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1.
Onco Targets Ther ; 17: 521-536, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948385

RESUMO

Introduction: The increasing incidence of cancer diseases necessitates the urgent exploration of new bioactive compounds. One of the trends in drug discovery is marine sponges which is gaining significant support due to the abundant production of natural pharmaceutical compounds obtained from marine ecosystems. This study evaluates the anticancer properties of an organic extract from the Red Sea sponge Callyspongia siphonella (C. siphonella) on HepG-2 and MCF-7 cancer cell lines. Methods: C. siphonella was collected, freeze-dried, and extracted using a methanol-dichloromethane mixture. The extract was analyzed via Liquid Chromatography-Mass Spectrometry. Cytotoxic effects were assessed through cell viability assays, apoptosis detection, cell cycle analysis, mitochondrial membrane potential assays, scratch-wound healing assays, and 3D cell culture assays. Results: Fifteen compounds were identified in the C. siphonella extract. The extract showed moderate cytotoxicity against MCF-7 and HepG-2 cells, with IC50 values of 35.6 ± 6.9 µg/mL and 64.4 ± 8 µg/mL, respectively, after 48 hours of treatment. It induced cell cycle arrest at the G2/M phase in MCF-7 cells and the S phase in HepG-2 cells. Apoptosis increased significantly in both cell lines, accompanied by reduced mitochondrial membrane potential. The extract inhibited cell migration, with notable reductions after 24 and 48 hours. In 3D cell cultures, the extract had IC50 values of 5.1 ± 2 µg/mL for MCF-7 and 166.4 ± 27 µg/mL for HepG-2 after 7 days of treatment, showing greater potency in MCF-7 spheres compared to HepG-2 spheres. Discussion and Conclusion: The anticancer activity is attributed to the bioactive compounds. The C. siphonella extract's ability to induce apoptosis, disrupt mitochondrial membrane potential, and arrest the cell cycle highlights its potential as a novel anticancer agent. Additional research is required to investigate the underlying mechanism by which this extract functions as a highly effective anticancer agent.

2.
World J Gastrointest Oncol ; 16(6): 2793-2803, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38994165

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) ranks sixth globally in cancer incidence and third in mortality rates. Unfortunately, over 70% of HCC patients forego the opportunity for curative surgery or liver transplantation due to inadequate physical examinations, poor physical condition, and limited organ availability upon diagnosis. Clinical guidelines endorse transarterial chemoembolization (TACE) as the frontline treatment for intermediate to advanced-stage HCC. Cryoablation (CRA) is an emerging local ablative therapy increasingly used in HCC management. Recent studies suggest that combining CRA with TACE offers complementary and synergistic effects, potentially improving long-term survival rates. However, the superiority of combined TACE + CRA therapy over TACE alone for HCC lesions equal to or exceeding 5 cm requires further investigation. AIM: To compare the efficacy and safety of TACE combined with CRA vs TACE alone in the treatment of HCC with a diameter of ≥ 5 cm. METHODS: PubMed, EMBASE, Cochrane Library, CNKI, Wanfang, and VIP databases were searched to retrieve all relevant studies on TACE and CRA up to July 2022. Meta-analysis was performed using RevMan 5.3 software. RESULTS: After screening according to the inclusion and exclusion criteria, 6 articles were included, including 2 randomized controlled trials and 4 nonrandomized controlled trials, with a total of 575 patients included in the meta-analysis. The results showed that the objective response rate [odds ratio (OR) = 2.56, 95% confidence interval (CI):1.66-3.96, P < 0.0001), disease control rate (OR = 3.03, 95%CI: 1.88-4.89, P < 0.00001), 1-year survival rate (OR = 3.79, 95%CI: 2.50-5.76, P < 0.00001), 2-year survival rate (OR = 2.34, 95%CI: 1.43-3.85, P = 0.0008), and 3-year survival rate (OR = 3.34, 95%CI: 1.61-6.94, P = 0.001) were all superior to those of the control group; the postoperative decrease in alpha-fetoprotein value (OR = 295.53, 95%CI: 250.22-340.85, P < 0.0001), the postoperative increase in CD4 value (OR = 10.59, 95%CI: 8.78-12.40, P < 0.00001), and the postoperative decrease in CD8 value (OR = 6.47, 95%CI: 4.44-8.50, P < 0.00001) were also significantly higher than those in the TACE-alone treatment group. CONCLUSION: Compared with TACE-alone treatment, TACE + CRA combined treatment not only improves the immune function of HCC patients with a diameter of ≥ 5 cm, but also enhances the therapeutic efficacy and long-term survival rate, without increasing the risk of complications. Therefore, TACE + CRA combined treatment may be a more recommended treatment for patients with HCC with a diameter of ≥ 5 cm.

