Resistance to 5-fluorouracil (5-FU) is a major obstacle in treating oral squamous cell carcinoma (OSCC). However, little is known about apoptosis resistance, which contributes to 5-FU resistance in ...OSCC.
We focussed on the cellular inhibitor of apoptosis protein 2 (cIAP2) on the basis of a DNA microarray data using parental and 5-FU-resistant OSCC cell lines. The effects of cIAP2 downregulation on 5-FU sensitivity and apoptosis were evaluated. An immunohistochemical analysis of cIAP2 and related proteins, cIAP1 and X-linked IAP, was performed in 54 OSCC patients who were treated with 5-FU-based chemoradiotherapy and surgery.
The downregulation of cIAP2 significantly enhanced the sensitivity of the 5-FU-resistant cells to 5-FU, with a significant increase in apoptosis. The immunohistochemical analysis demonstrated a high cIAP2 tumour expression to significantly correlate with the pathological response to chemoradiotherapy. Furthermore, a Cox regression analysis revealed the cIAP2 expression status (hazard ratio, 4.91; P=0.037) and the pathological response to chemoradiotherapy (hazard ratio, 0.418; P=0.016) to be significant prognostic factors for OSCC patients.
These novel findings demonstrate that cIAP2 may represent a potentially useful therapeutic target for improving the treatment and survival of OSCC patients, particularly in the setting of 5-FU resistance.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objective
The objective of this retrospective study was to describe the clinical and histopathological findings associated with intranasal tumours in degus.
Materials and Methods
Medical records of ...degus diagnosed with intranasal neoplasms on histopathological examination between the years 2007 and 2020 at one hospital were included in the study.
Results Medical records of degus
Twenty degus (10 males and 10 females) were eligible for inclusion. Initial clinical signs included sneezing, abnormal nasal sounds, and nasal discharge, followed by anorexia and frequent nose rubbing. On radiography, 15 out of 20 animals showed space‐occupying lesions in the nasal cavity. CT was performed in 16 animals and revealed various degrees of changes, including abnormal radiopacity within the nasal cavity and damaged nasal septum. Rhinostomy and excisional biopsy was performed in all 20 animals. Six out of 20 patients died during the perioperative period. Six and seven degus survived for 3 months and 1 year, respectively. One animal was lost to follow‐up. In 16 cases the histological diagnosis was consistent with fibromas, while in 4 cases with osteomas.
Clinical Significance
Intranasal neoplasms in degus are mostly benign mesenchymal tumours with various degrees of bone formation, which is unique to this animal species. This occurrence should be considered as an important differential diagnosis for upper respiratory tract disease in degus.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
The Water and Sanitation Agency of Faisalabad has tried to increase its revenue by increasing both its water demands and total number of customers. To this end, a pilot activity was ...implemented. Two selected pilot areas were hydraulically separated to increase water pressures within the areas. The results showed that the durations of water supply increased from 3.5 to 12 hours and from 6 to 18 hours per day in the pilot areas. The water pressure in each pilot area increased from 2 to 10 m and from 3 to 18 m, respectively. Wastewater contamination was also eliminated after increasing the water pressure. Customers were informed of these achievements through workshops, flyers, and banners on streets, which encouraged them to shift from a flat rate system to a metering system. Consequently, the total billed amounts for two pilot areas in March 2019 increased by 65.0% and 97.0%, compared with those from November 2016. The bill collection ratios also increased from 48.2% to 56.9% and from 48.1% to 60.6% during pilot activities. Improving services of water supply utilities through the formation of a water distribution area with an increase in water pressure is recommended as an effective method for revenue augmentation.
Broadcasting, in the context of ad-hoc networks, is a costly operation, and thus topology control has been proposed to achieve efficient broadcasting with low interference and low energy consumption. ...By topology control, each node optimizes its transmission power by maintaining network connectivity in a localized manner. Local Minimum Spanning Tree (LMST) is the state-of-the-art topology control algorithm, which has been proven to provide satisfactory performance. However, LMST almost always results in a 1-connected network, without redundancy to tolerate external factors. In this paper, we propose Local Tree-based Reliable Topology (LTRT), which is mathematically proven to guarantee k-edge connectivity while preserving the features of LMST. LTRT can be easily constructed with a low computational complexity of O(k(m + n log n)), where k is the connectivity of the resulting topology, n is the number of neighboring nodes, and m is the number of edges. Simulation results have demonstrated the efficiency of LTRT and its superiority over other localized algorithms.
Summary
Background
With the increasing use of biological agents for the treatment of psoriasis, the numbers of patients with interstitial lung disease (ILD) associated with biologics have also ...increased. Many of these cases were associated with tumour necrosis factor (TNF)‐α inhibitors, but cases associated with other families of biologics have also been reported in Japan.
Aim
To analyse the background factors of patients who developed ILD, and to discuss better management of biological treatment.
Method
We reviewed 246 patients with psoriasis who were treated with biological agents in our department to identify any pulmonary adverse events (AEs). Data on patients who developed ILD were extracted to analyse background factors, clinical type of psoriasis, time to onset of ILD, pre‐existing ILD, smoking habit and prescribed drugs.
