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Asian Journal of Andrology 2020Peripheral nerve damage, such as that found after surgery or trauma, is a substantial clinical challenge. Much research continues in attempts to improve outcomes after...
Peripheral nerve damage, such as that found after surgery or trauma, is a substantial clinical challenge. Much research continues in attempts to improve outcomes after peripheral nerve damage and to promote nerve repair after injury. In recent years, low-intensity pulsed ultrasound (LIPUS) has been studied as a potential method of stimulating peripheral nerve regeneration. In this review, the physiology of peripheral nerve regeneration is reviewed, and the experiments employing LIPUS to improve peripheral nerve regeneration are discussed. Application of LIPUS following nerve surgery may promote nerve regeneration and improve functional outcomes through a variety of proposed mechanisms. These include an increase of neurotrophic factors, Schwann cell (SC) activation, cellular signaling activations, and induction of mitosis. We searched PubMed for articles related to these topics in both in vitro and in vivo animal research models. We found numerous studies, suggesting that LIPUS following nerve surgery promotes nerve regeneration and improves functional outcomes. Based on these findings, LIPUS could be a novel and valuable treatment for nerve injury-induced erectile dysfunction.
Topics: Animals; Cell Proliferation; Cell Survival; Erectile Dysfunction; Humans; Male; Mitosis; Nerve Growth Factors; Nerve Regeneration; Penis; Peripheral Nerve Injuries; Pudendal Nerve; Schwann Cells; Signal Transduction; Ultrasonic Therapy; Ultrasonic Waves
PubMed: 31535626
DOI: 10.4103/aja.aja_95_19 -
BMC Surgery Aug 2019By comparing the long-term prognostic outcomes after pancreaticoduodenectomy (PD) and limited resection (LR), this study aimed to investigate the optimal surgical... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
By comparing the long-term prognostic outcomes after pancreaticoduodenectomy (PD) and limited resection (LR), this study aimed to investigate the optimal surgical modality for duodenal gastrointestinal stromal tumors (GISTs).
METHODS
Two authors independently searched PubMed, Web of Science, Embase, and the Cochrane Library for published articles comparing the long-term prognostic and clinicopathological factors of duodenal GIST patients undergoing PD versus LR. Relevant information was extracted and analyzed.
RESULTS
After screening, 10 items comprising 623 cases were eventually included. This meta-analysis explicitly indicated that PD treatment was associated with worse long-term prognosis (hazard ratio = 1.93; 95% confidence interval [CI], 1.39-2.69; p < 0.001; I = 0) and more complications (odds ratio [OR] = 2.90; 95% CI, 1.90-4.42; p < 0.001; I = 10%) than LR treatment. Nevertheless, for duodenal GISTs, PD was related to the following clinicopathological features: invasion of the second part of the duodenum (OR = 3.39; 95% CI, 1.69-6.79; p < 0.001; I = 50%), high-degree tumor mitosis (> 5/50 high-power fields; OR = 2.24; 95% CI, 1.42-3.52; p < 0.001; I = 0), and high-risk classification (OR = 3.17; 95% CI; 2.13-4.71; p < 0.001; I = 0).
CONCLUSIONS
Since PD is associated with worse long-term prognosis and more complications, its safety and efficacy should be ascertained. Our findings recommend the use of LR to obtain negative incision margins when conditions permit it.
