Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174: 12/25/18

Τρίτη 25 Δεκεμβρίου 2018

Dermoscopic Monitoring for Treatment and Follow-Up of Actinic Keratosis With 5-Aminolaevulinic Acid Photodynamic Therapy

Technology in Cancer Research &Treatment, Volume 17, Issue , January 2018.

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Association of Single-Nucleotide Polymorphisms in Monoubiquitinated FANCD2-DNA Damage Repair Pathway Genes With Breast Cancer in the Chinese Population

Technology in Cancer Research &Treatment, Volume 17, Issue , January 2018.

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Effect of individual and combined exposure of Fe 2 O 3 nanoparticles and oxytetracycline on their bioaccumulation by rice ( Oryza sativa L.)

Abstract

Purpose

It has been reported the bioaccumulation of γ-ferric oxide nanoparticles (Fe₂O₃ NPs) or oxytetracycline (OTC) in crops. However, there have been little references investigating their uptake and bioaccumulation in crops after the combined exposure. The present study focused on Fe₂O₃ NPs and OTC accumulation on root surface and in the tissues of rice (Oryza sativa L.) seedlings under combined exposure. And, the interactive influence mechanism was also discussed.

Materials and methods

Hydroponic experiments were conducted to investigate the Fe and OTC accumulation on root surface and in rice tissues under individual and combined exposure of Fe₂O₃ NPs and OTC. The dynamic change of particulate Fe, ionic Fe, and Fe plaque concentrations on root surface was determined under the influence of OTC from Fe₂O₃ NPs and Fe-EDTA exposure. Fe²⁺ from Fe-EDTA was selected in order to compare the Fe bioaccumulation from ionic Fe and nanoparticle Fe exposure. Hydrodynamic diameter and ζ-potential of Fe₂O₃ NPs in solution were investigated when OTC was present or not, and the changes of OTC concentrations were also determined during hydroponic culture. SEM, XRD, and TEM were used to analyze Fe₂O₃ NP distribution on root surface and inside root under the influence of OTC.

Results and discussion

OTC promoted surface-Fe and shoot-Fe accumulation in Fe₂O₃ NPs treatments, which was just an opposite result from Fe-EDTA treatments. Upon Fe₂O₃ NP exposure, Fe plaque was formed through the direct adsorption of NPs on the outside root surface and then incorporated into plaque as its crystalline components. OTC elevated notably surface-Fe accumulation mainly through increasing adsorption and precipitation of Fe₂O₃ NPs on the root surface due to low repulsive electrostatic interaction between NPs and the root surface after adding OTC. Fe₂O₃ NPs increased surface-OTC and root-OTC levels. Compared to Fe-EDTA, surface-Fe from NP treatments can hold strongly OTC due to Fe₂O₃ particle precipitated on root surface with high specific surface area. NPs reduced shoot-OTC under 25 mg L⁻¹ OTC, but not under 100 mg L⁻¹ OTC.

Conclusions

This study clearly demonstrates that Fe/OTC accumulation in rice was always in the order root surface > shoot > root, whether Fe₂O₃ NPs/OTC was individual or combined exposure. The combined exposure will increase their root surface distribution comparing with individual exposure, and Fe₂O₃ NPs increased also root-OTC levels, which could pose a potential risk to food safety in subsequent growth of rice.

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Balance assessment in people with COPD: An evidence-based guide

Chronic Respiratory Disease, Volume 16, Issue , January-December 2019.

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Soil N/P and C/P ratio regulate the responses of soil microbial community composition and enzyme activities in a long-term nitrogen loaded Chinese fir forest

Abstract

Aims

Long-term nitrogen (N) fertilization has been shown to profoundly affect the soil microorganisms and strongly result in several imbalances in element concentrations. The objective of this study was to examine links among the soil microorganisms, enzyme activities, and soil carbon (C), N, and phosphorus (P) stoichiometry in a subtropical Chinese fir (Cunninghamia lanceolata (Lamb.) Hook) plantation after continuous N fertilization for 13 years.

Methods

This study was performed in 25-year-old fir plantation along a fertilization gradient (0, 60, 120, and 240 kg N ha⁻¹ yr.⁻¹), designated as N0, N1, N2, and N3, respectively. Soil microbial properties, including the microbial community composition, as revealed by phospholipid fatty acids (PLFAs), and soil enzyme activities (i.e., sucrase, urease and catalase) were measured, and soil elemental stoichiometry was calculated based on soil C, N, and P concentrations. A redundancy analysis (RDA) was conducted to determine the relationship between soil C:N:P stoichiometry and soil microbial properties.

Results

Compared with the control (N0), N fertilization decreased the total PLFAs (−12.20%), bacteria (−14.33%), fungi (−12.97%), and actinomycetes (−17.11%) on average. Sucrase, urease and catalase activities were enhanced by low and middle levels of N (N1 and N2), but not with high level of N (N3). Long-term N fertilization decreased soil pH, C to N ratio (C/N), and C to P ratio (C/P), while increased soil C, N and N to P ratio (N/P). The RDA identified the first two axes of soil stoichiometry variation that explained 20.4% of the variation at the soil depth of 0–20 cm, 28.6% at 20–40 cm and 49.9% at 40–60 cm in PLFAs biomarkers and enzymes, respectively. Significant correlations between soil stoichiometry (soil N/P and C/P ratio) and soil microbial properties were found in this study.

Conclusions

These observations suggested that long-term N fertilization influenced soil microbial community composition and enzyme activities by changing the soil C/P and N/P ratios. Future studies are needed to consider the coupling relationships between soil microbial community composition, enzyme activities and elemental stoichiometry in different ecosystems under future climatic change.

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Inter-ictal network of focal epilepsy and effects of clinical factors on network activity.

Inter-ictal network of focal epilepsy and effects of clinical factors on network activity.

Clin Neurophysiol. 2018 Dec 16;130(2):251-258

Authors: Clemens B, Dömötör J, Emri M, Puskás S, Fekete I

Abstract
OBJECTIVE: Aim of the study was to explore the inter-ictal, resting-state EEG network in patients with focal epilepsy (FE) and to specify clinical factors that influence network activity.
METHODS: Functional EEG connectivity (EEGfC) differences were computed between 232 FE patients (FE group) and 77 healthy controls. EEGfC was computed among 23 cortical regions within each hemisphere, for 25 very narrow bands from 1 to 25 Hz. We computed independent effects for six clinical factors on EEGfC in the FE group, by ANOVA and post-hoc t-statistics, corrected for multiple comparisons by false discovery rate method.
RESULTS: Robust, statistically significant EEGfC differences emerged between the FE and the healthy control groups. Etiology, seizure type, duration of the illness and antiepileptic treatment were independent factors that influenced EEGfC. Statistically significant results occurred selectively in one or a few very narrow bands and outlined networks. Most abnormal EEGfC findings occurred at frequencies that mediate integrative and motor activities.
CONCLUSIONS: FE patients have abnormal resting-state EEGfC network activity. Clinical factors significantly modify EEGfC.
SIGNIFICANCE: Delineation of the FE network and modifying factors can open the way for targeted investigations and introduction of EEGfC into epilepsy research and practice.

PMID: 30583272 [PubMed - as supplied by publisher]

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Parents of a child with epilepsy: Views and expectations on receiving genetic results from Whole Genome Sequencing.

Parents of a child with epilepsy: Views and expectations on receiving genetic results from Whole Genome Sequencing.

Epilepsy Behav. 2018 Dec 21;90:178-190

Authors: Jaitovich Groisman I, Hurlimann T, Godard B

Abstract
PURPOSE: The use of Next Generation Sequencing technologies (NGS), such as Whole Genome Sequencing (WGS), is expected to improve the often complex and protracted course of treatment of patients with epilepsy by providing an earlier and more accurate diagnosis. As part of the "Personalized medicine in the treatment of epilepsy" project, which aimed to determine whether WGS could be used as a valuable "diagnostic tool" in pharmacoresistant epilepsies, we examined parents' expectations, hopes, and concerns upon receiving results related to their child's epilepsy, comorbidities, resistance to medication, and genetic information on unrelated conditions, and how these results could impact their and their child's life.
METHODS: Parents of 32 children participating in the genetic study completed either paper or online questionnaires. A descriptive analysis of responses and comments was conducted regarding parents' experience with their child's epilepsy, as well as their views on WGS, and expectations and concerns surrounding such test results.
RESULTS: Most respondents had trouble explaining the medical causes of their child's epilepsy (n = 27), and a majority (n = 26) feared that their child may be treated unjustly because of their epilepsy, although some acknowledged that their child had never actually been treated unjustly (n = 13). A majority of respondents had also experienced feelings of guilt due to their child's epilepsy (n = 23), and some expected WGS results to have an impact on those feelings. The anticipation of benefits for their child was the parents' primary reason to get involved in a genomic research project, closely followed by altruism. A majority expressed strong intentions to receive as many WGS results as possible, considering that any could be beneficial for them and their child, even when mutations were not found. Respondents were divided as to how and when to tell their child that they might have newly discovered predispositions to develop another disease. In proportion, more parents expressed concerns about sharing unexpected results with their family members compared with sharing results linked to epilepsy, comorbidities, and pharmacoresistance.
CONCLUSION: Our results reinforce the importance of having clear guidelines to help parents manage their expectations and better navigate the complexities of receiving and sharing WGS results. Despite the small size of our sample, we believe that our results are meaningful to clinical practice.

PMID: 30583270 [PubMed - as supplied by publisher]

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The effect of duloxetine on penicillin-induced epileptiform activity in rats.

The effect of duloxetine on penicillin-induced epileptiform activity in rats.

Neurol Res. 2018 Dec 24;:1-8

Authors: Esen M, Aygun H

Abstract
AIM: Previous studies showed the existence of a relationship between epilepsy and depression. Duloxetine is a potent and selective inhibitor of serotonin and norepinephrine reuptake (SNRI) used in the treatment of the major depressive disorder. The aim of the present study was to investigate the effect of duloxetine on penicillin-induced epileptiform activity in an experimental rat model of acute partial epilepsy.
METHOD: In this study, 35 male rats weighing 200-240 g were used. Under urethane anesthesia, tripolar electrodes were placed for electrocorticography (ECoG) recording. Duloxetine, at 1, 5, 10 or 30 mg/kg rates, was administered intraperitoneally 30 minutes after intracortical penicillin (500 IU) injection.
RESULTS: Duloxetine administrations of 1, 5, 10 and 30 mg/kg increased the mean frequency of epileptiform activity 10 minutes after Duloxetine injection compared to the control group (p < 0.05) without changing amplitude in all groups (p > 0.05).
CONCLUSION: The results showed proconvulsant effect of duloxetine in penicillin-induced epileptiform activity and indicated that it could pose complications risk for people with partial epilepsy.

