Causes of Death After Colorectal Cancer Diagnosis: A Population-Based Study.

Background: Non-cancer causes of death in patients with colorectal cancer (CRC) have not received much attention until now. The purpose of the current study is to investigate the non-cancer causes of death in patients with CRC at different periods of latency. Methods: Eligible patients with CRC were included from the Surveillance, Epidemiology, and End Results (SEER) database, and standardized mortality ratios (SMRs) were calculated using the SEER*Stat software 8.3.8. Results: A total of 475,771 patients with CRC were included, of whom 230,841 patients died during the follow-up period. Within 5 years, CRC was the leading cause of death. Over time, non-cancer causes of death account for an increasing proportion. When followed up for more than 10 years, non-cancer deaths accounted for 71.9% of all deaths worldwide. Cardiovascular diseases were the most common causes of non-cancer deaths, accounting for 15.4% of the total mortality. Patients had a significantly higher risk of death from septicemia within the first year after diagnosis compared with the general population (SMR, 3.39; 95% CI, 3.11-3.69). Within 5-10 years after CRC diagnosis, patients had a significantly higher risk of death from diabetes mellitus (SMR, 1.27; 95% CI, 1.19-1.36). During the course of more than 10 years, patients with CRC had a significantly higher risk of death from atherosclerosis (SMR 1.47; 95% CI, 1.11-1.9). Conclusions: Although CRC has always been the leading cause of death in patients with CRC, non-cancer causes of death should not be ignored. For patients with cancer, we should not only focus on anti-tumor therapies but also pay attention to the occurrence of other risks to prevent and manage them in advance.

[Effects of Feiliuping Ointment Containing Serum on EMT Related mRNA and Protein Expressions under Co-culture Conditions of A549 Cells and Macrophage].

Objective To observe the effects of Feiliuping Ointment (FLP) containing serum on A549 cell epithelial-mesenchymal transition (EMT) related mRNA and protein expressions under macro- phage co-culture conditions. Methods FLP containing serum was prepared. A co-culture system of A549 cells and macrophages was established. A549 cells were divided into 3 groups, i.e., the blank serum group (A549 +NRS) , the co-culture cells + blank serum group (co-culture + NRS) , the co-culture cells with FLP containing serum group (co-culture + FLP). The effects of FLP on A549 cell EMT related gene (SNAIL1, SNAIL2, ZEB1, CDH1, CDH2, VIM, TJP1, CLDN1, CTNNB1, FLRT1) and proteins (E-cadherin, N-cadher- in, ZO-1, Vimentin) expressions were observed under co-culture conditions by fluorescent quantitative PCR. Results A549 cells developed into mesenchymal-like cells in co-culture conditions, which could been blocked by FLP containing serum in part. Compared with the A549 +NRS group, mRNA expressions of SNAIL1, ZEB1, CTNNB1, FLRT1, CDH2, and VIM were up-regulated (P <0. 05), but the expression of TJP1 was down-regulated in the co-culture + NRS group (all P <0. 05). Compared with the co-culture + NRS group, mRNA expressions of SNAIL2, TJP1, CLDN1, CDH1, and VIM were up-regulated, but mRNA ex- pressions of CTNNB1, FLRT1, and CDH2 were down-regulated in the co-culture + FLP group (all P <0. 05). Immunofluorescent results showed that E-cadherin expressed on cell membrane and inside cytoplasm, and most expressed on cell membrane. N-cadherin expressed on cell membrane and inside cytoplasm, and most expressed inside cytoplasm. Vimentin expressed within the cytoplasm. ZO-1 expressed mainly in cell junction. Parts of the cell membrane were positively stained. Compared with the A549 +NRS group, mRNA expression of E-cadherin was down-regulated in A549 cells, and mRNA expressions of N-cadherin and Vi- mentin were up-regulated in the co-culture +NRP group. However, E-cadherin was up-regulated and protein expressions of N-cadherin and Vimentin were down-regulated after intervention of FLP containing serum. (all P <0. 05). Conclusion FLP could inhibit the EMT of A549 cells under co-culture conditions.

Fei-Liu-Ping ointment inhibits lung cancer growth and invasion by suppressing tumor inflammatory microenvironment.

