Hematology, Transfusion and Cell Therapy最新文献

{"title":"EFFECT OF XPC C.2815A>C VARIANT ON CELL CYCLE–RELATED GENE EXPRESSION IN OROPHARYNGEAL SQUAMOUS CELL CARCINOMA","authors":"Quézia Nascimento Martins Alves,&nbsp;Ericka Francislaine Dias Costa,&nbsp;Gustavo Jacob Lourenço,&nbsp;Carmen Silvia Passos Lima","doi":"10.1016/j.htct.2026.106298","DOIUrl":"10.1016/j.htct.2026.106298","url":null,"abstract":"<div><h3>Introduction</h3><div>Oropharyngeal squamous cell carcinoma (OPSCC) is an aggressive malignancy often diagnosed at advanced stages and associated with regional lymph node metastasis. Inherited single nucleotide variants (SNVs) have been suggested to influence cancer susceptibility and tumor progression by modulating DNA repair and cellular homeostasis. Recently, our group identified an association between the AA genotype of the XPC c.2815A&gt;C SNV and increased risk of OPSCC, as well as advanced nodal stage, but the molecular mechanisms underlying these associations remain unclear.</div></div><div><h3>Objective</h3><div>To evaluate whether distinct XPC c.2815A&gt;C SNV genotypes modulate the expression of XPC and other cell cycle-related genes in the OPSCC cell line (FaDu).</div></div><div><h3>Materials and Methods</h3><div>FaDu cells were cultivated in complete Roswell Park Memorial Institute (RPMI) 1640 medium supplemented with 5% fetal bovine serum and 1% penicillin–streptomycin. FaDu cells were transfected with pcDNA3.1 expression vectors carrying either the wild-type (allele A) or variant (allele C) XPC c.2815A&gt;C constructs, with the empty pcDNA3.1 vector used as a control. XPC expression was assessed at 24h, 48h, 72h, and 96h to confirm transfection efficiency. The 48h time point was selected for downstream analysis of the basal expression of cell cycle-related genes (CDKN2B, CCND1, CCND3, and STAT3), with ACTB used as the endogenous control. Gene expression was measured by real-time PCR, relative expression was calculated using the 2???Ct method, and statistical significance was assessed with the Student’s <em>t</em>-test (p = 0.05).</div></div><div><h3>Results</h3><div>Transfection with both wild-type and variant XPC c.2815A&gt;C constructs increased XPC expression compared with the empty pcDNA 3.1 vector (control; 1.00 arbitrary unit [AU]) at 24h (8.18 and 5.59 AUs, respectively). Expression decreased over time but remained higher than control at 48h (4.88 and 3.62 AUs), 72h (3.01 and 2.40 AUs), and 96h (1.85 and 2.08 AUs). At 48h under basal conditions, cells expressing the wild-type XPC c.2815A allele exhibited higher CDKN2B mRNA levels than cells expressing the variant c.2815C allele (1.66 vs. 1.00 AUs; p = 0.05). No consistent differences were observed for the other cell cycle–related genes assessed.</div></div><div><h3>Conclusion</h3><div>The present preliminary findings indicate that the XPC c.2815A&gt;C SNV alters its basal expression as well the basal expression of CDKN2B cycle–related gene in OPSCC. Cells expressing wild-type XPC c.2815A&gt;C A allele showed altered CDKN2B expression compared with the variant allele, indicating a potential genotype-dependent effect. Our data may provide a plausible explanation for the associations between XPC c.2815A&gt;C SNV and risk of OPSCC and tumor behavior seen in a previous study conducted by our research group.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106298"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452180","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":"QUALITATIVE AND SEMIQUANTITATIVE ASSESSMENT OF INTRALESIONAL UPTAKE MISMATCH BETWEEN FDG AND PSMA PET/CT IN NEOPLASTIC LESIONS","authors":"Adrhyann Jullyanne de Sousa Portilho,&nbsp;Maria Emilia Seren Takahashi,&nbsp;Simone Kuba,&nbsp;Natália Tobar Toledo Prudente da Silva,&nbsp;Murilo Oliveira Cerci,&nbsp;Carmino Antonio de Souza,&nbsp;Celso Dario Ramos","doi":"10.1016/j.htct.2026.106332","DOIUrl":"10.1016/j.htct.2026.106332","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Positron emission tomography/computed tomography (PET/CT) with [18F]FDG is widely used to assess tumor glycolytic metabolism, whereas [18F]PSMA-1007 or [68Ga]PSMA-11 PET/CT is associated with tumor neovascularization. Notably, some lesions exhibit an intralesional “mismatch”, in which different regions within the same lesion demonstrate higher uptake of either [18F]FDG or PSMA-targeted