Preventative and therapeutic vaccines for fungal infections: from concept to implementation

Many challenges confront the development of fungal vaccines for humans including differences in host susceptibility, varied pathogenic mechanisms employed by the different species of fungi and mechanisms of host resistance. Hence, no single antigen can be expected to serve as a pan fungal vaccine. Instead, it is likely that progress for fungal vaccines will have to be made at the level of each individual organism. In recent years, tremendous strides have been made in understanding the immunopathogenesis of medically important fungal infections and identifying putative vaccine candidates. Such discoveries will facilitate the introduction of fungal vaccines into the therapeutic armamentarium of clinicians. The fungi under discussion in this review include Candida spp., Aspergillus spp., Cryptococcus neoformans, Coccidioides spp., Histoplasma capsulatum, Blastomyces dermatitidis, Paracoccidioides brasiliensis and Pneumocystis jirovecii.     

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of gastric cancer with peritoneal carcinomatosis: evidence from an experimental study

Background  

Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has been considered as a promising treatment modality for gastric cancer with peritoneal carcinomatosis (PC). However, there have also been many debates regarding the efficacy and safety of this new approach. Results from experimental animal model study could help provide reliable information. This study was to investigate the safety and efficacy of CRS + HIPEC to treat gastric cancer with PC in a rabbit model.     

A 5-fluorouracil-loaded polydioxanone weft-knitted stent for the treatment of colorectal cancer

In-stents restenosis caused by tumour ingrowth is a major problem for patients undergoing stent displacement because the conventional stents often lack a sustained anti-tumour capability. The aim of this paper was to develop a weft-knitted polydioxanone stent which can slow release 5-fluorouracil (5-FU). In order to determine the most suitable drug concentration, the 5-FU safe concentration in vivo and appropriate loading percentage in the membranes were investigated, and then 5-FU-loaded poly-l-lactide membranes at concentration of 3.2%, 6.4% and 12.8% were coated onto the stent using electro-spinning method, respectively. The morphology, chemical structure and in vitro drug release property of the coating membranes were subsequently examined. Their anti-tumour activity and mechanism were assessed in vitro and in vivo using a human colorectal cancer cell line HCT-116 and tumour-bearing BALB/c nude mice. The half maximal inhibitory concentration (IC₅₀) and the median lethal dose (LD₅₀) demonstrated that the 6.4% and 12.8% membranes had better anti-tumour effects than pure 5-FU due to the sustainable drug releasing property of the coated membranes on the stent. The membranes possessing appropriate drug loading doses, such as 6.4% or 12.8% also provided better anti-in-stents restenosis effects than other groups tested. Therefore, it is concluded that the drug-loaded stents have great potential for the use in the treatment of intestinal cancers in the future.     

A generic concept for the implementation of medical image retrieval systems

This paper presents a technical framework to support the development and installation of system for content-based image retrieval in medical applications (IRMA). A strict separation of feature extraction, feature storage, feature comparison, and the user interfaces is suggested. This allows to reuse implemented components in different retrieval algorithms, which improves software quality, shortens the development cycle for applications, and allows to introduce standardized end-user interfaces. Based on the proposed framework, the IRMA engine has been established, which is currently used to evaluate content-based retrieval methods on a collection of 20,000 medical and 135,000 non-medical images.     

A proposal for the reporting of cancer by hospital pathologists

A proposal is presented that pathologists submit diagnostic information in each newly diagnosed case of cancer. An existing regional cancer incidence reporting system would be the recipient of these confidential data. The information could be used for monitoring the total cancer population within a geopolitical region. Problems that can be anticipated in planning for implementation of this proposal are addressed in general terms.     

The treatment of bruxism: A review and proposal for future research

The epidemiology, etiology, and psychological treatment of bruxism are reviewed. A methodological critique of treatment studies is also presented. Lastly, suggestions for future research are discussed.     

帕尼单抗在治疗转移性结直肠癌中的应用

结直肠癌是癌相关性死亡的第三大死因,转移性结直肠癌患者生存率明显下降,且不少患者对化疗产生耐药。帕尼单抗是第一个全人源单克隆治疗性抗体,选择性地与肿瘤细胞表面表皮生长因子受体特异性结合而发挥抗瘤效果,临床试验研究结果显示帕尼单抗对化疗耐药的转移性结直肠癌具有较好的疗效和安全性,在放射免疫显像及放射免疫治疗中也具有较好的应用前景。     

Molecular typing of colorectal cancer: applications in diagnosis and treatment

Molecular typing of colorectal cancer (CRC) is at an early stage of development with analysis of KRAS mutation status and DNA mismatch repair (MMR) deficiency representing the two major approaches currently in use for diagnosis and treatment-related purposes. RAS proteins act as molecular switches that regulate cellular processes including cell growth and survival. Activating KRAS mutations are found in 40–50% of colorectal adenomas and cancers. Detection of KRAS mutations guide the decision to use anti-EGFR antibody therapy, which is not effective in KRAS mutant cancers. MMR deficiency results in failure to repair replication-associated DNA errors, allowing persistence of mismatch mutations all over the genome, especially in regions of repetitive DNA known as microsatellites, giving rise to microsatellite instability (MSI). A high frequency of microsatellite instability (MSI-H) often with abnormal expression of MMR proteins is key to the diagnosis of Lynch Syndrome, but is also observed in ～15% of sporadic CRC.     

