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1.
Pract Radiat Oncol ; 14(2): 87-92, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38431371

RESUMO

Whole-brain radiation treatment is often considered for patients with leptomeningeal disease. There are limited reports of the development of radiation necrosis after whole-brain radiation treatment and fewer associating the presence of germline mutations with risk. We present a case report to highlight the need for consideration of radiosensitizing mutations when recommending radiation therapy.


Assuntos
Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/complicações , Irradiação Craniana/efeitos adversos , Encéfalo/diagnóstico por imagem , Necrose/etiologia
2.
Acta Gastroenterol Belg ; 87(1): 1-5, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38431784

RESUMO

Background: Endoscopic ultrasound (EUS)-guided cystogastrostomy is the treatment of choice for managing symptomatic pancreatic fluid collections (PFC). However, studies on the number of stents for optimal drainage of PFCs are limited. Hence, the present study was conducted to compare the outcome of single versus two double-pigtail stents for endoscopic drainage of PFCs. Methods: This is a single-center, retrospective analysis of patients undergoing endoscopic drainage of PFCs with minimal necrosis (pseudocyst or walled-off necrosis with <30% solid content) at a tertiary center in South India from October 2020 to October 2022. Post-procedure, patients were followed up for clinical improvement, and stents were removed after documentation of cyst size reduction on imaging. Results: Sixty-three patients (82.5% males, median age: 34 years) fulfilling the selection criteria were included. For single stent placement (n = 47), stents of size 8.5 Fr or 10 Fr were used, while for placement of two stents (n = 16), 7 Fr stents were used. The technical success rate was 100%. Intraprocedural and early postprocedural adverse events (all mild to moderate) were comparable between the groups (17.0% with single stent vs. 25.0% with two stents, p = NS). Clinical success was achieved in 93.6% of patients, with no difference between both groups. Three patients in the single stent group required additional procedures. All patients underwent successful stent removal after a median follow-up of 14 weeks. Conclusion: A single pigtail stent of 8.5 Fr or 10 Fr size for EUSguided cystogastrostomy provides efficacy and safety similar to that of two stents.


Assuntos
Cistos , Pseudocisto Pancreático , Masculino , Humanos , Adulto , Feminino , Estudos Retrospectivos , Pseudocisto Pancreático/cirurgia , Stents/efeitos adversos , Endossonografia/métodos , Drenagem/métodos , Necrose , Resultado do Tratamento
3.
Pediatr Surg Int ; 40(1): 64, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38433161

RESUMO

The aim of this study is to review the indications of pedicled flaps and analyze the results. A observational retrospective study of under 18-year-old oncology patients who required reconstructive surgery with pedicled flaps between 2011 and 2022 was performed. Demographic and clinical variables, indications, complications, and outcomes were collected. 236 patients were reviewed and 13 met inclusion criteria, eight girls and five boys (mean age: 10.6 years). Indications were Ewing's sarcoma (5), osteosarcoma (5), neuroblastoma, desmoid tumor, and neurofibroma. Preoperative PET-CT, MRI and bone scintigraphy were performed. The flaps were used on costal and extremity reconstruction: latissimus dorsi (5), pectoralis (2), medial gastrocnemius (2), combined latissimus dorsi, trapezius and serratus muscle, biceps femoris, fascio-neuro-cutaneous saphenous and cutaneous advancement-rotation. Two were performed on allograft and eight on prosthesis. All allowed immediate and complete closure. Six patients received intraoperative radiotherapy. One flap infection and two vascular complications were reported, a total necrosis, which required a new flap, and a partial necrosis, treated with a local plasty. Chemotherapy was resumed after 21 days (15-31). Mean follow-up time was 5.34 years. Flaps are an effective therapeutic option allowing reconstruction of large defects after pediatric oncologic surgeries. The most frequent complication was vascular.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Retalhos Cirúrgicos , Masculino , Feminino , Humanos , Criança , Adolescente , Estudos Retrospectivos , Extremidades , Necrose
4.
Artigo em Chinês | MEDLINE | ID: mdl-38433695

