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Original Article Open Access
Fabrication of Polymethyl Methacrylate Microspheres for Improving Immunogenicity of Tetanus Toxoid
Sellappan Mohan, Arumugam Nagarajan
Published online November 11, 2024
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2023.00005
Abstract
The polymer’s slow hydrolysis facilitates the sustained release of the immunogen, stabilizing the antigen encapsulated within the microspheres. As a result, microspheres ranging [...] Read more.

The polymer’s slow hydrolysis facilitates the sustained release of the immunogen, stabilizing the antigen encapsulated within the microspheres. As a result, microspheres ranging from 40 µm to 70 µm in diameter can be formed. This innovative microsphere formulation allows for efficient uptake by macrophages and other antigen-presenting cells. This study aimed to use biocompatible polymethyl methacrylate microspheres for the controlled delivery of antigens.

The potency of various formulations containing encapsulated tetanus toxoid (TT) with polymethyl methacrylate polymer microspheres was assessed using the toxin neutralization and challenge methods. The neutralization test was conducted on pooled sera two weeks after the initial immunization and weekly for four weeks following the booster dose administration. Scanning electron micrographs of the microspheres revealed drug leaching from spherical granular matrices.

The injection site showed a higher distribution of smaller microparticles, resulting in depot release. The polymer coating’s thickness was significantly lower compared to the 25% polymer microspheres. Concentrations ranging from 0.00024 mL to 0.00030 mL caused significant tetanic paralysis. Two weeks after the initial immunization, the antigenic activity of TT was below the minimum threshold, possibly due to insufficient levels of antigenic TT within the system within seven days post-immunization. The polymethacrylate microsphere elicited a notable immune response, but only the polymer concentration of 25% w/v met the I.P. requirements; lower polymer concentrations were ineffective.

The polymer’s slow hydrolysis facilitates the sustained release of the immunogen, stabilizing the antigen encapsulated within microspheres. Consequently, microspheres ranging from 40 µm to 70 µm in diameter can be assembled. This innovative microsphere formulation allows for efficient uptake by macrophages and other antigen-presenting cells.

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Case Report Open Access
Diagnosis of Lung Leishmaniasis by Bronchoalveolar Lavage Cytology in a Human Immunodeficiency Virus-infected Patient: A Case Report
Ahmed A. Ahmed, Y. Helen Zhang
Published online January 17, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00037
Abstract
Leishmaniasis is a systemic parasitic disease that can affect unusual sites such as the lungs. We report a case of a 45-year-old male with human immunodeficiency virus infection [...] Read more.

Leishmaniasis is a systemic parasitic disease that can affect unusual sites such as the lungs.

We report a case of a 45-year-old male with human immunodeficiency virus infection who presented with abdominal pain and vomiting. Imaging studies revealed minimal bilateral ground-glass opacities in the lungs, hepatosplenomegaly, and diffuse lymphadenopathy. A bronchoscopy with bronchoalveolar lavage cytology evaluation showed abundant macrophages containing numerous intracellular organisms with characteristic dot-like kinetoplasts, confirming the diagnosis of Leishmaniasis. Special stains for other infections were negative.

This case highlights the value of bronchoalveolar lavage cytology in diagnosing non-neoplastic lung pathologies, including parasitic infections like Leishmaniasis, thereby enabling prompt and targeted treatment.

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Original Article Open Access
Role of ELK3 in Ferroptosis of Rheumatoid Arthritis Fibroblast-like Synoviocytes
Yaqun Zhang, Huimin Shi, Lin Wang, Jihong Pan
Published online January 20, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00036
Abstract
Rheumatoid arthritis (RA) is an inflammatory arthritis characterized by chronic joint inflammation, cartilage degradation, and bone erosion. ELK3 is a transcriptional repressor [...] Read more.

Rheumatoid arthritis (RA) is an inflammatory arthritis characterized by chronic joint inflammation, cartilage degradation, and bone erosion. ELK3 is a transcriptional repressor that can affect cell proliferation, migration, invasion, apoptosis, and other cellular processes. The study aimed to clarify the effect of ELK3 in the biological activity and ferroptosis phenotype of RA fibroblast-like synoviocytes (FLS), and to reveal its molecular mechanism in regulating ferroptosis in RA FLS.

We investigated the impact of ELK3 on the biological activity and ferroptosis phenotype of RA FLS using real-time quantitative polymerase chain reaction, immunohistochemistry, Transwell assay, CCK-8 assay, and ferroptosis-related indicator kit. The molecular mechanism of ELK3 in RA FLS was further explored using Western blot, chromatin immunoprecipitation polymerase chain reaction, and other experiments.

ELK3 was highly expressed in RA. Silencing ELK3 inhibited the invasion and proliferation of RA FLS (both p < 0.05). After silencing ELK3 in imidazole ketone erastin-induced RA FLS, intracellular reactive oxygen species, lipid peroxidation levels, ferrous ion content, 4-Hydroxynonenal levels, and Malondialdehyde concentrations all increased. Additionally, ELK3 affects ferroptosis in RA FLS by regulating kelch-like ECH-associated protein 1 (p < 0.05).

