scholarly journals Synthesis, identification and in vivo studies of tumor-targeting agent peptide doxorubicin (PDOX) to treat peritoneal carcinomatosis of gastric cancer with similar efficacy but reduced toxicity

2014 ◽  
Vol 13 (1) ◽  
pp. 44 ◽  
Author(s):  
Li Tang ◽  
Rui Duan ◽  
Yan-jun Zhong ◽  
Raymond A Firestone ◽  
Ya-ping Hong ◽  
...  
2020 ◽  
Author(s):  
Tian Qi Zhang ◽  
Qingqiang Dai ◽  
Maneesh Kumarsing Beeharry ◽  
Zhenqiang Wang ◽  
Liping Su ◽  
...  

Abstract Background: Gastric Cancer (GC) is one of the leading causes of cancer-related deaths and mortality. Long non-coding RNAs (lncRNAs) such as SNHG12 play important roles in the pathogenesis and progression of cancers. However, the role and significanve of SNHG12 in the metastasis of GC has not yet been thoroughly investigated.Methods: The SNHG12 expression pattern was detected in GC tissue samples from our faculty and cell lines using quantitative reverse transcription PCR. In vivo and in vitro gain and loss assays were conducted to observe the effects of SNHG12 regulation on GC cell metastasis potential. The underlying mechanisms of SNHG12 regulation on EMT and metastatic potential of GC cells were further determined by quantitative reverse transcription PCR, western blotting, dual luciferase reporter assays, co-immunoprecipitation, immunoprecipitation, RIP assays, TOPFlash/FOPFlash reporter assays and Ch-IP assays.Results: SNHG12 was upregulated in GC tissues and cell lines. The expression levels of SNHG12 in GC samples was significantly related to tumor invasion depth, TNM staging and lymph node metastasis, and was associated with poorer DFS and OS in the GC patients. SNHG12 was significantly highly expressed in peritoneal metastatic tissues from GC patients and mice subjects, suggesting a possible role of SNHG12 in peritoneal carcinomatosis from GC. Further in vivo and in vitro gain and loss assays indicated that SNHG12 promoted GC metastasis and EMT. Based on hypothetical bioinformatic analysis findings, our mechanistic analyses revealed that miR-218-5p was a direct target of SNHG12 and suggested that both SNHG12 and miR-218-5p could collectively regulate YWHAZ, forming the SNHG12/ miR-218-5p/YWHAZ axis, hereby decreasing the ubiquitination of β-catenin, thus activating the β-catenin signaling pathway and facilitating metastasis and EMT. Further analysis also revealed that the transcription factor YY1 could negatively modulate SNHG12 transcription.Conclusions: Our findings demonstrate that SNHG12 is be a potential prognostic marker and therapeutic target for GC. Negatively modulated by transcription factor YYI, SNHG12 promotes GC metastasis and EMT by regulating the miR-218-5p/YWHAZ axis and hence activating the β-catenin signaling pathway. Furthermore, we discovered high SNHG12 expression could be related to peritoneal carcinomatosis from GC but this requires further validation.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jun Wang ◽  
Zhigang He ◽  
Bo Sun ◽  
Wenhai Huang ◽  
Jianbin Xiang ◽  
...  

Pleckstrin-2 (PLEK2) is a crucial mediator of cytoskeletal reorganization. However, the potential roles of PLEK2 in gastric cancer are still unknown. PLEK2 expression in gastric cancer was examined by western blotting and real-time PCR. Survival analysis was utilized to test the clinical impacts of the levels of PLEK2 in gastric cancer patients. In vitro and in vivo studies were used to estimate the potential roles played by PLEK2 in modulating gastric cancer proliferation, self-renewal, and tumourigenicity. Bioinformatics approaches were used to monitor the effect of PLEK2 on epithelial-mesenchymal transition (EMT) signalling pathways. PLEK2 expression was significantly upregulated in gastric cancer as compared with nontumour samples. Kaplan-Meier plotter analysis revealed that gastric cancer patients with higher PLEK2 levels had substantially poorer overall survival compared with gastric cancer patients with lower PLEK2 levels. The upregulation or downregulation of PLEK2 in gastric cancer cell lines effectively enhanced or inhibited cell proliferation and proinvasive behaviour, respectively. Additionally, we also found that PLEK2 enhanced EMT through downregulating E-cadherin expression and upregulating Vimentin expression. Our findings demonstrated that PLEK2 plays a potential role in gastric cancer and may be a novel therapeutic target for gastric cancer.


2020 ◽  
Vol 22 (2) ◽  
Author(s):  
Asghar Narmani ◽  
Monire Alsadat Afzali Arani ◽  
Javad Mohammadnejad ◽  
Ali Zaman Vaziri ◽  
Sedigheh Solymani ◽  
...  

Gut ◽  
2018 ◽  
Vol 68 (7) ◽  
pp. 1152-1161 ◽  
Author(s):  
De-Shen Wang ◽  
Ze-Xian Liu ◽  
Yun-Xin Lu ◽  
Hua Bao ◽  
Xue Wu ◽  
...  

