Decoding the possible mechanism of action of Paeoniflorigenone in combating Aflatoxin B1-induced liver cancer: an investigation using network pharmacology and bioinformatics analysis.

Moutan cortex has demonstrated antitumor properties attributed to its bioactive compound Paeoniflorigenone (PA). Nevertheless, there is limited research on the efficacy of PA in the prevention and treatment of hepatocellular carcinoma (HCC). We aimed to investigate the potential pharmacological mechanisms of PA in the treatment of Aflatoxin B1 (AFB1)-induced hepatocarcinogenesis using network pharmacology and bioinformatics analysis approaches. Through various databases and bioinformatics analysis approaches, 34 shared targets were identified as potential candidate genes for PA in fighting liver cancer caused by AFB1. Pathway analysis revealed involvement in cell cycle, HIF-1, and Rap1 pathways. A risk assessment model was developed using LASSO regression, showing an association between the identified genes and the tumor immune microenvironment. The genes within the risk model were found to be linked to the immune response in liver cancer. Molecular docking studies indicated that PA interacts with its targets through hydrogen bonding and hydrophobic interactions. This study provides insights into the possible mechanisms of PA in liver cancer treatment and offers a predictive model for assessing the risk level of individuals with liver cancer. These findings have significant implications for the therapeutic strategies in managing liver cancer patients.

Solamargine inhibits the growth of hepatocellular carcinoma and enhances the anticancer effect of sorafenib by regulating HOTTIP-TUG1/miR-4726-5p/MUC1 pathway.

Hepatocellular carcinoma (HCC) is one of the most common primary malignancies. Drug resistance has significantly prevented the clinical application of sorafenib (SF), a first-line targeted medicine for the treatment of HCC. Solamargine (SM), a natural alkaloid, has shown potential antitumor activity, but studies about antitumor effect of SM are obviously insufficient in HCC. In the present study, we found that SM significantly inhibited the growth of HCC and enhanced the anticancer effect of SF. In brief, SM significantly inhibited the growth of HepG2 and Huh-7 cells. The combination of SM and SF showed a synergistic antitumor effect. Mechanistically, SM downregulated the expression of long noncoding RNA HOTTIP and TUG1, followed by increasing the expression of miR-4726-5p. Moreover, miR-4726-5p directly bound to the 3'-UTR region of MUC1 and decreased the expression of MUC1 protein. Overexpression of MUC1 partially reversed the inhibitory effect of SM on HepG2 and Huh-7 cells viability, which suggested that MUC1 may be the key target in SM-induced growth inhibition of HCC. More importantly, the combination of SM and SF synergistically restrained the expression of MUC1 protein. Taken together, our study revealed that SM inhibited the growth of HCC and enhanced the anticancer effect of SF through HOTTIP-TUG1/miR-4726-5p/MUC1 signaling pathway. These findings will provide potential therapeutic targets and strategies for the treatment of HCC.

Fuzheng Kang-Ai decoction enhances the effect of Gefitinib-induced cell apoptosis in lung cancer through mitochondrial pathway.

BACKGROUND: Our previous clinical study has shown that Chinese herbal medicine (CHM) Fuzheng Kang-Ai (FZKA) decoction is effective in treating advanced lung cancer patients through prolonging the drug resistance to Gefitinib (GFTN). Our basic study found that FZKA decoction could enhance the inhibition effect of GFTN in lung cancer by inactivating PI3K/Akt pathway. Moreover, our recent work showed that FZKA induced lung cancer cell apoptosis via STAT3/Bcl-2/Caspase-3 pathway. Thus in this study, we aim to elucidate how FZKA enhances the effect of GFTN in lung cancer from the perspective of cell apoptosis. METHODS: Cell proliferation and colony formation assay were performed to detect the cell growth inhibition. Flow cytometry and TUNEL assay were carried out to test the cell apoptosis. Mitochondrial membrane potential (MMP) assay was done to measure the alteration of MMP. Caspase-3/-9 activity assay was used to test the activity of caspase-3/-9. Western blot and qRT-PCR were done to detect the expression of STAT3 and Bcl-2 family as well as Caspase-3/-9 and Cyt-C at protein and mRNA levels, respectively. Transient transfection was performed to silence STAT3 using siSTAT3. Animal model was done to validate the molecular mechanisms in vivo and immunohistochemistry was done to detect the expression of Bax and Caspase-3. RESULTS: Firstly, our results showed that FZKA enhanced the inhibition effect of GFTN in lung cancer both in vitro and in vivo. Secondly, cell apoptosis was enhanced when treating lung cancer cells with both FZKA and GFTN, a process involving the mitochondria and the Bcl-2 family. And Bcl-2 family was involved in this process. Interestingly, STAT3 plays a critical role on mediating the above process. Last but not the least, the enhanced effect of cell apoptosis induction of GFTN by FZKA was validated in animal model. CONCLUSION: Our findings conclude that Fuzheng Kang-Ai decoction enhances the effect of GFTN-induced cell apoptosis in lung cancer through the mitochondrial pathway, providing a novel molecular mechanism by which FZKA sensitizes to GFTN by delaying drug resistance in treating lung cancer patients.