radiotracers, suggesting distinct metabolic phenotypes and possible intratumoral heterogeneity. However, few studies have explored the combined use of these tracers. To evaluate the intralesional distribution of [18F]FDG and ([18F]PSMA-1007 or [68Ga]PSMA-11) in PET/CT images across malignancies using qualitative and semiquantitative parameters, aiming to investigate patterns of intralesional uptake mismatch. This retrospective cross-sectional study included patients with differentiated thyroid cancer, lung cancer, hepatocellular carcinoma, lymphoma, and multiple myeloma undergoing staging or restaging. All patients underwent both [18F]FDG and [18F]PSMA-1007 or [68Ga]PSMA-11 PET/CT within an interval. The largest soft-tissue lesion (or bone lesion with a soft-tissue component) with a maximum diameter = 4 cm was selected for analysis. PET/CT images were evaluated qualitatively and semiquantitatively. Qualitative assessment of intralesional tracer uptake differences was performed using a classification system. Intralesional PSMA distribution relative to FDG uptake was classified as peripheral (1), central (2), diffuse (3), or segmental (4). Semiquantitative parameters, including SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion metabolism (TLM; MTV × SUVmean), were measured with a PET/CT viewer plug-in for ImageJ (FIJI). MTV was defined using a fixed SUV threshold (= 2.5) for [18F]FDG and uptake above the mediastinal blood pool for PSMA tracers.Eleven patients were included: 3/11 (27%) thyroid cancer, 3/11 (27%) lung cancer, 2/11 (18%) hepatocellular carcinoma, 2/11 (18%) multiple myeloma, and 1/11 (9%) lymphoma (3 males, 8 females; mean age 63.4 ± 13.8 years). Visual analysis demonstrated predominantly peripheral PSMA uptake in 5/11 patients (46%), including all thyroid cancer cases. Segmental PSMA uptake was observed in 3/11 (27%), central uptake in 2/11 (18%), and diffuse uptake in 1/11 (9%). Median (range) SUVmax, SUVmean, MTV, and TLM for PSMA and FDG were respectively: 21.5 (4.9–73) vs 14.8 (4.1–36.6) [p = 0.4389]; 6.22 (2.93–12.5) vs 7 (3–17.6); [p = 0.9314]; 81.7 (3.3–228.9) vs. 77.2 (14.9–313.5) [p = 0.6665]; and 519.5 (9.7–1345.3) vs 716.2 (46.8–4229.2) [p = 0.5457].Intralesional uptake mismatch between FDG and PSMA is highly prevalent across neoplastic lesions from different malignancies. However, semiquantitative parameters did not differ significantly at the population level, possibly due to the limited sample size or because this phenomenon is predominantly spatial and not fully captured by global metrics. The frequent peripheral ","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106332"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452182","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":"ASSOCIATION OF CACHEXIA AND BODY COMPOSITION WITH CIRCULATING GROWTH DIFFERENTIATION FACTOR-15 (GDF-15) SERUM LEVELS IN PATIENTS WITH GASTRIC AND COLORECTAL CANCER","authors":"Fabíola Furtuoso Zarpelão,&nbsp;Renata Erbert Contriciani,&nbsp;Larissa Ariel Oliveira,&nbsp;Sandra Regina Branbilla,&nbsp;Leo Victor Kim,&nbsp;Luiz Roberto Lopes,&nbsp;Nelson Adami Andreollo,&nbsp;Maria Emilia Seren Takahashi,&nbsp;Jun Takahashi,&nbsp;Ligia M. Antunes Correa,&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.2026.106330","DOIUrl":"10.1016/j.htct.2026.106330","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Cancer-associated cachexia remains a primary focus of clinical research, with increasing attention on molecular targets such as Growth Differentiation Factor 15 (GDF-15). A recent Phase 2 trial showed that GDF-15 inhibition via ponsegromab improved body weight and physical activity, reinforcing its role as a key driver. While other targets are in development, evidence linking GDF-15 to muscle mass remains inconclusive, and gastric and colorectal cancers are underrepresented in these clinical studies. This landscape underscores the need to investigate the clinical implications of elevated GDF-15 levels across specific oncological populations.