Hematology, Transfusion and Cell Therapy最新文献

{"title":"GOLD(I) COMPLEX AUDMAP PROMOTES APOPTOTIC RESPONSES AND INHIBITS PROLIFERATION AND MIGRATION IN SK-MEL-28 HUMAN MELANOMA CELLS","authors":"Isabela Carvalho Diniz, Fernanda Van Petten Vasconcelos Azevedo, Ericka Francislaine Dias Costa, Jennyfer Castro da Silva, Camilla Abbehausen, Carmen Silvia Passos Lima","doi":"10.1016/j.htct.2026.106288","DOIUrl":"10.1016/j.htct.2026.106288","url":null,"abstract":"<div><h3>Introduction</h3><div>Metal-based chemotherapeutic agents, particularly platinum compounds, are widely used in cancer treatment; however, they are limited by systemic toxicity and drug resistance, highlighting the need for novel metallodrugs. Gold-based complexes have emerged as promising candidates due to their distinct mechanisms of action and notable antitumoral activity. Melanoma remains a highly aggressive malignancy with limited therapeutic options in advanced stages. Although several gold-based compounds have shown preclinical antitumoral potential, their effects in melanoma models remain insufficiently explored.</div></div><div><h3>Objectives</h3><div>To evaluate the in vitro antitumoral properties of the gold(I) complex (PPh3)Au(DMAP) (AuDMAP) in human melanoma cells.</div></div><div><h3>Methodology</h3><div>AuDMAP was evaluated in SK-MEL-28 melanoma cells, with non-tumoral HaCaT keratinocytes used as a comparative model. Cell viability and proliferation were assessed using MTT and SRB colorimetric assays. Cell migration was evaluated through the wound healing assay. Intracellular reactive oxygen species (ROS) levels were measured using the DCFH-DA assay and expressed as mean fluorescence intensity (MFI). Cell cycle distribution and cell death were evaluated by flow cytometry using 7-AAD and Annexin V-FITC/7-AAD staining, respectively. Transcriptional analysis was performed by quantitative PCR (qPCR).</div></div><div><h3>Results</h3><div>AuDMAP markedly reduced melanoma cell viability and proliferation in the low-nanomolar range, with an IC50 of ∼35.1 nM at 24h and 48h, showing greater inhibitory activity than cisplatin at concentrations = 34.4 µM (p = 0.001). In non-tumoral HaCaT keratinocytes, IC50 was ∼46,1 nM, indicating limited in vitro selectivity under the tested conditions. Based on these data, the 34.4 nM dose was selected for subsequent assays. At this concentration, AuDMAP significantly impaired melanoma cell migration, reducing wound closure percentage when compared to control, at both 24h (4.7% vs. 40.5%; p = 0.05) and 48h (1.6% vs. 74.6%; p = 0.05). In contrast, keratinocytes exhibited higher migratory activity, with increased wound closure at 24h (76.1% vs. 48.9%; p = 0.05) and 48h (85.8% vs. 48.9%; p = 0.05). Treatment with AuDMAP increased ROS levels in melanoma cells, expressed by a higher MFI at 24h (1154 vs. 637; p = 0.05) and 48h (1334 vs. 640; p = 0.05). In HaCaT keratinocytes, MFI was higher than control at 24h (1090 vs. 341; p = 0.05), but did not differ significantly at 48h (916 vs. 490; p > 0.05). No significant differences were found in melanoma cell cycle distribution. Conversely, analysis of cell death pathways revealed a predominance of early apoptotic markers in melanoma cells following AuDMAP treatment, at 24h (49.8% vs. 0.0%; p = 0.0001) and 48h (85.3% vs. 0.1%; p = 0.0001). In keratinocytes, no significant differences were observed at 24h (27.0% vs. 1.1%; p = 0.0001), whereas a significant in","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106288"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FDG PET/CT AND PSMA PET/CT IN EPITHELIOID SARCOMA STAGING: A CASE REPORT","authors":"Ellen Nogueira Lima,&nbsp;Natália Tobar Toledo Prudente da Silva,&nbsp;Mayara Silva,&nbsp;Allan de Oliveira Santos,&nbsp;José Barreto Campello Carvalheira,&nbsp;Maurício Etchebehere,&nbsp;Elba C.S.C. Etchebehere","doi":"10.1016/j.htct.2026.106327","DOIUrl":"10.1016/j.htct.2026.106327","url":null,"abstract":"<div><h3>Introduction</h3><div>Epithelioid sarcoma (ES) is a rare malignant soft-tissue neoplasm characterized by indolent growth, most commonly arising in the distal extremities, with a predilection for the hands and feet. ES poses a clinical diagnostic challenge, as its presentation may mimic benign conditions, particularly inflammatory or granulomatous lesions. ¹8F-FDG PET/CT is used for primary staging of soft tissue sarcomas, including ES. Although no studies have focused on PSMA and ES to date, the Prostate Specific Membrane Antigen (PSMA) may be an alternative for diagnosing and potentially treating these patients due to its Theranostic capabilities. We present a case of epithelioid sarcoma and evaluate the diagnostic performance of ¹8F-PSMA PET/CT compared to ¹8F-FDG PET/CT. Ethical Approval (CAAE: 30476720.9.0000.5404).