[Inflammatory factors and prostate cancer: Two-sample Mendelian randomization analysis].

OBJECTIVE: To evaluate the potential causal relationship between inflammatory factors and PCa using the two-sample Mendelian randomization (MR) method. METHODS: We selected summary statistics of genome-wide association studies (GWAS) (n = 14 824) on 91 inflammatory factors, with PCa as the outcome in the latest 9th edition of FinnGen database for MR analysis. We evaluated the causal relationship between inflammatory factors and PCa using the odds ratio (OR) and 95% confidence interval (CI) of such regression models as inverse variance weighting (IVW), MR-Egger regression, simple mode (SM), weighted mode (WM) and weighted median estimator (WME), with IVW as the main statistical method for this study. We further verified the results of MR by Bayesian analysis, and evaluated the heterogeneity of genetic instrumental variables, pleiotropic effects and sensitivity of single nucleotide polymorphisms (SNP) as instrumental variables to the exposure-outcome relationship by Cochran's Q test, MR-Egger intercept test and leave-one-out cross validation. RESULTS: IVW showed that among the 91 inflammatory factors, interleukin-22 receptor A1 (IL-22RA1) and sulfotransferase 1A1 (ST1A1) were correlated positively with the risk of PCa； IL-22RA1：IVW（OR ［95% CI］: 1.12 ［1.00－1.25］, P = 0.04）；ST1A1：IVW（OR ［95% CI］: 1.08 (1.00－1.16), P = 0. 03）, while Chemokine ligand 11 (CXCL11) and interleukin 17 A (IL-17 A) negatively with the risk of PCa； CXCL11：IVW（OR ［95% CI］: 0.88 ［0.81－0.95］, P = 0.00）；IL-17A：IVW（OR ［95% CI］: 0.91 ［0.84－0.98］, P = 0.02）. No potential horizontal pleiotropy was detected by MR-Egger intercept analysis (P > 0.05, IL-22RA1 = 0.885, ST1A1 = 0.949, CXCL11 = 0.391, IL-17A = 0.884), nor biased SNPs in the MR pleiotropy residual sum and outlier (MR-PRESSO) test (P > 0.05, IL-22RA1 = 0.479, ST1A1 = 0.629, CXCL11 = 0.326, IL-17A = 0.444), or heterogeneity P > 0.05, IL-22RA1 = 0.543, ST1A1 = 0.677, CXCL11 = 0.336, IL-17A = 0.494). Leave-one-out sensitivity analysis indicated no significant impact of individual SNP sites on the overall causal relationship prediction, suggesting the reliable results of analysis. CONCLUSION: Among the 91 inflammatory factors, IL-22RA1 and ST1A1 have a positive causal relationship, while CXCL11 and IL-17A have a negative causal relationship with PCa.

Analysis of radiotherapy impact on survival in resected stage I/II pancreatic cancer patients: a population-based study.

BACKGROUND: The application of radiotherapy (RT) in pancreatic cancer remains controversial. AIM: The aim of the study was to evaluate the efficacy of radiotherapy (neoadjuvant and adjuvant radiotherapy) for resectable I/II pancreatic cancer. METHODS: Fourteen thousand nine hundred seventy-seven patients with pancreatic cancer were identified from SEER database from 2004 to 2015. Multivariate analyses were performed to determine factors including RT on overall survival. Overall survival and overall mortality among the different groups were evaluated using the Kaplan-Meier method and Gray's test. RESULTS: Patients were divided into groups according to whether they received radiotherapy or not. The median survival time of all 14,977 patients without RT was 20 months, neoadjuvant RT was 24 months and adjuvant RT was 23 months (p < 0.0001). Median survival time of 2089 stage I patients without RT was 56 months, significantly longer than those with RT regardless of neoadjuvant or adjuvant RT (no RT: 56 months vs adjuvant RT: 37 months vs neoadjuvant RT: 27 months, P = 0.0039). Median survival time of 12,888 stage II patients with neoadjuvant RT was 24 months, adjuvant RT 22 months, significantly prolonged than those without radiotherapy (neoadjuvant RT: 24 months vs adjuvant RT: 22 months vs no RT: 17 months, P<0.0001). Neoadjuvant RT (HR = 1.434, P = 0.023, 95% CI: 1.051-1.957) was independent risk factors for prognosis of stage I patients, and adjuvant RT (HR = 0.904, P < 0.001, 95% CI: 0.861-0.950) predicted better outcomes for prognosis of stage II patients by multivariate analysis. The risk of cancer-related death caused by neoadjuvant RT in stage I and no-RT in stage II patients were significantly higher. CONCLUSIONS: The study identified a significant survival advantage for the use of adjuvant RT over surgery alone or neoadjuvant RT in treating stage II pancreatic cancer. RT was not associated with survival benifit in stage I patients.

Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways.

Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model. Additionally, GYII suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A better inhibitory effect on 4T1 cell proliferation and migration was found in the decomposed recipes (DR) of GYII. Moreover, heparanase expression and the degree of angiogenesis were reduced in tumor tissues. Western blot analysis showed decreased expression of heparanase and growth factors in the cells treated with GYII and its decomposed recipes (DR2 and DR3), and thereby a reduction in the phosphorylation of extracellular signal-regulated kinase (ERK) and serine-threonine kinase (AKT). These results suggest that GYII exerts anti-tumor growth and anti-metastatic effects in the murine breast cancer model. The anti-tumor activity of GYII and its decomposed recipes is, at least partly, associated with decreased heparanase and growth factor expression, which subsequently suppressed the activation of the ERK and AKT pathways.

Synergy of de-walled Ganoderma Lucidum spore powder (GLSP) on targeted therapy in advanced non-squamous non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutant: protocol for a randomized, double-blind, placebo-controlled study.

BACKGROUND: Osimertinib is regarded as a promising third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced non-squamous non-small cell lung cancer (NSCLC) patients who developed T790M. However the adverse effects, primarily fatigue, remain an overwhelming deficiency of Osimertinib, hindering it from achieving adequate clinical efficacy for such NSCLC. Ganoderma lucidum has been used for thousands of years in China to combat fatigue, while Ganoderma Lucidum spores powder (GLSP) is the main active ingredient. The aim of this study is to investigate whether GLSP is sufficiently effective and safe in improving fatigue and synergizing with Osimertinib in non-squamous NSCLC patients with EGFR mutant. METHOD/DESIGN: A total of 140 participants will be randomly assigned to receive either de-walled GSLP or placebo for a duration of 56 days. The primary outcome measure is the fatigue score associated with EGFR-TKI adverse reactions at week 8, evaluated by the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30). Secondary outcomes include evaluation of treatment effectiveness, assessment of quality of life (QoL), and exploration of immune indicators and gut microbiota relationships. Following enrollment, visits are scheduled biweekly until week 12. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2300072786. Registrated on June 25, 2023.

Oxycodone vs. sufentanil combined with quadratus lumborum block vs. transverse abdominis plane block in laparoscopic major gastrointestinal surgery: A randomized factorial trial protocol.

Background: Multimodal analgesia plays a key role in enhanced recovery after surgery. Herein, we describe a trial protocol investigating the effects of oxycodone-vs. sufentanil-based patient-controlled analgesia in combination with quadratus lumborum block (QLB) vs. transverse abdominis plane block (TAPB) on quality of recovery following major laparoscopic gastrointestinal surgery. Methods: and analysis: This is a prospective, randomized, controlled clinical trial with a 2 × 2 factorial design. A total of 120 adult patients undergoing laparoscopic major gastrointestinal surgery will be randomized, in a 1:1:1:1 ratio, to receive one of two patient-controlled analgesia regimens (based on oxycodone or sufentanil) and one of two regional blocks (QLB or TAPB). The primary outcome measure of this trial is the quality of recovery at 24 h after surgery, assessed using the 15-item quality of recovery (QoR-15) scale. The secondary outcomes include QoR-15 scores at 48 and 72 h after surgery; visceral and incisional pain at rest and while coughing at 1, 6, 24 and 48 h postoperatively; analgesic consumption within 0-24 h and 24-48 h postoperatively; need for rescue analgesia; postoperative flatus time; postoperative adverse events (sedation, nausea and vomiting, use of antiemetics, respiratory depression, and dizziness); and length of postoperative hospital stay. Discussion: The results of this trial will provide evidence for the optimal multimodal analgesic strategy to improve the quality of recovery for patients undergoing laparoscopic major gastrointestinal surgery. Trial registration: This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR2400080766).

