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1.
Am J Chin Med ; 49(2): 237-268, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33622213

RESUMO

Intestinal flora is essential for maintaining host health and plays a unique role in transforming Traditional Chinese Medicine (TCM). TCM, as a bodyguard, has saved countless lives and maintained human health in the long history, especially in this COVID-19 pandemic. Pains of diseases have been removed from the effective TCM therapy, such as TCM preparation, moxibustion, and acupuncture. With the development of life science and technology, the wisdom and foresight of TCM has been more displayed. Furthermore, TCM has been also inherited and developed in innovation to better realize the modernization and globalization. Nowadays, intestinal flora transforming TCM and TCM targeted intestinal flora treating diseases have been important findings in life science. More and more TCM researches showed the significance of intestinal flora. Intestinal flora is also a way to study TCM to elucidate the profound theory of TCM. Processing, compatibility, and properties of TCM are well demonstrated by intestinal flora. Thus, it is no doubt that intestinal flora is a core in TCM study. The interaction between intestinal flora and TCM is so crucial for host health. Therefore, it is necessary to sum up the latest results in time. This paper systematically depicted the profile of TCM and the importance of intestinal flora in host. What is more, we comprehensively summarized and discussed the latest progress of the interplay between TCM and intestinal flora to better reveal the core connotation of TCM.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Disbiose/microbiologia , Microbioma Gastrointestinal , Medicina Tradicional Chinesa , Doenças Autoimunes/microbiologia , Doenças Autoimunes/terapia , Doenças Cardiovasculares/microbiologia , Doenças Cardiovasculares/terapia , Diabetes Mellitus/microbiologia , Diabetes Mellitus/terapia , Eletroacupuntura , Gastroenteropatias/microbiologia , Gastroenteropatias/terapia , Humanos , Doenças Metabólicas/microbiologia , Doenças Metabólicas/terapia , Neoplasias/microbiologia , Neoplasias/terapia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade/microbiologia , Obesidade/terapia , Insuficiência Renal Crônica/microbiologia , Insuficiência Renal Crônica/terapia
2.
BMC Infect Dis ; 21(1): 74, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446122

RESUMO

BACKGROUND: Cancer patients are more likely to develop and die of bloodstream infection (BSI) than noncancer patients. Methicillin-resistant Staphylococcus aureus (MRSA), which is associated with immense mortality and economic burden worldwide, is not covered by the recommended initial antibiotic therapy for cancer patients with BSI. This systemic review was performed to estimate the global methicillin-resistant Staphylococcus aureus (MRSA) prevalence among bacteremia in patients with malignancy, and further study the predictors and mortality of cancer patients with MRSA bacteremia. METHODS: The PubMed and EMBASE databases were searched for studies published from Jan. 2000 to Mar. 2020 that provided primary data on the prevalence, predictors, or mortality of MRSA bacteremia in cancer patients. A random-effects model meta-analysis was performed to estimate the pooled prevalence of MRSA with 95% confidence intervals (95% CIs). RESULTS: The pooled prevalence of MRSA was 3% (95% CI 2-5%) among all bloodstream infections (BSIs) and 44% (95% CI 32-57%) among S. aureus bacteremia in cancer patients. Based on geographical stratification, the pooled prevalence was 5% in Africa (95% CI 1-14%), 1% in Americas (95% CI 1-2%), 2% in Europe (95% CI 1-4%), 4% in Western Pacific (95% CI 2-7%), 8% in South-east Asia (95% CI 4-14%) and 0% in Eastern Mediterranean (95% CI 0-3%). No significant temporal change in MRSA rates was detected in this analysis (R2 = 0.06; P = 0.24). Predictors for MRSA BSIs among cancer patients were identified by comparison with their methicillin-susceptible counterparts, and they were mainly related to healthcare-associated infections and immunosuppression. Finally, the 60-day mortality in adult cancer patients with MRSA BSIs was reported to be 12%, and the 6-month overall mortality was 43.2%, with community-onset infection, secondary BSI, and vancomycin MIC≥2 g/mL being the risk factors for mortality. CONCLUSIONS: Although the prevalence of MRSA BSIs among cancer patients is relatively low, it did not decline over time as MRSA BSIs in the general hospital population and the high mortality rate was related to MRSA BSIs in patients with malignancy.


