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Search Results: 1 - 10 of 714578 matches for " M. A. Nezami "
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Role of Anti Angiogenic Therapy in Prevention of Recurrence in Hormonal Positive Breast Cancer: A Secondary Prevention Strategy and Method of Therapy  [PDF]
M. A. Nezami, Jessica Garner
Journal of Cancer Therapy (JCT) , 2017, DOI: 10.4236/jct.2017.86046
Abstract: Existing literature supports the role of signaling protein vascular endothelial growth factor (VEGF) in tumor growth and metastasis and furthers its involvement in recurrence. In both experimental and clinical studies, VEGF has been shown to be a significant factor involved for aberrant blood vessel growth, and in fact is the target of several classes of antineoplastic drugs [1] [2] [3] [4]. That said, the current standard of care for estrogen receptor positive breast cancer (although improved over the last decade), has not provided a “meaningful preventive shift” since the discovery of angiogenesis and its role in induction of recurrence. In this article, we discuss an anti angiogenic therapy implementing natural compounds to inhibit the production of VEGF. We applied our preclinical data to justify the predicted effect on VEGF. We used liquid biopsy to monitor patients response to therapy as a surrogate for recurrence. We hypothesize that by inhibition of angiogenesis through this protocol, we are able to positively impact tumor recurrence. It is our experience that patients in our sample even with high recurrence scores (based on Oncotype Dx testing) had a major reduction in recurrence when estrogen blockers were combined with this protocol. We also propose longitudinal studies to compare outcomes with combinational therapies with estrogen blockers in highly expected to recur disease.
Proof of Concept in a Case Study of Glioblastoma Multiforme Successfully Treated with IV Quercetin in Combination with Leading Edge Gamma Knife and Standard Treatments  [PDF]
M. A. Nezami, Christopher Duma
Journal of Cancer Therapy (JCT) , 2018, DOI: 10.4236/jct.2018.96043
Abstract: The Stupp protocol has become standard of care for the treatment of glioblastoma (GBM) (since its publication in 2005) and has led to some limited survival improvements. This protocol, consists of radiotherapy and concomitant chemotherapy with temozolomide, an alkylating agent. Temozolomide + radiation, compared to radiation alone had added in average 3 months additional life span, 16 percent improved survival at 2 years. That said since 2005, the standard of care has not changed in regards to the treatment of early diagnosed aggressive or multifocal GBM, and unfortunately the expected survival is still poor with 75 percent of patients dying in less than 2 years and average survival of 15 months. In patients with multifocal tumors (such as the case below) the average survival is even worse with less than 4 months at her age [1]. Here we present a case study of a patient with advanced multifocal, and rapidly progressing Glioblastoma Multiforme treated with STUPP protocol in combination with IV Quercetin. The patient experienced improved quality of life and response, compared to historical data. It is our recommendation to investigate such combinational approach in patients with Glioblastoma, as in our case it proved to be safe and effective with improved quality of life and performance as well as clinical response and survival.
EMT and Anti-EMT Strategies in Cancer  [PDF]
M. A. Nezami, Steven Hager, Jessica Garner
Journal of Cancer Therapy (JCT) , 2015, DOI: 10.4236/jct.2015.611110
Abstract: This article discusses the role of epithelial mesenchymal transition (EMT) and addresses the scientific merits on epigenetic regulation of EMT. The importance of EMT as a prognostic biomarker is explored and the rationale on application of multitargeted epigenetic therapy is discussed. We describe a literature review of the epigenetic influence of such process and we present a potentially effective method to reverse the epigenetic switch in favor for MET, in a clinical setting. A case series of advanced solid tumors are summarized aiming at generating hypothesis for the future recommendations for clinical trials targeting the tumor’s biological behavior through inhibition of EMT. Hypothesis: We propose an integral and integrative approach that can modify tumor’s biological behavior through inhibition of EMT, and further reduce the chances of metastasis, that can translate to improved outcome and patient’s survival in advanced disease.
