Circulating tumor DNA (ctDNA) is one conventional type of liquid biopsy that can be collected to dynamically monitor disease status. However, its potential clinical value and concordance with ascites samples or tumor biopsy needs to be evaluated further for patients with ovarian cancer. Therefore, the present study compared the mutation profiles among ctDNA, paired tumor tissue and ascites samples to explore their possible clinical value in ovarian cancer. Targeted next‑generation sequencing was used to screen for mutations in 18 peripheral blood samples, six paired ascites samples and eight paired tumor tissues collected from patients with ovarian cancer. Functional analyses were performed using public databases. WebGestalt was used to perform Gene Ontology and pathway enrichment analyses. The cBioPortal for Cancer Genomics was used to assess therapeutic targets. Chilibot and Search Tool for the Retrieval of Interacting Genes/Proteins were used to obtain key genes and their functional interactions. Comparative analysis was performed among the three types of samples using Venn diagram. A total of 104 cancer‑associated mutant genes in ctDNA samples, 95 genes in tumor tissues and 44 genes in ascites samples were found. A cluster covering 10 genes, namely NOTCH2, NOTCH3, lysine methyltransferase 2A, PTEN, androgen receptor, DNA‑activated protein kinase catalytic subunit, hepatocyte nuclear factor 1 homeobox A, SRC, insulin receptor substrate 2 and SRY‑box transcription factor 10, was obtained by Chilibot analysis. This gene panel may have the potential to monitor metastasis and identify therapeutic targets in ovarian cancer. Taken together, the present study focused on the mutant genes in ctDNA, ascites and tumor tissues, and suggested that the integrated information of different samples could be examined to comprehensively reflect the mutational landscape in ovarian cancer. However, procedures and protocols to interpret and utilize the integrated information obtained from various forms of liquid biopsies will require optimization prior to their use for future clinical applications.
Abstract Background The aim of this study is to explore the expression and clinical relevance of CAF-associated markers, EZH2 and FOXM1 in gastric samples. Methods Protein expression were detected and evaluated by multi-plex immunofluorescence (mIF) in 93 cases of gastric cancer (GC) and 31 cases of gastric intraepithelial neoplasia (GIN). The correlation among their expression, and the relationship of them with clinicopathological parameters and prognosis in GC were then analyzed. Results FAP was specific expressed in the CAFs of GC samples, and thus be utilized as a CAF-associated marker in our subsequently analysis. The immunostaining of EZH2, FOXM1 and FAP were significantly upregulated in patients with GC tissues than in those normal gastric mucosa or GIN tissues. The average fluorescence intensity of FAP was slightly positively correlated with EZH2 in GC, GIN and normal samples, whereas the percentage of FAP positive cells has no correlation with that of EZH2. Both the percentage of positive cells and the average fluorescence intensity of FOXM1 were positively correlated with that of FAP and EZH2 in GC, GIN and normal samples, except for FOXM1 and EZH2 expression in normal tissue samples. No significant association was observed between FAP expression and any clinicopathological parameters, whereas the positive frequency of EZH2 and FOXM1 were correlated with tumor location significantly and tumor invasion depth, respectively. In addition, there was strong positive correlations between FAP protein expression and overall survival (OS) and disease-free survival (DFS), and EZH2 expression was positively associated with OS in patients with GC. Furthermore, EZH2 and FAP protein expression was an independent prognostic factor for OS and DFS, respectively. Conclusions These results suggest that both EZH2 and FOXM1 expression was positively associated with CAFs abundance in GC. They may be potential cellular target for therapeutic intervention, especially in patients with a large number of CAFs.
