Publications by authors named "Swati Goel"

20 Publications

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Howard University College of Medicine.

Acad Med 2020 Sep;95(9S A Snapshot of Medical Student Education in the United States and Canada: Reports From 145 Schools):S95-S98

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http://dx.doi.org/10.1097/ACM.0000000000003476DOI Listing
September 2020

Nucleic Acid-Sensing Pathways During SARS-CoV-2 Infection: Expectations versus Reality.

J Inflamm Res 2021 26;14:199-216. Epub 2021 Jan 26.

Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.

The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people and crippled economies worldwide. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for this pandemic has triggered avid research on its pathobiology to better understand the pathophysiology of COVID-19. In the absence of approved antiviral therapeutic strategies or vaccine platforms capable of effectively targeting this global threat, the hunt for effective therapeutics has led to many candidates being actively evaluated for their efficacy in controlling or preventing COVID-19. In this review, we gathered current evidence on the innate nucleic acid-sensing pathways expected to be elicited by SARS-CoV-2 and the immune evasion mechanisms they have developed to promote viral replication and infection. Within the nucleic acid-sensing pathways, SARS-CoV-2 infection and evasion mechanisms trigger the activation of NOD-signaling and NLRP3 pathways leading to the production of inflammatory cytokines, IL-1β and IL-6, while muting or blocking cGAS-STING and interferon type I and III pathways, resulting in decreased production of antiviral interferons and delayed innate response. Therefore, blocking the inflammatory arm and boosting the interferon production arm of nucleic acid-sensing pathways could facilitate early control of viral replication and dissemination, prevent disease progression, and cytokine storm development. We also discuss the rationale behind therapeutic modalities targeting these sensing pathways and their implications in the treatment of COVID-19.
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http://dx.doi.org/10.2147/JIR.S277716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847386PMC
January 2021

The expression of MDM2, MDM4, p53 and p21 in myeloid neoplasms and the effect of MDM2/MDM4 dual inhibitor.

Leuk Lymphoma 2021 01 14;62(1):167-175. Epub 2020 Sep 14.

Department of Pathology, Montefiore Medical Center, New York, NY, USA.

p53 together with its downstream product p21 plays an important role in tumorigenesis development. MDM2 and MDM4 are two p53 regulators. We studied the expression of p53, p21, MDM2, and MDM4 in a total of 120 cases of myeloid neoplasms including MDS, AML or MDS/MPN, and control, using single and double immunohistochemical stains. We found TP53 mutations had a worse outcome in patients with AML/MDS, and p53 expression detected by immunohistochemistry had a similar prognostic value. p21 expression was strongly related to TP53 mutation status, with loss of expression in almost all TP53 mutated cases. MDM2 and MDM4 were highly expressed in hematopoietic cells in both benign and neoplastic cells. MDM2/p53 double positive cells exceeded MDM4/p53 double positive cells in neoplastic cases. Finally, we observed that p21 protein expression was up regulated upon the use of ALRN-6924 (Aileron) while no significant changes were seen in p53, MDM2 and MDM4 expression.
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http://dx.doi.org/10.1080/10428194.2020.1817441DOI Listing
January 2021

ACVR1/JAK1/JAK2 inhibitor momelotinib reverses transfusion dependency and suppresses hepcidin in myelofibrosis phase 2 trial.

Blood Adv 2020 Sep;4(18):4282-4291

Gilead Sciences, Inc., Foster City, CA.