Assuntos
Bacteriemia/epidemiologia , Infecção Hospitalar/epidemiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Neoplasias/epidemiologia , Neoplasias/mortalidade , Infecções Estafilocócicas/epidemiologia , Adulto , África/epidemiologia , América/epidemiologia , Antibacterianos/uso terapêutico , Ásia Sudeste/epidemiologia , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Criança , Comorbidade , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Região do Mediterrâneo/epidemiologia , Neoplasias/microbiologia , Estudos Observacionais como Assunto , Prevalência , Fatores de Risco , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Vancomicina/uso terapêutico
3.
Artigo em Inglês | MEDLINE | ID: mdl-33317795

RESUMO

Gastrointestinal microbiota is vastly deregulated in cancer patients due to different factors, but the exact mechanisms of interaction between cancer and microbiome are still poorly understood. Current evidence suggests that alterations in the composition of the microbiota may affect efficacy and toxicity of anti-cancer therapies. Recent preclinical and clinical studies demonstrate different mechanisms and outcomes of deregulation of gut microbiome, and investigate effects of modulating gastrointestinal microbiota in cancer patients. This paper reviews effects of altered microbiome on anti-cancer management, including antibiotics, chemotherapy and immunotherapy, as well as possible outcomes of modulating altered microbiome by probiotics or faecal microbiome transplantation in cancer patients.


Assuntos
Antibacterianos/uso terapêutico , Transplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal/fisiologia , Imunoterapia/métodos , Neoplasias/microbiologia , Animais , Antibacterianos/farmacologia , Modelos Animais de Doenças , Humanos , Neoplasias/terapia
4.
Int J Mol Sci ; 21(24)2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33321934

RESUMO

Toll-like receptor 2 (TLR2) expressed on myeloid cells mediates the recognition of harmful molecules belonging to invading pathogens or host damaged tissues, leading to inflammation. For this ability to activate immune responses, TLR2 has been considered a player in anti-cancer immunity. Therefore, TLR2 agonists have been used as adjuvants for anti-cancer immunotherapies. However, TLR2 is also expressed on neoplastic cells from different malignancies and promotes their proliferation through activation of the myeloid differentiation primary response protein 88 (MyD88)/nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway. Furthermore, its activation on regulatory immune cells may contribute to the generation of an immunosuppressive microenvironment and of the pre-metastatic niche, promoting cancer progression. Thus, TLR2 represents a double-edge sword, whose role in cancer needs to be carefully understood for the setup of effective therapies. In this review, we discuss the divergent effects induced by TLR2 activation in different immune cell populations, cancer cells, and cancer stem cells. Moreover, we analyze the stimuli that lead to its activation in the tumor microenvironment, addressing the role of danger, pathogen, and microbiota-associated molecular patterns and their modulation during cancer treatments. This information will contribute to the scientific debate on the use of TLR2 agonists or antagonists in cancer treatment and pave the way for new therapeutic avenues.


Assuntos
Microbioma Gastrointestinal , Neoplasias/imunologia , Receptor 2 Toll-Like/metabolismo , Microambiente Tumoral/imunologia , Animais , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Humanos , Imunoterapia/métodos , Neoplasias/microbiologia , Neoplasias/terapia , Células-Tronco Neoplásicas/imunologia
5.
PLoS One ; 15(9): e0238889, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903280

