Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 97
Filtrar
2.
Cell Mol Immunol ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38942796

RESUMO

Metabolic changes play a crucial role in determining the status and function of macrophages, but how lipid reprogramming in macrophages contributes to tumor progression is not yet fully understood. Here, we investigated the phenotype, contribution, and regulatory mechanisms of lipid droplet (LD)-laden macrophages (LLMs) in hepatocellular carcinoma (HCC). Enriched LLMs were found in tumor tissues and were associated with disease progression in HCC patients. The LLMs displayed immunosuppressive phenotypes (with extensive expression of TREM2, PD-L1, CD206, and CD163) and attenuated the antitumor activities of CD8+ T cells. Mechanistically, tumor-induced reshuffling of cellular lipids and TNFα-mediated uptake of tumoral fatty acids contribute to the generation of triglycerides and LDs in macrophages. LDs prolong LLM survival and promote CCL20 secretion, which further recruits CCR6+ Tregs to HCC tissue. Inhibiting LLM formation by targeting DGAT1 and DGAT2, which catalyze the synthesis of triglycerides, significantly reduced Treg recruitment, and delayed tumor growth in a mouse hepatic tumor model. Our results reveal the suppressive phenotypes and mechanisms of LLM enrichment in HCC and suggest the therapeutic potential of targeting LLMs for HCC patients.

5.
Ann Surg Oncol ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38814549

RESUMO

BACKGROUND: The mechanism underlying the formation of gastric tumor deposits (TDs) is unclear. We aimed to explore the risk factors for the formation and prognostic value of TDs. METHODS: This retrospective analysis included 781 locally advanced gastric cancer (LAGC) patients from four medical institutions in China, from June 2014 to June 2018. The risk factors for TD formation and prognostic value were determined through univariate and multivariate analyses. RESULTS: Univariate analysis revealed that TD positivity was closely related to tumor diameter, Borrmann classification, differentiation degree, pT stage, pN stage, pTNM stage, and nerve and vascular invasion (p < 0.05). Multivariate logistic regression revealed that tumor diameter ≥ 5 cm (odds ratio [OR] 1.836, 95% confidence interval [CI] 1.165-2.894, p = 0.009) and vascular invasion (OR 2.152, 95% CI 1.349-3.433, p = 0.001) were independent risk factors for TD positivity. Multivariate Cox analysis revealed that TD positivity (OR 1.533, 95% CI 1.101-2.134, p = 0.011), tumor diameter ≥ 5 cm (OR 1.831, 95% CI 1.319-2.541, p < 0.001), pT4a stage (OR 1.652, 95% CI 1.144-2.386, p = 0.007), and vascular invasion (OR 1.458, 95% CI 1.059-2.008, p = 0.021) were independent risk factors for GC prognosis. The 5-year overall and disease-free survival of the TD-positive group showed significant effects among patients in the pT4a and pN3b stages (p < 0.05). CONCLUSIONS: TDs are closely related to tumor diameter and vascular invasion in LAGC patients, and TD positivity is an independent prognostic factor for LAGC patients, especially those at pT4a and pN3b stages.

6.
Langenbecks Arch Surg ; 409(1): 161, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38761214

RESUMO

PURPOSE: To explore the high-risk factors for rectal cancer No.253 lymph node metastasis (LNM) and to construct a risk nomogram for the individualized prediction of No.253 LNM. METHODS: This was a retrospective analysis of 425 patients with rectal cancer who underwent laparoscopic-assisted radical surgery. Independent risk factors for rectal cancer No.253 LNM was identified using multivariate logistic regression analysis, and a risk prediction nomogram was constructed based on the independent risk factors. In addition, the performance of the model was evaluated by discrimination, calibration, and clinical benefit. RESULTS: Multivariate logistic regression analysis showed that No.253 lymphadenectasis on CT (OR 10.697, P < 0.001), preoperative T4-stage (OR 4.431, P = 0.001), undifferentiation (OR 3.753, P = 0.004), and preoperative Ca199 level > 27 U/ml (OR 2.628, P = 0.037) were independent risk factors for No.253 LNM. A nomogram was constructed based on the above four factors. The calibration curve of the nomogram was closer to the ideal diagonal, indicating that the nomogram had a better fitting ability. The area under the ROC curve (AUC) was 0.865, which indicated that the nomogram had high discriminative ability. In addition, decision curve analysis (DCA) showed that the model could show better clinical benefit when the threshold probability was between 1% and 50%. CONCLUSION: Preoperative No.253 lymphadenectasis on CT, preoperative T4-stage, undifferentiation, and elevated preoperative Ca199 level were found to be independent risk factors for the No.253 LNM. A predictive model based on these risk factors can help surgeons make rational clinical decisions.


