Effects of ultrasound-guided alveolar recruitment manoeuvres compared with sustained inflation or no recruitment manoeuvres on atelectasis in laparoscopic gynaecological surgery as assessed by ultrasonography: a randomized clinical trial.

BACKGROUND: The majority of patients may experience atelectasis under general anesthesia, and the Trendelenburg position and pneumoperitoneum can aggravate atelectasis during laparoscopic surgery, which promotes postoperative pulmonary complications. Lung recruitment manoeuvres have been proven to reduce perioperative atelectasis, but it remains controversial which method is optimal. Ultrasonic imaging can be conducive to confirming the effect of lung recruitment manoeuvres. The purpose of our study was to assess the effects of ultrasound-guided alveolar recruitment manoeuvres by ultrasonography on reducing perioperative atelectasis and to check whether the effects of recruitment manoeuvres under ultrasound guidance (visual and semiquantitative) on atelectasis are superior to sustained inflation recruitment manoeuvres (classical and widely used) in laparoscopic gynaecological surgery. METHODS: In this randomized, controlled, double-blinded study, women undergoing laparoscopic gynecological surgery were enrolled. Patients were randomly assigned to receive either lung ultrasound-guided alveolar recruitment manoeuvres (UD group), sustained inflation alveolar recruitment manoeuvres (SI group), or no RMs (C group) using a computer-generated table of random numbers. Lung ultrasonography was performed at four predefined time points. The primary outcome was the difference in lung ultrasound score (LUS) among groups at the end of surgery. RESULTS: Lung ultrasound scores in the UD group were significantly lower than those in both the SI group and the C group immediately after the end of surgery (7.67 ± 1.15 versus 9.70 ± 102, difference, -2.03 [95% confidence interval, -2.77 to -1.29], P < 0.001; 7.67 ± 1.15 versus 11.73 ± 1.96, difference, -4.07 [95% confidence interval, -4.81 to -3.33], P < 0.001;, respectively). The intergroup differences were sustained until 30 min after tracheal extubation (9.33 ± 0.96 versus 11.13 ± 0.97, difference, -1.80 [95% confidence interval, -2.42 to -1.18], P < 0.001; 9.33 ± 0.96 versus 10.77 ± 1.57, difference, -1.43 [95% confidence interval, -2.05 to -0.82], P < 0.001;, respectively). The SI group had a significantly lower LUS than the C group at the end of surgery (9.70 ± 1.02 versus 11.73 ± 1.96, difference, -2.03 [95% confidence interval, -2.77 to -1.29] P < 0.001), but the benefit did not persist 30 min after tracheal extubation. CONCLUSIONS: During general anesthesia, ultrasound-guided recruitment manoeuvres can reduce perioperative aeration loss and improve oxygenation. Furthermore, these effects of ultrasound-guided recruitment manoeuvres on atelectasis are superior to sustained inflation recruitment manoeuvres. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR2100042731, Registered 27 January 2021, www.chictr.org.cn .

A Novel Strategy for Regulating mRNA's Degradation via Interfering the AUF1's Binding to mRNA.

The study on the mechanism and kinetics of mRNA degradation provides a new vision for chemical intervention on protein expression. The AU enrichment element (ARE) in mRNA 3'-UTR can be recognized and bound by the ARE binding protein (AU-rich Element factor (AUF1) to recruit RNase for degradation. In the present study, we proposed a novel strategy for expression regulation that interferes with the AUF1-RNA binding. A small-molecule compound, JNJ-7706621, was found to bind AUF1 protein and inhibit mRNA degradation by screening the commercial compound library. We discovered that JNJ-7706621 could inhibit the expression of AUF1 targeted gene IL8, an essential pro-inflammatory factor, by interfering with the mRNA homeostatic state. These studies provide innovative drug design strategies to regulate mRNA homeostasis.

Cucurbitacin B inhibits the migration and invasion of breast cancer cells by altering the biomechanical properties of cells.

