麝香保心丸防治阿霉素心脏毒性的临床研究

目的:观察麝香保心丸防治阿霉素心脏毒性的临床疗效.方法:选取2014年5月至2016年4月在我科行化疗的恶性肿瘤患者共50例,随机分为观察组和对照组各25例,两组均使用含阿霉素的方案进行化疗,观察组在上述基础上加用麝香保心丸(2粒/次,每天3次,温水吞服,化疗期间及化疗间歇期间均坚持服用),于化疗第3个周期结束后及第6个周期结束后分别接受左室射血分数(LVEF)、短轴缩短率(FS)、舒张早期与晚期充盈速度比值(A/E)、肌钙蛋白(cTnⅠ)、肌酸激酶同工酶(CK-MB)、B型尿钠肽(B-BNP)检测.结果:第6个周期化疗结束后,观察组的LVEF、FS、A/E的降低幅度均较对照组低,与对照组比较差异均有统计学意义(P＜0.05);观察组的cTnⅠ、CK-MB、B-BNP值升高幅度较对照组低,与对照组比较差异均有统计学意义(P＜0.05).结论:麝香保心丸可以明显减轻阿霉素的心脏毒性,值得在临床中进一步研究和运用.     

The effect of monohydroxyethylrutoside on doxorubicin-induced cardiotoxicity in patients treated for metastatic cancer in a phase II study

The purpose of this study was to investigate the cardioprotective effect of the semisynthetic flavonoid 7-monohydroxyethylrutoside (monoHER) on doxorubicin (DOX)-induced cardiotoxicity in a phase II study in patients with metastatic cancer. Eight patients with metastatic cancer were treated with DOX preceded by a 10 min i.v. infusion of 1500 mg m(-2) monoHER. Five patients were examined by endomyocardial biopsy after reaching a cumulative dose of 300 mg m(-2). Histopathological changes in the cardiomyocytes (Billingham score) were compared with those described in literature for patients treated with DOX only. The mean biopsy score of the patients was higher (2.7) than the mean score (1.4) of historical data of patients who received similar cumulative doses of DOX. Although there is a considerable variability in few investigated patients, it was indicative that monoHER enhanced DOX-induced cardiotoxicity. However, the antitumour activity of DOX seemed better than expected: three of the four patients with metastatic soft-tissue sarcoma had a partial remission and the fourth patient stable disease. It is likely that the relatively high dose of monoHER is responsible for the lack of cardioprotection and for the high response rate in patients with soft-tissue sarcoma possibly by depleting the glutathione defense system in both heart and tumour.     

肺癌缺氧A549细胞的microRNA芯片表达谱分析

目的:研究缺氧对肺腺癌A549细胞中microRNA表达谱的影响,分析靶基因参与的生物学功能和通路。方法:基于miRNA芯片技术和生物信息学分析方法,分析缺氧条件和正常氧条件下培养的A549细胞中差异表达的miRNA,并预测这些miRNA的靶基因,分析靶基因参与的生物学功能和通路。结果:本研究共筛选出14个差异表达miRNA,包括9个在缺氧细胞中上调miRNA和5个下调miRNA。上调和下调miRNA的靶基因都参与DNA转录、核染色质修饰等功能,并且都参与Wnt信号、TGF-β信号和MAPK信号通路。结论:缺氧的肺腺癌A549细胞中miRNA表达谱发生了显著改变,差异表达miRNA对某些基因具有调控作用。     

黄芪注射液预防多柔比星相关性心脏毒性反应的临床观察

目的:探讨黄芪注射液对多柔比星(阿霉素)相关性心脏毒性的保护作用。方法:58例恶性肿瘤患者,随机地分成观察组和对照组两组。观察组30例,在以ADM为主的一线方案化疗前3天予黄芪注射液50ml加入5%葡萄糖注射液250ml中静脉滴注,每日一次,两周一疗程;对照组28例,于化疗前3天开始服用VitE每次100mg,每日两次,辅酶Q10每次20mg,每日三次,两周一疗程。治疗前后检查心电图,超声心动图中左心室舒张末期内径(LVIDD)、左心室收缩末期内径(LVISD)、舒张早期与晚期充盈速度比值(A/E)、射血分数(EF)、短轴缩短率(FS)等各项指标。结果:在本组ADM化疗后,观察组与对照组间,虽然EF差异无显著性(P>0.05),但心电图异常改变及LVIDD、LVISD、A/E、、FS的差异有显著性(P<0.05)。结论:黄芪注射液是预防和减轻ADM引起的急性心脏毒性的较为理想的药物,对慢性心脏毒性发生的减轻也有益。     