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To investigate associations between body composition, radiodensity, and adipose tissue glucose uptake (via PET/CT) with plasma GDF-15 levels in gastric and colorectal cancer patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This prospective study included patients with gastric/gastroesophageal junction (GEJ) adenocarcinoma (n=67; 42 analyzed for GDF-15) and colorectal cancer (n=46; 38 analyzed for GDF-15). Data were managed via REDCap. Preoperative serum was analyzed for GDF-15 using Luminex®. Body composition was assessed by CT; cachexia followed GLIM (gastric) or Fearon (colorectal) criteria. Statistical analysis in Jamovi 2.3 included Shapiro-Wilk, × 2, Student’s t/Mann-Whitney U, and Spearman’s rank correlation (p&lt;0.05).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In the Gastric/GEJ cohort the median age was 63; 56.7% were male. Mean BMI was 24.5 (±5.05) kg/m²; however, cachexia (35.9%), sarcopenia (40.9%), and myosteatosis (39.4%) were prevalent. Cachectic patients had significantly higher GDF-15 (1028 ± 663 vs. 655 ± 293 pg/mL; p = 0.034). GDF-15 correlated with sarcopenia (rho=0.270, p=0.009), myosteatosis (rho=0.293, p=0.030), and negatively with skeletal muscle attenuation (rho=-0.451, p=0.003). No significant association was found with PET/CT glucose uptake (mean SUV) in visceral adipose tissue (VAT) (p=0.441), subcutaneous adipose tissue (SAT) (p=0.911), or muscle (p=0.072). In the Colorectal cohort the mean age was 62.5; 54.3% male. Mean BMI was 28.6 (± 5.1) kg/m²; cachexia (67.4%), myosteatosis (78.9%), and low muscularity (39.5%) were identified. GDF-15 levels did not differ by cachexia status (p=0.554) but were significantly higher in patients with weight loss (795 ± 400 vs. 404 ± 281pg/mL; p = 0.012). VAT area was significantly larger in patients with GDF-15 &gt;1000 pg/mL (230 ± 35 vs. 136 ± 72, p = 0.017). No association was found with PET/CT uptake in VAT (p=0.774) or SAT (p=0.518).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;GDF-15 was associated with cachexia and musculoskeletal impairment in gastric cancer, and with weight loss and visceral adiposity in colorectal cancer. The lack of correlation with PET/CT glucose uptake suggests GDF-15 influences tissue wasting independent of glucose metabolic alterations in these settings. The","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106330"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452286","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":"STRUCTURALLY MODIFIED IKAV PEPTIDES AS BIOLOGICALLY ACTIVE LIGANDS IN TRIPLE-NEGATIVE BREAST CANCER","authors":"André Vinicius Zolesi,&nbsp;Danielle Vieira Sobral,&nbsp;Flávio Lopes Alves,&nbsp;Fernanda Ferreira Mendonça,&nbsp;Luciana Malavolta,&nbsp;Leonardo Lima Fuscaldi","doi":"10.1016/j.htct.2026.106278","DOIUrl":"10.1016/j.htct.2026.106278","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction/Justification&lt;/h3&gt;&lt;div&gt;Breast cancer remains a public health challenge, and triple-negative breast cancer (TNBC) is its most aggressive subtype, characterized by high recurrence, early metastasis, and lack of hormone receptors and HER2 expression. TNBC cells overexpress molecular targets, such as integrins, which play a key role in adhesion, migration, and signaling. Laminin-111, enriched in the breast tumor microenvironment, generates bioactive fragments, such as IKVAV, that selectively interact with integrins a3ß1 and a6ß1 associated with aggressive tumor behavior. These fragments participate in tumor cell growth regulation, supporting IKVAV as a biologically active ligand for integrin-targeting strategies. Structural modification by histidine (H) insertion enables radiolabeling with Tc, reinforcing its potential application in molecular imaging.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;To synthesize structurally modified IKVAV peptides incorporating a H residue and to evaluate their in vitro interaction as biologically active ligands in TNBC (MDA-MB-231) cells.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and Methods&lt;/h3&gt;&lt;div&gt;IKVAV-NH2, HIKVAV-NH2, and N-acetyl-HIKVAV-NH2 were synthesized by solid-phase peptide synthesis using the Fmoc/tBu strategy and MBHAR resin. Purification and characterization were performed by RP-HPLC and mass spectrometry. For growth curve analysis, MDA-MB-231 cells were seeded in 6-well plates (5 × 104 cells/well) and treated with the respective peptides (IKVAV-NH2: 151.6 µM; HIKVAV-NH2: 90.3 µM; N-acetyl-HIKVAV-NH2: 113.2 µM). Viable cells were counted on days 1, 3, 5, and 7, comparing with non-treated control (CT). Data are presented as mean ± SD and the statistical analyses were performed applying Student’s t-test (significance set at p &lt; 0.05).