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1.
J Glob Health ; 14: 04123, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38939961

ABSTRACT

Background: Emotion-oriented approaches have demonstrated effectiveness in the care of the elderly. However, related studies have reported conflicting results. We aimed to explore the pooled effect of emotion-oriented approaches on the psychological outcomes and cognitive function of older adults through a meta-analysis of randomised controlled trials (RCTs). Methods: We searched eight databases - CINAHL, Cochrane, Embase, Ovid MEDLINE, PsycINFO, PubMed, Scopus, and Web of Science - for RCTs from inception to 11 January 2024. Participants aged 60 years or older who received emotion-oriented approaches as the intervention, and reported outcomes of interest in the studies were included. The primary outcome was psychological outcomes (depression, self-esteem, life satisfaction and loneliness), and the secondary outcome was global cognitive function. The pooled effect size was computed in comprehensive meta-analysis 3.0 software using Hedges' g (g) with random-effects model. Furthermore, heterogeneity was assessed through Cochrane's Q and I2 tests. The quality of the included studies was evaluated using the Cochrane Risk of Bias tool. To explore potential sources of heterogeneity, moderator analyses were conducted. Results: We included 37 RCTs and found that emotion-oriented approaches improve depression (g = -0.82, 95% CI = -1.08, -0.56), self-esteem (g = 0.98, 95% CI = 0.31, 1.64), life satisfaction (g = 0.63, 95% CI = 0.37, 0.88), loneliness (g = -2.22, 95% CI = -3.80, -0.64) and global cognitive function (g = 0.34, 95% CI = 0.19, 0.49) in older adults. We also observed significant follow-up effects on depression (g = -1.40, 95% CI = -2.45, -0.34) and loneliness (g = -3.48, 95% CI = 6.02, -0.94). Conclusions: Emotion-oriented approaches are promising interventions in improving psychological outcomes and global cognitive function in older adults. Health care workers should receive training to promote and integrate emotion-oriented approaches into routine care of older adults emphasising the importance of collaborative efforts among health care professionals and caregivers to ensure holistic care delivery.


Subject(s)
Cognition , Emotions , Randomized Controlled Trials as Topic , Humans , Aged , Depression , Middle Aged , Loneliness/psychology , Self Concept , Aged, 80 and over , Personal Satisfaction
2.
Nanomaterials (Basel) ; 14(11)2024 May 26.
Article in English | MEDLINE | ID: mdl-38869559

ABSTRACT

This study developed a DC-free technique that used dark-mode scanning capacitance microscopy (DM-SCM) with a small-area contact electrode to evaluate and image equivalent oxide thicknesses (EOTs). In contrast to the conventional capacitance-voltage (C-V) method, which requires a large-area contact electrode and DC voltage sweeping to provide reliable C-V curves from which the EOT can be determined, the proposed method enabled the evaluation of the EOT to a few nanometers for thermal and high-k oxides. The signal intensity equation defining the voltage modulation efficiency in scanning capacitance microscopy (SCM) indicates that thermal oxide films on silicon can serve as calibration references for the establishment of a linear relationship between the SCM signal ratio and the EOT ratio; the EOT is then determined from this relationship. Experimental results for thermal oxide films demonstrated that the EOT obtained using the DM-SCM approach closely matched the value obtained using the typical C-V method for frequencies ranging from 90 kHz to 1 MHz. The percentage differences in EOT values between the C-V and SCM measurements were smaller than 0.5%. For high-k oxide films, DM-SCM with a DC-free operation may mitigate the effect of DC voltages on evaluations of EOTs. In addition, image operations were performed to obtain EOT images showing the EOT variation induced by DC-stress-induced charge trapping. Compared with the typical C-V method, the proposed DM-SCM approach not only provides a DC-free approach for EOT evaluation, but also offers a valuable opportunity to visualize the EOT distribution before and after the application of DC stress.

