Abstract:
:Several single nucleotide polymorphisms (SNPs) influencing DNA repair capacity and apoptotic status may confer genetic predisposition to Philadelphia‑chromosome negative myeloproliferative neoplasms (PN‑MPNs), and influence therapeutic response and the clinical course. In the present study, whether SNPs in genes involved in apoptosis and the base excision repair (BER) pathway was evaluated. In addition, some known risk factors in PN‑MPNs that may influence survival and therapeutic response to hydroxyurea (HU) were analyzed, taking into account three items: Disease progression, predisposition to new non‑myeloid neoplasms and thrombotic events. The present study involved a total of 133 Caucasian Portuguese PN‑MPNs patients treated with HU, whereby 17 cases showed progression to myelofibrosis/leukemia, 11 developed new non‑myeloid neoplasms and 22 presented with thrombotic events. Progression to secondary myelofibrosis/leukemia is influenced by exposure to cytoreductive agents, and caspase and BER polymorphisms {globally, CASP8 3'untranslated region [odds ratio (OR)=0.24; 95% confidence interval (CI), 0.08‑0.69], XRCC1 Arg194Trp [OR=3.58; 95% CI, 0.98‑13.01]; for essential thrombocythemia patients CASP9 Arg173His [OR=11.27; 95% CI, 1.13‑112.28], APEX1 Asp148Glu [OR=0.28; 95% CI, 0.74‑1.03], and XRCC1 Arg194Trp [OR=6.60; 95% CI, 1.60‑27.06]}. Moreover, globally caspase and BER polymorphisms influenced the development of new nonmyeloid malignancies [CASP8 Asp270His (OR=5.90; 95% CI, 1.42‑24.62) and XRCC1 Arg399Gln (OR=0.27; 95% CI, 0.07‑1.03)]. On the other hand, only the BER pathway had a role in the presence of thrombotic events [XRCC1 Gln399Arg (OR=0.35; 95% CI, 0.14‑0.88)]. JAK2 mutation had no influence on these complications. Larger studies are required to confirm these results, and to provide conclusive evidence of association between these and other variants with PN‑MPNs therapeutic response and clinical evolution. However, this study may allow the development of drugs more directly targeted to the pathophysiology of the disease, with high efficacy, fewer adverse effects, contributing to compliance of patients with treatments. The clinical indication for classical drugs, including HU, may be guided by variant genes, which may provide additional beneficial effects.
journal_name
Mol Med Repjournal_title
Molecular medicine reportsauthors
Azevedo AP,Silva SN,Reichert A,Lima F,Júnior E,Rueff Jdoi
10.3892/mmr.2018.9535subject
Has Abstractpub_date
2018-12-01 00:00:00pages
5243-5255issue
6eissn
1791-2997issn
1791-3004journal_volume
18pub_type
杂志文章abstract::To determine the effect of the down-regulation of osteopontin (OPN) expression on the sensitivity of breast cancer cells to doxorubicin, a chemotherapeutic drug, OPN shRNA was used to transfect the OPN-positive breast cancer cell line MDA-MB-231. The expression of OPN mRNA and protein was analyzed by RT-PCR and Wester...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2011.679
更新日期:2012-02-01 00:00:00
abstract::Full‑thickness and large area defects of articular cartilage are unable to completely repair themselves and require surgical intervention, including microfracture, autologous or allogeneic osteochondral grafts, and autologous chondrocyte implantation. A large proportion of regenerative cartilage exists as fibrocartila...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.7009
更新日期:2017-09-01 00:00:00
abstract::Accumulating evidence suggests that Rho-associated kinase (ROCK) may be important in the pathogenesis of atherosclerosis and coronary vasospasm. In the present study, we investigated whether ROCK activity is increased in acute coronary syndrome (ACS) patients. Twenty-one patients with ACS (12 males, mean age 58.0±8.0 ...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2013.1463
更新日期:2013-07-01 00:00:00
abstract::Functional appliances correct dental malocclusion, partly by exerting an indirect mechanical stimulus on the condylar cartilage, initiating novel bone formation in the condyle. Angiopoietin is involved in the angiogenesis associated with novel bone formation. This study aimed to determine the expression of angiopoieti...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2013.1620
更新日期:2013-10-01 00:00:00
abstract::Although imatinib is effective in chronic myeloid leukemia treatment, imatinib resistance due to the T315I mutation and/or other mutations is a challenge to be overcome. However, how DNA mutation occurs, particularly the T315I mutation, remains unclear. In the current study, the mutagenesis of BCR‑ABL was analyzed via...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.7835
更新日期:2017-12-01 00:00:00
abstract::Dysregulation of microRNAs (miRNAs) is associated with the occurrence and development of clear cell renal cell carcinoma (ccRCC) through their participation in a number of critical biological processes. Therefore, an in‑depth investigation into miRNAs and their biological roles within ccRCC may provide useful insights...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2018.8755
更新日期:2018-05-01 00:00:00
abstract::Anticoagulant therapy is prescribed to millions of patients worldwide for the prevention and treatment of venous thrombosis. Evidence has indicated that edoxaban is a potential drug of oral anticoagulant in the acute treatment of venous thromboembolism. Hydrogen sulfide and homocysteine plasma concentration are indica...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.7574
更新日期:2017-11-01 00:00:00