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;IKVAV-NH2 presented a single, well-defined chromatographic peak and a compatible molar mass (528 g/mol), requiring no further purification. In contrast, HIKVAV-NH2 and N-acetyl-HIKVAV-NH2 initially showed two chromatographic peaks, with the minor peak corresponding to IKVAV-NH2, indicating incomplete H coupling. Co-injection and mass spectrometry confirmed this finding, necessitating additional purification. After purification, both peptides were obtained in pure form, with compatible molar masses (665 g/mol for HIKVAV-NH2 and 707 g/mol for N-acetyl-HIKVAV-NH2). Biological evaluation demonstrated that IKVAV-NH2 and HIKVAV-NH2 did not significantly affect MDA-MB-231 cell proliferation compared to CT: IKVAV-NH2 = (2.2 ± 0.7) × 105 versus CT = (2.0 ± 0.9) × 105 [day 7; p = 0.6322; n = 6]; HIKVAV-NH2 = (3.5 ± 0.4) × 105 versus CT = (3.1 ± 0.2) × 105 [day 7; p = 0.1444; n = 6]. In contrast, N-acetyl-HIKVAV-NH2 induced a significant increase in cell proliferation: N-acetyl-HIKVAV-NH2 = (7.6 ± 1.3) × 105 versus CT = (5.3 ± 0.9) × 105 [day 7; p = 0.0020; n = 5], indicating a distinct biological response following N-terminal acetylation. ","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106278"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452296","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":"LIQUID BIOPSY FOR NON-INVASIVE ASSESSMENT OF MGMT GENE METHYLATION IN GLIOBLASTOMA: A PILOT STUDY","authors":"Daniela Lima ,&nbsp;Andre Luiz Mencalha ,&nbsp;Priscyanne Barreto Siqueira ,&nbsp;Carmen Silvia Passos Lima ,&nbsp;Mary Ann Foglio","doi":"10.1016/j.htct.2026.106322","DOIUrl":"10.1016/j.htct.2026.106322","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Glioblastoma (GB) is the most common malignant brain tumor in adults, characterized by rapid progression and poor survival despite standard therapies, including surgery, radiotherapy, and temozolomide chemotherapy (CT). Promoter methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene is an important prognostic biomarker in GB patients, associated with increased sensitivity to CT. Conventional assessment of the promoter gene methylation relies on tumor biopsy. Tissue-based analyses indicate heterogeneous MGMT methylation in tumor, with the majority of tumors being unmethylated (49–59%), and smaller proportions partially methylated (5–20%) or fully methylated (3–30%). Nonetheless this technique is an invasive procedure that limits longitudinal monitoring. In this context, liquid biopsy has emerged as a non-invasive alternative, enabling the detection of genetic and epigenetic alterations in circulating DNA. This approach is particularly valuable when tumor tissue is insufficient, inaccessible, or unavailable, such as in patients who cannot undergo surgery. Although sensitivity and accuracy remain lower than tissue-based analysis, liquid biopsy represents a complementary or alternative method for MGMT methylation assessment and allows dynamic monitoring of MGMT status.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To evaluate the feasibility of liquid biopsy as a translational tool for the detection of MGMT promoter methylation in patients with GBM, exploring the potential of liquid biopsy as a non-invasive alternative to tissue-based analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and Methods&lt;/h3&gt;&lt;div&gt;In this prospective phase II pilot study, peripheral blood samples from 10 newly diagnosed GBM patients were analyzed. Serum was obtained by centrifugation at 2,500 rpm for 10 minutes and stored at -20°C until analysis. Serum DNA was extracted from 800 µL of serum. MGMT gene methylation was assessed by quantitative Methylation-Specific PCR (qMSP) with primers specific for methylated and unmethylated sequences following bisulfite conversion of DNA. qMSP reactions were performed in triplicate with an intercalating DNA dye. A sample was considered methylated if amplification occurred with the methylated MGMT primers, and unmethylated if amplification occurred only with the unmethylated MGMT primers.