Correlation analysis of interstitial maturity and prognosis of colorectal cancer:Meta-analysis

BACKGROUND To investigate the relationship between interstitial maturity and prognosis of colorectal cancer.AIM To examine the correlation between interstitial maturity and the prognosis of colorectal cancer.METHODS The paper database PubMed,EMBASE,Cochranelibrary,Springerlink,CNKI,and Wanfang database were searched until December 2023."tumor stroma maturity""desmoplastic stroma reaction""desmoplastic reaction""stroma reaction""degree of stroma reaction""stroma classification""stroma density""colorectal cancer""colon cancer""rectal cancer""prognosis"were searched for the search terms.Two system assessors independently screened the literature quality according to the inclusion exclusion criteria,Quality evaluation and data extraction were performed for the included literatures,and meta-analysis was performed for randomized control trials included at using Review Manager 5.2 software.RESULTS Finally,data of 9849 patients with colorectal cancer from 19 cosets in 15 literatures were included,including 4339 patients with mature type(control group),3048 patients with intermediate type(intermediate group)and 2456 patients with immature type(immature group).The results of meta-analysis showed:Relapse-free survival[hazard ratio(HR)=2.66,95%confidence interval(CI):2.30-3.08;P<0.00001],disease-free survival(HR=3.68,95%CI:2.33-5.81;P<0.00001)and overall survival(HR=1.70,95%CI:1.53-1.87;P<0.00001)were significantly lower than those in mature group(control group);relapse-free survival(HR=1.36,95%CI:1.17-1.59;P<0.0001)and disease-free survival rate(HR=1.85,95%CI:1.53-2.24;P<0.0001)was significantly lower than the mature group(control group).CONCLUSION There is the correlation between tumor interstitial maturity and survival prognosis of colorectal cancer,and different degrees of tumor interstitial maturity have a certain impact on the quality of life of colorectal cancer patients.

Numerical simulation of blood flow and interstitial fluid pressure in solid tumor microcirculation based on tumor-induced angiogenesis

A coupled intravascular-transvascular-interstitial fluid flow model is developed to study the distributions of blood flow and interstitial fluid pressure in solid tumor microcirculation based on a tumor-induced microvascular network. This is generated from a 2D nine-point discrete mathematical model of tumor angiogenesis and contains two parent vessels. Blood flow through the microvascular network and interstitial fluid flow in tumor tissues are performed by the extended Poiseuille＇s law and Darcy＇s law, respectively, transvascular flow is described by Starling＇s law; effects of the vascular permeability and the interstitial hydraulic conductivity are also considered. The simulation results predict the heterogeneous blood supply, interstitial hypertension and low convection on the inside of the tumor, which are consistent with physiological observed facts. These results may provide beneficial information for anti-angiogenesis treatment of tumor and further clinical research.

Tumor Interstitial Fluid and Postoperative Recurrence of Tumors: an Experimental Study for Verifying Hypothesis of "Tumor-phlegm Microenvironment"

Objective： To explore a method of extracting tumor interstitial fluid （TIF） which is similar to muddy phlegm in Chinese medicine （CM）, interleukin-8 （IL-8） in concentration was taken as the representative of the content of TIF, analyzed in the extracted TIF and the original tumor tissue, and examined to see whether TIF has an interfering effect on tumor recurrence. Methods： Tumor tissue was ground, centrifuged, and filtered for intercellular substances. Tumor-bearing Kunming S180 mice were raised for 21 days and then the tumors were removed to observe the influence of intervention with TIF, normal saline （NS） and a blank control on tumor recurrence. Results： The content of IL-8 in the filtered and unfiltered tumor tissue was not significantly different （P0.05）. Postoperative tumor recurrence in TIF intervention group was significantly higher than that in the NS intervention and control groups （60%, 12/20 vs. 20%, 4/20 vs. 15%, 3/20, χ2=11.058, P0.01）. Tumor cells grew vigorously and infiltrated to muscular tissue in TIF intervention group. Large numbers of tumor cells were seen necrotic in the NS intervention group, and small numbers of tumor cells were seen necrotic in the blank control group. Conclusions： TIF can be effectively extracted by the means described. It does not contain tumor cells, but its contents such as IL-8 may stimulate tumor cell growth and promote postoperative tumor recurrence, which provided preliminary experimental basis for hypothesis of ＂tumor-phlegm microenvironment＂.

Tumor Interstitial Fluid and Gastric Cancer Metastasis:An Experimental Study to Verify the Hypothesis of "Tumor-Phlegm Microenvironment"

Objective： To extract tumor interstitial fluid （TIF） from MKN-45 gastric cancer which is similar to ＂muddy phlegm＂ in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid （MKN-45 TIF） intervention on metastasis of gastric cancer and on the expressions of vascular endothelial growth factor （VEGF）, kinase insert domain containing receptor （KDR）, epithelial-cadherin （E-cad）, cyclooxygenase-2 （COX-2）, intercellular adhesion molecule-1 （ICAM-1） and telomerase genes and proteins in primary tumor tissue. Methods： An MKN-45 tumor-bearing model was established in 50 nude mice. The modeled animals were equally randomized to 5 groups： the simple tumor-bearing group （model group）, the normal saline （NS） via tail vein injection （i.v.） group （NS i.v. group）, MKN-45 TIF i.v. group （TIF i.v. group）, NS intraperitoneal injection （i.p.） group （NS i.p. group）, and MKN-45 TIF i.p. group （TIF i.p. group）. The TIF and NS intervention groups received injection （i.p. or i.v.） of MKN-45 TIF or NS twice a week, 0.2 mL at a time. After 8 weeks, the primary tumors were removed, weighed and HE stained to observe tumor metastasis. The primary tumor tissues were analyzed by immunohistochemistry and real-time quantitative PCR to detect expressions of VEGF, KDR, E-cad, COX-2, ICAM-1, and telomerase genes and proteins in different groups. Results： There were significant differences in tumor weight between TIF intervention groups and the model and NS intervention groups. Tumor metastasis was observed in all 5 groups, but the tumor metastasis rate in TIF intervention groups was significantly higher than those in the model and NS intervention groups. The gene and protein expressions of gastric cancer-related factors VEGF, KDR, COX-2, ICAM-1 and telomerase were unregulated while the gene and protein expressions of E-cad were downregulated in TIF intervention groups. Conclusions： TIF promotes tumor growth, invasion and metastasis of gastric cancer. These findings provide preliminary experimental clues for verifying the hypothesis of ＂tumor-phlegm microenvironment＂.