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1.
BMC Cancer ; 24(1): 855, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39026264

RESUMEN

BACKGROUND: Retroperitoneal liposarcoma (RLPS) constitutes the majority of retroperitoneal sarcomas. While surgical resection remains the sole curative approach, determining the optimal surgical strategy for RLPS remains elusive. This study addresses the ongoing debate surrounding the optimal surgical strategy for RLPS. METHODS: We recruited 77 patients with RLPS who underwent aggressive surgical policies. Patients were categorized into three surgical subtypes: suprapancreatic RLPS, pancreatic RLPS, and subpancreatic RLPS. Our standardized surgical strategy involved resecting macroscopically uninvolved adjacent organs according to surgical subtypes. We collected clinical, pathological and prognostic data for analyses. RESULTS: The median follow-up was 45.5 months. Overall survival (OS) and recurrence-free survival (RFS) were significantly correlated with multifocal RLPS, pathological subtype, recurrent RLPS and histological grade (P for OS = 0.011, 0.004, 0.010, and < 0.001, P for RFS = 0.004, 0.001, < 0.001, and < 0.001, respectively). The 5-Year Estimate OS of well-differentiated liposarcoma (WDLPS), G1 RLPS, de novo RLPS and unifocal RLPS were 100%, 89.4%, 75.3% and 69.1%, respectively. The distant metastasis rate was 1.4%. The morbidity rates (≥ grade III) for suprapancreatic, pancreatic, and subpancreatic RLPS were 26.7%, 15.6%, and 13.3%, respectively. The perioperative mortality rate is 2.6%. CONCLUSIONS: Standardized aggressive surgical policies demonstrated prognostic benefits for RLPS, particularly for G1 RLPS, WDLPS, unifocal RLPS, and de novo RLPS. This approach effectively balanced considerations of adequate exposure, surgical safety, and thorough removal of all fat tissue. G1 RLPS, WDLPS, unifocal RLPS, and de novo RLPS could be potential indications for aggressive surgical policies.


Asunto(s)
Liposarcoma , Neoplasias Retroperitoneales , Humanos , Liposarcoma/cirugía , Liposarcoma/patología , Liposarcoma/mortalidad , Neoplasias Retroperitoneales/cirugía , Neoplasias Retroperitoneales/patología , Neoplasias Retroperitoneales/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Pronóstico , Estudios de Seguimiento , Recurrencia Local de Neoplasia/cirugía , Estudios Retrospectivos , Anciano de 80 o más Años
2.
Int J Clin Oncol ; 29(7): 1035-1043, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38652434

RESUMEN

BACKGROUND: Multivisceral en bloc resection with the ipsilateral kidney is commonly performed in patients with retroperitoneal liposarcoma (RLPS). We evaluated the effect of nephrectomy on short- and long-term outcomes in patients with RLPS. METHODS: Data from a prospectively maintained database of the Peking University Cancer Hospital Sarcoma Center between April 2011 and August 2022 were analyzed. We classified the RLPS patients who underwent surgery into nephrectomy group (NP) and non-nephrectomy group (non-NP). Patients were matched using a 1:1 propensity score to eliminate baseline differences between groups. Postoperative renal function outcomes, major morbidity, and mortality were analyzed to compare short-term outcomes after nephrectomy. Differences in local recurrence-free survival (LRFS) and overall survival (OS) were compared by Kaplan-Meier analysis with respect to oncological benefits. RESULTS: In the matched cohort, patients in the NP group had significantly higher postoperative eGFR and CKD stages, but none required dialysis. Patients between NP and non-NP had a comparable major morbidity (p = 0.820) and 60-day mortality (p = 0.475). Patients in the NP group had a higher 5-year LRFS rates than those in the non-NP group (34.5 vs. 17.8%, p = 0.015), and similar 5-year OS rates (52.4 vs. 47.1%, p = 0.401). Nephrectomy was an independent risk factor for LRFS, but not for major morbidity or OS. CONCLUSIONS: RLPS resection with nephrectomy is related to a mild progression of renal impairment; however, dialysis is rare. En bloc nephrectomy for complete resection of RLPS is safe and improves local control.


Asunto(s)
Liposarcoma , Nefrectomía , Puntaje de Propensión , Neoplasias Retroperitoneales , Humanos , Masculino , Femenino , Nefrectomía/métodos , Liposarcoma/cirugía , Liposarcoma/patología , Liposarcoma/mortalidad , Persona de Mediana Edad , Neoplasias Retroperitoneales/cirugía , Neoplasias Retroperitoneales/patología , Neoplasias Retroperitoneales/mortalidad , Anciano , Adulto , Estudios Retrospectivos , Hospitales de Alto Volumen , Estimación de Kaplan-Meier , Resultado del Tratamiento
3.
J Surg Oncol ; 127(4): 633-644, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36444482

