A radiomics prognostic scoring system for predicting progression-free survival in patients with stageⅣnon-small cell lung cancer treated with platinum-based chemotherapy

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.

Associations of genetic polymorphisms of the transporters organic cation transporter 2(OCT2),multidrug and toxin extrusion 1(MATE1),and ATP-binding cassette subfamily C member 2(ABCC2) with platinum-based chemotherapy response and toxicity in non-small cel

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

Weight Loss and Gastrointestinal Symptoms in Advanced Cancer Patients Treated with Platinum-based Chemotherapy

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.

Determination of Residues and Safety Analysis of Metal Impurities in Platinum-based Antitumor Drugs

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.

Platinum-based nanopharmaceuticals used to overcome cisplatin resistance in vitro and in vivo

Cisplatin resistance still remains a major obstacle to successful treatment of cancer.The development of cellular resistance to platinum-based chemotherapies is often associated with reduced intracellular platinum concentrations.In some models,this reduction is due to abnormal membrane protein trafficking,resulting in reduced uptake by transporters at the cell surface.Given the central role of platinum drugs in the clinic.

In vitro antitumor activity and targeted sites of two novel platinum-based(II) complexes on SW620 colon cancer cell line

Objective:The aim of our study was to evaluate the in vitro antitumor activity of two novel platinum-based(II) complexes(2.3-pyridinedicarboxylic acid dehydrate platinum and 2.3-pyrazinedicarboxylic acid dehydrate platinum),which were concurrently provided with hydrophilic carboxyl group and lipophilic pyrazinyl or pyridyl group,on SW620 colorectal cancer cell line and the impact of the two compounds on the cell cycle and apoptosis of the cells when compared with the oxaliplatin,desiring the new ligand combined with hydrophilic and lipophilic properties would facilitate the transportation and transmembrane of the drugs,showing a better antitumor activity.Methods:After SW620 cells were treated with different doses of the three platinum-based agents for 24,48 and 72 h,the cell proliferation inhibition rate was determined using methyl thiazolyl tetrazolium(MTT) assay;the morphology of cells were evaluated under inverted microscope;the changes in cell cycle were determined using flow cytometry;the percent apoptosis was measured using Annexin V/PI double staining and the micromorphology of the cells after drug exposure was evaluated using scanning electron microscopy.Results:The evaluation on the proliferation inhibition rate revealed that the three platinum-based agents inhibited the SW620 cells in a time-and dose-dependent manner and showed different strengths as pyridine > pyrazine > Oxa.Under optical microscope,the morphological changes such as cell shrinkage,round cells and dead cells were frequently observed after drug exposure.Cell cycle determination showed that all of the three agents could function to block the cells converting from phase S to phase G2M.Apoptosis evaluation revealed that the three agents promoted the apoptosis of SW620 cells in a time-and dose-dependent manner and showed different strengths as pyridine > pyrazine > Oxa.Typical early and late apoptotic morphological changes could be detected during electron microscopy.Conclusion:The two novel platinum-based(II) complexes showed a stronger antitumor effect on SW620 cells than oxaliplatin,with the targeted site at a certain phase of cell cycle and apoptosis.

Research progress in the use of combinations of platinum-based chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors

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.

Data-driven structural descriptor for predicting platinum-based alloys as oxygen reduction electrocatalysts

Owing to increasing global demand for carbon neutral and fossil-free energy systems,extensive research is being conducted on efficient and inexpensive electrocatalysts for catalyzing the kinetically sluggish oxygen reduction reaction(ORR)at the cathode of fuel cells.Platinum(Pt)-based alloys are considered promising candidates for replacing expensive Pt catalysts.However,the current screening process of Pt-based alloys is time-consuming and labor-intensive,and the descriptor for predicting the activity of Pt-based catalysts is generally inaccurate.This study proposed a strategy by combining high-throughput first-principles calculations and machine learning to explore the descriptor used for screening Pt-based alloy catalysts with high Pt utilization and low Pt consump-tion.Among the 77 prescreened candidates,we identified 5 potential candidates for catalyzing ORR with low overpotential.Furthermore,during the second and third rounds of active learning,more Pt-based alloys ORR candidates are identi-fied based on the relationship between structural features of Pt-based alloys and their activity.In addition,we highlighted the role of structural features in Pt-based alloys and found that the difference between the electronegativity of Pt and heteroatom,the valence electrons number of the heteroatom,and the ratio of heteroatoms around Pt are the main factors that affect the activity of ORR.More importantly,the combination of those structural features can be used as structural descriptor for predicting the activity of Pt-based alloys.We believe the findings of this study will provide new insight for predicting ORR activ-ity and contribute to exploring Pt-based electrocatalysts with high Pt utiliza-tion and low Pt consumption experimentally.

