Immune checkpoint blockade in ovarian cancer

Summary

Increased numbers of tumour infiltrating T‑cells have long been associated with a better prognosis in ovarian cancer, which has led to the general assumption of a relevant impact of T‑cellular anti-tumour immunity in this disease. As a consequence of this knowledge, a multitude of immunologic therapies has emerged over the past years. Although some reports could evidence a successful induction of anti-tumour T‑cells, in general, these attempts did not translate into clinically significant activity. As has already been shown in other tumour entities, immune checkpoint blockade – mainly antibodies directed against PD-1 and PD-L1 – could possibly become a real "game changer" in ovarian cancer in the future.

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Multiple cytokine-producing primary cutaneous anaplastic large cell lymphoma

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Abdominal aortic thrombosis secondary to reactive thrombocytosis in a patient with iron deficiency anemia

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Frequency of silent cerebral ischemia in patients with transfusion-dependent β-thalassemia major compared to healthy individuals

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Editorial Board

Publication date: June 2016
Source:Gait & Posture, Volume 47





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Contents List

Publication date: June 2016
Source:Gait & Posture, Volume 47





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Agreement of the activPAL3 and activPAL for characterising posture and stepping in adults and children

Publication date: Available online 1 June 2016
Source:Gait & Posture
Author(s): Ceri Sellers, Philippa Dall, Margaret Grant, Ben Stansfield
Characterisation of physical activity and sedentary behaviour under free-living conditions is becoming increasingly important in light of growing evidence for the health implications of these behaviours. The integrity of long-term follow-up and the ability to compare outcomes between studies is critically dependent on the agreement of outcomes from successive generations of monitors. This study evaluated the agreement of the activPAL and second generation activPAL3 devices. Agreement was assessed in both adults (median 27.6y IQR 22.6) (n=20) and young people (median 12.0y IQR 4.1) (n=8) during standardised and daily living (ADL) test activities. During standardised activities; sedentary duration, upright duration, stepping duration and overall number of steps were all detected within small limits of agreement (≤5%). However, the activPAL characterised more steps during jogging than the activPAL3 (adults +8.36%, young people +6.80%). Also during ADL differences arose due to different posture characterisation in young people and lower step detection in the activPAL than the activPAL3 (adults −20.58%, young people −11.43%). Second-by-second posture analysis demonstrated high levels (>90%) of agreement for all activities between monitors. However, sensitivity (68.7%) and positive predictive value (78.8%) for adult stepping demonstrated disagreement between monitor interpretation of movement patterns during ADL. Agreement between monitor outcomes for standardised activities provides confidence that these outcomes can be considered almost equivalent. However, for characterisation of jogging and smaller movements during ADL it is likely that significant differences between monitor outcomes will arise.



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In the national epidemiological bulletins - a selection from current issues

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2016 European guideline on the management of non-gonococcal urethritis published

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Effects of previous episodes of influenza and vaccination in preventing laboratory-confirmed influenza in Navarre, Spain, 2013/14 season

We estimated whether previous episodes of influenza and trivalent influenza vaccination prevented laboratory-confirmed influenza in Navarre, Spain, in season 2013/14. Patients with medically-attended influenza-like illness (MA-ILI) in hospitals (n?=?645) and primary healthcare (n?=?525) were included. We compared 589 influenza cases and 581 negative controls. MA-ILI related to a specific virus subtype in the previous five seasons was defined as a laboratory-confirmed influenza infection with the same virus subtype or MA-ILI during weeks when more than 25% of swabs were positive for this subtype. Persons with previous MA-ILI had 30% (95% confidence interval (CI): ?7 to 54) lower risk of MA-ILI, and those with previous MA-ILI related to A(H1N1)pdm09 or A(H3N2) virus, had a, respectively, 63% (95% CI: 16-84) and 65% (95% CI: 13-86) lower risk of new laboratory-confirmed influenza by the same subtype. Overall adjusted vaccine effectiveness in preventing laboratory-confirmed influenza was 31% (95% CI: 5-50): 45% (95% CI: 12-65) for A(H1N1)pdm09 and 20% (95% CI: ?16 to 44) for A(H3N2). While a previous influenza episode induced high protection only against the same virus subtype, influenza vaccination provided low to moderate protection against all circulating subtypes. Influenza vaccine remains the main preventive option for high-risk populations.

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Hepatitis B and C surveillance and screening programmes in the non-EU/EEA Member States of the WHO European Region: survey findings from 10 countries, 2012

The hepatitis B virus (HBV) and hepatitis C virus (HCV) epidemics warrant a comprehensive response based on reliable population-level information about transmission, disease progression and disease burden, with national surveillance systems playing a major role. In order to shed light on the status of surveillance in countries of the World Health Organization (WHO) European Region outside of the European Union and European Economic Area (EU/EEA), we surveyed 18 countries in Central and Eastern Europe. Among the 10 countries that responded, the common features of many surveillance systems included mandatory surveillance, passive case-finding and the reporting of both acute and chronic HBV and HCV. Only some countries had surveillance systems that incorporated the tracking of associated conditions and outcomes such as cirrhosis and liver transplantation. Screening programmes for some key populations appeared to be in place in many countries, but there may be gaps in relation to screening programmes for people who inject drugs, prisoners, sex workers and men who have sex with men. Nonetheless, important components of a surveillance structure are in place in the responding study countries. It is advisable to build on this structure to develop harmonised HBV and HCV surveillance for all 53 Member States of the WHO European Region following the example of the system recently instituted in EU/EEA countries.

