Efficacy and safety of paclitaxel liposome versus paclitaxel in combination with carboplatin in the first-line chemotherapy for ovarian cancer:a multicenter,open-label,non-inferiority,randomized controlled trial

Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising its antitumor efficacy.Methods:This multicenter,open-label,non-inferiority randomized controlled trial(ChiCTR2000038555)evalu-ates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin(PLC vs.PC)as first-line therapy in patients with epithelial ovarian cancer.Results:An analysis of median progression-free survival(PFS)revealed non-inferior outcomes between 263 pa-tients in the PLC group and 260 patients in the PC group(32.3 vs.29.9 months,hazard ratio[HR],0.89[95%CI,0.64−1.25]),using a non-inferior margin of 1.3.Although the overall incidence of treatment-related adverse events was comparable between groups,the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen.Conclusion:The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of pa-clitaxel and carboplatin regarding therapeutic efficacy,with an enhanced safety profile marked by reduced non-hematologic toxicities.

Ability of human umbilical cord mesenchymal stem cells to repair chemotherapy-induced premature ovarian failure

BACKGROUND Premature ovarian insufficiency(POI)and premature ovarian failure(POF)have become one of the major problems threatening women of childbearing age.Studies have shown that stem cells transplanted from bone marrow,umbilical cord,peripheral blood and amniotic fluid can migrate and proliferate to the ovary,promote ovarian function repair,increase the number of follicles and granulosa cells at all levels of ovary,improve endocrine function,and can differentiate into oocytes in specific ovarian environment to restore fertility to some extent.AIM To study the ability of human umbilical cord mesenchymal stem cells(hUCMSCs)to repair ovarian injury after chemotherapy.METHODS A total of 110 female BALB/c mice(aged 7-8 wk old)with body masses of 16.0-20.0 g were selected.The mice were fed until 12 wk of age,and cyclophosphamide was administered by intraperitoneal injection for 14 consecutive days to induce premature ovarian failure in mice.Seventy-five mice with estrous cycle disorder were screened and randomly divided into 3 groups according to their body weight:model group,positive control group and hUCMSC group,and each group had 25 mice.Another 25 mice were used as negative controls.The mice in the hUCMSC group were injected with hUCMSCs in the tail vein,and the mice in the positive control group were given an oestradiol valerate solution and a medroxyprogesterone acetate solution in the tail vein.On the 1^st,15^th,30^th,45^th,and 60^th days after intravenous administration,vaginal smears were made to monitor the estrous cycles of the mice.The ovaries were weighed,and pathological sections were made to observe the morphology of the follicles;blood samples were collected to monitor the concentration of sex hormones(oestradiol and follicle-stimulating hormone).RESULTS The estrous cycles of the model group mice were disrupted throughout the experiment.Mice in the hUCMSC group and the positive control group resumed normal estrous cycles.The ovarian weight of the model group mice continued to decline.The ovarian weight of the hUCMSC group mice and the positive control group mice decreased first and then gradually increased,and the ovarian weight of the hUCMSC group mice was heavier than that of the positive control group mice.The difference was statistically significant(P<0.05).Compared with the negative control group,the model group experienced a decrease in oestradiol and an increase in follicle-stimulating hormone,and the difference was statistically significant(P<0.05).Compared with the model group,the hUCMSC and positive control groups experienced a slight increase in oestradiol and a decrease in follicle-stimulating hormone;the difference was statistically significant(P<0.05).The pathological examination revealed that the mouse ovaries from the model group were atrophied,the volume was reduced,the cortical and medullary structures were disordered,the number of follicles at all stages was significantly reduced,the number of atretic follicles increased,the number of primordial follicles and corpus luteum significantly decreased,and the corpus luteum had an irregular shape.Compared with those of the model group,the lesions of the hUCMSC and positive control groups significantly improved.CONCLUSION hUCMSCs can repair ovarian tissue damaged by chemotherapy to a certain extent,can improve the degree of apoptosis in ovarian tissue,and can improve the endocrine function of mouse ovaries.

