An ideal tumor treatment is supposed to eliminate the primary tumor and simultaneously trigger the host antitumor immune responses to prevent tumor recurrence and metastasis. Herein, a liposome encapsulating phosphoinositide 3-kinase gamma (PI3K ) inhibitor IPI-549 and photosensitizer chlorin e6 (Ce6), denoted by LIC, is prepared for colon cancer treatment. LIC internalized into CT26 cells generates reactive oxygen species (ROS) under laser irradiation to cause immunogenic tumor cell death, during which immunostimulatory signals such as calreticulin are released to further induce T lymphocyte-mediated tumor cell killing. Meanwhile, IPI-549 transported by liposome can inhibit PI3K in the myeloid-derived suppressive cells (MDSCs), resulting in downregulation of arginase 1 (Arg-1) and ROS to promote MDSCs apoptosis and reduce their immunosuppressive activity to CD8 + T cells. LIC-mediated immunogenic photodynamic therapy synergizes with MDSCstargeting immunotherapy, which significantly inhibits tumor growth via facilitating the dendritic cell maturation and tumor infiltration of CD8 + T cells while decreasing the tumor infiltration of immunosuppressive regulatory T cells, MDSCs, and M2-like tumor-associated macrophages. Moreover, the synergistic therapy increases the number of effector memory T cells (T EM ) in spleen, which suggests a favorable immune memory to prevent tumor recurrence and metastasis. The Ce6 and IPI-549-coloaded multifunctional nanodrug demonstrates high efficacy in colon cancer treatment.

BackgroundColon cancer has always been diagnosed at a late stage, which is associated with poor prognosis. The currently used serum tumor markers CEA and CA19-9 display low sensitivity and specificity and may not have diagnostic value in early stage colon cancer. Thus, there is an urgent need to identify novel serum biomarkers for use in the early detection of colon cancer.MethodsIn this study, the expression of DC-SIGN and DC-SIGNR in serum was detected by enzyme-linked immunosorbent assay (ELISA). DC-SIGN and DC-SIGNR expression was detected in cancer tissues by immunohistochemistry (IHC).ResultsThe level of sDC-SIGN was lower in patients than in the healthy controls, while the level of sDC-SIGNR in patients was higher than in the healthy controls. Both sDC-SIGN and sDC-SIGNR had diagnostic significances for cancer patients, and the combined diagnosis of these two markers was higher than both of them alone. Furthermore, there were significant differences between both sDC-SIGN and sDC-SIGNR in stage I/II patients and the healthy controls. Moreover, high sDC-SIGN level was accompanied with the long survival time. Additionally, DC-SIGNR was negative in the cancer foci and matched normal colon tissues but was weakly positive between the cancer foci. DC-SIGN staining was faint in matched normal colon tissues, strong in the tumor stroma and the invasive margin of colon cancer tissues, and negatively correlated with the sDC-SIGN level in serum from the same patient. Interestingly, the percent survival of patients with a DC-SIGN mean density of>0.001219 (the upper 95% confidence interval of matched normal colon tissues) was higher than for all other patients.ConclusionDC-SIGN and DC-SIGNR are blood-based molecular markers that can potentially be used for the diagnosis of early stage patients. Moreover, expression of DC-SIGN in serum and cancer tissues may affect the survival time for colon cancer patients.