Assuntos
Metástase Linfática , Estadiamento de Neoplasias , Nomogramas , Neoplasias Retais , Humanos , Masculino , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Neoplasias Retais/mortalidade , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Metástase Linfática/patologia , Idoso , Fatores de Risco , Adulto , Laparoscopia , Modelos Logísticos , Idoso de 80 Anos ou mais , Medição de Risco
7.
Surgery ; 176(1): 100-107, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38584073

RESUMO

BACKGROUND: The indications for splenic hilar lymph node dissection in advanced proximal gastric cancer without invasion of the greater curvature are controversial. We aimed to develop a preoperative nomogram for individualized prediction of splenic hilar lymph node metastasis in non-greater curvature advanced proximal gastric cancer. METHODS: From January 2014 to December 2021, 558 patients with non-greater curvature advanced proximal gastric cancer who underwent D2 lymphadenectomy (including splenic hilar lymph node) were retrospectively analyzed and divided into a training cohort (n = 361) and validation cohort (n = 197), depending on the admission time. A preoperative predictive nomogram of splenic hilar lymph node metastasis was established based on independent predictors identified by multivariate analysis, and the performance and prognostic value were confirmed. RESULTS: In the training and validation cohorts, 48 (13.3%) and 24 patients (12.2%) had pathologically confirmed splenic hilar lymph node metastasis, respectively. Tumor located in the posterior wall, tumor size ≥5 cm, Borrmann type IV, and splenic hilar lymph node lymphadenectasis on computed tomography were preoperative factors independently associated with splenic hilar lymph node metastasis. The nomogram developed based on these four parameters had a high concordance index of 0.850 (95% confidence interval, 0.793-0.907) and 0.825 (95% confidence interval, 0.743-0.908) in the training and validation cohorts, respectively, with well-fitting calibration plots and better net benefits in the decision curve analysis. In addition, disease-free survival and overall survival were significantly shorter in the high-risk group, with hazard ratios of 3.660 (95% confidence interval, 2.228-6.011; log-rank P < .0001) and 3.769 (95% confidence interval, 2.279-6.231; log-rank P < .0001), respectively. CONCLUSION: The nomogram has good performance in predicting the risk of splenic hilar lymph node metastasis in non-greater curvature advanced proximal gastric cancer preoperatively, which can help surgeons make rational clinical decisions.


Assuntos
Excisão de Linfonodo , Linfonodos , Metástase Linfática , Nomogramas , Baço , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Metástase Linfática/patologia , Estudos Retrospectivos , Idoso , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Baço/patologia , Gastrectomia/métodos , Prognóstico , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Período Pré-Operatório , Adulto , Cuidados Pré-Operatórios/métodos , Tomografia Computadorizada por Raios X
8.
Indian J Pathol Microbiol ; 67(1): 21-28, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38358184

RESUMO

Objective: To explore the relationships among the epithelial to mesenchymal transition (EMT)-related factors (SNAIL, TWIST, and E-Cadherin) and clinicopathological parameters and gastric mesangial tumor deposits (TDs) in advanced gastric cancer (AGC) patients and their value in gastric cancer prognosis judgment. Materials and Methods: The data of 190 patients who underwent radical resection of ACG were analyzed retrospectively, including 75 cases of TDs (+) and 115 cases of TDs (-). The expression of EMT-related transforming factors Snail, Twist, and E-cadherin in the primary tumor, paracancerous normal tissues, and TDs was detected by immunohistochemistry. Results: SNAIL and TWIST were overexpressed in primary tumors and TDs, whereas E-Cadherin was down-expressed in primary tumors. SNAIL was correlated significantly with tumor differentiation, lymph node metastases, and TDs (P < 0.05); TWIST was correlated strongly with tumor location, lymph node metastases, and TDs (P < 0.05); E-Cadherin was correlated closely with tumor differentiation and lymph node metastases (P < 0.05). Kaplan-Meier curves showed that SNAIL expression was correlated with DFS (P < 0.05), and TWIST expression was correlated with OS (P < 0.05). Tumor differentiation, lymph node metastasis, and TWIST expression were prognostic-independent risk factors of AGC patients (P < 0.05). Conclusion: The occurrence and development of gastric cancer and the formation of TDs may be related to EMT, analyzing the expression of EMT-related transforming proteins may be helpful to judge the prognosis of gastric cancer.


