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61.
62.
Rengaswami Rajaraman Duane L Guernsey Murali M Rajaraman Selva R Rajaraman 《Cancer cell international》2006,6(1):25-26
We describe the basic tenets of the current concepts of cancer biology, and review the recent advances on the suppressor role
of senescence in tumor growth and the breakdown of this barrier during the origin of tumor growth. Senescence phenotype can
be induced by (1) telomere attrition-induced senescence at the end of the cellular mitotic life span (MLS*) and (2) also by
replication history-independent, accelerated senescence due to inadvertent activation of oncogenes or by exposure of cells
to genotoxins. Tumor suppressor genes p53/pRB/p16INK4A and related senescence checkpoints are involved in effecting the onset
of senescence. However, senescence as a tumor suppressor mechanism is a leaky process and senescent cells with mutations or
epimutations in these genes escape mitotic catastrophe-induced cell death by becoming polyploid cells. These polyploid giant
cells, before they die, give rise to several cells with viable genomes via nuclear budding and asymmetric cytokinesis. This
mode of cell division has been termed neosis and the immediate neotic offspring the Raju cells. The latter inherit genomic
instability and transiently display stem cell properties in that they differentiate into tumor cells and display extended,
but, limited MLS, at the end of which they enter senescent phase and can undergo secondary/tertiary neosis to produce the
next generation of Raju cells. Neosis is repeated several times during tumor growth in a non-synchronized fashion, is the
mode of origin of resistant tumor growth and contributes to tumor cell heterogeneity and continuity. The main event during
neosis appears to be the production of mitotically viable daughter genome after epigenetic modulation from the non-viable
polyploid genome of neosis mother cell (NMC). This leads to the growth of resistant tumor cells. Since during neosis, spindle
checkpoint is not activated, this may give rise to aneuploidy. Thus, tumor cells also are destined to die due to senescence,
but may escape senescence due to mutations or epimutations in the senescent checkpoint pathway. A historical review of neosis-like
events is presented and implications of neosis in relation to the current dogmas of cancer biology are discussed. Genesis
and repetitive re-genesis of Raju cells with transient "stemness" via neosis are of vital importance to the origin and continuous
growth of tumors, a process that appears to be common to all types of tumors. We suggest that unlike current anti-mitotic
therapy of cancers, anti-neotic therapy would not cause undesirable side effects. We propose a rational hypothesis for the
origin and progression of tumors in which neosis plays a major role in the multistep carcinogenesis in different types of
cancers. We define cancers as a single disease of uncontrolled neosis due to failure of senescent checkpoint controls. 相似文献
63.
Murali K. Ravoori Masato Nishimura Sheela P. Singh Chunhua Lu Lin Han Brian P. Hobbs Sunila Pradeep Hyun J. Choi James A. Bankson Anil K. Sood Vikas Kundra 《PloS one》2015,10(6)
Purpose
To assess whether T1 relaxation time of tumors may be used to assess response to bevacizumab anti-angiogenic therapy. Procedures: 12 female nude mice bearing subcutaneous SKOV3ip1-LC ovarian tumors were administered bevacizumab (6.25ug/g, n=6) or PBS (control, n=6) therapy twice a week for two weeks. T1 maps of tumors were generated before, two days, and 2 weeks after initiating therapy. Tumor weight was assessed by MR and at necropsy. Histology for microvessel density, proliferation, and apoptosis was performed.Results
Bevacizumab treatment resulted in tumor growth inhibition (p<0.04, n=6), confirming therapeutic efficacy. Tumor T1 relaxation times increased in bevacizumab treated mice 2 days and 2 weeks after initiating therapy (p<.05, n=6). Microvessel density decreased 59% and cell proliferation (Ki67+) decreased 50% in the bevacizumab treatment group (p<.001, n=6), but not apoptosis.Conclusions
Findings suggest that increased tumor T1 relaxation time is associated with response to bevacizumab therapy in ovarian cancer model and might serve as an early indicator of response. 相似文献64.
Among new insights coming from the completion of sequencing of the human genome, reported in Nature and Science, are clues of how evolution has increased the complexity of species, and in particular how the genetic code has enabled this process. It is clear that life has not only evolved by increasing the number of genes, but also by ingeniously evolving an efficient code for expressing diversity in the building blocks (i.e. the amino acids). The rules of nucleic acid base pairing and the classification of amino acids according to hydrophobicity/hydrophilicity relationships define a binary DNA code, which determines the general biophysical characteristics of proteins. Sense and antisense strands can encode protein segments having inverted and complementary hydropathy. The underlying binary code controls association and dissociation of proteins and presumably represents a primordial code that might have emerged in the early stages of self-organizing biochemical cycles. It is the purpose of this communication to provide a perspective of the code in the context of a binary language from its primordial origin to its present day format and to propose to use this code as a genomic mining tool. 相似文献
65.
Characterisation of uterine sarcoma cell lines exhibiting MDR phenotype by vibrational spectroscopy 总被引:1,自引:0,他引:1
Murali Krishna C Kegelaer G Adt I Rubin S Kartha VB Manfait M Sockalingum GD 《Biochimica et biophysica acta》2005,1726(2):160-167
Multidrug resistance (MDR) enables cancer cells to escape cytotoxic insults of anticancer drugs. Rapid identification of cells exhibiting the MDR phenotype is very important since it can lead to an effective and individual patient based treatment plan. We have investigated a combined vibrational spectroscopic approach, using both micro-Raman and FTIR techniques, in order to characterise a sensitive human uterine sarcoma cell line MES-SA and its multidrug-resistant derivative Garf. In this study, these two complementary methods have been evaluated via the use of principal components analysis (PCA), for discrimination of cells exhibiting the MDR phenotype. Our results indicate that, though they inherently have different sensitivities, both Raman and IR methods can provide a good differentiation of cell phenotypes. 相似文献
66.
