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Impaired Granularity in T cell Subsets but not in B cell Favors the Carcinogenesis of the Breast: A Preliminary Study in Indonesian Women Cohort

Asian Pac J Cancer Prev. 2025 Jan 1;26(1):225-231. doi: 10.31557/APJCP.2025.26.1.225.

ABSTRACT

OBJECTIVE: The progress made in cancer immunology has led to the development of innovative therapeutic strategies. However, despite these advances, the superficial characteristics of immune cells have been frequently overlooked: This oversight may be attributed to a limited understanding of the intricate relationships between immune cells and their microenvironment. This study seeks to address this limitation by comprehensively examining cell size and granularity in breast cancer (BC) patients and healthy donors (HD).

METHODS: Peripheral blood mononuclear cell (PBMC) samples were isolated from BC patients and HD. We examined the size (FSC-A%rCV) and granularity (SSC-A%rCV) of immune cell subsets in both patient groups and HD using flowcytometry.

RESULTS: Despite the absence of statistically significant variations in cell size between BC and HD, visual examination reveals noticeable discrepancies. There is a substantial decrease in granularity in CD8 and CD4 T-cell populations in BC compared to HD which is not observed in B cells.

CONCLUSION: Our analysis shows that while the size of immune cells may not be significantly altered in breast cancer patients compared to healthy donors, a closer examination of cell granularity reveals a distinct pattern. Specifically, the T-cell populations, including CD8 and CD4 cells, exhibit a substantial decrease in granularity in BC compared to HD. In contrast, B cells remain unaffected, suggesting that the granularity of T cells is uniquely susceptible to perturbations in breast cancer. This observation highlights the importance of considering cell granularity as a critical aspect of immune cell function, particularly in the context of cancer development.

PMID:39874005 | DOI:10.31557/APJCP.2025.26.1.225

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Detection of H-Pylori in the Explanted Liver Tissue and the Enlarged Perihepatic Lymph Nodes of Cirrhotic Patients with Decompensated End-Stage Liver Disease Recruited for Liver Transplantation

Asian Pac J Cancer Prev. 2025 Jan 1;26(1):181-187. doi: 10.31557/APJCP.2025.26.1.181.

ABSTRACT

BACKGROUND: Helicobacter pylori bacteria colonize the gastric mucosa and contribute to the occurrence and development of gastrointestinal diseases. According to the WHO, H. pylori bacteria are considered class I carcinogen.

OBJECTIVES: To detect Helicobacter pylori organisms by IHC expression of anti-H. Pylori antibodies in the explanted liver tissue; and enlarged perihepatic lymph nodes of cirrhotic liver; to detect any relation between the presence of the organism and histopathological findings in the liver tissue.

MATERIALS AND METHODS: This retrospective cross-sectional study included forty cases of cirrhotic patients with decompensated end-stage liver, recruited for liver transplantation based on combined clinical, radiological, and histological data. Samples were immunohistochemically analyzed for anti-H-Pylori antibodies to detect Helicobacter pylori organisms in the explanted liver tissue and enlarged perihepatic lymph nodes. The presence of the organism was correlated with clinic-pathologic variables.

RESULTS: Eighty-five percent (34 cases) and seventy percent (28 cases) of cases were positive for anti-H-Pylori antibodies in the liver and lymph nodal tissues, respectively. More than eighty percent (14 cases) and half of the studied cases (8 cases) showed dysplasia in liver tissue expressing anti-H-Pylori-antibody in the liver tissue and the lymph nodes, respectively. All HCC cases expressed anti-H-Pylori antibody in the liver tissue and the lymph nodes. The relation between anti-H-Pylori antibody expression in lymph nodes and the presence of dysplasia or HCC in liver tissue was statistically significant (p-value = 0.037 and p-value = 0.041 respectively).

CONCLUSION: Our results conclude that there is a pathogenic role of extra-gastric H-Pylori colonization in lymph nodal tissue and in liver tissue, and it may be preventable by treating H. pylori, especially if treatment can be started very early.

