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1.

Object

This study aimed to investigate the role of lncRNA OIP5-AS1 in regulating radioresistance of colorectal cancer (CRC) cells.

Methods

Microarray analysis was used to screen out lncRNAs differentially expressed in radio-resistant CRC cell lines. Expression levels of OIP5-AS1, miR-369-3p and DYRK1A in CRC cell lines were measured by qRT-PCR. Protein expression of DYRK1A was determined by western blot. The target relationships among OIP5-AS1, miR-369-3p and DYRK1A were validated by dual luciferase reporter assay. Impacts of OIP5-AS1 or DYRK1A on CRC cellular activity and apoptosis were investigated by MTT assay, clonogenic survival assay and flow cytometry to analyze OIP5-AS1 or DYRK1A’s effect on radioresistance of CRC cells.

Results

LncRNA OIP5-AS1 and DYRK1A were down-regulated in radio-resistant CRC cell lines. OIP5-AS1 suppressed the expression of miR-369-3p, thus up-regulating DYRK1A, the downstream gene of miR-369-3p. OIP5-AS1 and DYRK1A impaired cell clonogenic survival and promoted cell apoptosis after irradiation, improving radiosensitivity of CRC cells.

Conclusion

LncRNA OIP5-AS1 suppressed cell viability, promoted radio-induced apoptosis, and enhanced the radiosensitivity of CRC cells by regulating DYRK1A expression through miR-369-3p.  相似文献   

2.

Background

Lung cancer is the leading cause of cancer-related death worldwide. Previous studies revealed that miR-183-5p is frequently involved in various human cancers. However, the exact role of miR-183-5p in regulating the pathogenesis of lung cancer remains unclear.

Method

Bioinformatic analysis, luciferase reporter assay, and Western blotting was used to investigate whether miR-183-5p directly bound to the 3′UTR of PIK3CA and prevented its translation. Furthermore, an si-miR-183-5p and PIK3CA siRNA was used to evaluate whether PIK3CA expression increased and whether cell proliferation, migration and invasion ability were promoted.

Results

miR-183-5p directly bound to the 3′UTR of PIK3CA and prevented its translation. miR-183-5p also acted as a tumor suppressor, and contrary to most studies, its expression was downregulated in lung cancer. Functional studies revealed that overexpression of miR-183-5p reduced cell proliferation, migration, and invasion and that miR-183-5p induced cell cycle arrest and increased cell apoptosis. PIK3CA expression, cell proliferation, migration and invasion ability increased. siRNA-mediated silencing of PIK3CA in lung cancer cells decreased their proliferation and invasive capabilities, suggesting that miR-183-5p inhibited cell proliferation and invasion of lung cancer cells at least partly through downstream targeting of PIK3CA.

Conclusion

Our studies suggest that miR-183-5p may function as a tumor suppressor in lung cancer via the miR-183-5p/PIK3CA regulatory axis and identify a potentially effective therapeutic strategy for lung cancer.  相似文献   

3.
4.

Background

Despite diverging levels of amyloid-β (Aβ) and TAU pathology, different mouse models, as well as sporadic AD patients show predictable patterns of episodic memory loss. MicroRNA (miRNA) deregulation is well established in AD brain but it is unclear whether Aβ or TAU pathology drives those alterations and whether miRNA changes contribute to cognitive decline.

Methods

miRNAseq was performed on cognitively intact (4 months) and impaired (10 months) male APPtg (APPswe/PS1L166P) and TAUtg (THY-Tau22) mice and their wild-type littermates (APPwt and TAUwt). We analyzed the hippocampi of 12 mice per experimental group (n =?96 in total), and employed a 2-way linear model to extract differentially expressed miRNAs. Results were confirmed by qPCR in a separate cohort of 4 M and 10 M APPtg and APPwt mice (n =?7–9 per group) and in human sporadic AD and non-demented control brain. Fluorescent in situ hybridization identified their cellular expression. Functional annotation of predicted targets was performed using GO enrichment. Behavior of wild-type mice was assessed after intracerebroventricular infusion of miRNA mimics.

