Liver resection and ablation for squamous cell carcinoma liver metastases.

BACKGROUND: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS). METHOD: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS. RESULTS: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30). CONCLUSION: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome.

Anthropogenic debris in the digestive tract of a southern right whale (Eubalaena australis) stranded in Golfo Nuevo, Argentina.

Over the past fifty years, interactions between anthropogenic debris and a wide range of marine species have increased. In cetaceans, the most frequent interactions have occurred through ingestion and/or entanglement, with results ranging from minor injuries to death in affected animals. While debris ingestion is widely documented in odontocetes, records are scarcer in mysticetes. This study describes the finding of plastic litter in the digestive tract of a southern right whale (Eubalaena australis) juvenile male, which was found dead on the shores of Golfo Nuevo, Chubut, Argentina in 2014. During the examination of intestinal contents, anthropogenic waste was found and classified as macro-debris (25 mm-1 m). Although this whale likely died of causes not related to this finding, it is the first record of anthropogenic debris ingestion for this species. This event adds information about the potential impact of human-made debris on a variety of aquatic species and ecosystems.

Improved algorithm with adaptive regularization for tomographic reconstruction of gas distributions using DOAS measurements.

Differential optical absorption spectroscopy (DOAS) is notably well suited for the retrieval of UV-absorbing trace gases present in the atmosphere. We combine multi-axis DOAS observations to perform a tomographic reconstruction of the distribution of gases emitted from different sources. We use a new algorithm based on a regularized minimization approach embedding key physical aspects of the solution to constrain the inversion. In this work, we take into account that the spatial sampling of the plume being scanned by the instruments is not homogeneous. Therefore, we introduce an adaptive approach with a locally tuned regularization weight according to the uncertainty levels introduced by the sampling scheme. We tested our approach on reconstructions of simulated gas distributions and different configurations applicable to multi-axis DOAS. Finally, our approach is applied to experimental data for the retrieval of the distribution of ${\rm NO}_2$NO2 within a plume cross section emitted from a group of stacks.

Conservative Management of Gallstone Disease in the Elderly Population: Outcomes and Recurrence.

BACKGROUND & AIMS: The prevalence of gallstone disease increases with age, being early cholecystectomy the most accepted treatment in the vast majority of patients in order to prevent complications and recurrence. The aim of this study is to determine the recurrence rate and its possible predictors after initial non-operative management. MATERIALS AND METHODS: We reviewed a consecutive series of patients, older than 65 years, admitted for a gallstone-related disease and treated with a non-operative management between January 2010 and December 2013. We analyzed comorbidities, clinical data, diagnosis, management, recurrence, and its treatment. Median follow-up after the discharge was 2 years. Recurrence was analyzed by a Kaplan-Meier survival curve. Possible recurrence's predictors were analyzed. RESULTS: The study included 226 patients. Mean age was 80.4 ± 7.2 years, 127 (56%) were female. The main causes of index hospitalization were acute cholecystitis (58%) and biliary pancreatitis (18.1%). After 2 years of follow-up, the recurrence rate was 39.8%; mean time to recurrence was 255.2 ± 42.1 days, 81% of patients recurred within 1 year. Bile duct disease implied a higher recurrence rate than the gallbladder disease group (52% vs 33%, p < 0.001). Subjects with two or more diagnoses during index admission presented higher recurrence rate (32% vs 49%, p < 0.001). CONCLUSION: More than a third of elderly patients could present a recurrence within 2 years after initial non-operative management. Early cholecystectomy should be considered at index admission in order to prevent recurrence.

Left-sided portal hypertension due to retroperitoneal fibrosis treated with an oesophagus preserving, modified Sugiura procedure.

Left-sided portal hypertension is a very uncommon condition and retroperitoneal fibrosis has rarely been reported as a cause. We present the case of a 77-year-old man with retroperitoneal fibrosis obstructing the splenic vein and causing recurrent episodes of upper gastrointestinal bleeding. Computed tomography showed a retroperitoneal mass as being responsible for the obstruction of the splenic vein, splenomegaly, and diffuse varices around the gastrosplenic and gastrohepatic ligaments. An oesophagus preserving, modified Sugiura procedure was performed with disconnection of the gastric vessels on the lesser curve of the stomach, preserving the pylorus branches of the nerves of Latarjet.

