Publications by authors named "Hamid Rezvani"

65 Publications

Characterization of NADPH Oxidase Expression and Activity in Acute Myeloid Leukemia Cell Lines: A Correlation with the Differentiation Status.

Antioxidants (Basel) 2021 Mar 23;10(3). Epub 2021 Mar 23.

University of Tours EA 7501, CNRS ERL 7001, LNOx Team, F-37032 Tours, France.

In acute myeloid leukemia (AML), a low level of reactive oxygen species (ROS) is associated with leukemic stem cell (LSC) quiescence, whereas a high level promotes blast proliferation. ROS homeostasis relies on a tightly-regulated balance between the antioxidant and oxidant systems. Among the oxidants, NADPH oxidases (NOX) generate ROS as a physiological function. Although it has been reported in AML initiation and development, the contribution of NOX to the ROS production in AML remains to be clarified. The aim of this study was to investigate the NOX expression and function in AML, and to examine the role of NOX in blast proliferation and differentiation. First, we interrogated the NOX expression in primary cells from public datasets, and investigated their association with prognostic markers. Next, we explored the NOX expression and activity in AML cell lines, and studied the impact of NOX knockdown on cell proliferation and differentiation. We found that NOX2 is ubiquitously expressed in AML blasts, and particularly in cells from the myelomonocytic (M4) and monocytic (M5) stages; however, it is less expressed in LSCs and in relapsed AML. This is consistent with an increased expression throughout normal hematopoietic differentiation, and is reflected in AML cell lines. Nevertheless, no endogenous NOX activity could be detected in the absence of PMA stimulation. Furthermore, knockdown, although hampering induced NOX2 activity, did not affect the proliferation and differentiation of THP-1 and HL-60 cells. In summary, our data suggest that NOX2 is a marker of AML blast differentiation, while AML cell lines lack any NOX2 endogenous activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox10030498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004739PMC
March 2021

Does saffron supplementation have favorable effects on liver function indicators? A systematic review and meta-analysis of randomized controlled trials.

Crit Rev Food Sci Nutr 2021 Mar 16:1-13. Epub 2021 Mar 16.

Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Several pharmaceutical and non-pharmaceutical approaches have been suggested to improve liver health. There is a large discrepancy in the effects of saffron supplementation on liver function in adults. To fill this knowledge gap, this systematic review and meta-analysis of randomized controlled trials (RCTs) assess the effects of saffron supplementation on liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). A systematic search current to August 2020 was performed in PubMed/Medline, Scopus, Web of Science, and Google Scholar using relevant keywords to detect eligible articles. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence (95% CI). Nine eligible trials were included in the final analysis. The pooled analysis revealed that serum ALT concentrations were significantly reduced using saffron compared to placebo (WMD: -2.39 U/L; 95% CI: -4.57 to -0.22;  = 0.03, = 87.9%,  < 0.001). However, saffron supplementation did not affect levels of serum AST (WMD: 1.12 U/L; 95% CI: -1.42 to 3.65;  = 0.39) or ALP (WMD: 4.32 U/L; 95% CI: -6.91 to 15.54;  = 0.78). In the dose-response analysis, we did not find a significant dose-response relationship between dosage and duration of saffron supplementation on serum levels of ALT, AST, and ALP. We found that saffron supplementation can reduce ALT serum concentrations without significant effects on other liver function indicators, including AST and ALP. Nevertheless, future large RCTs on diverse populations are needed to understand better the effects of saffron and its constituents on these enzymes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10408398.2021.1900059DOI Listing
March 2021

Lack of association between VEGF -2578C/A polymorphism and risk of colorectal cancer in an Iranian population.

Gastroenterol Hepatol Bed Bench 2020 ;13(Suppl1):S47-S52

Gastroenterology and Liver Diseases Research center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aim: Here, we evaluated the VEGF gene -2578C/A polymorphism as a potential susceptibility factor in colorectal cancer (CRC) occurrence amongst Iranian CRC patients.

Background: Vascular endothelial growth factor (VEGF) is a key regulatory factor in angiogenesis which plays essential roles in the development of malignancy in colorectal cancer (CRC), as the third most prevalent cancer worldwide.

Methods: VEGF -2578C/A polymorphism was evaluated in 200 CRC patients and 200 healthy control subjects via restriction fragment length polymorphism analysis.

Results: The frequencies of CC, AC and AA genotypes among CRC patients were 22.5%, 51% and 26.5%, respectively, with their respective genotype frequencies at 16%, 54% and 30% in control cohorts (P=0.247). The A allele frequency among the case group was 52% and for control group, it was 57%. C allele frequency in case and control groups was 48% and 43%, respectively (p=0.156). No significant association was observed (p=0.990) between this polymorphism and CRC stage.

Conclusion: Our findings provide limited support for the hypothesis that the -2578C/A VEGF are associated with increased risk of colorectal cancer in Iranian colorectal cancer patients and suggest instead that meta data studies, which have previously relied upon populations definitions such as 'Asian', should more specifically take into account country of origin when associating prognostic value to a given genotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881395PMC
January 2020

Critical role of Aquaporin-1 and telocytes in infantile hemangioma response to propranolol beta blockade.

Proc Natl Acad Sci U S A 2021 Feb;118(7)

Inserm, Biothérapie des Maladies Génétiques Inflammatoires et Cancers (BMGIC), UMR 1035, University of Bordeaux, F-33076 Bordeaux, France.