Momelotinib (MMB) is a JAK1/2 and ACVR1 inhibitor with demonstrated clinical activity in all 3 hallmarks of myelofibrosis (MF): anemia, constitutional symptoms, and splenomegaly. In this phase 2 open-label translational biology study (NCT02515630) of 41 transfusion-dependent patients with MF, we explored mechanisms underlying the favorable activity of MMB on MF-associated iron-restricted anemia, including its impact on serum hepcidin levels, and markers of iron storage and availability, erythropoiesis, and inflammation. A transfusion-independent response (TI-R), defined as red blood cell transfusion independence (TI) ≥12 weeks at any time on study, occurred in 17 patients (41%; 95% confidence interval [CI], 26%-58%), including 14 patients (34%; 95% CI, 20%-51%) who achieved TI-R by week 24. In addition, 78% of TI nonresponse (TI-NR) patients achieved a ≥50% decrease in transfusion requirement for ≥8 weeks. Adverse events (AEs) were consistent with previous studies of MMB in MF, with cough, diarrhea, and nausea as the most common. Twenty-one patients experienced grade ≥3 AEs, most commonly anemia and neutropenia. Consistent with preclinical data, daily MMB treatment led to an acute and persistent decrease in blood hepcidin associated with increased iron availability and markers of erythropoiesis. Baseline characteristics associated with TI-R were lower inflammation and hepcidin as well as increased markers of erythropoiesis and bone marrow function. Overall, the study demonstrates that MMB treatment decreases hepcidin in conjunction with improving iron metabolism and erythropoiesis, suggesting a mechanistic explanation for the reduced transfusion dependency observed in transfusion-dependent MF patients treated with MMB, thereby addressing the key unmet medical need in the MF population.
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http://dx.doi.org/10.1182/bloodadvances.2020002662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509854PMC
September 2020

Are patients with chronic rhinosinusitis with nasal polyps at a decreased risk of COVID-19 infection?

Int Forum Allergy Rhinol 2020 10 19;10(10):1182-1185. Epub 2020 Aug 19.

Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.

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http://dx.doi.org/10.1002/alr.22672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436719PMC
October 2020

Real-World Outcomes of Ruxolitinib Treatment for Polycythemia Vera.

Clin Lymphoma Myeloma Leuk 2020 10 29;20(10):697-703.e1. Epub 2020 May 29.

Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

Introduction: Ruxolitinib is approved for the treatment of polycythemia vera (PV) with hydroxyurea resistance or intolerance. Approval was based on the phase III RESPONSE trial, which demonstrated efficacy in a highly selected patient population.

Materials And Methods: To characterize the tolerability and outcomes of ruxolitinib outside of a clinical trial, we performed a multi-center retrospective analysis of patients with PV treated with ruxolitinib at 11 participating sites across the United States. Outcomes of interest included change in phlebotomy requirements after starting ruxolitinib and spleen response, as these were included in the primary composite outcome in the RESPONSE trial.

Results: One hundred twenty-six patients met eligibility criteria, and the median duration of follow-up was 22.4 months (range, 0-63.0 months). At 32 weeks after starting ruxolitinib, the percentage of patients who received at least 1 phlebotomy was significantly decreased compared with before ruxolitinib (37% vs. 56%; relative risk [RR], 0.66; 95% confidence interval [CI], 0.52-0.84; P < .001). Phlebotomy requirements were similarly decreased in patients who had received at least 3 phlebotomies prior to ruxolitinib initiation (28% vs. 17%; RR, 1.65; 95% CI, 1.13-2.40; P < .01). Resolution of palpable splenomegaly was also documented (48% vs. 20%; RR, 2.45; 95% CI, 1.70-3.53; P < .0001). A total of 9.5% of patients discontinued ruxolitinib owing to treatment-emergent adverse events, and 81.7% of patients were receiving ruxolitinib at last known follow-up.

Conclusion: These real-world results are similar to those reported from the RESPONSE trial, although additional follow-up is necessary to assess long-term outcomes and potential for late-onset toxicity.
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http://dx.doi.org/10.1016/j.clml.2020.05.019DOI Listing
October 2020

SpikeSegNet-a deep learning approach utilizing encoder-decoder network with hourglass for spike segmentation and counting in wheat plant from visual imaging.

Plant Methods 2020 18;16:40. Epub 2020 Mar 18.

2ICAR-Indian Agricultural Research Institute, New Delhi, India.

Background: High throughput non-destructive phenotyping is emerging as a significant approach for phenotyping germplasm and breeding populations for the identification of superior donors, elite lines, and QTLs. Detection and counting of spikes, the grain bearing organs of wheat, is critical for phenomics of a large set of germplasm and breeding lines in controlled and field conditions. It is also required for precision agriculture where the application of nitrogen, water, and other inputs at this critical stage is necessary. Further, counting of spikes is an important measure to determine yield. Digital image analysis and machine learning techniques play an essential role in non-destructive plant phenotyping analysis.