Initial clinical outcomes and prognostic variables in the implementation of a Code Sepsis in a high complexity University Hospital.

OBJECTIVE: To assess the impact of the first months of application of a Code Sepsis in a high complexity hospital, analyzing patient´s epidemiological and clinical characteristics and prognostic factors. METHODS: A long-term observational study was carried out throughout a consecutive period of seven months (February 2015 - September 2015). The relationship with mortality of risk factors, and analytic values was analyzed using uni- and multivariate analyses. RESULTS: A total of 237 patients were included. The in-hospital mortality was 24% at 30 days and 27% at 60 days. The mortality of patients admitted to Critical Care Units was 30%. Significant differences were found between the patients who died and those who survived in mean levels of creatinine (2.30 vs 1.46 mg/dL, p <0.05), lactic acid (6.10 vs 2.62 mmol/L, p <0.05) and procalcitonin (23.27 vs 12.73 mg/dL, p<0.05). A statistically significant linear trend was found between SOFA scale rating and mortality (p<0.05). In the multivariate analysis additional independent risk factors associated with death were identified: age > 65 years (OR 5.33, p <0.05), lactic acid > 3 mmol/L (OR 5,85, p <0,05), creatinine > 1,2 mgr /dL (OR 4,54, p <0,05) and shock (OR 6,57, P <0,05). CONCLUSIONS: The epidemiological, clinical and mortality characteristics of the patients in our series are similar to the best published in the literature. The study has identified several markers that could be useful at a local level to estimate risk of death in septic patients. Studies like this one are necessary to make improvements in the Code Sepsis programs.

MiR-29b antagonizes the pro-inflammatory tumor-promoting activity of multiple myeloma-educated dendritic cells.

Dendritic cells (DCs) have a key role in regulating tumor immunity, tumor cell growth and drug resistance. We hypothesized that multiple myeloma (MM) cells might recruit and reprogram DCs to a tumor-permissive phenotype by changes within their microRNA (miRNA) network. By analyzing six different miRNA-profiling data sets, miR-29b was identified as the only miRNA upregulated in normal mature DCs and significantly downregulated in tumor-associated DCs. This finding was validated in primary DCs co-cultured in vitro with MM cell lines and in primary bone marrow DCs from MM patients. In DCs co-cultured with MM cells, enforced expression of miR-29b counteracted pro-inflammatory pathways, including signal transducer and activator of transcription 3 and nuclear factor-κB, and cytokine/chemokine signaling networks, which correlated with patients' adverse prognosis and development of bone disease. Moreover, miR-29b downregulated interleukin-23 in vitro and in the SCID-synth-hu in vivo model, and antagonized a Th17 inflammatory response. All together, these effects translated into strong anti-proliferative activity and reduction of genomic instability of MM cells. Our study demonstrates that MM reprograms the DCs functional phenotype by downregulating miR-29b whose reconstitution impairs DCs ability to sustain MM cell growth and survival. These results underscore miR-29b as an innovative and attractive candidate for miRNA-based immune therapy of MM.

Development and validation of a bioanalytical method for quantification of LNA-i-miR-221, a 13-mer oligonucleotide, in rat plasma using LC-MS/MS.

LNA-i-miR-221, a 13-mer oligonucleotide, is a new miR-221 inhibitor that could be used as a novel drug for multiple myeloma. Herein, an ion-pair reversed phase liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantification of LNA-i-miR-221 in rat plasma. Plasma samples were prepared with an initial phenol/chloroform/isoamyl alcohol liquid-liquid extraction followed by a solid phase extraction. Chromatographic separation was performed with a gradient system on a HALO C18 column using hexafluoro-2-propanol/triethylamine buffer and methanol as mobile phase at a flow rate of 0.4 mL/min. Under these conditions LNA-i-miR-221 and the analogue internal standard are co-eluted at 1.2 min. The detection was carried out in multiple reaction monitoring (MRM) mode using a negative electrospray ionization (ESI) interface. The assay showed a good linearity within the calibration range 10-10000 ng/mL. The precision, accuracy, and recovery values were found to be <15% (<20% at LLOQ), 100 ±â€¯15%, and 97.6-103.7%, respectively. This method was successfully applied to measure the concentrations of LNA-i-miR-221 in plasma samples following the intravenous administration during a 4-week toxicity study in rats.

