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Chemotherapy is the standard treatment for small cell lung cancer (SCLC), but chemotherapy resistance and adverse reactions remain major problems. Although Traditional Chinese Medicine (TCM) is wildly applied for patients with SCLC in China, the evidence of TCM in the treatment for SCLC is limited. To evaluate the efficacy and safety of TCM combined with chemotherapy for patients with SCLC. We conducted a systematic search of PubMed, EMBASE, the Chinese National Knowledge Infrastructure, the VIP Information Database, and the Wanfang Database for randomized-controlled trials (RCTs) that are relevant. The included studies were reviewed by two investigators, with relevant data extracted independently. The effect estimate of interest was the relative risk (RR) or mean difference with 95% confidence intervals (95% CIs). 22 RCTs involving 1887 patients were included in this study. Compared with patients treated with chemotherapy© alone, those with Chinese herbal medicine and chemotherapy (TCM-C) had better therapeutic effects (RR = 1.295, 95% CI 1.205–1.391, P

Cancer-induced bone pain (CIBP) is a refractory form of pain that has a high incidence in advanced tumors. Src protein tyrosine kinase is mainly composed of six domains, with two states of automatic inhibition and activation. The modular domain allows Src to conveniently regulate by and communicate with a variety of proteins, directly or indirectly participate in each step of the CIBP process. Src is beneficial to the growth and proliferation of tumor cells, and it can promote the metastases of primary tumors to bone. In the microenvironment of bone metastasis, it mainly mediates bone resorption, activates related peripheral receptors to participate in the formation of pain signals, and may promote the generation of pathological sensory nerve fibers. In the process of pain signal transmission, it mainly mediates NMDAR and central glial cells to regulate pain signal intensity and central sensitization, but it is not limited to these two aspects. Both basic experimentation and clinical research have shown encouraging potential, providing new ideas and inspiration for the prevention and treatment of CIBP.

BackgroundAstragalus-containing traditional Chinese medicine (TCM) is widely used as adjunctive treatment to platinum-based chemotherapy (PBC) in patients with advanced gastric cancer (AGC) in China. However, evidence regarding its efficacy remains limited. This study aimed to evaluate the efficacy and safety of Astragalus-containing TCM combined with PBC in AGC treatment.MethodsWe searched for literature (up to July 19, 2020) in eight electronic databases. The included studies were reviewed by two researchers. The main outcomes were the objective response rate (ORR), disease control rate (DCR), survival rate, quality of life (QOL), adverse drug reactions (ADRs), and peripheral blood lymphocyte levels. The effect estimate of interest was the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs). Trial sequential analysis (TSA) was used to detect the robustness of the primary outcome and to calculate the required information size (RIS). Certainty of the evidence was assessed using the GRADE profiler.ResultsResults based on available literature showed that, compared with patients treated with PBC alone, those treated with Astragalus-containing TCM had a better ORR (RR: 1.24, 95% CI: 1.15–1.34, P < 0.00001), DCR (RR: 1.10, 95% CI: 1.06–1.14, P < 0.00001), 1-year survival rate (RR: 1.41, 95% CI: 1.09–1.82, P = 0.009), 2-year survival rate (RR: 3.13, 95% CI: 1.80–5.46, P < 0.0001), and QOL (RR: 2.03, 95% CI: 1.70–2.43, P < 0.00001 and MD: 12.39, 95% CI: 5.48–19.30, P = 0.0004); higher proportions of CD3+ T cells and CD3+ CD4+ T cells; higher ratio of CD4+/CD8+ T cells; nature killer cells; and lower incidence of ADRs. Subgroup analysis showed that both oral and injection administration of Astragalus-containing TCM increased tumor response. Whether treatment duration was ≥8 weeks or Astragalus-containing TCM could increase tumor response in AGC patients. Furthermore, Astragalus-containing TCM combined with oxaliplatin-based chemotherapy could increase the ORR and DCR; when with cisplatin, it could only increase the ORR.ConclusionCurrent low to moderate evidence revealed that Astragalus-containing TCM combined with PBC had better efficacy and less side effects in the treatment of AGC; however, more high-quality randomized studies are warranted.Systematic Review RegistrationPROSPERO, identifier CRD42020203486.

