Current treatment of ulcerative colitis

Ulcerative colitis (UC) is a chronic disease featuring re- current inflammation of the colonic mucosa. The goal of medical treatment is to rapidly induce a steroid-free remission while at the same time preventing complica- tions of the disease itself and its treatment. The choice of treatment depends on severity, localization and the course of the disease. For proctitis, topical therapy with 5-aminosalicylic acid (5-ASA) compounds is used. More extensive or severe disease should be treated with oral and local 5-ASA compounds and corticosteroids to induce remission. Patients who do not respond to this treatment require hospitalization. Intravenous steroids or, when refractory, calcineurin inhibitors (cyclosporine, tacrolimus), tumor necrosis factor-α antibodies (infliximab) or immunomodulators (azathioprine, 6-mercaptopurine) are then called for. Indications for emergency surgery include refractory toxic megacolon, perforation, and continuous severe colorectal bleeding. Close collaboration between gastroenterologist and surgeon is mandatory in order not to delay surgical therapy when needed. This article is intended to give a general, practice-orientated overview of the key issues in ulcerative colitis treatment. Recommendations are based on published consensus guidelines derived from national and international guidelines on the treatment of ulcerative colitis.

Growth factor receptors and related signalling pathways as targets for novel treatment strategies of hepatocellular cancer

Growth factors and their corresponding receptors are commonly overexpressed and/or dysregulated in many cancers including hepatocellular cancer （HCC）. Clinical trials indicate that growth factor receptors and their related signalling pathways play important roles in HCC cancer etiology and progression, thus providing rational targets for innovative cancer therapies. A number of strategies including monoclonal antibodies, tyrosine kinase inhibitors （＂small molecule inhibitors＂） and antisense oligonucleotides have already been evaluated for their potency to inhibit the activity and downstream signalling cascades of these receptors in HCC. First clinical trials have also shown that multi-kinase inhibition is an effective novel treatment strategy in HCC. In this respect sorafenib, an inhibitor of Raf-, VEGF- and PDGF-signalling, is the first multi-kinase inhibitor that has been approved by the FDA for the treatment of advanced HCC. Moreover, the serine-threonine kinase of mammalian target of rapamycin （mTOR） upon which the signalling of several growth factor receptors converge plays a central role in cancer cell proliferation, roTOR inhibition of HCC is currently also being studied in preclinical trials. As HCCs represent hypervascularized neoplasms, inhibition of tumour vessel formation via interfering with the VEGF/VEGFR system is another promising approach in HCC treatment. This review will summarize the current status of the various growth factor receptor-based treatment strategies and in view of the multitude of novel targeted approaches, the rationale for combination therapies for advanced HCC treatment will also be taken into account.

Testicular expression of survivin and human telomerase reverse transcriptase(hTERT)associated with spermatogenic function in infertile patients

Aim： To characterize the coexpression of survivin, an inhibitor of apoptosis （IAF）, and human telomerase reverse transcriptase （hTERT） in human testes with varying spermatogenic function. Methods： Transcript levels of survivin mRNA and hTERT mRNA were determined in normal testes （n = 11） and testes with defective spermatogenesis （n = 28） using real-time reverse-transcription polymerase chain reaction （RT-PCR）. The histological work-up was performed according to a modified Johnsen score. Results： Expressions of both survivin and hTERT were highest at median levels of 96.8 and 709 in normal spermatogenesis and dropped to 53.3 and 534 in testes with postmeiotic spermatogenic arrest （n = 10）. In severe spermatogenic failure （n = 18）, survivin expression was lacking in most specimens （n = 16）, whereas at least low levels of testicular hTERT expression were largely detectable with a normalized expression of 73 in premeiotic spermatogenic arrest （n = 7） and 45 in patients with Sertoli cell-only syndrome （SCOS） （n = 3）. Both survivin and hTERT expressions increased with a progressing Johnsen score （P for trend = 0.001）. Conclusion： Although both survivin and hTERT are correlated with spermatogenic function, they show different expression patterns in testes of infertile patients. These findings substantiate results from studies in the rodent testis suggesting a predominant expression of survivin in meiotically dividing germ cells. （Asian J Andro12006 Jan; 8： 95-100）

Tyrosine kinase of insulin-like growth factor receptor as target for novel treatment and prevention strategies of colorectal cancer

