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Hypertension (Dallas, Tex. : 1979) Nov 2023Maternal serum markers used for trisomy 21 screening are associated with placenta-mediated complications. Recently, there has been a transition from the traditional...
BACKGROUND
Maternal serum markers used for trisomy 21 screening are associated with placenta-mediated complications. Recently, there has been a transition from the traditional first-trimester screening (FTS) that included PAPP-A (pregnancy-associated plasma protein-A) and beta-hCG (human chorionic gonadotropin), to the enhanced FTS test, which added first-trimester AFP (alpha-fetoprotein) and PlGF (placental growth factor). However, whether elevated first-trimester AFP has a similar association with placenta-mediated complications to that observed for elevated second-trimester AFP remains unclear. Our objective was to estimate the association of first-trimester AFP with placenta-mediated complications and compare it with the corresponding associations of second-trimester AFP and other first-trimester serum markers.
METHODS
Retrospective population-based cohort study of women who underwent trisomy 21 screening in Ontario, Canada (2013-2019). The association of first-trimester AFP with placenta-mediated complications was estimated and compared with that of the traditional serum markers. The primary outcome was a composite of stillbirth or preterm placental complications (preeclampsia, birthweight less than third centile, or placental abruption).
RESULTS
A total of 244 990 and 96 167 women underwent FTS and enhanced FTS test screening, respectively. All markers were associated with the primary outcome, but the association for elevated first-trimester AFP (adjusted relative risk [aRR], 1.57 [95% CI, 1.37-1.81]) was weaker than that observed for low PAPP-A (aRR, 2.48 [95% CI, 2.2-2.8]), low PlGF (aRR, 2.28 [95% CI, 1.97-2.64]), and elevated second-trimester AFP (aRR, 1.97 [95% CI, 1.81-2.15]). When the models were adjusted for all 4 enhanced FTS test markers, elevated first-trimester AFP was no longer associated with the primary outcome (aRR, 0.77 [95% CI, 0.58-1.02]).
CONCLUSIONS
Unlike second-trimester AFP, elevated first-trimester AFP is not an independent risk factor for placenta-mediated complications.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Pregnancy Trimester, First; Placenta; alpha-Fetoproteins; Down Syndrome; Pregnancy-Associated Plasma Protein-A; Retrospective Studies; Cohort Studies; Placenta Growth Factor; Pregnancy Complications; Pregnancy Trimester, Second; Biomarkers; Pre-Eclampsia
PubMed: 37671572
DOI: 10.1161/HYPERTENSIONAHA.123.21568 -
Advances in Surgery Sep 2023Hepatocellular carcinoma occurs primarily in patients with cirrhosis and is an important cause of cancer death. Screening for hepatocellular carcinoma every 6 months... (Review)
Review
Hepatocellular carcinoma occurs primarily in patients with cirrhosis and is an important cause of cancer death. Screening for hepatocellular carcinoma every 6 months with ultrasound with or without alpha fetoprotein measurement is recommended by multiple professional societies. There are no randomized controlled trials in patients with cirrhosis documenting the effectiveness of screening in improving survival, however, making screening controversial. There are multiple retrospective and cohort studies, as well as pooled analyses that do show an association of screening with earlier stage at diagnosis, increased receipt of curative intent treatment, and improved overall survival. Though these studies are limited by lead and length time biases, they make compelling arguments in favor of screening. Additional research into barriers to receiving screening, barriers to receiving treatment, and the optimal screening modalities given the shift of cirrhosis etiology in the United States are needed to further improve patient outcomes.
Topics: Humans; United States; Carcinoma, Hepatocellular; Liver Neoplasms; Retrospective Studies; alpha-Fetoproteins; Liver Cirrhosis; Mass Screening
PubMed: 37536863
DOI: 10.1016/j.yasu.2023.03.003 -
Nature Communications Sep 2023The durable response rate to immune checkpoint blockade such as anti-programmed cell death-1 (PD-1) antibody remains relatively low in hepatocellular carcinoma (HCC),...
