Diagnostic accuracy of Golgi protein 73 in primary hepatic carcinoma using ELISA: a systematic review and meta-analysis.

BACKGROUND: Primary hepatic carcinoma (PHC) is currently one of the most common worldwide causes of cancer death. Golgi protein 73 (GP73) has been proposed as potential diagnostic marker. However, it is controversial because of inconsistent diagnostic accuracy in different studies. The aim of this study was to assess the diagnostic accuracy of GP73 for PHC. METHODS: All the studies relating to the diagnostic accuracy of GP73 for patients with PHC from 1978 to January 2013 were collected. Methodological quality was assessed by Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). The overall diagnostic sensitivity, specificity, and area under the receiver operating characteristic curve were used to evaluate the diagnostic accuracy of GP73 using Meta-DiSc statistical software. RESULTS: Altogether 5,637 subjects were included in the 25 selected studies. The sensitivity and specificity (95% confidence interval) of GP73 was 0.75 (0.73-0.76) and 0.84 (0.83 - 0.86), respectively. The area under the summary receiver operating characteristic curve (AUC) and Q* index of GP73 was 0.8616 and 0.8021. CONCLUSIONS: Serum GP73 has a relatively high diagnostic accuracy in primary hepatic carcinoma with better sensitivity and high specificity than AFP.

A study on the immunomodulation of polysaccharopeptide through the TLR4-TIRAP/MAL-MyD88 signaling pathway in PBMCs from breast cancer patients.

CONTEXT: Polysaccharopeptide (PSP), isolated from the Coriolus versicolor COV-1 strain, has been widely used as an immunoadjuvant for cancer immunotherapy. OBJECTIVE: The present study was undertaken to examine the role of PSP on the TLR4-TIRAP/MAL-MyD88 signaling pathway in peripheral blood mononuclear cells (PBMCs) from breast cancer patients. METHODS: For blockade of TLR4, cells were cultured with or without PSP and anti-TLR4 for 24 h, and then the mRNA and proteins (IL-12, IL-6, and TNF-α) levels in each group were detected by Q-PCR and ELISA. Meanwhile, Q-PCR and western blot analysis were used to detect the expression of TLR4-TIRAP/MAL-MyD88 pathway genes and proteins under the regulation of PSP. RESULTS: As anticipated, the transcription and expression of genes (IL-12 and TNF-α) in the anti-TLR4 group were significantly downregulated compared with the control group, while genes (IL-12, IL-6 and TNF-α) in the PSP group were significantly upregulated. Moreover, the mRNA levels in the PSP+anti-TLR4 group were significantly upregulated compared with the anti-TLR4 group. The results of ELISA were as the same as Q-PCR. Genes, kinase phosphorylation levels and proteins in the TLR4 pathway were significantly upregulated by PSP. CONCLUSIONS: Collectively, our study revealed that PSP has an immunoregulatory effect through regulation of the TLR4-TIRAP/MAL-MyD88 signaling pathway.

Diagnostic value of HE4 for ovarian cancer: a meta-analysis.

BACKGROUND: Ovarian cancer (OC) is the second most common gynecological cancer and the first cause of death from gynecological malignancy in Western Europe and the USA. While human epididymis-specific protein 4 (HE4) has been reported as a predictive diagnostic index, it has not been widely accepted because of inconsistent conclusions. The aim of this study was to evaluate the diagnostic value of HE4 systematically for ovarian cancer. METHODS: All relevant original studies about HE4 in the diagnosis of ovarian cancer published from January 1974 to May 2011 were retrieved. By measuring methodological qualities, 12 papers were selected for this study, while 531 articles were searched. The overall diagnostic sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-), and area under the receiver operating characteristic curve (AUC-ROC) were used to evaluate the diagnostic value of HE4 for ovarian cancer using the Meta-DiSc statistical software. RESULTS: There were 2607 subjects included in this meta-analysis. The sensitivity, specificity, LR+ and LR- (95% confidence interval) of HE4 was 0.800 (0.770-0.827), 0.916 (0.902-0.929), 10.271 (6.982-15.109) and 0.228 (0.181-0.287), respectively. The area under the summary receiver operating characteristic (sROC) curve of HE4 was 0.946. The index of Q* was 0.885. CONCLUSIONS: HE4 was found to be better than CA125 as an auxiliary indicator for the diagnosis of ovarian cancer in terms of better sensitivity, specificity, LR+ and LR-.

