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1.
Oncol Lett ; 28(1): 300, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38765791

RESUMO

Invasive papillary carcinoma (IPC) of the breast is a rare form of cancer. The current report documents a case of IPC characterized by a large tumor size and skin involvement. Surgical exploration revealed no evidence of axillary lymph node metastasis in breast cancer. Due to financial constraints, the patient opted solely for anastrozole endocrine therapy at a dosage of 1 mg/day for a period of 5 years post-surgery, foregoing other treatments such as radiotherapy and chemotherapy. Since discharge, 2.5 years have passed, during which the patient has been followed up via phone every 3 months, showing a good prognosis. A literature review indicated that IPC is prevalent amongst the elderly population and can be misdiagnosed due to its morphological, cytomorphological and immunophenotypic overlap with other types of papillary neoplasms. This tumor exhibits a more favorable prognosis compared with IDC, primarily attributed to its advantageous gene and molecular expression patterns, coupled with its decreased invasiveness. Despite limited evidence-based research on the treatment of IPC, the present case report, albeit with limitations, underscores the importance of avoiding over-treatment and suggests the feasibility of combining surgery with endocrine therapy for IPC.

2.
Front Oncol ; 14: 1374091, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601769

RESUMO

Invasive papillary carcinoma is a rare form of breast cancer that is more likely to occur in postmenopausal women. Previous studies have been limited to case reports and small retrospective studies, leading to low awareness of this type of tumor and difficult clinical management. According to the available literature, invasive papillary carcinoma exhibits unique pathological features and biological behaviors. Invasive papillary carcinoma is mostly luminal type, with a low rate of lymph node metastasis, which underlies its favorable prognosis. The effectiveness of adjuvant therapy in reducing tumor burden and improving prognosis in patients with invasive papillary carcinoma remains uncertain. Due to the rarity of the lesion, conducting prospective clinical trials is impractical. The use of biological models, such as organoids, can help alleviate the impact of the scarcity of this condition on research. In addition, invasive papillary carcinoma is affected by specific genomic events, and more extensive studies of gene expression profiling may provide molecular-level insights to make optimal therapeutic decisions.

3.
Gerontology ; 70(5): 491-498, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38479368

RESUMO

INTRODUCTION: We analyzed the effect of dexmedetomidine (DEX) as a local anesthetic adjuvant on postoperative delirium (POD) in elderly patients undergoing elective hip surgery. METHODS: In this study, 120 patients undergoing hip surgery were enrolled and randomly assigned to two groups: fascia iliaca compartment block with DEX + ropivacaine (the Y group, n = 60) and fascia iliaca compartment block with ropivacaine (the R group, n = 60). The primary outcomes: presence of delirium during the postanesthesia care unit (PACU) period and on the first day (D1), the second day (D2), and the third day (D3) after surgery. The secondary outcomes: preoperative and postoperative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), occurrence of insomnia on the preoperative day, day of operation, D1 and D2; HR values of patients in both groups before iliac fascia block (T1), 30 min after iliac fascia block (T2), at surgical incision (T3), 20 min after incision (T4), when they were transferred out of the operating room (T5) and after leaving the recovery room (T6) at each time point; VAS for T1, PACU, D1, D2; the number of patients requiring remedial analgesics within 24 h after blockade and related complications between the two groups. RESULTS: A total of 97 patients were included in the final analysis, with 11 and 12 patients withdrawing from the R and Y groups, respectively. The overall incidence of POD and its incidence in the PACU and ward were all lesser in the Y group than in the R group (p < 0.05). Additionally, fewer cases required remedial analgesia during the PACU period, and more vasoactive drugs were used for maintaining circulatory system stability in the Y group as compared to the R group (p < 0.05). At the same time, the incidence of intraoperative and postoperative bradycardia in the Y group was higher than that in the R group, accompanied by lower postoperative CRP and ESR (all p < 0.05). CONCLUSION: Ultrasound-guided high fascia iliaca compartment block with a combination of ropivacaine and DEX can reduce the incidence of POD, the use of intraoperative opioids and postoperative remedial analgesics, and postoperative inflammation in elderly patients who have undergone hip surgery, indicating that this method could be beneficial in the prevention and treatment of POD.


