The Cancer Press (E-Journal, Nastaran Center for Cancer Prevention - NCCP)
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Targeting Cancer Stem Cells: A Solution to Cancer Therapy
Get PDFOver the past several decades, accelerating scientific and technological advances have enabled researchers to make a great quantity of knowledge in the field of cancer biology. Numerous genes, mutant alleles, proteins, and signalling networks involved in the initiation and progression of cancer have been identified and some of the mechanisms deliberating resistance to therapy. Because of the limited efficacy of presently available treatment modalities, the cancer results to death and distress. One of the most important and complicated topics about the cancer is cancer stem cells (CSCs). The CSCs are immortal tumor-initiating cells that share some characteristics with normal stem/progenitor cells. Some of their important characteristics are self-renewal and multilineage differentiation. Since CSCs have potential resistance to chemotherapeutic agents as well as radiation therapy, it makes a serious challenge for current cancer treatments. There are various strategies for eradicating CSCs. Targeting of CSCs usually occurs by pharmacological targeting, immunotherapy and genetic targeting (miRNA,oncolytic virus). More recently, nanomedicine considerably extends the anticancer drugs, treatment strategies, and targeting CSCs. In this field, all currently available strategies could be divided into three major sections: Drug delivery targeting CSCs (nanocarriers such as nanoparticles (NPs), liposomes, micelles, nanotubes and nanogels), targeting genes of drug resistance and destruction the CSCs niches. In this review, we discussed some characteristics of CSCs and their therapeutic strategies
Cancer Gene Therapy to Restore P53 Function: A New Way for an Old Aim
Get PDFMillions of people are living with cancer having specific mutation in p53 gene while every single person is truly unique in genetic basis or clinical manifestation. The gene encodes transcription factor p53, which plays a central role in regulating cell cycle progression, senescence, differentiation, DNA repair and apoptosis in response to DNA damage or other stress signals. P53 activity is up regulated to initiate a cascade of biological events that ultimately results in prevention of tumor development. Mutations in p53 abrogate normal tumor suppressor functions, contributing to the survival and proliferation of abnormal cells. Cancer cells containing mutant p53 are associated with more aggressive disease, increased resistance to chemotherapy and radiation therapy, and poor prognosis. However the majority of p53 mutations are missense and great number of these mutants represent GOF (Gain of Function) effect resulting increased invasion and metastasis in tumors. These mutations confer a dominant-negative activity over the remaining wild-type allele by functionally inactive hetero-oligomers interactions of the mutants with the wild-type protein. Increasing evidence indicates that many p53 mutants also gain new oncogenic properties that are independent from wild-type p53. Several factors including type of p53 mutations in cancers may limit the efficacy and application of p53 gene therapy. As a result, there is a great interest in therapeutic strategies aimed at restoring the function of p53 for the treatment of cancer. Increasing evidence demonstrate that silencing GOF mutations (targeted antisense therapy) reduce the transactivation activity of mutant p53 and induce apoptosis in cells bearing these mutations then provide a potential strategy to inhibit the oncogenic functions of mutant p53 and improve mutant p53-targeted cancer therapies
Use of Bacterial Ghosts as Novel Drug Delivery Systems to Improve Cancer Treatment
Get PDFDespite the large number of various anti-cancer drugs on the market, proper delivery systems are needed to decrease serious toxic and non-curative side effects. In order to enhance compliance, several delivery systems such as polymeric micro- and nanoparticles, liposomal systems and erythrocyte ghosts have been developed. Bacterial ghosts (BGs) represent novel advanced delivery and targeting vehicles suitable for delivery of hydrophobic or water-soluble drugs. BGs are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. In particular, Doxorubicin-loaded bacterial ghosts have been used to target colon carcinoma cells. DOX, a cytotoxic drug commonly used in cancer therapy, was used as a model substance to demonstrate the delivery of moderate water-soluble drugs by BGs. The application of DOX with BGs increased the efficacy of treatment by two folds. The same effect was observed after incubation of leukemia cells and melanoma cells with DOX loaded BGs
Under-estimation and Over-estimation in Gastric Cancer Incidence Registry in Khorasan Provinces, Iran
Get PDFGastric cancer is a disease which the cells forming the inner lining of the stomach start to divide uncontrollably, forming a mass called a tumor. Patients with gastric cancer from low facility provinces like North and South Khorasans may diagnose and registered in full featured provinces like Razavi-Khorasan; this causes misclassification error. The presence of this error makes the registry systems inaccurate and unreliable for estimating the burden of cancer and policy making. Two approaches are recommended for reducing the effects of misclassification; the first is using a small validation sample and the second is a Bayesian analysis which provides subjective prior information for the subset of the parameters to correct the statistics. Data for this study extracted from Iranian annual of national cancer registration report in 2008. The age standardized rate due to gastric cancer [ICD-10; C16] were expressed as rate per/100,000 population for male and female of North, South and Razavi Khorasans. To correct the misclassification effect, a Bayesian approach was used with Poisson count regression and beta prior. The reported expected coverage of cancer incidence for Razavi-Khorasan was 155.5% and exceeds than what expected, whereas the North and South Khorasans have just observed respectively 34.8% and 41.4% of their expected coverage. The results of the Bayesian analysis indicated that there was about 34% misclassification in gastric cancer incidence registry from North and South Khorasans in Razavi-Khorasan. In planning for resource allocation, authorities should consider that, low incidence of gastric cancer in North and South Khorasans, may be the effect of misclassification and it is needed to allocate them more health facilities and improve their address registration accuracy using National ID, electric bill, etc.
