To determine whether lymphangiogenesis was associated with the development of colorectal carcinoma and whether the mean maximal diameter of lymphatic microvessels (LMMMD) or lymphatic microvessel density (LMVD) is associated with lymph node metastasis in early stage invasive colorectal carcinoma (T1 carcinoma), we used immunohistochemical staining with podoplanin to measure LMMMD and LMVD in intratumoral (LMMMDit, LMVDit) and peritumoral areas (LMMMDpt, LMVDpt) of T1 carcinomas (n=87). By comparing the LMMMD and LMVD in normal large intestine (n=10), adenoma (n=15), and Tis carcinoma (n=15), we found out that the LMVDpt in T1 carcinoma with lymphatic vessel invasion (LVI) was significantly high (P<0.001), and there was a significant decrease in LMMMDpt in T1 carcinoma (P=0.031). Both LMMMDpt and LMVDpt were significantly increased in the T1 carcinomas, with LVI compared with the T1 carcinomas without LVI (P=0.018, P=0.003). Multivariate analysis revealed that LVI and combined greater LMMMDpt and greater LMVDpt were associated with lymph node metastases (P=0.005, P=0.036). These results indicate that lymphangiogenesis might be induced in the surrounding tumor areas of the T1 colorectal carcinoma with LVI; thus, evaluation of the diameter and density of lymphatic microvessels is important in T1 colorectal carcinoma to predict lymph node metastases.

Abstract. Patients with the most common advanced human cancers such as lung, breast, uterus, and cancers of the digestive system almost always develop bone metastases, with painful and untreatable consequences. This study aimed to determine the prognostic implications of the neutrophil/lymphocyte (N/L) ratio in the peripheral blood of patients with malignant bone metastasis. Study participants were identified from a prospective cohort of cancer patients with bone metastasis. Data for the N/L ratios were obtained from clinical and pathological records and were analyzed together with other known prognostic factors in the multivariate and univariate analyses. The results showed the average N/L ratio of all 497 patients to be 4.25±2.44 (range 0.54-45.50 years). Multivariate analysis revealed that tumor type and a high N/L ratio were significantly associated with poor prognosis. For the high N/L ratio group, the estimated hazard ratio of death was 1.348 [95% confidence interval (CI), 1.062-1.712] compared with the low N/L ratio group. The average N/L ratio of the 225 patients in the surgery group was 2.79±2.46 (range 0.77-22.75 years). Multivariate analysis revealed that a preoperatively high N/L ratio (P=0.013; HR=2.945; 95% CI, 1.256-6.906) was significantly associated with poor prognosis after bone metastasis in the surgery group. In conclusion, the N/L ratio was confirmed to be an independent prognostic factor in patients with bone metastasis. Thus, the N/L ratio may serve as a clinically accessible and useful biomarker for patient survival.

These results suggest that the N/L ratio is an independent prognostic factor in rectal cancer, and the N/L ratio may serve as a clinically accessible and useful biomarker for patient survival.

Maggots (larvae of Lucilia sericata) have shown therapeutic effects on refractory wounds infected with bacteria, yet the bacterial killing mechanisms are unclear. Herein, we report the isolation and purification of an antibacterial protein from maggots (MAMP). MAMP demonstrated inhibitory activity against both standard strains and clinically isolated antibiotic-resistant strains of Staphylococcus aureus in vitro. The topical use of MAMP effectively decreased the viability of S. aureus and promoted wound healing in an S. aureus mouse skin infection model. MAMP exerted its antibacterial activity via a bactericidal mechanism based on observations using scanning electron and transmission electron microscopy. MAMP interacted with the bacterial cell membrane and disrupted the cell surface structure. In addition, MAMP had weak hemolytic activity at a high concentration. Taken together, MAMP exhibits potential use as a topical agent for treating bacterial infections.