Diagnostic value of pro-gastrin-releasing peptide for small cell lung cancer: a meta-analysis.

BACKGROUND: Lung cancer, of which 15%-20% is small cell lung cancer, is the leading cause of cancer mortality and shows a high incidence worldwide. While pro-gastrin-releasing peptide (ProGRP) has been reported as a predictive diagnostic factor, it has not been widely accepted because of inconsistent conclusions. The aim of this study was to systematically evaluate ProGRP as the diagnostic standard for small cell lung cancer. METHODS: All published studies on ProGRP in the diagnosis of small cell lung cancer from January 1994 to April of 2010 were retrieved. By measuring methodological qualities, 11 papers were selected for this study. The overall diagnostic sensitivity, specificity, and area under the receiver operating characteristic curve were used to evaluate ProGRP as the diagnostic standard for small cell lung cancer using Meta DiSc statistical software. RESULTS: There were 5146 subjects included in this meta-analysis. The sensitivity and specificity (95% confidence interval) of ProGRP was 0.716 (0.688-0.743) and 0.921 (0.909-0.932), respectively. The area under the summary receiver operating characteristic curve of ProGRP was 0.9236. The index of Q* was 0.8575. CONCLUSIONS: ProGRP has better sensitivity and high specificity as an auxiliary indicator for the diagnosis of small cell lung cancer.

[The protective effects of agmatine in zymosan induced acute lung injury in mice].

OBJECTIVE: To examine the protective effects of agmatine (AGM) administration on zymosan (ZYM)-induced inflammatory response and acute lung injury (ALI) in mice. METHODS: 32 adult male C57BL/6 mice were randomly divided into four groups (n=8 each) to receive i. p. administration of:() phosphate buffer saline (PBS, 0. 5 ml); © AGM (200 mg/kg); © ZYM (500 mg/kg)+PBS (0.5 ml),and ® AGM (200 mg/kg)-ZYM (500 mg/kg). Blood samples and peritoneal exudates were collected from the animals 12 hours after drug administration for concentration of tumor necrosis factor-a (TNF-a),interleukin-6 (IL-6) and nitric oxide (NO) by enzyme linked immunosorbent assay (ELISA). Lung tissue samples were also collected at the same time for histological examination, and determination of tissue content of TNF-a, IL-6, myeloperoxidase (MPO) activity and nuclear factor-KB p65 (NF-cB p65) DNA-binding activity. RESULTS: 12 hours after ZYM injection, the treated mice became lethargic, their activity and water consumption were both reduced, AGM greatly improved the general status, activity, and water consumption in treated mice, while attenuated the increase of TNF-a (ng/L: 252. 6+ 32. 1 vs. 421. 7- 76. 7, 295. 7 ± 78. 6vs. 592. 0 ± 84. 3, both P<0. 05) , IL-6 (ng/L: 2 198. 8 281.8 vs. 4 725. 3 615.4, 19 829. 3 ± 3 647. Ovs. 47 751. 3 ± 5 264.8, both P<0. 05) and NO (pmol/L: 33. 2 ± 4. 3 vs. 50. 2 ± 5. 2, 14.0 ± 3. 6 vs. 45.4 ± 5. 2, both P<0. 05) in serum and peritoneal exudates caused by ZYM. AGM also attenuated the increase of TNF-a (ng/L: 245. 7 ± 39. 1 vs. 378. 3 ± 67. 6, P<0. 05), IL-6 (ng/L: 810. 3 ± 175. 6 vs. 1 172. 4 ± 203.3,P <0. 05), MPO activity (ng/mg: 24. 9 4. 4 vs. 37. 3 5.8, P< 0. 05) and NF-iB p65 optical density(absorbance value: 0. 272 + 0. 029 vs. 0. 347 ± 0. 037, P 0.05) in the lung tissue seen in ZYM treated animals. There was no significant difference between normal PBS and AGM treated group in all the indexes examined. Histological examination demonstrated that ZYM treated animals had severe inflammatory reaction in lung tissues (manifested as vasodilatation and neutrophils infiltration) and AGM significantly reduced such injury. CONCLUSION: AGM can attenuate the ALI and inflammation induced by ZYM in mice.

