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1.
J Hepatocell Carcinoma ; 11: 1727-1740, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39281003

RESUMEN

Purpose: Lenvatinib and programmed cell death protein-1 (PD-1) inhibitor on infiltrative hepatocellular carcinoma (HCC) have obtained demonstrated efficacy and still need improvement. Hepatic arterial infusion chemotherapy (HAIC) has shown promising results for advanced HCC. This study aimed to compare the efficacy of HAIC combined Lenvatinib and PD-1 inhibitor versus Lenvatinib combined PD-1 inhibitor for infiltrative HCC. Patients and Methods: A total of 232 patients were enrolled. There were 114 patients received Lenvatinib combined PD-1 inhibitor (Len+PD-1 group) and 118 patients received HAIC combined Lenvatinib and PD-1 inhibitor (HAIC+Len+PD-1 group). Overall survival (OS), progression-free survival (PFS) and safety of patients were compared between the two groups by propensity score-matching (PSM). Results: The 6-, 12-, and 24-month OS rates were 93.8%, 65.1% and 13.4% in Len+PD-1 group, and 100%, 77.3% and 32.1% in HAIC+Len+PD-1 group, respectively. The 3-, 6-, and 12-month PFS rates were 86.4%, 45.7% and 14.1% in Len+PD-1 group, and 95.1%, 59.3% and 25.9% in HAIC+Len+PD-1 group, respectively. The HAIC+Len+PD-1 group had obviously better survival than the Len+PD-1 group both in OS (P=0.002) and PFS (P=0.004). Subgroup analysis revealed that OS in patients with metastasis was improved with HAIC+Len+PD-1 treatment. Patients with alpha-fetoprotein (AFP) response after treatment showed better survival than the non-response. In addition, HAIC+Len+PD-1 group showed manageable adverse events (AEs). Conclusion: Patient with infiltrative HCC, HAIC+Len+PD-1 treatment had longer OS and PFS than Len+PD-1 treatment. Early AFP response was an effective indicator of better survival and tumor response to therapy.


Infiltrative hepatocellular carcinoma (HCC) is an odd group that is not well adjudicated in the current staging systems, and treatment options for patients with infiltrative HCC are challenging with scant and insufficient clinical evidence. In this multi-center study, we innovatively analyzed the outcome of hepatic arterial infusion chemotherapy (HAIC) combined lenvatinib and PD-1 inhibitor (HAIC+Len+PD-1) was associated longer progression-free survival and overall survival than Lenvatinib plus PD-1 inhibitor combination (Len+PD-1) for patient with infiltrative HCC. In addition, further intragroup analysis revealed that OS of patients with and without metastasis in Len+PD-1 group was significant difference. However, no difference was observed in OS for patients with and without metastasis in HAIC+Len+PD-1 group. Patients with alpha-fetoprotein (AFP) response after treatment showed better survival than the non-response. Our research provides evidence that HAIC combined Lenvatinib and PD-1 inhibitor results in clinically significant improvements in infiltrative HCC. It could be recommended as a first choice for infiltrative HCC therapy.

2.
J Gastroenterol ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39289234

RESUMEN

BACKGROUND: Although atezolizumab plus bevacizumab (Atezo/Bev) therapy has been used as the preferred first-line treatment for advanced hepatocellular carcinoma (HCC), up to 26% of patients do not achieve disease control, suggesting alternative treatments might be more beneficial for such patients. We investigated key predictors for refractoriness to Atezo/Bev therapy, particularly in the first-line setting. METHODS: We retrospectively analyzed 302 patients with HCC who received Atezo/Bev therapy between October 2020 and September 2022 across nine hospitals in Japan. Refractoriness was defined as best overall response (BOR) of progressive disease or stable disease and a progression-free survival (PFS) of < 180 days (RECIST v1.1). Clinical benefit was defined as BOR of partial/complete response or stable disease with PFS of ≥ 180 days. Baseline characteristics and potential predictors, identified through literature review, were compared between these groups. Stratifications of overall survival (OS), and PFS were also assessed. RESULTS: Refractoriness was observed in 126 (41.7%) patients, while 154 (51.0%) achieved clinical benefit. Due to a significant association between the treatment line and refractory rate, the subsequent analysis focused on the first-line cohort (n = 214; 72 [33.6%] patients showed refractoriness). Among 13 potential predictors, the CRP and AFP in immunotherapy (CRAFITY) score had the best predictive performance, with refractory rates of 24.6%, 44.6%, and 57.9% in CRAFITY-0, 1, and 2 patients, respectively (p < 0.001). OS and PFS were also well-stratified by this scoring system. CONCLUSIONS: Approximately one-third of patients were refractory to first-line Atezo/Bev therapy. The CRAFITY score demonstrated superior performance in predicting refractoriness.