RESUMEN

BACKGROUND AND OBJECTIVES: Resection of retroperitoneal sarcoma (RPS) en bloc with pancreas is challenging and controversial. This single-center retrospective study aimed to analyze the impact of pancreatic resection (PR) and its different types on short- and long-term outcomes in patients with RPS. METHODS: Data from 242 consecutive patients with RPS who underwent surgical treatment at the Peking University Cancer Hospital Sarcoma Center between January 2010 and February 2021 were analyzed. Out of these, 90 patients underwent PR, including pancreaticoduodenectomy (PD) in 31 and distal pancreatectomy (DP) in 59. RESULTS: Patients in the PR group had a higher major morbidity (37.8% vs. 14.5%) and mortality (8.9% vs. 1.3%) than those in the non-PR group, with a similar 5-year overall survival (OS) rate (46.9% vs. 53.6%). Patients in the PD and DP groups had a slight difference in major morbidity (48.4% vs. 32.2%), mortality (6.4% vs. 10.2%), and 5-year OS rates (43.3% vs. 49.3%). The PR type was not an independent risk factor for major morbidity or OS. CONCLUSIONS: PR in RPS resection was associated with increased morbidity and mortality with minimal influence on survival. Patients with RPS undergoing PD and DP showed slight differences in terms of safety and OS.


Asunto(s)
Neoplasias Pancreáticas , Neoplasias Retroperitoneales , Sarcoma , Humanos , Pancreatectomía , Estudios Retrospectivos , Sarcoma/cirugía , Neoplasias Retroperitoneales/cirugía , Resultado del Tratamiento , Neoplasias Pancreáticas/cirugía
4.
Pancreatology ; 22(1): 112-122, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34764022

RESUMEN

BACKGROUND: Whether coeliac axis resection (CAR) results from tumour topography or a prognostic factor for distal pancreatic ductal adenocarcinoma (PDAC) remains unclear. We aimed to compare the clinicopathological data between distal pancreatectomy with en bloc CAR (DP-CAR) and distal pancreatectomy plus splenectomy (DP-S) and analyse the prognostic factors. METHODS: We retrospectively analysed clinicopathological data from 102 patients who underwent distal pancreatectomy for PDAC and the factors affecting disease-free survival (DFS) and overall survival (OS). Of these patients, 45 and 57 underwent DP-CAR and DP-S, respectively. RESULTS: DP-CAR was associated with more operative challenges than DP-S: more portomesenteric vein resections (48.9% vs. 14.0%), longer operations (320 vs. 242 min), and greater estimated blood loss (EBL) (600 vs. 200 ml). DP-CAR had larger tumours (5 vs. 4 cm), more perineural invasion (91.1% vs. 73.7%), and more microscopically positive surgical margins (20% vs. 3.5%), compared to DP-S. The major complication was clinically relevant postoperative pancreatic fistula (20.6%). The median DFS was 15.8 months and the median OS was 20.1 months. CAR was not associated with DFS or OS. EBL>700 ml, lymphovascular invasion (LVI), and adjuvant chemotherapy independently affected DFS and OS. CONCLUSION: DP-CAR was associated with larger tumours and more surgical challenges but not with poorer DFS and OS than DP-S. CAR was more likely to result from tumour topography rather than from an adverse prognostic factor for resected distal PDAC. EBL>700 ml, LVI, and adjuvant chemotherapy were independent factors affecting the survival of patients with distal PDAC who underwent surgical resection.


Asunto(s)
Carcinoma Ductal Pancreático/cirugía , Arteria Celíaca/cirugía , Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía , Esplenectomía , Anciano , Carcinoma Ductal Pancreático/patología , Arteria Celíaca/patología , Quimioterapia Adyuvante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Complicaciones Posoperatorias , Pronóstico , Estudios Retrospectivos , Neoplasias Pancreáticas
5.
J Surg Oncol ; 126(7): 1288-1298, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35943840

RESUMEN

BACKGROUND AND OBJECTIVES: Retroperitoneal sarcomas (RPSs) are difficult to manage, rare malignant tumors. This single-center, retrospective study aimed to analyze the treatment algorithm and outcomes of aggressive surgical treatment in patients with primary and recurrent RPS. METHODS: Data of 242 consecutive patients with RPS who underwent surgical treatment at the Peking University Cancer Hospital Sarcoma Center between January 2010 and February 2021 were collected and analyzed. Indications for surgery were based on the treatment algorithm. RESULTS: A total of 145 patients with primary RPS and 97 with recurrent RPS were included. The recurrent cohort comprised more patients with multifocal tumors than the primary cohort (64.9% vs. 15.2%). R0/R1 resection was achieved in 94.5% and 81.4% of the primary and recurrent RPS cases, respectively. Major complication rates in the primary and recurrent cohorts were 17.9% and 30.9%, respectively. During a median follow-up of 51 months, the estimated 5-year overall survival, local recurrence, and distant metastasis rates for patients with primary and recurrent RPS were 61.0% versus 37.1%, 47.4% versus 71.3%, and 18.4% versus 17.6%, respectively. CONCLUSIONS: Aggressive surgical treatment achieved good local control and long-term survival in patients with primary RPS, whereas the prognosis in patients with recurrence were significantly worse.


