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1.
Chemistry ; 29(46): e202301390, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37280159

RESUMO

Chemodivergent tandem radical cyclization offers exciting possibilities for the synthesis of structurally diverse cyclic compounds. Herein, we revealed a chemodivergent tandem cyclization of alkene-substituted quinazolinones under metal- and base-free conditions, this transformation is initiated by alkyl radicals produced from oxidant-induced α-C(sp3 )-H functionalization of alkyl nitriles or esters. The reaction resulted in the selective synthesis of a series of mono- and di-alkylated ring-fused quinazolinones by modulating the loading of oxidant, reaction temperature, and reaction time. Mechanistic investigations show that the mono-alkylated ring-fused quinazolinones is constructed by the key process of 1,2-hydrogen shift, whereas the di-alkylated ring-fused quinazolinones is mainly achieved through crucial steps of resonance and proton transfer. This protocol is the first example of remote second alkylation on the aromatic ring via α-C(sp3 )-H functionalization and difunctionalization achieved by association of two unsaturated bonds in radical cyclization.

2.
World J Clin Oncol ; 15(3): 456-463, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38576599

RESUMO

BACKGROUND: SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting (SWI/SNF) complexes and plays an essential role in oncogenesis. SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis. There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies. Programmed death 1 (PD-1) antibodies, known as immune checkpoint inhibitor antibodies, potentially play a role in treating gastrointestinal tract malignancies. CASE SUMMARY: We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum. For both patients, SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein, while TP53 gene mutations were observed via next-generation sequencing. Both patients were administered chemotherapy in combination with an anti-PD-1 antibody. The two patients exhibited completely different responses to treatment and had different prognoses. Case 1 experienced rapid progression after PD-1 infusion and chemotherapy, case 2 experienced a remarkable response after treatment, and the progression-free survival was more than 6 months. CONCLUSION: This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum. PD-1 combined with chemotherapy showed a certain efficacy in select patients, providing options for treating these highly malignant tumors. Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.

3.
Org Lett ; 26(24): 5074-5081, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38857312

RESUMO

The nickel/photoredox dual catalysis system is an efficient conversion platform for the difunctionalization of unsaturated hydrocarbons. Herein, we disclose the first dual nickel/photoredox-catalyzed intramolecular 1,2-arylsulfonylation of allenes, which can accurately construct a C(sp2)-C(sp2) bond and a C(sp3)-S bond. The reaction exhibits excellent chemoselectivity and regioselectivity, allowing modular conformations of a diverse series of 3-sulfonylmethylbenzofuran derivatives. Control experiments showed that the bipyridine ligand is crucial for the formation of a stable σ-alkyl nickel intermediate, providing the possibility for sulfonyl radical insertion. Meanwhile, the electrophilic sulfonyl radical facilitates further oxidative addition of the σ-alkyl nickel intermediate and inhibits addition with allenes. In addition, control experiments, cyclic voltammetry tests, Stern-Volmer experiments, and density functional theory calculations afford evidence for the Ni(0)/Ni(I)/Ni(II)/Ni(III) pathway in this 1,2-arylsulfonylation.

4.
Signal Transduct Target Ther ; 9(1): 69, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38531869

RESUMO

The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production. Herein, by using the established lipid nanoparticle (LNP)-encapsulated mRNA platform, we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses. In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies. More importantly, mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus (VACV) lethal challenge mouse model, and a unique mRNA antibody cocktail, Mix2a, exhibited superior in vivo protection by targeting both intracellular mature virus (IMV)-form and extracellular enveloped virus (EEV)-form viruses. In summary, our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform, highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as other emerging viruses.


