Prognostic implications of the EGFR polymorphism rs763317 and clinical variables among young Chinese lung cancer population.

The 5-year survival rate for patients with lung cancer, the world's second most frequent malignant tumor, is less than 20%, and its prognosis cannot be clearly predicted. Our aim was to analyze the epidermal growth factor receptor (EGFR) rs763317 (G>A) single nucleotide polymorphism and its association with prognosis in Chinese Han lung cancer patients. 839 patients with primary lung cancer were recruited, and genomic DNA was extracted and genotyped by SNPscan. Kaplan-Meier technique and multivariate Cox proportional hazards model were used to analyze the association between prognosis and EGFR polymorphism rs763317. A significant association after stratification by age, significantly increased lung cancer risk was associated with the AA homozygous genotype of rs763317 (adjusted hazard ratio = 2.53, 95% CI: 1.31-4.88, p=0.005), and conferred a poor survival for lung cancer patients (MST: median survival time: 13.6 months) compared with GG genotype (MST: 41.5 months), and in the recessive model AA genotype (AA vs. GG + GA; adjusted hazard ratio = 2.57, 95% CI: 1.34-4.93, p=0.004) who were young (<60 years) had a significantly increased risk of death. The EGFR polymorphism rs763617 might serve as a significant genetic marker for predicting the prognosis of lung cancer.

Xiaotan Sanjie decoction normalizes tumor permissive microenvironment in gastric cancer (Review).

Gastric cancer (GC) develops in a complex tissue environment, the tumor microenvironment (TME), which it relies on for persistent proliferation, migration, invasion and metastasis. Non­malignant stromal cell types within the TME are regarded as a clinical meaningful target with the lower risk of resistance and tumor relapse. Studies have revealed that the Xiaotan Sanjie decoction, which is formulated on the basis of the theory of phlegm syndrome, a Traditional Chinese Medicine concept, modulates released factors such as transforming growth factor­ß from tumor cells, immune cells, cancer­associated fibroblasts, extracellular matrix, as well as vascular endothelial growth factor involved in the process of angiogenesis within the TME. Clinical studies have also shown that the Xiaotan Sanjie decoction is associated with favorable survival and quality of life. The present review aimed to interpret the hypothesis that Xiaotan Sanjie decoction has the ability to normalize the GC tumor cells by influencing functions of stromal cells within the TME. The possible association between phlegm syndrome and the TME in GC was discussed in the present review. Overall, Xiaotan Sanjie decoction may be suitable to be added to tumor cell­directed agents or emerging immunotherapies becoming a desirable modality in the management of GC and acquire improved outcomes for patients with GC.

Research progress in targeted therapies for gastric cancer.

Patients with advanced gastric cancer experience rapid disease progression with limited survival, high mortality, and a lack of surgical options. Thus, radiochemotherapy or a combination of chemotherapeutics with targeted therapy is the mainstay of treatment. In comparison to the treatment of other malignant tumors, in gastric cancer, the development of molecularly targeted drugs has been relatively slow. Currently, there are two major classes of molecularly targeted drug regimens that have achieved a certain efficacy in clinical practice: anti-vascular endothelial growth factor (anti-VEGF) therapy and anti-epidermal growth factor receptor (anti-EGFR) therapy. Trastuzumab has been approved as the standard of care for first-line treatment in advanced human epidermal growth factor receptor 2 (HER2)-positive gastric cancer. Ramucirumab in combination with paclitaxel is the recommended regimen for second-line treatment, and apatinib is recommended as third-line treatment. This review summarizes the current status of targeted therapies in the treatment of gastric cancer and gives a perspective on the future.

Ziyin Huatan Recipe, a Chinese herbal compound, inhibits migration and invasion of gastric cancer by upregulating RUNX3 expression.

OBJECTIVES: Ziyin Huatan Recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo. METHODS: Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene. RESULTS: The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT. CONCLUSION: ZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.

Xiaotan Jieyu Prescription Alleviates Breast Precancerous Lesions through PI3K/Akt Signaling Pathway.

METHODS: The successfully established breast precancerous lesion rat model and normal healthy rats were randomly assigned into the blank (BLA), model (MOD), XTJY-low (LD), XTJY-medium (MD), XTJY-high (HD), and tamoxifen (TAM) groups. Different concentrations of XTJY and saline were supplied by intragastric administration for 4 consecutive weeks to assess the protective effect of XTJY on the progress of the breast precancerous lesion in rats involving the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. RESULTS: In this study, it determined that 10 mg/each rat DMBA-combined estrogen and progesterone induction for 10 weeks was the optimal condition for the establishment of the breast precancerous lesion rat model. In vivo administration of XTJY or TAM was found to inhibit the development of the breast precancerous lesion, and the occurrence rate of breast invasive carcinomas was decreased by about 50%. Furthermore, XTJY or TAM markedly reduced protein expressions of PI3K and p-Akt and increased protein expressions of PTEN. CONCLUSION: These data indicated that XTJY can significantly alleviate the development of breast precancerous lesions by inhibiting the activation of the PI3K/Akt signaling pathway. XTJY may be a promising drug for the treatment of precancerous lesions in breast cancer.