Early decline in left ventricular ejection fraction predicts doxorubicin cardiotoxicity in lymphoma patients

Thirty adult patients with non-Hodgkin's lymphoma were studied to evaluate prospectively the significance of early decline in left ventricular ejection fraction after low cumulative doxorubicin dose (200 mg x m(-2)) in predicting the later impairment of left ventricular function. Cardiac function was monitored with radionuclide ventriculography at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg x m(-2). Cardiotoxicity was defined as a decrease in left ventricular ejection fraction of more than 10% units to a final left ventricular ejection fraction < or =50%. Twenty-eight patients received doxorubicin > or =400 mg x m(-2) and were evaluable for cardiotoxicity. Clinical heart failure developed in two patients (7%) after a cumulative doxorubicin dose of 500 mg m(-2). Left ventricular ejection fraction decreased more than 10% absolute ejection fraction units to a final left ventricular ejection fraction < or =50% in 10 patients (36%). Left ventricular ejection fraction decreased from 56+/-1.5% to 53.6+/-1.5% (P=0.016) in patients with no cardiotoxicity, and from 60.8+/-2.4% to 41.8+/-2.0% (P<0.001) in patients with cardiotoxicity. For patients who developed cardiotoxicity, the fall in left ventricular ejection fraction after a cumulative doxorubicin dose of only 200 mg x m(-2) was highly significant (left ventricular ejection fraction 49.7+/-1.8%, P=0.001 vs baseline). In receiver operator characteristic analysis, the area under the curve for the decrease in left ventricular ejection fraction at a cumulative doxorubicin dose of 200 mg x m(-2) for predicting cardiotoxicity in all patients was 0.858. The decrease in left ventricular ejection fraction of more than 4% units after a cumulative doxorubicin dose of 200 mg x m(-2) had a 90% sensitivity and 72% specificity for predicting later cardiotoxicity. Our results show that the significant impairment of left ventricular function during doxorubicin therapy can be predicted early, already at low cumulative doxorubicin doses. This finding may be of value in identifying patients at high or low risk for the development of anthracycline cardiotoxicity.     

cTnT早期诊断蒽环类药物心脏毒性的实验研究

目的:研究血清肌钙蛋白T(cT-nT)浓度是否可以成为蒽环类药物心脏毒性早期诊断指标。方法:新西兰雄性兔44只,随机分为对照组(8只)和实验组(36只)。对照组新西兰兔注射等体积的生理盐水;实验组新西兰兔静脉注射多柔比星2 mg/(kg.次),1次/周,根据实验周数不同,实验组分为1周组(8只)、2周组(8只)、4周组(9只)和8周组(11只)。经胸超声心动图测量左室射血分数(LVEF)和左室短轴缩短分数(FS)以及E峰和A峰比值。血清GPBB浓度测量采用ELISA方法。心肌光镜Billingham评分和电镜检查评价多柔比星心脏毒性。结果:8周组新西兰兔LVEF、FS和E/A值均下降,P<0.05。与对照组相比,4周组新西兰兔血清cTnT浓度明显升高,P<0.05;8周组新西兰兔血清cTnT浓度显著高于其他组,P<0.05。光镜下4周组新西兰兔心肌损害比对照组严重,P<0.05;8周组新西兰兔心肌损害最严重,P<0.05。电镜下线粒体水肿和断裂可见于2周组、4周组和8周组,心肌损伤程度与多柔比星累积剂量有关。相关分析提示,血清cTnT浓度与多柔比星累积剂量(r=0.887,P<0.001)及血清cTnT浓度与...     

Subclinical doxorubicin-induced cardiotoxicity update: role of neutrophils and endothelium

Doxorubicin (DOX) is a highly effective chemotherapy agent that often causes cardiotoxicity. Despite a number of extensive studies, the risk for DOX cardiotoxicity remains unpredictable. The majority of the studies on DOX-induced cardiotoxicity have been focused on the effects on cardiomyocytes that lead to contractile dysfunction. The roles of systemic inflammation, endothelial injury and neutrophil recruitment, all induced by the DOX, are increasingly recognized as the mechanisms that trigger the development and progression of DOX-induced cardiomyopathy. This review explores recent data regarding the possible mechanisms and biomarkers of early subclinical DOX-associated cardiotoxicity.     

