Search

Tumors can induce the generation and accumulation of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) in a tumor microenvironment, contributing to tumor escape from immunological attack. Although dendritic cell-based cancer vaccines can initiate antitumor immune responses, tumor-educated dendritic cells (TEDCs) involved in the tolerance induction have attracted much attention recently. In this study, we investigated the effect of β-glucan on TEDCs and found that β-glucan treatment could promote the maturation and migration of TEDCs and that the suppressive function of TEDCs was significantly decreased. Treatment with β-glucan drastically decreased the levels of regulatory T (Treg) cells but increased the infiltration of macrophages, granulocytes and DCs in tumor masses, thus elicited Th1 differentiation and cytotoxic T-lymphocyte responses and led to a delay in tumor progression. These findings reveal that β-glucan can inhibit the regulatory function of TEDCs, therefore revealing a novel function for β-glucan in immunotherapy and suggesting its potential clinical benefit. β-Glucan directly abrogated tumor-educated dendritic cells-associated immune suppression, promoted Th1 differentiation and cytotoxic T-lymphocyte priming and improved antitumor responses.

Although observational studies have assessed the relationship between parity and thyroid cancer risk, the findings are inconsistent. To quantitatively assess the association, we conducted a systematic review and meta‐analysis. PubMed and Embase were searched up to January 2015. Prospective or case–control studies that evaluated the association between parity and thyroid cancer risk were included. We used the fixed‐effects model to pool risk estimates. After literature search, 10 prospective studies, 12 case‐control studies and 1 pooled analysis of 14 case‐control studies including 8860 patients were identified. The studies had fair methodological quality. Pooled analysis suggested that there was a significant association between parity and risk of thyroid cancer (RR for parous versus nulliparous: 1.09, 95% CI 1.03‐1.15; I2=33.4%). The positive association persisted in almost all strata of subgroup analyses based on study design, location, study quality, type of controls, and confounder adjustment, although in some strata statistical significance was not detected. By evaluating the number of parity, we identified that both parity number of 2 versus nulliparous and parity number of 3 versus nulliparous demonstrated significant positive associations (RR=1.11, 95% CI 1.01‐1.22; I2=31.1% and RR=1.16, 95% CI 1.01‐1.33; I2=19.6% respectively). The dose‐response analysis suggested neither a non‐linear nor linear relationship between the number of parity and thyroid cancer risk. In conclusion, this meta‐analysis suggests a potential association between parity and risk of thyroid cancer in females. However, the lack of detection of a dose‐response relationship suggests that further studies are needed to better understand the relationship.

The purpose of this study is to determine the associations between statin use and breast cancer survival and risk by performing a systematic review and meta-analysis. We searched PubMed, Embase and Web of Science up to August 2015 for identifying relevant prospective or case-control studies, or randomized clinical trials. Five prospective studies involving 60,911 patients reported the association between statin use and breast cancer mortality. Eleven prospective studies, 12 case-control studies and 9 randomized clinical trials involving 83,919 patients reported the association between statin use and breast cancer risk. After pooling estimates from all available studies, there was a significantly negative association between pre-diagnosis statin use and breast cancer mortality (for overall survival (OS): hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.54-0.84; for disease specific survival (DSS): HR = 0.72, 95% CI 0.53-0.99). There was also a significant inverse association between post-diagnosis statin use and breast cancer DSS (HR = 0.65, 95% CI 0.43-0.98), although the association with breast cancer OS did not reach statistical significance (HR = 0.71, 95% CI 0.48-1.07). Additionally, there was a non-linear relationship for the duration of post-diagnosis statin use with breast cancer specific mortality. On the other hand, with regards to the relationship between statin use and breast cancer risk, no significant association was detected. Our analyses suggest that although statin use may not influence breast cancer risk, the use of statin may be associated with decrease mortality of breast cancer patients. Further large-scale studies are warranted to validate our findings.