RESUMO

Objective:The purpose of this study was to analyze and summarize the clinical characteristics and diagnostic methods of tuberculous otitis media(TOM), to enrich clinical experience in diagnosis and treatment of tuberculous otitis media, so as to reduce missed diagnosis and misdiagnosis, and facilitate timely and effective therapy for better prognosis. Methods:This study retrospectively analyzed the clinical data of patients with tuberculous otitis media who were hospitalized in the Ear ward of our hospital and received surgical treatment from 2008 to 2022. The data of patients' clinical characteristics, radiological examination, intraoperative findings and therapeutic strategies were recorded and summarized. Results:A total of 23 cases (26 ears) of tuberculous otitis media were included in this retrospective study. The most common clinical symptoms were otorrhea(thin odorless fluid)(100%) and conductive hearing loss(100%), with a high incidence of facial paralysis(23.1%). It was not sensitive to traditional antibiotic treatment, eg. Levofloxacin (50% effective rate only), and relapsed soon after drug withdrawal. It was revealed that all the surgical views had gray and white tough granulation tissue hyperplasia(100%), and 23.1% with caseous necrosis. The purpose of surgery was to clear the lesion, reduce the recurrence rate of suppurative infection, and repair the function (hearing reconstruction or facial nerve decompression) as appropriate. The paraffin pathology of granulation tissue were reported as typical granulomatous inflammation and caseous necrosis with positive acid-fast staining, which was consistent with tuberculosis. Conclusion:It was easily confused by the clinical manifestations of tuberculous otitis media and common chronic suppurative otitis media. When met with the following conditions, we should pay highly attention to suspect tuberculous otitis media: The severity of local manifestations did not match with the length of the disease; with poor tympanic membrane at the early stage with no obvious cholesteatomas, with facial paralysis or hearing loss early onset; insensitive to traditional antibiotic treatment; with extensive granulation appeared in the tympanum and or mastoid cavity, with or without caseous necrosis or dead bone in the early days. The diagnosis should be confirmed based on the acid-fast staining of the histopathological section to detect positive acid-fast bacilli. Meanwhile, multiple laboratory examination methods(such as T-spot and PCR) should be integrated synchronously to help support the diagnosis.


Assuntos
Paralisia Facial , Otite Média , Tuberculose , Humanos , Estudos Retrospectivos , Otite Média/diagnóstico , Tuberculose/diagnóstico , Corantes , Antibacterianos , Necrose
5.
Eur Rev Med Pharmacol Sci ; 28(4): 1327-1339, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38436166

RESUMO

OBJECTIVE: The occurrence of nephrotoxicity and hepatotoxicity as a result of cisplatin administration is a major concern in clinical practice. This study examined the potential protective effects of administering mesenchymal stem cells (MSCs) on the renal and hepatic damage caused by cisplatin. Moreover, the study investigated the potential protective effects of administering Adipose-Derived Mesenchymal Stem Cells (ADMSC) to counteract the harmful effects of cisplatin-induced kidney and liver damage. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into three groups: normal control, cisplatin + saline, and cisplatin + ADMSC. Cisplatin was administered to induce toxicity, and ADMSC was administered intravenously as a potential therapeutic intervention. Biochemical parameters and histopathological changes were assessed in the kidney and liver tissues. Statistical analyses were performed using a one-way ANOVA. RESULTS: Cisplatin increased malondialdehyde (MDA), tumor necrosis factor alfa (TNF-alfa), IL-6, alanine transaminase (ALT), creatinine, Galectin-3, Tissue growth factor beta 1 (TGF-beta 1), compared to the normal control group. Cisplatin-MSC reduced these levels. Histopathology showed that cisplatin caused kidney tubular epithelial necrosis, luminal necrotic debris, tubular dilatation, interstitial inflammation, liver sinusoidal and central vein dilatation, congestion, necrosis, and cytoplasmic vacuolization. ADMSC administration significantly reduced histopathological changes. CONCLUSIONS: These findings highlight the potential therapeutic benefits of mesenchymal stem cell (MSC) administration in mitigating cisplatin-induced nephrotoxicity and hepatotoxicity. MSC treatment demonstrated protective effects by reducing oxidative stress, inflammatory markers, and histopathological alterations. Further investigations are warranted to elucidate the precise mechanisms underlying these protective effects and evaluate their clinical implications for managing cisplatin-induced organ damage.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Cisplatino , Masculino , Ratos , Animais , Ratos Sprague-Dawley , Cisplatino/toxicidade , Rim , Necrose
6.
PeerJ ; 12: e17044, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38426147