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Public preferences for vaccination programmes during pandemics caused by pathogens transmitted through respiratory droplets - a discrete choice experiment in four European countries, 2013

This study aims to quantify and compare preferences of citizens from different European countries for vaccination programme characteristics during pandemics, caused by pathogens which are transmitted through respiratory droplets. Internet panel members, nationally representative based on age, sex, educational level and region, of four European Union Member States (Netherlands, Poland, Spain, and Sweden, n?=?2,068) completed an online discrete choice experiment. These countries, from different geographical areas of Europe, were chosen because of the availability of high-quality Internet panels and because of the cooperation between members of the project entitled Effective Communication in Outbreak Management: development of an evidence-based tool for Europe (ECOM). Data were analysed using panel latent class regression models. In the case of a severe pandemic scenario, vaccine effectiveness was the most important characteristic determining vaccination preference in all countries, followed by the body that advises on vaccination. In Sweden, the advice of family and/or friends and the advice of physicians strongly affected vaccine preferences, in contrast to Poland and Spain, where the advice of (international) health authorities was more decisive. Irrespective of pandemic scenario or vaccination programme characteristics, the predicted vaccination uptakes were lowest in Sweden, and highest in Poland. To increase vaccination uptake during future pandemics, the responsible authorities should align with other important stakeholders in the country and communicate in a coordinated manner.

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European Medicines Agency publishes draft advice on the use of colistin products in animals, for consultation

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Clinical and histopathological features of fatal cases with dengue and chikungunya virus co-infection in Colombia, 2014 to 2015

We report clinical features and histopathological findings in fatal cases with dengue (DENV) and chikungunya (CHIKV) co-infection identified at the Colombian National Institute of Health between September 2014 and October 2015. Seven such cases were documented. Dengue serotype 2 virus was identified in six cases. All patients were adults and comorbidities were present in four. Fever, arthralgia or myalgia was present in all cases. The frequency of rash, haemorrhage, oedema, and gastrointestinal symptoms was variable. Laboratory findings such as thrombocytopenia, renal failure, and leukocyte count were also inconsistent between cases. Post-mortem tissue examination documented focal hepatocellular coagulative necrosis in three cases, incipient acute pericarditis in one and tubulointerstitial nephritis in one. This study provides evidence of mortality in patients with DENV and CHIKV co-infection. Fatal cases were characterised by variable clinical and laboratory features. Evaluation of histopathology of autopsy tissues provided evidence of the pathological consequences of the disease.

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ECDC's latest publications

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CAR-engineered cytokine-induced killer cells overcome treatment resistance of pre-B-ALL and enhance survival

Abstract

Pre-emptive cancer immunotherapy by donor lymphocyte infusion (DLI) using cytokine-induced killer (CIK) cells may be beneficial to prevent relapse with a reduced risk of causing graft-versus-host-disease (GvHD). CIK cells are a heterogeneous effector cell population including T cells (CD3⁺CD56^-), natural killer (NK) cells (CD3^-CD56⁺) and natural killer T (T-NK) cells (CD3⁺CD56⁺) that exhibit non-MHC-restricted cytotoxicity and are generated by ex vivo expansion of peripheral blood mononuclear cells (PBMC) in the presence of interferon (IFN)-γ, anti-CD3 antibody, interleukin-2 (IL-2) and interleukin-15 (IL-15). To facilitate selective target-cell recognition and enhance specific cytotoxicity against B-cell acute lymphoblastic leukemia (B-ALL), we transduced CIK cells with a lentiviral vector encoding a chimeric antigen receptor (CAR) that carries a composite CD28-CD3ζ domain for signaling and a CD19-specific scFv antibody fragment for cell binding (CAR 63.28.z). In vitro analysis revealed high and specific cell killing activity of CD19-targeted CIK/63.28.z cells against otherwise CIK-resistant cancer cell lines and primary B-ALL blasts, which was dependent on CD19 expression and CAR signaling. In a xenograft model in immunodeficient mice, treatment with CIK/63.28.z cells in contrast to therapy with unmodified CIK cells resulted in complete and durable molecular remissions of established primary pre-B-ALL. Our results demonstrate potent anti-leukemic activity of CAR-engineered CIK cells in vitro and in vivo, and suggest this strategy as a promising approach for adoptive immunotherapy of refractory pre-B-ALL. This article is protected by copyright. All rights reserved.

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Intravitreal vascular endothelial growth factor (VEGF) inhibitor injection in unrecognised early pregnancy

Summary

The use of intravitreal vascular endothelial growth factor (VEGF) inhibitor medications has widened considerably to include indications affecting females of reproductive age. Our patient was inadvertently exposed to bevacizumab within the first trimester when placental growth and fetal organogenesis take place and patient suffered pregnancy loss. There is insufficient information to suggest that such use is safe, nor is there definitive evidence to suggest that it causes harm. We advise that ophthalmologists discuss pregnancy with women of childbearing age undergoing intraocular anti-VEGF injections and in pregnant woman counselling is needed to explain the potential risks and benefits.

