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1.
Front Oncol ; 14: 1347248, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38505594

RESUMEN

Objective: Given high risks of major bleeding during retroperitoneal sarcoma(RPS) surgeries, severe complications and deaths are common to see perioperatively. Thus, effective anesthetic management is the key point to ensuring the safety of patients. This study aimed to introduce anesthesia management and mortalities in RPS patients receiving massive blood transfusions during surgeries. Methods: Records of RPS surgeries under general anesthesia from January 2016 through December 2021 were retrospectively retrieved from our database. Patients who received massive blood transfusions (MBT) exceeding 20 units in 24h duration of operations were finally included in this study. Demographics, modalities of anesthesia management, blood loss, transfusion, peri-anesthesia biochemical tests as well as morbidities and mortalities were collected. Risk factors of postoperative 60d mortality were determined through logistic regression in uni-and multi-variety analysis using the statistics software STATA 17.0. Results: A total of 70 patients (male 31) were included. The mean age was 50.1 ± 15.8 years. All patients received combined resections of sarcoma with involved organs under general anesthesia. Mean operation time and anesthesia time were 491.7 ± 131.1mins and 553.9 ± 132.6mins, respectively. The median intraoperative blood loss was 7000ml (IQR 5500,10000ml). Median red blood cells (RBC) and fresh frozen plasma (FFP) transfusion were 25.3u (IQR 20,28u), and 2400ml (IQR 2000,3000ml), respectively. Other blood products infusions included prothrombin complex concentrate (PCCs), fibrinogen concentrate (FC), platelet(plt) and albumin(alb) in 82.9% (58/70), 88.6% (62/70), 81.4% (57/70) and 12.9% (9/70) of patients. The postoperative severe complication rate(Clavien-Dindo grade≥3a) was 35.7%(25/70). A total of 7 patients (10%) died during the postoperative 60-day period. BMI, volumes of crystalloid infusion in anesthesia, and hemoglobin and lactate levels at the termination of operation were found significantly associated with postoperative occurrence of death in univariate analysis. In logistic multivariate analysis, extended anesthesia duration was found associated with postoperative venous thrombosis embolism (VTE) and severe complication. The lactate level at the immediate termination of the operation was the only risk factor related to perioperative death (p<0.05). Conclusion: RPS patients who endure MBT in surgeries face higher risks of death postoperatively, which needs precise and effective anesthesia management in high-volume RPS centers. Increased blood lactate levels might be predictors of postoperative deaths which should be noted.

2.
Front Med ; 2023 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-38157196

RESUMEN

Retroperitoneal liposarcoma (RLPS) is the main subtype of retroperitoneal soft sarcoma (RSTS) and has a poor prognosis and few treatment options, except for surgery. The proteomic and metabolic profiles of RLPS have remained unclear. The aim of our study was to reveal the metabolic profile of RLPS. Here, we performed proteomic analysis (n = 10), metabolomic analysis (n = 51), and lipidomic analysis (n = 50) of retroperitoneal dedifferentiated liposarcoma (RDDLPS) and retroperitoneal well-differentiated liposarcoma (RWDLPS) tissue and paired adjacent adipose tissue obtained during surgery. Data analysis mainly revealed that glycolysis, purine metabolism, pyrimidine metabolism and phospholipid formation were upregulated in both RDDLPS and RWDLPS tissue compared with the adjacent adipose tissue, whereas the tricarboxylic acid (TCA) cycle, lipid absorption and synthesis, fatty acid degradation and biosynthesis, as well as glycine, serine, and threonine metabolism were downregulated. Of particular importance, the glycolytic inhibitor 2-deoxy-D-glucose and pentose phosphate pathway (PPP) inhibitor RRX-001 significantly promoted the antitumor effects of the MDM2 inhibitor RG7112 and CDK4 inhibitor abemaciclib. Our study not only describes the metabolic profiles of RDDLPS and RWDLPS, but also offers potential therapeutic targets and strategies for RLPS.

