Rational Design of a Pan-Coronavirus Vaccine Based on Conserved CTL Epitopes

With the rapid global spread of the Coronavirus Disease 2019 (COVID-19) pandemic, a safe and effective vaccine against human coronaviruses (HCoVs) is believed to be a top priority in the field of public health. Due to the frequent outbreaks of different HCoVs, the development of a pan-HCoVs vaccine is of great value to biomedical science. The antigen design is a key prerequisite for vaccine efficacy, and we therefore developed a novel antigen with broad coverage based on the genetic algorithm of mosaic strategy. The designed antigen has a potentially broad coverage of conserved cytotoxic T lymphocyte (CTL) epitopes to the greatest extent, including the existing epitopes from all reported HCoV sequences (HCoV-NL63, HCoV-229E, HCoV-OC43, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2). This novel antigen is expected to induce strong CTL responses with broad coverage by targeting conserved epitopes against multiple coronaviruses.     

Targeting prostate cancer: Prostate-specific membrane antigen based diagnosis and therapy

The high incidence rates of prostate cancer (PCa) raise demand for improved therapeutic strategies. Prostate tumors specifically express the prostate-specific membrane antigen (PSMA), a membrane-bound protease. As PSMA is highly overexpressed on malignant prostate tumor cells and as its expression rate correlates with the aggressiveness of the disease, this tumor-associated biomarker provides the possibility to develop new strategies for diagnostics and therapy of PCa. Major advances have been made in PSMA targeting, ranging from immunotherapeutic approaches to therapeutic small molecules. This review elaborates the diversity of PSMA targeting agents while focusing on the radioactively labeled tracers for diagnosis and endoradiotherapy. A variety of radionuclides have been shown to either enable precise diagnosis or efficiently treat the tumor with minimal effects to nontargeted organs. Most small molecules with affinity for PSMA are based on either a phosphonate or a urea-based binding motif. Based on these pharmacophores, major effort has been made to identify modifications to achieve ideal pharmacokinetics while retaining the specific targeting of the PSMA binding pocket. Several tracers have now shown excellent clinical usability in particular for molecular imaging and therapy as proven by the efficiency of theranostic approaches in current studies. The archetypal expression profile of PSMA may be exploited for the treatment with alpha emitters to break radioresistance and thus to bring the power of systemic therapy to higher levels.     

Beta-catenin expression in hepatocellular carcinoma: a possible participation of beta-catenin in the dedifferentiation process

BACKGROUND: beta-Catenin is known as a multifunctional protein acting as a regulator of the cadherin-mediated cell-cell adhesion system and in the Wingless/Wnt signal transduction pathway. Recent studies reported mutation of the beta-catenin gene in some tissues of hepatocellular carcinoma (HCC). METHODS: 'Nodule-in-nodule' appearance is a feature of well-differentiated HCC containing a distinct nodule of less-differentiated cancer tissue inside, and it is presumed to be a morphological expression of the dedifferentiation process. The present study immunohistochemically investigated the beta-catenin expression according to the dedifferentiation process of HCC, that is, in small well-differentiated HCC with indistinct margins, HCC with a 'nodule-in-nodule' appearance, moderately differentiated HCC, which does not have a 'nodule-in-nodule' appearance, and sarcomatous HCC. RESULTS: The expression of beta-catenin was observed in approximately 70% of small well-differentiated HCC with indistinct margins. In HCC with a 'nodule-in-nodule' appearance, membranous expression of beta-catenin was higher in the well-differentiated cancer tissues than in the less-differentiated cancer tissues (P < 0.01), cytoplasmic expression was higher in the less-differentiated cancer tissues (P < 0.01), and nuclear expression was higher in the less-differentiated cancer tissues (P < 0.001). In moderately differentiated HCC, tumors with membranous expression of beta-catenin had more frequent intrahepatic metastasis than those without having the expression (P < 0.001). CONCLUSIONS: Accumulation of beta-catenin was already present in the early stage of HCC, and in less-differentiated cancer tissue the membranous expression of beta-catenin could be related to intrahepatic metastasis.     

Basic Clinical Study of an Easy and Effective Leukocytapheresis by the Use of Nonwoven Polyester Filter

Abstract: Leukocytapheresis (LCAP) is widely used for the treatment of immunological diseases. We studied a new treatment of LCAP using a nonwoven polyester filter. In a basic study, 30–70% of the lymphocytes were adsorbed. Also, 30–68% of the lymphocyte subsets were removed. This method was applied to 2 patients with corti-costeroid-resistant active ulerative colitis. Erosion, edema, bleeding, ulcer formation, and stenosis of the colon were almost completely repaired after 6 LCAP treatments. LCAP using a nonwoven polyester filter will be a very useful treatment for immunological diseases and extracorporeal immunomodulation.     