Author Correction: FAM46C is critical for the anti-proliferation and pro-apoptotic effects of norcantharidin in hepatocellular carcinoma cells.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Traditional Chinese medicine integrated with chemotherapy for stage IV non-surgical gastric cancer: a retrospective clinical analysis.

OBJECTIVE: Traditional Chinese medicine (TCM) is regarded as an important treatment for gastric cancer patients, especially for those in advanced stage. To evaluate the effects of TCM treatment on gastric cancer patients, the authors performed a retrospective study to report the result of the integrated treatment of TCM with chemotherapy for stage IV non-surgical gastric cancer. METHODS: In this study, 182 patients with stage IV and non-surgical gastric cancer were retrospectively analyzed to evaluate the effects of TCM integrated with chemotherapy. Among the 182 cases, 88 cases received integrated therapy consisting of TCM and chemotherapy, while 94 cases received chemotherapy alone. The overall survival and Karnofsky performance status (KPS) score were measured as the main outcome. RESULTS: The median overall survival of the integrated therapy group and chemotherapy group were 16.9 and 10.5 months, respectively. The 1-, 3- and 5-year survival rates of integrated therapy group vs. chemotherapy group were 70% vs. 32%, 18% vs. 4%, and 11% vs. 0%, respectively. There was a significant difference between the two groups (χ2 = 42.244, P > 0.001). After six-month treatment, KPS scores of the integrated therapy group and the chemotherapy group were 75.00 ± 14.78 and 60.64 ± 21.39, respectively (P > 0.001). The Cox regression analysis showed that TCM treatment is a protective factor for patients' overall survival. CONCLUSION: This study demonstrated that TCM integrated with chemotherapy may prolong overall survival and improve survival rate and life quality of patients with stage IV non-surgical gastric cancer.

FAM46C is critical for the anti-proliferation and pro-apoptotic effects of norcantharidin in hepatocellular carcinoma cells.

Norcantharidin (NCTD), a demethylated analog of cantharidin derived from Chinese traditional medicine blister beetle, has been currently used as an anticancer drug for various cancers including hepatocellular carcinoma (HCC). In this study, for a more comprehensive understanding of the targets of NCTD in HCC, next-generation RNA-Seq was utilized. We revealed that the expression of FAM46C, which has been reported as a tumor suppressor for multiple myeloma, was enhanced after NCTD treatment. Re-analysis of TCGA (The Cancer Genome Atlas) LIHC (liver hepatocellular carcinoma) dataset demonstrated that FAM46C expression was significantly lower in HCC tissues than in normal liver tissues. NCTD injection or FAM46C overexpression could mitigate diethylnitrosamine (DEN)-initiated HCC in mice. Ectopic expression of FAM46C in two HCC cell lines, SMCC-7721 and SK-Hep-1, significantly repressed cell proliferation, and increased cells population in G2/M phase and cell apoptotic rate. We also found that FAM46C overexpression caused a notable decrease in Ras expression, MEK1/2 phosphorylation and ERK1/2 phosphorylation. More importantly, FAM46C knockdown significantly weakened the biological effects of NCTD on HCC cells, which suggested NCTD exerted the anticancer functions partially through up-regulating FAM46C. In conclusion, FAM46C, a tumor suppressor for HCC, is important for the anti-proliferation and proapoptotic effects of NCTD.

[Effect of Jinlongshe Granule Drug-containing Serum on Tube Formation, Migration and Apoptosis of Human Lymphatic Endothelial Cells in vitro].