Propranolol, a nonselective β-adrenergic receptor (ADRB) antagonist, is the first-line therapy for severe infantile hemangiomas (IH). Since the incidental discovery of propranolol efficacy in IH, preclinical and clinical investigations have shown evidence of adjuvant propranolol response in some malignant tumors. However, the mechanism for propranolol antitumor effect is still largely unknown, owing to the absence of a tumor model responsive to propranolol at nontoxic concentrations. Immunodeficient mice engrafted with different human tumor cell lines were treated with anti-VEGF bevacizumab to create a model sensitive to propranolol. Proteomics analysis was used to reveal propranolol-mediated protein alteration correlating with tumor growth inhibition, and Aquaporin-1 (AQP1), a water channel modulated in tumor cell migration and invasion, was identified. IH tissues and cells were then functionally investigated. Our functional protein association networks analysis and knockdown of ADRB2 and AQP1 indicated that propranolol treatment and AQP1 down-regulation trigger the same pathway, suggesting that AQP1 is a major driver of beta-blocker antitumor response. Examining AQP1 in human hemangioma samples, we found it exclusively in a perivascular layer, so far unrecognized in IH, made of telocytes (TCs). Functional in vitro studies showed that AQP1-positive TCs play a critical role in IH response to propranolol and that modulation of AQP1 in IH-TC by propranolol or shAQP1 decreases capillary-like tube formation in a Matrigel-based angiogenesis assay. We conclude that IH sensitivity to propranolol may rely, at least in part, on a cross talk between lesional vascular cells and stromal TCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2018690118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896303PMC
February 2021

Targeting the mitochondrial trifunctional protein restrains tumor growth in oxidative lung carcinomas.

J Clin Invest 2021 Jan;131(1)

CELLOMET, Bordeaux, France.

Metabolic reprogramming is a common hallmark of cancer, but a large variability in tumor bioenergetics exists between patients. Using high-resolution respirometry on fresh biopsies of human lung adenocarcinoma, we identified 2 subgroups reflected in the histologically normal, paired, cancer-adjacent tissue: high (OX+) mitochondrial respiration and low (OX-) mitochondrial respiration. The OX+ tumors poorly incorporated [18F]fluorodeoxy-glucose and showed increased expression of the mitochondrial trifunctional fatty acid oxidation enzyme (MTP; HADHA) compared with the paired adjacent tissue. Genetic inhibition of MTP altered OX+ tumor growth in vivo. Trimetazidine, an approved drug inhibitor of MTP used in cardiology, also reduced tumor growth and induced disruption of the physical interaction between the MTP and respiratory chain complex I, leading to a cellular redox and energy crisis. MTP expression in tumors was assessed using histology scoring methods and varied in negative correlation with [18F]fluorodeoxy-glucose incorporation. These findings provide proof-of-concept data for preclinical, precision, bioenergetic medicine in oxidative lung carcinomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI133081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773363PMC
January 2021

Xeroderma Pigmentosum C (XPC) Mutations in Primary Fibroblasts Impair Base Excision Repair Pathway and Increase Oxidative DNA Damage.

Front Genet 2020 27;11:561687. Epub 2020 Nov 27.

University Grenoble Alpes, SyMMES/CIBEST UMR 5819 UGA-CNRS-CEA, Grenoble, France.

Xeroderma Pigmentosum C (XPC) is a multi-functional protein that is involved not only in the repair of bulky lesions, post-irradiation, via nucleotide excision repair (NER) but also in oxidative DNA damage mending. Since base excision repair (BER) is the primary regulator of oxidative DNA damage, we characterized, post-Ultraviolet B-rays (UVB)-irradiation, the detailed effect of three different XPC mutations in primary fibroblasts derived from XP-C patients on mRNA, protein expression and activity of different BER factors. We found that XP-C fibroblasts are characterized by downregulated expression of different BER factors including , , , , , and β. Such a downregulation was also observed at OGG1, MYH, and APE1 protein levels. This was accompanied with an increase in DNA oxidative lesions, as evidenced by 8-oxoguanine levels, immediately post-UVB-irradiation. Unlike in normal control cells, these oxidative lesions persisted over time in XP-C cells having lower excision repair capacities. Taken together, our results indicated that an impaired BER pathway in XP-C fibroblasts leads to longer persistence and delayed repair of oxidative DNA damage. This might explain the diverse clinical phenotypes in XP-C patients suffering from cancer in both photo-protected and photo-exposed areas. Therapeutic strategies based on reinforcement of BER pathway might therefore represent an innovative path for limiting the drawbacks of NER-based diseases, as in XP-C case.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2020.561687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728722PMC
November 2020

APC and AXIN2 Are Promising Biomarker Candidates for the Early Detection of Adenomas and Hyperplastic Polyps.

Cancer Inform 2020 11;19:1176935120972383. Epub 2020 Nov 11.

School of Medicine, University of Sunderland, Sunderland, UK.

Aberrant activation of the WNT/CTNNB1 pathway is notorious in colorectal cancer (CRC). Here, we demonstrate that the expression of specific and crucial WNT signaling pathway genes is linked to disease progression in colonic adenomatous (AP) and hyperplastic (HP) polyps in an Iranian patient population. Thus, we highlight potential gene expression profiles as candidate novel biomarkers for the early detection of CRC. From a 12-month study (2016-2017), 44 biopsy samples were collected during colonoscopy from the patients with colorectal polyps and 10 healthy subjects for normalization. Clinical and demographic data were collected in all cases, and mRNA expression of APC, CTNNB1, CDH1, AXIN1, and AXIN2 genes was investigated using real-time polymerase chain reaction (PCR). CTNNB1 and CDH1 expression levels were unaltered in AP and HP subjects, whereas mRNA expression of APC was decreased in AP contrasted with HP subjects, with a significant association between APC downregulation and polyp size. Although AXIN1 showed no changes between AP and HP groups, a significant association between AXIN1 and dysplasia grade was found. Also, significant upregulation of AXIN2 in both AP and HP subjects was detected. In summary, we have shown increased expression of AXIN2 and decreased expression of APC correlating with grade of dysplasia and polyp size. Hence, AXIN2 and APC should be explored as biomarker candidates for early detection of AP and HP polyps in CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1176935120972383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672736PMC
November 2020

The effect of Alpha-lipoic acid supplementation on endothelial function: A systematic review and meta-analysis.

