microRNA (miR)-612 shows anticancer activity in several types of cancers, yet its function in melanoma is still unclear. This study was undertaken to investigate the expression of miR-612 and its biological relevance in melanoma cell growth, invasion, and tumorigenesis. The expression and prognostic significance of miR-612 in melanoma were examined. The effects of miR-612 overexpression on cell proliferation, colony formation, tumorigenesis, and invasion were determined. Rescue experiments were conducted to identify the functional target gene(s) of miR-612. miR-612 was significantly downregulated in melanoma tissues compared to adjacent normal tissues. Low miR-612 expression was significantly associated with melanoma thickness, lymph node metastasis, and shorter overall, and disease-free survival of patients. Overexpression of miR-612 significantly decreased cell proliferation, colony formation, and invasion of SK-MEL-28 and A375 melanoma cells. In vivo tumorigenic studies confirmed that miR-612 overexpression retarded the growth of A375 xenograft tumors, which was coupled with a decline in the percentage of Ki-67-positive proliferating cells. Mechanistically, miR-612 targeted Espin in melanoma cells. Overexpression of Espin counteracted the suppressive effects of miR-612 on melanoma cell proliferation, invasion, and tumorigenesis. A significant inverse correlation (r = -0.376, P = 0.018) was observed between miR-612 and Espin protein expression in melanoma tissues. In addition, overexpression of miR-612 and knockdown of Espin significantly increased the sensitivity of melanoma cells to doxorubicin. Collectively, miR-612 suppresses the aggressive phenotype of melanoma cells through downregulation of Espin. Delivery of miR-612 may represent a novel therapeutic strategy against melanoma.
Park, Young-Hee;Kim, Sung-Chun;Kwon, Byung-Su;Jung, Heung-Su;Kim, Kuchan;Lee, Seong-Wook
Genomics & Informatics
/
v.2
no.1
/
pp.45-52
/
2004
The self-splicing group I intron from Tetrahymena thermophila has been demonstrated to perform splicing reaction with its substrate RNA in the trans configuration. In this study, we explored the potential use of the trans-splicing group I ribozymes to replace a specific RNA with a new RNA that exerts any new function we want to introduce. We have chosen thymidine phosphorylase (TP) RNA as a target RNA that is known as a valid cancer prognostic factor. Cancer-specific expression of TP RNA was first evaluated with RT-PCR analysis of RNA from patients with gastric cancer. We determined next which regions of the TP RNA are accessible to ribozymes by employing an RNA mapping strategy, and found that the leader sequences upstream of the AUG start codon appeared to be particularly accessible. A specific ribozyme recognizing the most accessible sequence in the TP RNA with firefly luciferase transcript as a 3' exon was then developed. The specific trans-splicing ribozyme transferred an intended 3' exon tag sequence onto the targeted TP transcripts, resulting in a more than two fold induction of the reporter activity in the presence of TP RNA in mammalian cells, compared to the absence of the target RNA. These results suggest that the Tetrahymena ribozyme can be a potent anti-cancer agent to modify TP RNAs in tumors with a new RNA harboring anti-cancer activity.
In order to develop a suitable secondary renal disease model and diagnostic markers of renal disease in the rat, the change of PIIIP (aminoterminal procollagen III peptide) in serum and hydroxyproline levels in the renal tissue that reflect the synthesis of extracellular matrix (ECM) during development of experimental renal diseases were observed. Two types of experimental primary diseases, diabetes mellitus administrated by streptozotocin (STZ, 75 mg/kg, i.p.) and liver cirrhosis produced by bile duct ligation/scission (BDL/s) operation, were induced. The hydroxyproline level increased according to the high PIIIP and NCl(carboxyterminal procollagen IV peptide) in Western blot analysis as early as 1 week in the STZ treated-rat kidney. Increased renal ECM was observed at 15 weeks in STZ and BDL/s model under the microscopic examination. High PAS positive reaction was found in capillary basement membrane in STZ treated-rats and mesangium in BDL/s operated rats at this time, showing the histological characteristics of diabetic nephropathy and cirrhotic glomerulonephritis in human, respectively. Such secondary renal failure were supported by additional tests including urinalysis and renal function test. The serum PIIIP detected by ELISA was a useful parameter to estimate synthesis rate of renal ECM during development of renal disease without extrarenal fibrosis i.e. liver cirrhosis in rats. This study is proposed that STZ treatment or BDL/s operation may be a suitable experimental animal model for the induction and development of chronic secondary renal diseases. Morover, it was found that hydroxyproline level in renal tissues was a good parameter of the change of renal ECM at the early stage of the diseases without apparent histological changes. Especially, serum PIIIP could be a choice as a diagnostic or prognostic marker during the development of renal diseases in rats.
