Journal of Cancer Therapy最新文献

{"title":"Curcumin Inhibits Prostate Cancer Bone Metastasis by Up-Regulating Bone Morphogenic Protein-7 <i>in Vivo.</i>","authors":"Thambi Dorai,&nbsp;Janane Diouri,&nbsp;Orla O'Shea,&nbsp;Stephen B Doty","doi":"10.4236/jct.2014.54044","DOIUrl":"https://doi.org/10.4236/jct.2014.54044","url":null,"abstract":"<p><p>A number of studies have focused on the beneficial properties of Curcumin (diferuloyl methane, used in South Asian cuisine and traditional medicine) such as the chemoprevention of cancer. Recent studies have also indicated that this material has significant benefits for the treatment of cancer and is currently undergoing several clinical trials. We have been interested in the application of this compound as a therapeutic agent for advanced prostate cancer, particularly the skeletal complications in this malignancy. Our earlier work indicated that this compound could inhibit the osteomimetic properties which occur in castration resistant prostate cancer cells, by interfering with the common denominators between these cancer cells and the bone cells in the metastatic tumor microenvironment, namely the osteoblasts and the osteoclast. We predicted that curcumin could break the vicious cycle of reciprocal stimulation that results in uncontrolled osteolysis in the bony matrix. In this work, we have evaluated the potential of this compound in inhibiting the bone metastasis of hormone refractory prostate cancer cells in an established animal model. Our results strongly suggest that curcumin modulates the TGF-<i>β</i> signaling that occurs due to bone matrix degradation by up-regulating the metastasis inhibitory bone morphogenic protein-7 (BMP- 7). This enhancement of BMP-7 in the context of TGF-<i>β</i>in the tumor microenvironment is shown to enhance the mesenchymal-to-epithelial transition. Most importantly, we show that as a result of BMP-7 up-regulation, a novel brown/beige adipogenic differentiation program is also up-regu- lated which plays a role in the inhibition of bone metastasis. Our results suggest that curcumin may subvert the TGF-<i>β</i>signaling to an alternative adipogenic differentiation program in addition to the previously established interference with the osteomimetic properties, thus inhibiting the bone metastatic processes in a chemopreventive as well as therapeutic setting.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"5 4","pages":"369-386"},"PeriodicalIF":0.0,"publicationDate":"2014-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4236/jct.2014.54044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32440617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALDH Activity Correlates with Metastatic Potential in Primary Sarcomas of Bone.","authors":"Nicholas Greco,&nbsp;Trevor Schott,&nbsp;Xiaodong Mu,&nbsp;Adam Rothenberg,&nbsp;Clifford Voigt,&nbsp;Richard L McGough,&nbsp;Mark Goodman,&nbsp;Johnny Huard,&nbsp;Kurt R Weiss","doi":"10.4236/jct.2014.54040","DOIUrl":"https://doi.org/10.4236/jct.2014.54040","url":null,"abstract":"<p><p>Osteosarcoma (OS), chondrosarcoma (CSA), and Ewings sarcoma (ES) are the most common primary malignancies of bone, and are rare diseases. As with all sarcomas, the prognosis of these diseases ultimately depends on the presence of metastatic disease. Survival is therefore closely linked with the biology and metastatic potential of a particular bone tumor's cells. Here we describe a significant correlation of aldehyde dehydrogenase (ALDH) activity and the presence/absence of distant metastases in ten consecutive cases of human bone sarcomas. Additionally, cultured human CSA cells, which are historically chemo- and radio-resistant, may be sensitive to the ALDH inhibitor, disulfiram. While it is premature to draw broad conclusions from such a small series, the importance of ALDH activity and inhibition in the metastatic potential of primary bone sarcomas should be investigated further.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"5 4","pages":"331-338"},"PeriodicalIF":0.0,"publicationDate":"2014-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200537/pdf/nihms610106.