Assuntos
Anestésicos Locais , Dexmedetomidina , Procedimentos Cirúrgicos Eletivos , Bloqueio Nervoso , Ropivacaina , Humanos , Dexmedetomidina/administração & dosagem , Masculino , Idoso , Feminino , Anestésicos Locais/administração & dosagem , Bloqueio Nervoso/métodos , Ropivacaina/administração & dosagem , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Cirúrgicos Eletivos/métodos , Fáscia , Idoso de 80 Anos ou mais , Delírio do Despertar/prevenção & controle , Delírio do Despertar/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Quadril/cirurgia , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos
4.
Int J Biol Macromol ; 264(Pt 2): 130695, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458278

RESUMO

The fibrillogenesis of amyloid ß-protein (Aß) gradually accumulates to form neurotoxic Aß aggregates in the human brain, which is the direct cause of Alzheimer's disease (AD) related symptoms. There are currently no effective therapies for AD. Brazilin, a natural polyphenol, inhibits Aß fibrillogenesis, disrupts the mature fibrils and alleviates the corresponding cytotoxicity, but it also has the high toxic. Therefore, brazilin-7-2-butenoate (B-7-2-B), a brazilin derivative, was designed and synthesized. B-7-2-B exhibited lower toxicity and stronger inhibitory effect on Aß aggregation than brazilin. B-7-2-B could prevent the formation of Aß fibrils and oligomers, and depolymerize pre-formed aggregates in a dose-dependent manner. Furthermore, B-7-2-B prominently alleviated the cytotoxicity and the oxidative stress induced by Aß aggregates in PC12 cells. The protective impacts of B-7-2-B were further demonstrated by using the Caenorhabditis elegans model, including decreasing the extent of Aß aggregation, improving the motility and sensation disorders. Eventually, B-7-2-B was proven to be no apparent damage to worms. In summarize, it can be concluded that B-7-2-B has the potential as a drug for treating AD.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Animais , Ratos , Humanos , Peptídeos beta-Amiloides/toxicidade , Caenorhabditis elegans , Benzopiranos/farmacologia , Células PC12 , Doença de Alzheimer/tratamento farmacológico , Amiloide
6.
Front Psychiatry ; 14: 1288117, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928911

RESUMO

Objective: We retrospectively analyzed the occurrence of postoperative delirium following hip surgery and the associated risk factors. The aim was to establish a clinical foundation for preventing postoperative delirium after hip surgery. Methods: We retrospectively selected elderly patients who had hip surgery at our hospital between January 2022 and August 2022. We included patients who experienced delirium in the observation group and those who did not encounter delirium in the control group. We then proceeded to compare various indicators among these two groups of patients. Results: We analyzed a total of 97 cases of hip surgery, and among them, 32 cases experienced postoperative delirium, resulting in an incidence rate of 32.9%. Various factors were found to be linked to the development of postoperative delirium, including age, height, gender (male), preoperative erythrocyte sedimentation rate (ESR), postoperative ESR, preoperative lactate levels, pain scores on the first day after surgery, type of surgical procedure, and the occurrence of delirium in the post-anesthesia care unit (PACU delirium). Additionally, it was observed that 75% of patients who had PACU delirium also experienced postoperative delirium. Conclusion: Postoperative delirium in patients who have hip surgery had an incidence rate of 32.9%. This phenomenon is linked to various factors that pose a risk, such as the patient age, height, gender, preoperative ESR levels, postoperative ESR levels, preoperative lactate levels, pain scores on the day following surgery, and the specific surgical procedure performed. The likelihood of experiencing delirium increases by 12% for every additional 10 years in patient age. Additionally, the occurrence of delirium in the PACU is a strong indicator of the likelihood of experiencing postoperative delirium.

