Search Results (150)

Background/Objectives: Prostate cancer (PC) exhibits marked disparities in incidence and mortality across ethnicities, with men of Sub-Saharan African (SSA) ancestry experiencing 1.7 and 2.0 times higher values, respectively, than European men (EUR). However, SSA preclinical models remain scarce (just one commercial cell line). In this study, we established and characterized a novel panel of PC cell lines derived from SSA patients using conditional reprogramming (CR), a method that enables efficient propagation of primary cells while maintaining their genotypic and phenotypic features. Methods: CR was applied to five SSA-PC samples, and successfully propagated samples were authenticated by STR and ~1 million SNP profiling, and extensively characterized for proliferative capacity, migratory behaviour, karyotyping and epithelial and prostate tumour lineage markers. To explore drug response profiles, a high-throughput screen (HTS) of 1280 clinically annotated compounds was conducted. Results: Three SSA-PC cell lines were successfully established and authenticated, and five potential drug hits were validated. A new finding was the reduced sensitivity of SSA-derived models (9.0 times difference compared to commercial EUR PC cell lines) to camptothecin, a TOP1 inhibitor, while being equally sensitive to epirubicin hydrochloride, a TOP2 inhibitor. The cardiac glycoside digoxin, anthelmintic pyrvinium pamoate and antirheumatic agent auranofin were also efficient drugs in the in vitro testing. Conclusions: These results support the relevance of SSA-derived PC models for preclinical drug screening and highlight the value of including ancestry-diverse models in oncobiology research. Full article

Background/Aim. We previously described four distinct breast cancer (BC)-associated adipose tissue (BCAAT) subtypes that have a significant impact on survival. In this exploratory study, we aimed to determine whether these BCAAT subtypes exhibit significant correlations with neoadjuvant and adjuvant therapies and BC molecular subtypes. Methods. Four BCAAT subtypes previously identified as fibroblast-rich (F^Rich_BCAAT), myofibroblast-rich (MyoF^Rich_BCAAT), vascular-rich (V^Rich_BCAAT), and mixed vascular- and inflammation-rich (VI^Rich_BCAAT) were analyzed according to their distribution in BC molecular subtypes, as well as in relation to neoadjuvant therapy and survival. Results. Triple-negative BC and Luminal B (LB) BC are related to V^Rich and VI^Rich BCAAT subtypes and were affected by Epirubicin/Cyclophosphamide (EC)+ paclitaxel (PTX) therapy, which significantly enhanced overall survival (OS) and disease-free survival (DFS). For the Luminal A (LA) BC subtype, EC + docetaxel (DTX) had significant impact on survival independent of BCAAT subtype. Conclusions. BCAAT subtypes strongly influenced neoadjuvant therapy response and survival depending on BC molecular subtype. Full article

A 51-year-old woman was admitted with a malodorous ulceration covering the whole area of both breasts, without visible breast contour or remnants of breast tissue. After excision of a skin nodule an invasive ductal carcinoma was diagnosed; grade-2, hormone receptor (HR)-positive, HER2-negative, Ki-67 at 25%. Computed tomography of the thorax and abdomen showed pulmonary and osseous metastases. Six cycles of systemic chemotherapy with epirubicin and cyclophosphamide at three-week intervals were administered, followed by endocrine therapy with letrozole. Almost four years later, palbociclib became available and it was added to the patient’s treatment. Loco-regional and distant disease control was achieved attaining maximum response at 11 months after initial diagnosis and since then the patient remains progression-free with good quality of life for more than eight years. This is to the best of our knowledge an extreme case of primary metastatic ulcerative breast cancer with complete local tissue destruction and markedly prolonged progression-free survival. As this is a single-case clinical observation, any conclusions have limited generalizability. Given the rarity of primary metastatic ulcerative breast cancer there are no specific evidence-based treatment guidelines available and published studies have high heterogeneity and low level of evidence, necessitating multidisciplinary approach on a case-by-case basis. Full article