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32758123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Automatic Approach for Satisfying Dose-Volume Constraints in Linear Fluence Map Optimization for IMPT.","authors":"Maryam Zaghian,&nbsp;Gino Lim,&nbsp;Wei Liu,&nbsp;Radhe Mohan","doi":"10.4236/jct.2014.52025","DOIUrl":"https://doi.org/10.4236/jct.2014.52025","url":null,"abstract":"<p><p>Prescriptions for radiation therapy are given in terms of dose-volume constraints (DVCs). Solving the fluence map optimization (FMO) problem while satisfying DVCs often requires a tedious trial-and-error for selecting appropriate dose control parameters on various organs. In this paper, we propose an iterative approach to satisfy DVCs using a multi-objective linear programming (LP) model for solving beamlet intensities. This algorithm, starting from arbitrary initial parameter values, gradually updates the values through an iterative solution process toward optimal solution. This method finds appropriate parameter values through the trade-off between OAR sparing and target coverage to improve the solution. We compared the plan quality and the satisfaction of the DVCs by the proposed algorithm with two nonlinear approaches: a nonlinear FMO model solved by using the L-BFGS algorithm and another approach solved by a commercial treatment planning system (Eclipse 8.9). We retrospectively selected from our institutional database five patients with lung cancer and one patient with prostate cancer for this study. Numerical results show that our approach successfully improved target coverage to meet the DVCs, while trying to keep corresponding OAR DVCs satisfied. The LBFGS algorithm for solving the nonlinear FMO model successfully satisfied the DVCs in three out of five test cases. However, there is no recourse in the nonlinear FMO model for correcting unsatisfied DVCs other than manually changing some parameter values through trial and error to derive a solution that more closely meets the DVC requirements. The LP-based heuristic algorithm outperformed the current treatment planning system in terms of DVC satisfaction. A major strength of the LP-based heuristic approach is that it is not sensitive to the starting condition.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"5 2","pages":"198-207"},"PeriodicalIF":0.0,"publicationDate":"2014-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261934/pdf/nihms617292.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32906529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SYK as a New Therapeutic Target in B-Cell Precursor Acute Lymphoblastic Leukemia.","authors":"Fatih M Uckun,&nbsp;Sanjive Qazi","doi":"10.4236/jct.2014.51015","DOIUrl":"https://doi.org/10.4236/jct.2014.51015","url":null,"abstract":"<p><p>The identification of SYK as a master regulator of apoptosis controlling the activation of the PI3-K/AKT, NF<i>κ</i>B, and STAT3 pathways-three major anti-apoptotic signaling pathways in B-lineage leukemia/lymphoma cells-prompts the hypothesis that rationally designed inhibitors targeting SYK may overcome the resistance of malignant B-lineage lymphoid cells to apoptosis and thereby provide the foundation for more effective multi-modality treatment regimens for poor prognosis B-precursor acute lymphoblastic leukemia (BPL). In recent preclinical proof-of-concept studies, a liposomal nanoparticle (LNP) formulation of a SYK substrate-binding site inhibitor, known as C61, has been developed as a nanomedicine candidate against poor prognosis and relapsed BPL. This nanoscale formulation of C61 exhibited a uniquely favorable pharmacokinetics and safety profile in mice, induced apoptosis in radiation-resistant primary leukemic cells taken directly from BPL patients as well as <i>in vivo</i> clonogenic BPL xenograft cells, destroyed the leukemic stem cell fraction of BPL blasts, and exhibited potent <i>in vivo</i> anti-leukemic activity in xenograft models of aggressive BPL. Further development of C61-LNP may provide the foundation for new and effective treatment strategies against therapy-refractory BPL.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"5 1","pages":"124-131"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32359653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smoking and Pancreatic Disease.","authors":"Mouad Edderkaoui,&nbsp;Edwin Thrower","doi":"10.4236/jct.2013.410A005","DOIUrl":"https://doi.org/10.4236/jct.2013.410A005","url":null,"abstract":"<p><p>Smoking is a major risk factor for chronic pancreatitis and pancreatic cancer. However, the mechanisms through which it causes the diseases remain unknown. In the present manuscript we reviewed the latest knowledge gained on the effect of cigarette smoke and smoking compounds on cell signaling pathways mediating both diseases. We also reviewed the effect of smoking on the pancreatic cell microenvironment including inflammatory cells and stellate cells.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"4 10A","pages":"34-40"},"PeriodicalIF":0.0,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6c/3b/nihms-558704.PMC3961826.