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1.
J Am Chem Soc ; 145(47): 25842-25849, 2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-37950853

RESUMO

New biocompatible methods for post-translational protein modification are challenging to develop but crucial to create improved chemical probes and optimize next-generation biologic therapies such as antibody-drug conjugates (ADCs). Herein, we describe the bottom-up construction of an aqueous nickel-catalyzed cross-coupling for the chemospecific arylation of cysteine residues on peptides and proteins and its use for the preparation of ADCs. A variety of arene linkages are exemplified, enabling the incorporation of small molecules, probes, and cytotoxic payloads. The utility of this new bioconjugation platform in a drug discovery setting is highlighted by the construction of novel ADCs with target-mediated in vitro cytotoxic activity.


Assuntos
Antineoplásicos , Imunoconjugados , Níquel , Antineoplásicos/química , Proteínas/química , Peptídeos/química , Imunoconjugados/química , Catálise
2.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(4): 676-683, 2023 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-37534651

RESUMO

OBJECTIVE: To evaluate the effect of equal temperature bladder irrigation on bladder spasm, postoperative bleeding, vital signs and discomfort of chills in patients of transurethral resection of prostate using meta-analysis. METHODS: Several electronic databases included Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, VIP, China Biology Medicine (CBM) were searched systematically for published randomized controlled trial about equal temperature bladder irrigation in patients with transurethral resection of prostate before November 20, 2019. Two reviewers selected independently the literature in the light of the inclusion and exclusion criteria, assessed the risk of bias by quality assessment and extracted data which were consisted of clinical efficacy indexes, such as incidence of bladder spasm, severity of bladder spasm, incidence of tube plugging, amount of bladder flushing fluid, time of bladder flushing, heart rate, systolic pressure, diastolic pressure, and incidence of chills. Data were pooled using fixed-effects model or random-effects model, and the summary effect measure was calculated by risk ratio (RR) or mean difference (MD) and 95% confidence interval (95%CI). Meta-analysis was performed by Review Manager 5.3 Software. RESULTS: In the study, 13 randomized controlled trails met the requirement with a total of 2 033 patients of transurethral resection of prostate were included, of whom 1 015 were carried out with equal temperature bladder irrigation and 1 018 with room temperature bladder irrigation. The results of meta-analysis showed that incidence of bladder spasm [RR=0.51, 95%CI (0.45, 0.57), P < 0.001], severity of bladder spasm [MD=-1.61, 95%CI (-2.00, -1.23), P < 0.001], incidence of urinary blockage [RR=0.29, 95%CI (0.19, 0.44), P < 0.001], dosage of bladder irrigation [MD=-6.75, 95%CI (-7.33, -6.17), P < 0.001], time of bladder rinse [MD=-7.60, 95%CI (-11.91, -3.29), P < 0.001], heart rate [MD=-13.68, 95%CI (-15.19, -12.17), P < 0.001], systolic pressure [MD=-29.26, 95%CI (-31.92, -26.59), P < 0.001], diastolic pressure [MD=-29.36, 95%CI (-31.75, -26.98), P < 0.001], incidence of chills and discomfort [MD=0.37, 95%CI (0.31, 0.44), P < 0.001] in equal temperature group of the patients with transurethral resection of prostate had significantly statistical difference compared with room temperature group. CONCLUSION: Based on current available evidence, equal temperature bladder irrigation reduced the incidence of bladder spasm and urinary blockage, relieved bladder spasm, reduced dosage and time of bladder irrigation, and hardly affected normal vital signs and increased the patient' s comfort.


Assuntos
Hiperplasia Prostática , Ressecção Transuretral da Próstata , Masculino , Humanos , Ressecção Transuretral da Próstata/efeitos adversos , Ressecção Transuretral da Próstata/métodos , Bexiga Urinária/cirurgia , Calafrios , Temperatura , Hiperplasia Prostática/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Clin Oncol (R Coll Radiol) ; 35(10): 630-639, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37507279

