从动物实验伦理问题问卷调查看医学伦理教育

通过对复旦大学和第二军医大学动物实验伦理问题的问卷调查,了解医学院校动物实验的现状及对待动物实验的看法并分析其引发的伦理学问题,从而探讨医学院校在动物实验中加强人文关爱精神及3R理论教育、培养医学生人文素养的措施和方法。     

Thioredoxin-Interact ing-Pro t e in [TXNIP] and Transglutaminase 2 [TGM2] Expression in Meningiomas of Different Grades and the Role of Their Expression in Meningioma Recurrence and Prognosis

Background: Meningiomas are common central nervous system (CNS) tumors that account for thirty percent of primary intracranial tumors.. The accuracy of predicting meningioma recurrence and progression is not enough. So, there is a real need for discovering recent factors for identification of the relapse risk, progression rates, which patients will need aggressive treatment and predicting and improving patients’ survival. Thioredoxin-interacting-protein [TXNIP] is an alpha-arrestin-protein family member that is mapped on chromosome 1-q21–22 and is found to participate in cellular redox reactions regulations and control. Transglutaminase 2 (TGM2) is a transglutaminase enzyme family member that is found in many human cells, it may act as an enzyme, a structural protein and also has multiple roles in many cellular activities. Aim of our study: It was to explore the expression of TXNIP, TGM2 and Ki-67 using immunohistochemistry in different pathological grades of meningiomas, and to investigate the relevance between their expressions, clinicopathological criteria, disease recurrence and prognosis of meningioma patients. Methods: we included 50 cases of meningioma of different pathological grades; all patients were managed according to their grade by surgery alone, with radiotherapy or combined modalities. Sections from paraffin blocks prepared from samples of all patients stained by TXNIP, TGM2 and Ki-67 using immunohistochemistry. Results: high expression of TXNIP in 28 out of 50 (56%) cases of meningioma of different pathological grades and was positively correlated with meningioma lower grade, low KI labeling index (p=0.000), adequacy of resection, negatively correlated with high incidence of recurrence after surgery and it was negatively correlated with meningioma higher pathological grades (p=0.000). We detected high expression of TGM2 in 21 out of 50 (42%) cases of meningioma and it was positively correlated with meningioma higher grade (p= 0.002), high KI labeling index (p=0.000), high incidence of recurrence after surgery, progression to higher pathological grades and was negatively correlated with adequacy of resection of meningioma (p=0.000). Conclusion: There is inverse relation between both [TXNIP and TGM2 expression in meningiomas and the combination of decreased expression of TXNIP and increased expression of TGM2 could predict risk of meningioma recurrence and progression in to higher pathological grades.     

Management of recurrent hepatocellular carcinoma after liver transplant

Hepatocellular carcinoma(HCC) is the leading cause of deaths in patients with hepatitis B or C, and its incidence has increased considerably over the past decade and is still on the rise. Liver transplantation(LT) provides the best chance of cure for patients with HCC and liver cirrhosis. With the implementation of the MELD exception system for patients with HCC waitlisted for LT, the number of recipients of LT is increasing, so is the number of patients who have recurrence of HCC after LT. Treatments for intrahepatic recurrence after transplantation and after other kinds of surgery are more or less the same, but long-term cure of posttransplant recurrence is rarely seen as it is a "systemic" disease. Nonetheless, surgicalresection has been shown to be effective in prolonging patient survival despite the technical difficulty in resecting graft livers. Besides surgical resection, different kinds of treatment are also in use, including transarterial chemoembolization, radiofrequency ablation, highintensity focused ultrasound ablation, and stereotactic body radiation therapy. Targeted therapy and modulation of immunosuppressants are also adopted to treat the deadly disease.     

Transient receptor potential vanilloid 4 regulates aquaporin-5 abundance under hypotonic conditions

Aquaporin-5 (AQP5) is expressed in epithelia of lung, cornea, and various secretory glands, sites where extracellular osmolality is known to fluctuate. Hypertonic aquaporin (AQP) induction has been described, but little is known about the effects of a hypotonic environment on AQP abundance. We report that, when mouse lung epithelial cells were exposed to hypotonic medium, a dose-responsive decrease in AQP5 abundance was observed. Hypotonic reduction of AQP5 was blocked by ruthenium red, methanandamide, and miconazole, agents that inhibit the cation channel transient receptor potential vanilloid (TRPV) 4 present in lung epithelial cells. Several observations indicate that TRPV4 participates in hypotonic reduction of AQP5, including a requirement for extracellular calcium to achieve AQP5 reduction; an increase in intracellular calcium in mouse lung epithelial (MLE) cells after hypotonic stimulation; and reduction of AQP5 abundance after addition of the TRPV4 agonist 4alpha-Phorbol-12,13-didecanoate (4alpha-PDD). Similarly, addition of hypotonic PBS to mouse trachea in vivo decreased AQP5 within 1 h, an effect blocked by ruthenium red. To confirm a functional interaction, AQP5 was expressed in control or TRPV4-expressing human embryonic kidney (HEK) cells. Hypotonic reduction of AQP5 was observed only in the presence of TRPV4 and was blocked by ruthenium red. Combined with earlier studies, these observations indicate that AQP5 abundance is tightly regulated along a range of osmolalities and that AQP5 reduction by extracellular hypotonicity can be mediated by TRPV4. These findings have direct relevance to regulation of membrane water permeability and water homeostasis in epithelia of the lung and other organs.     