Epigenetic Tumor Response to Hypoxia: An Epimutation Pattern and a Method of Multi Targeted Epigenetic Therapy (MTET)  [PDF]
M. A. Nezami, Steven Hager, Jessica Garner
Journal of Cancer Therapy (JCT) , 2016, DOI: 10.4236/jct.2016.74027
Abstract: In most cases, cancer develops as a result of non-inheritable somatic mutations (epimutations), acquired by the individual adult cell, during the evolution of the cell, and propagated into an expanding clone of progeny of the cells by natural selection [1]. The role of microenvironment in selection for such acquired mutations, or epimutations, is a focus of scientific research in carcinogenesis [2]. Here we describe a defective DNA response to hypoxia due to epigenetic aberrancies, in cancer cellular biology [3]. We also summarize a literature review on hypoxia mediated epigenetic responses, and its role in carcinogenesis and metastasis. Further, we review a novel method of treating hypoxic solid tumors with a combination of epigenetic modifiers with both in vitro and in vivo results in human, translating to an improved prognosis and clinical outcome. We propose that this approach both independently and synergistically (with the current standard of care) can provide an improved outcome.
A Novel Combined Approach for Metastatic Breast Cancer with Dural and Leptomeningeal Disease with an Impressive Clinical Outcome: A Case Study  [PDF]
Julie Taguchi, Christopher Duma, M. A. Nezami
Journal of Cancer Therapy (JCT) , 2018, DOI: 10.4236/jct.2018.93025
Abstract: Concurrent dural and leptomeningeal metastatic carcinomatosis are very rare and have a poor prognosis. Here we present a woman with advanced estrogen receptor (ER) positive and progesterone receptor (PR) positive breast cancer who presented with leptomeningeal disease. Patient underwent multi targeted epigenetic therapies applied in a protocol called MTET. She continued to respond to the interval treatment, which consisted only of the nutraceutical agents. Here we discuss her case in detail and we believe that such an example might be applied to other patients in this situation resulting clinical improvement and less toxicity.
Correlation of an ex Vivo Model with Clinical Application of an Epigenetic Modifier, Inhibiting Tumor Growth and Metastasis, in Resistant Cholangiocarcinoma—A Case Study  [PDF]
M. A. Nezami, Aron Gould Simon, Geoffrey Bartholomeusz
Journal of Cancer Therapy (JCT) , 2016, DOI: 10.4236/jct.2016.71006
Abstract: Bile duct cancer is a rare form of cancer, with approximately 2000 new cases diagnosed in the United States each year. The prognosis of this disease is very grave, especially in the form of intrahepatic (IHCC), as there is no person with stage four who lives for 5 years, and the average prognosis is less than a year, a majority of patients die in less than 6 months despite all therapies. It is suggested that one of the key elements in the disease progression is the intratumoral hypoxia inducible factor one alfa (HIF-1a) as a regulator of malignant behavior and recently described as a new prognostic indicator of IHCC. (9, 10) HIF is a key regulator under the microenvironmental (terrain) influence, and therefore studies of the cell lines in an in vitro environment where there is no hypoxia, usually fail to translate to a clinical outcome in vivo, unless the cells are transfected by full-length HIF-1alpha (fL HIF-1alpha) and dominant-negative HIF-1alpha (dn HIF-1alpha). To overcome this barrier, an ex vivo model is designed at MD Anderson experimental therapeutics where the patient tumor sample is transferred to the mice and treated with drugs, where the tumor can cross talk with the actual terrain and mimic the human stroma where the HIF can be triggered. Results show significant tumor necrosis on the intrahepatic cholangiocacinoma, only after 5 days of exposure to an experimental compound that is known to suppress hypoxia-induced accumulation of hypoxia-inducible factor-1α (HIF-1α) through inhibiting protein synthesis. (11, 12) Further this is explored in the same actual patient with terminal diagnosis, and proves itself with promising initial response. Here, we review this method and the clinical perspectives, and suggest this method to be studied in larger trials.
