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1.
J Clin Pharmacol ; 62(2): 206-219, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34435684

RESUMO

Population pharmacokinetic (PK) and exposure-safety analyses of alisertib were performed in children enrolled in 2 clinical trials: NCT02444884 and NCT01154816. NCT02444884 was a dose-finding study in children with relapsed/refractory solid malignancies (phase 1) or neuroblastomas (phase 2). Patients received oral alisertib 45 to 100 mg/m2 as powder-in-capsule once daily or twice daily for 7 days in 21-day cycles. Serial blood samples were collected up to 24 hours after dosing on cycle 1, day 1. NCT01154816 was a phase 2 single-arm study evaluating efficacy in children with relapsed/refractory solid malignancies or acute leukemias. Patients received alisertib 80 mg/m2 as enteric-coated tablets once daily for 7 days in 21-day cycles. Sparse PK samples were collected up to 8 hours after dosing on cycle 1, day 1. Sources of alisertib PK variability were characterized and quantified using nonlinear mixed-effects modeling to support dosing recommendations in children and adolescents. A 2-compartment model with oral absorption described by 3 transit compartments was developed using data from 146 patients. Apparent oral clearance and central distribution volume were correlated with body surface area across the age range of 2 to 21 years, supporting the use of body surface area-based alisertib dosing in the pediatric population. The recommended dose of 80 mg/m2 once daily enteric-coated tablets provided similar alisertib exposures across pediatric age groups and comparable exposure to that in adults receiving 50 mg twice daily (recommended adult dose). Statistically significant relationships (P < .01) were observed between alisertib exposures and incidence of grade ≥2 stomatitis and febrile neutropenia, consistent with antiproliferative mechanism-related toxicities.


Assuntos
Antineoplásicos/farmacocinética , Azepinas/farmacocinética , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacocinética , Pirimidinas/farmacocinética , Adolescente , Antineoplásicos/efeitos adversos , Azepinas/efeitos adversos , Superfície Corporal , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Modelos Biológicos , Estadiamento de Neoplasias , Neoplasias/patologia , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Adulto Jovem
2.
Nat Commun ; 13(1): 4567, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931744

RESUMO

Inefficient tumour treatment approaches often cause fatal tumour metastases. Here, we report a biomimetic multifunctional nanoplatform explicitly engineered with a Co-based metal organic framework polydopamine heterostructure (MOF-PDA), anethole trithione (ADT), and a macrophage membrane. Co-MOF degradation in the tumour microenvironment releases Co2+, which results in the downregulation of HSP90 expression and the inhibition of cellular heat resistance, thereby improving the photothermal therapy effect of PDA. H2S secretion after the enzymatic hydrolysis of ADT leads to high-concentration gas therapy. Moreover, ADT changes the balance between nicotinamide adenine dinucleotide/flavin adenine dinucleotide (NADH/FAD) during tumour glycolysis. ATP synthesis is limited by NADH consumption, which triggers a certain degree of tumour growth inhibition and results in starvation therapy. Potentiated 2D/3D autofluorescence imaging of NADH/FAD is also achieved in liquid nitrogen and employed to efficiently monitor tumour therapy. The developed biomimetic nanoplatform provides an approach to treat orthotopic tumours and inhibit metastasis.


Assuntos
Materiais Biomiméticos , Hipotermia , Neoplasias , Biomimética , Metabolismo Energético , Flavina-Adenina Dinucleotídeo/metabolismo , Humanos , NAD/metabolismo , Neoplasias/patologia , Microambiente Tumoral
4.
Nat Genet ; 54(8): 1192-1201, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35931863

RESUMO

Transcriptional heterogeneity among malignant cells of a tumor has been studied in individual cancer types and shown to be organized into cancer cell states; however, it remains unclear to what extent these states span tumor types, constituting general features of cancer. Here, we perform a pan-cancer single-cell RNA-sequencing analysis across 15 cancer types and identify a catalog of gene modules whose expression defines recurrent cancer cell states including 'stress', 'interferon response', 'epithelial-mesenchymal transition', 'metal response', 'basal' and 'ciliated'. Spatial transcriptomic analysis linked the interferon response in cancer cells to T cells and macrophages in the tumor microenvironment. Using mouse models, we further found that induction of the interferon response module varies by tumor location and is diminished upon elimination of lymphocytes. Our work provides a framework for studying how cancer cell states interact with the tumor microenvironment to form organized systems capable of immune evasion, drug resistance and metastasis.