Objective To observe the inhibitory effect of Jinlongshe Granule drug-containing serum (JG-DS) on tube formation, migration, and apoptosis of human lymphatic endothelial cells ( HLECs) in vitro. Methods JG-DS was prepared. The 3rd-passage HLECs were divided into the control group (cultured with normal saline containing serum) and the experimental group (cultured with JG-DS). After cultured for 12 h, the tube formation ability was detected by Matrigel assay, and the migration ability was determined by Transwell assay in the two groups. Cell apoptosis rate was detected by flow cytometry and Annexin-V-FITC/Pl staining method. Results The total length of tube was (3 084. 49 ?326. 27) p.m after acted by 10% JG-DS for 12 h, significantly shorter than that of the control group (7 058.93 ?4 567. 39) pm (P <0.01). The migration number of HLECs was (99 ?26), obviously lower than that of the control group (160 ?32; P <0.05). The apoptosis rate of the two groups was not statistically significant (P >0.05). Conclusion JG could inhibit the tube formation and migration of HLECs in vitro, which might be one of mechanisms for inhibiting tumor micro-lymphatics.

Anticancer effects of traditional Chinese herbs with phlegm-eliminating properties - An overview.

ETHONOPHARMACOLOGICAL RELEVANCE: Cancer is considered to be the second leading cause of human death. It is unsatisfactory that in the past decades, the treatment for cancer has not progressed as fast as it was expected, as only 50% of newly diagnosed patients could be cured even today. The development of cancer is a multifactorial process, involving tumor cells themselves, the interactions between tumor cells and their microenvironments, as well as the interactions between tumor cells and the host's immunity. Focusing on any single goal may bring limited benefits. AIM AND METHODS OF THE STUDY: Phlegm-eliminating herbs, which can reduce phlegm and eliminate pathological metabolites, are commonly used to treat cancer in China. However, the underlying molecular targets and efficacy of herbal medicines in cancer treatment still remain unclear. In this study, we reviewed the potential anticancer mechanisms of some phlegm-eliminating herbs and their active ingredients from the articles through such scientific databases as MEDLINE, PubMed, and Google Scholar. RESULTS: We found that the anticancer mechanisms of phlegm-eliminating herbs and ingredients include inducing apoptosis, anti-proliferation, preventing tumor invasion and metastasis, and reducing resistance to chemotherapy. In addition, some phlegm-eliminating herbs and their ingredients have anti-inflammatory and anti-metabolic syndrome effects. CONCLUSIONS: We suggest that the phlegm-eliminating herbs and ingredients are potential candidates for anticancer treatment and cancer prevention by playing a comprehensive role.

Three advantages of using traditional Chinese medicine to prevent and treat tumor.

Traditional Chinese medicine (TCM), an important component of complementary and alternative medicine, has evolved over thousands of years with its own unique system of theories, diagnostics and therapies. TCM has been increasingly used in the last decades and become well known for its significant role in preventing and treating cancer. We believe that TCM possesses advantages over Western medicine in specific aspects at a certain stage of cancer treatment. Here we summarize the advantages of TCM from three aspects: preventing tumorigenesis; attenuating toxicity and enhancing the treatment effect; and reducing tumor recurrence and metastasis.

[Study of the syndromes of traditional Chinese medicine in terms of metabonomics technology: the current situation and considerations].

Syndromes constitute a core aspect in the study of Chinese medicine, and research on the concept of syndromes is important to the study of the process of modernization of traditional Chinese medicine. However, it is somewhat challenging to define a syndrome due to the complexity inherent in the subject, even with the assistance of the reductionism approach of modern medicine. Holistic and dynamic in nature and attaching much importance to functional changes, the newly emerging metabonomics is in many ways inline with the concepts of syndrome differentiation of pathological states in traditional Chinese medicine. Therefore, metabonomics has comparatively strong advantages in the very respect of revealing the natural laws of syndrome differentiation. By reviewing and analyzing the current research on the concept of syndromes and the application of metabonomic technology to exploring the essential core of syndrome differentiation, the authors illustrated the potential commonalities. This would also show the issues requiring attention between the study of syndromes and the metabonomic technology. In the meantime this study reflected the core problems in detail and put forward suggestions with regard to reaching solutions.

A traditional Chinese herbal medicine compound preparation versus interventional therapy after resection of small hepatocellular carcinoma: 22-year follow-up.