3.
Radiol Case Rep ; 19(10): 4429-4434, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39185436

RESUMEN

Ectopic hepatocellular carcinoma (HCC) is defined as HCC arising from hepatic parenchyma located in an extrahepatic organ or tissue without any communication with the mother liver. It is very rare and difficult to diagnose by imaging alone. We report a case of a rare ectopic HCC mimicking a right para-aortic retroperitoneal mass and present a review of the literature. It is about a 79-year-old female patient, who presented with a progressive enlarged right paraaortic retroperitoneal mass, thought first to be leiomyosarcoma of vena cava on imaging. Subsequently, high alpha-fetoprotein (AFP) level and biopsy allowed the diagnosis of primary extrahepatic hepatocellular carcinoma.

4.
J Ultrasound Med ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39189734

RESUMEN

OBJECTIVES: Although serum screening for aneuploidies has become less prevalent, maternal-serum alpha-fetoprotein (MSAFP) screening for body-wall defects remains widespread. We explored whether MSAFP screening is associated with earlier omphalocele detection than ultrasound alone. METHODS: This is a retrospective cohort study of prenatally detected omphalocele cases at our center from 2007 to 2023. We explored the association between MSAFP screening, gestational age at omphalocele detection, and clinical outcomes. RESULTS: Among 101 pregnancies with prenatally diagnosed omphalocele, 27 (26.7%) had MSAFP screening. The median gestational age at MSAFP screening was 17 weeks 4 days. Of those who received MSAFP screening, 11 (41%) had values ≥2.5 multiples of the median (MoM) and 16 (59%) were not elevated. MSAFP results did not correlate with omphalocele size and were not associated with prenatal or postnatal outcomes. MSAFP screening did not result in earlier suspicion for or confirmation of omphalocele (P = .97 and P = .87, respectively). In contrast, first-trimester ultrasound screening was associated with earlier suspicion for and confirmation of omphalocele (P < .01 and P = .01, respectively). There were no clinical or demographic differences between those who received MSAFP screening and those who did not (including body mass index or commute distance to an urban center). CONCLUSION: MSAFP screening is not associated with earlier omphalocele detection. Furthermore, in pregnancies with prenatally diagnosed omphalocele, the results of MSAFP screening are not predictive of clinical outcomes.

5.
Ann Hepatol ; 29(6): 101540, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39151891

RESUMEN

INTRODUCTION AND OBJECTIVES: The increasing incidence of hepatocellular carcinoma (HCC) in China is an urgent issue, necessitating early diagnosis and treatment. This study aimed to develop personalized predictive models by combining machine learning (ML) technology with a demographic, medical history, and noninvasive biomarker data. These models can enhance the decision-making capabilities of physicians for HCC in hepatitis B virus (HBV)-related cirrhosis patients with low serum alpha-fetoprotein (AFP) levels. PATIENTS AND METHODS: A total of 6,980 patients treated between January 2012 and December 2018 were included. Pre-treatment laboratory tests and clinical data were obtained. The significant risk factors for HCC were identified, and the relative risk of each variable affecting its diagnosis was calculated using ML and univariate regression analysis. The data set was then randomly partitioned into validation (20 %) and training sets (80 %) to develop the ML models. RESULTS: Twelve independent risk factors for HCC were identified using Gaussian naïve Bayes, extreme gradient boosting (XGBoost), random forest, and least absolute shrinkage and selection operation regression models. Multivariate analysis revealed that male sex, age >60 years, alkaline phosphate >150 U/L, AFP >25 ng/mL, carcinoembryonic antigen >5 ng/mL, and fibrinogen >4 g/L were the risk factors, whereas hypertension, calcium <2.25 mmol/L, potassium ≤3.5 mmol/L, direct bilirubin >6.8 µmol/L, hemoglobin <110 g/L, and glutamic-pyruvic transaminase >40 U/L were the protective factors in HCC patients. Based on these factors, a nomogram was constructed, showing an area under the curve (AUC) of 0.746 (sensitivity = 0.710, specificity=0.646), which was significantly higher than AFP AUC of 0.658 (sensitivity = 0.462, specificity=0.766). Compared with several ML algorithms, the XGBoost model had an AUC of 0.832 (sensitivity = 0.745, specificity=0.766) and an independent validation AUC of 0.829 (sensitivity = 0.766, specificity = 0.737), making it the top-performing model in both sets. The external validation results have proven the accuracy of the XGBoost model. CONCLUSIONS: The proposed XGBoost demonstrated a promising ability for individualized prediction of HCC in HBV-related cirrhosis patients with low-level AFP.

