Effects of splenic lymphocytes isolated from the mouse of colorectal carcinoma with liver metastases induced by oncolytic herpes simplex virus type Ⅱ on colorectal carcinoma with pulmonary metastases in mice / 肿瘤研究与临床

Objective:To study the effect of splenic lymphocytes isolated from mouse models of colorectal carcinoma with liver metastases induced by oncolytic herpes simplex virus type Ⅱ(oHSV2) on the growth of pulmonary metastases of colorectal carcinoma.Methods:A total of 18 6-week-old BALB/c female mice were selected, colorectal carcinoma cell line CT26 of mice in logarithmic phase was inoculated at the right back (2×10 5 per mouse) and spleen (1×10 5 per mouse) of mice, and tumor cells had hematogenous metastasis to liver through splenic vein. CT26 colorectal carcinoma with liver metastases model was constructed. All mice were respectively divided into oHSV2 group and phosphatic buffered saline (PBS) group, 9 mice in each group according to the random number table method. Mice in oHSV2 group were treated with subcutaneous intratumoral multi-point injection of 100 μl oHSV2 (the multiplicity of infection was 1) for 6 cycles, while mice in PBS group were treated with subcutaneous intratumoral multi-point injection of 100 μl PBS for 6 cycles in total, once injection every other day; the survival of mice was analyzed by using Kaplan-Meier method and tumor growth was observed. The mice of both groups in mouse models of colorectal carcinoma with liver metastases were killed on day 20 and their splenic lymphocytes were isolated. After investigation of the most suitable inoculation number and the optimal observation time of colorectal carcinoma with pulmonary metastases CT26 cell lines, 9 6-week-old BALB/c female mice were divided into the experimental group, the negative control group and the blank control group according to the random number table method, with 3 mice in each group. Mice in the experimental group were injected with splenic lymphocytes (4×10 7 per mouse) and CT26 cells (2×10 5 per mouse) isolated from mouse models induced by oHSV2 via the tail vein, mice in the negative control group were injected with splenic lymphocytes (4×10 7 per mouse) and CT26 cells (2×10 5 per mouse) isolated from normal mice with same weeks old via the tail vein, and mice in the blank control group were injected with only CT26 cells (2×10 5 per mouse) via the tail vein. The above 3 groups were executed on day 10 after inoculation, and tumor growth, histopathological changes of mice were also observed; the survival of mice was analyzed by using Kaplan-Meier method. Results:In models of colorectal carcinoma with liver metastases, liver metastases lesions were not detected in 7 mice and 2 mice had 1-2 liver metastases lesions with long diameter less than 2 mm of oHSV2 group; in PBS group, 9 mice all had multiple liver metastases lesions with tumor long diameter ranging from 1 to 10 mm. And mice in oHSV2 group survived much longer than that of mice in PBS group ( P < 0.001). In models of pulmonary metastases, the optimal number of CT26 cells in mouse tail vein was 2×10 5 per mouse; the best observation time point was day 10 after tail vein injection. On day 24 after inoculation, all mice in the negative control group and the blank control group died, while mice in the experimental group all survived on day 60, and the difference of the overall survival in the above 3 groups was statistically significant ( P = 0.007). HE staining results showed that the lung tissues of the experimental group did not show clear tumor cells, whereas the lung tissues of the negative control group and the blank control group showed extensive diffuse tumor cells. Conclusions:Splenic lymphocytes produced by oHSV2 induction in mouse models of colorectal carcinoma with liver metastases can effectively inhibit the development of pulmonary metastases in colorectal carcinoma CT26 cell of mice.

Relationship between oncolytic viral therapy and tumor microenvironment or body immunity / 肿瘤研究与临床

The interaction between oncolytic virus (OV) and the tumor microenvironment or body immune system is critical to the outcome of antitumor therapy. The antitumor mechanism of OV is complex, which involves direct cytotoxic effects, immunogenicity change in tumor microenvironment, the role of tumor vasculature, and activating of the antitumor immunity response, to reach the goal of killing the tumor cells infected or uninfected, and confirming the continous favorable effects.

