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1.
J Exp Clin Cancer Res ; 43(1): 38, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38303018

RESUMO

Tumor-infiltrating T cells recognize, attack, and clear tumor cells, playing a central role in antitumor immune response. However, certain immune cells can impair this response and help tumor immune escape. Therefore, exploring the factors that influence T-cell infiltration is crucial to understand tumor immunity and improve therapeutic effect of cancer immunotherapy. The use of single-cell RNA sequencing (scRNA-seq) allows the high-resolution analysis of the precise composition of immune cells with different phenotypes and other microenvironmental factors, including non-immune stromal cells and the related molecules in the tumor microenvironment of various cancer types. In this review, we summarized the research progress on T-cell infiltration and the crosstalk of other stromal cells and cytokines during T-cell infiltration using scRNA-seq to provide insights into the mechanisms regulating T-cell infiltration and contribute new perspectives on tumor immunotherapy.


Assuntos
Neoplasias , Linfócitos T , Humanos , Citocinas , Imunoterapia , Neoplasias/terapia , Fenótipo , Microambiente Tumoral , Análise de Célula Única
2.
Pathol Oncol Res ; 29: 1611330, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37746555

RESUMO

Systemic capillary leak syndrome (SCLS) is a rare and complex adverse effect of immune checkpoint inhibitors (ICIs). The diagnosis of drug-induced SCLS is based on diffuse infusions of exudative fluid into the interstitial areas and the exclusion of other causes. The best management of ICIs-induced SCLS is not settled, though proper supportive care and corticosteroids were commonly applied as the first-line treatment. In our patient with advanced gastroesophageal junction squamous cell carcinoma, although ICIs-induced SCLS was successfully controlled with corticosteroids, the patient soon experienced cancer progress and died of pulmonary infections. Based on our experience and the reported cases by other hospitals, different stages of SCLS might respond differently to the same treatment. Therefore, a grading of ICIs-induced SCLS might help to stratify the patient for different treatment strategies. Besides, corticosteroids-sensitive patients, though waived from deadly SCLS, might be at higher risk of cancer progress and subsequent infections due to the application of corticosteroids. Considering that the inflammatory factors should be closely involved in the development of ICIs-induced SCLS, targeted therapy against the driver inflammatory cytokine might offer treatment regimens that are more effective and safer.


Assuntos
Síndrome de Vazamento Capilar , Carcinoma de Células Escamosas , Humanos , Síndrome de Vazamento Capilar/induzido quimicamente , Síndrome de Vazamento Capilar/diagnóstico , Síndrome de Vazamento Capilar/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma de Células Escamosas/complicações , Corticosteroides/uso terapêutico
3.
Invest New Drugs ; 41(5): 719-726, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37589864

RESUMO

Immune-related liver injuries are closely associated with the liver's fundamental state. Patients with advanced biliary tract carcinoma (BTC) have poor liver function. We evaluated the clinical data of immune-related liver injury in patients with advanced BTC and gastric cancer (GC) during immune checkpoint inhibitor (ICI) treatment between February 2019 and July 2022 at Peking University First Hospital. Twenty-five patients with advanced BTC were identified. Fifteen patients (60%) experienced immune-related liver injury during ICI treatment. We also evaluated the clinical status of patients with GC in another group receiving immunotherapy. The results demonstrated that the incidence of immune-related liver injury was higher in patients with BTC than in GC cancer (p=0.040). Multivariate analysis suggested that the type of malignant tumor and baseline liver function status were high-risk factors for grade 2 and higher immune-related liver injuries. Two patients were diagnosed with immune-related cholangitis. Both biliary enzymes can be decreased to a certain degree by corticosteroid and ursodeoxycholic acid (UDCA) therapy but are difficult to reduce to normal levels. Liver function normalized, and symptoms improved after local treatment for cholestasis (stent implantation or PTBD). We observed a higher incidence of immune-related liver injury after ICI treatment in patients with advanced BTC. Effect of baseline liver function on the incidence of liver injury associated with immunotherapy. Interventional therapy provides rapid relief from cholestasis and is an indispensable and effective approach to the treatment of immune-related cholangitis.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Sistema Biliar , Carcinoma , Colangite , Colestase , Neoplasias Gastrointestinais , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Colestase/tratamento farmacológico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias Gastrointestinais/tratamento farmacológico , Carcinoma/tratamento farmacológico , Fígado , Neoplasias do Sistema Biliar/tratamento farmacológico
4.
Int J Colorectal Dis ; 38(1): 198, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37466736