OBJECTIVE: To compare the long-term effectiveness of compound Ruanjianhugan(RJH)tablets and interventional therapy (IT) in patients after resection of small hepatocellular carcinoma (HCC). in 399 patients after resection of small HCC who were admitted between January 1987 and December 2008 in the Department of Hepatobiliary Surgery and Center of Minimally Invasive Surgery, First Affiliated Hospital of Guangxi Medical University. Four groups were based on different therapy modes: a TCM-only (TCMO) group, a TCM combined with interventional therapy (TCM-IT) group, an interventional therapy-only (ITO) group, and a simple operation (SO) group. Prognostic factors were correlated with overall survival (OS) and OS rates were calculated with the Kaplan-Meier method, and multivariate analyses for factors affecting survival were evaluated by the Cox proportional hazard model. RESULTS: The median OS was 151.20 months in the TCM-IT group, 43.87 months in the ITO group, and 20.77 months in the SO group. All survival rates of the TCMO group were higher than those of the other three groups (>50%). The 5-, 10-, and 15-year OS in the TCMO and ITO patients were 83.94%, 45.50%, and 71.22% and 33.34%, 55.58%, and 9.26%, respectively (risk ratio, 0.209; 95% confidence interval, 0.126-0.347; P = 0.000). Multivariate analysis revealed that the independent risk factors were therapy mode (P = 0.000), sex (P = 0.005), family history (P = 0.011), TNM classification of malignant tumor staging (P = 0.000), medical care-seeking behavior (P = 0.021), and maximum diameter (P = 0.030). CONCLUSION: Long-term oral use of compound RJH tablets may improve OS for small HCC after resection compared with IT.

Preventive effects of jiedu granules combined with cinobufacini injection versus transcatheter arterial chemoembolization in post-surgical patients with hepatocellular carcinoma: a case-control trial.

OBJECTIVE: To investigate the therapeutic effects of Jiedu granules, a Chinese medicine (CM) compound, plus cinobufacini injection, which was extracted from skin of Bufo bufo gargarizans Cantor, to prevent the recurrence of hepatocellular carcinoma (HCC) after surgical resection. METHODS: In this case-control trial, a total of 120 patients who stayed in Changhai Hospital were enrolled from December 2001 to December 2006. Sixty patients were treated with Jiedu granules plus cinobufacini injection to prevent tumor recurrence after operation (CM group) and 60 patients were treated with transcatheter arterial chemoembolization (TACE) after operation (TACE group). Progression-free survival (PFS) and overall survival (OS) rates were determined to evaluate the therapeutic effects of post-operative management of patients with HCC. RESULTS: PFS in the CM group was 18.07 months [95% confidence interval (CI): 12.49-23.65] and the 1-, 2-, 3-, 4- and 5-year PFS rates were 61%, 39%, 26%, 22% and 12%, respectively. PFS in the TACE group was 8.03 months (95% CI: 6.63-9.44) and the 1-, 2-, 3-, 4- and 5-year PFS rates were 34%, 11%, 7%, 2% and 0%, respectively. There was significant difference in survival rate between the two groups (P<0.01). The mean survival time (MST) of patients in the CM group was 49.53 months versus 39.90 months of the TACE group. The 1-, 2-, 3-, 4- and 5-year survival rates were 90%, 82%, 80%, 70% and 63%, respectively, in the CM group, and 79%, 70%, 60%, 60% and 36%, respectively, in the TACE group. There was significant difference in survival time between the two groups (P=0.045). CONCLUSIONS: Jiedu granules plus cinobufacini injection, a combination that is commonly used for post-operation management of HCC, can postpone tumor recurrence and metastasis, prolong the survival time and increase the survival rate of post-surgical patients with HCC. However, these findings need to be confirmed in a prospective, randomized controlled trial.

[Preventive effects of a sachet of Chinese herbs on influenza and its immune regulation].

OBJECTIVE: To study the clinical efficacy of Pihui Fanggan Sachet (PHFGS), a sachet of traditional Chinese herbs, in preventing influenza and its immune regulation on mice. METHODS: In clinical study, 239 children from Shanghai Baoshan Xubeihong Art Kindergarten were randomly divided into two groups according to different class; 118 children were treated with PHFGS for 45 days as treatment group and 121 children were as blank control. During the observation period, the incidence rate of influenza, the course of disease and the severity of symptoms were recorded. In experimental study, 40 Kunming mice were randomly divided into normal control group (normal mice treated or not treated with PHFGS), and immunocompromised group (immunocompromised mice treated or not treated with PHFGS). Immunocompromise was induced by intraperitoneal injection of 80 mg/kg cyclophosphamide for 3 days. Some mice in the normal control and immunocompromised groups were then treated with extracted solution of PHFGS through nasal cavity for one week. Spleen index, content of CD(3)(+) T cells and CD(4)(+) T cells, CD(4)(+)/CD(8)(+) ratio, activity of natural killer (NK) cells, serum level of interferon γ (INF-γ) and respiratory level of secretory immunoglobulin A (SIgA) were evaluated. RESULTS: The incidence rate of influenza in the treatment group was much lower than that in the blank control group (P<0.01), and the average course was shortened as compared with the control group (P<0.01). The fever, rhinocleisis, runny nose, and throat congestion in the treatment group were improved as compared with the blank control group (P<0.05, P<0.01). After injection of cyclophosphamide, the spleen index, content of CD(3)(+) T cells and CD(4)(+) T cells, CD(4)(+)/CD(8)(+) ratio, activity of NK cells, serum level of INF-γand respiratory level of SIgA in the immunocompromised group were significantly lower than those in the normal control group (P<0.05 or P<0.01), which indicated the immunosuppression. After treated with PHFGS for one week, the spleen index and the respiratory level of SIgA in the immunocompromised group were improved significantly. Although the content of CD(3)(+) T cells and CD(4)(+) T cells, CD(4)(+)/CD(8)(+) ratio and the serum level of INF-γ were improved, the differences did not reach the significant level. No significant effects on immune function of normal mice were observed. CONCLUSION: PHFGS can prevent influenza effectively by improving the immunity, especially the respiratory mucosal immune function.

