RESUMEN
BACKGROUND/OBJECTIVES: Obesity, characterized by abnormal fat accumulation and metabolic disturbances, presents a significant health challenge. Opuntia humifusa Raf., commonly known as Korean Cheonnyuncho, is rich in various beneficial compounds and has demonstrated antioxidant and anti-inflammatory effects. However, its potential impact on glucose and lipid metabolism, particularly in obese rats, remains unexplored. We aimed to investigate whether O. humifusa stems and fruits could beneficially alter glucose metabolism and lipid profiles in a rat model of high-fat diet (HFD)-induced obesity. MATERIALS/METHODS: Thirty-two rats were allocated into 4 groups: normal diet (NF), HFD control (HF), HFD treated with 2% O. humifusa stems (HF-OS), and HFD treated with 2% O. humifusa fruits (HF-OF). Experimental diets were administered for 6 weeks. At the end of the treatment, liver and fat tissues were isolated, and serum was collected for biochemical analysis. The major flavonoid from O. humifusa stems and fruits was identified and quantified. RESULTS: After 6 weeks of treatment, the serum fasting glucose concentration in the HF-OS group was significantly lower than that in the HF group. Serum fasting insulin concentrations in both HF-OS and HF-OF groups tended to be lower than those in the HF group, indicating a significant improvement in insulin sensitivity in the HF-OS group. Additionally, the HF-OS group exhibited a tendency towards the restoration of adiponectin levels to that of the NF group. CONCLUSION: The 2% O. humifusa stems contain abundant quercetin and isorhamnetin, which alter fasting blood glucose levels in rats fed a HFD, leading to a favorable improvement in insulin resistance.
RESUMEN
Accurate detection of homologous recombination deficiency (HRD) in cancer patients is paramount in clinical applications, as HRD confers sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors. With the advances in genome sequencing technology, mutational profiling on a genome-wide scale has become readily accessible, and our knowledge of the genomic consequences of HRD has been greatly expanded and refined. Here, we review the recent advances in HRD detection methods. We examine the copy number and structural alterations that often accompany the genome instability that results from HRD, describe the advantages of mutational signature-based methods that do not rely on specific gene mutations, and review some of the existing algorithms used for HRD detection. We also discuss the choice of sequencing platforms (panel, exome, or whole-genome) and catalog the HRD detection assays used in key PARP inhibitor trials.
RESUMEN
This review aimed to examine the effects of curcumin on chronic inflammatory metabolic disease by extensively evaluating meta-analyses of randomized controlled trials (RCTs). We performed a literature search of meta-analyses of RCTs published in English in PubMed®/MEDLINE up to 31 July 2023. We identified 54 meta-analyses of curcumin RCTs for inflammation, antioxidant, glucose control, lipids, anthropometric parameters, blood pressure, endothelial function, depression, and cognitive function. A reduction in C-reactive protein (CRP) levels was observed in seven of ten meta-analyses of RCTs. In five of eight meta-analyses, curcumin intake significantly lowered interleukin 6 (IL-6) levels. In six of nine meta-analyses, curcumin intake significantly lowered tumor necrosis factor α (TNF-α) levels. In five of six meta-analyses, curcumin intake significantly lowered malondialdehyde (MDA) levels. In 14 of 15 meta-analyses, curcumin intake significantly reduced fasting blood glucose (FBG) levels. In 12 of 12 meta-analyses, curcumin intake significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR). In seven of eight meta-analyses, curcumin intake significantly reduced glycated hemoglobin (HbA1c) levels. In eight of ten meta-analyses, curcumin intake significantly reduced insulin levels. In 14 of 19 meta-analyses, curcumin intake significantly reduced total cholesterol (TC) levels. Curcumin intake plays a protective effect on chronic inflammatory metabolic disease, possibly via improved levels of glucose homeostasis, MDA, TC, and inflammation (CRP, IL-6, TNF-α, and adiponectin). The safety and efficacy of curcumin as a natural product support the potential for the prevention and treatment of chronic inflammatory metabolic diseases.