RESUMO

AIMS: Pneumonitis is a common and potentially deadly complication of combined chemoradiation and immune checkpoint inhibition (CRT-ICI) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). In this study we sought to identify the risk factors for pneumonitis with CRT-ICI therapy in LA-NSCLC cases and determine its impact on survival. MATERIALS AND METHODS: We conducted a retrospective chart review of 140 patients with LA-NSCLC who underwent curative-intent CRT-ICI with durvalumab between 2018 and 2021. Pneumonitis was diagnosed by a multidisciplinary team of clinical experts. We used multivariable cause-specific hazard models to identify risk factors associated with grade ≥2 pneumonitis. We constructed multivariable Cox proportional hazard models to investigate the impact of pneumonitis on all-cause mortality. RESULTS: The median age of the cohort was 67 years; most patients were current or former smokers (86%). The cumulative incidence of grade ≥2 pneumonitis was 23%. Among survivors, 25/28 patients had persistent parenchymal scarring. In multivariable analyses, the mean lung dose (hazard ratio 1.14 per Gy, 95% confidence interval 1.03-1.25) and interstitial lung disease (hazard ratio 3.8, 95% confidence interval 1.3-11.0) increased the risk for pneumonitis. In adjusted models, grade ≥2 pneumonitis (hazard ratio 2.5, 95% confidence interval 1.0-6.2, P = 0.049) and high-grade (≥3) pneumonitis (hazard ratio 8.3, 95% confidence interval 3.0-23.0, P < 0.001) were associated with higher all-cause mortality. CONCLUSIONS: Risk factors for pneumonitis in LA-NSCLC patients undergoing CRT-ICI include the mean radiation dose to the lung and pre-treatment interstitial lung disease. Although most cases are not fatal, pneumonitis in this setting is associated with markedly increased mortality.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonia , Pneumonite por Radiação , Humanos , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Quimiorradioterapia/efeitos adversos , Pneumonia/etiologia , Pneumonia/complicações , Pneumonite por Radiação/epidemiologia , Pneumonite por Radiação/etiologia , Pneumonite por Radiação/tratamento farmacológico
4.
Zhonghua Zhong Liu Za Zhi ; 45(5): 402-409, 2023 May 23.
Artigo em Chinês | MEDLINE | ID: mdl-37188625

RESUMO

Objective: To study the diagnostic value of different detection markers in histological categories of endocervical adenocarcinoma (ECA), and their assessment of patient prognosis. Methods: A retrospective study of 54 patients with ECA in the Cancer Hospital, Chinese Academy of Medical Sciences from 2005-2010 were performed. The cases of ECA were classified into two categories, namely human papillomavirus-associated adenocarcinoma (HPVA) and non-human papillomavirus-associated adenocarcinoma (NHPVA), based on the 2018 international endocervical adenocarcinoma criteria and classification (IECC). To detect HR-HPV DNA and HR-HPV E6/E7 mRNA in all patients, we used whole tissue section PCR (WTS-PCR) and HPV E6/E7 mRNA in situ hybridization (ISH) techniques, respectively. Additionally, we performed Laser microdissection PCR (LCM-PCR) on 15 randomly selected HR-HPV DNA-positive cases to confirm the accuracy of the above two assays in identifying ECA lesions. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of markers to identify HPVA and NHPVA. Univariate and multifactorial Cox proportional risk model regression analyses were performed for factors influencing ECA patients' prognoses. Results: Of the 54 patients with ECA, 30 were HPVA and 24 were NHPVA. A total of 96.7% (29/30) of HPVA patients were positive for HR-HPV DNA and 63.3% (19/30) for HR-HPV E6/E7 mRNA, and 33.3% (8/24) of NHPVA patients were positive for HR-HPV DNA and HR-HPV E6/E7 mRNA was not detected (0/24), and the differences were statistically significant (P<0.001). LCM-PCR showed that five patients were positive for HR-HPV DNA in the area of glandular epithelial lesions and others were negative, which was in good agreement with the E6/E7 mRNA ISH assay (Kappa=0.842, P=0.001). Analysis of the ROC results showed that the AUC of HR-HPV DNA, HR-HPV E6/E7 mRNA, and p16 to identify HPVA and NHPVA were 0.817, 0.817, and 0.692, respectively, with sensitivities of 96.7%, 63.3%, and 80.0% and specificities of 66.7%, 100.0%, and 58.3%, respectively. HR-HPV DNA identified HPVA and NHPVA with higher AUC than p16 (P=0.044). The difference in survival rates between HR-HPV DNA (WTS-PCR assay) positive and negative patients was not statistically significant (P=0.156), while the difference in survival rates between HR-HPV E6/E7 mRNA positive and negative patients, and p16 positive and negative patients were statistically significant (both P<0.05). Multifactorial Cox regression analysis showed that International Federation of Obstetrics and Gynecology (FIGO) staging (HR=19.875, 95% CI: 1.526-258.833) and parametrial involvement (HR=14.032, 95% CI: 1.281-153.761) were independent factors influencing the prognosis of patients with ECA. Conclusions: HR-HPV E6/E7 mRNA is more reflective of HPV infection in ECA tissue. The efficacy of HR-HPV E6/E7 mRNA and HR-HPV DNA (WTS-PCR assay) in identifying HPVA and NHPVA is similar, with higher sensitivity of HR-HPV DNA and higher specificity of HR-HPV E6/E7 mRNA. HR-HPV DNA is more effective than p16 in identifying HPVA and NHPVA. HPV E6/E7 mRNA and p16 positive ECA patients have better survival rates than negative.