</div></div><div><h3>Case presentation</h3><div>A 34-year-old man presented with a lesion on the plantar region of the right foot with progressive growth over 9 months and weight loss. MRI showed a well-defined, lobulated, heterogeneous mass measuring 90 × 71 × 64 mm, with a focus of cystic degeneration, located on the plantar and medial surfaces of the midfoot. Histopathology was consistent with ES. A staging 18F-FDG PET/CT showed marked hypermetabolism in the ES as well as in locoregional lymph node metastases in the right popliteal fossa and peri-bronchial lymph nodes, in lung nodules, and in the distal portion of the tibia. After 24 hours, an 18F-PSMA PET/CT scan was performed. The comparison of 18F-PSMA PET/CT and 18F-FDG PET/CT showed higher PSMA uptake in the ES (SUVPSMA = 24; SUVFDG = 14); similar uptake in popliteal fossae lymph node metastases (SUVPSMA = 9; SUVFDG = 11) and peri-bronchial lymph nodes (SUVPSMA = 7; SUVFDG = 9); lower uptake in lung nodes (SUVPSMA = 3; SUVFDG = 10) and tibia (SUVPSMA = 5; SUVFDG = 15).</div></div><div><h3>Conclusion</h3><div>This report highlights the potential role of PSMA PET/CT in staging of patients with ES, demonstrating lesion detection comparable to that of FDG PET/CT while also offering a Theranostics perspective.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106327"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RELEASE PROFILE OF SILVER FROM A BACTERIAL CELLULOSE MEMBRANE LOADED WITH A SILVER-NIMESULIDE COMPLEX","authors":"Gisele Goulart da Silva ,&nbsp;Ilza Maria de Oliveira Sousa ,&nbsp;Pedro Paulo Corbi ,&nbsp;Leticia Pires de Oliveira ,&nbsp;Wilton Rogério Lustri ,&nbsp;Silmara Cristina Lazarini Frajácomo ,&nbsp;Vinnícius Henrique Cerqueira da Silva ,&nbsp;Marco Aurélio Zezzi Arruda ,&nbsp;Mary Ann Foglio ,&nbsp;Ana Lucia Tasca Gois Ruiz ,&nbsp;Carmen Silvia Passos Lima","doi":"10.1016/j.htct.2026.106326","DOIUrl":"10.1016/j.htct.2026.106326","url":null,"abstract":"<div><h3>Introduction</h3><div>Topical drug delivery systems have been developed with the aim of promoting localized pharmacological action in a prolonged and safe manner. Among the different strategies employed, bacterial cellulose membranes (BCM) stand out due to their ability to act as biocuratives applied directly on to cutaneous lesions. We previously evaluated the effects of a silver(I) complex with nimesulide (AgNMS) incorporated in devices based on BCM, named AgNMS@BCM, on topic skin squamous cell carcinoma (SSCC) treatment in pre-clinical experiments. The AgNMS showed antiproliferative effects in the SCC4, SCC15 and FaDu SCC lines, and the AgNMS@BCM induced reduction of tumor size up to 75%, without toxicity, in a skin carcinogenesis model in mice. Facing these exciting results, we are testing the efficacy and safety of AgNMS@BCM in humans in a phase I/II study. From a regulatory perspective, demonstrating the release of active compounds incorporated into a BCM is a fundamental requirement of health authorities, which makes specific release assays essential for the characterization of the drug release profile. Within this context, the objective of the present study was defined.</div></div><div><h3>Objective</h3><div>This study aimed to evaluate the silver(I) release profile from BCM impregnated with a AgNMS complex.</div></div><div><h3>Materials and Methods</h3><div>Release experiments were performed using Franz diffusion cells, employing BCM loaded with the AgNMS complex at a concentration of 0.5 mg/cm², with phosphate-buffered saline (PBS) 1% used as the receptor medium. Samples from the receptor medium were collected (300 µl) at predefined time intervals (0, 1, 4, 8, 12, and 24 h) and subsequently subjected to silver(I) quantification by inductively coupled plasma mass spectrometry (ICP-MS), with each sample analyzed in triplicate. In addition, the quantification of NMS by UV–Vis spectrophotometry, as well as morphological analyses by scanning electron microscopy, are currently underway.