Background Pancreatic cancer ranks fourth in deaths caused by cancers throughout the world. Gemcitabine chemotherapy is the primary method of treatment of advanced pancreatic cancer, and in asco2014, it is still first- line chemotherapy. However gemcitabine+fluorouracil regimens are also licensed and widely used worldwide. Clinical trials are the best way to evaluate drug efficacy. In this study, we performed a systematic review and a meta-analysis of randomized controlled trials (RCTs) to assess whether gemcitabine+fluoropyrimidine combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone. Materials and methods A quantitative up-to-date meta-analysis was undertaken to investigate the efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy for locally advanced or metastatic pancreatic cancer. Inclusion was limited to high-quality randomized clinical trials. Results A total of 12 studies were included in the present analysis, with a total of 3,038 patients recruited. The studies were divided into three subgroups including 5-FU / CAP / S-1 combined with gemcitabine. For the primary endpoint of overall survival (OS), gemcitabine-based combination therapy demonstrated significantly better outcome (HR, 0.88; 95% CI, 0.81-0.95) than gemcitabine monotherapy. The analysis of progression free survival (PFS) also provided a significant result for the combined therapy in a total of 8 trials (2,130 patients) (HR, 0.74; 95% CI, 0.63-0.86). With subgroup analysis according to the method of dosing delivery, we found that in the injection group with 3 trials (889 patients), a negative result was found (HR, 0.93; 95% CI, 0.77-1.12); while a positive result was observed in the oral group with 9 trials (2,149 patients) (HR, 0.87; 95% CI, 0.80-0.95). Conclusions Gemcitabine combination therapy provides a modest improvement of survival, but is associated with more toxicity compared with gemcitabine monotherapy.

Telomeres play a key role in the maintenance of chromosome integrity and stability, and telomere shortening is involved in initiation and progression of malignancies. The aim of this study was to determine whether telomere length is associated with the colorectal carcinoma.A total of 148 colorectal cancer (CRC) samples and corresponding adjacent non-cancerous tissues were evaluated for telomere length, P53 mutation, and cyclooxygenase-2 (COX-2) mutation detected by fluorescent immunohistochemistry. Telomere length was estimated by real-time PCR. Samples with a T/S1.0 have an average telomere length greater than that of the standard DNA; samples with a T/S1.0 have an average telomere length shorter than that of the standard DNA.Telomeres were shorter in CRCs than in adjacent tissues, regardless of tumor stage and grade, site, or genetic alterations (P=0.004). Telomere length in CRCs also had differences with COX-2 status (P=0.004), but did not differ with P53 status (P=0.101), tumor progression (P=0.244), gender (P=0.542), and metastasis (0.488). There was no clear trend between T/S optimal cut-off values (1 or1) and colorectal tumor progression, metastasis, gender, P53 and COX-2 status.These findings suggesting that telomere shortening is associated with colorectal carcinogenesis but does not differ with tumor progression, gender, and metastasis.

Breast cancer patients with positive epidermal growth factor receptor (EGFR) expression have significantly worse post-relapse prognosis than patients with negative EGFR expression. Vinorelbine (NVB) is usually reserved as a salvage therapy after anthracyclines and taxanes in patients with breast cancer. To see whether EGFR expression has a predictive value in NVB-mediated effect on human breast cancer cells, we examined 50 primary breast cancer samples. Of these, 42% were found to be NVB sensitive by ATP-tumour chemosensitivity assay. Sensitivity was correlated with EGFR expression level (p = 0.001). To dynamically examine EGFR's effect on NVB sensitivity in breast cancer cells, we used the real-time cell electronic sensing system with EGFR-positive and EGFR-negative breast cancer cell lines, MCF-7 and MDA-MB-435s, respectively. MCF-7 is NVB sensitive, while MDA-MB-435 is NVB resistant. NVB-induced cytotoxicity to MCF-7 can be partly reversed with inhibitory anti-EGFR antibody. NVB up-regulated EGFR expression in MCF-7 cells, which affects ERK1/2 phosphorylation. This cellular response mechanism may cause greater input to non-lethally damaged cells. These data suggest that EGFR expression can be used as a prognostic factor for breast cancer sensitivity to NVB, which could help identify appropriate treatments for breast cancer.