The durable response rate to immune checkpoint blockade such as anti-programmed cell death-1 (PD-1) antibody remains relatively low in hepatocellular carcinoma (HCC), mainly depending on an immunosuppressive microenvironment with limited number of CD8 T cells, especially stem-like CD8 T cells, in tumor tissues. Here we develop engineered microparticles (MPs) derived from alpha-fetoprotein (AFP)-overexpressing macrophages to load resiquimod (R848@M2pep-MPs) for enhanced anti-PD-1 therapy in HCC. R848@M2pep-MPs target and reprogram immunosuppressive M2-like tumor-associated macrophages (TAMs) into M1-like phenotype. Meanwhile, R848@M2pep-MPs-reprogrammed TAMs act as antigen-presenting cells, not only presenting AFP antigen to activate CD8 T cell-mediated antitumor immunity, but also providing an intra-tumoral niche to maintain and differentiate stem-like CD8 T cells. Combination immunotherapy with anti-PD-1 antibody generates strong antitumor immune memory and induces abundant stem-like CD8 T cell proliferation and differentiation to terminally exhausted CD8 T cells for long-term immune surveillance in orthotopic and autochthonous HCC preclinical models in male mice. We also show that the R848-loaded engineered MPs derived from macrophages overexpressing a model antigen ovalbumin (OVA) can improve anti-PD-1 therapy in melanoma B16-OVA tumor-bearing mice. Our work presents a facile and generic strategy for personalized cancer immunotherapy to boost anti-PD-1 therapy.
Topics: Male; Animals; Mice; Tumor-Associated Macrophages; alpha-Fetoproteins; Carcinoma, Hepatocellular; CD8-Positive T-Lymphocytes; Liver Neoplasms; Immunosuppressive Agents; Antigens, Neoplasm; Tumor Microenvironment
PubMed: 37704614
DOI: 10.1038/s41467-023-41438-9 -
Clinical and Experimental Hypertension... Dec 2023To evaluate the correlation between elevated maternal serum alpha-fetoprotein (AFP) in the second trimester and ischemic placental disease (IPD).
BACKGROUND
To evaluate the correlation between elevated maternal serum alpha-fetoprotein (AFP) in the second trimester and ischemic placental disease (IPD).
METHODS
A retrospective cohort study was conducted to analyze the data of 22,574 pregnant women who delivered in the Department of Obstetrics at Hangzhou Women's Hospital from 2018 to 2020, and were screened for maternal serum AFP and free beta-human chorionic gonadotropin (free β-hCG) in the second trimester. The pregnant women were divided into two groups: elevated maternal serum AFP group (n = 334, 1.48%); and normal group (n = 22,240, 98.52%). Mann-Whitney U-test or Chi-square test was used for continuous or categorical data. Modified Poisson regression analysis was used to calculate the relative risk (RR) and 95% confidence interval (CI) of the two groups.
RESULTS
The AFP MoM and free β-hCG MoM in the elevated maternal serum AFP group were higher than the normal group (2.25 vs. 0.98, 1.38 vs. 1.04) and the differences were all statistically significant (all < .001). Placenta previa, hepatitis B virus carrying status of pregnant women, premature rupture of membranes (PROM), advanced maternal age (≥35 years), increased free β-hCG MoM, female infants, and low birth weight (RR: 2.722, 2.247, 1.769, 1.766, 1.272, 0.624, 2.554 respectively) were the risk factors for adverse maternal pregnancy outcomes in the elevated maternal serum AFP group.
CONCLUSIONS
Maternal serum AFP levels during the second trimester can monitor IPD, such as IUGR, PROM, and placenta previa. Maternal women with high serum AFP levels are more likely to deliver male fetuses and low birth weight infants. Finally, the maternal age (≥35 years) and hepatitis B carriers also increased maternal serum AFP significantly.