Assuntos
Orthopoxvirus , Vacínia , Animais , Camundongos , Terapia Combinada de Anticorpos , Vacínia/prevenção & controle , Anticorpos Antivirais , Vaccinia virus/genética
5.
Bioorg Med Chem Lett ; 23(7): 2089-92, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23466230

RESUMO

A novel series of prodrugs containing dabigatran and methyl (E)-3-(4-hydroxy-2-methoxyphenyl)propenoate (methyl ferulate) were synthesized. All of them reveal the effect of thrombin-induced anti-platelet aggregation in vitro. In addition, in vivo experiment shows that one of the target compounds, X-2 (ED50=3.7 ± 1.0 µmol/kg) possesses a more potent activity for inhibiting venous thrombosis than that of dabigatran etexilate (ED50=7.8 ± 1.5 µmol/kg).


Assuntos
Desenho de Fármacos , Fibrinolíticos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Pró-Fármacos/farmacologia , Benzimidazóis/química , Benzimidazóis/farmacologia , Ácidos Cafeicos/química , Dabigatrana , Relação Dose-Resposta a Droga , Fibrinolíticos/síntese química , Fibrinolíticos/química , Humanos , Estrutura Molecular , Inibidores da Agregação Plaquetária/síntese química , Inibidores da Agregação Plaquetária/química , Pró-Fármacos/síntese química , Pró-Fármacos/química , Piridinas/farmacologia , Trombina/metabolismo , Trombose Venosa/tratamento farmacológico , beta-Alanina/análogos & derivados , beta-Alanina/química
7.
Front Oncol ; 13: 1165040, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37324019

RESUMO

Targeted therapy has been standardized in front-line therapies for metastatic colorectal cancer (mCRC), while explicit recommendations for third- or later-line are still lacking. This study evaluated the efficacy and safety of combining targeted therapy with chemotherapy in the third- or later-line treatment for mCRC via meta-analysis, providing evidence-based guidance for clinical or research practice. Comprehensive retrieval of related studies was conducted according to the PRISMA guideline. Studies were stratified with patient characteristics and pharmacological classification of the drugs. For the data available for quantitative analysis, pooled overall response rate, disease control rate, hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and adverse events rate with respective 95% confidence intervals (CIs) were calculated. A total of 22 studies (1,866 patients) were included in this meta-analysis. Data from 17 studies (1,769 patients) involving targets of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) were extracted for meta-analyses. The overall response rates for monotherapy and combined therapy were 4% (95% CI: 3%, 5%) and 20% (95% CI: 11%, 29%). The pooled HRs (combined therapy vs. mono) for OS and PFS were 0.72 (95% CI: 0.53, 0.99) and 0.34 (95% CI: 0.26, 0.45). Another five studies were included in narrative depiction, involving targets of BRAF, HER-2, ROS1, and NTRK. The findings of this meta-analysis indicate that VEGF and EGFR inhibitors manifest promising clinical response rates and prolonged survival in the treatment of mCRC with acceptable adverse events.

8.
Chem Asian J ; 18(18): e202300606, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37500593

RESUMO

The synergistic systems of photoredox and copper catalyst have already appeared as a novel formation of green synthetic chemistry, which open new avenues for chemical synthesis applications. We describe a novel strategy for the cyclization of alkyne-tethered α-bromocarbonyls initiated by the cleavage of C(sp3 )-Br bond via the collaboration of photoredox and copper catalyst. The present protocol exhibits mildness using economical copper catalyst and visible-light at room temperature. The gram-scale and sunlight irradiation experiments proceeded smoothly to show the practicality of the methodology. It is notable that the newly generated oxygen in the product originates from H2 O.