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Ten patients with a median age of 55.3 years (range: 34–76 years); five males and five females, newly diagnosed GB were evaluated. Of these, nine patients amplified only with primers specific for unmethylated MGMT and were classified as unmethylated, whereas one patient showed amplification with primers for methylated MGMT, indicating partial methylation. In our cohort of 10 patients with GB, although unmethylated MGMT was more frequente, the proportions of unmethylated and methylated samples identified by liquid biopsy were lower than those reported in primary tumors in literature.&lt;/div&gt;&lt;/div","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106322"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452338","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":"SYNTHESIS, CHARACTERIZATION AND ANTIPROLIFERATIVE ACTIVITIES OVER MELANOMA (SK-MEL-28) CELLS OF A NOVEL CO(II) COMPLEX WITH A NUCLEOBASE ANALOG","authors":"Lucas Zanoni Davoli,&nbsp;Pedro Paulo Corbi,&nbsp;Leticia Pires de Oliveira,&nbsp;Carmen Silvia Passos Lima,&nbsp;Gilberto Carlos Franchi Júnior,&nbsp;Gabriele Pereira Menezes","doi":"10.1016/j.htct.2026.106279","DOIUrl":"10.1016/j.htct.2026.106279","url":null,"abstract":"<div><h3>Introduction/Justification</h3><div>The increase in cancer incidence together with acquired resistance to conventional treatments, reinforces the urgent need for new therapeutic approaches. Skin cancer is the most common malignant neoplasm globally, and nucleic acid analogues like 5-fluorouracil (5-FU) have been used clinically to treat patients affected by this disease. At the same time, coordination chemistry has been consolidating itself as a promising strategy in the development of new antitumor agents. Among the metals of interest, cobalt(II) remains as a particularly attractive candidate, still largely unexplored, but with high therapeutic potential.</div></div><div><h3>Objectives</h3><div>The present work is dedicated to the synthesis and characterization of a novel cobalt(II) complex containing a nucleobase derivative, besides the evaluation of the in vitro antiproliferative activity of the compound over melanoma (SK-MEL-28) cells.</div></div><div><h3>Materials and methods</h3><div>The Co(II) complex was synthesised by deprotonation of the nucleobase analog (6-trifluoromethyluracil, Merck, 97% purity) in alkaline aqueous medium; In another flask, Co(II) bipyridine was prepared and then added to the nucleobase aqueous solution. The synthesis was stirred for 2h. Red crystals were obtained and collected. Elemental analyses (CHN) were performed using the CHNS/O Perkin Elmer 2400 analyzer. Antiproliferative activity of the complex was evaluated against melanoma (SK-MEL-28) and immortalized keratinocyte (HaCaT) cell lines using a colorimetric assay. Cells were treated with the complex. Cisplatin and the free nucleobase were used as positive controls. Cell growth inhibition was determined by absorbance at 540nm and IC50 values were calculated by sigmoidal regression.</div></div><div><h3>Results</h3><div>Elemental analysis confirmed the composition of the complex as C20H12CoF6N6O4. The cobalt(II) complex showed moderate antiproliferative activity over SK-MEL-28 cells, with IC50 ranging from 20 µM to 200 µM, while cisplatin showed IC50 value of 13.5 µM. Free nucleobase did not show antiproliferative effect even at the highest concentration tested.</div></div><div><h3>Conclusion</h3><div>A new cobalt(II) complex with the nucleic acid analogue 6-trifluoromethyluracil with composition C20H12CoF6N6O4 was obtained. The cobalt(II) complex has presented modest antiproliferative activity against SK-MEL-28 cells, while the free ligand did not show activity even at the highest concentration. Further analyses are envisaged to determine the structural formula of the complex besides the evaluation of its antiproliferative activities over other skin cancer cells.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106279"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452041","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":"LIPOSOMAL NANOFORMULATION OF A COPPER-BASED COMPLEX ASSOCIATED WITH PARPI MODULATES ANGIOGENIC PROCESSES IN ENDOTHELIAL CELLS","authors":"Gislaine Gonçalves Rocha ,&nbsp;Fernanda Cardoso da Silva ,&nbsp;Paula Marynella Alves Pereira Lima ,&nbsp;Samuel Cota Teixeira ,&nbsp;Helen Soares Valença Ferreira ,&nbsp;Raoni Pais Siqueira ,&nbsp;Lígia Nunes de Morais Ribeiro ,&nbsp;Wendell Guerra ,&nbsp;Cristina Ribas Furstenau ,&nbsp;Thaise