Hormonal therapy might be a better choice as maintenance treatment than capecitabine after response to first-line capecitabine-based combination chemotherapy for patients with hormone receptor-positive and HER2-negative,metastatic breast cancer

Background:Both hormonal therapy(HT) and maintenance capecitabine monotherapy(MCT) have been shown to extend time to progression(TTP) in patients with metastatic breast cancer(MBC) after failure of taxanes and anthracycline?containing regimens.However,no clinical trials have directly compared the efficacy of MCT and HT after response to first?line capecitabine?based combination chemotherapy(FCCT) in patients with hormone receptor(HR)?positive and human epidermal growth factor receptor 2(HER2)?negative breast cancer.Methods:We retrospectively analyzed the charts of 138 HR?positive and HER2?negative MBC patients who were in non?progression status after FCCT and who were treated between 2003 and 2012 at the Cancer Institute and Hospital,Chinese Academy of Medical Sciences,in Beijing,China.The median number of first?line chemotherapy cycles was 6(range,4–8);combined agents included taxanes,vinorelbine,or gemcitabine.Of these 138 patients,79 received MCT,and 59 received HT.Single?agent capecitabine was administered at a dose of 1250 mg/m2 twice daily for 14 days,followed by a 7?day rest period,repeated every 3 weeks.Of the 59 patients who received HT,37 received aromatase inhibitors(AIs),8 received selective estrogen receptor modulators(SERMs),and 14 received goserelin plus either AIs or SERMs.We then compared the MCT group and HT group in terms of treatment efficacy.Results:With a median follow?up of 43 months,patients in the HT group had a much longer TTP than patients in the MCT group(13 vs.8 months,P ease?free surviv= 0.011).When TTP was adjusted for age,menopausal status,Karnofsky performance status score,disal,site of metastasis,number of metastatic sites,and response status after FCCT,extended TTP was still observed for patients in the HT group(hazard ratio:0.63;95% confidence interval:0.44–0.93;P = 0.020).We also observed a trend of overall survival advantage for patients in the HT group vs.patients in the MCT group,but the difference was not significant(43 vs.37 months,P tients in the MCT g= 0.400).In addition,patients in the HT group gen?erally tolerated the treatment well,whereas paroup experienced grades 3–4 adverse events,the most frequent of which were hand?foot syndrome(15.8%) and hematologic abnormalities(7.6%).Conclusion:For HR?positive and HER2?negative MBC patients,HT might be considered a treatment after response to FCCT but prior to MCT as a long?term administration.

Liver transplantation for acute hepatic failure due to chemotherapy-induced HBV reactivation in lymphoma patients

Hepatitis B （HBV） reactivation induced by chemotherapy is problem encountered recently in the management of malignant diseases. Chemotherapy-induced HBV reacti- vation may ultimately lead to terminal acute liver failure. Liver transplantation （LT） currently remains the only definitive treatment option for such cases, but is generally denied to patients suffering from malignancy. Here, the authors describe 2 cases of cancer-free and HBV graft renfection-free survival after LT performed for terminal liver failure arising from HBV reactivation induced by chemotherapy for advanced stage lymphoma. These 2 cases, and some other reports in the literature, may suggest that patients suffering from hematologic malignan- cies and terminal liver disease can be considered for LT if the prognosis of their hematologic malignancy is good.

Treatment with Intensity-Modulated Radiation Therapy (IMRT) and Chemotherapy in Advanced Inoperable Non-Small Cell Lung Cancer (NSCLC): Toxicity, Survival and Patterns of Failure in Relation to Treatment with High and Low Radiation Dose