PMID:39874000 | DOI:10.31557/APJCP.2025.26.1.181

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Staging at Diagnosis and Survival of Hematologic Neoplasms in Children and Adolescents in Mato Grosso, Brazil: A Population-based Study

Asian Pac J Cancer Prev. 2025 Jan 1;26(1):171-179. doi: 10.31557/APJCP.2025.26.1.171.

ABSTRACT

OBJECTIVE: To apply the Toronto Childhood Cancer Staging Guidelines (TG) and Estimate the Observed Survival Probabilities for Pediatric Patients with Leukemia and Lymphoma.

METHODS: Staging at diagnosis was conducted according to tier 2 of the TG. The study cohort included patients aged 0 -19 years from the Population-Based Cancer Registry (PBCR) of Mato Grosso, diagnosed with leukemia and lymphoma between 2008 and 2017, with follow-up until December 31, 2022. Observed 60-month survivals were calculated using the Kaplan-Meier method.

RESULTS: Staging was assigned in 67.3% of cases (n=239), while in 32.7% (n=116), staging could not be applied due to incomplete data. Among the cases of acute lymphoblastic leukemia (ALL), 70.7% (n=133) were staged as CNS1, with an observed survival probability of 75.0%. For acute myeloid leukemia (AML), 42.2% (n=21) were staged as CNS-, with an estimated survival of 60.0%. Most Hodgkin lymphoma (HL) cases were staged as IIA/B (37.7%, n=23) and IIIA/B (21.3%, n=13), with survival probabilities of 91.3% and 91.7%, respectively. Among non-Hodgkin lymphoma (NHL) cases, 32.1% (n=18) were staged as stage III, with a survival probability of 70.6%.

CONCLUSION: The application of TG in the PBCR in Mato Grosso proved feasible, allowing for comparability of survival estimates across different stages. However, collecting tier 2 staging information will be a challenge for the PBCR due to incomplete information in medical records.

PMID:39873999 | DOI:10.31557/APJCP.2025.26.1.171

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Immunohistochemical Expression of VEGF and Microvessel Density (CD 34) in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma: Original Research

Asian Pac J Cancer Prev. 2025 Jan 1;26(1):147-151. doi: 10.31557/APJCP.2025.26.1.147.

ABSTRACT

BACKGROUND: Angiogenesis, the formation of new blood vessels from preexisting ones via capillary sprouting, is a crucial process in tumor growth and metastasis. As a tumor’s angiogenic capacity increases, its microvasculature, measured by micro vessel density (MVD), also increases. This study aims to evaluate the expression of Vascular Endothelial Growth Factor (VEGF) and CD34 in oral epithelial dysplasia and oral squamous cell carcinoma through immunohistochemical methods.

METHODS: The study analyzed a total of 40 formalin-fixed, paraffin-embedded tissue samples. These included 10 cases of normal buccal mucosa, 15 cases of oral epithelial dysplasia, and 15 cases of oral squamous cell carcinoma. Immunohistochemical staining was performed using monoclonal anti-VEGF and anti-CD34 antibodies. The intensity and area of staining for VEGF were assessed, and the mean MVD was calculated. Statistical analysis was conducted using Pearson’s chi-square test and one-way ANOVA.

RESULTS: The expression of VEGF and MVD (indicated by CD34 staining) were significantly higher in oral squamous cell carcinoma compared to oral epithelial dysplasia and normal buccal mucosa.

CONCLUSION: As tumors grow, angiogenesis increases proportionally with tumor volume and disease progression, contributing to tumorigenesis. VEGF serves as a critical mitogen for tumor vascularization, and MVD can be a useful indicator of disease progression.

PMID:39873996 | DOI:10.31557/APJCP.2025.26.1.147

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Thiosemicarbazone Complexes and 6-MP Suppress Acute Lymphoblastic Leukemia via the NOTCH Signaling Pathway and Regulation of LUNAR1 and NALT1 lncRNA

Asian Pac J Cancer Prev. 2025 Jan 1;26(1):59-66. doi: 10.31557/APJCP.2025.26.1.59.

