Cell hyperplasia and cancer-causing mutation
Cancer is a malignant tumor, is the main reason for the formation of a variety of cell gene mutation, resulting in the rapid proliferation of abnormal. In addition to out-of-control growth of cancer cells, but also invasion of the surrounding normal organizations, through the circulatory system or lymphoid tissue transferred to other organs. Based on the location of cancer, malignant degree, the development of the extent and the patient's physical state, cancer can be removed through surgery, chemotherapy, radiotherapy, immunotherapy, monoclonal antibody treatment, as well as other ways to heal.
The day after the body's immune system can be divided into humoral immunity (by B cells to produce antibodies to achieve the protective effect) and cellular immunity, cellular toxicity of T cells and natural killer cells are immune cells play an important role. Cellular toxicity of T cells can identify the target cells and destroy it. Natural killer cells from lymphoid bone marrow stem cells, the body's fight against cancer of the first line of defense against invasion, are mainly distributed in the peripheral blood and spleen, a small number in the lymph nodes and other tissues. Natural killer cells only recognize the specific tumor cell surface molecules, we can to eradicate it. Research indicates that natural killer cell activity and cancer recurrence, metastasis and survival of cancer patients are closely linked.
Traditional cancer treatment, mainly the rapid proliferation of cancer cells inhibited growth and induced apoptosis. Apoptosis is a cell of a basic physiological phenomenon in multicellular organisms during development and individual survival, the play does not require the removal or the role of abnormal cells. In the apoptosis process, the cells will shrink, and its DNA was endonuclease degrade to form with 180 to 200 base pairs of the fragment, and finally cracking into multiple apoptotic bodies were surrounding cells or phagocytic cells.
However, cancer cells are heterogeneous, a higher grade are often in the chemical drugs and radiation therapy has managed to survive, or escape of toxic cellular immune system cells and natural killer T cells to detect, leading to cancer after treatment frequent recurrence of the situation.
Cancer culprit
In recent years, it is difficult to cure cancer in understanding the reasons for the development of a breakthrough, scientists, including leukemia, breast, brain, lung, liver, ovarian cancer, prostate cancer, colorectal cancer, oral cancer and other cancers Organization found that the "cancer stem cells" existence. Cancer stem cells and normal stem cells have many similarities, such as self-renewal ability and differentiation, and cancer stem cells are likely derived from a variety of mutations occurred in the normal stem cells.
On the one hand, cancer stem cells because of their extremely slow growth rate, or even to stop a split in the state, on the other hand, because the performance of ABC transport proteins much more than the general tumor cells, it can not easily be killed by chemotherapy or radiotherapy. Cancer stem cells is not only a cancer recurrence after treatment and the loss of the original main reason for effective drug reaction, but also is likely to be malignant cancer metastasis culprits.
ABC transport proteins are a large group of ATP hydrolysis by the provision of energy transport protein, first discovered in E. coli of endometrial bilayer membrane, at present, including human and other species have been found more than 100 kinds, among a variety of cancers caused by Chemotherapy failed multiple disease-resistant P-glycoprotein most famous. P-glycoprotein and a variety of anti-cancer drugs can be combined through the ATP (adenosine triphosphate) hydrolysis to provide energy, the drugs from the cells emit, and reduce the intracellular concentration, weaken or even suppress its toxicity. P-glycoprotein emitting a high level of performance is usually poor prognosis of cancer patients, such as low response rates, high relapse rate, short survival periods of time.
Cancer stem cells, another characteristic is its experimental animals have excellent cancer in order to colorectal cancer cells in xenotransplantation as an example, in immune mice lacking only 500 stem cell transplantation can be formed tumor. If the general cancer cells, even if the transplant more than one million will not have a tumor. This shows that only the eradication of cancer stem cells, cancer is cured opportunities. Therefore identify such cells and normal cells with the general differences between stem cells and the development of these properties for cancer stem cells to wipe out the strategy of Cancer Research is currently one of the important issues.
Treatment of the new dawn
In fact, some recent research results show that selectively inhibit the growth of cancer stem cells or even annihilate it, and not a "mission impossible."
