NAT2＊6A, a haplotype of the N-acetyltransferase 2 gene, is an important biomarker for risk of anti-tuberculosis drug-induced hepatotoxicity in Japanese patients with tuberculosis

AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.

Pyrrolidine dithiocarbamate alleviates the anti-tuberculosis drug-induced liver injury through JAK2/STAT3 signaling pathway:An experimental study

Objective:To study the effect of pyrrolidine dithiocarbamate(PDTC) on the anti-tuberculosis drug-induced liver injury and the molecular mechanism. Methods:Clean male SD rats were selected as experimental animals and randomly divided into normal group,model group,PDTC group and AG490 group. Animal model of anti-tuberculosis drug-induced liver injury was established by intragastric administration isoniazid + rifampicin. PDTC group received intraperitoneal injection of PDTC,and AG490 group received intraperitoneal injection of AG490. Twenty-eight days after intervention,the rats were executed,and the liver injury indexes,inflammation indexes and oxidative stress indexes in serum as well as JAK2/STAT3 expression,liver injury indexes,inflammation indexes and oxidative stress indexes in liver tissue were determined. Results:p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissue as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of model group were significantly higher than those of normal group while p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissu as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of PDTC group and AG490 group were significantly lower than those of model group. Conclusions:PDTC can inhibit the inflammation and oxidative stress mediated by JAK2/STAT3 signaling pathway to alleviate the anti-tuberculosis drug-induced liver injury.

First Line Anti-Tuberculosis Drugs Resistance Patterns of <i>Mycobacterium tuberculosis</i>Isolates from Newly Diagnosed Cases of Tuberculosis

Introduction: Tuberculosis is a major cause of mortality and morbidity world-wide. Anti-tuberculosis drugs have been used for many decades but resistance to them is now widespread. Globally 5% of tuberculosis cases and in India 3% among new TB cases. This study was planned to know the pattern of first line anti-tuberculosis drug resistance in south Gujarat, Surat region in newly diagnosed patients of tuberculosis. Material and Methods: 350 samples were processed for homogenisation and concentration using 4% NAOH-2.9% trisodium citrate. Processed samples were inoculated in liquid medium that is MGIT (Mycobacterial growth indicator tube). Positive samples for M. tbwere processed further for first line anti-tuberculosis drugs sensitivity testing (DST). Reading was taken by using MicroMGIT system. Result: Out of 350 samples 59 (17%) were positive samples, of which 48 (13%) were M. tb and 11 (3%) were non tuberculous mycobacteria. Out of 48 samples 2% (1 isolate) was resistant to isoniazid and Rifampicin while 2% were monoresistant to isoniazide, 2% monoresistant to streptomycin. No rifampicin monoresistant was detected. Conclusion: Such study may help in control of tuberculosis at regional and national level which would in turn help in planning of measures to control Multi-drug resistance tuberculosis. Continuous surveillance should be applied to know the periodic changing patterns and trend in Drug resistant tuberculosis.

Use of Cost Effective Semi-Automated (Mannual/Micro) MGIT System over BACTEC 960 to Perform First Line Anti-Tuberculosis Drugs Sensitivity Testing

Introduction: Multi-drug resistant tuberculosis (MDR-TB) that is the tuberculosis that is resistant to at least 2 of the first line anti-tuberculosis drugs is fatal infectious disease. Cases of MDR-TB are now increasing with 30,000 cases of MDR-TB reported in 2013 by national TB programme. Rapid diagnosis of MDR-TB is extremely important for rapid treatment of patient and to prevent spread of MDR-TB to other. BACTEC 960 system helps in rapid diagnosis but purchase of expensive instrument for the same is the limitation. However, the same purpose can be solved by use of semi-automated MGIT system. Aims and Objectives: Aim of this study is to do drug sensitivity testing of the first line anti-tuberculosis drugs with the use of semi-automated MGIT systems. 350 newly registered and suspected cases of tuberculosis in tertiary care hospital were included. Samples were processed for digestion and decontamination and inoculated in MGIT tubes and also on LJ medium. Reading was taken using semi-automated MGIT system. Positive tubes were confirmed by rapid test for M. tuberculosis and then drug sensitivity was performed. Result: Out of 350 samples, 62% were sputum;33% were pleural fluid and rest 5% were lymph node, Ascetic fluid, CSF, pus. Average day of positivity by MGIT was 13 - 20 days as compared to 25 - 37 days by solid medium, which was statistically significant with p value Conclusion: Manual MGIT System is a simple, efficient, safe to use diagnostic system. It does not require any expensive/special instrumentation other than the UV lamp for detection of fluorescence. The rapidity by which mycobacteria are detected is the most important advantage of the Manual MGIT. In areas with limited resources where purchase of expensive instruments such as the MGIT960 is out of scope, the use of manual MGIT for rapid susceptibility testing for MDR-TB could be a possibility.