Results: In this study, an approach based on computer vision, particularly object detection, to recognize and count the number of spikes of the wheat plant from the digital images is proposed. For spike identification, a novel deep-learning network, SpikeSegNet, has been developed by combining two proposed feature networks: Local Patch extraction Network (LPNet) and Global Mask refinement Network (GMRNet). In LPNet, the contextual and spatial features are learned at the local patch level. The output of LPNet is a segmented mask image, which is further refined at the global level using GMRNet. Visual (RGB) images of 200 wheat plants were captured using LemnaTec imaging system installed at Nanaji Deshmukh Plant Phenomics Centre, ICAR-IARI, New Delhi. The precision, accuracy, and robustness (F score) of the proposed approach for spike segmentation are found to be 99.93%, 99.91%, and 99.91%, respectively. For counting the number of spikes, "analyse particles"-function of imageJ was applied on the output image of the proposed SpikeSegNet model. For spike counting, the average precision, accuracy, and robustness are 99%, 95%, and 97%, respectively. SpikeSegNet approach is tested for robustness with illuminated image dataset, and no significant difference is observed in the segmentation performance.

Conclusion: In this study, a new approach called as SpikeSegNet has been proposed based on combined digital image analysis and deep learning techniques. A dedicated deep learning approach has been developed to identify and count spikes in the wheat plants. The performance of the approach demonstrates that SpikeSegNet is an effective and robust approach for spike detection and counting. As detection and counting of wheat spikes are closely related to the crop yield, and the proposed approach is also non-destructive, it is a significant step forward in the area of non-destructive and high-throughput phenotyping of wheat.
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http://dx.doi.org/10.1186/s13007-020-00582-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079463PMC
March 2020

Anisocytosis is a poor prognostic factor in secondary polycythemia.

Leuk Lymphoma 2019 12 13;60(13):3287-3291. Epub 2019 Jun 13.

Department of Oncology, Montefiore Einstein Center for Cancer Care, Bronx, NY, USA.

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http://dx.doi.org/10.1080/10428194.2019.1622701DOI Listing
December 2019

North American ATLL has a distinct mutational and transcriptional profile and responds to epigenetic therapies.

Blood 2018 10 13;132(14):1507-1518. Epub 2018 Aug 13.

Department of Oncology, Montefiore Medical Center, Bronx, NY.

Adult T-cell leukemia lymphoma (ATLL) is a rare T cell neoplasm that is endemic in Japanese, Caribbean, and Latin American populations. Most North American ATLL patients are of Caribbean descent and are characterized by high rates of chemo-refractory disease and worse prognosis compared with Japanese ATLL. To determine genomic differences between these 2 cohorts, we performed targeted exon sequencing on 30 North American ATLL patients and compared the results with the Japanese ATLL cases. Although the frequency of TP53 mutations was comparable, the mutation frequency in epigenetic and histone modifying genes (57%) was significantly higher, whereas the mutation frequency in JAK/STAT and T-cell receptor/NF-κB pathway genes was significantly lower. The most common type of epigenetic mutation is that affecting EP300 (20%). As a category, epigenetic mutations were associated with adverse prognosis. Dissimilarities with the Japanese cases were also revealed by RNA sequencing analysis of 9 primary patient samples. ATLL samples with a mutated EP300 gene have decreased total and acetyl p53 protein and a transcriptional signature reminiscent of p53-mutated cancers. Most importantly, decitabine has highly selective single-agent activity in the EP300-mutated ATLL samples, suggesting that decitabine treatment induces a synthetic lethal phenotype in EP300-mutated ATLL cells. In conclusion, we demonstrate that North American ATLL has a distinct genomic landscape that is characterized by frequent epigenetic mutations that are targetable preclinically with DNA methyltransferase inhibitors.
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http://dx.doi.org/10.1182/blood-2018-01-824607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410908PMC
October 2018

Myelodysplastic Syndrome and Sweet's Syndrome Are Associated with a Mutation in Isocitrate Dehydrogenase 1.

Anticancer Res 2018 04;38(4):2201-2205

Department of Hemato-Oncology, Albert Einstein College of Medicine, Bronx, NY, U.S.A.