RESUMO

Background: Acute myocardial infarction (AMI) can occur suddenly, which may induce deadly outcomes, and the population suffering from AMI presents a younger trend. Necroptosis, the new cell necrosis type, is associated with the pathogenic mechanisms of diverse cardiovascular diseases (CVDs). Its diagnostic value and molecular mechanisms in AMI are still unclear. Objective: This study focused on determining key necroptosis-related genes as well as immune infiltration in AMI. Methods: We first examined the GSE66360 dataset for identifying necroptosis-related differentially expressed genes (NRDEGs). Thereafter, GO and functional annotation were performed, then a PPI network was built. In addition, "CIBERSORT" in R was applied in comparing different immune infiltration degrees in AMI compared with control groups. The receiver operating characteristic (ROC) curve was plotted to evaluate whether hub NRDEGs could be used in AMI diagnosis. Associations of immune cells with candidate NRDEGs biomarkers were examined by Spearman analysis. Finally, hub NRDEGs were validated by cell qPCR assays and another two datasets. Results: A total of 15 NRDEGs were identified and multiple enrichment terms associated with necroptosis were discovered through GO and KEGG analysis. Upon module analysis, 10 hub NRDEGs were filtered out, and the top six hub NRDEGs were identified after ROC analysis. These top six NRDEGs might have a certain effect on modulating immune infiltrating cells, especially for mast cells activated, NK cells activated and neutrophils. Finally, two AMI datasets and qPCR assay came to identical findings. Conclusion: Our results offer the reliable molecular biomarkers and new perspectives for necroptosis in AMI, which lay a certain foundation for developing novel anti-AMI therapeutic targets.


Assuntos
Infarto do Miocárdio , Necroptose , Humanos , Necroptose/genética , Infarto do Miocárdio/diagnóstico , Necrose/genética , Bioensaio , Grupos Controle
7.
Stud Health Technol Inform ; 310: 1579-1583, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426880

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world which ranks fourth in cancer deaths. Primary pathological necrosis is an effective prognostic indicator for hepatocellular carcinoma. We propose a GCN-based approach that mimics the pathologist's perspective for global assessment of necrosis tissue distribution to analyze patient survival. Specifically, we introduced a graph convolutional neural network to construct a spatial map with necrotic tissue and tumor tissue as graph nodes, aiming to mine the contextual information between necrotic tissue in pathological sections. We used 1381 slides from 303 patients from the First Affiliated Hospital of Zhejiang University School to train the model and used TCGA-LIHC for external validation. The C-index of our method outperforms the baseline by about 4.45%, which proves that the information about the spatial distribution of necrosis learned by GCN is meaningful for guiding patient prognosis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/diagnóstico , Hospitais , Aprendizagem , Necrose
8.
Adv Exp Med Biol ; 1444: 129-143, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38467977