PMID: 30582741 [PubMed - as supplied by publisher]

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Long-term cannabidiol treatment in patients with Dravet syndrome: An open-label extension trial.

Long-term cannabidiol treatment in patients with Dravet syndrome: An open-label extension trial.

Epilepsia. 2018 Dec 23;:

Authors: Devinsky O, Nabbout R, Miller I, Laux L, Zolnowska M, Wright S, Roberts C

Abstract
OBJECTIVE: Add-on cannabidiol (CBD) significantly reduced seizures associated with Dravet syndrome (DS) in a randomized, double-blind, placebo-controlled trial: GWPCARE1 Part B (NCT02091375). Patients who completed GWPCARE1 Part A (NCT02091206) or Part B, or a second placebo-controlled trial, GWPCARE2 (NCT02224703), were invited to enroll in a long-term open-label extension trial, GWPCARE5 (NCT02224573). We present an interim analysis of the safety, efficacy, and patient-reported outcomes from GWPCARE5.
METHODS: Patients received a pharmaceutical formulation of highly purified CBD in oral solution (100 mg/mL), titrated from 2.5 to 20 mg/kg/d over a 2-week period, with their existing medications. Based on response and tolerance, CBD could be reduced or increased up to 30 mg/kg/d.
RESULTS: By November 2016, a total of 278 patients had completed the original randomized trials, and 264 (95%) enrolled in this open-label extension. Median treatment duration was 274 days (range 1-512) with a mean modal dose of 21 mg/kg/d, and patients received a median of 3 concomitant antiepileptic medications. Adverse events (AEs) occurred in 93.2% of patients and were mostly mild (36.7%) or moderate (39.0%). Commonly reported AEs were diarrhea (34.5%), pyrexia (27.3%), decreased appetite (25.4%), and somnolence (24.6%). Seventeen patients (6.4%) discontinued due to AEs. Twenty-two of the 128 patients from GWPCARE1 (17.2%), all taking valproic acid, had liver transaminase elevations ≥3 times the upper limit of normal. In patients from GWPCARE1 Part B, the median reduction from baseline in monthly seizure frequency assessed in 12-week periods up to week 48 ranged from 38% to 44% for convulsive seizures and 39% to 51% for total seizures. After 48 weeks of treatment, 85% of patients/caregivers reported improvement in the patient's overall condition on the Subject/Caregiver Global Impression of Change scale.
SIGNIFICANCE: This trial shows that long-term CBD treatment had an acceptable safety profile and led to sustained, clinically meaningful reductions in seizure frequency in patients with treatment-resistant DS.

PMID: 30582156 [PubMed - as supplied by publisher]

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[PULMONARY EMBOLISM IN A PATIENT WITH KLINEFELTER SYNDROME].

[PULMONARY EMBOLISM IN A PATIENT WITH KLINEFELTER SYNDROME].

Harefuah. 2018 Dec;157(12):767-768

Authors: Saad T, Belsky V, Mahrom N, Amital H

Abstract
INTRODUCTION: Klinefelter syndrome (47, XXY) is the most common chromosomal aberration in males. It occurs in 0.15% of newborn males. The syndrome is related to increased mortality from a variety of medical problems including cardiovascular diseases, malignancies, nervous system disturbances, epilepsy and diabetes. In a review of the literature it was found that patients with the Klinefelter syndrome are more likely to develop thrombosis and pulmonary embolism. Even though the pathophysiological mechanism is still not entirely understood, we should consider the appropriate medical attention to the prevention and treatment of thromboembolic events in Klinefelter patients.

PMID: 30582308 [PubMed - in process]

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Mechanisms Underlying Aggressive Behavior Induced by Antiepileptic Drugs: Focus on Topiramate, Levetiracetam, and Perampanel.

Mechanisms Underlying Aggressive Behavior Induced by Antiepileptic Drugs: Focus on Topiramate, Levetiracetam, and Perampanel.

Behav Neurol. 2018;2018:2064027

Authors: Hansen CC, Ljung H, Brodtkorb E, Reimers A

Abstract
Antiepileptic drugs (AEDs) are effective against seizures, but their use is often limited by adverse effects, among them psychiatric and behavioral ones including aggressive behavior (AB). Knowledge of the incidence, risk factors, and the underlying mechanisms of AB induced by AEDs may help to facilitate management and reduce the risk of such side effects. The exact incidence of AB as an adverse effect of AEDs is difficult to estimate, but frequencies up to 16% have been reported. Primarily, levetiracetam (LEV), perampanel (PER), and topiramate (TPM), which have diverse mechanisms of action, have been associated with AB. Currently, there is no evidence for a specific pharmacological mechanism solely explaining the increased incidence of AB with LEV, PER, and TPM. Serotonin (5-HT) and GABA, and particularly glutamate (via the AMPA receptor), seem to play key roles. Other mechanisms involve hormones, epigenetics, and "alternative psychosis" and related phenomena. Increased individual susceptibility due to an underlying neurological and/or a mental health disorder may further explain why people with epilepsy are at an increased risk of AB when using AEDs. Remarkably, AB may occur with a delay of weeks or months after start of treatment. Information to patients, relatives, and caregivers, as well as sufficient clinical follow-up, is crucial, and there is a need for further research to understand the complex relationship between AED mechanisms of action and the induction/worsening of AB.

PMID: 30581496 [PubMed - in process]

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Therapeutic itinerary of children living with epilepsy in Kinshasa: Features, determinants, and relationships with behavioral problems and cognitive impairment.

Therapeutic itinerary of children living with epilepsy in Kinshasa: Features, determinants, and relationships with behavioral problems and cognitive impairment.

Epilepsy Behav. 2018 Dec 20;:

Authors: Matonda-Ma-Nzuzi T, Mampunza Ma Miezi S, Charlier-Mikolajczak D, Mvumbi DM, Malendakana F, Ntsambi GE, Mayemba JN, Mpaka DM, Mpembi MN, Lelo GM

Abstract
BACKGROUND: Epilepsy mostly affects children in sub-Saharan Africa. However, little is known about the therapeutic itinerary of these children living with epilepsy (CWE). This study aimed to describe the therapeutic itinerary of CWE in Kinshasa and to analyze its relationships with clinical features, behavioral problems, and cognitive impairment.
METHODS: This hospital-based study has included 104 CWE aged 6 to 17 years. The features of their therapeutic itinerary and their relationship with clinical features, behavioral problems, and cognitive impairment were vast majority of CWE (87%) has started their therapeutic itinerary by the Western medicine. The first source of information about epilepsy as well as the type of antiepileptic treatment varied with the socioeconomic status of families of CWE. The total duration of the therapeutic itinerary was shorter for the CWE who were living with both their parents (P = .038), who had generalized seizures (P = .0073) or who had no family history of epileptic seizures (P = .019). The CWE who had total behavioral problem, compared with the others, were putting more time (P = .021) to reach the Centre de Santé Mentale Telema (CSMT) after the suspicion or the diagnostic of epilepsy. The total duration of CWE who had cognitive impairment (P = .021) was longer than that of CWE who had not cognitive impairment.
CONCLUSION: The therapeutic itinerary of CWE in Kinshasa began with Western medicine. The remainder of this therapeutic itinerary looks like what is described in sub-Saharan literature with the majority of CWE seeking the healing based on beliefs. This study also shows that the therapeutic itinerary of CWE was associated with socioeconomic conditions, clinical features, behavioral problems, and cognitive impairment.

PMID: 30581077 [PubMed - as supplied by publisher]

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Suicide following acute admissions for physical illnesses across England and Wales.

Suicide following acute admissions for physical illnesses across England and Wales.

Psychol Med. 2018 03;48(4):578-591

Authors: Roberts SE, John A, Kandalama U, Williams JG, Lyons RA, Lloyd K

Abstract
BACKGROUND: The study aim was to establish and quantify suicide risk following acute admissions for all major physical illnesses, for confirmatory purposes, from two independent information sources from different countries.
METHODS: Record linkage of inpatient and death certificate data for 11 004 389 acute admissions for physical illnesses in England and 713 496 in Wales. The main outcome measure was standardised mortality ratios (SMRs) for suicide at 1 year following discharge from hospital.
RESULTS: There were 1781 suicides within 1 year of discharge in England (SMR = 1.7; 95% = 1.6-1.8) and 131 in Wales (SMR = 2.0; 1.7-2.3). Of 48 major physical illnesses that were associated with at least eight suicides in either country, there was high consistent suicide mortality (significant SMR >3) in both countries for constipation (SMR = 4.1 in England, 7.5 in Wales), gastritis (4.4 and 4.9) and upper gastrointestinal bleeding (3.4 and 4.5). There was high suicide mortality in one country for alcoholic liver disease, other liver disease and chronic pancreatitis; for epilepsy and Parkinson's disease; for diabetes, hypoglycaemia and hypo-osmolality & hyponatraemia; and for pneumonia, back pain and urinary tract infections.
CONCLUSIONS: There is little or no increased suicide mortality following acute admissions for most physical illnesses. Much of the increased suicide mortality relates to gastrointestinal disorders that are often alcohol related or specific chronic conditions, which may be linked to side effects from certain therapeutic medications. Acute hospital admissions for physical illnesses may therefore provide an opportunity for targeted suicide prevention among people with certain conditions, particularly alcohol related disorders.

PMID: 28714426 [PubMed - indexed for MEDLINE]

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Achyranthes aspera Linn. alleviates cerebral ischemia-reperfusion-induced neurocognitive, biochemical, morphological and histological alterations in Wistar rats.

Achyranthes aspera Linn. alleviates cerebral ischemia-reperfusion-induced neurocognitive, biochemical, morphological and histological alterations in Wistar rats.

