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991.
Gastric cancer is a worldwide health burden, which is still the second most common cause of cancer related deaths with little improvement of long-term survival during the past decades. Understanding the molecular nature of this disease and its precursor lesions has been under intense investigation and our review attempts to highlight recent progress in this field of cancer research. First, host-related genetic susceptibility is dealt with genes involved in inflammation and carcinogen metabolism. Next, role of overexpression of a proinflammatory cytokine (interleukin-1beta) and deletion of a cell-cell adhesion molecule (E-cadherin) are described in experimental mouse models of gastric carcinogenesis. Finally, the role of stem cells in gastric cancer is covered. 相似文献
992.
Cancer attractors: A systems view of tumors from a gene network dynamics and developmental perspective 总被引:1,自引:0,他引:1
Sui Huang Ingemar Ernberg Stuart Kauffman 《Seminars in cell & developmental biology》2009,20(7):869-876
Cell lineage commitment and differentiation are governed by a complex gene regulatory network. Disruption of these processes by inappropriate regulatory signals and by mutational rewiring of the network can lead to tumorigenesis. Cancer cells often exhibit immature or embryonic traits and dysregulated developmental genes can act as oncogenes. However, the prevailing paradigm of somatic evolution and multi-step tumorigenesis, while useful in many instances, offers no logically coherent reason for why oncogenesis recapitulates ontogenesis. The formal concept of “cancer attractors”, derived from an integrative, complex systems approach to gene regulatory network may provide a natural explanation. Here we present the theory of attractors in gene network dynamics and review the concept of cell types as attractors. We argue that cancer cells are trapped in abnormal attractors and discuss this concept in the light of recent ideas in cancer biology, including cancer genomics and cancer stem cells, as well as the implications for differentiation therapy. 相似文献
993.
In the nineteenth century, William B. Coley induced durable remission of inoperable metastatic sarcoma by repeatedly injecting live streptococcus bacilli and, subsequently, heat-killed bacterial extracts into the primary tumor. While Coley's contemporaries debated the veracity of his results, this bold treatment protocol established the new scientific field of immunology. In Coley's era, the scientific and medical communities lacked the prerequisite knowledge to validate and understand his treatment protocols. Today, a more comprehensive understanding of the human immune system, anchored by the discovery of the mammalian Toll-like receptor gene family in the 1990s, permits a mechanistic understanding of his results. Coley's cocktail of TLR agonists likely stimulated a complex cascade of cytokines, each of which plays a unique and vital role in the orchestration of the immune response. Here we explore Coley's legacy: a dissection of those cytokines which possess the immunostimulatory properties necessary to modulate the immune system and ameliorate human disease. The discussion is limited to molecules that have been able to show therapeutic promise in the clinical setting. 相似文献
994.
M. Cecilia Caino John Meshki Marcelo G. Kazanietz 《Apoptosis : an international journal on programmed cell death》2009,14(4):392-408
Cellular senescence is a potent anti-cancer mechanism controlled by tumor suppressor genes, particularly p53 and pRb, which
is characterized by the irreversible loss of proliferation. Senescence induced by DNA damage, oncogenic stimulation, or excessive
mitogenic input, serves as a barrier that counteracts cancer progression. Emerging evidence in cellular and in in vivo models
revealed the involvement of additional signaling players in senescence, including PML, CK2, Bcl-2, PI3K effectors such as
Rheb, Rho small GTPases, and cytokines. Recent studies have also implicated protein kinase C (PKC) isozymes as modulators
of senescence phenotypes and showed that phorbol esters, widely used PKC activators, can induce senescence in a number of
cancer cells. These novel findings suggest a complex array of cross-talks between senescence pathways and may have significant
implications in cancer therapy. 相似文献
995.
Avital Eisenberg-Lerner Adi Kimchi 《Apoptosis : an international journal on programmed cell death》2009,14(4):376-391
Autophagy is a cellular self-catabolic process in which cytoplasmic constituents are sequestered in double membrane vesicles
that fuse with lysosomes where they are degraded. As this catabolic activity generates energy, autophagy is often induced
under nutrient limiting conditions providing a mechanism to maintain cell viability and may be exploited by cancer cells for
survival under metabolic stress. However, progressive autophagy can be cytotoxic and autophagy can under certain settings
substitute for apoptosis in induction of cell death. Moreover, loss of autophagy is correlated with tumorigenesis and several
inducers of autophagy are tumor-suppressor genes. Thus, the relation of autophagy to cancer development is complex and depends
on the genetic composition of the cell as well as on the extra-cellular stresses a cell is exposed to. In this review we describe
the intricate nature of autophagy and its regulators, particularly those that have been linked to cancer. We discuss the multifaceted
relation of autophagy to tumorigenesis and highlight studies supporting a role for autophagy in both tumor-suppression and
tumor-progression. Finally, various autophagy-targeting therapeutic strategies for cancer treatment are presented.
This review is dedicated to the memory of Dr. Avner Eisenberg 1953–2004. 相似文献
996.