MicroRNA profiling in human medulloblastoma

Medulloblastoma is an aggressive brain malignancy with high incidence in childhood. Current treatment approaches have limited efficacy and severe side effects. Therefore, new risk-adapted therapeutic strategies based on molecular classification are required. MicroRNA expression analysis has emerged as a powerful tool to identify candidate molecules playing an important role in a large number of malignancies. However, no data are yet available on human primary medulloblastomas. A high throughput microRNA expression profiles was performed in human primary medulloblastoma specimens to investigate microRNA involvement in medulloblastoma carcinogenesis. We identified specific microRNA expression patterns which distinguish medulloblastoma differing in histotypes (anaplastic, classic and desmoplastic), in molecular features (ErbB2 or c-Myc overexpressing tumors) and in disease-risk stratification. MicroRNAs expression profile clearly differentiates medulloblastoma from either adult or fetal normal cerebellar tissues. Only a few microRNAs displayed upregulated expression, while most of them were downregulated in tumor samples, suggesting a tumor growth-inhibitory function. This property has been addressed for miR-9 and miR-125a, whose rescued expression promoted medulloblastoma cell growth arrest and apoptosis while targeting the proproliferative truncated TrkC isoform. In conclusion, misregulated microRNA expression profiles characterize human medulloblastomas, and may provide potential targets for novel therapeutic strategies.     

MicroRNA expression profiling is a potential diagnostic tool for thyroid cancer

BACKGROUND:

Approximately 30% of fine‐needle aspiration (FNA) biopsies of thyroid nodules are indeterminate or nondiagnostic. Recent studies suggest microRNA (miRNA, miR) is differentially expressed in malignant tumors and may have a role in carcinogenesis, including thyroid cancer. The authors therefore tested the hypothesis that miRNA expression analysis would identify putative markers that could distinguish benign from malignant thyroid neoplasms that are often indeterminate on FNA biopsy.

METHODS:

A miRNA array was used to identify differentially expressed genes (5‐fold higher or lower) in pooled normal, malignant, and benign thyroid tissue samples. Real‐time quantitative polymerase chain reaction was used to confirm miRNA array expression data in 104 tissue samples (7 normal thyroid, 14 hyperplastic nodule, 12 follicular variant of papillary thyroid cancer, 8 papillary thyroid cancer, 15 follicular adenoma, 12 follicular carcinoma, 12 Hurthle cell adenoma, 20 Hurthle cell carcinoma, and 4 anaplastic carcinoma cases), and 125 indeterminate clinical FNA samples. The diagnostic accuracy of differentially expressed genes was determined by analyzing receiver operating characteristics.

RESULTS:

Ten miRNAs showed >5‐fold expression difference between benign and malignant thyroid neoplasms on miRNA array analysis. Four of the 10 miRNAs were validated to be significantly differentially expressed between benign and malignant thyroid neoplasms by quantitative polymerase chain reaction (P < .002): miR‐100, miR‐125b, miR‐138, and miR‐768‐3p were overexpressed in malignant samples of follicular origin (P < .001), and in Hurthle cell carcinoma samples alone (P < .01). Only miR‐125b was significantly overexpressed in follicular carcinoma samples (P < .05). The accuracy for distinguishing benign from malignant thyroid neoplasms was 79% overall, 98% for Hurthle cell neoplasms, and 71% for follicular neoplasms. The miR‐138 was overexpressed in the FNA samples (P = .04) that were malignant on final pathology with an accuracy of 75%.

CONCLUSIONS:

MicroRNA expression differs for normal, benign, and malignant thyroid tissue. Expression analysis of differentially expressed miRNA could help distinguish benign from malignant thyroid neoplasms that are indeterminate on thyroid FNA biopsy. Cancer 2011. © 2011 American Cancer Society.     

Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer.

