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Systematic Review Open Access
Archana Haria, Jonathon Hill, Kylie J. Mansfield
Published online December 25, 2024
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Oncology Advances. doi:10.14218/OnA.2024.00027
Abstract
Breast cancer is the most common cancer among women, with hormone receptors playing a crucial role, not only in cancer cell growth but also as primary targets in breast cancer treatment. [...] Read more.

Breast cancer is the most common cancer among women, with hormone receptors playing a crucial role, not only in cancer cell growth but also as primary targets in breast cancer treatment. This systematic literature review aimed to summarize the current evidence on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) discordance rates between primary and recurrent breast cancer. Additionally, it seeks to identify how discordance affects prognosis, metastasis, and the potential evidence of primary tumor heterogeneity.

The databases Web of Science, Scopus, MEDLINE, and PubMed were searched for publications of original research in English from 2013 to 2023. Studies with paired histopathology from primary and recurrent breast cancer that employed immunohistochemistry and fluorescence in situ hybridization were included. Ten studies were deemed eligible for inclusion.

Concordance between primary and recurrent breast cancer was high for ER (80%), PR (65%), and HER2 (85%). Average discordance rates were: ER 19%, PR 34%, and HER2 15%, with PR discordance consistently being the highest. Loss of ER and PR receptors was observed more frequently than gain, while the opposite trend was noted for HER2. Loss of ER and PR was associated with a worse prognosis. Discordance was also observed in cases of tumor metastasis.

Discordance in receptor expression between primary and recurrent breast cancer was common, highlighting the importance of re-biopsy in recurrent or metastatic breast cancer, if possible. Patients who lost hormone receptors experienced worse outcomes, suggesting the development of treatment-resistant tumor clones.

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Editorial Open Access
Ben J. Gu
Published online March 25, 2025
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00000
Original Article Open Access
María Jesús Ramírez-Expósito, María Pilar Carrera-González, Cristina Cueto-Ureña, José Manuel Martínez-Martos
Published online March 19, 2025
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Oncology Advances. doi:10.14218/OnA.2024.00033
Abstract
The development and progression of breast cancer may be influenced by thyroid hormone levels. In this study, we investigated thyroid function in pre- and postmenopausal women with [...] Read more.

The development and progression of breast cancer may be influenced by thyroid hormone levels. In this study, we investigated thyroid function in pre- and postmenopausal women with breast cancer, with and without neoadjuvant chemotherapy (NCh).

The study included 198 women diagnosed with infiltrating ductal carcinoma: 83 did not receive NCh (39 premenopausal and 44 postmenopausal), while 115 underwent NCh before surgery (63 premenopausal and 52 postmenopausal). Additionally, 78 healthy volunteers, aged 28 to 69 years, served as the control group. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) were quantified using chemiluminescent immunoassays.

We observed a significant increase in serum TSH and fT4 levels in both pre- and postmenopausal women with breast cancer, regardless of NCh treatment, compared to control subjects. However, postmenopausal women with breast cancer who received NCh showed lower fT4 levels than their untreated counterparts. Notably, fT3 levels increased only in premenopausal women with breast cancer who underwent NCh, compared to both the premenopausal control group and untreated premenopausal breast cancer patients.

Altered thyroid function was observed in both pre- and postmenopausal women with breast cancer, characterized by increased TSH and fT4 levels. Neoadjuvant chemotherapy appeared to attenuate the rise in fT4 levels in postmenopausal women while elevating fT3 levels in premenopausal women. These findings highlight the importance of monitoring thyroid hormone profiles in women with breast cancer, considering menopausal status, given their potential influence on tumor progression and chemotherapy effectiveness.

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Letter to the Editor Open Access
Taha Yazal, Chia-Yang Li
Published online August 13, 2024
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00220
Original Article Open Access
David Izon, Olivia Wawryk, Damien McCarthy, Jennifer Soon, Sally Philip, Chris Kearney, Zhiheng Xu, Jianrong Zhang
Published online March 30, 2025
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Oncology Advances. doi:10.14218/OnA.2025.00006
Abstract
Emergency department (ED) presentations are associated with higher cancer mortality. This study aimed to investigate the prevalence, frequency, and risk factors in Australian patients [...] Read more.

