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2.
Proc Natl Acad Sci U S A ; 121(6): e2304619121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38289962

RESUMO

Resistance to neoadjuvant chemotherapy leads to poor prognosis of locally advanced rectal cancer (LARC), representing an unmet clinical need that demands further exploration of therapeutic strategies to improve clinical outcomes. Here, we identified a noncanonical role of RB1 for modulating chromatin activity that contributes to oxaliplatin resistance in colorectal cancer (CRC). We demonstrate that oxaliplatin induces RB1 phosphorylation, which is associated with the resistance to neoadjuvant oxaliplatin-based chemotherapy in LARC. Inhibition of RB1 phosphorylation by CDK4/6 inhibitor results in vulnerability to oxaliplatin in both intrinsic and acquired chemoresistant CRC. Mechanistically, we show that RB1 modulates chromatin activity through the TEAD4/HDAC1 complex to epigenetically suppress the expression of DNA repair genes. Antagonizing RB1 phosphorylation through CDK4/6 inhibition enforces RB1/TEAD4/HDAC1 repressor activity, leading to DNA repair defects, thus sensitizing oxaliplatin treatment in LARC. Our study identifies a RB1 function in regulating chromatin activity through TEAD4/HDAC1. It also provides the combination of CDK4/6 inhibitor with oxaliplatin as a potential synthetic lethality strategy to mitigate oxaliplatin resistance in LARC, whereby phosphorylated RB1/TEAD4 can serve as potential biomarkers to guide the patient stratification.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Oxaliplatina/farmacologia , Terapia Neoadjuvante/métodos , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/genética , Quimiorradioterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cromatina , Resultado do Tratamento , Fatores de Transcrição de Domínio TEA , Ubiquitina-Proteína Ligases , Proteínas de Ligação a Retinoblastoma
3.
Cell Rep Med ; 4(10): 101231, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37852187

RESUMO

Neoadjuvant chemotherapy (NAC) for rectal cancer (RC) shows promising clinical response. The modulation of the tumor microenvironment (TME) by NAC and its association with therapeutic response remain unclear. Here, we use single-cell RNA sequencing and spatial transcriptome sequencing to examine the cell dynamics in 29 patients with RC, who are sampled pairwise before and after treatment. We construct a high-resolution cellular dynamic landscape remodeled by NAC and their associations with therapeutic response. NAC markedly reshapes the populations of cancer-associated fibroblasts (CAFs), which is strongly associated with therapeutic response. The remodeled CAF subsets regulate the TME through spatial recruitment and crosstalk to activate immunity and suppress tumor progression through multiple cytokines, including CXCL12, SLIT2, and DCN. In contrast, the epithelial-mesenchymal transition of malignant cells is upregulated by CAF_FAP through MIR4435-2HG induction, resulting in worse outcomes. Our study demonstrates that NAC inhibits tumor progression and modulates the TME by remodeling CAFs.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Retais , Humanos , Fibroblastos Associados a Câncer/patologia , Terapia Neoadjuvante , Transcriptoma/genética , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/genética , Neoplasias Retais/patologia , Proliferação de Células , Microambiente Tumoral/genética
4.
Front Immunol ; 14: 1260112, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37781374

RESUMO

Background: The clinical progression of individuals afflicted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exhibits significant heterogeneity, particularly affecting the elderly population to a greater extent. Consequently, the association between nutrition and microbiota has garnered considerable interest. Hence, the objective of this study was to gather clinical data pertaining to the influence of diverse nutritional support interventions on the prognosis of geriatric patients with COVID-19, while additionally examining the fecal microbiota of these individuals to assess the repercussions of microecological alterations on their prognostic outcomes. Results: A total of 71 elderly patients diagnosed with severe COVID-19 were included in this study. These patients were subsequently divided into two groups, namely the enteral nutrition (EN) group and the parenteral nutrition (PN) group, based on the type of nutritional support therapy they received after admission. The occurrence of complications was observed in 10.4% of patients in the EN group, whereas it was significantly higher at 69.6% in the PN group (P<0.001). Furthermore, the 60-day mortality rate was 2.1% (1/48) in the EN group, while it was notably higher at 30.4% (7/23) in the PN group (P=0.001). To identify the independent predictors of 60-day mortality, stepwise logistic regression analysis was employed. Among different bacterial groups, Enterococcus_faecium (18.19%) and Pseudomonas_aeruginosa (1.91%) had higher average relative abundance in the PN group (P<0.05). However, the relative abundance of Ruminococcus was higher in the EN group. Further Spearman correlation analysis showed that Enterococcus_faecium was positively correlated with poor clinical prognosis, while Ruminococcus was negatively correlated with poor clinical prognosis. Conclusions: This study shows that the changes in the composition of intestinal flora in elderly COVID-19 patients receiving different nutritional support strategies may be related to different clinical outcomes. The abundance of Enterococcus_faecium in elderly COVID-19 patients receiving PN is significantly increased and is closely related to poor clinical outcomes. It highlights the potential of microbiome-centric interventions to mitigate and manage COVID-19 in older adults with different nutritional support options.