Three IL-receptor and CD33 molecule: Route, also known as IL-receptor CD123, mainly expressed in blood stem cells and precursor cells responsible for regulating cell growth and differentiation. Because of CD123 in about 80% of acute myeloid leukemia in patients with cancer have excessive levels of performance, therefore, as one of the treatment of the subject. CD33 molecules are mainly manifested in the monocyte, the former myeloid white blood cells, as well as undifferentiated leukemia and acute myeloid leukemia. Some scientists have for acute myeloid leukemia cancer stem cell-specific IL-Route and the CD33 receptor molecule designed highly selective drugs kill these cells.
Transcription factor NF-kB and phospholipid acyl inositol 3 - kinase: transcription factor NF-kB exists in almost all animal cells, which in the individual due to infection caused by an immune response plays an important regulatory role of NF-kB, therefore out of control may lead to cancer, inflammation, immune-related diseases, such as from happening. Inositol phospholipid acyl 3 - kinase is capable of manufacturing products such as lipid second message, and a variety of intracellular protein binding after it activated, thereby regulating cell proliferation, differentiation, survival, migration and other functions. Because NF-kB with phospholipid acyl inositol 3 - kinase signal transduction in tumor stem cells have abnormal activation of the phenomenon, so the researchers also make use of existing NF-kB with phospholipid acyl inositol 3 - kinase inhibitors slowed their growth.
mTOR: mTOR molecule is a kinase, is responsible for regulating cell proliferation signal transmission. When mTOR was upstream (such as growth factor and its cell-surface receptor binding) message activation may activate the downstream transmission of messages to cell differentiation or proliferation. When this adjustment mechanism got out of hand, would lead to abnormal cell proliferation and differentiation of incomplete formation of the tumor, so mTOR to become the development of new anti-cancer drug target.
Inhibition of inositol phospholipid acyl 3 - kinase downstream of mTOR, also found to increase anti-cancer drugs kill cancer cells the effect of etoposide. Etoposide is separated by Mandala grass compounds, currently used to treat, including small cell lung cancer, Kaposi's sarcoma, testicular cancer (germ cell cancer), acute leukemia, lymphoma and other tumors. Its role is through the inhibition mechanism of DNA topoisomerase II, the destruction of the double-stranded DNA helix structure, and inhibit proliferation of cancer cells.
Check point kinase: check point kinase with phosphoproteome functions, is responsible for cell division cycle in the S and G2 / M phase check-point monitoring. When the DNA damage, the One check points will be activated kinase, resulting in cell cycle arrest, providing the opportunity to repair damaged DNA. If DNA damage is too severe beyond repair, the kinase trigger apoptosis, in order to maintain intracellular genome integrity and stability. Tumor cells on the 1st check point kinase if there is missing, for the DNA damage caused by the sensitivity of anti-cancer drugs will increase, thus more prone to this type of drugs have been poisoned.
The performance of CD133 molecule (a variety of normal and cancer stem cells specific flag) of glioblastoma stem cells, as a result of its internal due to DNA damage has been activated kinase activity check points higher, so the repair of damaged DNA better ability of radiation therapy are also more resistant, but the resistance will be due to the cell I and II check point kinase inhibitors to reduce the processing.
Bone morphogenetic protein: a group of bone morphogenetic protein can induce bone and cartilage cells to generate hormones, it can with the special cell surface receptor binding, induced by a series of downstream message. In addition to bones and cartilage in addition, it will also affect the embryonic period of the heart and nervous system development. Scientists have discovered bone morphogenetic protein can promote CD133-positive GBM (pleomorphic blastoma collagen) in vitro differentiation of stem cells and to reduce its experimental animals the ability to form tumors.
Notch message conduction: Notch signal transduction, including skin, nerves, blood, muscle and many other organizations have a decisive impact on the fate, if an exception occurs the individual will lead to serious developmental defects and disease.
Recently, scientists have discovered the message conduction Notch inhibitors, not only by reducing the CD133-positive Medulloblastoma the number of stem cells to stop its formation in experimental animal tumors, but also lead to even more intense nestin-positive cells apoptosis. nestin is an intermediate filament protein, will be reflected in the development and new organizations, divided epithelial precursor cells and neural precursor cells. Nestin recently found in some tumors appear, but also pointed out that the literature nestin in colorectal cancer newborn vascular endothelial cells on the performance, but the volume of their performance with glioblastoma grade of positive correlation.
As a result of this strategy seems to be a normal stem cell growth and survival has not been an impact, it deserves a more in-depth studies to the early development of methods to cure cancer!
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