3.
Int J Med Sci ; 21(8): 1408-1413, 2024.
Article in English | MEDLINE | ID: mdl-38903923

ABSTRACT

The Sodium-glucose co-transporter 2 (SGLT2) inhibitor is an anti-glycemic agent that frequently used in type 2 diabetes mellitus (T2DM) with antioxidant effects. Endometrial cancer (EC) is a common gynecological malignancy that correlates with oxidative stress. The aim in the present study is to survey the potential association between the SGLT2 inhibitor administration and the incidence of EC by the application of the National Health Insurance Research Database (NHIRD) of Taiwan. A retrospective cohort study was directed and the T2DM participants were divided into the SGLT2 inhibitors users and non-SGLT2 inhibitors users. After matching, a total of 163,668 and 327,336 participants were included into the SGLT2 inhibitors and control groups, respectively. The primary outcome is regarded as the development of EC according to the diagnostic, image, and procedure codes. Cox proportional hazard regression was employed to generate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of EC between the two groups. There were 422 and 876 EC events observed in the SGLT2 inhibitors and control groups, respectively. The SGLT2 inhibitors group demonstrated a significantly lower incidence of EC formation compared to the control groups (aHR: 0.87, 95% CI: 0.76-0.99). In the subgroup analysis, the correlation between SGLT2 inhibitor administration and lower rate of EC existed in the T2DM individuals with aged under 60. Moreover, the association between SGLT2 inhibitor administration and lower EC incidence only presented in the T2DM population with SGLT2 inhibitor administration under one year (aHR: 0.58, 95% CI: 0.45-0.73). In conclusion, the administration of SGLT2 inhibitors correlates to lower incidence of EC in T2DM population.


Subject(s)
Diabetes Mellitus, Type 2 , Endometrial Neoplasms , Sodium-Glucose Transporter 2 Inhibitors , Humans , Female , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Endometrial Neoplasms/epidemiology , Middle Aged , Incidence , Taiwan/epidemiology , Retrospective Studies , Aged , Adult
4.
Int J Med Sci ; 21(8): 1428-1437, 2024.
Article in English | MEDLINE | ID: mdl-38903932

ABSTRACT

CD44 genetic variants have been found to be related to various cancers. However, to date, no study has demonstrated the involvement of CD44 polymorphisms in uterine cervical cancer in Taiwanese women. Therefore, we conducted a retrospective study, consecutively recruiting 113 patients with invasive cancer, 92 patients with high-grade cervical intraepithelial neoplasias, and 302 control women to assess the relationships among CD44 polymorphisms, cervical carcinogenesis, and patient survival. Real-time polymerase chain reaction was used to determine the genotypic distributions of six polymorphisms: rs1425802, rs187115, rs713330, rs11821102, rs10836347, and rs13347. The results revealed that women with the mutant homozygous genotype CC exhibited a higher risk of invasive cancer compared to those with the wild homozygous genotype TT [p=0.035; hazard ratio (HR)=10.29, 95% confidence interval (95% CI)=1.18-89.40] and TT/TC [p=0.032; HR=10.66, 95% CI=1.23-92.11] in the CD44 polymorphism rs713330. No significant association was found between CD44 genetic variants and clinicopathological parameters. Among the clinicopathological parameters, only positive pelvic lymph node metastasis (p=0.002; HR=8.57, 95% CI=2.14-34.38) and the AG/GG genotype compared to AA (p=0.014; HR=3.30, 95% CI=1.28-8.49) in CD44 polymorphism rs187115 predicted a higher risk of poor five-year survival, according to multivariate analysis. In conclusion, an important and novel finding revealed that Taiwanese women with the AG/GG genotype in CD44 polymorphism rs187115 exhibited a higher risk of poor five-year survival.


Subject(s)
Genetic Predisposition to Disease , Hyaluronan Receptors , Polymorphism, Single Nucleotide , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/mortality , Hyaluronan Receptors/genetics , Middle Aged , Adult , Retrospective Studies , Taiwan/epidemiology , Genotype , Aged , Uterine Cervical Dysplasia/genetics , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/mortality , Lymphatic Metastasis/genetics , Lymphatic Metastasis/pathology
5.
J Formos Med Assoc ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38821736