Assuntos
COVID-19 , Microbioma Gastrointestinal , Humanos , Idoso , COVID-19/terapia , SARS-CoV-2 , Prognóstico , Nutrição Parenteral/métodos
6.
Heliyon ; 9(5): e16190, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37215811

RESUMO

Introduction: Spinocerebellar ataxia type 3 (SCA3) is a common autosomal dominant hereditary ataxia, which is caused by a cytosine-adenine-guanine (CAG) repeat expansion on the causative gene ATXN3, usually with lower extremity ataxia as the first symptom, and effective treatment is scarce. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that regulates the cerebellum and the neural network connected to it. Methods: Herein, we report familial cases of SCA3 in two nephews and their aunt, each of whom was treated with high-frequency (5 Hz) rTMS. The rTMS treatment lasted 2 weeks, once daily for 5 consecutive days a week, about 20 minutes each session. The Scale for the Assessment and Rating of Ataxia (SARA), the International Cooperative Ataxia Rating Scale (ICARS), and proton magnetic resonance spectroscopy (1H-MRS) examination were evaluated before and after rTMS treatment. Results: We found that the ICARS scores improved significantly (p = 0.04), and the NAA/Cr values were elevated in vermis and both cerebellar hemispheres after rTMS treatment. Conclusion: Our study suggested that high-frequency rTMS therapy can contribute to the improvement of cerebellar NAA/Cr value of SCA3 patients, and improve posture and gait as well as limb kinetic function in SCA3 patients.

7.
Front Microbiol ; 14: 1097892, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37082183

RESUMO

Introduction: The essence of enterotypes is to stratify the entire human gut microbiota, and dysregulation of gut microbiota is closely related to the development of colorectal adenoma. Enterotypes may therefore be a useful target for the prevention of colorectal adenoma. However, the relationship between gut microbiota and colorectal adenoma has not been fully elucidated. In this study, we aimed to analyze the differences in gut microbiome composition between adenoma and control populations. Methods: We recruited 31 patients with colorectal adenoma and 71 non-adenoma controls. Patient demographics, risk factors, fecal samples from each subject were collected and metagenomic sequencing was performed. LEfSe analysis was used to reveal differences in intestinal microbiome composition. Multiple logistic regression analysis was used to determine the association between enterotypes and colorectal adenoma. Results: The results showed that Prevotella enterotype (enterotype 4) is only present in adenoma group. Logistic regression analysis showed that Prevotella enterotype was an independent risk factor for colorectal adenoma. Discussion: The Prevotella enterotype may increase the occurrence of colorectal adenoma through inflammatory association and interference with glucose and lipid metabolism in human body. In conclusion, the differences we observed between different enterotypes add a new potential factor to the development of colorectal adenoma.

