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1.
Zhonghua Wei Chang Wai Ke Za Zhi ; 27(3): 283-286, 2024 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-38532592

RESUMO

Objectives: To investigate the application value of laparoscopic double stapler firings and double stapling technique combined with rectal eversion and total extra-abdominal resection (LDER) in the anal preservation treatment of low rectal cancer. Methods: Inclusion criteria: (1) age was 18-70; (2) the distance of the lower tumor edge from the anal verge was 4-5 cm; (3) primary tumor with a diameter ≤3 cm; (4) preoperative staging of T1~2N1~2M0; (5) "difficult pelvis", defined as ischial tuberosity diameter<10 cm or body mass index>25 kg/m2; (6) patients with strong intention for sphincter preservation; (7) no preoperative treatment (e.g., chemotherapy, radiotherapy, molecular targeted therapy, or immunotherapy); (8) no lateral lymph node enlargement; (9) no previous anorectal surgery; (10) patients with good basic condition who could tolerate surgery. Exclusion criteria: (1) previously suffered from malignant tumors of the digestive tract or currently suffering from malignant tumors out of the digestive tract; (2) patients with preoperative anal dysfunction (Wexner score ≥ 10), or fecal incontinence. The specific surgical steps are as follows: the distal end of the rectum was dissected to the level of the interspace between internal and external sphincters of anal canal. Five centimeters proximal to the tumor, the mesorectum was ligated, and a liner stapler was used to transect the rectum. The distal rectum with the tumor were then everted and extracted through the anus. The rectum was transected 0.5-1.0 cm distal to the tumor with a linear stapler. Full thickness suture was used to reinforce the stump of the rectum, which was then brought back into the pelvic cavity. Finally, an end-to-end anastomosis between the colon and the rectum was performed. A retrospective descriptive study was performed of the clinical and pathological data of 12 patients with T1-T2 stage low rectal cancer treated with LDER at Henan Provincial People's Hospital from January 2020 to December 2022. Results: All 12 patients successfully completed LDER with sphincter preservation, without conversion to open surgery or changes in surgical approach. The median surgical time was 272 (155-320) minutes, with a median bleeding volume of 100 (50-200) mL. No protective stoma was performed, and all patients received R0 resection. The average hospital stay was 9 (7-15) days. There were no postoperative anastomotic leakage or perioperative deaths. All 12 patients received postoperative follow-up, with a median follow-up of 12 months (6-36 months) and a Wexner score of 8 (5-14) at 6 months postoperatively. There was no tumor recurrence or metastasis during the follow-up period. Conclusions: LDER is safe and effective for the treatment of low rectal cancer.


Assuntos
Laparoscopia , Neoplasias Retais , Humanos , Reto/cirurgia , Estudos Retrospectivos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Retais/cirurgia , Laparoscopia/métodos , Anastomose Cirúrgica
2.
Zhonghua Yi Xue Za Zhi ; 104(15): 1211-1215, 2024 Apr 16.
Artigo em Chinês | MEDLINE | ID: mdl-38487819

RESUMO

Next-generation sequencing (NGS) has laid the foundation for precision oncology care. NGS technologynot only represents an innovation in the methodology but also brings about a revolution in the concept of detecting gene alterations for targeted therapy and immunotherapy of cancers. As basic biomedical research and drug development progress, the landscape of biomarkers associated with gene alterations continues to evolve. Thus, the standardization of NGS-based gene alterations detection should take into account the characteristics of NGS methods and the gene alteration biomarkers. To be specific, whether employed as in vitro diagnostic products or laboratory-developed tests, the detection range can be expanded in response to changes in the clinical evidence level of biomarkers during the process of assay development and clinical application. Such adjustment needs the analytical validation results for supplemented genes or mutant sites within a predefined detection system, which will maximally fulfill the evolving clinical demands in cancer diagnosis and treatment, simultaneously mitigate potential risks effectively. This article primarily discusses the standardization pathway for NGS testing of gene alterations in cancer by focusing on the characteristics of NGS methods, gene alteration biomarkers, and the current status of the standardization of NGS application.


