

Dr. Xiao’s research goals are to study epigenetic changes in the immune system that may contribute to chronic conditions including obesity, diabetes, and cancer. By identifying changes, she hopes to develop new insights into the immunological impact of these chronic conditions. Ultimately, she hopes her research leads to the development of methods for preventing immunological complications associated with chronic conditions.

Researchers from past years hail from a variety of institutions, including:

2016 – Boston University; Boston, MA

2015 – The Wistar Institute; Philadelphia, PA

2014 – Vanderbilt University; Nashville, TN

Add your organization to the list of winners in 2018 when LKT Labs holds its next drawing at the AACR conference in Chicago, IL!

MYC is a frequently deregulated oncogene in many human cancers. It is normally responsible for facilitating cell growth and proliferation through the encoding of transcription factors. Since many types of cancers are dependent on the upregulation of MYC, reducing MYC protein levels by targeting its upstream regulators such as histone deacetylases (HDAC) and phophoinositide 3-kinases (PI3K) may be a viable and effective method of treatment.

CUDC-907 is an inhibitor of PI3K and class I and II HDACs. In a recent study published in Molecular Cancer Therapeutics, it was shown that PI3K and HDAC inhibition synergistically downregulated MYC protein levels and induced apoptosis in “double-hit” (DH) diffuse large B-cell lymphoma (DLBCL) cells. CUDC-907 suppressed the growth and survival of MYC-altered or MYC-dependent cancer cells through this downregulation of the MYC protein. Further research and development utilizing CUDC-907 in MYC-driven cancers may be pursued thanks to this study.

LKT Laboratories carries CUDC-907 as well as a number of other PI3K inhibitors for research use.

C8112 CUDC-907

PI3K inhibitor list

Kaiming S., Ruzanna A., et al. Dual HDAC and PI3K inhibitor CUDC-907 Downregulates MYC and Suppresses Growth of MYC-dependent Cancers. Mol Cancer Ther 2016.

Cabozantinib is a chemotherapeutic compound that has shown potential as a treatment for medullary thyroid cancer and other types of solid tumors. It is primarily known for its inhibition of c-Met and vascular endothelial growth factor receptor 2 (VEGFR-2). By inhibiting these tyrosine kinases Cabozantinib reduces tumor growth, metastasis, and angiogenesis.

In a 2016 study, cabozantinib showed activity against gastrointestinal stromal tumors (GIST). In many cases of GIST, oncogenic signaling is driven by KIT mutations. Tyrosine kinase inhibitors (TKI) such as imatinib have been used to treat GIST, but resistance to TKI caused by secondary mutations to KIT sometimes renders this treatment ineffective.

Cabozantinib was tested in patient-derived xenograft models of GIST, with each model carrying different KIT mutations. Three different models were examined in total, and in all three cabozantinib inhibited proliferative activity, even in those models that were imatinib-resistant. Compared to an imatinib treated group and a control group, cabozantinib also significantly reduced microvessel density in all three models.

From the study it was concluded that cabozantinib shows promising antitumor activity in both imatinib-sensitive and imatinib-resistant GIST models. The activity is achieved through the inhibition of tumor growth, proliferation, and angiogenesis, and may provide a valid alternate treatment method for GIST going forward.

C0006 Cabozantinib

I4802 Imatinib Mesylate

Gebreyohannes Y., Schoffski P., et al. Cabozantinib is Active against Human Gastrointestinal Stromal Tumor Xenografts Carrying Different KIT Mutations. Mol Cancer Ther; 15(12); 2845-52.

Piperlongumine is found in several species of the Piper plant and displays many beneficial characteristics, including antithrombotic, anti-inflammatory, anti-atherosclerotic, and chemotherapeutic activities. Isolated from the fruit of the long pepper, recent research has focused on the ability of this natural product to suppress tumor growth alone and in combination with other chemotherapeutic compounds.

In a study published in 2015, the effects of Piperlongumine were examined in pancreatic cancer cells. Pancreatic cancer is an aggressive malignancy with a relatively poor prognosis, even in cases where it is diagnosed early. There are few good options for chemotherapy.

In vitro, piperlongumine showed inhibition of pancreatic cancer cell lines, inhibited the activation of NF-kB, and also potentiated the apoptotic effects of gemcitabine, a nucleoside analog commonly used in the chemotherapeutic treatment of some cancers. Piperlongumine went on to show significant activity in vivo, where it suppressed tumor growth alone and enhanced the efficacy of gemcitabine in xenograft mouse models. These results were consistent with the downregulation of NF-kB activity and its target genes, decreased proliferation, and increased apoptosis in tumor remnants seen in the model.

The results of the study suggest both potential for piperlongumine as a stand-alone treatment for human pancreatic cancer, as well as a partner-chemotherapeutic with compounds like gemcitabine. Both piperlongumine and gemcitabine are available from LKT Labs for research use.

P3561 Piperlongumine

G1745 Gemcitabine Hydrochloride

Wang Y., Wu X., et al. Piperlongumine Suppresses Growth and Sensitizes Pancreatic Tumors to Gemcitabine in a Xenograft Mouse Model by Modulating the NF-kappa B Pathway. Cancer Prev. Res. Mar;9(3):234-44.

As of October 12th, 2016, LKT Laboratories has earned its MBE certification from the North Central Minority Supplier Development Council. The National Minority Supplier Development Council (NMSDC) advances business opportunities for certified minority business enterprises and is one of the nation’s leading corporate membership organizations.

End users may secure funding for resources provided by trusted minority-owned businesses such as those certified through the NMSDC. LKT Labs is proud to join this network of organizations.

Barasertib, also known as AZD-1152, is a highly selective aurora kinase B inhibitor. As an aurora kinase inhibitor, it has shown the ability to disrupt the cell cycle and consequently induce apoptosis in vitro. It has inhibited the growth of human colon, lung, and haematologic tumor xenografts in immunodeficient mice, and continues to be evaluated in various disease models.

In a 2016 study, barasertib inhibited the growth of small-cell lung cancer cells in vitro and in vivo. Small-cell lung cancer cells are good targets for aurora kinase inhibition, thanks to their rapid proliferation and high rates of MYC family amplification. Inhibitors of mitosis such as aurora kinase inhibitors have been effective in causing apoptosis in cells expressing high levels of MYC in other tumor types.

A panel of small-cell lung cancer lines with and without MYC family gene amplification was screened for growth inhibition by barasertib. The growth inhibition caused by barasertib correlated with cMYC amplification and cMYC gene expression in the panel. Small-cell lung cancer tumors with high cMYC amplification or gene expression may thus be good targets for barasertib and other aurora kinase B inhibitors.

LKT Labs sells a number of aurora kinase inhibitors, including AZD1152:

A9714 AZD-1152-HQPA

M4652 MLN-8237

T5996 Tozasertib

Z4900 ZM-447439 Trihydrate

References:

Helfrich B., Kim J., et al. Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLS Cell Lines In Vitro and In Vivo. Mol Cancer Ther; 15(10); 2314-22. PMID: 27496133.