Topics: Duodenal Neoplasms; Duodenum; Gastrointestinal Stromal Tumors; Humans; Margins of Excision; Middle Aged; Pancreaticoduodenectomy; Prognosis
PubMed: 31455328
DOI: 10.1186/s12893-019-0587-4 -
Head and Neck Pathology Jun 2020Solitary fibrous tumors (SFT) arising in the head and neck region are uncommon yet well-recognized entities. Their biologic behavior and management still need to be... (Meta-Analysis)
Meta-Analysis
Solitary fibrous tumors (SFT) arising in the head and neck region are uncommon yet well-recognized entities. Their biologic behavior and management still need to be elucidated. Systematically reviewing all published cases of SFT involving the head and neck region since 1991, a pooled meta-analysis was conducted to evaluate various demographic and tumor characteristics. 587 SFT in the head and neck have been reported; 343 met pooled analysis inclusion criteria. 61% of cases presented as a new mass; 89% were painless. Median onset of symptoms prior to evaluation was 8 months. Pre-operative local invasion and malignant histological features (hemorrhage, necrosis, mitoses > 4/10 hpf) were not statistically associated with decreased recurrence-free survival. Positive surgical margins was the only factor associated with shorter recurrence-free survival (p < 0.001). The evidence presented herein reveals novel associations between clinical presentation and tumor characteristics that provide otolaryngologists with new insight into SFT tumor behavior, thus prompting further investigations.
Topics: Head and Neck Neoplasms; Humans; Solitary Fibrous Tumors
PubMed: 31338745
DOI: 10.1007/s12105-019-01058-6 -
Journal of Assisted Reproduction and... Aug 2019Non-aneuploid recurrent pregnancy loss (RPL) affects approximately 100,000 pregnancies worldwide annually. Exome sequencing (ES) may help uncover the genetic etiology of...
PURPOSE
Non-aneuploid recurrent pregnancy loss (RPL) affects approximately 100,000 pregnancies worldwide annually. Exome sequencing (ES) may help uncover the genetic etiology of RPL and, more generally, pregnancy loss as a whole. Previous studies have attempted to predict the genes that, when disrupted, may cause human embryonic lethality. However, predictions by these early studies rarely point to the same genes. Case reports of pathogenic variants identified in RPL cases offer another clue. We evaluated known genetic etiologies of RPL identified by ES.
METHODS
We gathered primary research articles from PubMed and Embase involving case reports of RPL reporting variants identified by ES. Two authors independently reviewed all articles for eligibility and extracted data based on predetermined criteria. Preliminary and amended analysis isolated 380 articles; 15 met all inclusion criteria.
RESULTS
These 15 articles described 74 families with 279 reported RPLs with 34 candidate pathogenic variants in 19 genes (NOP14, FOXP3, APAF1, CASP9, CHRNA1, NLRP5, MMP10, FGA, FLT1, EPAS1, IDO2, STIL, DYNC2H1, IFT122, PADI6, CAPS, MUSK, NLRP2, NLRP7) and 26 variants of unknown significance in 25 genes. These genes cluster in four essential pathways: (1) gene expression, (2) embryonic development, (3) mitosis and cell cycle progression, and (4) inflammation and immunity.
CONCLUSIONS
For future studies of RPL, we recommend trio-based ES in cases with normal parental karyotypes. In vitro fertilization with preimplantation genetic diagnosis can be pursued if causative variants are found. Utilization of other sequencing technologies in concert with ES should improve understanding of the causes of early embryonic lethality in humans.
Topics: Abortion, Habitual; Female; Genes, Essential; Humans; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Exome Sequencing
PubMed: 31273585
DOI: 10.1007/s10815-019-01499-6 -
Topics in Current Chemistry (Cham) May 2019As the emergence of resistance to clinical cancer treatments poses a significant problem in cancer management, there is a constant need to explore novel anticancer...
Systematic Review on Cytotoxic and Anticancer Potential of N-Substituted Isatins as Novel Class of Compounds Useful in Multidrug-Resistant Cancer Therapy: In Silico and In Vitro Analysis.