Phytother Res 2020 Nov 18. Epub 2020 Nov 18.

Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

There is evidence that alpha-lipoic acid (ALA) supplementation plays an important role in preventing cardiovascular diseases. However, its effect, specifically, on endothelial function (EF) is unclear. Therefore, this systematic review and meta-analysis aimed to evaluate the effects of ALA supplementation on EF. Databases including PubMed/Medline, Scopus, and ISI Web of Science were searched to identify eligible publications from inception up to April 2020. Randomized controlled trials assessing the effect of ALA supplementation on flow-mediated dilation (FMD) levels in adults were included. The pooled results were obtained using the random-effects model and are expressed as weighted mean differences (WMD) with 95% confidence intervals (CI). Five studies including six effect sizes and 300 participants were included. ALA supplementation significantly increased FMD levels by 2.36% (95% CI: 1.21-3.51; p < .001), compared with the control. Subgroup analyses suggested that the effects of ALA on FMD could be changed by age and health status of the participants. Dose-response analysis also showed that ALA dosage had a significant non-linear effect on FMD levels. The results showed that ALA supplementation appears to improve the EF. However, the role of ALA supplementation in improving other biomarkers of EF requires further research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ptr.6959DOI Listing
November 2020

ABL Kinase Domain Mutations in Iranian Chronic Myeloid Leukemia Patients with Resistance to Tyrosine Kinase Inhibitors.

Lab Med 2021 Mar;52(2):158-167

Department of Hematology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, IR Iran.

Objective: Tyrosine kinase inhibitors (TKIs) are considered standard first-line treatment in patients with chronic myeloid leukemia. Because ABL kinase domain mutations are the most common causes of treatment resistance, their prevalence and assessment during treatment may predict subsequent response to therapy.

Methods: The molecular response in Bcr-Abl1IS was tested via quantitative real-time polymerase chain reaction. We used the direct sequencing technique to discover the mutations in the ABL kinase domain. The IRIS trial established a standard baseline for measurement - (100% BCR-ABL1 on the 'international scale') and a major molecular response (good response to therapy) was defined as a 3-log reduction in the amount of BCR-ABL1 - 0.1% BCR-ABL1 on the international scale.

Results: We observed 11 different mutations in 13 patients, including E255K, which had the highest mutation rate. A lack of hematologic response was found in 22 patients, who showed a significantly higher incidence of mutations.

Conclusion: Detection of kinase domain mutations is a reliable method for choosing the best treatment strategy based on patients' conditions, avoiding ineffective treatments, and running high-cost protocols in patients with acquired resistance to TKIs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/labmed/lmaa052DOI Listing
March 2021

Trisk 95 as a novel skin mirror for normal and diabetic systemic glucose level.

Sci Rep 2020 07 22;10(1):12246. Epub 2020 Jul 22.

Laboratory of Developmental Biology, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Aapistie 5A, 90220, Oulu, Finland.

Developing trustworthy, cost effective, minimally or non-invasive glucose sensing strategies is of great need for diabetic patients. In this study, we used an experimental type I diabetic mouse model to examine whether the skin would provide novel means for identifying biomarkers associated with blood glucose level. We first showed that skin glucose levels are rapidly influenced by blood glucose concentrations. We then conducted a proteomic screen of murine skin using an experimental in vivo model of type I diabetes and wild-type controls. Among the proteins that increased expression in response to high blood glucose, Trisk 95 expression was significantly induced independently of insulin signalling. A luciferase reporter assay demonstrated that the induction of Trisk 95 expression occurs at a transcriptional level and is associated with a marked elevation in the Fluo-4AM signal, suggesting a role for intracellular calcium changes in the signalling cascade. Strikingly, these changes lead concurrently to fragmentation of the mitochondria. Moreover, Trisk 95 knockout abolishes both the calcium flux and the mitochondrial phenotype changes indicating dependency of glucose flux in the skin on Trisk 95 function. The data demonstrate that the skin reacts robustly to systemic blood changes, and that Trisk 95 is a promising biomarker for a glucose monitoring assembly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-68972-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376074PMC
July 2020

Targeting Human Lung Adenocarcinoma with a Suppressor of Mitochondrial Superoxide Production.

Antioxid Redox Signal 2020 11 29;33(13):883-902. Epub 2020 Jun 29.

CELLOMET, Functional Genomics Center (CGFB), Bordeaux, France.

REDOX signaling from reactive oxygen species (ROS) generated by the mitochondria (mitochondrial reactive oxygen species [mtROS]) has been implicated in cancer growth and survival. Here, we investigated the effect of 5-(4-methoxyphenyl)-3H-1,2-dithiole-3-thione (AOL), a recently characterized member of the new class of mtROS suppressors (S1QELs), on human lung adenocarcinoma proteome reprogramming, bioenergetics, and growth. AOL reduced steady-state cellular ROS levels in human lung cancer cells without altering the catalytic activity of complex I. AOL treatment induced dose-dependent inhibition of lung cancer cell proliferation and triggered a reduction in tumor growth . Molecular investigations demonstrated that AOL reprogrammed the proteome of human lung cancer cells. In particular, AOL suppressed the determinants of the Warburg effect and increased the expression of the complex I subunit NDUFV1 which was also identified as AOL binding site using molecular modeling computer simulations. Comparison of the molecular changes induced by AOL and MitoTEMPO, an mtROS scavenger that is not an S1QEL, identified a core component of 217 proteins commonly altered by the two treatments, as well as drug-specific targets. This study provides proof-of-concept data on the anticancer effect of AOL on mouse orthotopic human lung tumors. A unique dataset on proteomic reprogramming by AOL and MitoTEMPO is also provided. Lastly, our study revealed the repression of NDUFV1 by S1QEL AOL. Our findings demonstrate the preclinical anticancer properties of S1QEL AOL and delineate its mode of action on REDOX and cancer signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/ars.2019.7892DOI Listing
November 2020

Efficacy and Safety of Proposed Bevacizumab Biosimilar BE1040V in Patients With Metastatic Colorectal Cancer: A Phase III, Randomized, Double-blind, Noninferiority Clinical Trial.