6.
Curr Oncol ; 31(8): 4225-4240, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39195298

RESUMEN

The relationship between antitumor response and tumor marker changes was evaluated in patients with advanced hepatocellular carcinoma treated with durvalumab plus tremelimumab (Dur/Tre). Forty patients were enrolled in this retrospective evaluation of treatment outcomes. According to the Response Evaluation Criteria for Solid Tumors version 1.1 at 8 weeks, the objective response (OR) rate was 25% and the disease control (DC) rate was 57.5%. The median alpha-fetoprotein (AFP) ratio at 4 weeks was 0.39 in patients who achieved OR at 8 weeks (8W-OR group), significantly lower than the 1.08 in the non-8W-OR group (p = 0.0068); however, it was 1.22 in patients who did not achieve DC at 8 weeks (non-8W-DC group), significantly higher than the 0.53 in the 8W-DC group (p = 0.0006). Similarly, the median des-γ-carboxy-prothrombin (DCP) ratio at 4 weeks was 0.15 in the 8W-OR group, significantly lower than the 1.46 in the non-8W-OR group (p < 0.0001); however, it was 1.23 in the non-8W-DC group, significantly higher than the 0.49 in the 8W-DC group (p = 0.0215). Early changes in tumor markers after Dur/Tre initiation were associated with antitumor response. In particular, changes in AFP and DCP at 4 weeks may offer useful biomarkers for early prediction of both response and progressive disease following Dur/Tre.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Neoplasias Hepáticas , Precursores de Proteínas , Protrombina , alfa-Fetoproteínas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/sangre , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/sangre , Masculino , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Persona de Mediana Edad , Anciano , Anticuerpos Monoclonales/uso terapéutico , Precursores de Proteínas/sangre , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Adulto , Resultado del Tratamiento , Anciano de 80 o más Años , Biomarcadores
7.
Gastro Hep Adv ; 3(3): 316-325, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39131145

RESUMEN

Background and Aims: Assessing aggressive biology at early-stage hepatocellular carcinoma (HCC) diagnosis remains challenging. Alpha-fetoprotein (AFP) is the only clinical biomarker of aggressive HCC. In this study, AFP, Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-γ-carboxy prothrombin (DCP) were measured at diagnosis prior to transplant evaluation and first cycle liver-directed therapy (LDT). Methods: The prospective cohort included 207 patients who received LDT as a bridge/downstage to transplant or definitive treatment plan between 2016 and 2022. Plasma AFP, AFP-L3, and DCP levels were measured at diagnosis and analyzed with other factors associated with treatment response and time-to-progression. Results: Biomarker phenotyping revealed 41% were triple negative, 30% expressed multiple biomarkers, and 12% express all 3 biomarkers. The biomarker profile was associated with target/overall response rate and time-to-progression (P < .001). Profiling stratified 1-year progression risk in nontransplant candidates, driven by coexpression of AFP and DCP in multivariate analysis controlling for tumor burden and staging. Conclusion: The biomarker panel at diagnosis established prognosis for LDT response and stratified 1-year HCC progression risk. AFP, AFP-L3, and DCP profiling isolated aggressive HCC biology at diagnosis and may have important implications in post-LDT surveillance and transplant wait time.