As the emergence of resistance to clinical cancer treatments poses a significant problem in cancer management, there is a constant need to explore novel anticancer agents which have the ability to overcome multidrug resistance (MDR) mechanisms. The search for the development of novel isatin-based antitumor agents accelerated after the approval by the Food and Drug Administration (FDA) of sunitinib malate, a C-3 isatin derivative, as a multitargeted receptor tyrosine kinase inhibitor. However, it is interesting to note that, over the last decade, various N-substituted analogs of isatin with intact carbonyl functionalities have been found to show more promising anticancer potential than its C-3 derivatives. Microtubule-targeting agents are a class of anticancer drugs which affect mitosis by targeting microtubules and suppressing their dynamic behavior. This review presents a systematic compilation of the in vitro cytotoxic and anticancer properties of various N-substituted isatins and illustrates their mechanism of action to overcome MDR by acting as microtubule-destabilizing agents. Predictions of the biological activities and cytotoxic effects of potential N-substituted isatins against various cancer cell lines have also been performed using the PASS computer-aided drug discovery program. Findings from such in vitro and in silico studies will act as a guide for the development of structure-activity relationship and will facilitate the design and exploration of more potent analogs of isatin with high potency and lower side effects for treatment of drug-resistant cancer. Mechanism of action of N-substituted isatin as microtubule-destabilizing agent on tumor cells. N-Substituted isatins bind to colchicine binding site on β-tubulin, which inhibits microtubule polymerization and thereby destabilizes microtubule dynamics, resulting in mitotic arrest leading to tumor cell growth suppression.
Topics: Antineoplastic Agents; Cell Proliferation; Computer Simulation; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; In Vitro Techniques; Isatin; Microtubules; Quantitative Structure-Activity Relationship
PubMed: 31073777
DOI: 10.1007/s41061-019-0240-9 -
Annals of Surgical Oncology May 2019This systematic review and meta-analysis aimed to investigate local recurrence (LR) rates among the three grades (benign, borderline, and malignant) of phyllodes tumors... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and meta-analysis aimed to investigate local recurrence (LR) rates among the three grades (benign, borderline, and malignant) of phyllodes tumors (PTs). The study also assessed various risk factors for LR.
METHODS
Electronic articles published between 1 January 1995 and 31 May 2018, were searched and critically appraised. The authors independently reviewed the abstracts and extracted data for LR rates and LR risk factors.
RESULTS
The review incorporated 54 studies with 9234 individual cases. The pooled LR rates were 8% for benign, 13% for borderline, and 18% for malignant PTs. The risk of LR was significantly increased by borderline versus benign PTs (odds ratio [OR] 2.00; 95% confidence interval [CI] 1.68-2.38) and malignant versus borderline PTs (OR 1.28; 95% CI 1.05-1.55). The significant risk factors for LR were mitoses, tumor border (infiltrating vs. pushing), stromal cellularity (moderate/severe vs. mild), stromal atypia (severe vs. mild/absent), stromal overgrowth (severe vs. mild/absent), and tumor necrosis (positive vs. negative). Age and tumor size were not associated with LR risk. The subgroup analysis showed that breast-conserving surgery versus mastectomy and positive versus negative surgical margins were significantly associated with an increased LR risk only in malignant PTs.
CONCLUSIONS
The risk of LR was significantly increased from benign to borderline to malignant PTs. Mitoses, tumor border, stromal cellularity, stromal atypia, stromal overgrowth, tumor necrosis, type of surgery, and surgical margin status may be risk factors for LR. Different management strategies could be considered for different PT grades.
Topics: Breast Neoplasms; Female; Humans; Neoplasm Recurrence, Local; Phyllodes Tumor; Risk Factors
PubMed: 30617873
DOI: 10.1245/s10434-018-07134-5 -
Turk Patoloji Dergisi 2018The aim of this study was to evaluate the prognostic factors of recurrence in uterine tumors resembling ovarian sex-cord tumors (UTROSCT) and to determine...
OBJECTIVE
The aim of this study was to evaluate the prognostic factors of recurrence in uterine tumors resembling ovarian sex-cord tumors (UTROSCT) and to determine clinical-pathological characteristics, treatment options and outcome.
MATERIAL AND METHOD
An electronic literature search was conducted from 1976 to 2018. After the comprehensive evaluation and conjunction with our case, the study included 79 cases.