AIM： To investigate the antineoplastic potency of the novel insulin-like growth factor 1 receptor （IGF-1R） tyrosine kinase inhibitor （TKI） NVP-AEW541 in cell lines and primary cell cultures of human colorectal cancer （CRC）. METHODS： Cells of primary colorectal carcinomas were from 8 patients. Immunostaining and crystal violet staining were used for analysis of growth factor receptor protein expression and detection of cell number changes, respectively. Cytotoxicity was determined by measuring the release of the cytoplasmic enzyme lactate dehydrogenase （LDH）. The proportion of apoptotic cells was determined by quantifying the percentage of sub-G1 （hypodiploid） cells. Cell cycle status reflected by the DNA content of the nuclei was detected by flow cytometry. RESULTS： NVP-AEW541 dose-dependently inhibited the proliferation of colorectal carcinoma cell lines and primary cell cultures by inducing apoptosis and cell cycle arrest. Apoptosis was characterized by caspase-3 activation and nuclear degradation. Cell cycle was arrested at the G1/S checkpoint. The NVP-AEW541-mediated cell cycle-related signaling involved the inactivation of Akt and extracellular signal-regulated kinase （ERK） 1/2, the upregulation of the cyclin-dependent kinase inhibitors p21^waf1/CIP1 and p27^kjp1, and the downregulation of the cell cycle promoter cyclin D1. Moreover, BAX was upregulated during NVP-AEW541-induced apoptosis, whereas Bcl-2 was downregulated. Measurement of LDH release showed that the antineoplastic effect of NVP-AEW541 was not due to general cytotoxicity of the compound. However, augmented antineoplastic effects were observed in combination treatments of NVP-AEW541 with either 5-FU, or the EGFR-antibody cetuximab, or the HMG-CoA-reductase inhibitor fluvastatin. CONCLUSION： IGF-1R-TK inhibition is a promising novel approach for either monoor combination treatment strategies of colorectal carcinoma and even for CRC chemoprevention.

Signaling pathways involved in the inhibition of epidermal growth factor receptor by erlotinib in hepatocellular cancer

AIM： To examine the underlying mechanisms of erlotinib-induced growth inhibition in hepatocellular carcinoma （HCC）. METHODS： Erlotinib-induced alterations in gene expression were evaluated using cDNA array technology; changes in protein expression and/or protein activation due to erlotinib treatment as well as IGF-1-induced EGFR transactivation were investigated using Western blotting. RESULTS： Erlotinib treatment inhibited the mitogen activated protein （MAP）-kinase pathway and signal transducer of activation and transcription （STAT）- mediated signaling which led to an altered expression of apoptosis and cell cycle regulating genes as demonstrated by cDNA array technology. Overexpression of proapoptotic factors like caspases and gadds associated with a down-regulation of antiapoptotic factors like Bcl-2, Bcl-XL or jun D accounted for erlotinib＇s potency to induce apoptosis. Downregulation of cell cycle regulators promoting the G1/S-transition and overexpression of cyclin-dependent kinase inhibitors and gadds contributed to the induction of a G1/G0-arrest in response to erlotinib. Furthermore, we displayed the transactivation of EGFR-mediated signaling by the IGF-1-receptor and showed erlotinib＇s inhibitory effects on the receptor-receptor cross talk. CONCLUSION： Our study sheds light on the understanding of the mechanisms of action of EGFR-TK- inhibition in HCC-cells and thus might facilitate the design of combination therapies that act additively or synergistically. Moreover, our data on the pathways responding to erlotinib treatment could be helpful in predicting the responsiveness of tumors to EGFR-TKIs in the future.

Gene therapy for gastric cancer:Is it promising?

Gastric cancer is one of the most common tumors worldwide. The therapeutic outcome of conventional therapies is inefficient. Thus, new therapeutic strategies are urgently needed. Gene therapy is a promising molecular alternative in the treatment of gastric cancer, including the replacement of defective tumor suppressor genes, the inactivation of oncogenes, the introduction of suicide genes, genetic immunotherapy, anti-angiogenetic gene therapy, and virotherapy. Improved molecular biological techniques and a better understanding of gastric carcinogenesis have allowed us to validate a variety of genes as molecular targets for gene therapy. This review provides an update of the new developments in cancer gene therapy, new principles, techniques, strategies and vector systems, and shows how they may be applied in the treatment of gastric cancer.

Targeted medical therapy of biliary tract cancer:Recent advances and future perspectives

The limited efficacy of cytotoxic therapy for advanced biliary tract and gallbladder cancers emphasizes the need for novel and more effective medical treatment options. A better understanding of the specific biological features of these neoplasms led to the development of new targeted therapies, which take the abundant expression of several growth factors and cognate tyrosine kinase receptors into account. This review will briefly summarize the status and future perspectives of antiangiogenic and growth factor receptor-based pharmacological approaches for the treatment of biliary tract and gallbladder cancers. In view of multiple novel targeted approaches, the rationale for innovative therapies, such as combinations of growth factor (receptor)-targeting agents with cytotoxic drugs or with other novel anticancer drugs will be highlighted.