RESUMO

Necroptosis is a regulated form of cell death involved in the development of various pathological conditions. In contrast to apoptosis, plasma membrane rupture (PMR) occurs in cells in the relatively early stage of necroptosis; therefore, necroptosis induces a strong inflammatory response. Stimuli, including tumor necrosis factor (TNF), interferon (IFN)α/ß, lipopolysaccharide, polyI:C, and viral infection, induce the formation of necrosomes that lead to membrane rupture and the release of intracellular contents, termed danger-associated molecular patterns (DAMPs). DAMPs are the collective term for molecules that normally reside in the cytoplasm or nucleus in living cells without inducing inflammation but induce strong inflammatory responses when released outside cells. Recent studies have provided a better understanding of the mechanisms underlying PMR and the release of DAMPs. Moreover, necroptosis is involved in various pathological conditions, and mutations in necroptosis-related genes can cause hereditary autoinflammatory syndromes. Thus, manipulating necroptosis signaling pathways may be useful for treating diseases involving necroptosis.


Assuntos
Apoptose , Necroptose , Humanos , Necrose/metabolismo , Apoptose/fisiologia , Morte Celular , Fator de Necrose Tumoral alfa/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
9.
BMC Cancer ; 24(1): 332, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475765

RESUMO

BACKGROUND AND OBJECTIVES: Almost one third of cancer patients in the United States will develop brain metastases on an annual basis. Surgical resection is indicated in the setting of brain metastases for reasons, such as maximizing local control in select patients, decompression of mass effect, and/or tissue diagnosis. The current standard of care following resection of a brain metastasis has shifted from whole brain radiation therapy to post-operative stereotactic radiosurgery (SRS). However, there is a significant rate of local recurrence within one year of postoperative SRS. Emerging retrospective and prospective data suggest pre-operative SRS is a safe and potentially effective treatment paradigm for surgical brain metastases. This trial intends to determine, for patients with an indication for resection of a brain metastasis, whether there is an increase in the time to a composite endpoint of adverse outcomes; including the first occurrence of either: local recurrence, leptomeningeal disease, or symptomatic radiation brain necrosis - in patients who receive pre-operative SRS as compared to patients who receive post-operative SRS. METHODS: This randomized phase III clinical trial compares pre-operative with post-operative SRS for brain metastases. A dynamic random allocation procedure will allocate an equal number of patients to each arm: pre-operative SRS followed by surgery or surgery followed by post-operative SRS. EXPECTED OUTCOMES: If pre-operative SRS improves outcomes relative to post-operative SRS, this will establish pre-operative SRS as superior. If post-operative SRS proves superior to pre-operative SRS, it will remain a standard of care and halt the increasing utilization of pre-operative SRS. If there is no difference in pre- versus post-operative SRS, then pre-operative SRS may still be preferred, given patient convenience and the potential for a condensed timeline. DISCUSSION: Emerging retrospective and prospective data have demonstrated some benefits of pre-op SRS vs. post-op SRS. This study will show whether there is an increase in the time to the composite endpoint. Additionally, the study will compare overall survival; patient-reported outcomes; morbidity; completion of planned therapies; time to systemic therapy; time to regional progression; time to CNS progression; time to subsequent treatment; rate of radiation necrosis; rate of local recurrence; and rate of leptomeningeal disease. TRIAL REGISTRATION NUMBER: NCT03750227 (Registration date: 21/11/2018).


Assuntos
Neoplasias Encefálicas , Radiocirurgia , Humanos , Estudos Retrospectivos , Radiocirurgia/métodos , Estudos Prospectivos , Resultado do Tratamento , Neoplasias Encefálicas/secundário , Necrose/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase III como Assunto
10.
Immunity ; 57(3): 429-445, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38479360

RESUMO

Diverse inflammatory conditions, from infections to autoimmune disease, are often associated with cellular damage and death. Apoptotic cell death has evolved to minimize its inflammatory potential. By contrast, necrotic cell death via necroptosis and pyroptosis-driven by membrane-damaging MLKL and gasdermins, respectively-can both initiate and propagate inflammatory responses. In this review, we provide insights into the function and regulation of MLKL and gasdermin necrotic effector proteins and drivers of plasma membrane rupture. We evaluate genetic evidence that MLKL- and gasdermin-driven necrosis may either provide protection against, or contribute to, disease states in a context-dependent manner. These cumulative insights using gene-targeted mice underscore the necessity for future research examining pyroptotic and necroptotic cell death in human tissue, as a basis for developing specific necrotic inhibitors with the potential to benefit a spectrum of pathological conditions.