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) that against programmed cell death protein-1 (PD-1) and its ligand PD-L1 have been approved as a promising treatment of many human cancers. However, the responses to these ICIs were limited in patients with ovarian cancer. Studies have indicated that the response to PD-1/PD-L1 blockade might be correlated with the PD-L1 expression level in cancer cells. Nucleophosmin (NPM/B23) was found to be a potential target for immunotherapy. Whether NPM/B23 plays a role in cancer-associated immunity, such as PD-1/PD-L1 axis, and its underlying mechanisms remain largely unknown in ovarian cancer. METHODS: We applied ovarian cancer cell lines as research models. The effect of modulating PD-L1 by NPM/B23 was subsequently confirmed via Western blot, flow cytometry, qRT-PCR, luciferase reporter assays, and immunoprecipitation. Protein stability and ubiquitin assay assays were used to analyze the interplay between NPM/B23 and NF-ĸB/p65 in PD-L1 regulation. The MOSEC/Luc xenograft mouse model was used to validate the role of NPM/B23-PD-L1 through tumor growth in vivo. RESULTS: Our results revealed that NPM/B23 negatively regulates PD-L1 expression via a protein complex with NF-κB/p65 and through an IFN-γ pathway. Moreover, NPM/B23 inhibitor/modulator sensitized ovarian cancer cells to the anti-PD-1 antibody by regulating PD-L1 expression in the immunocompetent mouse model. Compared to anti-PD-1 antibody alone, a combination of anti-PD-1 antibody and NPM/B23 inhibitor/modulator showed reduced tumorigenesis and increased CD8+ T-cell expansion, thus contributing to prolonged survival on MOSEC/Luc-bearing mouse model. CONCLUSION: Targeting NPM/B23 is a novel and potential therapeutic approach to sensitize ovarian cancer cells to immunotherapy.

6.
J Mol Med (Berl) ; 102(6): 819-830, 2024 06.
Article in English | MEDLINE | ID: mdl-38568327

ABSTRACT

We conducted a comprehensive metabolomic analysis of plasma samples obtained from pregnant women who displayed varying post-vaccination antibody titers after receiving mRNA-1273-SARS-CoV-2 vaccines. The study involved 62 pregnant women, all of whom had been vaccinated after reaching 24 weeks of gestation. To quantify post-vaccination plasma antibody titers, we employed binding antibody units (BAU) in accordance with the World Health Organization International Standard. Subsequently, we classified the study participants into three distinct BAU/mL categories: those with high titers (above 2000), medium titers (ranging from 1000 to 2000), and low titers (below 1000). Plasma metabolomic profiling was conducted using 1H nuclear magnetic resonance spectroscopy, and the obtained data were correlated with the categorized antibody titers. Notably, in pregnant women exhibiting elevated anti-SARS-CoV-2 antibody titers, reduced plasma concentrations of acetate and urea were observed. A significant negative correlation between these compounds and antibody titers was also evident. An analysis of metabolomics pathways revealed significant inverse associations between antibody titers and four distinct amino acid metabolic pathways: (1) biosynthesis of phenylalanine, tyrosine, and tryptophan; (2) biosynthesis of valine, leucine, and isoleucine; (3) phenylalanine metabolism; and (4) degradation of valine, leucine, and isoleucine. Additionally, an association between the synthesis and degradation pathways of ketone bodies was evident. In conclusion, we identified different metabolic pathways that underlie the diverse humoral responses triggered by COVID-19 mRNA vaccines during pregnancy. Our data hold significant implications for refining COVID-19 vaccination approaches in expectant mothers. KEY MESSAGES : Anti-SARS-CoV-2 antibody titers decline as the number of days since COVID-19 vaccination increases. Anti-SARS-CoV-2 antibody titers are inversely associated with acetate, a microbial-derived metabolite, and urea. Amino acid metabolism is significantly associated with SARS-CoV-2 antibody titers.


Subject(s)
Acetates , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Metabolomics , SARS-CoV-2 , Urea , Vaccination , Humans , Female , Pregnancy , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19/blood , Metabolomics/methods , SARS-CoV-2/immunology , Adult , Urea/blood , COVID-19 Vaccines/immunology , Metabolome , 2019-nCoV Vaccine mRNA-1273
7.
Article in English | MEDLINE | ID: mdl-38563816