Results

Six miRNAs (miR-10a-5p, miR-142a-5p, miR-146a-5p, miR-155-5p, miR-211-5p, miR-455-5p) are commonly upregulated between APPtg and TAUtg mice, and four of these (miR-142a-5p, miR-146a-5p, miR-155-5p and miR-455-5p) are altered in AD patients. All 6 miRNAs are strongly enriched in neurons. Upregulating these miRNAs in wild-type mice is however not causing AD-related cognitive disturbances.

Conclusion

Diverging AD-related neuropathologies induce common disturbances in the expression of neuronal miRNAs. 4 of these miRNAs are also upregulated in AD patients. Therefore these 4 miRNAs (miR-142a-5p, miR-146a-5p, miR-155-5p and miR-455-5p) appear part of a core pathological process in AD patients and APPtg and TAUtg mice. They are however not causing cognitive disturbances in wild-type mice. As some of these miRNA target AD relevant proteins, they may be, in contrast, part of a protective response in AD.
  相似文献   

5.

Background

Accumulation of amyloid β-peptide (Aβ) is implicated in the pathogenesis and development of Alzheimer’s disease (AD). Neuron-enriched miRNA was aberrantly regulated and may be associated with the pathogenesis of AD. However, regarding whether miRNA is involved in the accumulation of Aβ in AD, the underlying molecule mechanism remains unclear. Therefore, we conduct a systematic identification of the promising role of miRNAs in Aβ deposition, and shed light on the molecular mechanism of target miRNAs underlying SH-SY5Y cells treated with Aβ-induced cytotoxicity.

Results

Statistical analyses of microarray data revealed that 155 significantly upregulated and 50 significantly downregulated miRNAs were found on the basis of log2 | Fold Change |?≥?0.585 and P?< 0.05 filter condition through 2588 kinds of mature miRNA probe examined. PCR results show that the expression change trend of the selected six miRNAs (miR-6845-3p, miR-4487, miR-4534, miR-3622-3p, miR-1233-3p, miR-6760-5p) was consistent with the results of the gene chip. Notably, Aβ25–35 downregulated hsa-miR-4487 and upregulated hsa-miR-6845-3p in SH-SY5Y cell lines associated with Aβ-mediated pathophysiology. Increase of hsa-miR-4487 could inhibit cells apoptosis, and diminution of hsa-miR-6845-3p could attenuate axon damage mediated by Aβ25–35 in SH-SY5Y.

Conclusions

Together, these findings suggest that dysregulation of hsa-miR-4487 and hsa-miR-6845-3p contributed to the pathogenesis of AD associated with Aβ25–35 mediated by triggering cell apoptosis and synaptic dysfunction. It might be beneficial to understand the pathogenesis and development of clinical diagnosis and treatment of AD. Further, our well-designed validation studies will test the miRNAs signature as a prognostication tool associated with clinical outcomes in AD.
  相似文献   

6.

Introduction

The incidence of breast carcinoma (BC) has increased in the last years. Between 2 and 12% of patients diagnosed with BC will develop bilateral breast carcinoma (BBC). The treatment of these carcinomas is more aggressive than unilateral BC.

Purpose

To perform a retrospective qualitative analysis of BBC patients whose treatment has included brachytherapy (BT) and to present a revised literature on this issue.

Material and methods

The cases of BBC whose treatment included brachytherapy were revised. The literature on this issue was refreshed.

Results

Five women, aged between 54 and 78 at the time of the diagnosis, submitted to conservative surgery followed by external radiotherapy (RT) with boost of BT or exclusive BT (APBI), in the IPO-P BT Service between 2003 and 2016.

Discussion

The patients with BBC have slightly higher rates of local recurrences, mostly in the tumor bed, where there is a higher risk of local recurrence. Patients treated with BT had lower rates of recurrences than those treated with photons and electrons.

Conclusions

BBC represents a complex challenge for doctors, because in some cases there is a tendency to use more aggressive treatments and, at the same time, it is not easy to achieve the timing for the correct treatment.  相似文献   

7.
8.

Aim

To assess the feasibility of transferring to the University of Tsukuba Hospital for proton beam therapy (PBT) during intensive chemotherapy in children with Ewing sarcoma family of tumors (ESFT) who had been diagnosed and started their first-line treatment at prefectural or regional centers for pediatric oncology.