Assuntos
Apoptose , Gasderminas , Humanos , Animais , Camundongos , Necrose/metabolismo , Apoptose/fisiologia , Piroptose/fisiologia , Morte Celular , Inflamassomos/metabolismo , Proteínas Quinases/metabolismo
11.
Int J Mol Sci ; 25(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38474152

RESUMO

Necroptosis, a form of necrosis, and alterations in mitochondrial dynamics, a coordinated process of mitochondrial fission and fusion, have been implicated in the pathogenesis of cardiovascular diseases. This study aimed to determine the role of mitochondrial morphology in canonical necroptosis induced by a combination of TNFα and zVAD (TNF/zVAD) in H9c2 cells, rat cardiomyoblasts. Time-course analyses of mitochondrial morphology showed that mitochondria were initially shortened after the addition of TNF/zVAD and then their length was restored, and the proportion of cells with elongated mitochondria at 12 h was larger in TNF/zVAD-treated cells than in non-treated cells (16.3 ± 0.9% vs. 8.0 ± 1.2%). The knockdown of dynamin-related protein 1 (Drp1) and fission 1, fission promoters, and treatment with Mdivi-1, a Drp-1 inhibitor, had no effect on TNF/zVAD-induced necroptosis. In contrast, TNF/zVAD-induced necroptosis was attenuated by the knockdown of mitofusin 1/2 (Mfn1/2) and optic atrophy-1 (Opa1), proteins that are indispensable for mitochondrial fusion, and the attenuation of necroptosis was not canceled by treatment with Mdivi-1. The expression of TGFß-activated kinase (TAK1), a negative regulator of RIP1 activity, was upregulated and the TNF/zVAD-induced RIP1-Ser166 phosphorylation, an index of RIP1 activity, was mitigated by the knockdown of Mfn1/2 or Opa1. Pharmacological TAK1 inhibition attenuated the protection afforded by Mfn1/2 and Opa1 knockdown. In conclusion, the inhibition of mitochondrial fusion increases TAK1 expression, leading to the attenuation of canonical necroptosis through the suppression of RIP1 activity.


Assuntos
Dinâmica Mitocondrial , Necroptose , Ratos , Animais , Regulação para Baixo , Necrose/metabolismo , Mitocôndrias/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
12.
Cells ; 13(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38474369

RESUMO

Regulated necrosis, termed necroptosis, represents a potential therapeutic target for refractory cancer. Ceramide nanoliposomes (CNLs), considered potential chemotherapeutic agents, induce necroptosis by targeting the activating protein mixed lineage kinase domain-like protein (MLKL). In the present study, we examined the potential of pronecroptotic therapy using CNLs for refractory triple-negative breast cancer (TNBC), for which there is a lack of definite and effective therapeutic targets among the various immunohistological subtypes of breast cancer. MLKL mRNA expression in tumor tissues was significantly higher in TNBC patients than in those with non-TNBC subtypes. Similarly, among the 50 breast cancer cell lines examined, MLKL expression was higher in TNBC-classified cell lines. TNBC cell lines were more susceptible to the therapeutic effects of CNLs than the non-TNBC subtypes of breast cancer cell lines. In TNBC-classified MDA-MB-231 cells, the knockdown of MLKL suppressed cell death induced by CNLs or the active substance short-chain C6-ceramide. Accordingly, TNBC cells were prone to CNL-evoked necroptotic cell death. These results will contribute to the development of CNL-based pronecroptotic therapy for TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Apoptose , Necrose , Ceramidas/farmacologia
13.
Am J Case Rep ; 25: e943166, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38425030