Changes in cellular biomechanical properties affect cell migration and invasion. The natural compound Cucurbitacin B (CuB) has potent anticancer activity; however, the mechanism underlying its inhibitory effect on breast cancer metastasis needs further study. Here, we showed that low-dose CuB inhibited adhesion and altered the viscoelasticity of breast cancer cells, thereby, reducing cell deformability. In vitro and in vivo experiments proved that CuB effectively inhibited the migration and invasion of breast cancer cells. Further studies have found that CuB downregulated the expression of F-actin/vimentin/FAK/vinculin in breast cancer cells, altering the distribution and reorganization of cytoskeletal proteins in the cells. CuB inhibited signaling by the Rho family GTPases RAC1/CDC42/RhoA downstream of integrin. These findings indicate that CuB has been proven to mediate the reorganization and distribution of cytoskeletal proteins of breast cancer cells through RAC1/CDC42/RhoA signaling, which improves the mechanical properties of cell adhesion and deformation and consequently inhibits cell migration and invasion.

Pretreatment plasma D-dimer, fibrinogen, and platelet levels significantly impact prognosis in patients with epithelial ovarian cancer independently of venous thromboembolism.

OBJECTIVE: The study aimed to evaluate the prognostic value of pretreatment plasma dimerized plasmin fragment D (D-dimer), fibrinogen, and platelet levels in epithelial ovarian cancer (EOC) after adjusting for venous thromboembolism (VTE) and to screen out the patients with the greatest risk for poor prognosis. METHODS: The study comprised 190 patients with EOC. The plasma D-dimer, fibrinogen, and platelet levels were examined before treatment and analyzed with patient clinicopathological parameters, progression-free survival (PFS), and overall survival (OS). The survival analysis was performed using the Kaplan-Meier method, and prognostic factors were assessed using the Cox proportional hazards regression model. RESULTS: The incidences of elevated plasma D-dimer levels, hyperfibrinogenemia, and thrombocytosis were 40%, 42.11%, and 45.26%, respectively. Elevated plasma D-dimer level, hyperfibrinogenemia, and thrombocytosis were associated with advanced tumor stage (P < 0.001, P = 0.013, P < 0.001). In addition, the elevated plasma D-dimer levels were associated with macroscopic postoperative residual disease (P = 0.002) and VTE events (P = 0.006). In multivariate Cox regression model, plasma D-dimer, fibrinogen, and platelet levels were identified as independent prognostic factors for OS (P = 0.039, P = 0.002, and P = 0.049). However, plasma fibrinogen and platelet levels, but not D-dimer levels, had independent prognostic value for PFS (P = 0.012 and P = 0.022). Patients with at least any 2 abnormalities of plasma D-dimer, fibrinogen, and platelet levels showed shorter PFS and OS than did patients with at most 1 abnormality of 3 parameters (P < 0.001). CONCLUSIONS: Pretreatment plasma D-dimer, fibrinogen, and platelet levels, which impact prognosis independently of VTE, were demonstrated to be potential markers to predict disease progression and surgery outcome in patients with EOC. The combined use of plasma D-dimer, fibrinogen, and platelet levels may help to identify the high-risk populations for treatment decisions.

Network Pharmacology Based Elucidation of Molecular Mechanisms of Laoke Formula for Treatment of Advanced Non-Small Cell Lung Cancer.

OBJECTIVE: To explore the specific pharmacological molecular mechanisms of Laoke Formula (LK) on treating advanced non-small cell lung cancer (NSCLC) based on clinical application, network pharmacology and experimental validation. METHODS: Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of Chinese medicine (CM) treatment in 296 patients with NSCLC in Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2015. The compounds of LK were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the corresponding targets were performed from Swiss Target Prediction. NSCLC-related targets were obtained from Therapeutic Target Database and Comparative Toxicogenomics Database. Key compounds and targets were identified from the compound-target-disease network and protein-protein interaction (PPI) network analysis, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were used to predict the potential signaling pathways involved in the treatment of advanced NSCLC with LK. The binding affinities between key ingredients and targets were further verified using molecular docking. Finally, A549 cell proliferation and migration assay were used to evaluate the antitumor activity of LK. Western blot was used to further verify the expression of key target proteins related to the predicted pathways. RESULTS: Kaplan-Meier survival analysis showed that the overall survival of the CM group was longer than that of the non-CM group (36 months vs. 26 months), and COX regression analysis showed that LK treatment was an independent favorable prognostic factor (P=0.027). Next, 97 components and 86 potential targets were included in the network pharmacology, KEGG and GO analyses, and the results indicated that LK was associated with proliferation and apoptosis. Moreover, molecular docking revealed a good binding affinity between the key ingredients and targets. In vitro, A549 cell proliferation and migration assay showed that the biological inhibition effect was more obvious with the increase of LK concentration (P<0.05). And decreased expressions of nuclear factor κB1 (NF-κB1), epidermal growth factor receptor (EGFR) and AKT serine/threonine kinase 1 (AKT1) and increased expression of p53 (P<0.05) indicated the inhibitory effect of LK on NSCLC by Western blot. CONCLUSION: LK inhibits NSCLC by inhibiting EGFR/phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, NFκB signaling pathway and inducing apoptosis, which provides evidence for the therapeutic mechanism of LK to increase overall survival in NSCLC patients.