J Ethnopharmacol. 2019 Jan 10;228:58-69

Authors: Viswanatha GL, Venkataranganna MV, Prasad NBL, Shylaja H

Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: In the traditional system of Indian medicine, the whole plant and roots of Achyranthes aspera L have been extensively used to treat neurological conditions such as epilepsy and stroke by the various ethnic communities of India.
AIM OF THE STUDY: The present study was aimed to evaluate the cerebroprotective potential of methanol extract of A. aspera aerial parts (MeAA).
MATERIALS AND METHODS: Initially the MeAA was evaluated for total phenolic content and subjected to detailed liquid chromatography-mass spectrometry analysis. Additionally, it was evaluated for in vitro antioxidant activity in ferric reducing antioxidant power, 2, 2-diphenyl-1-picrylhydrazyl and oxygen radical absorbance capacity assays. Furthermore, in RAW 264.7 cell lines the effect of MeAA was evaluated on lipopolysaccharide-induced generation of reactive oxygen species, nitrite and tumor necrosis factor-α. Finally, the MeAA (400 and 800 mg/kg) was evaluated against ischemia-reperfusion (I/R)-induced brain injury in rats. In brief, male Wistar rats were allocated in to five groups (G-I to G-V, n = 10). G-I and G-II assigned as sham control and I/R control, and received only vehicle (carboxy methyl cellulose 0.5% w/v, 10 ml/kg, p.o.). G-III received quercetin (20 mg/kg, p.o.) and assigned as reference standard. G-IV and G-V group animals received 400 and 800 mg/kg oral doses of MeAA, respectively. All the treatments were given orally for a period of seven days and the parameters such as functional (neurological, cognitive and motor), morphological (edema and infarct area), biochemical (superoxide dismutase, catalase, reduced glutathione, lipid peroxidation, cytokines), and histopathological evaluations of the brain tissue was performed.
RESULTS: The MeAA exhibited 72.48 mg gallic acid equivalents/g of total phenolic content and the LC-MS/MS analysis showed acteoside, apigenin, and pentagalloyl glucose as major ingredients in the MeAA. In in vitro antioxidant assays, the MeAA showed good antioxidant activity with IC50 of 126.50 μg/ml in DPPH assay; FRAP and ORAC values of 759.65 and 979.4 in FRAP and ORAC assays, respectively. Further, the MeAA significantly suppressed the generation of ROS, nitrite and TNF-α in LPS activated RAW 264.7 cell lines. Besides, sixty mins of global cerebral ischemia followed by 24 h of reperfusion produced considerable alterations in neurobehavioral functions in the I/R control group compared to sham control, with a significant reduction in catalase and superoxide dismutase enzyme activities. Moreover, there was a significant reduction in reduced glutathione levels with increased lipid peroxidation. Furthermore, the levels of pro-inflammatory cytokines (TNF-α, IL-6, and ICAM-I) increased significantly and those of anti-inflammatory (IL-10) decreased. I/R insult increased the brain volume and aggravated cerebral infarct formation. Histopathological examination of the brain tissue revealed vascular congestion, cerebral edema, leukocyte infiltration, and brain tissue necrosis. Interestingly, seven days pretreatment with MeAA (800 mg/kg, p.o.) has offered significant protection against I/R-induced functional, morphological, biochemical and histopathological alterations in Wistar rats.
CONCLUSIONS: These findings suggest that the MeAA possesses potent cerebroprotective action through its antioxidant and anti-inflammatory mechanisms.

PMID: 30223049 [PubMed - indexed for MEDLINE]

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Stent-assisted Coil Embolization for a Ruptured Posterior Communicating Artery Pseudoaneurysm after Endoscopic Trans-sphenoidal Surgery for Pituitary Adenoma.

Stent-assisted Coil Embolization for a Ruptured Posterior Communicating Artery Pseudoaneurysm after Endoscopic Trans-sphenoidal Surgery for Pituitary Adenoma.

World Neurosurg. 2018 Dec 21;:

Authors: Morinaga Y, Nii K, Sakamoto K, Inoue R, Mitsutake T, Hanada H

Abstract
BACKGROUND: Intracranial pseudoaneurysm is a rare complication of endoscopic endonasal surgery. Herein, we describe two-staged stent-assisted coil embolization for posterior communicating artery pseudoaneurysm after endoscopic endonasal surgery for pituitary adenoma.
CASE DESCRIPTION: A 68-year-old man had a history of severe adult growth hormone secretion deficiency, requiring growth hormone replacement therapy; secondary adrenocortical hypofunction; hyperthyroidism; hypertension; constipation; glaucoma; and hyperuricemia. Five years ago, after initial endoscopic trans-sphenoidal surgery for pituitary adenoma, he was hospitalized for reoperation. Posterior communicating artery injury was observed during second endoscopic trans-sphenoidal surgery and pressure hemostasis was performed using a hemostatic preparation. Immediately post-surgery, a localized subarachnoid hemorrhage was observed. Sudden-onset impaired consciousness and respiratory disturbances ensued on postoperative day 7, and computed tomography of the head was performed. Recurrent subarachnoid hemorrhage was confirmed, and acute hydrocephalus secondary to third ventricular blockage was identified. Cerebral angiography was performed after urgent bilateral cerebral ventricular drainage under general anesthesia. A pseudoaneurysm was identified in the left posterior communicating artery, and coil embolization was performed. Six weeks post-surgery, LVIS® Jr. stent was placed in the posterior communicating artery. Recurrence of the aneurysm was not detected 6 months post-surgery. He underwent lumboperitoneal shunting for secondary normal pressure hydrocephalus after dual antiplatelet therapy discontinuation and is being followed-up as an outpatient with a modified Rankin Scale of 2 10 months post-surgery.
CONCLUSION: Two-staged stent-assisted coil embolization using LVIS® stent was effective for a posterior communicating artery pseudoaneurysm occurring after posterior communicating artery injury following endoscopic trans-sphenoidal surgery for follicle-stimulating hormone-producing pituitary adenoma.

PMID: 30583130 [PubMed - as supplied by publisher]

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The characteristics of cervical sagittal alignment at different C0-C2 correcting angles in fusion treatment of atlantoaxial dislocations.

The characteristics of cervical sagittal alignment at different C0-C2 correcting angles in fusion treatment of atlantoaxial dislocations.

World Neurosurg. 2018 Dec 21;:

Authors: Xiuru Z, Kun G, Huiqi X, Yanzheng G

Abstract
PURPOSE: To explore the appropriate range of C0-C2 correction angles by analyzing cervical sagittal alignment parameters and evaluating clinical outcomes.
METHODS: The pre-operative and postoperative radiographs, visual analogue scale (VAS), Japanese Orthopedic Association (JOA) score, and neck disability index (NDI) of 65 AAD patients were retrospectively collected. The C0-C2 angle, C2-C7 angle, and cervical sagittal vertical axis (cSVA) were measured from the radiographs, and an assessment of cervical disc degenerative disease (cDDD) was made. According to the 2-year postoperative C0-C2 angles, all patients were categorized into a ˂10° subgroup, 10°-20° subgroup and ˃20° subgroups.
RESULTS: The postoperative C2-C7 angles and cSVA of the 10-20° subgroup were significantly different from those of the ˂10° subgroup. The JOA of the 10-20° subgroup was significantly different from those of the ˂10° and ˃20° subgroups. All patients (26/26) in the 10-20° subgroup exhibited a cSVA 0-40 mm, 25% of patients (6/24) in the ˃20° subgroup exhibited a cSVA ˃40 mm, and 40% of patients (6/15) in the ˂10° subgroup showed a cSVA ˂0 mm. The postoperative incidence of cDDD did not increase in the 10-20° subgroup.
CONCLUSION: AAD patients with different C0-C2 postoperative angles had different cervical sagittal alignments and clinical outcomes. In our study, the patients within the C0-C2 10-20° subgroup exhibited superior clinical outcomes and cervical sagittal alignment.

PMID: 30583133 [PubMed - as supplied by publisher]

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"Radiation-induced moyamoya syndrome after proton therapy in a child with clival craniopharyngioma: natural history and surgical treatment".

"Radiation-induced moyamoya syndrome after proton therapy in a child with clival craniopharyngioma: natural history and surgical treatment".

World Neurosurg. 2018 Dec 21;:

Authors: Scala M, Vennarini S, Garrè ML, Tortora D, Cianchetti M, Fellin F, Lorentini S, Pavanello M

Abstract
BACKGROUND: Proton therapy has proven to be effective and safe in the treatment of radioresistant skull base tumors such as chordomas. Thanks to the peculiar physical properties of the proton beam, the radiation energy is delivered in a narrow space called the Bragg peak and the surrounding normal tissues receive a minimal amount of the radiation dose. This is important to lower the risk of radiation-induced damage, especially in children. However, local adverse effects in proximity to the target volume may occur. In particular, the development of moyamoya syndrome (MMS) has been rarely reported in children receiving proton beam therapy (PBT) for brain tumors.
CASE DESCRIPTION: We report on a child who developed rapidly progressive MMS after PBT for a clivus chordoma. A combined indirect revascularization procedure by encephalo-duro-arterio-synangiosis (EDAS) and encephalo-myo-synangiosis (EMS) was performed with good neuroradiological and clinical outcome.
CONCLUSIONS: Regardless of the presence of known risk factors for MMS, strict neuroimaging surveillance is indicated in all patients treated with radiotherapy, including those receiving PBT. We suggest that early revascularization procedure should be considered in patients with worsening symptoms and/or sign of neuroradiological progression of cerebral vasculopathy. This management of MMS could lower the risk of permanent neurological deficits and improve patients' quality of life.

PMID: 30583132 [PubMed - as supplied by publisher]

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The efficacy of gamma knife radiosurgery for cavernous malformation: a meta-analysis and review.

The efficacy of gamma knife radiosurgery for cavernous malformation: a meta-analysis and review.