8.
BMC Cancer ; 22(1): 1290, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36494680

RESUMO

BACKGROUND: Metabolic reprogramming is a hallmark of cancer, alteration of nucleotide metabolism of hepatocellular carcinoma (HCC) is not well-understood. MYBL2 regulates cell cycle progression and hepatocarcinogenesis, its role in metabolic regulation remains elusive. PATIENTS AND METHODS: Copy number, mRNA and protein level of MYBL2 and IMPDH1 were analyzed in HCC, and correlated with patient survival. Chromatin Immunoprecipitation sequencing (Chip-seq) and Chromatin Immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR) were used to explore the relationship between MYBL2 and IMPDH1. Metabolomics were used to analyze how MYBL2 affected purine metabolism. The regulating effect of MYBL2 in HCC was further validated in vivo using xenograft models. RESULTS: The Results showed that copy-number alterations of MYBL2 occur in about 10% of human HCC. Expression of MYBL2, IMPDH1, or combination of both were significantly upregulated and associated with poor prognosis in HCC. Correlation, ChIP-seq and ChIP-qPCR analysis revealed that MYBL2 activates transcription of IMPDH1, while knock-out of MYBL2 retarded IMPDH1 expression and inhibited proliferation of HCC cells. Metabolomic analysis post knocking-out of MYBL2 demonstrated that it was essential in de novo purine synthesis, especially guanine nucleotides. In vivo analysis using xenograft tumors also revealed MYBL2 regulated purine synthesis by regulating IMPDH1, and thus, influencing tumor progression. CONCLUSION: MYBL2 is a key regulator of purine synthesis and promotes HCC progression by transcriptionally activating IMPDH1, it could be a potential candidate for targeted therapy for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Progressão da Doença , Purinas , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Linhagem Celular Tumoral , IMP Desidrogenase/genética , IMP Desidrogenase/metabolismo , Transativadores/metabolismo , Proteínas de Ciclo Celular/metabolismo
9.
Front Surg ; 9: 886129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36329974

RESUMO

Purpose: The aim of this study was to identify the effect of different injection times on pain during colonoscopy procedure. Methods: In this retrospective study, the data of patients who underwent colonoscopy from June 2020 to September 2020 were assessed to investigate the effect of different injection time of sedative drugs (midazolam and dezocine). The primary endpoint was evaluating the pain intensity of the patients using visual analogue scale (VAS) immediately after colonoscopy . Results: A total of 152 patients were eligible for this study. Of them, 76 received midazolam and dezocine injection 1 min prior to the colonoscopy procedure (the 1 Min group) and the other 76 patients received the injection 3 min prior to the procedure (the 3 Min group). The vital signs of all patients were stable except for one patient who was diagnosed with inflammatory bowel disease in the 3 Min group. A transient drop in blood pressure for this patient was observed during colonoscopy but returned to normal after general treatment. The two groups had similar rates of cecal intubation (84.21% vs. 90.97%, P = 0.22), addition of sedative drugs during procedure (2.63% vs. 5.26%, P = 0.68), and adequate bowel preparation (Boston Bowel Preparation Scale ≥6, 61.84% vs. 61.84%, P = 1.0). However, patients in the 3 Min group had significantly lower VAS than those in the 1 Min group [0 (0, 1) vs. 1 (0, 2), P = 0.041]. Conclusion: The timing of drug injection during conscious sedation may affect pain control during colonoscopy, with 3 min prior to the procedure showing lower VAS.

10.
BMC Cancer ; 22(1): 806, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35864459

RESUMO

BACKGROUND: For colorectal cancer, preoperative (neoadjuvant) chemotherapy is more effective than postoperative chemotherapy because it not only eradicates micrometastases more effectively but also reduces the risk of incomplete intraoperative resection and tumor cell shedding. For the treatment of acute left-sided malignant colorectal obstruction, colorectal stents as well as stoma are being used to relieve the obstructive colorectal cancer, and as a bridge to surgery, allowing easy mobilization and resection of the colon. Neoadjuvant chemotherapy combined with self-expandable metal stents (SEMS) or neoadjuvant chemotherapy combined with decompressing stoma (DS) can be used as a bridge to elective surgery (BTS) as an alternative to emergency surgery in patients with acute left-sided malignant colorectal obstruction, but its benefit is uncertain. The purpose of this study was to evaluate the safety and feasibility of neoadjuvant chemotherapy as a bridge to surgery in the treatment of acute left-sided malignant colorectal obstruction. METHODS: Data from patients who were admitted with acute left-sided malignant colorectal obstruction between January 2012 and December 2020 were retrospectively reviewed, and patients with gastrointestinal perforation or peritonitis were excluded. We performed one-to-two propensity score matching to compare the stoma requirement, postoperative complications, and other short-term oncological outcomes between the neoadjuvant chemotherapy group and surgery group. RESULTS: There were no differences in intraoperative blood loss, operative time, one-year postoperative mortality, and postoperative tumor markers between the two groups. The 1-year recurrence-free survival (RFS) rates of neoadjuvant chemotherapy group and surgery group were 96.8 and 91.3% (p = 0.562). The neoadjuvant chemotherapy group was able to reduce stoma rate 1 year after surgery (p = 0.047). Besides, the neoadjuvant group significantly reduced postoperative bowel function time (p < 0.001), postoperative hospital stay (p < 0.001), total hospital stay (p = 0.002), postoperative complications (p = 0.017), reduction in need to stay in the intensive care unit (ICU) (p = 0.042). CONCLUSIONS: Neoadjuvant chemotherapy as a bridge to elective surgery in patients with acute left-sided malignant colorectal obstruction is safe and has many advantages. Prospective multicenter studies with large samples are needed to further evaluate the feasibility of neoadjuvant chemotherapy.