8.
Vet Med Sci ; 10(5): e1583, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39158971

RESUMEN

Alpha-fetoprotein (AFP) is a structural serum glycoprotein that plays vital roles in reproduction and mammalian development. Analysis of serum prolactin (PRL) is considered one of the useful methods for diagnosing pregnancy in Asian elephants. However, the expression profiles of AFP in pregnant and nonpregnant Asian elephants remain unclear, nor is the relationship with PRL. In this study, serum seven gonadal hormones and AFP in three pregnant and seven nonpregnant Asian elephants were analysed by via radioimmunoassay (RIA) and enzyme-linked immunosorbent (ELISA) assay. We found that the mean (±SD) concentration of prolactin (PRL) in pregnant (136.782 ± 30.987 ng/mL) elephants was significantly higher than that in nonpregnant elephants (52.803 ± 21.070 ng/mL; p ≤ 0.0005). The mean (±SD) concentration of AFP in pregnant elephants (11.598 ± 0.824 ng/mL) was significantly higher than that in nonpregnant elephants (7.200 ± 2.283 ng/mL; p ≤ 0.05). Furthermore, the AFP concentration was positively correlated with the PRL concentration in the 10 Asian elephants studied. In conclusion, our findings suggest that serum AFP concentration is a potential biomarker of pregnancy outcomes in Asian elephants.


Asunto(s)
Biomarcadores , Elefantes , Resultado del Embarazo , alfa-Fetoproteínas , Animales , Femenino , Embarazo , alfa-Fetoproteínas/análisis , alfa-Fetoproteínas/metabolismo , Elefantes/sangre , Elefantes/fisiología , Biomarcadores/sangre , Resultado del Embarazo/veterinaria , Preñez/sangre , Prolactina/sangre
9.
Ultrasound Med Biol ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39181805

RESUMEN

OBJECTIVE: To assess the diagnostic efficacy of the CEUS LI-RADS combined with a model constructed on the basis of age, sex, AFP, and PIVKA-II (ASAP) for the diagnosis of HCC in high-risk patients. METHODS: This retrospective study included 366 liver lesions from 366 patients who underwent liver CEUS. All liver lesions were characterized and categorized according to CEUS LI-RADS v2017. Two modified methods were applied: LR-3/4/M nodules accompanied by AFP > 200 ng/mL (Criterion 2) or ASAP model score > 0.5256 and CA 19-9 in the normal range (Criterion 3) were recategorized as LR-5. The reference criteria included histopathological or comprehensive imaging and the clinical follow-up results. The diagnostic performance was evaluated and compared by the sensitivity, specificity, PPV, and NPV. RESULTS: The incidence of HCC in LR-3, LR-4, LR-5, and LR-M was 33.3% (4/12), 86.4% (38/44), 98.5% (191/194) and 82.7% (81/98), respectively. After using Criterion 2 compared to CEUS LI-RADS v2017, the sensitivity of the modified LR-5 for diagnosing HCC increased from 60.8% to 70.7% (p < 0.01) with little effect on its specificity (94.2% vs. 92.3%, p = 1.00) or PPV (98.5% vs. 98.2%, p = 0.86). After using Criterion 3, the sensitivity of the modified LR-5 for the diagnosis of HCC was further improved to 86.9% (p < 0.01), and its specificity and PPV were not significantly changed (92.3% and 98.6%, both p > 0.05). CONCLUSION: CEUS LI-RADS combined with the serum biomarker-based ASAP model improved the sensitivity of LR-5 in diagnosing HCC with little effect on its specificity and PPV.

10.
Ann Lab Med ; 44(6): 507-517, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-38953114

RESUMEN

Background: The accurate measurement of α-fetoprotein (AFP) is critical for clinical diagnosis. However, different AFP immunoassays may yield different results. Appropriate AFP reference materials (RMs) were selected and assigned accurate values for applications with external quality assessment (EQA) programs to standardize AFP measurements. Methods: Forty individual clinical samples and six different concentrations of candidate RMs (Can-RMs, L1-L6) were prepared by the Beijing Center for Clinical Laboratories. The Can-RMs were assigned target values by performing five immunoassays, using WHO International Standard 72/225 as a calibrator, and sent to 45 clinical laboratories in Beijing for AFP measurements. The commutability of all RMs was assessed based on CLSI and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) approaches. Analytical performance was assessed for compliance based on accuracy (total error, TE), trueness (bias), and precision (CV). Results: The Can-RMs were commutable for all immunoassays using the CLSI approach and for 6 of 10 assay combinations using the IFCC approach. RMs diluted in WHO RM 72/225 were commutable among all assays with the CLSI approach, except for serum matrix (Autolumo vs. Roche analyzer) and diluted water matrix (Abbott vs. Roche/Mindray analyzer), whereas some inconclusive and non-commutable results were found using the IFCC approach. The average pass rates based on the TE, bias, and CV were 91%, 81%, and 95%, respectively. Conclusions: The commutability of the RMs differed between both evaluation approaches. The Can-RMs exhibited good commutability with the CLSI approach, suggesting their suitability for use with that approach as commutable EQA materials with assigned values and for monitoring the performance of AFP measurements.