RESUMO

BACKGROUND: Invasive fungal infection (IFI) detection requires application of complex case definitions by trained staff. Administrative coding data (ICD-10-AM) may provide a simplified method for IFI surveillance, but accuracy of case ascertainment in children with cancer is unknown. OBJECTIVE: To determine the classification performance of ICD-10-AM codes for detecting IFI using a gold-standard dataset (r-TERIFIC) of confirmed IFIs in paediatric cancer patients at a quaternary referral centre (Royal Children's Hospital) in Victoria, Australia from 1st April 2004 to 31st December 2013. METHODS: ICD-10-AM codes denoting IFI in paediatric patients (<18-years) with haematologic or solid tumour malignancies were extracted from the Victorian Admitted Episodes Dataset and linked to the r-TERIFIC dataset. Sensitivity, positive predictive value (PPV) and the F1 scores of the ICD-10-AM codes were calculated. RESULTS: Of 1,671 evaluable patients, 113 (6.76%) had confirmed IFI diagnoses according to gold-standard criteria, while 114 (6.82%) cases were identified using the codes. Of the clinical IFI cases, 68 were in receipt of ≥1 ICD-10-AM code(s) for IFI, corresponding to an overall sensitivity, PPV and F1 score of 60%, respectively. Sensitivity was highest for proven IFI (77% [95% CI: 58-90]; F1 = 47%) and invasive candidiasis (83% [95% CI: 61-95]; F1 = 76%) and lowest for other/unspecified IFI (20% [95% CI: 5.05-72%]; F1 = 5.00%). The most frequent misclassification was coding of invasive aspergillosis as invasive candidiasis. CONCLUSION: ICD-10-AM codes demonstrate moderate sensitivity and PPV to detect IFI in children with cancer. However, specific subsets of proven IFI and invasive candidiasis (codes B37.x) are more accurately coded.


Assuntos
Infecções Fúngicas Invasivas/epidemiologia , Neoplasias/microbiologia , Austrália/epidemiologia , Criança , Pré-Escolar , Current Procedural Terminology , Bases de Dados Factuais , Feminino , Humanos , Masculino , Registros Médicos , Estudos Retrospectivos , Centros de Atenção Terciária
6.
Life Sci ; 261: 118296, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32822716

RESUMO

Traditional methods for cancer therapy, including radiotherapy, chemotherapy, and immunotherapy are characterized by inherent limitations. Bacteria-mediated tumor therapy is becoming a promising approach in cancer treatment due to the ability of obligate or facultative anaerobic microorganisms to penetrate and proliferate in hypoxic regions of tumors. It is widely known that anaerobic bacteria cause the regression of tumors and inhibition of metastasis through a variety of mechanisms, including toxin production, anaerobic lifestyle and synergy with anti-cancer drugs. These features have the potential to be used as a supplement to conventional cancer treatment. To the best of our knowledge, no reports have been published regarding the most common tumor-targeting bacterial agents with special consideration of obligate anaerobes (such as Clostridium sp., Bifidobacterium sp.) and facultative anaerobes (including Salmonella sp., Listeria monocytogenes, Lactobacillus sp., Escherichia coli, Corynebacterium diphtheriae and Pseudomonas sp). In this review, we summarize the latest literature on the role of these bacteria in cancer treatment.


Assuntos
Bactérias Anaeróbias/fisiologia , Terapia de Alvo Molecular , Neoplasias/terapia , Animais , Antineoplásicos/farmacologia , Humanos , Neoplasias/microbiologia , Neoplasias/patologia , Resultado do Tratamento
7.
BMC Infect Dis ; 20(1): 558, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736609

RESUMO

BACKGROUND: Extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-PE) infections are frequent and highly impact cancer patients. We developed and validated a scoring system to identify cancer patients harboring ESBL-PE at the National Institute of Cancer of Colombia. METHODS: We retrospectively analyzed medical records of 1695 cancer patients. Derivation phase included 710 patients admitted between 2013 to 2015, ESBL-PE positive culture (n = 265) paired by month and hospitalization ward with Non-ESBL-PE (n = 445). A crude and weighted score was developed by conditional logistic regression. The model was evaluated in a Validation cohort (n = 985) with the same eligibility criteria between 2016 to 2017. RESULTS: The score was based on eight variables (reported with Odds Ratio and 95% confidence interval): Hospitalization ≥7 days (5.39 [2.46-11.80]), Hospitalization during the previous year (4, 87 [2.99-7.93]), immunosuppressive therapy during the previous 3 months (2.97 [1.44-6.08]), Neutropenia (1.90 [1.12-3.24]), Exposure to Betalactams during previous month (1.61 [1.06-2.42]), Invasive devices (1.51 [1.012-2.25]), Neoplasia in remission (2.78 [1.25-1.17]), No chemotherapy during the previous 3 months (1.90 [1.22-2.97]). The model demonstrated an acceptable discriminatory capacity in the Derivation phase, but poor in the Validation phase (Recipient Operating Characteristic Curve: 0.68 and 0.55 respectively). CONCLUSIONS: Cancer patients have a high prevalence of risk factors for ESBL-PE infection. The scoring system did not adequately discriminate patients with ESBL-PE. In a high-risk population, other strategies should be sought to identify patients at risk of resistant ESBL-PE infection.