RESUMO

PURPOSE: The study aimed to investigate the clinical characteristics, prognostic factors, survival times, and therapy outcomes of brain metastases (BM) from colorectal cancer (CRC). METHODS: The clinical characteristics of 25 patients with BM from CRC were retrospectively analyzed. The time of the occurrence of BM after diagnosis of CRC was recorded. Meanwhile, the time from the occurrence of lung, bone, liver, and other extracranial metastases to the occurrence of BM was also recorded. We evaluate the time factors affecting the length of the occurrence of BM and the potential prognostic factors after BM diagnosis. The influences of patients undergoing surgery-based comprehensive treatment, radiotherapy-based comprehensive treatment, and co-medication were also assessed. RESULTS: In patients with BM from CRC, lung metastases (13/25) occurred at a higher frequency than liver metastases (8/25) and bone metastases (6/25). The median time to the development of BM was much shorter (3.7 vs. 25.3 months, p = 0.027), with the brain being the origin site for the metastasis. The median overall survival reached 9.9 months. The interval between diagnosis of BM and bone, liver, and lung metastasis remains 3, 6.5, and 11 months, respectively. The brain lesions of patients with BM alone had higher rates in supratentorial (88.9%), while those with extracranial metastasis had a 62.5% incidence of infratentorial metastasis. The difference was statistically significant (p < 0.05). The time of occurrence of BM in patients aged 67 years and younger was 16.1 and 30.1 months, respectively. The differences between them were statistically significant (p = 0.043). The BM time for left- and right-sided colon cancer were 26.5 and 7.8 months, representing a statistically significant difference (p = 0.015). The time to onset of BM for patients with and without the resection of primary lesions was 25.4 and 4.5 months. Statistically significant differences are shown (p = 0.007). Univariate analysis demonstrated that the prognosis of patients was related to the KPS score, the number of BM, the treatment methods, and the occurrence of lung metastasis (p < 0.05). The multivariate analysis revealed that the treatment modality and lung metastasis were independent prognostic factors for CRC patients with BM. Right-sided CRC patients with BM have a poor prognosis (8.1 vs. 10.2 months, p = 0.31). Although median survival time was not significantly different between patients with and without bevacizumab combination therapy, bevacizumab therapy is associated with a better survival time (9.9 vs. 7.1 months, p = 0.27). CONCLUSION: Patients with left-sided CRC, especially those with lung metastases, are prone to brain metastases, and patients with brain metastases as the first metastatic site have a higher rate of supratentorial metastases. Young patients with right hemicolon cancer and patients who have not undergone primary lesion resection have a shorter time for the occurrence of BM. Patients with colorectal lung metastases, especially those young with right-sided CRC, require close imaging surveillance of BM. The prognosis of CRC patients with BM and lung metastases is poor, and comprehensive treatment based on surgery could significantly prolong patients' survival time.


Assuntos
Neoplasias Encefálicas , Neoplasias Colorretais , Neoplasias Pulmonares , Humanos , Prognóstico , Estudos Retrospectivos , Bevacizumab , Neoplasias Colorretais/patologia , Neoplasias Encefálicas/secundário , Neoplasias Pulmonares/secundário
5.
Ann Clin Microbiol Antimicrob ; 22(1): 49, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37365592

RESUMO

Aztreonam-avibactam is an important option against Enterobacterales producing metallo-ß-lactamases (MBLs). We obtained an aztreonam-avibactam-resistant mutant of an MBL-producing Enterobacter mori strain by induced mutagenesis. Genome sequencing revealed an Arg244Gly (Ambler position) substitution of SHV-12 ß-lactamase in the mutant. Cloning and susceptibility testing verified that the SHV-12 Arg244Gly substitution led to significantly reduced susceptibility to aztreonam-avibactam (MIC, from 0.5/4 to 4/4 mg/L) but with the loss of resistance to cephalosporins as tradeoff. Arg244 of SHV involves in the binding of avibactam by forming an arginine-mediated salt bridge and is a critical residue to interact with ß-lactams. Molecular modeling analysis demonstrated that the Arg244Gly substitution hindered the binding of avibactam to SHV with higher binding energy (from - 5.24 to -4.32 kcal/mol) and elevated inhibition constant Ki (from 143.96 to 677.37 µM) to indicate lower affinity. This substitution, however, resulted in loss of resistance to cephalosporins as tradeoff by impairing substrate binding. This represents a new aztreonam-avibactam resistance mechanism.