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The aim of present study was to investigate the clinical significances of mannose receptor (MR) and CD163 in colorectal cancer (CRC). Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were utilized for this analysis. Preoperative serum MR and CD163 levels ranged from 0.153 to 0.804 μg/ml (median = 0.359 μg/ml) and from 0.319 to 1.314 μg/ml (median = 0.685 μg/ml) in CRC patients respectively. Strikingly, preoperative serum levels of MR and CD163 were significantly increased in CRC patients than in healthy individuals (P< 0.0001). ROC analyses suggested that the optimum diagnostic cut-offs for serum MR and CD163 were 0.3485 μg/ml (AUC 0.7205, sensitivity 54.82%, and specificity 80.46%) and 0.6111 μg/ml (AUC 0.7463, sensitivity 62.65%, and specificity 80.46%) respectively. Detection of serum MR and CD163 together obviously enhanced the diagnostic accuracy (AUC 0.7968, sensitivity 69.28%, and specificity 77.01%). Then, preoperative serum MR and CD163 levels correlated significantly with serum CEA, CA19-9 and CA72-4 concentrations in CRC patients (P< 0.05). High MR and CD163 expression in serum was associated significantly with shorter overall survival (P< 0.05) and demonstrated as adversely prognostic factors (P< 0.05). Further, expression of MR and CD163 in CRC tissues was significantly higher than that in para-cancer tissues (P< 0.001). High expression of MR and CD163 in CRC tissues also correlated significantly with shorter overall survival (P< 0.05). MR and CD163 expression in serum or CRC tissues all correlated positively with the degree of lymphatic metastasis (P< 0.0001). In conclusion, MR and CD163 may be novel biomarkers for CRC patients.

Soluble mannose receptor (sMR) and soluble haemoglobin scavenger receptor (sCD163) are macrophage activation markers which have previously been demonstrated to be increased in patients with inflammation, auto-immunity and malignancies. To investigate the clinical diagnostic and prognostic significance of preoperative serum sMR and sCD163, the present study investigated 143 gastric cancer (GC) patients, 66 subjects with benign gastric disease and 59 healthy controls, using an ELISA assay. Preoperative serum levels of sMR and sCD163 ranged from 0.165 to 0.885 µg/ml (median=0.374 µg/ml) and from 0.291 to 1.760 µg/ml (median=0.628 µg/ml) in GC patients, respectively. The expression levels of sMR and sCD163 were elevated compared with all controls (P<0.0001). Receiver operating characteristic analyses suggested that the optimum diagnostic cut-offs for sMR and sCD163 were 0.3405 µg/ml [area under curve (AUC) 0.7284, sensitivity 61.54%, and specificity 73.60%] and 0.6645 µg/ml (AUC 0.7766, sensitivity 53.85%, and specificity 86.40%), respectively. Notably, the measurement of serum sMR and sCD163 levels in conjugation, markedly enhanced the diagnostic accuracy (AUC 0.8490, sensitivity 70.63% and specificity 84.00%). Preoperative serum sMR and sCD163 levels correlated significantly with serum carcinoembryonic antigen, CA199, CA724 and CA125 concentrations in GC patients (P<0.05), however this association was not observed with sMR and CA724. High preoperative serum sMR and sCD163 levels correlated significantly with shorter overall survival (P=0.0041; P<0.0001, respectively) and were demonstrated to act as adverse prognostic factors (P=0.006; P<0.001, respectively). Furthermore, preoperative serum sMR and sCD163 levels correlated positively with the degree of lymphatic and distant metastasis of GC. In conclusion, preoperative serum sMR and sCD163 may be novel diagnostic and prognostic markers for GC and further studies are required in order to elucidate the underlying molecular mechanisms of sMR and CD163 in the development and progression of GC.

Background Surgery is considered to be a potentially curative approach for gastric cancer. However, most cases are diagnosed at a very advanced stage for the lack of typical symptoms in the initial stage, which makes it difficult to completely surgical resect of tumors. Early diagnosis and precise personalized intervention are urgent issues to be solved for improving the prognosis of gastric cancer. Herein, we developed an RGD-modified ROS-responsive multifunctional nanosystem for near-infrared (NIR) imaging and photothermal therapy (PTT) against gastric cancer. Methods Firstly, the amphiphilic polymer was synthesized by bromination reaction and nucleophilic substitution reaction of carboxymethyl chitosan (CMCh) and 4-hydroxymethyl-pinacol phenylborate (BAPE). Then, it was used to encapsulate indocyanine green (ICG) and modified with RGD to form a smart multifunctional nanoparticle targeted to gastric cancer (CMCh-BAPE-RGD@ICG). The characteristics were determined, and the targeting capacity and biosafety were evaluated both in vitro and in vivo. Furthermore, CMCh-BAPE-RGD@ICG mediated photothermal therapy (PTT) effect was studied using gastric cancer cells (SGC7901) and SGC7901 tumor model. Results The nanoparticle exhibited suitable size (≈ 120 nm), improved aqueous stability, ROS-responsive drug release, excellent photothermal conversion efficiency, enhanced cellular uptake, and targeting capacity to tumors. Remarkably, in vivo studies suggested that CMCh-BAPE-RGD@ICG could accurately illustrate the location and margin of the SGC7901 tumor through NIR imaging in comparison with non-targeted nanoparticles. Moreover, the antitumor activity of CMCh-BAPE-RGD@ICG-mediated PTT could effectively suppress tumor growth by inducing necrosis and apoptosis in cancer cells. Additionally, CMCh-BAPE-RGD@ICG demonstrated excellent biosafety both in vitro and in vivo. Conclusion Overall, our study provides a biocompatible theranostic nanoparticle with enhanced tumor-targeting ability and accumulation to realize NIR image-guided PTT in gastric cancer.