Background/Objectives: Recurrent or metastatic adenoid cystic carcinoma (R/M ACC) has no standard systemic therapy. VEGFR-targeting tyrosine kinase inhibitors (TKIs) are commonly used first-line, though no international standard exists; cisplatin-based chemotherapy is an alternative. We retrospectively reviewed the cyclophosphamide–epirubicin–cisplatin (CEP) regimen to determine whether prior TKI exposure compromises subsequent chemotherapy efficacy. Methods: We studied 31 patients given CEP for progressive R/M ACC (2018–2023). Tumor response was assessed by RECIST 1.1. Molecular subtype was determined by c-MYC/p63 immunohistochemistry (ACC-I, c-MYC-positive/p63-negative; ACC-II, p63-positive/c-MYC-low or negative). Multivariable models used Firth’s penalized likelihood Cox regression. Next-generation sequencing (NGS) was available in 21 of 31 patients. Results: Thirty-one patients were enrolled (median age 48; 17 [54.8%] with prior TKI). At median follow-up of 22.6 months, the objective response rate (ORR) was 19.4%, disease control rate 71.0%, median progression-free survival (PFS) 5.3 months, and median overall survival (OS) 10.3 months. Prior TKI did not lower efficacy: ORR 17.6% vs. 21.4%, PFS hazard ratio 0.76 (p = 0.519). All six partial responses occurred in ACC-I tumors (35.3% vs. 0% in ACC-II, p = 0.021). In the NGS subset (5 PIK3CA-mutant), PIK3CA mutation (OS HR 6.19, p = 0.024) and bone metastasis (OS HR 5.84, p = 0.027) remained associated with shorter OS after adjustment. No treatment-related deaths occurred. Conclusions: CEP is active in R/M ACC, and prior TKI exposure did not appear to reduce efficacy. Higher response rates in ACC-I tumors and the apparent PIK3CA-related survival deficit are exploratory observations that need prospective testing before they can guide treatment. Full article

Background: Triple-negative breast cancer (TNBC) is associated with poor prognosis, highlighting the need for innovative therapeutic strategies. Chronomodulated chemotherapy yielded improved efficacy and tolerability in several malignancies; however, evidence in breast cancer remains limited. This study investigated the association between the time of day of administration (ToDA) of neoadjuvant chemotherapy (NAC) and clinical outcomes in patients with TNBC treated in a day hospital setting. Methods: This retrospective cohort included patients treated at Saint-Louis Hospital with neoadjuvant dose-dense, dose-intense cyclophosphamide–epirubicin followed by weekly paclitaxel. Infusion start times of each chemotherapy agent were systematically recorded. The primary endpoint was pathological complete response (pCR; Residual Cancer Burden [RCB] = 0). Secondary endpoints included RCB classes, early metabolic response, treatment tolerance, and 36-month event-free survival (EFS). Patients were classified into early or late infusion groups using multiple ToDA cut-offs, and cosine-based analyses were performed. Results: Ninety-four patients (median age 51 years) received NAC between 9:00 and 17:40 which aligns with the day hospital unit’s opening hours. With a median follow-up of 39.9 months, the pCR rate was 48.9%. No significant differences were observed between early and late infusion groups for any endpoint, regardless of ToDA cut-off or analytical approach. Conclusions: This first chronotherapeutic study in patients with early TNBC showed no association between ToDA of NAC administered between 9:00 and 17:40 and histological response or EFS. Although limited by sample size and the restricted infusion time window, our study provides novel data and methodological insights supporting further investigation of chronotherapy in patients with breast cancer. Full article