[Effect of Fuzheng Kang'ai Recipe Combined Gefitinib on Lung Cancer A549 Cells and Its Mecha- nism Research].

Objective To observe the effect of Fuzheng Kang'ai Recipe (FKR) combined ge- fitinib on the proliferation and apoptosis of lung cancer A549 cells , and to study its potential synergistic mechanish with gefitinib. Methods The effects of FKR (0. 211, 0. 316, 0. 474, 0. 711, 1. 067, 1. 600, 2. 400, 3. 600 mg/mL) combined gefitinib (3. 95, 5. 92, 8. 18, 13. 33, 20. 00, 30. 00, 45. 00, 67. 50 µmol/ L) on the proliferation of A549 cells were detected by MTT assay. The apoptosis of A549 cells in the control group (complete culture medium) , FKR (1. 6 mg/mL) , gefitinib (45 µmol/L) , and FKR plus gefitinib (1. 6 mg/mL +45 µmol/L) were detected by flow cytometry (FCM). Their expressions of epidermal growth factor receptor (EGFR) , phosphorylating epidermal growth factor receptor ( p-EGFR) , enhancer of zeste homolog 2 (EZH2), peroxisome proliferator-activated receptor-γ ( PPAR-γ) , and P53 protein in A549 cells were detected by Western blot. Results Both FKR and gefitinib could inhibit the proliferation of A549 cells. The apoptotic rate was 12. 6% ±4. 5% in the FKR combined gefitinib group, obviously higher than that of the FKR group (4. 6% ± 0. 7%) and the gefitinib group (7. 8% ± 2. 7%) , showing statistical difference (P <0. 05). Compared with the control group, the expressions of p-EGFR and EZH2 were sig- nificantly down-regulated (P <0. 05) , the expressions of PPAR-γ and P53 protein were up-regulated in the FKR combined gefitinib group (P <0. 05); the expression of EZH2 was down-regulated in the gefitinib group and the FKR group (P <0. 05) ; the expression of PPAR-y was up-regulated in the FKR group (P < 0. 05). Compared with the gefitinib group, the expression of p-EGFR was down-regulated, and the expression of PPAR-γ was up-regulated in the FKR combined gefitinib group (both P <0. 05). Compared with the FKR group, the expression of p-EGFR was down-regulated in the FKR combined gefitinib group (P < 0. 05). Conclusions Combination of FKR and gefitinib could significantly inhibit the proliferation and growth of A549 cells,and induce cell apoptosis. Its potential synergistic mechanism of anti-tumor activities might be associated with down-regulating mRNA expressions of p-EGFR and EZH2, and up-regulating protein expressions of PPAR-y and P53.

[Combination of Jianpi Liqi Yiliu Formula with Cytokine-induced Killer Cell Treatment for Advanced Hepatocellular Carcinoma].