Zeitaufgelöste Autofluoreszenz bei retinalen Gefäßverschlüssen

Background

Cellular metabolism can be evaluated using time-resolved autofluorescence. Because the fluorescence of ocular tissue is an accumulation of the fluorescence of several endogenous fluorophores, it is hard to determine the influence of a single fluorophore. In branch retinal artery occlusion, metabolic changes can be compared with normal tissue.

Method

Time-resolved autofluorescence was measured in two patients in two spectral channels, K1 (490–560 nm) and K2 (560–700 nm), and was 3-exponentially approximated and compared with representative results of a healthy eye.

Results

In K1, lifetime τ1 in the undersupplied tissue was weak, but τ2 was strongly elongated compared with the healthy tissue. In K2, the distribution of τ2 was identical in both tissues. In the healthy eye, there was an equal distribution of all lifetimes in corresponding fundus regions.

Conclusions

The elongation of τ1 in undersupplied tissue is probably caused by a reduced contribution of protein-bound FAD. The elongation of τ2 (about 500 ps) in healthy tissue, compared to about 1.5 ns in undersupplied tissue, is probably caused by protein-bound NADH, which is formed in glycolysis.     

The growth of brain tumors can be suppressed by multiple transplantation of mesenchymal stem cells expressing cytosine deaminase

Suicide genes have recently emerged as an attractive alternative therapy for the treatment of various types of intractable cancers.The efficacy of suicide gene therapy relies on efficient gene delivery to target tissues and the localized concentration of final geneproducts.     

Photofrin-mediated photodynamic therapy for treatment of early stage laryngeal malignancies

To evaluate the efficacy of PHOTOFRIN-mediated photodynamic therapy (PDT) for the treatment of Tis-T1N0M0 squamous cell carcinoma (SqCCa) of the larynx in patients not amenable to or who failed conventional head and neck treatment. This is a retrospective study of 26 patients with early stage Tis-T1 SqCCa of the larynx treated with PHOTOFRIN-mediated PDT. Intravenous PHOTOFRIN (porfimer-sodium) (dose 2.0 mg/kg) was administered outpatient, followed by intraoperative photoactivation at 630 nm via fiberoptic microlens surface delivery (surgical light dose 50–100 J/cm²) 48–60 h later. As much as 16 out of 26 patients (62%) have demonstrated complete remission (average follow-up 40 months). There were 10 patients who were noted to have partial remission with recurrence observed 2–33 months subsequently retreated with either repeated PDT therapy or conventional therapy. PHOTOFRIN-mediated photodynamic therapy can be used as a primary modality to treat Tis-T1N0M0 tumors of the larynx or for treatment for those who have failed prior surgery and/or radiation therapy. PDT allows for preservation of function and structure to maintain or improve voice with absence of systemic toxicity. Patients may have multiple drug administrations and laser light retreatment for local disease control.     