Jang, Hea Min;Baek, Hee Sun;Park, Sun-Hee;Kim, Yong-Lim;Kim, Chan-Duck;Jung, Hee-Yeon;Cho, Jang-Hee;Han, Man Hoon;Kim, Yong Jin;Cho, Min Hyun
Childhood Kidney Diseases
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v.24
no.2
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pp.91-97
/
2020
Purpose: Alport syndrome (AS) is one of the most common inherited renal diseases caused due to mutations of genes encoding specific proteins of the type IV collagen family, and its major clinical manifestations include progressive renal failure, sensorineural deafness, and ocular abnormalities. We investigated the clinical characteristics and long-term prognosis of AS in Korean pediatric and adult populations. Methods: We conducted a retrospective review of medical records of 33 children and adults who had been diagnosed or treated with AS from 1985 to 2019. Results: The mean age of the 33 patients diagnosed with AS was 16.2±13.6 years, and the male-to-female ratio was 2:1. At the first visit, recurrent gross hematuria was the most common initial symptom. In 10 of 33 patients (30.3%), sensorineural hearing loss (SNHL) was diagnosed, but none had ophthalmic problems. Moreover, 11 of 33 patients (33.3%) had advanced to end-stage renal disease (ESRD), and a significant difference was observed in the age of the patients who progressed to ESRD based on the presence or absence of SNHL (P=0.035). Conclusion: SNHL in AS can be an important prognostic factor for long-term deterioration of renal function. Further investigation is required to confirm the clinical course and the genetic characteristics of AS in Korea through prospective national cohort studies.
The most important concern to do parotidectomy is correct identification of the facial nerve and preservation of the nerve function. Many descriptions for the localization and branching types of the facial nerve trunk have existed. During the parotid surgery, it is necessary to have knowledges about the incidence and prognostic aspect of a invasion of the facial nerve by the parotid tumors. The method of the dissection and the surgical extent of the parotid gland would be decided not only by the anatomic variation of the facial nerve. but also the size and location of the tumor. Invasion of the facial nerve in parotid malignancies is the most significant factors affecting the prognosis, so radical parotidectomy which consists of the total extirpation of the parotid gland in conjunction with resection of the facial nerve is often required for proper management. Radical parotidectomy is advocated for the surgical treatment of high grade malignancies and in selective recurrent benign tumors intimately involving the facial nerve. Unfortunately, the morphologic and functional deficits created by sacrificing the facial nerve can be emotionally and physically traumatizing to the patient. Therefore, when the facial nerve is sacrificed, immediate reconstruction of the facial nerve should be necessary. Immediate nerve repair with direct anastomosis of the resected nerve ends or placement of a cable nerve graft provides the better cosmetic and functional results. Surgical resection remains the mainstay of treatment for cancer of the parotid gland, and there is general agreement that facial nerve should not be sacrificed unless the tumor is adherent to, or surrounds the nerve. The following statement is described general principles of troublesome management of the facial nerve during surgery for parotid tumor.