Gekko-sulfated glycopeptide inhibits tumor angiogenesis by targeting basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) is a therapeutic target of anti-angiogenesis. Here, we report that a novel sulfated glycopeptide derived from Gekko swinhonis Guenther (GSPP), an anticancer drug in traditional Chinese medicine, inhibits tumor angiogenesis by targeting bFGF. GSPP significantly decreased the production of bFGF in hepatoma cells by suppressing early growth response-1. GSPP inhibited the release of bFGF from extracellular matrix by blocking heparanase enzymatic activity. Moreover, GSPP competitively inhibited bFGF binding to heparin/heparan sulfate via direct binding to bFGF. Importantly, GSPP abrogated the bFGF-stimulated proliferation and migration of endothelial cells, whereas it had no inhibitory effect on endothelial cells in the absence of bFGF. Further study revealed that GSPP prevented bFGF-induced neovascularization and inhibited tumor angiogenesis and tumor growth in a xenograft mouse model. These results demonstrate that GSPP inhibits tumor angiogenesis by blocking bFGF production, release from the extracellular matrix, and binding to its low affinity receptor, heparin/heparan sulfate.

Proposal of a new classification for stage III colorectal cancer based on the number and ratio of metastatic lymph nodes.

BACKGROUND: The objective of this retrospective study was to determine whether the current staging system for stage III colorectal cancer (CRC) is appropriate and to assess the value of the metastatic lymph node ratio (LNR) in predicting the prognosis of patients with stage III CRC. METHODS: From 2000 to 2006 inclusively, 245 patients with stage III CRC underwent curative resection. The follow-up was closed in March 2012. Kaplan-Meier survival curves and log-rank tests were used for the survival analysis. RESULTS: Survival time of patients with T3N1M0 was significantly better than that for patients in other subgroups of stage IIIB and similar to that of patients with stage IIIA disease. The greatest survival difference was found with 0.30 as the LNR cutoff point for patients with current stage III CRC. Survival time of patients with LNR ≤ 0.30 was significantly better than that of those with LNR > 0.30. rN1 included stage III patients with LNR ≤ 0.30, and rN2 included patients with LNR > 0.30. Survival time of patients with T4aN1(rN2)M0 staging was significantly worse than that for patients with T4aN1(rN1)M0 staging and similar to that of patients with stage IIIC CRC. CONCLUSIONS: We propose an algorithm to incorporate LNR into the current American Joint Committee on Cancer staging system. In it the patients with T3N1M0 are excluded from the current stage IIIB and included in the stage IIIA group. Also, patients with T4aN1(rN2)M0 are excluded from the current stage IIIB group and included in the stage IIIC group.

Proposal of new classification for stage III breast cancer on the number and ratio of metastatic lymph nodes.

BACKGROUND: The objective of the retrospective study was to confirm whether the current staging system of stage III was appropriate for breast cancer. METHODS: Four hundred fifteen patients with breast cancer in stage III were analyzed. The survival analysis was performed by Kaplan-Meier. RESULTS: Survival time of the patients with T1N3M0 was significantly better than the patients with other subgroups of stage IIIC (T2,3,4N3M0) and similar that of patients with T4N0,1,2M0 who formed the stage IIIB group based on pN stage. Tumor size, number of positive lymph nodes and lymph node ratio (LNR) were associated with overall survival (OS). The greatest survival difference was found when 0.60 as the cutoff point of LNR for the patients with current stage IIIC (pN3). rN1 included the patients in pN3 with LNR ≤ 0.60 and rN2 included the patients in pN3 with LNR >0.60. Survival time of the patients with T1,2,3,4N3(rN1)M0 and T1N3(rN2)M0 was differently better than the patients with T2,3,4N3(rN2)M0 and similar that of patients with T4N0,1,2M0. CONCLUSION: We suggested current staging system should be modified combining pN with rN. We presumed the patients with T1N3M0 and T2,3,4N3(rN1)M0 disease were excluded from the current stage IIIC and included in stage IIIB group.