7.
PeerJ ; 11: e15013, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37070095

RESUMO

Background: Approximately 10-20% of patients diagnosed with prostate cancer (PCa) evolve into castration-resistant prostate cancer (CRPC), while nearly 90% of patients with metastatic CRPC (mCRPC) exhibit osseous metastases (BM). These BM are intimately correlated with the stability of the tumour microenvironment. Purpose: This study aspires to uncover the metabolism-related genes and the underlying mechanisms responsible for bone metastatic prostate cancer (BMPCa). Methods: Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets of PCa and BM were analyzed through R Studio software to identify differentially expressed genes (DEGs). The DEGs underwent functional enrichment via Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), with key factors screened by a random forest utilized to establish a prognostic model for PCa. The study explored the relationship between DEGs and the stability of the immune microenvironment. The action and specificity of CRISP3 in PCa was validated through western blot analysis, CCK-8 assay, scratch assay, and cellular assay. Results: The screening of GEO and TCGA datasets resulted in the identification of 199 co-differential genes. Three DEGs, including DES, HBB, and SLPI, were selected by random forest classification model and cox regression model. Immuno-infiltration analysis disclosed that a higher infiltration of naïve B cells and resting CD4 memory T cells occurred in the high-expression group of DES, whereas infiltration of resting M1 macrophages and NK cells was greater in the low-expression group of DES. A significant infiltration of neutrophils was observed in the high-expression group of HBB, while greater infiltration of gamma delta T cells and M1 macrophages was noted in the low-expression group of HBB. Resting dendritic cells, CD8 T cells, and resting T regulatory cells (Tregs) infiltrated significantly in the high-expression group of SLPI, while only resting mast cells infiltrated significantly in the low-expression group of SLPI. CRISP3 was established as a critical gene in BMPCa linked to DES expression. Targeting CRISP3, d-glucopyranose may impact tumour prognosis. During the mechanistic experiments, it was established that CRISP3 can advance the proliferation and metastatic potential of PCa by advancing epithelial-to-mesenchymal transition (EMT). Conclusion: By modulating lipid metabolism and maintaining immunological and microenvironmental balance, DES, HBB, and SLPI suppress prostate cancer cell growth. The presence of DES-associated CRISP3 is a harbinger of unfavorable outcomes in prostate cancer and may escalate tumor proliferation and metastatic capabilities by inducing epithelial-mesenchymal transition.


Assuntos
Neoplasias Ósseas , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/genética , Próstata , Neoplasias Ósseas/genética , Metabolismo dos Lipídeos , Linfócitos B , Microambiente Tumoral/genética
8.
Rev Esp Enferm Dig ; 115(12): 723-724, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36866839

RESUMO

MSP is a rare and atypical form of benign granulomatous inflammation characterised by tumour-like local proliferation of spindle-shaped histiocytes containing acid-fast positive mycobacteria, which should be differentiated from neoplastic lesions. A 26-year-old Chinese man complained an intermittent and mild right lower abdominal pain for 5 months in May 2022.Histopathology of biopsy samples showed Mycobacterial spindle cell pseudotumor (MSP). The test of Mycobacterium tuberculosis detected by polymerase chain reaction using intestinal tissue slice was negative. The metagenomic next-generation sequencing (BGI-Shenzhen) using formalin-fixation and paraffin-embedded intestine samples confirmed Mycobacterium tuberculosis complex (MTBC).


Assuntos
Soropositividade para HIV , Mycobacterium tuberculosis , Peritonite Tuberculosa , Tuberculose Gastrointestinal , Tuberculose dos Linfonodos , Masculino , Humanos , Adulto , Tuberculose Gastrointestinal/complicações , Tuberculose Gastrointestinal/diagnóstico
9.
Int Wound J ; 20(5): 1393-1401, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36336969