ABSTRACT

BACKGROUND: Acute Lymphoblastic Leukemia (ALL) is the most common type of leukemia among children. There are several types of drugs that are common in treating and controlling leukemia, including 6-M. Moreover, the anti-cancer effects of the Thiosemicarbazone-Ni complex were surveyed as well as 6-MP. The current study aimed to evaluate the effect of the Thiosemicarbazone-Ni complex in comparison with 6-MP on the expression of NALT1 and LUNAR1 LncRNAs and their target gene, NOTCH1, in the Jurkat E6.1 cell line.

MATERIALS AND METHODS: Jurkat E6.1 cell was treated with 6-MP with the concentrations of 1, 5, 10, and 25μM and 0.5, 1, 2, and 5μM of Ni-nanoparticles, loaded with Thiosemicarbazone complexes for 24, 48, and 72 h. Subsequently, the RNA extraction and cDNA synthesis were performed and the expression of NALT1, LUNAR1, NOTCH1, and GAPDH genes was surveyed by Real-time PCR. Finally, the results were analyzed by statistical analysis.

RESULTS: The highest significant reduction in the expression of LUNAR1 was observed at 6-MP at 10μM for the first 72 h and the Thiosemicarbazone-Ni complex showed its effective dose at 5μM for 48 h. The highest decrease in NOTCH1 expression was observed in 6-MP treatment at 10μM concentration for 24h and Ni-Thiosemicarbazone treatment, the significant decrease was at 0.5μM for 72h. The most significant reduction in NALT1 expression was observed in treatment with Ni-Thiosemicarbazone complex and 6-MP at the concentrations of 2 and 10μM respectively for 24h.

CONCLUSION: Given the association between the aforementioned genes and the positive effects of the drugs at achieved concentrations and times, it can be concluded that Thiosemicarbazone-Ni complex and 6-MP can show putative roles in regulating the expression of studied genes.

PMID:39873986 | DOI:10.31557/APJCP.2025.26.1.59

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Medical indemnity knowledge and awareness among international medical graduates in Ireland

Ir J Med Sci. 2025 Jan 28. doi: 10.1007/s11845-025-03887-7. Online ahead of print.

ABSTRACT

BACKGROUND: Medical indemnity (MI) has become an important topic in the era of increasing number of medico-legal cases in Ireland. However, there is a sensible difference in understanding and usage of medical indemnity between Irish and international medical graduates.

AIM: This study aimed to investigate the knowledge and awareness of medical indemnity among international medical graduates in Ireland.

METHODS: This was a descriptive study with an anonymous online survey including 19 questions about various aspects of MI. Analysis of the data was done using Microsoft Excel statistical analysis pack.

RESULTS: One hundred eighty-six doctors participated in the study, 34 (18.2%) consultants, 74 (39.8%) registrars, 72 (38.7%) Senior House Officers (SHOs) and 6 (3.2%) General Practitioners (GPs). Their knowledge and insurance coverage were deficient before working in Ireland. The majority did not have any educational session about clinical indemnity insurance when starting work in Ireland. While most consultants (88.2%) had supplemental MI (SMI) at the time of the study, only 41.9% of registrars and 38.9% of SHOs had SMI. In addition, there was a difference between consultants and Non-consultant Hospital Doctors (NCHDs) involvement in medico-legal cases. 32.2% of consultants were involved in medico-legal cases compared to 19% of registrars and 18% of SHOs.

CONCLUSION: There is a need to address clinical indemnity and supplemental clinical indemnity topics on induction days for international medical graduates working in Ireland, including clear information about professional protection arrangements with refresher meetings every six months especially during rotational placements.

PMID:39873966 | DOI:10.1007/s11845-025-03887-7

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The relationship between fatigue levels and psychosocial adjustment in elderly individuals with chronic obstructive pulmonary disease: A descriptive study

Ir J Med Sci. 2025 Jan 28. doi: 10.1007/s11845-025-03882-y. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with physical limitations and significant social, psychological, and behavioral challenges. This study investigates the relationship between fatigue levels and psychosocial adjustment in COPD patients, considering their sociodemographic characteristics.