Design, synthesis, and evaluation of 9-(pyrimidin-2-yl)-9H-carbazole derivatives disrupting mitochondrial homeostasis in human lung adenocarcinoma.

Since more than 85% of lung cancer cases are non-small cell lung cancer (NSCLC), finding novel agents with anti-tumor activities is meaningful for NSCLC patients. Mitochondria is essential for cellular energy metabolism in cancer, and regulating mitochondrial bioenergetics is emerging as a practical approach for cancer treatment and prevention. The carbazole scaffold is an active structure showing anti-cancer biological activity, and the structural diversity has been expanded through the improvement and optimization of synthesizing methods. To find novel carbazole derivatives with great anti-tumor potential and explore structures variety, we designed and synthesized a series of 9-(pyrimidin-2-yl)-9H-carbazole derivatives based on the previously reported Cp∗Rh(III)/H+ tandem catalytic system. With thoroughly bioactivity exploration, we found benzo[d] [1,3]dioxol-5-yl(9-(pyrimidin-2-yl)-9H-carbazol-1-yl)methanone (compound 5n) showed notable activity in disrupting the mitochondrial homeostasis, induced cell cycle arrest and apoptosis in human adenocarcinoma cells, and finally showed anti-tumor activity in an NSCLC-xenograft mice model.

Anti-migration effects of Gekko sulfated glycopeptide on human hepatoma SMMC-7721 cells.

Gekko swinhonis Guenther has been used as an anti-cancer drug in traditional Chinese medicine for hundreds of years. Previous studies showed that the Gekko sulfated polysaccharide-protein complex suppressed the proliferation and migration of hepatoma cells. Gekko sulfated glycopeptide α was obtained from Gekko sulfated polysaccharide-protein complex using papain hydrolysis. Gekko sulfated glycopeptide α inhibited the proliferation and migration of SMMC-7721 cells. The secretion of IL-8 and the concentration of intracellular calcium were decreased after Gekko sulfated glycopeptide α exposure. SMMC-7721 cells in the control group showed abnormal features, with a polygonal shape, whereas this changed to a spindle shape after the treatment with Gekko sulfated glycopeptide α. Actin filaments were distributed diffusely along the cell membrane in control cells, whereas those were polymerized and preferentially accumulated in the cytoplasm of treated cells. Microtubules distributed in the cytoplasm of untreated cells were located diffusely whereas those in treated cells were polymerized. Therefore, Gekko sulfated glycopeptide α inhibit the migration of hepatoma cells via reducing the secretion of IL-8 and the concentration of intracellular calcium, as well as regulating the reorganization of cytoskeleton.

Prunella vulgaris Polysaccharide Inhibits Growth and Migration of Breast Carcinoma-Associated Fibroblasts by Suppressing Expression of Basic Fibroblast Growth Factor.

OBJECTIVE: To study the effects of Prunella vulgaris polysaccharide (PVP) on human breast carcinoma-associated fibroblasts (CAFs). METHODS: Cell viability was detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-(3-carboxymethoxyphenyl)-2-4-sulfophenyl)-2H-tetrazolium (MTS) assay. Wound healing experiment and transwell migration assay were used to investigate the anti-migration effects. Flow cytometry was applied to detect cell apoptosis and cell cycle distribution. Reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to detect the expression of basic fibroblast growth factor (bFGF) in CAFs. Culture SKBr-3 with CAFs conditioned medium (CAFs-CM) to evaluate the indirect function on the proliferation of breast cancer SKBr-3 cells. RESULTS: PVP inhibited the viability of CAFs by inducing apoptosis (P <0.01) and arresting cell cycle (P <0.01). It also inhibited the migration of CAFs (P <0.01). bFGF promoted CAFs proliferation (P <0.01) and migration (P <0.01), protected CAFs from apoptosis (P <0.05) and reduced G0 phase to 49.06% (P <0.01). However, these effects of bFGF on CAFs could be abrogated by PVP. Culturing SKBr-3 with CAFs-CM, PVP could inhibit the viability of breast cancer SKBr-3 cells indirectly. Moreover, PVP reduced the mRNA expression (P <0.01) and protein secretion of bFGF (P <0.01) in CAFs. CONCLUSION: PVP could exert an anti-cancer effect on breast CAFs by inhibiting bFGF expression, thus inhibiting the growth of breast cancer SKBr-3 cells indirectly.

