Clinical outcomes of active specific immunotherapy in advanced colorectal cancer and suspected minimal residual colorectal cancer: a meta-analysis and system review

<p>Abstract</p> <p>Background</p> <p>To evaluate the objective clinical outcomes of active specific immunotherapy (ASI) in advanced colorectal cancer (advanced CRC) and suspected minimal residual colorectal cancer (suspected minimal residual CRC).</p> <p>Methods</p> <p>A search was conducted on Medline and Pub Med from January 1998 to January 2010 for original studies on ASI in colorectal cancer (CRC). All articles included in this study were assessed with the application of predetermined selection criteria and were divided into two groups: ASI in advanced CRC and ASI in suspected minimal residual CRC. For ASI in suspected minimal residual CRC, a meta-analysis was executed with results regarding the overall survival (OS) and disease-free survival (DFS). Regarding ASI in advanced colorectal cancer, a system review was performed with clinical outcomes.</p> <p>Results</p> <p>1375 colorectal carcinoma patients with minimal residual disease have been enrolled in Meta-analysis. A significantly improved OS and DFS was noted for suspected minimal residual CRC patients utilizing ASI (For OS: HR = 0.76, P = 0.007; For DFS: HR = 0.76, P = 0.03). For ASI in stage II suspected minimal residual CRC, OS approached significance when compared with control (HR = 0.71, P = 0.09); however, the difference in DFS of ASI for the stage II suspected minimal residual CRC reached statistical significance (HR = 0.66, P = 0.02). For ASI in stage III suspected minimal residual CRC compared with control, The difference in both OS and DFS achieved statistical significance (For OS: HR = 0.76, P = 0.02; For DFS: HR = 0.81, P = 0.03). 656 advanced colorectal patients have been evaluated on ASI in advanced CRC. Eleven for CRs and PRs was reported, corresponding to an overall response rate of 1.68%. No serious adverse events have been observed in 2031 patients.</p> <p>Conclusions</p> <p>It is unlikely that ASI will provide a standard complementary therapeutic approach for advanced CRC in the near future. However, the clinical responses to ASI in patients with suspected minimal residual CRC have been encouraging, and it has become clear that immunotherapy works best in situations of patients with suspected minimal residual CRC.</p

Prognostic value of the ascites characteristics in pseudomyxoma peritonei originating from the appendix

BackgroundPseudomyxoma peritonei (PMP) is a rare disease, with the overall survival (OS) influenced by many factors. To date, no ascites characteristics have been reported to predict OS of patients with PMP. The present study therefore aims to describe the ascites characteristics for PMP and identify prognostic factors for survival.MethodsBetween June 2010 and June 2020, 473 PMP patients who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were included in a retrospective study. Survival analysis was performed with the Kaplan–Meier method by the log-rank test and a Cox proportional hazards model. Associations between categorical variables were analyzed using the chi-squared test.ResultsAmong all included patients, 61% were women. The median OS was 47 months (range, 4–124 months) at the last follow-up in December 2020. Ascites characteristics can be divided into light blood ascites, “Jelly” mucus ascites, and faint yellow and clear ascites. Multivariate Cox analysis showed that the degree of radical surgery, ascites characteristics, and pathological grade were independently associated with OS in PMP patients. The chi-squared test documented that faint yellow “Jelly” ascites were related to low-grade PMP and light blood ascites were associated with high-grade PMP (P &lt; 0.01).ConclusionsLight blood ascites, incomplete cytoreduction surgery, and high-grade histopathology may predict poor OS in appendix-derived PMP

Mechanism of Bazhen decoction in the treatment of colorectal cancer based on network pharmacology, molecular docking, and experimental validation