Assuntos
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/terapia , Medicina de Precisão , Mutação , Imunoterapia , Padrões de Referência , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Biomarcadores
3.
Zhonghua Wei Chang Wai Ke Za Zhi ; 26(10): 940-946, 2023 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-37849264

RESUMO

Objective: To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury. Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded. Results: The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100-6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions: TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.


Assuntos
COVID-19 , Fístula , Obstrução Intestinal , Exenteração Pélvica , Lesões por Radiação , Humanos , Feminino , Exenteração Pélvica/efeitos adversos , Exenteração Pélvica/métodos , Qualidade de Vida , Estudos Retrospectivos , COVID-19/etiologia , Pelve , Reto , Lesões por Radiação/cirurgia , Lesões por Radiação/etiologia , Complicações Pós-Operatórias/etiologia , Obstrução Intestinal/etiologia , Fístula/etiologia
7.
Zhonghua Wai Ke Za Zhi ; 60(5): 436-440, 2022 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-35359084

RESUMO

Telemedicine, which integrates medicine, communication, engineering, information and other disciplines, is a hot emerging cross field in recent years. With the development of telecommunication technology and surgical robot, telesurgery is regarded as the "crown pearl" in telemedicine and has attracted more and more attention. As an extension of traditional surgery, telesurgery greatly extends the connotation and concept of surgery and embodies the great leap forward development of surgical technology. Despite the current limitations such as network delay, transparency of remote robot operation and team construction of surgeons, telesurgery has still formed a variety of innovative application scenarios and achieved rapid development in China in recent years. In view of the uneven distribution of medical resources in China and the epidemic of COVID-19 in the world, this paper puts forward the possible problems and solutions in the development of telesurgery, and looks forward to the feasibility of telesurgery technology in process of shifting the focus of medical and health care down to the community level, channeling resources accordingly.


Assuntos
COVID-19 , Procedimentos Cirúrgicos Robóticos , Robótica , Telemedicina , Atenção à Saúde , Humanos
8.
Zhonghua Fu Chan Ke Za Zhi ; 57(2): 117-124, 2022 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-35184472

RESUMO

Objective: To explore the expression of long non-coding RNA-myeloid differentiation factor 88 (lnc-MyD88) and its relationship with the prognosis of patients with epithelial ovarian cancer (EOC). Methods: A total of 70 EOC patients who underwent initial cytoreductive surgery and platinum-based drugs combined with paclitaxel for 6 to 8 courses were selected at Sichuan Cancer Hospital from January 2016 to January 2019. The fresh cancer tissue specimens were collected. In addition, 28 fresh normal ovarian tissues from patients who underwent surgery for benign gynecological diseases during the same period were collected as control group. Reverse transcription (RT) and real-time quantitative polymerase chain reaction (qPCR) were used to detect the expression of lnc-MyD88 and myeloid differentiation factor 88 (MyD88) mRNA in EOC tissues and normal ovarian tissues. The correlation between the expression of lnc-MyD88 and MyD88 mRNA in EOC was analyzed by Pearson's correlation coefficient. The relationship between lnc-MyD88 expression and clinicopathological characteristics of patients with EOC was analyzed. Kaplan-Meier method was used to calculate the survival rate of patients. The log-rank test was used for univariate survival analysis, and Cox proportional hazard model was used for multivariate survival analysis. Results: (1) RT-qPCR showed that the relative expression level of lnc-MyD88 and MyD88 mRNA in EOC were 0.009 (0.000-0.049) and 0.001 (0.000-0.006), respectively, which were significantly higher than those of normal ovarian tissues (all P<0.01); Pearson's correlation coefficient showed that the expression of lnc-MyD88 and MyD88 mRNA in EOC was positively correlated (r2=0.610, P<0.01). (2) The high expression rate of lnc-MyD88 in EOC patients with lymph node metastasis, distant metastasis and chemotherapy resistance (71%, 64% and 70%, respectively) were significantly higher than the patients in control group (41%, 40% and 35%, respectively; all P<0.05). There were no statistically significant in the high expression rate of lnc-MyD88 in EOC patients with different ages, pathological types, pathological grades, surgical pathological stages, postoperative residual lesion size, and ascites cancer cells (all P>0.05). (3) Univariate analysis showed that surgical pathological staging, lymph node metastasis, distant metastasis, postoperative residual tumor size, and high expression of lnc-MyD88 and MyD88 mRNA significantly affected the progression-free survival (PFS) and overall survival (OS) of EOC patients (all P<0.05), ascites cancer cells were the risk factors that significantly affected PFS in EOC patients (P=0.040); multivariate analysis showed that surgical pathological staging and high expression of lnc-MyD88 and MyD88 mRNA were independent factors affecting PFS and OS in EOC patients (all P<0.05), the size of residual lesions after surgery was an independent factor affecting PFS in EOC patients (P=0.001). Conclusions: The level of lnc-MyD88 expression in ovarian cancer tissues was significantly increased. Lnc-MyD88, as a molecular marker for the poor prognosis of EOC, is related to the expression of MyD88 in EOC, and may be involved in its expression regulation, thereby affecting the survival and prognosis of EOC patients.