World Neurosurg. 2018 Dec 21;:

Authors: Wen R, Shi Y, Gao Y, Xu Y, Xiong B, Li D, Gong F, Wang W

Abstract
OBJECTS: This meta-analysis is to evaluate the clinical efficacy of gamma knife radiosurgery for treating cavernous malformation.
METHODS: PUBMED, OVID EMBASE, and OVID MEDLINE electronic databases are searched. The primary outcome is hemorrhage rate and this meta-analysis is performed with REVMAN 5.3.
RESULTS: 9 studies are included in this meta-analysis. The overall RR of hemorrhage rate of pre-GKRS and post-GKRS is 6.08(95% CI: 5.04-7.35). The overall RR is 3.03(95% CI: 2.65-4.11) between the hemorrhage rate of pre-GKRS and the first 2 years of post-radiosurgery, and the overall RR is 12.13 (95% CI: 1.73-85.07) comparing pre-GKRS with 2 years after GKRS. There is no significant difference of the hemorrhage rate between the first 2 years of post-radiosurgery and 2 years after GKRS (RR =2.81, 95% CI: 0.20-13.42). The neurological deficiency is the commonest radiosurgery related complications.
CONCLUSION: Patients with cerebral CMs, especially who were deep seated and surgically inaccessible, seems to benefit from GKRS due to a reduction of annual hemorrhage rate in the first 2 years, and after that time, despite of a number of cases that suffer from negative side effects of radiation.

PMID: 30583131 [PubMed - as supplied by publisher]

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Rationales for a urodynamic study in patients with cervical spondylotic myelopathy.

Rationales for a urodynamic study in patients with cervical spondylotic myelopathy.

World Neurosurg. 2018 Dec 21;:

Authors: Kim IS, Kim YI, Hong JT, Lee DS

Abstract
BACKGROUND: Detrusor sphincter dyssynergia (DSD), involuntary detrusor contractions (IDC) and poor bladder compliance (PC) are relatively common urodynamic findings in cervical myelopathy. However, there is little information regarding the role of a urodynamic study (UDS) after decompression surgery for cervical spondylotic myelopathy (CSM).
METHODS: The urodynamic study was performed before and 6 months after decompression of CSM. The Japanese Orthopaedic Association (JOA) scores for cervical myelopathy and the Neck Disability Index (NDI) functional score were used. For male patients, the International Prostate Symptom Score (IPSS) was used, whereas the Urinary Distress Inventory (UDI-6) was applied in female patients.
RESULTS: The mean age was 61.3 years. Among the 32 patients, 17 patients completed the final follow-up, where neurogenic bladder was confirmed in 11 (64.7%) patients, with 7 patients having PC, 3 patients having IDC, and 6 patients having DSD. Four of the 7 PCs were normalized, 2 (phasic) of the 3 IDCs disappeared and 1 (terminal) IDC remarkably improved. Four of the 6 DSDs markedly improved. Before and after the decompression surgery, bladder compliance in the 17 patients was 45.52 ± 23.71 and 77.07 ± 39.85, respectively (p=0.004). Both JOA scores and NDI scores improved (p=0.007 and p=0.001, respectively). However, the IPSS and UDI-6 were not changed 6 months after surgery.
CONCLUSIONS: The neurogenic bladder could be partially controlled in CSM patients after surgical decompression. However, the neurogenic component in the UDS findings varied, and depending on the findings, further proper urological treatments after neurological decompression surgery should be considered.

PMID: 30583129 [PubMed - as supplied by publisher]

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Hip fracture rates and time trends in use of anti-osteoporosis medications in Denmark for the period 2005 to 2015: Missed opportunities in fracture prevention.

Hip fracture rates and time trends in use of anti-osteoporosis medications in Denmark for the period 2005 to 2015: Missed opportunities in fracture prevention.

Bone. 2018 Dec 21;:

Authors: Abrahamsen B, Skjødt MK, Vestergaard P

Abstract
BACKGROUND: Declining use of bisphosphonates (BP) in the United States and Europe may lead to a widening of the treatment gap for osteoporosis and an increase in fracture rates. However, a shift to non-bisphosphonates and to hospital administered i.v. BPs could lead to overestimation of the treatment gap if analyses are based exclusively on BP prescriptions. When a healthcare system successfully narrows the treatment gap by making appropriate use of anti-osteoporosis drugs, we would expect to see declining rates of osteoporotic fractures with much of the decrease being statistically attributable to medication uptake. We analysed a best-case scenario where all use of BPs, denosumab, raloxifene and PTH analogues - including the oncology area - was contrasted with the trend in hip fracture rates. This scenario also considered users of raloxifene and teriparatide as covered by osteoporosis drugs though the primary RCT for raloxifene showed no risk reduction in nonvertebral fractures and the RCT for teriparatide risk reductions for non-vertebral fractures but not hip fracture specifically. Sensitivity analyses were also done.
METHODS: We used aggregate statistics on hip fracture events and total use of the above medications estimating the number of persons potentially covered. The reduction in hip fracture rates attributable to treatment was estimated using the absolute risk reduction (ARR) found in real-world users of oral alendronate in Denmark with the ARR in the FIT primary prevention arm as an alternative scenario.
RESULTS: A plateau in use of osteoporosis medications occurred in 2014. Between 2005 and 2015, hip fracture rates declined by 30%. However, only up to 20% of the observed reduction in hip fracture rates was statistically attributable to treatment even in a best-case scenario. Sensitivity analyses where raloxifene and teriparatide were excluded did not impact on this finding.
DISCUSSION: Anti-osteoporosis treatment in Denmark reached a plateau in 2014 even in a best-case scenario where all dispensations were assumed to be for osteoporosis. Future studies may be able to distinguish between the oncology area and the osteoporosis indication as well as provide a delineation of age and gender demographics among users of hospital administered osteoporosis medications. About 80% of the decline in hip fracture rates appears to be due to factors other than osteoporosis medication. The plateau in use of osteoporosis treatment at a level that is too low to make a meaningful impact on societal fracture burden is problematic given the predicted increased age-specific hip fracture rates.

PMID: 30583122 [PubMed - as supplied by publisher]

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Combination therapy targeting the elevated interleukin-6 level reduces invasive migration of BRAF inhibitor-resistant melanoma cells.

Combination therapy targeting the elevated interleukin-6 level reduces invasive migration of BRAF inhibitor-resistant melanoma cells.

Mol Oncol. 2018 Dec 24;:

Authors: Mohapatra P, Prasad CP, Andersson T

Abstract
The identification of novel anti-metastatic therapeutic targets is necessary for improved treatment of patients with acquired BRAF inhibitor-resistant (BRAFi-R) melanoma, in whom metastasis is a major concern. Our present study focused on the identification of such targets to explore novel anti-metastatic therapeutic options for BRAFi-R melanoma patients. We confirmed the development of BRAFi resistance in our BRAFi-treated melanoma cell lines by demonstrating reduced sensitivity to BRAF inhibitors, increased ERK1/2 activity and increased WNT5A expression. Here, we demonstrated for the first time that high secretion of interleukin-6 (IL-6) was associated with increased invasive migration of BRAFi-R melanoma cells. This finding could be readily explained by the increased expression of WNT5A in BRAFi-R melanoma cells and the presence of an IL-6/WNT5A positive feedback loop in parental melanoma cells. Surprisingly, however, we found that the IL-6/WNT5A positive feedback loop present in parental melanoma cells was lost during the development of acquired BRAFi resistance, meaning that IL-6 and WNT5A signalling were independent events in BRAFi-R melanoma cells. Despite the absence of an IL-6/WNT5A loop, we found that both an IL-6 blocking antibody and the WNT5A antagonist Box5 alone impaired the elevated invasive migration of BRAFi-R melanoma cells, but combined use of the two was more effective. This impaired invasive migration of BRAFi-R melanoma cells correlated well with the reduction in Cdc42-GTPase activity and alterations of the actin cytoskeleton in these cells. In summary, our novel identification of IL-6 as a key independent promoter of the invasive migration of BRAFi-R melanoma cells stresses that a combination of a blocking IL-6 antibody and administration of the WNT5A antagonist Box5 might be an attractive anti-metastatic approach for future treatment of BRAFi-R melanoma patients.

PMID: 30582770 [PubMed - as supplied by publisher]

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The Emerging Role of Targeted Therapies for Advanced Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors.

The Emerging Role of Targeted Therapies for Advanced Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors.

Expert Rev Clin Pharmacol. 2018 Dec 24;:

Authors: Cloyd JM, Konda B, Shah MH, Pawlik TM

Abstract
INTRODUCTION: Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are a unique and complex neoplasm, exhibiting a wide spectrum of diverse clinical behaviors. The contemporary management of well-differentiated GEP-NETs is marked by the availability of a wide range of targeted therapies. Areas Covered: For patients with localized or oligometastatic disease, surgical resection remains the preferred approach and is associated with excellent long-term outcomes. For patients with unresectable but isolated liver metastases, multiple liver-directed therapies, including hepatic arterial based therapies and ablative techniques, exist. For patients with metastatic and progressive disease, a number of systemic therapies exist: molecular targeted agents, peptide receptor radionuclide therapy (PRRT), and systemic chemotherapy. Furthermore, somatostatin analogs (SSA) are an important component of therapy, both effectively controlling symptoms of hormonal overproduction and contributing to slowing tumor progression. Expert Opinion: In the near future, advances in our understanding of tumor biology, genetics, immunology, nanotechnology, and radiation pharmacology should only continue to expand the availability of targeted therapies, improving the outcomes of patients with GEP-NETs. We herein review the management of advanced well-differentiated GEP-NETS with a particular emphasis on the role of targeted therapies.

PMID: 30582383 [PubMed - as supplied by publisher]

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Telehealth in radiation oncology at the Townsville Cancer Centre: Service evaluation and patient satisfaction.

Telehealth in radiation oncology at the Townsville Cancer Centre: Service evaluation and patient satisfaction.

Clin Transl Radiat Oncol. 2019 Feb;15:20-25

Authors: Hamilton E, Van Veldhuizen E, Brown A, Brennan S, Sabesan S

Abstract
Purpose: Telehealth (TH) in Radiation Oncology at Townsville Cancer Centre (TCC) was implemented in July 2011 to provide cancer care closer to home to the regional and rural population. The aim of this study was to describe the service use and patient satisfaction.
Materials and methods: A retrospective audit of records was conducted for patients treated at TCC between July 2011 and December 2015. Data included patient demographics, diagnosis and treatment. Results of a patient satisfaction survey were summarised through descriptive statistics.
Results: A total of 1530 TH consultations were provided to 833 patients. 311 patient charts were audited (615 TH, 650 in-person, 151 phone consultations). Median distance from TCC to satellites was 327.3 km (21.6 to 1130.1). 71% were male and median age was 65 (23-94 years). Cancer diagnoses included prostate (32%), breast (12%) and head and neck (10%). 60% of patients underwent radiation therapy for curative intent, 22% palliative and 18% did not undergo treatment. 106 patients participated in the satisfaction survey (231 patients invited, response rate of 46%), with the overall positive response mainly attributed to advantages in travel and time savings. 54.7% of patients selected TH as their preference for future consultations, 34.9% indicated a mix of TH and in-person consultations, and only 1 patient (0.9%) indicating in-person only.
Conclusion: TH enables the delivery of radiation oncology consultations to rural and regional patients, with an overall high level of patient satisfaction. Patients welcomed the model for benefits of travel and time savings. Future directions include engaging with specialist, rural medical staff and patients to maximize access.

