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Prostate cancer is a heterogeneous disease showing variability both among individuals and within a patient. While most cases are indolent, aggressive tumors require early intervention. Accurately predicting tumor behavior is challenging, contributing to overdiagnosis but also undertreatment. Current imaging methods may miss the most malignant areas, leading to biopsies often capturing non-malignant prostate tissue even if cancer is present elsewhere in the organ. This non-malignant tissue, however, holds potential as a source for novel diagnostic and prognostic markers. Our clinical dataset comprises men with raised prostate-specific antigen but whose initial prostate needle biopsies only contained benign tissue. Half of the paired patients remained cancer-free for over eight years, while the others were diagnosed with prostate cancer within 30 months of follow-up. We share these initial benign biopsies to enable the exploration of morphological changes in non-malignant tissue and the potential for improved diagnostic accuracy in the early identification of patients with prostate cancer.

Introduction: Medication-related problems (MRPs) are common among older adults. The global population is ageing and there are health-related challenges linked to ageing in rural areas. Home-living rural older adults often face barriers to access healthcare, like long distances to healthcare services and poor continuity of care. Telepharmacy is the remote provision of pharmaceutical care, and telepharmacy could be of particular importance for rural older adults to improve their access to clinical pharmacy services and reduce the incidence of MRPs. The objective of this study is to develop and evaluate a novel telepharmacy service in primary care for home-living older adults in Northern Sweden’s rural areas. The primary objective is to evaluate the effect of the telepharmacy service regarding the identification, classification and resolution of MRPs.

Methods and analysis: This study will be conducted as a single-arm interventional study. A total of 100 people ≥65 years will receive the telepharmacy service for 12 weeks. The key principles of the telepharmacy service are to perform medication interviews and follow-up meetings with study participants, to conduct structured medication reviews, to conduct regular electronic medical record reviews and to have interprofessional collaboration with primary care physicians. All meetings will be conducted through video conferencing via a secure virtual care platform. Identified MRPs will be classified, and the acceptance rate of the pharmacists’ recommendations will be evaluated. The results will be presented with descriptive statistics. As secondary objectives, intra-individual changes in participants’ medication adherence, health-related quality of life and beliefs about medicines will be assessed through self-report questionnaires. Statistical analysis will be conducted using two-sided McNemar’s tests. Semi-structured interviews will also be conducted to explore participants’ and healthcare professionals’ experiences and attitudes towards this telepharmacy service.

Ethics and dissemination: This study has been granted ethical approval by the Swedish Ethical Review Authority (registration number 2022-03819-01 and 2024-08441-02). Participant informed consent is required. The results will be published in peer-reviewed journals and presented at scientific conferences.

Diagnostic needle biopsies that miss clinically significant prostate cancer (PCa) often sample benign tissue near hidden cancers. Such benign samples might still display subtle morphological signs of cancer elsewhere in the prostate. This study examined if artificial intelligence (AI) could detect these morphological clues in benign biopsies from men with elevated prostate-specific antigen (PSA) levels to predict subsequent diagnosis of clinically significant PCa within 30 months. We analysed biopsies from 232 men initially diagnosed as benign, matched for age, diagnosis year, and PSA levels-half were later diagnosed with PCa, while the rest remained cancer-free for at least eight years. The AI model accurately predicted future PCa diagnosis from initial benign biopsies (AUC = 0.82), highlighting patterns such as changes in stromal collagen and altered glandular epithelial cells. This demonstrates that AI analysis of routine haematoxylin-eosin biopsy sections can detect subtle signs indicating clinically significant PCa before it becomes histologically apparent. Such morphological patterns shed light on the broader tissue alterations induced by prostate cancer, even in benign tissue, potentially enhancing early detection and clinical decision-making.

We previously identified three molecular subtypes of prostate cancer (PC) bone metastases, MetA-C, with MetB linked to poor prognosis after androgen deprivation therapy (ADT). This study analyzed epithelial and stromal markers using immunohistochemistry, focusing on their relationship to MetA-C subtypes, spatial heterogeneities, and clinical outcomes after ADT. High tumor proliferation and low PSA expression were associated with MetB and poor outcomes after ADT. Most metastases contained tumor epithelial subclones with different morphologies. In the metastasis stroma, blood vessels and fibroblast-like cells expressed smooth muscle actin (SMA), platelet-derived growth factor β, stroma-derived factor 1 (SDF1), periostin (POSTN), and decorin (DCN). Compared to each other, MetB metastases had higher SMA and ERG + endothelial cell densities, while MetA cases showed higher SDF1 and DCN levels. Accordingly, high POSTN and ERG + densities were associated with poor outcomes after ADT, whereas high DCN indicated favorable prognosis. Low levels of AR-positive stromal cells were linked to poor outcomes. Macrophage and T-lymphocyte densities showed no significant associations with metastases subtypes or outcome. Two stroma subtypes were identified: subtype 1 with higher bone content, lower vessel density, MetA-enrichment and better prognosis compared to subtype 2 that exhibited higher tumor proliferation and lower PSA expression. Most metastases contained regions of both stroma subtypes.