Correction to: Improved plan quality with automated radiotherapy planning for whole brain with hippocampus sparing: a comparison to the RTOG 0933 trial.

In the original publication [1] figure legends 2 and 4 have been swapped. The original article was updated to rectify this error.

Improved plan quality with automated radiotherapy planning for whole brain with hippocampus sparing: a comparison to the RTOG 0933 trial.

BACKGROUND: Whole-brain radiation therapy (WBRT) with hippocampus sparing (HS) has been investigated by the radiation oncology working group (RTOG) 0933 trial for patients with multiple brain metastases. They showed a decrease of adverse neurocognitive effects with HS WBRT compared to WBRT alone. With the development of automated treatment planning system (aTPS) in the last years, a standardization of the plan quality at a high level was achieved. The goal of this study was to evaluate the feasibility of using an aTPS for the treatment of HS WBRT and see if the RTOG 0933 dose constraints could be achieved and improved. METHODS: Ten consecutive patients treated with HS WBRT were enrolled in this study. 10 × 3 Gy was prescribed according to the RTOG 0933 protocol to 92% of the target volume (whole-brain excluding the hippocampus expanded by 5 mm in 3-dimensions). In contrast to RTOG 0933, the maximum allowed point dose to normal brain was significantly lowered and restricted to 36.5 Gy. All patients were planned with volumetric modulated arc therapy (VMAT) technique using four arcs. Plans were optimized using Auto-Planning (AP) (Philips Radiation Oncology Systems) with one single AP template and optimization. RESULTS: All the constraints from the RTOG 0933 trial were achieved. A significant improvement for the maximal dose to 2% of the brain with a reduction of 4 Gy was achieved (33.5 Gy vs. RTOG 37.5 Gy) and the minimum hippocampus dose was reduced by 10% (8.1 Gy vs. RTOG 9 Gy). A steep dose gradient around the hippocampus was achieved with a mean dose of 27.3 Gy at a distance between 0.5 cm and 1 cm from the hippocampus. The effective working time to optimize a plan was kept below 6'. CONCLUSION: Automated treatment planning for HS WBRT was able to fulfil all the recommendations from the RTOG 0933 study while significantly improving dose homogeneity and decreasing unnecessary hot spot in the normal brain. With this approach, a standardization of plan quality was achieved and the effective time required for plan optimization was minimized.

Evaluación emocional del impacto del diagnóstico y tratamientos a padres de niños con desórdenes de la diferenciación sexual (DSD) / Emotion-focused evaluation of the impact on parents of diagnosis and treatment of children with disorders of sex development (DSD)