Assuntos
Neoplasias Colorretais , Obstrução Intestinal , Neoplasias Colorretais/complicações , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Estudos de Viabilidade , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/patologia , Obstrução Intestinal/cirurgia , Terapia Neoadjuvante/efeitos adversos , Complicações Pós-Operatórias , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
11.
Front Physiol ; 13: 880981, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574447

RESUMO

Background and Aims: Although the wait and watch (W&W) strategy is a treatment choice for locally advanced rectal cancer (LARC) patients who achieve clinical complete response (cCR) after neoadjuvant therapy (NT), the issue on consistency between cCR and pathological CR (pCR) remains unsettled. Herein, we aimed to develop a deep convolutional neural network (DCNN) model using endoscopic images of LARC patients after NT to distinguish tumor regression grade (TRG) 0 from non-TRG0, thus providing strength in identifying surgery candidates. Methods: A total of 1000 LARC patients (6,939 endoscopic images) who underwent radical surgery after NT from April 2013 to April 2021 at the Sixth Affiliated Hospital, Sun Yat-sen University were retrospectively included in our study. Patients were divided into three cohorts in chronological order: the training set for constructing the model, the validation set, and the independent test set for validating its predictive capability. Besides, we compared the model's performance with that of three endoscopists on a class-balanced, randomly selected subset of 20 patients' LARC images (10 TRG0 patients with 70 images and 10 non-TRG0 patients with 72 images). The measures used to evaluate the efficacy for identifying TRG0 included overall accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUROC). Results: There were 219 (21.9%) cases of TRG0 in the included patients. The constructed DCNN model in the training set obtained an excellent performance with good accuracy of 94.21%, specificity of 94.39%, NPV of 98.11%, and AUROC of 0.94. The validation set showed accuracy, specificity, NPV, and AUROC of 92.13%, 93.04%, 96.69%, and 0.95, respectively; the corresponding values in the independent set were 87.14%, 92.98%, 91.37%, and 0.77, respectively. In the reader study, the model outperformed the three experienced endoscopists with an AUROC of 0.85. Conclusions: The proposed DCNN model achieved high specificity and NPV in detecting TRG0 LARC tumors after NT, with a better performance than experienced endoscopists. As a supplement to radiological images, this model may serve as a useful tool for identifying surgery candidates in LARC patients after NT.

12.
Gastroenterol Rep (Oxf) ; 10: goab051, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35382164

RESUMO

Background: The resection of small colorectal polyps (≤10 mm) is routine for endoscopists. However, the management of one of its main complications, namely delayed (within 14 days) postpolypectomy bleeding (DPPB), has not been clearly demonstrated. We aimed to assess the role of coloscopy in the management of DPPB from small colorectal polyps and identify the associated factors for initial hemostatic success. Methods: We conducted a retrospective study of 69 patients who developed DPPB after the removal of colorectal polyps of ≤10 mm and underwent hemostatic colonoscopy at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between April 2013 and June 2021. Demographics, clinical variables, and colonoscopic features were collected independently. We applied univariate and multivariate analyses to assess factors associated with initial hemostatic success. Results: General colonoscopy without oral bowel preparation was successfully performed in all the patients, with a median duration of 23.9 (12.5-37.9) minutes. Among 69 patients, 62 (89.9%) achieved hemostasis after initial hemostatic colonoscopy and 7 (10.1%) rebled 2.7 ± 1.1 days after initial colonoscopic hemostasis and had rebleeding successfully controlled by one additional colonoscopy. No colonoscopy-related adverse events occurred. Multivariate analysis showed that management with at least two clips was the only independent prognostic factor for initial hemostatic success (odds ratio, 0.17; 95% confidence interval, 0.03-0.91; P = 0.04). All the patients who had at least two clips placed at the initial hemostatic colonoscopy required no further hemostatic intervention. Conclusions: Colonoscopy is a safe, effective, and not too time-consuming approach for the management of patients with DPPB of small colorectal polyps and management with the placement of at least two hemoclips may be beneficial.