PMID: 30582017 [PubMed]

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Ending 40 years of silence: Rationale for a new staging system for soft tissue sarcoma of the head and neck.

Ending 40 years of silence: Rationale for a new staging system for soft tissue sarcoma of the head and neck.

Clin Transl Radiat Oncol. 2019 Feb;15:13-19

Authors: Hahn E, Huang SH, Hosni A, Razak AA, Jones RL, Dickson BC, Sturgis EM, Patel SG, O'Sullivan B

Abstract
The tumor, node, metastases (TNM) anatomic staging system plays a pivotal role in cancer care, research, and cancer control activities. Since the first edition of the American Joint Committee on Cancer TNM staging classification published in 1977, soft tissue sarcomas have been staged in an anatomic site agnostic fashion whereby the primary tumor size (T) was categorized as T1 if <=5 cm and T2 if >5 cm; this remained unchanged through the 7th edition of the TNM. However, soft tissue sarcomas of the head and neck (STSHN) usually present smaller than sarcomas of other sites, but carry a disproportionate risk of local recurrence. Up to 70% of tumors are less than 5 cm at presentation, and therefore classified together as T1. Given the rarity of STSHN, there is a paucity of data to guide progress in their classification. Moreover, the majority of publications only report tumor size as less than or greater than 5 cm, presumably based on conventions of the TNM system that remained unchanged for 40 years, thereby affecting progress of STSHN classification. This formed the impetus for change in the 8th edition in 2 key ways: 1) several soft tissue sarcoma site based changes occurred including STSHN now having its own system, and 2) primary tumor size cut-offs of 2 cm and 4 cm used in STSHN now reflect sizes that head and neck specialists commonly encounter in their practice. This update was pragmatic in modifying the TNM from a system with a T category not serving STSHN and which was originally based on sarcoma data from non-head and neck anatomic sites. The background to this change is outlined which provides a framework in which data can be reported to generate evidence for future staging modifications.

PMID: 30582016 [PubMed]

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Insights into Endothelial Progenitor Cells: Origin, Classification, Potentials, and Prospects.

Insights into Endothelial Progenitor Cells: Origin, Classification, Potentials, and Prospects.

Stem Cells Int. 2018;2018:9847015

Authors: Chopra H, Hung MK, Kwong DL, Zhang CF, Pow EHN

Abstract
With the discovery of endothelial progenitor cells (EPCs) in the late 1990s, a paradigm shift in the concept of neoangiogenesis occurred. The identification of circulating EPCs in peripheral blood marked the beginning of a new era with enormous potential in the rapidly transforming regenerative field. Overwhelmed with the revelation, researchers across the globe focused on isolating, defining, and interpreting the role of EPCs in various physiological and pathological conditions. Consequently, controversies emerged regarding the isolation techniques and classification of EPCs. Nevertheless, the potential of using EPCs in tissue engineering as an angiogenic source has been extensively explored. Concomitantly, the impact of EPCs on various diseases, such as diabetes, cancer, and cardiovascular diseases, has been studied. Within the limitations of the current knowledge, this review attempts to delineate the concept of EPCs in a sequential manner from the speculative history to a definitive presence (origin, sources of EPCs, isolation, and identification) and significance of these EPCs. Additionally, this review is aimed at serving as a guide for investigators, identifying potential research gaps, and summarizing our current and future prospects regarding EPCs.

PMID: 30581475 [PubMed]

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Multicenter Phase 2 Study of Reduced-Dose CHOP Chemotherapy Combined With Rituximab for Elderly Patients With Diffuse Large B-Cell Lymphoma.

Multicenter Phase 2 Study of Reduced-Dose CHOP Chemotherapy Combined With Rituximab for Elderly Patients With Diffuse Large B-Cell Lymphoma.

Clin Lymphoma Myeloma Leuk. 2018 Nov 12;:

Authors: Park S, Jo JC, Do YR, Yang DH, Lim SN, Lee WS, Kim WS, Lee HS, Hong DS, Kim HJ, Shin HJ

Abstract
INTRODUCTION: Elderly patients are more prone to encounter some adverse factors when they receive chemotherapy compared to younger patients. Addition of rituximab to a reduced dose (RD) of cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy might improve patient outcomes with an improved toxicity profile when provided to elderly patients with diffuse large B-cell lymphoma.
PATIENTS AND METHODS: A total of 53 patients aged ≥ 65 years with diffuse large B-cell lymphoma diagnosed between August 2012 and December 2014 were enrolled onto this study. RD-R-CHOP regimen consisted of rituximab at 375 mg/m2, cyclophosphamide at 600 mg/m2, doxorubicin at 30 mg/m2, and vincristine at 1 mg on day 1 of each cycle and 40 mg of prednisone on days 1 to 5. Patients received granulocyte colony-stimulating factor if they experienced grade 3/4 neutropenia or febrile neutropenia during any cycle.
RESULTS: The median follow-up duration was 18 months (range, 1-44 months). Complete response and overall response rates were 64.1% and 81.1%, respectively. Three-year event-free and overall survival rates were 45.7% ± 8.4% and 62.7% ± 8.1%, respectively. Grade 3/4 neutropenia occurred in 20 patients (37.7%), while febrile neutropenia occurred in 7 patients (20.7%).
CONCLUSION: Outcomes of RD-R-CHOP chemotherapy were comparable to those of standard-dose R-CHOP or previous dose-adjusted R-CHOP chemotherapy. In the future, strategies such as tailored therapy based on geriatric assessment results are needed to determine the chemotherapeutic dosage.

PMID: 30581162 [PubMed - as supplied by publisher]

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A Psychosexual Rehabilitation Booklet Increases Vaginal Dilator Adherence and Knowledge in Women Undergoing Pelvic Radiation Therapy for Gynaecological or Anorectal Cancer: A Randomised Controlled Trial.

A Psychosexual Rehabilitation Booklet Increases Vaginal Dilator Adherence and Knowledge in Women Undergoing Pelvic Radiation Therapy for Gynaecological or Anorectal Cancer: A Randomised Controlled Trial.

Clin Oncol (R Coll Radiol). 2018 Dec 20;:

Authors: Lubotzky FP, Butow P, Hunt C, Costa DSJ, Laidsaar-Powell R, Carroll S, Thompson SR, Jackson M, Tewari A, Nattress K, Juraskova I

Abstract
AIMS: Women treated with pelvic radiation therapy (PRT) for gynaecological or anorectal cancer report a high number of sexual problems and unmet post-treatment psychosexual information needs. Currently, there is suboptimal adherence to recommended rehabilitation aids, such as vaginal dilators, and a paucity of resources to facilitate post-radiation rehabilitation and reduce distress in this population. This randomised controlled trial aimed to evaluate the effectiveness of a study-developed psychosexual rehabilitation booklet in this setting.
MATERIALS AND METHODS: Eighty-two women scheduled for PRT to treat gynaecological/anorectal cancer were randomised to receive the intervention booklet (n = 44) or standard information materials (n = 38). Self-report questionnaires administered at pre-treatment baseline and at 3, 6 and 12 months post-treatment assessed adherence with rehabilitation aids, booklet knowledge, anxiety, depression and sexual functioning/satisfaction.
RESULTS: Dilator adherence and booklet knowledge were significantly higher in the intervention group than in the control group (averaged over time points), with scores significantly increasing over time. Younger age and gynaecological cancer were significant predictors of greater dilator adherence. No significant group differences were found on psychological and sexual measures.
CONCLUSIONS: The psychosexual rehabilitation booklet was effective in educating women with gynaecological and anorectal cancers about PRT-related psychosexual side-effects and rehabilitation options, as well as promoting uptake of vaginal dilator use. Future research should elucidate the effectiveness of this booklet in women with greater psychological and sexual functioning needs.

PMID: 30580905 [PubMed - as supplied by publisher]

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Prostate cancer: the influence of stigma on quality of life and relationship satisfaction for survivors and their partners.

Prostate cancer: the influence of stigma on quality of life and relationship satisfaction for survivors and their partners.

J Psychosoc Oncol. 2018 Dec 22;:1-17

Authors: Wood A, Barden S, Terk M, Cesaretti J

Abstract
OBJECTIVES: Prostate cancer (PCa) stigma and its relationship to quality of life (QoL) is a relatively new finding. As the experiences of couples facing PCa are shared, the study examined the relationship between of PCa stigma, QoL, and relationship satisfaction of PCa survivors and their spouses.
DESIGN: A correlational design with dyadic data was used.
SAMPLE: Participants (N = 80 dyads) were PCa survivors and their spouses sampled from an oncology center and PCa support groups.
METHODS: Structural equation modeling was used to assess how stigma related to the QoL and relationship satisfaction of participants.
FINDINGS: Stigma had a negative association with QoL, but not relationship satisfaction. There were no significant demographic differences in regards to stigma.
CONCLUSION: Overall, stigma has a relationship with the experience of couples, but not with every aspect of their experience. Implications for psychosocial providers: Implications for clinicians in regards to addressing PCa stigma with clients and areas for future research are discussed.

PMID: 30580663 [PubMed - as supplied by publisher]

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Ten thousand attentive hours, rapid learning, dissemination of knowledge and the future of experience-based care in germ-cell tumors.

Icon for Silverchair Information Systems

Ten thousand attentive hours, rapid learning, dissemination of knowledge and the future of experience-based care in germ-cell tumors.

Ann Oncol. 2018 02 01;29(2):289-290

Authors: Nichols C, Tandstad T, Lowrance W, Daneshmand S

PMID: 29236938 [PubMed - indexed for MEDLINE]

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Curaxin CBL0137 Exerts Anticancer Activity via Diverse Mechanisms.