</div></div><div><h3>Results</h3><div>The results were expressed as mean ± standard deviation as a function of time, with the following values observed: T0 (6.82 ± 2.29), T1 – 1h (89.22 ± 23.04), T2 – 4h (248.95 ± 65.84), T3 – 8h (303.29 ± 56.31), T4 – 12h (454.76 ± 79.45), and T5 – 24h (455.78 ± 45.56). Overall, the data demonstrated that the BCM promotes a gradual release of the metallic complex up to 8h, followed by a release plateau at 12h and 24h.</div></div><div><h3>Conclusion</h3><div>Therefore, it can be concluded that BCM represents a promising sustained-release system for the AgNMS complex, meeting regulatory requirements for drug release characterization. This behavior supports the maintenance of the biocurative throughout the treatment period and reinforces the translational potential of AgNMS@BCM for clinical application in patients with SSCC.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106326"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METABOLIC ASSESSMENT OF VISCERAL ADIPOSE TISSUE IN PATIENTS WITH GASTRIC CANCER: AN EXPLORATORY ANALYSIS","authors":"Barbara Cipriano,&nbsp;Renata Erbert Contriciani,&nbsp;Fabíola Furtuoso Zarpelão,&nbsp;Leo Victor Kim,&nbsp;Larissa Ariel Oliveira Carrilho,&nbsp;Sandra Regina Branbilla,&nbsp;Luiz Roberto Lopes,&nbsp;Nelson Adami Andreollo,&nbsp;Maria Emilia Seren Takahashi,&nbsp;Ligia M. Antunes Correa,&nbsp;Jun Takahashi,&nbsp;Elba C.S.C. Etchebehere,&nbsp;Celso Dario Ramos,&nbsp;Maria Carolina Santos Mendes,&nbsp;José Barreto Campello Carvalheira","doi":"10.1016/j.htct.2026.106331","DOIUrl":"10.1016/j.htct.2026.106331","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Visceral adipose tissue (VAT) plays a key role in metabolic and inflammatory regulation and has increasingly been associated with cancer prognosis. Reduced VAT index, along with higher VAT radiodensity and glucose uptake, has been linked to poor outcomes in cancer patients. However, it remains unclear if these alterations result from lipolysis, systemic or tissue inflammation, or adipose tissue beiging/browning. This cross-sectional study aimed to characterize the metabolic profile of VAT in patients with gastric cancer (GC) by integrating imaging-based metabolic assessment with gene expression analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methodology&lt;/h3&gt;&lt;div&gt;This study analyzed a subgroup of 36 patients with histologically confirmed gastric adenocarcinoma treated at the Clinics Hospital of the University of Campinas (HC-UNICAMP). All patients underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). PET-derived metabolic activity of VAT was quantified using the mean standardized uptake value (SUVmean). VAT gene expression was evaluated using the nCounter system (Elements panel), targeting genes associated with adipocyte browning and differentiation, including UCP1, PPARGC1A, PRDM16, CIDEA, DIO2, TMEM26, CD137, TBX1, ZIC1, and LHX8. Clinical, nutritional, and inflammatory data were collected, stored and managed using REDCap. Statistical analyses were performed with Jamovi software (v.2.3.28). The study was approved by the Institutional Review Board (CAAE: 76237023.0.0000.5404). Results: Patients were stratified according to VAT radiodensity into low- and high-radiodensity groups based on the median value (16 and 20 patients, respectively). No significant differences were observed between groups regarding demographic or tumor-related characteristics. The high-radiodensity group exhibited a distinct anthropometric and body composition profile, characterized by lower body mass index, smaller waist circumference, and a lower visceral obesity. This group also presented significantly lower visceral and subcutaneous adipose tissue areas and indices, along with higher attenuation of both VAT (p &lt; 0.001) and SAT (p = 0.003). SUVmean increased in the high-radiodensity group (p &lt; 0.001). Gene expression analysis revealed no major differences between groups with low and high VAT 18F-FDG uptake, except for reduced DIO2 expression in the high-uptake group, suggesting attenuated local thyroid hormone–mediated thermogenic signalling. A trend toward higher PPARGC1A expression was observed in the high-uptake group, possibly reflecting early beige adipocyte differentiation, although canonical thermogenic and beige adipocyte markers remained unchanged. No significant differences were observed in systemic inflammatory markers between groups. Patients with lower VAT radiodensity demonstrated greater insulin sensitivity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;In GC patients, high VAT radiodensity and gluc","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106331"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"INTEGRATION