In non-irrigated agricultural fields in tropical zones, high temperature and water stress prevail during the main cropping season. Natural epizootics of Beauveria bassiana on lepidopteran pests occur during winter. Application of B. bassiana during hot months when pest populations are at their climax may prove an effective management strategy. Therefore, 29 isolates of B. bassiana were tested for their ability to germinate and grow in temperature and water availability conditions prevailing during the pest season in these fields. The effect of temperature cycles with 8 h duration of high temperature fluctuating with 16 h duration of lower temperature (similar to field conditions); low water availability; and a combination of these two stress conditions was studied. Germination and growth assays were done at fluctuating temperature cycles of 32, 35, 38, and 42+/-1 degrees C (8 h)/25+/-1 degrees C (16 h) and in media with water stress created by 10, 20, 30, and 40% polyethylene glycol (PEG 6000). Assays set at a continuous temperature of 25+/-1 degrees C with no PEG in the medium served as controls. Stress was assessed as percentage germination or as growth relative to control. Isolates showing 90% growth relative to the control at temperature cycles including high temperatures of 35 and 38+/-1 degrees C were identified. One isolate (ARSEF 2860) had a thermal threshold above 43 degrees C. At 25 degrees C, all but one isolate of B. bassiana showed >90% growth relative to the control in 10% PEG (-0.45 MPa). Some isolates were found with >90% growth relative to control in medium having 30% PEG with water availability (1.33 MPa), nearly equivalent to that in soils which induce permanent wilting point of plants. When isolates that showed >90% growth relative to the control at both stress conditions, were stressed simultaneously, a decrease in growth was observed. Growth was reduced by approximately 20% at 35+/-1 degrees C (8 h)/25+/-1 degrees C (16 h) and 10% PEG and was affected to a greater degree in combinations of harsher stress conditions. The isolate ARSEF 2860 with a thermal threshold of >43 degrees C showed approximately 80% relative growth at a combined stress of 38+/-1 degrees C (8 h)/25+/-1 degrees C (16 h) and 10% PEG. These findings will aid the selection of isolates for use in field trials in hot or dry agricultural climates. 相似文献
67.
The health and wellness of an individual are reliant on the integrated effects of mind, body, and spirit. This triad is intricately set within a backdrop of the environment, our earth. Western cultures often disregard this holism, especially this fourth component, in its considerations of wellness as described by modern medicine. This practice is unlike that of many of the traditional cultures in the world. These cultures focus more on balance in the context of environmental respect. Varied cultures share remarkable similarities in their healing modalities, especially considering the relative isolation from one to another—evidence that there is truth to the healing knowledge they possess. We are not disconnected from the natural world in terms of health, but dependent and interconnected within ourselves and to everything around us. Social change is required to assure that the practice of modern medicine evolves to incorporate this integral aspect of health and wellness, and this can be done through partnerships with traditional healers.There is a growing demand for wellness and earthly responsibility. It is time to appropriately learn from age-old societies and their healing traditions for they do have answers we are seeking in sustainability and harmony, environmental stewardship and planetary respect, and holistic health. For thousands of years, our ancestors have known the secrets of long life—this knowledge needs to be preserved through the apprenticeship of future generations. We propose a collaboration that develops mutually beneficial learning partnerships combining modern medical knowledge with the wisdom of traditional healers around the world. 相似文献
68.
Woochang Hwang Young-Rae Cho Aidong Zhang Murali Ramanathan 《Algorithms for molecular biology : AMB》2006,1(1):24-11
Background
The sparse connectivity of protein-protein interaction data sets makes identification of functional modules challenging. The purpose of this study is to critically evaluate a novel clustering technique for clustering and detecting functional modules in protein-protein interaction networks, termed STM. 相似文献69.
70.
Ling Ling Sadasivam Murali Gary S. Stein Andre J. van Wijnen Simon M. Cool 《Journal of cellular biochemistry》2010,109(6):1222-1231
Skeletal integrity is tightly regulated by the activity of osteoblasts and osteoclasts that are both under the control of extracellular glycosaminoglycans (GAGs) through their interactions with endogenous growth factors and differentiation‐promoting ligands. Receptor activator of NF‐kappa‐B ligand (RANKL), which is a tumor necrosis factor (TNF)‐related protein that is critical for osteoclast formation, is produced by osteoblasts and further modulated by certain types of GAGs. Using unfractionated osteoblast‐derived GAGs that reflect the complex tissue microenvironment within which osteoclasts reside, we demonstrate that these GAGs block the osteoclastogenic activity of RANKL. Furthermore, RANKL significantly reduces extracellular signal‐regulated protein kinase (ERK) activity, a putative suppressor of osteoclastogenesis, but osteoblast‐derived GAGs eliminate the inhibitory effects of RANKL on ERK activity. Notably, while imposing an anti‐osteoclastic effect, these GAGs also enhanced the proliferation of osteoblasts. Thus, the osteoblast microenvironment is a potent source of GAGs that promote bone anabolic activities. The anti‐osteoclastogenic and osteoblast‐related mitogenic activities of these GAGs together may provide a key starting point for the development of selective sugar‐based therapeutic compounds for the treatment of osteopenic disorders. J. Cell. Biochem. 109: 1222–1231, 2010. © 2010 Wiley‐Liss, Inc. 相似文献