Background/Objectives: Epirubicin, Olaparib, and Ribociclib are widely used anticancer agents whose serum concentrations exhibit significant inter-individual variability, supporting the need for reliable and robust analytical methods suitable for pharmacokinetic evaluation and therapeutic exposure assessment. Variations in metabolism, drug–drug interactions, organ function, and treatment regimens may substantially influence systemic exposure, highlighting the importance of accurate quantification in clinical practice. This study describes the development and validation of a solid-phase extraction–liquid chromatography–mass spectrometry (SPE–LC–MS) method for the simultaneous quantification of these drugs in human serum. Methods: Sample preparation was performed using Oasis PRiME HLB^® cartridges to ensure efficient clean-up, optimal recovery, and reduced matrix effects. Chromatographic separation was achieved using gradient elution with 0.1% formic acid and acetonitrile on a reversed-phase column, followed by single-quadrupole mass spectrometric (QDa) detection in the selected ion recording mode. The total run time was 13 min, enabling high-throughput analysis. Results: The method demonstrated good linearity (r > 0.997) over the tested concentration ranges, along with adequate selectivity, precision, accuracy, recovery, and stability, fulfilling the ICH M10 guideline validation criteria. No significant carry-over or interference from endogenous compounds was observed. Conclusions: Application to patient samples confirmed reliable performance in real clinical matrices and consistent quantification across different concentration levels. The proposed approach provides a potentially more accessible alternative in laboratories already equipped with LC-MS systems compared to LC-MS/MS platforms and can be applied in pharmacokinetic studies, representing a proof-of-concept for exposure assessment in oncology. Full article

Background/Objectives: Transarterial chemoembolization (TACE) is included in international guidelines for the treatment of hepatocellular carcinoma (HCC), but it is still not a standardized intervention in terms of vector and chemotherapy. This study aims to report on clinical and radiological outcomes of degradable starch microspheres TACE (DSM-TACE) with idarubicin and compare with DSM-TACE with an epirubicin protocol after a single session. Methods: This is a single-center retrospective study analyzing cirrhotic patients affected by HCC in early or intermediate stages. Primary objectives were to assess the safety and efficacy of a single DSM-TACE with 10 mg idarubicin in terms of adverse event (AE) occurrences evaluated via the CTCAE 5.0 system and mRECIST criteria with computed tomography (CT) at 3 months. The secondary purpose was to compare the procedural outcomes with those from patients treated with DSM-TACE with 50 mg epirubicin. Results: Thirty-seven patients were included, 19 treated with idarubicin (IDA group) and 18 with epirubicin (EPI group); demographic data and lesion characteristics were comparable. No major AE (grade ≥ 3) occurred overall. In the IDA group, the minor AE incidence was 52.7%: one patient presented with mild ascites, eight developed hyperbilirubinemia and one leucopenia. At the 3-month CT follow-up, mRECIST criteria reported an overall response rate (ORR) of 63.2% and a disease control rate (DCR) of 84.2%. No statistically significant differences were appreciable comparing both AE occurrence and mRECIST findings with the EPI group (50% minor AE, 77.8% ORR, 88.9% DCR). Conclusions: In this sample of cirrhotic patients with HCC, DSM-TACE with 10 mg idarubicin was safe and effective comparable to DSM-TACE with 50 mg epirubicin. Full article

Background: Therapeutic drug monitoring (TDM) is a promising strategy to personalize chemotherapy dosing, especially for agents with narrow therapeutic indices such as epirubicin. However, widespread adoption is hindered by logistical challenges associated with venous blood sampling and centralized laboratory workflows. Objective: This study aimed to perform a method-comparison validation of the True Dose^® TD-EPI microsampling kit by verifying analytical agreement between capillary and venous epirubicin measurements in real patient samples. The study focuses on analytical performance and does not constitute validation of the whole decentralized workflow, including unsupervised patient self-sampling. Methods: 13 patients with early-stage breast cancer receiving the first cycle of neoadjuvant or adjuvant epirubicin were enrolled. Capillary samples were collected using the finalized TD-EPI kit (Cap-TD) at 2.5 h (n = 13) and/or 48 h (n = 10) post-infusion and stored at room temperature for 72 h before analysis. Matched venous samples were analyzed using both conventional protein precipitation (“Traditional”) and a modified lab-based True Dose workflow (Lab-TD). Epirubicin concentrations were quantified via validated liquid chromatography–tandem mass spectrometry (LC–MS/MS). Results: Cap-TD concentrations showed strong agreement with Traditional venous values (r = 0.953), with minimal bias (mean difference = 0.013 μM) in Bland–Altman analysis. Passing–Bablok regression confirmed analytical equivalence. Intra-assay variability remained within ICH M10 guidelines (CV ≤ 15%), and recovery was unaffected by 72 h ambient storage. Lab-TD results closely matched Traditional workflows, supporting reproducibility. Conclusions: The TD-EPI kit enables accurate decentralized monitoring of epirubicin, eliminating the need for venous access, cold-chain logistics, or in-clinic sampling. These findings support its integration into personalized oncology care and future applications in home-based TDM. Trial Registration: This study is part of an approved protocol registered in the EU Clinical Trials Register (EUCT Number 2024-514818-12-00; EudraCT Number 2017-000641-44; registration date: 15 June 2017). Full article