OF NUTRITIONAL, CACHEXIA, AND INFLAMMATORY ASSESSMENT IN GASTRIC CANCER: A CASE REPORT","authors":"Larissa Ariel Oliveira Carrilho,&nbsp;Renata Erbert Contriciani,&nbsp;Leo Victor Kim,&nbsp;Fabíola Furtuoso Zarpelão,&nbsp;Sandra Regina Branbilla,&nbsp;Barbara Cipriano,&nbsp;Ligia M Antunes Correa,&nbsp;Maria Emilia Seren Takahashi,&nbsp;Jun Takahashi,&nbsp;Luiz Roberto Lopes,&nbsp;Nelson Adami Andreollo,&nbsp;Celso Dario Ramos,&nbsp;Elba C.S.C. Etchebehere,&nbsp;Maria Carolina Santos Mendes,&nbsp;José Barreto Campello Carvalheira","doi":"10.1016/j.htct.2026.106342","DOIUrl":"10.1016/j.htct.2026.106342","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Patients with gastric cancer are at high nutritional risk and frequently develop cancer cachexia, a condition associated with systemic inflammation and poorer treatment response and prognosis. Even in the absence of metastatic disease on standard imaging, metabolic and inflammatory alterations may already reflect the interaction between tumor biology and host response.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Case Report&lt;/h3&gt;&lt;div&gt;A 70-year-old female patient was diagnosed on October 11, 2023, with gastric cancer located in the antrum, pathological stage as IV (T3N2M1), ECOG 0. She underwent exclusive surgical treatment with partial gastrectomy on April 16, 2024, at the Hospital de Clínicas of UNICAMP. The PET-CT scan showed FDG uptake in the thickened gastric wall, but without signs of metastases. However, surgery identified metastasis in adipose tissue of the greater curvature/omentum. Preoperative nutritional assessment revealed severe weight loss (18.44% over 6 months), low Body Mass Index (19.9 kg/m²) and a low hand grip strength (10 kg). The patient was classified with severe malnutrition by the Patient-Generated Subjective Global Assessment (PG-SGA). Cachexia was diagnosed according to both Global Leadership Initiative on Malnutrition ‒ GLIM criteria (weight loss, low BMI, low muscle mass, reduced food intake, and systemic inflammation evidenced by a neutrophil-to-lymphocyte ratio [NLR] of 11.5) and Fearon criteria (weight loss, low BMI, low muscularity, and inflammation). Body composition assessment by computed tomography at the level of the third lumbar vertebra demonstrated low muscle mass (Skeletal Muscle Index -SMI of 34.6 cm²/m²). Preoperative plasma analysis using multiplex technology revealed elevated levels of GDF-15 (1825.76 pg/mL), associated with an altered inflammatory and metabolic profile, including IL-6 of 4.51 pg/mL, TNF-a of 2.64 pg/mL, interferon-? of 2.54 pg/mL, and insulin of 265.48. During follow-up, the patient experienced disease progression and died of sepsis, with an overall survival of 9 months. The study was approved by the local Ethics Committee (CAAE:76237023.0.0000.5404).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Discussion&lt;/h3&gt;&lt;div&gt;Although the patient underwent standard imaging procedures during initial staging, no radiological evidence of metastatic disease was identified. However, she already exhibited a preoperative phenotype characterized by systemic inflammation, low skeletal muscle mass, severe malnutrition, and established cachexia, conditions consistently associated with poorer prognosis in gastric cancer. The integration of imaging findings with body composition analysis, inflammatory biomarkers, and comprehensive nutritional assessment tools enabled the early identification of a high-risk clinical and nutritional profile that was not captured by anatomical staging alone. Elevated GDF-15 levels further support its role as a mediator of anorexia, muscle wasting, and adverse clinical outcomes, reinforcing its pot","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106342"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOCIAL INEQUALITIES IN CANCER: EPIDEMIOLOGICAL EVIDENCE AND IMPLICATIONS FOR PUBLIC HEALTH POLICIES","authors":"Andrea B. Von Zuben,&nbsp;Carmino Antonio de Souza","doi":"10.1016/j.htct.2026.106345","DOIUrl":"10.1016/j.htct.2026.106345","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Social inequalities in health represent one of the most persistent challenges in contemporary public health, affecting populations in both low-income and economically developed countries. Socioeconomic factors such as income, education, place of residence, race/ethnicity, and living conditions strongly shape disease risk, access to health services, quality