RESUMO

To explore the curative effect of insulin external application on burn wounds of diabetic patients with different depths. A retrospective analysis of 114 diabetic burn patients in the First Hospital of Hebei Medical University from June 2019 to June 2022. According to the different treatment methods, they were divided into study group (insulin therapy) and control group (conventional therapy) with 57 cases in each. The wound healing time, dressing changes, scar healing after wound healing and adverse events were compared between two groups. Pain level, serum inflammatory factors, vascular endothelial growth factor (VEGF) and oxidative stress factors before and after treatment were compared. The wound healing time (17.23 ± 2.18 vs 20.31 ± 2.09 days) and the number of dressing changes (7.01 ± 1.23 vs 8.93 ± 1.32 times) in study group were significantly lower than those in control group (P < 0.05). Before treatment, there was no difference in pain level, VEGF, interleukin-1 (IL-1), tumour necrosis factor-α (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD) between two groups (P > 0.05). However, the pain level, scar healing, IL-1, TNF-a and MDA in study group were significantly lower than those in control group after treatment (P < 0.05). And the VEGF and SOD in study group was significantly higher than that in control group (P < 0.05). External application of insulin can shorten the wound healing time of diabetic patients with different depths, reduce the number of dressing changes, promote scar healing after wound healing, relieve pain and reduce the level of inflammatory factors, which is worthy of clinical promotion.


Assuntos
Queimaduras , Diabetes Mellitus , Humanos , Insulina/uso terapêutico , Cicatriz , Fator A de Crescimento do Endotélio Vascular/metabolismo , Estudos Retrospectivos , Queimaduras/terapia , Interleucina-1/uso terapêutico , Superóxido Dismutase/metabolismo
10.
World J Surg Oncol ; 20(1): 395, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36510186

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) with haemangioblastoma-like characteristics is a type of RCC reported in recent years. RCC with (angio) leiomyomatous stroma (RCCLMS) was included as a provisional entity of the 2016 World Health Organization (WHO) classification. RCC with haemangioblastoma-like characteristics and leiomyomatous stroma is extremely rare. This is the first report of a rare tumour harbouring TSC2 and SETD2 variations. CASE PRESENTATION: The patient was a 38-year-old woman who presented with discomfort in the area of her right kidney. Ultrasound and enhanced CT showed a right renal mass, and clear cell renal cell carcinoma (CCRCC) was suspected; hence, robot-assisted laparoscopic nephron-sparing partial nephrectomy was performed. Gross examination revealed a well-circumscribed tumour measuring 2.0 cm × 1 cm × 0.7 cm under the renal capsule adjacent to the stripping edge that was greyish yellow and greyish red in colour. Histologic examination showed that the tumour consisted of three different structures: a CCRCC-like region, a haemangioblastoma-like region, and a focal leiomyomatous stroma component. Based on immunohistochemistry, the CCRCC-like region was diffusely strongly positive for AE1/AE3, vimentin, CAIX, PAX8, PAX2, CK7, and CAM5.2, partly positive for HNF1α, and negative for CD10, α-inhibin, NSE, S-100, CD34, and TFE3. The haemangioblastoma-like area was diffusely positive for vimentin, CAIX; partly positive for PAX8, PAX2, α-inhibin, and S-100; mostly positive for NSE; and slightly positive for HNF1α; the CD34 staining highlighted the complex capillary network. The Ki67 index was approximately 1-2% in the two above areas, and the leiomyomatous stroma was strongly positive for SMA. The whole-exon sequencing (WES) showed TSC2 and SETD2 variations. There was no progression after 18 months of follow-up. CONCLUSION: We report for the first time a unique case of RCC with haemangioblastoma-like features and leiomyomatous stroma accompanied by rare molecular abnormalities. Whether this is a new tumour entity or a variant of clear cell carcinoma remains to be determined. The biological behaviour and clinical characteristics need to be further examined.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Leiomioma , Humanos , Feminino , Adulto , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/genética , Neoplasias Renais/cirurgia , Neoplasias Renais/diagnóstico , Imuno-Histoquímica , Nefrectomia , Leiomioma/patologia , Biomarcadores Tumorais/genética
11.
Front Oncol ; 12: 983996, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36248999

RESUMO

Occurrences of breast cancer and thyroid cancer metachronously or synchronously are common for women, but axillary lymph node metastasis from both cancers is rarely seen. We report a patient who had two metastatic lymph nodes from papillary thyroid carcinoma after axillary lymph node dissection with mastectomy. Papillary thyroid carcinoma diagnosis was ensured after thyroidectomy. A literature review revealed that even the co-occurrence of breast cancer and thyroid cancer is not rare, but the etiology behind this phenomenon is not elucidated well. Genetic disorders, thyroid dysfunction, and hormone receptors may be relevant. Considering the rareness of axillary lymph node metastasis of thyroid cancer, adjuvant therapy and surgery treatment for this kind of case should be considered elaborately.

