BACKGROUND

The survival advantage of HER2-positive breast cancer from targeted treatment is commonly undermined by catastrophic health expenditure (CHE), particularly in resource-limited areas. Recognizing that financial catastrophe leads to non-adherence to treatment and dissaving practices, we examined the out-of-pocket (OOP) expenses of patients with HER2-positive breast cancer.

OBJECTIVE

The study aimed to estimate the median total per-cycle out-of-pocket expenditure of HER2-positive breast cancer treatment from the patient perspective, in public and private clinics, evaluate the association of catastrophic health expenditure with non-adherence to treatment, and describe dissaving practices.

METHODS

This was a cross-sectional micro-costing analysis of the treatment of HER2-positive breast cancer from the patient perspective from a tertiary cancer center and select private clinics in the Philippines. Random sampling of patients with HER2-positive breast cancer was done. Using a validated questionnaire, a guided interview was administered. Catastrophic health expenditure was estimated as having OOP of >20% of the household income. OOP costs were assessed retrospectively from the time of confirmed HER2 diagnosis up to the date of survey, while household income referred to the corresponding period. The proportion of patients experiencing catastrophic health expenditure was computed. Fisher's exact was used to assess for any association between CHE and non-adherence to treatment. Descriptive statistics were used to report dissaving practices. All statistical analyses were performed using Stata analytical software version 12.

RESULTS

A total of 101 patients participated in the study. The mean age of participants from the tertiary cancer center and private clinics were 52 and 58 years old respectively. Patients from the private clinics had a median total OOP expenditure of PhP 54,737.06 (IQR = PhP 102,670.00), compared with patients from tertiary cancer center who had a median total OOP expenditure of PhP 13,920.66 (IQR = PhP 20,830.00). The overall prevalence of CHE (90.9%, 95% CI 0.81, 0.95) and nonadherence to treatment with trastuzumab (79%, 95% CI 0.70, 0.87) were high, and similar in both groups. A number of dissaving practices such as resignation from work, borrowing money from friends, selling assets were observed.

CONCLUSION

The high rate of CHE and treatment delay among patients with HER2-positive breast cancer were not addressed by the existing cancer programs. Most OOP expenditure was for trastuzumab. Current cancer support programs have potential to address the financial impact of their treatment.

Human ; Therapeutics ; Survival ; Patients ; Neoplasms ; Philippines ; Health Expenditures ; Breast Neoplasms

BACKGROUND

Early-stage endometrial cancer often presents with favorable survival rates, but high-risk factors, including TP53 mutations and high-grade serous pathology, can lead to recurrence and poor prognosis. The standard primary treatment for endometrial cancer is surgical staging, and lymph node metastases significantly impact adjuvant therapy decisions. The subgroup of p53-abnormal (p53abn) indicates the worst prognosis and potential benefits from adjuvant chemotherapy. Molecular classification, while recommended, faces practical challenges due to resource constraints.

OBJECTIVES

The study aimed to assess the incidence of p53 abnormal expression in clinical stage 1 endometrial cancer cases that underwent surgery at a government tertiary hospital, and assess its relationship with clinicopathologic factors and pelvic and paraaortic lymph node metastasis (LNM).

METHODS

A cross-sectional retrospective analysis was conducted on clinical early-stage endometrial cancer cases that underwent surgical primary treatment between January 2018 and December 2022. Patient records were reviewed to gather demographics, surgical information, and pathological evaluations. Preoperative clinical staging was determined through imaging, and surgical staging involved comprehensive lymphadenectomy. Immunohistochemistry studies for p53 were carried out on formalin-fixed paraffin-embedded tissue samples.