OBJECTIVE: To evaluate the clinical efficacy of Jianpi Liqi Yiliu Formula (JLYF) combined with cytokine-induced killer (CIK) cells for treating patients with advanced hepatocellular carcinoma (HCC). METHODS: Between January 2011 and January 2014, 60 advanced HCC patients were enrolled in this study, who were assigned to the treatment group and the control group according to their willingness for taking JLYF, 30 cases in each group. All patients received CIK cell treatment: 1 x 109-3 x 109 each time, by intravenous dripping from the 1st day to the 3rd day, once per day. Besides, patients in the treatment group took JLYF decoction, while those in the control group took Chinese medical decoction by syndrome typing. All patients received treatment of at least two cycles. The time to progression (TTP) , overall survival (OS), disease control rate (DCR), performance status scale (PS), Child-Pugh scale, and adverse reactions were observed, and subgroup analyzed. RESULTS: To May 31, 2014, all patients reached the clinical endpoint. TTP was 3.5 months (95% Cl: 3.30-4.10) in the treatment group, better than that (2.5 months, 95% CI: 2.32-2.68) of the control group (P < 0.05). DCR was 36.7% in the treatment group and 30.0% in the control group (P > 0.05). OS was 5.2 months (95% CI: 4.53-5.87) in the treatment group and 4.6 months (95% CI: 4.06-5.14) in the control group (P > 0.05). The PS scale was 1.60 ± 0.10 after treatment, lower than that (1.80 ± 0.09) before treatment in the treatment group (P < 0.05). When the PS scale was 0-2 or Child-Pugh scale was class A, TTP was longer in the treatment group than in the control group (P < 0.05). No adverse reaction occurred in the two groups during the treatment course. CONCLUSIONS: The combination of JLYF with ClK cell treatment could prolong advanced HCC patients' TTP, improve PS scale, as compared with syndrome typed Chinese medical decoction treatment group. Besides, when the PS scale was 0-2 or Child-Pugh scale was class A, it was a better treatment program for advanced HCC patients.

[Treating primary liver cancer patients by Pi-strengthening and Qi-regulating method: univariate and multivariate analyses of their prognoses].

OBJECTIVE: To evaluate the prognostic factors in treating primary liver cancer (PLC) patients by Pi-strengthening and qi-regulating method (PSQRM), thus providing evidence and optimizing Pi-strengthening and qi-regulating program. METHODS: Clinical data of 151 PLC patients treated by PSQRM at Oncology Department, Guangdong Provincial Hospital of Traditional Chinese Medicine from May 2007 to March 2009 were retrospectively analyzed. The univariate analysis was determined to analyze possible prognostic factors. Selected key factors were introduced into the COX proportional hazard model, and multivariate analysis was carried out. RESULTS: The 1-year survival rate was 21.85%, the median survival time was 6.80 months, and the mean survival time was 8.98 months. The univariate analysis showed that Chinese medicine (CM) syndrome types, clinical symptoms at the initial diagnosis, ascites, tumor types, ratios of foci, portal vein tumor thrombus, intrahepatic metastasis, a-fetoprotein (AFP) levels, total bilirubin classification, albumin classification, Child-Pugh classification, and domestic staging of liver cancer were significant prognostic factors (P < 0.05). The statistic data of multivariate analysis indicated that CM syndrome types, ascites, tumor types, portal vein tumor thrombus, AFP levels, Child-Pugh classification, and domestic staging of liver cancer were independent factors influencing prognosis (P < 0.05). CONCLUSION: The prognosis of PLC treated with PSQRM is determined by multiple factors including CM syndrome types, ascites, tumor types, portal vein tumor thrombus, AFP levels, Child-Pugh classification, and domestic staging of liver cancer.

Complete response in patient with locally advanced lung large cell neuroendocrine carcinoma under sintilimab plus platinum-based chemotherapy: A case report.

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is an uncommon subtype of lung cancer with bleak prognosis. Its optimal treatment remains undetermined due to its malignancy. A 66-year-old man diagnosed with unresectable locally advanced LCNEC exhibited partial radiographic response to chemo-immunotherapy. He underwent salvage surgery after 4 rounds of docetaxel/nedaplatin (DP) regimen plus sintilimab, a highly selective monoclonal antibody which targets human anti-programmed death-ligand 1 (PD-L1). In addition, the pathologic examination of the excision demonstrated that there were no viable residuary tumor cells. This case indicates that neoadjuvant chemo-immunotherapy might benefit patients with locally advanced LCNEC, which deserves further investigation.

[The distribution of Chinese medicine syndrome types in primary liver cancer and their differences of the survival time: a clinical study].