MicroRNA-147b promotes lung adenocarcinoma cell aggressiveness through negatively regulating microfibril-associated glycoprotein 4 (MFAP4) and affects prognosis of lung adenocarcinoma patients.

BACKGROUND: Lung adenocarcinoma (LUAD) is widely known as the leading cause of death in patients with lung cancer. Extensive evidence has determined that microRNAs (miRNAs) exert critical effects on various biological processes in tumorigenesis. microRNA-147b (miR-147b) has been reported to serve as an oncogenic molecule in colorectal cancer and hepatocellular carcinoma, however, its prognostic value and biological effect in LUAD remain rare. MATERIALS AND METHODS: miR-147b and microfibril-associated glycoprotein 4 (MFAP4) data were collected from The Cancer Genome Atlas (TCGA) database to determine their expression levels in LUAD tissues. Kaplan-Meier method was used to plot the overall survival curves for the prognostic power of miR-147b and MFAP4 identification. Chi-square test was utilized to demonstrate the association between clinical characteristics and miR-147b or MFAP4 in LUAD. Luciferse reporter assay was implemented to identify the correlation between miR-147b and MFAP4. The mRNA and protein levels were detected by qRT-PCR and western blotting, respectively. To explore the effects of miR-147b and its potential mechanism in LUAD, cell counting kit 8 (CCK-8), colony formation and transwell assays were performed in LUAD cells with abnormal expression of miR-147b or/and MFAP4. RESULTS: Our results showed that miR-147b was up-regulated in LUAD tissues and cell lines, which induced poor outcome. Conversely, MFAP4, the putative target gene of miR-147b, was down-regulated in LUAD. The expression of MFAP4 in LUAD cells was negatively regulated by miR-147b. Results of experiments in vitro revealed that miR-147b could promote cell proliferation, colony formation, invasion and migration, while up-regulation of MFAP4 suppressed the impacts of miR-147b on cell malignant aggressiveness in A549 and Calu-3 cells. CONCLUSION: In conclusion, these findings determined that miR-147b contributed to the progression of LUAD via targeting MFAP4. Thus, understanding the potential mechanism of miR-147b/MFAP4 may improve the treatment of cancers, especially LUAD.

[Using a new generation of classification system of antineoplastic drugs to guide Chinese medicine research].

A new generation of classification system of antineoplastic drugs was put forward based on comparing the first with the second generation classification system of antineoplastic drugs. Antineoplastic drugs are divided into cytotoxic drug, cells biological behavior regulator, biological response modifier and biochemical modulator. The using of biological response modifier (immune modulator for instance) and biochemical modulator are supplementary methods for Western medicine treatment in tumor, because the cytotoxic effects of Chinese herbs are lower than those of chemotherapeutic drugs. For the new breakthrough of Chinese medicine oncology research, new idea, new technology and new target should be used, the Chinese medicine mechanism should be studied from a new view. Reversing abnormal biological behavior of tumor cells by Chinese medicine could be an important breakthrough of Chinese medicine oncology research.

Origin of cancer stem cells: the role of self-renewal and differentiation.