Purpose: To investigate the clinical value of serum miR-221-3p and miR-122-5p expression levels in the diagnosis and prognosis of gastric cancer. Materials and Methods: Serum samples from 141 gastric cancer cases (gastric cancer group), 110 gastric polyps (gastric polyp group), and 75 healthy people (healthy control) were used to detect miR-221-3p and miR-122-5p expression using real-time reverse transcription polymerase chain reaction. Results: Serum miR-221-3p expression was significantly higher in the gastric cancer group than in the gastric polyp group, and it was significantly lower than that before operation. The miR-221-3p expression was significantly higher in the death group than in the survival group. The proliferation and migration ability significantly increased and the apoptosis rate significantly decreased by miR-221-3p transfection in gastric cancer cells. In contrast, the function of miR-122-5p in gastric cancer cells was opposite of miR-221-3p. Serum miR-221-3p expression was negatively correlated with that of miR-122-5p in gastric cancer. Serum miR-221-3p and miR-122-5p expressions were significantly correlated with the degree of differentiation, tumor, node, metastasis stage, lymph node metastasis, and invasion depth. miR-221-3p and miR-122-5p expression levels were independent prognostic factors for postoperative gastric cancer. In the diagnosis and predicting prognosis of gastric cancer, receiver operating characteristic analysis revealed that the area under curve of combined detection of serum miR-221-3p and miR-122-5p expression had a greater diagnostic effect than either single maker. Conclusions: The miR-221-3p and miR-122-5p are involved in the development of gastric cancer, and they have important clinical values in gastric cancer diagnosis and prognosis.
Purpose : This study was to compare the difference Trunk Control Test(TCT), Postural Assessment Scale for Stroke(PASS-TC), and Trunk Impairment Scale(TIS) and its subscales in relation to the difference MBI(Modified Barthel Index), BBS(Berg Balance Scale), and to establish the association between MBI, BBS, Fugl Meyer-motor function(FM-M), and to predict MBI-subscales from the variables. Methods : 58 stroke patients, attending a rehabilitation programme, participated in the study. Trunk control was measured with the use of the TCT, PASS-TC, TIS, and the performance of Activities daily living was obtained by MBI, and dynamic balance ability(by BBS). Trunk control scores from the difference MBI, BBS were compared using the 1-way ANOVA(Mann Whitney U test) and the data were analyzed using Pearson product correlation. Multiple stepwise regression analyses were performed to identify prognostic factors for ADL subscale. Results : Trunk control scores showed significant differences between MBI(F=2.139~13.737, p<.05~.001), BBS(t=3.491~7.705, p<.01~.001). It was significantly related with value of the MBI(r=.25~.50), BBS(r=.38~.68), FMM( r=.31~.48). Stepwise linear regression analysis showed an additional, significant contribution of the TCT, in addition to the PASS-TC, dynamic sitting balance subscale of the TIS for measures of MBI subscales. Conclusion : Measures of trunk control were significantly related with values of MBI, BBS score, so the management of trunk rehabilitation after stroke should be emphasized. The use of both quantitative and qualitative scales was shown to be a good measuring instrument for the classification of the general performance of the stroke patients. Further study about trunk control is needed using a longitudinal study design.
Background: The prognostic factors for patients with full-thickness rotator cuff tears (RCTs) include tear size, muscle atrophy and fatty infiltration. However, the influence of early coexisting degenerative changes on RCT outcomes is unappreciated. The purpose of this study was to calculate the impact that pre-existing partial glenohumeral cartilaginous changes have on patients undergoing arthroscopic RCT repair. Methods: A study of 54 patients undergoing arthroscopic RCT repair was undertaken. The presence of co-existing patches of glenohumeral degenerative cartilaginous changes and RCT size was recorded at surgery. Pre- and postoperative outcomes were assessed using traditional (Oxford Shoulder Score [OSS], 5-level EuroQol-5D [EQ-5D-5L] questionnaire and EuroQol visual analog scale [EQ-VAS]) and patient-centric re-formatted prisms. Outcomes were assessed as an entire dataset, and sub-group analysis was performed according to the grade of co-existing arthritis and tear size. Results: Significant improvements (p<0.05) in clinical outcomes were recognized when assessed using either the traditional or reformatted prisms (average % improvements in OSS, EQ-5D-5L and EQ-VAS were 47%, 33% and 43%, respectively; average improvements in pain, function, and psychological well-being were 48%, 33% and, 29%, respectively). Positive gain was noted in all sub-groups of arthritic grading and tear size. Conclusions: Good clinical outcomes can be achieved following RCT repair even in the presence of local partial degenerative cartilage changes and advancing tear size. These benefits are patient-centered but require RCT repairability.