Primary gastrointestinal non-Hodgkin lymphoma (PGI NHL) is one of the most common types of extranodal lymphoma, accounting for ~30-50% of all extranodal lymphomas. The aim of the present study was to investigate the clinical characteristics, diagnosis, treatment and prognosis of patients with PGI NHL. A total of 46 patients with PGI NHL (mean age, 50 years) were enrolled in this study, with a male:female ratio of 1.3:1. The most common site of PGI NHL was the stomach (52.2%), followed by the colon (34.8%) and small intestine (8.7%). The most common symptoms of PGI NHL included abdominal pain or discomfort (91.3%), loss of appetite (65.2%) and weight loss (56.5%) and the most common pathological subtype of PGI NHL was diffuse large B-cell lymphoma (DLBCL) (78.3%). Lesions were identified in 95.7% of PGI NHL patients under preoperative endoscopic examination, whereas the diagnosis rate was only 21.7% during preoperative endoscopic biopsy. All 46 patients underwent surgical treatment and 36 also received postoperative chemotherapy or radiotherapy. The follow-up time was 6-70 months in 37 PGI NHL patients, with 1-, 3- and 5-year survival rates of 81.1, 62.16 and 50.0%, respectively. The 5-year survival rate differed significantly according to clinical stage (P=0.002) and tumor size (P=0.0017) among patients with PGI NHL. However, there was no statistically significant difference in the 5-year survival rate between patients who received surgery alone and those who received surgery plus postoperative chemotherapy or radiotherapy (P=0.1371). Furthermore, there were no statistically significant differences in gender (P=0.127), clinical stage (P=0.828), histological subtype (P=1.000) and surgical modality (P=0.509) between patients with primary gastric non-Hodgkin lymphoma (PG NHL) and those with primary intestinal non-Hodgkin lymphoma (PI NHL). In conclusion, PGI NHLs are a heterogeneous group of diseases, whereas clinical stage and tumor size were identified as adverse prognostic factors of PGI NHL. Further studies, including a larger number of patients treated with surgery alone, are required in order to elucidate the precise role of surgery combined with postoperative chemotherapy or radiotherapy in the prognosis of PGI NHL.

Metastasis, a life-threatening complication of cancer, leads to the majority of cases of cancer-associated mortality. Unfortunately, the underlying molecular and cellular mechanisms of cancer metastasis remain to be fully elucidated. C-type lectins are a large group of proteins, which share structurally homologous carbohydrate-recognition domains (CRDs) and possess diverse physiological functions, including inflammation and antimicrobial immunity. Accumulating evidence has demonstrated the contribution of C-type lectins in different steps of the metastatic spread of cancer. Notably, a substantial proportion of C-type lectins, including selectins, mannose receptor (MR) and liver and lymph node sinusoidal endothelial cell C-type lectin, are important molecular targets for the formation of metastases in vitro and in vivo. The present review summarizes what has been found regarding C-type lectins in the lymphatic and hematogenous metastasis of cancer. An improved understanding the role of C-type lectins in cancer metastasis provides a comprehensive perspective for further clarifying the molecular mechanisms of cancer metastasis and supports the development of novel C-type lectins-based therapies the for prevention of metastasis in certain types of cancer.