Diagnosis of poorly differentiated adenocarcinoma of the stomach by confocal laser endomicroscopy: A case report.

BACKGROUND: In recent years, confocal laser endomicroscopy (CLE) has become a new endoscopic imaging technology at the microscopic level, which is extensively performed for real-time in vivo histological examination. CLE can be performed to distinguish benign from malignant lesions. In this study, we diagnosed using CLE an asymptomatic patient with poorly differentiated gastric adenocarcinoma. CASE SUMMARY: A 63-year-old woman was diagnosed with gastric mucosal lesions, which may be gastric cancer, in the small curvature of the stomach by gastroscopy. She consented to undergo CLE for morphological observation of the gastric mucosa. Through the combination of CLE diagnosis and postoperative pathology, the intraoperative CLE diagnosis was considered to be reliable. According to our experience, CLE can be performed as the first choice for the diagnosis of gastric cancer. CONCLUSION: CLE has several advantages over pathological diagnosis. We believe that CLE has great potential in the diagnosis of benign and malignant gastric lesions.

MicroRNA-103a-3p Promotes Cell Proliferation and Invasion in Non-Small-Cell Lung Cancer Cells through Akt Pathway by Targeting PTEN.

BACKGROUND: Increasing evidence has suggested that microRNA- (miR-) 103a-3p is crucial for cancer progression. However, the specific mechanism of miR-103a-3p in non-small-cell lung cancer (NSCLC) remains unclear until now. So, it is particularly urgent to clarify the mechanism between them. METHODS: qRT-PCR and western blot were used to measure the expression of miR-103a-3p, PTEN, Akt, and p-Akt. Cell biology experiment was applied to detect the biological function of miR-103a-3p in NSCLC cell lines. Moreover, bioinformatics analysis, luciferase reporter assay, and functional complementation analysis were carried out to investigate the target gene. RESULTS: miR-103a-3p was highly expressed in primary NSCLC samples and cell lines. miR-103a-3p mimics promoted the proliferation and invasion of NSCLC cells; miR-103a-3p inhibitor had the opposite effect. A double luciferase reporter gene experiment revealed that miR-103a-3p directly targets the PTEN mRNA 3'UTR region. siPTEN inhibited the proliferation and invasion of NSCLC cells. Further mechanistic studies showed that both overexpression of miR-103a-3p and PTEN knockdown reduced the expression of the p-Akt protein. Overexpression of PTEN partially reversed the cancer-promoting effect of miR-103a-3p. CONCLUSION: miR-103a-3p promotes the progression of NSCLC via Akt signaling by targeting PTEN, highlighting the role of miR-103a-3p/PTEN/Akt signaling and suggesting miR-103a-3p as a novel therapeutic target for NSCLC.

A novel antibody-drug conjugate, HcHAb18-DM1, has potent anti-tumor activity against human non-small cell lung cancer.

Cluster of differentiation 147 (CD147), a transmembrane protein of the immunoglobulin superfamily, is a potential target of treatment against human non-small cell lung cancer (NSCLC). Although there have been exciting advances in epidermal growth factor receptor (EGFR)-targeted therapy for NSCLC in recent years, additional novel targeted agents are needed to improve the efficiency and to offer more options for patients. Antibody-drug conjugates (ADCs) utilize a chemical linker to conjugate cytotoxic drugs to a monoclonal antibody to maximize the delivery to target cells and minimize the delivery to other normal cells. The aim of this study was to prepare a novel anti-CD147 conjugate and examine the tumoricidal effect on NSCLC in vitro and in vivo. HcHAb18 was conjugated to the drug maytansinoid 1 (DM1) via a non-cleavable thioether linker (SMCC) to prepare HcHAb18-DM1 with an appropriate drug-antibody ratio (DAR). NSCLC cell lines expressing different levels of CD147 were tested in vitro to determine internalization, cell cycle arrest and cytotoxicity. In vivo efficacy and safety of HcHAb18-DM1 were evaluated in NSCLC xenograft mouse models. We found that HcHAb18-DM1 displayed an impressive potency in vitro and in vivo with a favorable safety profile. Upon binding to CD147, HcHAb18 could be internalized and delivered the payload DM1 to disturb mitotic spindle formation by microtubules. Target cells were arrested at G2/M phase and HcHAb18-DM1 exerted antiproliferative activity in vitro. Antigen-antibody binding and target cells with high growth rate were two integral prerequisites for exerting anti-tumor activity of HcHAb18-DM1. Therefore, we suggest HcHAb18-DM1 is a promising CD147-targeted therapeutic for NSCLC.

Expression levels of transcription factors c-Fos and c-Jun and transmembrane protein HAb18G/CD147 in urothelial carcinoma of the bladder.

