Cell Research

Shanghai, August 7, 2012 / biological Valley BIOON / - Shanghai Jiaotong University School of Feng Lixin research group recently found that spermatogonial stem cells can be induced to form egg. In the course of normal development, on the mesodermal cells derived primordial germ progenitor cells (primordial germ cells, PGCs) is a common precursor cell spermatogonial stem cells and oocytes. Previous studies have found that under certain culture conditions, the spermatogonial stem cells can be induced into pluripotent stem cells. Other studies have shown that pluripotent embryonic stem cells can be differentiated to develop into PGCs and egg cells. Spermatogonial stem cells to differentiate into the egg cell research has not been reported. Li-Xin Feng research group induced spermatogonial stem cell-derived egg the size of the body normal egg and the expression egg specific markers, in vitro fertilization and the formation of parthenogenetic embryos. Y and on the X chromosome of changes in gene expression, and to maintain the spermatogonial stem cell-associated gene is turned off, while the oocyte-specific expression of the gene on the X chromosome are activated. Meanwhile, stem cell-derived egg cells lost the father epigenetic imprinting, the epigenetic imprinting matrilateral. This study demonstrated the spermatogonial stem cells have the potential egg cells were induced to show its strong plasticity. The study may provide an ideal model for the analysis of molecular and epigenetic regulation of reproductive cell fate, and the establishment of epigenetic imprinting. Related research was recently published in the journal Cell & Bioscience.

August 23, 2012 News / biological Valley BIOON / A lysophosphatidic acid receptor 1 (LPAR1) inhibitor Debio-0719 by inducing cancer cells of mice into hibernation to inhibit tumor metastasis, Research Papers in the August 21 issue of the Journal of the National Cancer Institute magazine. The transfer is a major cause of mortality in cancer patients. "Triple negative" breast cancer patients with high-risk metastatic potential. In addition, breast cancer and prostate cancer are known to have variability, such as these types of tumors may be a long period of dormancy that this disease is silently lurking. Related factors induced or break the tumor cells dormant poorly understood, but it is clear that the extension of the tumor cells of Sleep is a cancer treatment strategy. In order to determine the impact of the the LPA1 inhibitor of metastatic cells dormant, the National Cancer Institute, Key Laboratory of Molecular Pharmacology, Jean-Claude A. Marshall, MSc, Ph.D., and colleagues in both the invasion of the "triple negative" breast cancer metastasis model system that mouse 4T1 breast cancer model and human MDA-MB-231 human breast cancer cell model analysis of the flavor of tumor size, distant metastasis and their molecular characteristics. The results showed that Debio-0719 or shRNA suppression LPA1 significantly inhibit the formation of metastases without affecting primary bit size of the tumor. Debio-0719 treated mice was found in remote organs, such as lung and liver cancer cells, but no longer have the proliferative capacity, molecular markers showing a dormant state. The authors noted that, no influence the LPA1 inhibitor on the primary bit in either tumor model of tumor growth. Accordingly, it usually will not be deemed to drugs to develop. Their data indicate that might develop new activity for example, can induce the dormant metastatic cells to enter the new compounds may have anti-tumor prospects.

A experimental drug study contraposing common gene mutation in melanoma ,confirmed that the drug dabrafenib successfully shrink the tumor lesions of melanoma in patients with brain metastases, the effective rate reaches to 90%. The result of this international Phase I clinical drug trials published in an internationally renowned journal The Lancet, in the May 18. BRAF gene encodes a serine / threonine protein kinase B-Raf, which is closely related to cell growth regulation. In melanoma, BRAF mutations often cause disorders of cell growth regulation. Dabrafenib plays a role in mutant type BRAF - Val600. In order to confirm its safety and tolerability and provide dose reference for phase II trials in clinical, the researchers recruited 184 patients with solid tumors for test, including 156 patients with metastatic melanoma. According to the accelerated dose titration method, after systematic Dabrafenib treatment, the researchers found no cases of treatment discontinuation and death due to drug side-effect. Moreover, Dabrafenib also has anti-cancer effects on other BRAF mutation-type solid tumors, such as gastrointestinal solid tumors, non-small cell lung cancer, ovarian cancer, and so on

Recent studies have shown that myeloid cells can make distant organs easily allow colony formation of spread tumor cell. However, the specific mechanism has been unknown. On May 14, Cancer Cell published a paper titled "S1PR1-STAT3 Signaling Is Crucial for Myeloid Cell Colonization at Future Metastatic Sites" to reveal its molecular mechanism. The researchers found that up-regulation of sphingosine-1 - phosphorylated receptor -1 (S1PR1)- STAT3 signaling pathway in the tumor cells, can increase S1PR1-STAT3 level in the targeted cell within tumor metastasis parts, resulting in the microenvironment that can easily accept metastatic tumour in distant tissues of the body. Inhibitiing function of S1PR1 or STAT3 in myeloid cells , we can undermine the existing microenvironment for easy transferation. Activation of S1PR1-STAT3 signaling pathway ,can ennable myeloid cells to pass through the blood vessels to form microenvironment that is conducive to tumor metastasis in distant organs , mediating continued survival and proliferation of their own and other stromal cells. Aafter analysis of cancer patients’lymph nodes that contain none tumor cells, compared with normal lymph node cells, tumor specimens of patients showed higher myeloid-like cell infiltration, high level activation of STAT3 and enhancements of cell survival signal.

With the presence of protein RalA and RalB ,cells replicate in the form of promoting cancer invasiion. However, until now, no studies have investigated in the impact of RAL proteins on human cancer, which is very important for the development of drugs targeting these proteins. Recently, a study published in Cancer Research journal stated clearly that the presence of protein RalA and RalB is related to tumor invasion. However,Dan Theodorescu, the author of the paper from Cancer Center University in Colorado, said that the presence or absence of these proteins are not character to predict the invasive cancer. RalA and RalB will lead to a cascade changes of oncogene (gene expression). Theodorescu and his colleagues found markers of these changes, upregulation and down-regulation can predict invasive cancer.Theodorescu said that RAL protein does not promote cancer development, but RAL proteins will lead to genetic changes and thus drive cancer development. Theodorescu state that enzyme RAL of GTP family is RAS oncogene family members currently known. These GTP enzymes of Ras family are present in leukemia, lung cancer, colon cancer and other types of cancer.Researchers have been trying to find a specific target for cancer therapy. And we believe that the RAL family is a good therapeutic target of cancer.