The clinical application of opioids may be accompanied by a series of adverse consequences, such as opioid tolerance, opioid-induced hyperalgesia, opioid dependence or addiction. In view of this issue, clinicians are faced with the dilemma of treating various types of pain with or without opioids. In this review, we discuss that Src protein tyrosine kinase plays an important role in these adverse consequences, and Src inhibitors can solve these problems well. Therefore, Src inhibitors have the potential to be used in combination with opioids to achieve synergy. How to combine them together to maximize the analgesic effect while avoiding unnecessary trouble provides a topic for follow-up research.

The wingless-related integration site (Wnt) signaling pathway plays an essential role in embryonic development and nervous system regulation. It is critically involved in multiple types of neuropathic pain (NP), such as HIV-related NP, cancer pain, diabetic neuralgia, multiple sclerosis-related NP, endometriosis pain, and other painful diseases. Wnt signaling is also implicated in the pain induced by sciatic nerve compression injury and selective spinal nerve ligation. Thus, the Wnt signaling pathway may be a potential therapeutic target for NP.

Background: Small cell lung cancer (SCLC) tends to respond well to the standard treatment of chemotherapy, but disease progression, chemotherapy resistance, and adverse reactions still remain major problems that have long limited its effectiveness. Although Traditional Chinese Medicine (TCM) is wildly applied for patients with SCLC in China, using TCM in the treatment for SCLC is still in the absence of sufficient evidence.Purpose: To evaluate the efficacy and safety of TCM combined with the first lines chemotherapy for SCLC.Method: In this perspective, two-center cohort studies, overall survival (OS), progression free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were compared between patients who received chemotherapy with or without TCM, with adverse events (AEs) also on the list of comparison.Results: When the follow-up ended, 168 patients were included in this study. Compared with patients treated with chemotherapy alone (non-TCM group), those with TCM and chemotherapy (TCM group) had better PFS (adjusted HR 0.552, 95% CI 0.389–0.783, P=0.01), median PFS (11.83 months vs. 8.60 months, P = 0.004), rates of ORR (85.88% vs 75.90% after second cycle treatment, 61.2% vs. 43.4% after fourth cycle treatment), rates of DCR(100% vs 98.80% after second cycle treatment, 95.3% vs. 89.2% after fourth cycle treatment). The number of cases with leukopenia, anorexia, constipation, fatigue, nausea in patients receiving TCM treatment is lower than those in patients not receiving TCM (P < 0.05). There was no difference between the two groups in median OS (23.4 months vs. 20.1 months, P = 0.301). Subgroup analysis showed there was no difference between the two groups in median OS with 34.5 months vs. 22.6 months for LS-SCLC (P=0. 586) and 18.5 months vs. 17.37 months for ES-SCLC (P=0.162). Patients in the TCM group have better median PFS than patients in the non-TCM group for both LS-SCLC and ES-SCLC with 14.73 months vs. 9.2 months (P=0.040) and 9.53 months vs. 7.47 months (P=0.007) respectively.Conclusion: This study indicated that TCM combined with chemotherapy for SCLC may prolong PFS, improve therapeutic effect, reduce the side effects of chemotherapy, but may not be effective in the prolongation of OS. More large-scale and higher quality clinical studies are warranted to support our findings.Clinical registration number: ChiCTR2000040151. (http://www.chictr.org.cn)

Background and purpose: Pancreatic cancer is an insidious and highly lethal disease. Recognition and treatment of pancreatic cancer precursor lesions (PCPL) are important measures and can improve patient survival rate. Shuangshen Granules (SSG) have been prescribed for use in clinical practice for more than seven years and are widely used to treat the precursor lesions of various tumours. In this study, we used network pharmacology to explore the pharmacological mechanisms through which SSG suppress PCPL. We aimed to provide a basis for further research and the development of small, molecular, natural chemical drugs.Methods: We first searched databases and screened the bioactive components of SSG and the related targets acting on PCPL to construct a component-target network. Then, network topology analysis was used to analyse the hub target of SSG acting on PCPL. Enrichment analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were also performed to determine the potential pathways. Finally, molecular docking simulations were carried out to investigate the interactions between PCPL-target proteins and the active components of SSG.Results: Seven of the main components of SSG affected PCPL, with 100 key targets including 16 hub targets. In addition, GO and KEGG enrichment analysis revealed that SSG regulated 111 molecular functions, 46 cellular components, 2334 biological processes, and 144 related signalling pathways, of which 26 were closely related to PCPL. Results of molecular docking analysis showed that the PCPL-related targets had strong binding properties with the active components of SSG, quercetin, and ginsenoside rh2, mainly TNF, IL-6, AKT1, TP53, and EGFR.Conclusion: This study has revealed the pharmacological and molecular mechanisms through which SSG acts on PCPL. It also provides powerful evidence to support the exploration of the pharmacological mechanisms of action and clinical applications of traditional Chinese medicine.

