Background:Platinum-based chemotherapy is the first-line treatment of non-small cell lung cancer(NSCLC);it is therefore important to discover biomarkers that can be used to predict the efficacy and toxicity of this tr...Background:Platinum-based chemotherapy is the first-line treatment of non-small cell lung cancer(NSCLC);it is therefore important to discover biomarkers that can be used to predict the efficacy and toxicity of this treatment.Four important transporter genes are expressed in the kidney,including organic cation transporter 2(OCT2),multidrug and toxin extrusion 1(MATEl),ATP-binding cassette subfamily B member 1 {ABCB1),and ATP-binding cassette subfamily C member 2(ABCC2),and genetic polymorphisms in these genes may alter the efficacy and adverse effects of platinum drugs.This study aimed to evaluate the association of genetic polymorphisms of these transporters with platinumbased chemotherapy response and toxicity in NSCLC patients.Methods:A total of 403 Chinese NSCLC patients were recruited for this study.All patients were newly diagnosed with NSCLC and received at least two cycles of platinum-based chemotherapy.The tumor response and toxicity were evaluated after two cycles of treatment,and the patients' genomic DNA was extracted.Seven single-nucleotide polymorphisms in four transporter genes were selected to investigate their associations with platinum-based chemotherapy toxicity and response.Results:OCT2 rs316019 was associated with hepatotoxicity(P = 0.026) and hematological toxicity(P = 0.039),and MATEl rs2289669 was associated with hematological toxicity induced by platinum(P = 0.016).In addition,ABCC2rs717620 was significantly associated with the platinum-based chemotherapy response(P = 0.031).ABCB1 polymorphisms were associated with neither response nor toxicity.Conclusion:OCT2 rs316019,MATEl rs2289669,and ABCC2 rs717620 might be potential clinical markers for predicting chemotherapy toxicity and response induced by platinum-based treatment in NSCLC patients.Trial registration Chinese Clinical Trial Registry展开更多
Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemothe...Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemotherapy.Methods:In this retrospective study,four independent cohorts of stageⅣNSCLC patients treated with platinum-based chemotherapy were included for model construction and validation(Discovery:n=159;Internal validation:n=156;External validation:n=81,Mutation validation:n=64).First,a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography(CT)images of each patient.Then,a radiomics signature was constructed using the least absolute shrinkage and selection operator method(LASSO)penalized Cox regression analysis.Finally,an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.Results:The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts(All P<0.05).On the multivariable analysis,independent factors for PFS were radiomics signature,performance status(PS),and N stage,which were all selected into construction of RPSS.The RPSS showed significant prognostic performance for predicting PFS in discovery[C-index:0.772,95%confidence interval(95%CI):0.765-0.779],internal validation(C-index:0.738,95%CI:0.730-0.746),external validation(C-index:0.750,95%CI:0.734-0.765),and mutation validation(Cindex:0.739,95%CI:0.720-0.758).Decision curve analysis revealed that RPSS significantly outperformed the clinicopathologic-based model in terms of clinical usefulness(All P<0.05).Conclusions:This study established a radiomics prognostic scoring system as RPSS that can be conveniently used to achieve individualized prediction of PFS probability for stageⅣNSCLC patients treated with platinumbased chemotherapy,which holds promise for guiding personalized pre-therapy of stageⅣNSCLC.展开更多
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 ty...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.展开更多
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 ce...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.展开更多
