Recent Progress in Nanoscale Covalent Organic Frameworks for Cancer Diagnosis and Therapy

Covalent organic frameworks(COFs)as a type of porous and crystalline covalent organic polymer are built up from covalently linked and periodically arranged organic molecules.Their precise assembly,welldefined coordination network,and tunable porosity endow COFs with diverse characteristics such as low density,high crystallinity,porous structure,and large specific-surface area,as well as versatile functions and active sites that can be tuned at molecular and atomic level.These unique properties make them excellent candidate materials for biomedical applications,such as drug delivery,diagnostic imaging,and disease therapy.To realize these functions,the components,dimensions,and guest molecule loading into COFs have a great influence on their performance in various applications.In this review,we first introduce the influence of dimensions,building blocks,and synthetic conditions on the chemical stability,pore structure,and chemical interaction with guest molecules of COFs.Next,the applications of COFs in cancer diagnosis and therapy are summarized.Finally,some challenges for COFs in cancer therapy are noted and the problems to be solved in the future are proposed.

Translational research case studies:Development of antibodies for cancer diagnosis and therapy

Antibodies are primary tools in several areas of biomedical sciences, including basic research, diagnostics, and molecular therapeutics. Antibodies are widely used in diagnostic applications for clinical medicine. Analysis of cells and tissues in pathology laboratories includes the use of antibodies on tissue sections. Further, antibodies are making rapid inroads into medical therapeutics, driven by technological evolution from chimeric and humanized to fully human antibodies. The therapeutic antibody market has the potential to reach $30 billion by 2010. Our lab has developed a monoclonal antibody, named Met4 that was raised against the extracellular domain of Met specifically with the goal of measuring Met in FFPE tissues. The Met receptor kinase is expressed on the cell surface of a significant number and variety of human primary solid tumors and in their metastases. The characterization of the Met4 antibody suggests it should possess adequate performance for quantification of Met expression in clinical specimens. We have also generated a fully human Fab fragment against EGFR; conjugated it to taxol as an immuno-chemotherapy agent; and investigated its in vitro antitumor efficacy on EGFR positive A431 epidermoid carcinoma cells.

Nanomedicine has opened new avenues for cancer diagnosis and therapy

A crucial feature of nanoparticles,such as liposomes,magnetic nanoparticles,quantum dots,metallic nanoparticles,silica nanoparticles,polymersomes and dendrimers etc.,is their higher accumulation in the tumor than in normal tissues1-3.Various nanoparticles have been intensively used as vehicles to deliver

Discussion of diagnosis and therapy strategy for pineal region tumors

Objective To define optimal diagnosis and theraputic strategy of pineal region tumors. Methods Clinicalmaterials of 154 cases with pineal region tumors were analyzed retrospectively. Results The patients with pineal region tumors often complained of increased intracranial pressure and ocular movement deficiency.

Clinical implications of interleukins-31, 32, and 33 in gastric cancer

BACKGROUND Gastric cancer(GC) is one of the most common malignancies in China with a high morbidity and mortality.AIM To determine whether interleukin(IL)-31, IL-32, and IL-33 can be used as biomarkers for the detection of GC, via evaluating the correlations between their expression and clinicopathological parameters of GC patients.METHODS Tissue array(n = 180) gastric specimens were utilised. IL-31, IL-32, and IL-33 expression in GC and non-GC tissues was detected immunohistochemically. The correlations between IL-31, IL-32, and IL-33 expression in GC and severity of clinicopathological parameters were evaluated. Survival curves were plotted using the Kaplan-Meier method/Cox regression. Circulating IL-31, IL-32, and IL-33 were detected by ELISA.RESULTS We found that the expression levels of IL-31, IL-32, and IL-33 were all lower in GC than in adjacent non-GC gastric tissues(P < 0.05). IL-33 in peripheral blood of GC patients was significantly lower than that of healthy individuals(1.50 ± 1.11 vs 9.61 ± 8.00 ng/m L, P <0.05). Decreased IL-31, IL-32, and IL-33 in GC were observed in younger patients(< 60 years), and IL-32 and IL-33 were lower in female patients(P < 0.05). Higher IL-32 correlated with a longer survival in two GC subgroups: T4 invasion depth and TNM I-II stage. Univariate/multivariate analysis revealed that IL-32 was an independent prognostic factor for GC in the T4 stage subgroup. Circulating IL-33 was significantly lower in GC patients at TNM stage IV than in healthy people(P < 0.05).CONCLUSION Our findings may provide new insights into the roles of IL-31, IL-32, and IL-33 in the carcinogenesis of GC and demonstrate their relative usefulness as prognostic markers for GC. The underlying mechanism of IL-31, IL-32, and IL-33 actions in GC should be further explored.