abstract::The present study aimed to determine the profile of differentially expressed circular RNAs (circRNAs) in infertile patients treated with acupuncture and moxibustion and verify the role of acupuncture and moxibustion in altering endometrial receptivity (ER). High‑throughput RNA sequencing and bioinformatics analysis of...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2019.10386
更新日期:2019-08-01 00:00:00
abstract::Parkinson's disease (PD) is a type of movement disorder caused by loss of dopamine‑producing neurons in the midbrain. In order to identify the synergistic microRNA (miRNA) pattern in PD, miRNA and mRNA double expression profiles of PD were downloaded. Differentially expressed miRNA and mRNA were identified [P<0.01, fo...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2014.2837
更新日期:2015-02-01 00:00:00
abstract::We extracted cucurmosin (CUS) from the sarcocarp of Cucrubita moschata (pumpkin). Recently, a number of studies have indicated that CUS has cytotoxic properties and induces apoptosis in a number of human tumor cells. However, the detailed mechanisms are largely unknown. The aim of this study was to confirm CUS's antic...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2011.605
更新日期:2012-01-01 00:00:00
abstract::Prostate cancer (PCa) is the second most common cancer amongst males worldwide. In the current study, microarray datasets GSE3325 and GSE6919 from the Gene Expression Omnibus database were screened to identify candidate genes that are associated with the progression of PCa. A total of 273 differentially expressed gene...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2019.10799
更新日期:2020-01-01 00:00:00
abstract::To identify the key genes and pathways in the development of hepatocellular carcinoma (HCC) from hepatitis B virus (HBV)‑positive liver cirrhosis, differentially expressed genes (DEGs) between HCC and liver cirrhosis tissue samples from the GSE17548 gene expression profile dataset were screened. A total of 1,845 DEGs ...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2018.9494
更新日期:2018-12-01 00:00:00
abstract::The present study aimed to investigate the anticancer effect of sorafenib combined with silencing of activating transcription factor 2 (ATF2) in hepatocellular carcinoma (HCC) cells and to assess the underlying molecular mechanisms. Huh‑7 HCC cell line was selected for the present study. Small interfering RNA (siRNA)‑...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2018.8921
更新日期:2018-06-01 00:00:00
abstract::Gastric cancer is the fourth most common malignancy and the third leading cause of cancer‑associated deaths worldwide. It has previously been demonstrated that microRNAs (miRNAs) are actively involved in the pathogenesis of gastric cancer. Therefore, miRNAs have been proposed as promising therapeutic targets in gastri...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.7167
更新日期:2017-10-01 00:00:00
abstract::Cyclin-dependent kinase inhibitor 3 (CDKN3) belongs to the dual-specificity protein phosphatase family, which is hypothesized to regulate cell cycle progression in tumor cells. However, whether CDKN3 is a potential therapeutic target for breast cancer remains to be elucidated. The present in vitro study aimed to inves...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2016.5401
更新日期:2016-08-01 00:00:00
abstract::Aspergillus fumigatus is one of the most common opportunistic pathogenic fungi, surviving in various environmental conditions. Maintenance of the redox homeostasis of the fungus relies upon the well‑organized regulation between reactive oxygen species generated by immune cells or its own organelles, and the activated ...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2016.4839
更新日期:2016-03-01 00:00:00
abstract::Bone morphogenetic protein 2 (BMP2) is a growth factor that is involved in the development and progression of various types of cancer. However, the epigenetic regulation of the expression of BMP2 and the association between BMP2 expression and drug resistance in breast cancer remains to be elucidated. The present stud...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2014.2276
更新日期:2014-08-01 00:00:00
abstract::Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The most significant histological property of AF is atrial fibrosis, but the underlying mechanism is not clear. In this study we investigated the expression of miR-133 and miR-30, anti-fibrotic microRNAs (miRNAs), in chronic AF in canines. A tot...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2012.831
更新日期:2012-06-01 00:00:00
abstract::Millions of infants and children are exposed to anesthesia every year during medical care. Sevoflurane is a volatile anesthetic that is frequently used for pediatric anesthesia. However, previous reports have suggested that the administration of sevoflurane promotes neurodegeneration, raising concerns regarding the sa...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2016.5586
更新日期:2016-10-01 00:00:00
abstract::Idiopathic normal pressure hydrocephalus (iNPH) is caused by the accumulation of cerebrospinal fluid (CSF) and is characterized by gait disturbance, urinary incontinence, and dementia. iNPH dementia is treatable by shunt operation; however, since the cognitive symptoms of iNPH are often similar to those of other demen...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.7015
更新日期:2017-09-01 00:00:00
abstract::The mechanisms underlying cancer radioresistance remain unclear. Several studies have found that increased glucose transporter‑1 (GLUT‑1) expression is associated with radioresistance. Recently, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway was reported to be involved in the control of GLUT‑1...