OBJECTIVE: To explore the distribution of Chinese medicine (CM) syndrome types in primary liver cancer (PLC) and their differences of the survival time. METHODS: From May 2007 to March 2009, recruited were 151 PLC inpatients at Department of Tumor, Guangdong Provincial Hospital of Traditional Chinese Medicine. Their survival time were statistically calculated. Patients' average survival time and median survival time were calculated using Kaplan-Meier method. The Log-rank test was used to analyze their differences of survival time among different CM syndrome types. RESULTS: The proportion of CM syndrome types in PLC patients were ranked from high to low as follows: mutual accumulation of dampness and blood stasis syndrome [MADBSS, 43.0% (65/151)], Gan-stagnation Pi-deficiency syndrome [GSPDS, 34.4% (52/151)], qi stagnation blood stasis syndrome [QSBSS, 9.3% (14/151)], retention of damp-heat syndrome [RDHS, 8.6%(13/151)], and Gan-Shen yin deficiency syndrome [GSYDS, 4.6% (7/ 151)]. The median survival time of different CM syndrome types were ranked from longer to shorter as follows: GSPDS (14.77 months), QSBSS (6.13 months), RDHS (5.27 months), MADBSS (4.78 months), and GSYDS (0.80 months). The mean survival times were ranked from longer to shorter as follows: GSPDS (12.40 months), QSBSS (8.84 months), MADBSS (6.99 months), RDHS (7.08 months), and GSYDS (0.72 months). There was statistical difference in the difference of the survival time among different CM syndrome types (P < 0.05). CONCLUSIONS: GSPDS and MADBSS were the most common CM syndrome types in PLC patients. There was difference in the survival time between GSPDS and MADBSS/between RDHS and GSYDS. There was difference in the survival time between MADBSS and GSYDS. Patients of GSPDS might get the best prognosis, while patients of GSYDS might get the poorest prognosis.

The negative effect of concomitant medications on immunotherapy in non-small cell lung cancer: An umbrella review.

BACKGROUND: Conflicting results about the effect of concomitant medications on immunotherapy in non-small cell lung cancer (NSCLC) were reported by many meta-analyses (MAs), and the certainty of evidence linking concomitant medications with immunotherapy efficacy has not been quantified, which may cause some evidence to be misinterpreted. METHODS: Four databases including Embase, Cochrane Library, PubMed, and Web of Science were searched from inception to January 2023 in English. Based on prospective or retrospective clinical controlled trials including immunotherapy with concomitant medications or not in NSCLC, quantitative MAs reporting the efficacy of immunotherapy with binary direct comparison and enough extractable data were collected. The methodological quality, reporting quality, and risk of bias of included MAs were evaluated respectively. New meta-analyses were conducted and their evidence certainty was classified as nonsignificant, weak, suggestive, highly suggestive, or convincing. RESULTS: Fifteen MAs with 5 medications were included. After being assessed by AMSTAR-2, PRISMA, and ROBIS, the major shortcomings were focused on the registration of protocol, literature retrieval or data extraction, implementation of sensitivity analysis or evidence certainty assessment, and incomplete reporting in the section of method and result. New pooled analyses indicated that antibiotics (HR = 1.545[1.318-1.811]), steroids (HR = 1.784[1.520-2.093]), proton pump inhibitors (PPIs) (HR = 1.303[1.048-1.621]) and opioids (HR = 1.910[1.213-3.006]) could shorten overall survival (OS) in patients with NSCLC receiving immunotherapy. Besides, antibiotics (HR = 1.285[1.129-1.462]) and steroids (HR = 1.613[1.315-1.979]) were harmful to progression-free survival (PFS) in these patients significantly. No negative effect was found in nonsteroidal anti-inflammatory drugs and the objective response rate of all medications. High-level evidence suggested that using PPIs before or after the initiation of immunotherapy and using steroids during the first-course immunotherapy could weaken the OS of patients with NSCLC. Meanwhile, the negative effects of antibiotics and opioids on OS or PFS were only supported by moderate or low-level evidence. CONCLUSIONS: The concurrent usage of PPIs or steroids adversely affects the survival of patients with NSCLC receiving immunotherapy. Future investigations are required to ascertain whether these adverse effects are primarily attributed to the comorbidities or the concurrent medications.

The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers.