9.
Emerg Microbes Infect ; 12(1): 2191741, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36920800

RESUMO

Pulmonary anthrax is the most fatal clinical form of anthrax and currently available injectable vaccines do not provide adequate protection against it. Hence, next-generation vaccines that effectively induce immunity against pulmonary anthrax are urgently needed. In the present study, we prepared an attenuated and low protease activity Bacillus anthracis strain A16R-5.1 by deleting five of its extracellular protease activity-associated genes and its lef gene through the CRISPR-Cas9 genome editing system. This mutant strain was then used to formulate a lethal toxin (LeTx)-free culture supernatant extract (CSE) anthrax vaccine, of which half was protective antigen (PA). We generated liquid, powder, and powder reconstituted formulations that could be delivered by aerosolized intratracheal inoculation. All of them induced strong humoral, cellular, and mucosal immune responses. The vaccines also produced LeTx neutralizing antibodies and conferred full protection against the lethal aerosol challenges of B. anthracis Pasteur II spores in mice. Compared to the recombinant PA vaccine, the CSE anthrax vaccine with equal PA content provided superior immunoprotection against pulmonary anthrax. The preceding results suggest that the CSE anthrax vaccine developed herein is suitable and scalable for use in inhalational immunization against pulmonary anthrax.


Assuntos
Vacinas contra Antraz , Antraz , Bacillus anthracis , Camundongos , Animais , Antraz/prevenção & controle , Vacinas contra Antraz/genética , Antígenos de Bactérias/genética , Pós , Bacillus anthracis/genética , Vacinas Sintéticas , Peptídeo Hidrolases , Anticorpos Antibacterianos
10.
Zhonghua Yu Fang Yi Xue Za Zhi ; 46(1): 67-9, 2012 Jan.
Artigo em Zh | MEDLINE | ID: mdl-22490144

RESUMO

OBJECTIVE: To evaluate the protective performance of a positive pressure bio-protective clothing against viral aerosol. METHODS: The suspension of indicating virus phage Phi-X174 was made for viral aerosol generating in a hermetic cabin. The diameter of viral aerosol particles were measured with a aerodynamics size analyzer. By adjusting the inner humidity of the cabin, the protective efficiency of the positive pressure bio-protective clothing against viral aerosol in high and low windshield conditions was determined with Andersen six-stage air sampler sampling and plage forming unit (PFU) counting, respectively. RESULTS: The mass median diameter of Phage Phi-X174 aerosol particles was about 0.922 µm and the background concentration is beyond 2 × 104 particles/m³. The protective efficiency of the clothing against phage Phi-X174 aerosol particles was above 99.9% under different test conditions with the range of viral aerosol concentration between 0 - 23 PFU/m³. Airflow (P = 0.84), environment humidity conditions (P = 0.33) and sampling time (P = 0.07) did not affect the protective efficiency statistically. CONCLUSION: The positive pressure bio-protective clothing provided a relatively high efficiency against phage Phi-X174 aerosol regardless of airflow rate, environment humidity and sampling time.


Assuntos
Roupa de Proteção , Aerossóis , Bacteriófago phi X 174 , Bioterrorismo/prevenção & controle , Desenho de Equipamento , Umidade , Exposição Ocupacional/prevenção & controle , Pressão , Fatores de Tempo , Viroses/prevenção & controle
11.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 24(4): 215-8, 2012 Apr.
Artigo em Zh | MEDLINE | ID: mdl-22464573