El Hospital Garrahan realiza la atención interdisciplinaria de niños con "Anomalías de la Diferenciación Sexual". Es importante conocer el estado emocional de los padres de los pacientes con diagnóstico de DSD (Disorders of Sex Development).para comprender y acompañar de la mejor manera el proceso por el que deberán atravesar estas familias. El objetivo del trabajo es: Identificar indicadores de vulnerabilidad y/o afectación psicoemocional de los padres, empleando para ello entrevistas semidirigidas e instrumentos científicamente validados .Se aplicaron Escalas de ansiedad, de depresión, Cuestionario de Salud SF-36, el Pediatric Inventory for Parents (PIP), y el Cuestionario de afrontamiento para adultos CAE. Se realizó un estudio Descriptivo de corte transversal. Resultados. Se entrevistaron 53 padres. El promedio de edad 28 años. El 24,5% pertenece al Cono Urbano, 11,3% a CABA, y 22,6% a otras provincias . Nivel educativo: primaria completa 49%, secundaria 24,5%, estudios terciarios y universitarios 5,6%y 3,7%, no terminaron la primaria 9,4%, secundario 7,8%. En cuanto a la información recibida, diagnóstico, estudios, indicaciones, y recomendaciones para la asignación de sexo de sus hijos, y las medidas al respecto; 49% alcanzó una comprensión regular, 13,2% tenía una mala calidad de información, 37% logró una buena información . El CAE describe las estrategias para hacer frente a situaciones estresantes, el refugio en creencias y la religión presentó la mayor cantidad el 64%, los estilos de afrontamiento evaluación emocional abierta y la autofocalización negativa (54% y 52% respectivamente), focalización en la solución del problema (45%), la reevaluación positiva de las situaciones (35%) y la evitación (23%). El recurso menos utilizado es la búsqueda de apoyo social (19%). Otra de las variables estudiadas fue la depresión como indicador de malestar,se utilizó el test de Hamilton, presentando No depresión (38,3%), depresión ligera/menor (25%), depresión mayor (13,3%), depresión moderada y depresión severa (5% cada una), y un porcentaje no contestó (13,3%). En el PIP, perciben que la comunicación de información médica es estresante en un 37,3% y también sienten que debe esforzarse para comprenderla en un 52,9%. Los cuidados médicos que deben asumir representan un factor estresante para el 58,8%, y creen necesitar esforzarse para asumirlos el 70,6%. Por otro lado consideran que tener que manejar las relaciones familiares paralelas a la situación de enfermedad de sus hijos es estresante en un 60,8%, debiendo esforzarse para afrontarlas en un 41,2% de los casos (AU)

At Garrahan Hospital children with "sex differentiation anomalies" are managed in a multidisciplinary team. It is important to know the emotional state of the parents of patients with a diagnosis of disorders of sex development (DSDs) in order to understand and best accompany the family in the process they have to go through. The aim of this study was to identify markers of vulnerability and/or psycho-emotional affectation of the parents, using semistructured interviews and scientifically validated instruments. The Scales of Anxiety, of Depression, the Short Form (SF-36) Health Survey, the Pediatric Inventory for Parents (PIP), and the coping questionnaire for adults (CAE) were used. A descriptive cross-sectional study was performed. Results: 53 parents were interviewed. Mean age was 28 years. Overall, 24.5% was from Greater Buenos Aires, 11.3% from the city of Buenos Aires, and 22.6% from other provinces. Educational level: 49% completed primary school, 24.5% completed secondary school, and 5.6% and 3.7% completed tertiary or university education; 9.4% had not completed primary and 7.8% secondary school. Regarding information received,: 49% had a regular understanding, 13.2% had a poor understanding, and 37% had a good understanding of the information. The CAE describes strategies to cope with stressful situations; beliefs and religion were the most common in 64%, strategies of open emotion-focused coping and self-blame (54% and 52%, respectively), problem-focused coping (45%), a positive reappraisal of the situations (35%), and denial (23%). The least used coping resource was looking for social support (19%). Other variables studied were depression as a marker of discomfort: The Hamilton Rating Scale for Depression was used, showing No depression (38.3%), mild/minor depression (25%), major depression (13.3%), moderate and severe depression (5% each), and a percentage did not respond (13.3%). Using the PIP it was found that medical communication was found to be stressful in 37.3% and 52.9% felt they had to make an effort to understand the information. The medical care the parents have to assume was a stressing factor for 58.8%, and 70.6% believed they had to make an effort to assume the care. On the other hand, 60.8% believed that having to manage family relationships parallel to the disease situation of their children was stressful, and it was felt by 41.2% they had to make an effort to cope with that situation (AU)

A gene expression inflammatory signature specifically predicts multiple myeloma evolution and patients survival.