METHODS: A descriptive study was conducted with 160 COPD patients hospitalized in the Pulmonology Department of a university hospital. Data were collected via face-to-face interviews using a patient information form, the COPD and Asthma Fatigue Scale (CAFS), and the Psychosocial Adjustment to Illness Scale-Self-Report (PAIS-SR). Statistical analyses included Independent Sample t-test, One-Way ANOVA, Mann-Whitney U test, Kruskal-Wallis test, and Spearman correlation analysis, with significance set at p < 0.05.

RESULTS: The mean age of participants was 68.70 ± 9.41 years; 71.9% were male, and 67.9% had COPD for over six years. Most participants (74.4%) reported limitations in daily living activities due to the disease, and 91.9% reported having social support. Mean scores were 58.03 ± 15.80 on the CAFS and 64.19 ± 6.41 on the PAIS-SR. Significant differences were observed in fatigue and psychosocial adjustment scores based on gender, social support, and disease impact on daily activities (p < 0.05). A weak positive correlation was found between fatigue levels and psychosocial adjustment (p < 0.05).

CONCLUSIONS: COPD patients experience moderate-to-high fatigue levels and challenges in psychosocial adjustment, with fatigue negatively influencing adjustment. Interventions should focus on enhancing coping strategies, addressing psychosocial needs, and leveraging social support systems to improve patient outcomes.

PMID:39873964 | DOI:10.1007/s11845-025-03882-y

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Efficacy and Safety of Proactive Therapy with 2% Crisaborole Ointment in Children with Mild-to-Moderate Atopic Dermatitis: A Randomized Controlled Study

Paediatr Drugs. 2025 Jan 28. doi: 10.1007/s40272-025-00682-w. Online ahead of print.

ABSTRACT

BACKGROUND: The effectiveness of crisaborole for proactive treatment of atopic dermatitis (AD) is not well established.

OBJECTIVES: This study aims to investigate the efficacy and safety of a proactive treatment strategy with 2% crisaborole ointment for managing mild-to-moderate AD in children.

PATIENTS AND METHODS: In this 16-week randomized-controlled trial, children aged 2-17 years with mild-to-moderate AD were enrolled. All participants received treatment with 0.1% mometasone furoate cream for 2 weeks. Those with an IGA score of ≤ 1 were randomly assigned in a 1:1 ratio to either the proactive treatment group, which received crisaborole combined with emollient twice daily, or the reactive treatment group, which received emollients alone, and in the event of disease relapse, both groups received 0.1% mometasone furoate cream as rescue treatment.

RESULTS: Of the 153 patients screened, 142 were randomized; 73 to the proactive treatment group and 69 to the reactive treatment group. At the end of the 16-week trial, the proactive treatment group had a relapse rate of 43.84%, significantly lower than the 71.01% relapse rate in the reactive group (P = 0.001). Additionally, the proactive treatment group demonstrated a significant reduction in the need for mometasone furoate prescriptions at weeks 4, 8, 12, and 16 (P < 0.05). Improvements were also observed in IGA, EASI, PP-NRS, and POEM scores at 12 weeks (P < 0.05). No significant differences in adverse events were found between the groups (χ2 = 2.237, P = 0.135).

CONCLUSIONS: Proactive treatment with crisaborole ointment for children older than 2 years with mild-to-moderate AD effectively reduces flare-ups and reliance on topical corticosteroids, demonstrating good tolerability and safety.

CHINESE CLINICAL TRIAL REGISTRY: ChiCTR2100054340 (Date of Trial Registration: 14 December 2021).

PMID:39873962 | DOI:10.1007/s40272-025-00682-w

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Self-perceived and measured visual function, the impact of eye-disease, wellbeing, social determinants, and personality traits in Swedish 70-year-olds-results from the Gothenburg H70 Study

Acta Ophthalmol. 2025 Jan 28. doi: 10.1111/aos.17440. Online ahead of print.

ABSTRACT

PURPOSE: To explore the potential correlation between subjective and measured visual function, as well as to analyse the influence of eye disease, socioeconomic factors and emotional dimensions.