RESUMO

OBJECTIVE: To investigate the modulatory function of statin therapy on circulating microRNA-92a (miR-92a) in patients with coronary heart disease (CHD), and to evaluate the possibility of miR-92a as a new target of treatment for endothelial dysfunction. METHODS: A case control study was conducted. Prevalence of abnormal blood fat content, statin treatment rate, and attainment rate of low density lipoprotein-cholesterol (LDL-C) lowered to expected level in 236 patients with CHD were analyzed. Relationship between statin therapy in patients with type 2 diabetes mellitus (DM), and level of LDL-C and circulating miR-92a expression was analyzed by multivariate general linear factorial analysis. The incidence of acute coronary syndrome (ACS) was compared in patients with CHD receiving statin therapy in all groups. RESULTS: Prevalence of abnormal LDL-C was 95.7% (112/117) in CHD patients of non-statin therapy group, and 47.5% (112/236) of patients with CHD who should receive statin therapy but did not. Attainment rate of lowering of LDL-C to expected level in statin therapy group was 27.7% (33/119). LDL-C level (mmol/L) was significantly lower in statin therapy group than that in non-statin therapy group (2.457 ± 0.802 vs. 3.218 ± 1.130, Z = -9.760, P = 0.001), and incidence of ACS was significantly lower in statin therapy group than that in non-statin therapy group [33.6% vs. 71.8%, χ(2) = 34.491, P = 0.001]. There was no significant difference in incidence of ACS between patients with or without attaining the expected low value of LDL-C in statin therapy group [33.3% vs. 33.7%,χ(2) = 0.002, P = 0.968]. Circulating miR-92a expression was significantly higher in patients with stable angina pectoris (SAP) complicated with DM than those without DM (0.492 vs. -0.121, Z = -3.038, P = 0.002). It was found that statin therapy could down regulate miR-92a expression in patients with SAP complicated with DM as compared with that with non-statin therapy (0.419 vs. 0.687, Z = 1.289, P = 0.072). There was no significant difference in circulating miR-92a expression between statin therapy and non-statin therapy in patients with SAP without co-existing DM (-0.032 vs. -0.198, Z = -0.614, P = 0.539). Multivariate general linear factorial analysis showed that statin therapy was the major influential factor on LDL-C level in patients with CHD (F = 22.863, P = 0.001), and complicating DM was the major influential factor on circulating miR-92a expression in patients with SAP (F = 9.641, P = 0.003). CONCLUSION: Regulation of circulating miR-92a expression may be considered as a new clinical target for statin treating endothelial dysfunction in patients with CHD.


Assuntos
Doença das Coronárias/sangue , Doença das Coronárias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , MicroRNAs/sangue , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/complicações , Idoso , Estudos de Casos e Controles , LDL-Colesterol/sangue , Doença das Coronárias/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Biomed Environ Sci ; 35(9): 821-829, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36189997

RESUMO

Objective: This study aimed to investigate the regulation of histone-like nucleoid structuring protein (H-NS) on biofilm formation and cyclic diguanylate (c-di-GMP) synthesis in Vibrio parahaemolyticus RIMD2210633. Methods: Regulatory mechanisms were analyzed by the combined utilization of crystal violet staining, quantification of c-di-GMP, quantitative real-time polymerase chain reaction, LacZ fusion, and electrophoretic-mobility shift assay. Results: The deletion of hns enhanced the biofilm formation and intracellular c-di-GMP levels in V. parahaemolyticus RIMD2210633. H-NS can bind the upstream promoter-proximal DNA regions of scrA, scrG, VP0117, VPA0198, VPA1176, VP0699, and VP2979 to repress their transcription. These genes encode a group of proteins with GGDEF and/or EAL domains associated with c-di-GMP metabolism. Conclusion: One of the mechanisms by which H-NS represses the biofilm formation by V. parahaemolyticus RIMD2210633 may be via repression of the production of intracellular c-di-GMP.


Assuntos
Vibrio parahaemolyticus , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes , GMP Cíclico/análogos & derivados , Regulação Bacteriana da Expressão Gênica , Violeta Genciana , Histonas/genética , Histonas/metabolismo , Vibrio parahaemolyticus/genética
13.
Emerg Microbes Infect ; 11(1): 2350-2358, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36069671

RESUMO

Zika virus (ZIKV) is primarily transmitted through mosquito bites and sexual contact, and vertical transmission of ZIKV has also been observed in humans. In addition, ZIKV infection via unknown transmission routes has been frequently reported in clinical settings. However, whether ZIKV can be transmitted via aerosol routes remains unknown. In this study, we demonstrated that aerosolized ZIKV is fully infectious in vitro and in vivo. Remarkably, intratracheal (i.t.) inoculation with aerosolized ZIKV led to rapid viremia and viral secretion in saliva, as well as robust humoral and innate immune responses in guinea pigs. Transcriptome analysis further revealed that the expression of genes related to viral processes, biological regulation and the immune response was significantly changed. Together, our results confirm that aerosolized ZIKV can result in systemic infection and induce both innate and adaptive immune responses in guinea pigs, highlighting the possibility of ZIKV transmission via aerosols.