[Immunoregulatory activity of polysaccharopeptide and Astragalus polysaccharides on EAC tumor-bearing mice].

OBJECTIVE: To investigate the immunoregulatory activities of polysaccharopeptide and astragalus polysaccharides on EAC tumor-bearing mice. METHOD: Ehrlich's ascites carcinoma (EAC) Kunming (KM) mice were used to establish the animal model for solid tumor. Mice were randomly divided into six groups (n = 10): NS group (NS, 10 mL x kg(-1) x d(-1)), AMD group (AMD, 4 mg x kg(-1) x d(-1), 0.2 mL, only for the first 3 days), PSP group (PSP, 250 mg x kg(-1) x d(-1), 0.2 mL), APS group (APS, 250 mg x kg(-1) x d(-1), 0.2 mL), complex prescription group (PSP + APS, 250 mg x kg(-1) x d(-1), 0.1 mL) and combined treat group (AMD + PSP + APS, same dosage as above). After thirty days of treatment, immunocytochemical method was employed to detect the changes of T-lymphocyte subsets in the PBMC of tumor-bearing mice. Subsequently, the organ indexes and tumor inhibition rate were calculated and compared with those of control group. RESULT: Percentage of CD3+, CD4+ T-cell and the ratio of CD4+/CD8+ were obviously prominence in the PSP and PSP + APS groups compared with those of NS group (0.05), percentage of CD8+ T-cell was significantly decreased compared with that of AMD group; percentage of CD3+, CD4+ T-cell were obviously increased in AMD + PSP + APS group relative to that of AMD group; the thymus index of AMD group was significantly decreased compared with that of NS group, but the thymus index of AMD + PSP + APS group was obviously increased compared with that of AMD group; the weight of tumor in each administration group was significantly decreased compared with that of NS group. CONCLUSION: PSP and PSP + APS complex prescription showed the remarkable immunoregulation on EAC mice with chemotherapy or not.

Clinical studies of immunomodulatory activities of Yunzhi-Danshen in patients with nasopharyngeal carcinoma.

OBJECTIVES: Nasopharyngeal carcinoma (NPC) is a prevalent tumor in Hong Kong. The immune system of such patients could be adversely affected during the course of conventional chemotherapy or radiotherapy. We investigated the immunomodulatory effects of Traditional Chinese Medicine (TCM) Yunzhi-Danshen capsules in NPC patients treated with radiotherapy. DESIGN: Randomized, double-blind, placebo-controlled 16-week study. SETTING/LOCATION: The Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong. SUBJECTS: Twenty-seven (27) patients with histologically proven NPC, at least 18 years of age. METHODS: Twenty-seven patients with histologically proven NPC were recruited to take Yunzhi (3.6 g daily) and Dangshem (1.4 g daily) in the form of 12 combination capsules (TCM group) or placebo (12 capsules) daily for 16 weeks, respectively. Flow cytometry was used to assess the percentages and absolute counts of human lymphocyte subsets in whole blood. Plasma concentration of soluble interleukin-2 receptor and soluble tumor necrosis factor receptor 2 was measured by enzyme-linked immunosorbent assay (ELISA). Ex vivo production of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-10 in the whole blood assay culture supernatant was measured by ELISA. RESULTS: The decreases in percentage and absolute count of T lymphocytes in the TCM group were less than those in the placebo group after they took the capsules for 16 weeks (both p < 0.05). Furthermore, the decreases in absolute count of T suppressor cells plus cytotoxic T lymphocytes, and T helper cells in the TCM group were significantly lower than those in the placebo group after they took the capsules for 16 weeks (both p < 0.05). CONCLUSION: These results suggest that Yunzhi-Danshen can exert an immunomodulating effect in alleviating lymphopenia during radiotherapy in NPC patients.

Immunomodulatory activities of Yunzhi and Danshen in post-treatment breast cancer patients.