BACKGROUND: This study was designed to demonstrate that efficacy [progression-free survival (PFS)] of CAELYX [pegylated liposomal doxorubicin HCl (PLD)] is non-inferior to doxorubicin with significantly less cardiotoxicity in first-line treatment of women with metastatic breast cancer (MBC). PATIENTS AND METHODS: Women (n=509) with MBC and normal cardiac function were randomized to receive either PLD 50 mg/m2 (every 4 weeks) or doxorubicin 60 mg/m2 (every 3 weeks). Cardiac event rates were based on reductions in left ventricular ejection fraction as a function of cumulative anthracycline dose. RESULTS: PLD and doxorubicin were comparable with respect to PFS [6.9 versus 7.8 months, respectively; hazard ratio (HR)=1.00; 95% confidence interval (CI) 0.82-1.22]. Subgroup results were consistent. Overall risk of cardiotoxicity was significantly higher with doxorubicin than PLD (HR=3.16; 95%CI 1.58-6.31; P<0.001). Overall survival was similar (21 and 22 months for PLD and doxorubicin, respectively; HR=0.94; 95%CI 0.74-1.19). Alopecia (overall, 66% versus 20%; pronounced, 54% versus 7%), nausea (53% versus 37%), vomiting (31% versus 19%) and neutropenia (10% versus 4%) were more often associated with doxorubicin than PLD. Palmar-plantar erythrodysesthesia (48% versus 2%), stomatitis (22% versus 15%) and mucositis (23% versus 13%) were more often associated with PLD than doxorubicin. CONCLUSIONS: In first-line therapy for MBC, PLD provides comparable efficacy to doxorubicin, with significantly reduced cardiotoxicity, myelosuppression, vomiting and alopecia.     

Anticancer prodrugs of butyric acid and formaldehyde protect against doxorubicin-induced cardiotoxicity

Formaldehyde has been previously shown to play a dominant role in promoting synergy between doxorubicin (Dox) and formaldehyde-releasing butyric acid (BA) prodrugs in killing cancer cells. In this work, we report that these prodrugs also protect neonatal rat cardiomyocytes and adult mice against toxicity elicited by Dox. In cardiomyocytes treated with Dox, the formaldehyde releasing prodrugs butyroyloxymethyl diethylphosphate (AN-7) and butyroyloxymethyl butyrate (AN-1), but not the corresponding acetaldehyde-releasing butyroyloxydiethyl phosphate (AN-88) or butyroyloxyethyl butyrate (AN-11), reduced lactate dehydrogenase leakage, prevented loss of mitochondrial membrane potential (DeltaPsim) and attenuated upregulation of the proapoptotic gene Bax. In Dox-treated mice, AN-7 but not AN-88 attenuated weight-loss and mortality, and increase in serum lactate dehydrogenase. These findings show that BA prodrugs that release formaldehyde and augment Dox anticancer activity also protect against Dox cardiotoxicity. Based on these observations, clinical applications of these prodrugs for patients treated with Dox warrant further investigation.     

MicroRNA expression profiling in prostate cancer

MicroRNAs (miRNA) are small, endogenously expressed noncoding RNAs that negatively regulate expression of protein-coding genes at the translational level. Accumulating evidence, such as aberrant expression of miRNAs, suggests that they are involved in the development of cancer. They have been identified in various tumor types, showing that different sets of miRNAs are usually deregulated in different cancers. To identify the miRNA signature specific for prostate cancer, miRNA expression profiling of 6 prostate cancer cell lines, 9 prostate cancer xenografts samples, 4 benign prostatic hyperplasia (BPH), and 9 prostate carcinoma samples was carried out by using an oligonucleotide array hybridization method. Differential expression of 51 individual miRNAs between benign tumors and carcinoma tumors was detected, 37 of them showing down-regulation and 14 up-regulation in carcinoma samples, thus identifying those miRNAs that could be significant in prostate cancer development and/or growth. There was a significant trend (P=0.029) between the expression of miRNAs and miRNA locus copy number determined by array comparative genomic hybridization, indicating that genetic aberrations may target miRNAs. Hierarchical clustering of the tumor samples by their miRNA expression accurately separated the carcinomas from the BPH samples and also further classified the carcinoma tumors according to their androgen dependence (hormone naive versus hormone refractory), indicating the potential of miRNAs as a novel diagnostic and prognostic tool for prostate cancer.     

Early cardiotoxicity of the CHOP regimen in aggressive non-Hodgkin's lymphoma.