Objective This study assessed the weight loss changes and gastrointestinal symptoms in patients with advanced tumors receiving platinum-containing chemotherapy.Methods We retrospectively reviewed 297 patients with adv...Objective This study assessed the weight loss changes and gastrointestinal symptoms in patients with advanced tumors receiving platinum-containing chemotherapy.Methods We retrospectively reviewed 297 patients with advanced cancers[124 gastrointestinal(GI)cancer patients,119 lung cancer patients and 54 head and neck cancer(HNC)patients]receiving first-line chemotherapy at Tongji Hospital.The patients’changes in body weight,body mass index(BMI),and biochemical parameters(serum haemoglobin and albumin levels)were compared before and after two chemotherapy cycles.Results More than half[54.88%(163/297)]of the patients had experienced unintentional weight loss in the 6 months before chemotherapy,and weight loss≥5%and≥10%of the body mass was noted in 35.69%and 20.20%of the patients,respectively.After two cycles of platinum-based chemotherapy,the proportions of patients with a>5%reduction in body weight among patients with GI,lung,and head and neck cancers were 47.5%(59/124),44.53%(53/119),and 46.2%(25/54),respectively.The patients with GI and lung cancers were more vulnerable to extreme weight loss(≥10%)than those with HNC(P=0.025).The serum hemoglobin levels were also remarkably decreased relative to those before chemotherapy(all P<0.05).Common GI symptoms reported by all patients included anorexia(61.28%),vomiting(52.53%),and nausea(51.18%).A higher proportion of patients with≥10%weight loss experienced anorexia and vomiting(OR=12.21 and 3.61,P=0.008 and 0.047,respectively).Conclusions For advanced cancer patients receiving platinum-based chemotherapy,the GI symptoms are the major factor related to their nutritional status.Appropriate nutritional screening,evaluation and treatment should be applied during the treatment of cancer in order to reduce GI symptoms and improve the patient’s nutritional status.展开更多
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 tre...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.展开更多
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 sign...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.展开更多
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 chemotherap...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.展开更多
The residual metal impurities in cisplatin, carboplatin and oxaliplatin were determined by ICP-AES. The samples were ignited and dissolved with HCl:HNO 3 (3:1). The method is simple and accurate. By the determination ...The residual metal impurities in cisplatin, carboplatin and oxaliplatin were determined by ICP-AES. The samples were ignited and dissolved with HCl:HNO 3 (3:1). The method is simple and accurate. By the determination of the metal residues in the samples, the calculated actual daily exposure and concentration of the metal Pd, Ir, Rh, Ru, Mo, Ni, Cr, V, Cu, Mn, Fe and Zn that were less than the permitted daily exposures (PDE) and the limited concentration permitted in the EMEA guideline on the specification limits for residues of metal catalysts or metal reagents [1] . The metal residues can de adequately removed from the active pharmaceutical ingredients and the corresponding drugs. The trace metal residues will not affect human health and lead to the safety hazard by the intravenous injection.展开更多
In the past decade,the advent of the epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)has dramatically influenced the therapeutic strategies for treating lung cancer,but with tumor progression and...In the past decade,the advent of the epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)has dramatically influenced the therapeutic strategies for treating lung cancer,but with tumor progression and drug resistance,patients will ultimately develop reduced sensitivity to EGFR-TKIs.How can we delay the emergence of drug resistance? What is the next strategy after drug resistance? How to reasonably combine platinum-based chemotherapy and EGFR-TKIs? These questions are currently the focus of lung cancer research.Clinical studies have reported that platinum-based chemotherapy can increase the sensitivity to EGFR-TKIs.However,results of pre-clinical and clinical studies have been inconsistent.The mechanisms of platinum chemotherapy and EGFR-TKIs are still unknown due to the lack of systematic research.Therefore,systematic studies are required to show the mechanisms of EGFR-TKIs and chemotherapy agents and define the markers sensitive to their combinations when given concurrently or sequentially.展开更多
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...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.展开更多
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 pati...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.展开更多
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 pop...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.展开更多
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 ...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.展开更多
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 A...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.展开更多