Background: Sweet's syndrome (SS) is a febrile neutrophilic dermatosis that has been clinically linked to hematological malignancies, particularly myelodysplastic syndrome (MDS), in a number of case series. Many epigenetic changes underlying MDS have been identified, such as a mutation in the isocitrate dehydrogenase 1 (IDH1) gene, which causes DNA hypermethylation and alteration of a number of genes that lead to leukemogenesis. However, the pathogenesis of malignancy-associated SS is unknown.

Case Report: We present two patients who were diagnosed with SS and concomitant IDH1-mutated MDS. Immunohistochemical staining of their skin lesions showed neutrophils diffusely positive for the IDH1 mutation.

Conclusion: These cases demonstrate that IDH1 mutation may be implicated in the pathogenesis of malignancy-associated SS. Future investigation to elucidate this pathway is warranted. Establishing this molecular link can provide an earlier identification of patients with SS who are also at increased risk for developing MDS.
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http://dx.doi.org/10.21873/anticanres.12462DOI Listing
April 2018

Hispanic ethnicity is associated with younger age at presentation but worse survival in acute myeloid leukemia.

Blood Adv 2017 Nov 26;1(24):2120-2123. Epub 2017 Oct 26.

Department of Oncology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY.

SEER data and a Bronx validation cohort demonstrate that Hispanics present with AML at younger age but have shorter survival than whites.Increased frequency of high-risk mutations in Hispanics provides a potential biologic explanation for poorer outcomes in Hispanics.
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http://dx.doi.org/10.1182/bloodadvances.2017007013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737118PMC
November 2017

Role of Dysregulated Cytokine Signaling and Bacterial Triggers in the Pathogenesis of Cutaneous T-Cell Lymphoma.

J Invest Dermatol 2018 05 8;138(5):1116-1125. Epub 2017 Nov 8.

Department of Pathology, New York University School of Medicine, New York, New York, USA; Laura and Isaac Perlmutter Cancer Institute, New York University School of Medicine, New York, New York, USA. Electronic address:

Cutaneous T-cell lymphoma is a heterogeneous group of lymphomas characterized by the accumulation of malignant T cells in the skin. The molecular and cellular etiology of this malignancy remains enigmatic, and what role antigenic stimulation plays in the initiation and/or progression of the disease remains to be elucidated. Deep sequencing of the tumor genome showed a highly heterogeneous landscape of genetic perturbations, and transcriptome analysis of transformed T cells further highlighted the heterogeneity of this disease. Nonetheless, using data harvested from high-throughput transcriptional profiling allowed us to develop a reliable signature of this malignancy. Focusing on a key cytokine signaling pathway previously implicated in cutaneous T-cell lymphoma pathogenesis, JAK/STAT signaling, we used conditional gene targeting to develop a fully penetrant small animal model of this disease that recapitulates many key features of mycosis fungoides, a common variant of cutaneous T-cell lymphoma. Using this mouse model, we show that T-cell receptor engagement is critical for malignant transformation of the T lymphocytes and that progression of the disease is dependent on microbiota.
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http://dx.doi.org/10.1016/j.jid.2017.10.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5912980PMC
May 2018

Granular Cell Tumour of the Tongue: Report of a Case.

J Clin Diagn Res 2017 Jun 1;11(6):ZJ01-ZJ02. Epub 2017 Jun 1.

Research Officer, Department of Pulmonary Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.

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http://dx.doi.org/10.7860/JCDR/2017/28946.10006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535500PMC
June 2017

Socioeconomic burden of participation in clinical trials in patients with myeloproliferative neoplasms.

Eur J Haematol 2017 Jul 5;99(1):36-41. Epub 2017 May 5.

Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.

Objective: To determine the financial and psycho-social impact of participation in clinical trials of patients with BCR/ABL-negative myeloproliferative neoplasms (MPN).

Methods: An international, observational cross-sectional study was performed in 143 consecutive MPN patients (51% myelofibrosis, 36% polycythemia vera, 13% essential thrombocythemia), 68% from Italy, 17% from USA, and 15% from Spain.

Results: Thirty-five percent of patients reported having spent more money during the trial than in previous treatments and 21% having missed more workdays. Twelve percent replied that they would not have participated in the trial if the financial consequences would have been known beforehand. In 10% of the patients, the interpersonal relationships were more affected during the trial than in previous treatment but, overall, 91% subjects believed that participating in the clinical trial was worth the financial or emotional suffering. Concerning patients' suggestions, 54% of them indicated that the number of visits required for the trial should be clearly specified in the informed consent, 60% recommended travel cost reimbursement, and 23% hotel cost reimbursement.