BACKGROUND: Lung cancer is one of the leading causes of cancer-related mortality worldwide. Conventional chemotherapy and radiotherapy are the primary therapeutic methods for lung cancer with the use of combination therapies gaining popularity. The frequency and duration of treatment, as well as, managing lung cancer by targeting multiple aspects of cancer biology is often limited by toxicity to the patient. There are many naturally occurring anticancer agents that have a high degree of efficacy and low toxicity, offering a viable and safe approach for the treatment of lung cancer. The herbs traditionally used in Chinese medicine for anticancer treatment offer great potential to enhance the efficacy of conventional therapy. In this study, we evaluated the synergistic effects of Fei-Liu-Ping (FLP) ointment in treating lung cancer; a known anticancer Chinese herbal based formula. METHODS: In this study, A549 human lung carcinoma cell line and Lewis lung carcinoma xenograft mouse model were used. In addition, we utilized an in vitro co-culture system to simulate the tumor microenvironment in order to evaluate the molecular mechanisms of FLP treatment. RESULTS: FLP treatment significantly inhibited tumor growth in the Lewis lung xenograft by 40 percent, compared to that of cyclophosphamide (CTX) of 62.02 percent. Moreover, combining FLP and CTX inhibited tumor growth by 83.23 percent. Upon evaluation, we found that FLP treatment reduced the concentration of serum pro-inflammatory cytokines IL-6, TNF-α, and IL-1ß. In addition, we also found an improvement in E-cadherin expression and inhibition of N-cadherin and MMP9. We found similar findings in vitro when we co-cultured A549 cells with macrophages. FLP treatment inhibited A549 cell growth, invasion and metastasis, in part, through the regulation of NF-κB and altering the expression of E-cadherin, N-cadherin, MMP2 and MMP9. CONCLUSIONS: FLP exerts anti-inflammatory properties in the tumor microenvironment, which may contribute to its anticancer effects. FLP treatment may be a promising therapy for inflammation associated lung cancer treatment alone, or in combination with conventional therapies and may prevent lung cancer metastasis.

A systematic review and meta-analysis on the use of traditional Chinese medicine compound kushen injection for bone cancer pain.

PURPOSE: Bone cancer pain presents a clinical challenge with limitations of current treatments. Compound kushen injection (CKI) is a well-known traditional Chinese medicine (TCM) formulation in treatment of patients with bone cancer pain. The objective of this study is to assess the efficacy and safety of CKI for bone cancer pain. METHODS: A systematic literature search was conducted in nine databases until December 2012 to identify randomized controlled trials (RCTs) of CKI versus current western therapies for bone cancer pain. The primary outcome was total pain relief rate. The secondary outcomes were the quality of life and adverse events at the end of treatment course. The methodological quality of RCTs was assessed independently using six-item criteria according to the Cochrane Collaboration, and the level of evidence was assessed by the GRADE approach. All data were analyzed using Review Manager 5.1.0. RESULTS: Seven RCTs with 521 patients from 2010 to 2012 were identified. Compared with radiotherapy or bisphosphonates, seven RCTs showed significant effects of CKI for improving pain relief in patients with bone cancer pain (n = 521, risk ratio (RR) = 1.25, 95 % CI (95 % confidence intervals (CI)), 1.13 to 1.38, p < 0.0001)), three RCTs for improving Karnofsky scoring (KPS) increase rate (n = 305, RR = 1.62, 95 % CI, 1.32 to 1.99, p < 0.00001), 1 RCT for increasing KPS scores (n = 78, mean difference (MD) = 10.43, 95 % CI 4.76 to 16.10, p = 0.0003). 4 RCTs reported adverse effects in both the treatment and control groups. The patients treated with CKI achieved statistically significant reductions of incidences of leukopenia (n = 276, RR = 0.32, 95 % CI, 0.21 to 0.47, p < 0.00001) and nausea (n = 78, RR = 0.15, 95 % CI, 0.06 to 0.34, p < 0.00001). No severe adverse events were found and no treatment was stopped because of adverse events of CKI in the treatment groups. However, the studies were deemed to have a high risk of bias. CONCLUSION: This systematic review showed positive but weak evidence of CKI for bone cancer pain because of the poor methodological quality and the small quantity of the included trials. Future rigorously designed RCTs are required.

Involvement of protease-activated receptor 2 in nociceptive behavior in a rat model of bone cancer.

Treatment for bone cancer pain remains a clinical challenge due to a poor understanding of the underlying mechanisms. Protease-activated receptor 2 (PAR2), a receptor for inflammatory proteases, has been implicated in nociceptive signaling under both normal and pathologic pain states. However, little is known of the role of PAR2 in cancer-induced bone pain. Here we investigated the potential role of PAR2 in a rat model of bone cancer pain. The model of bone cancer pain was induced by inoculating Walker 256 into the tibia bone cavity of rats and verified by X-ray imaging, pathology, and behavior assessments. The rats with bone cancer exhibited marked mechanical allodynia, thermal hyperalgesia, and signs of spontaneous nocifensive behavior. Subcutaneous administration of the PAR2 antagonist FSLLRY-NH2 almost completely abolished mechanical allodynia and thermal hyperalgesia but had no effects on spontaneous pain behavior in the rats with bone cancer. Immunohistochemical study revealed that the expression of PAR2 was significantly increased in large- and medium-sized dorsal root ganglia (DRG) neurons but not in small-sized neurons after Walker 256 inoculation. These results suggest that the increased expression of PAR2 in the DRG may contribute to the development of mechanical allodynia and thermal hyperalgesia associated with bone cancer rats. PAR2 might become a novel target for the treatment of pain in patients with bone cancer.