The Nature of Active Sites for Plasmon-Mediated Photothermal Catalysis and Heat-Coupled Photocatalysis in Dry Reforming of Methane

Solar energy-induced catalysis has been attracting intensive interests and its quantum efficiencies in plasmon-mediated photothermal catalysis(P-photothermal catalysis)and external heat-coupled photocatalysis(E-photothermal catalysis)are ultimately determined by the catalyst structure for photo-induced energetic hot carriers.Herein,different catalysts of supported(TiO_(2)-P25 and Al_(2)O_(3))platinum quantum dots are employed in photo,thermal,and photothermal catalytic dry reforming of methane.Integrated experimental and computational results unveil different active sites(hot zones)on the two catalysts for photo,thermal,and photothermal catalysis.The hot zones of P-photothermal catalysis are identified to be the metal-support interface on Pt/P25 and the Pt surface on Pt/Al_(2)O_(3),respectively.However,a change of the active site to the Pt surface on Pt/P25 is for the first time observed in E-photothermal catalysis(external heating temperature of 700℃).The hot zones contribute to the significant enhancements in photothermal catalytic reactivity against thermocatalysis.This study helps to understand the reaction mechanism of photothermal catalysis to exploit efficient catalysts for solar energy utilization and fossil fuels upgrading.

Ordered mesoporous carbon supported bifunctional PtM(M=Ru,Fe,Mo)electrocatalysts for a fuel cell anode

The deposition onto an ordered mesoporous carbon（OMC）support of well dispersed PtM（M = Ru,Fe,Mo）alloy nanoparticles（NPs）were synthesized by a direct replication method using SBA-15 as the hard template,furfuryl alcohol and trimethylbeneze as the primary carbon sources,and metal acetylacetonate as the alloying metal precursor and secondary carbon source.The physicochemical properties of the PtM-OMC catalysts were characterized by N2 adsorption-desorption,X-ray diffraction,transmission electron microscopy,X-ray absorption near edge structure,and extended X-ray absorption fine structure.The alloy PtM NPs have an average size of 2-3 nm and were well dispersed in the pore channels of the OMC support.The second metal（M）in the PtM NPs was mostly in the reduced state,and formed a typical core（Pt）-shell（M）structure.Cyclic voltammetry measurements showed that these PtM-OMC electrodes had excellent electrocatalytic activities and tolerance to CO poisoning during the methanol oxidation reaction,which surpassed those of typical activated carbon-supported PtRu catalysts.In particular,the PtFe-OMC catalyst,which exhibited the best performance,can be a practical anodic electrocatalyst in direct methanol fuel cells due to its superior stability,excellent CO tolerance,and low production cost.

High Expression of ERCC1 Is a Poor Prognostic Factor in Chinese Patients with Non-small Cell Lung Cancer Receiving Cisplatin-based Therapy