RESULTS

A total of 233 endometrial cancer cases were included. The mean age at diagnosis was 53.7 years. Common comorbidities included hypertension (47.2%) and dyslipidemia (20.6%). Most cases were endometrioid histology (82.8%) and low-grade tumors (85.8%). Tumor grade (p=0.010), myometrial invasion (p<0.001) and lymphovascular space invasion (p<0.001) significantly correlated with lymph node metastasis. However, tumor size and p53abn were not significantly associated with lymph node metastasis. p53abn overexpression was significantly associated with non-endometrioid histology at 33% and Grade 3 tumors at 23%. Preoperative grading demonstrated moderate reliability (0.51) with postoperative grading, with an agreement of 65.4%.

CONCLUSION

Tumor grade, myometrial invasion, and LVSI were all significantly associated with lymph node involvement. While p53 immunohistochemical stains show promise in predicting metastasis and has been associated with tumor aggressiveness, this should still be correlated with clinicopathological parameters to carry out a more accurate risk stratification of early-stage patients.

Therapeutics ; Survival Rate ; Risk Factors ; Recurrence ; Prognosis ; Pathology ; Endometrial Neoplasms ; Immunohistochemistry ; Tumor Suppressor Protein P53 ; Lymph Node Excision ; Risk Assessment

BACKGROUND

Cyanotic congenital heart disease (CHD) accounts for 20% of all cardiac malformations with an estimated incidence of 2.5–3 per 1,000 live births. An increasing number of patients now survive into adolescence, with or without intervention, forming a unique group requiring specialized care.

OBJECTIVE

To determine factors influencing survival among adolescents with unrepaired cyanotic CHD.

METHODOLOGY

This single-center case-control study was conducted from 2017 to 2022 in a specialized tertiary center in the Philippines. Sample size was based on a 2.6% total fatality rate among infants who underwent CHD operations. Binary logistic regression was used to identify significant predictors of survival, with pRESULTS

Among 125 subjects, 58% (72/125) were males with a median age of 16 years. The median age at diagnosis was 1 year and 1 month; 73% resided outside Metro Manila. Most patients were New York Heart Association (NYHA) Class I (49%), with Tetralogy of Fallot as the most common diagnosis (52%) and 26% had palliative procedures. Predictors of survival included place of origin (OR 0.38, 95% CI 0.15–0.95, p = 0.039), oxygen saturation (OR 1.12, 95% CI 1.06–1.17, pCONCLUSION

Optimizing oxygenation, improving access to care and strengthening targeted interventions are crucial for enhancing survival among adolescents with unrepaired cyanotic CHD.

Human ; Male ; Female ; Adolescent: 13-18 Yrs Old ; Adolescent ; Heart Defects, Congenital ; Survival

BACKGROUND

Cyanotic congenital heart disease (CHD) accounts for 20% of all cardiac malformations with an estimated incidence of 2.5–3 per 1,000 live births. An increasing number of patients now survive into adolescence, with or without intervention, forming a unique group requiring specialized care.

OBJECTIVE

To determine factors influencing survival among adolescents with unrepaired cyanotic CHD.

METHODOLOGY

This single-center case-control study was conducted from 2017 to 2022 in a specialized tertiary center in the Philippines. Sample size was based on a 2.6% total fatality rate among infants who underwent CHD operations. Binary logistic regression was used to identify significant predictors of survival, with pRESULTS

Among 125 subjects, 58% (72/125) were males with a median age of 16 years. The median age at diagnosis was 1 year and 1 month; 73% resided outside Metro Manila. Most patients were New York Heart Association (NYHA) Class I (49%), with Tetralogy of Fallot as the most common diagnosis (52%) and 26% had palliative procedures. Predictors of survival included place of origin (OR 0.38, 95% CI 0.15–0.95, p = 0.039), oxygen saturation (OR 1.12, 95% CI 1.06–1.17, pCONCLUSION

Optimizing oxygenation, improving access to care and strengthening targeted interventions are crucial for enhancing survival among adolescents with unrepaired cyanotic CHD.