Background: Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2017 Edition) in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition (2019 Edition) was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years. Key Messages: Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People’s Republic of China in December 2019.

To investigate the effect of a modified Banxia Xiexin decoction (MBXD) plus chemotherapy on postoperative adverse reaction in patients with stage Ⅲ colon cancer in patients whose symptoms were identified as cold-heat complicated pattern in terms of the theory of Traditional Chinese Medicine (TCM).A prospective non-randomized control study of patients with stage Ⅲ colon cancer in Beijing Shijitan Hospital and Guang'anmen Hospital between January 2012 and December 2013. A total of 80 patients were divided into experimental group (MBXD + chemotherapy) and control group (chemotherapy). The adverse reactions, life quality and disease-free survival (DFS) were compared between the two groups.The cold-heat complex pattern was released in 94.3% of patients in experimental group whereas 62.2% in control group (P0.05). Life quality was improved in 24 vs 14 cases, stabilized in 9 vs 14 cases whereas decreased in 2 vs 15 cases in experimental group and control group, respectively (P0.05). The average DFS was 22.371 months in experimental group, while 13.932 months in control group (P0.05).MBXD combined with chemotherapy may significantly relieve clinical symptoms, reduce chemotherapy associated adverse effects, improve life quality, and prolong DFS of patients with stage Ⅲ colon cancer (cold-heat complicated pattern).

ObjectiveP-cadherin can act both as a tumour suppressor and an oncogene. The clinical prognostic value of P-cadherin overexpression in breast cancer (BC) remains unclear. We conducted a study-level meta-analysis to determine whether P-cadherin expression can help predict prognosis in BC.MethodsA systematic literature search was performed to review eligible studies and clarify the relationship between P-cadherin overexpression and overall survival (OS), disease-free survival (DFS), pathological features, molecular subtypes and molecular phenotypes in BC.ResultsThirty-one studies including 12 332 patients were included. P-cadherin overexpression was correlated with significantly worse OS (HR=1.77, p<0.00001) than P-cadherin-negative. P-cadherin overexpression could lead to high histological grade (OR=3.33, pConclusionsP-cadherin was found to be associated with invasiveness and metastasis. P-cadherin expression can probably be a useful biomarker for predicting poor survival and may act as an independent prognostic predictor.

Objective: To evaluate Xi huang pill combined with chemotherapy for tumor treatment in a meta-analysis. Materials and Methods: We searched PubMed, Excerpta Medica Database, the Cochrane Library, the China National Knowledge Infrastructure, and the Weipu database and Wanfang Databases for eligible studies. We manually searched for printed journals and relevant textbooks. Statistical analyses were performed with Review Manager 5.3 (Cochrane Community, London, United Kingdom) and STATA 12.0 software packages. Results: Fifteen studies were included. Xi huang pill combined with chemotherapy could enhance response (risk ratio [RR] =1.35, 95% confidence interval [95% CI]: 1.14–1.60, P < 0.0004), improve disease control (RR = 1.13, 95% CI: 1.05–1.21, P = 0.0006), prolong overall survival (hazard ratio = 0.80, 95% CI: 0.08–0.98, P = 0.03), improve patient quality of life (RR = 1.35, 95% CI: 1.10–1.67, P < 0.004), reduce 2–4° leukocyte (white blood cell) and platelet count due to chemotherapy (pooled RR = 0.42, 95% CI = 0.30–0.60, pooled RR = 0.42, 95% CI = 0.25–0.72, respectively). Conclusion: Xi huang pill combined with chemotherapy can enhance the short-term efficacy and overall survival, alleviate treatment-induced side effects, and serve as a suitable regimen for the treatment of patients with tumors. However, the findings of the current study require validation in further high-quality trials.