Background:To investigate the role of fibroblast growth factor 2(FGF2)in chemotherapy resistance of colon cancer.Methods:An HCT116/5-fluorouracil(5-FU)-resistant cell line was established,and FGF2 levels were detected...Background:To investigate the role of fibroblast growth factor 2(FGF2)in chemotherapy resistance of colon cancer.Methods:An HCT116/5-fluorouracil(5-FU)-resistant cell line was established,and FGF2 levels were detected in a sensitive cell group(HCT116)and a resistant cell group(HCT1116-R)using different methods.Fibroblast growth factor 2 levels in the medium were determined by enzyme-linked immunoassay.The protein expressions of FGF2,fibroblast growth factor receptor 1(FGFR1),and phospho-FGFR1 were assessed by Western blotting,and FGF2 mRNA levels were detected by quantitative real-time polymerase chain reaction.Fibroblast growth factor 2 recombinant protein was added to sensitive cells,and FGFR inhibitor AZD4547 was added to resistant cells,and the cell survival rate was determined using the cell counting kit-8 method and the protein expressions of PI3K(phosphatidylinositol 3 kinase),p-PI3K(phospho-PI3K),Akt(protein kinase B),p-Akt(phospho-Akt),mammalian target of rapamycin(mTOR),p-mTOR(phospho-mTOR),Bad(Bcl-xL/Bcl-2-associated death promoter),NF-κB(nuclear factorκB),GSK-3(glycogen synthase kinase-3),FKHR(forkhead box protein O1),and PTEN(phosphatase and tensin homolog deleted on chromosome ten)were detected by Western blotting.Results:Fibroblast growth factor 2 protein and mRNA expression levels in the HCT116-R group were significantly higher than those in the HCT116 group.Fibroblast growth factor 2 increased the survival rate of HCT116 cells;improved tolerance to 5-FU;upregulated p-PI3K,p-Akt,and p-mTOR;and downregulated Bad.The FGFR inhibitor AZD4547 decreased cell survival rate and tolerance to 5-FU;downregulated p-PI3K,p-Akt,and p-mTOR expression;and upregulated Bad.Conclusions:Fibroblast growth factor 2 promotes chemotherapy tolerance in colon cancer cells by activating the Akt/mTOR and Akt/Bad signaling pathways downstream of PI3K.展开更多
Pancreatic cancer is a malignant tumor with poor prognosis.The treatment of pancreatic cancer depends on the tumor stage and type,and includes local treatment(surgery,radiotherapy and ablation intervention)and systemi...Pancreatic cancer is a malignant tumor with poor prognosis.The treatment of pancreatic cancer depends on the tumor stage and type,and includes local treatment(surgery,radiotherapy and ablation intervention)and systemic therapy(chemotherapy,targeted therapy and immunotherapy).We read with great interest the review“Effective combinations of anti-cancer and targeted drugs for pancreatic cancer treatment”published on World J Gastroenterol and intended to share some of our perspectives in pancreatic cancer treatment.This review presents the therapeutic effects of the combination of gemcitabine and targeted drugs,which gives us a deeper insight into the combination treatments for pancreatic cancer.展开更多
Objective Anthracycline chemotherapeutic agents have significant cardiotoxicity.The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular(LV)myocardial stiffness in breast cancer ...Objective Anthracycline chemotherapeutic agents have significant cardiotoxicity.The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular(LV)myocardial stiffness in breast cancer patients by measuring the intrinsic wave velocity propagation(IVP),and evaluating the potential clinical value of IVP in detecting early LV diastolic function impairment.Methods A total of 68 newly diagnosed breast cancer patients,who were treated with anthracycline-based chemotherapy,were analyzed.Transthoracic echocardiography was performed at baseline(T0),and after 1,2,3,4 and 8 chemotherapeutic cycles(T1,T2,T3,T4 and T5,respectively).Then,the IVP,LV strain parameters[global longitudinal strain(GLS),longitudinal peak strain rate at systole(LSRs),longitudinal peak strain rate at early diastole(LSRe),longitudinal peak strain rate at late diastole(LSRa),and the E/LSRe ratio],and conventional echocardiographic parameters were obtained and further analyzed.A relative reduction of>15%in GLS was considered a marker of early LV subclinical dysfunction.Results Compared to the T0 stage,IVP significantly increased at the T1 stage.However,there were no significant changes in GLS,LSRs,or LSRe between the T0 and T1 stages.These parameters significantly decreased from the T2 stage.LSRa started to significantly decrease at the T5 stage,and the E/LSRe ratio started to significantly increase at the T3 stage(all P<0.05).At the T0 stage,IVP(AUC=0.752,P<0.001)had a good predictive value for LV subclinical dysfunction after chemotherapy.Conclusions IVP is a potentially sensitive parameter for the early clinical assessment of anthracycline-related cardiac diastolic impairment.展开更多