Self-assembling bile pigments for cancer diagnosis and therapy

Nanomaterials that integrate multiple functions provide promising opportunities for noninvasive and targeted cancer diagnosis and therapy.However,the unclear metabolic pathway to nanomaterials brought difficulties to clinical application.Selfassembling bile pigments are endogenous functional materials with excellent biocompatibility and low toxicity.Functional materials based on endogenous bile pigments provide a decent solution to this dilemma.In this review,the features and functions of self-assembling bile pigments are discussed in detail for cancer diagnosis and treatment applications.Emphases are put on the intrinsic physicochemical characteristics of bile pigments and their applications,including drug delivery,photoacoustic imaging,photothermal therapy,and anti-inflammation therapy.This review will promote the exploration of these areas and tremendously realize the innovative applications of self-assembling biliverdin/bilirubin nanomaterials toward cancer diagnosis and therapy.

Clinical misdiagnosis of solid pseudopapillary tumour of pancreas

Background Since being reclassified by WHO in 1996, solid pseudopapillary tumour (SPT) of pancreas has been recognized as the internationally accepted name. Clinicians are lacking in knowledge of this rare disease so the misdiagnosis and inappropriate therapy are hard to avoid. The clinic data on 22 patients were summarized to study the misdiagnosis and treatment of a sample of SPTs. Methods Twenty-two female patients with SPT were studied retrospectively and divided into two groups, the misdiagnosed group and the correctly diagnosed one. The analyses were performed with Fisher test with accurate probability for categorical data, and Krusdal-Wallis test for ranked data.Results The rate of misdiagnosis in this sample was 45.5%. The misdiagnosed SPTs were apt to be the incomplete capsule ones (P=0.020), which resulted in obvious difficulties during operation (P=0.024). In the misdiagnosed SPT group, the medical expenses increased significantly (P=0.042), and the number of days in hospital greater than in correctly diagnosed group (P=0.041).Conclusions Although SPT has low malignancy with excellent prognosis after surgical treatment in most patients, the misdiagnosis of SPT increases the social and economic burdens on patients. It is important to analyse the causes of misdiagnosis.

Diagnosis and treatment of autoimmune pancreatitis： analysis of six cases

Autoimmune pancreatitis （AIP） is a rare and special type of chronic pancreatitis, which was earlier referredto as lymphoplasmacytic sclerosing pancreatitis （LPSP）, idiopathic duct destructive pancreatitis, or granulocyte epithelial lesion-positive pancreatitis. The concept of AIP was not coined by Yoshida until 1995.1 Although AIP was initially reported in Japan, USA and Europe, AIP cases have increased rapidly in China in the last few years.

Novel directions of precision oncology:circulating microbial DNA emerging in cancer-microbiome areas

Microbiome research has extended into the cancer area in the past decades.Microbes can affect oncogenesis,progression,and treatment response through various mechanisms,including direct regulation and indirect impacts.Microbiota-associated detectionmethods and agents have been developed to facilitate cancer diagnosis and therapy.Additionally,the cancermicrobiome has recently been redefined.The identification of intra-tumoral microbes and cancer-related circulating microbial DNA(cmDNA)has promoted novel research in the cancer–microbiome area.In this review,we define the human system of commensal microbes and the cancer microbiome from a brand-new perspective and emphasize the potential value of cmDNA as a promising biomarker in cancer liquid biopsy.We outline all existing studies on the relationship between cmDNA and cancer and the outlook for potential preclinical and clinical applications of cmDNA in cancer precision medicine,as well as critical problems to be overcome in this burgeoning field.

Therapeutic efficacy of transcatheter arterial embolization of primary hepatocellular carcinoma: discrepancy in different histopathologic subtypes

Objective To evaluate preliminarily the therapeutic efficacy of transcatheter arterial embolization (TAE) for different histopathologic subtypes of primary hepatocellular carcinoma (HCC). Methods A retrospective study of 226 patients with histopathologically diagnosed primary HCC was performed. The patients were treated with either single TAE, surgical resection of tumor alone, or TAE combined with surgical resection. Follow up information was achieved in 157 of 226 patients. Comparative analyses of survival data and image findings were performed with correlation to histopathologic classification and different therapeutic methods,respectively. Results Eight histopathologic subtypes of primary HCC were found in this group, including HCC of trabecular pattern, pseudoglandular pattern, fibrolamellar HCC and sclerosing HCC, as well as HCC of clear cell, of small cell, poorly differentiated or undifferentiated HCC, and hormonally active HCC. The accumulated survival rate for these 157 patients was 74.52% of 1 year, 53.50% of 2 years, 31.85% and 14.01% of 3 and 5 years, respectively. Fibrolamellar HCC and clear cell HCC had relatively higher survival rate (25.00% and 33.22% of 5 years, respectively) than that of other subtypes, and the median survival time of the latter was 71 months. The mean survival time was 25.06 months (SE=1.87) in single TAE group, 30.38 (SE=2.05) months in surgical resection, and 72 months (SE=6.90) in TAE combined with resection. Conclusions Discrepancies do exist in therapeutic effect of different subtypes of HCC. In this study, clear cell HCC was more sensitive to TAE than other subtypes, and, in contrast, small cell HCC and poorly differentiated or undifferentiated HCC were of lower sensitivity to TAE.