多杀巴斯德菌致假体周围感染

目的分析多杀巴斯德菌致假体周围感染的特点。方法计算机检索Pubmed、Cochrane Library、Web of Science数据库自1998年1月至2018年1月多杀巴斯德菌引起假体周围感染的相关文献,根据纳入标准与排除标准进一步筛选。结果共收集9篇文献。其中6篇来自欧洲国家,3篇来自美国。入选文献中共10例患者。平均年龄70(57～84)岁,女性患者6例。膝关节感染7例,髋关节感染2例,肩关节感染1例。8例与猫接触相关,1例与马接触相关,1例与狗接触相关。5例合并既往病史,其中4例与多杀巴斯德菌假体周围感染危险因素相关。5例X线报告中2例X线发现有假体松动。白细胞计数、C反应蛋白、血浆沉降率均高于正常值,6例关节穿刺液培养结果均为阳性。在抗生素治疗加手术干预的所有病例中,≥1年随访结果显示治愈。结论多杀巴斯德菌假体周围感染患者多数存在明确的动物接触史。早期诊断并通过手术加抗生素治疗可以获得良好的预后。

CD2 deficiency partially prevents small bowel inflammation and improves parasite control in murine Toxoplasma gondii infection

To investigate whether bowel inflammation and/or parasite control is altered in the absence of the T cell adhesion molecule CD2.

Transplantation of an eight-organ multivisceraI graft in a patient with frozen abdomen after complicated Crohn's disease

To report an extended multivisceral transplantation （MVTx） including right kidney and ascending colon in a patient with complicated Crohn＇s disease （CD）. A 36-year old female suffering from short bowel syndrome and frozen abdomen due to fistulizing CD after multiple abdominal operations underwent MVTx of eight organs including stomach, pancreatoduodenal complex, liver, intestine, ascending colon, right kidney, right adrenal gland, and greater omentum in November 2003. Immunosuppression consisted of alemtuzumab, tacrolimus and steroids. The patient was off parenteral nutrition by postoperative wk 3. She experienced one episode of pneumonia. The patient recovered completely and discharged 2.5 mo and was doing well 30 mo after MVTx. This is one of the very rare cases in which a complete mulitivisceral graft of eight abdominal organs was transplanted orthotopically.

Effects of the Modified Linggui Zhugan Decoction(加味苓桂术甘汤) Combined with Short-term Very Low Calorie Diets on Glycemic Control in Newly Diagnosed Type 2 Diabetics

Objective:To evaluate the effects of the modified Linggui Zhugan Decoction(加味苓桂术甘汤) combined with short-term very low calorie diets(VLCDs) on glycemic control in newly diagnosed type 2 diabetes mellitus(T2DM) patients.Methods:A total of 20 subjects with newly diagnosed T2DM were treated with the modified Linggui Zhugan Decoction(one-month administration) combined with short-term VLCDs(5 days),and 3-months follow-up.A standard 75-g oral-glucose-tolerance test(OGTT) indexes fasting plasma glucose(FPG),post-prandial 0.5 h and 2 h plasma glucose(P0.5hPG,P2hPG),glycated hemoglobin A1C(GHbA1C),body weight,body mass index(BMI),insulin function,insulin resistance index,incidence of hypoglycemia,and the liver and renal functions were evaluated before and after treatment.Correlations of BMI with insulin function and insulin resistance were also assessed.Results:After the treatment,the patients' plasma glucose decreased steadily,FPG decreased from 5.8±0.9 mmol/L at pre-treatment to 5.0±0.6 mmol/L at 3-months follow-up(P<0.05),and P2hPG decreased from 11.7±3.8 mmol/L at pre-treatment to 6.9±0.9 mmol/L at 3-months follow-up(P<0.01).The level of GHbA1C declined from(6.47±1.24)% at pre-treatment to(6.14±0.99)% at 3-months follow-up(P<0.01).Body weight and BMI also declined significantly.Insulin resistance index was improved obviously and no event of hypoglycemia occurred.Part of the patients companied with fatty liver had a transient increase in hepatic transaminase during the treatment,but it turned to normal after the treatment.Conclusions:The modified Linggui Zhugan Decoction combined with short-term VLCDs can be safely implemented for steady glycemic control in newly diagnosed T2DM patients.

Quality Evaluation of Image Recording Strategies for Limited Angle Tomography

In this paper we propose a new method for evaluating image recording strategies for limited angle tomography. In limited angle tomography exact three-dimensional （3-D） reconstruction is not achievable. With this method a metric for the reachable reconstruction quality by defined X-ray source trajectories is calculated. The result of our method is independent of reconstruction algorithms. Our approach is based on the gradients of the scanned volume and their grade of determinability. Compared to simulated reconstruction accuracy with simultaneous algebraic reconstruction techniques, the method of evaluation shows the same dependencies on X-ray source trajectories. By using the proposed method different source trajectories for a limited angle range are comparable with respect to the reachable reconstruction quality.