Asunto(s)
Estándares de Referencia , alfa-Fetoproteínas , alfa-Fetoproteínas/análisis , alfa-Fetoproteínas/normas , Humanos , Inmunoensayo/normas , Inmunoensayo/métodos , Calibración , Control de Calidad , Laboratorios Clínicos/normas
11.
Cell Stem Cell ; 31(9): 1327-1343.e5, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38986609

RESUMEN

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Transforming growth factor beta (TGF-ß) is highly expressed in the liver tumor microenvironment and is known to inhibit immune cell activity. Here, we used human induced pluripotent stem cells (iPSCs) to produce natural killer (NK) cells engineered to mediate improved anti-HCC activity. Specifically, we produced iPSC-NK cells with either knockout TGF-ß receptor 2 (TGFBR2-KO) or expression of a dominant negative (DN) form of the TGF-ß receptor 2 (TGFBR2-DN) combined with chimeric antigen receptors (CARs) that target either GPC3 or AFP. The TGFBR2-KO and TGFBR2-DN iPSC-NK cells are resistant to TGF-ß inhibition and improved anti-HCC activity. However, expression of anti-HCC CARs on iPSC-NK cells did not lead to effective anti-HCC activity unless there was also inhibition of TGF-ß activity. Our findings demonstrate that TGF-ß signaling blockade is required for effective NK cell function against HCC and potentially other malignancies that express high levels of TGF-ß.


Asunto(s)
Carcinoma Hepatocelular , Células Madre Pluripotentes Inducidas , Células Asesinas Naturales , Neoplasias Hepáticas , Transducción de Señal , Factor de Crecimiento Transformador beta , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/inmunología , Factor de Crecimiento Transformador beta/metabolismo , Receptor Tipo II de Factor de Crecimiento Transformador beta/metabolismo , Receptor Tipo II de Factor de Crecimiento Transformador beta/genética , Animales , Línea Celular Tumoral , Ratones
12.
World J Urol ; 42(1): 429, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39037463

RESUMEN

PURPOSE: To evaluate the association between serum alpha-fetoprotein (AFP) half-life (HL) and prognosis in prepubertal children with elevated AFP values 3 to 4 weeks after surgery for testicular yolk sac tumors (YST). METHODS: Prepubertal patients with testicular YST treated with radical orchiectomy between January 2016 and December 2022 were retrospectively reviewed. Negative outcomes were defined as relapse, metastasis or death. Univariate and multivariate logistic regression analyses were conducted to select risk factors for negative outcomes. RESULTS: A total of 42 patients were eventually enrolled into the study. Patients were divided into non-negative and negative outcomes groups, consisting of 35 and 7 patients, respectively. Thirty-five patients were stage I, two cases were stage II, and five cases were stage IV, according to the Children's Oncology Group staging system. The overall survival (OS) rate was 100%. Average AFP values significantly decreased after resection (P < 0.001). A significant positive correlation was shown between pre- and postoperative AFP values (r = 0.60, P < 0.001). Long AFP HL was considered as an independent risk factor for negative outcomes in YST patients underwent radical orchiectomy (P = 0.04). The cut-off value for AFP HL was 5.78 days, regardless of age division. CONCLUSION: Testicular YST is a relatively rare disease in children with an OS of 100%, and salvage chemotherapy is effective even in grade IV patients. The postoperative AFP HL was significantly associated with prognosis in prepubertal patients with testicular YST. The cut-off value for AFP HL is 5.78 days regardless of the effect of physiological AFP elevation.