Purpose: To investigate the toxicity, survival and patterns of failure in patients with advanced lung cancer treated with intensity modulated radiation therapy (IMRT) and chemotherapy. Methods and Materials: Retrospective chart review of 68 total patients: 46 academic and 22 community center. Endpoints: Grade ≥ 3 pneumonitis, Grade ≥ 2 esophagitis, local, regional and distant failure, progression-free survival (PFS) and overall survival (OS). Results: For the academic center patients, median follow-up was 19.2 months. Esophagitis: 0% Grade 3, 35% Grade 2, no significant difference between dose bins: <70 Gy vs. 70 Gy, 25% vs. 45% (p = 0.22), <66 Gy vs. 66 - 70 Gy, 28% vs. 39% (p = 0.53). Lung dose metrics and PTV size were not associated with Grade ≥ 3 pneumonitis. Esophageal V35, V50, and mean dose but not PTV size was associated with Grade 2 esophagitis. 1 year local, regional and distant failure = 6.5%, 6.5%, and 30.4%. No endpoint differences were seen between dose bins, though patients with smaller PTVs treated with 70 Gy did demonstrate improved OS (ns) when compared to those treated with <70 Gy. Community Center: Median follow-up 6.2 months with 15% Grade 2 esophagitis, no Grade 3 esophagitis. Two patients (9%) experienced Grade ≥ 3 pneumonitis. Conclusions: IMRT chemoradiation was well tolerated in a population with advanced NSCLC both in the academic and community settings. Severe pneumonitis rates were low and comparable to other series using IMRT and chemotherapy. Esophagitis was mild and associated with V35, V50 and mean dose. No significant benefit was seen for higher doses regarding survival, local, regional or distant control despite that higher dose bins had smaller tumors. Though not statistically significant, we did find a trend toward worse OS for <70 Gy when the PTV was less than the median PTV.

Sequential chemotherapy and icotinib as first-line treatment for advanced epidermal growth factor receptor-mutated non-small cell lung cancer

BACKGROUND Icotinib could have potential effect and tolerability when used sequentially with chemotherapy for advanced epidermal growth factor receptor(EGFR)-mutated non-small cell lung cancer(NSCLC).AIM To evaluate the efficacy and safety of chemotherapy followed by icotinib maintenance therapy as first-line treatment for advanced EGFR-mutated NSCLC.METHODS This multicenter,open-label,pilot randomized controlled trial enrolled 68 EGFRmutated stage IIIB/IV NSCLC patients randomized 2:3 to the icotinib alone and chemotherapy+icotinib groups.RESULTS The median progression-free survival in the icotinib alone and chemotherapy+icotinib groups was 8.0 mo(95%CI:3.84-11.63)and 13.4 mo(95%CI:10.18-16.33),respectively(P=0.0249).No significant differences were found in the curative effect when considering different cycles of chemotherapy or chemotherapy regimen(all P>0.05).CONCLUSION A sequential combination of chemotherapy and EGFR-tyrosine kinase inhibitor is feasible for stage IV EGFR-mutated NSCLC patients.

Fulminant hepatic failure resulting from small-cell lung cancer and dramatic response of chemotherapy

Prompt treatment in tumor-associated encephalopathy may prolong survival. We describe a 69-year-old male patient who was presented with fulminant hepatic failure, secondary to small-cell lung carcinoma with rapidly progressing encephalopathy. Both symptoms remitted following chemotherapy, suggesting swift diagnosis and administration of chemotherapy to be effective in treatment of fulminant hepatic failure and encephalopathy.

Efficacy of cetuximab combination with chemotherapy in non-small cell lung cancer first-line setting:the summary based on publications

Objective： The combination of cetuximab with standard chemotherapy was not widely studied though it was recommended by NCCN 2009 to apply in non-small cell lung cancer （NSCLC） first-line setting. The aim of this study was to summary the efficacy and safety profiles of all the NSCLC patients available in openly published papers treated with above mentioned regimens. Methods： The PubMed database was used to search all the papers on NSCLC associated with cetuximab treatment, and only the clinical trails applied cetuximab combined with doublets cytotoxic chemotherapy in first-line setting till to 30 November 2009 were collected. And the medians and their 95% CI of objective response rate （ORR）, progression free survival （PFS）, overall survival （OS）, and the common adverse events were calculated. Results： （1） Eight papers including 1032 patients were collected, and all cases were at advanced stage. （2） The ratio of male and female patients was 1.6, 50.1% patients were adenocarcinoma and 28.2% patients were squamous cell carcinoma （SCC）, 90.0% patients were PS = 0-1, and 78.2% patients were white ethnic. （3） The disease control rate （DCR）, ORR, PFS, and OS were 65.2% （95% CI： 60.7%-69.7%）, 33.2% （95% CI： 30.3%-36.1%）, 5.0 months （95% CI： 4.7-5.3） and 10.9 months （95% Cl： 9.6-12.2）, respectively. Conclusion： This is the first study to summarize the efficacy and safety profiles of cetuximab combined with chemotherapy in NSCLC first-line setting based on all available patients. The addition of cetuximab caused promising prognosis and acceptable side effects excepting higher incidence of neutropenia, and febrile neutropenia.