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Long-term outcomes in radically treated synchronous vs. metachronous oligometastatic non-small-cell lung cancer

Abstract

Background

Radical treatment for oligometastatic non-small-cell lung cancer (NSCLC) has a curative potential for selected patients. The present retrospective study was designed to examine the relevance of synchronous vs. metachronous manifestations as a potential prognostic factor when ablative treatments are performed in oligometastatic disease.

Methods

Seventy-five patients with radically treated oligometastatic NSCLC were identified, of whom 39 presented with synchronous and 36 with metachronous metastatic manifestations. For patients with synchronous metastases, an additional therapy of the thoracic locoregional disease with a curative intent (either surgery or radiochemotherapy) was required. All patients with metachronous metastases had a documented remission of the primary tumor. Ablative treatment of the complete extent of oligometastatic disease consisted (as a minimum requirement) of either complete surgical resection or definitive ablative stereotactic radiotherapy. A comparative survival analysis of two groups of patients with oligometastatic NSCLC (synchronous vs. metachronous) and a complementary analysis of prognostic factors for the whole group of patients (by means of Cox regression analysis) was performed. Endpoints were median overall and progression-free survival (OS, PFS, respectively).

Results

Of the 75 patients, 57 presented with a solitary metastasis, in only 7 patients metastastatic lesions were present in ≥2 organs and 66 patients had a Karnofsky performance score (KPS) of 80 % or 90 %. The median follow-up was 54.0 months (95 % CI 28–81), the median OS 21.8 months (16.1–27.6) and the median PFS 13.7 months (9.7–17.6). In univariable Cox regression analysis, no single clinical factor was significantly associated with OS. For PFS both 'metastatic involvement of ≥2 organs vs. 1 organ' (hazard ratio (HR) 0.43, 0.23–0.83, p = 0.012) and a 'KPS of 90 % vs. 70–80 %' (HR 4.32, 1.73–10.89, p = 0.02) were significant prognostic factors as calculated by multivariable analysis. Comparing the cohorts with synchronous (n = 39) vs. metachronous oligometastases (n = 36), no differences in median OS and PFS were found. Both cohorts were well-balanced except for the KPS, which was significantly superior in patients with synchronous oligometastases.

Conclusions

Radical treatment of oligometastatic NSCLC was associated with acceptable long-term survival rates in patients with good KPS and it was equally effective for synchronous and metachronous manifestations.

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Ultrasound screening for cholangiocarcinoma could detect premalignant lesions and early-stage diseases with survival benefits: a population-based prospective study of 4,225 subjects in an endemic area

Abstract

Background

Thailand has a high incidence of cholangiocarcinoma (CCA), particularly in the north and northeastern regions. Most CCA patients come at a late, unresectable stage and presently no optimal screening test for CCA has been established. We determined the prevalence of CCA in a remote northern village and explored if screening could lead to early detection and survival benefits.

Methods

A 5-year population-based study was started in October, 2011 for consented Thai individuals, aged 30–60 years. The screening program comprised blood testing, stool examination and serial ultrasonography every 6 months.

Results

During the first 3 years, 4,225 eligible individuals were enrolled. CCA was detected in 32 patients, with a mean age of 51.9 years (41–62 years), and 21/32 cases were at a curative resectable stage. The prevalence rate of CCA was 165.7 per 100,000 and one- and two-year incidence rate was 236.7/100,000 and 520.7/100,000, respectively. One- and 2-year overall survival rates of CCA patients were 90.9 and 61.5 %, respectively. Prognosis was better in resectable cases with 100 % 1-year and 77.8 % 2-year survival rates. Interestingly, premalignant pathological lesions (stage 0) were identified in 11 cases with 100 % 3-year survival rate. Serum biomarkers and alkaline phosphatase were not sufficient to detect early-stage disease. In 22 patients, stool samples were positive for Opistorchis viverrini, based on polymerase chain reaction.

Conclusion

Detection of premalignant lesions and early-stage resectable CCA by ultrasonography resulted in improved clinical outcome. Ultrasonography should be offered as a first screening tool for CCA in an endemic area until other useful biological markers become available.

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Clinical characteristics and prognosis of 272 postterm choriocarcinoma patients at Peking Union Medical College Hospital: a retrospective cohort study

Abstract

Background

The objective of our study was to investigate the clinical characteristics and prognosis of postterm choriocarcinoma patients at Peking Union Medical College Hospital within the past 30 years.

Methods

The clinical characteristics and pertinent follow-up data of 272 patients with postterm choriocarcinoma diagnosed from December 1985 through December 2014 in our hospital were reviewed. The clinical characteristics of two cohorts cut off at 2006 were compared using χ ² tests. Risk factors of prognosis were estimated by multivariate Cox proportional regression analysis.

Results

The most common initial symptom was abnormal uterine bleeding. After individualized treatment 239 patients (87.9 %) achieved complete remission, including 140 patients received initial treatment of 5-fluorouracil-based multidrug chemotherapy. There were almost no statistically significant differences in the clinical characteristics and survival rates between the two cohorts. The results of the multivariate analysis showed that history of resistance to multidrug chemotherapy, liver metastasis and FIGO score greater than 12 were independent risk factors of prognosis.

