Effectiveness and economic evaluation of rhTPO and rhIL-11 in the treatment of cancer therapy induced thrombocytopenia based on real-world research.

Objective: Based on real-world research, we aimed to evaluate the effectiveness and economy of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin 11 (rhIL-11) in the treatment of cancer therapy induced thrombocytopenia (CTIT). Methods: We retrospectively collected clinical data of patients with CTIT who were treated with rhTPO or rhIL-11 in a single cancer hospital from January 2020 to December 2021. Propensity score matching (PSM) was applied to eliminate confounding factors. The measurements of effectiveness analysis were the platelet compliance rate, days of medication, days of compliance, highest platelet count after medication, platelet count elevation before and after medication, and the lowest platelet count after next-cycle cancer therapy. The economic evaluation was performed according to the results of the effectiveness evaluation. At the same time, patients were stratified according to type of tumor and grade of thrombocytopenia for subgroup analysis. Results: A total of 262 patients were collected and 174 patients were enrolled after PSM, 87 in the rhTPO group and 87 in the rhIL-11 group. In all patients, there were no significant differences in the platelet compliance rate, mean days of medication, median days of compliance, median highest platelet count after medication, and the median platelet count elevation before and after medication between the two groups (p > 0.05), but the median lowest platelet count after next-cycle cancer therapy in the rhTPO group was lower than that in the rhIL-11 group (p = 0.014). The subgroup analysis showed that the rhTPO group had longer mean days of medication than the rhIL-11 group in patients with hematological malignancies (p = 0.042), and a lower median lowest platelet count after next-cycle cancer therapy in patients with grade I/II thrombocytopenia than rhIL-11 group (p = 0.022), with no significant difference in other outcome indicators (p > 0.05). As there was no statistically significant difference in platelet compliance rate between the two groups, the cost-minimization analysis showed that the rhIL-11 group had lower treatment costs than the rhTPO group. Conclusion: RhTPO and rhIL-11 showed similar effectiveness in the treatment of CTIT, but rhIL-11 was more advantageous in economic cost.

Research progress of hydroxychloroquine and autophagy inhibitors on cancer.

PURPOSE: Hydroxychloroquine (HCQ), the analog of chloroquine, augments the effect of chemotherapies and radiotherapy on various tumors identified in the current clinical trials. Meanwhile, the toxicity of HCQ retinopathy raises concern worldwide. Thus, the potent autophagy inhibitors are urgently needed. METHODS: A systematic review was related to 'hydroxychloroquine' or 'chloroquine' with 'clinical trials,' 'retinopathy' and 'new autophagy inhibitors.' This led to many cross-references involving HCQ, and these data have been incorporated into the following study. RESULTS: Many preclinical studies indicate that the combination of HCQ with chemotherapies or radiotherapies may enhance the effect of anticancer, providing base for launching cancer clinical trials involving HCQ. The new and more sensitive diagnostic techniques report a prevalence of HCQ retinopathy up to 7.5%. Lys05, SAR405, verteporfin, VATG-027, mefloquine and spautin-1 may be potent autophagy inhibitors. CONCLUSION: Additional mechanistic studies of HCQ in preclinical models are still required in order to answer these questions whether HCQ actually inhibits autophagy in non-selective tumors and whether the extent of inhibition would be sufficient to alter chemotherapy or radiotherapy sensitivity.

The Role of RhoJ in Endothelial Cell Biology and Tumor Pathology.

Background. RhoJ, an endothelially expressed member of Cdc42 (cell division cycle 42) subfamily of Rho GTPase, plays an important role in endocytic pathway, adipocyte differentiation, endothelial motility, tube formation, and focal adhesion. RhoJ is a selective and effective therapeutic target in tumor tissues or retinopathy. Methods. A systematic review was related to "small Rho GTPase" or "RhoJ" with "endothelial motility, tube formation and focal adhesion" and "tumor therapy". This led to many cross-references involving RhoJ and these data have been incorporated into the following study. Results. We have grouped the role of RhoJ according to three main effects: RhoJ regulates endocytic pathway and adipocyte differentiation in early studies, and RhoJ shows an important role in endothelial cell biology; furthermore, RhoJ blockade serves as a target in tumor vasculature and enhances the effects of anticancer drug. Conclusions. More research is necessary to understand the role of RhoJ in many aspects, on the basis of current knowledge of the role of RhoJ blockade in tumor vessels, there are opportunities for the therapy of tumor, and RhoJ is expressed outside tumour vasculature and is involved in wound healing. Taking advantage of the opportunities could result in a development in tumor therapy.

IL-1ß: a key modulator in asthmatic airway smooth muscle hyper-reactivity.