Programmed cell death protein-1 (PD-1) is a checkpoint receptor expressed on the surface of various immune cells. PD-L1, the natural receptor for PD-1, is mainly expressed in tumor cells. Studies have indicated that PD-1 and PD-L1 are closely associated with the progression of human cancers and are promising biomarkers for cancer therapy. Moreover, the interaction of PD-1 and PD-L1 is one of the important mechanism by which human tumors generate immune escape. This article provides a review on the role of PD-L1/PD-1, mechanisms of immune response and resistance, as well as immune-related adverse events in the treatment of anti-PD-1/PD-L1 immunotherapy in human cancers. Moreover, we summarized a large number of clinical trials to successfully reveal that PD-1/PD-L1 Immune-checkpoint inhibitors have manifested promising therapeutic effects, which have been evaluated from different perspectives, including overall survival, objective effective rate and medium progression-free survival. Finally, we pointed out the current problems faced by PD-1/PD-L1 Immune-checkpoint inhibitors and its future prospects. Although PD-1/PD-L1 immune checkpoint inhibitors have been widely used in the treatment of human cancers, tough challenges still remain. Combination therapy and predictive models based on integrated biomarker determination theory may be the future directions for the application of PD-1/PD-L1 Immune-checkpoint inhibitors in treating human cancers.

Acupuncture combined with opioids for cancer pain: a pilot pragmatic randomized controlled trial.

OBJECTIVE: Given the existing evidence for the analgesic effect of acupuncture, the current study aimed to assess whether acupuncture could be feasible and manageable as an adjunctive therapy for cancer pain in a real-world hospital setting. METHODS: Thirty patients in an Oncology department with moderate or severe pain were recruited and randomized to an adjunctive acupuncture group or control group, who received pharmacotherapy for pain management without acupuncture. The duration of the treatment course was 1 week with a 2-week follow-up. In total, four acupuncture sessions were administered, on days 1/2/4/6 of the trial. Pain intensity was measured using a numerical rating scale (NRS) and the daily opioid dose was recorded. RESULTS: The overall trends favored acupuncture for both pain intensity and daily opioid consumption. The proportion of participants experiencing at least a 2-point reduction in the NRS at the end of the treatment was 93% (n = 14/15) for the acupuncture group and 57% (n = 8/14) for the control group (risk difference (RD) 36.1%, 95% confidence interval (CI) [7.4%-65.0%]; relative risk (RR) 1.63, 95% CI [1.02-2.62]; p = 0.04). There were no serious adverse events and no dropouts during the treatment. CONCLUSION: This pilot study showed that adding acupuncture to routine analgesia for patients with cancer pain was feasible and acceptable to patients. The clinical effects of adding acupuncture as an adjunctive therapy need to be further evaluated. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR1800017023 (Chinese Clinical Trial Registry).

[Corrigendum] Traditional Chinese medicine, Fuzheng Kang­Ai decoction, inhibits metastasis of lung cancer cells through the STAT3/MMP9 pathway.

Following the publication of the above article, an interested reader drew to the authors' attention that various of the data panels shown for the cell migration assay experiments in Figs. 2B and 3 appeared to show overlapping regions, such that they were not generated from discretely performed experiments.The authors have re-examined their original data, and realize that the figures in question were assembled incorrectly. In addition, the authors have also realized that certain of the western blotting data panels in Figs. 5 and 6 had likewise been assembled incorrectly. The corrected versions of Figs. 2, 3, 5 and 6 are shown on the next two pages. All these corrections were approved by all authors. The authors regret that these errors were included in the paper, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum. They also wish to emphasize that the errors made during the compilation of the figures did not substantially alter any of the major conclusions reported in the study, and apologize to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 16: 2461-2468, 2017; DOI: 10.3892/mmr.2017.6905].

Prognostic significance of programmed cell death-ligand 1 expression on circulating tumor cells in various cancers: A systematic review and meta-analysis.