Conclusions

Postterm choriocarcinoma patients were usually accompanied by several high-risk factors that should received combined chemotherapy to prevent delay in adequate treatment. 5-fluorouracil-based multidrug chemotherapy, which has been applied at PUMCH for several decades, can be an effective initial treatment for postterm choriocarcinoma patients. More emphasis should be placed on those who have history of resistance to multidrug chemotherapy, liver metastasis or a FIGO score greater than 12.

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Future Biomedical Devices to Benefit from High Speed Flexible Electronics

At the University of Wisconsin-Madison important work is being done developing high speed, stretchable integrated electronic circuits that could be used for biomedical applications. Consisting of tiny twisted-pair wires, similar to the arrangement of wires inside of Ethernet cables, the team's devices can be pulled on without degrading the electric signals flowing within while being shielded from external interference.

The power lines are only .64 millimeters wide while supporting frequencies up to 40 GHz, making them capable of transmitting microwave signals and eventually being compatible with the coming 5G wireless standard. This will allow the technology to be integrated within skin-worn wearables and other devices that can talk directly to other systems via 5G cellular networks.

From the study abstract in Advanced Functional Materials:

Detailed analysis, simulations, and experimental results show that the stretchable transmission line has negligible changes in performance when stretched and is operable on skin through suppressed radiated emission achieved with the twisted-pair geometry. Furthermore, stretchable microwave low-pass filter and band-stop filter are demonstrated using the twisted-pair structure to show the feasibility of the transmission lines as stretchable passive components. These concepts form the basic elements used in the design of stretchable microwave components, circuits, and subsystems performing important radio frequency functionalities, which can apply to many types of stretchable bioelectronics for radio transmitters and receivers.

Paper in Advanced Functional Materials: Stretchable Twisted-Pair Transmission Lines for Microwave Frequency Wearable Electronics

Via: UW–Madison

The post Future Biomedical Devices to Benefit from High Speed Flexible Electronics appeared first on Medgadget.

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Effect of 18 F-fluorodeoxyglucose extravasation on time taken for tumoral uptake to reach a plateau: animal and clinical PET analyses

Abstract

Objective

The present study aimed to investigate the effect of ¹⁸F-fluorodeoxyglucose (FDG) extravasation on the time taken for tumoral uptake to reach a plateau.

Methods

For the animal experiment, FDG extravasation was conducted in the tails of HCT116 tumor-bearing xenograft mice models in three groups (no extravasation, 40 % extravasation, and 80 % extravasation; n = 5, each). Dynamic positron emission tomography (PET) images were acquired over a period of 2 h following injection. Time–activity curves for FDG in the tails and tumors were calculated. For the clinical experiment, 22 patients (male:female, 14:8; age range, 70.8 ± 9.2 years) were subjected to PET/computed tomography (PET/CT) 1 h after the injection of FDG. The inclusion criteria were as follows: (1) submitted to both whole-body and subsequent regional scanning; (2) entire extravasation activity visualized in the whole-body images; (3) tumor visualized on both whole-body and additional regional images; and (4) status of tumor either confirmed by biopsy or clinically suspected for malignancy. The standardized uptake values (SUVs) of the tumors (on the whole-body and additional PET images) and extravasation sites were recorded.

Results

There were no significant differences in the time taken for tumoral uptake to reach a plateau and that to reach minimum activity at the extravasation site among the three groups of mice. However, the mean tumoral activity and activity at the extravasation site were negatively correlated at 1 h post-injection. According to the clinical PET findings, the differences in SUV between the whole-body and regional images were not significantly correlated with the interval between injection of FDG and start of whole-body scanning, interval between the start of whole-body scanning and start of regional scanning, extravasation volume, maximum SUV of the extravasation site, or total activity at the extravasation site.

Conclusions

The time taken for tumoral uptake to reach a plateau is not affected by extravasation, even at extensive degrees. Thus, in routine practice, the imaging time of approximately 60 min post-injection need not be modified even if extravasation is identified. However, tumor SUV may be underestimated in cases of extravasation.

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Increased 18 F-fluorodeoxyglucose accumulation in bilateral adrenal glands of the patients suffering from vasovagal reaction due to blood vessel puncture

Abstract

Objective

The purpose of the study was to evaluate the hypothesis that patients having a vasovagal reaction (VVR) after blood vessel puncture show increased FDG accumulation in bilateral adrenal glands.

Methods

Over the past 8 years, 26 patients experienced a VVR after blood vessel puncture following intra-venous injection of FDG at our institution. Of the 26 patients, 16 underwent multiple-occasion FDG-PET/CT scans while suffering a VVR at only one examination. All 16 patients had no morphological abnormality in the adrenal glands on FDG-PET/CT and follow-up examination. For the 16, we retrospectively reviewed the FDG-PET/CT scan with respect to the adrenal glands and compared the result to that for the FDG-PET/CT scan of the same patient when there was no VVR event. We used both visual analysis and semi-quantitative analysis employing either maximum standardized uptake value (SUVmax) or adrenal-to-liver (A/L) SUVmax ratio.