Araújo","doi":"10.1016/j.htct.2026.106317","DOIUrl":"10.1016/j.htct.2026.106317","url":null,"abstract":"<div><div>Angiogenesis is a highly regulated process and essential for the progression of solid tumors, as it ensures the continuous supply of oxygen and nutrients to metabolically dysregulated cells. This process involves degradation of the basement membrane, activation, proliferation, and migration of endothelial cells and is controlled by a balance between pro- and antiangiogenic factors, which is frequently disrupted in cancer. In this context, the tumor microenvironment plays a decisive role, as it integrates tumor, inflammatory, stromal, and endothelial cells that cooperate to induce neovascularization. Copper-based metal complexes have gained prominence due to their antitumor and antiangiogenic potential, acting through the induction of DNA damage, modulation of cell migration, and interference with molecular pathways associated with angiogenesis. The copper complex CBP-01N, combined with a PARP inhibitor (PARPi), has previously demonstrated synergistic antitumor effects, enhanced by its incorporation into a nanocolloidal liposomal system (LUV/CBP-01N-PARPi). Liposomal systems stand out as drug delivery carriers due to their biocompatibility, lipophilic nature, and compound stability, thereby optimizing biological efficacy. However, the effects of this nanoformulation on angiogenesis have not yet been described. Thus, the aim of this study was to characterize the antiangiogenic effects of the nanocolloidal system LUV/CBP-01N-PARPi by evaluating its influence on key processes, such as endothelial cell migration and neovascularization, using in vitro and ex vivo models. ECV 304 endothelial cells were used to assess cell viability by resazurin reduction and to determine the IC50. Functional assays of horizontal migration (wound healing) were performed to evaluate cell motility, while in vitro angiogenesis was investigated using the Matrigel tube formation assay. Neovascularization was also analyzed in an ex vivo murine aortic ring model. Based on the resazurin reduction assay, it was possible to determine subtoxic concentrations that did not promote significant changes in cell viability, which were then used in subsequent assays. At subtoxic concentrations, LUV/CBP-01N-PARPi significantly inhibited horizontal migration of endothelial cells and reduced in vitro tubular structure formation by approximately 40%. In the ex vivo murine aortic ring model, treatment with the nanoformulation significantly inhibited neovascularization, reducing the area occupied by vascular sprouts by approximately 80%. These findings consistently demonstrate the antiangiogenic activity of the nanoformulation, indicating that LUV/CBP-01N-PARPi presents promising antiangiogenic potential that warrants further investigation as a therapeutic strategy for tumor treatment, particularly for aggressive tumors in which angiogenesis is significantly activated.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106317"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452047","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":"EX VIVO DRUG SCREENING AS A CRITERION FOR PATIENT SELECTION IN CLINICAL TRIALS","authors":"Samara de Sousa Mariano ,&nbsp;Leandro de Paula Henrique Assis ,&nbsp;Juliana Ronchi Correa ,&nbsp;Maria Luiza Silva Pires ,&nbsp;Aryannny Paula Sousa Ferreira ,&nbsp;Manuella Munuera Hoff Rosati ,&nbsp;Nathalia Moreno Cury ,&nbsp;Adrielli Caroline Soares ,&nbsp;João Meidanis ,&nbsp;Amilcar C. de Azevedo ,&nbsp;Jose Andres Yunes","doi":"10.1016/j.htct.2026.106314","DOIUrl":"10.1016/j.htct.2026.106314","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Traditional clinical trials rely on the random allocation of patients into control and treatment groups, a model that reduces bias but fails to account for individual biological heterogeneity, which is particularly relevant in pediatric acute lymphoblastic leukemia (ALL). We propose that integrating functional drug screening into clinical trial design can transform this paradigm by enabling biologically informed randomization. In this model, primary leukemic cells from each patient are tested ex vivo against candidate drugs prior to clinical trial enrollment, allowing the identification of individuals who are functionally sensitive to specific therapies. This strategy enables rational patient selection, maximizing therapeutic benefit