3.
BMC Surg ; 23(1): 88, 2023 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-37046258

RESUMEN

BACKGROUND: Aggressive angiomyxoma (AAM) is a rare mesenchymal tumor that mostly arises from the pelvic and perineal soft tissues. Few studies reported its characteristics and outcomes previously due to its rarity and challenges of treatments. This study aimed to investigate the clinical characteristics as well as surgical and short-term survival outcomes of primary abdominopelvic AAM. METHODS: Medical records of patients who were admitted to surgery with pathological confirmation of primary abdominopelvic AAM at Peking University International Hospital from January 2016 through December 2021 were retrospectively retrieved from our retroperitoneal tumor database. Demographics, operative outcomes and pathological findings were collected. Patients received followed-up routinely after the surgery. Survival probabilities were calculated and determined through Kaplan-Meier analysis. RESULTS: A total of 12 consecutive patients (male/female 4:8) were included in this study. The median age was 45 years old. The clinical presentation varied among individuals, consisting of 2 abdominal discomforts, 4 constipations, 1 lumbago, 1 prolonged menstruation, and 1 buttock swelling. R0/R1 resection was achieved in 100% of patients. Postoperatively, 50% of patients developed various complications including 3 fistulas and 3 wound infections. No operative mortality was observed. Histopathology of all patients was suggestive of AAM. Immunohistochemistry was done with a 91.7% positive rate for estrogen and progesterone receptors. The median recurrence-free survival time was 38 months. There were no cases of deceased or presented with distal metastasis during a median of 42 months' follow-up. CONCLUSIONS: The clinical manifestations of abdominopelvic AAM are mostly atypical. Surgical resection with curative intents remains the mainstay treatment of this disease, which was strongly suggested in experienced sarcoma centers due to the high probability of severe postoperative complications. In addition, long-term follow-up is necessary due to the high rate of local recurrences.


Asunto(s)
Mixoma , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Pelvis/patología , Derivación y Consulta , Mixoma/diagnóstico , Mixoma/cirugía , Recurrencia Local de Neoplasia/cirugía
5.
J Transl Med ; 21(1): 26, 2023 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-36641471

RESUMEN

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a deadly gastrointestinal malignancy, and chemotherapy resistance is a key factor leading to its poor prognosis. M2 tumor-associated macrophages (M2-TAMs) may be an important cause of chemoresistance in ESCC, but its exact mechanism is still unclear. METHODS: In order to study the role of M2-TAMs in ESCC chemoresistance, CCK-8, clone formation assay, flow cytometric apoptosis assay, qRT-PCR, western blotting, and serum-free sphere formation assays were used. In vivo animal experiments and human ESCC tissues were used to confirm the findings. RESULTS: In vitro and in vivo animal experiments, M2-TAMs reduced the sensitivity of ESCC cells to cisplatin. Mechanistically, M2-TAMs highly secreted TGF-ß1 which activated the TGFßR1-smad2/3 pathway to promote and maintain the stemness characteristic of ESCC cells, which could inhibit the sensitivity to cisplatin. Using TGFß signaling inhibitor SB431542 or knockdown of TGFßR1 could reverse the cisplatin resistance of ESCC cells. In 92 cases of human ESCC tissues, individuals with a high density of M2-TAMs had considerably higher levels of TGF-ß1. These patients also had worse prognoses and richer stemness markers. CONCLUSION: TGF-ß1 secreted from M2-TAMs promoted and maintained the stemness characteristic to induce cisplatin resistance in ESCC by activating the TGFß1-Smad2/3 pathway.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Animales , Humanos , Carcinoma de Células Escamosas de Esófago/patología , Cisplatino/farmacología , Cisplatino/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/patología , Línea Celular Tumoral , Proliferación Celular
6.
Ann Rheum Dis ; 82(5): 688-697, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36720581