Concurrent chemotherapy and reduced - dose cranial spinal irradiation followed by conformal posterior fossa tumor bed boost for average - risk medulloblastoma: efficacy and patterns of failure

PURPOSE:To review the efficacy and patterns of failure in average-risk medulloblastoma patients treated withconcurrent chemotherapy and reduced-dose cranial spinal irradiation and a conformal tumor bed boost.METH-ODS AND MATERIALS:Thirty-three patients with average risk(defined as<==1.5 cm(2)of residual tumorafter resection,age>3 years,and no involvement of the cerebrospinal fluid or spine)medulloblastoma werediagnosed at our institution between January 1994 and December 2001.They were enrolled in an institutional

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study

BACKGROUND FOLFIRINOX regimen is the first-line reference chemotherapy(L1)in advanced pancreatic ductal adenocarcinoma(aPDAC).FOLFOXIRI,a schedule with a lower dose of irinotecan and no bolus 5-fluorouracil,has demonstrated efficacy and feasibility in colorectal cancer.AIM To investigate the potential clinical value of FOLFOXIRI in patients with aPDAC in routine clinical practice.METHODS Analyses were derived from all consecutive aPDAC patients treated in L1 between January 2011 and December 2017 in two French institutions,with either FOLFOXIRI(n=165)or FOLFIRINOX(n=124)regimens.FOLFOXIRI consisted of irinotecan(165 mg/m2),oxaliplatin(85 mg/m2),leucovorin(200 mg/m2)and 5-fluorouracil(3200 mg/m2 as a 48-h continuous infusion)every 2 wk.Ninety-six pairs of patients were selected through propensity score matching,and clinical outcomes of the two treatment regimens were compared.RESULTS Median overall survival was 11.1 mo in the FOLFOXIRI and 11.6 mo in the FOLFIRINOX cohorts,respectively.After propensity score matching,survival rates remained similar between the two regimens in terms of overall survival(hazard ratio=1.22;P=0.219)and progression-free survival(hazard ratio=1.27;P=0.120).The objective response rate was 37.1%in the FOLFOXIRI group vs 47.8%in the FOLFIRINOX group(P=0.187).Grade 3/4 toxicities occurred in 28.7%of patients in the FOLFOXIRI cohort vs 19.5%in the FOLFIRINOX cohort(P=0.079).FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events.Hematopoietic growth factors were used after each chemotherapy cycle and the low hematological toxicity rates were below 5%with both regimens.CONCLUSION FOLFOXIRI is feasible in L1 in patients with aPDAC but does not confer any therapeutic benefit as compared with FOLFIRINOX.The low hematological toxicity rates strengthened the relevance of primary prophylaxis with hematopoietic growth factors.

Serum basic fibroblast growth factor and interleukin-1βpredict the effect of first-line chemotherapy in patients with advanced gastric cancer