Asunto(s)
Neoplasias Retroperitoneales , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Algoritmos , Recurrencia Local de Neoplasia/patología , Neoplasias Retroperitoneales/patología , Estudios Retrospectivos , Sarcoma/patología , Tasa de Supervivencia , Resultado del Tratamiento , Toma de Decisiones Clínicas
6.
Int J Med Sci ; 19(13): 1977-1988, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36438917

RESUMEN

Purpose: Retroperitoneal liposarcoma (RLPS) is a rare malignancy without effective treatment. Since current treatment for unresectable RLPS is unsatisfactory, immunotherapy and targeted therapy are urgently needed. Siglec-15 is a transmembrane protein highly homologous to PD-L1 and is involved in tumor immune escape. The biological function of Siglec-15 in RLPS, its prognostic relevance and its relationship with PD-L1 need to be further clarified. In this study, we aimed to explore the biological function of Siglec-15 in sarcomas through bioinformatics analysis, and we also evaluated Siglec-15 and PD-L1 expression in RLPS samples. The relationship between the expression of Siglec-15 and PD-L1 and their clinicopathological relevance and prognostic value were also investigated in clinical RLPS patients. Methods: The RNA sequencing data of 259 sarcoma cases and 48 RLPS cases from TCGA were used to analyze the Siglec-15 expression and the differentially expressed genes (DEG) related with Siglec-15 expression. In addition, DEGs were subsequently analyzed through the gene ontology (GO)/ Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network. Tumor specimens were obtained from 91 RLPS patients of our sarcoma center, and Siglec-15 and PD-L1 expression were evaluated using immunohistochemistry. The correlation between the expression level of these two markers as well as their correlation with clinicopathological factors and prognosis of RLPS patients was also assessed. Results: GEPIA analysis showed that the high expression of Siglec-15 was associated with poor sarcoma OS (P=0.034). A total of 682 differential genes were identified between the high and low expression groups of Siglec-15 in RLPS. Enrichment analysis of the KEGG pathway showed that Siglec-15 was related to the Hippo signaling pathway and the neuroactive ligand-receptor interaction. GO annotation analysis showed that the expression of Siglec-15 may thus be able to affect serine hydrolase activity, alongside signal receptor activator activity. The top 5 genes with the largest number of connection points are APOA1, F2, AHSG, AMBP, SERPINC1. In subsequent studies, we used 91 liposarcoma samples from our center for verification. Siglec-15 was expressed in 84.6% of RLPS cases, whereas PD-L1 was expressed in 17.6% of RLPS cases. A negative correlation was observed between Siglec-15 and PD-L1 expression (P=0.020). In this group of RLPS patients, high Siglec-15 expression was correlated with poorer disease-free survival (DFS) (P=0.021), and it was an independent predictor of DFS (hazard ratio: 2.298; 95% confidence interval: 1.154-4.576; P=0.018). However, we did not find a correlation between PD-L1 expression and overall survival or DFS in RLPS patients. Conclusion: The DEG and signaling pathways identified in the study could provide a preliminary understanding of the underlying molecular mechanisms of Siglec-15 in the development and progression of RLPS. High expression of Siglec-15 was a negative independent predictive factor for DFS of RLPS. The negative relationship between Siglec-15 and PD-L1 expression suggested that the Siglec-15 pathway might be an important supplement to PD-L1 treatment.


Asunto(s)
Liposarcoma , Neoplasias Retroperitoneales , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico , Humanos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biología Computacional , Liposarcoma/genética , Liposarcoma/metabolismo , Sarcoma/genética , Sarcoma/metabolismo , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico/genética , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico/metabolismo , Neoplasias Retroperitoneales/genética , Neoplasias Retroperitoneales/metabolismo
7.
Int J Med Sci ; 19(8): 1241-1253, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35928724

RESUMEN

Retroperitoneal liposarcoma (RLPS) is one of the most common subtypes of retroperitoneal soft tissue sarcomas. It is characterized by poor sensitivity to radiotherapy and chemotherapy and a low success rate of complete surgical resection. However, there are few reliable preclinical RLPS models for target discovery and therapy research. In this study, we aimed to establish RLPS patient-derived xenograft (PDX) models that are useful for biological research and preclinical drug trials. A total of 56 freshly resected RLPS tissues were subcutaneously transplanted into non-obese diabetic-severe combined immune deficient (NOD-SCID) mice, with subsequent xenotransplantation into second-generation mice. The tumor engraftment rate of first generation PDXs was 44.64%, and higher success rates were obtained from implantations of dedifferentiated, myxous, pleomorphic, high-grade liposarcomas and those with retroperitoneal organ infiltration. The first- and second- generation PDX models preserved the histopathological morphology, gene mutation profiles and MDM2 amplification of the primary tissues. PDX models can also provide the benefit of retaining original tumor biology and microenvironment characteristics, such as abnormal adipose differentiation, elevated Ki67 levels, high microvessel density, cancer-associated fibroblast presence, and tumor-associated macrophage infiltration. Overall survival (OS) and disease-free survival (DFS) of patients with successful first-generation PDX engraftment were significantly poorer than those with failed engraftment. Treatment with MDM2 inhibitor RG7112 significantly suppressed tumor growth of DDLPS PDX in mice. In conclusion, we successfully established RLPS PDX models that were histologically, genetically, and molecularly consistent with the original tissues. These models might provide opportunities for advancing RLPS tumor biology research, facilitating the development of novel drugs, particularly those targeting MDM2 amplification, adipose differentiation process, angiogenesis, cancer-associated fibroblasts, and so on.