RESUMO

BACKGROUND Pneumatosis intestinalis (PI) is an uncommon condition that is not specific to any particular disease. Currently, there is no specific clinical guideline for treating and diagnosing PI. Furthermore, there are numerous causes of PI, which makes it difficult for clinicians - internal medicine physicians as well as surgeons - to take a clinical approach to diagnosis and treatment. CASE REPORT We present 3 clinical scenarios with PI. In the first patient there was a solitary image of PI, which was treated successfully with parenteral nutrition and intravenous antibiotics, and he was discharged after 5 days. The other 2 cases, which involve gas in the hepatic portal vein (HPVG), were handled in 2 distinct ways: surgically and conservatively. One needed diagnostic laparoscopy with necrotic segmentectomy and was discharged from the hospital on postoperative day 16. The last patient, received resuscitation treatment due to severe comorbidities and inability to tolerate surgery. After 3 days, abdominal CT scan revealed no signs of remaining PI. However, the patient was terminally discharged after 7 weeks of treatment due to septic shock caused by sacrococcygeal ulcer and urinary tract infection. By drawing comparisons among these 3 scenarios, we aim to highlight certain indicators for conservative treatment success. CONCLUSIONS PI with HPVG is a sign of severe prognosis, which often requires surgical intervention. However, the decision to manage conservatively or surgically depends on the patient's condition and other criteria such as peritonitis, free fluid in the abdominal cavity, and the presence of shock. Physicians should also weigh the benefits and risks of surgical intervention in critically ill patients.


Assuntos
Cavidade Abdominal , Laparoscopia , Masculino , Humanos , Veia Porta , Necrose , Tomografia Computadorizada por Raios X/métodos
14.
J Biochem Mol Toxicol ; 38(3): e23678, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38444079

RESUMO

This study aims to investigate the effects of lycopene on apoptotic, autophagic, and necrotic pathways, oxidative status, and DNA damage in diabetic nephropathy at the molecular level. The sample of the study includes seven groups: lycopene (L), high glucose (G), high glucose + lycopene (GL), and control (C) groups tested at 12 and 24 h. The expression levels of genes in oxidative, apoptotic, autophagic, and necrotic cell death pathways are determined by reverse transcription-quantitative polymerase chain reaction analysis. The comet assay method is used for the analysis of DNA damage. It is observed that adding lycopene to high glucose for protective purposes reduces the expression of genes related to apoptosis, autophagy, and necrosis, as well as the DNA damage index, compared to cells given high glucose alone. Lycopene can be a safe and effective alternative agent.


Assuntos
Autofagia , Dano ao DNA , Humanos , Licopeno/farmacologia , Morte Celular , Necrose , Glucose/farmacologia
15.
Kyobu Geka ; 77(2): 146-149, 2024 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-38459865

RESUMO

A 58-year-old man was admitted to our hospital with fever and neck swelling after dental treatment. He was diagnosed with a cervical abscess and underwent cervical abscess drainage, but 1 week later he developed descending necrotizing mediastinitis and was referred to our department. He underwent mediastinal and pleural drainage, but neck abscess was recured, Re-debridment of the neck abscess resulted in bleeding from right subclavian vein. The bleeding was successfully stopped with TacoSeal after L-shaped sternotomyand dissection of sternocleidomostoid muscle.


Assuntos
Mediastinite , Traumatismos Torácicos , Masculino , Humanos , Pessoa de Meia-Idade , Mediastinite/etiologia , Mediastinite/cirurgia , Abscesso/diagnóstico por imagem , Abscesso/etiologia , Abscesso/cirurgia , Veia Subclávia/diagnóstico por imagem , Veia Subclávia/cirurgia , Desbridamento , Necrose/cirurgia , Drenagem/métodos
16.
BMC Cancer ; 24(1): 303, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448852

