Immune adjuvants are immune modulators that have been developed in the context of infectious vaccinations.There is currently a growing interest in immune adjuvants due to the development of immunotherapy against cance...Immune adjuvants are immune modulators that have been developed in the context of infectious vaccinations.There is currently a growing interest in immune adjuvants due to the development of immunotherapy against cancers.Immune adjuvant mechanisms of action are focused on the initiation and amplification of the inflammatory response leading to the innate immune response,followed by the adaptive immune response.The main activity lies in the support of antigen presentation and the maturation and functions of dendritic cells.Most immune adjuvants are associated with a vaccine or incorporated into the new generation of m RNA vaccines.Few immune adjuvants are used as drugs.Hydroxyapatite(HA)ceramics and azoximer bromide(AZB)are overlooked molecules that were used in early clinical trials,which demonstrated clinical efficacy and excellent tolerance profiles.HA combined in an autologous vaccine was previously developed in the veterinary field for use in canine spontaneous lymphomas.AZB,an original immune modulator derived from a class of heterochain aliphatic polyamines that is licensed in Russia,the Commonwealth of Independent States,and Slovakia for infectious and inflammatory diseases,is and now being developed for use in cancer with promising results.These two immune adjuvants can be combined in various immunotherapy strategies.展开更多
The Tongon mine, the largest gold mine in C?te d’Ivoire, has been in operation since April 2010. However, to our knowledge to date, no study has been conducted on metallic contamination in suspended particulate matte...The Tongon mine, the largest gold mine in C?te d’Ivoire, has been in operation since April 2010. However, to our knowledge to date, no study has been conducted on metallic contamination in suspended particulate matter (PM<sub>10</sub> and PM<sub>2.5</sub>) where there is a lack of information on the carcinogenic and non-carcinogenic risk to human health associated with the exposure of populations in the Tongon area to these pollutants. The general objective of this study is to evaluate the level of contamination of PM<sub>10</sub>;PM<sub>2.5</sub> by heavy metals and their impact on the health of populations exposed to these pollutants in the Tongon gold mine area. The sampling and measurement of suspended particulate matter (PM<sub>10</sub> and PM<sub>2.5</sub>) were done using a MiniVol TAS passive air sampler. Heavy metal concentrations were determined by inductively coupled plasma mass spectroscopy (Nex ION 2000 ICP-MS, USA). The results indicate that the average concentrations of suspended particles (PM<sub>2.5</sub> and PM<sub>10</sub>) obtained are all above the recommended exposure limits. In addition, among the heavy metals contained in the suspended particles, the concentrations of arsenic and nickel are high and all above the standard limit values. The assessment of the health risks related to the inhalation of PM<sub>10</sub> particles reveals that their inhalation over a long period could cause a carcinogenic risk.展开更多
AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. ...AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological status.Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco exposure.In ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.展开更多
Two new compounds 7-hydroxy-5-O-（β-D-glucopyranoside） flavan （1） and （Z）-4＇,6＇-dihydroxy-2＇-O-（β-D-glucopyranoside） chalcone （2）, along with eight known compounds, were isolated from the stem bark of Dr...Two new compounds 7-hydroxy-5-O-（β-D-glucopyranoside） flavan （1） and （Z）-4＇,6＇-dihydroxy-2＇-O-（β-D-glucopyranoside） chalcone （2）, along with eight known compounds, were isolated from the stem bark of Drypetes parvifolia （Euphorbiaceae）. Their structures were established on the basis of spectroscopic analysis and chemical evidence.展开更多
BACKGROUND Thymic epithelial carcinomas are rare and have a poor prognosis.Treatment of thymic epithelial carcinoma is multimodal and includes surgery,post-operative radiation therapy,adjuvant and neoadjuvant chemothe...BACKGROUND Thymic epithelial carcinomas are rare and have a poor prognosis.Treatment of thymic epithelial carcinoma is multimodal and includes surgery,post-operative radiation therapy,adjuvant and neoadjuvant chemotherapy,or exclusive chemotherapy based on disease resectability.However,there is currently no standard treatment regimen for metastatic and recurrent thymic carcinoma.CASE SUMMARY A 45-year-old Caucasian male,with no past medical history,presented with hepatalgia and a cervical mass.A computed tomography(CT)scan showed multiple suspect lesions in the lungs,liver,and anterior mediastinum associated with mediastinal and cervical adenopathy.CT-guided percutaneous biopsies of the liver lesions and anterior mediastinal mass were performed,confirming the histopathology of thymic epithelial carcinoma.Management consisted of several chemotherapy regimens and radiation therapy,administered between April 2016 and December 2018.The patient achieved complete metabolic response.Fluorodeoxyglucose positron emission tomography/CT performed in June 2019 showed disease relapse,with reappearance of a large hypermetabolic hepatic mass and involvement of mediastinal and axillary lymph nodes.Intravenous pembrolizumab(200 mg,every 3 wk)was administered after two prior systemic therapies.The patient’s response to treatment was last documented on March 5,2020.CONCLUSION Pembrolizumab was successful in treatment of a patient with programmed deathligand 1-negative metastatic thymic carcinoma,pretreated with chemotherapy.展开更多