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32200937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signal Transduction Pathways Mediated by Secreted and Non-secreted Forms of intact Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) and its 1-97 N-terminal Fragment in PC-3 Human Prostate Cancer Cells.","authors":"Hanief M Shahjee, Benjamin Kefas, Nisan Bhattacharyya, Mohamed K Radwan","doi":"10.4236/jct.2013.48152","DOIUrl":"10.4236/jct.2013.48152","url":null,"abstract":"<p><p>Our previous results indicated that both the secreted and the intracellular form of full length and 1-97 N-terminal fragment of IGFBP-3 induces apoptosis in PC-3 human prostate cancer cells in an IGF-dependent and independent manner. This study was undertaken to delineate possible down-stream signaling pathways that are involved in this process. Intact IGFBP-3 and its N-terminal 1-97 fragments with or without a signal pro-peptide was fused to YFP and expressed in PC-3 human prostate cancer cells. In some cases, the putative IGF-binding site present in full length IGFBP-3 and its N-terminal fragment was also mutated. Extent of apoptosis was quantified using FACS. Up-regulation of total Stat-1 and activation of phospho-Stat-1 was shown by western blot. TGF-β signal was measured by luciferase reporter assay. Results from inhibitor studies indicated that both the Caspase 8 and caspase 9 pathways are involved in IGFBP-3 (non-secreted form) induced apoptosis in PC-3 cells. Exogenous addition of IGFBP-3 to PC-3 cells increased Stat-1 protein expression/tyrosine phosphorylation. Interestingly, results also showed that knockdown of Stat-1 by siRNA potentiated the IGFBP-3 induced apoptosis in PC-3 cells. In addition, both full-length IGFBP-3 and its 1-97 N-terminal fragments inhibited TGFβ signaling in these cells. This is the first report that compares the signal transduction pathways involved in apoptotic pathways mediated by IGFBP-3 in PC-3 human prostate cancer cells. Non-secreted form of full length IGFBP-3 and its N-terminal fragments induced apoptosis in PC-3 cells via activation of caspase 8 and caspase 9. We noted that both secreted and non-secreted forms of IGFBP-3 are involved in modulating Stat-1 and TGF-β pathways to induce apoptotic actions in PC-3 cells. Surprisingly, only non-secreted form of IGFBP-3 and its N-terminal fragments are involved in the induction of apoptosis in PC-3 cells via caspase 8 and caspase 9 activation. These studies clearly demonstrate that secreted and non-secreted FL and its 1-97 N-terminal fragments induce apoptosis in PC-3 cells by regulating different mechanistic pathways.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"4 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836558/pdf/nihms526111.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31900803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cks1: Structure, Emerging Roles and Implications in Multiple Cancers.","authors":"Vinayak Khattar,&nbsp;Jaideep V Thottassery","doi":"10.4236/jct.2013.48159","DOIUrl":"https://doi.org/10.4236/jct.2013.48159","url":null,"abstract":"<p><p>Deregulation of the cell cycle results in loss of normal control mechanisms that prevent aberrant cell proliferation and cancer progression. Regulation of the cell cycle is a highly complex process with many layers of control. One of these mechanisms involves timely degradation of CDK inhibitors (CKIs) like p27^Kip1 by the ubiquitin proteasomal system (UPS). Cks1 is a 9 kDa protein which is frequently overexpressed in different tumor subtypes, and has pleiotropic roles in cell cycle progression, many of which remain to be fully characterized. One well characterized molecular role of Cks1 is that of an essential adaptor that regulates p27^Kip1 abundance by facilitating its interaction with the SCF-Skp2 E3 ligase which appends ubiquitin to p27^Kip1 and targets it for degradation through the UPS. In addition, emerging research has uncovered p27^Kip1-independent roles of Cks1 which have provided crucial insights into how it may be involved in cancer progression. We review here the structural features of Cks1 and their functional implications, and also some recently identified Cks1 roles and their involvement in breast and other cancers.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"4 8","pages":"1341-1354"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32148524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Aryl Hydrocarbon Receptor: A Target for Breast Cancer Therapy.","authors":"Joann B Powell,&nbsp;Gennifer D Goode,&nbsp;Sakina E Eltom","doi":"10.4236/jct.2013.47137","DOIUrl":"https://doi.org/10.4236/jct.2013.47137","url":null,"abstract":"<p><p>The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates a battery of genes in response to exposure to a broad class of environmental poly aromatic hydrocarbons (PAH). AhR is historically characterized for its role in mediating the toxicity and adaptive responses to these chemicals, however mounting evidence has established a role for it in ligand-independent physiological processes and pathological conditions, including cancer. The AhR is overexpressed and constitutively activated in advanced breast cancer cases and was shown to drive the progression of breast cancer. In this article we will review the current state of knowledge on the possible role of AhR in breast cancer and how it will be exploited in targeting AhR for breast cancer therapy.