Asunto(s)
Curcumina , Inflamación , Enfermedades Metabólicas , Ensayos Clínicos Controlados Aleatorios como Asunto , Curcumina/farmacología , Curcumina/administración & dosificación , Humanos , Inflamación/tratamiento farmacológico , Enfermedades Metabólicas/tratamiento farmacológico , Enfermedad Crónica , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Resistencia a la Insulina , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Metaanálisis como Asunto , Antioxidantes/farmacologíaRESUMEN
Objective: Effective functional biomarkers that can be readily used in clinical practice to predict poly(ADP-ribose) polymerase inhibitor (PARPi) sensitivity are lacking. With the widespread adoption of PARPi maintenance therapy in ovarian cancer, particularly in patients with BRCA mutation or HR deficiencies, accurately identifying de novo or acquired resistance to PARPi has become critical in clinical practice. We investigated RAD51 immunohistochemistry (IHC) as a functional biomarker for predicting PARPi sensitivity in ovarian cancer. Methods: Ovarian cancer patients who had received PARPi and had archival tissue samples prior to PARPi exposure ("pre-PARPi") and/or after progression on PARPi ("post-PARPi") were selected. RAD51 IHC expression was semi-quantitatively evaluated using the H-score in geminin (a G2/S phase marker)- and γH2AX (a DNA damage marker)-positive tissues. A RAD51 H-score of 20 was used as the cutoff value. Results: In total, 72 samples from 56 patients were analyzed. The median RAD51 H-score was 20 (range: 0-90) overall, 10 (0-190) in pre-PARPi samples (n = 34), and 25 (1-170) in post-PARPi samples (n = 19). Among patients with BRCA mutations, RAD51-low patients had better progression-free survival (PFS) after PARPi treatment than RAD51-high patients (P = 0.029). No difference was found in PFS with respect to the genomic scar score (P = 0.930). Analysis of matched pre- and post-PARPi samples collected from 15 patients indicated an increase in the RAD51 H-score upon progression on PARPi, particularly among pre-PARPi low-RAD51-expressing patients. Conclusion: RAD51 is a potential functional IHC biomarker of de novo and acquired PARPi resistance in BRCA-mutated ovarian cancer and can be used to fine-tune ovarian cancer treatment.
RESUMEN
Human epidermal growth factor receptor-2 (HER2)-targeting drugs are increasingly being incorporated into therapeutic paradigms for non-breast cancers, yet studies on HER2 expression in ovarian cancer (OC) are inadequate. Here, we studied the HER2 status and dynamic changes in OC by reviewing the records of patients who underwent HER2 testing at a single institution. Clinical parameters, including histology, BRCA status, and immunohistochemistry (IHC), were evaluated alongside HER2 expression, timing, and anatomical location. Among 200 patients, 28% and 6% exhibited expression scores of 2+ and 3+, respectively. HER2 3+ scores were observed in 23%, 11%, 9%, and 5% of mucinous, endometrioid, clear cell, and high-grade serous tumors, respectively, and were exclusively identified in BRCA-wildtype, mismatch repair-proficient, or PD-L1-low-expressing tumors. The TP53 mutation rate was low, whereas ARID1A, KRAS, and PIK3CA mutations were relatively more prevalent with HER2 scores of 2+ or 3+ than with 0 or 1+. Four of the five tumors with an HER2 3+ score exhibited ERBB2 amplification. Among 19 patients who underwent multiple time-lagged biopsies, 11 showed increased HER2 expression in subsequent biopsies. Patients with HER2-overexpressing OC exhibited distinct histological, IHC, and genomic profiles. HER2-targeting agents are potential options for BRCA-wildtype patients, particularly as later lines of treatment.