Breast cancer is the most common cancer among women worldwide. Discomfort and fatigue are usually arisen from anticancer therapy such as surgery, radiotherapy, chemotherapy, hormonal therapy, or combination therapy, because of the suppressed immunological functions. Yunzhi (Coriolus versicolor) can modulate various immunological functions in vitro, in vivo, and in human clinical trials. Danshen (Salvia miltiorrhiza) has been shown to benefit the circulatory system by its vasodilating and anti-dementia activity. The purpose of this clinical trial was to evaluate the immunomodulatory effects of Yunzhi-Danshen capsules in post-treatment breast cancer patients. Eighty-two patients with breast cancer were recruited to take Yunzhi [50 mg/kg body weight, 100% polysaccharopeptide (PSP)] and Danshen (20 mg/kg body weight) capsules every day for a total of 6 months. EDTA blood samples were collected every 2 months for the investigation of immunological functions. Flow cytometry was used to assess the percentages and absolute counts of human lymphocyte subsets in whole blood. Plasma level of soluble interleukin-2 receptor (sIL-2R) was measured by enzyme-linked immunosorbent assay (ELISA). Results showed that the absolute counts of T-helper lymphocytes (CD4+), the ratio of T-helper (CD4+)/T suppressor and cytotoxic lymphocytes (CD8+), and the percentage and the absolute counts of B-lymphocytes were significantly elevated in patients with breast cancer after taking Yunzhi-Danshen capsules, while plasma slL-2R concentration was significantly decreased (all p < 0.05). Therefore, the regular oral consumption of Yunzhi-Danshen capsules could be beneficial for promoting immunological function in post-treatment of breast cancer patients.

Safety and efficacy of Ganoderma lucidum (lingzhi) and San Miao San supplementation in patients with rheumatoid arthritis: a double-blind, randomized, placebo-controlled pilot trial.

OBJECTIVE: To examine the efficacy of popular Chinese herbs used in a traditional Chinese medicine (TCM) combination of Ganoderma lucidum and San Miao San (SMS), with purported diverse health benefits including antioxidant properties in rheumatoid arthritis (RA). METHODS: We randomly assigned 32 patients with active RA, despite disease-modifying antirheumatic drugs, to TCM and 33 to placebo in addition to their current medications for 24 weeks. The TCM group received G lucidum (4 gm) and SMS (2.4 gm) daily. The primary outcome was the number of patients achieving American College of Rheumatology (ACR) 20% response and secondary outcomes included changes in the ACR components, plasma levels, and ex vivo-induced cytokines and chemokines and oxidative stress markers. RESULTS: Eighty-nine percent completed the 24-week study. Fifteen percent in the TCM group compared with 9.1% in the placebo group achieved ACR20 (P > 0.05). Pain score and patient's global score improved significantly only in the TCM group. The percentage, absolute counts, and CD4+/CD8+/natural killer/B lymphocytes ratio were unchanged between groups. CD3, CD4, and CD8 lymphocyte counts and markers of inflammation including plasma interleukin-18 (IL-18), interferon-gamma (IFNgamma)-inducible protein 10, monocyte chemoattractant protein 1, monokine induced by IFNgamma, and RANTES were unchanged. However, in an ex vivo experiment, the percentage change of IL-18 was significantly lower in the TCM group. Thirteen patients reported 22 episodes (14 in placebo group and 8 in TCM group) of mild adverse effects. CONCLUSION: G lucidum and San Miao San may have analgesic effects for patients with active RA, and were generally safe and well tolerated. However, no significant antioxidant, antiinflammatory, or immunomodulating effects could be demonstrated.

Immunomodulatory effects of lingzhi and san-miao-san supplementation on patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune joint disease. We evaluated a standard preparation of Lingzhi (Ganoderma lucidum) and San-Miao-San (Rhizoma atractylodis, Cortex phellodendri, Radix achyranthes bidentatae) capsules (TCM group) for its supplementary treatment efficacy for RA. There was no significant difference in the absolute count, percentage, and ratios of CD4(+)/CD8(+)/natural killer/B lymphocytes between the TCM and placebo groups after taking the capsules (all p > 0.05). There was no significant change in concentrations of plasma cytokines of interferon-gamma-induced protein-10 (IP-10), monocyte chemoattractant protein-1, monokine induced by IFN-gamma, regulated upon activation normal T-cell expressed and secreted, interleukin (IL)-8, and IL-18 after taking the capsules for 8 and 24 weeks (all p > 0.05). The percentage change in ex vivo-induced level of inflammatory cytokine IL-18 was significantly lower in the TCM group than in the placebo group after taking the capsules for 24 weeks (p < 0.05). Therefore, Lingzhi and San-Miao-San capsules might exert a beneficial immunomodulatory effect in patients with rheumatoid arthritis.