癌相关抗原125对慢性肝病合并腹水的诊断价值

检测慢性肝病合并腹水形成患者血浆及腹水中CA12 5水平 ,探讨其临床意义。采用ELISA法检测 141例慢性肝病患者血浆CA12 5值 ,对 40例合并腹水的慢性肝病同时测腹水CA12 5值。结果显示 ( 1)慢性肝病合并腹水形成者血浆CA12 5值显著高于无腹水形成者 (P <0 0 1) ;( 2 )腹水中CA12 5值显著高于血浆中值 (P <0 0 1) ,且二者呈正相关 (r=0 965 ,P <0 0 1) ;( 3 )大量放腹水后 ,血浆中及腹水中CA12 5值显著下降 ,且腹水CA12 5值下降的幅度大于血浆CA12 5值下降的幅度 (P <0 0 1)。提示CA12 5是诊断慢性肝病合并腹水形成的一项敏感指标     

慢性病毒性肝炎肝细胞凋亡与Fas抗原和病毒表达的相互关系

为探讨病毒性肝炎肝细胞凋亡及其与病毒和Ｆａｓ抗原表达的关系，应用原位末端标记技术检测一组慢性乙、丙型肝炎患者肝组织中细胞凋亡状况，并以免疫组化方法检测病毒和Ｆａｓ抗原表达。结果３１例患者中，２５例肝组织中检出末端标记阳性细胞，散布于肝小叶和肝窦内，部分炎症坏死灶中和胆管上皮细胞也可检出阳性细胞；组织炎症活动度较大者和病毒抗原阳性者凋亡指数较高；凋亡细胞可为病毒抗原阳性和阴性；Ｆａｓ抗原阳性与阴性组间凋亡程度无显著差异。提示病毒性肝炎患者感染和未感染病毒的肝细胞均可发生凋亡，其机制有待进一步研究。     

日本血吸虫感染中循环抗原动态变化及其机制研究

探讨日本血吸虫感染中循环抗原动态变化及其机制。感染日本血吸虫的ＢＡＬＢ／ｃ小鼠淋巴结Ｂ细胞和小鼠骨髓瘤细胞融合，制备抗血吸虫循环抗原不同表位的单克隆抗体组合后为探讨针，检测日本血吸虫病患者和健康人血清；晚期血吸虫病患者脾血和外周血；感染日本血吸虫兔和小鼠的门脉血和外周血。     

Comparative analysis of cancer-associated antigen CA-195, CA19-9 and carcinoembryonic antigen in diagnosis,follow-up and monitoring of response to chemotherapy in patients with gastrointestinal cancer

Summary To establish further the clinical significance of the CA-195 tandem immunoradiometric assay in gastrointestinal malignancies, the sera of a total of 222 subjects have been analysed and compared with assays of the classical gastrointestinal tumour markers, CA19-9 and carcinoembryonic antigen (CEA). CA-195 elevations above normal (>10 U/ml) were noted in 51/72 (70.8%) colorectal, 15/15 (100%) pancreatic, and in 6/12 (50%) gastric cancer patients. Whereas CA19-9 was increased (>37 U/ml) in 65%, 93%, and 42% of cases, only 54% colorectal, 45% pancreatic, and 42% gastric cancer patients had pathologically elevated serum CEA levels (>5 ng/ml). No abnormal increase of both CA-195 and CA19-9 was found in healthy volunteers, whereas 3/20 (smoking) individuals had CEA levels slightly above normal. With a 29% false-positive rate noted among 103 patients with benign gastroinestinal disorders, the specifity of CA-195 was superior to that of CA19-9 (58%) and comparable with that of CEA (31%). A significant correlation between CA-195 levels and the clinical/pathological stage of disease was noted in colorectal (P<0.01) and pancreatic cancer patients (P<0.007). Preliminary results of serial measurements of CA-195 in colorectal cancer suggest that this new marker protein, which has no cross-reactivity with CEA, may be useful as a non-invasive test for postoperative surveillance of patients to detect disease recurrence, and serve to complement (though certainly not replace) standard clinical measurements of response to chemotherapy.Abbreviation CEA carcinoembryonic antigen