while minimizing unnecessary exposure to ineffective treatments. To test this hypothesis, we performed ex vivo functional screening using the ELDA platform (Ex Vivo Leukemia Drug Advisor), which consists of primary ALL cells cultured in a 3D collagen matrix with bone marrow stromal co-culture, followed by time-lapse brightfield microscopy imaging every 30 minutes for 72 hours and automated viability analysis based on membrane dynamics. A total of 114 primary pediatric ALL samples were screened with docetaxel, vincristine, clofarabine, and cytarabine. Results showed that only ∼10% of samples were sensitive to docetaxel. These sensitive samples were subsequently validated in vivo using PDX (patient-derived xenograft) mouse models, in which immunocompromised mice were engrafted with leukemic cells and treated with docetaxel, vincristine, or control. Leukemia progression was monitored by peripheral blood flow cytometry (human CD45/mouse CD45). The docetaxel-treated group showed the longest survival, outperforming vincristine, a drug of standard pediatric ALL therapy, demonstrating that docetaxel can be therapeutically superior in a functionally selected subgroup. Similarly, we identified patients who were functionally resistant to cytarabine (standard chemotherapy) but sensitive to clofarabine. In vivo validation in PDX models confirmed improved survival in the clofarabine-treated group compared to the cytarabine-treated group, consistent with ex vivo functional predictions. Previous clinical trials evaluating docetaxel or the substitution of cytarabine with clofarabine in pediatric ALL failed to demonstrate population-level benefit, leading to the rejection of these strategies. Our data suggest that these negative outcomes may reflect the lack of functional patient stratification, whereby true responder subpopulations are diluted within unselected cohorts. We conclude that ex vivo functional drug screening enables the identification of biologically defined responder subgroups, redefining clinical trial randomization as a biologically driven process. This approach has the potential to reshape clinical trial design, optimize drug development, and establish a truly functional precision medicine framework in pedia","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106314"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452111","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":"CHECKPOINT MOLECULES ON TUMOR CELLS: A PARADIGM SHIFT IN CANCER THERAPY","authors":"Vahid Vahedian ,&nbsp;João Agostinho Machado Neto ,&nbsp;Keli Lima ,&nbsp;Parviz Azimnasab-sorkhabi","doi":"10.1016/j.htct.2026.106347","DOIUrl":"10.1016/j.htct.2026.106347","url":null,"abstract":"<div><div>Over the past two decades, immune checkpoint pathways have fundamentally reshaped the oncology therapeutic landscape of oncology. Molecules such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte activation gene 3 (LAG-3), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), T-cell immunoglobulin and mucin domain-3 (TIM-3), and V-domain Ig suppressor of T-cell activation (VISTA) are classically viewed as key regulators of adaptive immunity, particularly controlling the activation, exhaustion, and tolerance of T cells.[1,2] Their clinical targeting through immune checkpoint blockade (ICB) has yielded unprecedented survival benefits in multiple malignancies, positioning checkpoint modulation as a cornerstone of modern immunotherapy. However, recent studies have revealed a paradigm shift in this conceptual framework: tumor cells themselves can express immune checkpoint molecules, including both canonical (e.g., PD-L1, PD-1) and noncanonical forms. This tumor-intrinsic expression challenges the traditional immune-centric view of checkpoint biology. Rather than functioning solely as ligands for immune receptors, these molecules can engage in autocrine and paracrine signaling, shaping the tumor microenvironment (TME) and conferring selective growth and survival advantages to malignant cells. Importantly, tumor-intrinsic checkpoint expression has been documented in a broad spectrum of cancers, including melanoma, pancreatic ductal adenocarcinoma, triple-negative breast cancer, glioblastoma, colorectal cancer, and non-small cell lung cancer. This emerging evidence suggests that immune checkpoint expression by tumor cells is not a mere epiphenomenon but a strategic adaptation that contributes to immune evasion, tumor progression, and therapeutic resistance. It adds a new dimension to our understanding of tumor-immune interactions and has profound implications for current therapeutic strategies targeting checkpoint pathways. These findings suggest that immune checkpoint expression by tumor cells is not merely a passive mimicry of immune regulation but an active driver of tumor fitness, plasticity, and therapeutic resistance.