3.
BMJ Case Rep ; 17(7)2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39038874

RESUMO

Adenoid cystic carcinoma (ACC) is a rare tumour of the salivary glands characterised by distant metastases, mainly to lungs and bone. Isolated metastasis to the liver is unusual. We present the case of a woman with an ACC of the submandibular gland (pT1N0) who underwent radical submandibular gland excision and selective neck dissection. Preoperative imaging identified a liver lesion with features suggestive of a haemangioma. Two-year postoperatively, a surveillance CT neck/trunk showed an increase in size of the left liver lobe lesion. Subsequent MR liver and US-guided biopsy confirmed the lesion to be metastatic ACC. The patient underwent a successful left lateral liver sectionectomy. She remains disease-free 2.5 years after her liver resection. A literature search revealed only four other similar cases. This report highlights that even early-stage ACCs of the salivary gland may present with synchronous solitary liver metastasis which can be effectively treated with curative surgery.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias Hepáticas , Neoplasias da Glândula Submandibular , Humanos , Carcinoma Adenoide Cístico/secundário , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/cirurgia , Carcinoma Adenoide Cístico/diagnóstico por imagem , Feminino , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias da Glândula Submandibular/patologia , Neoplasias da Glândula Submandibular/secundário , Neoplasias da Glândula Submandibular/cirurgia , Tomografia Computadorizada por Raios X , Pessoa de Meia-Idade , Glândula Submandibular/patologia , Glândula Submandibular/cirurgia , Hepatectomia , Imageamento por Ressonância Magnética , Esvaziamento Cervical
4.
Biomed Pharmacother ; 177: 117059, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38955086

RESUMO

Hepatic cancer is one of the main causes of cancer-related death worldwide. Cancer stem cells (CSCs) are a unique subset of cancer cells that promote tumour growth, maintenance, and therapeutic resistance, leading to recurrence. In the present work, the ability of a ruthenium complex containing 1,3-thiazolidine-2-thione (RCT), with the chemical formula [Ru(tzdt)(bipy)(dppb)]PF6, to inhibit hepatic CSCs was explored in human hepatocellular carcinoma HepG2 cells. RCT exhibited potent cytotoxicity to solid and haematological cancer cell lines and reduced the clonogenic potential, CD133+ and CD44high cell percentages and tumour spheroid growth of HepG2 cells. RCT also inhibited cell motility, as observed in the wound healing assay and transwell cell migration assay. RCT reduced the levels of Akt1, phospho-Akt (Ser473), phospho-Akt (Thr308), phospho-mTOR (Ser2448), and phospho-S6 (Ser235/Ser236) in HepG2 cells, indicating that interfering with Akt/mTOR signalling is a mechanism of action of RCT. The levels of active caspase-3 and cleaved PARP (Asp214) were increased in RCT-treated HepG2 cells, indicating the induction of apoptotic cell death. In addition, RCT modulated the autophagy markers LC3B and p62/SQSTM1 in HepG2 cells and increased mitophagy in a mt-Keima-transfected mouse embryonic fibroblast (MEF) cell model, and RCT-induced cytotoxicity was partially prevented by autophagy inhibitors. Furthermore, mutant Atg5-/- MEFs and PentaKO HeLa cells (human cervical adenocarcinoma with five autophagy receptor knockouts) were less sensitive to RCT cytotoxicity than their parental cell lines, indicating that RCT induces autophagy-mediated cell death. Taken together, these data indicate that RCT is a novel potential anti-liver cancer drug with a suppressive effect on CSCs.


Assuntos
Apoptose , Morte Celular Autofágica , Neoplasias Hepáticas , Células-Tronco Neoplásicas , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Humanos , Apoptose/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Células Hep G2 , Morte Celular Autofágica/efeitos dos fármacos , Tiazolidinas/farmacologia , Animais , Camundongos , Movimento Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química
5.
Chem Biodivers ; : e202400959, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39077790

RESUMO

Genus Asparagus is well known for its pharmacological activities and ethnopharmacological applications.  In folk medicine, it is used in the management of several diseases such as diabetes, inflammations, and rheumatism. This work aimed to investigate the potential of Asparagus densiflorus meyeri root & aerial parts extracts as cytotoxic and anti-inflammatory and the investigation of their chemical profile. GC analysis & Folin-Ciocalteu and gravimetric methods were used respectively to estimate the lipoidal, phenolic, and saponin contents. MTT assay was conducted using two cell lines (MCF-7 & HepG2) to investigate the cytotoxic and anti-inflammatory activity using TNF-α stimulated MCF-7 cells through monitoring the level of nitric oxide release and NF-κB gene expression. Preliminary phytochemical investigation indicated that both extracted parts are equally rich in saponins, flavonoids, carbohydrates and/or glycosides, and sterols and/or triterpenes. Palmitic acid and ß sitosterol represented the major saturated fatty acids and sterol, respectively. A significant cytotoxic activity against MCF-7 cells was recorded for DCM extract (IC50 26.13 µg/ml). All tested extracts showed a significant decrease in NO release and NF-κB gene expression thus it possesses a potential anti-inflammatory activity. A. densiflorus meyeri is considered a good candidate as a food supplement for protection from malignancy.