Assuntos
Neoplasias Gástricas , Fatores de Transcrição , Humanos , Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Relevância Clínica , Transição Epitelial-Mesenquimal , Extensão Extranodal , Metástase Linfática , Prognóstico , Estudos Retrospectivos , Fatores de Transcrição da Família Snail/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Fatores de Transcrição/metabolismo
9.
Cancer Lett ; 585: 216638, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38266805

RESUMO

Recent studies have suggested that therapeutic upregulation of CCAAT/enhancer binding protein α (C/EBPα) prevents hepatocellular carcinoma (HCC) progression. However, the mechanisms underlying this outcome are not fully understood. In this study, we investigated the expression and functional roles of C/EBPα in human HCC, with a focus on monocytes/macrophages (Mφs). Paraffin-embedded tissues were used to visualize C/EBPα expression and analyze the prognostic value of C/EBPα+ monocytes/Mφs in HCC patients. The underlying regulatory mechanisms were examined using human monocyte-derived Mφs. The results showed that the expression of C/EBPα on monocytes/Mφs was significantly decreased in intra-tumor tissues compared to the corresponding peri-tumor tissues. C/EBPα+ monocytes/Mφs displayed well-differentiation and antitumor capacities, and the accumulation of these cells in tissue was associated with antitumor immune responses and predicted longer overall survival (OS) of HCC patients. Mechanistic studies demonstrated that C/EBPα was required for Mφ maturation and HLA-DR, CD169 and CD86 expression, which initiates antitumor cytotoxic T-cell responses; however, these effects were inhibited by monocyte autocrine IL-6- and IL-1ß-induced suppression of mTOR1 signaling. Reprogramming Mφs via the upregulation of C/EBPα may provide a novel strategy for cancer immunotherapy in patients with HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Macrófagos/metabolismo , Monócitos/metabolismo
10.
J Cell Mol Med ; 28(3): e18094, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38214430

RESUMO

Lung cancer is a leading cause of cancer-related deaths worldwide. Recent studies have identified pyroptosis, a type of programmed cell death, as a critical process in the development and progression of lung cancer. In this study, we investigated the effect of EEBR, a new compound synthesized by our team, on pyroptosis in non-small cell lung cancer cells (NSCLC) and the underlying molecular mechanisms. Our results demonstrated that EEBR significantly reduced the proliferation and metastasis of NSCLC cells in vitro. Moreover, EEBR-induced pyroptosis in NSCLC cells, as evidenced by cell membrane rupture, the release of cytokines such as interleukin-18 and interleukin-1 beta and the promotion of Gasdermin D cleavage in a Caspase-1-dependent manner. Furthermore, EEBR promoted the nuclear translocation of NF-κB and upregulated the protein level of NLRP3. Subsequent studies revealed that EEBR-induced pyroptosis was suppressed by the inhibition of NF-κB. Finally, EEBR effectively suppressed the growth of lung cancer xenograft tumours by promoting NSCLC pyroptosis in animal models. Taken together, our findings suggest that EEBR induces Caspase-1-dependent pyroptosis through the NF-κB/NLRP3 signalling cascade in NSCLC, highlighting its potential as a candidate drug for NSCLC treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Humanos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Piroptose , Caspase 1/metabolismo , Inflamassomos/metabolismo
11.
Haematologica ; 109(1): 72-83, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37470150