Asunto(s)
Tumor del Seno Endodérmico , Neoplasias Testiculares , alfa-Fetoproteínas , Humanos , Masculino , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/análisis , Neoplasias Testiculares/sangre , Neoplasias Testiculares/cirugía , Neoplasias Testiculares/patología , Pronóstico , Estudios Retrospectivos , Preescolar , Niño , Tumor del Seno Endodérmico/sangre , Tumor del Seno Endodérmico/cirugía , Tumor del Seno Endodérmico/patología , Orquiectomía , Lactante
13.
Medicina (Kaunas) ; 60(7)2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39064538

RESUMEN

Background: Alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9) are two tumor markers that are widely used in the differential diagnosis in patients with primary liver tumors. Very high levels of AFP are sporadically observed in patients with intrahepatic cholangiocarcinoma (ICC) and may cause an incorrect initial diagnosis of hepatocellular carcinoma (HCC). Methods: Two cases of tumors in cirrhotic livers were described, in which the initial diagnosis, based on very high AFP levels (Patient I: 10,464 ng/mL, Patient II: 2212 ng/mL, reference range: ≤8.04 ng/mL) was HCC. In addition, the PubMed database was searched for cases of ICC with elevated AFP. Discussion: In both individuals, liver cirrhosis was diagnosed, but there was no typical rapid "washout" in the contrast-enhanced computed tomography. Based on the histological assessment of samples obtained in the core biopsies, the initially assumed diagnosis of HCC was changed to ICC in both cases. Only nine cases of patients with ICC and high AFP levels were found in the PubMed database. The AFP levels ranged from slightly elevated to over 16,000 ng/mL. Conclusions: A very high AFP level does not necessarily correlate with the presence of HCC. Therefore, the diagnosis has to be verified histologically, when the radiological imaging is uncertain in patients with liver cirrhosis.


Asunto(s)
Neoplasias de los Conductos Biliares , Biomarcadores de Tumor , Colangiocarcinoma , Errores Diagnósticos , alfa-Fetoproteínas , Humanos , alfa-Fetoproteínas/análisis , Colangiocarcinoma/sangre , Colangiocarcinoma/diagnóstico , Masculino , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/análisis , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/sangre , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagen , Persona de Mediana Edad , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/diagnóstico , Diagnóstico Diferencial , Anciano , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/complicaciones , Femenino , Tomografía Computarizada por Rayos X/métodos
14.
Bioelectrochemistry ; 160: 108773, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38972159

RESUMEN

A biofunctional immunosensor combining photoelectrochemical (PEC) and electrochemical (EC) was proposed for the quantitative detection of the liver cancer marker alpha-fetoprotein (AFP) in human blood. BiVO4/BiOI-MWCNTs photoactive materials were first prepared on conductive glass FTO, and the photoelectrode was functionalized by chitosan and glutaraldehyde. Then, the AFP capture antibody (Ab1) was successfully modified on the photoelectrode, and the label-free rapid detection of AFP antigen was achieved by PEC. In addition, Au@PdPt nanospheres were also used as a marker for binding to AFP detection antibody (Ab2). Due to the excellent catalytic properties of Au@PdPt in EC reaction, a signal increase in the EC response can be achieved when Ab2 binds to the AFP antigen, which ensures high sensitivity for the detection of AFP. The detection limits of PEC and EC are 0.050 pg/mL and 0.014 pg/mL, respectively. The sensor also possesses good specificity, stability and reproducibility, shows excellent performance in the detection of clinical samples and has good clinical applicability.


Asunto(s)
Técnicas Biosensibles , Bismuto , Técnicas Electroquímicas , Oro , Vanadatos , alfa-Fetoproteínas , alfa-Fetoproteínas/análisis , alfa-Fetoproteínas/inmunología , Oro/química , Humanos , Bismuto/química , Vanadatos/química , Técnicas Electroquímicas/métodos , Técnicas Biosensibles/métodos , Inmunoensayo/métodos , Nanotubos de Carbono/química , Paladio/química , Límite de Detección , Platino (Metal)/química , Nanopartículas del Metal/química , Anticuerpos Inmovilizados/química , Anticuerpos Inmovilizados/inmunología
15.
World J Gastrointest Oncol ; 16(6): 2463-2475, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38994169