Assuntos
Adenocarcinoma , Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Infecções por Papillomavirus/diagnóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia , Prognóstico , Proteínas Oncogênicas Virais/genética , Papillomavirus Humano , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patologia , RNA Mensageiro/genética , Papillomaviridae/genética , RNA Viral/análise , RNA Viral/genética
6.
Zhonghua Yi Xue Za Zhi ; 102(40): 3181-3185, 2022 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-36319171

RESUMO

Objective: To analyze the clinical features and risk factors of herpes zoster and the risk factors of postherpetic neuralgia (PHN). Methods: A total of 2 840 patients diagnosed with herpes zoster in Peking University People's Hospital from January 2021 to April 2022 were included. The patients with herpes zoster were aged (59±16), and of which 1 314 (46.3%) patients were male. The patients were divided into PHN group and non-PHN group according to whether the patients with herpes zoster developed PHN. And there were 442 (15.6%) patients developed PHN aged (68±12), and of which 189 (42.8%) were male. The information and medical history of PHN group and non-PHN group were collected. The information of the use of glucocorticoids, immunosuppressive agents, biological agents and targeted medicine within 2 months before herpes zoster occurred, history of surgery within 6 months before herpes zoster occurred, and the duration of PHN were collected. Logistic regression analysis was used to analyze the risk factors of PHN. Results: Out of 2 840 patients, 2 056 (72.4%) with herpes zoster aged 50 years and above. Intercostal nerves was mostly involved in patients with herpes zoster, with a total of 1 532(53.9%). Hypertension (465 cases, 16.4%) accounted for the highest number of patients with chronic diseases, followed by diabetes (337 cases, 11.9%) and coronary heart disease (283 cases, 10.0%). Rheumatoid arthritis (41 cases, 1.4%) accounted for the highest number of patients with connective tissue diseases, followed by Sjogren's syndrome (31 cases, 1.1%), systemic lupus erythematosus (28 cases, 1.0%). Logistic regression analysis showed that age≥50 years old (OR: 4.581; 95%CI: 3.131-6.705),lesion on the upper limb and shoulder (OR: 1.858; 95%CI: 1.129-3.059), hypertension (OR: 1.963; 95%CI: 1.513-2.546) and immunosuppressive treatments (OR: 2.170; 95%CI: 1.254-3.753) were independent risk factors for PHN (all P<0.05). Conclusions: Herpes zoster mostly occurs in people aged 50 and above, and mainly affected intercostal nerves. The most common complications are hypertension and rheumatoid arthritis. Age≥50, lesion on upper limbs and shoulders, hypertension, and immunosuppressive treatments may be independent risk factors of PHN.


Assuntos
Artrite Reumatoide , Herpes Zoster , Hipertensão , Neuralgia Pós-Herpética , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Neuralgia Pós-Herpética/complicações , Herpes Zoster/complicações , Herpesvirus Humano 3 , Fatores de Risco , Hipertensão/complicações , Artrite Reumatoide/complicações
7.
Zhonghua Yi Xue Za Zhi ; 102(36): 2861-2867, 2022 Sep 27.
Artigo em Chinês | MEDLINE | ID: mdl-36153871