Foot ulcers are common in diabetic patients,have a cumulative lifetime incidence rate as high as 25%and frequently become infected.The spread of infection to soft tissue and bone is a major causal factor for lowerlimb...Foot ulcers are common in diabetic patients,have a cumulative lifetime incidence rate as high as 25%and frequently become infected.The spread of infection to soft tissue and bone is a major causal factor for lowerlimb amputation.For this reason,early diagnosis and appropriate treatment are essential,including treatment which is both local(of the foot)and systemic(metabolic),and this requires coordination by a multidisciplinary team.Optimal treatment also often involves extensive surgical debridement and management of the wound base,effective antibiotic therapy,consideration for revascularization and correction of metabolic abnormalities such as hyperglycemia.This article focuses on diagnosis and management of diabetic foot infections in the light of recently published data in order to help clinicians in identification,assessment and antibiotic therapy of diabetic foot infections.展开更多
Cancer cell growth is associated with immune surveillance failure.Nowadays,restoring the desired immune response against cancer cells remains a major therapeutic strategy.Due to the recent advances in biological knowl...Cancer cell growth is associated with immune surveillance failure.Nowadays,restoring the desired immune response against cancer cells remains a major therapeutic strategy.Due to the recent advances in biological knowledge,efficient therapeutic tools have been developed to support the best bio-clinical approaches for immune precision therapy.One of the most important successes in immune therapy is represented by the applicational use of monoclonal antibodies,particularly the use of rituximab for B-cell lymphoproliferative disorders.More recently,other monoclonal antibodies have been developed,to inhibit immune checkpoints within the tumor microenvironment that limit immune suppression,or to enhance some immune functions with immune adjuvants through different targets such as Toll-receptor agonists.The aim is to inhibit cancer proliferation by the diminishing/elimination of cancer residual cells and clinically improving the response duration with no or few adverse effects.This effect is supported by enhancing the number,functions,and activity of the immune effector cells,including the natural killer(NK)lymphocytes,NKT-lymphocytes,γδT-lymphocytes,cytotoxic T-lymphocytes,directly or indirectly through vaccines particularly with neoantigens,and by lowering the functions of the immune suppressive cells.Beyond these new therapeutics and their personalized usage,new considerations have to be taken into account,such as epigenetic regulation particularly from microbiota,evaluation of transversal functions,particularly cellular metabolism,and consideration to the clinical consequences at the body level.The aim of this review is to discuss some practical aspects of immune therapy,giving to clinicians the concept of immune effector cells balancing between control and tolerance.Immunological precision medicine is a combination of modern biological knowledge and clinical therapeutic decisions in a global vision of the patient.展开更多
文摘Immune adjuvants are immune modulators that have been developed in the context of infectious vaccinations.There is currently a growing interest in immune adjuvants due to the development of immunotherapy against cancers.Immune adjuvant mechanisms of action are focused on the initiation and amplification of the inflammatory response leading to the innate immune response,followed by the adaptive immune response.The main activity lies in the support of antigen presentation and the maturation and functions of dendritic cells.Most immune adjuvants are associated with a vaccine or incorporated into the new generation of m RNA vaccines.Few immune adjuvants are used as drugs.Hydroxyapatite(HA)ceramics and azoximer bromide(AZB)are overlooked molecules that were used in early clinical trials,which demonstrated clinical efficacy and excellent tolerance profiles.HA combined in an autologous vaccine was previously developed in the veterinary field for use in canine spontaneous lymphomas.AZB,an original immune modulator derived from a class of heterochain aliphatic polyamines that is licensed in Russia,the Commonwealth of Independent States,and Slovakia for infectious and inflammatory diseases,is and now being developed for use in cancer with promising results.These two immune adjuvants can be combined in various immunotherapy strategies.
文摘The Tongon mine, the largest gold mine in C?te d’Ivoire, has been in operation since April 2010. However, to our knowledge to date, no study has been conducted on metallic contamination in suspended particulate matter (PM<sub>10</sub> and PM<sub>2.5</sub>) where there is a lack of information on the carcinogenic and non-carcinogenic risk to human health associated with the exposure of populations in the Tongon area to these pollutants. The general objective of this study is to evaluate the level of contamination of PM<sub>10</sub>;PM<sub>2.5</sub> by heavy metals and their impact on the health of populations exposed to these pollutants in the Tongon gold mine area. The sampling and measurement of suspended particulate matter (PM<sub>10</sub> and PM<sub>2.5</sub>) were done using a MiniVol TAS passive air sampler. Heavy metal concentrations were determined by inductively coupled plasma mass spectroscopy (Nex ION 2000 ICP-MS, USA). The results indicate that the average concentrations of suspended particles (PM<sub>2.5</sub> and PM<sub>10</sub>) obtained are all above the recommended exposure limits. In addition, among the heavy metals contained in the suspended particles, the concentrations of arsenic and nickel are high and all above the standard limit values. The assessment of the health risks related to the inhalation of PM<sub>10</sub> particles reveals that their inhalation over a long period could cause a carcinogenic risk.