RESUMEN

OBJECTIVES: Retroperitoneal fibrosis (RPF) is a rare autoimmune disease with fibrous tissue growth and inflammation in retroperitoneum. Its current treatments involve long-term uptake of glucocorticoids (e.g., prednisone) for controlling inflammation; however, side effects are common. We strived for an improved therapy for fibrosis remission while reducing side effects. METHODS: We surveyed gene-disease-drug databases and discovered that mammalian target of rapamycin (mTOR) was a key signalling protein in RPF and the mTOR inhibitor compound sirolimus affected many RPF pathways. We designed a therapy combining a gradual reduction of prednisone with a long-term, stable dosage of sirolimus. We then implemented a single-arm clinical trial and assessed the effects in eight RPF patients at 0, 12 and 48 weeks of treatment by measuring fibrous tissue mass by CT, markers of inflammation and kidney functions by lab tests, immune cell profiles by flow cytometry and plasma inflammatory proteins by Olink proteomics. RESULTS: With the combined therapy, fibrous tissue shrunk about by half, markers of acute inflammation reduced by 70% and most patients with abnormal kidney functions had them restored to normal range. Molecularly, fibrosis-related T cell subsets, including TH2, TH17 and circulating TFH cells, were reduced and tumour necrosis factor and related cytokines restored to healthy levels. No severe long-term side effects were observed. CONCLUSIONS: Our combined therapy resulted in significant fibrosis remission and an overall regression of the immune system towards healthy states, while achieving good tolerance. We concluded that this new therapy had the potential to replace the steroid monotherapy for treating RPF.


Asunto(s)
Fibrosis Retroperitoneal , Humanos , Fibrosis Retroperitoneal/tratamiento farmacológico , Prednisona/uso terapéutico , Sirolimus/uso terapéutico , Fibrosis , Inflamación , Serina-Treonina Quinasas TOR
7.
Ann Surg ; 278(2): 267-273, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35866666

RESUMEN

OBJECTIVE: The Transatlantic Australasian Retroperitoneal Sarcoma Working Group conducted a retrospective study on the disease course and clinical management of ganglioneuromas. BACKGROUND: Ganglioneuromas are rare tumors derived from neural crest cells. Data on these tumors remain limited to case reports and single-institution case series. METHODS: Patients of all ages with pathologically confirmed primary retroperitoneal, intra-abdominal, and pelvic ganglioneuromas between January 1, 2000, and January 1, 2020, were included. We examined demographic, clinicopathologic, and radiologic characteristics, as well as clinical management. RESULTS: Overall, 328 patients from 29 institutions were included. The median age at diagnosis was 37 years with 59.1% of patients being female. Symptomatic presentation comprised 40.9% of cases, and tumors were often located in the extra-adrenal retroperitoneum (67.1%). At baseline, the median maximum tumor diameter was 7.2 cm. One hundred sixteen (35.4%) patients underwent active surveillance, whereas 212 (64.6%) patients underwent resection with 74.5% of operative cases achieving an R0/R1 resection. Serial tumor evaluations showed that malignant transformation to neuroblastoma was rare (0.9%, N=3). Tumors undergoing surveillance had a median follow-up of 1.9 years, with 92.2% of ganglioneuromas stable in size. With a median follow-up of 3.0 years for resected tumors, 84.4% of patients were disease free after resections, whereas recurrences were observed in 4 (1.9%) patients. CONCLUSIONS: Most ganglioneuromas have indolent disease courses and rarely transform to neuroblastoma. Thus, active surveillance may be appropriate for benign and asymptomatic tumors particularly when the risks of surgery outweigh the benefits. For symptomatic or growing tumors, resection may be curative.


Asunto(s)
Ganglioneuroma , Neuroblastoma , Neoplasias Retroperitoneales , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Femenino , Adulto , Masculino , Estudios Retrospectivos , Ganglioneuroma/cirugía , Neoplasias Retroperitoneales/cirugía , Sarcoma/cirugía , Sarcoma/patología , Progresión de la Enfermedad
8.
Radiat Oncol ; 17(1): 215, 2022 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-36578082

RESUMEN

BACKGROUND: Neoadjuvant radiotherapy (NRT) for resectable retroperitoneal sarcoma (RPS) has been shown to be systematically feasible. Whether NRT has equivalent or better clinical effects compared to surgery alone for RPS patients remains controversial. METHODS: We performed a systematic literature search of PubMed, Web of Science, Embase, ASCO Abstracts, and Cochrane library databases for studies in humans with defined search terms. Articles were independently assessed by 2 reviewers, and only randomized controlled trials and cohort studies were included. The hazard ratios (HRs) of overall survival (OS), recurrence-free survival (RFS), and local recurrence (LR) were extracted from included studies. Heterogeneity among study-specific HRs was assessed by the Q statistic and I2 statistic. Overall HR was assessed by random-effects or fixed-effects models. Publication bias was tested by Begg's tests, and the quality of each study was assessed with the Newcastle Ottawa Scale. RESULTS: A total of 12 eligible studies with 7778 resectable RPS patients were finally included in this study. The pooled analysis revealed the distinct advantages of NRT as compared to surgery alone, including longer OS (HR = 0.81, P < 0.001), longer RFS (HR = 0.58, P = 0.04), and lower LR (HR = 0.70, P = 0.03). No evidence of publication bias was observed. CONCLUSION: NRT is likely to be beneficial for resectable RPS patients in terms of OS and RFS. However, more multicenter clinical trials are needed to confirm these findings.


