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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 -
Cells Jun 2021Telomeres are aging biomarkers, as they shorten while cells undergo mitosis. The aim of this study was to evaluate whether psychiatric disorders marked by psychological...
Telomeres are aging biomarkers, as they shorten while cells undergo mitosis. The aim of this study was to evaluate whether psychiatric disorders marked by psychological distress lead to alterations to telomere length (TL), corroborating the hypothesis that mental disorders might have a deeper impact on our physiology and aging than it was previously thought. A systematic search of the literature using MeSH descriptors of psychological distress ("Traumatic Stress Disorder" or "Anxiety Disorder" or "depression") and telomere length ("cellular senescence", "oxidative stress" and "telomere") was conducted on PubMed, Cochrane Library and ScienceDirect databases. A total of 56 studies (113,699 patients) measured the TL from individuals diagnosed with anxiety, depression and posttraumatic disorders and compared them with those from healthy subjects. Overall, TL negatively associates with distress-related mental disorders. The possible underlying molecular mechanisms that underly psychiatric diseases to telomere shortening include oxidative stress, inflammation and mitochondrial dysfunction linking. It is still unclear whether psychological distress is either a cause or a consequence of telomere shortening.
Topics: Humans; Mental Disorders; Mitochondria; Oxidative Stress; Telomere; Telomere Shortening
PubMed: 34200513
DOI: 10.3390/cells10061423 -
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 -
Journal of Clinical Medicine Apr 2023Chorangiocarcinoma is a very rare and misdiagnosed placental neoplasm. The unique morphologic features of the lesion distinguish it from other trophoblastic tumors and... (Review)
Review
Chorangiocarcinoma is a very rare and misdiagnosed placental neoplasm. The unique morphologic features of the lesion distinguish it from other trophoblastic tumors and vascular abnormalities. We present a systematic review of the literature to provide clarity on chorangiocarcinoma entity and biology. A literature search was carried out in December 2022 using the keywords "Placental chorangiocarcinoma", "Chorangioma", "Placenta", and "Throphoblast proliferation". Articles published from 1988 to 2022 were obtained from Scopus, Google Scholar, and PUBMED. In our review, we examined maternal age, gestational age at the time of delivery, parity, type of pregnancy, placental weight, ultrasound features of the placenta, macroscopic examination and tumor size, microscopic examination, immunostaining, maternal beta-human chorionic gonadotropin, fetal and maternal outcome. Eight manuscripts were detected. They are all case reports. The macroscopic characteristics of the lesions were represented by the presence of a grey-yellow-white color well-demarcated round nodule. Microscopically, all the authors described typical aspects of malignancy as a high rate of mitosis, nuclear atypia and necrotic areas. In some cases, the presence of AE1/AE3 cytoplasmic positivity, p63 nuclear staining, and beta-human chorionic gonadotropin (BHCG) were reported. A good fetal outcome was reported in all cases of newborns with normal birth weight, except one with fetal growth restriction. Maternal outcome was good in all cases except one with maternal lung metastasis three months after delivery. The clinical course has probably underestimated the real incidence of the pathology. Only greater knowledge of its histology and its clinical course will allow us to evaluate the real prevalence of the disease.
PubMed: 37176506
DOI: 10.3390/jcm12093065 -
Cancer Cell International 2020One of the most prominent features of tumor cells is uncontrolled cell proliferation caused by an abnormal cell cycle, and the abnormal expression of cell cycle-related... (Review)
Review
One of the most prominent features of tumor cells is uncontrolled cell proliferation caused by an abnormal cell cycle, and the abnormal expression of cell cycle-related proteins gives tumor cells their invasive, metastatic, drug-resistance, and anti-apoptotic abilities. Recently, an increasing number of cell cycle-associated proteins have become the candidate biomarkers for early diagnosis of malignant tumors and potential targets for cancer therapies. As an important cell cycle regulatory protein, Cell Division Cycle 25C (CDC25C) participates in regulating G2/M progression and in mediating DNA damage repair. CDC25C is a cyclin of the specific phosphatase family that activates the cyclin B1/CDK1 complex in cells for entering mitosis and regulates G2/M progression and plays an important role in checkpoint protein regulation in case of DNA damage, which can ensure accurate DNA information transmission to the daughter cells. The regulation of CDC25C in the cell cycle is affected by multiple signaling pathways, such as cyclin B1/CDK1, PLK1/Aurora A, ATR/CHK1, ATM/CHK2, CHK2/ERK, Wee1/Myt1, p53/Pin1, and ASK1/JNK-/38. Recently, it has evident that changes in the expression of CDC25C are closely related to tumorigenesis and tumor development and can be used as a potential target for cancer treatment. This review summarizes the role of CDC25C phosphatase in regulating cell cycle. Based on the role of CDC25 family proteins in the development of tumors, it will become a hot target for a new generation of cancer treatments.
PubMed: 32518522
DOI: 10.1186/s12935-020-01304-w -
Frontiers in Oncology 2022The indications for sentinel lymph node biopsy (SLNB) for thin melanoma are still unclear. This meta-analysis aims to determine the positive rate of SLNB in thin...
BACKGROUND
The indications for sentinel lymph node biopsy (SLNB) for thin melanoma are still unclear. This meta-analysis aims to determine the positive rate of SLNB in thin melanoma and to summarize the predictive value of different high-risk features for positive results of SLNB.