A proposal for evaluation of treatment in experimental fat embolism

The efficiency of various treatments of clinical fat embolism is difficult to assess because of the wide range in the severity of the syndrome. Similarly, in experimental fat embolism, the efficiency of treatment has usually been based on studies employing non-fatal doses of fat. For use in studying experimental fat embolism, we propose a technique based on the comparison of LD₅₀'s of two groups of animals injected with fat: a control group versus a treated group. With this method, the efficiency of treatment is based on the survival of animals receiving larger doses of fat which is the ultimate goal in therapy (i.e., survival with an otherwise fatal dose of fat) and it also allows for the biological variability of animals in response to toxic injections of fat.     

Advanced colorectal polyps with the molecular and morphological features of serrated polyps and adenomas: concept of a 'fusion' pathway to colorectal cancer

AIM: To establish and explain the pattern of molecular signatures across colorectal polyps. METHODS AND RESULTS: Thirty-two sessile serrated adenomas (SSA), 10 mixed polyps (MP), 15 traditional serrated adenomas (SA), 49 hyperplastic polyps (HP) and 84 adenomas were assessed for mutation of KRAS and BRAF and aberrant expression of p53. The findings were correlated with loss of expression of O-6-methylguanine DNA methyltransferase (MGMT). KRAS mutation occurred more frequently (26.5%) than BRAF mutation (4.8%) in adenomas (P < 0.001) and particularly in adenomas with villous architecture (50%). Loss of expression of MGMT correlated with KRAS mutation in small tubular adenomas (P < 0.04). BRAF mutation was frequent in HPs (67%) and SSAs (81%), while KRAS mutation was infrequent (4% and 3%, respectively). Of MPs and SAs, 72% had either BRAF or KRAS mutation. Aberrant expression of p53 was uncommon overall, but occurred more frequently in MPs and SAs (12%) than adenomas (1%) (P < 0.04) and there was concordant loss of expression of MGMT. CONCLUSIONS: Molecular alterations that are characteristic of the serrated pathway and adenoma-carcinoma sequence can co-occur in a minority of advanced colorectal polyps that then show morphological features of both pathways. These lesions account for only 2% of colorectal polyps, but may be relatively aggressive.     

Recent advances in diagnosis and treatment of colorectal cancer

There are several methods to detect colon cancer in asymptomatic people; questionnaire, fecal occult blood test, barium enema study, endoscopy and so on. In our study, patients with colon cancer were easily differentiated from normal subjects by analyses of questionnaire responses, but early cancer was not differentiated well. Immunological fecal occult blood test was enough to screen out cancer correctly. Contrast barium enema and colonoscopy have been necessary to diagnose colon cancer and other lesions. Fine lesions 2-3 mm in diameter can be diagnosed by the skillful double contrast method and more diminutive lesions by the dyeing and magnifying colonoscopy. Endoscopic ultrasonography (EUS) can provide useful information for the diagnosis of cancer. At present, EUS provides information concerning the extension of colorectal cancer with considerable reliability. The video endoscope system with the CCD chip is electronically transmitted to a video processor for display by a television monitor. Application of a computer at the level of image processing is expected to open a new field in endoscopic diagnosis.     

Genotyping of colorectal cancer for cancer precision medicine: Results from the IPH Center for Molecular Pathology

Cancer precision medicine has opened up new avenues for the treatment of colorectal cancer (CRC). To fully realize its potential, high‐throughput sequencing platforms that allow genotyping beyond KRAS need to be implemented and require performance assessment. We comprehensively analyzed first‐year data of 202 consecutive formalin‐fixed paraffin embedded (FFPE) CRC samples for which prospective genotyping at our institution was requested. Deep targeted genotyping was done using a semiconductor‐based sequencing platform and a self‐designed panel of 30 CRC‐related genes. Additionally, microsatellite status (MS) was determined. Ninety‐seven percent of tumor samples were suitable for sequencing and in 88% MS could be assessed. The minimal drop‐out rates of 6 and 25 cases, respectively were due to too low amounts or heavy degradation of DNA. Of 557 nonsynonymous mutations, 90 (16%) have not been described in COSMIC at the time of data query. Forty‐three cases (22%) had double‐ or triple mutations affecting a single gene. Sixty‐four percent had genetic alterations influencing oncological therapy. Eight percent of patients (MSI phenotype: 6%; mutated POLE: 2%) were potentially eligible for treatment with immune checkpoint inhibitors. Of 56% of KRASwt CRC that potentially qualified for anti‐EGFR treatment, 30% presented with mutations in BRAF/NRAS. Mutated PIK3CA was detected in 21%. In conclusion, we here present real‐life routine diagnostics data that not only demonstrate the robustness and feasibility of deep targeted sequencing and MS‐analysis of FFPE CRC samples but also contribute to the understanding of CRC genetics. Most importantly, in more than half of the patients our approach enabled the selection of the best treatment currently available. © 2016 Wiley Periodicals, Inc.