Clin Ther 2020 05 22;42(5):848-859. Epub 2020 Apr 22.

Department of Medical Oncology, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Purpose: The purpose of this study was to compare the efficacy and safety of a proposed bevacizumab biosimilar to those of the reference product in patients with metastatic colorectal cancer (mCRC).

Methods: This Phase III, multicenter, randomized, double-blind (patient- and assessor-blind), active-controlled, 2-armed, parallel-group, noninferiority trial was conducted in patients with histologically verified colorectal cancer with evidence of at least 1 metastasis. Patients with mCRC were randomized 2:1 to receive 5 mg/kg IV of either study drug plus FOLFIRI-3 (with repeated irinotecan 100 mg/m 60-min infusion on day 3) or the reference drug plus FOLFIRI-3 every 2 weeks for 1 year. Progression-free survival (PFS) was the primary end point, and overall survival, objective response rate, and time to treatment failure as well as safety and immunogenicity were secondary end points. The population assessable for PFS was per protocol, and the intention-to-treat population was used for sensitivity analysis. Safety was assessed based on reports of adverse events, laboratory test results, and vital sign measurements.

Findings: A total of 126 patients were enrolled; PFS values in the biosimilar and reference arms were 232 days (7.7 months) and 210 days (7 months), respectively (P = 0.47). The hazard ratio of the biosimilar arm versus the reference arm was 0.79 in the per-protocol population (90% CI, 0.46-1.35; P = 0.47). The upper limit for the 2-sided 90% CI was lower than the margin of 1.44, indicating that the biosimilar drug was noninferior to the reference drug. The hazard ratio for overall survival in the intent-to-treat population was 0.99 (95% CI, 0.55-1.80; P = 0.99). The difference between other efficacy end points among the groups was not statistically significant. No significant difference was observed in the comparison of the two arms for safety. The antidrug antibody was positive in 1 patient in each arm.

Implications: The proposed biosimilar BE1040V was noninferior to the reference product in terms of efficacy in the treatment of mCRC, and tolerability was comparable between the 2 drugs. ClinicalTrials.gov identifier: NCT03288987.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinthera.2020.03.009DOI Listing
May 2020

Study of the Relationship between ERCC1 Polymorphisms and Response to Platinum-based Chemotherapy in Iranian Patients with Colorectal and Gastric Cancers.

Iran J Pharm Res 2019 ;18(4):2163-2171

Food Safety Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

This study was designed to evaluate the effect of excision repair cross complementing group 1 (ERCC1) rs11615 codon 118C/T gene polymorphisms on treatment outcomes in Iranian patients receiving oxaliplatin-based regimens for colorectal (CRC) and gastric cancers (GC). Patients, who were candidates to receive oxaliplatin-based chemotherapy, entered into the study. In 2-week intervals, the patients received combination regimen of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) for 3 months. ERCC1 rs11615 codon 118C/T polymorphism was tested by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) method using patients' peripheral blood lymphocytes. The tumor response to chemotherapy was evaluated by examining the size of the tumor using CT scan. Association between response rates, according to the RECIST criteria, and patients' genotypes was evaluated. Any relationship between response rate and possible explanatory factors was also determined. Overall, 40 patients (13 females (32.5%), and 27 males (67.5%)) enrolled in the study. Four patients (10.0%) carried the homo-zygous mutation (T/T genotype), ten patients (25.0%) were heterozygous (C/T genotype), and twenty-six patients (65%) were homo-zygous (C/C genotype). Response rate were 30.77%, 20.00%, and 0.00% for the genotypes C/C, C/T, and T/T, respectively. No significant association between response rate and genotypes was observed ( = 0.64). Patients with well- and moderately-differentiated histological grade of the tumor showed a better response rate (100.00% of 2 patients and 66.66% of 12 patients, respectively) compared to those with poorly differentiated (0.00% of 26 patients) histological grade ( < 0.001). Further multicenter studies are recommended to confirm conclusively our findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22037/ijpr.2019.1100827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059040PMC
January 2019

Circulating tumor DNA applications in monitoring the treatment of metastatic colorectal cancer patients.

Gastroenterol Hepatol Bed Bench 2019 ;12(Suppl1):S14-S21

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Colorectal cancer is the third most common cancer worldwide. New cancer treatment strategies such as monoclonal antibodies against growth factor and angiogenesis receptors have improved the overall survival (OS) and progression-free survival (PFS) in metastatic colorectal cancer (mCRC) patients. However, acquired resistance could happen after these therapies. Circulating tumor DNA (ctDNA) is the DNA fraction derived from tumor cells which could be applied as a non-invasive method for detecting tumor mutations before, during, and after therapies. Here, we reviewed most of the studies examining ctDNA as treatment monitoring in mCRC patients who receive different target therapies. Also, we compared ctDNA with other existing cancer-treatment monitoring methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2019

Circulating tumor DNA applications in monitoring the treatment of metastatic colorectal cancer patients.