Background

The treatment of ESFT relies on a multidisciplinary approach using intensive neoadjuvant and adjuvant chemotherapies with surgery and radiotherapy. Multi-agent chemotherapy comprising vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide (VDC-IE) is widely used for ESFT, and the interval between each course is very important for maintaining the intensity and effect of chemotherapy.

Materials and methods

Clinical information of patients who received PBT and VDC-IE between April 2009 and May 2016 was collected retrospectively. The intervals between each course of VDC-IE and adverse events were assessed.

Results

Fifteen patients were evaluated. No delays in the intervals of chemotherapy due to transfer were observed. There were no adverse events caused during/just after transfer and no increases in adverse events. The estimated 4-year overall and event-free survival rates were 94.6% and 84.8%, respectively.

Discussion

Although the results of efficacy are preliminary, survival rates were comparable with past studies. More experience and follow-up are required to further assess the efficacy of PBT for patients with ESFT.

Conclusion

Multidisciplinary therapy for children with ESFT involving transfer to our hospital for PBT during VDC-IE was feasible without treatment delay or an increase in adverse events.  相似文献   

9.

Background

Posaconazole is used for the prophylaxis of invasive fungal disease (IFD). Previous studies have shown it to be cost-effective compared to fluconazole/itraconazole. However, posaconazole has never been economically evaluated in developing countries.

Aims

The aim of the present study was to perform a cost-effectiveness analysis of posaconazole compared to fluconazole in public (SUS) and private hospitals (PHS) in Brazil.

Methods

A cost-effectiveness simulation was conducted on the basis of a pivotal study on the use of posaconazole in acute myeloid leukemia (AML) patients, adjusting the costs to Brazilian data.

Results

A pharmacoeconomic analysis was performed on a hypothetical sample of 100 patients in each drug group. The total cost of posaconazole use alone was USD$ 220,656.31, whereas that for fluconazole was USD$ 83,875.00. Our results showed that patients with IFD remain hospitalized for an additional 12 days, at an average cost of USD$ 850.85 per patient per day. The total money spent by PHS for 100 patients for 100 days was USD$ 342,318.00 for the posaconazole group and USD$ 302,039.00 for the fluconazole group. An analysis of sensitivity (10%) revealed no intergroup difference.

Conclusions

In Brazil posaconazole is cost-effective, and should be considered for the prophylaxis of patients with AMD/myelodysplasia (AML/MDS) undergoing chemotherapy.  相似文献   

10.

Aim

This study evaluated the frequency and long-term dynamics of early and late post irradiation damage after proton–photon or photon therapy for locally advanced prostate cancer.

Background

The results of a randomized study of proton–photon or photon therapy using several fractionation regimes were analyzed in 272 patients with high and intermediate risk of progression.

Materials and methods

Three variants of proton boost fractionation were studied sequentially: 3.0 (8 daily fractions), 4.0 (5 fractions, 3 or 5 fractions/week), and 5.5 (3 fractions, 3 fractions/week) Gy(RBE).

Results

A significant decrease in the severity of both acute and late gastrointestinal injuries is achievable with a proton beam. The dynamics of late gastrointestinal and genitourinary toxicity over a 10-year period were generally characterized by a decrease in severity of morbidity by 30% and 15%, respectively.

Conclusions

Local irradiation with a fractional dose of 3.0–5.5 Gy(RBE) and a cumulative dose of 28.0–28.8 Gy(RBE) for protons significantly reduces the early and late rectitis severity, but does not reduce the risk of lower urinary tract injuries. Fractionation regimens do not significantly differ in toxicity levels.  相似文献   

11.
12.

Aim

The present retrospective study was to compare toxicity and survival outcomes in a group of low-risk PCa patients treated with either the preoperative planning technique (145?Gy) or the real-time IoP technique (160?Gy).

Background

The two most common permanent seed implantation techniques are preoperative planning (PP) with 145?Gy and real-time intraoperative planning (IoP) with 160?Gy. Although IoP has largely replaced PP at many centres in recent years, few studies have directly compared these two techniques.