ObjectiveBazhen Decoction (BZD) is a common adjuvant therapy drug for colorectal cancer (CRC), although its anti-tumor mechanism is unknown. This study aims to explore the core components, key targets, and potential mechanisms of BZD treatment for CRC.MethodsThe Traditional Chinese Medicine Systems Pharmacology (TCMSP) was employed to acquire the BZD’s active ingredient and targets. Meanwhile, the Drugbank, Therapeutic Target Database (TTD), DisGeNET, and GeneCards databases were used to retrieve pertinent targets for CRC. The Venn plot was used to obtain intersection targets. Cytoscape software was used to construct an “herb-ingredient-target” network and identify core targets. GO and KEGG pathway enrichment analyses were conducted using R language software. Molecular docking of key ingredients and core targets of drugs was accomplished using PyMol and Autodock Vina software. Cell and animal research confirmed Bazhen Decoction efficacy and mechanism in treating colorectal cancer.ResultsBZD comprises 173 effective active ingredients. Using four databases, 761 targets related to CRC were identified. The intersection of BZD and CRC yielded 98 targets, which were utilized to construct the “herb-ingredient-target” network. The four key effector components with the most targets were quercetin, kaempferol, licochalcone A, and naringenin. Protein-protein interaction (PPI) analysis revealed that the core targets of BZD in treating CRC were AKT1, MYC, CASP3, ESR1, EGFR, HIF-1A, VEGFR, JUN, INS, and STAT3. The findings from molecular docking suggest that the core ingredient exhibits favorable binding potential with the core target. Furthermore, the GO and KEGG enrichment analysis demonstrates that BZD can modulate multiple signaling pathways related to CRC, like the T cell receptor, PI3K-Akt, apoptosis, P53, and VEGF signaling pathway. In vitro, studies have shown that BZD dose-dependently inhibits colon cancer cell growth and invasion and promotes apoptosis. Animal experiments have shown that BZD treatment can reverse abnormal expression of PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53 genes. BZD also increases the ratio of CD4+ T cells to CD8+ T cells in the spleen and tumor tissues, boosting IFN-γ expression, essential for anti-tumor immunity. Furthermore, BZD has the potential to downregulate the PD-1 expression on T cell surfaces, indicating its ability to effectively restore T cell function by inhibiting immune checkpoints. The results of HE staining suggest that BZD exhibits favorable safety profiles.ConclusionBZD treats CRC through multiple components, targets, and metabolic pathways. BZD can reverse the abnormal expression of genes such as PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53, and suppresses the progression of colorectal cancer by regulating signaling pathways such as PI3K-AKT, P53, and VEGF. Furthermore, BZD can increase the number of T cells and promote T cell activation in tumor-bearing mice, enhancing the immune function against colorectal cancer. Among them, quercetin, kaempferol, licochalcone A, naringenin, and formaronetin are more highly predictive components related to the T cell activation in colorectal cancer mice. This study is of great significance for the development of novel anti-cancer drugs. It highlights the importance of network pharmacology-based approaches in studying complex traditional Chinese medicine formulations

Targeting tissue factor on tumour cells and angiogenic vascular endothelial cells by factor VII-targeted verteporfin photodynamic therapy for breast cancer in vitro and in vivo in mice

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to develop a ligand-targeted photodynamic therapy (tPDT) by conjugating factor VII (fVII) protein with photosensitiser verteporfin in order to overcome the poor selectivity and enhance the effect of non-targeted PDT (ntPDT) for cancer. fVII is a natural ligand for receptor tissue factor (TF) with high affinity and specificity. The reason for targeting receptor TF for the development of tPDT is that TF is a common but specific target on angiogenic tumour vascular endothelial cells (VEC) and many types of tumour cells, including solid tumours and leukaemia.</p> <p>Methods</p> <p>Murine factor VII protein (mfVII) containing a mutation (Lys341Ala) was covalently conjugated via a cross linker EDC with Veterporfin (VP) that was extracted from liposomal Visudyne, and then free VP was separated by Sephadex G50 spin columns. fVII-tPDT using mfVII-VP conjugate, compared to ntPDT, was tested <it>in vitro </it>for the killing of breast cancer cells and VEGF-stimulated VEC and <it>in vivo </it>for inhibiting the tumour growth of breast tumours in a mouse xenograft model.</p> <p>Results</p> <p>We showed that: (i) fVII protein could be conjugated with VP without affecting its binding activity; (ii) fVII-tPDT could selectively kill TF-expressing breast cancer cells and VEGF-stimulated angiogenic HUVECs but had no side effects on non-TF expressing unstimulated HUVEC, CHO-K1 and 293 cells; (iii) fVII targeting enhanced the effect of VP PDT by three to four fold; (iii) fVII-tPDT induced significantly stronger levels of apoptosis and necrosis than ntPDT; and (iv) fVII-tPDT had a significantly stronger effect on inhibiting breast tumour growth in mice than ntPDT.</p> <p>Conclusions</p> <p>We conclude that the fVII-targeted VP PDT that we report here is a novel and effective therapeutic with improved selectivity for the treatment of breast cancer. Since TF is expressed on many types of cancer cells including leukaemic cells and selectively on angiogenic tumour VECs, fVII-tPDT could have broad therapeutic applications for other solid cancers and leukaemia.</p

Table_1_Latitudinal trends in the structure, similarity and beta diversity of plant communities invaded by Alternanthera philoxeroides in heterogeneous habitats.docx