13.
Front Surg ; 9: 755298, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360431

RESUMO

Objective: This study was designed to investigate whether it is useful and necessary to add a T2 level thoracic paravertebral block (TPVB) based on brachial-cervical plexus block to avoid incomplete anesthesia in elderly patients undergoing deltopectoral approach proximal humeral fracture (PHF) surgery. Materials and Methods: This study involved 80 patients scheduled for PHF surgery who were randomized to receive either IC block (combined interscalene brachial plexus with superficial cervical plexus block) or ICTP block (T2 TPVB supplemented with IC block). The primary outcome was the success rate of regional anesthesia. The patient who experienced incomplete block was administered with intravenous remifentanil for rescue, or conversion to general anesthesia (GA) if remifentanil was still ineffective. Secondary outcomes included requirements of rescue anesthesia, sensory block of the surgical region, the incidence of adverse reactions, and block procedure-related complications. Results: The success rate of regional anesthesia in the ICTP group was higher compared with the IC group (77.5 vs. 52.5%, p = 0.019). Intravenous remifentanil was required in 32.5% of patients in the IC group and 17.5% in the ICTP group, respectively. Conversion to GA was performed in 15% of patients in the IC group and 5% in the ICTP group. Sensory block at the medial proximal upper arm was achieved in 85% of patients in the ICTP group, whereas 10% in the IC group (p < 0.001). There was no difference between the groups with respect to the incidence of intraoperative adverse reactions. No block-related complications occurred in either group. Conclusion: Adding a T2 TPVB is helpful to decrease, but not absolutely avoid the occurrence of incomplete regional anesthesia during PHF surgery in elderly patients. However, considering the potential risks, it is not an ideal option while a minor dose of remifentanil can provide a satisfactory rescue effect. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03919422.

14.
Front Surg ; 9: 715422, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35252320

RESUMO

BACKGROUND: Combined anesthesia can be a promising option for hip surgery when neuraxial anesthesia is contraindicated. Lumbar and sacral plexus blocks, and femoral nerve and lateral femoral cutaneous (LFC) nerve blocks in combination with general anesthesia (GA) are commonly used in elderly patients undergoing arthroplasty for hip fracture surgery. However, no study has compared these two anesthetic strategies in the perioperative period. METHODS: A total of 41 elderly patients scheduled for arthroplasty for hip fracture surgery were randomized into group A (n = 20) and group B (n = 21). Group A received femoral nerve block, LFC nerve blocks, and GA, and group B received lumbar plexus block, sacral plexus block, and GA. Primary outcomes were incidences of hemodynamic events and changes in blood pressure (BP) and heart rate (HR). Secondary outcomes included time and drug consumption, infusion and bleeding volume, eyes opening time after surgery, and postoperative quality recovery rate. RESULTS: Compared with group B, group A showed a lower incidence of intraoperative hypotension (p < 0.001), higher BP [including mean arterial pressure (MAP), systolic BP (SBP), and diastolic BP (DBP)] following induction (IN), and higher HR from mid-surgery. Time required for nerve blockade (p < 0.001) and ephedrine consumption was significantly shorter in group A (p < 0.001), while sufentanil consumption was higher as compared to group B (p = 0.002). No significant differences in other intraoperative parameters and postoperative quality recovery rate were reported during the observation. CONCLUSION: Our pilot data indicate that compared with lumbar and sacral plexus blocks, femoral nerve and LFC nerve blocks may provide more stable intraoperative hemodynamics and a comparable postoperative recovery for elderly patients undergoing arthroplasty for hip fracture under GA. Further studies with a larger sample size are needed to derive stronger evidence.