Assuntos
Neoplasias , Microambiente Tumoral , Animais , Transição Epitelial-Mesenquimal/genética , Perfilação da Expressão Gênica , Interferons , Camundongos , Neoplasias/patologia , Microambiente Tumoral/genética
5.
J Immunol Res ; 2022: 1345971, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935577

RESUMO

IL-28B, belonging to type III interferons (IFN-λs), exhibits a potent antitumor activity with reduced regulated T cells (Tregs) population, yet the effect of IL-28B on the tumor microenvironment (TME) and if IL-28B can downregulate Tregs directly in vitro are still unknown. In this study, we investigated the effects of IL-28B on Tregs in the spleen and TME in H22 tumor-bearing mice and verified the downregulation of IL-28B on Tregs in vitro. We found that rAd-mIL-28B significantly inhibited tumor growth and reduced the frequency of splenic CD4+Foxp3+ T cells. The levels of CXCL13, ICAM-1, MCP-5, and IL-7 in the serum, and the levels of IL-15 and sFasL in the tumor tissue decreased significantly after rAd-mIL-28B treatment relative to rAd-EGFP. Furthermore, the percentage of CD8+ cells in the TME was significantly increased in the rAd-mIL-28B group compared with the untreated group. In vitro, splenocytes were stimulated with anti-CD3/CD28 and IL-2 in the presence of TGF-ß with or without IL-28B for three days and followed by flow cytometric, RT-PCR, and IL-10 production analysis. The results showed that IL-28B significantly reduced the proportion of induced Foxp3+ cells. It demonstrated that IL-28B may be used as a promising immunotherapy strategy against cancer.


Assuntos
Neoplasias , Microambiente Tumoral , Animais , Fatores de Transcrição Forkhead , Camundongos , Neoplasias/patologia , Linfócitos T Reguladores , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/farmacologia
6.
Front Immunol ; 13: 948297, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936007

RESUMO

Despite the significant clinical advances with the use of immune checkpoint inhibitors (ICIs) in a wide range of cancer patients, response rates to the therapy are variable and do not always result in long-term tumor regression. The development of ICI-resistant disease is one of the pressing issue in clinical oncology, and the identification of new targets and combination therapies is a crucial point to improve response rates and duration. Antigen processing and presentation (APP) pathway is a key element for an efficient response to ICI therapy. Indeed, malignancies that do not express tumor antigens are typically poor infiltrated by T cells and unresponsive to ICIs. Therefore, improving tumor immunogenicity potentially increases the success rate of ICI therapy. In this review, we provide an overview of the key elements of the APP machinery that can be exploited to enhance tumor immunogenicity and increase the efficacy of ICI-based immunotherapy.


Assuntos
Apresentação de Antígeno , Neoplasias , Antígenos de Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia , Neoplasias/tratamento farmacológico , Neoplasias/patologia
7.
BMC Cancer ; 22(1): 840, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918650

RESUMO

BACKGROUND: Tumour mutation burden (TMB), defined as the number of somatic mutations per megabase within the sequenced region in the tumour sample, has been used as a biomarker for predicting response to immune therapy. Several studies have been conducted to assess the utility of TMB for various cancer types; however, methods to measure TMB have not been adequately evaluated. In this study, we identified two sources of bias in current methods to calculate TMB. METHODS: We used simulated data to quantify the two sources of bias and their effect on TMB calculation, we down-sampled sequencing reads from exome sequencing datasets from TCGA to evaluate the consistency in TMB estimation across different sequencing depths. We analyzed data from ten cancer cohorts to investigate the relationship between inferred TMB and sequencing depth. RESULTS: We found that TMB, estimated by counting the number of somatic mutations above a threshold frequency (typically 0.05), is not robust to sequencing depth. Furthermore, we show that, because only mutations with an observed frequency greater than the threshold are considered, the observed mutant allele frequency provides a biased estimate of the true frequency. This can result in substantial over-estimation of the TMB, when the cancer sample includes a large number of somatic mutations at low frequencies, and exacerbates the lack of robustness of TMB to variation in sequencing depth and tumour purity. CONCLUSION: Our results demonstrate that care needs to be taken in the estimation of TMB to ensure that results are unbiased and consistent across studies and we suggest that accurate and robust estimation of TMB could be achieved using statistical models that estimate the full mutant allele frequency spectrum.


Assuntos
Biomarcadores Tumorais , Neoplasias , Biomarcadores Tumorais/genética , Humanos , Mutação , Neoplasias/patologia , Sequenciamento Completo do Exoma
8.
J Nanobiotechnology ; 20(1): 359, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918698

RESUMO

The conversion of tumor-promoting M2 macrophage phenotype to tumor-suppressing M1 macrophages is a promising therapeutic approach for cancer treatment. However, the tumor normally provides an abundance of M2 macrophage stimuli, which creates an M2 macrophage-dominant immunosuppressive microenvironment. In our study, docetaxel (DTX) as chemotherapeutic modularity was loaded into M1 macrophage-derived exosomes (M1-Exo) with M1 proinflammatory nature to establish DTX-M1-Exo drug delivery system. We found that DTX-M1-Exo induced naïve M0 macrophages to polarize to M1 phenotype, while failed to repolarize to M2 macrophages upon Interleukin 4 restimulation due to impaired mitochondrial function. This suggests that DTX-M1-Exo can achieve long-term robust M1 activation in immunosuppressive tumor microenvironment. The in vivo results further confirmed that DTX-M1-Exo has a beneficial effect on macrophage infiltration and activation in the tumor tissues. Thus, DTX-M1-Exo is a novel macrophage polarization strategy via combined chemotherapy and immunotherapy to achieve great antitumor therapeutic efficacy.


Assuntos
Exossomos , Neoplasias , Docetaxel/farmacologia , Exossomos/genética , Humanos , Imunoterapia , Macrófagos , Neoplasias/patologia , Microambiente Tumoral
9.
Front Immunol ; 13: 951247, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935945

RESUMO

Background: Immunotherapy has achieved great success in cancer. Nevertheless, many patients cannot benefit from immune checkpoint blockade therapy because of the scantiness of CD8+ T cell infiltration in the tumor microenvironment (TME). CXCL11 is known as a regulator that influences T-cell infiltration into tumors. However, the role of CXCL11 in pan-cancer is still unclear. Methods: In this study, we investigated the expression and function of CXCL11 across 33 types of cancers based on datasets from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database. We analyzed the CXCL11 differential expression in tumor tissue and nontumoral tissue and in different stages of cancers. Moreover, the correlations among CXCL11 expression, prognosis, mismatch repair, tumor mutation burden (TMB), microsatellite instability (MSI), tumor microenvironment, and immune-related genes were evaluated. Results: CXCL11 expression was significantly higher in tumoral tissue than in nontumoral tissue for most types of cancer. Improved CXCL11 expression was related to an inconsistent prognosis in different cancers. CXCL11 was positively associated with CD8+ T cells and T follicular helper cells in the TME. High expression of CXCL11 was positively related to TMB in BLCA, BRCA, CESC, COAD, LGG, LUAD, OV, SKCM, STAD, THYM, and UCEC. A positive correlation between CXCL11 and MSI was found in COAD and UVM. Moreover, functional analysis of CXCL11 showed that high CXCL11 expression was significantly related to immune-relevant pathways. Conclusions: CXCL11 might function as a prognostic and immunotherapy marker across cancers. Further investigation into CXCL11 might provide promising insights to improve cancer therapy.


Assuntos
Quimiocina CXCL11/metabolismo , Imunoterapia , Neoplasias , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linfócitos T CD8-Positivos , Quimiocina CXCL11/genética , Humanos , Fatores Imunológicos , Instabilidade de Microssatélites , Neoplasias/genética , Neoplasias/patologia , Neoplasias/terapia , Prognóstico , Microambiente Tumoral
10.
Proc Natl Acad Sci U S A ; 119(32): e2200879119, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35925889