BACKGROUND The incidence and mortality rates of gastric cancer in China are the second-highest in the world,and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis.AIM To explore the predictive potential of serum basic fibroblast growth factor and interleukin-1βlevels for the effect of first-line chemotherapy in patients with advanced gastric cancer.METHODS From the gastric cancer patients admitted to our hospital from May 2019 to April 2023,84 patients were selected and randomly and equally assigned to the experimental or control group.The FLOT group received the FLOT chemotherapy regimen(composed of oxaliplatin+calcium folinate+fluorouracil+paclitaxel),while the SOX group received the SOX chemotherapy regimen(composed of oxaliplatin+tiga capsules).The clinical efficacy,tumor marker levels,adverse reactions,and survival rates of the two groups were compared 7 days after the end of the relevant treatments.RESULTS The target effective rate of the FLOT group was 54.76%,which was much higher than that of the SOX group(33.33%;P<0.05).After treatment,both the groups demonstrated lower levels of cancer antigen(CEA),carbohydrate antigen 199(CA199),and peptide tissue antigen(TPS).For several patients before treatment(P<0.05).Third and fourth grades.In terms of adverse reactions,the level of white blood cells in both the groups was lower.Moreover,the incidence of hand-foot skin reactions in these two study groups was lower(P<0.05),while those of peripheral neuritis,vomiting,diarrhea,and abnormal liver function were significant(P<0.05).No statistically significant difference was noted between the two groups(P<0.05).The 1-year survival rate was higher in the FLOT group(P<0.05).CONCLUSION The FLOT regimen was effective in reducing the serum CEA,CA199,and TPS levels as well as in improving the 1-year survival rate of patients with good tolerability,making it worthy of clinical promotion and application.

Human embryonic stem cell-derived mesenchymal stem cells improved premature ovarian failure

BACKGROUND Premature ovarian failure(POF)affects many adult women less than 40 years of age and leads to infertility.According to previous reports,various tissue-specific stem cells can restore ovarian function and folliculogenesis in mice with chemotherapy-induced POF.Human embryonic stem cells(ES)provide an alternative source for mesenchymal stem cells(MSCs)because of their similarities in phenotype and immunomodulatory and anti-inflammatory characteristics.Embryonic stem cell-derived mesenchymal stem cells(ES-MSCs)are attractive candidates for regenerative medicine because of their high proliferation and lack of barriers for harvesting tissue-specific MSCs.However,possible therapeutic effects and underlying mechanisms of transplanted ES-MSCs on cyclophosphamide and busulfan-induced mouse ovarian damage have not been evaluated.AIM To evaluate ES-MSCs vs bone marrow-derived mesenchymal stem cells(BMMSCs)in restoring ovarian function in a mouse model of chemotherapy-induced premature ovarian failure.METHODS Female mice received intraperitoneal injections of different doses of cyclophosphamide and busulfan to induce POF.Either human ES-MSCs or BMMSCs were transplanted into these mice.Ten days after the mice were injected with cyclophosphamide and busulfan and 4 wk after transplantation of the ESMSCs and/or BM-MSCs,we evaluated body weight,estrous cyclicity,folliclestimulating hormone and estradiol hormone concentrations and follicle count were used to evaluate the POF model and cell transplantation.Moreover,terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labeling,real-time PCR,Western blot analysis and immunohistochemistry and mating was used to evaluate cell transplantation.Enzyme-linked immunosorbent assay was used to analyze vascular endothelial growth factor,insulin-like growth factor 2 and hepatocyte growth factor levels in ES-MSC condition medium in order to investigate the mechanisms that underlie their function.RESULTS The human ES-MSCs significantly restored hormone secretion,survival rate and reproductive function in POF mice,which was similar to the results obtained with BM-MSCs.Gene expression analysis and the terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labeling assay results indicated that the ES-MSCs and/or BM-MSCs reduced apoptosis in the follicles.Notably,the transplanted mice generated new offspring.The results of different analyses showed increases in antiapoptotic and trophic proteins and genes.CONCLUSION These results suggested that transplantation of human ES-MSCs were similar to BM-MSCs in that they could restore the structure of the injured ovarian tissue and its function in chemotherapy-induced damaged POF mice and rescue fertility.The possible mechanisms of human ES-MSC were related to promotion of follicular development,ovarian secretion,fertility via a paracrine effect and ovarian cell survival.