6.
J Clin Med ; 13(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38892843

RESUMO

Background: This study systematically reviewed the association between metabolic-dysfunction-associated steatotic liver disease (MASLD) and the development of hepatic cancer. Previous research has highlighted MASLD as a predisposing condition. Aim: To collect recent global data on the relationship between MASLD and hepatic cancer. Methods: A systematic review was conducted, which included an analysis of studies on the relationship between MASLD and the incidence of hepatic cancers, focusing on the role of fibrosis and MASLD severity as predictors of cancer risk. Following standard methodological frameworks for the assessment of longitudinal studies, the review gathered information on fibrosis scores, hepatocellular carcinoma (HCC) incidence, and other types of hepatic neoplasms. Results: A total of 522 studies were initially identified, of which 6 studies were appropriate for the review. They collectively revealed that the stage of fibrosis in MASLD is a significant independent predictor of mortality and liver-related events, with higher fibrosis stages correlating with greater risk. Longitudinal data showed that increases in FIB-4 scores were linked to a higher risk of developing HCC and cirrhosis. MASLD was also associated with an increased risk of non-hepatic cancers such as colorectal cancer in males and breast cancer in females. The severity of MASLD was found to be a modifiable risk factor for biliary tract cancer (BTC), with the risk further amplified by diabetes. Moreover, lifestyle factors and comorbidities, such as smoking and diabetes, were identified as modifiers of cancer risk in MASLD patients. Conclusions: The systematic review identified the association between MASLD and an elevated risk of hepatic cancer, establishing a clear link between the severity of liver fibrosis and the incidence of HCC and other hepatic neoplasms. This supports the need for screening for hepatic cancer in patients with MASLD, particularly in the presence of advanced fibrosis or other risk-modifying factors.

7.
Skin Res Technol ; 30(5): e13737, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38769705

RESUMO

BACKGROUND: Chronic inflammation has been shown to promote cancer progression. Rosacea is indeed a long-term inflammatory skin condition and had been reported to link with increased risk for several types of malignancies, but evidence for causality is lacking. OBJECTIVES: To systematically estimate the causal relationship between rosacea and several types of cancer, including cutaneous malignant melanoma (CMM), cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), actinic keratosis (AK), thyroid cancer, breast cancer, glioma and hepatic cancer, as well as explore the potential underlying pathogenesis. METHODS: We conducted a bidirectional two-sample Mendelian randomization study to probe the potential causal relationships between rosacea and several types of cancer. Instrumental variables were established using genome-wide significant single nucleotide polymorphisms associated with rosacea and cancers. The assessment of causality was carried out through multiple methods, and the robustness of the results was evaluated via sensitivity analyses. RESULTS: There was no significant indication of causal effects of rosacea on CMM (pivw = 0.71), cSCC (pivw = 0.45), BCC (pivw = 0.90), AK (pivw = 0.73), thyroid cancer (pivw = 0.59), glioma (pivw = 0.15), and hepatic cancer (pivw = 0.07), but the genetic risk of rosacea was associated with an increased susceptibility to human epidermal growth factor receptor (HER)-negative malignant neoplasm of breast (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.02-1.18; pivw = 0.01). TANK (TRAF family member associated nuclear factor kappa B (NFKB) activator) was identified as a common protective gene for both rosacea (OR, 0.90; 95% CI, 0.82-0.99; pivw = 0.048) and HER-negative malignant neoplasm of the breast (OR, 0.86; 95% CI, 0.75-0.98; pivw = 0.032), which was primarily enriched in the negative regulation of NF-κB signal transduction and may contribute to the genetic links between rosacea and this subtype of breast cancer. CONCLUSIONS: Our findings provide suggestive evidence for causal links between rosacea and HER-negative malignant neoplasm of the breast risk.