ABSTRACT

OBJECTIVE: The endometrial cancer is a disorder with elevated oxidative stress. The high oxidative stress resulting from hyperglycemia can lead to diabetic retinopathy (DR) development which is a complication of type 2 diabetes mellitus. Accordingly, we aim to evaluate the potential relationship between the endometrial cancer and following DR development. METHODS: A retrospective cohort study was conducted using the National Health Insurance Research Database (NHIRD) of Taiwan. Individuals diagnosed with endometrial cancer were matched to the non-endometrial cancer patients in a 1:4 ratio. The major outcomes are the presence of DR, diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) according to diagnostic codes. Cox proportional hazard regression was used to show the adjusted hazard ratio (aHR) with 95% confidence interval (CI) of major outcomes between groups. RESULTS: There were 99 (2.3%), 20 (0.5%), and 14 (0.3%) cases with DR, DME and PDR in the endometrial cancer group, respectively. Another 303 (1.8%), 35 (0.2%), and 27 (0.2%) with DR, DME and PDR were observed in the control group, respectively. The endometrial cancer group revealed a significantly higher incidence of DR compared with the control group (aHR 1.51, 95% CI 1.20-1.90, P < 0.001). The cumulative probability of DR was also higher in the endometrial cancer group than in the control group (P < 0.001). The relationship between endometrial cancer and DR was significantly higher in patients aged over 70 years (P = 0.008). In addition, a higher incidence of DR was found during the first 5 years after the endometrial cancer diagnosis (P < 0.001). CONCLUSIONS: The endometrial cancer correlates to a higher incidence of subsequent DR, especially within first 5 years of endometrial cancer diagnosis.

8.
J Cancer ; 15(8): 2354-2360, 2024.
Article in English | MEDLINE | ID: mdl-38495489

ABSTRACT

Oral squamous cell carcinoma (OSCC) is a prevalent and lethal malignancy with a diverse etiology. LINC00312 is a long intergenic non-coding RNA that functions as a signal hub to regulate the progression and treatment of head and neck cancer. The aim of this study was to evaluate the effect of LINC00312 single nucleotide polymorphisms (SNPs) on the development of oral cancer. Two LINC00312 SNPs, namely rs12497104 and rs164966, were investigated among 469 male patients with cancer of buccal mucosa and 1194 gender- and age-matched controls. No significant correlation was observed between these two SNPs and the occurrence of OSCC in the case and control groups. While assessing the clinicopathological features, carriers of at least one minor allele of rs164966 (GA and GG) were less prone to develop lymph node metastasis (adjusted odds ratio [AOR], 0.666; 95% confidence interval [CI], 0.447-0.991; p=0.045) in comparison with homozygous carriers of the major allele (AA). Subsequent stratifying surveys revealed that this genetic association with nodal spread was seen only in cases who habitually chewed betel quid (AOR, 0.616; 95% CI, 0.386-0.985; p=0.042) or smoked cigarettes (AOR, 0.612; 95% CI, 0.393-0.953; p=0.029), but undetected in cases free of these main behavioral risks. Our results indicate an interactivity of LINC00312 rs164966 with lifestyle-related risks on modulating OSCC progression.

9.
Am J Chin Med ; 52(2): 565-581, 2024.
Article in English | MEDLINE | ID: mdl-38480502

ABSTRACT

L48H37 is a synthetic curcumin analog that has anticancer potentials. Here, we further explored the anticancer effect of L48H37 on oral cancer cells and its mechanistic acts. Cell cycle distribution was assessed using flow cytometric analysis. Apoptosis was elucidated by staining with PI/Annexin V and activation of the caspase cascade. Cellular signaling was explored using apoptotic protein profiling, Western blotting, and specific inhibitors. Our findings showed that L48H37 significantly reduced the cell viability of SCC-9 and HSC-3 cells, resulting in sub-G1 phase accumulation and increased apoptotic cells. Apoptotic protein profiling revealed that L48H37 increased cleaved caspase-3, and downregulated cellular inhibitor of apoptosis protein 1 (cIAP1) and X-linked inhibitor of apoptosis protein (XIAP) in SCC-9 cells, and the downregulated cIAP1 and XIAP in both oral cancer cells were also demonstrated by Western blotting. Meanwhile, L48H37 triggered the activation of caspases and mitogen-activated protein kinases (MAPKs). The involvement of c-Jun N-terminal kinase (JNK) and p38 MAPK (p38) in the L48H37-triggered apoptotic cascade in oral cancer cells was also elucidated by specific inhibitors. Collectively, these findings indicate that L48H37 has potent anticancer activity against oral cancer cells, which may be attributed to JNK/p38-mediated caspase activation and the resulting apoptosis. This suggests a potential benefit for L48H37 for the treatment of oral cancer.