RESUMO

Treatment options for relapsed and refractory acute myeloid leukemia patients (R/R AML) are limited. This retrospective cohort study compares safety and efficacy of fludarabine, cytarabine, and idarubicin (FLA-IDA) without or with venetoclax (FLAVIDA) in patients with R/R AML. Thirty-seven and 81 patients received one course FLA-IDA with or without a 7-day course of venetoclax, respectively. The overall response rate (ORR) was significantly higher in FLAVIDA compared to FLAIDA- treated patients (78% vs. 47%; P=0.001), while measurable residual disease was negative at a similar proportion in responding patients (50% vs. 57%), respectively. Eighty-one percent and 79% of patients proceeded to allogeneic hematopoietic cell transplantation or donor lymphocyte infusion after FLAVIDA and FLA-IDA, respectively. Event-free and overall survival were similar in FLAVIDA- and FLA-IDA-treated patients. Refractory patients could be salvaged more successfully after FLA-IDA compared to FLAVIDA pretreatment. Neutrophil and platelet recovery times were similar in the venetoclax and the control group. In conclusion, short-term venetoclax in combination with FLA-IDA represents an effective treatment regimen in R/R AML identifying chemosensitive patients rapidly and inducing measurable residual disease-negative remission in a high proportion of R/R AML patients.


Assuntos
Idarubicina , Leucemia Mieloide Aguda , Humanos , Idarubicina/uso terapêutico , Citarabina , Estudos Retrospectivos , Fator Estimulador de Colônias de Granulócitos , Leucemia Mieloide Aguda/tratamento farmacológico , Vidarabina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
12.
Surg Endosc ; 38(2): 1059-1068, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38082018

RESUMO

BACKGROUND: Patients with T1-3N0M0 gastric cancer (GC) who undergo radical gastrectomy maintain a high recurrence rate. The free cancer cells in the mesogastric adipose connective tissue (Metastasis V) maybe the reason for recurrence in these individuals. We aimed to evaluate whether D2 lymphadenectomy plus complete mesogastrium excision (D2 + CME) was superior to D2 lymphadenectomy with regard to safety and oncological efficacy for T1-3N0M0 GC. METHODS: Patients with T1-3N0M0 GC who underwent radical resection from January 2014 to July 2018 were retrospectively analyzed; there were 323 patients, of whom 185 were in the D2 + CME group and 138 in the D2 group. The primary endpoint was 5-year disease-free survival (DFS). Secondary endpoints include the 5-year overall survival (OS), recurrence pattern, morbidity, mortality, and surgical outcomes. RESULTS: D2 + CME was associated with less intraoperative bleeding loss, a greater number of lymph nodes harvested, and less time to first postoperative flatus, but the postoperative morbidity was similar. The 5-year DFS was 95.6% (95% CI 92.7-98.5%) and 90.4% (95% CI 85.5-95.3%) in the D2 + CME group and the D2 group, respectively, with a hazard ratio (HR) of 0.455 (95% CI 0.188-1.097; p = 0.071). In terms of recurrence patterns, local recurrence was more prone to occur in the D2 group (p = 0.031). Subgroup analysis indicated that for patients with T1b-3N0M0 GC, the 5-year DFS in the D2 + CME group was considerably greater than that in the D2 group (95.3% [95% CI 91.6-99.0%] vs. 87.6% [95% CI 80.7-94.5%], HR 0.369, 95% CI 0.138-0.983; log-rank p = 0.043). CONCLUSION: Laparoscopic D2 + CME for T1-3N0M0 GC is safe and feasible. Furthermore, it not only reduces the local recurrence rate but also improves the 5-year DFS in cases of T1b-3N0M0 GC.


Assuntos
Laparoscopia , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Excisão de Linfonodo , Linfonodos/patologia , Gastrectomia
14.
Front Surg ; 10: 1267477, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37942003

RESUMO

Background: Paravertebral block (PVB) has been increasingly popular for postoperative analgesia. However, few studies estimated the efficacy and safety of multiple PVB using thoracoscope-assisted technique for intraoperative analgesia and postoperative pain management for video-assisted thoracoscopic lobectomy (VATS LOBECTOMY). Methods: A total of 120 patients scheduled to undergo VATS LOBECTOMY were randomly assigned into two groups: a placebo group and a PVB group in a ratio of 1:2. Thoracoscopic-guided multi-point PVB was carried out with 0.5% ropivacaine (PVB group) or 0.9% NaCl (placebo group) at the beginning and the end of surgery. The primary endpoint was consumption of intraoperative opioid. Results: Consumption rate of intraoperative opioids was significantly lower in the PVB group (878.14 ± 98.37 vs. 1,432.20 ± 383.53 for remifentanil; 123.83 ± 17.98 vs. 266.42 ± 41.97 for fentanyl). Postoperatively, significantly longer duration of using patient-controlled intravenous analgesia for the first time, reduced times of analgesic pump pressing, and less rescue analgetic consumption were observed in the PVB group. Visual analog scale scores at rest and during exercising were significantly lower in the PVB group at all time points within the first 48 h after surgery. The PVB group was also associated with significantly higher total QoR-40 scores and lower incidence of analgesia-related adverse events. Conclusions: Thoracoscopic-guided multiple PVB was a simple and effective technique in controlling pain both intra- and postoperatively for VATS LOBECTOMY. It was also associated with the absence of detrimental effects attributed to opioid overuse and benefits of the early resumption of activity and physical function recovery. Therefore, this regional anesthesia technique should be advocated as part of a multimodal analgesia protocol for VATS LOBECTOMY.