Assuntos
Infecção por Zika virus , Zika virus , Animais , Cobaias , Humanos , Imunidade Humoral , Transmissão Vertical de Doenças Infecciosas , Viremia , Zika virus/fisiologia
14.
BJU Int ; 107(3): 486-92, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20735389

RESUMO

OBJECTIVE: To investigate the association of RUNX1 rs2253319 with clinicopathological characteristics of prostate cancer (PCa) and disease recurrence after radical prostatectomy (RP). PATIENTS AND METHODS: Taking advantage of the systematic stage and grade for each tumor in a cohort of 314 patients with localized PCa receiving RP, we evaluated the associations of RUNX1 rs2253319 with age at diagnosis, preoperative prostate-specific antigen (PSA) level, Gleason score, surgical margin, pathologic stage, status of lymph node metastasis, and PSA recurrence after RP. RESULTS: The minor allele, T, and the minor homozygote TT genotype of RUNX1 rs2253319 were significantly associated with a 1.49- to 2.76-fold higher risk for advanced pathologic stage and a 3.35- to 9.52-fold higher risk for lymph node metastasis. RUNX1 rs2253319 TT genotype was also associated with poorer PSA-free survival compared with the major homozygote CC genotype in Kaplan-Meier analysis (log-rank test, P= 0.038) and multivariate Cox proportional hazards model adjusting for age and PSA concentration (P= 0.045). CONCLUSION: RUNX1 rs2253319 is associated with adverse clinicopathological features and might be a prognostic factor for the recurrence of PSA in patients with PCa receiving RP.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Recidiva Local de Neoplasia/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Próstata/genética , Idoso , Alelos , Métodos Epidemiológicos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia
15.
World J Clin Cases ; 9(34): 10652-10658, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-35004997

RESUMO

BACKGROUND: The treatment of small-cell lung cancer (SCLC) has progressed little in recent years because of its unique biological activities and complex genomic alterations. Chemotherapy combined with radiotherapy has been widely accepted as the first-line treatment for SCLC. CASE SUMMARY: Here, we present a 68-year-old male smoker who was diagnosed with SCLC of the right lung. After several cycles of concurrent chemoradiotherapy, the tumor progressed with broad metastasis to liver and bone. Histopathological examination showed an obvious transformation to adenocarcinoma, probably a partial recurrence mediated by the chemotherapy-based regimen. A mixed tumor as the primary lesion and transformation from SCLC or/and tumor stem cells may have accounted for the pathology conversion. We adjusted the treatment schedule in accord with the change in phenotype. CONCLUSION: Although diffuse skeletal and hepatic metastases were seen on a recent computed tomography scan, the patient is alive, with intervals of progression and shrinkage of his cancer.

16.
Transl Cancer Res ; 10(3): 1583-1593, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35116483

RESUMO

The diagnosis of lung cancer has long been a problem facing clinicians worldwide, and the emergence of electromagnetic navigation bronchoscopy (ENB) has played a critical role in the early diagnosis of lung cancer. Compared with other types of biopsy techniques (e.g., transthoracic needle biopsy, bronchoscopy, thoracoscopic biopsy, and thoracotomy), ENB guarantees high diagnostic accuracy and safety. In recent years, with the continuous development of ENB technology, the scope of its epitaxy has also expanded. This technology is no longer a simple auxiliary diagnosis test but an innovative technology that simultaneously assists in surgical treatment, opening new avenues of research for the treatment of early-stage lung cancer. However, ENB, as a human-mediated operating system, has some limitations and uncertainties in its actual clinical application and promotion, which need to be addressed as we continue to develop ENB technology. In response to the bottleneck in developing ENB technology in current clinical diagnosis and treatment, relevant scientific research and development personnel and clinicians have also performed continuing exploration and improvement of methods. However, to completely overcome the limitations of ENB, more technological innovations are needed. In this review, we describe the current major clinical application directions, application advantages, and limitations of ENB.