Effect of Oxycodone-Based Multimodal Analgesia on Visceral Pain After Major Laparoscopic Gastrointestinal Surgery: A Randomised, Double-Blind, Controlled Trial.

Purpose: Oxycodone is a potent µ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia on postoperative pain following major laparoscopic gastrointestinal surgery. Methods: In this randomised double-blind controlled trial, 40 adult patients were randomised (1:1, stratified by type of surgery) to receive oxycodone- or sufentanil-based multimodal analgesia, comprising bilateral transverse abdominis plane blocks, intraoperative dexmedetomidine infusion, flurbiprofen axetil, and oxycodone- or sufentanil-based patient-controlled analgesia. The co-primary outcomes were time-weighted average (TWA) of visceral pain (defined as intra-abdominal deep and dull pain) at rest and on coughing during 0-24 h postoperatively, assessed using the numerical rating scale (0-10) with a minimal clinically important difference of 1. Results: All patients completed the study (median age, 64 years; 65% male) and had adequate postoperative pain control. The mean (SD) 24-h TWA of visceral pain at rest was 1.40 (0.77) in the oxycodone group vs 2.00 (0.98) in the sufentanil group (mean difference=-0.60, 95% CI, -1.16 to -0.03; P=0.039). Patients in the oxycodone group had a significantly lower 24-h TWA of visceral pain on coughing (2.00 [0.83] vs 2.98 [1.26]; mean difference=-0.98, 95% CI, -1.66 to -0.30; P=0.006). In the subgroup analyses, the treatment effect of oxycodone vs sufentanil on the co-primary outcomes did not differ in terms of age (18-65 years or >65 years), sex (female or male), or type of surgery (colorectal or gastric). Secondary outcomes (24-h TWA of incisional and shoulder pain, postoperative analgesic usage, rescue analgesia, adverse events, and patient satisfaction) were comparable between groups. Conclusion: For patients undergoing major laparoscopic gastrointestinal surgery, oxycodone-based multimodal analgesia reduced postoperative visceral pain in a statistically significant but not clinically important manner. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2100052085).

Prognostic and immunological potential of PPM1G in hepatocellular carcinoma.

Liver hepatocellular carcinoma (LIHC) remains one of the most common causes of cancer death. Prior research suggested that the PPM1G gene is involved in LIHC. To explore the role of PPM1G in LIHC, we used several online databases. Expression profiling was performed via the Gene Expression Profiling Interactive Analysis (GEPIA), Hepatocellular Carcinoma Database (HCCDB), Oncomine and Human Protein Atlas (HPA) platforms. Mutation profiles were investigated via cBio Cancer Genomics Portal (cBioPortal). Survival analysis was performed via the Kaplan-Meier (KM) plotter and International Cancer Genome Consortium (ICGC) platforms. The biological function of PPM1G was analyzed via the Enrichr database. The influence of PPM1G expression in the tumor immune microenvironment was assessed via Tumor Immune Estimation Resource (TIMER). PPM1G expression was upregulated in various tumors, including LIHC. Overexpression of PPM1G was associated with poor prognosis in LIHC. PPM1G expression might be regulated by promoter methylation, copy number variations (CNVs) and kinases and correlate with immune infiltration. The gene ontology (GO) terms associated with high PPM1G expression were mRNA splicing and the cell cycle. The results suggest that PPM1G is correlated with the prognosis of LIHC patients and associated with the tumor immune microenvironment in LIHC.

Heparanase is a novel biomarker for immune infiltration and prognosis in breast cancer.

Heparanase (HPSE), an endoglycosidase that cleaves heparan sulfate, regulates a variety of biological processes that promote tumor progression. In this study, we analyzed the correlation between HPSE expression and prognosis in cancer patients, using multiple databases (Oncomine, TIMER, PrognoScan, GEPIA, Kaplan-Meier plotter, miner v4.1, DAVID). HPSE expression was significantly increased in bladder, breast, lung, and stomach cancer compared to matched normal tissues. The increased HPSE expression correlated with poor prognosis and increased immune infiltration levels of B cells, CD8+ and CD4+ T cells, macrophages, neutrophils and dendritic cells in bladder and breast cancer. In breast cancer, the high HPSE expression was associated with basal-like subtypes, younger age (0-40), advanced Scarff-Bloom-Richardson grade, Nottingham Prognostic Index and p53 mutation status. In addition, using a mouse model of breast cancer, our data showed that HPSE upregulated IL-10 expression and promoted macrophage M2 polarization and T cell exhaustion. Together, our data provide a novel immunological perspective on the mechanisms underlying breast cancer progression, and indicate that HPSE may serve as a biomarker for immune infiltration and prognosis in breast cancer.