Secondary lymphoma develops in the setting of heart failure when treating breast cancer: A case report

BACKGROUND Cardiovascular side effects occur frequently during anti-cancer treatment, and there is a growing concern that they may lead to premature morbidity and death. CASE SUMMARY A 32-year-old woman was diagnosed with breast cancer. After comprehensive treatment with neoadjuvant chemotherapy, surgery, postoperative adjuvant chemotherapy, postoperative adjuvant radiotherapy, and endocrine therapy, her breast cancer was cured. However, heart failure associated with anti-cancer treatment presented, most probably related to chemotherapy containing anthracycline. After active treatment, her cardiac function returned to normal. Unfortunately, follow-up visits revealed a second primary malignancy, lymphoma. After multiple courses of chemotherapy combined with targeted therapy, her lymphoma acquired complete remission and no cardiotoxicity was observed again. Heart failure related to breast treatment may be reversible. CONCLUSION Using alternatives to anthracycline in patients with lymphoma who are at risk of cardiac failure may preserve cardiac function.

Neutropenic Fever in Lung Cancer:Clinical Aspects Related to Mortality and Antibiotic Failure

Background and objectives:Lung cancer(LC)is the leading cause of cancer death.Patients treated with chemotherapy are at risk of developing chemotherapy-induced febrile neutropenia(FN),a potentially life-threatening complication.The aims of this study were(1)to characterize FN admissions of patients with LC in a pulmonology department,and(2)to determine associations between patient profiles,first-line antibiotic failure(FLAF)and mortality.Methods:Retrospective observational case-series,based on the analysis of medical records of LC patients that required hospitalization due to chemotherapy-induced FN.Results:A total of 42 cases of FN were revised,corresponding to 36 patients,of which 86.1%were male,with a mean age of 66.71±9.83 years.Most patients had a performance status(PS)equal or less than 1,and metastatic disease was present in 40.5%(n=17).Respiratory tract infections accounted for 42.9%(n=18)of FN cases,and multidrug-resistant Staphylococcus aureus was the most isolated agent.The mortality rate was 16.7%(n=7),and the FLAF was 26.2%(n=11).Mortality was associated with a PS≥2(P=0.011),infection by a Gram-negative agent(P=0.001)and severe anemia(P=0.048).FLAF was associated with longer hospitalizations(P=0.020),PS≥2(P=0.049),respiratory infections(P=0.024),and infection by a Gram-negative(P=0.003)or multidrug-resistant agent(P=0.014).Conclusions:Lower PS,severe anemia,and infections by Gram-negative or multi-resistant agents seem to be associated with worse outcomes in FN patients.

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1

BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab treatment.Programmed cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.AIM To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of PD-L1.METHODS This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.RESULTS A total of 124 patients was included in this analysis.Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy.While 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line chemotherapy.The numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),respectively.The results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

An infusible biologically active adhesive for chemotherapy-related heart failure in elderly rats

Chemotherapy-induced cardiotoxicity with subsequent heart failure(HF)is a major cause of morbidity and mortality in cancer survivors worldwide.Chemotherapy-induced HF is exceptionally challenging as it generally manifests in patients who are typically not eligible for left ventricular device implantation or heart transplantation.To explore alternative treatment strategies for cancer survivors suffering from chemotherapy-induced HF,we developed a minimally invasive infusible cardiac stromal cell secretomes adhesive(MISA)that could be delivered locally through an endoscope-guided intrapericardial injection.To mimic the typical clinical presentation of chemotherapy-induced HF in elder patients,we established an aged rat model in which restrictive cardiomyopathy with sequential HF was induced via consecutive doxorubicin injections.In vitro,we prove that MISA not only enhanced cardiomyocytes proliferation potency and viability,but also inhibited their apoptosis.In vivo,we prove that MISA improved the ventricular contractility indexes and led to beneficial effects on histological and structural features of restrictive cardiomyopathy via promoting cardiomyocyte proliferation,angiogenesis,and mitochondrial respiration.Additionally,we also evaluated the safety and feasibility of MISA intrapericardial delivery in a healthy porcine model with an intact immune system.In general,our data indicates that MISA has a strong potential for translation into large animal models and ultimately clinical applications for chemotherapy-induced HF prior to the final option of heart transplantation.