Assuntos
Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Rosácea , Neoplasias Cutâneas , Humanos , Rosácea/genética , Neoplasias Cutâneas/genética , Feminino , Melanoma/genética , Carcinoma Basocelular/genética , Carcinoma de Células Escamosas/genética , Fatores de Risco , Predisposição Genética para Doença/genética , Neoplasias da Mama/genética , Ceratose Actínica/genética , Neoplasias da Glândula Tireoide/genética , Glioma/genética , Neoplasias Hepáticas/genética , Masculino
8.
BMJ Case Rep ; 17(5)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38782444

RESUMO

Glycogen storage disease type 1A (GSD1A), also known as Von Gierke's disease, is a rare autosomal recessive disorder affecting glycogen metabolism in the liver. It most commonly presents in infancy with hypoglycaemia and failure to thrive, but cases have been reported as undiagnosed until adulthood. A woman in her early 20s with diabetes mellitus presented with right upper quadrant pain and was found to have several haemorrhagic hepatic adenomas. This patient had insulin-dependent diabetes since a pancreatectomy at age 9 months due to continued episodes of hypoglycaemia and suspected insulinoma. During the hospital stay, the hepatic adenomas were embolised, but significant lactic acidosis and hypoglycaemia continued. Further workup revealed a chronic lactic acid level, during several hospital stays, of above 5 mmol/L. After cytology of hepatic tissue ruled out hepatocellular carcinoma, the patient was discharged and recommended to follow-up for genetic testing, which confirmed the diagnosis of GSD1A.


Assuntos
Hiperinsulinismo Congênito , Doença de Depósito de Glicogênio Tipo I , Neoplasias Hepáticas , Humanos , Feminino , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/diagnóstico , Hiperinsulinismo Congênito/genética , Hiperinsulinismo Congênito/diagnóstico , Doença de Depósito de Glicogênio Tipo I/complicações , Doença de Depósito de Glicogênio Tipo I/genética , Doença de Depósito de Glicogênio Tipo I/diagnóstico , Adulto , Adenoma de Células Hepáticas/genética , Adenoma de Células Hepáticas/diagnóstico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/genética , Adulto Jovem , Adenoma/genética , Adenoma/diagnóstico , Adenoma/complicações , Adenoma/cirurgia , Diagnóstico Diferencial
9.
BMJ Case Rep ; 17(5)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38697678

RESUMO

A woman in her 60s was diagnosed with a metastatic, unresectable rare histological type of liver cancer; combined hepatocellular cholangiocarcinoma. She had palliative chemotherapy, initially with gemcitabine and cisplatin, and then with oxaliplatin, L-folinic acid and fluorouracil. Both treatment strategies demonstrated disease progression, and somatic mutation profiling revealed no actionable mutations. The patient was started on immuno-oncology (IO) with nivolumab and ipilimumab, followed by maintenance nivolumab. She has achieved a sustained ongoing partial response since the start of this therapy for at least 12 months. The outcome in this patient is in keeping with the growing evidence of the role that IO agents have in metastatic biliary tract cancer and also serves to highlight their importance in mixed histology liver tumours.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Nivolumabe , Humanos , Feminino , Colangiocarcinoma/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Nivolumabe/uso terapêutico , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ipilimumab/uso terapêutico , Resultado do Tratamento
10.
Med Oncol ; 41(5): 106, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575697

RESUMO

Recent advances in nanotechnology have offered novel ways to combat cancer. By utilizing the reducing capabilities of Lactobacillus acidophilus, silver nanoparticles (AgNPs) are synthesized. The anti-cancer properties of AgNPs have been demonstrated in previous studies against several cancer cell lines; it has been hypothesized that these compounds might inhibit AMPK/mTOR signalling and BCL-2 expression. Consequently, the current research used both in vitro and in silico approaches to study whether Lactobacillus acidophilus AgNPs could inhibit cell proliferation autophagy and promote apoptosis in HepG2 cells. The isolated strain was identified as Lactobacillus acidophilus strain RBIM based on 16 s rRNA gene analysis. Based on our research findings, it has been observed that this particular strain can generate increased quantities of AgNPs when subjected to optimal growing conditions. The presence of silanols, carboxylates, phosphonates, and siloxanes on the surface of AgNPs was confirmed using FTIR analysis. AgNPs were configured using UV-visible spectroscopy at 425 nm. In contrast, it was observed that apoptotic cells exhibited orange-coloured bodies due to cellular shrinkage and blebbing initiated by AgNP treatment, compared to non-apoptotic cells. It is worth mentioning that AgNPs exhibited remarkable selectivity in inducing cell death, specifically in HepG2 cells, unlike normal WI-38 cells. The half-maximum inhibitory concentration (IC50) values for HepG2 and WI-38 cells were 4.217 µg/ml and 154.1 µg/ml, respectively. AgNPs induce an upregulation in the synthesis of inflammation-associated cytokines, including (TNF-α and IL-33), within HepG2 cells. AgNPs co-treatment led to higher glutathione levels and activating pro-autophagic genes such as AMPK.Additionally, it resulted in the suppression of mTOR, MMP-9, BCL-2, and α-SMA gene expression. The docking experiments suggest that the binding of AgNPs to the active site of the AMPK enzyme leads to inhibiting its activity. The inhibition of AMPK ultimately results in the suppression of the mechanistic mTOR and triggers apoptosis in HepG2 cells. In conclusion, the results of our study indicate that the utilization of AgNPs may represent a viable strategy for the eradication of liver cancerous cells through the activation of apoptosis and the enhancement of immune system reactions.