Chemotherapy for breast cancer is given on the basis of empirical information from clinical trials, an approach which falls to take into account the known heterogeneity of chemosensitivity between patients. This study aimed to demonstrate the degree of heterogeneity of chemosensitivity in breast cancers. In this study, we examined the heterogeneity of chemosensitivity in breast cancer specimens (n = 50) using an ex vivo ATP-tumor chemosensitivity assay (ATP-TCA). Assay evaluability was 92% in surgical biopsies or pleural aspirates. A variety of chemosensitivity agents were tested. We found that the most active single agent tested was paclitaxel, to which 65.9% of samples were sensitive. Combinations of agents also showed more strong sensitivity cases. The Adriamycin+5-FU demonstrated a strong sensitivity in 23 of 43 (52.3%) of samples. Adriamycin+paclitaxel was more effective, with strong sensitivity in 37 of 43 cases tested (86.0%). There was a marked heterogeneity of chemosensitivity in breast cancer. Chemosensitivity testing may provide a practical method of testing new regimens before clinical trials in breast cancer patients.

Pancreatic fibrosis is the hallmark of chronic pancreatitis, currently an incurable disease. Pancreatitis fibrosis is caused by deposition of extracellular matrix (ECM) and the underlying pathological mechanism remains unclear. In addition to its broad biological activities, TGF-beta is a potent pro-fibrotic factor and many in vitro studies using cell systems have implicated a functional role of TGF-beta in the pathogenesis of pancreatic fibrosis. We analyzed the in vivo role of TGF-beta pathway in pancreatic fibrosis in this study. Smad7, an intracellular inhibitory protein that antagonizes TGF-beta signaling, was specifically expressed in the pancreas using a transgenic mouse model. Chronic pancreatitis was induced in the mouse with repeated administration of cerulein. Smad7 expression in the pancreas was able to significantly inhibit cerulein-induced pancreatic fibrosis. Consistently, the protein levels of collagen 1 and fibronectin were decreased in the Smad7 transgenic mice. In addition, alpha-smooth muscle actin, a marker of activated pancreas stellate cells, was reduced in the transgenic mice. Taken together, these data indicate that inhibition of TGF-beta signaling by Smad7 is able to protect cerulein-induced pancreatic fibrosis in vivo. (C) 2008 Elsevier B.V. All rights reserved.

The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been recently shown to be dysregulated in several cancers. However, the mechanisms underlying the role of MALAT1 in breast cancer remain unclear. Herein, we showed that MALAT1 was aberrantly increased in breast cancer tissues and cells. MALAT1-siRNA inhibited breast cancer cell proliferation and cell cycle progression in vitro and in vivo. Furthermore, MALAT1 acted as an endogenous potent regulator by directly binding to miR-124 and down-regulating miR-124 expression. In addition, MALAT1 reversed the inhibitory effect of miR-124 on breast cancer proliferation and was involved in the cyclin-dependent kinase 4 (CDK4) expression. Taken together, our data highlight the pivotal role of MALAT1 in breast cancer tumorigenesis. Moreover, the present study elucidated the MALAT1-miR-124-CDK4/E2F1 signaling pathway in breast cancer, which might provide a new approach for tackling breast cancer.

The association between parity and endometrial cancer risk is inconsistent from observational studies. We aimed to quantitatively assess the relationship by summarizing all relevant epidemiological studies. PubMed (MEDLINE), Embase and Scopus were searched up to February 2015 for eligible case–control studies and prospective studies. Random-effects model was used to pool risk estimations. Ten prospective studies, 35 case-control studies and 1 pooled analysis of 10 cohort and 14 case-control studies including 69681 patients were identified. Pooled analysis revealed that there was a significant inverse association between parity and risk of endometrial cancer (relative risk (RR) for parous versus nulliparous: 0.69, 95% confidence interval (CI) 0.65–0.74; I2 = 76.9%). By evaluating the number of parity, we identified that parity number of 1, 2 or 3 versus nulliparous demonstrated significant negative association (RR = 0.73, 95% CI 0.64–0.84, I2 = 88.3%; RR = 0.62, 95% CI 0.53–0.74, I2 = 92.1%; and RR = 0.68, 95% CI 0.65–0.70, I2 = 20.0% respectively). The dose-response analysis suggested a nonlinear relationship between the number of parity and endometrial cancer risk. The RR decreased when the number of parity increased. This meta-analysis suggests that parity may be associated with a decreased risk of endometrial cancer. Further studies are warranted to replicate our findings.