Multiple myeloma (MM) is closely dependent on cross-talk between malignant plasma cells and cellular components of the inflammatory/immunosuppressive bone marrow milieu, which promotes disease progression, drug resistance, neo-angiogenesis, bone destruction and immune-impairment. We investigated the relevance of inflammatory genes in predicting disease evolution and patient survival. A bioinformatics study by Ingenuity Pathway Analysis on gene expression profiling dataset of monoclonal gammopathy of undetermined significance, smoldering and symptomatic-MM, identified inflammatory and cytokine/chemokine pathways as the most progressively affected during disease evolution. We then selected 20 candidate genes involved in B-cell inflammation and we investigated their role in predicting clinical outcome, through univariate and multivariate analyses (log-rank test, logistic regression and Cox-regression model). We defined an 8-genes signature (IL8, IL10, IL17A, CCL3, CCL5, VEGFA, EBI3 and NOS2) identifying each condition (MGUS/smoldering/symptomatic-MM) with 84% accuracy. Moreover, six genes (IFNG, IL2, LTA, CCL2, VEGFA, CCL3) were found independently correlated with patients' survival. Patients whose MM cells expressed high levels of Th1 cytokines (IFNG/LTA/IL2/CCL2) and low levels of CCL3 and VEGFA, experienced the longest survival. On these six genes, we built a prognostic risk score that was validated in three additional independent datasets. In this study, we provide proof-of-concept that inflammation has a critical role in MM patient progression and survival. The inflammatory-gene prognostic signature validated in different datasets clearly indicates novel opportunities for personalized anti-MM treatment.

EZH2 is increased in paediatric T-cell acute lymphoblastic leukemia and is a suitable molecular target in combination treatment approaches.

BACKGROUND: T-cell Acute Lymphoblastic Leukemia (ALL) represents about 10-15 % of pediatric ALL cases. EZH2, one of the components of Polycomb group proteins (PRC2) complex, catalyzes the trimethylation of histone H3 lysine 27 that is associated with transcriptional repression and tumor development. METHODS: We examined the expression levels of PRC2 complex in primary samples of T cells ALL at diagnosis by western blotting and real time PCR. We evaluated the effect of 3-deazaneplanocin-A (DZNep), an EZH2 inhibitor, alone and in combination with Daunoblastine on cell viability, apoptotic death and cell cycle distribution of T cell established Jurkat cell line. RESULTS: EZH2 was expressed in 75 % samples at different extents mainly with high expression level. SUZ12 was expressed in 60 % samples and EED in all samples, respectively. The Kaplan-Meier analysis shows that T-ALL expressing EZH2 had a lower probability of disease-free survival (DFS) compared to T-ALL negative for EZH2 (23 % vs 100 %) (p = 0.01). The EZH2 inhibitor DZNep used in combination with Daunoblastine was synergistic in inducing growth inhibition and increasing the apoptosis in T-ALL Jurkat cells at 48 and 72 h paralleled by EZH2 decreased expression. Moreover, the combination decreased the activity of Erk-1/2 proliferation enzymes with no effects on Akt survival pathway. CONCLUSIONS: The evaluation of EZH2 expression in pediatric T-ALL can be useful in predict the clinical outcome of the patients and EZH2 can be a useful target to improve the efficacy of conventional chemotherapy in this subset of patients with bad prognosis.

Evaluation of image quality, radiation dose and diagnostic performance of dual-energy CT datasets in patients with hepatocellular carcinoma.

AIM: To evaluate image quality and diagnostic accuracy of different dual-energy computed tomography (DECT) datasets for identification of hepatocellular carcinoma (HCC), assess the reliability of virtual unenhanced (VU) images in replacing standard unenhanced (SU) images, and quantify effective dose (ED) at different tube voltages. MATERIAL AND METHODS: Thirty cirrhotic patients underwent liver contrast-enhanced DECT. Two blinded observers retrospectively evaluated conventional unenhanced and VU images, 140 kVp/80 kVp/mixed tube potential arterial datasets and conventional portal-venous/late phases in consensus. Final diagnosis was based on pathological proof or imaging criteria. Image quality, ED, sensitivity, and specificity of arterial datasets were calculated. RESULTS: Thirty-eight HCC and 18 benign lesions were detected at 80 kVp, 33 HCC and 22 benign lesions were detected at 140 kVp, and 36 HCC and 20 benign lesions were detected at mixed tube potentials. Final diagnosis confirmed 37 HCC and 20 benign lesions. There was no significant difference in diagnostic confidence between 80 kVp, 140 kVp, and mixed tube potential arterial datasets (p>0.05). Image quality was adequate for all datasets, with increased quality at higher tube potential (80 versus 140 kVp, p=0.001; mixed versus 140 kVp, p=0.001; 80 kVp versus mixed, p=0.0024). Significant ED reduction was observed between 140 and 80 kVp datasets (p<0.001). CONCLUSIONS: The 140 kVp dataset provided higher image quality. The 80 kVp images were more sensitive in detecting HCC. VU images are adequate in replacing SU images. The ED of the 80 kVp dataset was significantly lower.