Asunto(s)
Neoplasias Ováricas , Receptor ErbB-2 , Femenino , Humanos , Mutación , Tasa de Mutación , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Receptor ErbB-2/metabolismoRESUMEN
BACKGROUND: Uptake of postnatal care (PNC) is low and inequitable in many countries, and immigrant women may experience additional challenges to access and effective use. As part of a larger study examining the views of women, partners, and families on routine PNC, we analysed a subset of data on the specific experiences of immigrant women and families. METHODS: This is a subanalysis of a larger qualitative evidence synthesis. We searched MEDLINE, PUBMED, CINAHL, EMBASE, EBM-Reviews and grey literature for studies published until December 2019 with extractable qualitative data with no language restrictions. For this analysis, we focused on papers related to immigrant women and families. Two reviewers screened each study independently; inclusion was agreed by consensus. Data abstraction and quality assessment were carried out using a study-specific extraction form and established quality assessment tools. Study findings were identified using thematic analysis. Findings are presented by confidence in the finding, applying the GRADE-CERQual approach. FINDINGS: We included 44 papers, out of 602 full-texts, representing 11 countries where women and families sought PNC after immigrating. All but one included immigrants to high-income countries. Four themes were identified: resources and access, differences from home country, support needs, and experiences of care. High confidence study findings included: language and communication challenges; uncertainty about navigating system supports including transportation; high mental health, emotional, and informational needs; the impact of personal resources and social support; and the quality of interaction with healthcare providers. These findings highlight the importance of care experiences beyond clinical care. More research is also needed on the experiences of families migrating between low-income countries. CONCLUSIONS: Immigrant families experience many challenges in getting routine PNC, especially related to language, culture, and communication. Some challenges may be mitigated by improving comprehensive and accessible information on available services, as well as holistic social support. TRIAL REGISTRATION NUMBER: CRD42019139183.
Asunto(s)
Emigrantes e Inmigrantes , Atención Posnatal , Embarazo , Humanos , Femenino , Accesibilidad a los Servicios de Salud , Apoyo Social , Personal de SaludRESUMEN
AIM: We investigated the efficacy and safety of durvalumab (D) with or without tremelimumab (T) in addition to single-agent chemotherapy (CT) in patients with platinum-resistant recurrent ovarian cancer (PROC) lacking homologous recombination repair (HRR) gene mutations. PATIENTS AND METHODS: KGOG 3045 was an open-label, investigator-initiated phase II umbrella trial. Patients with PROC without HRR gene mutations who had received ≥2 prior lines of therapy were enrolled. Patients with high PD-L1 expression (TPS ≥25%) were assigned to arm A (D + CT), whereas those with low PD-L1 expression were assigned to arm B (D + T75 + CT). After completing arm B recruitment, patients were sequentially assigned to arms C (D + T300 + CT) and D (D + CT). RESULTS: Overall, 58 patients were enrolled (5, 18, 17, and 18 patients in arms A, B, C, and D, respectively). The objective response rates were 20.0, 33.3, 29.4, and 22.2%, respectively. Grade 3-4 treatment-related adverse events were observed in 20.0, 66.7, 47.1, and 66.7 of patients, respectively, but were effectively managed. Multivariable analysis demonstrated that adding T to D + CT improved progression-free survival (adjusted HR, 0.435; 95% CI, 0.229-0.824; P = 0.011). Favorable response to chemoimmunotherapy was associated with MUC16 mutation (P = 0.0214), high EPCAM expression (P = 0.020), high matrix remodeling gene signature score (P = 0.017), and low FOXP3 expression (P = 0.047). Patients showing favorable responses to D + T + CT exhibited significantly higher EPCAM expression levels (P = 0.008) and matrix remodeling gene signature scores (P = 0.031) than those receiving D + CT. CONCLUSIONS: Dual immunotherapy with chemotherapy showed acceptable response rates and tolerable safety in HRR non-mutated PROC, warranting continued clinical investigation.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Anticuerpos Monoclonales , Antígeno B7-H1 , Neoplasias Ováricas , Humanos , Femenino , Molécula de Adhesión Celular Epitelial , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosAsunto(s)
Neoplasias Ováricas , Femenino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma Epitelial de Ovario , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Ftalazinas/efectos adversosRESUMEN