Materials and methods

Retrospective study of 408 patients with low-risk PCa treated with permanent seed implant brachytherapy at our institution between October 2003 and December 2014. Of these, 187 patients were treated with PP at a dose of 145?Gy while 221 received real-time IoP with 160?Gy.

Results

At a median follow up of 90 months, 5- and 8-year rates of biochemical relapse-free survival (BRFS) were 94.8% and 86% with the IoP technique versus 90.8% and 83.9%, respectively, with PP. The maximum dose to the urethra was <217?Gy with both techniques. Despite the higher dose, IoP did not cause any significant increase in toxicity (p?=?0.11).

Conclusions

The present study shows that real-time intraoperative brachytherapy at a dose of 160?Gy yield better biochemical control than preoperative planning at 145?Gy. In addition, urinary toxicity did not increase, despite the dose escalation, probably because the dose constraints to the urethra were met despite the increased dose escalation. These findings support the use of real-time IoP.  相似文献   

13.
14.

Background

The role of culture-independent techniques (galactomannan, (1-3)-β-d-glucan) in the early diagnosis of invasive fungal diseases (IFD) is well assessed in hematological patients, but there are no clear conclusions in patients with chronic obstructive pulmonary disease (COPD).

Aims

To study the usefulness of nonculture-based techniques in the diagnosis of IFD in COPD-patients at risk for IFD.

Methods

A prospective observational study based on monitoring COPD patients at risk for IFD during 2007–2010 was carried out. The presence of galactomannan, (1-3)-β-d-glucan and an indirect immunofluorescence of Candida albicans germ tube specific antibodies (CAGTA) were performed.

Results

Among 43 COPD patients, 16 (37.2%) were diagnosed with IFD: seven cases were proven IFD (five invasive candidemia – IC, one invasive aspergillosis – IA and a rhinocerebral zygomycosis) and nine probable IFD (seven IA and two IC). In the diagnosis of IC and IA, the negative predictive value (NPV) of (1-3)-β-d-glucan was 100%. Regarding CAGTA in IC, NPV was 96.2%. Finally, NPV of galactomannan in IA was 91.2%. The area under the ROC curve for (1-3)-β-d-glucan in IC and for the rest of the IFD cases was 0.86 (95% CI, 0.79–0.93) and 0.60 (95% CI, 0.43–0.77), for CAGTA in IC was 0.83 (95% CI, 0.74–0.91) and for galactomannan in IA was 0.71 (95% CI, 0.56–0.85). Positive (1-3)-β-d-glucan preceded the growth of Candida (average of 1.7 days) in blood culture.

Conclusions

In COPD patients at risk for IFD the assayed techniques are especially useful to rule out the presence of IFD.  相似文献   

15.

Background

Candida tropicalis is an increasingly important human pathogen which usually affects neutropenic oncology patients with common hematogenous seeding to peripheral organs and high mortality rates. Candida pathogenicity is facilitated by several virulence attributes, including secretion of hydrolytic enzymes; however, little is known regarding the C. tropicalis ability to secrete them and their role in the disease.

Aims

To confirm by molecular means the identification of 187 clinical isolates (127 from blood, 52 from urine, and 8 from diverse clinical origins) phenotypically identified as C. tropicalis, and to investigate their in vitro aspartyl proteinase, phospholipase, esterase, hemolysin, DNase and coagulase activities.

Methods

The molecular confirmation was performed by ITS sequencing, and the enzymatic determinations were conducted using plate assays with specific substrates, with the exception of coagulase, which was determined by the classical tube test.

Results

The majority of the strains exhibited a very strong or strong activity of aspartyl proteinase, phospholipase and esterase. A 4.7% of the bloodstream isolates were hemolysin producers, and all were negative for the coagulase and DNase assays.

Conclusions

Very strong activities of aspartyl proteinase, phospholipase and esterase profiles were detected, and a statistical association between phospholipase production and blood and urine isolates was found.  相似文献   

16.

Introduction

Numerous studies have shown that economic crises are linked to a worsening of health conditions of the population. During the current economic crisis in Spain, there have been significant cuts in social and health services and a general worsening of the emotional well-being of the population. All these changes could have an impact on the health of the population, especially in the most vulnerable groups like older people.