Curaxin CBL0137 Exerts Anticancer Activity via Diverse Mechanisms.

Front Oncol. 2018;8:598

Authors: Jin MZ, Xia BR, Xu Y, Jin WL

Abstract
Chemotherapy with or without radiation remains the first choice for most cancers. However, intolerant side effects and conventional drug resistance restrict actual clinical efficacy. Curaxin CBL0137 is designed to regulate p53 and nuclear factor-κB simultaneously and to prevent the resistance caused by a single target. Functionally, CBL0137 exhibits an antitumor activity in multiple cancers, including glioblastoma, renal cell carcinoma, melanoma, neuroblastoma, and small cell lung cancer (SCLC). Mechanistically, CBL0137 is originally identified to act by facilitates chromatin transcription (FACT) complex. Further investigations reveal that several pathways, such as NOTCH1 and heat shock factor 1 (HSF1), are involved in the process. CBL0137 has been reported to target cancer stem cells (CSCs) and enhance chemotherapy/monotherapy efficacy. The translational advance of CBL0137 into clinical practice is expected to provide a promising future for cancer treatment.

PMID: 30581774 [PubMed]

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Loss of Nuclear Functions of HOXA10 Is Associated With Testicular Cancer Proliferation.

Loss of Nuclear Functions of HOXA10 Is Associated With Testicular Cancer Proliferation.

Front Oncol. 2018;8:594

Authors: Chen R, Li H, Li Y, Fazli L, Gleave M, Nappi L, Dong X

Abstract
Background: HOXA10 is a key transcriptional factor that regulates testis development as reported from previous transgenic mouse models and human inherited diseases. However, whether it also plays important roles in promoting the development of testicular cancer is not well-understood. Objective: To study the expression of HOXA10 and its regulated signaling pathways in testicular cancers. Design, Setting, and Participants: A tissue microarray was constructed with benign and cancerous testis. TCam2, NT-2, and NCCIT cell models were applied in this study. Intervention: Immunohistochemistry and immunofluorescence were performed to measure the expression and cellular localization of HOXA10 in testicular cancer tissues and cell models. Cell proliferation and cell cycling rates were determined by BrdU incorporation and flow cytometry assays. HOXA10 transcriptomes were profiled with Ampliseq RNA-seq in testicular cancer cells. Immunoblotting assays were used to detect HOXA10-regulated signaling. Results: HOXA10 is a nuclear protein in benign spermatocytes. Reduced nuclear expression and increased cytoplasmic expression of HOXA10 are associated with testicular cancers. These changes are consistent in both seminoma and non-seminoma. Enhanced HOXA10 expression in testicular cancer cell models inhibits cell proliferation and delays cell cycle progression through G2/M phases. These functions of HOXA10 mainly affect the TP53, cKit, STAT3, AKT, and ERK signaling pathways. Conclusions: Loss of nuclear functions of HOXA10 enhances proliferation of testicular cancer cells, suggesting that downregulation of HOXA10 transcription activity may promote the development of testicular cancers.

PMID: 30581773 [PubMed]

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Human Wharton's Jelly Stem Cell (hWJSC) Extracts Inhibit Ovarian Cancer Cell Lines OVCAR3 and SKOV3 in vitro by Inducing Cell Cycle Arrest and Apoptosis.

Human Wharton's Jelly Stem Cell (hWJSC) Extracts Inhibit Ovarian Cancer Cell Lines OVCAR3 and SKOV3 in vitro by Inducing Cell Cycle Arrest and Apoptosis.

Front Oncol. 2018;8:592

Authors: Kalamegam G, Sait KHW, Ahmed F, Kadam R, Pushparaj PN, Anfinan N, Rasool M, Jamal MS, Abu-Elmagd M, Al-Qahtani M

Abstract
Ovarian cancer is a highly lethal and the second highest in mortality among gynecological cancers. Stem cells either naïve or engineered are reported to inhibit various human cancers in both in-vitro and in-vivo. Herein we report the cancer inhibitory properties of human Wharton's jelly stem cell (hWJSC) extracts, namely its conditioned medium (hWJSC-CM) and cell lysate (hWJSC-CL) against two ovarian cancer cell lines (OVCAR3 and SKOV3) in-vitro. Cell metabolic activity assay of OVCAR3 and SKOV3 cells treated with hWJSC-CM (12.5, 25, 50, 75, 100%) and hWJSC-CL (5, 10, 15, 30, and 50 μg/ml) demonstrated concentration dependent inhibition at 24-72 h. Morphological analysis of OVCAR3 and SKOV3 cells treated with hWJSC-CM (50, 75, 100%) and hWJSC-CL (15, 30, and 50 μg/ml) for 24-72 h showed cell shrinkage, membrane damage/blebbings and cell death. Cell cycle assay demonstrated an increase in the sub-G1 and G2M phases of cell cycle following treatment with hWJSC-CM (50, 75, 100%) and hWJSC-CL (10, 15, and 30 μg/ml) at 48 h. Both OVCAR3 and SKOV3 cells demonstrated mild positive expression of activated caspase 3 following treatment with hWJSC-CM (50%) and hWJSC-CL (15 μg/ml) for 24 h. Cell migration of OVCAR3 and SKOV3 cells were inhibited following treatment with hWJSC-CM (50%) and hWJSC-CL (15 μg/ml) for 48 h. Tumor spheres (TS) of OVCAR3 and SKOV3 treated with hWJSC-CM (50, 75, 100%) and hWJSC-CL (10, 15, 30 μg/ml) for 48 h showed altered surface changes including vacuolations and reduction in size of TS. TS of OVCAR3 and SKOV3 also showed the presence of few ovarian cancer stem cells (CSCs) in minimal numbers following treatment with hWJSC-CM (50%) or hWJSC-CL (15 μg/ml) for 48 h. Real-time gene expression analysis of OVCAR3 and SKOV3 treated with hWJSC-CM (50%) or hWJSC-CL (15 μg/ml) for 48 h demonstrated decreased expression of cell cycle regulatory genes (cyclin A2, Cyclin E1), prostaglandin receptor signaling genes (EP2, EP4) and the pro-inflmmatory genes (IL-6, TNF-α) compared to untreated controls. The results indicate that hWJSC-CM and hWJSC-CL inhibit ovarian cancer cells at mild to moderate levels by inducing cellular changes, cell cycle arrest, apoptosis, decreasing the expression of CSC markers and related genes regulation. Therefore, the stem cell factors in hWJSCs extracts can be useful in cancer management.

PMID: 30581772 [PubMed]

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Technical Advances in Single-Cell RNA Sequencing and Applications in Normal and Malignant Hematopoiesis.

Technical Advances in Single-Cell RNA Sequencing and Applications in Normal and Malignant Hematopoiesis.

Front Oncol. 2018;8:582

Authors: Huang XT, Li X, Qin PZ, Zhu Y, Xu SN, Chen JP

Abstract
Single-cell RNA sequencing (scRNA-seq) has been tremendously developed in the past decade owing to overcoming challenges associated with isolation of massive quantities of single cells. Previously, cell heterogeneity and low quantities of available biological material posed significant difficulties to scRNA-seq. Cell-to-cell variation and heterogeneity are fundamental and intrinsic characteristics of normal and malignant hematopoietic cells; this heterogeneity has often been ignored in omics studies. The application of scRNA-seq has profoundly changed our comprehension of many biological phenomena, including organ development and carcinogenesis. Hematopoiesis, is actually a maturation process for more than ten distinct blood and immune cells, and is thought to be critically involved in hematological homeostasis and in sustaining the physiological functions. However, aberrant hematopoiesis directly leads to hematological malignancy, and a deeper understanding of malignant hematopoiesis will provide deeper insights into diagnosis and prognosis for patients with hematological malignancies. Here, we aim to review the recent technical progress and future prospects for scRNA-seq, as applied in physiological and malignant hematopoiesis, in efforts to further understand the hematopoietic hierarchy and to illuminate personalized therapy and precision medicine approaches used in the clinical treatment of hematological malignancies.

PMID: 30581771 [PubMed]

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Thoracic Damage Control: Let's Think About Intrathoracic Packing.

Thoracic Damage Control: Let's Think About Intrathoracic Packing.

Am J Case Rep. 2018 Dec 24;19:1526-1529

Authors: Prezman-Pietri M, Rabinel P, Périé G, Georges B, Brouchet L, Vardon Bounes F

Abstract
BACKGROUND In cases of hemorrhagic shock following thoracic trauma, thoracotomy is indicated as primary surgical management, as a chest tube might lead to exsanguination. Thoracic packing is an alternative, particularly in severe injury trauma. CASE REPORT A 48-year-old male was involved in an accident in which 2 cars collided. The patient suffered from right-sided hemothorax due to diaphragm rupture and stripping of the diaphragmatic pillar. A right anterolateral thoracotomy revealed an active bleed due to diaphragmatic pillar stripping and laceration with liver herniation. Right thoracic packing was established to stop the bleeding. CONCLUSIONS The primary objectives of thoracic damage control are to prevent cardiac tamponade, to control intrathoracic bleeding and massive air embolism or bronchopleural fistula, and to allow open cardiac massage. These patients represent challenging cases of both rapid therapeutic decision-making and operative intervention. Thoracic packing is a part of damage control in cases of hemorrhagic shock after thoracic trauma.

PMID: 30581190 [PubMed - in process]

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Exogenous interleukin-1α signaling negatively impacts acquired chemoresistance and alters cell adhesion molecule expression pattern in colorectal carcinoma cells HCT116.

Exogenous interleukin-1α signaling negatively impacts acquired chemoresistance and alters cell adhesion molecule expression pattern in colorectal carcinoma cells HCT116.