16.
J Cell Mol Med ; 25(18): 8821-8835, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34363324

RESUMO

Non-small-cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer cases. TBC1D23, a member of the TBC/RABGAP family, is widely expressed in human tissues; however, its role in NSCLC is currently unknown. Immunohistochemical analysis was conducted on 173 paraffin-embedded lung tissue sections from patients with NSCLC from 2014 to 2018 at the First Affiliated Hospital of China Medical University. MTT, colony formation assay, cell cycle assay, scratch assay, transwell assay, Western blotting and real-time PCR were employed on multiple NSCLC cell lines modified to knock down or overexpress TBC1D23/RAB11A. Immunoprecipitation, immunoprecipitation-mass spectrometry, immunofluorescence and flow cytometry were performed to explore the interaction between TBC1D23 and RAB11A and TBC1D23 involvement in the interaction between RAB11A and ß1 integrin in the para-nucleus. TBC1D23 was correlated with tumour size, differentiation degree, metastasis, TNM stage and poor prognosis. TBC1D23 was involved in the interaction between RAB11A and ß1 integrin in the para-nucleus, thus activating the ß1 integrin/FAK/ERK signalling pathway to promote NSCLC. Furthermore, TBC1D23 promoted NSCLC progression by inducing cell proliferation, migration and invasion. This study indicated the relationship between TBC1D23 expression and the adverse clinicopathological characteristics of patients with NSCLC, suggesting that TBC1D23 may be an important target for NSCLC treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Integrina beta1/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico
17.
Endocr Pract ; 27(5): 401-407, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33934750

RESUMO

OBJECTIVE: Poorly differentiated thyroid carcinoma (PDTC) is the primary cause of death in patients with nonanaplastic follicular cell-derived thyroid carcinoma. We purposed to identify the clinical and pathological characteristics of PDTC and their relationship with prognosis. METHODS: A retrospective analysis was conducted on patients diagnosed with PDTC at our institution from 2010 to 2018. All of their histopathology slides were reviewed by 2 experienced pathologists based on the Turin criteria. Furthermore, information regarding clinical characteristics, pathological characteristics, treatment strategy, and follow-up events were collected. The Kaplan-Meier method was used for survival analysis, while the log-rank test was used to compare survival curves. Then, the Cox proportional hazards model was used to perform univariate and multivariate analyses. RESULTS: Twenty-six patients with PDTC who met the Turin criteria were enrolled in this study. The median follow-up period of the included 26 patients was 76 months, while the 3- and 5-year survival rates were 40% and 18%, respectively. Notably, univariate analysis revealed that tumor size >4 cm (P = .038), extrathyroidal extension (ETE) (P = .020), distant metastases (P = .047), poorly differentiated areas >60% (P = .049), and Ki-67 labeling index >30% (P = .040) were associated with poor prognosis. On the other hand, multivariate analysis identified ETE (P = .007) and distant metastases (P = .031) as independent risk factors for poor prognosis. CONCLUSION: PDTC is a rare carcinoma with high invasiveness and poor prognosis. Patients with ETE or distant metastases may have adverse outcomes.


Assuntos
Adenocarcinoma Folicular , Carcinoma , Neoplasias da Glândula Tireoide , Adenocarcinoma Folicular/diagnóstico , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico
18.
Oncogene ; 40(10): 1806-1820, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33564069

RESUMO

Fatty acid metabolism is essential for the biogenesis of cellular components and ATP production to sustain proliferation of cancer cells. Long-chain fatty acyl-CoA synthetases (ACSLs), a group of rate-limiting enzymes in fatty acid metabolism, catalyze the bioconversion of exogenous or de novo synthesized fatty acids to their corresponding fatty acyl-CoAs. In this study, systematical analysis of ACSLs levels and the amount of fatty acyl-CoAs illustrated that ACSL1 were significantly associated with the levels of a broad spectrum of fatty acyl-CoAs, and were elevated in human prostate tumors. ACSL1 increased the biosynthesis of fatty acyl-CoAs including C16:0-, C18:0-, C18:1-, and C18:2-CoA, triglycerides and lipid accumulation in cancer cells. Mechanistically, ACSL1 modulated mitochondrial respiration, ß-oxidation, and ATP production through regulation of CPT1 activity. Knockdown of ACSL1 inhibited the cell cycle, and suppressed the proliferation and migration of prostate cancer cells in vitro, and growth of prostate xenograft tumors in vivo. Our study implicates ACSL1 as playing an important role in prostate tumor progression, and provides a therapeutic strategy of targeting fatty acid metabolism for the treatment of prostate cancer.