Results

On visual analysis of the FDG-PET/CT with VVR, accumulations in both of the adrenal glands was judged positive, defined as higher than the hepatic accumulation, in 84 % of the cases. The SUVmax in the right adrenal gland was 2.79 ± 0.69 with VVR and 1.92 ± 0.33 without VVR; this value in the left adrenal gland was 3.07 ± 0.71 with VVR and 2.05 ± 0.39 without. Mean SUVmax of both adrenal glands was 2.93 ± 0.66 with VVR and 1.98 ± 0.35 without. The A/L SUVmax ratio in the right adrenal gland was 1.02 ± 0.26 with VVR and 0.69 ± 0.11 without; this value in the left was 1.11 ± 0.23 with VVR and 0.74 ± 0.15 without. The mean A/L SUVmax ratio of both adrenal glands was 1.06 ± 0.24 with VVR and 0.72 ± 0.13 without. Each parameter with VVR was significantly higher than that without. For the two adrenal glands, the mean SUVmax with VVR was 48 % higher than that without VVR.

Conclusions

We confirmed the hypothesis that patients having a VVR after blood vessel puncture show increased FDG accumulation in their bilateral adrenal glands. This may reflect hyper-metabolism of the adrenal glands in synthesizing and secreting catecholamine.

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18 F-FDG uptake by rectal cancer is similar in mucinous and nonmucinous histological subtypes

Abstract

Purpose

PET/CT has been considered limited for the evaluation of mucinous colorectal tumors due to low ¹⁸F-FDG uptake. The aim of our study was to compare PET/CT variables in mucinous (MC) and nonmucinous (NMC) rectal adenocarcinomas.

Methods

Consecutive patients with cT2-4N0-2M0 rectal cancer included in a prospective clinical trial were reviewed. PET/CT was performed for primary baseline staging. Visual and quantitative analysis included SUVmax and SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). PET/CT parameters were compared according to histological subtypes.

Results

Overall, 73 patients were included (18 mucinous and 55 nonmucinous). SUVmax values were similar between MC and NMC (19.7 vs. 16.6; p = 0.5). MTV and TLG values were greater in the MC group (103.9 vs. 54.1; p = 0.007 and 892.5 vs. 358.8; p = 0.020) due to larger tumor volumes of MC.

Conclusions

Metabolic parameters at baseline PET/CT for patients with rectal cancer are similar in mucinous and nonmucinous histological subtypes.

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Phosphoprotein Phosphatase 1 Is Required for Extracellular Calcium-Induced Keratinocyte Differentiation

Extracellular calcium is a major regulator of keratinocyte differentiation in vitro and appears to play that role in vivo, but the mechanism is unclear. We have previously demonstrated that, following calcium stimulation, PIP5K1α is recruited by the E-cadherin-β-catenin complex to the plasma membrane where it provides the substrate PIP2 for both PI3K and PLC-γ1. This signaling pathway is critical for calcium-induced generation of second messengers including IP3 and intracellular calcium and keratinocyte differentiation. In this study, we explored the upstream regulatory mechanism by which calcium activates PIP5K1α and the role of this activation in calcium-induced keratinocyte differentiation. We found that treatment of human keratinocytes in culture with calcium resulted in an increase in serine dephosphorylation and PIP5K1α activation. PP1 knockdown blocked extracellular calcium-induced increase in serine dephosphorylation and activity of PIP5K1α and induction of keratinocyte differentiation markers. Knockdown of PLC-γ1, the downstream effector of PIP5K1α, blocked upstream dephosphorylation and PIP5K1α activation induced by calcium. Coimmunoprecipitation revealed calcium induced recruitment of PP1 to the E-cadherin-catenin-PIP5K1α complex in the plasma membrane. These results indicate that PP1 is recruited to the extracellular calcium-dependent E-cadherin-catenin-PIP5K1α complex in the plasma membrane to activate PIP5K1α, which is required for PLC-γ1 activation leading to keratinocyte differentiation.

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Can Technology Improve the Quality of Colonoscopy?

Abstract

In order for screening colonoscopy to be an effective tool in reducing colon cancer incidence, exams must be performed in a high-quality manner. Quality metrics have been presented by gastroenterology societies and now include higher adenoma detection rate targets than in the past. In many cases, the quality of colonoscopy can often be improved with simple low-cost interventions such as improved procedure technique, implementing split-dose bowel prep, and monitoring individuals' performances. Emerging technology has expanded our field of view and image quality during colonoscopy. We will critically review several technological advances in the context of quality metrics and discuss if technology can really improve the quality of colonoscopy.