Asthma is a chronic inflammatory disorder of the airway. It is characterized by airway hyper-reactivity, which can be attributed to the chronically inflamed airway. However, the molecular mechanism is still under investigation. In this article, we have shown that IL-1ß is a key molecule that can orchestrate both Toll-like receptor and muscarinic receptor pathways, and that antagonizing the function of IL-1ß has a promising future as a potential drug target for asthma treatment. IL-1ß can activate NF-κB pathways via Toll-like receptors, and NF-κB will eventually transactivate the genes of cytokines, chemokines, proteins of the complement system, adhesion molecules and immune receptors involved in inflammation. IL-1ß can activate eosinophils, which can release major basic protein (MBP) to antagonize the M2 receptors leading to excessive acetylcholine release. Acetylcholine has an effect on M3 receptors, which are related to airway smooth muscle contraction and mucus production. IL-1ß is reported to activate COX-2 resulting in heterologous desensitization of adenylate cyclase and impairs relaxation of the ASM. IL-1ß is involved in mediation of neutrophilic inflammation. Identification of the prominent role of IL-1ß in asthma could lead to successful use of anti-IL1ß agents.

The utility of chloroquine in cancer therapy.

BACKGROUND: The anti-malarial drug chloroquine has recently been discovered as a novel anti-tumor agent. This article is to review the recent development of chloroquine being used in cancer therapy. METHODS: PubMed, ScienceDirect and ClinicalKey served as the major databases. Key words included 'chloroquine', 'cancer', and 'autophagy'. The publication date was up to June 2015. RESULTS: Chloroquine mainly executes its anti-tumor function through inhibition of autophagy. It can accumulate inside the lysosome resulting in lysosomal membrane permeabilization (LMP) which will eventually lead to apoptosis. Chloroquine has been shown to stabilize p53 and induce p53-dependent apoptosis or cell cycle arrest. It can also inhibit ABC (ATP-binding cassette) family protein. The anti-cancer effect of chloroquine has been observed both in vitro and in vivo. However, it is considered more as a potential chemotherapy and radiotherapy sensitizer rather than an antineoplastic. CONCLUSION: Although the utility of chloroquine is promising in cancer therapy, some safety issues have been brought to attention, and further studies on safety profile and the signs of clinical activity of chloroquine including its derivatives should be conducted.

Rapid and sensitive headspace gas chromatography-mass spectrometry method for the analysis of ethanol in the whole blood.

BACKGROUND: For the forensic aim, a sensitive and specific method using headspace gas chromatography coupled with mass spectrometry (GC/MS) has been developed for the quantitative determination of ethanol in blood using n-propanol as internal standard. GC was performed in isothermal mode with a GC run-time of 5.0 min. METHODS: The quantification was performed using selected ions monitoring mode adopting a quantitative ion and qualifier ion for ethanol and the internal standard. RESULTS: The method was linear (r(2) = 0.999, in the concentration range of 39.5-1,262.9 µg/ml), specific, sensitive (limit of quantification and limit of detection of 39.5 and 0.4 µg/ml, respectively), and robust. A slightly modified method was also developed for the quantification of 50 commonly abused drunken in blood. The method used an isothermal GC program with a run-time of 5.0 min. The quantification was performed using selected ions monitoring mode and integrating the area under the peak using n-propanol as an internal standard. The method was linear 40-1,263 µg/ml and sensitive. CONCLUSIONS: The method was proved superior in speed and selectivity to previously reported methods and was successfully applied to the pharmacokinetic study of ethanol.

Penehyclidine hydrochloride: a potential drug for treating COPD by attenuating Toll-like receptors.

BACKGROUND: The aim of this review was to evaluate and summarize the available scientific information on penehyclidine hydrochloride (PHC) for the treatment of chronic obstructive pulmonary disease (COPD) as a result of its ability to attenuate Toll-like receptors. Penehyclidine hydrochloride is an anticholinergic drug manufactured in China, with both antimuscarinic and antinicotinic activity. PHC is used widely in the clinic as a reversal agent in cases of organic phosphorus poisoning and soman poisoning, but also may also have an important role as a bronchodilator in the treatment of obstructive airway disease, including asthma and, in particular, COPD. METHODS: Our bibliographic sources included the CAPLUS, MEDLINE, REGISTRY, CASREACT, CHEMLIST, CHEMCATS, and CNKI databases, updated to September 2012. In order to assess the data in detail, we used the search terms "penehyclidine hydrochloride," "COPD," "muscarinic receptor," and "toll-like receptors." Papers were restricted to those published in the English and Chinese languages, and to "paper" and "review" as the document type. Patents were also reviewed. RESULTS: Our survey mainly yielded the results of research on PHC and the mechanisms of COPD. COPD is a preventable and treatable disease with some significant extrapulmonary manifestations that may contribute to its severity in some patients. Recently, it has been shown that muscarinic receptors may interact with Toll-like receptors. Basic and clinical studies of the relationship between the mechanism of action and the effects of PHC in the respiratory tract have been studied by a number of laboratories and institutions. The main advantages of PHC are that it has few M(2) receptor-associated cardiovascular side effects and attenuates Toll-like receptors. CONCLUSION: PHC may be a promising candidate agent in the treatment of COPD in the future because of its ability to attenuate Toll-like receptors. This review should be of help to those intending to research this topic further.