Asunto(s)
Neoplasias Retroperitoneales , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Estudios Multicéntricos como Asunto , Terapia Neoadyuvante , Neoplasias Retroperitoneales/radioterapia , Neoplasias Retroperitoneales/cirugía , Sarcoma/radioterapia , Sarcoma/cirugía
9.
J Coll Physicians Surg Pak ; 32(9): 1212-1215, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36089724

RESUMEN

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare and aggressive inflammatory myofibroblastic tumour (IMT) variant. This report identifies the first case of EIMS with leukemoid reaction. This is also the first case in which pancreatic infiltration occurred from the disease onset. A 14-year male patient presented with an 18×18×10 cm mass at the retroperitoneal space and a white blood cell (WBC) count of 85×109/L. The mass and the invaded tissues were surgically removed with tumour-free margins. Histopathology and bone marrow aspiration confirmed the diagnosis of EIMS with leukemoid reaction. The tumour recurred with hepatic and pulmonary metastasis one month after the surgery. WBC count also increased progressively with the tumour recurrence. There is no consensus on the treatment of EIMS. Since ALK rearrangement presents in all the EIMS cases, surgical resection combined with crizotinib or other targeted drugs may improve the prognosis. Key Words: Sarcoma, Soft tissue neoplasms, Leukemoid reaction, Crizotinib.


Asunto(s)
Reacción Leucemoide , Sarcoma , Neoplasias de los Tejidos Blandos , Crizotinib/uso terapéutico , Humanos , Reacción Leucemoide/diagnóstico , Reacción Leucemoide/etiología , Masculino , Recurrencia Local de Neoplasia , Sarcoma/diagnóstico , Sarcoma/cirugía
10.
Artículo en Inglés | MEDLINE | ID: mdl-36100250

RESUMEN

Background: Retroperitoneal schwannomas are rare. The purpose of this study was to present our experience with the diagnosis and treatment of 67 such tumors. Methods: Retrospective analysis of 67 patients with retroperitoneal schwannoma admitted to Peking University International Hospital from 2015 to 2021. Results: 67 patients presented with retroperitoneal schwannomas, 37 cases had no obvious clinical symptoms. 62 cases were completely excised, 5 cases were subtotal resection, 7 cases were combined with organ resection. The intraoperative blood loss was 300ml (20-9000ml), the tumor maximum size was 9cm (2.5-26cm), post-complication occurred in 6 cases (9.0%). Compared with abdominal retroperitoneal tumors, pelvic retroperitoneal tumors had larger tumor volume, more bleeding, higher proportion of block resection, and longer postoperative hospitalization time (P<0.05). The residual mass progressed slowly in 5 patients with subtotal resection, and no obvious malignant transformation occurred. Conclusion:Complete resection of schwannoma can achieve a good long-term prognosis. Patients with residual tumor after surgery progress slowly and rarely become malignant. We recommend early resection after the discovery of a pelvic retroperitoneal schwannoma. Keywords: Schwannoma; Retroperitoneal neoplasms; Postoperative complications.