基金supported by the National High-tech R&D Program of China(863 Program)(2012AA02A517)National Natural Science Foundation of China(81173129,81202595,81373490,81273595)
文摘Background:Platinum-based chemotherapy is the first-line treatment of non-small cell lung cancer(NSCLC);it is therefore important to discover biomarkers that can be used to predict the efficacy and toxicity of this treatment.Four important transporter genes are expressed in the kidney,including organic cation transporter 2(OCT2),multidrug and toxin extrusion 1(MATEl),ATP-binding cassette subfamily B member 1 {ABCB1),and ATP-binding cassette subfamily C member 2(ABCC2),and genetic polymorphisms in these genes may alter the efficacy and adverse effects of platinum drugs.This study aimed to evaluate the association of genetic polymorphisms of these transporters with platinumbased chemotherapy response and toxicity in NSCLC patients.Methods:A total of 403 Chinese NSCLC patients were recruited for this study.All patients were newly diagnosed with NSCLC and received at least two cycles of platinum-based chemotherapy.The tumor response and toxicity were evaluated after two cycles of treatment,and the patients' genomic DNA was extracted.Seven single-nucleotide polymorphisms in four transporter genes were selected to investigate their associations with platinum-based chemotherapy toxicity and response.Results:OCT2 rs316019 was associated with hepatotoxicity(P = 0.026) and hematological toxicity(P = 0.039),and MATEl rs2289669 was associated with hematological toxicity induced by platinum(P = 0.016).In addition,ABCC2rs717620 was significantly associated with the platinum-based chemotherapy response(P = 0.031).ABCB1 polymorphisms were associated with neither response nor toxicity.Conclusion:OCT2 rs316019,MATEl rs2289669,and ABCC2 rs717620 might be potential clinical markers for predicting chemotherapy toxicity and response induced by platinum-based treatment in NSCLC patients.Trial registration Chinese Clinical Trial Registry
基金supported by the National Key Research and Development Plan of China(No.2017YFC1309100)the National Science Fund for Distinguished Young Scholars(No.81925023)the National Natural Scientific Foundation of China(No.81771912,81901910,82072090,and 82001986)。
文摘Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemotherapy.Methods:In this retrospective study,four independent cohorts of stageⅣNSCLC patients treated with platinum-based chemotherapy were included for model construction and validation(Discovery:n=159;Internal validation:n=156;External validation:n=81,Mutation validation:n=64).First,a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography(CT)images of each patient.Then,a radiomics signature was constructed using the least absolute shrinkage and selection operator method(LASSO)penalized Cox regression analysis.Finally,an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.Results:The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts(All P<0.05).On the multivariable analysis,independent factors for PFS were radiomics signature,performance status(PS),and N stage,which were all selected into construction of RPSS.The RPSS showed significant prognostic performance for predicting PFS in discovery[C-index:0.772,95%confidence interval(95%CI):0.765-0.779],internal validation(C-index:0.738,95%CI:0.730-0.746),external validation(C-index:0.750,95%CI:0.734-0.765),and mutation validation(Cindex:0.739,95%CI:0.720-0.758).Decision curve analysis revealed that RPSS significantly outperformed the clinicopathologic-based model in terms of clinical usefulness(All P<0.05).Conclusions:This study established a radiomics prognostic scoring system as RPSS that can be conveniently used to achieve individualized prediction of PFS probability for stageⅣNSCLC patients treated with platinumbased chemotherapy,which holds promise for guiding personalized pre-therapy of stageⅣNSCLC.
文摘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.
基金the National Key Research and Development Program of China(Grant No.:2022YFC3501700)the Key-Area Research and Development Program of Guangdong Province,China(Grant No.:2020B1111110001)the Youth Program of the National Natural Science Foundation of China(Grant No.:82003939).
文摘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.