BACKGROUND: To determine the incidence of early cardiotoxicity induced by the CHOP regimen in patients with aggressive non-Hodgkin's lymphoma (NHL) and to identify associated risk factors. PATIENTS AND METHODS: A retrospective analysis included 135 consecutive patients who had been treated with the CHOP (cyclophosphamide, doxorubicin, vincristin, prednisone) regimen as first-line therapy between 1994 and 2000. The cardiac evaluation was based on a determination of the resting left ventricular ejection function (LVEF) by gated blood-pool imaging. Cardiotoxicity was defined as a significant decrease in LVEF or clinical evidence of congestive heart failure (CHF). RESULTS: Twenty-seven (20%) patients developed a cardiac event within 1 year of treatment. Among these, 14 patients had clinical signs of CHF. Three patients died suddenly from presumed cardiac causes. In multivariate analysis, a cumulative dose of doxorubicin >200 mg/m(2) [odds ratio (OR) = 4.2, P = 0.005)] and age over 50 years (OR = 2.9, P = 0.03) appeared to be significant risk factors. CONCLUSION: Early clinical and subclinical cardiotoxicity was frequent in patients receiving the CHOP regimen. The threshold of the cumulative dose of doxorubicin appeared to be low: at doses >200 mg/m(2), 27% of patients had cardiac events. Elderly patients appeared to be at higher risk. The development of cardioprotective strategies or alternative treatments are mandatory for aggressive NHL patients.     

The use of cardiac biopsy to demonstrate reduced cardiotoxicity in AIDS Kaposi's sarcoma patients treated with pegylated liposomal doxorubicin

Background: Pegylated liposomal doxorubicin (PL-DOX) has been shown in preclinical models to induce less cardiotoxicity than non-liposomal doxorubicin. Endomyocardial biopsy is a highly sensitive and specific method for detecting anthracycline-induced cardiac damage.Patients and methods: Myocardial tissue from ten KS patients who had received cumulative PL-DOX (20 mg/m²/biweekly) of 440–840 mg/m² was evaluated for evidence of anthracycline-induced cardiac damage. Controls were assembled from patients who had received cumulative doxorubicin doses of 174–671 mg/m² in two earlier cardiac biopsy protocols. Two control groups were selected on the basis of both cumulative (±10 mg/m²) and peak doxorubicin dose (60 or 20 mg/m², control group 1), or peak dose alone (20 mg/m², control group 2).Results: PL-DOX patients had significantly lower biopsy scores compared with those of doxorubicin controls despite higher cumulative doses of anthracycline. The median biopsy scores for the PL-DOX and doxorubicin groups, respectively, were 0.3 vs. 3.0 (P = 0.002, Cochran–Mantel–Haenszel row mean difference test) for group 1 and 1.25 for group 2 (P < 0.001, Wilcoxon rank-sum test).Conclusions: Less severe cardiac changes were seen in patients given PL-DOX relative to historical control patients given comparable cumulative doses of doxorubicin.     

MicroRNA profiling of Chinese primary glioblastoma reveals a temozolomide-chemoresistant subtype

Accumulating evidence demonstrates that defining molecular subtypes based on objective genetic alterations may permit a more rational, patient-specific approach to molecular targeted therapy across various cancers. The objective of this study was to subtype primary glioblastoma (pGBM) based on MicroRNA (miRNA) profiling in Chinese population. Here, miRNA expression profiles from 82 pGBM samples were analyzed and 78 independent pGBM samples were used for qRT-PCR validation. We found that two distinct subgroups with different prognosis and chemosensitivities to temozolomide (TMZ) in Chinese pGBM samples. One subtype is TMZ chemoresistant (termed the TCR subtype) and confers a poor prognosis. The other subtype is TMZ-chemosensitive (termed the TCS subtype) and confers a relatively better prognosis compared with the TCR subtype. A classifier consisting of seven miRNAs was then identified (miR-1280, miR-1238, miR-938 and miR-423-5p (overexpressed in the TCR subtype); and let-7i, miR-151-3p and miR-93 (downregulated in the TCR subtype)), which could be used to assign pGBM samples to the corresponding subtype. The classifier was validated using both internal and external samples. Meanwhile, the genetic alterations of the TCR and TCS subtypes were also analyzed. The TCR subtype was characterized by no IDH1 mutation, and EGFR and Ki-67 overexpression. The TCS subtype displayed the opposite situation. Taken together, the results indicate a distinct subgroup with poor prognosis and TMZ-chemoresistance.     