RESUMO

Objective: To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on minimal residual disease (MRD) in patients with multiple myeloma (MM). Method: From August 2018 to August 2021, 92 patients newly diagnosed with MM who had received either the bortezomib combined with cyclophosphamide and dexamethasone (VCD) or the bortezomib, lenalidomide and dexamethasone (VRD) induction regimens followed by sequential ASCT were assessed for overall survival (OS) and the MRD negative rate. The differences in efficacy at 100 days after transplantation were assessed according to factors, including age, risk stratification, target organ damage, and pre-transplant regimen, etc. Results: Among the 92 patients, there were 45 males and 47 females, with a median age of 57.3 (35-67) years. Fifty-seven patients received the VCD regimen, and 35 received VRD as induction regimen. Forty-three patients received busulphan combined with cyclophosphamide and etoposide (BCV), and 49 patients received high-dose melphan (HDM) regimen as pre-transplantation treatment. After transplantation, the total complete remission (CR) rate of 92 patients increased from 23.9% (22/92) to 58.7% (54/92), and the MRD negative rate increased from 4.4% (4/92) to 33.7% (31/92), and the differences were statistically significant (all P<0.05). After transplantation, the MRD negative rates of patients with PR, VGPR and ≥CR before transplantation were 17.6% (6/34), 33.3% (12/36) and 59.1% (13/22), respectively (P=0.006). The CR rates of patients with or without plasmacytoma at initial diagnosis were 36.4% (4/11) and 65.4% (53/81), respectively (P=0.029), and the MRD negative rates were 18.2% (2/11) and 39.5% (32/81), respectively (P=0.037), and the differences were statistically significant. The MRD negative rates in high-risk patients and standard-risk group were 30.5% (12/28) and 42.9% (18/59), respectively (P=0.258). For patients who achieved efficacy above VGPR before transplantation, the MRD negative rates after transplantation in VCD-induced group and VRD group were 29% (9/31) and 59.3% (16/27), respectively (P=0.033), and in BCV group and HDM group were 24% (6/25) and 57.6% (19/33), respectively (P=0.016), the differences between the groups were both statistically significant. Conclusion: ASCT can overcome the adverse factors such as high-risk cytogenetic abnormalities, and significantly improve the CR rate and MRD negative rate of MM patients. However, the benefit for patients with plasmacytoma at initial diagnosis is not as good as that of patients without.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Plasmocitoma , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib , Bussulfano/uso terapêutico , Ciclofosfamida/uso terapêutico , Dexametasona/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Humanos , Lenalidomida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Neoplasia Residual , Plasmocitoma/tratamento farmacológico , Transplante de Células-Tronco , Transplante Autólogo , Resultado do Tratamento
8.
Artigo em Chinês | MEDLINE | ID: mdl-35866278

RESUMO

Objective: To summarize the clinical features, treatments and outcomes of patients with SMARCB1(INI-1)-deficient sinonasal carcinoma (SDSC). Methods: Fifteen patients who were diagnosed as SDSC in Beijing Tongren Hospital from October 2016 to June 2021 were retrieved, including nine males and six females, ranged from 25 to 78 years old. For TNM stage, one case was in stage T2, one case was in stage T3, 13 cases were in stage T4; 13 cases were in stage N0, two cases were in stage N2; 14 cases were in stage M0, one case was in stage M1. The most common paranasal sinus affected by tumor was the ethmoid sinus. Five patients were treated by radical surgical resection combined with postoperative adjuvant therapy, four patients treated by neoadjuvant therapy with surgical resection, three patients treated by surgical resection only, one patient treated by neoadjuvant therapy with concurrent chemoradiotherapy, one patient treated by preoperative radiotherapy with surgery, and one patient received palliative chemotherapy. Immunohistochemical analysis was performed in all cases. The Kaplan-Meier method was used to draw the survival curve, and the Log-rank test was used to compare the difference to 20 undifferentiated carcinoma patients with positive INI-1 expression in the same period. Results: Immunohistochemical analysis showed the complete absence of INI-1 expression in the tumor nuclei in all 15 cases. The follow-up information was available with a median follow-up time of 21 months (3-56 months). The 3-year overall survival rate, disease specific survival rate, disease-free survival rate and metastasis-free survival rate were 58.9%, 58.9%, 36.4% and 31.2%, respectively. Disease-free survival in SDSC patients was significantly lower compared with undifferentiated carcinoma patients with positive INI-1 expression (HR=2.87,95%CI:0.92~8.91,P=0.043). Cox regression analysis showed that patients with comprehensive treatment based on surgery had a better prognosis than others (HR=8.61,95%CI:1.38~53.73,P=0.021). Conclusion: SDSC is a highly aggressive malignant tumor with the characteristics of easy recurrence, early metastasis and poor prognosis. INI-1 immunohistochemical analysis is recommended in the pathologically poorly differentiated sinonasal carcinoma. Comprehensive treatment based on radical resection may be the first choice for SDSC patients.