Assuntos
Neoplasias Epiteliais e Glandulares , Neoplasias Ovarianas , RNA Longo não Codificante , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/uso terapêutico , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/patologia , Prognóstico , RNA Longo não Codificante/genética
11.
Zhonghua Nei Ke Za Zhi ; 61(2): 205-209, 2022 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-35090257

RESUMO

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disease. Gastrointestinal involvement is rarely seen in PNH. This study aims to analyze the clinical features in PNH patients complicated with ischemic bowel disease. Clinical date of 6 patients were collected at Peking Union Medical College Hospital from January 2010 to December 2020. The clinical manifestations, laboratory tests,imaging, endoscopic,and histopathological features and treatment were analyzed.Five in 6 patients were men, with a median age of 31 years old at onset. Most of disease course were recurrent episodes of chronic disease, with abdominal pain (5/6) and gastrointestinal bleeding (5/6). Laboratory examinations showed pancytopenia, reticulocytosis, elevated serum lactate dehydrogenase, high D-dimer and C-reactive protein levels in all patients. Multiple segments of small intestine were the most commonly involved and colon was also affected. Abdominal CT scan showed thickening and roughness or exudation of the intestinal wall (6/6), increased mesenteric density or "comb sign"(4/6), and cholestasis or gallbladder stones (5/6). Endoscopic manifestations included irregular shallow ulcers in the annular cavity (5/6), swelling mucosa with well-defined margins (6/6). Pathological biopsy revealed chronic inflammation of mucosa. The efficacy of steroids combined with anticoagulant therapy was better than that of steroids alone. Ischemic bowel disease in PNH patients is different from typical ischemic enteritis. Young patients, involvement of intestine with multiple segments are common characteristics. The anticoagulant is an essential agent for these patients.


Assuntos
Hemoglobinúria Paroxística , Adulto , Hemoglobinúria Paroxística/complicações , Hemoglobinúria Paroxística/tratamento farmacológico , Humanos , Intestinos , Isquemia , Masculino , Tomografia Computadorizada por Raios X
13.
Zhonghua Yi Xue Za Zhi ; 101(5): 350-354, 2021 Feb 02.
Artigo em Chinês | MEDLINE | ID: mdl-34645254