RESUMO

BACKGROUND: Soft tissue sarcomas (STSs) are a heterogeneous group of tumors. Wide surgical resection is standard, often combined with neoadjuvant chemotherapy, radiotherapy, or both. Studies have shown the predictive value of tumor necrosis in bone sarcoma (BS); however, the role of necrosis in STS after neoadjuvant therapies is still unclear. This study aimed to investigate the role of chemo- and radiotherapy in the formation of tumor necrosis and to evaluate the influence of tumor necrosis on overall survival and local recurrence-free survival. Data from BS patients and patients who did not receive neoadjuvant therapy were compared. METHODS: A total of 779 patients with STS or BS were treated surgically. In all patients, tumor-specific factors such as type, size, or grading and the type of adjuvant therapy were documented. Local recurrence (LR), the diagnosis of metastatic disease, and survival during follow-up were evaluated. RESULTS: A total of 565 patients with STS and 214 with BS were investigated. In STS, 24.1% G1 lesions, 34.1% G2 lesions, and 41.8% G3 lesions were observed. Two hundred twenty-four of the patients with STS and neoadjuvant therapy had either radiotherapy (RTx) (n = 80), chemotherapy (CTx) (n = 93), or both (n = 51). Three hundred forty-one had no neoadjuvant therapy at all. In STS, tumor necrosis after neoadjuvant treatment was significantly higher (53.5%) than in patients without neoadjuvant therapy (15.7%) (p < 0.001). Patients with combined neoadjuvant chemo-/radiotherapy had substantially higher tumor necrosis than those with radiotherapy alone (p = 0.032). There was no difference in tumor necrosis in patients with combined chemo-/radiotherapy and chemotherapy alone (p = 0.4). The mean overall survival for patients with STS was 34.7 months. Tumor necrosis did not influence survival in a subgroup of G2/3 patients. In STS with no neoadjuvant therapy and grading of G2/3, the correlation between necrosis and overall survival was significant (p = 0.0248). There was no significant correlation between local recurrence (LR) and necrosis. CONCLUSION: STS shows a broad spectrum of necrosis even without neoadjuvant chemo- or radiotherapy. After CTx or/and RTx necrosis is enhanced and is significantly pronounced with a combination of both. There is a trend toward higher necrosis with CTx than with RTx. Grading substantially influences the necrosis rate, but necrosis in soft-tissue sarcoma following neoadjuvant therapy does not correlate with better survival or a lower local recurrence rate, as in bone sarcomas.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Sarcoma/radioterapia , Neoplasias de Tecidos Moles/terapia , Prognóstico , Tetradecilsulfato de Sódio , Necrose
17.
Cell Death Dis ; 15(3): 196, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459004

RESUMO

Cancer metabolism mainly includes carbohydrate, amino acid and lipid metabolism, each of which can be reprogrammed. These processes interact with each other to adapt to the complicated microenvironment. Ferroptosis is a regulated cell death induced by iron-dependent lipid peroxidation, which is morphologically different from apoptosis, necrosis, necroptosis, pyroptosis, autophagy-dependent cell death and cuprotosis. Cancer metabolism plays opposite roles in ferroptosis. On the one hand, carbohydrate metabolism can produce NADPH to maintain GPX4 and FSP1 function, and amino acid metabolism can provide substrates for synthesizing GPX4; on the other hand, lipid metabolism might synthesize PUFAs to trigger ferroptosis. The mechanisms through which cancer metabolism affects ferroptosis have been investigated extensively for a long time; however, some mechanisms have not yet been elucidated. In this review, we summarize the interaction between cancer metabolism and ferroptosis. Importantly, we were most concerned with how these targets can be utilized in cancer therapy.