Assuntos
Antibacterianos , Aztreonam , Humanos , Aztreonam/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , beta-Lactamases/genética , beta-Lactamases/metabolismo , Cefalosporinas/farmacologia , Enterobacter/genética , Mutação , Testes de Sensibilidade Microbiana , Combinação de Medicamentos , Ceftazidima/farmacologia
6.
Antonie Van Leeuwenhoek ; 116(7): 643-651, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37101063

RESUMO

Two Enterobacter strains 155092T and 170,225 were isolated from clinical samples, pus and sputum, from two hospitalised patients separately, in China. Preliminary identification using Vitek II microbiology system assigned the strains to the Enterobacter cloacae complex. The two strains were subjected to genome sequencing and genome-based taxonomy analysis with type strains of all Enterobacter species and those within closely related genera Huaxiibacter, Leclercia, Lelliottia, and Pseudoenterobacter. The average nucleotide identity (ANI) and in silico DNA-DNA hybridisation (isDDH) values between the two strains were 98.35% and 89.4%, respectively, suggesting that they belong to one species. The two strains had the highest ANI (95.02% and 95.04%) with the type strain of Enterobacter quasiroggenkampii. Their highest isDDH values, also seen with the type strain of E. quasiroggenkampii, were 59.5% and 59.8%, well below the 70% cutoff to define species. The two strains were also characterised for morphological and biochemical features by a set of experiments and observations. The abilities of metabolising gelatin and L-rhamnose could differentiate the two strains from all currently known Enterobacter species. Collectively, the two strains represent a novel Enterobacter species, for which we propose Enterobacter pseudoroggenkampii sp. nov. as the species name. The type strain of this novel species is155092T (= GDMCC 1.3415T = JCM 35646T). The two strains also carried multiple virulence factors comprising aerobactin-encoding iucABCD-iutA and salmochelin-encoding iroN. The two strains also had chromosomally located qnrE, a gene associated with reduced susceptibility to quinolones, suggesting that this species is a potential reservoir of qnrE genes.


Assuntos
Enterobacter , Quinolonas , Humanos , Análise de Sequência de DNA , Ácidos Graxos , Filogenia , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , RNA Ribossômico 16S/genética , Enterobacteriaceae/genética , China
7.
J Antimicrob Chemother ; 78(5): 1288-1294, 2023 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-36995982

RESUMO

BACKGROUND: We found a carbapenem-resistant Escherichia coli without known carbapenemase-encoding genes and performed a study to identify the possible new carbapenemase. METHODS: The production of carbapenemase was examined using the modified carbapenem inactivation method. The strain was subjected to short- and long-read genome sequencing and the complete genome was obtained by hybrid assembly. The gene encoding a potential new OXA-type carbapenemase was cloned. The enzyme was purified and was then subjected to kinetic assays. Molecular docking analysis of the enzyme was performed using the MOE software suite. Mating experiments were attempted to obtain the plasmid carrying the corresponding gene. RESULTS: We identified and characterized a novel class D carbapenem-hydrolysing ß-lactamase, OXA-1041, in a carbapenem-resistant E. coli clinical strain. OXA-1041 had 89.77% (237/264) amino acid identity with OXA-427, a known carbapenemase. By cloning in an E. coli laboratory strain, blaOXA-1041 was found to reduce susceptibility to ertapenem by 16 times (MIC 0.25 versus 0.016 mg/L) and meropenem by four times (MIC 0.06 versus 0.016 mg/L) but did not significantly reduce susceptibility to imipenem and doripenem. Enzyme kinetic measurement of purified OXA-1041 showed that OXA-1041 could hydrolyse ertapenem and meropenem with a turnover number (kcat)/Michaelis constant (KM) of 8.57 and 3.63 mM-1s-1, respectively. The complete genome contained a single plasmid (223 341 bp, IncF, containing five replicons), which was self-transmissible. blaOXA-1041 was downstream of insertion sequence ISCR1 and there were three tandem copies of ISCR1-blaOXA-1041-creDΔ (encoding an envelope protein) on this plasmid. CONCLUSIONS: The above findings suggest OXA-1041 is a new plasmid-encoded carbapenemase with preferential activity against ertapenem.