Human ; Male ; Female ; Adolescent: 13-18 Yrs Old ; Adolescent ; Heart Defects, Congenital ; Survival

OBJECTIVE: To entrap carvacrol (CAR) in bovine serum albumin nanoparticles (BSANPs) to form CAR-loaded BSANPs (CAR@BSANPs) and to explore the anti-cancer effects in breast adenocarcinoma cells (MCF-7 cells) treated with CAR and CAR@BSANPs. METHODS: A desolvation method was used to synthesize BSANPs and CAR@BSANPs. The BSANPs and CAR@BSANPs were characterized by several physicochemical methods, including visual observation, high-resolution field emission scanning electron microscopy, Fourier transform infrared spectroscopy, and high-performance liquid chromatography. MCF-7 cells were used and analyzed after 24 h of exposure to CAR and CAR@BSANPs at half-maximal inhibitory concentration. The anti-proliferative, apoptotic, reactive oxygen species (ROS), and nitric oxide (NO) scavenging activity as well as gene expression analysis were investigated by the cell viability assay, phase-contrast microscopy, 2',7'-dichlorofluorescein-diacetate assay, Griess-Illosvoy colorimetric assay, and quantitative real-time polymerase chain reaction, respectively. RESULTS: CAR and CAR@BSANPs showed anti-proliferative, apoptotic, ROS generation, and NO scavenging effects on MCF-7 cells. Expression profile of B-cell lymphoma 2-like 11 (BCL2L11), vascular endothelial growth factor A (VEGFA), hypoxia inducible factor factor-1α (HIF1A), BCL2L11/apoptosis regulator (BAX), and BCL2L11/Bcl2 homologous antagonist/killer 1 (BAK1) ratios revealed downregulated genes; and BAX, BAK1, and CASP8 were upregulated by CAR and CAR@BSANPs treatment. In vitro anticancer assays of the CAR and CAR@BSANPs showed that CAR@BSANPs demonstrated higher therapeutic efficacy in the MCF-7 cells than CAR. CONCLUSIONS CAR and CAR@BSANPs affect gene expression and may subsequently reduce the growth and proliferation of the MCF-7 cells. Molecular targeting of regulatory genes of the MCF-7 cells with CAR and CAR@BSANPs may be an effective therapeutic strategy against breast cancer.
Humans ; Cymenes ; Nanoparticles/ultrastructure* ; MCF-7 Cells ; Breast Neoplasms/genetics* ; Apoptosis/drug effects* ; Serum Albumin, Bovine/chemistry* ; Monoterpenes/therapeutic use* ; Adenocarcinoma/genetics* ; Cell Proliferation/drug effects* ; Reactive Oxygen Species/metabolism* ; Female ; Cell Survival/drug effects* ; Animals ; Gene Expression Regulation, Neoplastic/drug effects* ; Nitric Oxide/metabolism* ; Cattle

OBJECTIVE: To investigate the effects of Bushen Huoxue Granule on the ubiquitin-proteasome system (UPS) in an in vitro model of Parkinson's disease. METHODS: After treated with 1-methyl-4-phenylpyridinium (MPP⁺, 1 mmol/L) for 24 h, the cells were incubated with drug-free serum, Madopar-containing serum or Bushen Huoxue Granule-containing serum (BCS, 5%, 10%, and 20%) for another 24 h. The levels of α-synuclein (α-syn), tyrosine hydroxylase (TH) and UPS-related proteins were detected by Western blot. The expression levels of α-syn in PC12 cells were also analyzed by Western blot after treated with proteasome inhibitor MG132 and WT-α-syn plasmid transfection, respectively, as well as the alterations induced by subsequent BCS intervention. Immunocytochemistry was performed to determine the changes in α-syn phosphorylation at serine 129 (pSer129-α-syn) expression. The 20S proteasome levels were measured by enzyme-linked immunosorbnent assay. RESULTS: BCS (volume fraction ⩽20%) intervention could alleviate the MMP⁺-induced cell viability decrease (P<0.05). In the MPP⁺ treated cells, α-syn was up-regulated, while TH and proteins of UPS such as ubiquitin (Ub), Ub binding with Ub-activating enzyme (UBE1), Parkin and Ub C-terminal hydrolase-1 (UCHL-1) were down-regulated (P<0.05). BCS intervention could attenuate the above changes (P<0.05). The activity of BCS on blocking α-syn accumulation was weakened by MG132 (P<0.05). While α-syn level was significantly increased in cells transfected with plasmid, and reduced by BCS intervention (P<0.05). pSer129-α-syn was increased in MPP⁺-induced PC12 cells, whereas decreased by later BCS intervention (P<0.05). The 20S proteasome activity of MPP⁺-induced PC12 cells was decreased, but increased after BCS intervention (P<0.05). CONCLUSION BCS intervention protected UPS function, increased 20S proteasome activity, promoted pathological α-syn clearance, restored cell viability, and reversed the damage caused by MPP⁺ in the in vitro model of Parkinson's disease.
PC12 Cells ; alpha-Synuclein/metabolism* ; Rats ; Animals ; 1-Methyl-4-phenylpyridinium/toxicity* ; Proteasome Endopeptidase Complex/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Ubiquitin/metabolism* ; Cell Survival/drug effects* ; Phosphorylation/drug effects* ; Tyrosine 3-Monooxygenase/metabolism*