Ethnopharmacological relevance Traditional Chinese medicine Shuangshen granules (SSG) have been used to treat lung cancer patients with Qi deficiency and blood stasis for decades. According to clinical experience, SSG indeed improve the quality of life and prolong the survival time of patients with lung cancer after surgery. Each of the components herbs was proved to be effective in anti-cancer therapy. Both the American ginseng and notoginseng belong to genus Panax of the family Araliaceae. Preclinical and clinical studies demonstrated that ginsenosides of them have anti- or preventive activities to various tumors, including cancers of gastric, breast, liver, lung, ovarian, colon, melanoma and leukemia. PDS, such as ginsenoside Rb1, and PTS, such as ginsenoside Rg1 are the main anticancer compositions. Cordyceps sinensis had also been found effective in inhibiting tumour growth and metastasis, especially on tumour associated immune cells, such as macrophages. However, limited information is available regarding potential mechanisms of SSG. Myeloid-derived suppressor cell (MDSC)-mediated immunosuppression, which is closely associated with poor clinical outcomes in cancer patients, may be the target of SSG, which regulate immune function. Aim of the study The present study aimed to explore whether SSG attenuate the differentiation of bone marrow cells (BMCs) into MDSCs by blocking the mTOR signalling, leading to the suppression of lung metastasis. Materials and methods First, we observed the differentiation of BMCs into MDSCs in vitro and in vivo. BMCs were cultured alone or co-cultured with Lewis lung carcinoma (LLC) cell supernatant in vitro. The effects of different concentrations of SSG, or LLC cell supernatant as a control, on BMC differentiation were detected by flow cytometry and western blotting. Male C57BL/6J mice were subcutaneously implanted with LLC cells, and SSG were administered by gavage twice daily before and after implantation for 7 or 14 days, respectively. The tumour weight, proportion of MDSCs, presence of CD11b+Ly6C+Ly6G– and CD11b+Ly6C+Ly6G+ cells in the bone marrow, blood, and lungs, as well as the expression levels of differentiation-related proteins in the bone marrow and lungs were evaluated. Results SSG attenuated the differentiation of BMCs into MDSCs, and reduced the fraction of CD11b+Ly6C+Ly6G+ cells by inhibiting the mTOR/S6K1/Myc signalling pathway. In vivo, SSG attenuated differentiation-associated protein markers and reduced the fractions of MDSCs and CD11b+Ly6C+Ly6G+ cells in the bone marrow, blood, and lungs. In addition, SSG administration reduced the tumour weight and inhibited lung metastasis. Conclusions SSG may reduce lung metastasis by attenuating BMC differentiation into CD11b+Ly6C+Ly6G+ cells by inhibiting mTOR signalling in vitro and in vivo.

Epithelial-mesenchymal transition (EMT), plays a vital role in hepatocellular carcinoma (HCC) development and metastasis. Norcantharidin (NCTD; 7-oxabicyclo (2.2.1) heptane-2,3-dicarboxylic anhydride) plays anticancer roles in the regulation of tumor cell proliferation, apoptosis and migration. However, the molecular mechanism of HCC EMT and the effects of NCTD in the HCC EMT process have been either poorly elucidated or not studied. In this study, HCC EMT was induced by the treatment of IL-6 and various concentrations of NCTD (0, 30, 60 and 120 µM) were treated with HCC cell lines, HCCLM3 and SMMC-7721. We investigated the effect of NCTD on the invasion of HCC cells by using Transwell assay. Immunofluorescence staining, western blot analysis and quantitative RT-PCR were performed to evaluate the protein and mRNA expression levels of HCC cells. Here, using cell line models, our data demonstrated that interleukin 6 (IL-6) induced EMT through the JAK/STAT3/TWIST pathway in HCC. Moreover, our studies revealed that NCTD markedly inhibited IL-6-induced EMT and cell invasiveness. Signaling studies revealed that NCTD sufficiently suppressed JAK/STAT3/TWIST signaling to reverse the IL-6-promoting effects. Collectively, these data provide evidence for the use of NCTD as a potential anticancer drug in HCC metastatic patients.