11.
Ann Transl Med ; 10(14): 785, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35965811

RESUMEN

Background: Complete resection (CR) serves as the standard of surgical treatment for retroperitoneal liposarcoma (RPLS). Unfortunately, even at referral centers, recurrence rates are high, and CR may not address multifocal diseases, which are a common phenomenon in RPLS. We sought to retrospectively compare the clinical outcomes of RPLS patients treated with total (ipsilateral) retroperitoneal lipectomy (TRL) and CR. Because TRL remove potentially multifocal tumors in the fat, patients may have a better prognosis than CR. Methods: Patients with primary/first-recurrent RPLS who had been treated at 5 referral centers were recruited from December 2014 to June 2018. Multivariable Cox regression analyses were conducted to determine the effects of demographic, operative, and clinicopathological variables on the following primary endpoints: local recurrence (LR), local recurrence-free survival (LRFS), and overall survival (OS). Results: A total of 134 patients were enrolled in this retrospective study, 53 of whom underwent TRL, and 81 of whom underwent CR. The 2 groups were comparable in terms of age, gender, presentation (primary vs. first-recurrent RPLS), number of tumors (unifocal vs. multifocal) at presentation, and Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade. The TRL group had higher levels of preoperative hemoglobin (Hb) (13 vs. 12.5 g/dL; P=0.008) and a lower amount of intraoperative blood loss (400 vs. 500 mL; P=0.034), but there were no significant differences in the length of hospital stay (23 vs. 22 d; P=0.47) or complications (32 vs. 30; P=0.82) between the 2 groups. In a subset of patients with multifocal tumors at initial presentation, OS was more prolonged in those treated with TRL than those treated with CR (P=0.0272). Based on the multivariable analysis, primary liposarcoma and a low FNCLCC grade were associated with decreased LR and improved OS. Conclusions: TRL is a safe procedure that positively affects the OS of patients with multifocal RPLS. This novel strategy deserves further investigation in prospective studies.

12.
Cell Commun Signal ; 20(1): 128, 2022 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-36008839

RESUMEN

BACKGROUND: Retroperitoneal liposarcoma (RPLS) is a specific soft tissue sarcoma with a high recurrence rate. The short isoform of transient receptor potential cation channel subfamily M member 2 (TRPM2-S) plays an important role in the regulation of reactive oxygen species (ROS). However, the association between TRPM2-S and RPLS and its underlying mechanisms remains unclear. METHODS: The expression of both TRPM2-S and TRPM2-L in RPLS tissues was verified by kimmunohistochemistry (IHC). The regulation on Ca2+ influx by TRPM2-S was evaluated by Fluo-4 AM staining. The effect of TRPM2-S on cell proliferation and apoptosis was tested by 5-Ethynyl-2'-deoxyuridine (EdU) staining and Flow cytometry respectively. The level of cellular ROS was assessed by the DCFH-DA probe. Different concentrations of H2O2 were used to provide oxidative stress on RPLS cells. The underlying mechanisms were further explored by Western blotting. RESULTS: The IHC assays showed that TRPM2-S, but not TRPM2-L, was prognostic in RPLS. Low TRPM2-S level was associated with poor disease-free survival (DFS). Calcium influx signal intensity was significantly decreased under TRPM2-S overexpression, which resulted in a decrease in the levels of FOXO3a and PTEN. Correspondingly, the levels of pERK, pAKT, pP65, pGSK-3ß, Bcl-2, and ß-catenin were upregulated, and cellular ROS was gently increased under TRPM2-S overexpression. Moreover, TRPM2-S slightly promoted cell proliferation and inhibited apoptosis of RPLS cell lines under normoxia, but largely increased apoptosis rates under oxidative stress. The cleaved caspase3 was significantly upregulated by TRPM2-S overexpression under oxidative stress. N-Acetyl-L-cysteine (NAC), a small molecule antioxidant, could largely rescue RPLS cells from the apoptosis induced by H2O2. CONCLUSION: TRPM2-S exerts Janus-faced effects in RPLS by increasing the ROS levels via inhibition on FOXO3a, which promotes cell proliferation under normoxia but induces apoptosis under oxidative stress. Video abstract.


Asunto(s)
Canales Catiónicos TRPM , Apoptosis , Calcio/metabolismo , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/farmacología , Liposarcoma , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Retroperitoneales
13.
Technol Cancer Res Treat ; 21: 15330338221087831, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35440255