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Serum biomarkers play an important role in the early diagnosis and prognosis of HCC. Because a certain percentage of HCC patients are negative for alpha-fetoprotein (AFP), the diagnosis of AFP-negative HCC is essential to improve the detection rate of HCC. AIM: To establish an effective model for diagnosing AFP-negative HCC based on serum tumour biomarkers. METHODS: A total of 180 HCC patients were enrolled in this study. The expression levels of GP73, des-γ-carboxyprothrombin (DCP), CK18-M65, and CK18-M30 were detected by a fully automated chemiluminescence analyser. The variables were selected by logistic regression analysis. Several models were constructed using stepwise backward logistic regression. The performance of the models was compared using the C statistic, integrated discrimination improvement, net reclassification improvement, and calibration curves. The clinical utility of the nomogram was assessed using decision curve analysis (DCA). RESULTS: The results showed that the expression levels of GP73, DCP, CK18-M65, and CK18-M30 were significantly greater in AFP-negative HCC patients than in healthy controls (P < 0.001). Multivariate logistic regression analysis revealed that GP73, DCP, and CK18-M65 were independent factors for diagnosing AFP-negative HCC. By comparing the diagnostic performance of multiple models, we included GP73 and CK18-M65 as the model variables, and the model had good discrimination ability (area under the curve = 0.946) and good goodness of fit. The DCA curves indicated the good clinical utility of the nomogram. CONCLUSION: Our study identified GP73 and CK18-M65 as serum biomarkers with certain application value in the diagnosis of AFP-negative HCC. The diagnostic nomogram based on CK18-M65 combined with GP73 demonstrated good performance and effectively identified high-risk groups of patients with HCC.

16.
J Hepatocell Carcinoma ; 11: 1251-1263, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38979083

RESUMEN

Purpose: This study aimed to assess the prognostic significance of alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (u-HCC) who underwent hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab. Methods: A retrospective review was conducted on patients with u-HCC receiving treatment with HAIC combined with lenvatinib and camrelizumab. Early AFP response was defined as a >20% decrease in AFP within 4 weeks, and AFP response as a >75% decrease in AFP within 8 weeks. The correlation between early AFP response, AFP response, therapeutic response, overall survival (OS), and progression-free survival (PFS) was investigated. Results: The study included 63 patients. AFP responders exhibited superior objective response rates compared to AFP non-responders, as determined by RECIST v1.1 or mRECIST criteria (45.5 vs. 18.2%, p=0.014, or 81.8 vs. 48.5%, p=0.013). Furthermore, early AFP responders demonstrated prolonged OS (not reached vs. 8.0 months, p<0.001) and PFS (13.3 vs. 3.0 months, p= 0.018) relative to early AFP non-responders. Similarly, AFP responders exhibited improved OS (not reached vs. 9.0 months, p<0.001) and PFS (19.3 vs. 5.1 months, p=0.002) compared to AFP non-responders. Multivariate analysis results indicated that both early AFP response and AFP response independently predicted OS [hazard ratio (HR) 2.963, 95% confidence interval (CI) 1.333-6.585, p=0.008, and HR 6.182, 95% CI 1.780-21.466, p=0.004] and PFS (HR 2.186, 95% CI 1.107-4.318, p=0.024, and HR 3.078, 95% CI 1.407-6.730, p=0.005), serving as significant prognostic values. Conclusion: Early AFP response and AFP response serve as predictive biomarkers for the effectiveness of HAIC combined with lenvatinib and camrelizumab in patients with u-HCC.

17.
Anal Chim Acta ; 1318: 342953, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39067928

RESUMEN

BACKGROUND: Developing biosensors with antifouling properties is essential for accurately detecting low-concentration biomarkers in complex biological matrix, which is imperative for effective disease diagnosis and treatment. Herein, an antifouling electrochemical aptasensor qualifying for probing targets in human serum was explored based on newly-devised peptides that could form inverted U-shaped structures with long-term stability. RESULTS: The inverted U-shaped peptides (U-Pep) with two terminals of thiol groups grafted onto the Au-modified electrode showcase superior antifouling properties in terms of high stability against enzymatic hydrolysis and long acting against biofouling in actual biofluids. The construction of the outlined antifouling electrochemical aptasensor just involved the fabrication of Au-deposited poly(3,4 ethylenedioxythiophene) (Au/PEDOT) modified electrode, followed by one-step co-incubation in the peptides and the aptamer probes with the Au/PEDOT electrode. Taking a typical biomarker of alpha-fetoprotein (AFP) for detection, this elegant antifouling aptasenor demonstrated a nice response for probing the target AFP with a low detection limit of 0.27 pg/mL and a wide linear scope of 1.0 pg/mL to 1.0 µg/mL, and furthermore qualified for assaying of AFP in human serum samples with satisfactory accuracy and feasibility. SIGNIFICANCE: This engineering strategy of U-Pep with long-lasting antifouling efficacy opens a new horizon for high-performance antifouling biosensors suitable for detection in complex bifluids, and it could spark more inspiration for a follow-up exploration of other featured antifouling biomaterials.