Asunto(s)
Liposarcoma , Animales , Modelos Animales de Enfermedad , Xenoinjertos , Humanos , Liposarcoma/genética , Ratones , Ratones Endogámicos NOD , Ratones SCID , Neoplasias Retroperitoneales , Microambiente Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto
8.
Int J Clin Oncol ; 26(1): 145-153, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33068222

RESUMEN

BACKGROUND: Local recurrence is the most difficult postoperative challenge and the leading cause of death in patients with retroperitoneal liposarcoma (RLPS). We aimed to establish a postoperative nomogram exclusively focused on RLPS for predicting local recurrence-free survival (LRFS). METHODS: A cohort of 124 patients after surgical resection with curative intent in the Peking University Cancer Hospital Sarcoma Center were included in the study. Demographic, clinicopathologic, and treatment variables were analyzed using the Cox regression model. Significant clinically relevant variables in multivariable analysis were incorporated into the RLPS-specific nomogram. The discriminative ability and predictive accuracy of the nomogram were assessed by calculating the concordance index and drawing a calibration plot. RESULTS: At a median follow-up of 26.5 (interquartile range 10.9-39.4) months, 71 patients had recurrent disease. The 3-year and 5-year LRFS rates were 35.6% (95% confidence interval, 27.0-46.9%) and 28.2% (95% CI 15.8-38.6%), respectively. Multivariate analysis identified the French Federation of Cancer Centers Sarcoma Group (FNCLCC) grade and completeness of resection as independent predictors of LRFS. Variables included in our nomogram were: presentation status, multifocality, completeness of resection, histologic subtypes, and FNCLCC grade. The concordance index of our nomogram was 0.732 (95% CI 0.667-0.797) and the calibration plot was excellent. CONCLUSIONS: Our novel nomogram for patients with resected RLPS could improve recurrence risk stratification to explore molecular analysis associated with recurrence.


Asunto(s)
Liposarcoma , Nomogramas , China , Humanos , Liposarcoma/cirugía , Recurrencia Local de Neoplasia/cirugía , Pronóstico , Neoplasias Retroperitoneales , Estudios Retrospectivos
9.
J Sci Food Agric ; 101(2): 486-496, 2021 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-32643802

RESUMEN

BACKGROUND: Aspergillus flavus, a saprophytic fungus, is regularly detected in oil-enriched seeds. During colonization, this organism releases aflatoxins that pose a serious risk to food safety and human health. Therefore, an eco-friendly biological approach to inhibit the pathogen is desirable. RESULTS: Experimental results indicated that A. flavus spores could not germinate in potato dextrose broth culture medium, when the concentration of Sub3 exceeded 0.15 g L-1 . Morphological evaluation performed by flow cytometry and scanning electron microscopy indicated that spores were shrunken and pitted following Sub3 exposure. Physiological assessment using propidium iodide, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine iodide, 2,7-dichlorodihydrofluorescein diacetate and 4',6-diamidino-2-phenylindole staining revealed damaged cell membranes, decreased mitochondrial membrane potential, increased intracellular reactive oxygen species levels, and elevated large nuclear condensation and DNA fragmentation. Moreover, mitochondrial dehydrogenase activity was reduced by 29.42% and 45.48% after treatment with 0.1 and 0.15 g L-1 Sub3, respectively. Additionally, colonization capacity in peanut was significantly decreased, and the number of spores on seeds treated with Sub3 was decreased by 26.86% (0.1 g L-1 ) and 77.74% (0.15 g L-1 ) compared with the control group. CONCLUSION: Sub3 likely inhibits A. flavus by crossing the cell wall and targeting the cell membrane, disrupting mitochondrial energy metabolism, and inducing DNA damage, leading to spore death. Thus, Sub3 may provide a useful biocontrol strategy to control A. flavus growth in peanuts. © 2020 Society of Chemical Industry.


Asunto(s)
Antifúngicos/farmacología , Arachis/microbiología , Aspergillus flavus/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Mitocondrias/metabolismo , Aspergillus flavus/genética , Aspergillus flavus/crecimiento & desarrollo , Fragmentación del ADN/efectos de los fármacos , Metabolismo Energético/inmunología , Almacenamiento de Alimentos , Mitocondrias/efectos de los fármacos , Semillas/microbiología , Esporas Fúngicas/efectos de los fármacos , Esporas Fúngicas/genética , Esporas Fúngicas/crecimiento & desarrollo
10.
Int J Med Sci ; 17(18): 3073-3081, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33173428

RESUMEN

Patient-derived xenograft (PDX) models are effective preclinical cancer models that reproduce the tumor microenvironment of the human body. The methods have been widely used for drug screening, biomarker development, co-clinical trials, and personalized medicine. However, the low success rate and the long tumorigenesis period have largely limited their usage. In the present studies, we compared the PDX establishment between hepatocellular cancer (HCC) and metastatic liver cancer (MLC), and identified the key factors affecting the transplantation rate of PDXs. Surgically resected tumor specimens obtained from patients were subcutaneously inoculated into immunodeficient mice to construct PDX models. The overall transplantation rate was 38.5% (20/52), with the HCC group (28.1%, 9/32) being lower than MLC group (56.2%, 9/16). In addition, HCC group took significantly longer latency period than MLC group to construct PDX models. Hematoxylin and eosin staining results showed that the histopathology of all generations in PDX models was similar to the original tumor in all three types of cancer. The transplantation rate of PDX models in HCC patients was significantly associated with blood type (P=0.001), TNM stage (P=0.023), lymph node metastasis (P=0.042) and peripheral blood CA19-9 level (P=0.049), while the transplantation rate of PDX models in MLC patients was significantly associated with tumor size (P=0.034). This study demonstrates that PDX models can effectively reproduce the histological patterns of human tumors. The transplantation rate depends on the type of original tumor. Furthermore, it shows that the invasiveness of the original liver cancer affects the possibility of its growth in immunodeficient mice.