RESUMO

Objective: To evaluate the long-term efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) in the treatment of isolated dystonia, and explore the factors influencing the results. Methods: The clinical data of 23 consecutive patients with isolated dystonia treated with STN-DBS in the Department of Neurosurgery, Tangdu Hospital, Air Force Military Medical University from December 2004 to December 2014,were retrospectively analyzed. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to quantify the dystonia symptoms and signs. Multiple linear regression analysis was used to explore the influencing factors of the results. Results: The age of the 23 patients including 8 females and 15 males was 19(10, 27) years old. The follow-up time was 5-12 years, with an average of (8.1±1.8) years.Compared with the preoperative period, the BFMDRS movement score decreased by 30.1 [95% confidence interval (CI): 12.3-47.8)] points, 34.7 (95%CI: 17.0-52.4) points, 34.1 (95%CI: 16.4-51.8) points and 34.0 (95%CI: 16.3-51.7) points (all P<0.001) respectively at 1 year, 3 years, 5 years after surgery and the last follow-up, the average improvement rates were (56.0±20.2)%, (65.3±24.0)%, (64.4±25.1)% and (64.3±25.1)%;the disability score decreased by 6.9 (95%CI: 1.4-12.3)points, 8.7 (95%CI: 3.3-14.2)points, 9.0 (95%CI: 3.6-14.5)points, and 9.2 (95%CI: 3.7-14.7) points (all P<0.001), the average improvement rates were (42.9±17.1)%, (55.5±23.2)%, (57.8±24.8)% and (58.7±24.8)%. Patients with DYT1-positive dystonia had higher rates of improvement in movement and disability scores than patients with DYT1-negative, but there was no statistically significant difference. Multiple linear regression analysis showed that gender, age at onset, course of disease, preoperative movement or disability score had no linear relationship with long-term results (improvement rate of movement or disability score) (both P>0.05). Conclusions: STN-DBS is effective and long-lasting in the treatment of isolated dystonia, but no reliable predictor has been found.


Assuntos
Estimulação Encefálica Profunda , Distonia , Adulto , Distonia/terapia , Feminino , Globo Pálido , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
14.
Zhonghua Zhong Liu Za Zhi ; 43(8): 843-849, 2021 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-34407589

RESUMO

Objective: To evaluate the value of next generation sequencing (NGS) in the genetic testing of Lynch syndrome. Methods: Immunohistochemical method was used to detect the expressions of DNA mismatch repair (MMR) proteins, including MutL homolog 1 (MLH1), PMS1 homolog 2 (PMS2), MutS homolog 2 (MSH2) and MutS homolog 6 (MSH6) in colorectal cancer, gastric cancer and endometrial cancer tissues collected from Shandong Provincial Hospital between 2016 and 2018. The genomic DNA of 45 patients who were suspected with Lynch syndrome was extracted from non-cancerous tissue paraffin samples, which were postoperatively confirmed by microscope. The mutations of 12 genes including MLH1 and MSH2 were detected using NGS. The germline mutant sites and significance were analyzed by bioinformatics technology and further confirmed by using Sanger sequencing. Results: The immunohistochemical results showed that the 45 cases of suspected Lynch syndrome included 22 cases of MLH1 and PMS2 deficient expression, 16 cases of MLH2 and MSH6 deficient expression, and 7 cases of MMR proteins normal expression. The NGS result showed that 28 cases of adjacent sample from colon cancer patients included 4 cases of MLH1 pathogenic mutation, 1 case of suspected MLH1 mutation, 2 cases of MLH2 pathogenic mutation, 2 cases of suspected MLH2 mutation. No MMR gene mutation was found in adjacent samples of 6 cases of rectal cancer, 6 cases of gastric cancer and 7 cases of colorectal cancer with MMR normal expression. One case of MLH1 or MHL2 pathogenic mutation and one case of MLH1 suspected mutation was detected in adjacent samples of 5 cases of endometrial cancer. Moreover, NGS also detected many other genes mutations and unreported gene mutation sites. Pathogenic and suspected MLH1 and MSH2 mutations were verified by Sanger sequencing. Conclusions: High-throughput NGS is a quick, accurate and reliable technique to identify gene variants in suspected Lynch syndrome patients. It has a wide application prospect for gene testing of tumors associated with Lynch syndrome.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA/genética , Feminino , Testes Genéticos , Mutação em Linhagem Germinativa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Instabilidade de Microssatélites , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo
15.
Zhonghua Yi Xue Za Zhi ; 101(20): 1523-1528, 2021 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-34044521