Circulating tumor DNA (ctDNA) may aid in personalizing ovarian cancer therapeutic options. Here, we aimed to assess the clinical utility of serial ctDNA testing using tumor-naïve, small-sized next-generation sequencing (NGS) panels. A total of 296 patients, including 201 with ovarian cancer and 95 with benign or borderline disease, were enrolled. Samples were collected at baseline (initial diagnosis or surgery) and every 3 months after that, resulting in a total of 811 blood samples. Patients received adjuvant therapy based on the current standard of care. Cell-free DNA was extracted and sequenced using an NGS panel of 9 genes: TP53, BRCA1, BRCA2, ARID1A, CCNE1, KRAS, MYC, PIK3CA, and PTEN. Pathogenic somatic mutations were identified in 69.2% (139/201) of patients with ovarian cancer at baseline but not in those with benign or borderline disease. Detection of ctDNA at baseline and/or at 6 months follow-up was predictive of progression-free survival (PFS). PFS was significantly poorer in patients with detectable pathogenic mutations at baseline that persisted at follow-up than in patients that converted from having detectable ctDNA at baseline to being undetectable at follow-up; survival did not differ between patients without pathogenic ctDNA mutations in baseline or follow-up samples and those that converted from ctDNA positive to negative. Disease recurrence was also detected earlier with ctDNA than with conventional radiologic assessment or CA125 monitoring. These findings demonstrate that serial ctDNA testing could effectively monitor patients and detect minimal residual disease, facilitating early detection of disease progression and tailoring of adjuvant therapies for ovarian cancer treatment. SIGNIFICANCE: In ovarian cancer, serial circulating tumor DNA testing is a highly predictive marker of patient survival, with a significantly improved recurrence detection lead time compared with conventional monitoring tools.
Asunto(s)
ADN Tumoral Circulante , Neoplasias Ováricas , Humanos , Femenino , ADN Tumoral Circulante/genética , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Biomarcadores de Tumor/genética , MutaciónRESUMEN
Objectives: In Nepal, where increasing numbers of married couples live apart due to migration, progress in reducing unmet need for family planning (UMN) is stagnant. This study aims to identify spatial patterns of UMN of married women and spousal separation in Nepal and explore associations between UMN and spousal separation at individual- and district-levels. Methods: We used 2016 Nepal Demographic and Health Surveys data to conduct spatial and multilevel logistic analyses. Results: This study shows evidence of similar geographical patterns in UMN of married women and spousal separation. At the individual level, women living with their spouses had 88% (aOR = 0.12, 95% CI 0.11-0.13) decreased odds of experiencing UMN compared to those living apart from their spouses. While not statistically significant, increasing odds of UMN were observed with higher prevalence of spousal separation at the district level. Conclusion: This study contributes to the existing literature by showing similar geographical patterns of UMN and spousal separation across Nepal and demonstrating both individual and contextual effects of spousal separation on UMN among married women. Theoretical and policy implications are discussed.
Asunto(s)
Conducta Anticonceptiva , Servicios de Planificación Familiar , Humanos , Femenino , Nepal , Análisis Multinivel , EspososRESUMEN
Genomic hypomethylation has recently been identified as a determinant of therapeutic responses to immune checkpoint blockade (ICB). However, it remains unclear whether this approach can be applied to cell-free DNA (cfDNA) and whether it can address the issue of low tumor purity encountered in tissue-based methylation profiling. In this study, we developed an assay named iMethyl, designed to estimate the genomic hypomethylation status from cfDNA. This was achieved through deep targeted sequencing of young LINE-1 elements with > 400,000 reads per sample. iMethyl was applied to a total of 653 ICB samples encompassing lung cancer (cfDNA n = 167; tissue n = 137; cfDNA early during treatment n = 40), breast cancer (cfDNA n = 91; tissue n = 50; PBMC n = 50; cfDNA at progression n = 44), and ovarian cancer (tissue n = 74). iMethyl-liquid predicted ICB responses accurately regardless of the tumor purity of tissue samples. iMethyl-liquid was also able to monitor therapeutic responses early during treatment (3 or 6 weeks after initiation of ICB) and detect progressive hypomethylation accompanying tumor progression. iMethyl-tissue had better predictive power than tumor mutation burden and PD-L1 expression. In conclusion, our iMethyl-liquid method allows for reliable noninvasive prediction, early evaluation, and monitoring of clinical responses to ICB therapy.