Chemotherapy and drug resistance status of malaria parasite in northeast India

India reports the highest number of malaria cases in Southeast Asia,of which Plasmodium falciparum contribute more than half of the cases every year.North eastern states of India contribute only 3.96%of country’s population but account for】10%of total reported malaria cases.11%of Plasmodium falciparum cases and 20%of malaria related deaths annually.In India,chloroquine resistance was reported for the first time from northeast region and since then chloroquine treatment failure is being reported from many parts of the region.Increased chloroquine treatment failure has led to change of the drug policy to artemisinin combination therapy as first line of malaria treatment in the region.However,replacing chloroquine to artemisinin combination therapy has not shown significant difference in the overall malaria incidence in the region,The present review addresses the current malaria situation of northeastern region of India in the light of antimalarials drug resistance.

Research progress in tumor angiogenesis and drug resistance in breast cancer

Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, via exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted.

Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.

The Effectiveness of Surgical Methods of Treatment of Pulmonary Tuberculosis for Patients with Multidrug Resistant at Adequate Chemotherapy (Retrospective, Case Control, Comparative Research)

In this article, there are given results of comparative studying of efficiency of surgical and conservative treatment of 277 patients with multidrug resistant tuberculosis. The effectiveness of the surgical treatment of the main group of patients against the background of chemotherapy with anti-TB chemotherapy with the drugs of the reserve line has been compared with two control groups: Group I—Surgical intervention was implemented with drugs of the first line, Group II—Chemotherapy was conducted with anti-TB drugs of the second line without surgical intervention. Treatment outcomes in three groups were stated after cohort investigation, and following results were obtained: Effectiveness of surgical treatment of patients of the main group with MDR TB treated with anti-TB drugs of the second line constituted 98.0% versus 53.7% in the Group II. Effectiveness of conservative treatment of patients in III (control) Group constituted 74.4%. Analysis of results obtained showed that the outcomes in the main group after regimen completed were higher by 1.8 times than in patients operated against the background of treatment with the drugs of the first line and by 1.3 times higher than effectiveness in patients in the Group III (P < 0.01). Effectiveness of the treatment in the Group II was obtained through implementation of collapse-surgical interventions. In this article, the statistical program STAT 10 was applied.

Role of targeting ferroptosis as a component of combination therapy in combating drug resistance in colorectal cancer

Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.

HIGH DOSE INTRA-ARTERIAL HEPATIC INFUSIONAL CHEMOTHERAPY WITH DRUG FILTRATION (HAI-F) FOR PRIMARY LIVER CANCER(A PRELIMINARY REPORT)

Fifteen patients with unresectable hepatocellular carcinoma were treated with unresectable hepatocellular carcinoma were treated with high dose MMC or ADR via hepatic artery with drug filtration in our hospital from April to December 1988. Among them, 11 cases (73%) had symptoms relief, 3 cases (20%) tumor minimal remission and AFP decreased in 4 cases (33%). One case dide of hep'atoma 8 months after HAI-F and another case was followed up only 2 months after treatment, the remaining 13 cases are alive for 5 to 10 months after HAI-F. The reasons of unsatisfactory results were analyzed and possible ways of improvement were suggested.

Shenqi Fuzheng injection alleviates chemotherapy-induced cachexia by restoring glucocorticoid signaling in hypothalamus

Chemotherapy-induced cachexia(CIC)is a debilitating condition characterized by weight loss,muscle atrophy,and anorexia[1].While peripheral mechanisms of cachexia have been extensively studied,the involvement of the central nervous system(CNS)in CIC is often overlooked.Chemotherapeutic drugs cause stress responses and inflammation,which may impact the hypothalamus and disrupt systemic energy and neuroendocrine functions.Understanding hypothalamic roles in regulating these processes can provide insights into CIC's mechanisms and aid in developing novel therapies.

Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

Advances in Transdermal Drug Delivery for Cancer Therapy

Transdermal drug delivery offers a promising alternative to traditional cancer therapies by providing a non-invasive,controlled,and targeted delivery of therapeutic agents.This paper explores the advancements,benefits,and challenges associated with transdermal drug delivery systems(TDDS)in cancer treatment.It highlights the mechanisms of action,key technologies,and the potential impact on patient outcomes.By examining recent studies and clinical trials,this paper aims to provide a comprehensive overview of the efficacy,safety,and prospects of transdermal drug delivery in oncology.

Application and Effect Evaluation of the Integrated“5A and 3+3”Management Model in the Safe Medication Use for Chemotherapy Patients

Objective:To explore the application and effect evaluation of the integrated“5A and 3+3”management model in ensuring safe medication use for chemotherapy patients.Methods:A total of 100 intravenous chemotherapy patients admitted to the oncology department of Shaanxi Provincial People’s Hospital were randomly divided into two groups using a random number list method.Both groups received conventional nursing management during chemotherapy,while the study group additionally received the integrated“5A and 3+3”safety management model.The nursing intervention effects between the two groups were compared.Results:After the intervention,the study group showed higher levels of self-management ability,compliance,and nursing satisfaction compared to the control group.The overall incidence of adverse events during hospitalization was lower in the study group,with statistically significant differences(P<0.05).The knowledge scores of medical staff in the study group,related to the prevention and treatment of chemotherapy drug side effects,daily symptom management,and daily life management,were higher than those in the control group,with statistically significant differences(P<0.05).Conclusion:Implementing the integrated“5A and 3+3”model in the safe medication management of intravenous chemotherapy patients can effectively enhance patients’self-management abilities and compliance,improve medical staff’s ability to safely administer chemotherapy drugs,reduce adverse events caused by chemotherapy,and increase patient satisfaction.

STMN1在胶质瘤中表达的临床意义及其与患者替莫唑胺化疗耐药的相关性

目的分析微管解聚蛋白1(STMN1)在胶质瘤中表达的临床意义及其与患者替莫唑胺化疗耐药的相关性。方法收集78例胶质瘤患者临床资料进行研究。依照患者替莫唑胺化疗疗效耐药情况分为耐药组(17例)和非耐药组(61例)。比较2组一般资料、STMN1表达;STMN1与胶质瘤患者耐药因子表达的相关性;二元逻辑回归分析STMN1与胶质瘤患者替莫唑胺化疗耐药的关系;受试者工作特征曲线(ROC)下面积(AUC)评价STMN1对胶质瘤患者替莫唑胺化疗耐药的预测效能。结果2组年龄、体质量指数、性别、肿瘤类型比较,差异无统计学意义(P>0.05)。耐药组STMN1相对蛋白表达量(0.48±0.07)高于非耐药组(0.42±0.05),差异有统计学意义(t=3.991,P=0.000)。P-gP、MGMT阳性患者STMN1水平均高于P-gP、MGMT阴性患者,hMLH、hMSH2阳性患者STMN1水平均低于hMLH、hMSH2阴性患者,差异有统计学意义(P<0.05)。二元逻辑回归分析结果显示,STMN1可能是胶质瘤患者替莫唑胺化疗耐药的独立危险因素(OR>1,β>0,P<0.05),STMN1与胶质瘤患者替莫唑胺化疗耐药呈正相关关系(γ=8.305,P=0.003)。STMN1预测胶质瘤患者替莫唑胺化疗耐药的AUC为0.720,特异度较高,但灵敏度较低。STMN1预测胶质瘤患者替莫唑胺化疗耐药的相对蛋白表达量阈值为0.485。结论STMN1表达在胶质瘤替莫唑胺化疗耐药患者癌组织中异常升高,STMN1可能与替莫唑胺化疗耐药有关,STMN1表达越高,胶质瘤患者替莫唑胺化疗耐药的风险可能越高。

化疗诱导的周围神经病变的发病机制及治疗进展

化疗诱导的周围神经病变(chemotherapy-induced peripheral neuropathy,CIPN)是指使用抗肿瘤药物导致外周神经功能紊乱而表现出来的一些症状与体征,与化疗药物呈剂量相关性。CIPN的发病机制尚未完全明确,且现有的治疗药物和治疗方法疗效有限,因此探究CIPN的发病机制、研发新的治疗药物和治疗方法,解决未被满足的临床需求具有重要科学价值和社会意义。该文将从分子和细胞层面阐述CIPN的发病机制,以及对CIPN的治疗进展进行综述,为临床治疗提供参考,为未来研究提供方向。