BACKGROUND: Self-renewal and differentiation potential is the feature of stem cells. Differentiation is usually considered to be a one-way process of specialization as cells develop the functions of their ultimate fate and lose their immature characteristics, such as self-renewal. Progenitor cells, the products of stem cells losing the activity of self-renewal, could differentiate to mature cells, which have the feature of differentiation and lose the activity of self-renewal. The roles for cancer stem cells have been demonstrated for some cancers. However, the origin of the cancer stem cells remains elusive. METHODS: This review focuses on current scientific controversies related to the establishment of the cancer stem cells--in particular, how self-renewal and differentiation block might contribute to the evolution of cancer. RESULTS: Cancer stem cells may be caused by transforming mutations occurring in multi-potential stem cells, tissue-specific stem cells, progenitor cells, mature cells and cancer cells. Progenitor cells obtain the self-renewal activity by activating the self-renewal-associated genes rather than dedifferentiate to tissue special stem cells. The transform multi-potential stem cells gain the differentiation feature of special tissue by differentiating to cancer cells. Mature cells and cancer cells may dedifferentiate or reprogram to cancer stem cells by genetic and / or epigenetic events to gain the self-renewal activity and lose some features of differentiation. The cancer-derived stem cells are not the "cause", but the "consequence" of carcinogenesis. The genetic program controlling self-renewal and differentiation is a key unresolved issue. CONCLUSION: Cancer stem cells may be caused by disturbance of self-renewal and differentiation occurring in multi-potential stem cells, tissue-specific stem cells, progenitor cells, mature cells and cancer cells.

Sublingual Nodules: Diagnostic Markers of Metastatic Breast Cancer.

OBJECTIVE: To evaluate the diagnostic significance of sublingual nodules for metastasis of patients with breast cancer and further to explore the mechanisms of sublingual nodules. METHODS: The image data of 117 in-patients with breast cancer in stage I-IV in Tianjin Medical University Cancer Institute and Hospital from December 2009 to September 2011 were assessed retrospectively. All photos of patients' tongue were recorded by the digital camera of uniform type within 1 month after serological examination and regular re-examined by computed tomography (CT), magnetic resonance imaging and positron emission tomography CT. The presence of sublingual nodules was the positive standard. Chi square test and two-independent-sample test were used to determine the diagnostic value between the status of sublingual nodules and Clinico-pathological characteristics. The optimal cut-off of uric acid (UA) level to diagnose sublingual nodules was determined by receiver operating curve (ROC) analysis. RESULTS: Breast cancer patients with sublingual nodules had a higher risk of recurrence and/or metastasis than patients without it (P<0.001). Sublingual nodules was significantly correlated with increased serum UA level (P=0.001). The optimal cut-off value of UA level to diagnose sublingual nodules was 290 µmol/L. Furthermore, the elevated serum UA level (≥290 µmol/L) was significantly related to breast cancer recurrence and/or metastasis (P<0.001). CONCLUSIONS: Sublingual nodules were potential diagnostic markers for metastatic breast cancer. The formation of sublingual nodules was associated with elevated level of serum UA.

Higenamine enhances the antitumor effects of cucurbitacin B in breast cancer by inhibiting the interaction of AKT and CDK2.

Cucurbitacin B (Cu B), a tetracyclic triterpenoid derived from Trichosanthes kirilowii Maxim, exhibits anticancer effects against various types of tumor. Higenamine, isolated from Radix Aconiti Lateralis Preparata, has been used as a dietary supplement for regulating metabolic function. The present study suggested that higenamine enhances Cu B-induced cytotoxicity in breast cancer cells and in vivo. Network pharmacology analysis was used to identify the possible mechanism of action. Cu B alone inhibited breast cancer cell growth, induced apoptosis, and arrested the cell cycle in the G2/M phase. Cu B combined with higenamine potentiated the cytotoxic effect of Cu B, resulting in the enhanced induction of apoptosis and G2/M arrest. The network pharmacology analysis also found that the major predicted targets of Cu B in breast cancer were AKT, endoplasmic reticulum, farnesyltransferase, CAAX box, α, platelet-derived growth factor receptor α, peroxisome proliferator-activated receptor, RET proto-oncogene, and vascular endothelial growth factor A. The possible targets of higenamine involved in the synergic action were cyclin A2, cyclin-dependent kinase 2 (CDK2), dihydrofolate reductase, and protein kinase CAMP­activated catalytic subunit α. The associated pathways were summarized by Kyoto Encyclopedia of Genes and Genomes pathway analysis, and it was hypothesized that higenamine may enhance the antitumor effects of Cu B in breast cancer through inhibition of the interaction of AKT and CDK2. The protein expression was assayed by western blot analysis. The combined treatment also resulted in significant inhibition of growth in vivo.

Effects of aqueous extracts of Aconitum carmichaeli, Rhizoma bolbostemmatis, Phytolacca acinosa, Panax notoginseng and Gekko swinhonis Guenther on Bel-7402 cells.

