Hsa-miR-625 Upregulation Promotes Apoptosis in Acute Myeloid Leukemia Cell Line by Targeting Integrin-linked Kinase Pathway

Background: Growing evidence has demonstrated that microRNAs have a major effect on development of different types of cancer including AML. The overexpression of miR-625 could decrease tumorgenesis of acute myeloid leukemia cell lines through Integrin-linked kinase signaling pathway and reducing the associated oncogenes.  The aim of this study is to evaluate the effect of hsa-miR-625 upregulation on apoptosis and proliferation of KG1 cell line via ILK signaling pathway. Methods: The KG-1 cell line was transfected with pLenti-III-premir625-GFP through viral method. Then, expression of miR-625 and genes were analyzed by quantitative PCR. Western blotting was used to evaluate for the protein level. Apoptosis was investigated by flow cytometry. Cell cycle analysis with PI and CCK-8 assay were performed to evaluate proliferation. Results: KG-1 cells transfected with pLenti-III-pre mir625-GFP construct showed a significant increase in cell apoptosis. Gene expression of ILK and NF-κB were downregulated and AKT, c-fos, Caspase3, cyclin D1, KLF-4, OCT-4 and Nanog were upregulated but no alteration in GSK3 expression profile was observed. Downregulation of NF-κB and upregulation of Caspase 3 and p-β-catenin protein levels were indicated (p<0.05). Conclusion: MiR-625 can be a promising approach to aid in the treatment of AML. However, further studies are required in this respect.     

Early Surgical Intervention for Diaphragmatic Paralysis in a Neonate; Report of a Case and Literature Review

Background

Diaphragmatic paralysis in newborns is related to brachial plexus palsy. It can cause respiratory failure necessitating prolonged mechanical ventilation and subsequent extubation failure.

Case Presentation

We present a two-hour-old male newborn with a birth weight of 4500 grams who had a right-sided brachial plexus palsy and right diaphragmatic paralysis due to shoulder dystocia. He developed respiratory distress due to isolated paralysis of the right hemi diaphragm. The clinical course was progressive, his condition worsening despite oxygen application. Physical examination, chest X-rays and M-mode ultrasonography of the diaphragm confirmed the diagnosis diaphragmatic paralysis. Surgical plication of diaphragm was done earlier than the usual time because of recurrent extubation failure. Diaphragmatic plication led to rapid improvement of pulmonary function and allowed discontinuation of mechanical ventilation in less than 3 days.

Conclusion

Early diaphragmatic plication enhances weaning process and may prevent or minimize the morbidity associated with long-term mechanical ventilation in a neonate with diaphragmatic paralysis.     

High coexpression of CCL2 and CX3CL1 is gender‐specifically associated with good prognosis in soft tissue sarcoma patients

Chemokines are involved in both the negative and positive regulation of inflammatory processes, angiogenesis and cancer/cancer stem cell proliferation as well as the chemoattraction of tumor cells to metastatic sites. The aim of this study was to measure the mRNA expression levels of three chemokines, CCL2, CCL7 and CX3CL1, in soft tissue sarcomas (STSs) and to assess the correlations between these levels as well as their correlations with clinicopathological data and the disease‐specific survival of STS patients. The mRNA levels of CCL2, CCL7 and CX3CL1 were analyzed in tumor tissues from 126 STS patients using qPCR. Low mRNA expression of CCL2 and CX3CL1 was significantly correlated with a worse prognosis (RR = 1.98; p = 0.019 and RR = 2.10; p = 0.014; multivariate Cox's regression analysis). A combined low expression of CCL2 and CX3CL1 was associated with a significantly increased risk of tumor‐related death as compared to patients with high expression levels of both chemokines (RR = 3.08; p = 0.003). A gender‐specific multivariate analysis revealed that female STS patients with low CX3CL1 mRNA expression had a 3.46‐fold increased risk of death (p = 0.004). Low expression of both CCL2 and CX3CL1 mRNAs resulted in an additive 5.37‐fold increased risk of tumor‐related death (p = 0.003) as compared to those with high expression of both parameters in female patients. In conclusion, this is the first study to show a significant correlation between combined low expression of CCL2 and CX3CL1 and a poor prognosis for STS patients, particularly in female patients.     

Role of liver transplantation in the management of hepatoblastoma in the pediatric population

Hepatoblastoma (HB) is the most common primary liver tumor in children and accounts for two-thirds of all malignant liver neoplasms in the pediatric population. For patients with advanced HB (unresectable or unresponsive to chemotherapy), combined treatment with chemotherapy and liver transplantation is an excellent option. The etiology of HB is mostly obscure because of its extreme rarity although some inherited syndromes and very low birth weight have been associated with it. The prognosis for children with HB has significantly improved in the past three decades thanks to advancements in chemotherapy, surgical resection and postoperative care. In 2002 a surgical staging system called pretreatment extent of disease (PRETEXT) was designed to allow a universal, multidisciplinary approach to patients with HB. Between one-third to two-thirds of patients initially present with unresectable tumors or distant metastases, but up to 85% of these tumors become operable after neoadjuvant chemotherapy. Patients with PRETEXT categories 1, 2, and some 3 are referred for neoadjuvant chemotherapy followed by surgical resection with the goal of complete tumor removal. Classic treatments regimens include a combination of cisplatin, fluorouracil, and vincristine or cisplatin and doxorubicin. Liver transplantation is the only treatment option for unresectable HB. In 2010 the pediatric end-stage liver disease, a pediatric-specific scoring system that determines a patient’s ranking on the liver transplant list, began to award additional “exception” points for patients with HB. We analyzed the Standard Transplant Analysis and Research dataset to assess the impact of changes in exception point criteria for HB on outcomes after liver transplantation at Texas Children’s Hospital in Houston, Texas. We found that patients who were listed for transplantation with current HB exception criteria experienced a shorter waitlist time but survival was similar between the two eras.