Assuntos
Carcinoma , Neoplasias dos Seios Paranasais , Seios Paranasais , Adulto , Idoso , Carcinoma/diagnóstico , Carcinoma/patologia , Carcinoma/terapia , Seio Etmoidal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias dos Seios Paranasais/diagnóstico , Neoplasias dos Seios Paranasais/terapia , Prognóstico , Estudos Retrospectivos , Proteína SMARCB1
9.
Eur Rev Med Pharmacol Sci ; 26(10): 3522-3533, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35647833

RESUMO

OBJECTIVE: Glioblastoma (GBM) is the most common and aggressive primary malignant tumor of the central nervous system in adults with high recurrence and mortality rates. Although radiotherapy and temozolomide have become the standard therapeutic regimen for GBM as adjuvant chemoradiotherapy after surgical resection, clinical outcomes remain suboptimal. In recent years, targeted antiangiogenic therapy has attracted considerable attention, but its therapeutic efficacy and safety are still controversial. MATERIALS AND METHODS: Randomized controlled trials (RCTs) of chemoradiotherapy with or without bevacizumab for the treatment of glioblastoma were collected by searching on the Pubmed, Embase, Cochrane, Ovid, Scopus, Web of Science, and Google Scholar databases from the date of database establishment to February 2022. Meta-analysis was performed using RevMan 5.3 software after two investigators independently screened the literature, extracted data, and assessed the risk bias of included studies. RESULTS: A total of 7 RCTs were included. The meta-analysis showed that bevacizumab in combination with chemoradiotherapy was superior to chemoradiotherapy alone in terms of progression-free survival (PFS), with a statistically significant difference. Interestingly, bevacizumab in combination with chemoradiotherapy improved PFS more significantly in recurrent glioblastoma than in newly diagnosed glioblastoma. However, for overall survival (OS), the combination of bevacizumab with chemoradiotherapy was similar to chemoradiotherapy alone, which was not significantly different. With regard to safety, the incidence of most adverse events was higher in the combination of bevacizumab and chemoradiotherapy than in chemoradiotherapy alone, especially in terms of hematologic adverse events. CONCLUSIONS: Current evidence suggests that angiogenesis inhibitor-containing chemoradiotherapy regimens are preferentially recommended for patients with recurrent glioblastoma to prolong their progression-free survival, provided that safety is acceptable, but this does not confer a significant benefit on overall patient survival.


Assuntos
Glioblastoma , Adulto , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Temozolomida
11.
J Paediatr Child Health ; 58(5): 782-790, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34761458

RESUMO

AIM: Early-life environmental exposure, which has important implications in the pathogenesis of inflammatory bowel disease (IBD), is not well understood in Asian children. We examined environmental factors prior to the development of childhood IBD in a Southeast Asian population. METHODS: We conducted a case control study in IBD diagnosed before 18 years of age and controls matched by gender, age and ethnicity. A questionnaire recording medical, family, dietary and social histories, home environment, childhood diseases and immunisation status was used. RESULTS: In a multivariate analysis involving 70 children with IBD (Crohn's disease (CD) = 38; ulcerative colitis (UC) = 32) and 140 controls, childhood acute gastroenteritis (odds ratio (OR): IBD 6.9; CD 7.8; UC 5.8) and excessive antibiotic usage in early childhood (OR: IBD 5.3; CD 4.2; UC 4.8) were significantly associated with IBD, CD and UC. Having a fish or turtle aquarium (OR 6.0), major stressful life events (OR 5.6) and attending the same school concurrently with a sibling (OR 2.9) were significant risk factors for IBD. Duration of breastfeeding >6 months (OR: IBD 0.4; UC 0.2) and safe water consumption (OR: IBD 0.2; UC 0.2) reduced the odds of having IBD and UC, respectively. Being vaccinated for rotavirus reduced the odds of developing IBD (OR 0.1). CONCLUSIONS: Several risk and protective factors were identified in this environmental risk study in Southeast Asian children with IBD. This knowledge has important implications in understanding disease aetiology and future prevention strategies to reduce the development of IBD in Southeast Asian children.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Animais , Estudos de Casos e Controles , Pré-Escolar , Doença Crônica , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/etiologia , Fatores de Risco
13.
Zhonghua Nei Ke Za Zhi ; 60(4): 345-349, 2021 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-33765704