Topics: Pregnancy; Infant; Humans; Female; Male; Adult; alpha-Fetoproteins; Placenta Previa; Retrospective Studies; Placenta; Chorionic Gonadotropin, beta Subunit, Human
PubMed: 36849437
DOI: 10.1080/10641963.2023.2175848 -
Indian Journal of Surgical Oncology May 2024Liver cancer is one of the most prevalent types of cancer and a major contributor to the socioeconomic burden worldwide. The pathogenesis of hepatocellular carcinoma... (Review)
Review
Liver cancer is one of the most prevalent types of cancer and a major contributor to the socioeconomic burden worldwide. The pathogenesis of hepatocellular carcinoma (HCC) is contributed by various etiological factors like virus infection, excessive alcohol consumption, exposure to toxins, or metabolic disorders. Majority of patients are diagnosed with late-stage HCC, which restricts its management to only palliative care. HCC, if diagnosed early, increases the survival and quality of life. Currently available biomarker (alpha-fetoproteins) have several limitations, that impede the early diagnosis and staging of cancer. This warrants the continous search in pursuit of a novel biomarker. Several research works in diverse areas have contributed to the identification of various novel biomarkers that have shown multifaceted application in early disease diagnosis, which further aid in targeted and effective therapy that can prevent cancer progression. This improves the overall health status of the patient along with significant reduction in caretaker's burden. With the aid of novel technologies, several biomarkers have been investigated and validated in mutliple preliminary research works. Therefore in this review, we have outlined various novel biomarkers that showed promising outcomes in their trials and we have highlighted the developing areas that act as game changers in cancer diagnosis and management.
PubMed: 38817995
DOI: 10.1007/s13193-023-01858-x -
Cancers Aug 2023Transarterial chemoembolization (TACE) is used as a bridging treatment in liver transplant candidates with hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is the...
Transarterial chemoembolization (TACE) is used as a bridging treatment in liver transplant candidates with hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is the main tumor marker used for HCC surveillance. The aim of this study was to assess the potential of using the AFP change after the first TACE in the prediction of complete tumor necrosis. The study comprised 101 patients with HCC who underwent liver transplantation (LT) after TACE in the period between January 2011 and December 2020. The ΔAFP was defined as the difference between the AFP value before the first TACE and AFP either before the second TACE or the LT. The receiver operator characteristics (ROC) curves were used to identify an optimal cut-off value. Complete tumor necrosis was found in 26.1% (18 of 69) and 6.3% (2 of 32) of patients with an initial AFP level under and over 100 ng/mL, respectively ( = 0.020). The optimal cut-off value of ΔAFP for the prediction of complete necrosis was a decline of ≥10.2 ng/mL and ≥340.5 ng/mL in the corresponding subgroups. Complete tumor necrosis rates were: 62.5% (5 of 8) in patients with an initial AFP < 100 ng/mL and decline of ≥10.2 ng/mL; 21.3% (13 of 61) in patients with an initial AFP < 100 ng/mL and decline of <10.2 ng/mL; 16.7% (2 of 12) in patients with an initial AFP > 100 ng/mL and decline of ≥340.5 ng/mL; and null in 20 patients with an initial AFP > 100 ng/mL and decline of <340.5 ng/mL, respectively ( = 0.003). The simple scoring system, based on the initial AFP and AFP decline after the first treatment, distinguished between a high, intermediate and low probability of complete necrosis, with an area under the ROC curve of 0.699 (95% confidence intervals 0.577 to 0.821, = 0.001). Combining the initial AFP with its change after the first treatment enables early identification of the efficacy of TACE.