Identification of Novel MicroRNAs and Their Targets in Leukemia Cancers: A Computational Approach
Get PDFMicroRNAs (miRNAs), one of the most abundant groups of regulatory non coding RNAs in multicellular organisms, play important roles in many fundamental cellular processes. More than four hundred miRNAs have been identified in humans and the deregulated expression of miR-NA has been also shown in many cancers. Despite the postulated in-volvement of miRNAs in tumourigenesis, there are only a few exam-ples where an oncogene or a tumour suppressor has been identified as a miRNA target. Here, we present an in silico analysis of potential miR-NA- MYC interactions. We showed evidence for the regulation of c-MYC, one of the most potent and frequently deregulated oncogenes, via the predicted binding site in transcriptional and post transcriptional re-gions. In this work, bioinformatics approach for the prediction and vali-dation of possible targets for miRNAs has been used. A list of putative targets is available and validation of which would be experimentally validated
Cell Adhesion Molecules and Cancer
Get PDFTheodor Boveri in 1914 recognized the significance of changes in the adhesion of tumor cells to the development of cancer. Cell adhesion is essential in all aspects of in verte-brate cells such as cell growth, cell migration and cell differentiation. The majority of adhesion molecules fall into one of four families: cadherins, integrins, immunoglobulin superfamily (IgSF) and selectins. The cadherins are a family of homophilic CAMs (cell adhesion moleculs), Ca2+ dependent. The most important members of cadherins are E-cadherins (epithelial), P-cadherins (placental) and N-cadherins (neural). Immunoglobu-lin superfamily CAMs (IgSF CAMs) are either homophilic or heterophilic and bind in-tegrins, growth factor receptors cadherins or different IgSF CAMs. The integrins are a family of heterophilic CAMs that bind IgSF CAMs or the extracellular matrix. The se-lectins are a family of heterophilic CAMs that bind fucosylated carbohydrates, e.g. mu-cins. They are calcium-dependent. The three family members are E-selectin (endothelial (, L-selectin (leukocyte) and P-selectin (platelet). Recent experimental results indicate that, as well as mediating intercellular and cell–matrix interactions, cell-adhesion mole-cules also directly modulate signal transduction. Changes in the expression or function of cell-adhesion molecules can therefore contribute to tumor progression via altering the adhesion status of the cell or affecting cell signaling. The ability to colonize a specific organ has been correlated with the preferential adhesion of the cancer cells to endotheli-al cells derived from the target organ. This review summarizes recent findings about role of adhesion molecules in the tumor progression
Cancer Prevention by Synbiotics Effect of Fiber-Rich Sourdough Fermentation
Get PDFSourdough is a very complex biological system, which obtained from water and cereal fermentation. Sourdough fermentation usually consists of combinations of probiotic lactobacilli starters and prebiotic dietary fibers called synbiotics which have a synergistic effect, greater than that of either the probiotic or prebiotic administered individually. Preliminary research suggests that synbiotics offer anti-cancer benefits to the human body. The risk of lung, colon, liver, breast and bladder cancer may be reduced with the help of synbiotic effects. The most promising research is the ability of synbiotics to improve the health of cancer patients undergoing radiation therapy. Proposed mechanisms of action of probiotics lactobacilli starters and prebiotics dietary fibers in cancer include binding of carcinogens, alteration in gut microbiota formation and metabolism of carcinogens, stimulation suppression of carcinogenesis, improvement in epithelial barrier function, anti-inflammatory effects, inductance of apoptosis, and inductance of protective enzymes. Briefly these mechanisms and synbiotics effect of fiber-rich sourdough fermentation in cancer prevention will be discussed in this mini review
Circulating Tumor Cells (CTCs) in Early Cancer Detection, Prognosis Evaluation and Monitoring Cancer Drug Efficacy
Get PDFTumour metastasis refers to the spread of cancer cells from the initial site of primary tumor to a distant secondary location. Cancerous tumor usually possesses a very large number of cells with genetic mutations which motivate them to grow, proliferate, and then, invade the local surrounding tissues. As the tumor grows larger, some of the cells are dislodged from the main tumor and carried away by the blood or lymphatic vessels. These "circulating tumor cells" or CTCs possess important information about the primary tumor from which they are detached. In fact, the presence and quantity of CTCs in the cancer patients' blood stream have been known to correlate directly to the stage of cancer as well as the effectiveness of cancer therapies. The ability to isolate and enrich a large number of intact CTCs for analysis and characterisation will be pivotal for deepening our understanding of the metastatic process. However, the extremely low abundance of CTCs in the blood makes enumeration and characterisation a huge technical challenge. their isolation is still a major challenge, very rare information is available regarding their nature and behaviour
Understanding the Controversy in Cancer Stem Cell and Circulating Tumor Cell
Get PDFNew evidences have been raised suggesting that, cancers, as well as normal tissues, might also be hierarchically organized. Thus a minor fraction of tumor cells, endowed with stem cell-like features, and so termed cancer stem cells (CSCs), have been known as responsible for tumor initiation and maintenance. Another cell group which has caused controversies and circulates freely in the peripheral blood of cancer encountered patients is circulating tumor cells (CTCs). They defined as tumor cells that either primary sites or metastases are culprit of them. Characteristics and detection methods of CTCs and CSCs and their therapeutic application have been explored in this review with focus on their similarities and differences