Assuntos
Neoplasias Hepáticas , Nanopartículas Metálicas , Humanos , Prata/farmacologia , Prata/química , Proteínas Quinases Ativadas por AMP , Nanopartículas Metálicas/química , Metaloproteinase 9 da Matriz , Apoptose , Neoplasias Hepáticas/tratamento farmacológico , Serina-Treonina Quinases TOR , Proteínas Proto-Oncogênicas c-bcl-2 , Extratos Vegetais/química
11.
BMJ Case Rep ; 17(3)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38479827

RESUMO

Castleman disease (CD) is a rare, benign lymphoproliferative disorder with characteristic histopathological features, but variable aetiology, presentation, treatment and prognosis. It is broadly classified based on its location and histopathological features, with unicentric hyaline vascular disease presenting most commonly. We present a case of primary, unicentric hepatic CD that was incidentally found on imaging and managed with laparoscopic resection.


Assuntos
Hiperplasia do Linfonodo Gigante , Transtornos Linfoproliferativos , Humanos , Hiperplasia do Linfonodo Gigante/diagnóstico por imagem , Hiperplasia do Linfonodo Gigante/cirurgia , Prognóstico
12.
Int J Pharm ; 654: 123975, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38452833

RESUMO

Targeted therapies enhance the efficacy of tumour screening and management while lowering side effects. Multiple tumours, including liver cancer, exhibit elevated levels of folate receptor expression. This research attempted to develop surface-functionalised bosutinib cubosomes against hepatocellular carcinoma. The novelty of this work is the anti-hepatic action of bosutinib (BST) and folic acid-modified bosutinib cubosomes (BSTMF) established through proto-oncogene tyrosine-protein kinase (SrC)/ focal adhesion kinase(FAK), reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and cell cytotoxicity. Later, the in-vivo pharmacokinetics of BSTMF were determined for the first time. The strong affinity of folic acid (FA) for folate receptors allows BSTMF to enter cells via FA receptor-mediated endocytosis. The particle size of the prepared BSTMF was 188.5 ± 2.25 nm, and its zeta potential was -20.19 ± 2.01 mV, an encapsulation efficiency of 90.31 ± 3.15 %, and a drug release rate of 76.70 ± 2.10 % for 48 h. The surface architecture of BSTMF was identified using transmission electron microscopy (TEM) and Atomic force microscopy (AFM). Cell-line studies demonstrated that BSTMF substantially lowered the viability of Hep G2 cells compared to BST and bosutinib-loaded cubosomes (BSTF). BSTMF demonstrated an elevated BST concentration in tumour tissue than in other organs and also displayed superior pharmacokinetics, implying that they hold potential against hepatic cancers. This is the first study to show that BSTMF may be effective against liver cancer by targeting folate receptors and triggering SrC/FAK-dependent apoptotic pathways. Multiple parameters demonstrated that BSTMF enhanced anticancer targeting, therapeutic efficacy, and safety in NDEA-induced hepatocellular carcinoma.


Assuntos
Compostos de Anilina , Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Nitrilas , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Ácido Fólico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Linhagem Celular Tumoral , Tamanho da Partícula
13.
BMJ Case Rep ; 17(2)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38417945

RESUMO

Alagille syndrome (AGS) is a genetic disorder due to mutations in the JAGGED 1 or NOTCH 2 genes leading to multisystemic manifestations. Though these patients are at risk of developing various liver tumours, no cases of hepatoblastoma among young children with cirrhosis in AGS have been reported. We report a male toddler, with cirrhosis due to AGS who developed a hepatoblastoma. He underwent a liver transplant for decompensated chronic liver disease with marked pruritus, very high alpha-fetoprotein levels and malignant liver lesions on positron emission tomography CT. His explant histology revealed a paucity of bile ducts and liver lesions turned out to be hepatoblastoma for which he received postoperative chemotherapy. The genetic testing sent before transplantation confirmed the clinical diagnosis of AGS. Hepatoblastoma should be suspected in any child with AGS presenting with a right upper quadrant mass even in the setting of chronic liver disease.