RESUMEN

Background: Prophylactic ureteral catheters placement (PUCP) was advocated as an effective strategy for decreasing ureteral morbidities in colorectal surgeries. However, whether it should be routinely used prior to primary retroperitoneal liposarcoma (PRLS) surgeries remains unknown. Methods: It was a retrospective study, conducted at a tertiary sarcoma center. Medical records of patients with PRLS undergoing surgeries from January 2015 through December 2018 were reviewed. Primary endpoint was the rate of ureteral morbidities during and after retroperitoneal liposarcoma resection procedures. Univariate and multivariate analyses determined risk factors associated with ureteral injury (UI) in patients undergoing surgeries. Results: A total of 55 patients of PRLS were included. Fourteen (25.5%) patients underwent PUCP, with 1 UI (7.1%) identified. In 41 patients with no PUCP, 15 (36.6%) exhibited UIs during and post surgeries. There were significant improvements of UIs in group PUCP, compared with patients without PUCP (P < .05). Resection surgeries combined with colectomy and tumor-ureter relationship were 2 risk factors significantly associated to UIs (P < .01). Conclusions: PUCP might be an effective way of preventing UIs in patients with PRLS. It could be suggested especially in patients with ureter encased by tumor or anticipated colectomy during the surgical process.


Asunto(s)
Liposarcoma , Neoplasias Retroperitoneales , Uréter , Humanos , Neoplasias Retroperitoneales/cirugía , Estudios Retrospectivos , Uréter/lesiones , Uréter/cirugía , Catéteres Urinarios
14.
Antioxid Redox Signal ; 36(1-3): 1-14, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34409847

RESUMEN

Aims: Hyperhomocysteinemia (HHcy) has been considered as a risk factor for cardiovascular disease, Alzheimer's disease, nonalcoholic fatty liver, and many other pathological conditions. Vitamin B6, Vitamin B12, and folate have been used to treat HHcy in clinics. However, at present, clinical therapies of HHcy display unsatisfactory effects. Here, we would like to explore a new mechanism involved in homocysteine (Hcy) metabolic disorders and a novel target for HHcy treatment. The key enzymes involved in Hcy metabolism deserve more insightful investigation. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the intracellular Hcy metabolism. Until now, the effect of post-translational modification on the bioactivity of MTHFR still remains unclear. This study aimed at exploring the relationship between MTHFR S-sulfhydration and its bioactivity, and at identifying the contribution of an elevated Hcy level on MTHFR bioactivity. Results: By both in vivo and in vitro studies, we observed the following results: (i) The bioactivity of MTHFR was positively associated with its S-sulfhydration level; (ii) MTHFR was modified at Cys32, Cys130, Cys131, Cys193, and Cys306 by S-sulfhydration under physiological conditions; (iii) Hydrogen sulfide (H2S) deficiency caused the decrease of MTHFR S-sulfhydration level and bioactivity in HHcy, which resulted in further aggravation of HHcy; and (iv) H2S donors reversed the decreased bioactivity of MTHFR in HHcy, thus reducing the excessive Hcy level. Innovation and Conclusion: Our study suggested that H2S could improve MTHFR bioactivity by S-sulfhydration, which might provide a candidate therapeutic strategy for HHcy. Antioxid. Redox Signal. 36, 1-14.


Asunto(s)
Hiperhomocisteinemia , Metilenotetrahidrofolato Reductasa (NADPH2) , Ácido Fólico/uso terapéutico , Homocisteína , Humanos , Hiperhomocisteinemia/complicaciones , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/metabolismo , Oxidación-Reducción , Vitamina B 12/fisiología , Vitamina B 12/uso terapéutico
15.
Radiat Oncol ; 16(1): 196, 2021 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-34620197

RESUMEN

BACKGROUND: Adjuvant therapy is a promising treatment to improve the prognosis of cancer patients, however, the evidence base driving recommendations for adjuvant radiotherapy (ART) or chemotherapy (ACT) in retroperitoneal sarcomas (RPS) primarily hinges on observational data. The aim of this study was to evaluate the effectiveness of adjuvant therapy in the management of RPS patients. METHODS: We searched PubMed, Web of Science, Embase, ASCO Abstracts, and Cochrane Library for comparative studies (until December 2020) of adjuvant therapy versus surgery alone. Data on the following endpoints were evaluated: overall survival (OS), local recurrence (LR), recurrence-free survival (RFS), and metastasis-free survival (MFS). Data were summarized as hazard ratios (HR) with 95% confidence intervals (CI). Risk of bias of studies was assessed with Begg's and Egger's tests. RESULTS: A total of 15 trials were eligible, including 9281 adjuvant therapy and 21,583 surgery alone cases (20 studies for OS, six studies for RFS, two studies for LR, and two studies for MFS). Meta-analysis showed that ART was associated with distinct advantages as compared to surgery alone, including a longer OS (HR = 0.80, P < 0.0001), a longer RFS (HR = 0.61, P = 0.0002), and a lower LR (HR = 0.31, P = 0.005). However, this meta-analysis failed to demonstrate a benefit of ACT for RPS patients, including OS (HR = 1.11, P = 0.19), RFS (HR = 1.30, P = 0.09) and MFS (HR = 0.69, P = 0.09). In the sensitivity analysis, ACT was associated with a worse OS (HR = 1.19, P = 0.0002). No evidence of publication bias was observed. CONCLUSIONS: Overall, the quality of the evidence was moderate for most outcomes. The evidence supports that ART achieved a generally better outcome as compared to surgery alone.