Results
Pulmonary AEs were seen in 22 cases, of which 11 were diagnosed as drug‐induced ILD. The causative drugs were mainly TNF‐α inhibitors, accounting for eight cases (six treated with infliximab, two with adalimumab). The remaining three cases were associated with secukinumab, ustekinumab and ixekizumab (n = 1 each). Notably, these three cases also had a history of drug‐induced ILD.
Conclusion
Patients with a history of drug‐induced ILD seem to be more susceptible to developing another ILD induced by biologics, even if treated with interleukin‐17 inhibitors. Thorough screening of risk factors and evaluation for eligibility, and careful monitoring during treatment are the best solutions to avoid serious pulmonary AE. Early detection and precise diagnosis of pulmonary AEs, especially differentiation from infectious diseases, is essential for managing biological treatment.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
In dogs, there are several idiopathic meningoencephalitides, such as necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis (NLE), and granulomatous meningoencephalomyelitis (GME). ...Although they are often assumed to be immune mediated, the etiology of these diseases remains elusive. In this study, the histopathology of the lesions caused by these conditions and the inflammatory cell populations produced in response to them were examined among dogs affected with GME, NME, or NLE to understand their pathogeneses. The brain tissues of dogs with NME (n = 25), NLE (n = 5), or GME (n = 9) were used. The inflammatory cells were identified by immunohistochemistry using antibodies against CD3, IgG, CD20, CD79acy, and CD163. In NME and NLE, malacic changes were located in the cerebral cortex, as well as the cerebral white matter and thalamus, respectively. The distribution of the brain lesions in NME and NLE was breed specific. In GME, granulomatous lesions that were mostly composed of epithelioid macrophages were observed in the cerebral white matter, cerebellum, and brainstem. Although the proportions of IgG-, CD20-, and CD79acy-positive cells (B cells) were not significantly different among the GME, NME, and NLE lesions, that of CD3-positive cells (T cells) was increased in GME. In NME and NLE, CD163-positive cells (macrophages) had diffusely infiltrated the cerebral cortex and white matter, respectively. However, in GME, CD163-positive cells accumulated around the blood vessels in the cerebral and cerebellar white matter. The distributions of these lesions were quite different among GME, NME, and NLE, whereas there were no marked differences in the proportions of inflammatory cells.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Nucleostemin (NS) is essential for the maintenance of stem cell properties, the functions of which remain poorly understood in cancer cells. The purpose of this study was to explore the impact of NS ...on malignancy and its clinical significance in oral squamous cell carcinoma (OSCC) patients.
We investigated the effects of NS on the proliferation and invasion of OSCC using NS-overexpressing or -knockdown OSCC cells. We assessed the activation of the STAT3 (signal transducer and activator of transcription 3) signalling pathway and the downstream targets in the cells with different expression levels of NS. An immunohistochemical analysis of NS was also performed in 54 OSCC patients who were treated with preoperative chemoradiotherapy and surgery.
The overexpression of NS significantly enhanced the proliferation and invasive potential of OSCC cells. On the other hand, downregulation of NS suppressed the invasiveness of the cells. The alterations of these malignant phenotypes were associated with the activation of STAT3 signalling and its downstream targets. An immunohistochemical analysis demonstrated that a high NS tumour expression level significantly correlated with an advanced T-stage and N-stage. Furthermore, a Cox regression analysis revealed that the NS status (hazard ratio, 9.09; P=0.002) was a significant progression factor for OSCC patients.
Our results suggest that targeting NS may provide a promising treatment for highly malignant OSCC.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract We previously reported that the anti-inflammatory cytokine interleukin (IL)-4 induced selective clearance of oligomeric β-amyloid (Aβ1–42 ) in rat primary type 2 microglial cells. For the ...present study, we investigated whether IL-4 and IL-13 could activate microglial cells to induce Aβ clearance in vivo and improve cognitive deficits in APP23 mice, which are amyloid precursor protein transgenic mice. We administered an intracerebral microinjection of a mixture of IL-4 and IL-13 or of saline vehicle into one hemisphere of APP23 mice and their wild-type littermates, 4.5 and 9 months old, after which we evaluated the effects of these treatments on spatial learning and memory by Morris Water Maze test and on accumulated amounts of Aβ. The cytokine injection significantly improved memory deficits of 4.5-month-old APP23 mice, but did not do so in 9-month-old APP23 mice, even though similar Aβ reductions were observed in both age groups of APP23 mice in the ipsilateral neocortex. The cytokine injection improved memory impairment of 9-month-old wild-type (WT) mice in the probe trial. Immunohistochemical analysis of the 4.5-month-old APP23 mice revealed the presence of increased numbers of microglial cells at 2 days after the cytokine injection. In addition to induced CD36 expression in the activated microglia, increased expression of neprilysin, mainly in neurons, suggested that the cytokines improved the cognitive deficits via degradation and clearance of intra- and extraneuronal Aβ peptides, of buffer-extractable nonplaque form. Double immunostaining also revealed that most of the activated microglia had the M2-like phenotype. This unique mechanism of IL-4/IL-13–induced clearance of Aβ may provide an additional strategy to prevent and/or cure Alzheimer's disease at early stage.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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