METHODS
Four databases were searched for literature on SLNB performed in patients with thin melanoma published between January 2000 and December 2020. The overall positive rate and positive rate of each high-risk feature were calculated and obtained with 95% confidence intervals (CIs). Both unadjusted odds ratios (ORs) and adjusted ORs (AORs) of high-risk features were analyzed. Pooled effects were estimated using random-effects model meta-analyses.
RESULTS
Sixty-six studies reporting 38,844 patients with thin melanoma who underwent SLNB met the inclusion criteria. The pooled positive rate of SLNB was 5.1% [95% confidence interval (CI) 4.9%-5.3%]. Features significantly predicted a positive result of SLNB were thickness≥0.8 mm [AOR 1.94 (95%CI 1.28-2.95); positive rate 7.0% (95%CI 6.0-8.0%)]; ulceration [AOR 3.09 (95%CI 1.75-5.44); positive rate 4.2% (95%CI 1.8-7.2%)]; mitosis rate >0/mm2 [AOR 1.63 (95%CI 1.13-2.36); positive rate 7.7% (95%CI 6.3-9.1%)]; microsatellites [OR 3.8 (95%CI 1.38-10.47); positive rate 16.6% (95%CI 2.4-36.6%)]; and vertical growth phase [OR 2.76 (95%CI 1.72-4.43); positive rate 8.1% (95%CI 6.3-10.1%)].
CONCLUSIONS
The overall positive rate of SLNB in thin melanoma was 5.1%. The strongest predictor for SLN positivity identified was microsatellites on unadjusted analysis and ulceration on adjusted analysis. Breslow thickness ≥0.8 mm and mitosis rate >0/mm both predict SLN positivity in adjusted analysis and increase the positive rate to 7.0% and 7.7%. We suggest patients with thin melanoma with the above high-risk features should be considered for giving an SLNB.
PubMed: 35155254
DOI: 10.3389/fonc.2022.817510 -
Asian Pacific Journal of Cancer... 2012The vascular endothelial growth factor (VEGF) mediates vasculogenesis and angiogenesis through promoting endothelial cell growth, migration and mitosis, and has... (Review)
Review
BACKGROUND
The vascular endothelial growth factor (VEGF) mediates vasculogenesis and angiogenesis through promoting endothelial cell growth, migration and mitosis, and has involvement in cancer pathogenesis, progression and metastasis. However, the prognostic value of VEGF in patients with prostate cancer remains controversial.
OBJECTIVES
The aim of our study was to evaluate the prognostic value of VEGF in prostate cancer, and summarise the results of related research on VEGF.
METHODS
In accordance with an established search strategy, 11 studies with 1,529 patients were included in our meta-analysis. The correlation of VEGF-expression with overall survival and progression-free survival was evaluated by hazard ratio, either given or calculated.
RESULTS
The studies were categorized by introduction of the author, demographic data in each study, prostate cancer-relatived information, VEGF cut-off value, VEGF subtype, methods of hazard ratio (HR) estimation and its 95% confidence interval (CI). High VEGF-expression in prostate cancer is a poor prognostic factor with statistical significance for OS (HR=2.32, 95%CI: 1.40-3.24). However, high VEGF-expression showed no effect on poor PFS (HR=1.30, 95%CI: 0.88-1.72). Using Begg's, Egger's test and funnel plots, we confirmed lack of publication bias in our analysis.
CONCLUSION
VEGF might be regarded as a prognostic maker for prostate cancer, as supported by our meta-analysis. To achieve a more definitive conclusion enabling the clinical use of VEGF in prostate cancer, we need more high-quality interventional original studies following agreed research approaches or standards.
Topics: Biomarkers, Tumor; Clinical Trials as Topic; Humans; Male; Meta-Analysis as Topic; Prognosis; Prostatic Neoplasms; Vascular Endothelial Growth Factor A
PubMed: 23317235
DOI: 10.7314/apjcp.2012.13.11.5665 -
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 -
Frontiers in Oncology 2022Digital pathology with whole-slide imaging (WSI) has many potential clinical and non-clinical applications. In the past two decades, despite significant advances in WSI...
OBJECTIVE
Digital pathology with whole-slide imaging (WSI) has many potential clinical and non-clinical applications. In the past two decades, despite significant advances in WSI technology adoption remains slow for primary diagnosis. The aim of this study was to identify common pitfalls of WSI reported in validation studies and offer measures to overcome these challenges.
METHODS
A systematic search was conducted in the electronic databases Pubmed-MEDLINE and Embase. Inclusion criteria were all validation studies designed to evaluate the feasibility of WSI for diagnostic clinical use in pathology. Technical and diagnostic problems encountered with WSI in these studies were recorded.
RESULTS
A total of 45 studies were identified in which technical issues were reported in 15 (33%), diagnostic issues in 8 (18%), and 22 (49%) reported both. Key technical problems encompassed slide scan failure, prolonged time for pathologists to review cases, and a need for higher image resolution. Diagnostic challenges encountered were concerned with grading dysplasia, reliable assessment of mitoses, identification of microorganisms, and clearly defining the invasive front of tumors.
CONCLUSION
Despite technical advances with WSI technology, some critical concerns remain that need to be addressed to ensure trustworthy clinical diagnostic use. More focus on the quality of the pre-scanning phase and training of pathologists could help reduce the negative impact of WSI technical difficulties. WSI also seems to exacerbate specific diagnostic tasks that are already challenging among pathologists even when examining glass slides with conventional light microscopy.
PubMed: 35785212
DOI: 10.3389/fonc.2022.918580 -
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