of care, and survival. Many of these differences constitute inequities, as they are avoidable, systematic, and socially unjust. Cancer is a key field in which such inequities are expressed, since major diagnostic and therapeutic advances coexist with marked social differences in incidence, stage at diagnosis, and mortality. Studying inequities in cancer therefore allows the understanding of structural mechanisms underlying health inequalities. In this context, population-based registries and health information systems are strategic tools to identify social gradients, monitor trends, and support targeted public health interventions, as illustrated by the study conducted in Campinas.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;Analyze social inequalities in cancer incidence and mortality and discuss their implications for public health policies using population-based data.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and Methods&lt;/h3&gt;&lt;div&gt;A study was conducted in Campinas, Brazil, using data from the Population-Based Cancer Registry and the Mortality Information System from 2010 to 2019. Cancer cases and deaths were classified by tumor site (ICD-10). Socioeconomic conditions were assessed using an area-based social vulnerability index. Age-standardized incidence and mortality rates were calculated and compared across vulnerability strata to identify social gradients and temporal trends. Analyses were based on anonymized secondary data and followed ethical research standards.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of incident cancer cases and cancer-related deaths recorded between 2010 and 2019 were analyzed. Incidence rates tended to be higher in less vulnerable areas for selected cancer types, whereas mortality rates were consistently higher in more socially vulnerable strata. Marked inequalities were identified for specific cancers. Cancers of the cervix, stomach, oral cavity, and prostate showed substantially higher mortality rates in the most vulnerable areas compared with the least vulnerable ones. In contrast, breast and colorectal cancers presented higher incidence in less vulnerable areas, but with smaller or reversed differences in mortality, indicating differential access to early diagnosis and effective treatment. Temporal analyses revealed that social inequalities in cancer mortality persisted throughout the study period and, for some cancer sites, increased over time.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;These findings reinforce that cancer inequities are not random phenomena, but rather systematic patterns associated with socioeconomic context, access to health se","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106345"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OPTIMIZATION AND STANDARDIZATION OF IN-HOUSE SYNTHESIS METHODOLOGY OF THE 68GA-PSMA RADIOPHARMACEUTICAL FOR APPLICATION IN THE THERANOSTIC MODEL OF NEOPLASMS","authors":"Caroline Torricelli ,&nbsp;Vânia Pereira de Castro Rodrigues ,&nbsp;Natália Tobar Toledo Prudente da Silva ,&nbsp;Sibila Grallert ,&nbsp;Luciana Malavolta ,&nbsp;Elba C.S.C. Etchebehere","doi":"10.1016/j.htct.2026.106329","DOIUrl":"10.1016/j.htct.2026.106329","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Advances in the identification of molecular targets in tumor cells have enabled the development of more precise diagnostic and therapeutic approaches in oncology, through the use of radiopharmaceuticals. In this context, theranostics has gained relevance by integrating diagnosis and therapy within a single molecular platform. Among these agents, 68Ga-PSMA is widely used for prostate cancer imaging and has also demonstrated potential in other PSMA-expressing neoplasms, supporting diagnosis, treatment planning, and therapy response assessment.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;This study aims to optimize and standardize the in-house synthesis of 68Ga-PSMA radiopharmaceutical, ensuring reproducibility, safety, and technical feasibility, with a focus on its application in the theranostic model for non-prostatic neoplasms.