Subject(s)
Curcumin , Mouth Neoplasms , Humans , Caspases/metabolism , Curcumin/pharmacology , Cell Line, Tumor , Apoptosis , p38 Mitogen-Activated Protein Kinases/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Caspase 3/metabolism , Mouth Neoplasms/drug therapy , Inhibitor of Apoptosis Proteins/pharmacology
10.
NPJ Biofilms Microbiomes ; 10(1): 22, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38480743

ABSTRACT

Gut microbiota rearrangement induced by cold temperature is crucial for browning in murine white adipose tissue. This study provides evidence that DUSP6, a host factor, plays a critical role in regulating cold-induced gut microbiota rearrangement. When exposed to cold, the downregulation of intestinal DUSP6 increased the capacity of gut microbiota to produce ursodeoxycholic acid (UDCA). The DUSP6-UDCA axis is essential for driving Lachnospiraceae expansion in the cold microbiota. In mice experiencing cold-room temperature (CR) transitions, prolonged DUSP6 inhibition via the DUSP6 inhibitor (E/Z)-BCI maintained increased cecal UDCA levels and cold-like microbiota networks. By analyzing DUSP6-regulated microbiota dynamics in cold-exposed mice, we identified Marvinbryantia as a genus whose abundance increased in response to cold exposure. When inoculated with human-origin Marvinbryantia formatexigens, germ-free recipient mice exhibited significantly enhanced browning phenotypes in white adipose tissue. Moreover, M. formatexigens secreted the methylated amino acid Nε-methyl-L-lysine, an enriched cecal metabolite in Dusp6 knockout mice that reduces adiposity and ameliorates nonalcoholic steatohepatitis in mice. Our work revealed that host-microbiota coadaptation to cold environments is essential for regulating the browning-promoting gut microbiome.


Subject(s)
Gastrointestinal Microbiome , Animals , Humans , Mice , Adiposity , Cold Temperature , Dual-Specificity Phosphatases/metabolism , Gastrointestinal Microbiome/physiology , Obesity
11.
Sci Total Environ ; 919: 170768, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38340838

ABSTRACT

Mangroves are transition areas connecting land, freshwater, and the ocean, where a great amount of organic carbon accumulates in the soil, forming a considerable carbon sink. However, the soil might also be a source of greenhouse gas (GHG) emissions. This study hypothesized that measuring GHG emissions solely during low tides can represent diurnal GHG emissions in mangroves. Methane (CH4) and carbon dioxide (CO2) emissions were quantified during tidal cycles using an ultraportable gas analyzer in Kandelia obovata (without pneumatophores) and Avicennia marina (with pneumatophores) mangroves in summer and fall. The results showed that the CH4 fluxes varied greatly during tidal cycles, from -1.25 to 96.24 µmol CH4 m-2 h-1 for K. obovata and from 2.86 to 2662.00 µmol CH4 m-2 h-1 for A. marina. The CO2 fluxes ranged from -4.23 to 20.65 mmol CO2 m-2 h-1 for K. obovata and from 0.09 to 24.69 mmol CO2 m-2 h-1 for A. marina. The diurnal variation in GHG levels in mangroves is predominantly driven by tidal cycles. The peak emissions of CH4 and CO2 were noted at the beginning of the flooding tide, rather than during daytime or nighttime. While the patterns of the CO2 fluxes during tidal cycles were similar between K. obovata and A. marina mangroves, their CH4 flux patterns during the tidal cycles differed. Possibly due to different transport mechanisms, CO2 emissions are primarily influenced by surface soils, whereas CH4 is predominantly emitted from deeper soils, thus being influenced by root structures. To reduce the uncertainty in measuring GHG emissions in mangrove soils during a tidal cycle, it is advisable to increase the number of GHG flux measurements during the period spanning 30 min before and after the beginning of the flooding and ebbing tides.