Assuntos
Coenzima A Ligases/genética , Ácidos Graxos/metabolismo , Lipogênese/genética , Neoplasias da Próstata/genética , Trifosfato de Adenosina/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Ácidos Graxos/genética , Xenoenxertos , Humanos , Masculino , Camundongos , Oxirredução , Neoplasias da Próstata/patologia
19.
Commun Biol ; 4(1): 22, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33398073

RESUMO

Nerve growth factor (NGF) contributes to the progression of malignancy. However, the functional role and regulatory mechanisms of NGF in the development of neuroendocrine prostate cancer (NEPC) are unclear. Here, we show that an androgen-deprivation therapy (ADT)-stimulated transcription factor, ZBTB46, upregulated NGF via ZBTB46 mediated-transcriptional activation of NGF. NGF regulates NEPC differentiation by physically interacting with a G-protein-coupled receptor, cholinergic receptor muscarinic 4 (CHRM4), after ADT. Pharmacologic NGF blockade and NGF knockdown markedly inhibited CHRM4-mediated NEPC differentiation and AKT-MYCN signaling activation. CHRM4 stimulation was associated with ADT resistance and was significantly correlated with increased NGF in high-grade and small-cell neuroendocrine prostate cancer (SCNC) patient samples. Our results reveal a role of the NGF in the development of NEPC that is linked to ZBTB46 upregulation and CHRM4 accumulation. Our study provides evidence that the NGF-CHRM4 axis has potential to be considered as a therapeutic target to impair NEPC progression.


Assuntos
Adenocarcinoma/metabolismo , Carcinoma Neuroendócrino/etiologia , Fator de Crescimento Neural/metabolismo , Neoplasias da Próstata/metabolismo , Fatores de Transcrição/metabolismo , Adenocarcinoma/tratamento farmacológico , Antagonistas de Androgênios/efeitos adversos , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/patologia , Estudos de Casos e Controles , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Células PC-3 , Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Receptor Muscarínico M4/metabolismo
20.
Transl Res ; 231: 102-112, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33321257

RESUMO

Gastric cancer (GC) is a highly prevalent malignancy featured by dismal oncological outcomes. Accumulating pieces of evidence have consensus over the therapeutic significance of extracellular vesicles (EVs) and its role in carcinogenesis. Here, we planned to uncover EVs' role in GC by shuttling microRNA-1290 (miR-1290) and to identify the possible molecular mechanism associated with Grhl2, PD-L1, and ZEB1. Grhl2 was under-expressed in GC tissues, exhibiting a negative correlation with PD-L1 expression. In addition, Grhl2 promoted T cell proliferation by down-regulating PD-L1 via inhibiting ZEB1, while miR-1290 was found to negatively regulate Grhl2. EVs were also isolated from GC cells or normal gastric epithelial cells and identified with the presence of EV markers. miR-1290 expression was determined to be enriched in the EVs derived from GC cells and observed to promote the suppressive action of GC cells on T cell activation by up-regulating PD-L1 via the Grhl2/ZEB1 pathway in the co-culture system of GC cells with or without treatment of EVs with T cells. Moreover, we also developed a mouse model of GC and injected the EVs derived from miR-1290-inhibitor-treated GC cells into the tumor-bearing mice for further validation of mechanism in vivo. Intriguingly, the pivotal role of EVs-shuttled miR-1290 as an oncomiR was demonstrated in vivo. Collectively, we found that miR-1290 in EVs secreted from GC cells contributed to immune escape through the Grhl2/ZEB1/PD-L1 axis.


Assuntos
Antígeno B7-H1/metabolismo , Proteínas de Ligação a DNA/metabolismo , MicroRNAs/metabolismo , Fatores de Transcrição/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígeno B7-H1/genética , Linhagem Celular , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Vesículas Extracelulares , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C3H , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Neoplasias Experimentais , Neoplasias Gástricas , Fatores de Transcrição/genética , Adulto Jovem , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética
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