Assuntos
Carbapenêmicos , Escherichia coli , Carbapenêmicos/farmacologia , Carbapenêmicos/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Meropeném , Ertapenem/farmacologia , Simulação de Acoplamento Molecular , beta-Lactamases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Testes de Sensibilidade Microbiana
8.
Eur J Clin Microbiol Infect Dis ; 42(4): 513-517, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36773190

RESUMO

We found a carbapenem-resistant Enterobacter clinical strain which was susceptible to cefotaxime and ceftazidime. This unusual susceptibility profile promoted the investigation. This strain had blaFRI-11, a rare carbapenemase-encoding gene, on a 93,864-bp plasmid containing two replicons of IncFII(pECLA) and IncFIA(HI1). FRI-11, FRI-2, FRI-3, FRI-4, FRI-6, FRI-7, and FRI-9 belong to the same group of FRI ß-lactamases based on the amino acid sequence similarity and their encoding genes are carried by plasmids containing an IncFII(pECLA) replicon. Awareness should be raised towards FRI carbapenemases that are plasmid-encoded and confer an unusual carbapenem-resistant but 3rd-generation-cephalosporin-susceptible resistance profile.


Assuntos
Antibacterianos , Enterobacter , Humanos , Enterobacter/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , beta-Lactamases/genética , beta-Lactamases/metabolismo , Carbapenêmicos/farmacologia , Plasmídeos/genética , Testes de Sensibilidade Microbiana
10.
Artigo em Inglês | MEDLINE | ID: mdl-35976100

RESUMO

Strain 155047T was recovered from human sputum in China in 2021. Preliminary species identification based on limited phenotypic tests assigned the strain to the genus Enterobacter of the family Enterobacteriaceae. The genome sequence of the strain was obtained and had ≤84.43 % average nucleotide identity (ANI) and ≤26.3 % in silico DNA-DNA hybridization (isDDH) values with the genomes of type strains of known Enterobacteriaceae species. The highest ANI and isDDH matches were with Lelliottia nimipressuralis and Enterobacter asburiae, respectively. The ANI and isDDH values support that the strain belongs to a novel species of the family Enterobacteriaceae. Phylogenomic analysis based on core genes revealed that strain 155047T was located in the Enterobacter-Leclercia-Lelliottia-Pseudenterobacter lineage. The highest ANI and average amino acid identity values between 155047T and any species of the Enterobacter-Leclercia-Lelliottia-Pseudenterobacter lineage were 84.43 % and 90.21 %, respectively, lower than the maximum inter-genus pairwise values. This indicates that 155047T belongs to a novel species of a novel genus in the lineage. Strain 155047T could be differentiated from Enterobacter, Lelliottia, Leclercia and Pseudenterobacter species by a negative reaction for ß-galactosidase and the ability to produce acid from l-fucose but not from sucrose. The names Huaxiibacter gen. nov. and Huaxiibacter chinensis sp. nov. are proposed for the novel genus and species, respectively. The type strain is 155047T (= GDMCC 1.2980T=JCM 35262T).


Assuntos
Ácidos Graxos , Escarro , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Humanos , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
11.
Curr Med Sci ; 42(2): 348-356, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35419673