13.
Dis Colon Rectum ; 65(4): 590-598, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34775404

RESUMO

BACKGROUND: Postoperative benign anastomotic stricture is associated with colorectal anastomosis following surgery for colorectal cancer. Endoscopic stricturotomy is a novel technique that has been demonstrated to be safe and effective for the treatment of colorectal anastomotic stricture in several case reports and series. OBJECTIVE: We designed this study to investigate the efficacy of endoscopic stricturotomy for postoperative benign anastomotic stricture in patients for colorectal cancer. The primary outcomes were stricture-recurrence-free survival and reoperation-free survival. DESIGN: This is a retrospective study. SETTING: This study presents a single-center experience. PATIENTS: This retrospective study included patients with colorectal cancer who underwent surgical resection and developed anastomotic stricture between January 2014 and June 2019 and were treated with endoscopic stricturotomy. MAIN OUTCOME MEASURES: Immediate technical success of endoscopic stricturotomy and the factors associated with success and recurrence were investigated. RESULTS: Endoscopic stricturotomy was performed in 57 patients, and immediate technical success was achieved in 84% of the patients. The mean follow-up was 31.3 (15.8) months (range, 9-74 months). Postoperative benign anastomotic stricture recurred in 11 patients after initial successful endoscopic stricturotomy; 10 of the 11 recurrent patients accepted reoperation. Univariate and multivariate analysis indicated that length of stricture ≥1 cm was an independent risk factor for failure of the initial endoscopic stricturotomy (OR, 9.423; 95% CI, 1.729-51.350; p = 0.010) and the recurrence of postoperative benign anastomotic stricture after the initial endoscopic stricturotomy (OR, 13.521; 95% CI, 2.305-79.306; p = 0.004). LIMITATIONS: The study was limited by its small sample size and retrospective design. CONCLUSIONS: Endoscopic stricturotomy is a safe and effective technique for postoperative benign anastomotic stricture. However, if the length of the stricture is ≥1 cm, endoscopic stricturotomy may not be effective, and recurrence of postoperative benign anastomotic stricture is also likely. See Video Abstract at http://links.lww.com/DCR/B739. ESTRICTUROTOMA ENDOSCPICA PARA PACIENTES CON ESTRICCIN ANASTOMTICA BENIGNA POSTOPERATORIA PARA EL CNCER COLORRECTAL: ANTECEDENTES:La estenosis anastomótica benigna postoperatoria se asocia con anastomosis colorrectal después de la cirugía para el cáncer colorrectal. La estricturotomia endoscópica es una técnica novedosa que se ha demostrado que es segura y efectiva para el tratamiento de la estenosis anastomótica colorrectal en varios informes de casos o series.OBJETIVO:Diseñamos este estudio para investigar la eficacia de la estricturotomia endoscópica para la estenosis anastomótica benigna postoperatoria en pacientes con cáncer colorrectal. El resultado primario fue la supervivencia libre de restricción estricta y la supervivencia libre de reoperación.DISEÑO:Este es un estudio retrospectivo.CONFIGURACIÓN:Este estudio presenta una experiencia de un solo centro.PACIENTES:Este estudio retrospectivo incluyó pacientes con cáncer colorrectal que se sometieron a resección quirúrgica y desarrollaron estenosis anastomótica entre enero de 2014 y junio de 2019 y tratados con estricturotomia endoscópica.MEDIDAS PRINCIPALES DE RESULTADO:Éxito técnico inmediato y estenosurotomía endoscópica, los factores asociados con el éxito y la recurrencia.RESULTADOS:Se realizó estricturotomia endoscópica en 57 pacientes, y se logró un éxito técnico inmediato en el 84% de los pacientes. El seguimiento medio fue de 31,3 (15,8) meses (rango, 9 a 74 meses), el POBAS se repitió en 11 pacientes después del éxito inicial de ESt. 10 de los 11 pacientes recurrentes aceptaron la reoperación. El análisis univariado y multivariado indicó que la longitud de la estenosis ≥1 cm era un factor de riesgo independiente para el fracaso de la estricturotomia endoscópica inicial (odds ratio = 9,423; IC del 95% = 1.729-51.350; p = 0.010) y la recurrencia de estenosis anastomótica benigna postoperatoria después de la estricturotomia endoscópica inicial (odds ratio = 13,521; IC del 95% = 2,305-79,306; p = 0.004).LIMITACIONES:El estudio estuvo limitado por su pequeño tamaño de muestra y diseño retrospectivo.CONCLUSIONES:La estricturotomia endoscópica es una técnica segura y efectiva para la estructura anastomótica benigna postoperatoria. Sin embargo, si la longitud de la estenosis es ≥1 cm, la estricturotomia endoscópica puede no ser efectiva y también es probable que se repita la estenosis anastomótica benigna postoperatoria. Consulte Video Resumen en http://links.lww.com/DCR/B739.