基金the National Natural Science Foundation of China(No.81703215,81974381)Beijing Xisike Clinical Oncology Research Foundation(No.Y-Q201801-059,81974381)。
文摘Objective This study assessed the weight loss changes and gastrointestinal symptoms in patients with advanced tumors receiving platinum-containing chemotherapy.Methods We retrospectively reviewed 297 patients with advanced cancers[124 gastrointestinal(GI)cancer patients,119 lung cancer patients and 54 head and neck cancer(HNC)patients]receiving first-line chemotherapy at Tongji Hospital.The patients’changes in body weight,body mass index(BMI),and biochemical parameters(serum haemoglobin and albumin levels)were compared before and after two chemotherapy cycles.Results More than half[54.88%(163/297)]of the patients had experienced unintentional weight loss in the 6 months before chemotherapy,and weight loss≥5%and≥10%of the body mass was noted in 35.69%and 20.20%of the patients,respectively.After two cycles of platinum-based chemotherapy,the proportions of patients with a>5%reduction in body weight among patients with GI,lung,and head and neck cancers were 47.5%(59/124),44.53%(53/119),and 46.2%(25/54),respectively.The patients with GI and lung cancers were more vulnerable to extreme weight loss(≥10%)than those with HNC(P=0.025).The serum hemoglobin levels were also remarkably decreased relative to those before chemotherapy(all P<0.05).Common GI symptoms reported by all patients included anorexia(61.28%),vomiting(52.53%),and nausea(51.18%).A higher proportion of patients with≥10%weight loss experienced anorexia and vomiting(OR=12.21 and 3.61,P=0.008 and 0.047,respectively).Conclusions For advanced cancer patients receiving platinum-based chemotherapy,the GI symptoms are the major factor related to their nutritional status.Appropriate nutritional screening,evaluation and treatment should be applied during the treatment of cancer in order to reduce GI symptoms and improve the patient’s nutritional status.
基金supported by the National Natural Science Foundation of China (Grant No. 81973861)Zhejiang Provincial Ministry Medical and Health Co-construction Major Project (Grant No. 20214355173)+2 种基金Zhejiang Science and Technology Department“Vanguard”“Leading Goose”research (Grant No. 2023C03044)Zhejiang Provincial Health“Leading Talents”ProjectZhejiang Medical and Health Science and Technology Project (Grant No. 2022KY558)。
文摘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.
基金This study received support for Open Access Publikationskosten from the DFG.
文摘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.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Ministry of Science and ICT(MSIT)(No.2021R1A2C2012808)Technology Innovation Program(Alchemist Project)(No.20012378)funded by the Ministry of Trade,Industry&Energy(MOTIE),South Korea.
文摘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.
基金The national SME technology innovation fund(11C26215305898)Kunming SME technology innovation fund(CJ2011040)
文摘The residual metal impurities in cisplatin, carboplatin and oxaliplatin were determined by ICP-AES. The samples were ignited and dissolved with HCl:HNO 3 (3:1). The method is simple and accurate. By the determination of the metal residues in the samples, the calculated actual daily exposure and concentration of the metal Pd, Ir, Rh, Ru, Mo, Ni, Cr, V, Cu, Mn, Fe and Zn that were less than the permitted daily exposures (PDE) and the limited concentration permitted in the EMEA guideline on the specification limits for residues of metal catalysts or metal reagents [1] . The metal residues can de adequately removed from the active pharmaceutical ingredients and the corresponding drugs. The trace metal residues will not affect human health and lead to the safety hazard by the intravenous injection.
文摘In the past decade,the advent of the epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)has dramatically influenced the therapeutic strategies for treating lung cancer,but with tumor progression and drug resistance,patients will ultimately develop reduced sensitivity to EGFR-TKIs.How can we delay the emergence of drug resistance? What is the next strategy after drug resistance? How to reasonably combine platinum-based chemotherapy and EGFR-TKIs? These questions are currently the focus of lung cancer research.Clinical studies have reported that platinum-based chemotherapy can increase the sensitivity to EGFR-TKIs.However,results of pre-clinical and clinical studies have been inconsistent.The mechanisms of platinum chemotherapy and EGFR-TKIs are still unknown due to the lack of systematic research.Therefore,systematic studies are required to show the mechanisms of EGFR-TKIs and chemotherapy agents and define the markers sensitive to their combinations when given concurrently or sequentially.
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
基金supported by the National Natural Science Foundation of China (no. 81904109)the Natural Science Project of Hunan Provincial Department of Science and Technology (no.2023JJ30361, no. 2019JJ50344).