RESUMO

OBJECTIVE: This study aimed to evaluate the relationships between the albumin/globulin ratio (AGR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) and clinicopathological information for gastric cancer patients. In addition, the prognostic values of these hematological parameters for resectable gastric cancer patients undergoing a total gastrectomy were determined. METHODS: A total of 245 patients with gastric cancer who underwent a total gastrectomy at our hospital between January 1, 2005, and December 30, 2015, were enrolled into this study. The preoperative AGR, NLR, and PLR in the serum samples of the patients were measured. The relationships between the hematological parameters and the disease-free survival (DFS) as well as overall survival (OS) were analyzed by statistical analysis. RESULTS: The cutoff values of AGR, NLR, and PLR were 1.57, 3.5, and 193, respectively. Univariate analyses demonstrated that a low AGR, a high NLR, and a high PLR were significant risk factors for a poor prognosis. According to multivariate analysis, a high PLR was found to be independently associated with a poor survival. Additionally, when age was considered as a stratified factor, univariate analyses demonstrated that a low AGR had the tendency to be correlated with a shorter DFS in nonelderly patients (<65 years old). A low AGR was significantly correlated with a shorter DFS and OS in elderly patients (≥65 years old). CONCLUSION: AGR, NLR, and PLR are independent risk factors associated with a poor gastric cancer survival by univariate analysis, and AGR is an independent risk factor for predicting DFS and OS in elderly patients (≥65 years old) with gastric cancer after total gastrectomy.


Assuntos
Neoplasias Gástricas , Idoso , Gastrectomia , Humanos , Linfócitos/patologia , Neutrófilos/patologia , Prognóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
13.
Cancer Immunol Immunother ; 71(6): 1443-1451, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34689233

RESUMO

BACKGROUND: Treatment strategies are limited for patients with chemotherapy refractory microsatellite stable (MSS) colorectal cancer. We aim to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with regorafenib in this population in routine clinical practice. METHODS: We retrospectively analyzed patients with advanced or metastatic colorectal cancer who received at least one dose of ICIs combined with regorafenib in 14 Chinese medical centers. The primary outcome was objective response rate (ORR). This study was registered at ClinicalTrials.gov on February 2020 (NCT04771715). RESULTS: Eighty-four patients received ICIs combined with regorafenib from January 2019 to January 2021. Most patients (91%) received two or more systemic treatment lines before the study treatment. Seventy-six patients (90%) had confirmed MSS status. At a median follow-up of 5.5 months, four patients achieved partial response (5%) and 37 patients achieved stable disease (45%) as the best response. The median progression-free survival (PFS) was 3.1 months, and the median overall survival was 17.3 months. Eleven patients (13%) remained progression-free for more than 6 months. Baseline liver metastasis (HR 1.98, 95%CI 1.07-3.69, P = 0.03) and neutrophil-lymphocyte ratio (NLR) of ≥ 1.5 (HR 2.83, 95%CI 1.00-7.98, P = 0.05) were associated with shorter PFS in multivariate analysis. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 16 patients (19%). CONCLUSION: The combination of ICIs with regorafenib can be a valuable treatment option for a proportion of patients with chemotherapy refractory MSS colorectal cancer. Patients with no liver metastasis and a low NLR at baseline may derive most benefit from this strategy.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Repetições de Microssatélites , Compostos de Fenilureia/uso terapêutico , Piridinas , Estudos Retrospectivos
14.
Support Care Cancer ; 30(3): 2121-2129, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34677650

RESUMO

PURPOSE: Chemotherapy-related bacterial infection is a common side effect in patients receiving chemotherapy. The purpose of this study was to determine the risk factors and characteristics of bacterial infection in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma patients treated with combined chemotherapy. METHODS: Patients with metastatic gastric or GEJ adenocarcinoma were followed up from 2013 to 2016 at Peking University First Hospital in China. Patients were treated with multiple cycles of combined chemotherapy. The incidence rate of bacterial infection and patients' clinical data were manually reviewed. RESULTS: A total of 154 patients were eligible and were enrolled in this study. A median of 6 chemotherapy cycles were administered (range, 1-14 cycles). Chemotherapy-related bacterial infections were observed in 36 of 154 patients (23.4%). Pulmonary is the most common site of infections. Ninety-four percent of patients with bacterial infection during chemotherapy received broad-spectrum antibiotics. The independent risk factors for chemotherapy-related bacterial infection identified by multivariable analysis were Nutritional Risk Screening 2002 (NRS2002) ≥ 3 (P = 0.008), ≥ grade 3 neutropenia (P = 0.028), and Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 2 (P = 0.042). CONCLUSIONS: Nearly a quarter of patients with metastatic gastric or GEJ adenocarcinoma who received combined chemotherapy had bacterial infection in this study. The proportion of broad-spectrum antibiotics used in patients with infection is very high. Improving nutritional status may help reduce the incidence of bacterial infection.