Gastroenterol Hepatol Bed Bench 2019 ;12(Suppl1):S14-S21

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Colorectal cancer is the third most common cancer worldwide. New cancer treatment strategies such as monoclonal antibodies against growth factor and angiogenesis receptors have improved the overall survival (OS) and progression-free survival (PFS) in metastatic colorectal cancer (mCRC) patients. However, acquired resistance could happen after these therapies. Circulating tumor DNA (ctDNA) is the DNA fraction derived from tumor cells which could be applied as a non-invasive method for detecting tumor mutations before, during, and after therapies. Here, we reviewed most of the studies examining ctDNA as treatment monitoring in mCRC patients who receive different target therapies. Also, we compared ctDNA with other existing cancer-treatment monitoring methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2019

Decreased CCN3 in Systemic Sclerosis Endothelial Cells Contributes to Impaired Angiogenesis.

J Invest Dermatol 2020 07 16;140(7):1427-1434.e5. Epub 2020 Jan 16.

University of Bordeaux, Inserm, BMGIC, UMR1035, Bordeaux, France; Department of Dermatology and Pediatric Dermatology, National Center for Rare Skin Disorders, Hôpital Saint André, Bordeaux, France.

Systemic sclerosis (SSc) is a rare and severe connective tissue disease combining autoimmune and vasculopathy features, ultimately leading to organ fibrosis. Impaired angiogenesis is an often silent and life-threatening complication of the disease. We hypothesize that CCN3, a member of the CCN family of extracellular matrix proteins, which is an antagonist of the profibrotic protein CCN2 as well as a proangiogenic factor, is implicated in SSc pathophysiology. We performed skin biopsies on 26 patients with SSc, both in fibrotic and nonfibrotic areas for 17 patients, and collected 18 healthy control skin specimens for immunohistochemistry and cell culture. Histological analysis of nonfibrotic and fibrotic SSc skin shows a systemic decrease of papillary dermis surface as well as disappearance of capillaries. CCN3 expression is systematically decreased in the dermis of patients with SSc compared with healthy controls, particularly in dermal blood vessels. Moreover, CCN3 is decreased in vitro in endothelial cells from patients with SSc. We show that CCN3 is essential for endothelial cell migration and angiogenesis in vitro. In conclusion, CCN3 may represent a promising therapeutic target for patients with SSc presenting with vascular involvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2019.11.026DOI Listing
July 2020

XPC beyond nucleotide excision repair and skin cancers.

Mutat Res 2019 Oct - Dec;782:108286. Epub 2019 Jul 8.

PRASE, Laboratory of Stem Cells, Lebanese University, Beirut, Lebanon; Biology Department, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon. Electronic address:

Xeroderma pigmentosum group C (XPC) has been known as a DNA damage recognition factor of bulky adducts and as an initiator of global genome nucleotide excision repair (GG-NER). XP-C patients have been shown to have a predisposition to develop skin and certain internal cancers. Recent studies have shown that XPC presents several functional and molecular interactions with fundamental players in several other DNA repair pathways including base excision repair (BER). Furthermore, novel clues indicate that XPC is involved in transcription regulation in the cell. In this review, association between abnormal XPC activity as well as several XPC polymorphisms with the incidence of non-skin tumors is discussed. We also review the current literature regarding the roles of XPC in different DNA repair pathways, highlighting its tumor suppressor activity that may occur independently of its conventional function in NER. Deciphering the NER-independent involvement of XPC in onset and progress of non-skin cancers will have positive implications on prognosis and therapy of cancers with XPC deficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mrrev.2019.108286DOI Listing
March 2020

UVB-induced DHODH upregulation, which is driven by STAT3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis.

Oncogenesis 2019 Sep 24;8(10):52. Epub 2019 Sep 24.

Univ. Bordeaux, INSERM, BMGIC, UMR 1035, F-33076, Bordeaux, France.

The leading cause of cutaneous squamous cell carcinomas (cSCCs) is exposure to ultraviolet radiation (UV). Unlike most other cancers, the incidence rates of cSCCs are still on the rise and the treatment options currently available are limited. We have recently found that dihydroorotate dehydrogenase (DHODH), which is the rate-limiting enzyme in the de novo pyrimidine synthesis pathway, plays a critical role in UVB-induced energy metabolism reprogramming. Using a multistage model of UVB radiation-induced skin cancer, we show that UVB-induced DHODH upregulation is mainly regulated transcriptionally by STAT3. Our results indicate that chronic inhibition of DHODH by leflunomide (LFN) blocks UVB-induced tumor initiation. Human tumor xenograft studies showed that LFN treatment reduces growth of established tumors when used in combination with a genotoxic agent, 5-fluorouracil (5-FU). Our data suggest that DHODH is a promising target for chemoprevention and combination therapy of UVB-induced cSCCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41389-019-0161-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760220PMC
September 2019

Targeting Myeloperoxidase Disrupts Mitochondrial Redox Balance and Overcomes Cytarabine Resistance in Human Acute Myeloid Leukemia.

Cancer Res 2019 Oct 29;79(20):5191-5203. Epub 2019 Jul 29.

Centre de Recherches en Cancérologie de Toulouse, UMR1037, Inserm, Equipe Labellisée LIGUE 2018, Toulouse, France.