RESUMO

Objective: To explore the clinical characteristics of patients with pituitary thyrotropin-secreting adenoma and evaluate the effect of preoperative short-acting octreotide treatment on hyperthyroidism. Methods: A retrospective analysis was performed in 40 patients with pituitary thyrotropin adenoma diagnosed in Beijing Tiantan Hospital from January 2008 to January 2018. The general data, laboratory examinations and imaging findings were reviewed and analyzed. The clinical effect of preoperative octreotide on hyperthyroidism was evaluated. Results: The age of onset year of the 40 patients (male: female = 24∶16) was (30.5±5.1) years. Among them, 35 patients (87.5%) were with macroadenoma. The most common symptoms were thyroid hypermetabolism syndrome, followed by headache, dizziness, visual field damage and hypogonadism. The thyroid function of 30 patients (75%) recovered to normal within 3-5 days after the octreotide treatment. The total effective rate of the octreotide was 90.0%. The level of free thyroxine (FT4) before treatment in patients with more than 10 times of effective cumulative dose was significantly higher than that in patients with less than 10 doses. Conclusions: Thyroid hypermetabolism syndrome and pituitary occupying effect are the most common clinical manifestations of thyrotropin-secreting adenoma. Preoperative octreotide treatment can effectively control hyperthyroidism. The level of FT4 is a crucial factor affecting the efficacy of octreotide.


Assuntos
Adenoma , Neoplasias Hipofisárias , Adenoma/tratamento farmacológico , Feminino , Humanos , Masculino , Octreotida/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Estudos Retrospectivos , Tireotropina
14.
J Dent Res ; 100(8): 858-867, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33655785

RESUMO

Metastasis, a powerful prognostic indicator of oral squamous cell carcinoma (OSCC), is chiefly responsible for poor cancer outcomes. Despite an increasing number of studies examining the mechanisms underlying poor outcomes, the development of potent strategies is hindered by insufficient characterization of the crucial regulators. Long noncoding RNAs (lncRNAs) have recently been gaining interest as significant modulators of OSCC metastasis; however, the detailed mechanisms underlying lncRNA-mediated OSCC metastasis remain relatively uncharacterized. Here, we identified a novel alternative splice variant of oral cancer overexpressed 1 (ORAOV1), named as ORAOV1-B, which was subsequently validated as an lncRNA and correlated with OSCC lymph node metastasis; significantly increased invasion and migration were observed in ORAOV1-B-overexpressing OSCC cells. RNA pulldown and mass spectrometry identified Hsp90 as a direct target of ORAOV1-B, and cDNA microarrays suggested TNFα as a potential downstream target of ORAOV1-B. ORAOV1-B was shown to directly bind to and stabilize Hsp90, which maintains the function of client proteins, receptor-interaction protein, and IκB kinase beta, thus activating the NF-κB pathway and inducing TNFα. Additionally, TNFα reciprocally enhanced p-NF-κB-p65 and the downstream epithelial-mesenchymal transition. ORAOV1-B effects were reversed by a TNFα inhibitor, demonstrating that TNFα is essential for ORAOV1-B-regulated metastatic ability. Consistent epithelial-mesenchymal transition in the ORAOV1-B group was demonstrated via an orthotopic model. In the metastatic model, ORAOV1-B significantly contributed to OSCC-related lung metastasis. In summary, the novel splice variant ORAOV1-B is an lncRNA, which significantly potentiates OSCC invasion and metastasis by binding to Hsp90 and activating the NF-κB-TNFα loop. These findings demonstrate the versatile role of ORAOV1 family members and the significance of genes located within 11q13 in promoting OSCC. ORAOV1-B might serve as an attractive OSCC metastasis intervention target.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Proteínas de Neoplasias/genética , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Bucais/genética , NF-kappa B/metabolismo , Metástase Neoplásica , Fator de Necrose Tumoral alfa
16.
Clin Transl Oncol ; 23(2): 296-310, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32548796