journal_title:Molecular medicine reports
pub_type: 杂志文章,评审
doi:10.3892/mmr.2014.2888
更新日期:2015-03-01 00:00:00
abstract::In this study, we aimed to explore the radio-sensitization of the SHG44 glioma cell line by Aidi injection and the possible mechanisms involved. The growth curve, cloning efficiency and divisional index of the SHG44 cell line were observed. The inhibition ratio was determined by MTT assay, the change in the cell cycle...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2012.836
更新日期:2012-06-01 00:00:00
abstract::Hepatic glycoprotein (gp78), a membrane-anchored E3 ubiquitin ligase, has been reported to be involved in regulating lipid and energy metabolism in animals, and cell death‑inducing DFFA‑like effector c (cidec) has emerged as an important regulator of metabolism, which has been implicated in the process of fat differen...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.6834
更新日期:2017-08-01 00:00:00
abstract::Colorectal cancer has become a disease with one of the highest incidence rates worldwide, and liver metastasis threatens the prognosis of colorectal cancer. MicroRNA (miR)‑200 and miR‑141 have been confirmed to be aberrantly expressed in colorectal cancer, however, whether miR‑200 and miR‑141 are involved in the progr...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2017.7538
更新日期:2017-11-01 00:00:00
abstract::Following the publication of the above article, an interested reader drew to the authors' attention that a pair of the data panels shown in Fig. 4 contained overlapping data. After having consulted their original data, the authors realized that a total of three panels featured in Figs. 4 and 6 had been erroneously sel...
journal_title:Molecular medicine reports
pub_type: 杂志文章,已发布勘误
doi:10.3892/mmr.2020.11278
更新日期:2020-09-01 00:00:00
abstract::Vitamin A deficiency (VAD) caused by malnutrition and certain intestinal diseases induces visual impairments, including night blindness and photoreceptor cell dysfunction as indicated by reduced a‑ and b‑waves in an electroretinogram (ERG). The effects of VAD on the inner retinal layer cells, including amacrine and ga...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2014.2852
更新日期:2015-02-01 00:00:00
abstract::Pseudomonas aeruginosa continues to be a predominant cause of infections with high intrinsic resistance to antibiotics, resulting in treatment failure. P. aeruginosa is the leading cause of respiratory infections among cystic fibrosis (CF) patients. Resistance to carbapenem antibiotics among P. aeruginosa has been rep...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2014.2685
更新日期:2015-01-01 00:00:00
abstract::In order to observe the effects of cyclin E gene silencing by small interfering RNA (siRNA) on the growth, proliferation, invasion and apoptosis of esophageal cancer cell lines, including EC9706, Eca109 and KYSE30, siRNA vectors targeting cyclin E gene were constructed and then tran...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2013.1280
更新日期:2013-03-01 00:00:00
abstract::Monitoring minimal residue disease (MRD) is an effective approach to evaluate the response to chemotherapy, and it is used to select the ideal therapeutic strategy and to predict the recurrence during therapy for hematological disorders. The Wilm's tumor 1 (WT1) gene, which is highly expressed in >80% of patients with...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2019.10440
更新日期:2019-09-01 00:00:00
abstract::Cervical cancer (CC) is a frequently occurring cancer in women with a high mortality rate. Despite improvements to therapeutic strategies, the survival outcome for patients with CC remains poor. Therefore, the present study aimed to investigate the molecular mechanism underlying CC inhibition involving microRNA (miR)‑...
journal_title:Molecular medicine reports
pub_type: 杂志文章
doi:10.3892/mmr.2020.11552
更新日期:2020-12-01 00:00:00