BACKGROUND: The prognostic significance of programmed cell death-ligand 1 (PD-L1) expression on circulating tumor cells (CTCs) has been explored but is still in controversy. We performed, for the first time, a meta-analysis to systematically evaluate its prognostic value in human cancers. METHODS: Literature databases were searched for eligible studies prior to June 30, 2021. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for the associations of pre-treatment and post-treatment PD-L1+ CTCs with progression-free survival (PFS) and overall survival (OS). Subgroup analyses with regards to cancer type, treatment, CTC enrichment method, PD-L1 detection method, cut-off, and specifically the comparison model were performed. RESULTS: We included 30 eligible studies (32 cohorts, 1419 cancer patients) in our analysis. Pre-treatment PD-L1+ CTCs detected by immunofluorescence (IF) tended to predict better PFS (HR = 0.55, 95% CI 0.28-1.08, p = 0.084) and OS (HR = 0.61, 95% CI 0.36-1.04, p = 0.067) for immune checkpoint inhibitor (ICI) treatment, but were significantly associated with unfavorable survival for non-ICI therapies (PFS: HR = 1.85, 95% CI 1.21-2.85, p = 0.005; OS: HR = 2.44, 95% CI 1.69-3.51, p < 0.001). Post-treatment PD-L1+ CTCs predicted markedly worse PFS and OS. The prognostic value was obviously modulated by comparison models. Among patients with detectable CTCs, PD-L1+ individuals had comparable survival to PD-L1- individuals, except ICI treatment for which PD-L1+ may predict better PFS (HR = 0.42, 95% CI 0.17-1.06, p = 0.067). Patients with PD-L1+ CTCs had worse survival prognosis compared to those without PD-L1+ CTCs in overall analysis (PFS: HR = 2.10, 95% CI 1.59-2.77, p < 0.001; OS: HR = 2.55, 95% CI 1.70-3.81, p < 0.001) and in most subgroups. CONCLUSIONS: Our analysis demonstrated that PD-L1 positive expression on CTCs predicted better survival prognosis for ICI treatment but worse survival for other therapies, which thus can be potentially used as a prognostic marker of malignant tumor treatment. However, the prognostic value of PD-L1+ CTCs for ICI treatment needs validation by more large-scale studies in the future.

Positive Role of Chinese Herbal Medicine in Cancer Immune Regulation.

Complementary and alternative medicine (CAM) plays a critical role in treating cancer patients. Traditional Chinese Medicine (TCM) is the main component of CAM. TCM, especially Chinese Herbal Medicine (CHM), has been increasingly used in China, some other Asian countries and European countries. It has been proven to enhance the efficacy of chemotherapy, radiotherapy, targeted-therapy, and immunotherapy. It lessens the damage caused by these therapies. CHM functions on cancer by inhibiting tumor progression and improving an organism's immune system. Increasing evidence has shown that many CHM exert favorable effects on the immune regulation. We will summarize the role of CHM on patient's immune system when treating cancer patients. Our evidence reveals that single herbs, including their extracts, compound formulations, and preparations, will provide current advances on CHM study, especially from the perspective of immune regulation and novel insights for CHM application in clinic. The main herbs used to treat cancer patients are health-strengthening (Fu-Zheng) herbs and pathogen eliminating (Qu-Xie) herbs. The key mechanism is regulating the immune system of cancer patients. Firstly, health-strengthening herbs are mainly functioned as immune regulatory effectors on cancer. Secondly, some of the compound formulations mainly strengthen the health of patients by regulating the immune system of cancer patients. Lastly, some Chinese medicine preparations are widely used to treat cancer for their properties of spiriting vital energy and anti-cancer effects, mainly by improving immunity. CHM plays a positive role in regulating patients' immune system, which helps cancer patients to fight against cancer itself and finally improves patients' life quality.

MicroRNA-24 in Cancer: A Double Side Medal With Opposite Properties.

MicroRNA-24 (miR-24) has been widely studied in a variety of human cancers, which plays different roles in specific type of cancers. In the present review, we summarized the recent surveys regarding the role of miR-24 in different human cancers. On the one hand, miR-24 was reported to be down-regulated in some types of cancer, indicating its role as a tumor suppressor. On the other hand, it has shown that miR-24 was up-regulated in some other types of cancer, even in the same type of cancer, suggesting the role of miR-24 being as an oncogene. Firstly, miR-24 was dysregualted in human cancers, which is related to the clinical performance of cancer patients. Thus miR-24 could be used as a potential non-invasive diagnostic marker in human cancers. Secondly, miR-24 was associated with the tumor initiation and progression, being as a promoter or inhibitor. Therefore, miR-24 might be an effective prognostic biomarker in different type of cancers. Lastly, the abnormal expression of miR-24 was involved in the chemo- and radio- therapies of cancer patients, indicating the role of miR-24 being as a predictive biomarker to cancer treatment. Totally, miR-24 contributes to tumorigenesis, tumor progression, and tumor therapy, which closely related to clinic. The present review shows that miR-24 plays a double role in human cancers and provides plenty of evidences to apply miR-24 as a potential novel therapeutic target in treating human cancers.