12.
Int J Biol Sci ; 20(3): 818-830, 2024.
Article in English | MEDLINE | ID: mdl-38250159

ABSTRACT

Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), with high affinity to a myriad of RNA transcripts, has been shown to elicit promotive effects on tumorigenesis and metastasis. Yet, the functional involvement of IGF2BP2 in the progression of oral squamous cell carcinoma (OSCC) remains poorly understood. In this study, we showed that IGF2BP2 was upregulated in head and neck cancer, and high levels of IGF2BP2 were associated with poor survival. In in vitro experiments, IGF2BP2 promoted migration and invasion responses of OSCC cells. Moreover, we identified an IGF2BP2-regulated gene, EREG, which functioned as a modulator of OSCC invasion downstream of IGF2BP2. In addition, EREG expression triggered the epithelia-mesenchymal transition (EMT) in OSCC, as evidenced by the observation that knockdown of EREG weakened the induction of EMT mediated by IFG2BP2, and replenishment of EREG favored the EMT in IGF2BP2-depleted cells. Such IGF2BP2-regulated EREG expression, EMT, and cell invasion were dependent on the activation of FAK/Src signaling pathway. Collectively, these findings suggest that EREG, serving as a functional mediator of IGF2BP2-regulated EMT and cell invasion in oral cancer, may be implicated as a potential target for antimetastatic therapies.


Subject(s)
Mouth Neoplasms , RNA-Binding Proteins , Squamous Cell Carcinoma of Head and Neck , Humans , Epiregulin , Epithelial-Mesenchymal Transition/genetics , Mouth Neoplasms/genetics , RNA-Binding Proteins/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Up-Regulation/genetics
13.
Environ Toxicol ; 39(2): 794-802, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37782689

ABSTRACT

HO-3867, a synthetic curcumin analog, has displayed various tumor-suppressive characteristics and improved bioabsorption over its parent compound. However, its influences on the development of hepatocellular carcinoma (HCC) are poorly defined. To address this, we tested the anticarcinogenic impact of HO-3867 and investigated the underlying mechanisms in fighting liver cancer. Our result demonstrated that HO-3867 reduced the viability of HCC cells, accompanied by promotion of cell cycle arrest at the sub-G1 stage and apoptotic responses. Furthermore, a distinctive profile of apoptosis associated proteins, encompassing elevated heme oxygenase-1 (HO-1) level and caspase activation, was detected in HO-3867-stimulated HCC cells. In addition, such HO-3867-mediated elevation in caspase activation was dampened by pharmacological suppression of p38 activities. Taken together, our findings unveiled that HO-3867 triggered cell cycle arrest and apoptotic events in liver cancer, involving a p38-mediated activation of caspase cascades. These data highlighted a usefulness of curcumin or its analogs on the management of hepatocarcinogenesis.


Subject(s)
Carcinoma, Hepatocellular , Curcumin , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Curcumin/pharmacology , Apoptosis , Heme Oxygenase-1 , Caspases , Caspase 3/metabolism , Cell Line, Tumor , p38 Mitogen-Activated Protein Kinases/metabolism
14.
J Gynecol Oncol ; 35(1): e5, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37743058

ABSTRACT

OBJECTIVE: Lynch syndrome (LS) is a hereditary cancer predisposition syndrome with a significantly increased risk of colorectal and endometrial cancers. Current standard practice involves universal screening for LS in patients with newly diagnosed colorectal or endometrial cancer using a multi-step screening protocol (MSP). However, MSP may not always accurately identify LS cases. To address this limitation, we compared the diagnostic performance of immediate germline sequencing (IGS) with MSP in a high-risk group. METHODS: A total of 31 Taiwanese women with synchronous or metachronous endometrial and colorectal malignancies underwent MSP which included immunohistochemical staining of DNA mismatch repair (MMR) proteins, MLH1 promoter hypermethylation analysis, and germline sequencing to identify pathogenic variants. All patients who were excluded during MSP received germline sequencing for MMR genes to simulate IGS for the detection of LS. RESULTS: Our findings indicate that IGS surpassed MSP in terms of diagnostic yield (29.0% vs. 19.4%, respectively) and sensitivity (90% vs. 60%, respectively). Specifically, IGS successfully identified nine LS cases, which is 50% more than the number detected through MSP. Additionally, germline methylation analysis revealed one more LS case with constitutional MLH1 promoter hypermethylation, bringing the total LS cases to ten (32.3%). Intriguingly, we observed no significant differences in clinical characteristics or overall survival between patients with and without LS in our cohort. CONCLUSION: Our study suggests that IGS may potentially offer a more effective approach compared to MSP in identifying LS among high-risk patients. This advantage is evident when patients have been pre-selected utilizing specific clinical criteria.


Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis , Endometrial Neoplasms , Humans , Female , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Biomarkers, Tumor/analysis , Early Detection of Cancer/methods , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Germ Cells/chemistry , Germ Cells/metabolism , Germ Cells/pathology , DNA Mismatch Repair/genetics , MutL Protein Homolog 1/genetics , DNA Methylation
15.
Adv Healthc Mater ; 13(2): e2302268, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37748773

ABSTRACT

Combination immunotherapy has emerged as a promising strategy to address the challenges associated with immune checkpoint inhibitor (ICI) therapy in breast cancer. The efficacy of combination immunotherapy hinges upon the intricate and dynamic nature of the tumor microenvironment (TME), characterized by cellular heterogeneity and molecular gradients. However, current methodologies for drug screening often fail to accurately replicate these complex conditions, resulting in limited predictive capacity for treatment outcomes. Here, a tumor-microenvironment-on-chip (TMoC), integrating a circulation system and ex vivo tissue culture with physiological oxygen and nutrient gradients, is described. This platform enables spatial infiltration of cytotoxic CD8+ T cells and their targeted attack on the tumor, while preserving the high complexity and heterogeneity of the TME. The TMoC is employed to assess the synergistic effect of five targeted therapy drugs and five chemotherapy drugs in combination with immunotherapy, demonstrating strong concordance between chip and animal model responses. The TMoC holds significant potential for advancing drug development and guiding clinical decision-making, as it offers valuable insights into the complex dynamics of the TME.


Subject(s)
CD8-Positive T-Lymphocytes , Neoplasms , Animals , Tumor Microenvironment , Immunotherapy/methods , Neoplasms/drug therapy , Treatment Outcome
16.
Eur Arch Otorhinolaryngol ; 281(3): 1473-1481, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38127096

ABSTRACT

PURPOSE: By radiomic analysis of the postcontrast CT images, this study aimed to predict locoregional recurrence (LR) of locally advanced oropharyngeal cancer (OPC) and hypopharyngeal cancer (HPC). METHODS: A total of 192 patients with stage III-IV OPC or HPC from two independent cohort were randomly split into a training cohort with 153 cases and a testing cohort with 39 cases. Only primary tumor mass was manually segmented. Radiomic features were extracted using PyRadiomics, and then the support vector machine was used to build the radiomic model with fivefold cross-validation process in the training data set. For each case, a radiomics score was generated to indicate the probability of LR. RESULTS: There were 94 patients with LR assigned in the progression group and 98 patients without LR assigned in the stable group. There was no significant difference of TNM staging, treatment strategies and common risk factors between these two groups. For the training data set, the radiomics model to predict LR showed 83.7% accuracy and 0.832 (95% CI 0.72, 0.87) area under the ROC curve (AUC). For the test data set, the accuracy and AUC slightly declined to 79.5% and 0.770 (95% CI 0.64, 0.80), respectively. The sensitivity/specificity of training and test data set for LR prediction were 77.6%/89.6%, and 66.7%/90.5%, respectively. CONCLUSIONS: The image-based radiomic approach could provide a reliable LR prediction model in locally advanced OPC and HPC. Early identification of those prone to post-treatment recurrence would be helpful for appropriate adjustments to treatment strategies and post-treatment surveillance.


Subject(s)
Hypopharyngeal Neoplasms , Mouth Neoplasms , Oropharyngeal Neoplasms , Humans , Hypopharyngeal Neoplasms/diagnostic imaging , Hypopharyngeal Neoplasms/therapy , Radiomics , Oropharyngeal Neoplasms/diagnostic imaging , Oropharyngeal Neoplasms/therapy , Risk Factors , Retrospective Studies
18.
Microbiol Spectr ; 11(6): e0147123, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-37905800

ABSTRACT

IMPORTANCE: Of 123 identified isolates from the fruit surface, C. tropicalis was the most frequently found species, followed by Meyerozyma caribbica and Candida krusei. All three fluconazole-resistant C. tropicalis were non-susceptible to voriconazole and belonged to the same predominant genotype of azole-resistant C. tropicalis causing candidemia in patients in Taiwan. Our findings provide evidence that fruit should be washed before eaten not only to remove chemicals but also potential drug-resistant pathogenic microbes, especially for immunocompromised individuals. To keep precious treatment options in patients, we not only continuously implement antimicrobial stewardship in hospitals but also reducing/stopping the use of agricultural fungicide classes used in human medicine.