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106347"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452115","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":"RADIOLABELING OF THE DOTA-C6-ANTI-EGFR PEPTIDE WITH GALLIUM-68: A PRELIMINARY STUDY OF SYNTHESIS, COMPLEXATION, AND RADIOCHEMICAL STABILITY","authors":"Aline Morais de Souza ,&nbsp;Leonardo Yumoto Carvalheira ,&nbsp;Caiubi Rodrigues de Paula Santos ,&nbsp;Marycel Rosa Felisa Figols de Barboza ,&nbsp;Leonardo Lima Fuscaldi ,&nbsp;Luciana Malavolta","doi":"10.1016/j.htct.2026.106283","DOIUrl":"10.1016/j.htct.2026.106283","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction/Justification&lt;/h3&gt;&lt;div&gt;Peptides with high affinity for molecular targets overexpressed in tumor tissues have been widely explored for the development of radiopharmaceuticals with theranostic potential. Previous studies from our group demonstrated that the EEEEYFELV peptide fragment exhibits high affinity for the epidermal growth factor receptor (EGFr), with promising cellular internalization and tumor specificity. Structural modification using spacers and chelators is essential to enable stable complexation with metallic radionuclides while preserving receptor interaction, supporting the development of peptide-based radiotracers.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;To evaluate the radiolabeling of the DOTA-C6-anti-EGFr peptide with gallium-68 and to investigate labeling yield, radiochemical purity, and preliminary stability.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and Methods&lt;/h3&gt;&lt;div&gt;The anti-EGFr peptide was synthesized by solid-phase synthesis (SPFS) and modified with the e-aminocaproic acid (C6) spacer. The DOTA chelating agent was conjugated to the peptide using DIPEA/TBTU in DMF/DCM (1:1). Radiolabeling of DOTA-C6-anti-EGFr was performed manually with [68Ga]GaCl3 eluted from a 68Ge–68Ga with 6 mL of 0.1 M HCl (∼12.21 mCi/mL) and purified in a cationic filter with acetone. Approximately 500 µL of eluate was added to 40 µL of peptide solution (1 mg/mL) and 1 mL of 0.2 M sodium acetate buffer (pH 4.0), followed by heating at 95°C for 15 minutes. The radiolabeled product was purified using a Sep-Pak C18 cartridge with 50% ethanol. Radiochemical purity of the final product was determined using ascending thin-layer chromatography (iTLC) with 0.1 M ammonium acetate in methanol (1:1) as the mobile phase.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The DOTA-C6-anti-EGFr peptide was successfully synthesized with a yield of 18.3%. After purification step, preliminary radiolabeling with 68Ga resulted in a radiochemical yield of approximately 78%. iTLC analysis showed a retention factor (Rf) of 0.9–1.0 for the radiolabeled peptide, while free [68Ga]GaCl3 presented an Rf of 0.0–0.1, indicating effective separation between the product and radiochemical impurities. A preliminary stability study demonstrated maintenance of radiochemical purity over time, with values of 93.84 ± 0.00% at time zero, 92.84 ± 7.16% after 30 minutes, and 87.62 ± 3.97% after 90 minutes. These results suggest efficient formation and satisfactory short-term stability of the DOTA–68Ga complex under the evaluated conditions.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Preliminary data indicate that the DOTA-C6-anti-EGFr conjugate exhibits favorable behavior for radiolabeling with gallium-68, reinforcing the potential of this conjugation strategy for applications in molecular radiopharmacy. Further studies optimizing labeling parameters, purification, and stability, as well as cell binding and internalization assays in glioblastoma models, are planned to confirm and further develo","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 ","pages":"Article 106283"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147452118","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}