Asunto(s)
Neoplasias de la Mama , Ácidos Nucleicos Libres de Células , Neoplasias Pulmonares , Humanos , Femenino , Ácidos Nucleicos Libres de Células/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Leucocitos Mononucleares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Genómica/métodos , Pulmón/patología , Biomarcadores de Tumor/genéticaRESUMEN
BACKGROUND: Poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis) are becoming the standard of care for epithelial ovarian cancer (EOC). Recently, clinical trials of triple maintenance therapy (PARPi+anti-angiogenic agent+anti-PD-1/L1) are actively ongoing. Here, we investigated the immunological effects of PARPi or triple maintenance therapy on T cells and their impact on clinical responses. METHODS: We collected serial blood from EOC patients receiving PARPi therapy (cohort 1: PARPi, n = 49; cohort 2: olaparib+bevacizumab+pembrolizumab, n = 31). Peripheral T cells were analyzed using flow cytometry and compared according to the PARPi response. Progression-free survival (PFS) was assessed according to prognostic biomarkers identified in a comparative analysis. RESULTS: Regulatory T cells (Tregs) were suppressed by PARPi therapy, whereas PD-1 was not significantly changed. Short PFS group exhibited a higher percentage of baseline PD-1+Tregs than long PFS group, and the patients with high percentage of PD-1+Tregs before treatment showed poor PFS in cohort 1. However, the expression of PD-1 on Tregs significantly decreased after receiving triple maintenance therapy, and the reduction in PD-1+Tregs was associated with superior PFS in cohort 2 (P = 0.0078). CONCLUSION: PARPi suppresses Tregs, but does not affect PD-1 expression. Adding anti-PD-1 to PARPi decreases PD-1+Tregs, which have negative prognostic value for PARPi monotherapy.
Asunto(s)
Antineoplásicos , Neoplasias Ováricas , Humanos , Femenino , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/uso terapéutico , Linfocitos T Reguladores , Antineoplásicos/uso terapéutico , Poli(ADP-Ribosa) PolimerasasRESUMEN
Osteoporosis is a health condition that involves weak bone mass and a deteriorated microstructure, which consequently lead to an increased risk of bone fractures with age. In elderly people, a fracture attributable to osteoporosis elevates mortality. The objective of this review was to examine the effects of macronutrients on bone mineral density (BMD), bone turnover markers (BTMs), and bone fracture in elderly people based on human studies. A systematic search was conducted in the PubMed®/MEDLINE® database. We included human studies published up to April 2023 that investigated the association between macronutrient intake and bone health outcomes. A total of 11 meta-analyses and 127 individual human studies were included after screening the records. Carbohydrate consumption seemed to have neutral effects on bone fracture in limited studies, but human studies on carbohydrates' effects on BMD or/and BTMs are needed. The human studies analyzed herein did not clearly show whether the intake of animal, vegetable, soy, or milk basic proteins has beneficial effects on bone health due to inconsistent results. Moreover, several individual human studies indicated an association between eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and osteocalcin. Further studies are required to draw a clear association between macronutrients and bone health in elderly people.