[Effect of shenfu injection for attenuating the toxicity of cisplatin-based regimens in treating non-small cell lung cancer].

OBJECTIVE: To observe the effect of Shenfu Injection (SFI) for attenuating the toxicity of chemotherapy in treating non-small-cell lung cancer (NSCLC), by the regimens of combined Cisplatin (DDP) with new chemotherapeutic agents, Taxol (TXT), Vinorelbine (NVB) and Gemcitabine (GEM), respectively. METHODS: One hundred and thirty-three patients with NSCLC, who were scheduled to be treated by at least 2 cycles of chemotherapy, with regimen TP (45 cases), NP (42 cases) and GP (46 cases), were enrolled. They were randomized into 2 groups: 67 cases in the SFI pre-treated group and 66 cases in the SFI post-treated group, on them SFI was administered for 10 successive days on the 1st, 2nd, 3rd day of the 1st and the 2nd cycle, respectively. The effects of SFI on toxicity of the three regimens were observed through a self-controlled crossover design. RESULTS: The hemato-toxicity (the toxicity on leukocyte, neutrophil, hemoglobin and platelet) and the digestive toxicity (represented as vomiting, constipation or diarrhea) of chemotherapy revealed in the treated stage (the cycle treated with SFI) were all less than those in the control stage (the cycle untreated with SFI), no matter when SFI was applied, all showed statistical significance (P < 0.05 or P < 0.01). Besides, SFI showed a better toxicity attenuating effect on patients of qi-deficiency and phlegm-dampness type (P < 0.01). CONCLUSION: SFI can relieve the hemato-toxicity and the digestive toxicity of chemotherapy by regimen of combining DDP with TXT, NVB or GEM, and the effect is more significant on patients of qi-deficiency and phlegm-dampness type.

Application of Traditional Chinese Medicines as Personalized Therapy in Human Cancers.

Although lots of great achievements have been gained in the battle against cancer during the past decades, cancer is still the leading cause of death in the world including in developing countries such as China. Traditional Chinese medicine (TCM) is popular in Chinese and East Asian societies as well as some other Western countries and plays an active role in the modern healthcare system including patients with cancer, which may act as a potential effective strategy in treating human cancers. In this review, we aimed to introduce the mechanisms of TCM compound, as an option of individualized therapy, in treating cancer patients from the perspective of both Chinese and Western medicine. In the view of traditional Chinese medicine theory, individualized treatment for human cancers based on syndrome type benefits the cancer patients with personalized conditions. Balancing Qi, Xue, Yin and Yang, eliminating phlegm and removing dampness is how TCM compound functions on cancer patients. While in the view of Western medicine, inhibiting cancer cell growth and metastasis as well as improving immune status is how herbal compounds act on cancer patients. We also summarized the applications of TCM compound in human cancers, which will shed light on the clinical application of TCM compound on patients with cancer. TCM compound could be used as a complementary and alternative medicine (CAM) in human cancers. It could be applied in cancer patients with cancer-related fatigue (CRF). In addition, it is a good method for alleviating the side effects of both radiotherapy and chemotherapy. Therefore, TCM compound plays a critical role in treating patients with cancer, which has a promising strategy in the field of cancer management.

Decoction of Chinese Herbal Medicine Fuzheng Kang-Ai Induces Lung Cancer Cell Apoptosis via STAT3/Bcl-2/Caspase-3 Pathway.