基金Supported by the Grants From Ligue Nationale Contre le Cancer,Comités Départementaux de la Manche,de l'Orne et du Calvados and from Université de Metz
文摘AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological status.Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco exposure.In ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.
基金One of the authors(J.Wandji)is grateful for grant(No.F/2624-3F)from the International Foundation for Science(Sweden)the sponsorship of the"UniversitéParis Descartes,France"during his multiple research visits in Paris.
文摘Two new compounds 7-hydroxy-5-O-（β-D-glucopyranoside） flavan （1） and （Z）-4＇,6＇-dihydroxy-2＇-O-（β-D-glucopyranoside） chalcone （2）, along with eight known compounds, were isolated from the stem bark of Drypetes parvifolia （Euphorbiaceae）. Their structures were established on the basis of spectroscopic analysis and chemical evidence.
文摘BACKGROUND Thymic epithelial carcinomas are rare and have a poor prognosis.Treatment of thymic epithelial carcinoma is multimodal and includes surgery,post-operative radiation therapy,adjuvant and neoadjuvant chemotherapy,or exclusive chemotherapy based on disease resectability.However,there is currently no standard treatment regimen for metastatic and recurrent thymic carcinoma.CASE SUMMARY A 45-year-old Caucasian male,with no past medical history,presented with hepatalgia and a cervical mass.A computed tomography(CT)scan showed multiple suspect lesions in the lungs,liver,and anterior mediastinum associated with mediastinal and cervical adenopathy.CT-guided percutaneous biopsies of the liver lesions and anterior mediastinal mass were performed,confirming the histopathology of thymic epithelial carcinoma.Management consisted of several chemotherapy regimens and radiation therapy,administered between April 2016 and December 2018.The patient achieved complete metabolic response.Fluorodeoxyglucose positron emission tomography/CT performed in June 2019 showed disease relapse,with reappearance of a large hypermetabolic hepatic mass and involvement of mediastinal and axillary lymph nodes.Intravenous pembrolizumab(200 mg,every 3 wk)was administered after two prior systemic therapies.The patient’s response to treatment was last documented on March 5,2020.CONCLUSION Pembrolizumab was successful in treatment of a patient with programmed deathligand 1-negative metastatic thymic carcinoma,pretreated with chemotherapy.
基金Supported by Institut National de la SantéEt de la Recherche Médicale,the French Speaking Association for Diabetes and Metabolic Diseases(ALFEDIAM grant)the University of Montpellier 1,the Languedoc-Roussillon Area(Chercheur d'avenir Grant) and the City of Nmes
文摘Foot ulcers are common in diabetic patients,have a cumulative lifetime incidence rate as high as 25%and frequently become infected.The spread of infection to soft tissue and bone is a major causal factor for lowerlimb amputation.For this reason,early diagnosis and appropriate treatment are essential,including treatment which is both local(of the foot)and systemic(metabolic),and this requires coordination by a multidisciplinary team.Optimal treatment also often involves extensive surgical debridement and management of the wound base,effective antibiotic therapy,consideration for revascularization and correction of metabolic abnormalities such as hyperglycemia.This article focuses on diagnosis and management of diabetic foot infections in the light of recently published data in order to help clinicians in identification,assessment and antibiotic therapy of diabetic foot infections.
文摘Cancer cell growth is associated with immune surveillance failure.Nowadays,restoring the desired immune response against cancer cells remains a major therapeutic strategy.Due to the recent advances in biological knowledge,efficient therapeutic tools have been developed to support the best bio-clinical approaches for immune precision therapy.One of the most important successes in immune therapy is represented by the applicational use of monoclonal antibodies,particularly the use of rituximab for B-cell lymphoproliferative disorders.More recently,other monoclonal antibodies have been developed,to inhibit immune checkpoints within the tumor microenvironment that limit immune suppression,or to enhance some immune functions with immune adjuvants through different targets such as Toll-receptor agonists.The aim is to inhibit cancer proliferation by the diminishing/elimination of cancer residual cells and clinically improving the response duration with no or few adverse effects.This effect is supported by enhancing the number,functions,and activity of the immune effector cells,including the natural killer(NK)lymphocytes,NKT-lymphocytes,γδT-lymphocytes,cytotoxic T-lymphocytes,directly or indirectly through vaccines particularly with neoantigens,and by lowering the functions of the immune suppressive cells.Beyond these new therapeutics and their personalized usage,new considerations have to be taken into account,such as epigenetic regulation particularly from microbiota,evaluation of transversal functions,particularly cellular metabolism,and consideration to the clinical consequences at the body level.The aim of this review is to discuss some practical aspects of immune therapy,giving to clinicians the concept of immune effector cells balancing between control and tolerance.Immunological precision medicine is a combination of modern biological knowledge and clinical therapeutic decisions in a global vision of the patient.