Objective： to determine the role of excision repair cross-complementing group 1 gene （ERCC1） and ribonucleotide reductase subunit M1 （RRM1） expression in predicting response and survival in Chinese patients with advanced stage non-small cell lung cancer （NSCLC） treated with platinum-based chemotherapy. Methods： Formalin-fixed, paraffin-embedded biopsy tissues were retrospectively obtained from 160 advanced NSCLC patients. mRNA expression levels of ERCC1 and RRM1 were determined by real-time PCR. Results： Associations between mRNA expression level of ERCC1 and RRM1 and clinic-pathologic parameters were analyzed. One handred and forty two （88.75%） specimens were successfully amplified. mRNA expression level of ERCC1 and RRM1 was negatively associated with tumor response. ERCC1 expression levels ranged from 0.01 to 78.79 [median 0.63, mean 4.25 and standard deviation （SD） 9.23] and RRM1 from 0.00 to 30.91 （median 0.63, mean 0.87 and SD 3.36）. By adopting cut-off values according to median expression levels, we found that MST in patients with low ERCC1 mRNA levels was significantly longer in overall population than in patients with higher levels （18.63 versus 13.69 months, log-rank 5.73, P=0.017）, but we did not found the survival benefit of the patients with low expression level of RRM1. （19.07 versus 14.88, log-rank 1.66, P=0.197）. Further, in the multivariable Cox regression model analysis we found that low level of ERCC1 expression, the presence of weight loss and target therapy, were significant prognostic factors for survival. Conclusion： ERCC1 expression is associated with patients’ survival in Chinese advanced NSCLC patients treated with platinum-based regimen and may serve as a biomarker in predicting tumor response and clinical outcome in the patient population.

Mechanisms of acquired resistance of BRCA1/2-driven tumors to platinum compounds and PARP inhibitors

Molecular pathogenesis of tumors arising in BRCA1/2 germ-line mutation carriers usually includes somatic inactivation of the remaining allele of the involved gene.Consequently,BRCA1/2-driven cancers are sensitive to platinum-based therapy and poly(ADP-ribose)polymerase inhibitors(PARPi).Long-term exposure to these drugs may result in the emergence of secondary BRCA1/2 mutations,which restore the open-reading frame of the affected allele.This platinum/PARPi crossresistance mechanism applies both for BRCA1 and BRCA2 genes and has been repeatedly validated in various laboratory models and multiple clinical studies.There are some other routes associated with the partial rescue of BRCA1/2 function or the development of BRCA1/2-independent pathways for genomic maintenance;however,their actual clinical relevance remains to be established.In addition,studies on the short-term neoadjuvant therapy for ovarian cancer revealed that even chemonaive BRCA1-driven tumors contain a small proportion of BRCA1-proficient cells.These pre-existing cells with retained BRCA1 heterozygosity rapidly repopulate the tumor mass during platinum exposure,but become outcompeted by BRCA1-deficient cells during therapy holidays.Understanding of the platinum/PARPi resistance pathways has led to the development of novel therapeutic approaches,which aim to improve the management of BRCA1/2-related cancers and are currently undergoing preclinical and clinical evaluation.

Pembrolizumab-emerging treatment of pulmonary sarcomatoid carcinoma: A case report

BACKGROUND Few studies have addressed the efficacy of pembrolizumab in pulmonary sarcomatoid carcinoma(PSC),a rare,previously rapidly fatal subtype of nonsmall-cell lung cancer.CASE SUMMARY We report the case of a 69-year-old man presented with respiratory distress caused by a large left upper lung lobe mass diagnosed as PSC with programmed death-ligand 1 expressed on more than 50 percent of tumor cells.The patient was started on pembrolizumab and,after 5 cycles,there was a more than 80 percent decrease in the size of the tumor mass.Further decrease was seen at the end of 10 cycles.The patient has been tolerating pembrolizumab well,with no limiting side-effects.Fourteen months after first coming into the hospital,he remains asymptomatic.CONCLUSION Pembrolizumab appears as a viable emerging treatment for PSC.

Esophageal metastasis of stem cell-subtype hepatocholangio carcinoma:Rare presentation of a rare tumor

Hepatocholangiocarcinoma(c HCC-ICC) is a rare primary hepatic tumor defined by the presence of histological features of both hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(ICC). Its prevalence ranges from 1%-5% of all primary liver cancers. We report the case of a 55-year-old cirrhotic male patient admitted to our university hospital for dysphagia, revealing a 10 cm lower-third esophageal metastasis of an unresectable c HCC-ICC with stemcell features. Computed tomography and abdominal magnetic resonance imaging scans revealed multiple hepatic lesions combining features of both HCC and ICC, associated with synchronous bone metastasis. Histological and immunohistochemical analyses of biopsies from the esophageal lesion and the hepatic tumor confirmed the diagnosis of c HCC-ICC with a stem cell-subtype, according to the World HealthOrganization classification. After a multidisciplinary meeting, the patient was treated with chemotherapy. He received two cycles of a gemcitabine plus cisplatin regimen before bone progression, and he died 3 mo after the initial diagnosis.