Emergency department (ED) presentations are associated with higher cancer mortality. This study aimed to investigate the prevalence, frequency, and risk factors in Australian patients diagnosed with malignant skin cancers.

This data-linkage cohort study examined adult patients presenting to the ED at the Royal Melbourne and Western Health hospitals within 12 months of a malignant skin cancer diagnosis. Multivariable logistic and Poisson regressions were used to analyze factors influencing the prevalence and frequency of ED presentations.

A total of 3,873 patients were diagnosed with skin malignancies between 2010 and 2018, of which 631 were diagnosed with melanoma. The prevalence of ED presentation was 29%, representing 2,119 episodes of care (median: 0; range: 0–14). Risk factors for a higher prevalence and frequency included: age ≥75 years (odds ratio (OR) = 1.78 [95% confidence interval 1.47–2.15]; incidence risk ratio (IRR) = 1.52 [1.35–1.70]); male (OR = 1.17 [1.01–1.36]; IRR = 1.23 [1.12–1.35]); socioeconomic status levels of 0–30% (OR = 1.59 [1.24–2.03]; IRR = 1.69 [1.45–1.96]) and 71–100% (OR = 1.30 [1.07–1.58]; IRR = 1.27 [1.12–1.45]); preferred language other than English (OR = 1.47 [1.17–1.84]; IRR = 1.49 [1.32–1.69]); and experience with any systemic therapy or radiotherapy (OR = 3.77 [2.12–6.71]; IRR = 2.36 [1.82–3.05]). Age < 65 years was protective (OR = 0.72 [0.59–0.89]; IRR = 0.78 [0.68–0.90]). Other preferred languages and cancer treatment experience were also risk factors in the sub-cohort with melanoma.

This study reports the prevalence and frequency of ED presentations following a skin cancer diagnosis and their association with socioeconomic and linguistic factors in Australia. Increased awareness of these factors could help address health inequities and potentially reduce the need for ED presentations.

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Original Article Open Access
Xixuan Wang, Shuling Chen, Jing Fan, Yuxiang Gong, Hongli Liu, Lili Wang, Xiaoning Feng, Hui Zhou, Wenquan Zeng, Changhua Yi, Caiyun Zhang, Qingfang Xiong, Hao Ren, Yongfeng Yang
Published online February 25, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00452
Abstract
Patients with cirrhosis are at an increased risk of bacterial infection (BI), which is the most common precondition for acute-on-chronic liver failure (ACLF). In this study, we [...] Read more.

Patients with cirrhosis are at an increased risk of bacterial infection (BI), which is the most common precondition for acute-on-chronic liver failure (ACLF). In this study, we aimed to evaluate the ability of mitochondria-related indicators (mitochondrial mass and mitochondrial membrane potential (MMP)) of T cells in peripheral blood to predict BI and ACLF within 90 days in cirrhotic patients.

We prospectively studied mitochondria-related indicators in various T cells from 235 cirrhotic patients at the Second Hospital of Nanjing. The outcomes of interest were BI and ACLF.

The restricted cubic spline analysis showed that the MMP of CD8+ T cells had a linear relationship with the risk of BI and ACLF (both P < 0.001). Multivariable Cox regression analysis demonstrated that the MMP of CD8+ T cells was an independent risk factor for both BI and ACLF (BI: hazard ratio 0.96, 95% confidence interval 0.94–0.98; P < 0.001; ACLF: hazard ratio 0.94, 95% confidence interval 0.90–0.97; P < 0.001). The MMP of CD8+ T cells exhibited better diagnostic efficacy than traditional indices in predicting BI (C index: 0.75). The MMP of CD8+ T cells, when combined with traditional models (Child-Turcotte-Pugh and model for end-stage liver disease score), improved their diagnostic efficiency in predicting both BI and ACLF. Additionally, the MMP of CD8+ T cells showed a significant negative correlation with inflammation-related markers (P < 0.05). Mitochondrial damage and abnormally activated mitochondrial autophagy were observed in CD8+ T cells from cirrhotic patients with low MMP.