Material and methods

The evolution of life expectancy and healthy life years in the period 2004-2014 have been examined in order to examine the health status of people aged 65 years and over in Spain during the economic crisis.

Results

Changes are observed in the evolution of healthy life years of people aged 65 years and over, particularly in the case of women.

Conclusions

The results do not show that the current economic crisis has had a negative impact on the health conditions of older people in Spain, but there has been a decline in their well-being and quality of life.  相似文献   

17.

Objective

The current study proposes an automated machine learning approach for the quantification of cells in cell death pathways according to DNA fragmentation.

Methods

A total of 17 images of kidney histological slide samples from male Wistar rats were used. The slides were photographed using an Axio Zeiss Vert.A1 microscope with a 40x objective lens coupled with an Axio Cam MRC Zeiss camera and Zen 2012 software. The images were analyzed using CellProfiler (version 2.1.1) and CellProfiler Analyst open-source software.

Results

Out of the 10,378 objects, 4970 (47,9%) were identified as TUNEL positive, and 5408 (52,1%) were identified as TUNEL negative. On average, the sensitivity and specificity values of the machine learning approach were 0.80 and 0.77, respectively.

Conclusion

Image cytometry provides a quantitative analytical alternative to the more traditional qualitative methods more commonly used in studies.  相似文献   

18.

Objective

A new method was presented to prepare clinical-grade human adipose-derived stromal stem cells (ASCs) and its safety in vitro, such as biological characteristics and genetic features alteration were investigated.

Methods

The morphology of the ASCs which were cultured in vitro using serum-free medium was observed. Cell cycle and CD markers profile were tested by flow cytometry, while karyotype was analyzed by the chromosome G-banding technology. Growth factors expression was tested by ELISA and tumor-related genes were analyzed by the real-time PCR, respectively.

Results

ASCs were adult stem cells with spindle shape. The proliferation ratio of ASCs began to slow down after 10 passages, and was significant after 15 passages. Cell cycle analysis revealed that the percentage of G2 phase and S phase cells was stable. There was no obvious missing, translocation or dislocation in terms of karyotype. Expression level of tumor relevant genes and cytokines at different passages had no significant difference.

Conclusions

The clinical-grade ASCs prepared with this new method, less than ten passages, was safe for clinical trials.  相似文献   

19.

Objective

To determine the frequency of successful aging (SA) and its relationship with frailty in an elderly population.

Material and methods

An analytical cross-sectional study of subjects ≥60 years of age seen as outpatients in a general hospital. Successful aging was defined as scores of ≥ 90 in the Barthel index and ≤ 2 in the Pfeiffer test. Frailty was determined using the Fried criteria.

Results

The study included 400 subjects (272 women and 128 men), with a mean age of 71.6 ± 8.2 years. The SA frequency was 40.4%. frail status was statistically higher in non-successful aging subjects than in SA subjects (161.7 versus 7.9%; P<.001). Women were more frequently frail, while being a pensioner/retired and married were associated less frequently with frailty.

Conclusions

Successful aging is associated with a lower level of frailty.  相似文献   

20.

Aim

Does coping with the loss of ability depend on self-esteem and emotional control?

Background

Persons who experience losses in two dimensions, i.e. health and ability can deal with the loss by physical therapy, and also by mental and socio-professional rehabilitation. But far and foremost, it is the personality of the person who experiences the loss that matters most.

Materials and methods

The study included 37 patients after mastectomy. They were divided into two groups according to the time elapsed from cancer diagnosis. The study was conducted using the Questionnaire on Coping With Ability Loss (P. Wolski), Self-Esteem Loss (M. Rosenberg,) and the Courtauld Emotional Control Scale – CECS.

Results

In Group I, the higher level of acceptance in the QCAL test, the higher self-esteem. The more depression experienced by individuals, the lower is their level of self-esteem or the less depression experienced, the higher the self-esteem. In Group II, the higher the level of depression, the lower the level of anger. The greater the struggle, the lower level of anger. The lower the level of depression and struggle, the higher the level of emotion control.

Conclusions

Women diagnosed no longer than five years back do not differ from those diagnosed further back in terms of copying with the loss of ability, self-esteem and emotional control.  相似文献   

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