Asunto(s)
Carcinoma Hepatocelular/patología , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/secundario , Hígado/patología , Microambiente Tumoral , Animales , Carcinoma Hepatocelular/cirugía , Neoplasias Colorrectales/cirugía , Femenino , Hepatectomía , Humanos , Hígado/cirugía , Neoplasias Hepáticas/cirugía , Masculino , Ratones , Persona de Mediana Edad , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
11.
Appl Microbiol Biotechnol ; 103(23-24): 9515-9527, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31720772

RESUMEN

Aspergillus flavus is the main cause of postharvest agricultural commodity loss. In this study, puroindoline A (PINA) protein was expressed in Escherichia coli, purified, and its antifungal properties against A. flavus were characterized. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that the molecular weight of the recombinant PINA protein was approximately 44 kDa. PINA exerted a powerful antifungal effect against A. flavus at 42.42 µg/mL on potato dextrose agar culture medium. Flow cytometry and scanning electron microscopy revealed that the spore morphology was damaged by PINA exposure; spores were depressed and broken, suggesting that the cell wall was impaired. Transmission electron microscopy and propidium iodide staining illustrated significant changes in intracellular spore structure, indicating cell membrane damage. 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine iodide staining indicated decreased mitochondrial membrane potential. Large nuclear condensation and DNA fragmentation were detected by 4',6-diamidino-2-phenylindole staining. The expression of genes related to the cell wall, cell membrane, and spore germination significantly changed in PINA-treated cells; this illustrated the probable mode of PINA action on A. flavus through cell wall destruction and triggered cell membrane, mitochondrial, and DNA damage leading to cell death. The antifungal mechanism of wheat PINA protein on A. flavus has been demonstrated in this study, and has potential application in preventing postharvest loss in the agricultural industry.


Asunto(s)
Antifúngicos/farmacología , Aspergillus flavus/efectos de los fármacos , Escherichia coli/genética , Proteínas de Plantas/biosíntesis , Antifúngicos/aislamiento & purificación , Membrana Celular/efectos de los fármacos , Fragmentación del ADN , Proteínas de Plantas/genética , Proteínas de Plantas/farmacología , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/farmacología , Esporas Fúngicas/efectos de los fármacos , Triticum/microbiología
12.
Med Sci Monit ; 24: 961-969, 2018 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-29449525

RESUMEN

BACKGROUND There is no standard surgical approach for the management of retroperitoneal sarcoma. The aim of this clinical study was to describe the experience of an anterior approach to en bloc resection in left-sided retroperitoneal sarcoma with adjacent organ involvement. MATERIAL AND METHODS This retrospective clinical study included 25 patients who were diagnosed with left-sided retroperitoneal sarcoma and underwent tumor resection at a single center between May 2012 and July 2017. All patients had tumors that were adjacent to the left colon, pancreas, left kidney, left adrenal gland, and psoas major; some of the tumors were adjacent to the diaphragm, stomach, and small intestine. An anterior approach was used to remove the left-sided retroperitoneal tumor with the adhesive organs en bloc, an approach that is described in detail. The value of this surgical approach was evaluated based on the histopathological findings, postoperative complications, and patient follow-up. RESULTS The median number of resected organs, in addition to the retroperitoneal tumor, was 8 (range, 6-10). Complete macroscopic tumor resection was achieved in 23 cases (92%). Twenty-four patients (96%) had tumor infiltration of at least one organ or the surrounding fat. Three patients (12%) experienced Grade III and IV postoperative morbidities. The one-year disease-free survival rate was 91.3% among patients with macroscopically complete resections. The one-year overall survival rate was 83.2%. CONCLUSIONS In selected patients, left-sided retroperitoneal sarcoma associated with local organ involvement can be surgically managed using an anterior approach with en bloc resection of adjacent organs.


