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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 -
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 -
Scientific Reports Sep 2015Many types of KIT mutations have been observed in gastrointestinal stromal tumors (GISTs), but their prognostic and predictive significance are still unclear. A... (Meta-Analysis)
Meta-Analysis Review
Many types of KIT mutations have been observed in gastrointestinal stromal tumors (GISTs), but their prognostic and predictive significance are still unclear. A meta-analysis and literature review were conducted to estimate the contribution of KIT mutations in prognostic parameters and clinic-pathological significance of GISTs. A total of 18 relevant articles from PubMed, EMBASE and Web of Science databases were included in this study. The frequency of KIT mutation was significantly increased in the GIST patients with higher mitosis (≥5/50 high-power fields (HPFs) and larger size (≥5 cm) of tumors than in those with lower MI (≤5/50HPFs) and smaller size (≤5 cm) of GISTs respectively. The rate of KIT mutation was not significantly changed between GISTs in stomachs and in small intestines. KIT mutational status has prognostic significance for patients' outcome. GIST patients with KIT exon 9 mutations have higher risk of progression than those with exon 11 mutations. 5 year relapse-free survival (RFS) rate was significantly higher in patients with KIT exon 11 deletion than in those with other type of KIT exon 11 mutations. The deletion involving KIT exon 11, particularly codons 557-558, is a valuable predictor of prognosis for patients with GISTs.
Topics: Exons; Gastrointestinal Stromal Tumors; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Mutation; Odds Ratio; Prognosis; Proto-Oncogene Proteins c-kit; Receptor, Platelet-Derived Growth Factor alpha; Risk
PubMed: 26349547
DOI: 10.1038/srep13718