Combining of chemotherapy with targeted therapy for advanced biliary tract cancer:A systematic review and meta-analysis

BACKGROUND Targeted therapy(TT)has resulted in controversial efficacy as first-line treatment for biliary tract cancer(BTC).More efficacy comparisons are required to clarify the overall effects of chemotherapy(CT)combined with TT and CT alone on advanced BTC.AIM To conduct a meta-analysis of the available evidence on the efficacy of CT combined with TT for advanced BTC.METHODS The PubMed,EMBASE,ClinicalTrials,Scopus and Cochrane Library databases were systematically searched for relevant studies published from inception to August 2022.Only randomized clinical trials(RCTs)including comparisons between the combination of gemcitabine-based CT with TT and CT alone as firstline treatment for advanced BTC were eligible(PROSPERO-CRD42022313001).The odds ratios(ORs)for the objective response rate(ORR)and hazard ratios(HRs)for both progression-free survival(PFS)and overall survival(OS)were calculated and analyzed.Subgroup analyses based on different targeted agents,CT regimens and tumor locations were prespecified.RESULTS Nine RCTs with a total of 1361 individuals were included and analyzed.The overall analysis showed a significant improvement in ORR in patients treated with CT+TT compared to those treated with CT alone(OR=1.43,95%CI:1.11-1.86,P=0.007)but no difference in PFS or OS.Similar trends were observed in the subgroup treated with agents targeting epidermal growth factor receptor(OR=1.67,95%CI:1.17-2.37,P=0.004)but not in the subgroups treated with agents targeting vascular endothelial growth factor receptor or mesenchymal-epithelial transition factor.Notably,patients who received a CT regimen of gemcitabine+oxaliplatin in the CT+TT arm had both a higher ORR(OR=1.75,95%CI:1.20-2.56,P=0.004)and longer PFS(HR=0.83,95%CI:0.70-0.99,P=0.03)than those in the CT-only arm.Moreover,patients with cholangiocarcinoma treated with CT+TT had significantly increased ORR and PFS(ORR,OR=2.06,95%CI:1.27-3.35,PFS,HR=0.79,95%CI:0.66-0.94).CONCLUSION CT+TT is a potential first-line treatment for advanced BTC that leads to improved tumor control and survival outcomes,and highlighting the importance of CT regimens and tumor types in the application of TT.

Treatment failure and associated factors among first line patients on highly active antiretroviral therapy in Ethiopia:a systematic review and meta-analysis

Background:Antiretroviral therapy(ART)restores immune function and reduces human immunodeficiency virus(HIV)related adverse outcomes.The results of previous studies in Ethiopia were replete with inconsistent findings;nonexistence of national representative figures and determinant factors are found as significant gap.The aim of this systematic review and meta-analysis was to assess the existing evidence on ART treatment failure and associated factors in Ethiopia.Methods:Relevant studies on ART treatment failure were retrieved from international databases:PubMed,Google Scholar,Scopus,and Science Direct systematically prior to March 14,2019.All identified studies reporting the proportion of first line treatment failure among HIV patients in Ethiopia were included.Two authors independently extracted all necessary data using a standardized data extraction format.A random-effects model was used to calculate pooled estimates and associated factors in Stata/se Version-14.The Cochrane Q test statistics and I2 tests were used to assess the heterogeneity of the studies.Results:From 18 articles reviewed;the pooled proportion of first line treatment failure among ART users in Ethiopia was 15.3%(95%CI:12,18.6)with(I2=97.9%,p<0.001).The subgroup analysis by World Health Organization(WHO)treatment failure assessment criteria were carried out,accordingly the highest prevalence(11.5%)was noted on immunological and the lowest(5.8%)was observed virological treatment failure.We had found poor adherence(OR=8.6,95%CI:5.6,13.4),not disclosed(OR=2.1,95%CI:1.5,3.0),advanced WHO clinical stage III/IV(OR=2.4,95%CI:1.5,3.8),change in regimen(OR=2.5,95%CI:1.6,3.9)and being co-infected(OR=2.56,95%CI:2.2,3.0)were statistically significant factors for treatment failure.Conclusion:In this study,treatment failure among ART users in Ethiopia was significant.Adherence,co-infection,advanced WHO clinical stage,regimen change,and disclosure are determinant factors for treatment failure.Therefore,improve drug adherence,prevent co-infection,close follow up,and prevent HIV-drug resistance are required in future remedial efforts.