Assuntos
Síndrome de Alagille , Hepatoblastoma , Neoplasias Hepáticas , Humanos , Masculino , Lactente , Pré-Escolar , Síndrome de Alagille/complicações , Síndrome de Alagille/diagnóstico , Síndrome de Alagille/genética , Hepatoblastoma/complicações , Hepatoblastoma/diagnóstico , Hepatoblastoma/genética , Tomografia Computadorizada por Raios X , Neoplasias Hepáticas/complicações , Cirrose Hepática/complicações
14.
Heliyon ; 10(3): e24794, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38333871

RESUMO

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers causing the highest mortality rate worldwide. Treatment options of surgery, radiation, cytotoxic drugs and liver transplantation suffer significant side effects and a high frequency of relapse. Stem cell therapy has been proposed as a new effective therapy, however, controversial reports are emerging on the role of mesenchymal stem cells in cancer. In this work, we aimed to assess the regenerative capacities of adipose mesenchymal stem cells when exposed to serum from HCC patients, by assessing the effect of the sera on modulating the regenerative capacities of h-AMSCs and the cancer properties in HCC cells. This will pave the way for maximizing the efficacy of MSCs in cancer therapy. Our data show that HCC serum-treated hA-MSCs suffered oncogene-induced senescence as shown by their altered morphology and ameliorated proliferation and differentiation. The cells were enlarged with small irregular nuclei, swollen rough endoplasmic reticulum cisternae, and aging lysosomes typified by dark residual bodies. HCC serum-treated Huh-7 cancer cells on the other hand displayed higher tumor aggressiveness as depicted by altered morphology, increased cellular proliferation and migration, and decreased percentage of early and late apoptotic cells. Our findings provide evidence that exposure of hA-MSCs to the serum of HCC patients decreases their regenerative capacities and should be considered when employed as a potential therapy in HCC patients.

15.
Biomed Mater ; 19(2)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38215478

RESUMO

Hepatocellular carcinoma remains a challenging contributor to the global cancer and related mortality, and claims approximately 800,000 deaths each year. Dysregulation or loss of function mutations involving the tumor suppressor gene, phosphatase and tensin homolog deleted on chromosome ten (PTEN), has been well-characterized in various cancers to elicit anomalous cell proliferation and oncogenic transformation. However, the delivery and bioavailability of genes/drugs of interest to carcinomas remains a serious bottleneck behind the success of any anti-cancer formulation. In this study, we have engineered nanoliposomes containing PTEN plasmids, plumbagin, and antioxidant cerium oxide nanoparticles (Lipo-PTEN-Plum) to restore the PTEN expression and inhibit the AKT/PI3K pathway. The Lipo-PTEN-Plum was quasi-spherical in shape with ∼110 nm diameter and ∼64% plumbagin loading efficiency. The Lipo-PTEN-Plum was successfully internalized HepG2 cells, restore PTEN expression and inhibit PI3K/AKT pathway to induce death in cells grown in monolayer and in form of spheroids. Mechanistically, the formulation showed G2/M cell cycle arrest, DNA damage and apoptosis in hepatic cancer cells. Other cellular events such as Caspase-7 overexpression and PI3K (phosphoinositide 3-kinase), AKT (a serine/threonine protein kinase), PARP [Poly (ADP-ribose) polymerases], and mTOR (Mammalian target of rapamycin) inhibition led to the apoptosis in hepatic cancer cells. The mRNA expression profile of PTEN, PI3K, AKT3, Caspase-7, PARP and mTOR proteins, primarily controlling the cancer cell proliferation and apoptosis, suggest that exogenous supply of PTEN could regulate the expression of oncogenic proteins and thus cancer progression.


Assuntos
Neoplasias Hepáticas , Naftoquinonas , Fosfatidilinositol 3-Quinases , Humanos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Caspase 7/genética , Caspase 7/farmacologia , Antioxidantes , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Proliferação de Células , Linhagem Celular Tumoral , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Apoptose , Plasmídeos , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo
16.
Expert Opin Drug Saf ; : 1-7, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38288971

RESUMO

BACKGROUND: Hepatic cancer is a common cancer in clinical practice. Current drug therapies for this condition include targeted therapy, chemotherapy, and immunotherapy. Tumor lysis syndrome (TLS) is the most serious complication of oncology treatment. According to the literature, several cases reported TLS occurred with targeted therapies for hepatic cancer. METHODS: Reporting odds ratio and information component were used to measure the disproportionate signals for TLS associated with targeted therapies, using data from the FDA's Adverse Event Reporting System (FAERS). A stepwise sensitivity analysis was conducted to test the robustness of signals. Time-to-onset analysis was used to describe the latency of TLS events associated with targeted therapies. The Bradford Hill criteria were used to perform a global assessment of the evidence. RESULTS: Sorafenib, lenvatinib, cabozantinib, and bevacizumab showed higher disproportionate signals for TLS than chemotherapy. The median number of days to TLS occurrence after drug therapy was 5.5, 6.5, and 6.5 days for sorafenib, lenvatinib, and bevacizumab, respectively. CONCLUSIONS: There is a significant association between tumor lysis syndrome and targeted therapies for hepatic carcinoma, with particularly strong signals for sorafenib and lenvatinib. Clinicians should be aware of the potential for tumor lysis syndrome in targeted therapies for hepatic carcinoma.