Asunto(s)
Fracturas Óseas , Osteoporosis , Animales , Humanos , Anciano , Densidad Ósea , Fracturas Óseas/etiología , Fracturas Óseas/prevención & control , Osteoporosis/metabolismo , Nutrientes , Remodelación ÓseaRESUMEN
In this multicenter, open-label, single-arm, Phase II study with Simon two-stage optimum design (NCT04361370), we investigate the efficacy and safety of triplet maintenance (olaparib, pembrolizumab, bevacizumab) in patients with platinum-sensitive recurrent ovarian cancer who are wild-type for BRCA 1/2. A total of 44 patients were enrolled, and the median follow-up duration was 22.9 months (interquartile range: 17.4-24.7). The primary outcome was 6-months progression-free survival (PFS), which was 88.6% (95% confidence interval [CI] 75.4-96.2), meeting the pre-specified primary endpoint. The secondary outcomes reported here include median PFS, 12-months PFS, and overall survival and safety. The median PFS was 22.4 months (20.4-∞), with a 12-months PFS rate of 84.0% (95% CI 69.3-92.0). The median overall survival was 28.6 months (27.3-∞). The combination demonstrated tolerable toxicity with manageable side effects. Other secondary outcomes include time-to-progression, time to subsequent treatment, time to second treatment and PFS2; however, this data is not reported, as treatment is still ongoing in a majority of patients. Exploratory analysis shows that patients who were homologous recombination deficiency-positive or had a programmed death-ligand 1 combined positive score ≥1 showed a favorable response (P = 0.043 and P < 0.001, respectively). Thus, triplet maintenance shows durable efficacy with tolerable safety in patients with platinum-sensitive recurrence.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Neoplasias Ováricas , Humanos , Femenino , Bevacizumab/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Carcinoma Epitelial de Ovario , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genéticaRESUMEN
Choosing an optimal concomitant drug for combination with poly-ADP ribose polymerase (PARP) inhibitor based on patient-specific biomarker status may help increase to improve treatment efficacy in patients with ovarian cancer. However, the efficacy and safety of different PARP inhibitor-based combinations in patients with homologous recombination repair (HRR) mutations have not been evaluated in ovarian cancer. In this sub-study of Korean Gynecologic Oncology Group (KGOG) 3045, we compared the efficacy and safety of two olaparib-based combinations and biomarkers of patients with platinum-resistant ovarian cancer with HRR gene mutations. Patients were randomized to receive either olaparib (200 mg twice a day) + cediranib (30 mg daily) (Arm 1, n = 16) or olaparib (300 mg) + durvalumab (1,500 mg once every 4 weeks) (Arm 2, n = 14). The objective response rates for Arm 1 and Arm 2 were 50.0% and 42.9%, respectively. Most patients (83.3%) had BRCA mutations, which were similarly distributed between arms. Grade 3 or 4 treatment-related adverse events were observed in 37.5% and 35.7% of the patients, respectively, but all were managed properly. A high vascular endothelial growth factor signature was associated with favorable outcomes in Arm 1, whereas immune markers (PD-L1 expression [CPS ≥10], CD8, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio) were associated with favorable outcomes in Arm 2. The activation of homologous recombination pathway upon disease progression was associated with poor response to subsequent therapy. Based on comprehensive biomarker profiling, including immunohistochemistry, whole-exome and RNA sequencing and whole blood-based analyses, we identified biomarkers that could help inform which of the two combination strategies is appropriate given a patient's biomarker status. Our findings have the potential to improve treatment outcome for patients with ovarian cancer in the PARP inhibitor era.
Asunto(s)
Antineoplásicos , Neoplasias Ováricas , Femenino , Humanos , Antineoplásicos/uso terapéutico , Biomarcadores , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/inducido químicamente , Ftalazinas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Reparación del ADN por Recombinación , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
OBJECTIVE: We aimed to investigate the oncologic outcomes of patients with endometrial cancer who underwent sentinel lymph node (SLN) biopsy without ultrastaging compared with that of those who underwent lymphadenectomy (LND). METHODS: Patients with endometrial cancer who underwent staging with SLN biopsy or LND during 2006 - 2021 were analyzed using propensity score matching (PSM). SLN metastasis was examined using hematoxylin and eosin staining, without ultrastaging. Progression-free survival (PFS) was compared between the two groups before and after PSM using age, histology, and stage as covariates. Clinical variables such as recurrence patterns and lymphatic complications, were assessed. RESULTS: After excluding 213 patients who underwent validation LND with SLN biopsy, 902 were identified. The demographics of the remaining patients differed according to histology, myometrial invasion depth, and stage. Lymph node metastasis was less frequent in the SLN group than in the LND group (9.4% vs. 3.8%, p=0.004). The recurrence rates within 2 years were lower in the SLN group. The SLN group exhibited significantly superior 2-year and overall PFS than the LND group. Among patients with uterus-confined disease, overall PFS was favorable for SLN biopsy. After matching, differences in PFS were no longer observed, although the lymphocele and lymphedema rates were significantly lower in the SLN group. CONCLUSION: In patients with endometrial cancer, SLN biopsy without ultrastaging did not compromise survival outcomes and was associated with significantly reduced lymphatic complication rates compared with LND. Therefore, SLN biopsy can be recommended for patients with endometrial cancer without definitive preoperative evidence of distant metastasis.