Background: Neoadjuvant systemic therapy (NST), whose primary purposes include response assessment and treatment individualization, is a key strategy in the treatment of HER2-positive breast cancer. This study investigated the predictive value of the magnetic resonance imaging (MRI)-derived tumor volume reduction rate (δV1) for the early identification of pathological complete response (pCR) during NST and established clinically applicable δV1 thresholds for patient stratification. Methods: HER2-positive breast cancer patients who received THP (taxane, trastuzumab, pertuzumab) followed by epirubicin/cyclophosphamide (EC) were enrolled. MRI was performed at baseline, after THP, and after EC. Tumor volumes were manually segmented using 3D Slicer, and δV1/δV2 were calculated via Python (version3.13). Longest diameter reduction rates (δL1/δL2) were recorded. pCR (ypT0/is ypN0) was the primary endpoint. Receiver operating characteristic (ROC) analysis determined predictive accuracy, and logistic regression identified independent predictors. Thresholds for δV1 were explored, and subgroup analyses were conducted by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. Results: Overall, 59.3% of patients achieved pCR. δV1 demonstrated superior predictive accuracy compared with longest diameter reduction (δL1), with an AUC of 0.745 (95% CI: 0.642–0.847) vs. 0.634 (95% CI: 0.512–0.757). A δV1 cutoff of 0.85 discriminated responders (68.4% vs. 41.4%, p = 0.016), while one of 0.91 represented the optimal predictive threshold. In multivariate analysis, δV1 was independently associated with pCR (OR = 1227.1, 95% CI: 6.86–219,562; p = 0.007), along with HER2 3+ expression (OR = 4.24, 95% CI: 1.26–14.31; p = 0.020). Among HR-positive patients, δV1 < 0.93 identified a subgroup with significantly lower pCR rates (19.0% vs. 81.0%, p < 0.001). Conclusions: δV1 is a reliable and early MRI-based imaging biomarker for predicting pCR in HER2-positive breast cancer. Defining thresholds such as 0.85 and 0.91 supports early therapeutic stratification and may help identify patients who could benefit from anthracycline-containing regimens. Full article

Background/Objectives: Glioblastoma (GBM) is a fatal tumor in the central nervous system (CNS) with a poor prognosis. Preventing tumors from post-surgical recurrence is a significant clinical challenge, since current methods deliver chemotherapeutic agents in a rapid manner and are not effective against the residual tumor cells. To address these limitations, we develop a blue light-crosslinking hydrogel which can be rapidly gelled in situ and tightly adhere on the tissues for controlled chemotherapy, radiotherapy, and enhanced laser interstitial thermal therapy (LITT) to inhibit residual tumor cells from post-surgical recurrence. Methods: We utilize gelatin-MA based hydrogel with crosslinker VA-086 as hydrogel scaffold to encapsulate small-molecule drugs (Epirubicin and Cisplatin) and LITT agent polypyrrole-coated graphine oxide (PPy@GO). The mixture can form into hydrogel in situ by blue light irradiation and performed chemo-LITT and radio therapy simultaneously. Then we determine the prevailing factors that affect efficient encapsulation of therapeutic agents within hydrogels, efficiency of gelation, LITT enhancement, and drug release. Then evaluate efficiency in human cancer cells and an in vivo tumor model. Results: Our results demonstrate that 18 wt% Gelatin MA formulation achieved >95% gelation within 2 min, with drug-loaded gels forming within 5 min. The gelation can perform both in vitro and in vivo without affect the drug efficiency. This multi-treatment system can effectively prevent tumor recurrence and significantly prolong the medium survival of glioma-bearing (MBR-614 or U87-MGFL) mice to above 65 days compared with the control group (36 days). Conclusions: The results demonstrated promising effect of this system as a multi-therapeutic platform which combined chemo-LITT and RT. This synergistic strategy presents a new approach to the development of a local drug delivery system for the prevention of brain tumor recurrence. Full article