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The effect of methanol rhizome extract of Nymphaea lotus Linn. (Nymphaeaceae) in animal models of diarrhoea

Publication date: 22 August 2016
Source:Journal of Ethnopharmacology, Volume 190
Author(s): Fatima Hauwa Bello, Bilkisu B. Maiha, Joseph A. Anuka
Ethnopharmacological relevanceNymphaea lotus, which is widely distributed throughout tropical Africa, enjoys a number of ethnomedical uses in Nigeria. Traditionally, the rhizomes of N. lotus are used to cure diarrhoea.Aim of studyThis study aims to evaluate the antidiarrhoeal activity of the methanol rhizome extract of N. lotus plant in laboratory animals.Materials and methodsThe extract was screened for activity against castor oil-induced diarrhoea and magnesium sulphate-induced diarrhoea as well as effect on gastric transit time in mice. The effect of methanol rhizome extract of Nymphaea lotus on the perfused isolated tissue preparation was also determined.ResultsFor castor oil-induced diarrhoea, the extract at doses of 200, 400 and 800mg/kg produced significant reduction in the frequency of diarrhoea (at p<0.001, p<0.001 and p<0.01 respectively). The extract at 800mg/kg produced a significant delay in onset of diarrhoea (p<0.05) comparable to loperamide (3mg/kg). The frequency of magnesium sulphate-induced diarrhoea was also significantly reduced in the groups treated with 200, 400 and 800mg/kg of the extract at p<0.001, p<0.001 and p<0.01 respectively. At doses of 200mg/kg and 400mg/kg, the protection produced was comparable to loperamide, 3mg/kg.All treated groups produced significant reduction in the transit of charcoal meal along the intestinal tract at p<0.001. The extract at low concentration (4×10⁻⁴–6.4×10⁻²mg/ml) had contractile effect on the tone of contraction of the rabbit jejunum while at higher concentrations (8×10⁻²–512×10⁻²mg/ml) produced significant reduction in the tone and rate of spontaneous contraction of rabbit jejunum. The extract at lower concentrations (4×10⁻⁴–2×10⁻²mg/ml) has no effect on contraction of the guinea pig ileum while higher concentrations (4×10⁻²–512×10⁻²mg/ml) produced significant relaxant activity on guinea pig ileum.ConclusionThis study has shown that the methanol rhizome extract of N. lotus has antidiarrhoeal properties thus justifying its use by the local population for this purpose.

Graphical abstract

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The combination effects of Shen-Ling-Bai-Zhu on promoting apoptosis of transplanted H22 hepatocellular carcinoma in mice receiving chemotherapy

Publication date: 22 August 2016
Source:Journal of Ethnopharmacology, Volume 190
Author(s): Shengyan Xi, Ying Peng, Gerald Y. Minuk, Mengmeng Shi, Biqian Fu, Jiaqi Yang, Qian Li, Yuewen Gong, Lifeng Yue, Lili Li, Jinhua Guo, Yang Peng, Yanhui Wang
Ethnopharmacological relevanceShen-Ling-Bai-Zhu Powder (SLBZP) is a classic traditional Chinese medical formula that has been used for several decades in the treatment of patients with gastrointestinal malignancies. Whether SLBZP is best employed as single agent or adjunctive therapy has yet to be determined as does the mechanism whereby SLBZP exerts its anti-tumor effects.Aim of the studyTo investigate the effects of SLBZP alone and in combination with Cytoxan (CTX) on tumor growth, malignant cell apoptosis and Akt/Nuclear Factor kappa B (NF-КB) signaling in a murine model of hepatocellular carcinoma (HCC) receiving chemotherapy.Materials and methodsSixty-four adult mice developed HCC following subcutaneous inoculation with H22 hepatocellular carcinoma cells. Seven days later, all received chemotherapy with CTX (200mg/kg) once. Mice were then randomized into eight study groups (N=8/group). Three groups were treated with different concentrations of SLBZP alone (6.00, 3.00, 1.5g/kg), three with SLBZP (6.00, 3.00, 1.5g/kg) plus CTX (20mg/kg), one with CTX (20mg/kg) alone (positive control), and one with physiologic saline (untreated, negative control). All groups were treated for 14 days. Tumor size, histology and serum or tissue levels and/or mRNA expression of PDGF-BB, VEGF, Ang-1, Ang-2, NF-КB, B-cell lymphoma-2 (Bcl-2); B-cell lymphoma-extra large (Bcl-xL); X-linked inhibitor of apoptosis (XIAP), Survivin, Caspase-3, Caspase-9, Caspase-7, Akt and phosphorylated Akt expression were documented at the end of treatment.ResultsCompared to untreated negative controls, tumor sizes were decreased in the CTX alone, SLBZP (M)+CTX and SLBZP (H)+CTX groups (−52%,−53% and −58% respectively). Tumor cell density was decreased in all treated groups but most apparent in the SLBZP (H)+CTX group. Electron microscopic evidence of apoptosis was also most apparent in this group. Serum and/or tissue levels and expression of PDGF-BB, VEGF, Ang-1, Ang-2, their downstream signaling proteins and anti-apoptotic markers were lowest and pro-apoptotic markers highest in SLBZP (H)+CTX treated mice.ConclusionsIn this chemotherapy-induced animal model of HCC, SLBZP was most efficacious as adjunctive therapy and appears to act by inhibiting tumor growth promoters and anti-apoptotic proteins while enhancing pro-apoptotic proteins.

Graphical abstract

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Phase II multicentre trial of oral quisinostat, a histone deacetylase inhibitor, in patients with previously treated stage IB–IVA mycosis fungoides/Sézary syndrome

Summary

Background

Quisinostat is a hydroxamate, second-generation, orally available pan-histone deacetylase inhibitor.

Objectives

To evaluate the efficacy and safety of oral quisinostat in patients with previously treated cutaneous T-cell lymphoma (CTCL).