OBJECTIVES: To explore the underlying pharmacological mechanisms and its potential effects of Chinese medicine herbal formula Sini Powder (SNP) on hepatocellular carcinoma (HCC). METHODS: The active components of SNP and their in vivo distribution were identified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Construction of component-target-disease networks, protein-protein interaction network, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking were employed to analyze the active components and anti-HCC mechanisms of SNP. Cell viability assay and wound healing assay were utilized to confirm the effect of SNP-containing serum (2.5%, 5.0%, 10%, 20%, and 40%), isoprenaline or propranolol (both 10, 100, and 1,000 µ mol/L) on proliferation and migration of HepG 2 or Huh7 cells. Meanwhile, the effect of isoprenaline or propranolol on the β 2 adrenergic receptor (ADRB2) mRNA expression on HepG2 cells were measured by real-time quantitative reverse transcription (RT-qPCR). Mice with subcutaneous tumors were either subjected to chronic restraint stress (CRS) followed by SNP administration (364 mg/mL) or directly treated with SNP (364 mg/mL). These two parallel experiments were performed to validate the effects of SNP on stress responses. Stress-related proteins and hormones were quantified using RT-qPCR, enzyme-linked immunosorbent assay, and immunohistochemistry. Metagenomic sequencing was performed to confirm the influence of SNP on the gut microbiota in the tumor-bearing CRS mice. RESULTS: The distribution of the 12 active components of SNP was confirmed in various tissues and feces. Network pharmacology analysis confirmed the anti-HCC effects of the 5 active components. The potential anti-HCC mechanisms of SNP may involve the epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC) and signal transducer and activator of transcription 3 (STAT3) pathways. SNP-containing serum inhibited the proliferation of HepG2 and Huh7 cells at concentrations of 2.5% and 5.0%, respectively, after 24 h of treatment. Furthermore, SNP suppressed tumor progression in tumor-bearing mice exposed to CRS. SNP treatment also downregulated the expressions of stress-related proteins and pro-inflammatory cytokines, primarily by modulating the gut microbiota. Specifically, the abundance of Alistipes and Prevotella, which belong to the phylum Bacteroidetes, increased in the SNP-treated group, whereas Lachnospira, in the phylum Firmicutes, decreased. CONCLUSION SNP can combat HCC by alleviating stress responses through the regulation of gut microbiota.
Animals ; Gastrointestinal Microbiome/drug effects* ; Liver Neoplasms/microbiology* ; Carcinoma, Hepatocellular/microbiology* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Powders ; Cell Proliferation/drug effects* ; Mice ; Molecular Docking Simulation ; Cell Line, Tumor ; Hep G2 Cells ; Receptors, Adrenergic, beta-2/genetics* ; Stress, Physiological/drug effects* ; Cell Movement/drug effects* ; Male ; Protein Interaction Maps/drug effects* ; Cell Survival/drug effects* ; Proto-Oncogene Mas