Assuntos
Fístula Anastomótica , Neoplasias Retais , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Humanos , Complicações Pós-Operatórias/cirurgia , Neoplasias Retais/cirurgia , Estudos Retrospectivos
14.
Adv Sci (Weinh) ; 8(23): e2100759, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34881526

RESUMO

Dysregulation of the cell cycle machinery leads to genomic instability and is a hallmark of cancer associated with chemoresistance and poor prognosis in colorectal cancer (CRC). Identifying and targeting aberrant cell cycle machinery is expected to improve current therapies for CRC patients. Here,upregulated polo-like kinase 1 (PLK1) signaling, accompanied by deregulation of cell cycle-related pathways in CRC is identified. It is shown that aberrant PLK1 signaling correlates with recurrence and poor prognosis in CRC patients. Genetic and pharmacological blockade of PLK1 significantly increases the sensitivity to oxaliplatin in vitro and in vivo. Mechanistically, transcriptomic profiling analysis reveals that cell cycle-related pathways are activated by oxaliplatin treatment but suppressed by a PLK1 inhibitor. Cell division cycle 7 (CDC7) is further identified as a critical downstream effector of PLK1 signaling, which is transactivated via the PLK1-MYC axis. Increased CDC7 expression is also found to be positively correlated with aberrant PLK1 signaling in CRC and is associated with poor prognosis. Moreover, a CDC7 inhibitor synergistically enhances the anti-tumor effect of oxaliplatin in CRC models, demonstrating the potential utility of targeting the PLK1-MYC-CDC7 axis in the treatment of oxaliplatin-based chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Proteínas de Ciclo Celular/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Oxaliplatina/uso terapêutico , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Animais , Neoplasias Colorretais/metabolismo , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Transdução de Sinais/efeitos dos fármacos , Quinase 1 Polo-Like
15.
Ann Transl Med ; 9(20): 1595, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790801

RESUMO

BACKGROUND: Defecation disorders after ileostomy reversal are among the most common complications for rectal cancer patients, and significantly diminish their quality of life. The aim of this study was to identify the risk factors associated with frequent defecation early after ileostomy reversal for rectal cancer patients. METHODS: We retrospectively collected the data of rectal cancer patients who underwent ileostomy reversal from January 2018 to December 2019 at the Sixth Affiliated Hospital of Sun Yat-sen University. We divided patients into two groups: a no frequent defecation group (≤7 times/day) and a frequent defecation group (>7 times/day). RESULTS: Of the 264 included patients, 59 patients (22.35%) had frequent defecation within 1 month after ileostomy closure and were defined as the frequent defecation group. There were no significant differences between the two groups in terms of gender, age, hypertension, and diabetes. Univariate and multivariate analyses showed that proctitis (P=0.04) and anastomotic stenosis (P=0.02) were independent risk factors for frequent defecation. Four factors, including proctitis, anastomotic stenosis, hypertension, and age were included to construct the nomogram. The consistency index of the nomogram was 0.949 and the area under the curve value was 0.623. CONCLUSIONS: For rectal cancer patients, proctitis and anastomotic stenosis were correlated with frequent defecation within 1 month after ileostomy closure. Surgeons should pay attention to the rectal examination before ileostomy reversal surgery.