Chemotherapies alter cellular redox balance and reactive oxygen species (ROS) content. Recent studies have reported that chemoresistant cells have an increased oxidative state in hematologic malignancies. In this study, we demonstrated that chemoresistant acute myeloid leukemia (AML) cells had a lower level of mitochondrial and cytosolic ROS in response to cytarabine (AraC) and overexpressed myeloperoxidase (MPO), a heme protein that converts hydrogen peroxide to hypochlorous acid (HOCl), compared with sensitive AML cells. High MPO-expressing AML cells were less sensitive to AraC and . They also produced higher levels of HOCl and exhibited an increased rate of mitochondrial oxygen consumption when compared with low MPO-expressing AML cells. Targeting MPO expression or enzyme activity sensitized AML cells to AraC treatment by triggering oxidative damage and sustaining oxidative stress, particularly in high MPO-expressing AML cells. This sensitization stemmed from mitochondrial superoxide accumulation, which impaired oxidative phosphorylation and cellular energetic balance, driving apoptotic death and selective eradication of chemoresistant AML cells and . Altogether, this study uncovers a noncanonical function of MPO enzyme in maintaining redox balance and mitochondrial energetic metabolism, therefore affecting downstream pathways involved in AML chemoresistance. SIGNIFICANCE: These findings demonstrate the role of myeloperoxidase in the regulation of ROS levels and sensitivity of AML cells to cytarabine, an essential chemotherapeutic backbone in the therapy of AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-19-0515DOI Listing
October 2019

Loss of Epidermal HIF-1α Blocks UVB-Induced Tumorigenesis by Affecting DNA Repair Capacity and Oxidative Stress.

J Invest Dermatol 2019 09 13;139(9):2016-2028.e7. Epub 2019 Mar 13.

University of Bordeaux, Institut National de la Santé et de la Recherche Médicale, Biothérapie des Maladies Génétiques Inflammatoires et Cancers, U1035, F-33000 Bordeaux, France; Centre de Référence pour les Maladies Rares de la Peau, Centre Hospitalier Universitaire de Bordeaux, France. Electronic address:

HIF-1α is constitutively expressed in mouse and human epidermis. It plays a crucial role in skin physiology, including the response of keratinocytes to UVR. However, little information is available about its role in photocarcinogenesis. Using a multistage model of UVB radiation-induced skin cancer, we show that the knockout of Hif-1α in the epidermis prevents tumorigenesis but at the same time triggers the formation of hyperkeratotic plaques. Our results indicate that the absence of oncogenic transformation in Hif-1α-ablated mice is related to increased DNA repair in keratinocytes, whereas the formation of hyperkeratotic plaques is caused by an increase in the levels of reactive oxygen species. Indeed, impairing the DNA repair machinery by ablating xeroderma pigmentosum C restored the UVB-induced neoplastic transformation of Hif-1α-ablated keratinocytes, whereas the development of hyperkeratotic plaques was blocked by chronic antioxidant treatment. We conclude that HIF-1α plays a procarcinogenic role in UVB-induced tumorigenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2019.01.035DOI Listing
September 2019

Adding Oral Pioglitazone to Standard Induction Chemotherapy of Acute Myeloid Leukemia: A Randomized Clinical Trial.

Clin Lymphoma Myeloma Leuk 2019 04 19;19(4):206-212. Epub 2019 Jan 19.

Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Background: The hypothesis of an effect by thiazolidinedione on leukemia cells was proposed 2 decades ago, but there is little clinical evidence regarding its efficacy. We evaluated the safety and efficacy of adding pioglitazone to standard induction chemotherapy in patients with acute myeloid leukemia (AML).

Patients And Methods: In this randomized clinical trial, newly diagnosed AML patients were randomized to 1 of 2 groups. Patients in both groups received cytarabine (100 mg/m per day for 7 days) and daunorubicin (60 mg/m per day for 3 days). Patients in the pioglitazone group additionally received oral pioglitazone (45 mg per day). The 2 groups were compared according to remission rate, laboratory findings, and adverse events during treatment.

Results: Forty patients were evaluated, 20 patients in each group. The complete remission rate was 20% more in the pioglitazone group compared to the control group (P = .202). Complications due to pioglitazone discontinuation were observed in 2 cases. The mean serum alanine aminotransferase in the fourth treatment week was significantly more in pioglitazone group compared to the control group (65.5 vs. 33.6 mg/dL, P = .039). The mean serum creatinine in all treatment phases was significantly higher in the pioglitazone group compared to the control group (P < .05). There were no significant differences between the 2 groups regarding other laboratory findings (P > .05).

Conclusion: Adding pioglitazone to cytarabine and daunorubicin increased the remission rate in AML patients compared to control subjects. Although this difference in remission rate between the 2 groups was not statistically significant, it could be important in the clinical setting. Pioglitazone may provide benefits as an adjuvant therapy for AML patients without causing serious adverse events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clml.2019.01.006DOI Listing
April 2019

Leukemia inhibitory factor signaling in Xenopus embryo: Insights from gain of function analysis and dominant negative mutant of the receptor.

Dev Biol 2019 03 19;447(2):200-213. Epub 2018 Dec 19.

Univ. Bordeaux, INSERM U1035, BMGIC, F-33076 Bordeaux, France. Electronic address:

Leukemia inhibitory factor (LIF) is a cytokine member of the interleukin 6 family (IL6) of cytokines. It signals through a heterodimer receptor complex that consists of the LIF receptor (or LIFR formerly known as gp190) and the Interleukin 6 signal transducer (or IL6ST formerly known as gp130). LIF signaling is mediated mainly by signal transducer and activator of transcription 3 (STAT3) and has a wide variety of biological activities with pleiotropic effects on many cell types and organs among which are stem cell renewal and implantation process in mammalian embryo. Despite the wealth of data on LIF in mammalian cells, there is a paucity of information on its functions in lower vertebrates. Here, we provide information on the status and the function of LIF signaling in Xenopus amphibian. The IL6 cytokine family is highly conserved in Xenopus genome both at ligands and receptors levels. All cytokines and receptors of the family, except oncostatin M (OSM) and IL27, can be identified in the genome including the orthologs of LIF, cardiotrophin 1 (CTF1), ciliary neurotrophic factor (CNTF), cardiotrophin like cytokine factor 1 (CLCF1), LIFR, IL6ST, IL6R, IL11RA and CNTFR. Lif mRNA is zygotically expressed after midblastula transition while lifr and il6st are maternally expressed. We have investigated the functions of LIF in Xenopus early development with a gain-of-function analysis combined to the use of a dominant negative form of the receptor. The overexpression of Xenopus lif in embryo activates STAT3 phosphorylation and induces a dramatic phenotype where embryos are ventralised and show a reduction of anterior structures with microcephaly. This results mainly from BMP signal stimulation and antagonism towards IGF signals. In addition, most embryos develop tumor-like cell masses according to both autonomous and non-autonomous processes. Through the use of a dominant negative form of the receptor, we demonstrate for the first time that a functional LIF signaling is required for normal vertebrate kidney development. Owing to its experimental advantages, the Xenopus embryo constitutes a useful model to identify the molecular actors that may account for the pleiotropic functions of LIF and their role in vertebrate development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ydbio.2018.12.020DOI Listing
March 2019