OBJECTIVE: To explore the main components and potential mechanisms of Sangqi Qingxuan Liquid in the treatment of arterial vascular endothelial cells (AVECs) injury in hypertension through network pharmacology. METHODS: Traditional Chinese Medicine Systems Pharmacology and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID) were used to screen the active components of Sangqi Qingxuan Liquid (SQQX), which met the oral utilization rate and drug similarity criteria. An active component-target network was constructed using Cytoscape 3.6 software. A protein-protein interaction (PPI) network of targets associated with SQQX treatment for hypertension was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The Metascape database was used to perform enrichment analysis of gene ontology biological functions and MSigDB pathway enrichment analysis of proteins in the PPI network. Further analysis of the main components of SQQX was performed using UPLC-MS. Based on the results of network pharmacology, the mechanism of SQQX to improve the injury of AVECs in hypertension was verified through lentiviral transfection by Wnt/ β -catenin signaling pathway. AVECs induced by angiotensin II (Ang II ) was used to establish a model of endothelial function injury in hypertension. Cell viability, intracellular nitric oxide content, malonaldehyde content, and superoxide dismutase activity were measured to determine the optimal induction conditions. The optimal intervention conditions for SQQX were determined based on cell viability, cellular DNA activity, and the gradient method. The cells were further divided into blank, model, overexpression lentivirus negative control, overexpression lentivirus, overexpression lentivirus + SQQX intervention (2.47 mg/mL, 12 h), inhibition lentivirus negative control, inhibition lentivirus, and inhibition lentivirus + SQQX intervention (2.47 mg/mL, 12 h) groups. Finally, quantitative real-time PCR and Western blotting were performed to analyze the molecular mechanisms of SQQX in the Wnt/ β -catenin signaling pathway. RESULTS: The main SQQX components were betaine, buddleoside, and chlorogenic acid, in descending order. Network pharmacology analysis screened 12 pathways associated with the hypertensive vascular endothelium. The results showed that 1 µ mol/L for 12 h was the optimal condition for Ang II to induce AVECs injury, and 2.47 mg/mL SQQX intervention for 12 h was the optimal condition for treating AVECs injury. In the experimental validation based on the interaction network of the Wnt/ β -catenin signaling pathway, SQQX significantly decreased the expressions of β -catenin, Smad2, peroxisome proliferator-activated receptors (PPARs), endothelial nitric oxide synthase (eNOS), and endothelin-1 (ET-1) caused by the β -catenin overexpression lentivirus (P<0.05 or P<0.01). The function of vascular endothelial cells can be improved by the β -catenin inhibition lentivirus, and no obvious changes were observed after further intervention with SQQX. CONCLUSION SQQX may protect against AVECs injury by regulating the Wnt/β -catenin signaling pathway.
Drugs, Chinese Herbal/therapeutic use* ; beta Catenin/metabolism* ; Hypertension/metabolism* ; Endothelial Cells/metabolism* ; Protein Interaction Maps/drug effects* ; Humans ; Wnt Signaling Pathway/drug effects* ; Network Pharmacology ; Endothelium, Vascular/injuries* ; Cell Survival/drug effects* ; Angiotensin II/pharmacology* ; Nitric Oxide/metabolism*