15.
Cancer Immunol Res ; 11(10): 1400-1413, 2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37467346

RESUMO

Cholesterol is often enriched in tumor microenvironment (TME); however, its impact on disease progression varies in different tissues and cells. Monocytes/macrophages (Mφ) are major components and regulators of the TME and play pivotal roles in tumor progression and therapeutic responses. We aimed to investigate the profile, effects, and regulatory mechanisms of Mφ cholesterol metabolism in the context of human hepatocellular carcinoma (HCC). Here, we found that patients with high serum levels of cholesterol had shorter survival times and lower response rates to anti-PD-1 treatment. However, the cholesterol content in tumor-infiltrating monocytes/Mφ was significantly lower than that in their counterparts in paired nontumor tissues. The expression of the cholesterol efflux transporter, ABCA1, was upregulated in tumor monocytes/Mφ, and ABCA1 upregulation positively associated with decreased cellular cholesterol content and increased serum cholesterol levels. Mechanistically, autocrine cytokines from tumor-treated monocytes increased LXRα and ABCA1 expression, which led to the generation of immature and immunosuppressive Mφ. Although exogenous cholesterol alone had little direct effect on Mφ, it did act synergistically with tumor-derived factors to promote ABCA1 expression in Mφ with more immunosuppressive features. Moreover, high numbers of ABCA1+ Mφ in HCC tumors associated with reduced CD8+ T-cell infiltration and predicted poor clinical outcome for patients. Our results revealed that dysregulated cholesterol homeostasis, due to the collaborative effects of tumors and exogenous cholesterol, drives the generation of immunosuppressive Mφ. The selective modulation of cholesterol metabolism in Mφ may represent a novel strategy for cancer treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Macrófagos/metabolismo , Monócitos/metabolismo , Colesterol/metabolismo , Colesterol/farmacologia , Microambiente Tumoral
16.
Anal Chem ; 95(29): 10903-10912, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37439544

RESUMO

Application of the prostate-specific antigen (PSA) test, which measures PSA levels in blood, is standard in prostate cancer (PCa) screening. However, because PSA levels may be elevated for reasons other than PCa, it leads to high rates of misdiagnosis and overtreatment. Recently, alteration in the N-glycan sialylation of PSA, specifically increased levels of α2-3-linked N-acetylneuraminic acid (α2-3-Neu5Ac or α2-3-sialic acid), was identified as a potential biomarker for clinically significant PCa. Here, we introduce a robust top-down native mass spectrometry (MS) approach, performed using a combination of α2-3-Neu5Ac-specific and nonspecific neuraminidases and employing center-of-mass monitoring (CoMMon), for quantifying the levels of α2-3-Neu5Ac as a fraction of total N-linked Neu5Ac present on PSA extracted from blood serum. To illustrate the potential of the assay for clinical diagnosis and disease staging of PCa, the percentages of α2-3-Neu5Ac on PSA (%α23PSA) in the serum of low-grade (International Society of Urological Pathology Grade Group/GG1), intermediate-grade (GG2), and high-grade (GG3,4,5) PCa individuals were measured. We observed a high sensitivity (85.5%) and specificity (84.6%) for discrimination of GG1 from clinically significant GG2-5 patients when using a %α23PSA test cut-off of 28.0%. Our results establish that the %α23PSA in blood serum PSA, which can be precisely measured in a non-invasive manner with our dual neuraminidase native MS/CoMMon assay, can discriminate between clinically significant PCa (GG2-5) and low-grade PCa (GG1). Such discrimination has not been previously achieved and represents an important clinical need. This assay could greatly improve the standard PSA test and serve as a valuable PCa diagnostic tool.


Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Ácido N-Acetilneuramínico , Neoplasias da Próstata/patologia , Biomarcadores , Biópsia Líquida , Biópsia
17.
Eur J Surg Oncol ; 49(11): 106975, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37474342

RESUMO

BACKGROUND: There is no consensus on whether adjuvant chemotherapy (AC) is effective for hepatoid adenocarcinoma of the stomach (HAS). The aim of this study was to investigate the relationship between AC and the long-term prognosis of patients with HAS. METHODS: The clinicopathological data of 239 patients with primary HAS who underwent radical surgery from April 1, 2004 to December 31, 2019 in 14 centers in China were retrospectively analyzed. Patients were divided into the AC group (127 patients) and the nonadjuvant chemotherapy (NAC) group (112 patients). RESULTS: Kaplan‒Meier (KM) analysis showed that there were no significant differences in the 1-year3-year overall survival rate (OS) and 1-year, 3-year recurrence-free survival rate (RFS) between the AC group and the NAC group (1-year OS: 85.6% vs. 79.8%, 3-year OS: 59.8% vs. 62.4%, 1-year RFS: 69.8% vs. 74.4%, 3-year RFS: 57.2% vs. 55.9%, all P > 0.05). The subpopulation treatment effect pattern plots (STEPP) did not show treatment heterogeneity of AC in patients with HAS. The proportions of local recurrence and metastasis sites in the two groups were similar. Although the smoothed hazard curves of the NAC and AC groups crossed, the peak hazard time was later in the AC group (5.9 and 4.7 months), and the peak hazard rate was lower (0.032 and 0.038, P = 0.987). CONCLUSION: The current AC regimen may not significantly improve the survival of patients with HAS after radical surgery.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Quimioterapia Adjuvante , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia
18.
Sheng Wu Gong Cheng Xue Bao ; 39(4): 1684-1695, 2023 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-37154332

RESUMO

C-fos is a transcription factor that plays an important role in cell proliferation, differentiation and tumor formation. The aim of this study was to clone the goat c-fos gene, clarify its biological characteristics, and further reveal its regulatory role in the differentiation of goat subcutaneous adipocytes. We cloned the c-fos gene from subcutaneous adipose tissue of Jianzhou big-eared goats by reverse transcription-polymerase chain reaction (RT-PCR) and analyzed its biological characteristics. Using real-time quantitative PCR (qPCR), we detected the expression of c-fos gene in the heart, liver, spleen, lung, kidney, subcutaneous fat, longissimus dorsi and subcutaneous adipocytes of goat upon induced differentiation for 0 h to 120 h. The goat overexpression vector pEGFP-c-fos was constructed and transfected into the subcutaneous preadipocytes for induced differentiation. The morphological changes of lipid droplet accumulation were observed by oil red O staining and bodipy staining. Furthermore, qPCR was used to test the relative mRNA level of the c-fos overexpression on adipogenic differentiation marker genes. The results showed that the cloned goat c-fos gene was 1 477 bp in length, in which the coding sequence was 1 143 bp, encoding a protein of 380 amino acids. Protein structure analysis showed that goat FOS protein has a basic leucine zipper structure, and subcellular localization prediction suggested that it was mainly distributed in the nucleus. The relative expression level of c-fos was higher in the subcutaneous adipose tissue of goats (P < 0.05), and the expression level of c-fos was significantly increased upon induced differentiation of subcutaneous preadipocyte for 48 h (P < 0.01). Overexpression of c-fos significantly inhibited the lipid droplets formation in goat subcutaneous adipocytes, significantly decreased the relative expression levels of the AP2 and C/EBPß lipogenic marker genes (P < 0.01). Moreover, AP2 and C/EBPß promoter are predicted to have multiple binding sites. In conclusion, the results indicated that c-fos gene was a negative regulatory factor of subcutaneous adipocyte differentiation in goats, and it might regulate the expression of AP2 and C/EBPß gene expression.