Assuntos
Adenocarcinoma , Infecções Bacterianas , Neoplasias Esofágicas , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/epidemiologia , Junção Esofagogástrica , Humanos , Fatores de Risco , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/epidemiologia
15.
Asia Pac J Clin Nutr ; 30(1): 51-59, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33787040

RESUMO

BACKGROUND AND OBJECTIVES: The present study aimed to determine the correlation between Controlling Nutritional Status (CONUT) score and prognosis in gastric cancer patients undergoing total gastrectomy. METHODS AND STUDY DESIGN: The clinical data of 245 gastric cancer patients who underwent total gastrectomy in Peking University, First Hospital between January1st 2005 and December 30th 2015 were retrospectively collected. According to the CONUT level, they were divided into high CONUT (>3) group and low CONUT (≤3) group. The relationship between CONUT and the disease-free survival (DFS) and overall survival (OS) were analyzed by statistical analysis. RESULTS: The results showed that the optimal cutoff value for CONUT to predict the 5-year survival was 3 and CONUT had a higher area under the ROC curve (AUC) for 5-year disease free survival (DFS) and overall survival (OS) prediction. Additionally, when age was considered as a stratified factor, univariate analyses demonstrated that high CONUT correlated with shorter DFS in non-elderly (<65) patients and shorter DFS and OS in elderly (≥65) patients. CONCLUSIONS: High CONUT was significantly correlated with older age, advanced TNM-stage, higher Ki-67 and pathological subtype. Patients with high pre-operative high CONUT levels should be given more observation and constant follow-up after surgery.


Assuntos
Neoplasias Gástricas , Idoso , Gastrectomia , Humanos , Pessoa de Meia-Idade , Estado Nutricional , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia
16.
NPJ Precis Oncol ; 5(1): 1, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479506

RESUMO

Little is known of the patterns of expression of ACE2 and TMPRSS2 or the clinical characteristics of COVID-19 in patients with COVID-19 and colorectal cancer. We found in both bulk and single-cell RNA-seq profiles that ACE2 and TMPRSS2 were expressed at high levels on tumor and normal colorectal epithelial tissues. Clinically, patients with colorectal cancer and COVID-19 were more likely to have lymphopenia, higher respiratory rate, and high hypersensitive C-reactive protein levels than matched patients with COVID-19 but without cancer. These results suggest that patients with colorectal cancer may be particularly susceptible to SARS-CoV-2 infection. Further mechanistic studies are needed to support our findings.

17.
Cancer Biol Ther ; 21(11): 990-993, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33121320

RESUMO

Docetaxel is an important anti-microtubule agent used to treat a variety of solid tumors, including breast cancer; notably, docetaxel-containing regimens improve outcomes for patients in metastatic, adjuvant, and neoadjuvant settings. However, the effectiveness of docetaxel in clinical practice can be compromised by suboptimal management of side effects. Here, we report two cases of docetaxel-based chemotherapy regimens in patients who exhibited invasive ductal breast cancer and underwent two different clinical treatment approaches. A 58-year-old postmenopausal female received salvage treatment with 8 cycles of docetaxel (67 mg/m2), and a 74-year-old female received 1 cycle of docetaxel (100 mg/m2). The two patients exhibited considerable hearing loss two days later. Of note, both patients had no hearing loss symptoms prior to docetaxel. Thus, ototoxicity may be a side effect of docetaxel that should be considered during treatment.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/complicações , Docetaxel/efeitos adversos , Ototoxicidade/etiologia , Antineoplásicos/farmacologia , Docetaxel/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade , Ototoxicidade/fisiopatologia
18.
Zhongguo Fei Ai Za Zhi ; 23(10): 889-896, 2020 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-33070515