OBJECTIVE: To explore the anti-photoaging properties of salvianolic acid B (Sal B). METHODS: The optimal photoaging model of human immortalized keratinocytes (HaCaT cells) were constructed by expose to ultraviolet B (UVB) radiation. The cells were divided into control, model and different concentrations of Sal B groups. Cell viability was measured via cell counting kit-8. Subsequently, the levels of oxidative stress, including reactive oxygen species (ROS), hydroxyproline (Hyp), catalase (CAT), and glutathione peroxidase (GSH-Px) were detected using the relevant kits. Silent information regulator 1 (SIRT1) protein level was detected using Western blot. The binding pattern of Sal B and SIRT1 was determined via molecular docking. RESULTS: Sal B significantly increased the viability of UVB-irradiated HaCaT cells (P<0.05 or P<0.01). Sal B effectively scavenged the accumulation of ROS induced by UVB (P<0.05 or P<0.01). In addition, Sal B modulated oxidative stress by increasing the intracellular concentrations of Hyp and CAT and the activity of GSH-Px (P<0.05 or P<0.01). The Western blot results revealed a substantial increase in SIRT1 protein levels following Sal B administration (P<0.05). Moreover, Sal B exhibited good binding affinity toward SIRT1, with a docking energy of -7.5 kCal/mol. CONCLUSION Sal B could improve the repair of photodamaged cells by alleviating cellular oxidative stress and regulating the expression of SIRT1 protein.
Humans ; Sirtuin 1/metabolism* ; Ultraviolet Rays ; Oxidative Stress/radiation effects* ; Keratinocytes/metabolism* ; Molecular Docking Simulation ; Benzofurans/pharmacology* ; Skin Aging/radiation effects* ; Reactive Oxygen Species/metabolism* ; Cell Survival/radiation effects* ; HaCaT Cells ; Hydroxyproline/metabolism* ; Glutathione Peroxidase/metabolism* ; Catalase/metabolism* ; Depsides

OBJECTIVES: Hypoxia/reoxygenation (H/R) injury is a critical pathological process during liver transplantation. Kazinol B has known anti-inflammatory, anti-apoptotic, and metabolic regulatory properties, but its protective mechanism in H/R-induced liver injury remains unclear. This study aims to investigate the protective effects and underlying mechanisms of Kazinol B in H/R-induced hepatocyte injury. METHODS: An ischemia-reperfusion model was established in healthy adult male Sprague-Dawley rats, and an in vitro H/R model was created using cultured hepatocytes. Hepatocytes were treated with Kazinol B (0-100 μmol/L) to assess cytotoxicity and protective effects. Cell viability was evaluated using the cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) release assays. Expression of apoptosis-related proteins, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad), and cleaved caspase-3, was detected by Western blotting. Reactive oxygen species (ROS) levels were assessed via fluorescence probes, and inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured using enzyme-linked immunosorbent assay (ELISA). TdT-mediated nick end labeling (TUNEL) staining was performed to assess DNA damage and apoptosis. RESULTS: Kazinol B had no significant effect on hepatocyte viability at 0-50 μmol/L, but showed cytotoxicity at 100 μmol/L (P<0.05). At 0.1-20 μmol/L, Kazinol B significantly improved cell survival, reduced LDH release, decreased apoptosis, and attenuated DNA damage (all P<0.001). At 10 μmol/L, Kazinol B markedly down-regulated Bad and cleaved caspase-3 (both P<0.05), and up-regulated Bcl-2 (P<0.01). It also dose-dependently reduced ROS levels and inflammatory cytokines TNF-α and IL-1β (all P<0.01). Both in vitro and in vivo, Kazinol B inhibited activation of the c-Jun N-terminal kinase (JNK) pathway without affecting extracellular regulated protein kinase (ERK) signaling (P>0.05). TUNEL staining showed that the protective effect of Kazinol B against apoptosis was partially reversed by the JNK agonist anisomycin (P<0.01). CONCLUSIONS Kazinol B mitigates hepatocyte injury induced by H/R by inhibiting the JNK signaling pathway. Its protective effect is associated with suppression of oxidative stress and inflammation, indicating its potential as a hepatoprotective agent.
Animals ; Hepatocytes/pathology* ; Rats, Sprague-Dawley ; Male ; Rats ; Reperfusion Injury/prevention & control* ; Apoptosis/drug effects* ; Reactive Oxygen Species/metabolism* ; MAP Kinase Signaling System/drug effects* ; Cell Survival/drug effects* ; Cell Hypoxia ; Cells, Cultured