Assuntos
Infecções por Enterobacteriaceae/etiologia , Enterobacteriaceae/metabolismo , Neoplasias/complicações , beta-Lactamases/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Colômbia/epidemiologia , Enterobacteriaceae/patogenicidade , Infecções por Enterobacteriaceae/epidemiologia , Feminino , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias/microbiologia , Razão de Chances , Prevalência , Estudos Retrospectivos , Fatores de Risco
8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(4): 567-572, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32691569

RESUMO

Objective: To identify the risk factors of ESKAPE pathogens infection and related death in cancer patients, and to supply evidence for clinical precaution and diagnosis. Methods: A retrospective study of clinical and experimental data of cancer patients with bloodstream infection were carried out in Sichuan Cancer Hospital from 2013 to 2018. The clinical feature, predisposing factors and risk factors of death in ESKAPE group and non-ESKAPE group were analyzed by univariate analysis and multivariate logistic regression. Results: A total of 753 patients were enrolled in the study. Totally 795 pathogenic bacteria strains were isolated from blood culture and there were 278 ESKAPE strains, which took up 34.97% of isolated strains. Univariate analysis and multivariate logistic regression analysis showed that gender of male, multiple pathogens, history of exposure to enzyme inhibitors and agranulocytosis were independent risk factors of ESKAPE pathogens bloodstream infection. Peritoneal infection and combined fungal infection were independent risk factors of ESKAPE bloodstream infection related death. Conclusion: The bloodstream infection of ESKAPE pathogens is a problem worthy of clinical attention for cancer patients with neutrophil deficiency, previous antibiotic exposure, and fungal infection and peritoneal infection.


Assuntos
Bacteriemia , Neoplasias , Antibacterianos/uso terapêutico , Bacteriemia/complicações , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , China/epidemiologia , Humanos , Masculino , Micoses/complicações , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/microbiologia , Neutrófilos/patologia , Doenças Peritoneais/complicações , Doenças Peritoneais/microbiologia , Estudos Retrospectivos , Fatores de Risco
9.
BMC Infect Dis ; 20(1): 452, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600270

RESUMO

BACKGROUND: Bacterial infections are the most frequent complications in patients with malignancy, and the epidemiology of nosocomial infections among cancer patients has changed over time. This study aimed to evaluate the characteristics, antibiotic resistance patterns, and prognosis of nosocomial infections due to multidrug-resistant (MDR) bacteria in cancer patients. METHODS: This retrospective observational study analyzed cancer patients with nosocomial infections caused by MDR from August 2013 to May 2019. The extracted clinical data were recorded in a standardized form and compared based on the survival status of the patients after infection and during hospitalization. The data were analyzed using independent samples t-test, Chi-square test, and binary logistic regression. P-values < 0.05 were considered significant. RESULTS: One thousand eight patients developed nosocomial infections during hospitalization, with MDR strains detected in 257 patients. Urinary tract infection (38.1%), respiratory tract infection (26.8%), and bloodstream infection (BSI) (12.5%) were the most common infection types. Extended-spectrum ß-lactamase producing Enterobacteriaceae (ESBL-PE) (72.8%) members were the most frequently isolated MDR strains, followed by Acinetobacter baumannii (11.7%), and Stenotrophomonas maltophilia (6.2%). The results of multivariate regression analysis revealed that smoking history, intrapleural/abdominal infusion history within 30 days, the presence of an indwelling urinary catheter, length of hospitalization, and hemoglobin were independent factors for in-hospital mortality in the study population. The isolated MDR bacteria exhibited high rates of sensitivity to amikacin, meropenem, and imipenem. CONCLUSIONS: The burden of nosocomial infections due to MDR bacteria is considerably high in oncological patients, with ESBL-PE being the most predominant causative pathogen. Our findings suggest that amikacin and carbapenems actively against more than 89.7% of MDR isolates. The precise management of MDR bacterial infections in cancer patients may improve the prognosis of these individuals.


Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/efeitos dos fármacos , Neoplasias/microbiologia , Idoso , Antibacterianos/farmacologia , China/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/mortalidade , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
10.
J Immunother Cancer ; 8(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32675312

RESUMO

BACKGROUND: Pandemic COVID-19 by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) infection is facilitated by the ACE2 receptor and protease TMPRSS2. Modestly sized case series have described clinical factors associated with COVID-19, while ACE2 and TMPRSS2 expression analyses have been described in some cell types. Patients with cancer may have worse outcomes to COVID-19. METHODS: We performed an integrated study of ACE2 and TMPRSS2 gene expression across and within organ systems, by normal versus tumor, across several existing databases (The Cancer Genome Atlas, Census of Immune Single Cell Expression Atlas, The Human Cell Landscape, and more). We correlated gene expression with clinical factors (including but not limited to age, gender, race, body mass index, and smoking history), HLA genotype, immune gene expression patterns, cell subsets, and single-cell sequencing as well as commensal microbiome. RESULTS: Matched normal tissues generally display higher ACE2 and TMPRSS2 expression compared with cancer, with normal and tumor from digestive organs expressing the highest levels. No clinical factors were consistently identified to be significantly associated with gene expression levels though outlier organ systems were observed for some factors. Similarly, no HLA genotypes were consistently associated with gene expression levels. Strong correlations were observed between ACE2 expression levels and multiple immune gene signatures including interferon-stimulated genes and the T cell-inflamed phenotype as well as inverse associations with angiogenesis and transforming growth factor-ß signatures. ACE2 positively correlated with macrophage subsets across tumor types. TMPRSS2 was less associated with immune gene expression but was strongly associated with epithelial cell abundance. Single-cell sequencing analysis across nine independent studies demonstrated little to no ACE2 or TMPRSS2 expression in lymphocytes or macrophages. ACE2 and TMPRSS2 gene expression associated with commensal microbiota in matched normal tissues particularly from colorectal cancers, with distinct bacterial populations showing strong associations. CONCLUSIONS: We performed a large-scale integration of ACE2 and TMPRSS2 gene expression across clinical, genetic, and microbiome domains. We identify novel associations with the microbiota and confirm host immunity associations with gene expression. We suggest caution in interpretation regarding genetic associations with ACE2 expression suggested from smaller case series.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Neoplasias/imunologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Serina Endopeptidases/metabolismo , Idoso , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Conjuntos de Dados como Assunto , Feminino , Microbioma Gastrointestinal/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Antígenos HLA/sangue , Antígenos HLA/imunologia , Humanos , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/microbiologia , Neoplasias/patologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , RNA-Seq
13.
Biochim Biophys Acta Rev Cancer ; 1874(1): 188388, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32589907

RESUMO

Bacteria have long been known as one of the primary causative agents of cancer, however, recent studies suggest that they can be used as a promising agent in cancer therapy. Because of the limitations that conventional treatment faces due to the specific pathophysiology and the tumor environment, there is a great need for the new anticancer therapeutic agents. Bacteriotherapy utilizes live, attenuated strains or toxins, peptides, bacteriocins of the bacteria in the treatment of cancer. Moreover, they are widely used as a vector for delivering genes, peptides, or drugs to the tumor target. Interestingly, it was found that their combination with the conventional therapeutic approaches may enhance the treatment outcome. In the genome editing era, it is feasible to develop a novel generation of therapeutic bacteria with fewer side effects and more efficacy for cancer therapy. Here we review the current knowledge on the dual role of bacteria in the development of cancer as well as cancer therapy.


Assuntos
Bactérias/metabolismo , Neoplasias/microbiologia , Neoplasias/terapia , Antineoplásicos/metabolismo , Antineoplásicos/uso terapêutico , Bactérias/genética , Bactérias/patogenicidade , Infecções Bacterianas/complicações , Infecções Bacterianas/microbiologia , Terapia Biológica , Carcinogênese , Sistemas de Liberação de Medicamentos , Engenharia Genética , Humanos , Imunoterapia , Neoplasias/etiologia
14.
J Food Sci ; 85(6): 1872-1890, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32460371