17.
Vet Radiol Ultrasound ; 65(2): 121-129, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38279767

RESUMO

Stereotactic body radiation therapy (SBRT) is an increasingly used alternative treatment option for nonresectable hepatocellular carcinoma (HCC) in people. Comparatively, the publication of SBRT of dogs with HCC is limited. The objective of this retrospective, descriptive case series was to evaluate the clinical outcomes and toxicity data of SBRT in dogs with HCC and imaging-documented primary liver tumors using volumetric-modulated arc therapy delivery at two private institutions. Medical records of 14 dogs treated between 2018 and 2023 were reviewed. All dogs had macroscopic tumors, and 9 of 14 dogs had HCC diagnoses confirmed on cytology or histopathology. The median longest tumor diameter was 5.5 cm. The median percentage of planning target volume relative to liver volume was 27.1%. Most dogs were treated with three daily fractions of 7-7.5 Gy. All dogs completed their radiotherapy protocols. Three of nine HCC dogs experienced partial responses and clinical improvement. Five of nine HCC dogs had stable disease. Overall median survival time was 164 days for nine HCC dogs (range: 93-706 days). One late grade 5 liver and two late grade 3 kidney side effects were reported. One dog received repeated SBRT to the same HCC treatment field, and one dog had two courses of SBRT to bifocal HCC treatment fields, both with no more than grade 2 acute and chronic toxicities.


Assuntos
Carcinoma Hepatocelular , Doenças do Cão , Neoplasias Hepáticas , Radiocirurgia , Humanos , Cães , Animais , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/veterinária , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/veterinária , Carcinoma Hepatocelular/patologia , Radiocirurgia/efeitos adversos , Radiocirurgia/veterinária , Radiocirurgia/métodos , Estudos Retrospectivos , Doenças do Cão/radioterapia , Doenças do Cão/etiologia
18.
China Pharmacy ; (12): 283-289, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1006611

RESUMO

OBJECTIVE To investigate the attenuation and synergism of Hugan buzure recipe (HBR) combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism. METHODS Eight nude mice were selected from 40 nude mice as the blank group (normal saline), and the remaining nude mice were inoculated with hepatoma cells Huh7 to establish the tumor-bearing model. The 32 modeled nude mice were randomly allocated to four groups: model group (normal saline, ig), HBR group (0.69 g/kg, ig), oxaliplatin group (10 mg/kg, ip), and combination group (intraperitoneal injection of 0.69 g/kg HBR+intragastric administration of 10 mg/kg oxaliplatin), with 8 mice in each group. Administer drug/normal saline once a day for 32 consecutive days; administer subcutaneous injection once every 7 days for a total of 5 times. During the experiment, the general condition of nude mice in each group was observed, and the tumor volume was measured every 4 days. On the 30th day of administration, the thermal stimulation paw withdrawal latency of nude mice in each group were detected. The tumor inhibition rate, spleen coefficient, the number of red blood cells, white blood cells and platelets in the whole blood of nude mice in each group, and the content of aspartate aminotransferase (AST) and creatinine in serum were detected after the end of administration. HE staining was used to observe the pathological changes in tumor tissues in nude mice in each group. The expression of microtubule-associated protein 1 light chain 3 (LC3),selective autophagy adaptor protein p62, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), and Caspase-3 protein in tumor tissues. RESULT Compared with the model group, the tumor volume, tumor weight, white blood cells,red blood cells in the whole blood and spleen coefficients of nude mice in the oxaliplatin group were significantly decreased (P<0.01); the thermal stimulation paw withdrawal latency, AST and creatinine in serum were significantly increased (P<0.05 or P<0.01). Compared with the oxaliplatin group, the tumor volume and tumor weight of nude mice in the combination group were significantly decreased (P<0.01); the white blood cells, red blood cells and platelets in the whole blood and spleen coefficients of nude mice were significantly increased (P<0.05 or P<0.01); the thermal stimulation paw withdrawal latency, AST and creatinine in serum were significantly decreased (P<0.01); the expression levels of LC3, Bax and Caspase-3 proteins in tumor tissues of nude mice were significantly increased (P<0.01), and the expression levels of p62 and Bcl-2 proteins were significantly decreased (P<0.01). CONCLUSIONS HBR enhances the tumor inhibition rate of oxaliplatin by inducing apoptosis and autophagy, and can alleviate the peripheral neurotoxicity, hematological toxicity, hepatorenal toxicity, and immune organ toxicity caused by oxaliplatin in nude mice.