Cytokine. 2018 Dec 21;114:38-46

Authors: Grigaitis P, Jonusiene V, Zitkute V, Dapkunas J, Dabkeviciene D, Sasnauskiene A

Abstract
Proinflammatory cytokine and chemokine signaling from the tumor microenvironment is thought to be crucial for developing and sustaining colorectal cancer by regulating a multitude of pathways associated with a variety of cellular mechanisms. Among these pathways there is acquired chemoresistance, which is usually a major obstacle in the way towards successful chemotherapeutic treatment of advanced colorectal cancer cases. Despite of an emerging body of data published on the role of cytokine signaling network in cancer, little is known about the effects of the upstream cytokine interleukin-1α (IL-1α) signaling to the cancer cells. In this study we have shown that the increase in exogenous IL-1α signaling increases chemosensitivity of both chemosensitive and chemoresistant colorectal cancer cell lines, treated with a widely used cytotoxic antimetabolite 5-fluorouracil (5-FU). This was a result of increased cell death but not of the changes in 5-FU-induced cell cycle arrest. Noticeably, combined exogenous IL-1α and 5-FU treatment had significant effects on the expression of cell adhesion molecules, suggesting a decrease in adhesion-dependent chemoresistance and, on the other hand, an increase in metastatic potential of the cells. These results lead to a conclusion that modulation of IL-1 receptor activity could have applications as a part of combination therapy for advanced and highly metastatic colorectal cancers.

PMID: 30583087 [PubMed - as supplied by publisher]

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Synthesis and biological evaluation OF N-biphenyl-nicotinic based Moiety compounds: A new class of antimitotic agents for the treatment of Hodgkin lymphoma.

Synthesis and biological evaluation OF N-biphenyl-nicotinic based Moiety compounds: A new class of antimitotic agents for the treatment of Hodgkin lymphoma.

Cancer Lett. 2018 Dec 21;:

Authors: Porcelli L, Stolfa D, Stefanachi A, Di Fonte R, Garofoli M, Iacobazzi RM, Silvestris N, Guarini A, Cellamare S, Azzariti A

Abstract
We previously demonstrated that some N-biphenylanilides caused cell-cycle arrest at G2/M transition in breast cancer cells. Among them we choose three derivatives, namely PTA34, PTA73 and RS35 for experimentation in solid tumor cell lines, classical Hodgkin Lymphoma (cHL) cell lines and bona fide normal cell lines. Almost all tumor cells were sensitive to compounds in the nanomolar range whereas, they were not cytotoxic to normal ones. Interestingly the compounds caused a strong G2/M phase arrest in cHL cell lines, thus, here we investigated whether they affected the integrity of microtubules in such cells. We found that they induced a long prometaphase arrest, followed by induction of apoptosis which involved mitochondria. PTA73 and RS35 induced the mitotic arrest through the fragmentation of microtubules which prevented the kinethocore-mitotic spindle interaction and the exit from mitosis. PTA34 is instead a tubulin-targeting agent because it inhibited the tubulin polymerization as vinblastine. As such, PTA34 maintained the Cyclin B1-CDK1 regulatory complex activated during the G2/M arrest while inducing the inactivation of Bcl-2 through phosphorylation in Ser70, the degradation of Mcl-1 and a strong activation of BIML and BIMS proapoptotic isoforms. In addition PTA34 exerted an antiangiogenic effect by suppressing microvascular formation.

PMID: 30583077 [PubMed - as supplied by publisher]

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Rafoxanide, an organohalogen drug, triggers apoptosis and cell cycle arrest in multiple myeloma by enhancing DNA damage responses and suppressing the p38 MAPK pathway.

Rafoxanide, an organohalogen drug, triggers apoptosis and cell cycle arrest in multiple myeloma by enhancing DNA damage responses and suppressing the p38 MAPK pathway.

Cancer Lett. 2018 Dec 21;:

Authors: Xiao W, Xu Z, Chang S, Li B, Yu D, Wu H, Xie Y, Wang Y, Xie B, Sun X, Kong Y, Lan X, Bu W, Chen G, Gao L, Wu X, Shi J, Zhu W

Abstract
Rafoxanide is used in veterinary medicine for the treatment of fascioliasis. We previously repositioned the drug as the inhibitor of B-Raf V600E, but its anti-tumor effect in human cancer has never been reported. In this study, we investigated the effects of rafoxanide in multiple myeloma (MM) in vitro and in vivo. We found that rafoxanide inhibited cell proliferation and overcame the protective effect of the bone marrow (BM) microenvironment on MM cells. Rafoxanide induced cell apoptosis by reducing mitochondrial membrane potential (MMP) and regulating the caspase pathway, while having no apparent toxic effect on normal cells. Rafoxanide also inhibited DNA synthesis and caused cell cycle arrest by regulating the cdc25A-degradation pathway. In addition, rafoxanide enhanced the DNA damage response by up-regulating the expression of γ-H2AX, and suppressed activation of the p38 MAPK pathway by down-regulating p38 MAPK phosphorylation and Stat1 phosphorylation. Rafoxanide treatment inhibited tumor growth, with no significant side effects, in an MM mouse xenograft model. Combination of rafoxanide with bortezomib or lenalidomide significantly induced synergistic cytotoxicity in MM cells. Finally, rafoxanide had anti-proliferation effect on both wild type and B-Raf V600E mutated MM cells. And the weaker anti-MM activity of rafoxanide than vemurafenib may indicate other potential mechanisms besides targeting B-Raf V600E mutation. Collectively, our results provide a rationale for use of this drug in MM treatment.

PMID: 30583070 [PubMed - as supplied by publisher]

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MicroRNA-221 regulates osteosarcoma cell proliferation, apoptosis, migration, and invasion by targeting CDKN1B/p27.

MicroRNA-221 regulates osteosarcoma cell proliferation, apoptosis, migration, and invasion by targeting CDKN1B/p27.

J Cell Biochem. 2018 Dec 23;:

Authors: Hu XH, Zhao ZX, Dai J, Geng DC, Xu YZ

Abstract
MicroRNAs (miRNAs, miR) are of critical importance in growth and metastasis of cancer cells; however, the underlying functions of miRNAs in osteosarcoma (OS) remain largely unknown. This study was aimed to elucidate the role of miR-221 in regulating the biological behavior of OS cells. The proliferation ability was examined by cell counting kit-8 (CCK-8) and cell cycle assay. The abilities of cell migration, invasion, and apoptosis were monitored by transwell assay and flow cytometry, respectively. The effect of miR-221 on cyclin-dependent kinase inhibitor 1B (CDKN1B) expression was evaluated by luciferase assays, real-time polymerase chain reaction, and Western blot analysis. We found that miR-221 was elevated in OS cell lines compared with the normal osteoblastic cell line. Transfection of the miR-221 inhibitor into MG63 and U-2OS cell lines obviously suppressed cell proliferation, migration, and invasion, which is accompanied with cell cycle arrest in G0/G1 phase. Furthermore, luciferase reporter assays indicated that CDKN1B is directly targeted by miR-221 in OS cells. Knockdown of CDKN1B inhibited the effects of miR-221 inhibitor, along with decreased Bax and caspase-3 and increased cyclin E, cyclin D1, Bcl-2, Snail, and Twist1 expression. The results suggested that miR-221 might act as a potentially useful target for treatment of OS.

PMID: 30582227 [PubMed - as supplied by publisher]

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MicroRNA-329-mediated PTTG1 downregulation inactivates the MAPK signaling pathway to suppress cell proliferation and tumor growth in cholangiocarcinoma.

MicroRNA-329-mediated PTTG1 downregulation inactivates the MAPK signaling pathway to suppress cell proliferation and tumor growth in cholangiocarcinoma.

J Cell Biochem. 2018 Dec 23;:

Authors: Hu ZG, Zheng CW, Su HZ, Zeng YL, Lin CJ, Guo ZY, Zhong FD, Yuan GD, He SQ

Abstract
Cholangiocarcinoma (CCA) is a severe malignancy usually producing a poor prognosis and high mortality rate. MicroRNAs (miRNAs) have been reported in association with CCA; however, the role miR-329 plays in the CCA condition still remains unclear. Therefore, this study was conducted to explore the underlying mechanism of which miR-329 is influencing the progression of CCA. This work studied the differential analysis of the expression chips of CCA obtained from the Gene Expression Omnibus database. Next, to determine both the expression and role of pituitary tumor transforming gene-1 (PTTG1) in CCA, the miRNAs regulating PTTG1 were predicted. In the CCA cells that had been intervened with miR-329 upregulation or inhibition, along with PTTG1 silencing, expression of miR-329, PTTG1, p-p38/p38, p-ERK5/ERK5, proliferating cell nuclear antigen (PCNA), Cyclin D1, Bcl-2-associated X protein (Bax), B-cell CLL/lymphoma 2 (Bcl-2), and caspase-3 were determined. The effects of both miR-329 and PTTG1 on cell proliferation, cell-cycle distribution, and apoptosis were also assayed. The miR-329 was likely to affect the CCA development through regulation of the PTTG1-mediated mitogen-activated protein kinase (MAPK) signaling pathway. The miR-329 targeted PTTG1, leading to inactivation of the MAPK signaling pathway. Upregulation of miR-329 and silencing of PTTG1 inhibited the CCA cell proliferation, induced cell-cycle arrest, and subsequently promoted apoptosis with elevations in Bax, cleaved caspase-3, and total caspase-3, but showed declines in PCNA, Cyclin D1, and Bcl-2. Moreover, miR-329 was also found to suppress the tumor growth by downregulation of PTTG1. To summarize, miR-329 inhibited the expression of PTTG1 to inactivate the MAPK signaling pathway, thus suppressing the CCA progression, thereby providing a therapeutic basis for the CCA treatment.

PMID: 30582202 [PubMed - as supplied by publisher]

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Repressing of NHERF1 inhibits liver cancer progression by promoting the production of ROS.

Repressing of NHERF1 inhibits liver cancer progression by promoting the production of ROS.