Ethnopharmacological relevance Ulcerative colitis were prone to develop into ulcerrelated colorectal cancer with high risk of mortality. Shaoyao Decoction (SYD), a compound prescription of Chinese traditional medicine, was reported to have anti-colorectal cancer effect. Thus this study mainly investigated the protective and preventive effect of SYD against oxidative damages and inflamatory response through in vivo and in vitro experiments. Aim of the study Shaoyao decoction (SYD), a compound prescription of traditional Chinese medicine, is effective in treating ulcerative colitis. The increased levels of reactive oxygen species (ROS) in inflammatory cells potentially drive the development of carcinomas. Nuclear factor-erythroid 2-related factor 2 (Nrf2) has became a novel target for the prevention of colorectal cancer (CRC). In this study, we assessed the antioxidation effect of SYD against colitis associated colorectal cancer through in vivo and in vitro experiments. Materials and methods In vivo AOM/DSS-induced murine model of colon cancer and in vitro H2O2-induced oxidative stress in HT-29 cells model were conducted. To determine the antioxidant activity of SYD, protein expression of Nrf2 and its downstream genes were detected by western blot, RT-PCR and Enzyme-linked immunosorbent assay. Results Both in vivo and in vitro experiments demonstrated that SYD exerts antioxidant effect through activation of Nrf2 pathway and upregulation expression of Nrf2 downstream genes. SYD is shown to have preventive effect against colitis-associated colorectal cancer. Conclusions These observations suggest that SYD is effective in the enhancement of antioxidant ability via activation of Nrf2 pathway and the up-regulation of Nrf2-downstream phase II enzymes expression. The anti-inflammation and antioxidant action of SYD together contributes to the prevention and treatment of ulcerrelated colorectal cancer.

Background: Many studies were performed to explore the correlation between taxane-based chemotherapy and the risk of breast cancer-related lymphedema (BCRL), however, with inconsistent results. Hence, the purpose of this study is to evaluate whether taxane-based chemotherapy is a risk factor for BCRL. Methods: A comprehensive systematic search of clinical trials published in the PubMed, Embase and the Cochrane Library databases will be conducted to identify eligible studies up to the date of December 31, 2018. We will employ risk ratios with 95% confidence intervals (95% CIs) to estimate the correlations between taxane-based chemotherapy and BCRL. Meta-analysis will be performed using Stata SE version 12.0 software. Results: The results of this systematic review and meta-analysis will provide a high-quality synthesis of existing evidence of the correlations between taxane-based chemotherapy and the risk of BCRL. Conclusion: The protocol will provide updated evidence for the use of taxane-based chemotherapy in postoperative breast cancer patients. Ethics and dissemination: It is not necessary for ethical approval because it is based on published studies. The protocol will be disseminated in a peer-reviewed journal or presented at a topic-related conference. Trial registration: This systematic review protocol has been registered with a number of CRD42019123989.

Background: P-cadherin is a calcium-dependent cell–cell adhesion glycoprotein. It has been implicated in invasiveness and metastasis. However, the clinical prognostic value of overexpression of P-cadherin in patients with breast cancer (BC) remains unsettled. Methods: A systematic literature search will be performed in all available databases to quantitatively review eligible studies and identify all relevant data, which could be used to detect the relationship between overexpression of P-cadherin and overall survival (OS), disease-free survival (DFS), and clinicopathological parameters. Hazard ratio and 95% confidence intervals (CIs) or P value will be employed as effect measures to estimate the correlation between P-cadherin and the oncologic outcomes including overall survival (OS), disease-free survival (DFS). Odds ratios (ORs) and the 95% CIs will be evaluated for the pooled analysis of the correlation between P-cadherin expression and clinicopathological features. We will use the Review Manager (Revman) 5.3.5 software (Cochrane Community, London, United Kingdom) and STATA 14 software (version 14.0; Stata Corp, College Station, TX) to perform the meta-analysis to calculate the data. Results: The review will provide a high-quality synthesis of current evidence of the prognostic role of P-cadherin in BCs. The results will be published in a peer-reviewed journal. Conclusion: We hope that the results of this study will provide significant evidence to assess whether the expression of P-cadherin is associated with poor prognosis in patients with BC. PROSPERO registration number: This meta-analysis protocol has been registered in the PROSPERO network with registration number: CRD42019119880.