RESULTS
The median age at initial diagnosis was 49 years (range; 16-86 years). The age was under 40 years in 21 (26.6%) patients. Whereas 68 patients underwent at least hysterectomy, 9 patients had organ sparing surgery. There was necrosis in 4 (5.1%) patients, atypia in 16 (20.3%) patients, and infiltrative tumor border in 34 (43%) patients. At least one mitosis per 10 high power fields was determined in 36 (45.5%) patients. The tumor involved at least part of the myometrium in 54 (68.3%) patients. Median follow-up time was 30 months (range; 3-296 months). Recurrence was determined in 5 (6.3%) patients. The disease free survival (DFS) was significantly related only to surgery type. None of the pathologic features were associated with DFS. The 5-year DFS was 86% and 96% in patients who underwent organ sparing surgery or not, respectively (p=0.038).
CONCLUSION
The accurate pathologic diagnosis of UTROSCT has great value in shaping surgical management and management during the follow-up period. Organ sparing surgery was related to poor DFS. Although recurrence is rare, it should be kept in mind for patients with UTROSCT.
Topics: Disease-Free Survival; Female; Humans; Hysterectomy; Middle Aged; Neoplasm Recurrence, Local; Organ Sparing Treatments; Sex Cord-Gonadal Stromal Tumors; Uterine Neoplasms
PubMed: 30421416
DOI: 10.5146/tjpath.2018.01429 -
Journal of Cellular and Molecular... Jul 2018Septins are a conserved family of cytoskeletal GTPases present in different organisms, including yeast, drosophila, Caenorhabditis elegans and humans. In humans, septins...
Septins are a conserved family of cytoskeletal GTPases present in different organisms, including yeast, drosophila, Caenorhabditis elegans and humans. In humans, septins are involved in various cellular processes, including exocytosis, apoptosis, leukemogenesis, carcinogenesis and neurodegeneration. Septin 7 is unique out of 13 human septins. Mammalian septin 6, septin 7, septin 2 and septin 9 coisolate together in complexes to form the core unit for the generation of the septin filaments. Physiological septin filaments are hetero-oligomeric complexes consisting of core septin hexamers and octamers. Furthermore, septin 7 plays a crucial role in cytokinesis and mitosis. Septin 7 is localized to the filopodia and branches of developing hippocampal neurons, and is the most abundant septin in the adult rat forebrain as well as a structural component of the human and mouse sperm annuli. Septin 7 is crucial to the spine morphogenesis and dendrite growth in neurons, and is also a structural constituent of the annulus in human and mouse sperm. It can suppress growth of some tumours such as glioma and papillary thyroid carcinoma. However, the molecular mechanisms of involvement of septin 7 in human disease, especially in the development of cancer, remain unclear. This review focuses on the structure, function and mechanism of septin 7 in vivo, and summarizes the role of septin 7 in cell proliferation, cytokinesis, nervous and reproductive systems, as well as the underlying molecular events linking septin 7 to various diseases, such as Alzheimer's disease, schizophrenia, neuropsychiatric systemic lupus erythematosus, tumour and so on.