MicroRNA expression profiling in human Barrett's carcinogenesis

Barrett's esophagus (BE) is characterized by the native stratified squamous epithelium (N) lining the esophagus being replaced by a columnar epithelium with intestinal differentiation (Barrett's mucosa; BM). BM is considered as the main risk factor for esophageal adenocarcinoma (Barrett's adenocarcinoma; BAc). MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting messenger RNAs and they are reportedly dysregulated in BM. To test the hypothesis that a specific miRNA expression signature characterizes BM development and progression, we performed miRNA microarray analysis comparing native esophageal mucosa with all the phenotypic lesions seen in the Barrett's carcinogenic process. Specimens were collected from 14 BE patients who had undergone esophagectomy, including: 14 with N, 14 with BM, 7 with low-grade intraepithelial neoplasia, 5 with high-grade intra-epithelial neoplasia and 11 with BAc. Microarray findings were further validated by quantitive real-time polymerase chain reaction and in situ hybridization analyses using a different series of consecutive cases (162 biopsy samples and 5 esophagectomies) of histologically proven, long-segment BE. We identified a miRNA signature of Barrett's carcinogenesis consisting of an increased expression of 6 miRNAs and a reduced expression of 7 miRNAs. To further support these results, we investigated target gene expression using the Oncomine database and/or immunohistochemical analysis. We found that target gene expression correlated significantly with miRNA dysregulation. Specific miRNAs are directly involved in BE progression to cancer. miRNA profiling significantly expands current knowledge on the molecular history of Barrett's carcinogenesis, also identifying molecular markers of cancer progression.     

MicroRNA expression profiling in bladder cancer: the challenge of next‐generation sequencing in tissues and biofluids

Bladder cancer (BC) is a heterogeneous disease characterized by a high recurrence rate that necessitates continuous cystoscopic surveillance. MicroRNAs (miRNAs) are detectable in tissues and biofluids such as plasma/serum and urine. They represent promising biomarkers with potential not only for detecting BC but also informing on prognosis and monitoring treatment response. In this review, the many aspects of the application of next‐generation sequencing (NGS) to evaluate miRNA expression in BC is discussed, including technical issues as well as a comparison with results obtained by qRT‐PCR. The available studies investigating miRNA profiling in BC by NGS are described, with particular attention to the potential applicability on biofluids. Altered miRNA levels have been observed in BC tissues by NGS, but these results so far only partially overlapped among studies and with previous data obtained by qRT‐PCR. The discrepancies can be ascribed to the small groups of BC patients sequenced. The few available studies on biofluids are mainly focused on implementing RNA isolation and sequencing workflow. Using NGS to analyze miRNAs in biofluids can potentially provide results comparable to tissues with no invasive procedures for the patients. In particular, the analyses performed on exosomes/microvesicles appear to be more informative. Thanks to the improvement of both wet‐lab procedures and pipelines/tools for data analyses, NGS studies on biofluids will be performed on a larger scale. MiRNAs detected in urine and serum/plasma will demonstrate their potentiality to describe the variegated scenario of BC and to become relevant clinical markers.     

MicroRNA profiling with correlation to gene expression revealed the oncogenic miR-17-92 cluster to be up-regulated in osteosarcoma

Osteosarcomas are genetically complex tumors with abundant structural and numerical alterations. The molecular pathogenesis of the disease is, however, still poorly understood. Aside from various oncogenes and tumor suppressor genes, deregulated microRNAs (miRNAs) are known to influence tumor development and biology. We therefore investigated six well-established osteosarcoma cell lines (HOS58, U2-OS, Saos-2, MNNG/HOS, SJSA-1, and MG-63) for genome-wide miRNA expression (miRBase Version 15.0, http://www.mirbase.org/) and correlated our findings with gene expression. Cultured osteoblasts (hFOB 1.19) and mesenchymal stem cells (L87/4) were used as normal references. Focusing only on miRNAs that were deregulated in the majority of osteosarcoma cell lines, we identified several miRNAs with oncogenic and tumor suppressor properties, including various members of the oncogenic miR-17-92 cluster. In addition, several genes involved in differentiation (RGMB, LRRC17), cell cycle control (CCNE1), and apoptosis (LIMA1, CAMK2N1) were found to be deregulated in osteosarcoma cell lines, most likely due to altered miRNA expression patterns. Our findings indicate a crucial impact of deregulated miRNAs with consecutive changes in gene expression in osteosarcomas, which strongly suggests pathogenetic and potentially therapeutic implications.