Asunto(s)
Aptámeros de Nucleótidos , Incrustaciones Biológicas , Técnicas Biosensibles , Técnicas Electroquímicas , Oro , Péptidos , Humanos , Técnicas Biosensibles/métodos , Péptidos/química , Oro/química , Aptámeros de Nucleótidos/química , Incrustaciones Biológicas/prevención & control , Electrodos , Polímeros/química , alfa-Fetoproteínas/análisis , Límite de Detección , Compuestos Bicíclicos Heterocíclicos con Puentes
18.
Nanomaterials (Basel) ; 14(13)2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38998732

RESUMEN

Highly sensitive and specific biomarker detection is of outstanding importance for the diagnosis and treatment of cancers. Herein, we developed robust photoelectrochemical (PEC) biosensors with low background noise and high sensitivity based on a heterojunction, which can improve semiconductor photoelectric properties by limiting the recombination of photogenerated electron-hole pairs and successfully widening the range of light absorption. Alpha-fetoprotein (AFP) was used as a target model to examine the analytical performances of the designed PEC biosensors. ZnO/Cs3MnBr5 heterogeneous film with a uniform porous structure and large surface area enhanced electron transfer and biomolecule immobilization, and significantly increased the photocurrent response. Under the optimal conditions, the designed PEC biosensor exhibited a linear detection range of 0.01-500 ng/mL and a detection limit of 12 pg/mL. In addition, this PEC biosensor performed well when testing human serum samples and exhibited good repeatability, stability over time, and specificity, showing enormous potential for the detection of cancer markers in future biological and clinical research.

19.
Surg Oncol ; 55: 102097, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39029425

RESUMEN

BACKGROUNDS: Several studies have indicated that BALAD score which includes the HCC tumor markers of HCC, AFP, AFP-L3%, DCP, and serum albumin and bilirubin value were good predictors of HCC patients for all treatment modalities. In this study, we aim to clarify the impact of BALAD score as the prognostic factor for HCC patients after curative surgery. METHODS: This study investigated 578 patients who underwent hepatectomy for HCC between January 2003 and May 2013. Cumulative recurrence rate, overall survival (OS), and clinicopathological parameters were analyzed according to the level of BALAD score. RESULTS: In patients with higher BALAD score, recurrence rate and OS was poor (p = 0.0015 and p < 0.0001, respectively). Multivariate analyses revealed independent risk factors for recurrence to be male (hazard ratio [HR] 1.52, P = 0.011), HCV-antibody positive (HR 1.33, P = 0.019), multiple tumors (HR 2.16, P < 0.0001), microvascular invasion (HR 1.45, P = 0.0035) and higher BALAD score (RR 1.70, P = 0.015). The independent risk factors for OS were multiple tumors (HR 1.52, P = 0.014), microvascular invasion (HR 1.53, P = 0.012), and higher BALAD score (RR 2.51, P = 0.0012). CONCLUSION: BALAD score is associated with high recurrence rate and poor overall survival of the patients who underwent curative liver resection for HCC.


Asunto(s)
Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Recurrencia Local de Neoplasia , Humanos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Masculino , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Hepatectomía/mortalidad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Femenino , Persona de Mediana Edad , Tasa de Supervivencia , Pronóstico , Estudios de Seguimiento , Anciano , Biomarcadores de Tumor/metabolismo , Factores de Riesgo , Estudios Retrospectivos , Adulto , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/análisis
20.
Cureus ; 16(6): e61480, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38952613

RESUMEN

Hepatoblastoma is one of the pediatric tumors with genetic and intrauterine risk factors. It is typically asymptomatic at diagnosis, at which time most patients have metastasis to the lungs and are in an advanced stage of liver disease. We report an interesting case of a 13-month-old child who presented with a one-month history of abdominal distention. A review of the systems was unremarkable but a physical examination revealed a well-appearing child with abdominal distention, normal vital signs, and an abdominal mass. Abdominal imaging revealed a well-defined heterogeneously-enhancing mass arising from the right hepatic lobe and laboratory results were consistent with a diagnosis of hepatoblastoma. The mass was resected and the patient underwent chemotherapy with continued follow-up management. We shed light on pediatric hepatoblastoma and its clinical presentation, pathology, and laboratory and imaging findings, to aid clinicians in diagnosing the condition correctly.

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