PubMed: 37568778
DOI: 10.3390/cancers15153962 -
Molecular Biotechnology Oct 2023Hepatocellular carcinoma (HCC) is the primary malignancy of hepatocytes and the second most common cause of cancer-related mortality across the globe. Despite... (Review)
Review
Hepatocellular carcinoma (HCC) is the primary malignancy of hepatocytes and the second most common cause of cancer-related mortality across the globe. Despite significant advancements in screening, diagnosis, and treatment modalities for HCC, the mortality-to-incidence ratio remain unacceptably high. A recent study indicates that a minor population of HCCs are AFP negative or express the normal range of AFP levels. Although it is a gold standard and a more reliable biomarker in the advanced stage of HCC and poorly differentiated tumors, it does not serve as a suitable means for screening HCC. AFP plays a significant role in the development and progression of HCC and understanding its role is crucial. By examining the molecular mechanisms involved in AFP-mediated tumorigenesis, we can better understand HCC pathogenesis and identify potential therapeutic targets. This article details the role of alpha-fetoprotein (AFP) in the carcinogenic transformation of hepatocytes. The article also focuses on information about the structure, biosynthesis, and regulation of AFP at the gene level. Additionally, it discusses the immune evasion, metastasis, and control of gene expression that AFP mediates during HCC.
PubMed: 37782430
DOI: 10.1007/s12033-023-00890-0 -
European Radiology Oct 2023
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Friends; Biomarkers, Tumor; Magnetic Resonance Imaging
PubMed: 37548693
DOI: 10.1007/s00330-023-09934-0 -
Surgical Oncology Clinics of North... Jan 2024Hepatocellular carcinoma (HCC) surveillance is recommended by professional society guidelines given a consistent association with reduced HCC-related mortality. HCC... (Review)
Review
Hepatocellular carcinoma (HCC) surveillance is recommended by professional society guidelines given a consistent association with reduced HCC-related mortality. HCC surveillance should be performed using semiannual abdominal ultrasound and alpha-fetoprotein, although this combination has suboptimal sensitivity and can miss more than one-third of HCC at an early stage. There are promising emerging blood-based and imaging-based strategies, including abbreviated MRI and biomarker panels; however, these require further validation before routine use in clinical practice. HCC surveillance is underused in clinical practice due to patient-related and provider-related barriers, highlighting a need for interventions to improve surveillance utilization in clinical practice.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Ultrasonography
PubMed: 37945138
DOI: 10.1016/j.soc.2023.06.005 -
Translational Oncology Oct 2023Gastric cancer is one of the most common malignant tumors in the world. Alpha fetoprotein (AFP)-positive gastric cancer (AFPP-GC) is considered a special entity among...
Gastric cancer is one of the most common malignant tumors in the world. Alpha fetoprotein (AFP)-positive gastric cancer (AFPP-GC) is considered a special entity among gastric cancers. There is still controversy regarding the clinicopathological characteristics and prognosis of AFPP-GC, and the potential mechanism underlying its high malignant potential is still unclear. A comprehensive description of AFPP-GC genomic characteristics and regulatory mechanisms is lacking. This study analyzed the pathological characteristics and prognosis of AFPP-GC by utilizing clinical samples. The results showed that AFPP-GC has a poor prognosis and a high of risk liver metastasis. Tissue transcriptome sequencing showed that genes with high expression in AFPP-GC were involved in the activation of various cancer pathways, and genes with low expression were involved in the immune response. Single-sample gene set enrichment analysis showed that overexpression of AFP in AFPP-GC significantly inhibited the infiltration of CD8 T cells. To further explore the genomic characteristics of AFPP-GC, the signaling pathway by which AFP regulates the invasion and metastasis of AFPP-GC cells was discussed. The results showed that AFPP-GC may promote cell invasion by regulating the PTEN/AKT1/SOX5/CES1 signaling axis. This study reveals the molecular mechanism underlying the increased malignant potential of AFPP-GC vs. AFP-negative gastric cancer (AFPN-GC). This provides important information for individualized treatment of AFPP-GC.
PubMed: 37478671
DOI: 10.1016/j.tranon.2023.101737