文摘Background:To investigate the role of fibroblast growth factor 2(FGF2)in chemotherapy resistance of colon cancer.Methods:An HCT116/5-fluorouracil(5-FU)-resistant cell line was established,and FGF2 levels were detected in a sensitive cell group(HCT116)and a resistant cell group(HCT1116-R)using different methods.Fibroblast growth factor 2 levels in the medium were determined by enzyme-linked immunoassay.The protein expressions of FGF2,fibroblast growth factor receptor 1(FGFR1),and phospho-FGFR1 were assessed by Western blotting,and FGF2 mRNA levels were detected by quantitative real-time polymerase chain reaction.Fibroblast growth factor 2 recombinant protein was added to sensitive cells,and FGFR inhibitor AZD4547 was added to resistant cells,and the cell survival rate was determined using the cell counting kit-8 method and the protein expressions of PI3K(phosphatidylinositol 3 kinase),p-PI3K(phospho-PI3K),Akt(protein kinase B),p-Akt(phospho-Akt),mammalian target of rapamycin(mTOR),p-mTOR(phospho-mTOR),Bad(Bcl-xL/Bcl-2-associated death promoter),NF-κB(nuclear factorκB),GSK-3(glycogen synthase kinase-3),FKHR(forkhead box protein O1),and PTEN(phosphatase and tensin homolog deleted on chromosome ten)were detected by Western blotting.Results:Fibroblast growth factor 2 protein and mRNA expression levels in the HCT116-R group were significantly higher than those in the HCT116 group.Fibroblast growth factor 2 increased the survival rate of HCT116 cells;improved tolerance to 5-FU;upregulated p-PI3K,p-Akt,and p-mTOR;and downregulated Bad.The FGFR inhibitor AZD4547 decreased cell survival rate and tolerance to 5-FU;downregulated p-PI3K,p-Akt,and p-mTOR expression;and upregulated Bad.Conclusions:Fibroblast growth factor 2 promotes chemotherapy tolerance in colon cancer cells by activating the Akt/mTOR and Akt/Bad signaling pathways downstream of PI3K.
文摘Pancreatic cancer is a malignant tumor with poor prognosis.The treatment of pancreatic cancer depends on the tumor stage and type,and includes local treatment(surgery,radiotherapy and ablation intervention)and systemic therapy(chemotherapy,targeted therapy and immunotherapy).We read with great interest the review“Effective combinations of anti-cancer and targeted drugs for pancreatic cancer treatment”published on World J Gastroenterol and intended to share some of our perspectives in pancreatic cancer treatment.This review presents the therapeutic effects of the combination of gemcitabine and targeted drugs,which gives us a deeper insight into the combination treatments for pancreatic cancer.
基金the Hubei Province Health and Famliy Planning Scientific Research Project(No.WJ2023M011)the Department of Finance of Hubei Province(No.3890750).
文摘Objective Anthracycline chemotherapeutic agents have significant cardiotoxicity.The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular(LV)myocardial stiffness in breast cancer patients by measuring the intrinsic wave velocity propagation(IVP),and evaluating the potential clinical value of IVP in detecting early LV diastolic function impairment.Methods A total of 68 newly diagnosed breast cancer patients,who were treated with anthracycline-based chemotherapy,were analyzed.Transthoracic echocardiography was performed at baseline(T0),and after 1,2,3,4 and 8 chemotherapeutic cycles(T1,T2,T3,T4 and T5,respectively).Then,the IVP,LV strain parameters[global longitudinal strain(GLS),longitudinal peak strain rate at systole(LSRs),longitudinal peak strain rate at early diastole(LSRe),longitudinal peak strain rate at late diastole(LSRa),and the E/LSRe ratio],and conventional echocardiographic parameters were obtained and further analyzed.A relative reduction of>15%in GLS was considered a marker of early LV subclinical dysfunction.Results Compared to the T0 stage,IVP significantly increased at the T1 stage.However,there were no significant changes in GLS,LSRs,or LSRe between the T0 and T1 stages.These parameters significantly decreased from the T2 stage.LSRa started to significantly decrease at the T5 stage,and the E/LSRe ratio started to significantly increase at the T3 stage(all P<0.05).At the T0 stage,IVP(AUC=0.752,P<0.001)had a good predictive value for LV subclinical dysfunction after chemotherapy.Conclusions IVP is a potentially sensitive parameter for the early clinical assessment of anthracycline-related cardiac diastolic impairment.