Sequential and Dual Inhibition of Pleiotropic Targets in Cancer—A Novel Strategy to Sensitize Tumor Cells to Targeted Therapies and Overcome Resistance  [PDF]
M. Nezami
Journal of Cancer Therapy (JCT) , 2019, DOI: 10.4236/jct.2019.102013
Abstract: In this paper we discuss the rationale of applying a “sequential” targeted therapy with a specific application in clinical practice, given our understanding of cancer heterogenous and dynamic biology. We explore the advantages of “single inhibition” to combinational therapies and dual inhibition on key pathways, as well as a multi-step approach to use “oncological addiction” and “oncogenic shock” as a suicide plan for cancer. We specifically explain how the downstream targets can be used to “create” feedback loops in an advantage for creating actionable targets in upstream signaling molecules. We apply this hypothesis in the clinical setting, with superior outcomes shown in a series of case studies. We conclude that “sequential and dual inhibition” can be considered a meaningful approach to checkmate the tumor, with minimum chance of tumor resistance. We recommend further clinical studies to generate further hypotheses based on each actionable target.
Evidence Based Medicine, in Precision Oncology  [PDF]
M. Nezami, Steve Hager
Journal of Cancer Therapy (JCT) , 2018, DOI: 10.4236/jct.2018.99057
Abstract: The disagreements in clinical data and therapy recommendations extracted from different sources/studies are a common finding in oncology research. Knowingly “biology is less reproducible than physics and mechanic engineering”, in order to overcome the disagreements and to find common grounds, we still rely on meta-analysis and systemic reviews for the highest level of evidence. To gather systemic review data base, a bibliographic search usually is conducted in the PubMed and in Cochrane Central Register of Controlled Trials databases to address a common clinical challenge. That said, frequently due to common conflicts between articles outcomes, an opinion of a third investigator is sought. Here in this article, we propose a rationale that could explain the differences in outcomes as a result of imperfect understanding of the current research database secondary to the unique biology of the tumor, rather than statistical interpretation on findings. We believe that the differences in findings merely are based on blinded inclusion criteria, and lack of accurate companion diagnostics to correlate the magnitude of response to each therapy. The objective of this article is to discuss a strategy to overcome such discordance by providing quantitative biological measures for genomic classification and correlation of tumor response to the selected targeted therapy. We further review such analysis in a case series of Her 2 positive breast cancer and conclude that
Evaluation of Feezing Tolerance of Chickpea (Cicer arietinum L.) Genotypes under Controlled Conditions
A. Nezami,A. Bagheri,H. Rahimian,M. Kafi
Journal of Science and Technology of Agriculture and Natural Resources , 2007,
Abstract: The present experiment was aimed to evaluate the freezing tolerance of two cold tolerant (MCC426 and MCC252) and a cold susceptible (MCC505) chickpea genotypes. The study was carried out in a split-plot factorial design with three replications. Factorial arrangement of genotype and acclimation (acclimation and non acclimation) were imposed as main plot and temperatures (0, -4, -8, -12, 16, -20oC) as subplot. The effect of freezing temperature (FT) on plant survival was significantly different among genotypes (p
Serological ELISA Test (IgM & IgG) for Prospective Study of Cytomegalovirus (CMV) Infection in Pregnant Women
M Rajaii,N Nezami,A Pourhassan,B Naghili
Iranian Journal of Public Health , 2009,
Abstract: "nBackground: Cytomegalovirus (CMV) infection is associated with significant maternal and fetal consequences. The aim of pre-sent study was to determine the current prenatal CMV seroprevalence in Eastern Azerbaijan and evaluate the routine labora-tory diagnostic techniques of anti-CMV immunoglobulin M (IgM) and immunoglobulin G (IgG)."nMethods: During the present prospective cross-sectional study, 125 women referred to No. 1 Laboratory of Specialized Clin-ics of Tabriz University of Medical Sciences and seeking prenatal care were evaluated during 2003-2006. CMV IgG and IgM antibodies were determined with ELISA technique. Statistical analyses were performed using the SPSS statistical pack-age version 13.0."nResults: Eight four percent of the subjects were seropositive. Out of 20 subjects with primary seronegativity, 12 (9.6%) re-mind seronegative during reexaminations and follow up, but eight (6.4%) subjects showed primary infection in the second to third trimesters of gestation. In two (1.6%) of these eight subjects, IgM was persisted for more than 20 months."nConclusion: Results showed a similar seroprevalence of CMV in Eastern Azerbaijan. Also, we found that ELISA IgM test was not an appropriate method for differentiation of past or recent CMV infections especially in the pregnant women.
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