Revisiting Influences on Tumor Development: Focusing on Laboratory Housing

Spontaneous tumors are reported to occur in 45% to 71% of Sprague-Dawley rats, yet few studies have considered the effect of the sedentary condition of standard laboratory cages on tumorigenesis. Tumor profiles and tumor promoting hormone prolactin were compared in female Sprague-Dawley rats (108) that were allocated into 3 groups: those housed without outside activity (SED group), with twice-weekly 1-h sessions of physical activity in large box (PA group), and with regular voluntary running-wheel exercise (EX). Compared with the EX group, SED rats had more and larger tumors throughout most of their lifespan; tumor profiles of PA rats were similar to those of the SED group. A larger percentage of animals in the SED group had tumors (54%), compared with EX rats (38%). At 64 wk, tumors in SED animals included thyroid carcinoma, malignancy, mammary fibroadenoma, cystadenoma, and granuloma, whereas benign mammary gland cysts were most common in EX. Prolactin levels were highest in SED animals at 24 and 52 wk. In conclusion, increased tumor number, increased tumor size, type of spontaneous tumor, and increased prolactin in rats were associated with standard laboratory housing, which limited physical activity, and were not primarily due to aging.Knowledge about the underlying causes of mammary tumor development has been advanced by the use of rodent models for various reasons, including their relatively short lifespan and the ability to experimentally induce tumorigenesis. Most studies have investigated experimentally induced tumor growth, but such experiments are unlikely to predict the incidence of spontaneous tumor development. After the first year of age, spontaneous tumor development typically occurs at the rate of 45% to 71% in laboratory rats, in which the percentage of females with tumors is almost double that in males.^7,13 This high percentage of tumor-bearing rats probably reflects the effects of sex, age, and tumor-promoting hormones on tumorigenesis. However, a potentially overlooked factor is the sedentary cage environment of virtually all laboratory animals. The detrimental effect of the chronic, low-activity environment typical of a standard cage on aging and disease is supported indirectly by research indicating that regular exercise mitigates tumor growth.^{1,8,10,11,15,17} An environment whereby an animal engages in extremely low levels of physical activity over a long period of time is likely to have a strong influence-more than has been previously appreciated- on spontaneous tumor development. The influence of residing in a standard cage on spontaneous tumor development in laboratory rats has not been studied systematically over a typical lifespan.The paradigm in which animals that reside solely in standard caging serve as referent controls in experiments has recently been questioned because of research indicating health consequences associated with long-term physical inactivity.^1,3 Nevertheless, providing laboratory animals access to physical activity is complicated in some experimental designs due to different feeding regimens, surgical interventions, and so on. The effect of regular access to exercise on tumor number and size in laboratory animals depends on whether the exercise is forced (increases tumors) or voluntary (decreases tumors).^9,15,17 Prolactin (PRL) secretion plays an important regulatory role in tumorigenesis. Reducing PRL secretion in animals through voluntary exercise may attenuate tumor development.¹ In contrast, when exercise is forced, stress-related hormones and tumor development increase.¹⁰ The danger in not providing laboratory animals access to physical activity and, in effect, forcing animals to be sedentary is that the types of hormonal and metabolic changes associated with being sedentary can affect the spontaneous development of tumors.⁶ Long-term studies that assess the influence of housing on spontaneous tumor development are sparse. Furthermore, why the rate of tumor development in female rats is typically twice that of male rats is unclear.^7,13,16 A systematic long-term investigation on the environment influences tumor development throughout the life of female rats is needed.The purpose of this study was to determine how spontaneous tumor growth in female Sprague–Dawley rats residing in standard cages compared with that in animals that had access to regular voluntary exercise or to twice-weekly 1-h access to voluntary physical activity outside a standard cage. Unlike most previous studies in which tumors were chemically induced in exercise and sedentary groups, this study addressed naturally occurring or spontaneous tumors.     

Experience from a real-life cohort: outcome of 606 patients with hepatocellular carcinoma following transarterial chemoembolization

Background: Hepatocellular carcinoma (HCC) is one of the most lethal cancers. Transarterial chemoembolization (TACE) has been accepted as the standard care for intermediate stage disease.

Methods: In this study, we characterized 606 with HCC patients from Hannover Medical School treated with TACE.

Results: 606 with HCC patients treated with TACE were identified between 2000 and 2015. Most patients (59.8%) were at intermediate stage. Following TACE, most patients subsequently received systemic therapy or best supportive care (BSC), whereas 227 (37.5%) patients were bridged to potentially curative local treatments. Depending on subsequent therapies, median post-TACE survival ranged from 7 to 162 months. Ascites, cholinesterase, c-reactive and alpha-feto protein and tumor size were identified as prognostic factors. These factors as well as the HAP, mHAP-II and STATE score also determined post-TACE survival independent of subsequent therapies. Hepatic function progressively deteriorated with repeated TACE sessions. Despite that, post-TACE survival was not shortened in frequently treated patients (≥5 times) as compared to patients treated 4 times or less (p?=?not significant [n.s.]). Patients treated ≥5 times with TACE received significantly more often systemic therapy following TACE (37.3%) as compared to patients with 3–4 (30.1%), 2 (27.4%) and 1 (21.8%) sessions (p?<?.05).

Conclusion: TACE is performed in a heterogeneous population as bridging therapy to other local treatments and palliative therapy. The long-term survival following TACE is determined by baseline tumor, patient-related factors and by subsequent therapies. Post-TACE survival is not shorter in patients with frequent treatments (≥5), and the rate of subsequent systemic treatments is higher compared to less frequently treated patients.