A Hypercoagulable Hematological Metastasis Breast Cancer Model.

BACKGROUND: The hypercoagulable status, which forms a vicious cycle with hematogenous metastasis, is a common systemic alteration in cancers. As modeling is a key approach in research, a model which is suitable for studying how the hypercoagulable status promotes hematogenous metastasis in breast cancer is urgently needed. METHODS: Based on the tumor-bearing period (TBP) and postoperative incubation period (PIP), 4T1-breast cancer models were constructed to evaluate coagulation and tumor burden to generate multiple linear regression-based lung metastasis prediction formula. Platelets and 4T1 cells were cocultured for 30 min or 24 h in vitro to evaluate the early and late phases of their crosstalk, and then the physical characteristics (concentration and size) and procoagulant activity of the coculture supernatants were assayed. RESULTS: The multiple linear regression model was constructed as log10 (photon number) = 0.147 TBP + 0.14 PIP + 3.303 (TBP ≤ 25 and PIP ≤ 17) to predict lung metastasis. Coculture of platelets and 4T1 cells contributed to the release of extracellular vesicles (EVs) and the development of the hypercoagulable status. CONCLUSIONS: In vivo and in vitro hypercoagulable status models were developed to explore the mechanism of hypercoagulable status which is characterized by platelet activation and promotes hematogenous metastasis in breast cancer.

Identification of FAM107A as a potential biomarker and therapeutic target for prostate carcinoma.

FAM107A may have a dual role in regulating the biological functions of tumors; however, its role in prostate adenocarcinoma (PRAD) remains unknown. We analyzed FAM107A expression by employing databases to clarify its potential prognostic value for PRAD, as well as its role in the pathogenesis of PRAD. We observed that the FAM107A expression level is decreased in PRAD, and the reduced expression is considerably associated with poor overall survival and progression-free survival (PFS). To explore the mechanism of FAN107A in PRAD, we performed an immune cell infiltration analysis and a gene set enrichment analysis. The results showed that FAM107A expression is positively related to mast cells and natural killer cells. The Wnt signaling pathway, the MAPK signaling pathway, and the immune responses are differentially enriched in the FAM107A high-expression phenotype. The FAM107A low-expression phenotype is linked to apoptosis-induced DNA fragmentation and DNA methylation in PRAD. To assess the relationship between the clinical features and the FAM107A expression, we performed a logistic regression analysis and observed that a decreased FAM107A expression is associated with poor prognostic features, including the T stage, the N stage, the Gleason score, residual tumors, and the TP53 status. Our multivariate Cox regression results showed that the Gleason score, the primary therapy outcome, and the FAM107A expression are independent prognostic factors in PFS. In summary, we consider FAM107A an independent risk factor for PFS in PRAD. Moreover, several pathways may reveal the role of FAM107A in triggering carcinogenesis. These discoveries provide novel perspectives for future research to elucidate the pathogenic mechanism underlying PRAD.

Huayu Pill () Promotes Fluorescent Doxorubicin Delivery to Tumors in Mouse Model of Lung Cancer.

OBJECTIVE: To study the effect and mechanism of Huayu Wan (, HYW) in combination of chemotherapy of tumor treatment. METHODS: HYW serum was added in Lewis cells to assess its impact on fluorescent doxorubicin delivery in vitro. Then, Lewis tumor cells was implanted in C57BL/6 mice via xenograft transplantation. Tumor growth was measured and signal intensity corresponding to blood flow was assessed by laser doppler perfusion imaging (LDPI). Finally, the effect of HYW on the effificacy of doxorubicin was studied. RESULTS: HYW can improve the transfer of fluorescent doxorubicin into cells. The blood flow signal in the tumor tissues of the HYW group was higher than that of the control group (P<0.01). Furthermore, HYW improved drug delivery of doxorubicin to tumor tissues, and this activity was associated with HYW-induced microvascular proliferation (P<0.01). CONCLUSIONS: HYW can promote microangiogenesis and increase blood supply in tumor tissues, which in turn may increase the risk of metastasis. At the same time, HYW increases drug delivery and improves the effificacy of chemotherapy drugs through vascular proliferation. Therefore, rational judgment must be exercised when considering applying HYW to an antitumor regimen.