Topics: Alzheimer Disease; Calcium; Cell Cycle Proteins; Cell Proliferation; Humans; Lupus Vasculitis, Central Nervous System; Nervous System; Schizophrenia; Septins
PubMed: 29602250
DOI: 10.1111/jcmm.13623 -
Oncotarget Aug 2017Polo-like kinases 1 (PLK1), a key regulator of mitosis, plays an essential role in maintaining genomic stability. Up-regulation of PLK1 was found in tumorigenesis and... (Review)
Review
Polo-like kinases 1 (PLK1), a key regulator of mitosis, plays an essential role in maintaining genomic stability. Up-regulation of PLK1 was found in tumorigenesis and tumor progression of diverse cancers. However, the clinicopathological and prognostic implications of PLK1 in breast cancer (BC) have yet to be unveiled. Therefore, using PubMed, Web of Science, Embase, and Chinese databases, we conducted a meta-analysis to define the potential clinical value of PLK1 in BC. Eleven eligible articles with 2481 patients enrolled were included in the present meta-analysis, of which eight studies reported on the relationship between PLK1 expression and clinicopathological features, and nine studies provided survival data in BC patients. Furthermore, the results revealed that high PLK1 levels were significantly associated with larger tumor size (OR=1.703, 95%CIs: 1.315-2.205, <0.001), higher pathological grading (OR=6.028, 95%CIs: 2.639-13.772, <0.001), and lymph node metastasis (OR= 1.524, 95%CIs: 1.192-1.950, =0.001). Moreover, PLK1 was found to be a valuable factor for distinguishing lobular BC from ductal BC with the pooled OR=0.215(95%CIs: 0.083-0.557, =0.002). Analysis of included data showed that high PLK1 expression significantly indicated worse overall survival for BC patients (HR= 3.438, 95%CIs: 2.293-5.154, <0.001), as well as worse cancer specific survival and disease-free survival (HR=2.414, 95%CIs: 1.633-3.567, <0.001 and HR= 2.261, 95%CIs: 1.796-2.951, <0.001, respectively). This quantitative meta-analysis suggests that high PLK1 expression is a credible indicator for the progression of BC and confirms a higher risk of a worse survival rate in patients with BC.
PubMed: 28915707
DOI: 10.18632/oncotarget.17301 -
Chinese Clinical Oncology Aug 2017Tumor treating fields (TTF, Optune®), one of the low-intensity alternating electric fields, have been demonstrated to disrupt mitosis and inhibit tumor growth with... (Review)
Review
BACKGROUND
Tumor treating fields (TTF, Optune®), one of the low-intensity alternating electric fields, have been demonstrated to disrupt mitosis and inhibit tumor growth with antimitotic properties in a variety of tumor types. The Food and Drug Administration (FDA) of the United States approved TTF for recurrent GBM and newly diagnosed GBM in 2011 and 2015, respectively.
METHODS
A systematic review was conducted regarding the relevant studies published between January 1, 2000, and May 31, 2017 in PubMed database. The search term included "Tumor Treating Fields", "Optune", "TTF", "Novocure", and "GBM". This review summarizes the mechanism of action, efficacy, and adverse events based on pre-clinical studies and clinical trials for TTF in GBM.
RESULTS
Pre-clinical studies showed that TTF could inhibit tumor growth in vitro and in vivo by disrupting mitosis, inducing cell cycle arrest and apoptosis. Two randomized phase III trials evaluated the efficacy and safety of TTF in GBM patients. It was revealed that the combination of TTF and standard chemotherapy (temozolomide) prolonged the progression-free survival (PFS) and overall survival (OS) without systemic safety issues in newly diagnosed GBM (EF-14 trial). For recurrent GBM, the efficacy of TTF monotherapy was shown to be equivalent in PFS and OS without systemic adverse events when compared to the control group that received best physicians-chosen chemotherapies (EF-11 trial).
CONCLUSIONS
The advantages of TTF in GBM treatment, including non-invasive antitumor effect, superior therapeutic benefit in combination with chemotherapy, and minimal systematic toxicity, have been demonstrated in pre-clinical data and randomized phased III clinical trials. Future investigations will be needed to explore combinations of chemotherapy, radiation therapy, targeted therapy, as well as immunotherapy with this novel anti-tumor treatment modality to achieve additive or synergistic therapeutic benefit for GBM and other solid tumors.
Topics: Antineoplastic Agents, Alkylating; Brain Neoplasms; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Dacarbazine; Disease-Free Survival; Electric Stimulation Therapy; Glioblastoma; Humans; Randomized Controlled Trials as Topic; Safety; Temozolomide; Treatment Outcome; United States
PubMed: 28841803
DOI: 10.21037/cco.2017.06.29