RESUMO

Cancer represents a major disease burden worldwide. Despite continuous advances obtained in medical therapies recently, resistance to standard drugs and adverse effects still represent important causes of therapeutic failure. There is growing evidence that the gut microbiota can affect the response to chemo- and immunotherapeutic drugs by modulating efficacy and/or toxicity, and diet is the most important factor affecting the gut microbiota. In this study, we assessed the auxiliary antitumor effects of immunomodulatory fungal proteins from Hericium erinaceus (HEP) administered with the chemotherapy drug 5-Fluorouracil (5-Fu), and we attempted to identify new potential prebiotic bacteria for auxiliary antitumor treatment. There were 1,455 proteins identified from H. erinaceus. In a xenografted mouse model of cancer, HEP with 5-Fu significantly suppressed tumor growth, inhibited inflammatory markers such as interferon (IFN)-γ, interleukin (IL)-1ß, IL-2, IL-6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS), and regulated the expression of Akt, CCDN1, CKD4, FOXM1, MMP7, MYC, PPAR-α, and PPAR-γ. 16S rRNA sequencing showed that HEP ameliorated the dysbacteriosis induced by 5-Fu, as it inhibited certain aerobic and microaerobic bacteria including Parabacteroides, Flavobacteriaceae, Christensenellaceae, Anoxybacillus, Aggregatibacter, Comamonadaceae, Planococcaceae, Desulfovibrionaceae, Sporosarcina, Staphylococcus, Aerococcaceae, and Bilophila in the xenografted mice, and increase some probiotic bacteria such as Bifidobacterium, Gemellales, Blautia, Sutterella, Anaerostipes, Roseburia, Lachnobacterium, Lactobacillus, and Desulfovibrio. This demonstrates that HEP could promote the antitumor efficacy of 5-Fu by improving the microbiota composition, the immune inflammatory response, and homeostasis.


Assuntos
Basidiomycota/química , Disbiose/tratamento farmacológico , Disbiose/microbiologia , Proteínas Fúngicas/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Neoplasias/microbiologia , Prebióticos/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Disbiose/induzido quimicamente , Disbiose/imunologia , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Proteínas Fúngicas/química , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
15.
Science ; 368(6494): 973-980, 2020 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-32467386

RESUMO

Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, including breast, lung, ovary, pancreas, melanoma, bone, and brain tumors. We found that each tumor type has a distinct microbiome composition and that breast cancer has a particularly rich and diverse microbiome. The intratumor bacteria are mostly intracellular and are present in both cancer and immune cells. We also noted correlations between intratumor bacteria or their predicted functions with tumor types and subtypes, patients' smoking status, and the response to immunotherapy.


Assuntos
Bactérias/classificação , Microbiota , Neoplasias/microbiologia , Bactérias/genética , Bactérias/isolamento & purificação , Mama/microbiologia , Colo/microbiologia , Feminino , Humanos , Imunoterapia , Pulmão/microbiologia , Macrófagos/microbiologia , Masculino , Neoplasias/terapia , Ovário/microbiologia , RNA Ribossômico 16S/genética
17.
Rev Mal Respir ; 37(4): 299-307, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-32273116

RESUMO

BACKGROUND: Quantitative PCR to detect Pneumocystis jirovecii (Pj) is a new tool for the diagnosis of Pneumocystis jirovecii pneumonia (PJP). The yield of this technique, in cases of low fungal burden, when the standard technique using immunofluorescence (IF) is negative, needs to be evaluated. METHODS: We retrospectively reviewed the charts of all patients with a positive PCR but negative IF test (PCR+/IF-) in bronchoalveolar lavage (BAL) fluid performed over one year. We used an algorithm based on underlying immunosuppression, clinical picture, thoracic CT scan appearances, existence of an alternative diagnosis and the patient's outcome on treatment. Using this, each case was classified as probable PJP, possible PJP or colonization. RESULTS: Among the 416 BAL performed, 48 (12%) were PCR+/IF- and 43 patients were analyzed. Patients were mostly male (56%) with a median age of 60 years. Thirty-five (84%) were immunocompromised: 4 (9%) HIV-infected patients, 26 (60%) with hematologic or solid organ cancer, 3 (7%) were renal transplant recipients. Seven (16%) were classified as probable PPJ and 9 (21%) as possible PJP. Patients with a probable or possible PJP were more frequently admitted to the ICU (P<0.02) and had higher risk of death (P<0.01) when compared to those with colonization. Median PCR levels were very low and were not different between PJP or colonized patients (P=0.23). CONCLUSIONS: Among patients with a positive Pj PCR in BAL but with negative IF, only 37% had probable or possible PJP and PCR could not discriminate PJP from colonization.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Infecções Fúngicas Invasivas/diagnóstico , Infecções por Pneumocystis/diagnóstico , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Humanos , Hospedeiro Imunocomprometido , Infecções Fúngicas Invasivas/microbiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/microbiologia , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/microbiologia , Infecções por Pneumocystis/microbiologia , Infecções por Pneumocystis/patologia , Pneumocystis carinii/genética , Pneumonia por Pneumocystis/genética , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase em Tempo Real/normas , Estudos Retrospectivos , Transplantados/estatística & dados numéricos
19.
Adv Exp Med Biol ; 1219: 77-91, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130694