RESUMO

BACKGROUND: Solitary pulmonary nodules (SPNs) frequently bother oncologists. The differentiation of malignant from benign nodules with non-invasive approach remains a tough challenge. This study was designed to assess the diagnostic accuracy of dynamic computed tomography (CT), dynamic magnetic resonance imaging (MRI), fluorine 18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET), and technetium 99 m (99mTc) depreotide single photon emission computed tomography (SPECT) for SPNs. METHODS: Electronic databases of MEDLINE, PubMed, EMBASE, and Cochrane Library were searched to identify relevant trials. The primary evaluation index of diagnostic accuracy was areas under the summary receiver-operating characteristic (SROC) curve. The results were analyzed utilizing Stata 12.0 statistical software. RESULTS: Seventy-three trials incorporating 7956 individuals were recruited. Sensitivities, specificities, positive likelihood ratios, negative likelihood ratios, diagnostic score, diagnostic odds ratios, and areas under the SROC curve with 95% confidence intervals were, respectively, 0.92 (0.89-0.95), 0.64 (0.54-0.74), 2.60 (1.98-3.42), 0.12 (0.08-0.17), 3.10 (2.62-3.59), 22.24 (13.67-36.17), and 0.91 (0.88-0.93) for CT; 0.92 (0.86-0.95), 0.85 (0.77-0.90), 6.01 (3.90-9.24), 0.10 (0.06-0.17), 4.12 (3.41-4.82), 61.39 (30.41-123.93), and 0.94 (0.92-0.96) for MRI; 0.90 (0.86-0.93), 0.73 (0.65-0.79), 3.28 (2.56-4.20), 0.14 (0.10-0.19), 3.16 (2.69-3.64), 23.68 (14.74-38.05), and 0.90 (0.87-0.92) for 18F-FDG PET; and 0.93 (0.88-0.96), 0.70 (0.56-0.81), 3.12 (2.03-4.81), 0.10 (0.06-0.17), 3.43 (2.63-4.22), 30.74 (13.84-68.27), and 0.93 (0.91-0.95) for 99mTc-depreotide SPECT. CONCLUSION: The dynamic MRI, dynamic CT, 18F-FDG PET, and 99mTc-depreotide SPECT were favorable non-invasive approaches to distinguish malignant SPNs from benign. Moreover, from the viewpoint of cost-effectiveness and avoiding radiation, the dynamic MRI was recommendable for SPNs.


Assuntos
Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada por Raios X/métodos , Estudos de Coortes , Intervalos de Confiança , Diagnóstico Diferencial , Fluordesoxiglucose F18 , Humanos , Funções Verossimilhança , Compostos de Organotecnécio , Curva ROC , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Somatostatina/análogos & derivados
17.
Clin Radiol ; 76(3): 238.e9-238.e15, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33213835

RESUMO

AIM: To assess the feasibility and preliminary diagnostic performances of relaxation times derived from synthetic magnetic resonance imaging (syMRI) for differentiating nasopharyngeal carcinoma from nasopharyngeal benign lymphoid hyperplasia, and to assess the influence of tissue segmentation method on relaxation estimates. MATERIALS AND METHODS: Fifty participants with nasopharyngeal carcinoma (NPC) and 40 participants with benign hyperplasia (NPH) who underwent syMRI examination were enrolled prospectively. T1, T2, and proton density (PD) values were obtained from four different regions of interest (ROIs), namely, partial-section, single-section, three-sections, and whole-lesion. The metrics between NPC and NPH or among different ROIs were compared using Student's t-test or one-way ANOVA. The area under curve (AUC) was calculated to assess the performance of metrics obtained from different ROIs to differentiate NPC and NPH. RESULTS: The T1, T2, and PD values for NPH were significantly higher than those for NPC, regardless of the type of ROI used, except for the PD value obtained from the whole-lesion ROI. The T2 values obtained from the single-section ROI showed the highest diagnostic accuracy in distinguishing NPC from NPH, with an AUC of 0.894, sensitivity of 0.900, and specificity of 0.800. Additionally, the T1, T2, and PD values for nasopharyngeal lesions showed no statistical difference among different kinds of ROI, except for the difference in T1 value between partial-section and other methods. CONCLUSION: Quantitative analysis of syMRI has the potential to distinguish NPC from NPH. Moreover, different types of ROI showed limited influence on the relaxation time estimation for nasopharyngeal lesions.