RESUMO

The value of anti-CTLA-4 antibodies in cancer therapy is well established. However, the broad application of currently available anti-CTLA-4 therapeutic antibodies is hampered by their narrow therapeutic index. It is therefore challenging and attractive to develop the next generation of anti-CTLA-4 therapeutics with improved safety and efficacy. To this end, we generated fully human heavy chain-only antibodies (HCAbs) against CTLA-4. The hIgG1 Fc domain of the top candidate, HCAb 4003-1, was further engineered to enhance its regulatory T (Treg) cell depletion effect and to decrease its half-life, resulting in HCAb 4003-2. We tested these HCAbs in in vitro and in vivo experiments in comparison with ipilimumab and other anti-CTLA4 antibodies. The results show that human HCAb 4003-2 binds human CTLA-4 with high affinity and potently blocks the binding of B7-1 (CD80) and B7-2 (CD86) to CTLA-4. The results also show efficient tumor penetration. HCAb 4003-2 exhibits enhanced antibody-dependent cellular cytotoxicity function, lower serum exposure, and more potent anti-tumor activity than ipilimumab in murine tumor models, which is partly driven by a substantial depletion of intratumoral Tregs. Importantly, the enhanced efficacy combined with the shorter serum half-life and less systemic drug exposure in vivo potentially provides an improved therapeutic window in cynomolgus monkeys and preliminary clinical applications. With its augmented efficacy via Treg depletion and improved safety profile, HCAb 4003-2 is a promising candidate for the development of next generation anti-CTLA-4 therapy.


Assuntos
Cadeias Pesadas de Imunoglobulinas , Imunoterapia , Neoplasias , Linfócitos T Reguladores , Animais , Citotoxicidade Celular Dependente de Anticorpos , Antígeno CTLA-4/imunologia , Humanos , Cadeias Pesadas de Imunoglobulinas/farmacologia , Ipilimumab/farmacologia , Camundongos , Neoplasias/patologia , Neoplasias/terapia
11.
PLoS One ; 17(8): e0270571, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35939431

RESUMO

The clinical profiles and outcomes of patients with neurotrophic tropomyosin receptor kinase fusion-positive (NTRK+) solid tumors receiving standard of care other than tropomyosin receptor kinase inhibitor (TRKi) targeted therapy have not been well documented. Here, we describe the clinical characteristics of patients with NTRK+ tumors treated in clinical practice using information from a United States electronic health record-derived clinicogenomic database. We also compared survival outcomes in NTRK+ patients and matched NTRK fusion-negative (NTRK-) patients and investigated the clinical prognostic value of NTRK fusions. NTRK positivity was defined by the presence of a fusion or rearrangement involving NTRK1/2/3, determined using NGS (Foundation Medicine, Inc.). NTRK+ patients (n = 28) were diagnosed with locally advanced/metastatic solid tumors between January 1, 2011 and December 31, 2019 and had received no TRKis (e.g., entrectinib or larotrectinib) during their patient journey. The unselected NTRK-population comprised 24,903 patients, and the matched NTRK-cohort included 280 patients. NTRK+ patients tended to be younger, were more commonly not smokers, and had a shorter time from advanced diagnosis to first NGS report, compared with unselected NTRK-patients; however, these differences were not significant. Median overall survival (OS) from advanced/metastatic diagnosis was 10.2 months (95% CI, 7.2-14.1) for the NTRK+ cohort versus 10.4 months (95% CI, 6.7-14.3) for the matched NTRK-cohort; hazard ratio for death in NTRK+ versus matched NTRK-patients was 1.6 (95% CI, 1.0-2.5; P = 0.05). Genomic co-alterations were rare in the NTRK+ cohort (only two of 28 patients had a co-alteration). Overall, while hazard ratios suggest NTRK fusions may be a negative prognostic factor of survival, there are no significant indications of any favorable impact of NTRK fusions on patient outcomes. TRKis, with their high response rate and good tolerability, are likely to improve outcomes for patients compared with existing standard-of-care treatments.


Assuntos
Segunda Neoplasia Primária , Neoplasias , Fusão Gênica , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Segunda Neoplasia Primária/tratamento farmacológico , Proteínas de Fusão Oncogênica/genética , Inibidores de Proteínas Quinases/uso terapêutico , Receptor trkA/genética , Tropomiosina/genética
12.
Cancer Cell ; 40(8): 787-791, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35944497

RESUMO

Metastasis, the major cause of cancer death, represents one of the major challenges in oncology. Scientists are still trying to understand the biological basis underlying the dissemination and outgrowth of tumor cells, why these cells can remain dormant for years, how they become resistant to the immune system or cytotoxic effects of systemic therapy, and how they interact with their new microenvironment. We asked experts to discuss some of the unknowns, advances, and areas of opportunity related to cancer metastasis.