The aim of the present study was to investigate the prognostic significance of the expression of transcription factors, c-Fos, c-Jun and transmembrane protein CD147, in urothelial carcinoma of the bladder (UCB). The current study investigated the clinical significance of these factors in the development, progression and survival analysis of UCB. Immunohistochemistry was employed to analyze c­Fos, c­Jun and CD147 expression in 41 UCB cases and 34 non­cancerous human bladder tissues. These results were scored in a semi­quantitative manner based on the intensity and percentage of tumor cells that presented immunoreactivity. Protein levels of CD147, c­Fos and c­Jun expression were upregulated in 22 (53.7%), 10 (24.4%) and 9 (22.0%) UCB cases, respectively. High levels of c­Jun correlated with the AJCC cancer staging manual (7th edition; P=0.038). Univariate analysis revealed that upregulated CD147 (P=0.038) or c­Jun (P=0.008) was associated with poor overall survival (OS), respectively. Further analysis revealed that either CD147­c­Fos­c­Jun co­expression (P=0.004), or CD147­c­Jun co­expression (P=0.037) and c­Fos­c­Jun co­expression (P<0.001) were associated with poor OS. Multivariate analysis suggested that either upregulation of CD147, c­Jun or c­Fos were independent risk indicators for death in UCB patients. Increased expression of c­Jun or CD147, as well as co­expression of CD147­c­Jun, c­Jun­c­Fos or CD147­c­Jun­c­Fos has prognostic significance for UCB patients. Therefore, high CD147 and c­Jun expression may serve roles in tumor progression and may be diagnostic and therapeutic targets in UCB whether alone or in combination.

Metuzumab enhanced chemosensitivity and apoptosis in non-small cell lung carcinoma.

Targeted therapeutics is used as an alternative treatment of non-small cell lung cancer (NSCLC); however, treatment effect is far from being satisfactory, and therefore identification of new targets is needed. We have previously shown that metuzumab inhibit tumor growth in vivo. The present study was performed to investigate the anti-tumor efficacy of metuzumab combined with gemcitabine and cisplatin (GP), paclitaxel and cisplatin (TP) or navelbine and cisplatin (NP) regimens in multiple NSCLC cell lines. Our results demonstrate that, in comparison to single agent metuzumab or GP treated cells, metuzumab combined with GP display inhibitory effects on tumor growth. Furthermore, we found that metuzumab elevated the sensitivity of cell lines to gemcitabine, which was identified by MTT assay. Flow cytometric analysis showed that metuzumab combined with gemcitabine (GEM) treatment led to an obvious G1 arrest and an elevated apoptosis in A549, NCI-H460 and NCI-H520 cells. Western blot analysis also demonstrated a significantly reduced level of cyclin D1, Bcl-2, and an obviously increase level of Bax and full-length caspase-3 in A549, NCI-H460 and NCI-H520 cells treated with metuzumab/gemcitabine combination in comparison with single agent treated cells. In addition, metuzumab/gemcitabine treated A549, NCI-H460 and NCI-H520 cells also demonstrated a significantly increase in deoxycytidine kinase (dCK) protein level compared with single agent metuzumab or gemcitabine treated cells. Xenograft models also demonstrated that this metuzumab/gemcitabine combination led to upregulation of dCK. Taken together, the mechanisms of metuzumab combined with GP repress tumor growth were that the combined treatment significantly inhibited the tumor cell proliferation, apoptosis and cell cycle in vitro and in vivo and at least partially by induction of dCK expression. Our results suggested that metuzumab could significantly enhance chemosensitivity of human NSCLC cells to gemcitabine. Metuzumab/gemcitabine combination treatment may be a potentially useful therapeutic regimen for NSCLC patients.

[One case of esophageal carcinoma defect after operation for repair with platysma myocutaneous flap].

Cervical esophageal carcinoma is rare, the lack of early clinical manifestations, early diagnosis is difficult, easily missed or misdiagnosed, especially at present for the method of repairing defect of cervical esophagus cancer after operation. In many mainstream, the repair methods with free jejunum, gastric pull up, and anterolateral thigh flap freeforearm flap. We used the platysma skin flap to repair of cervical esophagus defect which is worthy of reference,report as follows now.

Preclinical pharmacokinetics, tolerability, and pharmacodynamics of metuzumab, a novel CD147 human-mouse chimeric and glycoengineered antibody.

Metuzumab is an affinity-optimized and nonfucosylated anti-CD147 human-mouse chimeric IgG1 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC). The purpose of this study was to characterize the pharmacokinetics, safety, and antitumor activities of metuzumab in mouse, rat, and monkey. The ADCC activity was assessed by a lactate dehydrogenase release assay. The pharmacokinetics of metuzumab were determined in Sprague-Dawley rats and in cynomolgus monkeys. Single- and repeat-dose toxicology studies of the i.v. administration of high-dose metuzumab were conducted in cynomolgus monkeys. Mice bearing human tumor xenografts were used to evaluate the antitumor efficacy of metuzumab. The ADCC potency of metuzumab was enhanced compared with the nonglycoengineered parental antibody. Metuzumab also effectively inhibited tumor growth in A549 and NCI-H520 xenograft models. In the monkey model, the total clearance of metuzumab decreased with increasing dose. The nonspecific clearance in monkeys was estimated to be 0.53 to 0.92 mL/h/kg. In single- and repeat-dose toxicology studies in cynomolgus monkeys, metuzumab did not induce any distinct or novel adverse findings and was well tolerated at all tested doses. These preclinical safety data facilitated the initiation of an ongoing clinical trial of metuzumab for the treatment of non-small cell lung cancer (NSCLC) in China.

[One case of operation excision facial pyogenic granuloma].

Pyogenic granuloma also known as granulomatous type capillary hemangioma, telangiectatic granuloma, lobular capillary hemangioma, is not really a tumor, its nature is still controversial. A rare clinical entity. I Division in treating facial pyogenic granuloma in 1 cases, the report is as follows.