Role of Mediterranean diet in preventing platinum based gastrointestinal toxicity in gynecolocological malignancies: A single Institution experience

BACKGROUND Gynecological malignancies represent a major cause of death in women and are often treated with platinum-based regimens.Patients undergoing chemotherapy suffer from alterations in nutritional status which may worsen gastrointestinal(GI)toxicities,quality of life and affect the overall prognosis.Indeed,assuring a good nutritional status and limiting toxicities during treatment are still major goals for clinicians.AIM To assess the role of Mediterranean Diet(MD)in reducing GI toxicities in patients with gynecological cancers treated with platinum-based regimens.METHODS We conducted an observational study on 22 patients with gynecological tumors treated with a platinum-based chemotherapy at Candiolo Cancer Institute FPO/IRCCS between January 2018 and June 2018.The food and frequency(FFQ)and the Patient-Reported Outcomes Common Terminology Criteria For Adverse Events(PRO-CTCAE)questionnaires were administered at baseline and at every Day 1 of each cycle.To evaluate the differences in GI toxicities the study population was divided in two groups according to the currently validated Mediterranean Diet Serving Score(MDSS)at baseline.RESULTS Patients with high MDSS reported a trend toward lower GI toxicities according to PRO-CTCAE at each timepoint(first evaluation:P=0.7;second:P=0.52;third:P=0.01).In particular,difference in nausea frequency and gravity(P<0.001),stomach pain frequency and gravity(P=0.01 and P=0.02),abdomen bloating frequency and gravity(P=0.02 and P=0.03),and interference with daily activities(P=0.02)were highly statistically significant at the end of treatment.More than 60%of patients changed their food habits during chemotherapy mainly because of GI toxicities.A higher reduction of food intake,both in terms of caloric(P=0.29)and of single nutrients emerged in the group experiencing higher toxicity.CONCLUSION Our results show that adherence to MD possibly reduces GI toxicity and prevents nutritional status impairment during chemotherapy treatment.Bigger studies are needed to confirm our results.

HPLC Method Research of Picoplatin-a New Platinum Anti-cancer Drug and Its Impurities

Purpose: To establish a HPLC testing method of the content of bulk picoplatin and its impurities. Method: the separation was perform on a C18 column(4.6 mm×250 mm, 5 m) with potassium dihydrogen phosphate-aceton-itrile as the mobile phase at a flow rate of 1.0 mL/min. The detecting wavelength was set at 210 nm, and the column temperature was set at 30℃. Result: in the method validation, the linear relationship modulus of picoplatin is 0.9999, the systemic precision is 0.44%, the method precision is 0.74%, the average recovery rate is 99.62%, the LOD and LOQ of picoplatin is 0.2 ng and 1.0 ng. The average resolution of picoplatin and its impurities is more than 2. Conclusion: The established method is good specificity, high sensitivity, and good repeatability which could provide scientific evidence for the quality control of picoplatin and its impurities.