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Material and Methods&lt;/h3&gt;&lt;div&gt;This prospective study is being conducted at the Nuclear Medicine Service of the Hospital de Clínicas (NMS/HC) - Unicamp and was approved by the Research Ethics Committee (approval number 6,698,585/2024; CAAE 30476720.9.0000.5404). In an automated synthesis module, 68GaCl3 is eluted from a commercial 68Ge/68Ga generator and used for radiolabeling the PSMA-11 peptide. The reaction is performed in acetate buffer at 85°C for 5 minutes, followed by purification, sterilization, and dilution for clinical use. Quality control procedures are being implemented and optimized. To date, radiochemical purity of 68Ga-PSMA has been assessed by thin-layer chromatography (TLC) using TLC-SG and iTLC-SG as stationary phases, with 0.1M sodium citrate and ammonium acetate/methanol (1:1) as mobile phases, respectively. The pH of the final product has been determined. Current analyses include radiochemical yield and purity and chromatographic peak behavior expressed as retention factors (Rf), while stability studies are planned. In parallel, safety procedures and clinical protocols are being developed in collaboration with radiopharmacy and nuclear medicine specialists. Following optimization and standardization of the in-house synthesis methodology, 68Ga-PSMA will be implemented for clinical imaging in patients selected at NMS/Unicamp, supporting theranostic applications in accordance with ethical standards.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Initial in-house 68Ga-PSMA syntheses were successfully performed, demonstrating consistent radiochemical performance across independent productions (n = 7). Radiochemical purity assessed by TLC showed a mean value of 92.5 ± 3.3% and was further confirmed by direct activity measurement of segmented TLC strips using a dose calibrator, with a mean of 99.2 ± 0.7%. The final radiolabeled product presented an appropriate pH of 5.2 ± 0.3. Chromatographic analysis demonstrated the expected migration profiles. Using ammonium acetate/methanol (1:1) as the mobile phase, 68Ga-PSMA migrated with the solvent front (Rf = 0.9‒1.0), whereas with","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106329"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PROSPECTS FOR THE PRODUCTION OF THERAPEUTIC RADIOISOTOPES BASED ON INSTALLED CAPACITY IN ARGENTINA AND BRAZIL","authors":"Fabio Luiz Navarro Marques ,&nbsp;Emiliano Pozzi ,&nbsp;Ana Clarisa López Bularte ,&nbsp;Oscar Pozzi ,&nbsp;Frederico Antonio Genezini ,&nbsp;Emerson Bernardes ,&nbsp;Isolda Costa","doi":"10.1016/j.htct.2026.106355","DOIUrl":"10.1016/j.htct.2026.106355","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Therapeutic radioisotopes were first used in clinical practice in 1941 to treat thyroid cancer, using a mixture of &lt;sup&gt;131&lt;/sup&gt;I/&lt;sup&gt;133&lt;/sup&gt;I produced in a cyclotron. Nowadays, high-purity &lt;sup&gt;131&lt;/sup&gt;I is still used to treat thyroid disease, but it is produced in nuclear reactors. From the 1980s to the 2010s, new radioisotopes were introduced for cancer treatment, including beta (β) emitter &lt;sup&gt;90&lt;/sup&gt;Y, &lt;sup&gt;153&lt;/sup&gt;Sm, and &lt;sup&gt;166&lt;/sup&gt;Ho. By the end of 2010, &lt;sup&gt;177&lt;/sup&gt;Lu emerged as a promising radioisotope for theranostic applications, and by 2020, &lt;sup&gt;161&lt;/sup&gt;Tb was identified as a promising new radioisotope due to its simultaneous β and Auger-electron emission. Also, the alpha emitters &lt;sup&gt;211&lt;/sup&gt;At, &lt;sup&gt;225&lt;/sup&gt;Ac, &lt;sup&gt;212&lt;/sup&gt;Pb, and &lt;sup&gt;213&lt;/sup&gt;Bi have proven effective in cancer treatment.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Requirements for radioisotopes production&lt;/h3&gt;&lt;div&gt;The production of these radioisotopes depends on specific nuclear reactions requiring either high-energy charged particles or high neutron fluxes. For &lt;sup&gt;225&lt;/sup&gt;Ac, several methods were tested, one of the oldest is &lt;sup&gt;232&lt;/sup&gt;Th(p,x)&lt;sup&gt;225&lt;/sup&gt;Ac, &gt;100 MeV. However, this route is controversial because it co-produces &lt;sup&gt;227&lt;/sup&gt;Ac, a long half-life (21.7 y) alpha emitter, that makes impossible it uses in humans; alternatively &lt;sup&gt;226&lt;/sup&gt;Ra(p,2n)&lt;sup&gt;225&lt;/sup&gt;Ac ≥ 30 MeV; other possibility is &lt;sup&gt;226&lt;/sup&gt;Ra(g,n)&lt;sup&gt;225&lt;/sup&gt;Ra (β)&lt;sup&gt;225&lt;/sup&gt;Ac has been in use to produce &lt;sup&gt;225&lt;/sup&gt;Ac with the higher radionuclide purity, &lt;sup&gt;209&lt;/sup&gt;Bi(α,2n)&lt;sup&gt;211&lt;/sup&gt;At, but with alpha particles not higher than 29-28 MeV to avoid production to &lt;sup&gt;211&lt;/sup&gt;Po, &lt;sup&gt;151&lt;/sup&gt;Eu(&lt;sup&gt;3&lt;/sup&gt;He,5n)&lt;sup&gt;149&lt;/sup&gt;Tb 40-70 MeV. Beyond the production of standard beta-emitting radioisotopes, current research focuses on the &lt;sup&gt;160&lt;/sup&gt;Gd(n,γ)&lt;sup&gt;161&lt;/sup&gt;Gd(β)&lt;sup&gt;161&lt;/sup&gt;Tb (thermal neutron flux, in the range of 10&lt;sup&gt;13&lt;/sup&gt; to 10&lt;sup&gt;14&lt;/sup&gt; n.cm&lt;sup&gt;-2&lt;/sup&gt;.s&lt;sup&gt;-1&lt;/sup&gt;).