METHODS: Semi-structured interviews, physical examinations and functional tests (n = 1203). Demographics covered sex, marital status, education, household economy, smoking and alcohol. Participants (born in 1944) rated their visual function (n = 533); those misjudging (n = 48) were studied. Group A (n = 18) had low presenting visual acuity (PVA) but reported good vision; Group B (n = 30) had normal PVA but reported low vision. Control group (n = 485) matched subjective and measured visual function. Ophthalmic examination tested visual acuity (VA), visual field and contrast sensitivity (CS). Psychometric tests: NEO-FFI, sense of coherence (SOC) and Montgomery-Åsberg Depression Rating Scale (MADRS).

STATISTICAL TESTS: chi-square, t-tests, Mann-Whitney U test and logistic regression.

RESULTS: Of the population, 91% made correct assumptions about their vision. The 9% who made incorrect assumptions about their vision ability (combining groups A + B) were more likely to live alone (p = 0.02) and had lower household incomes compared to the control group (p = 0.04). Additionally, the exhibited significantly lower PVA and BCVA, a higher prevalence of visual field defects (p = 0.02) and lower CS, mean 1.63 (p = 0.005). Group A (3.4%) were women (p = 0.002) with the personality of extraversion, mean 40.0 (p = 0.01). Group B (5.6%) had more self-reported eye diseases (p = 0.01), lower CS (p = 0.01), lower educational level (p = 0.03) and border significantly lower SOC (p = 0.06).

CONCLUSIONS: The perception of visual function is shaped by awareness of an eye disease but is additionally influenced by sex, socioeconomic factors and emotional parameters.

PMID:39873951 | DOI:10.1111/aos.17440

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Safety and Efficacy of Lotilaner Ophthalmic Solution (0.25%) in Treating Demodex Blepharitis: Pooled Analysis of Two Pivotal Trials

Ophthalmol Ther. 2025 Jan 28. doi: 10.1007/s40123-024-01089-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Lotilaner ophthalmic solution (0.25%) is the first United States Food and Drug Administration (US FDA)-approved drug for treating Demodex blepharitis. In pivotal trials, it was found to be well tolerated and demonstrated a significant reduction in collarettes and mite density after a 6-week treatment regimen. This study aimed to report the safety and efficacy profile of lotilaner ophthalmic solution (0.25%) from a pooled analysis of two pivotal trials in patients with Demodex blepharitis.

METHODS: Pooled data were analyzed from two randomized, double-masked, vehicle-controlled clinical trials [phase 2b/3 Saturn-1 (NCT04475432) and phase 3 Saturn-2 (NCT04784091)] in which patients with Demodex blepharitis were randomly assigned in a 1:1 ratio to receive either lotilaner ophthalmic solution (0.25%) (study group) or the vehicle formulation without lotilaner (control group), twice daily for 6 weeks. The outcome measures were the proportion of patients with 0-2 collarettes (grade 0 collarettes), mite eradication, erythema cure, and the proportion of patients with ≤ 10 collarettes (grade 0 or 1 collarettes) at day 43.

RESULTS: Overall, 833 participants were randomized to receive either the study drug (N = 415) or vehicle (N = 418). On day 43, 49.8% of patients in the study group vs. 9.9% in the control group (p < 0.0001) had collarette grade 0 (0-2 collarettes). A reduction to ≤ 10 collarettes (grade 0 or 1 collarettes) was achieved in 85.1% of patients in study group vs. 28.0% in control group (p < 0.0001). The proportion of patients achieving mite eradication (60.2% vs. 16.1%, p < 0.0001) and erythema cure (24.9% vs. 7.9%, p < 0.0001) were also statistically significantly higher in the study group compared to the control group. The rates of adverse events were low in both studies, with no serious drug-related ocular adverse events reported. As many as 92% of patients rated the study drop as neutral to very comfortable.

CONCLUSIONS: Twice-daily treatment with lotilaner ophthalmic solution (0.25%) for 6 weeks demonstrated statistical significance for all outcome measures compared to the vehicle control, with low rates of adverse events and a high rate of drop comfort.

PMID:39873946 | DOI:10.1007/s40123-024-01089-5