Overexpression of adiponectin prevents hepatocyte steatosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effect of adiponectin on hepatocyte steatosis.</p><p><b>METHODS</b>L02 cells were transfected with pEGFP-N1-AdipoQ, a plasmid encoding pEGFP-adiponectin fusion protein, or pEGFP-N1. Lipid droplets in the hepatocytes were observed by oil red staining at 72 h. The contents of TG, FFA and glycerol in hepatocytes were measured.</p><p><b>RESULTS</b>Compared to cells transfected with pEGFP-N1-AdipoQ plasmid, much more lipid droplets were observed in cells transfected with pEGFP-N1 plasmid. TG, FFA and glycerol contents in L02 cells and L02/pEGFP-N1 cells were significantly higher than those in L02/pEGFP-N1-AdipoQ cells.</p><p><b>CONCLUSIONS</b>Overexpression of adiponectin prevent hepatocyte steatosis.</p>

[Effects of CO2 and 5% dextrose solution on expression of CD44 and ICAM-1 in endometrial carcinoma cells].

OBJECTIVE: To investigate the effects of 5% dextrose solution and different CO2 pressures on expression of adhesion molecules (including CD44 and ICAM-1) of endometrial carcinoma cells in vitro. To provide experimental base for the safety question of hysteroscope operation and the selection of better distending medium for the patients with suspected endometrial cancer. METHODS: Endometrial cancer cells (HEC-1-B) were put in 5% dextrose, 70 mmHg 100% CO2, 100 mmHg 100% CO2 at 37 degrees C, the control group was not given any administration, respectively for 1 hour. Expression of CD44 and ICAM-1 were measured at 0, 12, 24, 48 and 72 hours by using flow cytometry. RESULTS: The expression of CD44 and ICAM-1 increased significantly at 0 h-72 h after the cells were exposed to 5% dextrose, 70 mmHg 100% CO2, 100 mmHg 100% CO2 for 1 hour (P<0.05) respectively, and returned to the control levels by 72 h. With the increase of the CO2 pressure, the expression of the CD44 and ICAM-1 increased (P<0.05). The expression of the CD44 and ICAM-1 totally increased significantly compared with control. CONCLUSION: Both high pressure CO2 (100 mmHg) and 5% dextrose solution can increase the expression of CD44 and ICAM-1 in endometrial cancer cells, and may promote the capability of adhesion of endometrial cancer cells. Lower CO2 pressure does not change the expression of CD44 and ICAM-1 in endometrial cancer cells, therefore the low CO2 pressure (70 mmHg) is safer as distending medium for the patients with suspected endometrial cancer.

Underlying mechanism of penehyclidine hydrochloride on isolated rat uterus.

We investigated the underlying mechanisms of penehyclidine hydrochloride (PHC), a novel selective anticholinergic drug on isolated rat uterus. The method of radio-immunity assay was further employed to determine cyclic adenosine mono phosphate (cAMP) levels in isolated rat uterus for comparing with selective effect on muscarinic receptor subtypes. In the assay, PHC could decrease the content of cAMP in isolated rat uterus, but the difference was not statistically significant at dose of 10 mumol/L. In conclusion, our results suggested that PHC has no or poor effect on M(2) receptor subtypes in isolated rat uterus.

Characterization of the effect of penehyclidine hydrochloride on muscarinic receptor subtypes mediating the contraction of guinea-pig isolated gastrointestinal smooth muscle.

OBJECTIVES: The aim was to characterize the effect of penehyclidine hydrochloride, which mediates the relaxation of guinea-pig isolated gastrointestinal smooth muscle, on muscarinic receptor subtypes. METHODS: Radioimmune assay was used to determine cAMP levels in isolated guinea-pig gastrointestinal smooth muscle to compare the selective effects of penehyclidine hydrochloride on muscarinic receptor subtypes. KEY FINDINGS: The results indicated that the relaxing effect of penehyclidine hydrochloride on isolated gastrointestinal smooth muscle contraction induced by acetylcholine was stronger than that of atropine (based on PA2 values). In the radioimmune assay, penehyclidine hydrochloride increased the cAMP content in isolated guinea-pig stomach smooth muscle and decreased the cAMP content in isolated guinea-pig intestinal smooth muscle, but the difference was not statistically significant at a dose of 10 mumol/l. CONCLUSIONS: The results suggest that penehyclidine hydrochloride has little or no effect on M2 receptor subtypes in guinea-pig gastrointestinal smooth muscle.