Abstract. Several investigators have suggested that the granulocyte/lymphocyte (G/L) ratio is a good indicator for the evaluation of the condition of a tumour-bearing host, although its prognotic significance is unclear. To further investigate the clinical applications of the G/L ratio, we injected 1x10 5 and 1x106 Lewis lung carcinoma cells (3LLc) into the feet of 4-week-old C57BL/6 mice separated into groups A, B, C and D (1x10 5 cells) and E, F, G and H (1x10 6 cells). For the observation of tumour metastasis and G/L ratio, the mice in groups A-D were sacrificed on days 11, 14, 17 and 21 after inoculation with the 3LLc cells, and the mice in groups E-H on days 7, 11, 14 and 17. The results suggest that in mice the number of granulocytes increases with time after 3LLc cell injection (P<0.05). We also retrospectively investigated the correlation between G/L ratio, clinicopathologic features and prognosis in 62 patients with gastric carcinoma. There was a significant correlation between the G/L ratio and tumour weight (r=0.746, P<0.05), as well as a significant difference between the G/L ratio and the extent of metastases (P<0.05). Additionally, the G/L ratio was significantly associated with lymph node metastasis and higher tumour stage, tumour progression (P=0.017) and 5-year survival (P=0.013). In conclusion, the G/L ratio is associated with tumour progression and shorter survival. The close correlation between G/L ratio and tumour stage or lymph node status suggests that it could be used to predict tumour metastasis, prognosis and overall survival in patients with gastric carcinoma before they undergo surgical treatment.

Cytokines exhibit a pleiotropic effect in the regulation of the immune cell function, tumor growth and antitumor immune responses. A total of 30 patients with colorectal carcinoma were enrolled on this study and their levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, serum granulocyte colony-stimulating factor (sG-CSF) and serum macrophage colony-stimulating factor (sM-CSF) were measured preoperatively using ELISA. Tumor-infiltrating granulocyte (TIG), tumor-associated macrophage (TAM), G-CSF and M-CSF expression in tumor cells were examined using immunostaining. This study revealed abnormal levels of cytokines in patients, including IL-1β (1/30, 3.3%), IL-6 (16/30 53.3%), IL-81 (15/30, 50%), TNF-α (4/21, 19%), sG-CSF (17/30, 56.7%) and sM-CSF (4/21, 19%). There was a positive linear correlation between IL-6 and sM-CSF (P=0.017, R=0.517). sG-CSF was significantly associated with a deeper tumor invasion (P=0.039) and a more advanced tumor stage (P=0.023). The granulocyte/lymphocyte (G/L) ratio was associated with abnormal levels of sG-CSF. Logistic univariate analysis revealed that TIGs were a risk factor for lymph node metastasis (0.019) and TAMs were a risk factor for depth of invasion (0.029), but this was not confirmed in logistic multivariate analysis. In conclusion, IL-6, IL-8, sM-CSF and sG-CSF may indirectly promote tumor growth, progression and metastasis by changing the leukocyte populations in the blood and the tumor microenvironment.

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Abstract. Several lines of evidence indicate that tumourinfiltrating granulocytes (TIGs) promote tumour growth and progression. However, the prognostic significance of TIGs, the relationship beween TIGs and Fas ligand (FasL) expressed on tumour cells remains unclear and warrants investigation. Using immunnostaining, we retrospectively investigated TIGs and FasL in 130 tissue specimens from gastric carcinoma. We analyzed the correlation among these markers, their association with clinicopathologic features and prognosis. The number of TIGs was significantly associated with FasLexpression (P=0.002). Further, TIGs were significantly associated with depth of tumour invasion, lymph node metastasis and tumour stage. Calculating the prognostic relevance, in multivariate analysis, TIGs [relative risk (RR)=1.014; 95% CI=1.002-1.027; P=0.015] and tumour stage were statistically significant factors for survival. Our results suggest that TIGs are conveniently measured by the immunostaining method, and possibly serve as an independent factor of prognosis in patients with gastric carcinoma. This is based on the fact that TIGs were significantly associated with tumour stage and shorter survival time.