The MMP of CD8+ T cells could serve as a valuable predictor of BI and ACLF within 90 days in cirrhotic patients.

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Review Article Open Access
Eliete A. Alvin, Anna Victótria Borges, Hugo Félix Perini, Marcos Vinícius da Silva, Anielle Christine A. Silva
Published online December 25, 2024
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00007
Abstract
Neglected tropical diseases (NTDs) encompass a range of infectious diseases prevalent in tropical and subtropical regions, often overlooked despite their substantial health impacts [...] Read more.

Neglected tropical diseases (NTDs) encompass a range of infectious diseases prevalent in tropical and subtropical regions, often overlooked despite their substantial health impacts and high mortality rates. Current treatments for NTDs frequently cause severe side effects due to the pharmacokinetic properties of drugs, which can be harmful even at therapeutic doses. There is a pressing need for innovative diagnostic and therapeutic strategies to mitigate these side effects and improve diagnostic capabilities, as many NTDs lack adequate diagnostic tools. Nanotechnology presents a promising avenue to address these challenges. Nanomaterials possess unique characteristics that enable dual functionality in disease diagnosis and treatment. When conjugated with drugs, nanomaterials can enhance the efficacy of treatments for parasitic diseases while reducing the toxicity associated with conventional medications. Nanomaterial-drug conjugates also serve as efficient carriers, improving drug delivery systems for existing NTD treatments and minimizing adverse effects. This study explores recent advancements in conjugating nanomaterials with drugs for the treatment and diagnosis of NTDs. A comprehensive review of primary database sources reveals significant gaps in current research, underscoring the vast potential for developing novel therapeutic and diagnostic tools. These innovations could revolutionize the management of NTDs, ushering in more effective and safer treatment modalities in the future.

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Original Article Open Access
Mengjiao Sun, Xiaoqing Wu, Zhandong Lin, Congyue Zhang, Jiawei Cui, Yaoyao Mao, Yue Shi, Jiaming Zhang, Yuemin Nan
Published online March 12, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00481
Abstract
Heme oxygenase 1 (HO-1) has an influential yet insufficiently investigated effect on Sirtuin 1 (SIRT1), a histone deacetylase activated by nicotinamide adenine dinucleotide, which [...] Read more.

Heme oxygenase 1 (HO-1) has an influential yet insufficiently investigated effect on Sirtuin 1 (SIRT1), a histone deacetylase activated by nicotinamide adenine dinucleotide, which may impact the transforming growth factor-β (TGF-ß)/Smad3 pathway in nonalcoholic fatty liver disease (NAFLD)-related liver fibrosis. This study aimed to elucidate the regulation of NAFLD-related liver fibrosis induced by HO-1 through the SIRT1/TGF-ß/Smad3 pathway.

HO-1 induction and inhibition were established in C57BL/6J mice fed a methionine- and choline-deficient (MCD) diet. Additionally, wild-type mice were fed either a normal diet or an MCD diet. Hematoxylin and eosin, Masson’s trichrome, and Sirius Red staining were used to assess hepatic steatosis, inflammation, and fibrosis. In vitro, plasmid overexpression and small interfering RNA silencing of HO-1 were performed in LX-2 cells. Cell viability was assessed using the Cell Counting Kit-8, and apoptosis was evaluated via terminal deoxynucleotidyl transferase dUTP nick-end labeling and immunofluorescence. Flow cytometry was employed to assess apoptosis and reactive oxygen species production. Western blot and real-time quantitative reverse transcription polymerase chain reaction were used to analyze the mRNA and protein expression of genes related to HO-1, SIRT1, the TGF-ß signaling pathway, and fibrosis.