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Reactor and cyclotron production capability in Argentina and Brazil&lt;/h3&gt;&lt;div&gt;Argentina and Brazil have installed 10 research reactors, but only three of them, RA-3 (10 MW, neutron 1-1.4 × 10&lt;sup&gt;14&lt;/sup&gt;) and RA-10 (30 MW, 1.4-2.5 × 10&lt;sup&gt;14&lt;/sup&gt; (expected to be critical in 2027), by CNEA, in Argentina, and the IEA-R1 (4.5 MW, 1 × 10&lt;sup&gt;14&lt;/sup&gt;) in Brazil have the capacity to produce of therapeutic radioisotopes in commercial scale. From these, Ra-3 is producing &lt;sup&gt;99&lt;/sup&gt;Mo, &lt;sup&gt;51&lt;/sup&gt;Cr, &lt;sup&gt;131&lt;/sup&gt;I and &lt;sup&gt;177&lt;/sup&gt;Lu, and &lt;sup&gt;161&lt;/sup&gt;Tb under R&amp;D production. Currently, the IEA-R1 is not producing radioisotopes, but it is planned to return to the production of &lt;sup&gt;131&lt;/sup&gt;I and start the &lt;sup&gt;177&lt;/sup&gt;Lu production in 2026. Furthermore, Brazil has begun construction of the Brazilian Multipurpose Reactor (RMB), which will operate at 30 MW and is scheduled to begin operations in 2032. There are 26 cyclotrons install","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106355"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147449091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EVALUATION OF NEW RADIOLABELED ANTI-EGFR PEPTIDE MODIFIED BY BIS(SEMICARBAZONE) METAL CHELATOR AS THERANOSTIC STRATEGY IN COLORECTAL AND HEAD AND NECK CANCERS","authors":"Amanda Helena Tejada,&nbsp;Gilberto Carlos Franchi Júnior,&nbsp;Gustavo Jacob Lourenço,&nbsp;Carmen Silvia Passos Lima","doi":"10.1016/j.htct.2026.106316","DOIUrl":"10.1016/j.htct.2026.106316","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Colorectal cancer (CRC) and head and neck squamous cell carcinoma (HNSCC) remain major challenges in oncology due to their high incidence, aggressive behavior, and frequent resistance to targeted therapies. Dysregulation of the epidermal growth factor receptor (EGFR) signaling pathway is a common molecular hallmark of both malignancies and is strongly associated with poor prognosis. Although anti-EGFR therapies are clinically available, their efficacy is limited by intrinsic and acquired resistance mechanisms, including RAS mutations in CRC and activation of alternative signaling pathways in HNSCC. These limitations highlight the need for innovative strategies that combine precise molecular targeting with alternative mechanisms of tumor control. In this context, nuclear medicine theranostics, integrating diagnosis and therapy within a single molecular platform, represents a promising approach.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;This study aims to evaluate, in preclinical models, a novel radiolabeled anti-EGFR peptide (coded for intellectual property protection) conjugated to a bis(semicarbazone) metal chelator as a potential theranostic agent for colorectal and head and neck cancers.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and Methods&lt;/h3&gt;&lt;div&gt;A bis(semicarbazone)-based bifunctional chelator was synthesized and conjugated to a coded anti-EGFR peptide, enabling stable coordination with diagnostic (68Ga) and therapeutic (67Cu/64Cu) radionuclides. The resulting compound will be characterized in terms of radiochemical purity and stability. In vitro studies will be conducted using EGFR-positive CRC and HNSCC cell lines, employing both two-dimensional cultures and three-dimensional spheroid models to evaluate binding specificity, internalization, cytotoxicity, and mechanisms of cell death. Molecular effects on proliferative and apoptotic signaling pathways will be investigated. In vivo experiments will include biodistribution, acute toxicity, and imaging evaluation by micro-PET/SPECT/CT in healthy mice and tumor-bearing xenograft models, as well as assessment of antitumor efficacy in therapeutic settings.