Conclusions: Physicians and pharmaceutical companies involved in clinical trials with patients with hematological diseases should be aware of these problems and make efforts to attenuate the socioeconomic burden of participation in the trials.
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http://dx.doi.org/10.1111/ejh.12887DOI Listing
July 2017

Odontogenic Myxoma of Mandible with Unusual (Sunburst) Appearance: A Rare Case Report.

J Clin Diagn Res 2016 May 1;10(5):ZJ05-7. Epub 2016 May 1.

Professor and Head, Department of Oral Medicine, Diagnosis and Radiology, Goa Dental College & Hospital , Goa, India .

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http://dx.doi.org/10.7860/JCDR/2016/20123.7812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948558PMC
May 2016

Bone marrow fibrosis in primary myelofibrosis: pathogenic mechanisms and the role of TGF-β.

Stem Cell Investig 2016 26;3. Epub 2016 Feb 26.

1 Steward Carney Hospital, 2100 Dorchester Avenue, Dorchester, MA, USA ; 2 Albert Einstein College of Medicine, Bronx, NY, USA ; 3 University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

Primary myelofibrosis (PMF) is a Philadelphia chromosome negative myeloproliferative neoplasm (MPN) with adverse prognosis and is associated with bone marrow fibrosis and extramedullary hematopoiesis. Even though the discovery of the Janus kinase 2 (JAK2), thrombopoietin receptor (MPL) and calreticulin (CALR) mutations have brought new insights into the complex pathogenesis of MPNs, the etiology of fibrosis is not well understood. Furthermore, since JAK2 inhibitors do not lead to reversal of fibrosis further understanding of the biology of fibrotic process is needed for future therapeutic discovery. Transforming growth factor beta (TGF-β) is implicated as an important cytokine in pathogenesis of bone marrow fibrosis. Various mouse models have been developed and have established the role of TGF-β in the pathogenesis of fibrosis. Understanding the molecular alterations that lead to TGF-β mediated effects on bone marrow microenvironment can uncover newer therapeutic targets against myelofibrosis. Inhibition of the TGF-β pathway in conjunction with other therapies might prove useful in the reversal of bone marrow fibrosis in PMF.
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http://dx.doi.org/10.3978/j.issn.2306-9759.2016.02.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923632PMC
June 2016

Primary care-based interventions for intimate partner violence: a systematic review.

Am J Prev Med 2014 Feb;46(2):188-94

Department of Family Medicine and Community Health, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Public Health Initiatives, University of Pennsylvania, Philadelphia, Pennsylvania; Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania.

Context: Primary care providers are uniquely positioned to respond to patients' disclosure of intimate partner violence (IPV). However, the research on primary care-based IPV interventions has not been systematically synthesized, making it difficult for providers, policymakers, and researchers to understand how to effectively intervene in the primary care setting. This systematic review summarizes primary care-based interventions for patients experiencing IPV.

Evidence Acquisition: PubMed, PsycINFO, and CINAHL were searched from their start through September 2012; this search was augmented by bibliographic review and consultation with experts. Eligible studies included English-language, peer-reviewed articles that assessed patient-level impact of IPV interventions that originated from patients' visits to a primary care provider.

Evidence Synthesis: Of 80 potentially eligible studies, 17 met eligibility criteria. The majority of interventions recruited women from reproductive care sites. Interventions tended to be brief, delivered by nonphysicians, and focused on empowerment, empathetic listening, discussion of the cycle of violence and safety, and referral to community-based resources. Thirteen studies demonstrated at least one intervention-related benefit. Six of 11 articles measuring IPV persistence found reductions in future violence; two of five measuring safety-promoting behaviors found increases; and six of ten measuring IPV/community resource referrals found enhanced use. Some studies also documented health improvements.

Conclusions: The majority of studies demonstrated patient-level benefit subsequent to primary care IPV interventions, with IPV/community referrals the most common positively affected outcome.
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http://dx.doi.org/10.1016/j.amepre.2013.10.001DOI Listing
February 2014

T cell-derived IL-17 mediates epithelial changes in the airway and drives pulmonary neutrophilia.