Asunto(s)
Neoplasias Endometriales , Ganglio Linfático Centinela , Femenino , Humanos , Supervivencia sin Progresión , Ganglio Linfático Centinela/cirugía , Ganglio Linfático Centinela/patología , Biopsia del Ganglio Linfático Centinela , Escisión del Ganglio Linfático/efectos adversos , Ganglios Linfáticos/patología , Neoplasias Endometriales/patología , Metástasis Linfática/patología , Estadificación de NeoplasiasRESUMEN
OBJECTIVE: To evaluate the landscape of gene alterations and immunohistochemistry (IHC) profiles of patients with ovarian cancer for targeted therapy and investigate the real-world experience of applying precision medicine. METHODS: Patients diagnosed with ovarian cancer between January 2015 and May 2021 at Severance Hospital and who underwent tumor next-generation sequencing (NGS) were reviewed. Data on germline mutation, IHC markers for mismatch repair deficiency (MMRd), programmed death ligand 1 (PD-L1) expression, and human epidermal growth factor receptor 2 (HER2) expression were acquired. The use of matched therapy and its clinical outcomes were evaluated. RESULTS: Of the 512 patients who underwent tumor NGS, 403 underwent panel-based germline testing. In patients who underwent both tests, tumor NGS identified 39 patients (9.7%) with BRCA mutations and 16 patients (4.0%) with other homologous recombination repair (HRR)-associated gene mutations, which were not found in germline testing. The most common single nucleotide variants were TP53 (82.2%), ARID1A (10.4%), PIK3CA (9.7%), and KRAS (8.4%). Copy number aberrations were found in 122 patients. MMRd was found in 3.2% of patients, high PD-L1 expression in 10.1%, and HER2 overexpression in 6.5%. Subsequently, 75 patients (14.6%) received a poly (ADP-ribose) polymerase inhibitor based on BRCA mutation and 11 patients (2.1%) based on other HRR-associated gene mutations. Six patients (1.2%) with MMRd underwent immunotherapy. Twenty-eight patients (5.5%) received other matched therapies targeting HER2, fibroblast growth factor receptor, folate receptor alpha, RAS, and PIK3CA. CONCLUSION: A comprehensive review of germline mutation, IHC, and tumor NGS helped identify candidates for precision therapy in patients with ovarian cancer, a proportion of whom received matched therapy.
Asunto(s)
Antígeno B7-H1 , Neoplasias Ováricas , Humanos , Femenino , Antígeno B7-H1/genética , Antígeno B7-H1/uso terapéutico , Medicina de Precisión , Inmunohistoquímica , Neoplasias Ováricas/terapia , Neoplasias Ováricas/tratamiento farmacológico , Secuenciación de Nucleótidos de Alto Rendimiento , Fosfatidilinositol 3-Quinasa Clase I/genética , Fosfatidilinositol 3-Quinasa Clase I/uso terapéutico , MutaciónRESUMEN
The prevalence of metabolic syndrome (MetS) and its cost are increasing due to lifestyle changes and aging. This study aimed to develop a deep neural network model for prediction and classification of MetS according to nutrient intake and other MetS-related factors. This study included 17,848 individuals aged 40-69 years from the Korea National Health and Nutrition Examination Survey (2013-2018). We set MetS (3-5 risk factors present) as the dependent variable and 52 MetS-related factors and nutrient intake variables as independent variables in a regression analysis. The analysis compared and analyzed model accuracy, precision and recall by conventional logistic regression, machine learning-based logistic regression and deep learning. The accuracy of train data was 81.2089, and the accuracy of test data was 81.1485 in a MetS classification and prediction model developed in this study. These accuracies were higher than those obtained by conventional logistic regression or machine learning-based logistic regression. Precision, recall, and F1-score also showed the high accuracy in the deep learning model. Blood alanine aminotransferase (ß = 12.2035) level showed the highest regression coefficient followed by blood aspartate aminotransferase (ß = 11.771) level, waist circumference (ß = 10.8555), body mass index (ß = 10.3842), and blood glycated hemoglobin (ß = 10.1802) level. Fats (cholesterol [ß = -2.0545] and saturated fatty acid [ß = -2.0483]) showed high regression coefficients among nutrient intakes. The deep learning model for classification and prediction on MetS showed a higher accuracy than conventional logistic regression or machine learning-based logistic regression.