The signaling pathways of Epstein-Barr virus-encoded latent membrane protein 2A (LMP2A) in latency and cancer 总被引:1,自引:0,他引:1
Epstein-Barr virus (EBV) is a ubiquitous virus with infections commonly resulting in a latency carrier state. Although the
exact role of EBV in cancer pathogenesis remains not entirely clear, it is highly probable that it causes several lymphoid
and epithelial malignancies, such as Hodgkin’s lymphoma, NK-T cell lymphoma, Burkitt’s lymphoma, and nasopharyngeal carcinoma.
EBV-associated malignancies are associated with a latent form of infection, and several of these EBV-encoded latent proteins
are known to mediate cellular transformation. These include six nuclear antigens and three latent membrane proteins. Studies
have shown that EBV displays distinct patterns of viral latent gene expression in these lymphoid and epithelial tumors. The
constant expression of latent membrane protein 2A (LMP2A) at the RNA level in both primary and metastatic tumors suggests
that this protein might be a driving factor in the tumorigenesis of EBV-associated malignancies. LMP2A may cooperate with
the aberrant host genome, and thereby contribute to malignant transformation by intervening in signaling pathways at multiple
points, especially in the cell cycle and apoptotic pathway. This review summarizes the role of EBV-encoded LMP2A in EBV-associated
viral latency and cancers. We will focus our discussions on the molecular interactions of each of the conserved motifs in
LMP2A, and their involvement in various signaling pathways, namely the B-cell receptor blockade mechanism, the ubiquitin-mediated
(Notch and Wnt) pathways, and the MAPK, PI3-K/Akt, NK-κB and STAT pathways, which can provide us with important insights into
the roles of LMP2A in the EBV-associated latency state and various malignancies. 相似文献
997.
998.
Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer
Yu-Chih Chen Yi-Wei Chen Han-Shui Hsu Ling-Ming Tseng Pin-I Huang Kai-Hsi Lu Dow-Tien Chen Lung-Kuo Tai Ming-Chi Yung Shih-Ching Chang Hung-Hai Ku Shih-Hwa Chiou Wen-Liang Lo 《Biochemical and biophysical research communications》2009,385(3):307-313
Aldehyde dehydrogenase 1 (ALDH1) has been considered to be a marker for cancer stem cells. However, the role of ALDH1 in head and neck squamous cell carcinoma (HNSCC) has yet to be determined. In this study, we isolated ALDH1-positive cells from HNSCC patients and showed that these HNSCC-ALDH1+ cells displayed radioresistance and represented a reservoir for generating tumors. Based on microarray findings, the results of Western blotting and immunofluorescent assays further confirmed that ALDH1+-lineage cells showed evidence of having epithelial-mesenchymal transition (EMT) shifting and endogenously co-expressed Snail. Furthermore, the knockdown of Snail expression significantly decreased the expression of ALDH1, inhibited cancer stem-like properties, and blocked the tumorigenic abilities of CD44+CD24−ALDH1+ cells. Finally, in a xenotransplanted tumorigenicity study, we confirmed that the treatment effect of chemoradiotherapy for ALDH1+ could be improved by Snail siRNA. In summary, it is likely that ALDH1 is a specific marker for the cancer stem-like cells of HNSCC. 相似文献
999.
Jing Zhou 《Biochemical and biophysical research communications》2009,386(3):521-585
This study was aimed at exploring a novel pretargeting system based upon bifunctional nucleic acid molecules that are comprised of a nucleic acid aptamer and a nucleic acid tail. The properties of bifunctional molecules were investigated by both theoretical prediction and experimental determination. Different from the algorithm-based structure prediction, the experimental data showed that some nucleic acid tails could significantly decrease the binding capability of the aptamer. It was also found that the effectiveness of bifunctional molecules in labeling cells was dependent on the hybridization length. Based on these understandings, one bifunctional molecule was selected to study pretargeting. The results demonstrated that the bifunctional molecule could not only bind to target cells, but also hybridize with its complementary oligonucleotide on the cell surface. Thus, bifunctional nucleic acid molecules hold great potential for pretargeting applications. 相似文献
1000.
Yingjia Zhang 《Biochemical and biophysical research communications》2009,386(4):729-1925
As a member of the class III histone deacetylases, Sirtuin-2 (SIRT2) is critical in cell cycle regulation which makes it a potential target for cancer therapeutics. In this study, we identified a novel SIRT2 inhibitor, AC-93253, with IC50 of 6 μM in vitro. The compound is selective, inhibiting SIRT2 7.5- and 4-fold more potently than the closely related SIRT1 and SIRT3, respectively. AC-93253 significantly enhanced acetylation of tubulin, p53, and histone H4, confirming SIRT2 and SIRT1 as its cellular targets. AC-93253 as a single agent exhibited submicromolar selective cytotoxicity towards all four tumor cell lines tested with a therapeutic window up to 200-fold, comparing to any of the three normal cell types tested. Results from high content analysis suggested that AC-93253 significantly triggered apoptosis. Taken together, SIRT2 selective inhibitor AC-93253 may serve as a novel chemical scaffold for structure-activity relationship study and future lead development. 相似文献