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results (Expected)&lt;/h3&gt;&lt;div&gt;It is expected that the radiolabeled peptide–chelator conjugate will demonstrate high radiochemical stability and selective interaction with EGFR-overexpressing tumor cells. In vitro assays are anticipated to show efficient tumor targeting, adequate penetration in three-dimensional tumor models, and induction of tumor cell death through radiation-mediated mechanisms. In vivo studies are expected to reveal favorable pharmacokinetic profiles, enhanced tumor uptake, limited nonspecific accumulation, and acceptable safety margins.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This project is expected to generate robust preclinical evidence supporting the use of a bis(semicarbazone)-modified, radiolabeled anti-EGFR peptide as an innovative theranostic platform for colorectal and head and n","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106316"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IN VITRO EVALUATION OF THE ANTITUMOR ACTIVITY AND CUTANEOUS PERMEABILITY OF A SILVER-BASED METAL DRUG COMBINED WITH A MONOTERPENE FOR SKIN CANCER TREATMENT","authors":"Daniele Affonso,&nbsp;Juliana Carron,&nbsp;Gabriele Pereira Menezes,&nbsp;Henrique Vinícius Cerqueira da Silva,&nbsp;João Ernesto Carvalho,&nbsp;Marco Aurélio Zezzi Arruda,&nbsp;Pedro Paulo Corbi,&nbsp;Ana Lucia Tasca Gois Ruiz,&nbsp;Carmen Silvia Passos Lima","doi":"10.1016/j.htct.2026.106308","DOIUrl":"10.1016/j.htct.2026.106308","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Skin cancer, including squamous cell carcinoma (SCC) and cutaneous melanoma (CM), is highly prevalent and strongly associated with ultraviolet radiation exposure. Limitations of conventional therapies highlight the need for new therapeutic strategies, and metal-based drugs have emerged as promising alternatives due to their anticancer potential. However, their topical application is limited by the skin barrier, and the association with the monoterpene carvone, a well-described skin permeation enhancer, represents a strategy to improve local therapeutic efficacy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To evaluate the in vitro combination index (CI), apoptosis and the cutaneous permeation of a silver complex derived from nucleobases (Ag-1) associated with carvone.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Material and Methods&lt;/h3&gt;&lt;div&gt;The Ag-1 complex was synthesized and quantified at the Institute of Chemistry, University of Campinas, and carvone was obtained commercially. At the School of Medical Sciences, University of Campinas, SCC hypopharynx (FaDu), tongue (SCC-9) and melanoma (SK-MEL-28) cells were treated with Ag-1 (0.8–12 µM), alone or combined with carvone. Cell viability was assessed by the sulforhodamine B assay, and the CI was calculated as the ratio between the 50% growth inhibition (GI50) of the Ag-1 + carvone/GI50 of the Ag-1 alone, using the Chou-Talalay method. The phosphatidylserine externalization analysis was performed using the Annexin V Apoptosis Kit, which includes annexin V and 7-AAD conjugates, followed by flow cytometric analysis using a BD FACSVerse™ system. In vitro permeation studies were conducted using Franz diffusion cells with poly (vinyl alcohol) (PVA, 3% w/v) films applied onto polytetrafluoroethylene (PTFE) membranes. Samples were collected at 0h, 12h, 24h, and 48h, and silver permeation was quantified by inductively coupled plasma mass spectrometry (ICP-MS), monitoring the 107Ag isotope.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Ag-1 in combination with carvone resulted in synergistic effect in the FaDu cell line with GI50 &lt; 2 µM, CI = 0.8, SCC-9 GI50 &lt; 4 µM, CI = 0.3 and SK-MEL-28 with GI50 &lt; 6 µM, CI = 0.6). The combination of Ag-1 with carvone increased early apoptotic cell death (annexin V?/7-AAD?) compared to untreated group in FaDu, SK-MEL-28 and SCC-9 (26.7 ± 12.6 versus 55.5 ± 11.8, 27.9 ± 11.6 versus 59.8 ± 13.6, 12.2 ± 10.8 versus 57.3 ± 11.6, respectively; p &lt; 0.05). Permeated silver concentrations were higher for the carvone-containing (CC) formulation compared to the carvone-free (CF) formulation at T0 (114.04 ± 1.52 µg L&lt;sup&gt;-1&lt;/sup&gt; versus 53.39 ± 3.52 µg L&lt;sup&gt;-1&lt;/sup&gt;, respectively; p &lt; 0.05), T24 (230.76 ± 11.93 µg L&lt;sup&gt;-1&lt;/sup&gt; versus 130.65 ± 43.46 µg L&lt;sup&gt;-1&lt;/sup&gt;, respectively; p &lt; 0.01) and T48 (359.17 ± 46.53 µg L&lt;sup&gt;-1&lt;/sup&gt; versus 164.43 ± 40.55 µg L&lt;sup&gt;-1&lt;/sup&gt;, respectively; p &lt; 0.001) hours.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Ag-1 combined with carv","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106308"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}