Increasing evidence suggests that the failure of lung cancer treatment may occur as a result of tumor invasion and metastasis. Signal transducer and activator of transcription 3 (STAT3), an epithelial-mesenchymal transition-inducing transcription factor, is a key signaling molecule involved in the proliferation, apoptosis, invasion and metastasis of tumor cells. Sinomenine is an alkaloid compound with an antineoplastic potential against a variety of cancer cells. The aim of the present study was to assess the antitumor mechanisms of sinomenine in the A549 human lung cancer cell line. The results demonstrated that sinomenine manifested dose-dependent cytotoxicity and induced apoptosis in A549 cells. The protein expression of Janus kinase 2, STAT3, phosphorylated-STAT3, Snail, N-cadherin and vimentin decreased in sinomenine-treated cells, while E-cadherin protein expression increased. The regulation of STAT3, N-cadherin and E-cadherin by sinomenine was further confirmed by reverse transcription-quantitative polymerase chain reaction and immunofluorescent staining. It was demonstrated that sinomenine exerts inhibitory effects on A549 human lung cancer cell invasion, possibly through the inhibition of STAT3 signaling. These results provide a novel insight into the role of sinomenine in the treatment of non-small cell lung cancer.

Introduction Estrogen receptor β (ERβ) always lacks expression in estrogen-dependent tumors, which may result from gene inactivation by methylation. In this study, we aimed to determine whether aberrant methylation of the ERβ promoter is associated with decreased ERβ gene expression in breast cancer. Material and methods ERβ methylation status was determined for 132 pairs of breast cancer and adjacent normal tissues via the MethyLight method. Additionally, mRNA relative expression was quantified by real-time polymerase chain reaction (RT-PCR) to determine whether aberrant methylation had a negative correlation with expression. The correlation of ERβ promoter methylation and clinical parameters is also discussed. Results Methylation was observed in 96 (72.7%) breast cancer samples, and the median percentage of fully methylated reference (PMR) among methylated tissues was 0.83. Meanwhile, 94 (71.2%) adjacent normal tissues were methylated and the median PMR was 0.48. Compared to adjacent normal tissues, the methylation level of breast cancer was significantly higher (p < 0.001) and mRNA expression was much lower (p < 0.001). There was a significant correlation between ERβ methylation and mRNA expression in adjacent normal breast tissues (p = 0.004). In addition, the methylation rate of cancer tissues whose maximum diameter < 3 cm was significantly higher than those > 3 cm (p = 0.025). Conclusions ERβ promoter methylation level varies between cancerous and adjacent normal breast tissues. There was significant downregulation of ERβ methylation expression in pre-cancerous stages of breast cancer. Therefore, demethylation drugs may offer a potential strategy for preventing the development of pre-cancerous cells.

Background: Small cell lung cancer (SCLC) is an aggressive disease. Chemotherapy is the standard treatment for SCLC, but the resistance and the adverse effects of Chemotherapy still remains a major problem. Although Chinese herbal medicine (traditional Chinese medicine) is wildly applied for patients with SCLC in China, the evidence of traditional Chinese medicine in the treatment for SCLC is limited. Method: We conducted a systematic search of PubMed, EMBASE, the Chinese National Knowledge Infrastructure, the VIP Information Database, and the Wanfang Database for relevant studies. Only randomized controlled trials were included. Two investigators independently reviewed the included studies and extracted relevant data. The effect estimate of interest was the relative risk or mean difference with 95% confidence intervals. Ethics and dissemination: Ethical approval is not required, as this study is based on the review of published research. This review will be published in a peer-reviewed journal and disseminated both electronically and in print. INPLASY registration number: INPLASY2020110055