Comparing serum levels of zinc, copper, certain antioxidant vitamins and dietary intakes in acute lymphoblastic leukemia (ALL) patients before and after chemotherapy.

Am J Blood Res 2018 5;8(3):21-28. Epub 2018 Oct 5.

Department of Nutrition, School of Public Health, Iran University of Medical Sciences Tehran, Iran.

Acute lymphoblastic leukemia (ALL) is a malignant hematologic disease. Cancer and its treatments can affect biological functions and change the nutritional status of patients. Zinc and copper are important cofactors for several enzymes and play an important role in maintaining the integrity of DNA. In ALL, we have oxidative conditions in the body that can cause oxidative damage to lipids and the production of malondialdehyde (MDA). So that the aim of this study is comparing serum levels of copper, zinc and inflammation before and after chemotherapy. Thirty ALL patients between 15 to 65 years old participated in this study. A blood sample of 10 cc was taken before and after eight course of chemotherapy. We observed a significant increase in serum zinc as well as a significant decrease in serum copper, vitamin D and Malondialdehyde. We have not seen any significant differences in hs-CRP after chemotherapy. These changes might be due to chemotherapy and changing lifestyle of patients toward healthy eating nutrition and serum vitamin D get worse and because of sedentary life style in these patients there is an essential need to anthropometric measurements during treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261838PMC
October 2018

Pigmentation abnormalities in nucleotide excision repair disorders: Evidence and hypotheses.

Pigment Cell Melanoma Res 2019 01 13;32(1):25-40. Epub 2018 Jul 13.

Univ. Bordeaux, Inserm, BMGIC, UMR 1035, Bordeaux, France.

Skin pigmentation abnormalities are manifested in several disorders associated with deficient DNA repair mechanisms such as nucleotide excision repair (NER) and double-strand break (DSB) diseases, a topic that has not received much attention up to now. Hereditary disorders associated with defective DNA repair are valuable models for understanding mechanisms that lead to hypo- and hyperpigmentation. Owing to the UV-associated nature of abnormal pigmentary manifestations, the outcome of the activated DNA damage response (DDR) network could be the effector signal for alterations in pigmentation, ultimately manifesting as pigmentary abnormalities in repair-deficient disorders. In this review, the role of the DDR network in the manifestation of pigmentary abnormalities in NER and DSB disorders is discussed with a special emphasis on NER disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pcmr.12720DOI Listing
January 2019

Redox mechanism of levobupivacaine cytostatic effect on human prostate cancer cells.

Redox Biol 2018 09 31;18:33-42. Epub 2018 May 31.

Univ. Bordeaux, 146 rue Léo Saignat, F-33076 Bordeaux, France; INSERM U1211, F-33076 Bordeaux, France; Cellomet, CGFB, 146 Rue léo Saignat, F-33000 Bordeaux, France. Electronic address:

Anti-cancer effects of local anesthetics have been reported but the mode of action remains elusive. Here, we examined the bioenergetic and REDOX impact of levobupivacaine on human prostate cancer cells (DU145) and corresponding non-cancer primary human prostate cells (BHP). Levobupivacaine induced a combined inhibition of glycolysis and oxidative phosphorylation in cancer cells, resulting in a reduced cellular ATP production and consecutive bioenergetic crisis, along with reactive oxygen species generation. The dose-dependent inhibition of respiratory chain complex I activity by levobupivacaine explained the alteration of mitochondrial energy fluxes. Furthermore, the potency of levobupivacaine varied with glucose and oxygen availability as well as the cellular energy demand, in accordance with a bioenergetic anti-cancer mechanism. The levobupivacaine-induced bioenergetic crisis triggered cytostasis in prostate cancer cells as evidenced by a S-phase cell cycle arrest, without apoptosis induction. In DU145 cells, levobupivacaine also triggered the induction of autophagy and blockade of this process potentialized the anti-cancer effect of the local anesthetic. Therefore, our findings provide a better characterization of the REDOX mechanisms underpinning the anti-effect of levobupivacaine against human prostate cancer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.redox.2018.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019688PMC
September 2018

Energy Metabolism Rewiring Precedes UVB-Induced Primary Skin Tumor Formation.