RESUMO

Objective: To explore the effect of protein disulfide isomerase (PDI) in diabetic ischemic heart disease. Methods: We established an in vitro model of high glucose and hypoxia/reoxygenation in H9c2 rat myocardial cells. Cultured cells were divided into four groups: Control, high glucose (HG), hypoxia/reoxygenation (H/R) and HG+H/R. Changes in PDI expression mediated by PDI adenovirus(Ad-PDI) infection and siRNA(PDI-siRNA) transfection in myocardial cells were observed by inverted fluorescence microscopy. We also measured lactate dehydrogenase(LDH) activity and malondialdehyde(MDA) and high molecular weight(HMW)-APN concentrations. PDI, APN, cleaved caspase-3, and glucose regulated protein 78 (Grp78) protein expression were detected. Results: PDI expression was significantly decreased in the HG, H/R and HG+H/R groups compared to the Control group; however, LDH activity[(179.7±10.4) U/L、(218.4±18.4) U/L、(328.2±5.3) U/L vs (91.0±11.0) U/L], MDA concentration[(7.0±0.4) µmol/L、(10.0±1.0) µmol/L、(11.7±1.0) µmol/L vs (4.2±1.8) µmol/L], cleaved caspase-3, and Grp78 expression were increased. Interestingly, APN and HMW-APN expression were decreased [(2.01±0.21) µg/L、(1.64±0.27) µg/L、(1.20±0.14) µg/L vs (2.62±0.12) µg/L, all P<0.05]. Over expression of PDI attenuated high glucose and hypoxia/reoxygenation induced apoptosis and oxidative stress in H9c2 cardiomyocytes(all P<0.05), and simultaneously increased APN and HMW-APN expression [(2.86±0.03) µg/L vs (3.03±0.10) µg/L、(2.06±0.05) µg/L vs (2.31±0.06) µg/L、(1.83±0.07) µg/L vs (1.96±0.11) µg/L、(1.20±0.06) µg/L vs (1.39±0.09) µg/L]. PDI-siRNA transfection increased LDH activity, MDA concentration, and cleaved caspase-3 and Grp78 expression, and decreased APN and HMW-APN expression [(0.75±0.09) µg/L vs (0.59±0.09) µg/L、(0.62±0.04) µg/L vs (0.53±0.05) µg/L、(0.55±0.14) µg/L vs (0.51±0.12) µg/L、(0.48±0.12) µg/L vs (0.35±0.08) µg/L] in response to different treatments in cultured H9c2 cardiomyocytes (all P<0.05). Conclusion: PDI may regulate the expression of APN and HMW-APN, and play an important role in the function of diabetic ischemia-reperfusion cardiomyocytes.


Assuntos
Hiperglicemia , Miócitos Cardíacos , Animais , Apoptose , Hipóxia Celular , Hipóxia , Miócitos Cardíacos/metabolismo , Isomerases de Dissulfetos de Proteínas/metabolismo , Ratos
16.
Zhonghua Zhong Liu Za Zhi ; 43(5): 533-540, 2021 May 23.
Artigo em Chinês | MEDLINE | ID: mdl-34034472