Subject(s)
Antifungal Agents , Candida tropicalis , Humans , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Candida tropicalis/genetics , Fruit , Fluconazole/pharmacology , Voriconazole , Microbial Sensitivity Tests , Drug Resistance, Fungal
19.
Endocr Relat Cancer ; 30(11)2023 11 01.
Article in English | MEDLINE | ID: mdl-37655726

ABSTRACT

Steroid cell tumors, not otherwise specified (SCT-NOS), are uncommon ovarian neoplasms accompanied by virilization symptoms due to hyperandrogenism, which are malignant in approximately one-third of the cases. Given the rarity of SCT-NOS, their molecular underpinnings have not yet been studied in depth. In this case series, we performed the first comprehensive analysis of the genetic landscape of this rare ovarian tumor. A detailed clinicopathological description of an index case is also provided. Over a 20-year period, a total of eight patients were seen at our institution. Total nucleic acids (RNA and DNA) were extracted from evaluable formalin-fixed, paraffin-embedded tumor specimens (n = 7) and subjected to TruSight Oncology 500 testing and/or exome sequencing. The results identified pathogenic variants in several hypoxia-related genes - including HIF1A, VHL, SDHB, SRC, IDH2, and FOXO4. As the first comprehensive genetic analysis of SCT-NOS, this study shows that dysregulation in the hypoxia signaling pathway is a key molecular feature of this rare tumor. Clinically, long-term follow-up with periodic measurements of androgen levels should be pursued in all cases since recurrences may occur several years after the initial diagnosis.


Subject(s)
Ovarian Neoplasms , Sex Cord-Gonadal Stromal Tumors , Female , Humans , Ovarian Neoplasms/metabolism , Sex Cord-Gonadal Stromal Tumors/genetics , Sex Cord-Gonadal Stromal Tumors/complications , Sex Cord-Gonadal Stromal Tumors/diagnosis , Virilism/complications , Virilism/diagnosis , Hypoxia/complications , Steroids
20.
J Cell Mol Med ; 27(21): 3395-3403, 2023 11.
Article in English | MEDLINE | ID: mdl-37724356

ABSTRACT

Oral squamous cell carcinoma (OSCC) is a common malignant disease associated with a high mortality rate and heterogeneous disease aetiology. Cyclin dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1), is a long noncoding RNA that has been shown to act as a scaffold, sponge, or signal hub to promote carcinogenesis. Here, we attempted to assess the effect of CDKN2B-AS1 single-nucleotide polymorphisms (SNPs) on the susceptibility to OSCC. Five CDKN2B-AS1 SNPs, including rs564398, rs1333048, rs1537373, rs2151280 and rs8181047, were analysed in 1060 OSCC cases and 1183 cancer-free controls. No significant association of these five SNPs with the risk of developing OSCC was detected between the case and control group. However, while examining the clinical characteristics, patients bearing at least one minor allele of rs1333048 (CA and CC) were more inclined to develop late-stage (stage III/IV, adjusted OR, 1.480; 95% CI, 1.129-1.940; p = 0.005) and large-size (greater than 2 cm in the greatest dimension, adjusted OR, 1.347; 95% CI, 1.028-1.765; p = 0.031) tumours, as compared with those homologous for the major allele (AA). Further stratification analyses demonstrated that this genetic correlation with the advanced stage of disease was observed only in habitual betel quid chewers (adjusted OR, 1.480; 95% CI, 1.076-2.035; p = 0.016) or cigarette smokers (adjusted OR, 1.531; 95% CI, 1.136-2.063; p = 0.005) but not in patients who were not exposed to these major habitual risks. These data reveal an interactive effect of CDKN2B-AS1 rs1333048 with habitual exposure to behavioural risks on the progression of oral cancer.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , RNA, Long Noncoding , Humans , Carcinoma, Squamous Cell/genetics , Mouth Neoplasms/genetics , Risk Factors , Polymorphism, Single Nucleotide/genetics , Squamous Cell Carcinoma of Head and Neck , RNA, Long Noncoding/genetics
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