RESUMO

Several aspects of the human physiology are controlled by the microbiota that plays a key role in health and disease. In fact, microbial dysbiosis is associated with numerous diseases, including several types of cancer such as colon, gastric, esophageal, pancreatic, laryngeal, breast and gallbladder carcinomas.Metabolic symbiosis between non-malignant cells and the resident microbita is crucial for the host homeostasis. However, cancer cells are able to repurpose the pre-existing metabolic symbiosis, being able to recycle those relations and also create novel metabolic symbiosis, leading to profound alterations on the local microenvironment.In here we will explore some of these symbiotic metabolic interactions between bacteria and non-malignant cells in two different contexts: colon and uterine cervix. The way malignant cells are able to recycle these normal interactions and also create novel types of symbiotic metabolic relations will also be discussed.The knowledge of these complex interactions and recycling mechanisms is of extreme importance for cancer treatment, as new therapeutic targets could be developed.


Assuntos
Bactérias/metabolismo , Células Epiteliais/metabolismo , Neoplasias/metabolismo , Neoplasias/microbiologia , Simbiose , Colo do Útero/citologia , Colo do Útero/metabolismo , Colo do Útero/microbiologia , Colo/citologia , Colo/metabolismo , Colo/microbiologia , Feminino , Humanos , Microbiota/fisiologia
20.
BMC Infect Dis ; 20(1): 228, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188401

RESUMO

BACKGROUND: Vancomycin-resistant enterococcus (VRE) is an important cause of infection in immunocompromised populations. Few studies have described the characteristics of vanB VRE infection. We sought to describe the epidemiology, treatment and outcomes of VRE bloodstream infections (BSI) in a vanB predominant setting in malignant hematology and oncology patients. METHODS: A retrospective review was performed at two large Australian centres and spanning a 6-year period (2008-2014). Evaluable outcomes were intensive care admission (ICU) within 48 h of BSI, all-cause mortality (7 and 30 days) and length of admission. RESULTS: Overall, 106 BSI episodes were observed in 96 patients, predominantly Enterococcus faecium vanB (105/106, 99%). Antibiotics were administered for a median of 17 days prior to BSI, and 76/96 (79%) were neutropenic at BSI onset. Of patients screened before BSI onset, 49/72 (68%) were found to be colonised. Treatment included teicoplanin (59), linezolid (6), daptomycin (2) and sequential/multiple agents (21). Mortality at 30-days was 31%. On multivariable analysis, teicoplanin was not associated with mortality at 30 days. CONCLUSIONS: VRE BSI in a vanB endemic setting occurred in the context of substantive prior antibiotic use and was associated with high 30-day mortality. Targeted screening identified 68% to be colonised prior to BSI. Teicoplanin therapy was not associated with poorer outcomes and warrants further study for vanB VRE BSI in cancer populations.


Assuntos
Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/epidemiologia , Neoplasias/microbiologia , Enterococos Resistentes à Vancomicina , Adulto , Idoso , Antibacterianos/uso terapêutico , Austrália , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Proteínas de Bactérias , Enterococcus faecium/isolamento & purificação , Enterococcus faecium/patogenicidade , Feminino , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Estudos Retrospectivos , Resultado do Tratamento , Enterococos Resistentes à Vancomicina/patogenicidade
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