RESUMEN
Purpose: This study aimed to investigate genomic and immunohistochemical (IHC) profiles and immunotherapy outcomes in patients with cervical cancer. Methods: Patients with recurrent cervical cancer who underwent tumor next-generation sequencing (NGS) with the TruSight Oncology 500 panel at Yonsei Cancer Center between June 2019 and February 2022, were identified. Patients who received treatment with checkpoint inhibitors during the same period were also identified. Clinical information, including histology, stage, human papillomavirus (HPV) genotype, IHCs profile, and therapy outcome, was reviewed. Results: We identified 115 patients treated for recurrent cervical cancer, including 74 patients who underwent tumor NGS. Most of these 74 patients were initially diagnosed with advanced stage (63.6%) and had squamous cell histology (52.7%), and high-risk HPV (76.9%). Based on IHC analysis, the programmed death-ligand 1 combined positive score (PD-L1 CPS) was higher in patients with squamous cell carcinoma (SCC) than in those with adeno or mucinous types (P=0.020). HER2 receptor expression of 2+ and 3+ were identified in 5 and 1 patients, respectively, and significantly varied based on histology (p=0.002). Among the 74 patients, single nucleotide variants (SNVs) and copy number variations (CNVs) were identified in 60 (81.1%) and 13 patients (17.6%), respectively. The most common SNVs were PIK3CA, TP53, STK11, FAT1, and FBXW7 mutations. Mutations in PIK3CA, with two hotspot mutations, were frequently observed in patients with SCC histology, whereas mutations in TP53 were frequently observed in patients with non-SCC histology. Additionally, variations in FAT1 were exclusively identified in patients with SCC histology. Mutations in homologous recombination repair-associated genes were identified in 18 patients (24.3%). The most frequent CNV alteration was CCNE1 amplification. Moreover, among the 36 patients who underwent NGS and received immunotherapy, the tumor mutational burden and microsatellite instability were significantly correlated with immunotherapy duration. During this timeframe, 73 patients received pembrolizumab monotherapy, among whom a small portion showed a durable response. Conclusion: Comprehensive genomic and IHC profiling may help identify potential candidates for targeted immunotherapy in patients with cervical cancer.
RESUMEN
Cardiometabolic disorders are characterised by a cluster of interactive risk determinants such as increases in blood glucose, lipids and body weight, as well as elevated inflammation and oxidative stress and gut microbiome changes. These disorders are associated with onset of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). T2DM is strongly associated with CVD. Dietary advanced glycation end products (dAGEs) attributable from modern diets high in sugar and/or fat, highly processed foods and high heat-treated foods can contribute to metabolic etiologies of cardiometabolic disorders. This mini review aims to determine whether blood dAGEs levels and tissue dAGEs levels are determinants of the prevalence of cardiometabolic disorders through recent human studies. ELISA (enzyme-linked immunosorbent assay), high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) for blood dAGEs measurement and skin auto fluorescence (SAF) for skin AGEs measurement can be used. Recent human studies support that a diet high in AGEs can negatively influence glucose control, body weight, blood lipid levels and vascular health through the elevated oxidative stress, inflammation, blood pressure and endothelial dysfunction compared with a diet low in AGEs. Limited human studies suggested a diet high in AGEs could negatively alter gut microbiota. SAF could be considered as one of the predictors affecting risks for cardiometabolic disorders. More intervention studies are needed to determine how dAGEs are associated with the prevalence of cardiometabolic disorders through gut microbiota changes. Further human studies are conducted to find the association between CVD events, CVD mortality and total mortality through SAF measurement, and a consensus on whether tissue dAGEs act as a predictor of CVD is required.