Late detection, peritoneal dissemination, chemoresistance and weak response to targeted therapeutics lead to high mortality in ovarian cancer. More efficient and specific tumor imaging and therapeutic agents are needed to improve the resection rate of surgery and to eliminate residual disease. The expression patterns of follicle-stimulating hormone (FSH) receptor make it a suitable target for ovarian cancer. Here, we report a strategy to develop an organic near-infrared probe for FSH receptor-targeted tumor imaging and photothermal therapy. The FSH-Rh760 probe was conjugated from the Rh760 fluorophore with the FSH β subunit 33-53 peptide. FSH-Rh760 specifically distinguished peritoneal metastatic ovarian cancerous foci from surrounding normal tissues with a high tumor-to-background ratio. The fluorescence signals in tumors peaked at 2 h and were cleared at 120 h postinjection. FSH-Rh760 treatment rapidly increased the abdomen temperature of mice up to ∼43 °C upon exposure to a near-infrared laser and effectively suppressed peritoneal tumor growth with tumor specificity. No significant systemic toxicities were observed. This study demonstrates the targeting ability and biocompatibility of FSH receptor-targeted theranostics and highlights its potential for clinical application in imaging-guided precision tumor resection and photothermal therapy to eliminate cancer lesions intraoperatively and postoperatively.
Chemotherapy is an important treatment for ovarian cancer. However, conventional chemotherapy has inevitable drawbacks due to side effects from nonspecific biodistribution of the chemotherapeutic drugs. To solve such problem, targeted delivery approaches were developed. The targeted delivery approaches combine drug carriers with the targeting system and can preferentially bring drugs to the targeted sites. Follicle-stimulating hormone receptor (FSHR) is an ovarian cancer-specific receptor. By using a peptide derived from FSH (amino acids 33-53 of the FSH beta chain, named as FSH33), we developed a conjugated nanoparticle, FSH33-NP, to target FSHR in ovarian cancer. FSH33-NP was tested for recognition specificity and uptake efficiency on FSHR-expressing cells. Then, the antitumor efficiency of paclitaxel (PTX)-loaded FSH33-NP (FSH33-NP-PTX) was determined. FSH33-NP-PTX displayed stronger antiproliferation and antitumor effects compared with free PTX or naked PTX-loaded nanoparticles (NP-PTX) both in vitro and in vivo. In summary, this novel FSH33-NP delivery system showed very high selectivity and efficacy for FSHR-expressing tumor tissues. Therefore, it has good potential to become a new therapeutic approach for patients with ovarian cancer.
[Objective]To analyze the incidence of clinical and pathological characters and its changing tendency of cervical cancer,who had been treated in our hospital in nearly five years,and investigate the related problems of the diagnosis and treatments.[Methods]1 598 patients of cervical cancer were studied by retrospective analysis,who had been treated in our hospital from Nov.2005 to Apr.2010.The patients were divided into three groups by ages(A group≤35year old age,B group36 to 45year old age,and C group≥46year old age).Their clinical characters were reviewed and compared.[Results]The age range of the cases was 17-82,the average age was 43.07±9.01,and the peak age was 35-46(56.2%).The number of cervical cancer patients diagnosed in the hospital in 2009 was 0.7 times more than that in 2006.The number of patients with constant pregnancy(G≥3)and constant giving-birth(P≥2)were 1 182(74%)and 699(43.7%).The proportion of I-Ⅱa in three groups were 77.3%,72.2% and 62.3%,the ≤35 years old group and 36-45 years old group had evidently higher ratios in comparison with≥46 years old age groups,and significant differences was found between them(P﹤0.001).The proportion of Ⅱb-Ⅳ in three groups were 22.7%,27.7% and 37.7%,the≥46 years old group had evidently higher ratios of in comparison with other age groups,and there was significant difference between them(P﹤0.001).The main symptom of≤35 years old group and 36-45 years old group was contact bleeding(≤35 55.2%,36-45 47.3%).The main symptom of≥46 years old group was post-menopause bleeding(31.8%).The squamous cell was the main pathological type(88%).96.7% of the patients had surgically treated,we preserved fertility function in the 94.1%of young women.[Conclusion]The cases of cervical cancer increased year by year,and the average age of cervical cancer decreased than before.In order to reach early diagnosis and early treatment,the government and medical workers should enhance the survey and health education in reproductive age women,especially the women ≤35 years old and over 46 years old.In order to increase the quality of life,appropriate treatments should be taken according to the age of patients.
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