Assuntos
Ferroptose , Neoplasias , Humanos , Neoplasias/genética , Apoptose , Necrose , Peroxidação de Lipídeos , Aminoácidos , Microambiente Tumoral
18.
Int J Nanomedicine ; 19: 2675-2690, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505168

RESUMO

Purpose: 5-fluorouracil (5-FU) is a first-line chemotherapeutic agent used to treat colorectal cancer (CRC). However, 5-FU induces drug resistance and activation of cancer stem cells (CSCs). In the present study, we designed a novel biocompatible nanomedicine system with high efficacy and biocompatibility by synthesizing mesoporous silica nanoparticle (MSN)-structured ZnO and gold ions. Oleuropein (OLP) is a phenolic compound derived from olive leaves that exerts anti-cancer effects. Therefore, we synthesized OLP-loaded ZnO/Au MSNs (ZnO/Au/OLP MSNs) and examined their anti-cancer effects on 5-FU-resistant CRC cells. Methods: ZnO/Au MSNs were synthesized and functionalized, and their physical and chemical compositions were characterized using UV-visible spectroscopy, dynamic light scattering, and transmission electron microscopy (TEM). Their effects were assessed in terms of cellular proliferation capacity, migration and invasion ability, colony-forming ability, spheroid-forming ability, reactive oxygen species (ROS) production, and mitochondrial membrane depolarization. Results: ZnO/Au MSNs were mostly composed of various ions containing ZnO and gold ions, had a spheroid phenotype, and exhibited no cytotoxicity. ZnO/Au/OLP MSNs reduced cell viability and CSC formation and induced apoptosis of 5-FU-resistant CRC cells via necrosis via ROS accumulation and DNA fragmentation. Conclusion: ZnO/Au/OLP MSNs exhibited anti-cancer activity by upregulating necrosis. These results revealed that ZnO/Au/OLP MSNs are a novel drug delivery system for 5-FU CRC therapy.


Assuntos
Neoplasias Colorretais , Glucosídeos Iridoides , Nanopartículas , Óxido de Zinco , Humanos , Dióxido de Silício/química , Espécies Reativas de Oxigênio , Nanopartículas/química , Fluoruracila/farmacologia , Necrose , Ouro/química , Íons , Neoplasias Colorretais/tratamento farmacológico , Porosidade
20.
FASEB J ; 38(6): e23555, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38498346

RESUMO

Dysregulated inflammation-resolution programs are associated with atherosclerosis progression. Resolvins, in part, mediate inflammation-resolution programs. Indeed, Resolvin D2 (RvD2) activates GPR18, a G-protein-coupled receptor, and limits plaque progression, though the cellular targets of RvD2 remain unknown. Here, we developed a humanized GPR18 floxed ("fl/fl") and a myeloid (Lysozyme M Cre) GPR18 knockout (mKO) mouse. We functionally validated this model by assessing efferocytosis in bone marrow-derived macrophages (BMDMs) and found that RvD2 enhanced efferocytosis in the fl/fl, but not in the mKO BMDMs. To understand the functions of RvD2-GPR18 in atherosclerosis, we performed a bone marrow transfer of fl/fl or mKO bone marrow into Ldlr-/- recipients. For these experiments, we treated each genotype with either Vehicle/PBS or RvD2 (25 ng/mouse, 3 times/week for 3 weeks). Myeloid loss of GPR18 resulted in significantly more necrosis, increased cleaved caspase-3+ cells and decreased percentage of Arginase-1+ -Mac2+ cells without a change in overall Mac2+ plaque macrophages, compared with fl/fl➔Ldlr-/- transplanted mice. RvD2 treatment decreased plaque necrosis, the percent of cleaved caspase-3+ cells and increased the percent of Arginase-1+ -Mac2+ cells in fl/fl➔Ldlr-/- mice, but not in the mKO➔Ldlr-/- transplanted mice. These results suggest that GPR18 plays a causal role in limiting atherosclerosis progression and that RvD2's ability to limit plaque necrosis is in part dependent on myeloid GRP18.


Assuntos
Arginase , Aterosclerose , Ácidos Docosa-Hexaenoicos , Camundongos , Animais , Caspase 3 , Macrófagos , Inflamação , Aterosclerose/genética , Necrose , Receptores Acoplados a Proteínas G/genética
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