胃癌类器官模型应用于个性化药物筛查的可行性

背景:术后辅助化疗是治疗胃癌的常用方法,但患者对化疗的反应存在很大的差异,需要一种新的临床治疗前模型,来指导胃癌患者的个性化药物治疗。目的:构建基于胃癌组织的类器官模型,探讨其在个性化药物筛查中的应用价值。方法:收集20例胃癌患者术中切除的组织标本,消化分解后与基质胶混合种板,添加含有表皮生长因子和成纤维细胞生长因子10的类器官培养基进行培养。采用苏木精-伊红染色和免疫组化染色对胃癌类器官及原始肿瘤组织进行病理形态学及免疫分子标记同质性验证。通过对卡铂、伊立替康、氟尿嘧啶、奥沙利铂、紫杉醇、表阿霉素等6种药物进行药物敏感性筛查,评估胃癌类器官模型用于药物筛查的可行性。结果与结论:成功培养14例胃癌类器官,类器官的形态及生长特性存在个体性差异,所有类器官均可稳定传代、冻存、复苏。胃癌类器官保留了与原发肿瘤相同的形态学特征及免疫分子表达。6例类器官对6种化疗药物表现出了不同的药物敏感性,初步证实了胃癌类器官作为体外药物筛查模型具有可行性。

胃癌药物治疗专家共识

目的 指导胃癌(GC)的临床治疗用药,提高患者生存率,改善患者生存质量,为临床医师治疗决策提供参考。方法 由重庆大学附属肿瘤医院肿瘤内科专家组成员采用名义群体法共同讨论确定《胃癌药物治疗专家共识》编写大纲。编写组专家针对大纲涉及内容进行系统检索、分析、归纳及总结,并根据我国现状、临床需求和研究证据初步拟定推荐建议。重庆市医学肿瘤学分会化疗学组及重庆市医药生物技术协会肿瘤罕见病疑难病专委会专家经过多轮会议讨论,对推荐建议进行修订,以投票形式确定最终共识内容和推荐等级。结果与结论 本共识内容包括胃癌的围手术期药物治疗、晚期转移性胃癌一线药物治疗、晚期转移性胃癌二线药物治疗、晚期胃癌三线及三线以上药物治疗、胃癌腹膜转移的药物治疗。本共识的发布为我国医疗机构在胃癌的个体化用药方面提供了规范化管理的建议,对提高胃癌的临床疗效、用药安全具有重要意义。

铂类耐药卵巢癌发病机制及治疗策略研究进展

虽然当前卵巢癌治疗方案在不断优化,但手术结合化疗仍是上皮性卵巢癌的主要治疗手段。以R0为目标的卵巢癌肿瘤细胞减灭术结合个体化的化疗方案的应用,使得部分患者5年生存率有了很大的提升,但晚期患者的5年生存率仍然不足30%。化疗耐药是造成卵巢癌患者死亡率居高不下的主要原因,逆转卵巢癌的耐药性是当前临床及科研工作者急需解决的难题。卵巢癌耐药机制错综复杂,主要包括药物转运、药物代谢、细胞凋亡、DNA损伤修复、表观遗传学改变等,此外多药耐药、自噬、肿瘤代谢重组、免疫、肿瘤干细胞等在卵巢癌耐药方面也发挥着重要作用。基于对各种耐药机制的深刻理解,联合用药在提高化疗敏感性、改善患者预后中具有广泛应用前景。本文就当前铂耐药卵巢癌的发病机制及治疗策略的研究进展进行综述。

肠道菌群对乳腺癌化疗疗效及相关不良反应的影响概述

随着乳腺癌发病率的上升和化疗的广泛应用,化疗药物的疗效及不良反应成为关注焦点。微生物与乳腺癌的发展及治疗反应之间存在潜在的关联,益生菌具有调节肠道菌群等作用,在乳腺癌化疗中的潜在价值日益受到重视。本文对肠道菌群对乳腺癌化疗疗效及不良反应的调节作用进行综述,预测其对化疗效果及不良反应的影响,聚焦益生菌改善乳腺癌化疗后不良反应的积极作用,为优化乳腺癌化疗方案,提高综合治疗效果,改善患者生活质量提供科学依据。