17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 122-130, 2021 Feb.
Artigo em Zh | MEDLINE | ID: mdl-33554808

RESUMO

OBJECTIVE: To investigate the effect of neutrophil/lymphocyte ratio (NLR) and monocyte/lymphocyte ratio (MLR) in the valuation prognosis of patients with multiple myeloma (MM). METHODS: The clinical data of 82 patients with initially diagnosed MM admitted to Gansu Provincial People's Hospital was analyzed retrospectively. NLR and MLR were calculated based on blood routine results respectively. The optimal cut-off point of NLR and MLR was determined according to the ROC curve, and the patients were divided into the high NLR/MLR group and the low NLR/MLR group. The general data, biochemical indicators and prognosis of the patients in each groups were compared respectively. The prognostic significance of the high NLR/MLR group and the low NLR/MLR group in patients between different treatment regimens and different clinical characteristics were analyzed. Risk stratification was designed based on NLR and high MLR as two risk factors, and the effect of risk factors, on the prognosis of MM patients were compared. RESULTS: ROC curve analysis determined that the optimal cut-off point of NLR was 3.1 (sensitivity 75%, specificity 70.7%) and the optimal cut-off point of MLR was 0.34 (sensitivity 83.3%, specificity 53.4%). The lactate dehydrogenase (LDH) and mean platelet volume (MPV) were correlated to NLR and MLR (P<0.05). There were no significant difference in age, sex, serum calcium (Ca), ß 2-microglobulin (ß 2-MG), albumin (Alb), hemoglobin (Hb), platelet (PLT), serum creatinine (Cr), bone marrow plasma cell ratio and ISS stage between the two groups (P>0.05). The OS rate of patients with higher NLR and MLR was lower than those with low NLR and MLR and showed poor prognosis; Further analysis showed that there were statistically significant differences in OS time among patients with different MLR and NLR in the new drug treatment group and the traditional chemotherapy group, as well as patients in different age stratification groups, different ß 2-MG stratification groups and different serum creatinine stratification groups. Patients with 2 risk factors showed a poorer prognosis than those with 0-1 risk factor. CONCLUSION: Elevated NLR and MLR are associated with poor prognosis in MM patients and may serve as the cost-effective and readily available prognostic biomarkers.


Assuntos
Mieloma Múltiplo , Neutrófilos , Plaquetas , Humanos , Linfócitos , Monócitos , Prognóstico , Estudos Retrospectivos
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 152-157, 2021 Feb.
Artigo em Zh | MEDLINE | ID: mdl-33554812

RESUMO

OBJECTIVE: To analyze the risk factors, distribution of pathogenic strains and tolerance of pulmonary infection in patients with multiple myeloma(MM) during bortezomib chemotherapy. METHODS: The clinical data of 85 patients with multiple myeloma treated by bortezomib in our hospital from January 2015 to January 2019 was analyzed. The patients were divided into infection group and control group according to whether they were infected. The tolerance, pathogen distribution, and related risk factors were retrospectively analyzed. RESULTS: Pulmonary infection rate was 55.29% in 85 MM patients. The proportions of the patients with anemia, neutropenia, and ECOG score ≥2 points in the infection group were significantly higher than those in the control group (P<0.05). In this study, 30 strains of pathogenic bacteria were detected, with gram-negative bacteria accounting for 60%, gram-positive bacteria for 33.33%, fungi for 3.3% and tuberculosis bacteria for 3.3%. Pseudomonas aeruginosa, klebsiella pneumoniae, streptococcus pneumoniae, staphylococcus aureus accounted showed the highest proportion. Most of MM patients with pulmonary infection showed a heterprognosis after two weeks antibiotic treatment, while 3 patients died. About 30 percent of early deaths were due to pulmonary infections. CONCLUSION: Anemia, neutropenia, ECOG score ≥2 points are the major clinical characteristics of the multiple myeloma patients with pulmonary infections. Pulmonary infection is an important cause of early death in patients with multiple myeloma. Pathogenic bacteria are mainly composed of gram-negative bacteria. Beta-lacta/ beta-lactamase inhibitor combinations or Carbapenems are effective empiric treatment for controlling the progression of pulmonary infection.