Assuntos
Neoplasias , Microambiente Tumoral , Humanos , Sistema Imunitário/patologia , Metástase Neoplásica/patologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia
13.
Cancer Cell ; 40(8): 865-878.e6, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35944502

RESUMO

The rapidly emerging field of computational pathology has demonstrated promise in developing objective prognostic models from histology images. However, most prognostic models are either based on histology or genomics alone and do not address how these data sources can be integrated to develop joint image-omic prognostic models. Additionally, identifying explainable morphological and molecular descriptors from these models that govern such prognosis is of interest. We use multimodal deep learning to jointly examine pathology whole-slide images and molecular profile data from 14 cancer types. Our weakly supervised, multimodal deep-learning algorithm is able to fuse these heterogeneous modalities to predict outcomes and discover prognostic features that correlate with poor and favorable outcomes. We present all analyses for morphological and molecular correlates of patient prognosis across the 14 cancer types at both a disease and a patient level in an interactive open-access database to allow for further exploration, biomarker discovery, and feature assessment.


Assuntos
Aprendizado Profundo , Neoplasias , Algoritmos , Genômica/métodos , Humanos , Neoplasias/genética , Neoplasias/patologia , Prognóstico
14.
Spinal Cord Ser Cases ; 8(1): 71, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918325

RESUMO

INTRODUCTION: Cauda equina syndrome (CES) is most caused by lumbar disc herniation, and the associated treatment involves prompt surgical decompression. Rarer causes of CES include perineural (Tarlov) cysts. CLINICAL PRESENTATION: A 62-year-old female with history of rheumatoid arthritis, hip and knee replacements, and chronic low back pain presented with worsening back pain, left leg weakness and pain for 6 weeks, and bowel/bladder incontinence with diminished sensation in the perianal region for 24 h prior to presentation. MRI demonstrated severe spinal stenosis at L4-S1, central disc herniation at L5-S1, and compression of the cauda equina, consistent with CES. A lumbar decompression was performed. Patient did well at 2-week follow up, but presented 5 weeks post-discharge with increased left leg pain/weakness and genitalia anesthesia. Imaging was unremarkable. Two months later, the patient presented with diminished sensation in the buttocks and bilateral lower extremities and bowel/bladder incontinence. Imaging demonstrated a large cystic presacral mass with involvement of the left sciatic foramen and S3 neural foramen. A team of plastic, orthopedic, and neurological surgeons performed an S3 sacral laminectomy, foraminotomy, partial sacrectomy, and S3 rhizotomy, and excision of the large left hemorrhagic pudendal mass. Final pathology demonstrated a perineural cyst with organizing hemorrhage. On follow-up, the patient's pain and weakness improved. CONCLUSION: CES-like symptoms were initially attributed to a herniated disk. However, lumbar decompression did not resolve symptoms, prompting further radiographic evaluation at two separate presentations. This represents the first reported case of a pudendal tumor causing symptoms initially attributed to a herniated disc.


Assuntos
Síndrome da Cauda Equina , Deslocamento do Disco Intervertebral , Neoplasias , Radiculopatia , Assistência ao Convalescente , Síndrome da Cauda Equina/diagnóstico , Síndrome da Cauda Equina/etiologia , Síndrome da Cauda Equina/cirurgia , Feminino , Humanos , Deslocamento do Disco Intervertebral/diagnóstico , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Vértebras Lombares/cirurgia , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/patologia , Dor , Alta do Paciente
15.
Nat Cell Biol ; 24(8): 1192-1201, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35941364

RESUMO

Intratumour heterogeneity (ITH) is a hallmark of cancer that drives tumour evolution and disease progression. Technological and computational advances have enabled us to assess ITH at unprecedented depths, yet this accumulating knowledge has not had a substantial clinical impact. This is in part due to a limited understanding of the functional relevance of ITH and the inadequacy of preclinical experimental models to reproduce it. Here, we discuss progress made in these areas and illuminate future directions.