[Towards better understanding the definition of cancerous toxin].

The author explained the definition and its scientific value of "cancerous toxin" proposed by Professor Chang-quan Ling, pointing out that it is helpful for better understanding the pathogenic factor and guiding the diagnosis and treatment of cancer. In regard to the new definition of "cancerous toxin", the author put forward three key issues which should be solved in the field of integrated Chinese and Western medicine. First, the pathological property of cancerous toxin should be uncovered. Second, the relationship between cancerous toxin and syndrome differentiation or dosage of herbs need be further explored. Last, the cause of cancerous toxin is still unknown.

[Characteristics of sublingual vein and expressions of vascular endothelial growth factor and hypoxia-inducible factor 1alpha proteins in sublingual tissues of Beagle dogs with portal hypertension].

OBJECTIVE: To observe sublingual vein characteristics and the expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1alpha (HIF-1alpha) proteins in sublingual tissues of Beagle dogs with cirrhotic portal hypertension. METHODS: Twelve Beagle dogs were randomly divided into normal control group and cirrhotic portal hypertension group. There were 6 dogs in each group. A canine model of cirrhosis portal hypertension was established by injecting dimethylnitrosamine (DMN) into portal vein once a week for 7 weeks. The characteristics of sublingual vein were observed. Portal venous pressure was measured by using bioelectric recording techniques. The expressions of VEGF and HIF-1alpha proteins in sublingual vein were detected by immunohistochemical method. RESULTS: The shape and color of sublingual vein in beagle dogs in the cirrhotic portal hypertension group changed obviously as compared with the normal control group. Immunohistochemical results showed that there were almost no expressions of VEGF and HIF-1alpha proteins in sublingual tissues in the normal control group; however, the expressions of VEGF and HIF-1alpha proteins in sublingual tissues in the cirrhotic portal hypertension group significantly increased. CONCLUSION: Changes of portal pressure may lead to the formation of the abnormal sublingual vein by increasing the expressions of VEGF and HIF-1alpha proteins in sublingual tissues in Beagle dogs with portal hypertension.

[Dose-response patterns of Radix Glycyrrhizae in Shanghan Lun].

In order to explore the dose-response patterns of Gancao (Radix Glycyrrhizae) in Shanghan Lun (Treatise on Febrile Diseases), all prescriptions containing Gancao in Shanghan Lun were analyzed by frequency and hierarchical clustering analysis. The doses of Gancao used in Shanghan Lun ranged from six zhu (Chinese unit, and one zhu is equal to 0.65 g) to four liang (Chinese unit, and one liang is equal to 15.625 g). Doses of one, two, three or four liang were commonly used. One liang Gancao as juvantia was usually matched with Mahuang (Herba Ephedrae), Xingren (Semen Armeniacae) and Guizhi (Ramulus Cinnamomi) for restricting the excessive diaphoresis of Mahuang. Two liang Gancao was often matched with some couple drugs, such as Guizhi and Shaoyao (Radix Paeoniae), Shigao (Gypsum Fibrosum) and Zhimu (Rhizoma Anemarrhenae), Fuzi (Radix Aconiti Lateralis) and Ganjiang (Rhizoma Zingiberis), for warming yang to supplement qi, nourishing yin, detoxifying Fuzi, and preventing qi impairment from heat evil. Three liang Gancao was mainly matched with Banxia (Rhizoma Pinelliae) or Renshen (Radix Ginseng) for treating middle energizer emesis. Four liang Gancao was matched with Ganjiang or tonifying herbs for invigorating vital qi and relieving spasm in deficiency syndromes with contraction, palpitation or diarrhea. Gancao is used for treating many syndromes in Shanghan Lun. It is frequently used to treat excess or heat syndromes with one or two liang in a dose and deficiency or cold syndromes with three or four liang in a dose.