RESUMO

Objective: To investigate the effect of circBANP on radiosensitivity of colorectal cancer cells and subcutaneous transplanted tumor in nude mice and its potential molecular mechanism. Methods: The carcinoma and adjacent normal mucosal tissues of 20 patients with colorectal cancer who were surgically resected in Henan People's Hospital from January 2018 to January 2019 were selected. The radio-resistant colorectal cancer cell LoVo/R was established. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of circBANP and miR-338-3p. The radiation sensitivity was determined by cell clone formation experiment. Cell vitality was detected by using methyl thiazolyl tetrazolium (MTT). The expressions of autophagy-related protein microtubule-associated protein light chain 3 (LC3) and p62 were detected by western blot. The fluorescence intensity of LC3 in cells was detected by immunofluorescence assay. The downstream microRNAs (miRNAs) of circBANP were predicted by Circular RNA Interactome website and further verified by dual luciferase reporter gene assay. The transplanted tumor model of LoVo/R cells in nude mice was established, and the effect of circBANP on the growth of transplanted tumor after radiation was observed. Results: The expression levels of circBANP and miR-338-3p in colorectal cancer tissues were 3.21+ 0.29 and 0.47+ 0.04, respectively, which were significantly higher than 1.00+ 0.07 and 1.00+ 0.05 in adjacent tissues (P<0.05). The circBANP expression level of LoVo/R cells was 3.21±0.34, higher than 1.00±0.07 of LoVo cells (P<0.05), and the expression level of miR-338-3p of LoVo/R cells was 0.33±0.04, lower than 1.00±0.08 of LoVo cells (P<0.05). After 4 Gy irradiation, compared with the control group, the viability of LoVo/R cells in the circBANP silencing group [(34±4)% vs (62±6)%, P<0.05], the cell survival fraction (0.07±0.02 vs 0.27±0.04, P<0.05) were decreased, and the radiation sensitization ratio was 1.843, the expression of LC3Ⅱ/Ⅰin LoVo/R cells increased while p62 expression decreased, the cell autophagy was observed. Autophagy inhibitor chloroquine reversed the increased expression of LC3Ⅱ/Ⅰ and inhibited expression of p62 in LoVo/R cells induced by radiation, and promoted the suppression of cell viability and survival induced by radiation, the radiotherapy sensitization ratio was 1.780. Compared with control group after 4 Gy irradiation, the relative fluorescence intensity of LC3 in circBANP silencing LoVo/R cells decreased (0.11±0.01 vs 1.00±0.12, P<0.05), the expression of LC3-Ⅱ/Ⅰdecreased (1.25±0.13 vs 3.84±0.39, P<0.05) while p62 expression increased (2.76±0.29 vs 1.00±0.08, P<0.05). As predicted by Circular RNA Interactome website and confirmed by double luciferase reporter gene assay, miR-338-3p was the target gene of circBANP. The relative fluorescence intensity of LC3 in circBANP silencing + anti-miR-338-3p + 4 Gy group increased (7.32±0.72 vs 1.00±0.09, P<0.05), the expression level of LC3-Ⅱ/Ⅰ increased (4.13±0.43 vs 2.31±0.23, P<0.05) while p62 expression decreased (0.34±0.03 and 1.00±0.11, P<0.05), the radiotherapy sensitization ratio was 0.596. Nude mice subcutaneously transplanted tumor experiment showed that the tumor volume and weight of circBANP silencing group on 13, 16, 19, 22, 25, 28, and 31 days were lower than those of control group (P<0.05), while the tumor volume and weight of circBANP silencing + anti-miR-338-3p group on days of 13, 16, 19, 22, 25, 28 and 31 after inoculated were higher than those of circBANP+ anti-miR-NC group (P<0.05). Conclusions: CircBANP can regulate the radiosensitivity of colorectal cancer cells by regulating the expression of miR-338-3p, and affect the growth of transplanted tumor in nude mice. CircBANP may be a potential target for enhancing radiosensitivity of colorectal cancer cells.


Assuntos
Neoplasias Colorretais , MicroRNAs , Animais , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/radioterapia , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , Tolerância a Radiação/genética
17.
Zhonghua Xue Ye Xue Za Zhi ; 42(4): 288-294, 2021 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-33979972

RESUMO

Objective: To investigate the safety and efficacy of venetoclax with low-dose cytarabine (LDAC) in Chinese patients with acute myeloid leukemia (AML) who are unable to tolerate intensive induction chemotherapy. Methods: Adults ≥ 18 years with newly diagnosed AML who were ineligible for intensive chemotherapy were enrolled in this international, randomized, double-blind, placebo-controlled trial. Globally, patients (n=211) were randomized 2∶1 to either venetoclax with LDAC or placebo with LDAC in 28-d cycles, with LDAC on days 1-10. The primary endpoint was OS; the secondary endpoints included response rates, event-free survival, and adverse events. Results: A total of 15 Chinese patients were enrolled (venetoclax arm, n=9; placebo arm, n=6) . The median age was 72 years (range, 61-86) . For the primary analysis, the venetoclax arm provided a 38% reduction in death risk compared with the placebo[hazard ratio (HR) , 0.62 (95%CI 0.12-3.07) ]. An unplanned analysis with an additional 6 months of follow-up demonstrated a median OS of 9.0 months for venetoclax compared with 4.1 months for placebo. The complete remission (CR) rates with CR with incomplete blood count recovery (CRi) were 3/9 (33%) and 0/6 (0%) , respectively. The most common non-hematologic adverse effects (venetoclax vs placebo) were hypokalemia[5/9 (56%) vs 4/6 (67%) ], vomiting[4/9 (44%) vs 3/6 (50%) ], constipation[2/9 (22%) vs 4/6 (67%) ], and hypoalbuminemia[1/9 (11%) vs 4/6 (67%) ]. Conclusion: Venetoclax with LDAC demonstrated meaningful efficacy and a manageable safety profile in Chinese patients consistent with the observations from the global VIALE-C population, making it an important treatment option for patients with newly diagnosed AML who are otherwise ineligible for intensive chemotherapy.