Asunto(s)
Especificidad de Órganos , Neoplasias Retroperitoneales/cirugía , Sarcoma/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Neoplasias Retroperitoneales/diagnóstico por imagen , Neoplasias Retroperitoneales/epidemiología , Sarcoma/diagnóstico por imagen , Sarcoma/epidemiología , Tomografía Computarizada por Rayos X
13.
Dig Surg ; 35(6): 532-538, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29275422

RESUMEN

AIMS: To compare the short- and long-term outcomes in patients with pancreatic benign or borderline neoplasm who underwent central pancreatectomy (CP) and distal pancreatectomy (DP). METHODS: The inclusion criteria were as follows: (1) single benign or low-grade malignant tumor; (2) tumor confined to the pancreatic neck or proximal body; and (3) tumor amenable to either CP or DP. Short and long-term outcomes, including complications, pancreatic exocrine and endocrine function, and quality of life (QoL) were analyzed retrospectively. RESULTS: Sixteen patients who underwent CP and 26 patients who underwent DP were included. The median follow-up period was 53 months (range 21-117 months). Patients undergoing CP were significantly more likely to experience complications (68.7 vs. 23%, p = 0.003) especially grade B/C postoperative pancreatic fistula (62.5 vs. 23%, p = 0.011) than those undergoing DP. During the long-term follow-up, 2 patients in the DP group developed new-onset diabetes mellitus, but no patient in CP group developed this condition (8 vs. 0%, p = 0.382). Evidence of exocrine insufficiency, including severe diarrhea or steatorrhea, was not observed in either group. Both groups were equally satisfied with the overall health status and overall QoL. CONCLUSION: CP is associated with excellent pancreatic function but a significantly increased postoperative morbidity and risk compared to DP. Therefore, the indication of CP should be chosen strictly.


Asunto(s)
Pancreatectomía/métodos , Fístula Pancreática/etiología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Adulto , Diabetes Mellitus/etiología , Insuficiencia Pancreática Exocrina/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Páncreas/fisiopatología , Pancreatectomía/efectos adversos , Satisfacción del Paciente , Complicaciones Posoperatorias/etiología , Calidad de Vida , Estudios Retrospectivos , Resultado del Tratamiento
14.
FEBS J ; 291(9): 2009-2022, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38380733

RESUMEN

Laminaripentaose (L5)-producing ß-1,3-glucanases can preferentially cleave the triple-helix curdlan into ß-1,3-glucooligosaccharides, especially L5. In this study, a newly identified member of the glycoside hydrolase family 64, ß-1,3-glucanase from Streptomyces pratensis (SpGlu64A), was functionally and structurally characterized. SpGlu64A shared highest identity (30%) with a ß-1,3-glucanase from Streptomyces matensis. The purified SpGlu64A showed maximal activity at pH 7.5 and 50 °C, and exhibited strict substrate specificity toward curdlan (83.1 U·mg-1). It efficiently hydrolyzed curdlan to produce L5 as the end product. The overall structure of SpGlu64A consisted of a barrel domain and a mixed (α/ß) domain, which formed an unusually wide groove with a crescent-like structure. In the two complex structures (SpGlu64A-L3 and SpGlu64A-L4), two oligosaccharide chains were captured and the triple-helical structure was relatively compatible with the wide groove, which suggested the possibility of binding to the triple-helical ß-1,3-glucan. A catalytic framework (ß6-ß9-ß10) and the steric hindrance formed by the side chains of residues Y161, N163, and H393 in the catalytic groove were predicted to complete the exotype-like cleavage manner. On the basis of the structure, a fusion protein with the CBM56 domain (SpGlu64A-CBM) and a mutant (Y161F; by site-directed mutation) were obtained, with 1.2- and 1.7-fold increases in specific activity, respectively. Moreover, the combined expression of SpGlu64A-CBM and -Y161F improved the enzyme activity by 2.63-fold. The study will not only be helpful in understanding the reaction mechanism of ß-1,3-glucanases but will also provide a basis for further enzyme engineering.


Asunto(s)
Oligosacáridos , Streptomyces , beta-Glucanos , Streptomyces/enzimología , Streptomyces/genética , Especificidad por Sustrato , beta-Glucanos/metabolismo , Oligosacáridos/metabolismo , Oligosacáridos/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Modelos Moleculares , Glucano 1,3-beta-Glucosidasa/metabolismo , Glucano 1,3-beta-Glucosidasa/genética , Glucano 1,3-beta-Glucosidasa/química , Secuencia de Aminoácidos , Glicósido Hidrolasas/genética , Glicósido Hidrolasas/metabolismo , Glicósido Hidrolasas/química , Dominio Catalítico , Cristalografía por Rayos X , Hidrólisis , Concentración de Iones de Hidrógeno , Cinética
15.
Clin Rheumatol ; 43(5): 1551-1558, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38578510

RESUMEN

OBJECTIVE: To identify risk factors for the development of non-thyroidal illness syndrome (NTIS) in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective analysis of 517 SLE patients and 1034 age-and sex-matched healthy population was conducted to compare the prevalence of NTIS in these two groups, and to analyze the laboratory and clinical characteristics of SLE patients with NTIS. Finally Logistic regression analysis was used to determine the risk factors for NTIS in SLE patients. RESULTS: The prevalence of NTIS in the SLE patients was significantly higher than that in controls (39.7% vs. 1.0%, P < 0.001). In SLE patients, compared with euthyroidism patients, NTIS patients exhibited higher levels of neutrophils, hepatic enzymes, kidney damage markers, inflammatory markers and SLE disease activity index (SLEDAI). They also had a higher incidence of organ insufficiency and positive antibodies such as anti-ds-DNA antibodies and anti-SSA antibodies. However, NTIS patients had lower levels of hemoglobin, lymphocytes, platelets, serum albumin, and complement. Additionally, NTIS patients had a shorter duration of lupus and lower utilization of disease-modifying antirheumatic drugs (DMARDs) (P < 0.05). Logistic regression analysis showed that elevated SLEDAI (OR = 1.060, 95%CI 1.022-1.099, P = 0.002), elevated systemic immune-inflammation index (SII) (OR = 1.003, 95%CI 1.001-1.007, P = 0.026), elevated erythrocyte sedimentation rate (ESR) (OR = 1.019, 95%CI 1.010-1.028, P < 0.001), and hepatic insufficiency (OR = 1.916, 95% CI 1.173-3.131, P = 0.009) were independent risk factors for the development of NTIS in SLE. DMARDs treatment (OR = 0.495, 95% CI 0.306-0.799, P < 0.001) was an independent protective factor for NTIS. CONCLUSIONS: Inflammatory activity in SLE patients is associated with the development of NTIS. Key Points • Inflammatory activity indexes such as SLEDAI, SII, and ESR are independent risk factors for NTIS in SLE patients.