Clinicopathological features of the primary gastric neuroendocrine neoplasms / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to investigate the clinicopathological features of different histological types of primary gastric neuroendocrine neoplasms (including the esophagogastric junction), and to analyze the characteristics and difficulties in diagnosis of all the subtypes of this disease.</p><p><b>METHODS</b>75 cases of primary gastric neuroendocrine neoplasms (including the esophagogastric junction) were included in this study. The expressions of several markers including somatostatin, synaptophysin, chromogranin A, CD56, S-100, neuron-specific enolase and CD57 were assayed in all the specimens by immunohistochemical staining, and their significance in the diagnosis and prognosis of gastric neuroendocrine neoplasms were assessed. In addition, the relationship between various clinical parameters such as tumor location, histological types, depth of invasion and metastasis was also analyzed.</p><p><b>RESULTS</b>The incidence of gastric neuroendocrine neoplasms accounted for 1.5% of gastric cancer in the same period, and the proportion of each subtype was 53.3% (40/75) in G3, 29.3% (22/75) in MANEC, 16.0% in G1(12/75), and 1.3% (1/75) in G2, respectively. 41.7% (5/12) of the G1 showed multifocal lesions, accompanyied with neuroendocrine cell hyperplasia in the gastric mucosa. 54.67% (41/75) of the NEN located in the esophagogastric junction. The lymph node metastasis of MANEC is unique. The coincidence rate in diagnosis of preoperative biopsies and postoperative specimen was 75.0% (9/12) in G1, 72.7% (16/22) in MANEC, and 25.0% (10/40) in G3, respectively.</p><p><b>CONCLUSIONS</b>Gastric neuroendocrine neoplasms occur mainly in the esophagogastric junction, and most of them were highly malignant. The coincidence rate of preoperative and postoperative pathological diagnosis for primary gastric neuroendocrine neoplasms is low. Therefore, it should be very cautious when diagnosis of this disease is made in a preoperative biopsy.</p>

Detection and clinical implication of aneuploidy of chromosomes 11 and 20 in gastric adenocarcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to find out the value of chromosome aneuploidy in early diagnosis and prediction of postoperative recurrence of gastric adenocarcinoma (GAC).</p><p><b>METHODS</b>Tissue samples, including 49 GAC, pairing pericancerous mucosa and normal gastric mucosa from the distant cutting margin were use in this study. Two centromere probes, Cen11 and Cen20 specific for chromosomes 11 and 20 were analyzed by FISH . The clinicopathological data were summarized.</p><p><b>RESULTS</b>The incidence of aneuploidy of chromosome 11 in the tumors, pericancerous mucosa and normal gastric mucosa from the distant cutting margin were 83.7%, 40.8%, and 16.3%, respectively (P < 0.001), and those of chromosome 20 were 87.8%, 53.1%, and 16.3%, respectively (P < 0.001). The aneuploidy of Cen 11 displayed a significant correlation with Lauren's claasification, and lymph node metastasis (P < 0.05 for both). The pericancerous mucosa and normal gastric mucosa from the distant cutting margin displayed mainly chronic inflammatory changes, intestinal metaplasia and dysplasia.</p><p><b>CONCLUSIONS</b>Aneuploidy of Cen11 and Cen20 in pericancerous mucosa may be used as a candidate marker for early diagnosis of gastric adenocarcinoma and may have a predictive value of postoperative recurrence.</p>

Progress of colorectal neuroendocrine neoplasm / 国际肿瘤学杂志

Colorectal neuroendocrine neoplasm (NEN) is originated from colorectal neuroendocrine cells.The incidence of colorectal NEN is low,however it has been increasing in recent years.As the research work has gone further,WHO has graded colorectal NEN to neuroendocrine tumor,neuroendocrine carcinoma,mixed gland-neuroendocrine carcinoma and hyperplastic and pre-neoplastic lesions.Although colorectal NEN cells can produce hormones and have endocrine functions,the clinical symptoms may not be shown.The diagnosis and treatment for colorectal NEN are different according to different classifications and stages.

Expression of annexin A1 and PCNA in pancreatic cancer and their correlation / 中华胰腺病杂志

Objective To investigate the expressions of the annexin A1 ( ANXA1 ) in pancreatic cancer and the correlations with proliferating cell nuclear antigen (PCNA). Methods Tissue microarray instrument was used to construct the chip. There were 39 samples of normal pancreas tissue, 42 samples of pancreatic cancer, 7 samples of islet cell tumor and 8 samples of ampullary carcinoma. The expressions of ANXA1 and PCNA protein were examined by immunohistochemistry and their correlation was analyzed. Results The off-chip rate of tissue chips after immunohistochemistry was 11.7% ～ 13.3%, which could satisfy the needs for experiment. Immunohistochemical results of pancreatic cancer tissue microarray showed that the positive rate of ANXA1 expression in pancreatic cancer was 71.4% (30/42), which was significantly higher when compared with that of normal pancreas tissue ( 18.4%, 7/38; P < 0. 01 ). The positive rate of PCNA expression in pancreatic cancer was 73.8% (31/42), which was significantly higher than that of normal pancreas tissue (22.2%, 8/36; P < 0.01 ). The expression of ANXA1 had a significant correlation with PCNA in pancreatic cancer ( P < 0.01 ). Conclusions The expression of ANXA1 protein was significantly increased in pancreatic cancer. The expression of ANXA1 was significantly correlated with the expression of PCNA.