Biochem Biophys Res Commun. 2018 Dec 20;:

Authors: Sun J, Li P, Yang J

Abstract
NHERF1/EBP50 is a PDZ-scaffold protein initially identified as an organizer and modulator of transporters and channels at the apical side of epithelia via actin-binding ezrin-moesin-radixin proteins. Presently, hepatocellular carcinoma (HCC) is one of the most deadly cancers in the world and has no effective therapeutic strategies. In the present study, we attempted to explore the role of NHERF1 in regulating liver cancer progression. The results indicated that NHERF1 was significantly expressed in liver tumor samples compared to the corresponding adjacent normal tissues. HCC patients with low NHERF1 exhibited better survival rate. Additionally, repressing NHERF1 expression markedly down-regulated the cell proliferation. G0/G1 transition was highly induced by NHERF1 knockdown, accompanied with reduced expressions of Cyclin D1 and cyclin-dependent kinase 4 (CDK4), as well as the enhanced expression of p27, phosphatase and tensin homolog (PTEN) and p53. Moreover, NHERF1 suppression significantly induced apoptosis in liver cancer cells by promoting the activation of Caspase-3 and poly (ADP-ribose) polymerase (PARP). We also observed a remarkable increase of reactive oxygen species (ROS) production in NHERF1-knockdown cells, along with c-Jun-N-terminal kinase (JNK) phosphorylation. Importantly, suppressing ROS production abolished NHERF1 knockdown-induced JNK activation. Moreover, cell cycle-regulatory proteins meditated by NHERF1 knockdown in liver cancer cells were abrogated by the pre-treatment of ROS scavenger. Further, restraining ROS generation also diminished NHERF1 knockdown-induced apoptosis. In vivo, we also found that NHERF1 knockdown markedly reduced the tumor growth. In conclusion, the results suggested that NHERF1 played an essential role in regulating liver cancer progression, and repressing NHERF1 expression exhibited significant anticancer effects via the induction of G0/G1 phase arrest, apoptosis and ROS generation.

PMID: 30581004 [PubMed - as supplied by publisher]

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Human Wharton's Jelly Stem Cell (hWJSC) Extracts Inhibit Ovarian Cancer Cell Lines OVCAR3 and SKOV3 in vitro by Inducing Cell Cycle Arrest and Apoptosis.

Human Wharton's Jelly Stem Cell (hWJSC) Extracts Inhibit Ovarian Cancer Cell Lines OVCAR3 and SKOV3 in vitro by Inducing Cell Cycle Arrest and Apoptosis.

Front Oncol. 2018;8:592

Authors: Kalamegam G, Sait KHW, Ahmed F, Kadam R, Pushparaj PN, Anfinan N, Rasool M, Jamal MS, Abu-Elmagd M, Al-Qahtani M

PMID: 30581772 [PubMed]

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Jinlong Capsule (JLC) inhibits proliferation and induces apoptosis in human gastric cancer cells in vivo and in vitro.

Jinlong Capsule (JLC) inhibits proliferation and induces apoptosis in human gastric cancer cells in vivo and in vitro.

Biomed Pharmacother. 2018 Nov;107:738-745

Authors: Li D, Ni T, Tao L, Jin F, Wang H, Feng J, Zhu G, Qian Y, Ding Y, Sunagagwa M, Liu Y

Abstract
BACKGROUND: As a representative traditional Chinese medicine made by modern pharmaceutical technology, Jinlong Capsule (JLC) has been used for several decades to treat liver cancer with significantly improved clinical outcomes as adjuvant therapy. JLC consists of three medicinal animals including freshly prepared Bungarus, Agkistrodon and Gecko. The active components were extracted by the process of modern cryogenic and biochemical separation from raw animals. However, the specific molecular mechanisms underlying the antitumor activities of JLC were not fully investigated. In the current study, experiments were carried out to examine the effect of JLC on anti-proliferative, pro-apoptotic activities of human gastric cancer (GC) cell lines in vivo and in vitro.
METHODS: MTT assay was used to observe the viability of MGC-803 and BGC-823 cells treated with JLC. Apoptosis and cell cycle distribution of MGC-803 and BGC-823 cells induced by JLC were analyzed by flow cytometry. Western blot assay was used to detect the effect of JLC on apoptosis-related proteins, including Bax, Bcl-2, survivin and caspase-3. Transmission electron microscopy (TEM) was used to evaluate the microstructure of apoptotic GC cells. Tumor growth in vivo was monitored using live-imaging system. Immunohistochemical staining (IHC) was used to examine the expression of apoptosis-related proteins in tumor tissues.
RESULTS: Our data indicated that JLC inhibited proliferation and induced apoptosis of MGC-803 and BGC-823 cells in a concentration-dependent manner. JLC significantly inhibited tumor growth in nude mice. Both in vivo and in vitro studies showed that JLC could downregulate the expression of Bcl-2 and survivin, whereas upregulate the levels of bax and caspase-3. JLC had significant antitumor effects in human GC through cell cycle arresting. Besides, JLC altered the microstructure of GC cells.
CONCLUSION: These findings demonstrate that JLC can be considered as a promising candidate in GC treatment.

PMID: 30138896 [PubMed - indexed for MEDLINE]

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Long non-coding RNA SNHG5 sponges miR-26a to promote the tumorigenesis of osteosarcoma by targeting ROCK1.

Long non-coding RNA SNHG5 sponges miR-26a to promote the tumorigenesis of osteosarcoma by targeting ROCK1.

Biomed Pharmacother. 2018 Nov;107:598-605

Authors: Wang Z, Wang Z, Liu J, Yang H

Abstract
BACKGROUND: Osteosarcoma (OS) is one of the most common invasive malignancies of the bone. The long non-coding RNA (lncRNA) SNHG5 (small nucleolar RNA host gene 5) has been consistently shown to be involved in many cancers, although its precise function in osteosarcoma remains poorly understood. In this study, we investigated the role of SNHG5 in OS progression and the underlying mechanism.
METHODS: SNHG5 expression in 32 OS tissues and 4 OS cell lines was measured by quantitative real-time PCR (qRT-PCR). Migration, invasion, proliferation and cell cycle profiles were analyzed by established assays to determine the biological functions of SNHG5 and miR-26a in OS cells. The binding sites of miR-26a in SNHG5 and ROCK1 were predicted by the RNAhybrid 2.2 program. Luciferase reporter assay was then used to validate the direct targeting of SNHG5 with miR-26a and of Rho-associated coiled coil-containing protein kinase 1 (ROCK1) with miR-26a. The effect of SNHG5 on the ROCK signaling pathway was assessed by western blotting.
RESULTS: Elevated expression of SNHG5 was correlated with poor clinical outcome and prognosis in OS patients. SNHG5 functioned as a sponge for miR-26a and promoted proliferation, invasion and migration, and accelerated G1 to S phase transition in OS cells. SNHG5 functioned as a competing endogenous RNA (ceRNA) for miR-26a and activated the ROCK signaling pathway through the miR-26a-ROCK1 axis.
CONCLUSION: SNHG5 acts as an oncogene in OS via the SNHG5-miR-26a-ROCK1 axis and is therefore a potential novel therapeutic target for OS treatment.

PMID: 30114643 [PubMed - indexed for MEDLINE]

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Cell cycle, cell division, and cell death.

Cell cycle, cell division, and cell death.

Mol Biol Cell. 2017 03 15;28(6):693-694

Authors: Coller HA, Desai A

PMID: 28292908 [PubMed - indexed for MEDLINE]

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DNA replication stress: NoCut to the rescue.

DNA replication stress: NoCut to the rescue.

Cell Cycle. 2017 02;16(3):233-234

Authors: Amaral N, Brownlow N, Mendoza M

PMID: 27464067 [PubMed - indexed for MEDLINE]

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Carthamus Tinctorius L. extract attenuates cardiac remodeling in L-NAME-induced hypertensive rats by inhibiting the NADPH oxidase-mediated TGF-b1 and MMP-9 pathway

Publication date: Available online 24 December 2018

Source: Annals of Anatomy - Anatomischer Anzeiger

Author(s): Sarawoot Bunbupha, Poungrat Pakdeechote, Putcharawipa Maneesai, Parichat Prachaney, Pattanapong Boonprom

Abstract

Carthamus tinctorius L. (CT) has been widely used in Asian countries as a beverage and a folk medicine. The current study investigates the effect of CT extract on cardiac remodeling and possible mechanisms involved in N_w-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague–Dawley rats were administrated with L-NAME (40 mg/kg/day) for five weeks to induce hypertension. Hypertensive rats were treated with CT extract (300 mg/kg/day) or captopril (5 mg/kg/day) or vehicle for a further two weeks. Treatment of hypertensive rats with CT extract or captopril significantly decreased systolic blood pressure, left ventricular (LV) hypertrophy and fibrosis, small intramyocardial coronary artery remodeling, and cardiac weight index. CT extract or captopril increased plasma nitric oxide metabolite (NOx) levels and reduced plasma transforming growth factor b1 (TGF-b1) level, together with downregulation of cardiac TGF-b1 and matrix metalloproteinases-9 (MMP-9) expression. In addition, decreased plasma malondialdehyde (MDA) levels, consistent with downregulation of NADPH oxidase subunit gp91^phox expression in heart tissue, was also observed after CT extract or captopril treatment. These findings suggest that CT extract alleviates cardiac remodeling in L-NAME-induced hypertensive rats, which is possibly related to inhibition of the NADPH oxidase-mediated TGF-b1-MMP-9 pathway.

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The Role of the Basolateral Amygdala in Dreaming

Publication date: Available online 25 December 2018

Source: Cortex

Author(s): Yvonne Blake, David Terburg, Ross Balchin, Jack van Honk, Mark Solms

Abstract

Neuroimaging studies have repeatedly shown amygdala activity during sleep (REM and NREM). Consequently, various theorists propose central roles for the amygdala in dreaming - particularly in the generation of dream affects, which seem to play a major role in dream plots. However, a causal role for the amygdala in dream phenomena has never been demonstrated. The traditional first step in determining this role is to observe the functional effects of isolated lesions to the brain structure in question. However, circumscribed bilateral amygdala lesions are extremely rare. Furthermore, the treatment of the amygdala as a unitary structure is problematic, as the basolateral and centromedial amygdala (BLA and CMA) may serve very different functions.

We analysed 23 dream reports collected from eight adult patients with bilateral calcification of the BLA as a result of a very rare genetic condition called Urbach-Wiethe Disease (UWD). We compared these dream reports to 52 reports collected from 17 matched controls. Given that the BLA has been implicated in various affective processes in waking life, we predicted that the emotional content of the patients' dreams would differ from that of controls. Due to the exploratory nature of this research, a range of different dream characteristics were analysed.

A principal components analysis run on all data returned three key factors, namely pleasantness, length and danger. The UWD patients' dream reports were significantly more pleasant and significantly shorter and less complex than control reports. No differences were found in levels of threat or danger.

The results support some current hypotheses concerning the amygdala's role in dreaming, and call others into question. Future research should examine whether these UWD patients show generally impaired emotional episodic memory due to BLA damage, which could explain some of the current findings.

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Τρίτη 25 Δεκεμβρίου 2018

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