Assuntos
Citarabina , Leucemia Mieloide Aguda , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes , China , Citarabina/uso terapêutico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Sulfonamidas
18.
Zhonghua Zhong Liu Za Zhi ; 43(4): 449-456, 2021 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-33902207

RESUMO

Objective: To investigate the expression of circular ribonucleic acid ABCB10 (circABCB10) in colorectal cancer tissues and cells and its effects on cell biological behavior, radiosensitivity and growth of subcutaneous xenografts. Methods: The tumor tissue and adjacent tissue from colorectal cancer patients treated in Henan People's Hospital were collected from January 2018 to December 2018. Quantitative polymerase chain reaction (qPCR) was used to detect the expressions of circABCB10 and miR-217, cell viability was detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT), cell apoptosis rate was detected by flow cytometry, cell migration and invasion were detected by Transwell method, cell radiosensitivity was detected by colony formation assay. The downstream miRNAs of circABCB10 were predicted by Circular RNA Interactome and verified by the dual luciferase reporter gene experiment. The effect of circABCB10 on the growth of transplanted tumor was examined in nude mice. Results: The expression level of circABCB10 mRNA in colorectal cancer tissues was (3.97±2.12), higher than (1.13±0.64) in adjacent tissues (P<0.05). The expression level of circABCB10 mRNA in FHC cells was (1.00±0.09), lower than that (4.53±0.44) in SW480, (3.12±0.32) in HCT116 and (3.51±0.36) in HT29 cells, respectively (all P<0.05). The MTT results showed that the absorbance values of SW480 cells in si-circABCB10-1 group at 48 and 72 hours after transfection were (0.36±0.04) and (0.43±0.04), lower than (0.48±0.05) and (0.82±0.08) in circ-negative control (NC) group, respectively (all P<0.05). The number of migrating cells and invasive cells in si-circABCB10-1 group were (45±8) and (34±7), lower than (106±21) and (84±15) in circ-NC group, respectively (all P<0.01). The radiosensitization ratio was 1.632. The results of subcutaneous transplantation assay showed that the tumor volume and tumor weight of the si-circABCB10-1 group were significantly lower than circ-NC group after 8 days of inoculation ( all P<0.05). MiR-217 is a target gene of circABCB10. Inhibition of miR-217 reversed the inhibitory effect of circABCB10 silencing on cell proliferation, migration, invasion and subcutaneous xenograft growth in nude mice and the radiosensitization activity. Conclusion: Silence of circABCB10 can up-regulate the expression of miR-217 to inhibit the proliferation, migration, invasion and growth of subcutaneous xenografts and increase the radiosensitivity of SW480 cells, which reveals the underlying molecular mechanism of colorectal cancer progression and provides a new sensitizing target for clinical radiotherapy of colorectal cancer.


Assuntos
Neoplasias Colorretais , MicroRNAs , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , RNA Circular
19.
Zhonghua Yi Xue Za Zhi ; 101(13): 904-907, 2021 Apr 06.
Artigo em Chinês | MEDLINE | ID: mdl-33789372

RESUMO

There has consistently growing value of molecular detection to deliver clinical results for diagnosis, classification, prognosis, curative effect prediction and monitoring minimal residual disease of hematological neoplasms. Currently, some clinical laboratories are adopting hematological neoplasms-associated molecular detection in in our country. The increasing demands for clinical testing require that the particular attention need to be paid to the building of the team of professional staff. At present, it is vital to cultivate two kinds of specialized personnel: the technical personnel who are educated in clinical medicine and skilled in developing molecular tests; and the trained managers who are adept at quality control for molecular testing.


Assuntos
Neoplasias Hematológicas , Laboratórios , Humanos , Controle de Qualidade
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