Alterations in deoxyribonucleoside triphosphate (dNTP) pools have been linked to increased mutation rates and genome instability in unicellular organisms and cell cultures. However, the role of dNTP pool changes in tumor development in mammals remains unclear. In this study, we present a mouse model with a point mutation at the allosteric specificity site of ribonucleotide reductase, RRM1-Y285A. This mutation reduced ribonucleotide reductase activity, impairing the synthesis of deoxyadenosine triphosphate (dATP) and deoxyguanosine triphosphate (dGTP). Heterozygous Rrm1^+/Y285A mice exhibited distinct alterations in dNTP pools across various organs, shorter lifespans and earlier tumor onset compared with wild-type controls. Mutational spectrum analysis of tumors revealed two distinct signatures, one resembling a signature extracted from a human cancer harboring a mutation of the same amino acid residue in ribonucleotide reductase, RRM1^Y285C. Our findings suggest that mutations in enzymes involved in dNTP metabolism can serve as drivers of cancer development.

Introduction: Medication-related hospital admissions (MRAs) are common among older people. Persons with cognitive impairment are especially vulnerable to adverse drug effects. At the same time, increased home health care and social support could theoretically prevent medication-related problems. This study aims to estimate the proportion of MRAs and explore their relationship with cognitive impairment in a population of acutely admitted older people.

Methods: This cross-sectional study comprised 300 individuals aged 75 years or older admitted to an acute medical ward. Two assessors identified possibly MRAs using the Assessment Tool for Hospital Admissions Related to Medications 10 (AT-HARM10). Screening for cognitive impairment was performed during ward stay using a 4-item test related to time orientation. Prevalence odds ratios between cognitive test scores and MRAs were analysed through logistic regression.

Results: Using AT-HARM10, 108 out of 300 admissions (36%) were classified as possibly MRAs by both assessors. Moreover, MRAs were least common among patients with the lowest cognitive test scores. There was an association regarding MRAs when the lowest test score was treated as a cut-off and compared against a reference category comprising all other scores (OR, 0.31 [95% CI 0.10–0.93]; p = 0.037) in a logistic regression model adjusted for cohabitation and home health care.

Conclusion: Approximately one-third of the hospital admissions among acutely admitted older people were considered at least possibly medication-related. Hence, there is still a great need to manage medication-related problems and reduce MRAs in this vulnerable population. Using a 4-item instrument to screen for cognitive impairment, there was a negative association between MRA and lowest cognitive test score. Further exploration of the relationship between MRAs and cognitive impairment may indicate appropriate components and target populations for interventions that aims to reduce the risk of MRA.

In the present study we have investigated whether Caveolin-1 expression in non-malignant and malignant prostate tissue is a potential prognostic marker for outcome in prostate cancer patients managed by watchful waiting. Caveolin-1 was measured in prostate tissues obtained through transurethral resection of the prostate from 395 patients diagnosed with prostate cancer. The majority of the patients (n = 298) were followed by watchful waiting after diagnosis. Tissue microarrays constructed from malignant and non-malignant prostate tissue were stained with an antibody against Caveolin-1. The staining pattern was scored and related to clinicopathologic parameters and outcome. Microdissection and qRT-PCR analysis of Cav-1 was done of the prostate stroma from non-malignant tissue and stroma from Gleason 3 and 4 tumors. Cav-1 RNA expression was highest in non-malignant tissue and decreased during cancer progression. High expression of Caveolin-1 in tumor stroma was associated with significantly longer cancer specific survival in prostate cancer patients. This association remained significant when Gleason score and local tumor stage were combined with Caveolin-1 in a Cox regression model. High stromal Caveolin-1 immunoreactivity in prostate tumors is associated with a favourable prognosis in prostate cancer patients managed by watchful waiting. Caveolin-1 could possibly become a useful prognostic marker for prostate cancer patients that are potential candidates for active surveillance.

The high accuracy of DNA replication is achieved through the nucleotide selectivity of DNA polymerases, polymerase proofreading, and the mismatch repair (MMR) system that act in series. While defects in proofreading and MMR are strongly associated with the development of cancers, decreased nucleotide selectivity due to mutations in replicative DNA polymerases is an uncommon driver of cancer development. Because nucleotide selectivity can also be decreased by imbalanced dNTP pools, we investigated to what extent imbalanced dNTP pools can induce cancers. To this end we developed a mouse model with a mutation in the allosteric specificity site of ribonucleotide reductase, which is responsible for the balanced production of dNTPs. These mice had ~2-fold increased dCTP and dTTP levels and normal dATP and dGTP levels. Despite this mild dNTP pool imbalance, mutant mice had a higher incidence and an earlier onset of cancers, and these were different from the cancers that developed in wild-type controls. Because dNTP pool imbalances can be caused by defects in a plethora of genes, we propose that decreased nucleotide selectivity might be a major factor contributing to the development of spontaneous cancers.