ObjectiveTo monitor trastuzumab resistance and determine the underlying mechanisms for the limited response rate and rapid emergence of resistance of HER2+ metastatic gastric cancer (mGC).DesignTargeted sequencing of 416 clinically relevant genes was performed in 78 paired plasma and tissue biopsy samples to determine plasma-tissue concordance. Then, we performed longitudinal analyses of 97 serial plasma samples collected from 24 patients who were HER2+  to track the resistance during trastuzumab treatment and validated the identified candidate resistance genes.ResultsThe results from targeted sequencing-based detection of somatic copy number alterations (SCNA) of HER2 gene were highly consistent with fluorescence in situ hybridisation data, and the detected HER2 SCNA was better than plasma carcinoembryonic antigen levels at predicting tumour shrinkage and progression. Furthermore, most patients with innate trastuzumab resistance presented high HER2 SCNA during progression compared with baseline, while HER2 SCNA decreased in patients with acquired resistance. PIK3CA mutations were significantly enriched in patients with innate resistance, and ERBB2/4 genes were the most mutated genes, accounting for trastuzumab resistance in six (35.3%) and five (29.4%) patients in baseline and progression plasma, respectively. Patients with PIK3CA/R1/C3 or ERBB2/4 mutations in the baseline plasma had significantly worse progression-free survival. Additionally, mutations in NF1 contributed to trastuzumab resistance, which was further confirmed through in vitro and in vivo studies, while combined HER2 and MEK/ERK blockade overcame trastuzumab resistance.ConclusionLongitudinal circulating tumour DNA sequencing provides novel insights into gene alterations underlying trastuzumab resistance in HER2+mGC.


Author(s):  
Karim Daliri ◽  
Neda Seifi-Shalamzari ◽  
Maryam Saeida-Ardekani ◽  
Sedigheh Ekraminasab ◽  
Hossein Neamatzadeh

Background: Dental caries also known as baby bottle tooth decay, is a critical public health problem around the world for which Streptococcus mutans (S.mutans) has been introduced as the main infectious etiology. In the past two decades, nanotechnology has permitted the development of new materials with antimicrobial properties. The aim of this study was to compare the bactericidal and bacteriostatic effects of three golden nanoparticles (SP, NR, and CS) on S.mutans. Methods: To determine the minimum inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs), a liquid dilution method was applied. Results: All golden nanoparticles (GNPs) showed antimicrobial activity with no statistically significant differences (> 0.05) in MIC or MBC. Conclusion: Our findings revealed that the size and shape of the nanoparticles did not significantly affect the antimicrobial properties of the GNPs. This finding might be useful for achieving important clinical effects with reduced toxicity in the management of early childhood caries in future in vivo studies.


Cancer ◽  
2011 ◽  
Vol 118 (11) ◽  
pp. 2986-2996 ◽  
Author(s):  
Li-Hua Shao ◽  
Shao-Ping Liu ◽  
Jin-Xuan Hou ◽  
Yan-Hua Zhang ◽  
Chun-Wei Peng ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ting-Ting Wu ◽  
Jun Lu ◽  
Pei-Qiu Zheng ◽  
Shen-Lin Liu ◽  
Jian Wu ◽  
...  

Background.Yiqi Huayu Jiedu Decoction (YHJD) can obviously improve the quality of life of those patients with gastric cancer and prolong their survival.Methods. In vitro experiments, we observe YHJD’s effect on the cells’ proliferation by MTT assay. Cell adhesion assay, wound-healing assay, and Transwell invasion assay serve to detect its influence on cells’ adhesion, migration, and invasion, respectively. Inhibitor (10 μM/L of SB431542) and activator (10 ng/mL of TGF-β) of TGF-β/Smad pathway were used to estimate whether YHJD’s impact on the biological behavior of gastric cancer cells was related to TGF-β/Smad pathway. In in vivo studies, YHJD was administered to the nude mice transplanted with gastric cancer to observe its effect on the tumor. Western blotting and immunohistochemical assay were used to test relevant cytokines of TGF-β/Smad pathway and epithelial-mesenchymal transition (EMT) in MGC-803 cells and the tumor bearing nude mice.Results.YHJD inhibited proliferation, adhesion, migration, and invasion of MGC-803 gastric cancer cells in vitro. In in vivo studies, YHJD reduced the volume of the transplanted tumors. It also enhanced the expression of E-cadherin and decreased the levels of N-cadherin, TGF-β, Snail, and Slug in both MGC-803 cells and the transplanted tumor by western blot assay. The immunohistochemical assay revealed that YHJD raised E-cadherin in the tumors of the mice; on the contrary, the expression of N-cadherin, Twist, vimentin, TGF-βR I, p-Smad2, p-Smad3, Snail, and Slug reduced.Conclusion. YHJD can effectively inhibit the invasion and metastasis of gastric cancer cells. The mechanism may be related to TGF-β/Smad pathway.


1989 ◽  
Vol 17 (5) ◽  
pp. 309-318 ◽  
Author(s):  
Yukio Miyamoto ◽  
Mariko Nakatani ◽  
Masahiro Ida ◽  
Takashi Ishikawa ◽  
Norio Okazawa ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document