Methods

Patients received quisinostat 8 mg or 12 mg on days 1, 3 and 5 of each week in 21-day treatment cycles. Primary efficacy end point was cutaneous response rate (RR) based on the modified Severity Weighted Assessment Tool (mSWAT). Secondary end points included global RR, duration of response (DOR) in skin, progression-free survival (PFS), pruritus relief, safety and pharmacodynamic markers.

Results

Eight of 26 (25 evaluable) patients achieved ≥ 50% reduction in mSWAT score at least once, with confirmed cutaneous response in six (RR 24%). There was a low global RR of 8%. DOR in skin ranged from 2·8 to 6·9 months. Median PFS was 5·1 months. Pruritus relief was more frequent in cutaneous responders (67%) than nonresponders (32%). Serial tumour biopsies revealed an increase in acetylated tubulin, indicating a target effect of histone deacetylase 6. Twenty-one of 26 (81%) patients were withdrawn from the study before or at clinical cut-off; five (19%) continued to receive treatment with quisinostat. The most common drug-related adverse events were nausea, diarrhoea, asthenia, hypertension, thrombocytopenia and vomiting. Grade 3 drug-related adverse events included hypertension, lethargy, pruritus, chills, hyperkalaemia and pyrexia.

Conclusions

Quisinostat 12 mg three times weekly is active in the treatment of patients with relapsed or refractory CTCL, with an acceptable safety profile. Combination therapy with other drugs active in CTCL may be appropriate.

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Perioperative management of novel oral anticoagulants in skin surgery: a national survey

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Genetics and metabolic deregulation following cancer initiation: A world to explore

Publication date: August 2016
Source:Biomedicine & Pharmacotherapy, Volume 82
Author(s): Rodrigo Pinheiro Araldi, Diego Grando Módolo, Paulo Luiz de Sá Júnior, Sílvio Roberto Consonni, Rodrigo Franco de Carvalho, Franco Peppino Roperto, Willy Beçak, Rita de Cassia Stocco
Cancer is a group of highly complex and heterogeneous diseases with several causes. According to the stochastic model, cancer initiates from mutation in somatic cells, leading to genomic instability and cell transformation. This canonical pathway of carcinogenesis is related to the discovery of important mechanisms that regulate cancer initiation. However, there are few studies describing genetic and metabolic alterations that deregulate transformed cells, resulting in epithelial–mesenchymal transition (EMT) and its most dramatic consequence, the metastasis. This review summarizes the main genetics and metabolic changes induced by reactive oxygen species (ROS) that lead to EMT.



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Editorial Board

Publication date: June 2016
Source:Photodiagnosis and Photodynamic Therapy, Volume 14





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Guttiferone K impedes cell cycle re-entry of quiescent prostate cancer cells via stabilization of FBXW7 and subsequent c-MYC degradation

Guttiferone K impedes cell cycle re-entry of quiescent prostate cancer cells via stabilization of FBXW7 and subsequent c-MYC degradation

Cell Death and Disease 7, e2252 (June 2016). doi:10.1038/cddis.2016.123

Authors: Z Xi, M Yao, Y Li, C Xie, J Holst, T Liu, S Cai, Y Lao, H Tan, H-X Xu & Q Dong

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Raptor hunted by caspases

Raptor hunted by caspases

Cell Death and Disease 7, e2242 (June 2016). doi:10.1038/cddis.2016.153

Authors: R Martin, M Thome, F Martinon & N Fasel

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Endoplasmic reticulum stress eIF2α–ATF4 pathway-mediated cyclooxygenase-2 induction regulates cadmium-induced autophagy in kidney

Endoplasmic reticulum stress eIF2α–ATF4 pathway-mediated cyclooxygenase-2 induction regulates cadmium-induced autophagy in kidney

Cell Death and Disease 7, e2251 (June 2016). doi:10.1038/cddis.2016.78

Authors: B Luo, Y Lin, S Jiang, L Huang, H Yao, Q Zhuang, R Zhao, H Liu, C He & Z Lin

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Transglutaminase 2 has opposing roles in the regulation of cellular functions as well as cell growth and death

Transglutaminase 2 has opposing roles in the regulation of cellular functions as well as cell growth and death

Cell Death and Disease 7, e2244 (June 2016). doi:10.1038/cddis.2016.150

Authors: H Tatsukawa, Y Furutani, K Hitomi & S Kojima

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A20 prevents chronic liver inflammation and cancer by protecting hepatocytes from death

A20 prevents chronic liver inflammation and cancer by protecting hepatocytes from death

Cell Death and Disease 7, e2250 (June 2016). doi:10.1038/cddis.2016.154

Authors: L Catrysse, M Farhang Ghahremani, L Vereecke, S A Youssef, C Mc Guire, M Sze, A Weber, M Heikenwalder, A de Bruin, R Beyaert & G van Loo

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Proteolytic degradation and potential role of onconeural protein cdr2 in neurodegeneration

Proteolytic degradation and potential role of onconeural protein cdr2 in neurodegeneration

Cell Death and Disease 7, e2240 (June 2016). doi:10.1038/cddis.2016.151

Authors: J-Y Hwang, J Lee, C-K Oh, H W Kang, I-Y Hwang, J W Um, H C Park, S Kim, J-H Shin, W-Y Park, R B Darnell, H-D Um, K C Chung, K Kim & Y J Oh