Background: Neoadjuvant chemotherapy (NACT) is widely used in patients with high-risk HER2-amplified (HER2+) or triple negative early breast cancer (TNBC). Advantages of NACT include allowing less extensive surgery, assessing response to treatment and guiding adjuvant therapy. NACT-related toxicities are common and can result in treatment alterations and hospitalisation, which may adversely impact outcomes. Aim: To assess NACT treatment in Hawke’s Bay (HB), New Zealand, by evaluating pathologic complete response (pCR) rates and toxicities of different regimens. Method: Data were retrospectively obtained from medical records of NACT patients. pCR rates were compared to results from the previous literature. Toxicity was assessed by recording severe (grade 3 or above) toxicities, treatment-limiting toxicities (those leading to dose reductions, dose delays or early cessation) and hospitalisations for different NACT regimens. Results: A total of 71 NACT patients were included. pCR rates for HER2+ disease and TNBC were 19/45 (42%) and 8/24 (33%), respectively. The most common severe toxicities were diarrhoea, anaemia and febrile neutropaenia (all 16%) in FEC-D (5-fluorouracil/epirubicin/cyclophosphamide + docetaxel +/− carboplatin +/− immunotherapy) patients, neutropaenia (50%) in FEC-DH (FEC-D + trastuzumab +/− pertuzumab) patients and diarrhoea (38%) in TCH (docetaxel/carboplatin/trastuzumab +/− pertuzumab) patients. Comparing treatment-limiting toxicity in FEC-DH vs. TCH, 9/16 (56%) vs. 13/21 (62%) had dose reduction, 2/16 (13%) vs. 8/21 (38%) had dose delay, 1/16 (6%) vs. 5/21(24%) had early cessation and 6/16 (38%) vs. 13/21 (62%) were hospitalised, respectively. Conclusions: NACT was associated with high rates of severe and treatment-limiting toxicity. Despite this, pCR rates were consistent with the previous literature. With the caveat of small patient numbers, FEC-DH-based therapy was associated with fewer dosing delays, early cessations and hospitalisations compared with TCH-based therapy. Full article

In addition to killing malignant cells, effective cancer therapies must also promote the development of an immunostimulatory tumor microenvironment (TME). Macrophages are the most abundant immune cell population within the TME. These highly plastic cells play key roles in tumor progression, chronic inflammation, immunosuppression, and metastasis. Although increasing research efforts focus on manipulating macrophage functions, relatively little is known about how standard anticancer strategies, especially chemotherapeutic agents, influence the composition, polarization state, and functional behavior of macrophage subpopulations. Chemotherapeutic agents remain a primary treatment option for many types of cancer, including breast and cervical cancers. In this study, we used epirubicin and doxorubicin at near-therapeutic concentrations and examined their effects on macrophage functions in co-culture with MDA-MB-231 breast cancer and HeLa cervical cancer cell lines. We demonstrated that the presence of tumor cells led to increased expression of the M2 macrophage marker CD206, a change that was reduced by both chemotherapeutic agents. The production of macrophage-derived chemokines, such as IP-10 and IL-8, was also altered by tumor presence and drug exposure. A striking finding was that the co-presence of chemotherapeutic agents and MDA-MB-231 cells synergistically altered macrophage motility. This effect was not observed in monocultures. Furthermore, the presence of tumor cells reduced the susceptibility of pro-inflammatory M1 macrophages to drug-induced cell death. These results indicate that chemotherapy can reshape the macrophage landscape in the TME. We highlight that the combined effects of tumor cell presence and chemotherapy modulate the composition, phenotype, and migration of macrophage subtypes differently than either factor alone. Full article