The Kernohan-Woltman notch phenomenon (KWNP) refers to an intracranial lesion causing massive side-to-side mass effect which leads to compression of the contralateral cerebral peduncle against the free edge of the cerebellar tentorium. Diagnosis is based on "paradoxical" motor deficit ipsilateral to the lesion associated with radiologic evidence of damage to the contralateral cerebral peduncle. To date, there is scarce evidence regarding KWNP associated neuroimaging patterns and motor function prognostic factors. A systematic review was conducted on Medline database from inception to July 2021 looking for English-language articles concerning KWNP, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The research yielded 45 articles for a total of 51 patients. The mean age was 40.7 years-old and the male/female sex ratio was 2/1. 63% of the patients (32/51) suffered from head trauma with a majority of acute subdural hematomas (57%, 29/51). 57% (29/51) of the patients were in the coma upon admission and 47% (24/51) presented pupil anomalies. KWNP presented the neuroimaging features of compression ischemic stroke located in the contralateral cerebral peduncle, with edema in the surrounding structures and sometimes compression stroke of the cerebral arteries passing nearby. 45% of the patients (23/51) presented a good motor functional outcome; nevertheless, no predisposing factor was identified. A Glasgow coma scale (GCS) of more than 3 showed a trend (p=0.1065) toward a better motor functional outcome. The KWNP is a regional compression syndrome oftentimes caused by sudden and massive uncal herniation and leading to contralateral cerebral peduncle ischemia. Even though patients suffering from KWNP usually present a good overall recovery, patients with a GCS of 3 may present a worse motor functional outcome. In order to better understand this syndrome, future studies will have to focus on more personalized criteria such as individual variation of tentorial notch width.
Ernest Spitzer;Benjamin Camacho;Blaz Mrevlje;Hans-Jelle Brandendburg;Claire B. Ren
Journal of Cardiovascular Imaging
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v.31
no.3
/
pp.135-141
/
2023
BACKGROUND: Global longitudinal strain (GLS) is an accurate and reproducible parameter of left ventricular (LV) systolic function which has shown meaningful prognostic value. Fast, user-friendly, and accurate tools are required for its widespread implementation. We aim to compare a novel web-based tool with two established algorithms for strain analysis and test its reproducibility. METHODS: Thirty echocardiographic datasets with focused LV acquisitions were analyzed using three different semi-automated endocardial GLS algorithms by two readers. Analyses were repeated by one reader for the purpose of intra-observer variability. CAAS Qardia (Pie Medical Imaging) was compared with 2DCPA and AutoLV (TomTec). RESULTS: Mean GLS values were -15.0 ± 3.5% from Qardia, -15.3 ± 4.0% from 2DCPA, and -15.2 ± 3.8% from AutoLV. Mean GLS between Qardia and 2DCPA were not statistically different (p = 0.359), with a bias of -0.3%, limits of agreement (LOA) of 3.7%, and an intraclass correlation coefficient (ICC) of 0.88. Mean GLS between Qardia and AutoLV were not statistically different (p = 0.637), with a bias of -0.2%, LOA of 3.4%, and an ICC of 0.89. The coefficient of variation (CV) for intra-observer variability was 4.4% for Qardia, 8.4% 2DCPA, and 7.7% AutoLV. The CV for inter-observer variability was 4.5%, 8.1%, and 8.0%, respectively. CONCLUSIONS: In echocardiographic datasets of good image quality analyzed at an independent core laboratory using a standardized annotation method, a novel web-based tool for GLS analysis showed consistent results when compared with two algorithms of an established platform. Moreover, inter- and intra-observer reproducibility results were excellent.
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