Cell Rep 2018 06;23(12):3621-3634

Inserm U 1035, BMGIC, 33076 Bordeaux, France; Université de Bordeaux, 146 rue Léo Saignat, 33076 Bordeaux, France; Centre de Référence pour les Maladies Rares de la Peau, CHU de Bordeaux, France. Electronic address:

Although growing evidence indicates that bioenergetic metabolism plays an important role in the progression of tumorigenesis, little information is available on the contribution of reprogramming of energy metabolism in cancer initiation. By applying a quantitative proteomic approach and targeted metabolomics, we find that specific metabolic modifications precede primary skin tumor formation. Using a multistage model of ultraviolet B (UVB) radiation-induced skin cancer, we show that glycolysis, tricarboxylic acid (TCA) cycle, and fatty acid β-oxidation are decreased at a very early stage of photocarcinogenesis, while the distal part of the electron transport chain (ETC) is upregulated. Reductive glutamine metabolism and the activity of dihydroorotate dehydrogenase (DHODH) are both necessary for maintaining high ETC. Mice with decreased DHODH activity or impaired ETC failed to develop pre-malignant and malignant lesions. DHODH activity represents a major link between DNA repair efficiency and bioenergetic patterning during skin carcinogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2018.05.060DOI Listing
June 2018

Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinomas: A Single Center Study from Iran

Asian Pac J Cancer Prev 2018 Jan 27;19(1):111-114. Epub 2018 Jan 27.

Hematology and Oncology Department, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran. Email:

Introduction: Lung cancer is the fifth leading tumor in Iran, and while its incidence remains relatively low, it has been increasing steadily. Targeted therapies have brought new hope to patients with non small cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) gene is the prototype member of the type I receptor tyrosine kinase (TK) family and plays a pivotal role in cell proliferation and differentiation. Studies from Asian countries have revealed a higher frequency of EGFR mutations than in the West. The aim of this study was to measure the frequency and type of EGFR mutations in a group of Iranian patients with lung adenocarcinomas. Methods: Formalin fixed paraffin embedded (FFPE) lung adenocarcinoma tissues from 103 Iranian patients were sequentially tested for EGFR mutations by the polymerase chain reaction (PCR) followed by direct nucleotide sequencing of exons 18, 19, 20, and 21. Patient’s demographics and other clinical details were obtained from the medical records of hospitals affiliated to Iran University of Medical Sciences, Tehran, Iran. Statistical analyses were performed with SPSS v.20. Results: EGFR mutations were detected in 25/103 (24.3%) patients. The most frequent was an exon 21 point mutation (L858R) (15 patients; 60%), followed by one in exon 19 (10 patients; 40%). The frequency of EGFR mutations in never-smoker patients was significantly higher than in smokers (68% versus 32%; p < 0. 01). Conclusion: EGFR mutation frequency is higher than in the West but lower than in East Asian and almost equal to reported rates for Indian and North African populations. Smoking is negatively associated with EGFR mutations in Iranian lung adenocarcinomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22034/APJCP.2018.19.1.111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844603PMC
January 2018

NADPH Oxidases and Their Roles in Skin Homeostasis and Carcinogenesis.

Antioxid Redox Signal 2018 05 17;28(13):1238-1261. Epub 2017 Nov 17.

1 Inserm U 1035, Bordeaux, France .

Significance: Skin protects the body from dehydration, pathogens, and external mutagens. NADPH oxidases are central components for regulating the cellular redox balance. There is increasing evidence indicating that reactive oxygen species (ROS) generated by members of this enzyme family play important roles in the physiology and pathophysiology of the skin. Recent Advances: NADPH oxidases are active producers of ROS such as superoxide and hydrogen peroxide. Different isoforms are found in virtually all tissues. They play pivotal roles in normal cell homeostasis and in the cellular responses to various stressors. In particular, these enzymes are integral parts of redox-sensitive prosurvival and proapoptotic signaling pathways, in which they act both as effectors and as modulators. However, continuous (re)activation of NADPH oxidases can disturb the redox balance of cells, in the worst-case scenario in a permanent manner. Abnormal NADPH oxidase activity has been associated with a wide spectrum of diseases, as well as with aging and carcinogenesis.

Critical Issues: Sunlight with its beneficial and deleterious effects induces the activation of NADPH oxidases in the skin. Evidence for the important roles of this enzyme family in skin cancer and skin aging, as well as in many chronic skin diseases, is now emerging.

Future Directions: Understanding the precise roles of NADPH oxidases in normal skin homeostasis, in the cellular responses to solar radiation, and during carcinogenesis will pave the way for their validation as therapeutic targets not only for the prevention and treatment of skin cancers but also for many other skin-related disorders. Antioxid. Redox Signal. 28, 1238-1261.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/ars.2017.7282DOI Listing
May 2018

Oral Ciprofloxacin Prophylaxis in Patients Undergoing High DoseTherapy and Autologous Hematopoietic Stem Cell Transplantation.

Iran J Pharm Res 2016 ;15(Suppl):159-163

Islamic Azad University in Medical Sciences, Tehran, Iran.

Antibiotic prophylaxis is usually used in allogeneic stem cell transplantation, but its use in Autologous Stem Cell Transplantation (ASCT) is controversial. We evaluated the efficacy of ciprofloxacin prophylaxis in ASCT. To identify the efficacy of ciprofloxacin on the incidence of neutropenic fever and its complications, 72 patients that had been admitted to Taleghani Hospital for ASCT between 2010 and 2012 were evaluated in our study. Oral ciprofloxacin 500 mg every 12 h was administered to 30 patients on the same day of high dose chemotherapy until the first febrile episode or until the recovery of neutropenia and the results were analyzed and compared with the historical control group 42 other transplanted patients who had not previously received ciprofloxacin. The incidence of neutropenic fever was 80% with no difference between the two groups. But in ciprofloxacin group, duration of fever (1.7 days VS 3.5 days P=0.017), hospitalization due to stem cell transfusion (18.2 days VS 12.2 days p=0.03), incidence of bacteremia 3.3 % VS 33.3%, p=0.002) and platelet recovery (13.9 VS 17.7 days= 0.035) and platelet transfusions (P=0.04) were significantly lower than the control group no side effects and no delay in. Based on this study oral ciprofloxacin prophylaxis is rational, efficacious and economic in ASCT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242361PMC
January 2016