16.
J Laparoendosc Adv Surg Tech A ; 31(4): 416-422, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32924769

RESUMO

Background: Traction-assisted endoscopic resection is an approach to provide better procedural outcomes than conventional endoscopic procedure in treating gastric or esophageal epithelial lesions. Submucosal tumors (SMTs) are challenging to resect endoscopically due to the difficulty in exposure and high incidence of full-thickness resection. In this study, we investigated the efficacy of snare traction-assisted method, served as an "extra hand," for upper gastrointestinal SMTs. Methods: From June 2019 to May 2020, we used the snare traction-assisted method to treat 11 patients with 12 upper gastrointestinal SMTs in the Sixth Affiliated Hospital, Sun Yat-sen University. The duration of the procedures and the outcomes were recorded. Results: A total of 11 patients with 12 lesions were treated by snare traction-assisted endoscopic resection. The mean procedure time was 26.8 ± 8.3 minutes. En bloc resection was achieved in all the 12 lesions. The mean length of the specimens was 11.5 ± 4.0 mm. Full-thickness resection was performed in four lesions. The patients were discharged in 5.0 days after procedures without delayed bleeding or other complication reported. Conclusion: Snare traction-assisted method is an effective tool for endoscopic resection of upper gastrointestinal SMTs. Further prospective studies comparing the snare traction-assisted method with the conventional procedure are necessary.


Assuntos
Ressecção Endoscópica de Mucosa/efeitos adversos , Endoscopia/métodos , Neoplasias Gástricas/cirurgia , Tração , Adulto , Idoso , Feminino , Humanos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
17.
Int J Colorectal Dis ; 35(9): 1703-1709, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32458392

RESUMO

BACKGROUND: Postoperative anastomotic bleeding is considered a rare but life-threatening complication. There is no standard treatment strategy for this emergency condition. The aim of this study was to report our experiences in the management of postoperative anastomotic bleeding in patients with colorectal cancer. METHODS: We analyzed the general characteristics, treatments, and outcomes of patients with anastomotic bleeding after surgery for colorectal carcinoma at the Sixth Affiliated Hospital of Sun Yat-Sen University between July 2013 and September 2019 retrospectively. A univariate and multivariate analysis was performed to find protective factors for endoscopic hemostasis. Risk factors for anastomotic leakage after colonoscopy were also analyzed. RESULTS: A total of 9870 patients underwent surgeries for colorectal carcinoma between July 2013 and September 2019. Colonoscopies were performed in 78 cases with postoperative anastomotic bleeding. The effective rate of initial endoscopic hemostasis was 81% (63/78). In univariate and multivariate analysis, hemoclip therapy (odds ratio = 4.572; 95%CI 1.305-16.017; P = 0.017) and postoperative anastomotic bleeding within 5 days (odds ratio = 3.639; 95%CI 1.045-12.675; P = 0.042) are protective factors for endoscopic hemostasis. Comorbidity was associated with an increased risk for anastomotic leakage. CONCLUSIONS: Colonoscopy seems to be an effective way to achieve hemostasis for patients with anastomotic bleeding after surgery for colorectal carcinoma. It may be more effective in the early postoperative period, and hemoclip appears to be the first choice to control postoperative anastomotic bleeding.


Assuntos
Neoplasias Colorretais , Hemorragia Pós-Operatória , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , Humanos , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/terapia , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco
18.
Int J Colorectal Dis ; 34(12): 2201-2204, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31735986