J Immunol 2013 Sep 21;191(6):3100-11. Epub 2013 Aug 21.

Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.

Th17 cells are a proinflammatory subset of effector T cells that have been implicated in the pathogenesis of asthma. Their production of the cytokine IL-17 is known to induce local recruitment of neutrophils, but the direct impact of IL-17 on the lung epithelium is poorly understood. In this study, we describe a novel mouse model of spontaneous IL-17-driven lung inflammation that exhibits many similarities to asthma in humans. We have found that STAT3 hyperactivity in T lymphocytes causes an expansion of Th17 cells, which home preferentially to the lungs. IL-17 secretion then leads to neutrophil infiltration and lung epithelial changes, in turn leading to a chronic inflammatory state with increased mucus production and decreased lung function. We used this model to investigate the effects of IL-17 activity on airway epithelium and identified CXCL5 and MIP-2 as important factors in neutrophil recruitment. The neutralization of IL-17 greatly reduces pulmonary neutrophilia, underscoring a key role for IL-17 in promoting chronic airway inflammation. These findings emphasize the role of IL-17 in mediating neutrophil-driven pulmonary inflammation and highlight a new mouse model that may be used for the development of novel therapies targeting Th17 cells in asthma and other chronic pulmonary diseases.
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http://dx.doi.org/10.4049/jimmunol.1301360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822005PMC
September 2013

Design and synthesis of novel derivatives of all-trans retinoic acid demonstrate the combined importance of acid moiety and conjugated double bonds in its binding to PML-RAR-alpha oncogene in acute promyelocytic leukemia.

Leuk Lymphoma 2010 Jun;51(6):1108-14

Albert Einstein College of Medicine, Bronx, NY, USA.

The binding of all-trans retinoic acid (ATRA) to retinoid receptor-alpha (RAR-alpha) relieves transcriptional repression induced by the promyelocytic leukemia-retinoic acid receptor (PML-RAR) oncoprotein. The ATRA molecule contains a cyclohexenyl ring, a polyene chain containing conjugated double alkene bonds, and a terminal carboxyl group. To determine the contributions of these structural components of ATRA to its clinical efficacy, we synthesized three novel retinoids. These consisted of either a modified conjugated alkene backbone with an intact acid moiety (13a) or a modified conjugated alkene backbone and conversion of the acid group to either an ester (13b) or an aromatic amide (13c). Reporter assays demonstrated that compound 13a successfully relieved transcriptional repression by RAR-alpha, while 13b and 13c could not, demonstrating the critical role of the acid moiety in this binding. However, only ATRA was able to significantly inhibit the proliferation of APL cells while 13a, 13b, or 13c was not. Furthermore, only 13a led to partial non-significant differentiation of NB4 cells, demonstrating the importance of C9-C10 double bonds in differentiation induced CD11 expression. Our results demonstrate that both the acid moiety and conjugated double bonds present in the ATRA molecule are important for its biological activity in APL and have important implications for the design of future novel retinoids.
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http://dx.doi.org/10.3109/10428191003786766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104194PMC
June 2010

Mechanism of action of lenalidomide in hematological malignancies.

J Hematol Oncol 2009 Aug 12;2:36. Epub 2009 Aug 12.

Department of Medicine, Albert Einstein College of Medicine, Bronx, USA.

Immunomodulatory drugs lenalidomide and pomalidomide are synthetic compounds derived by modifying the chemical structure of thalidomide to improve its potency and reduce its side effects. Lenalidomide is a 4-amino-glutamyl analogue of thalidomide that lacks the neurologic side effects of sedation and neuropathy and has emerged as a drug with activity against various hematological and solid malignancies. It is approved by FDA for clinical use in myelodysplastic syndromes with deletion of chromosome 5q and multiple myeloma. Lenalidomide has been shown to be an immunomodulator, affecting both cellular and humoral limbs of the immune system. It has also been shown to have anti-angiogenic properties. Newer studies demonstrate its effects on signal transduction that can partly explain its selective efficacy in subsets of MDS. Even though the exact molecular targets of lenalidomide are not well known, its activity across a spectrum of neoplastic conditions highlights the possibility of multiple target sites of action.
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http://dx.doi.org/10.1186/1756-8722-2-36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736171PMC
August 2009