Decoction of Chinese herbal medicine (CHM) Fuzheng Kang-Ai (FZKA for short) has been applied as adjuvant treatment strategy in advanced lung cancer patients for decades. We previously showed that FZKA decoction inhibited proliferation of non-small cell lung cancer (NSCLC) cells through activation of AMP-activated protein kinase alpha (AMPKα) signaling pathway, followed by inducing insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and forkhead homeobox type O3a (FOXO3a) proteins, and enhanced the inhibition effect of gefitinib in lung cancer cell growth via inactivating PI3-K/Akt-mediated suppressing of cell surface-associated mucin-1 (MUC1) expression. In this study, we investigated the molecular mechanism by which FZKA decoction affected cell apoptosis in lung cancer cells. Our results show that FZKA induced apoptosis in lung cancer cells. Mechanistically, FZKA activated the caspase-3, PARP, and caspase-9 activities. Both antiapoptotic and proapoptotic proteins from Bcl-2 family were deregulated by FZKA exposure in lung cancer cells. In addition, FZKA reduced protein expressions of signal transducer and activator of transcription 3 (STAT3) and Jun activation domain-binding protein 1 (Jab1), while it concomitantly increased p21 protein. Moreover, the inhibitor of caspase-3 resisted the effect of FZKA on induction of apoptosis. Finally, exogenous overexpression of STAT3 overcame FZKA-inhibited protein expressions of Bcl-2 and myeloid cell leukemia-1 (Mcl-1) as well as Bax and blocked FZKA-induced activities of caspase-3 and caspase-9. Our results show that FZKA decoction promotes lung cancer cell apoptosis through STAT3/Bcl-2/caspase-3 signaling pathways. This study unveils potential novel molecular mechanism by which FZKA controls growth of human lung cancer cells.

Gefitinib plus Fuzheng Kang'ai Formula () in Patients with Advanced Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of Fuzheng Kang'ai Formula (, FZKA) plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations. METHODS: A randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage IIIB/IV non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefitinib (250 mg/day orally) plus FZKA (250 mL, twice per day, orally); 35 cases] or G group (gefitinib 250 mg/day orally; 35 cases) according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities. The primary endpoint [progression-free survival (PFS)] and secondary endpoints [median survival time (MST), objective response rate (ORR), disease control rate (DCR) and safety] were observed. RESULTS: No patient was excluded after randomization. GF group had significantly longer PFS and MST compared with the G group, with median PFS of 12.5 months (95% CI 3.30-21.69) vs. 8.4 months (95% CI 6.30-10.50; log-rank P<0.01), MST of 21.5 months (95% CI 17.28-25.73) vs. 18.3 months (95% CI 17.97-18.63; log-rank P<0.01). ORR and DCR in GF group and G group were 65.7% vs. 57.1%, 94.3% vs. 80.0%, respectively (P>0.05). The most common toxic effects in the GF group and G group were rash or acne (42.8% vs. 57.1%, P>0.05), diarrhea (11.5% vs. 31.4%, P<0.05), and stomatitis (2.9% vs. 8.7%, P>0.05). CONCLUSION: Patients with advanced non-small cell lung cancer selected by EGFR mutations have longer PFS, MST with less toxicity treated with gefitinib plus FZKA than gefitinib alone.

Shenmai injection for the treatment of cancer-related fatigue in advanced non-small cell lung cancer patients undergoing chemotherapy: study protocol for a randomized controlled trial.

BACKGROUND: Cancer-related fatigue (CRF) is the most common symptom in patients with advanced non-small cell lung cancer (NSCLC) undergoing treatment with chemotherapy. However, evidence upon which to base management strategies is scarce. Traditional Chinese Medicine (TCM) has been shown to be beneficial to patients with CRF. Chinese herbal injections should be administered under an evidence-based approach. This trial aims to assess the efficacy and safety of the addition of the Shenmai injection (SMI) to conventional therapy for CRF in NSCLC patients undergoing chemotherapy. METHODS/DESIGN: The study is a two-group, prospective, randomized controlled trial (RCT) designed to evaluate the efficacy and safety of SMI for CRF NSCLC patients undergoing chemotherapy. Eligible participants will be randomized to either a treatment group receiving a 5-day Shenmai injection regimen plus conventional therapy or a control group receiving only conventional therapy. The primary outcome is fatigue, assessed using severity scores from the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F) measurement system. Secondary outcomes include symptom distress scores, depression, sleep disorders, quality of life, and levels of immunologic indicators. Assessments will be carried out at baseline and on day 5 (the end of the intervention). DISCUSSION: This study can provide evidence to support clinical decision-making in the management of CRF in NSCLC patients undergoing chemotherapy in a way that can be scaled up and used throughout China. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( chictr.org.cn ), ChiCTR-INR-17013737 . Registered on 6 December 2017.