Assuntos
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/patologia
18.
Drug Deliv ; 29(1): 2513-2538, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35915054

RESUMO

Increasing evidences show that unmodified extracellular vesicles (EVs) derived from various cells can effectively inhibit the malignant progression of different types of tumors by delivering the bioactive molecules. Therefore, EVs are expected to be developed as emerging anticancer drugs. Meanwhile, unmodified EVs as an advanced and promising nanocarrier that is frequently used in targeted delivery therapeutic cargos and personalized reagents for the treatment and diagnosis of cancer. To improve the efficacy of EV-based treatments, researchers are trying to engineering EVs as an emerging nanomedicine translational therapy platform through biological, physical and chemical approaches, which can be broaden and altered to enhance their therapeutic capability. EVs loaded with therapeutic components such as tumor suppressor drugs, siRNAs, proteins, peptides, and conjugates exhibit significantly enhanced anti-tumor effects. Moreover, the design and preparation of tumor-targeted modified EVs greatly enhance the specificity and effectiveness of tumor therapy, and these strategies are expected to become novel ideas for tumor precision medicine. This review will focus on reviewing the latest research progress of functionalized EVs, clarifying the superior biological functions and powerful therapeutic potential of EVs, for researchers to explore new design concepts based on EVs and build next-generation nanomedicine therapeutic platforms.


Assuntos
Antineoplásicos , Vesículas Extracelulares , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Vesículas Extracelulares/metabolismo , Humanos , Nanomedicina , Neoplasias/patologia
19.
Pan Afr Med J ; 42: 34, 2022.
Artigo em Francês | MEDLINE | ID: mdl-35910049

RESUMO

Chemotherapy-induced neutropenia (FN) is the most common infectious complication in pediatric oncology. To our knowledge, no pediatric research has been published in Tunisia. The purpose of our study was to describe the features of FN among Tunisian children and to investigate factors correlated with FN. We conducted a prospective study of children with chemotherapy-induced FN at the Department of Pediatric Medicine A of the Tunis Children´s Hospital from July 2019 to December 2019. We recorded 50 episodes of FN in 32 patients whose mean age was 5.3 years (3 months-16 years). We included 26 patients with solid tumors (81%) and six patients with hemopathies (18.7%). The mean time between last treatment and fever onset was 10.67 days. Bacteriological investigation was contributory in 18% of cases and mainly showed gram positive cocci. Therapeutic protocol including 1st line empirical antibiotic therapy (3rd generation cephalosporin with aminoglycoside) was effective in 62% of cases. Mortality rate of patients with FN was 2%. The statistical study did not reveal any factor of correlation with late-onset neutropenia. In conclusion, our results are consistent with literature data on bacteriological documentation and mortality. Our 1st line treatment option based on 3rd generation cephalosporin associated with aminoglycoside was effective in 2/3 of the cases. In the future, oral antibiotics may be considered in patients at low risk for infection.


Assuntos
Antineoplásicos , Neutropenia Febril Induzida por Quimioterapia , Neoplasias , Aminoglicosídeos/uso terapêutico , Antibacterianos , Antineoplásicos/efeitos adversos , Cefalosporinas/uso terapêutico , Neutropenia Febril Induzida por Quimioterapia/complicações , Neutropenia Febril Induzida por Quimioterapia/tratamento farmacológico , Criança , Pré-Escolar , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Estudos Prospectivos
20.
Oxid Med Cell Longev ; 2022: 3142306, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910836

RESUMO

Immunotherapy is at the cutting edge of modern cancer treatment. Innovative medicines have been developed with varying degrees of success that target all aspects of tumor biology: tumors, niches, and the immune system. Oncolytic viruses (OVs) are a novel and potentially immunotherapeutic approach for cancer treatment. OVs reproduce exclusively in cancer cells, causing the tumor mass to lyse. OVs can also activate the immune system in addition to their primary activity. Tumors create an immunosuppressive environment by suppressing the immune system's ability to respond to tumor cells. By injecting OVs into the tumor, the immune system is stimulated, allowing it to generate a robust and long-lasting response against the tumor. The essential biological properties of oncolytic viruses, as well as the underlying mechanisms that enable their usage as prospective anticancer medicines, are outlined in this review. We also discuss the increased efficacy of virotherapy when combined with other cancer medications.


Assuntos
Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Imunoterapia , Neoplasias/patologia , Estudos Prospectivos
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