Asunto(s)
Neoplasias Retroperitoneales/terapia , Sarcoma/terapia , Quimioterapia Adyuvante , Humanos , Sesgo de Publicación , Radioterapia Ayuvante , Neoplasias Retroperitoneales/mortalidad , Sarcoma/mortalidad
17.
Free Radic Biol Med ; 164: 20-33, 2021 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-33418108

RESUMEN

Sp1-CSE-H2S pathway plays an important role in homocysteine-metabolism, whose disorder can result in hyperhomocysteinemia. H2S deficiency in hyperhomocysteinemia has been reported, while the underlying mechanism and whether it in turn affects the progress of hyperhomocysteinemia are unclear. This study focused on the post-translational modification of Sp1/CSE and revealed four major findings: (1) Homocysteine-accumulation augmented CSE's nitration, inhibited its bio-activity, thus caused H2S deficiency. (2) H2S deficiency inhibited the S-sulfhydration of Sp1, down-regulated CSE and decreased H2S further, which in turn weakened CSE's own S-sulfhydration. (3) CSE was S-sulfhydrated at Cys84, Cys109, Cys172, Cys229, Cys252, Cys307 and Cys310, among which the S-sulfhydration of Cys172 and Cys310 didn't affect its enzymatic activity, while the S-sulfhydration of Cys84, Cys109, Cys229, Cys252 and Cys307 was necessary for its bio-activity. (4) H2S deficiency trapped homocysteine-metabolism into a vicious cycle, which could be broken by either blocking nitration or restoring S-sulfhydration. This study detected a new mechanism that caused severe hyperhomocysteinemia, thereby provided new therapeutic strategies for hyperhomocysteinemia.


Asunto(s)
Sulfuro de Hidrógeno , Hiperhomocisteinemia , Cistationina gamma-Liasa/genética , Humanos , Sulfuro de Hidrógeno/metabolismo , Hiperhomocisteinemia/genética , Procesamiento Proteico-Postraduccional , Factor de Transcripción Sp1
18.
Transl Cancer Res ; 10(5): 2247-2254, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-35116542

RESUMEN

BACKGROUND: To compare the differences in the diagnosis of retroperitoneal tumors among multi-slice spiral computed tomography (MSCT), magnetic resonance imaging (MRI), and ultrasound (US). METHODS: Sixty cases of retroperitoneal tumors admitted in our hospital from January 2016 to January 2019 were collected and related data were analyzed. After admission, patients were examined by MSCT, MRI, and US, and the pathological results of the patients were used as the controls. The differences in the diagnosis of retroperitoneal tumors were compared with the results of MSCT, MRI, and US. RESULTS: Thirteen cases of benign tumors were diagnosed by MSCT, 47 cases were malignant, and 1 case was false benign, with diagnosis accuracy, sensitivity and specificity of 98.33%, 97.92% and 92.30%, respectively. Thirteen cases of benign tumors were diagnosed by MRI, 47 cases of malignant tumors, and 1 case was false benign, with diagnosis accuracy, sensitivity and specificity of 98.33%, 97.92%, and 92.30%, respectively. Fourteen cases of benign tumor were diagnosed by US, 46 cases were malignant, and 2 cases was false benign, with diagnosis accuracy, sensitivity and specificity of 96.67%, 97.92%, and 85.71%, respectively. There were no statistically significant differences in the accuracy, sensitivity, and specificity of MSCT, MRI, and US in the diagnosis of retroperitoneal tumors (P>0.05). CONCLUSIONS: MSCT, MRI, and US tests are highly accurate, sensitive, and specific in the diagnosis of retroperitoneal tumors.

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