CD44v6 in peripheral blood and bone marrow of patients with gastric cancer as micro-metastasis

AIM： To detect the expression of CD44 correlated with the ability of micro-metastasis in peripheral blood and bone marrow of patients with gastric cancer and to deduce its clinical significance. METHODS： Preoperative peripheral blood and bone marrow specimens from 46 patients with gastric cancer and 6 controls were studied by semi-quantitative RTPCR amplification of CD44v6mRNA. Preoperative and postoperative peripheral blood specimens from 40 patients with gastric cancer and 14 controls were studied by quantitative RT-PCR amplification of CD44v6mRNA in the corresponding period. RESULTS： Semi-quantitative RT-PCR amplification showed that CD44v6mRNA expression of peripheral blood and bone marrow was positive in 39 （84.8%） and 40 （86.9%） of 46 patients with gastric cancer, respectively. In peripheral blood, CD44v6mRNA expression was positive for diffuse type in 30 （93.8%） of 32 patients and for intestinal type in 9 （64.3%） of 14 patients. On the other hand, in bone marrow, CD44v6mRNA expression was positive for diffuse type in 31 （96.9%） of 32 patients and for intestinal type in 10 （71.4%） of 14 patients. There was a significant difference between the diffuse type and intestinal type. Quantitative RTopCR amplification demonstrated that CD44v6mRNA was not expressed in the peripheral blood of controls and CD44v6mRNA expression was positive for preoperative peripheral blood in 40 patients with gastric cancer, the expression levels being from 4.9 × 10^2 to 3.2× 10^5 copies/g RNA. The average expression level of CD44v6mRNA in peripheral blood was 3.9 × 10^10 copies/g RNA. The expression levels of CD44v6mRNA in peripheral blood in gastric cancer patients after curative operation increased from 5.5 × 100 to 7.6 × 10 copies/g RNA （P = 0.00496）. After curative operation, the expression level decreased markedly. CONCLUSION： Semi-quantitative and quantitative RTPCR amplification for CD44v6mRNA is a sensitive and specific method for the detection of micro-metastasis in peripheral blood and bone marrow, which might be used as an indicator of tumor burden and therapeutic effect.

Emerging landscapes of nanosystems based on pre-metastatic microenvironment for cancer theranostics

The emergence of disseminated metastasis is the leading cause of mortality in patients with malignant tumor.The pre-metastatic microenvironment,including the primary tumor-derived components,pre-metastatic niche(PMN),circulating tumor cells(CTCs),micro-metastases,and tumor immune microenvironment(TIM),are the crucial factors to initiate metastasis and form macro-metastases.It may be a more promising strategy for directly targeting pre-metastatic microenvironment-interrelated factors and cells before they have the chance to form secondary tumors to prevent metastasis.During recent years,a variety of nanosystems,with specific microstructures and functional properties,have been devised to selectively target pre-metastatic cells components and interrelated molecular,and exhibited strong potential on anti-metastatic therapy by absorbing and neutralizing primary tumor-derived components,preventing establishment of the PMN,eliminating the CTCs,eradicating the micro-metastases and modulating the TIM.In this review,we comprehensively review the emerging nanosystems based on the pre-metastatic microenvironments.Hopefully,this review can cast new lights for early preventing and attenuating metastatic progression.