RESUMO

BACKGROUND: The incidence of colorectal cancer, especially located in distal colorectum, is rising markedly in young patients. Conventional adenomas and serrated polyps have been widely recognized as precursors of colorectal cancer. AIM: To investigate the correlation of polyp feature with polyp location in patients under age 50. METHOD: Patients under age 50 who had received colonoscopy were included from 2010 to 2018. Clinical data including number, location, size, and histopathology of polyps were collected. Odd ratios and 95% confidence interval of adenomas with their location were calculated. RESULT: In total, 25,636 patients aged 18-49 were enrolled, among which 4485 patients had polyps, with polyp detection rate of 17.5%. A total of 2484 and 2387 patients had conventional adenomas and serrated polyps, respectively. 76.0% advanced adenomas and 69.5% ≥ 10-mm serrated polyps were located in the distal colorectum. The detection rate of advanced adenomas was higher in patients aged 45-49. Patients with adenomas especially advanced adenomas in the distal colorectum were more likely to have advanced adenoma in the proximal colon. CONCLUSION: Among patients under age 50, advanced adenomas and ≥ 10-mm serrated polyps were predominantly in the distal colorectum. Advanced adenomas tended to be found in patients aged 45-49. Our results might explain the rising trend of distal colorectal cancer and emphasize the necessity for colonoscopy screening among these populations.


Assuntos
Pólipos Adenomatosos/patologia , Pólipos do Colo/patologia , Neoplasias Colorretais/patologia , Pólipos Adenomatosos/epidemiologia , Adolescente , Adulto , Distribuição por Idade , China/epidemiologia , Pólipos do Colo/epidemiologia , Colonoscopia , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Carga Tumoral , Adulto Jovem
19.
Wideochir Inne Tech Maloinwazyjne ; 14(3): 353-365, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31534564

RESUMO

INTRODUCTION: The benefit of transanal total mesorectal excision (TaTME) for mid and low rectal cancer is conflicting. AIM: To assess and compare the short-term outcomes of TaTME with conventional laparoscopic total mesorectal excision (LaTME) for middle and low rectal cancer. MATERIAL AND METHODS: We searched PubMed, Embase and Cochrane Library databases for studies addressing TaTME versus conventional LaTME for rectal cancer between 2008 and December 2018. Randomized controlled trials (RCTs) and retrospective studies which compared TaTME with LaTME were included. RESULTS: Twelve retrospective case-control studies were identified, including a total of 899 patients. We did not find significant differences in overall intraoperative complications, blood loss, conversion rate, operative time, overall postoperative complication, anastomotic leakage, ileus, or urinary morbidity. Also no significant differences in oncological outcomes including circumferential resection margin (CRM), positive CRM, distal margin distance (DRM), positive DRM, quality of mesorectum, number of harvested lymph nodes, temporary stoma or local recurrence were found. Although the TaTME group had better postoperative outcomes (readmission, reoperation, length of hospital stay) on average, the difference did not reach statistical significance. CONCLUSIONS: Transanal total mesorectal excision offers a safe and feasible alternative to LaTME although the clinicopathological features were not superior to LaTME in this study. Currently, with the lack of evidence on benefits of TaTME, further evaluation of TaTME requires large randomized control trials to be conducted.

20.
J Laparoendosc Adv Surg Tech A ; 29(11): 1397-1404, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31414963

RESUMO

Aim: There is still no consensus on whether laparoscopic surgery can be routinely recommended as a safe approach for complex Crohn's disease (CD). Methods: PubMed, Embase, and Cochrane library databases were searched (up to February 2019). Comparative studies reporting laparoscopic surgery for complex CD (LC group) comparing with simple CD (LS group) were included. The outcomes were blood loss, operative time, conversion rate, length of hospital stay, postoperative complications, and reoperation rate within 30 days after surgery. Results: Thirteen retrospective studies with 1120 participants were included. The LC group has significantly more blood loss (weighted mean difference [WMD] 43.64 mL; 95% confidence interval (CI) 8.37-78.91; P = .020), longer operative time (WMD 17.59 minutes; 95% CI 6.38-28.81; P = .002), higher conversion rate (WMD 2.04%; 95% CI 1.43-2.91; P < .001), and longer length of hospital stay (WMD 0.86 day; 95% CI 0.53-1.19; P < .001). Overall postoperative complication rates (WMD 0.98; 95% CI 0.71-1.34; P = .90) did not differ significantly between the 2 groups. Conclusions: LC is safe and feasible with comparable postoperative complications, although there is a more blood loss, longer operative time, higher conversion rate, and longer length of hospital stay.


Assuntos
Doença de Crohn/complicações , Doença de Crohn/cirurgia , Laparoscopia , Perda Sanguínea Cirúrgica , Conversão para Cirurgia Aberta , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Reoperação , Resultado do Tratamento
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