RESUMO

Small cell lung cancer (SCLC) is a type of malignancy with poor prognosis, and no advance in medication has been made for about 30 years except immune checkpoint inhibitor (ICI), which demonstrated efficacy in recent years. The response rate of programmed death-1 (PD-1) inhibitor alone or its combination with cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor as subsequent therapy was 10%-33% and the response duration was persistent. The combination of programmed death ligand-1 (PD-L1) inhibitor with chemotherapy resulted in longer survival versus chemotherapy alone. Nevertheless, comparing with immunotherapy-sensitive tumors such as non-small cell lung cancer (NSCLC), efficacy in SCLC is still unsatisfied and this is maybe associated with its immune inhibitory characteristics. This review describes the current research about immune characteristics of SCLC, including tumor infiltrating of lymphocytes (TIL) and immune inhibitory cells, PD-L1 and major histocompatibility complex (MHC) expression in tumor as well as changes of peripheral immune cells. We also review the prognostic and predictive values of these immune characteristics.
.


Assuntos
Antígeno CTLA-4/imunologia , Neoplasias Pulmonares/imunologia , Carcinoma de Pequenas Células do Pulmão/imunologia , Animais , Antígeno CTLA-4/genética , Humanos , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Linfócitos do Interstício Tumoral/imunologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/genética
19.
Front Oncol ; 10: 892, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32695661

RESUMO

Purpose: To assess the benefit of post-mastectomy radiotherapy (PMRT) in breast cancer (BC) patients with T1-2N1M0 who developed pathologically negative lymph nodes (ypN0) after undergoing neoadjuvant chemotherapy (NAC) and mastectomy. Patients and Materials: Patients with T1-2 tumors and positive lymph node(s) who became pN0 after NAC and mastectomy were screened from our prospectively maintained database. The primary endpoint was recurrence-free survival (RFS), and the secondary endpoints were local recurrence-free survival (LRFS) and overall survival (OS). Propensity-score matching (PSM) was conducted for the comparison between PMRT and non-PMRT groups. Results: Of the 142 eligible patients, 110 (77.5%) received PMRT, and 32 (22.5%) did not. The median follow-up time was 72 months. Univariate analyses showed that the 5-year RFS, LRFS, and OS rates were 88.7, 94.5, and 96.1, respectively, with PMRT and 72.4, 90.1, and 95.0% without PMRT (p = 0.028; p = 0.151; p = 0.971). Multivariate analyses established PMRT as a significant prognostic factor for RFS rate (HR, 0.411; 95% CI, 0.175-0.968; p = 0.042). After a PSM analysis (64 in the PMRT group vs. 32 in the non-PMRT group), PMRT remained significant, with improved RFS in univariate and multivariate analysis (with 5-year RFS rates of 90.1 vs. 72.4%, respectively, p = 0.016; HR, 0.323, 95%CI, 0.115-0.913, p = 0.033). In the subgroup of 48 (33.8%) patients with pathologic complete responses (pCR, ypT0, and ypN0) after NAC, PMRT did not affect RFS (HR, 0.226; 95% CI, 0.034-1.500; p = 0.123). Conclusions: PMRT might benefit pT1-2N1M0 patients with pN0 after NAC. Patients with pCR might consider omitting PMRT. Prospective studies are needed to assess the effect of PMRT on this specific patient population.

20.
Onco Targets Ther ; 13: 151-161, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021263

RESUMO

PURPOSE: Various reports found a relationship between lymphocyte-related blood parameters (LRBP), including absolute lymphocyte counts (ALC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) and prognosis of breast cancer. Most of the studies focused on LRBP pre-treatment. Seldom have studies focused on LRBP during radiotherapy. We intended to perform a retrospective cohort study on the prognostic value of LRBP at the time point of lowest ALC during radiotherapy for breast cancer. PATIENTS AND METHODS: A total of 158 female patients were included in radiotherapy group because of the strict limitation standards of complete routine blood test results at pre-treatment and pre-operation, and at least once a week during radiotherapy. Besides 221 patients, including the 158 patients of radiotherapy group, were adopted in pre-treatment group and pre-operation group. RESULTS: ALC and PLR at the time point of lowest ALC during radiotherapy are prognostic predictors of breast cancer, and lower ALC and higher PLR are independent significant predictors of poor DFS. Besides, lower ALC, higher NLR and higher PLR at both pre-treatment and pre-operation were found to be independent variables for predicting poor DFS. CONCLUSION: LRBP at pre-treatment, pre-operation, and during radiotherapy may serve as predictors of outcomes of breast cancer.

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