Background Increasing studies were performed to explore the prognostic value of E-cadherin in prostatic carcinoma, however, with inconsistent results. Hence, this systematic review is aimed to evaluate the prognostic role of E-cadherin in patients with prostatic carcinoma (PCa). Methods A comprehensive literature search in all available databases will be conducted to identify eligible studies. We will employ hazard ratios (HRs) and 95% confidence intervals (95% CIs) to estimate the correlations between E-cadherin expression and overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), progression-free survival (PFS) and clinicopathological features. Meta-analysis will be performed using Review Manager (Revman) 5.3.5 software (Cochrane Community, London, United Kingdom) and STATA 14 software (version 14.0; Stata Corp, College Station, TX). Results This study will provide a high-quality synthesis of current evidence of the correlations between snail expression and OS, DFS/RFS, PFS and clinicopathological features. Conclusion The study will provide updated evidence to assess whether the expression of E-cadherin is in association with poor prognosis in patients with PCa. Ethics and dissemination It is not necessary for ethical approval because individuals cannot be identified. The protocol will be disseminated in a peer-reviewed journal or presented at a relevant conference. Prospero registration number This systematic review protocol has been registered in the PROSPERO network (No. CRD42019128353).

Gastric cancer has a high morbidity and mortality. Chemotherapy regimens are routine advanced stage gastric cancer (AGC) treatment protocols, but most of these drugs have side-effects such as myelosuppression and gastrointestinal disorders. Cinobufacini, an extractive from TCM, could suppress cell proliferation and inhibit gastric cancer. In this study, we comprehensively reviewed the literature on the efficacy comparison between Cinobufacini injection combined with chemotherapy and chemotherapy solely used in AGC treatment. We extracted data for from six electronic databases to evaluate the efficacy of Cinobufacini injection on AGC patients. Twelve studies with a total of 853 patients were finally included in our study. The results indicated that Cinobufacini injection could increase response rate and disease control rate of chemotherapy on AGC, improve the life quality of AGC patients, increase leukocytes, improve anemia, improve hand-foot syndrome induced by chemotherapy, and relieve cancer pain. This study has its own limitations that prevented us from drawing a definite conclusion and more well-designed clinical trials of TCM are needed.

Herbal analgesic Xiaozheng Zhitong Paste (XZP) and related modifications are often used in traditional Chinese medicine to manage cancer pain. However, its underlying mechanism remains unknown. To investigate the effects and mechanism of XZP on bone cancer pain in a rat model of breast cancer-induced bone pain, a bone cancer pain model was established by inoculating Walker 256 cells into Wistar rats. Bone cancer-bearing rats were topically treated with different doses of XZP or injected with 5 mg/kg of osteoprotegerin (OPG) as positive control. Bone destruction, bone mineral content (BMC) and bone mineral density (BMD) were analyzed by radiology. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were examined to determine pain levels. Trypsin, TNF-α and IL-1β serum levels were determined using enzyme-linked immunosorbent assay (ELISA). Central sensitization markers such as c-Fos, GFAP, IBA1 and CGRP, as well as proteinase-activated receptor 2 (PAR2) signaling pathway mediators such as PAR2, PKC-γ, PKA and TRPV1, were determined by quantitative RT-PCR and western blotting assay. XZP treatment significantly mitigated bone cancer-related nociceptive behavior, bone damage, BMC and BMD; and decreased radiological scores in rats. XZP treatment significantly inhibited IBA1, GFAP, c-Fos and CGRP expressions in the spinal cord; and significantly mitigated trypsin, TNF-α and IL-1β serum levels. Furthermore, PAR2, PKC-γ, PKA and TRPV1 relative mRNA levels and protein expression in bone lesions were significantly reduced in rats treated with XZP. XZP significantly alleviates breast cancer-induced bone pain by inhibiting the PAR2 signaling pathway.

// Weidong Li 1,3,* , Shakir M. Saud 2,3,* , Matthew R. Young 3 , Guohong Chen 4 , Baojin Hua 1 1 Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China 2 Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA 3 Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland, USA 4 Department of Urinary Surgery, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China * These authors have contributed equally to this work Correspondence to: Baojin Hua, email: // Guohong Chen, email: // Keywords : AMP activated kinase, cancer, prevention, treatment Received : February 02, 2015 Accepted : February 26, 2015 Published : March 20, 2015 Abstract AMP-activated protein kinase (AMPK) is an important mediator in maintaining cellular energy homeostasis. AMPK is activated in response to a shortage of energy. Once activated, AMPK can promote ATP production and regulate metabolic energy. AMPK is a known target for treating metabolic syndrome and type-2 diabetes; however, recently AMPK is emerging as a possible metabolic tumor suppressor and target for cancer prevention and treatment. Recent epidemiological studies indicate that treatment with metformin, an AMPK activator reduces the incidence of cancer. In this article we review the role of AMPK in regulating inflammation, metabolism, and other regulatory processes with an emphasis on cancer, as well as, discuss the potential for targeting AMPK to treat various types of cancer. Activation of AMPK has been found to oppose tumor progression in several cancer types and offers a promising cancer therapy. This review evaluates the evidence linking AMPK with tumor suppressor function and analyzes the molecular mechanisms involved. AMPK activity opposes tumor development and progression in part by regulating inflammation and metabolism.

