Development of a unique small molecule modulator of CXCR4.

Background: Metastasis, the spread and growth of tumor cells to distant organ sites, represents the most devastating attribute and plays a major role in the morbidity and mortality of cancer. Inflammation is crucial for malignant tumor transformation and survival. Thus, blocking inflammation is expected to serve as an effective cancer treatment.

Application of metabolic PET imaging in radiation oncology.

Positron emission tomography (PET) is a noninvasive imaging technique that provides functional or metabolic assessment of normal tissue or disease conditions and is playing an increasing role in cancer radiotherapy planning. (18)F-Fluorodeoxyglucose PET imaging (FDG-PET) is widely used in the clinic for tumor imaging due to increased glucose metabolism in most types of tumors; its role in radiotherapy management of various cancers is reviewed. In addition, other metabolic PET imaging agents at various stages of preclinical and clinical development are reviewed.

Potential Biomarker of L-type Amino Acid Transporter 1 in Breast Cancer Progression.

Purpose: L-type amino acid transporter 1 (LAT1) is essential for the transport of large neutral amino acids. However, its role in breast cancer growth remains largely unknown. The purpose of the study is to investigate whether LAT1 is a potential biomarker for the diagnosis and treatment of breast cancer.

Metabolic positron emission tomography imaging in cancer detection and therapy response.

Positron emission tomography (PET) is a noninvasive imaging technique that provides a functional or metabolic assessment of normal tissue or disease conditions. Fluorine 18-fluorodeoxyglucose PET imaging (FDG-PET) is widely used clinically for tumor imaging due to increased glucose metabolism in most types of tumors, and has been shown to improve the diagnosis and subsequent treatment of cancers. We review its use in cancer diagnosis, staging, restaging, and assessment of response to treatment.

Current molecular imaging positron emitting radiotracers in oncology.

Molecular imaging is one of the fastest growing areas of medical imaging. Positron emission tomography (PET) has been widely used in the clinical management of patients with cancer. Nuclear imaging provides biological information at the cellular, subcellular, and molecular level in living subjects with non-invasive procedures.

Dipyrimidine amines: a novel class of chemokine receptor type 4 antagonists with high specificity.

The C-X-C chemokine receptor type 4 (CXCR4)/stromal cell derived factor-1 (SDF-1 or CXCL12) interaction and the resulting cell signaling cascade play a key role in metastasis and inflammation. On the basis of the previously published CXCR4 antagonist 5 (WZ811), a series of novel nonpeptidic anti-CXCR4 small molecules have been designed and synthesized to improve potency. Following a structure-activity profile around 5, more advanced compounds in the N,N'-(1, 4-phenylenebis(methylene)) dipyrimidin-2-amines series were discovered and shown to possess higher CXCR4 binding potential and specificity than 5.

Discovery of small molecule CXCR4 antagonists.

In light of a proposed molecular mechanism for the C-X-C chemokine receptor type 4 (CXCR4) antagonist 1 (AMD3100), a template with the general structure 2 was designed, and 15 was identified as a lead by means of an affinity binding assay against the ligand-mimicking CXCR4 antagonist 3 (TN14003). Following a structure-activity profile around 15, the design and synthesis of a series of novel small molecular CXCR4 antagonists led to the discovery of 32 (WZ811). The compound shows subnanomolar potency (EC50 = 0.

Blockade of invasion and metastasis of breast cancer cells via targeting CXCR4 with an artificial microRNA.

miRNAs have been shown to function as regulatory molecules and to play an important role in cancer progression. Very little is currently known about the increasing invasion and metastasis of breast cancer due to the loss of expressive levels of certain miRNAs in breast tumor cells. In order to determine whether the CXCR4/SDF-1 pathway is regulated by expression of miRNAs, we designed and synthesized pre-miRNA against CXCR4.

CXC chemokine receptor-4 antagonist blocks both growth of primary tumor and metastasis of head and neck cancer in xenograft mouse models.

Squamous cell carcinoma of the head and neck (SCCHN) metastasizes to the lymph nodes and lungs. We have generated previously an orthotopic mouse model for head and neck metastasis and did in vivo selection of SCCHN cells through four rounds of serial metastases. A subpopulation of 686LN cells with high metastatic potential (686LN-Ms) was isolated.

Artificial tumor model suitable for monitoring 31P and 13C NMR spectroscopic changes during chemotherapy-induced apoptosis in human glioma cells.

An artificial tumor method was developed to study cells inside the sensitive volume of an NMR spectrometer during growth and apoptosis. The tumor was composed of a 50:50 mixture of tightly packed porous-collagen and nonporous-polystyrene microspheres. The porous collagen served as a growth surface for the tumor cells, and the nonporous polystyrene served as a structural support to limit compression of the packed bed during perfusion.