AIM: To investigate the anticancer activity of a chinese medical mixture, WRCP (warming and relieving Cold Phlegm), on hepatocarcinoma Bel-7402 cells. METHODS: Fingerprints of WRCP, which were composed of aqueous extracts of Aconitum carmichaeli, Rhizoma bolbostemmatis, Phytolacca acinosa, Panax notoginseng and Gekko swinhonis Guenther, and aconitine, which could be isolated from Aconitum carmichaeli and have the potential toxicity, were identified by high pressure liquid chromatography. Bel-7402 cells were grown in the presence of WRCP, As(2)O(3) or all-trans-retinoic acid (ATRA). Cell proliferation and viability were determined by trypan blue stain. Apoptosis and cell cycle of Bel-7402 cells were detected by flow cytometry. Morphologic and ultrastructural variations were determined under optic and electronic microscopy. The secretion of alpha-fetoprotein and albumin was detected by radioimmunoassay. RESULTS: The average quality of aconitine is 1.15 +/- 0.10 microg per 7.5 g extracts. WRCP could suppress the proliferation and viability of Bel-7402 cells. The percentage of apoptosis cells and S phase cells increased on WRCP-treated cells. Treated with WRCP, Bel-7402 cells showed ultrastructural features of differentiation. The alpha-fetoprotein secretion decreased while the albumin secretion increased (P < 0.001, P < 0.001, respectively) markedly in WRCP-treated cells. CONCLUSION: WRCP can affect the proliferation, differentiation and apoptosis of Bel-7402 cells. It can arrest cells in S phase and has strong cytotoxicity to Bel-7402 cells.

Bone marrow-derived cells: roles in solid tumor. Minireview.

The role of cancer stem cells has been demonstrated for some cancers. Recently, research indicated that solid tumors may originate from bone marrow stem cells. Bone marrow-derived cells have recently been shown to contribute to stromal formation, especially angiogenesis and lymphvasculogenesis. Moreover, the interaction and the cell fusion between cancer cells and bone mesenchymal stem cells could enhance the aggregative ability of cancer cells. Bone marrow derived cells home to tumor-specific pre-metastatic sites to provide a permissive niche for incoming tumor cells. Since bone marrow-derived cells play an important role in carcinogenesis, angiogenesis and metastasis, bone marrow-derived cells are not only the tool for cancer therapy, but also the targets for cancer therapy.

Bone marrow cells: the source of hepatocellular carcinoma?

Whether the stem cells or the mature cells are the origination of hepatocellular carcinoma is uncertain. Recently, researches have shown that some cancer stem cells could derive from adult stem cells. Moreover, gastric cancer could originate from bone marrow stem cells. Hematopoiesis and the hepatic environment are known to have a close relationship at the time of hepatic development and systemic diseases. Here we propose a new carcinogenetic model of hepatocellular carcinoma. Chronic liver injury could recruit bone marrow stem cells to the liver. Bone marrow cells take part in liver regeneration by differentiating to oval cells and hepatocytes. Persistent regeneration results in hyperproliferation, an increased rate of transforming mutations. Extracellular matrix remodeling triggers a cascade of events that inhibits the transactivation potential of liver-specific transcription factors, blocks the maturation of stem cells, and then results in hepatocellular carcinoma.

Network pharmacology-based and clinically relevant prediction of the active ingredients and potential targets of Chinese herbs in metastatic breast cancer patients.

Chinese Herbal Medicine (CHM) plays a significant role in breast cancer treatment. We conduct the study to ascertain the relative molecular targets of effective Chinese herbs in treating stage IV breast cancer.Survival benefit of CHM was verified by Kaplan-Meier method and Cox regression analysis. A bivariate correlation analysis was used to find and establish the effect of herbs in complex CHM formulas. A network pharmacological approach was adopted to explore the potential mechanisms of CHM.Patients in the CHM group had a median survival time of 55 months, which was longer than the 23 months of patients in the non-CHM group. Cox regression analysis indicated that CHM was an independent protective factor. Correlation analysis showed that 10 herbs were strongly correlated with favorable survival outcomes (P<0.01). Bioinformatics analyses suggested that the 10 herbs might achieve anti-breast cancer activity primarily through inhibiting HSP90, ERα and TOP-II related pathways.