Pain is one of the most common and distressing symptoms suffered by patients with progression of cancer. Using a rat model of bone cancer, recent findings suggest that proteinase-activated receptor 2 (PAR2) signaling pathways contribute to neuropathic pain and blocking PAR2 amplifies antinociceptive effects of systemic morphine. The purpose of our study was to examine the underlying mechanisms responsible for the role of PAR2 in regulating bone cancer-evoked pain and the tolerance of systemic morphine. Breast sarcocarcinoma Walker 256 cells were implanted into the tibia bone cavity of rats and this evoked significant mechanical and thermal hyperalgesia. Our results showed that the protein expression of PAR2 and its downstream pathways (protein kinases namely, PKCe and PKA) and transient receptor potential vanilloid 1 (TRPV1) were amplified in the dorsal horn of the spinal cord of bone cancer rats compared to control rats. Blocking spinal PAR2 by using FSLLRY-NH2 significantly attenuated the activities of PKCe/PKA signaling pathways and TRPV1 expression as well as mechanical and thermal hyperalgesia. Also, inhibition of PKCe/PKA and TRPV1 significantly diminished the hyperalgesia observed in bone cancer rats. Additionally, blocking PAR2 enhanced the attenuations of PKCe/PKA and cyclic adenosine monophosphate induced by morphine and further extended analgesia of morphine via μ-opioid receptor (MOR). Our data revealed specific signaling pathways, leading to bone cancer pain, including the activation of PAR2, downstream PKCe/PKA, TRPV1 and resultant sensitization of MOR. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of bone cancer pain often observed in clinics.

Background and Objectives Bone cancer pain affects the quality of life of cancer patients. This study was aimed at investigating the analgesic effects of combined therapies with an antagonist of proteinase-activated receptor (PAR) 2 and morphine on pain-related behaviors in a rat model of bone cancer pain. Methods Female Wistar rats were inoculated intramedullarily with Walker 256 cells into their tibias. The analgesic effects of intraperitoneal treatment with morphine and/or intrathecal with the PAR2 antagonist, FSLLRY-NH2, on bone cancer pain–related behaviors in rats were examined. Results Treatment with morphine at 3 or 10 mg/kg significantly improved limb-use and weight-bearing scores and reduced the number of spontaneous flinches in rats. Treatment with FSLLRY-NH2 at 10 mmol/L also significantly improved limb use and weight bearing scores, and reduced the number of spontaneous flinches in rats. Combination a sub-analgesic dose of FSLLRY-NH2 (0.1 mmol/L) and morphine further elevated limb-use and weight-bearing scores and reduced the number of flinches compared with the effects of morphine alone in rats. Conclusions Our data indicate that the combination of morphine and FSLLRY-NH2 has potent analgesic effects on bone cancer pain and our findings may aid in design of new strategies for the treatment of bone cancer pain.

Tongue diagnosis is one of the most important diagnostic tools in traditional Chinese medicine and has been verified for thousands of years. However, its subjectivity and repeatability has been disputed continuously. The tongue coating as the primary coverage of tongue diagnosis provides more objectivity and reproducibility due to its relatively clear molecular basis; it also has a close relationship with many system diseases and may be used as a potentially valuable disease diagnostic tool. This article describes the material basis of the tongue coating, including its biology (epithelial cells, blood cells, vascular endothelial cells, and bacteria) and its metabolites; moreover, we summarize the diseases that are most correlated with the tongue coating. This will be valuable not only for fundamental research of tongue diagnosis but also for the diagnosis and differential diagnosis of disease. We suppose that the tongue coating could serve as a valuable auxiliary diagnosis tool in many diseases, and more research should focus on how to colligate the various information about the tongue and provide useful information for disease diagnosis.