Assuntos
Mieloma Múltiplo , Bortezomib , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos
19.
Ann Surg Oncol ; 17(1): 312-22, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19777185

RESUMO

BACKGROUND: Approximately one-third of prostate cancer (PCa) patients show biochemical failure after radical prostatectomy (RP) and are prone to develop metastasis with significant mortality. Although aberrant Wnt/beta-catenin (CTNNB1) signaling has been observed in numerous types of human cancers, including PCa, to our knowledge there is currently no information on the role of Wnt signaling gene polymorphisms in PCa. METHODS: We comprehensively studied the contribution of genetic variations in CTNNB1 and adenomatous polyposis coli (APC), one of the key genes encoding the CTNNB1 destruction complex, to PCa risk and prognosis after RP using a hospital-based case-control study. We selected and genotyped 13 tagged single-nucleotide polymorphisms (tSNP) to predict common variants across entire APC and CTNNB1 genes in 307 patients with clinically localized PCa who received RP and 371 unaffected controls. RESULTS: Four tSNPs (rs3846716, rs2431238, rs41115, and rs565453) and a specific haplotype (GTAAGA) in the APC tumor suppressor gene were associated with a 0.57- to 0.71-fold lower risk of localized PCa. The association of tSNPs with prostate-specific antigen (PSA) recurrence in PCa patients was then analyzed by Kaplan-Meier analysis and Cox regression model. Interestingly, we found that the APC rs3846716 GA/AA genotypes were also significantly associated with poorer PSA-free survival (log-rank test, P = 0.037) compared with the GG genotype. CONCLUSIONS: This is the first report documenting the potential prognostic role of the APC rs3846716 GA/AA genotype on PSA recurrence after RP.


Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Recidiva Local de Neoplasia/genética , Polimorfismo de Nucleotídeo Único/genética , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , beta Catenina/genética , Idoso , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prognóstico , Prostatectomia , Neoplasias da Próstata/cirurgia , Taxa de Sobrevida , Resultado do Tratamento
20.
Ann Surg Oncol ; 17(6): 1675-81, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20204532

RESUMO

BACKGROUND: Bone metastases are the most critical complication of prostate cancer (PCa), resulting in severe morbidity and mortality. Tumor necrosis factor receptor superfamily member 11b (TNFRSF11B) is a critical regulator between PCa cells and the bone environment. Recently, TNFRSF11B rs10505346 has been implicated in PCa risk in the Cancer Genetic Markers of Susceptibility genomewide association study. However, the association between this variant and biochemical failure in PCa patients receiving radical prostatectomy (RP) has not been determined. METHODS: Associations of TNFRSF11B rs10505346 with age at diagnosis, preoperative prostate-specific antigen (PSA) level, Gleason score, pathologic stage, surgical margin, and PSA recurrence were evaluated in a cohort of 314 localized PCa patients receiving RP. The prognostic significance on PSA recurrence was assessed by Kaplan-Meier analysis and Cox regression model. RESULTS: The mean level of preoperative PSA and the relative risks of PSA recurrence after RP were lower in individuals with T allele than in those with the G allele at TNFRSF11B rs10505346 (P = 0.019 and 0.014, respectively). The T allele of rs10505346 remained a protective factor against PSA recurrence (P = 0.022) in multivariate Cox regression model after considering all clinicopathological risk factors except PSA level. CONCLUSIONS: Our data suggest that TNFRSF11B rs10505346 is associated with PSA level and might be a prognostic factor for the recurrence of PSA in PCa patients receiving RP.


Assuntos
Biomarcadores Tumorais/genética , Osteoprotegerina/genética , Polimorfismo Genético , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Idoso , Alelos , Estudos de Coortes , Progressão da Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias da Próstata/genética
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