Asunto(s)
Antirreumáticos , Lupus Eritematoso Sistémico , Humanos , Estudios Retrospectivos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Inflamación/complicaciones , Linfocitos , Antirreumáticos/uso terapéutico , Índice de Severidad de la Enfermedad
16.
J Cancer Res Clin Oncol ; 150(7): 343, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38981922

RESUMEN

PURPOSE: Radical resection of retroperitoneal liposarcoma (RLPS) may necessitate vascular resection and reconstruction. The study was conducted to assess surgical outcomes of surgery for RLPS with major vascular involvement. METHODS: Patients with RLPS who underwent surgical resection at the Sarcoma Center of Peking University Cancer Hospital between April 2011 and December 2022 were identified from a prospectively maintained database. Patients were classified into two groups: vascular resection and non-vascular resection groups. A propensity score matching analysis was performed to eliminate baseline differences between the groups. Surgical details and postoperative outcomes were analyzed. Furthermore, prognostic factors for local recurrence-free survival (LRFS) and overall survival (OS) were assessed. RESULTS: Overall, 199 patients were identified and the median follow-up period was 48 (interquartile range [IQR] 45-69) months. Vascular resection was performed in 42 (21%) patients, 25 of whom had vascular infiltration. A total of 39 patients had vascular replacement and 3 patients underwent partial resection (side-wall resection). Vascular resection was burdened by higher rates of major morbidity (38% vs. 14%, p < 0.001) and 30-day mortality (7.1% vs. 1.3%, p = 0.005). After propensity-matched analysis, patients who underwent vascular resection had 5-year LRFS and OS rates comparable to those without vascular involvement. Major vascular resection was not an independent risk factor for LRFS or OS. CONCLUSIONS: Although accompanied by increased risks of major morbidity and mortality, the major vascular resection enabled radical resection in patients with advanced RLPS, affording comparable 5-year LRFS and OS rates compared to those who did not.


Asunto(s)
Liposarcoma , Puntaje de Propensión , Neoplasias Retroperitoneales , Humanos , Neoplasias Retroperitoneales/cirugía , Neoplasias Retroperitoneales/patología , Neoplasias Retroperitoneales/mortalidad , Masculino , Femenino , Liposarcoma/cirugía , Liposarcoma/patología , Liposarcoma/mortalidad , Persona de Mediana Edad , Anciano , Procedimientos Quirúrgicos Vasculares/métodos , Adulto , Estudios Retrospectivos , Resultado del Tratamiento , Pronóstico , Hospitales de Alto Volumen
17.
Sci Total Environ ; 927: 172169, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38582126

RESUMEN

A large amount of metal tailings causes many environmental issues. Thus, the techniques for their ecological restoration have garnered extensive attention. However, they are still in the exploratory stage. Biological soil crusts (BSCs) are a coherent layer comprising photoautotrophic organisms, heterotrophic organisms and soil particles. They are crucial in global terrestrial ecosystems and play an equal importance in metal tailings. We summarized the existing knowledge on BSCs growing on metal tailings. The main photosynthetic organisms (cyanobacteria, eukaryotic algae, lichens, and mosses) of BSCs exhibit a high heavy metal(loid) (HM) tolerance. BSCs also have a strong adaptability to other adverse conditions in tailings, such as poor structure, acidification, and infertility. The literature about tailing BSCs has been rapidly increasing, particularly after 2022. The extensive literature confirms that the BSCs distributed on metal tailings, including all major types of metal tailings in different climatic regisions, are common. BSCs perform various ecological functions in tailings, including HM stress reduction, soil structure improvement, soil nutrient increase, biogeochemical cycle enhancement, and microbial community restoration. They interact and accelerate revegetation of tailings (at least in the temperate zone) and soil formation. Restoring tailings by accelerating/inducing BSC formation (e.g., resource augmentation and inoculation) has also attracted attention and achieved small-scale on-site application. However, some knowledge gaps still exist. The potential areas for further research include the relation between BSCs and HMs, large-scale quantification of tailing BSCs, application of emerging biological techniques, controlled laboratory experiments, and other restoration applications.