SANT, a novel Chinese herbal monomer combination, decreasing tumor growth and angiogenesis via modulating autophagy in heparanase overexpressed triple-negative breast cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus mongholicus, Solanum nigrum Linn, Lotus plumule, Ligusticum are widely used traditional herbal medicines for cancer treatment in China. They were typical drugs selected from Gubenyiliu II and series of formula (GYII), which were developed on the foundation of YIQIHUOXUEJIEDU theory. In the present study, four active ingredients (Astragaloside IV, α-solanine, neferine, and 2,3,5,6-tetramethylpyrazine) derived from medicines above were applied in combination as SANT. AIM OF THE STUDY: Triple-negative breast cancer (TNBC) is a serious threat to women's health worldwide. Heparanase (HPSE) is often up-regulated in breast cancer with the properties of facilitating tumorigenesis and influencing the autophagy process in cancer cells. This study aimed at evaluating the anti-tumor potential of SANT in treating HPSE related TNBC both in-vitro and in-vivo. MATERIALS AND METHODS: In this study, we explored the correlation between HPSE expression and survival of breast cancer patients in databases. We performed MTS, trans-well and wound scratch assays to assess the impact of SANT on cell proliferation and migration. Confocal microscopy observation and western blots were applied to verify the autophagy flux induced by SANT. Mice models were employed to evaluate the efficacy and safety of SANT in-vivo by tumor weights and volumes or serum index, respectively. To analyze the underlying mechanisms of SANT, we conducted human autophagy PCR array and angiogenesis proteome profiler on tumor tissues. RESULTS: Patients with elevated HPSE expression were associated with a poor outcome in both RFS (P = 1.7e-12) and OS (P = 0.00016). SANT administration significantly inhibited cancer cells' proliferation and migration, enhanced autophagy flux, and slightly reduced the active form of HPSE in-vitro. SANT also suppressed tumor growth and angiogenesis in-vivo. Human autophagy PCR array results indicated that SANT increased the ATG16L1, ATG9B, ATG4D gene expressions while decreased TMEM74 and TNF gene expressions.Angiogenesis proteome profiler results showed SANT reduced protein level of HB-EGF, thrombospondin-2, amphiregulin, leptin, IGFBP-9, EGF, coagulation factor III, and MMP-9 (pro and active form) in tumor, raised the protein expression of serpin E1 and platelet factor 4. CONCLUSIONS: These findings indicated that herbal compounds SANT may be a promising candidate in anti-cancer drug discovery. It also provides novel strategies for using natural compounds to achieve optimized effect.

A network-based predictive gene expression signature for recurrence risks in stage II colorectal cancer.

The current criteria for defining the recurrence risks of stage II colorectal cancer (CRC) are not robust; therefore, we aimed to explore novel gene signatures to predict recurrence risks and to reveal the underlying mechanisms of stage II CRC. First, the gene expression profiles of 124 patients with stage II CRC from The Cancer Genome Atlas (TCGA) database were obtained to screen differentially expressed genes (DEGs). A total of 202 DEGs, including 128 upregulated and 74 downregulated, were identified in the recurrence group (n = 24) compared to the nonrecurrence group (n = 100). Furthermore, the top 5 DEGs (ZNF561, WFS1, SLC2A1, MFI2, and PTGR1) were identified by random forest variable hunting, and four (ZNF561, WFS1, SLC2A1, and PTGR1) were selected to create a four-gene recurrent model (GRM), with an area under the curve (AUC) of 0.882 according to the receiver operating characteristic curve, and the robust diagnostic effectiveness of the GRM was further validated with another gene expression profiling dataset (GSE12032), with an AUC of 0.943. The diagnostic effectiveness of the GRM regarding recurrence was associated with poor disease-free survival in all stages of CRC. In addition, gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed 18 enriched functions and 6 enriched pathways. Four genes, ABCG2, CACNA1F, CYP19A1, and TF, were identified as hub genes by the protein-protein interaction network, which further validated that these genes were correlated with a poor pathologic stage and overall survival in all stages of CRC. In conclusion, the GRM can effectively classify stage II CRC into groups of high and low risks of recurrence, thereby making up for the prognostic value of the traditional clinicopathological risk factors defined by the National Comprehensive Cancer Network guidelines. The hub genes may be useful therapeutic targets for recurrence. Thus, the GRM and hub genes could offer clinical value in directing individualized and precision therapeutic regimens for stage II CRC patients.