MCD-fed mice developed significant liver damage, including steatosis, inflammatory infiltration, and pericellular fibrosis. Zinc protoporphyrin treatment exacerbated these conditions. Corroborating these findings, silencing HO-1 in LX-2 cells increased the expression of fibrosis-related genes. Furthermore, HO-1 overexpression not only increased SIRT1 expression but also reduced the activity of key regulatory factors in the TGF-ß signaling pathway, suggesting a potential interaction between HO-1 and the SIRT1/TGF-ß pathway.

HO-1 inhibits the activation of the TGF-ß/Smad3 pathway in NAFLD-related liver fibrosis through SIRT1. These findings provide insights into new therapeutic strategies for treating NAFLD-associated liver fibrosis.

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Original Article Open Access
Mengxiao Liu, Ji Li, Kui Yu, Qian Yu, Shuying Li
Published online March 30, 2025
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Oncology Advances. doi:10.14218/OnA.2025.00003
Abstract
In recent years, it has been found that Lycium barbarum can repair liver damage and promote liver regeneration. Additionally, the polysaccharides contained in Lycium barbarum have [...] Read more.

In recent years, it has been found that Lycium barbarum can repair liver damage and promote liver regeneration. Additionally, the polysaccharides contained in Lycium barbarum have anticancer properties and can induce apoptosis in cancer cells. Molecular docking, a mature computer-aided method, is widely used in drug discovery. This study aimed to verify the efficacy of active ingredients of Lycium barbarum in the treatment of liver cancer by molecular docking.

The effect of the active ingredients of Lycium barbarum in the treatment of liver cancer was verified by molecular docking, based on a previous study that examined the impact of Lycium barbarum on liver cancer using network pharmacology.

The binding energies of the key active ingredients and core targets were all less than −5.0 kcal/mol (1 kcal = 4.184 J), with most of them being less than −7.0 kcal/mol. This indicates that the key active ingredients and core targets have good binding ability, with most demonstrating strong binding affinity.

Most of the active ingredients in wolfberry can spontaneously bind to the core target protein, thereby playing a therapeutic role in liver cancer.

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Original Article Open Access
Anil K. Philip, Betty Annie Samuel, Bassim A Mohammed, Hayder A Al-Aubaidy
Published online December 25, 2024
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00027
Abstract
Poor bioavailability and a short half-life limit the therapeutic efficacy of ibuprofen. This study developed floating nanoballoons to enhance ibuprofen’s bioavailability and sustain [...] Read more.

Poor bioavailability and a short half-life limit the therapeutic efficacy of ibuprofen. This study developed floating nanoballoons to enhance ibuprofen’s bioavailability and sustain its anti-inflammatory effects through improved gastric retention.

Ibuprofen-loaded nanoballoons were synthesized using solvent evaporation with ethyl cellulose as the polymer matrix. The formulation was characterized for morphology, buoyancy, drug loading, and release kinetics. In vivo studies assessed the anti-inflammatory efficacy in acute and chronic inflammation models using male Sprague-Dawley rats.

The nanoballoons exhibited optimal characteristics, including 96% buoyancy and a drug loading efficiency of 96.54 ± 1.32%. Scanning Electron Microscopy revealed a spherical morphology with a porous structure. Drug release followed a biphasic pattern: an initial release of 35.23 ± 2.13% over 2 h, followed by sustained release reaching 97.54 ± 1.30% at 12 h. In acute inflammation studies, the nanoballoon formulation showed superior edema inhibition (68.12%) compared to pure ibuprofen (51.67%). Chronic inflammation studies demonstrated significant improvements in inflammatory markers: reduced TNF-α (19.12 ± 0.48 vs. 31.11 ± 1.23 pg/mL), hs-CRP (201.7 ± 11.02 vs. 232.12 ± 11.33 ng/mL), and IL-6 (100.01 ± 18.40 vs. 135 ± 11.22 pg/mL), with increased anti-inflammatory IL-10 (507.18 ± 10.11 vs. 276.11 ± 19.16 pg/mL).

The developed floating nanoballoon system significantly enhanced ibuprofen’s bioavailability and anti-inflammatory efficacy, presenting a promising gastro-retentive delivery platform for poorly water-soluble drugs.

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