A Pt/MnV_(2)O_(6) nanocomposite for the borohydride oxidation reaction

Problems associated with carbon support corrosion under operating fuel cell conditions require the identification of alternative supports for platinum-based nanosized electrocatalysts.Platinum supported on manganese vanadate(Pt/MnV_(2)O_(6))was prepared by microwave irradiation method and characterized using X-ray diffraction,Fourier-transform infrared spectroscopy,X-ray photoelectron spectroscopy,scanning electron microscopy with energy dispersive spectroscopy,and transmission electron microscopy.The borohydride oxidation reaction(BOR)on Pt/MnV_(2)O_(6) was studied in highly alkaline media using voltammetry,chronoamperometry,and electrochemical impedance spectroscopy.BOR electrocatalytic activity of Pt/MnV_(2)O_(6) was also compared with that of commercial Pt/C(46 wt%Pt)electrocatalyst.The apparent activation energy of BOR at Pt/MnV_(2)O_(6) was estimated to be 32 k J mol^(-1) and the order of reaction to be 0.51,indicating that borohydride hydrolysis proceeds in parallel with its oxidation.Long-term stability of Pt/MnV_(2)O_(6) under BOR typical conditions was observed.A laboratory-scale direct borohydride fuel cell assembled with a Pt/MnV_(2)O_(6) anode reached a specific power of 274 W g^(-1).Experimental results on Pt/MnV_(2)O_(6) were complemented by DFT calculations,which indicated good adherence of Pt to MnV_(2)O_(6),beneficial for electrocatalyst stability.

THE EFFECT OF COLD DEFORMATION AND HEAT TREATMENT ON COEFFCIENT OF STRAIN RESISTANCE

The coefficient of strain resistance for metals,solid solutions and ordering alloys in annealing state decreases,while K increases in cold working state.The value K of pure metals and solid solutions invaraibly decreases with temperature increass.The main factors influencing the coefHcient of strain resistance are crystal defect,dispersion and degree of atomic arrangement.

Recent advances and trends of single-atom catalysts for proton exchange membrane fuel cell cathodes

Proton exchange membrane fuel cells(PEMFCs),which have the advantages of high-power density,zero emission,and low noise,are considered ideal electrochemical conversion systems for converting hydrogen(H2)and oxy-gen(O_(2))/air into electricity.However,the oxygen reduction reaction(ORR),which is accompanied by multiple electrons,results in voltage loss and low conversion efficiency of PEMFCs.Currently,PEMFCs mainly use high-load precious platinum(Pt)to promote the ORR process;however,the high cost of Pt hinders the widespread commercialization of PEMFCs.Over the past few years,metal-nitrogen-carbon single-atom catalysts(M-N-C SACs)have attracted considerable attention and have been recognized as potential Pt-based catalysts owing to their outstanding ORR activity.This review briefly introduces the components of PEMFCs.Second,we discuss the catalytic mechanisms of the M-N-C SACs for the ORR.Third,the latest advances in noble,non-noble,and heteroatom-doped M-N-C SACs used as ORR and PEMFCs cathode catalysts are systematically reviewed.In sum-mary,we have outlined the current challenges and proposed a future perspective of M-N-C SACs for PEMFCs cathodes.

The microbiome and ovarian cancer: insights, implications, and therapeutic opportunities

Ovarian cancer is the leading cause of gynecologic cancer death in the United States.Most ovarian cancer patients are diagnosed with advanced-stage disease,which poses a challenge for early detection and effective treatment.At present,cytoreductive surgery and platinum-based chemotherapy are foundational for patients with newly diagnosed ovarian cancer,but unfortunately,most patients will recur and die of their disease.Therefore,there is a significant need to seek innovative,novel approaches for early detection and to overcome chemoresistance for ovarian cancer patients.The microbiome,comprising diverse microbial communities inhabiting various body sites,is vital in maintaining human health.Changes to the diversity and composition of the microbial communities impact the microbiota-host relationship and are linked to diseases,including cancer.The microbiome contributes to carcinogenesis through various mechanisms,including altered host immune response,modulation of DNA repair,upregulation of pro-inflammatory pathways,altered gene expression,and dysregulated estrogen metabolism.Translational and clinical studies have demonstrated that specific microbes contribute to ovarian cancer development and impact chemotherapy’s efficacy.The microbiome is malleable and can be altered through different approaches,including diet,exercise,medications,and fecal microbiota transplantation.This review provides an overview of the current literature regarding ovarian cancer and the microbiome of female reproductive and gastrointestinal tracts,focusing on mechanisms of carcinogenesis and options for modulating the microbiota for cancer prevention and treatment.Advancing our understanding of the complex relationship between the microbiome and ovarian cancer may provide a novel approach for prevention and therapeutic modulation in the future.