Heparanase from triple­negative breast cancer and platelets acts as an enhancer of metastasis.

Triple­negative breast cancer (TNBC), which is characterized by inherently aggressive behavior and lack of recognized molecular targets for therapy, poses a serious threat to women's health worldwide. However, targeted treatments have yet to be made available. A crosstalk between tumor cells and platelets (PLT) contributing to growth, angiogenesis and metastasis has been reported in numerous cancers. Heparanase (Hpa), the only mammalian endoglycosidase that cleaves heparan sulfate, has been demonstrated to contribute to the growth, angiogenesis and metastasis of numerous cancers. Hypoxia affects the growth, angiogenesis and metastasis of nearly all solid tumors, and the ability of Hpa to promote invasion is enhanced in hypoxia. However, whether Hpa can strengthen the crosstalk between tumor cells and PLT, and whether enhancing the biological function of Hpa in TNBC promotes malignant progression, have yet to be fully elucidated. The present study, based on bioinformatics analysis and experimental studies in vivo and in vitro, demonstrated that Hpa enhanced the crosstalk between TNBC cells and PLT to increase the supply of oxygen and nutrients, while also conferring tolerance of TNBC cells to oxygen and nutrient shortage, both of which are important for overcoming the stress of hypoxia and nutritional deprivation in the tumor microenvironment, thereby promoting malignant progression, including growth, angiogenesis and metastasis in TNBC. In addition, the hypoxia­inducible factor­1a (HIF-1a)/vascular endothelial growth factor­a (VEGF- a)/phosphorylated protein kinase B (p-)Akt axis may be the key pathway involved in the effects of Hpa on the biological processes mentioned above. Therefore, improving local hypoxia, anti­Hpa treatment and inhibiting PLT activation may improve the prognosis of TNBC.

Scutellaria barbata and Hedyotis diffusa herb pair for breast cancer treatment: Potential mechanism based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The Scutellaria barbata and Hedyotis diffusa (SH) herb pair is extensively used in Traditional Chinese Medicine for efficacy enhancement in cancer treatment in China and Asian countries. Superior clinical efficacy observations based on high dosages (≥60 g) motivated us to explore appropriate dosages and the underlying mechanisms of action. AIM OF THE STUDY: To explore the efficacy and potential mechanisms of actions of SH through in vitro and in vivo experiments and network pharmacology. MATERIALS AND METHODS: SH lyophilized powder (SHLP) was prepared from decoctions and the active ingredients were identified using high performance liquid chromatography (HPLC). Proliferation and migration experiments in vitro and tumor growth in vivo were performed to evaluate the effects of SHLP on breast cancer. Corresponding potential target genes for SHLP components and breast cancer were extracted from established databases and the Protein-Protein Internetwork of shared genes were constructed using STRING database. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation clusters were acquired and the top 30 pathways were presented. At last, as one of pathways indicated by enriched results, apoptosis was validated with flow cytometric analysis and caspase-3, 8, 9 activities. RESULTS: Seventy-five ingredients were identified from SHLP by HPLC. High SHLP doses inhibited proliferation and migration of three types of breast cancer cells in vitro and tumor growth in nude mice. After target genes extraction and intersection, the top 30 KEGG clusters were enriched, including PI3K-Akt, cell cycle and other related pathways like VEGF, Micro-RNAs and NF-κB, besides, key genes in apoptosis were mapped. In the last, apoptosis was validated by flow cytometric analysis and caspase-3, 8, 9 activities after SHLP treatment. CONCLUSION: High SHLP dosages inhibited breast cancer in vitro and in vivo, enriched by network pharmacology and confirmed by flow cytometric analysis and caspase activation, with apoptosis was identified as one of the mechanisms of action of SHLP. SHLP administration with higher doses is recommended for clinical usage.

Efficacy of acupuncture in the prevention and treatment of chemotherapy-induced nausea and vomiting in patients with advanced cancer: a multi-center, single-blind, randomized, sham-controlled clinical research.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is a common and distressing side effect. We conducted this clinical trial to compare the effectiveness of true acupuncture vs. sham acupuncture in controlling chemotherapy-induced nausea and vomiting (CINV) among patients with advanced cancer. METHODS: A total of 134 participants were randomly allocated into true acupuncture (TA) (n = 68) and sham acupuncture (SA) (n = 66) groups. Participants in both groups received acupuncture session twice on the first day of chemotherapy, and once consecutively on the following 4 days. The primary outcome was using the Common Terminology Criteria for Adverse Events (CTCAE) to assess CINV. The secondary outcome measures were the Eastern Cooperative Oncology Group score (ECOG), Simplified Nutritional Appetite Questionnaire (SNAQ), and Hospital Anxiety and Depression scale (HADS). RESULTS: Compared to the SA group, the TA group didn't show significant improvement in complete response rates of chemotherapy-induced nausea and vomiting (all P > 0.05). However, the TA group could modestly reduce the severity of nausea (from day-3 to day-21, P < 0.05) or vomiting (from day-4 to day-21, P < 0.05), which is notably superior to the control group. Besides, TA promoted the nutritional status of patients with a significantly higher score comparing to the SA group on day 14 (21.82 vs.20.12, P = 0.003) and day 21 (22.39 vs. 20.43, P = 0.001). No apparent differences were found in anxiety and depression assessment between these groups. Participants in both groups were well tolerant of acupuncture therapy. There was no adverse event occurs in our study. CONCLUSION: Acupuncture as an adjunctive approach could alleviate the severity of chemotherapy-induced nausea and vomiting compared to the sham control, even though the effect of acupuncture in preventing CINV occurring is relatively modest.

Establishment of a murine breast tumor model by subcutaneous or orthotopic implantation.

A number of murine models are used to mimic the pathology of breast cancer. Tissue inoculation and cell inoculation using orthotopic implantation (OS) and subcutaneous implantation (SQ) are commonly used to generate murine models to investigate cancer. However, limited information is available in regard to the variations of these methods. The present study compared growth, metastasis, survival and histopathology of tumors produced using OS and SQ to characterize features of the tumors produced by the two distinct methods. Additionally, the present study aimed at providing increased options for investigators when designing experiments. 4T1-luc2 cell suspension or 4T1-luc2 tissue suspension was inoculated using either OS or SQ into BALB/c mice. Tumor growth and metastasis were detected using an in vivo imaging system and calipers. Excised tumors and lung were assessed by tissue staining with hematoxylin and eosin, and the vessel marker cluster of differentiation 31. The results of the present study revealed that the cell suspension generated breast tumors of increased size, which was visualized and determined, following inoculation, using calipers at an earlier time point compared with tumors produced by tissue suspension. The increasing bioluminescent trend of OS tumors was more marked compared with that of SQ tumors. The volume of OS tumor was increased with decreased variation, compared with that of SQ tumors. In addition, the OS tumor exhibited increased microvessel density. Bioluminescent signals and histological results in regard to metastasis were consistent: OS implantation produced increased lung metastasis compared with that of SQ implantation, although they exhibited similar survival times. The results of the present study indicated that the inocula from distinct sources (tissue or cell) affected tumor growth. Furthermore, breast tumor progression and histopathological characteristics were distinct between OS and SQ, whereas OS exhibited increased malignant behavior. Understanding the characteristics of murine breast cancer models established by diverse methods may aid investigators to select appropriate animal models, according to the requirements of the study.

Chinese Medicine Yishen Jiangu Granules () on Aromatase Inhibitor-Associated Musculoskeletal Symptoms.

OBJECTIVE: To assess the effectiveness of Yishen Jiangu Granules (, YSJGG) on aromatase inhibitor-associated musculoskeletal symptoms (AIMSS). METHODS: A single-arm, open-label study was conducted in 34 postmenopausal women with breast cancer who experienced AIMSS. Patients were treated with YSJGG for 12 weeks (12.4 g orally twice daily). The primary outcome was a change in the mean worst pain score of Brief Pain Inventory-Short Form (BPI-SF) over 12 weeks, and the second outcomes included changes in pain severity and pain-related interference of BPI-SF and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Modified Score for the Assessment of Chronic Rheumatoid Affections of the Hands (M-SACRAH), the Functional Assessment of Cancer Therapy-Breast (FACT-B), bone mineral density (BMD) and blood indices such as calcium (Ca), phosphate (P), and alkaline phosphatase (ALP). RESULTS: Of 37 women recruited, 30 initiated the therapy and 24 were evaluable at 12 weeks. The primary outcome (BPI-SF worst pain scores) achieved a 2.17-point reduction compared with baseline (5.75±1.87 vs 3.58±2.15, P<0.01). There were reductions in pain severity (decreased 1.65, P<0.01) and pain-related interference (decreased 2.55, P<0.01). The changes in WOMAC and M-SACRAH scores were similar to BPI-SF (P<0.05). In the FACT-B, only physical well-being and functional well-being were improved compared with baseline (P<0.05). No clinical differences were found in BMD, Ca, P and ALP. CONCLUSION: YSJGG is an effective and well-tolerated agent to reduce AIMSS.

EFFECT OF RUANGANJIEDU DECOCTION INHIBIT EXPERIMENTAL HEPATIC FIBROSIS OF RATS.

BACKGROUND: RuanGanJieDu (RGJD) is a traditional Chinese medicine comprising nine Chinese medicinal herbs. The clinical use of RGJD by us was found that it has a good control effect on hepatic fibrosis (HF) patient. In order to further investigate the Anti-fibrosis mechanism of RGJD, hence this experiment has been carried out. METHODS: After treatment, the general conditions of rats in each group were observed. The liver tissues morphology and HF phases were observed under light microscope. The weights of livers and spleens were recorded; the indices of liver and spleen were calculated. The α-SMA and E-cadherin of the liver tissues were determined by Immunohistochemistry, and the contents of ALT AST and PCIII+PCIV+HA+LN in rat serum were detected by ELISA. RESULTS: After treatment, the rats in model group presented with abdominal distention and rough hair, lethargy and mental sluggishness, slow movement and irritability; Most rats in RGJD group and colchicine(Col) group were in good spirits and no obvious abnormal motion state. The RGJD had shown significant effects in improving the liver tissue morphology. The HF phases of RGJD group and Col group mainly distributed in the S1-S2 phases, were finer than the model group in the S3 phase (P<0.05). The wet weights and indices of livers and spleens in RGJD group were lower than the control groups (P<0.05). Moreover, the expressions of E-cadherin, α-SMA and the serum levels of AST, ALT and PCIII+ PCIV in RGJD group were obviously decreased than the control groups except HA and LN(P<0.05). CONCLUSION: RGJD can improve the liver tissue morphology and reduce serum biochemical and collagen indices of HF, which proved a better curative effect of Chinese medicine than Col on HF and improving liver function.

Risk of peripheral edema in cancer patients treated with MEK inhibitors: a systematic review and meta-analysis of clinical trials.

BACKGROUND: MEK inhibitors are a group of drugs that have shown reliable effects in the treatment of metastatic melanoma and non-small-cell lung cancer. Peripheral edema is an adverse event associated with MEK inhibitors; however, there has been no systematic attempt to evaluate peripheral edema data observed with these agents. This meta-analysis aimed to determine the risk of peripheral edema in cancer patients treated with MEK inhibitors. MATERIALS AND METHODS: The authors searched PubMed, the Cochrane Library, EMBASE, and Clinical Trials.gov without language restriction. The final search was conducted on January 9, 2017. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for dichotomous data. Heterogeneity was calculated and reported via Tau2, Chi2, and I2 analyses. RESULTS: A total of 13 eligible studies were obtained. Patients treated with MEK inhibitors (Trametinib and Selumetinib) had an increased risk overall of peripheral edema (RR = 3.05, 95% CI = 1.98-4.70; p < .00001), but the MEK inhibitors (Trametinib and Selumetinib) did not increase the risk of high grade edema (RR = 1.88, 95% CI = 0.66-5.35; p = .24). Sub-group analysis, based on cancer type (melanoma vs non-melanoma), found that the peripheral edema risk in melanoma patients is higher than that in non-melanoma patients (p = .03). However, no significant difference was observed in terms of high-grade edema and other sub-groups (trametinib vs selumetinib; monotherapy vs combination). Due to the absence of cobimetinib data, the result about cobimetinib was not involved. CONCLUSION: This meta-analysis reveals that the use of MEK inhibitors is associated with an increased risk of peripheral edema in cancer patients. Oncologists should be aware of the risk and perform regular assessments.