Assuntos
Adipogenia , Cabras , Animais , Cabras/genética , Diferenciação Celular/genética , Adipogenia/genética , Regulação da Expressão Gênica , Proteínas/genética , Clonagem Molecular
19.
Surg Laparosc Endosc Percutan Tech ; 33(4): 339-346, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37235723

RESUMO

BACKGROUND: Both 3-dimensional (3D) laparoscopy and membrane anatomy are topics of great interest in the treatment of gastric cancer. The purpose of this study was to evaluate the safety, feasibility, and efficacy of 3D laparoscopic-assisted D2 radical gastrectomy for locally advanced gastric cancer (LAGC) under the guidance of membrane anatomy. PATIENTS AND METHODS: Retrospectively analyzed the clinical data of 210 patients who underwent 2-dimensional (2D)/3D laparoscopic-assisted D2 radical gastrectomy under the guidance of membrane anatomy for LAGC. Compared the differences between the two groups in surgical outcomes, postoperative recovery, postoperative complications, and 2-year overall survival and disease-free survival. RESULTS: The baseline data of the 2 groups were comparable ( P > 0.05). The amount of intraoperative bleeding in the 2D and 3D laparoscopy groups was 100.1 ± 48.75 mL and 74.29 ± 47.33 mL, respectively, with a significant difference between the two groups ( P < 0.001). The time to first exhaust and first liquid diet intake and length of postoperative hospital stay was shorter in the 3D laparoscopy group, with significant differences between the two groups [3 (3-3) days vs 3(3-2) days, P = 0.009; 7 (8-7) days vs 6 (7-6) days, P < 0.001; and 13 (15-11) days vs 10 (11-9) days, P < 0.001]. There were no significant differences in operation time, number of lymph node dissections, incidence of postoperative complications, or 2-year overall survival and disease-free survival between the two groups ( P > 0.05). CONCLUSIONS: Three-dimensional laparoscopic-assisted D2 radical gastrectomy for LAGC under the guidance of membrane anatomy is safe and feasible. It can reduce intraoperative bleeding, accelerate postoperative recovery, and does not increase operative complications, the long-term prognosis is similar to that of the 2D laparoscopy group.


Assuntos
Laparoscopia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Resultado do Tratamento , Estudos Retrospectivos , Gastrectomia/métodos , Excisão de Linfonodo/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
20.
Surg Endosc ; 37(6): 4990-5003, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37157036

RESUMO

OBJECTIVE: Retrospectively analyzed the short- and long-term efficacy between laparoscopic D2 lymphadenectomy plus regional complete mesogastrium excision (D2 + rCME) and traditional laparoscopic D2 in the treatment of patients with locally advanced gastric cancer (LAGC), in order to obtain more evidence for D2 + rCME gastrectomy. METHODS: A total of 599 LAGC patients who underwent laparoscopy-assisted radical gastrectomy from January 2014 to December 2019, including 367 cases in the D2 + rCME group and 232 cases in the D2 group. Intraoperative and postoperative clinicopathological parameters, postoperative complications and long-term survival in the two groups were statistically analyzed. RESULTS: No significant differences in the positive rate of mesogastric tumor deposits, the number of positive lymph nodes and postoperative length of stay were found between the two groups (P > 0.05). In the D2 + rCME group, intraoperative blood loss was significantly reduced (84.20 ± 57.64 ml vs. 148.47 ± 76.97 ml, P < 0.001), the time to first postoperative flatus and first liquid diet intake were significantly shortened (3[2-3] days vs. 3[3-3] days, P < 0.001; 7[7-8] days vs. 8[7-8] days, P < 0.001), and the number of lymph nodes dissected was greater (43.57 ± 16.52 pieces vs. 36.72 ± 13.83 pieces, P < 0.001). The incidence of complications did not significantly differ between the D2 + rCME group (20.7%) and D2 group (19.4%) (P > 0.05). Although there was no statistically difference in 3-year OS and DFS between the two groups. However, the trend was better in D2 + rCME group. In subgroup analysis, patients with positive tumor deposits (TDs) in the D2 + rCME group had significantly better 3-year DFS compared With D2 group (P < 0.05). CONCLUSION: Laparoscopic D2 + rCME is safe and feasible for the treatment of LAGC and is characterized by less bleeding, greater lymph node dissection and rapid recovery, without increasing postoperative complications. D2 + rCME group showed a better trend of long-term efficacy, especially significant beneficial for LAGC patients who with positive TDs.


Assuntos
Laparoscopia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Estudos Retrospectivos , Extensão Extranodal , Excisão de Linfonodo , Gastrectomia/efeitos adversos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA