We present a 63-year-old man with a history of prostate adenocarcinoma (mCRPC), widespread skeletal and multiple lymph node metastases, who was referred for 177Lu-PSMA therapy. In second course of therapy, posttreatment scan showed multiple foci of increased activity throughout the liver, compatible with diffuse hepatic metastases, which were not seen in the diagnostic and the first posttreatment scans and SPECT/CT images. This unexpected finding turned the case into a clinical dilemma, leaving the medical team uncertain about how best to proceed to ensure the most appropriate care. Eventually, a liver FNA confirmed the presence of metastatic prostatic adenocarcinoma.

Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in men. Acinar adenocarcinoma accounts for 90% of primary prostatic cancers. Carcinoma of the basal cells of the prostate is extremely rare, making up less than 1% of prostate cancer diagnoses. As opposed to adenocarcinoma, basal cell-type carcinoma of the prostate (BCCP) does not usually secrete PSA and most commonly presents with symptoms of typical BPH. Due to its nonspecific symptoms and absence of PSA secretion, it is often diagnosed at the locally advanced stage. In part due to its rarity, there are no standardized treatment protocols. Agent Orange (AO) is a pesticide utilized by the US Military during the Vietnam War, which was contaminated with polychlorinated dibenzo-dioxins (PCDDs). These compounds have been linked to the development of various malignancies, including prostate cancer, although a direct causal relationship remains unproven. We present the case of a US Vietnam Veteran with Agent Orange exposure who was diagnosed with multiple distinct types of prostate cancer, including BCCP. He was initially found to have BCCP on pathological evaluation of prostate tissue from a prostatic resection for BPH. He was treated with definitive radiotherapy. He subsequently developed a recurrence of prostate cancer, but on this occasion, he was found to have localized prostatic adenocarcinoma and was treated with salvage High Intensity-Focused Ultrasound (S-HIFU). He remained without recurrence to the time of the writing of this report, 60 months after undergoing S-HIFU. Upon review of the literature, there is a lack of data regarding the environmental exposures of patients who develop BCCP, as well as a lack of documentation of rare subtypes of prostate cancers that have been identified in AO-exposed Veterans. Further studies on this subject would be beneficial, as there are millions of US veterans alive who had exposure to PCDDs during the Vietnam War and the more recent Global War on Terror.

SBRT plus abiraterone acetate and ADT versus abiraterone acetate and ADT in oligometastatic castrate-resistant prostate cancer (ARTO): long-term, unplanned overall survival analysis of an open-label, randomised, phase 2 trial.

Microvascular and stromal normalization combined with nano-immunotherapy: A synergistic strategy to overcome drug delivery barriers in solid tumors.

Molecular theranostics has revolutionized the field of personalized medicine, specifically augmenting "precision oncology" and is now integral in the management of malignancies like differentiated thyroid carcinoma, neuroendocrine tumors, and metastatic carcinoma prostate. The potential of theranostics is huge with possible applications in a variety of tumors, including at their early stages. This article will focus on the advancements in nuclear theranostics-highlighting the expanded indications of already established radionuclide therapies like peptide receptor radionuclide therapy (PRRT), prostate specific membrane antigen radioligand therapy (PRLT), and meta-iodobenzylguanidine therapy (MIBG therapy); and also on novel radiolabeled theranostic agents targeting fibroblast activated protein (FAPI-based radiopharmaceuticals), chemokine receptor targeting agents (pentixfor/pentixather), integrins, cholecystokinin receptors and their potential applications.

F-18 DOPA PET/CT is well established in the evaluation of neuroendocrine tumors and pheochromocytoma/paraganglioma. Prostatic uptake is not part of its usual physiological biodistribution, and its significance in conventional prostate adenocarcinoma remains unclear. We report intense incidental prostatic F-18 DOPA uptake in a 60-year-old man undergoing evaluation for persistently elevated normetanephrines. PET/CT showed 2 highly avid foci in the posterior-inferior prostate. Multiparametric MRI was not suspicious, but biopsy revealed acinar adenocarcinoma, Gleason score 3+3, ISUP grade 1, without neuroendocrine marker expression. This finding represents a potential diagnostic pitfall and supports cautious interpretation of focal pelvic F-18 DOPA uptake.

Chronic inflammation associated with infection has been implicated in prostate cancer (PCa) progression, yet the immunological mechanisms linking sexually transmitted pathogens to tumor development remain incompletely understood. Trichomonas vaginalis (Tv), the most prevalent nonviral sexually transmitted parasite worldwide, has been associated with prostatic inflammation and increased PCa risk. However, how Tv-induced inflammation influences tumor progression has not been clearly defined. Here, we investigated whether Tv-induced epithelial inflammation promotes Th17 differentiation and drives prostate tumor progression through intratumoral IL-17 receptor (IL-17R) signaling. Conditioned media of prostate epithelial cells (PECs, RWPE-1 cell line) was prepared by infection without (CM) and with Tv (TCM). Human CD4+ T cells were isolated using the CD4+ isolation kit from human peripheral blood. Conditioned medium of CD4+ T cells was prepared by incubation with CM (T-CM) or TCM (T-TCM). Conditioned media from Tv-stimulated PECs induced robust production of IL-6 and IL-1β, which promoted IL-6/IL-1R-dependent differentiation of human CD4⁺ T cells into Th17 cells. Conditioned media from these Th17 cells enhanced proliferation and migration of prostate epithelial and cancer cells and activated IL-17R-TRAF6-NF-κB signaling pathways. Using a syngeneic mouse prostate cancer model in C57BL/6 mice, we found that IL-17R neutralization significantly reduced tumor growth without affecting Th17 cell abundance, supporting the involvement of tumor-intrinsic IL-17R signaling in Tvs-associated tumor progression. Spatial transcriptomic analysis further revealed enrichment of IL-17R-associated proliferative and invasive gene programs in Tvs-treated tumors. Consistently, analysis of prostate adenocarcinoma datasets showed that IL17RA expression was associated with proliferative and invasive signatures and poorer clinical outcomes. Collectively, these findings identify a Tv-Th17-IL-17R signaling axis linking infection-induced inflammation to tumor-intrinsic oncogenic signaling in prostate cancer, highlighting IL-17R signaling as a potential therapeutic target in inflammation-associated PCa.

The MMP14 gene, which encodes the only membrane-bound collagenase, is highly expressed in malignant tumors and plays a decisive role in invasiveness. This study investigated the transcriptional regulation of MMP14 by the TGF-β cytokine and hypoxia in PC3 prostate carcinoma cells. Bioinformatic analysis confirmed the presence of key regulatory elements in the MMP14 promoter, specifically the HRE (for HIF-1α) and SMAD binding sites. Three 5' deletion fragments of the MMP14 promoter (P1: -1251/+75; P2: -649/+75; P3: -176/+75) were cloned for functional analysis. PC3 cells were treated with TGF-β, the hypoxia-mimetic CoCl2, and the combination. Gene and protein expression were analyzed using Real-Time PCR and Immunofluorescence Cytochemistry (IFC), respectively, while promoter activities were assessed via a Luciferase reporter assay. COL1A expression was also evaluated to explore its association with MMP14-mediated extracellular matrix remodeling. Hypoxia emerged as the dominant inductive factor. MMP14 mRNA and protein levels were significantly elevated under hypoxic and combined TGF-β/CoCl2 conditions. Promoter analysis revealed that the full-length P1 construct was consistently upregulated by all treatments. However, the shorter P2 and P3 fragments exhibited a decrease in activity with TGF-β alone, suggesting a complex, region-specific regulation predominantly influenced by hypoxic signaling. Critically, COL1A1 mRNA expression was observed in hypoxic groups with elevated MMP14 levels, indicating a possible inverse relationship between MMP14 induction and COL1A-associated extracellular matrix remodeling. Hypoxia is the primary driver of MMP14 induction and protein accumulation in PC3 cells, with TGF-β acting as a complex co-regulator whose activating effect is potentiated under low-oxygen stress. These findings highlight the contribution of the HIF/MMP14 axis to invasion-associated molecular regulation in prostate cancer.

Malignant laryngeal lesions are most commonly primary tumors, predominantly squamous cell carcinoma. Metastatic involvement of the larynx is extremely rare. Among metastatic tumors, renal cell carcinoma, melanoma, lung cancer, and breast cancer represent the most frequent primary sources, whereas metastasis from prostate adenocarcinoma is exceptionally uncommon. Here, we present a case of vocal cord metastasis from prostate adenocarcinoma that was initially detected on 68Ga-PSMA PET/CT and remained clinically silent for a prolonged period.

Trophoblast cell-surface antigen 2 evaluation in intraepithelial neoplasia and intraductal carcinoma of the prostate: An immunopathological study.

Allicin, an organosulfur compound derived from garlic, exhibits effective cellular activities, but its administration is often hindered by poor bioavailability and relative instability. To address these limitations, Soluplus-based polymeric micelles were engineered to encapsulate allicin and evaluated for their chemosensitizing or chemoprotective capacity with doxorubicin. The micelles displayed uniform spherical nanoparticles (~ 74nm, PDI ~ 0.21) with nearly complete encapsulation efficiency. Compared with free allicin, micellar formulations showed markedly reduced release (~ 16% vs. ~50%) at physiological temperature, indicating improved drug retention. Stability assessments revealed particle size and zeta potential were time-dependent but unaffected by temperature. FTIR confirmed successful encapsulation, while thermogravimetric analysis demonstrated thermal stability up to 250-300°C. In vitro, treatment with the allicin-Soluplus micelles prior to doxorubicin treatment exhibited a cell-model-dependent modulation of doxorubicin response. A partial protective metabolic response was observed in myocardial cells H9C2 and colorectal adenocarcinoma CACO2 cells. An opposite effect was observed on prostate adenocarcinoma DU145 cells, in which allicin exhibited a chemosensitizing effect with doxorubicin. These preliminary in vitro findings highlight Soluplus micelles as a promising delivery platform to stabilize allicin and potentiate its therapeutic effect in oncotherapy.

Prevention is desirable to reduce suffering and death from prostate cancer. However, a clinical-grade intervention for the prevention of this malignancy is still lacking. This study was undertaken to determine the feasibility of prostate cancer prevention by broccoli constituent sulforaphane (SFN) because epidemiological studies have suggested an inverse association between intake of broccoli and the risk of prostate cancer. Oral administration of 1 mg SFN/mouse (three times/week) to 5-week-old male Hi-Myc transgenic mice for 5 weeks decreased the incidence of prostatic adenocarcinoma in situ by about 54% without causing weight loss or any other side effects. Existing literature strongly implicates fatty acid synthesis in prostate cancer progression. Therefore, we determined the effect of SFN treatment on fatty acid synthesis. Prostate cancer prevention by SFN in Hi-Myc mice was accompanied by a decrease in: (a) the uptake of 11C-acetate in the prostate of live mice; (b) plasma levels of fatty acid synthesis intermediates acetyl-CoA and malonyl-CoA; (c) circulating levels of total free fatty acids (TFFA); (d) downregulation of fatty acid synthesis enzyme proteins acetyl-CoA carboxylase 1 and fatty acid synthase; and (e) plasma levels of interkeukin-10 and interleukin-12. Because prostate cancer in Hi-Myc mice is driven by Myc, we determined the effect of overexpression of c-Myc in 22Rv1 cells on TFFA level. Overexpression of c-Myc conferred partial protection against TFFA suppression by SFN treatment. In summary, this study reveals that SFN administration prevents prostate cancer development in Hi-Myc mice by suppressing fatty acid synthesis.

Endocrine-disrupting chemicals (EDCs) are important environmental risk factors for urogenital malignancies, but the shared molecular mechanisms underlying their carcinogenic effects remain poorly understood. Here, we systematically investigated the common pro-tumorigenic mechanisms of 12 prevalent EDCs, including anthracene, benzo[a]pyrene (BaP), bisphenol A, clofenotane, di(2-ethylhexyl) phthalate, diazinon, dibutyl phthalate, glyphosate, malathion, perfluorooctanoic acid, polychlorinated biphenyls, and triclosan, across four urogenital cancers, including bladder cancer (BLCA), renal cell carcinoma (RCC), prostate adenocarcinoma (PRAD), and testicular germ cell tumor (TGCT). By integrating network toxicology and protein-protein interaction analysis, we identified shared hub targets linking EDC exposure to tumor progression. EGFR and CASP3 were identified as core targets in BLCA, EGFR and CASP9 in RCC, and CASP3, ESR1, and EGFR in PRAD, whereas KIT emerged as a broadly relevant target in TGCT. Molecular docking and molecular dynamics simulations supported the stable binding of EDCs to these targets. Among the predicted interactions, BaP showed strong binding affinity for CASP9 (ΔG = -9.8 kcal/mol) and was therefore selected for experimental validation. Analysis of TCGA data showed that elevated CASP9 expression was significantly associated with poorer overall survival in patients with RCC. In 786-O and ACHN cells, chronic exposure to an environmentally relevant concentration of BaP significantly increased CASP9 protein stability without altering its mRNA expression, suggesting post-transcriptional regulation. Collectively, these findings identify shared molecular targets of EDCs across urogenital cancers and provide new mechanistic insight into EDC-driven tumor progression, prioritizing potential biomarkers and therapeutic targets for environmentally related malignancies.

SET protein expression in canine neoplasms: evaluation of predictive potential.

Identification of a novel class of early exon ALK rearrangements across two pan-tumor sequencing databases.

A 76-year-old man with mildly elevated prostate-specific antigen (PSA, 5.44ng/mL) and a PI-RADS 5 lesion on multiparametric MRI underwent dual-tracer PET/CT. 68Ga-PSMA PET/CT revealed focal intense uptake in one prostatic lobe, while 18F-FDG PET/CT demonstrated avid uptake in the contralateral lobe. Histopathology confirmed synchronous high-grade prostatic adenocarcinoma (Gleason 9) and sarcomatoid carcinoma with osteosarcomatous differentiation. This discordant dual-tracer pattern highlights the complementary role of PSMA and FDG PET/CT in detecting molecularly divergent synchronous prostatic malignancies.

ABSTRACTPenile metastasis from prostate cancer is rare and is associated with a poor prognosis; however, there is currently a lack of high‐level evidence to guide the management of this condition. This case report describes a 68‐year‐old male with prostate cancer who developed a penile metastasis during follow‐up. This occurred despite stable prostate‐specific antigen (PSA) levels after treatment with androgen deprivation therapy, combined with endocrine therapy and radiotherapy. Imaging studies and intraoperative frozen section pathology suggested a penile tumor. The patient subsequently underwent total penectomy combined with urinary diversion surgery. Postoperative histopathology confirmed poorly differentiated adenocarcinoma consistent with metastatic prostatic adenocarcinoma exhibiting morphological changes related to prior therapy. This case highlights the importance of maintaining clinical suspicion for penile metastasis in prostate cancer patients with stable PSA levels, especially in the context of tumor dedifferentiation, to facilitate early diagnosis and appropriate intervention.

Bone metastases represent a devastating complication of primary cancers, significantly impacting patient survival and quality of life. Accelerating the development of novel and effective chemotherapeutic drugs requires reliable in vitro models. Current in vitro models largely rely on conventional 2D set-ups, while 3D spheroid cultures are emerging. However, the correlation between these 2D and 3D configurations regarding chemotherapeutic efficacy remains poorly defined due to discrepancies in cellular assessment methodologies. To achieve a direct, unconfounded comparison of cellular responses to cisplatin treatment, identical analytical assays were deployed across both 2D and 3D culture models. Cisplatin sensitivity was comparatively evaluated in metastatic human cancer cell lines (PC3 prostate adenocarcinoma and MDA-MB-231 breast adenocarcinoma) cultured in conventional 2D monolayers versus biomaterial-free 3D spheroids. Proliferation and viability assays were used to assess cytotoxicity, with human Bone Marrow Stromal Cells (hBMSCs) as non-malignant controls. Additionally, the effects of acute (24-hour) versus continuous cisplatin exposure regimens on cellular behavior were examined, and drug sensitivity was subsequently correlated with cell doubling time. For all cell types, 3D spheroid cultures exhibited significantly lower sensitivities to cisplatin compared to 2D cultures. This is likely related to both the dimensionality of the 3D spheroids, as evidenced by time- and concentration-dependent cisplatin penetration into hBMSC spheroids, and cell proliferation, as a correlation between cisplatin sensitivity and cell doubling time was observed across the various cell types used. Finally, we showed that continuous exposure to cisplatin affects cell viability in 2D and 3D culture models in a manner comparable to limited exposure during the initial 24 hours of culture, and that cisplatin sensitivity correlates with cell doubling time. Methodological similarities in analyzing cell viability were maintained for both 2D and 3D cell culture models when exploring cisplatin. Their dimensionality hampers penetration of cisplatin into the core of 3D spheroids. Overall, our data underscore the dependence of cisplatin sensitivity on the dimensionality of in vitro models (2D vs. 3D.

Bispecific antibodies targeting tumor-associated antigens and CD3 are promising therapeutic agents for both solid and hematologic cancers. CD3-bispecifics induce T cell activation and cytotoxicity; however, prolonged TCR stimulation can lead to chromatin rewiring and T cell dysfunction, thereby limiting their full therapeutic potential. Here, we investigate the combination of CD3-bispecifics with the DNA hypomethylating agent decitabine and observe enhanced synergistic tumor growth inhibition in various preclinical models. Utilizing a PSMAxCD3 bispecific antibody for treatment of prostate carcinoma and in vivo humanized mouse disease models, we catalog, at the single-cell level, the dynamics of T cell epigenetic states during bispecific therapy and in combination with decitabine. Importantly, this combination strategy preserves a TCF-1+ T cell population and delays acquisition of a dysfunctional state at both chromatin and protein levels. At the DNA methylation level, TCR stimulation in the presence of decitabine maintains a naive-like pattern in gene loci associated with T cell stemness. This study provides a resource for understanding the evolution of T cell states during immunotherapy and mechanistic support for combining epigenetic modifiers with CD3-bispecifics in the clinic.

A patient with metastasized prostate adenocarcinoma underwent 18F-PSMA-11 PET/CT restaging following 177Lu-PSMA-617 treatment and rising PSA-level. The maximum intensity projection image (right-side of the figure) demonstrated an intense homogenous tracer uptake throughout the bone marrow containing skeleton, whereas CT images showed specific bone metastases but no diffuse involvement, and previously known lymph node and liver metastases exhibited significantly reduced or absent uptake (see also left-side of the image, 18F-PSMA-11 MIP prior to 177Lu-PSMA-617 therapy). None of the patients that underwent imaging with the same tracer-batch demonstrated similar findings excluding free 18F as a potential cause for the imaging findings. Furthermore, the patient did not suffer from any bone marrow disorder previously reported to present with diffuse bone marrow uptake on PSMA-targeting PET/CT imaging [1, 2]. Of interest, the patient had received recombinant human erythropoietin, 100µg of Aranesp, 24h prior to imaging to treat his renal failure associated anemia. At this dose, Aranesp reaches a nanomolar concentration in the bone marrow resulting in stimulation of the Tissue Protective Receptor on endothelial cells leading to the creation of a massive systemic reservoir of PSMA-positive neovasculature that outcompetes PSMA-expressing prostate carcinoma lesions for radiotracer availability [3, 4]. This may explain the diffuse marrow uptake and the decreased visibility of known metastases [4]. The effect of erythropoietin on bone marrow mobilization and neovascularization can persist for 7-10 days [5]. This should be taken into consideration in order to avoid erroneous interpretation of 18F-PMSA-11 PET/CT imaging and unnecessary bone marrow toxicity of 177Lu-PSMA-617 treatment.