19.
Arq. gastroenterol ; 61: e23151, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1557109

RESUMO

ABSTRACT Background: Spontaneous regression (SR) is defined as the partial or complete disappearance of a tumor, in the absence of a specific treatment. Evidence of the SR in hepatocellular carcinoma (HCC) is rare. Objective: The authors aimed to review all the cases of SR of HCC in two reference centers of Southern Brazil, highlighting the main characteristics. Methods: Data of all patients with HCC were retrospectively reviewed looking for the occurrence of SR in patients from two tertiary centers in Southern Brazil, in the last five years. The diagnosis of cirrhosis was established according to clinical, laboratory and imaging data, as well as upper endoscopy or histopathological examination when necessary. The diagnosis of HCC was based on typical findings according to radiologic criteria (LIRADS) or histopathological examination. Spontaneous regression was defined as a partial or complete involution of a HCC in the absence of a specific therapy. Results: From all cases of HCC in the last 5 years (n=433), there were five cases of SR. Three (60%) were men, the mean age was 62.6 (50.0-76.0) years, and the etiology was HCV in 3 (60%). Complete regression was observed in three patients (60%), one patient (20%) presented partial regression, and one (20%) relapesed and died. The time of follow-up varied between 12 and 21 months. In this presentation, it was highlighted one case of SR observed after COVID-19 infection in a patient with cirrhosis. The possible mechanisms involved in this situation were reviewed, emphasizing the most common like hypoxia and immunological. There were also one patient submitted to a surgical procedure as a possible fator involved and three patients without obvious risk factors. Conclusion: This phenomenon will possibly contribute to a better understanding of the pathophysiological mechanisms of HCC.


RESUMO Contexto: A evidência da regressão espontânea (RE) no carcinoma hepatocelular (CHC) é rara. Objetivo: Revisar todos os casos de RE de CHC em dois centros de referência do Sul do Brasil, destacando as principais características. Métodos: Os dados de todos os pacientes com CHC foram revisados retrospectivamente buscando a ocorrência de RE em pacientes de dois centros terciários do Sul do Brasil, nos últimos 5 anos. O diagnóstico de cirrose foi estabelecido de acordo com dados clínicos, laboratoriais e de imagem, além de endoscopia digestiva alta ou exame histopatológico quando necessário. O diagnóstico de CHC foi baseado em achados típicos de acordo com critérios radiológicos (LIRADS) ou exame histopatológico. A RE foi definida como uma involução parcial ou completa de um CHC na ausência de terapia específica. Resultados: Do total de casos de CHC nos últimos 5 anos (n=433), houve cinco casos de RE. Três (60%) eram homens, a média de idade foi de 62,6 (50,0-76,0) anos, a etiologia foi virus da hepatite C em 3 (60%). A regressão completa foi observada em três pacientes (60%), um paciente (20%) apresentou regressão parcial e um (20%) apresentou recidiva e evoluiu a óbito. O tempo de seguimento variou entre 12 e 21 meses. Nesta apresentação foi destacado um caso (20%) de RE observado após infecção por COVID-19 em paciente com cirrose. Foram revisados os possíveis mecanismos envolvidos nesta situação, enfatizando os mais comuns como hipóxia e imunológicos. Houve também um paciente submetido a procedimento cirúrgico como possível fator envolvido e três pacientes sem fatores de risco evidentes. Conclusão: Este fenômeno possivelmente contribuirá para uma melhor compreensão dos mecanismos fisiopatológicos do CHC.

20.
BMJ Case Rep ; 16(12)2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38061854

RESUMO

Managing large solitary hepatocellular carcinoma (HCC) remains challenging as guidelines recommend a palliative approach given the general poor prognosis without accounting for variations in the underlying tumour biology. Surgical resection provides significantly better survival than other modalities for HCC, but only a small proportion of patients with large tumours qualify for surgical resection. Recently, with technological advances in radiation therapy, stereotactic body radiation therapy (SBRT) has emerged as an alternative treatment option for HCC . In this paper, we present a patient who was diagnosed with a 13 cm HCC with vascular invasion. SBRT was delivered as a locoregional therapy followed by immunotherapy with the outcome of complete pathological response observed on right hemi-hepatectomy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirurgia , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fator A de Crescimento do Endotélio Vascular , Imunoterapia , Resultado do Tratamento , Estudos Retrospectivos
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