Dose-dense chemotherapy shortens the interval between chemotherapy cycles and has shown improved outcomes in high-risk breast cancer patients. We retrospectively evaluated the efficacy and safety of dose-dense chemotherapy in 80 breast cancer patients treated at our hospital from 2020 to 2024. The regimen included epirubicin and cyclophosphamide followed by paclitaxel or docetaxel, with pegfilgrastim support. The overall treatment completion rate was 82.5%. Of the 80 patients, 55 underwent neoadjuvant chemotherapy, and the pathological complete response rate was significantly higher in triple-negative breast cancer (59.1%) compared to that in luminal-type cancer (9.1%). Common adverse events included anemia, liver dysfunction, myalgia, and peripheral neuropathy. Febrile neutropenia occurred in 8.8% of patients, with some cases linked to pegfilgrastim body pod use, particularly in individuals with low subcutaneous fat. Notably, two patients developed pneumocystis pneumonia, potentially associated with steroid administration. Despite these toxicities, most were manageable and resolved after treatment. Our findings support the efficacy of dose-dense chemotherapy, particularly in triple-negative breast cancer, while highlighting the importance of individualized supportive care and vigilance regarding hematologic and infectious complications. Full article

Background: Drug therapy remains the principal management strategy for malaria but is increasingly challenged by the emergence of drug-resistant malaria parasites. The need for new antimalarial drugs is urgent, yet drug discovery and development are hindered by high costs, long durations, and safety concerns that prevent approval. The current study aimed to determine antiplasmodial activities of approved drugs in combination with artemether (ART) and lumefantrine (LU). Methods: Using the SYBR Green I assay test, this study investigated the efficacy of epirubicin (EPI) and pelitinib (PEL) combined with ART and LU at fixed drug–drug ratios (4:1, 3:1, 1:1, 1:2, 1:3 and 1:4) and volume/volume. These combinations, as well as single drug treatments, were tested against cultured strains of Plasmodium falciparum (W2, DD2, D6, 3D7 and F32-ART) and fresh and cultured clinical isolates. The fifty percent inhibition concentration (IC₅₀) and a mean sum of fifty percent fractional inhibition concentration (FIC₅₀) were determined. Results: Synergism was observed when EPI was combined with both ART and LU across all fixed ratios with a mean of mean FIC₅₀ values of <0.6. The combination of LU and EPI against the 3D7 strain demonstrated the highest efficacy with a synergism FIC₅₀ value of 0.18. Most combinations of PEL with ART and LU showed antagonism (FIC₅₀ > 1) when tested against strains of P. falciparum and clinical isolates. Conclusions: This study underscores the utility of alternative drug discovery and development strategies to bypass cost, time, and safety barriers, thereby enriching the antimalarial drug pipeline and accelerating the transition from lab to market. Full article

A novel nanocomposite based on electrochemically reduced graphene oxide (ERGO) and electropolymerized polyproflavine (PPFL) was obtained within a “one-pot” synthesis from natural deep eutectic solvent (NADES). NADES consisted of citric acid, glucose, and water in a molar ratio of 1:1:6. The synthesis was carried out in potentiostatic mode by consequent potential application in cathodic and anodic areas. The composite was applied to develop the impedimetric DNA sensor for anthracycline determination. The sensor has provided linear range from 10 nM to 0.1 mM for doxorubicin, from 1 pM to 10 nM for epirubicin, and from 10 pM to 10 nM for idarubicin, with the limit of detection 3 nM, 1 pM, and 5 pM, respectively. The concentrations of doxorubicin below 10 nM did not have any other influence on epirubicin and idarubicin determination despite their molecular structure similarity. The sensor developed was used for the determination of anticancer medications, such as doxorubicin, epirubicin, and idarubicin, in their standard solutions, pharmaceuticals, artificial, and human urine samples. It is worth noting that the additions of mannitol and lactose, which are the stabilizers of the pharmaceuticals, exhibited an interfering effect on the sensor response. Full article