A double-blind, placebo-controlled randomized trial to evaluate the efficacy of docosahexaenoic acid supplementation on hepatic fat and associated cardiovascular risk factors in overweight children with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Very little information is available on whether docosahexaenoic acid (DHA) supplementation has a beneficial effect on liver fat and cardiovascular disease (CVD) risk factors in children with nonalcoholic fatty liver disease (NAFLD). In a double-blind, placebo-controlled randomized trial we investigated whether 6-month treatment with DHA improves hepatic fat and other fat depots, and their associated CVD risk factors in children with biopsy-proven NAFLD. METHODS AND RESULTS: Of 58 randomized children, 51 (25 DHA, 26 placebo) completed the study. The main outcome was the change in hepatic fat fraction as estimated by magnetic resonance imaging. Secondary outcomes were changes in visceral adipose tissue (VAT), epicardial adipose tissue (EAT), and left ventricular (LV) function, as well as alanine aminotransferase (ALT), triglycerides, body mass index-standard deviation score (BMI-SDS), and insulin sensitivity. At 6 months, the liver fat was reduced by 53.4% (95% CI, 33.4-73.4) in the DHA group, as compared with 22.6% (6.2-39.0) in the placebo group (P = 0.040 for the comparison between the two groups). Likewise, in the DHA group VAT and EAT were reduced by 7.8% (0-18.3) and 14.2% (0-28.2%), as compared with 2.2% (0-8.1) and 1.7% (0-6.8%) in the placebo group, respectively (P = 0.01 for both comparisons). There were no significant between-group changes for LV function as well as BMI-SDS and ALT, while fasting insulin and triglycerides significantly decreased in the DHA-treated children (P = 0.028 and P = 0.041, respectively). CONCLUSIONS: DHA supplementation decreases liver and visceral fat, and ameliorates metabolic abnormalities in children with NAFLD.

Selective targeting of IRF4 by synthetic microRNA-125b-5p mimics induces anti-multiple myeloma activity in vitro and in vivo.

Interferon regulatory factor 4 (IRF4) is an attractive therapeutic target in multiple myeloma (MM). We here report that expression of IRF4 mRNA inversely correlates with microRNA (miR)-125b in MM patients. Moreover, we provide evidence that miR-125b is downregulated in TC2/3 molecular MM subgroups and in established cell lines. Importantly, constitutive expression of miR-125b-5p by lentiviral vectors or transfection with synthetic mimics impaired growth and survival of MM cells and overcame the protective role of bone marrow stromal cells in vitro. Apoptotic and autophagy-associated cell death were triggered in MM cells on miR-125b-5p ectopic expression. Importantly, we found that the anti-MM activity of miR-125b-5p was mediated via direct downregulation of IRF4 and its downstream effector BLIMP-1. Moreover, inhibition of IRF4 translated into downregulation of c-Myc, caspase-10 and cFlip, relevant IRF4-downstream effectors. Finally, in vivo intra-tumor or systemic delivery of formulated miR-125b-5p mimics against human MM xenografts in severe combined immunodeficient/non-obese diabetic mice induced significant anti-tumor activity and prolonged survival. Taken together, our findings provide evidence that miR-125b, differently from other hematologic malignancies, has tumor-suppressor activity in MM. Furthermore, our data provide proof-of-concept that synthetic miR-125b-5p mimics are promising anti-MM agents to be validated in early clinical trials.