Silencing ELK3 leads to decreased invasion and proliferation of RA FLS, affecting their biological activity. ELK3 inhibits ferroptosis by suppressing its transcriptional activity through binding to the kelch-like ECH-associated protein 1 promoter. This suggests that ELK3 may be a potential target for RA therapy.

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Mini Review Open Access
Hepatic Biliary Adenofibroma: Histological Characteristics, Diagnostic Challenges, and Its Role as a Precursor to Intrahepatic Cholangiocarcinoma
Xiaoyan Liao, Xuchen Zhang
Published online December 24, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00044
Abstract
Hepatic biliary adenofibroma is an exceedingly rare biliary neoplasm that primarily affects adults. It typically presents as a solitary mass composed of low-grade microcystic and [...] Read more.

Hepatic biliary adenofibroma is an exceedingly rare biliary neoplasm that primarily affects adults. It typically presents as a solitary mass composed of low-grade microcystic and tubuloglandular bile duct structures, which are lined by low columnar to cuboidal non-mucin-producing biliary epithelium and supported by abundant fibrous stroma. Histologically, it resembles the Von Meyenburg complex but is much larger in size and often shows cytologic atypia. Although considered benign, emerging case studies and analyses suggest that biliary adenofibroma may serve as a precursor lesion to intrahepatic cholangiocarcinoma. However, its extreme rarity, coupled with an incompletely understood histogenesis, perpetuates diagnostic uncertainty and may lead to misclassification with other similar entities. This review consolidates the current understanding of the histopathological and molecular characteristics of biliary adenofibroma, highlights its differential diagnosis, explores its potential progression to cholangiocarcinoma, and discusses unresolved questions while proposing future research directions.

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Systematic Review Open Access
Receptor Discordance between Primary and Recurrent Breast Cancer: A Systematic Literature Review
Archana Haria, Jonathon Hill, Kylie J. Mansfield
Published online December 25, 2024
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.

Full article
Original Article Open Access
Thyroid-stimulating Hormone and Thyroid Hormones in Women with Breast Cancer: Effects of Neoadjuvant Chemotherapy and Menopausal Status
María Jesús Ramírez-Expósito, María Pilar Carrera-González, Cristina Cueto-Ureña, José Manuel Martínez-Martos
Published online March 19, 2025
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.

Full article
Original Article Open Access
Post-diagnosis Emergency Department Presentation and Demographic Factors in Malignant Skin Cancers: A Data-linkage Cohort Study
David Izon, Olivia Wawryk, Damien McCarthy, Jennifer Soon, Sally Philip, Chris Kearney, Zhiheng Xu, Jianrong Zhang
Published online March 30, 2025
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.

Full article
Mini Review Open Access
Advances in Neuroendoscopic Treatment of Pituitary Tumors
Xing Huang, Xiaobing Jiang
Published online March 25, 2025
Neurosurgical Subspecialties. doi:10.14218/NSSS.2024.00008
Abstract
Pituitary tumors are common intracranial neoplasms that can cause significant morbidity due to hormonal dysregulation and compression of surrounding structures. Despite advancements [...] Read more.

Pituitary tumors are common intracranial neoplasms that can cause significant morbidity due to hormonal dysregulation and compression of surrounding structures. Despite advancements in surgical techniques, challenges persist in treating large, invasive, or recurrent tumors, where complete resection is often difficult. The molecular and genetic mechanisms underlying pituitary tumorigenesis are not yet fully understood, limiting the development of targeted therapies. This review provides a comprehensive overview of recent advancements in neuroendoscopic treatment of pituitary tumors, with a focus on pathogenesis, technological innovations, clinical outcomes, and future directions. We highlight the potential of neuroendoscopic surgery to improve patient outcomes while addressing persistent challenges, such as the steep learning curve and limitations in instrument maneuverability. Future research should prioritize enhancing instrument design, developing 3D and augmented reality visualization systems, and improving training programs to further advance neuroendoscopic techniques.

Full article
Review Article Open Access
Applications of Molecular Genetic Testing in Hematopoietic and Lymphocytic Neoplasms
Weiqiang Zhao
Published online December 25, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00042
Abstract
The number of molecular abnormalities identified in hematopoietic and lymphocytic neoplasms has grown exponentially over the past decades. Patients with genetic biomarker-matched [...] Read more.

The number of molecular abnormalities identified in hematopoietic and lymphocytic neoplasms has grown exponentially over the past decades. Patients with genetic biomarker-matched targeted therapies have experienced significantly improved survival rates. Modern molecular laboratories, equipped with advanced technologies such as next-generation sequencing, can simultaneously test hundreds of genes and thousands of hotspots in a single run with multiple samples analyzed side by side. Bioinformatics tools provide seamless, evidence-based information to determine whether the detected mutations are benign or pathogenic, somatic or germline, druggable or diagnostic. This review is divided into five sections, each aiming to provide a comprehensive overview of the genetic landscape of myeloid and lymphocytic neoplasms. It highlights the challenges and proposes potential solutions to facilitate interpretation and maximize the clinical utility of molecular profiling results.

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Original Article Open Access
Verify the Therapeutic Effect of Effective Components of Lycium Barbarum on Hepatocellular Carcinoma Based on Molecular Docking
Mengxiao Liu, Ji Li, Kui Yu, Qian Yu, Shuying Li
Published online March 30, 2025
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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