Assuntos
Imageamento por Ressonância Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Adulto , Diagnóstico Diferencial , Estudos de Viabilidade , Feminino , Humanos , Hiperplasia , Masculino , Pessoa de Meia-Idade , Nasofaringe/diagnóstico por imagem , Nasofaringe/patologia , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto Jovem
18.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 38(11): 843-845, 2020 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-33287479

RESUMO

Objective: To explore the effect of occupational nickel exposure on blood glucose related indicators of workers. Methods: In March 2019, five electroplating enterprises and one plastic hardware enterprise were selected by cluster sampling method. 159 nickel plating workers were selected as the contact group, and 66 administrative personnel of the same enterprise were selected as the control group. The serum nickel concentration, fasting blood glucose (FPG) , fasting insulin (FIns) and glycosylated hemoglobin (HbA1c) were measured in the contact group and the control group. The differences of blood glucose related indexes between the two groups were compared, and the risk factors of abnormal blood glucose indexes were analyzed. Results: Compared with the control group, the blood nickel concentration and detection rate of nickel in the contact group were higher, the levels of FIns were lower, and the proportion of HbA1c was higher in the contact group (P<0.05) . Stratified analysis showed that compared with the control group, the blood glucose index of men in the contact group changed significantly (P<0.05) ; logistic regression analysis showed that male was an independent influencing factor for decreased FIns (OR=8.264, P<0.05) . Conclusion: Long term exposure to nickel can affect the blood glucose related indexes such as fins and HbA1c.


Assuntos
Níquel , Exposição Ocupacional , Glicemia , Galvanoplastia , Humanos , Masculino , Exposição Ocupacional/análise , Fatores de Risco
19.
Zhonghua Bing Li Xue Za Zhi ; 49(12): 1249-1254, 2020 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-33287508

RESUMO

Objective: To investigate the clinicopathological characteristics and molecular genetics of atypical renal cysts. Methods: Six cases of atypical renal cysts were collected from Zhejiang Provincial People's Hospital, Hangzhou, China, between February 2014 and February 2019. The clinicopathological characteristics and disease progression were analyzed. The 3p deletion and trisomy of chromosomes 7 and 17 were detected using fluorescence in situ hybridization (FISH). Results: All of the 6 patients were male, aged 43-63 years (median: 52 years). Preoperative Bosniak classification showed 4 cases of grade Ⅱ, 1 case of grade Ⅰ and 1 of grade Ⅲ. Histologically, atypical renal cysts appeared as unilocular or multilocular cysts, lined by multilayered flattened or cuboidal-shaped clear or eosinophilic cells. They often showed short papillary projections, and lacked solid or nodular growth of the lesional cells within the wall or septa of the cysts. Histologically, these cysts could be classified into three categories: acquired cystic disease-associated renal cell carcinoma (ACKD-RCC)-like (3 cases), clear cell type (2 cases), and eosinophilic papillary type (1 case). Two cases of ACKD-RCC-like atypical renal cysts were accompanied by clear cell renal cell carcinomas. On immunohistochemical staining, ACKD-RCC-like atypical renal cysts were focally CK7+/AMACR+/CD57+, the clear-cell type atypical renal cysts were CK7+/CAⅨ+, and eosinophilic papillary type atypical renal cysts were CK7+/AMACR+. FISH analyses showed that one case of ACKD-RCC-like atypical renal cysts had trisomy 17 and one case of clear cell type had 3p deletion, while no signal abnormality was detected in the other cases. The six patients were followed up for 13 to 70 months (median: 27 months), and no evidence of renal cell carcinoma was noted. Conclusion: Atypical renal cysts are a group of lesions that are heterogeneous in clinical, histological and immunophenotypical and molecular genetic features. FISH analyses suggest that a subset of the cases may be precursors of currently known renal cell carcinomas. Extensively sampling and careful observation of the histological characteristics of the cyst wall are important for distinguishing atypical renal cysts from extensively cystic renal cell carcinomas.


Assuntos
Cistos , Doenças Renais Císticas , Neoplasias Renais , Adulto , China , Humanos , Hibridização in Situ Fluorescente , Doenças Renais Císticas/genética , Neoplasias Renais/genética , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade
20.
Br J Surg ; 107(13): 1713-1718, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33090456
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