Studies have shown that microRNAs (miRNAs) are involved in the malignant progression of human cancer. However, little is known about the potential role of miRNAs in breast carcinogenesis. miR-124 expression in breast cancer tissue was measured by quantitative real-time PCR (qRT-PCR). Target prediction algorithms and luciferase reporter gene assays were used to investigate the target of miR-124. Breast cancer cells growth was regulated by overexpression or knockdown miR-124. At the end of the study, tumor-bearing mice were tested to confirm the function of miR-124 in breast cancer. In this study, we demonstrated that the expression of miR-124 was significantly downregulated in breast cancer tissues compared with matched adjacent non-neoplastic tissues. We identified and confirmed that cyclin-dependent kinase 4 (CDK4) was a direct target of miR-124. Overexpression of miR-124 suppressed CDK4 protein expression and attenuated cell viability, proliferation, and cell cycle progression in MCF-7 and MDA-MB-435S breast cancer cells in vitro. Overexpression of CDK4 partially rescued the inhibitory effect of miR-124 in the breast cancer cells. Moreover, we found that miR-124 overexpression effectively repressed tumor growth in xenograft animal experiments. Our results demonstrate that miR-124 functions as a growth-suppressive miRNA and plays an important role in inhibiting tumorigenesis by targeting CDK4.

Breast cancer patients with positive epidermal growth factor receptor (EGFR) expression have significantly worse post-relapse prognosis than patients with negative EGFR expression. Vinorelbine (NVB) is usually reserved as a salvage therapy after anthracyclines and taxanes in patients with breast cancer. To see whether EGFR expression has a predictive value in NVB-mediated effect on human breast cancer cells, we examined 50 primary breast cancer samples. Of these, 42% were found to be NVB sensitive by ATP-tumour chemosensitivity assay. Sensitivity was correlated with EGFR expression level (p = 0.001). To dynamically examine EGFR's effect on NVB sensitivity in breast cancer cells, we used the real-time cell electronic sensing system with EGFR-positive and EGFR-negative breast cancer cell lines, MCF-7 and MDA-MB-435s, respectively. MCF-7 is NVB sensitive, while MDA-MB-435 is NVB resistant. NVB-induced cytotoxicity to MCF-7 can be partly reversed with inhibitory anti-EGFR antibody. NVB up-regulated EGFR expression in MCF-7 cells, which affects ERK1/2 phosphorylation. This cellular response mechanism may cause greater input to non-lethally damaged cells. These data suggest that EGFR expression can be used as a prognostic factor for breast cancer sensitivity to NVB, which could help identify appropriate treatments for breast cancer.

Ke-Qing Qian1, Heng Ye1, Yi-Wen Xiao1, Yong-Yi Bao2, Chun-Jian Qi11Department of Oncology; 2Department of Pathology, the Changzhou No. 2 People’s Hospital Affiliated to Nanjing Medical University, Changzhou, ChinaAbstract: Tumor lysis syndrome (TLS), a result of rapid cell lysis following tumor therapy, is a well recognized complication during the treatment of rapidly growing tumors. TLS rarely occurs in solid tumors. We present a case report of TLS in a patient with primary retroperitoneal soft tissue sarcoma. TLS occurred in the patient after four days’ combinational chemotherapy with cisplatin, adriamycin, and dacarbazine. These drugs were selected on the basis of an ex vivo ATP-based tumor sensitivity assay. TLS was properly controlled in the patient with concomitant remission of the sarcoma. Therefore, precautions should be taken to avoid this potentially fatal complication during treatment of solid tumors, especially with tumors highly sensitive to drugs.Keywords: tumor lysis syndrome, retroperitoneal soft tissue sarcoma, ATP-based tumor sensitivity assay (ATP-TCA)