Asunto(s)
Restauración y Remediación Ambiental , Microbiología del Suelo , Contaminantes del Suelo , Suelo , Suelo/química , Contaminantes del Suelo/análisis , Restauración y Remediación Ambiental/métodos , Metales Pesados/análisis , Ecosistema , Metales/análisis , Minería
18.
Biosci Trends ; 17(1): 54-62, 2023 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-36775297

RESUMEN

Delayed gastric emptying (DGE) after aggressive resection of retroperitoneal sarcoma (RPS) has rarely been described. This study aimed to determine the incidence and characteristics of DGE after surgery for RPS and explore its potential risk factors. Patients with RPS who had undergone surgery between January 2010 and February 2021 were retrospectively analyzed. DGE was defined and graded according to the International Study Group of Pancreatic Surgery classification and classified as primary or secondary to other complications. Patients with clinically relevant DGE (crDGE, grade B+C) were compared to those with no or mild DGE (grade A). Multivariate logistic regression analysis of clinicopathological and surgical parameters was performed to identify risk factors for crDGE. Of the 239 patients studied, 69 (28.9%) had experienced DGE and 54 (22.6%) had experienced crDGE. Patients with primary and secondary DGE accounted approximately half and half. The most common concurrent complications included abdominal infection, postoperative pancreatic fistula, and abdominal bleeding. Patients with crDGE were more likely to have multifocal tumors and the liposarcoma subtype, with a larger tumor size, longer operating time, more resected organs, and a history of combined resection of the stomach, pancreas, small intestine, and/or colon. In multivariate analysis, the tumor size, operating time, and combined pancreatic resection were independent risk factors for crDGE. In conclusion, the current results indicated that approximately one-fourth of patients experienced DGE after aggressive surgery for RPS and that DGE was primary or secondary to other underlying conditions. A large tumor involving long, difficult surgery and combined pancreatic resection highly predicted the incidence of crDGE. The prevention and management of DGE remain challenging.


Asunto(s)
Gastroparesia , Neoplasias Retroperitoneales , Sarcoma , Humanos , Gastroparesia/epidemiología , Gastroparesia/etiología , Estudios Retrospectivos , Pancreaticoduodenectomía/efectos adversos , Incidencia , Factores de Riesgo , Complicaciones Posoperatorias/etiología , Sarcoma/complicaciones
19.
Acta Crystallogr D Struct Biol ; 78(Pt 6): 735-751, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35647921

RESUMEN

Prolyl oligopeptidases (POPs) are atypical serine proteases that are unique in their involvement in the maturation and degradation of prolyl-containing peptide hormones and neuropeptides. They are potential pharmaceutical targets for the treatment of several neurodegenerative disorders, such as Alzheimer's disease. In this study, the catalytic and substrate-regulatory mechanisms of a novel bacterial POP from Microbulbifer arenaceous (MaPOP) were investigated. The crystal structure revealed that the catalytic triad of MaPOP was covered by the central tunnel of an unusual ß-propeller domain. The tunnel not only provided the sole access to the active site for oligopeptides, but also protected large structured peptides or proteins from accidental proteolysis. The enzyme was able to cleave angiotensin I specifically at the carboxyl side of the internal proline residue, but could not hydrolyze long-chain bovine insulin B in vitro. Like the ligand-free structure, MaPOP bound to the transition-state analog inhibitor ZPR was also in a closed state, which was not modulated by the common `latching loop' found in other POPs. The substrate-assisted catalytic mechanism of MaPOP reported here may represent a common mechanism for all POPs. These results may facilitate a better understanding of the catalytic behavior of POPs under physiological conditions.


Asunto(s)
Alteromonadaceae , Prolil Oligopeptidasas , Animales , Catálisis , Bovinos , Gammaproteobacteria , Simulación de Dinámica Molecular , Serina Endopeptidasas/química
20.
Biosci Trends ; 15(6): 382-389, 2022 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-34840236

RESUMEN

The occurrence of peritoneal sarcomatosis (PS) in patients with retroperitoneal sarcoma (RPS) indicates a poor prognosis. However, the appropriate treatment modality remains unclear. This study aimed to identify its prognostic factors and further explore the role of macroscopically complete excision (CE) in the management of PS. A retrospective database was established to evaluate patients with RPS who underwent resection between January 2011 and January 2019. Univariate and multivariate survival analyses were performed to analyze the prognostic factors and identify the population that will optimally benefit from CE. This study included a total of 49 patients with PS from 211 patients with RPS, and 34 (69.4%) patients of whom with PS underwent CE successfully. The median follow-up time was 36.0 months. There were 8 patients excluded because of loss to follow-up (n = 4) or death from complications within 90 days postoperatively (n = 4). The CE group had a marginally better prognosis compared to the macroscopically incomplete excision (IE) group (median disease-specific survival: 20 months vs. 8 months). Multivariate survival analysis demonstrated that completeness of operation (CE vs. IE) was the only independent prognostic factor in PS patients (P = 0.042). There was no significant difference in the overall complications between the CE and IE groups (P = 0.205). In conclusion, completeness of macroscopical excision is an independent prognostic predictor of PS. If technically possible, CE is a feasible strategy to improve the prognosis of selected patients with PS.


Asunto(s)
Neoplasias Retroperitoneales , Sarcoma , Humanos , Estudios Retrospectivos , Sarcoma/cirugía , Tasa de Supervivencia
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