Variations in latitudinal gradients could lead to changes in the performance and ecological effects of invasive plants and thus may affect the species composition, distribution and interspecific substitution of native plant communities. However, variations in structure, similarity and beta (β) diversity within invaded communities across latitudinal gradients in heterogeneous habitats remain unclear. In this study, we conducted a two-year field survey along 21°N to 37°N in China, to examine the differential effects of the amphibious invasive plant Alternanthera philoxeroides on native plant communities in terrestrial and aquatic habitats. We compared the differences in the invasion importance value (IV), species distribution, community similarity (Jaccard index and Sorenson index) and β diversity (Bray−Curtis index and βsim index) between terrestrial and aquatic communities invaded by A. philoxeroides, as well as analyzed their latitudinal trends. We found that the IV of A. philoxeroides and β diversity in aquatic habitats were all significantly higher than that of terrestrial, while the terrestrial habitat had a higher community similarity values. The aquatic A. philoxeroides IV increased with increasing latitude, while the terrestrial IV had no significant latitudinal trend. With increasing latitude, the component proportion of cold- and drought-tolerant species in the terrestrial communities increased, and the dominant accompanying species in the aquatic communities gradually changed from hygrophytes and floating plants to emerged and submerged plants. In addition, the aquatic communities had lower community similarity values and higher β diversity in higher latitudinal regions, while terrestrial communities had the opposite parameters in these regions. Our study indicates that the bioresistance capacities of the native communities to invasive A. philoxeroides in heterogeneous habitats are different; A. philoxeroides invasion leads to higher community homogenization in terrestrial habitats than in aquatic habitats, and terrestrial communities experience more severe homogenization in higher latitudinal regions. These findings are crucial for predicting the dynamics of invasive plant communities under rapid global change.</p

Probiotics and Prebiotics as Dietary Supplements for the Adjunctive Treatment of Type 2 Diabetes

In modern lifestyles, high-fat diets and prolonged inactivity lead to more people developing type 2 diabetes (T2D). Based on the modern pathogenesis of T2D, food, and its components have become one of the top concerns for patients. Recent studies have found that dysbiosis and gut-related inflammation are more common in T2D patients. Probiotics and prebiotics play complementary roles in the gut as dietary supplements. Together, they may help improve dysbiosis and intestinal inflammation in people with T2D, increase the production of blood glucose-lowering hormones such as incretin, and help reduce insulin resistance and lower blood glucose. Therefore, changing the dietary structure and increasing the intake of probiotics and prebiotics is expected to become a new strategy for the adjuvant treatment of T2D

Effects of Glucomannan Supplementation on Type II Diabetes Mellitus in Humans: A Meta-Analysis

The hypoglycemic and lipid-lowering effects of glucomannan are widely known, and it is a potential effective treatment for type II diabetes. In this study, we evaluated the effects of glucomannan supplementation on blood-lipid-related indicators, blood-glucose-related indicators, blood pressure (BP), and body weight (BW) in patients suffering from type II diabetes. We searched databases including PubMed, Cochrane, the comprehensive biomedical research database (Embase), Web of Science, and China National Knowledge Infrastructure (CNKI) for literature on glucomannan and type II diabetes. Six randomized controlled trials (RCTs) were eligible (n = 440 participants) to be included in our analysis. Glucomannan not only reduced the total cholesterol (TC) (MD &minus;0.38 [95% CI: &minus;0.61, &minus;0.15], p = 0.001) and low-density lipoprotein (LDL) levels (MD &minus;0.35 [95% CI: &minus;0.52, &minus;0.17], p &lt; 0.0001) compared with the control group, but also reduced the fasting blood glucose (FBG) (MD &minus;1.08 [95% CI: &minus;1.65, &minus;0.50], p = 0.0002), 2 h postprandial blood glucose (P2hBG) (MD &minus;1.92 [95% CI: &minus;3.19, &minus;0.65], p = 0.003), fasting insulin (FINS) (MD &minus;1.59 [95% CI: &minus;2.69, &minus;0.50], p = 0.004), and serum fructosamine (SFRA) levels (SMD &minus;1.19 [95% CI: &minus;1.74, &minus;0.64], p &lt; 0.0001). Our analysis indicates that glucomannan is an effective nutritional intervention for type II diabetes

A Single Strain of Lactobacillus (CGMCC 21661) Exhibits Stable Glucose- and Lipid-Lowering Effects by Regulating Gut Microbiota

Type 2 diabetes (T2D) is usually accompanied by obesity and nonalcoholic fatty-liver-related insulin resistance. The link between T2D and dysbiosis has been receiving increasing attention. Probiotics can improve insulin sensitivity by regulating imbalances in microbiota, but efficacy varies based on the probiotic used. This study screened the main strain in the feces of healthy adult mice and found it to be a new Lactobacillus (abbreviated as Lb., named as CGMCC No. 21661) after genetic testing. We designed the most common Bifidobacterium longum subsp. longum (CGMCC1.2186, abbreviated as B. longum. subsp.), fecal microbiota transplantation (FMT), and Lb. CGMCC No. 21661 protocols to explore the best way for modulating dysbiosis to improve T2D. After 6 weeks of gavage in T2D mice, it was found that all three protocols had a therapeutic alleviating effect. Among them, compared with the B. longum. subsp. and FMT, the Lb. CGMCC No. 21661 showed a 1- to 2-fold decrease in blood glucose (11.84 &plusmn; 1.29 mmol/L, p &lt; 0.05), the lowest HOMA-IR (p &lt; 0.05), a 1 fold increase in serum glucagon-like peptide-1 (5.84 &plusmn; 1.1 pmol/L, p &lt; 0.05), and lowest blood lipids (total cholesterol, 2.21 &plusmn; 0.68 mmol/L, p &lt; 0.01; triglycerides, 0.4 &plusmn; 0.15 mmol/L, p &lt; 0.01; Low-density lipoprotein cholesterol, 0.53 &plusmn; 0.16 mmol/L, p &lt; 0.01). In addition, tissue staining in the Lb. CGMCC No. 21661 showed a 2- to 3-fold reduction in T2D-induced fatty liver (p &lt; 0.0001), a 1- to 2-fold decrease in pancreatic apoptotic cells (p &lt; 0.05), and a significant increase in colonic mucus layer thickness (p &lt; 0.05) compared with the B. longum. subsp. and FMT. The glucose and lipid lowering effects of this Lb. CGMCC No. 21661 indicate that it may provide new ideas for the treatment of diabetes

Spatial heterogeneity of cyanobacteria-inoculated sand dunes significantly influences artificial biological soil crusts in the Hopq Desert (China)

Artificial biological soil crusts (ABSCs), formed by inoculating Microcoleus vaginatus Gom. and Scytonema javanicum Born. et Flah. onto the topsoil of desert dunes, proved to be effective tools for the stabilization of moving dunes and promotion of soil fertility. As dominant driving forces in arid habitats, the abiotic environmental conditions of undulating dunes produce a gradient of abiotic stresses on cyanobacteria. Cyanobacteria are considered pioneering phototrophs in early soil crust communities in deserts. In this study, the development of ABSCs under various environmental site conditions was investigated using 16S rRNA-based polymerase chain reaction, denaturing gradient gel electrophoresis (DGGE), and soil property measurements. After inoculation in 2002 and long-term development, patchy moss crusts were observed on the dunes. All of the available sequenced bands in the DGGE gels belonged to Oscillatoriales and Nostocales. The dominant Nostocales genus in the ABSCs was still Scytonema; however, more Oscillatoriales genera were identified, which belonged to Microcoleus and Phormidium. The cyanobacterial compositions of different slope types were significantly distinct (p&nbsp;&lt;&nbsp;0.05), particularly those from windward slopes. The crusts of the top-dune slopes were more heterogeneous. In addition, the soil physicochemical properties and richness indices of the windward slopes were significantly lower than those of the leeward and interdune slopes (p&nbsp;&lt;&nbsp;0.05). Compared with uninoculated control dunes, all of the inoculated dunes had far higher biodiversities. &copy; 2013 Springer-Verlag Berlin Heidelberg.Artificial biological soil crusts (ABSCs), formed by inoculating Microcoleus vaginatus Gom. and Scytonema javanicum Born. et Flah. onto the topsoil of desert dunes, proved to be effective tools for the stabilization of moving dunes and promotion of soil fertility. As dominant driving forces in arid habitats, the abiotic environmental conditions of undulating dunes produce a gradient of abiotic stresses on cyanobacteria. Cyanobacteria are considered pioneering phototrophs in early soil crust communities in deserts. In this study, the development of ABSCs under various environmental site conditions was investigated using 16S rRNA-based polymerase chain reaction, denaturing gradient gel electrophoresis (DGGE), and soil property measurements. After inoculation in 2002 and long-term development, patchy moss crusts were observed on the dunes. All of the available sequenced bands in the DGGE gels belonged to Oscillatoriales and Nostocales. The dominant Nostocales genus in the ABSCs was still Scytonema; however, more Oscillatoriales genera were identified, which belonged to Microcoleus and Phormidium. The cyanobacterial compositions of different slope types were significantly distinct (p < 0.05), particularly those from windward slopes. The crusts of the top-dune slopes were more heterogeneous. In addition, the soil physicochemical properties and richness indices of the windward slopes were significantly lower than those of the leeward and interdune slopes (p < 0.05). Compared with uninoculated control dunes, all of the inoculated dunes had far higher biodiversities