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Inhibition of tumor growth and metastasis simultaneously is an important issue for tumor therapy. The CXCR4/CXCL12 axis plays a crucial role in cancer metastasis, and the blocking of the CXCR4/CXCL12 axis is an effective way of inhibiting cancer metastasis. Combretastatin A4 nanodrug (CA4-NPs), a neogenesis blood vascular disrupting agent, can accumulate around blood vessels and disrupt tumor neogenesis of blood vessels more efficaciously than typical small molecular drug combretastatin A4 phosphate (CA4P). However, in this work, we find that the CXCR4 expression is significantly enhanced in CA4-NPs-treated tumor tissues in a metastatic orthotopic 4T1 mammary adenocarcinoma mouse model. Considering that the overexpression of CXCR4 can promote tumor cell metastasis, a novel cooperative strategy that utilizes plerixafor (PLF, CXCR4 antagonist) with CA4-NPs for inhibiting tumor growth and metastasis simultaneously is developed. The combination of CA4-NPs (60 mg kg-1 on CA4 basis) + PLF shows remarkably enhanced antitumor efficacy. The tumor growth inhibition rate of the combination group reaches 91.3%, significantly higher than those of non-cooperative groups. In addition, the number of lung metastasis foci of the combination group is least among all groups. This cooperative strategy provides a useful method for inhibiting tumor growth and metastasis simultaneously, and gives the evidence to support the clinical use of the combination of vascular disruption agents and CXCR4 antagonists.
This article was published in the following journal.
Name: Biomaterials science
Tumor-associated enzyme-activated prodrugs can potentially improve the selectivity of chemotherapeutics. However, the paucity of tumor-associated enzymes which are essential for prodrug activation usu...
There is a strong relationship between tissue factor (TF) and cancer. Many cancer cells express high levels of both full-length TF and alternatively spliced (as) TF. TF expression in cancer is associa...
Prostate cancer is one of the most common malignant tumors in men, and inhibiting metastasis is a key event but still a major challenge in prostate cancer treatment. Cancer-associated fibroblasts (CAF...
Diosmetin is a natural flavonoid obtained from citrus fruits and some medicinal herbs. Previous studies have reported the anti-cancer activity of diosmetin in some types of tumors. However, it is stil...
The system of hepatocyte growth factor (HGF) and its receptor c-Met plays a critical role in tumor invasive growth and metastasis. The mortality rate of colorectal cancer (CRC), one of the most common...
This is a study evaluating the safety and effectiveness of Combretastatin A4 Phosphate (CA4P) combined with the chemotherapy drugs, carboplatin and paclitaxel. The full treatment and obse...
This phase II trial studies how well whole brain radiation therapy works with standard temozolomide chemo-radiotherapy and plerixafor in treating patients with glioblastoma (brain tumor). ...
The purpose of this research study is to determine if Plerixafor can release cells into the blood and make them more sensitive to killing by Cytarabine and Daunorubicin, an anti-cancer dru...
RATIONALE: Combretastatin A4 phosphate may stop the growth of anaplastic thyroid cancer by stopping blood flow to the tumor. PURPOSE: This phase II trial is studying how well combretastat...
Malignant cells frequently produce many tumor growth factors to autocidal or endocrinal proliferate growth, metastasis,or angiogenesis about tumor cells. By studying tumor growth factors i...
Hypoxic conditions in tumor cells due to the tumor outgrowing its blood supply. It is associated with increased METASTASIS and resistance to RADIOTHERAPY and DRUG THERAPY.
A malignant tumor composed of cells showing differentiation toward sebaceous epithelium. The tumor is solitary, firm, somewhat raised, more or less translucent, and covered with normal or slightly verrucose epidermis. It may be yellow or orange. The face and scalp are the commonest sites. The growth can be slow or rapid but metastasis is uncommon. Surgery cures most of the cases. (From Rook et al., Textbook of Dermatology, 4th ed, pp2403-4)
An extracellular matrix glycoprotein from platelets and a variety of normal and transformed cells of both mesenchymal and epithelial origin. Thrombospondin-1 is believed to play a role in cell migration and proliferation, during embryogenesis and wound repair. Also, it has been studied for its use as a potential regulator of tumor growth and metastasis.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (TUMOR MARKERS, BIOLOGICAL) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...