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A ribosome-related signature in peripheral blood CLL B cells is linked to reduced survival following treatment

A ribosome-related signature in peripheral blood CLL B cells is linked to reduced survival following treatment

Cell Death and Disease 7, e2249 (June 2016). doi:10.1038/cddis.2016.148

Authors: T Sbarrato, E Horvilleur, T Pöyry, K Hill, L C Chaplin, R V Spriggs, M Stoneley, L Wilson, S Jayne, T Vulliamy, D Beck, I Dokal, M J S Dyer, A M Yeomans, G Packham, M Bushell, S D Wagner & A E Willis

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Toll-like receptor 4 modulates the cochlear immune response to acoustic injury

Toll-like receptor 4 modulates the cochlear immune response to acoustic injury

Cell Death and Disease 7, e2245 (June 2016). doi:10.1038/cddis.2016.156

Authors: R R Vethanayagam, W Yang, Y Dong & B H Hu

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Role of long non-coding RNA-RNCR3 in atherosclerosis-related vascular dysfunction

Role of long non-coding RNA-RNCR3 in atherosclerosis-related vascular dysfunction

Cell Death and Disease 7, e2248 (June 2016). doi:10.1038/cddis.2016.145

Authors: K Shan, Q Jiang, X -Q Wang, Y -N -Z Wang, H Yang, M -D Yao, C Liu, X -M Li, J Yao, B Liu, Y -Y Zhang, Yong J & B Yan

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Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model

Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model

Cell Death and Disease 7, e2243 (June 2016). doi:10.1038/cddis.2016.134

Authors: A Gomez-Cadena, C Urueña, K Prieto, A Martinez-Usatorre, A Donda, A Barreto, P Romero & S Fiorentino

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Erianin induces G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells in vitro and in vivo

Erianin induces G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells in vitro and in vivo

Cell Death and Disease 7, e2247 (June 2016). doi:10.1038/cddis.2016.138

Authors: H Wang, T Zhang, W Sun, Z Wang, D Zuo, Z Zhou, S Li, J Xu, F Yin, Y Hua & Z Cai

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A transcription factor 7-like 1-lipocalin 2 axis in the differentiation of keratinocytes

A transcription factor 7-like 1-lipocalin 2 axis in the differentiation of keratinocytes

Cell Death and Disease 7, e2241 (June 2016). doi:10.1038/cddis.2016.152

Authors: Y Liu, H Cheng, S Xiao & Y Xia

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Continuous exposure of pancreatic cancer cells to dietary bioactive agents does not induce drug resistance unlike chemotherapy

Continuous exposure of pancreatic cancer cells to dietary bioactive agents does not induce drug resistance unlike chemotherapy

Cell Death and Disease 7, e2246 (June 2016). doi:10.1038/cddis.2016.157

Authors: P Fan, Y Zhang, L Liu, Z Zhao, Y Yin, X Xiao, N Bauer, J Gladkich, J Mattern, C Gao, P Schemmer, W Gross & I Herr

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TMEM2 inhibits hepatitis B virus infection in HepG2 and HepG2.2.15 cells by activating the JAK–STAT signaling pathway

TMEM2 inhibits hepatitis B virus infection in HepG2 and HepG2.2.15 cells by activating the JAK–STAT signaling pathway

Cell Death and Disease 7, e2239 (June 2016). doi:10.1038/cddis.2016.146

Authors: X Zhu, C Xie, Y-m Li, Z-l Huang, Q-y Zhao, Z-x Hu, P-p Wang, Y-r Gu, Z-l Gao & L Peng

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Short-term treatment outcomes in human immunodeficiency virus type-1 and hepatitis B virus co-infections

Co-infection of HIV with HBV is common in West Africa but little information is available on the effects of HBV on short-term therapy for HIV patients. A 28 day longitudinal study was conducted to examine shor...

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Solvent responsive catalyst improves NMR sensitivity via efficient magnetisation transfer

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC03185D, Communication

Amy J Ruddlesden, Simon B Duckett
A bidentate iridium carbene complex, Ir([small kappa]C,O-L1)(COD), has been synthesised which contains a strongly electron donating carbene ligand that is functionalised by a cis-spanning phenolate group. This complex acts as a...
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A single-stranded {Gd18} nanowheel with symmetric polydentate diacylhydrazone ligand

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC02208A, Communication

Kai Wang, Zilu Chen, Hua-Hong Zou, kun hu, Hai-Ye Li, Zhong Zhang, Wei-Yin Sun, Fupei Liang
An unprecedented {Gd18} nanowheel was solvothermally synthesized with a novel diacylhydrazone ligand. It features a rare single-stranded skeleton just like a Reuleaux triangle with vertices buckled in, represents the highest...
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Hierarchical Construction of Cross-Junction of Molecular Wires with Covalent and Noncovalent Interactions at the Liquid/Solid Interface

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC02975B, Communication

Yanxia Yu, Ling Yang, chunhua Liu, Weiquan Tian, Yan Wang, Shengbin Lei
Hierarchical networks, constructed by non-covalent bond stabilized cross junctions of covalent one-dimensional molecular wires, are synergistically formed at the liquid/solid interface through in situ on-surface condensation of aromatic amine and...
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