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"4 7","pages":"1177-1186"},"PeriodicalIF":0.0,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4236/jct.2013.47137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32539280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Saporin Conjugated Monoclonal Antibody to the Transcobalamin Receptor TCblR/<i>CD</i>320 Is Effective in Targeting and Destroying Cancer Cells.","authors":"Edward V Quadros,&nbsp;Yasumi Nakayama,&nbsp;Jeffrey M Sequeira","doi":"10.4236/jct.2013.46122","DOIUrl":"https://doi.org/10.4236/jct.2013.46122","url":null,"abstract":"<p><p>Cobalamin uptake into cells is mediated by the <i>CD</i>320 receptor for transcobalamin-bound cobalamin. Optimum receptor expression is associated with proliferating cells and therefore, in many cancers this receptor expression is up regulated. Delivering drugs or toxins via this receptor provides increased targeting to cancer cells while minimizing toxicity to the normal tissues. Saporin conjugated monoclonal antibodies to the extracellular domain of TCblR were effectively internalized to deliver a toxic dose of Saporin to some cancer cell lines propagating in culture. Antibody concentration of 2.5 nM was effective in producing optimum inhibition of cell proliferation. The cytotoxic effect of mAb-Saporin appears to be dictated primarily by the level of receptor expression and therefore normal primary cells expressing low levels of <i>CD</i>320 were spared while tumor cell lines with higher <i>CD</i>320 expression were destroyed. Targeting the pathway for cellular uptake of vitamin B₁₂ via the <i>CD</i>320 receptor with toxin-antibody conjugates appears to be a viable treatment strategy for certain cancers that over expresses this receptor.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"4 6","pages":"1074-1081"},"PeriodicalIF":0.0,"publicationDate":"2013-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32104854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Colorectal Cancer Screening Behaviors and Knowledge among At-Risk Hispanics in Southern New Mexico.","authors":"Janeth I Sanchez,&nbsp;Rebecca Palacios,&nbsp;Beti Thompson,&nbsp;Vanessa Martinez,&nbsp;Mary A O'Connell","doi":"10.4236/jct.2013.46A2003","DOIUrl":"https://doi.org/10.4236/jct.2013.46A2003","url":null,"abstract":"<p><strong>Purpose: </strong>Colorectal cancer (CRC) mortality rates in New Mexico (NM) continue to be higher than national rates. Hispanic CRC mortality rates in NM surpass those of overall Hispanics in the US. This study was designed to characterize and understand factors contributing to low CRC screening rates in this border region.</p><p><strong>Methods: </strong>A CRC Knowledge Assessment Survey (KAS) was administered in either English or Spanish to 247 individuals attending community events throughout southern NM. A subset of these individuals completed an online CRC risk assessment survey managed by the National Cancer Institute (NCI). Data analysis tested for significant differences in knowledge, physician-patient CRC interactions, CRC risk level perception, and screening rates across diverse ethnic and age groups.</p><p><strong>Results: </strong>Both CRC knowledge and physician-patient CRC interactions were positively associated with participant screening history. Significant age and ethnic differences for CRC knowledge, physician-patient CRC interactions, and screening history in the NM border sample were also seen. Age-eligible Hispanics (50+) as well as those less than 50 years of age had lower CRC knowledge and were less likely to engage in physician-patient CRC interactions than non-Hispanic Whites (NHWs). The age-eligible Hispanics also reported lower CRC screening rates than their NHW counterparts.</p><p><strong>Conclusions: </strong>Low CRC knowledge and limited physician-patient CRC interactions appear to contribute to low screening rates in this NM population. Expanding education and outreach efforts for this border population are essential to promote early CRC detection and thereby decrease overall CRC mortality rates.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"4 6B","pages":"15-25"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33332868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}