PD-1抑制剂联合安罗替尼治疗二线化疗失败的老年晚期非小细胞肺癌的效果

目的 探究程序性死亡受体1(PD-1)抑制剂联合安罗替尼治疗二线化疗失败的老年晚期非小细胞肺癌(NSCLC)的临床疗效。方法 选取2019年1月—2021年4月泰州市第二人民医院收治的106例二线化疗失败的老年晚期NSCLC患者作为研究对象,按照随机数字表法分为单药组和联合组,各53例。单药组采用安罗替尼治疗,联合组采用PD-1抑制剂联合安罗替尼治疗。比较两组的疾病控制率、毒副反应发生情况、生存率、肿瘤标志物[细胞角蛋白19片段抗原21-1(CYFRA21-1)、癌胚抗原(CEA)、糖类抗原125(CA125)]、血管新生指标[血管内皮生长因子(VEGF)-A、VEGF受体2(VEGFR2)]、血清驱动蛋白超家族蛋白(KIF)C1、N-钙黏蛋白、生活质量核心量表(QLQ-C30)评分。结果 联合组疾病控制率高于单药组(P<0.05);治疗2个周期后,联合组血清CYFRA21-1、CA125、CEA、VEGF-A、VEGFR2、KIFC1及N-钙黏蛋白水平均低于单药组(P<0.05),QLQ-C30评分低于单药组(P<0.05);两组各毒副反应总发生率比较,差异均无统计学意义(P>0.05);Kaplan-Meier生存分析显示,联合组累积生存率高于单药组(P<0.05)。结论 PD-1抑制剂联合安罗替尼治疗二线化疗失败的老年晚期NSCLC效果显著,可有效调节血清KIFC1、N-钙黏蛋白表达,抑制VEGF-A、VEGFR2水平,降低肿瘤标志物水平,提高生活质量,延长生存时间,安全性高。

参附汤抑制铁死亡缓解化疗药物心脏毒性研究

目的:本研究拟验证参附汤这一经典名方是否通过铁死亡缓解心力衰竭。方法:网络药理学寻找参附汤、心力衰竭、铁死亡重叠基因。Metascape数据库进行基因本体(GO)富集分析及富集分析和京都基因和基因组百科全书(KEGG)通路预测。用阿霉素对H9C2细胞造心肌细胞损伤模型,测定细胞活力、Fe2+含量、铁死亡marker蛋白、蛋白酪氨酸激酶2(JAK2)-信号转导及转录激活蛋白3(STAT3)信号通路表达。C57小鼠阿霉素注射4周造心力衰竭模型,测定左室心射血分数,观察心肌形态学改变,测定肌肉Fe2+含量,免疫组织化学检测验证心肌相关蛋白表达水平。结果:网络药理学研究证实,共有13个重叠基因。PTGS2蛋白等为参附汤基于铁死亡对心力衰竭调控的核心节点。GO功能分析证实,生物过程相关条目有11个,细胞组分3个;分子功能3个。KEGG预测分信号通路4条。Jak-STAT等通路是心力衰竭主要机制。分子对接证实对接能均小于-5 kcal/mol。参附注射液含药血清汤提高细胞活力,减少铁含量,抑制铁死亡marker蛋白,JAK2-STAT3信号通路。动物实验证实,参附注射液改善了小鼠心肌细胞形态学改变,增加了心功能,佐证了细胞实验中铁死亡及JAK2-STAT3调控机制研究。结论:本研究证实铁死亡是参附汤对心力衰竭调控机制,丰富了参附汤调控心肌死亡途径的科学证据。