Ericka Francislaine Dias Costa , Ana Maria Castro Ferreira , Marilda Mazzali , Gustavo Jacob Lourenço , Carmen Silvia Passos Lima
{"title":"ROLE OF GENETIC VARIABILITY IN METABOLIC PATHWAYS ON CISPLATIN-INDUCED KIDNEY INJURY IN HEAD AND NECK CANCER PATIENTS","authors":"Ericka Francislaine Dias Costa , Ana Maria Castro Ferreira , Marilda Mazzali , Gustavo Jacob Lourenço , Carmen Silvia Passos Lima","doi":"10.1016/j.htct.2025.103767","DOIUrl":"10.1016/j.htct.2025.103767","url":null,"abstract":"<div><h3>Introduction/Justification</h3><div>Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy responsible for approximately 5.0% of global cancer deaths. The standard treatment for locally advanced HNSCC involves cisplatin (CDDP)-based chemotherapy and radiotherapy, which can lead to significant adverse effects, particularly nephrotoxicity. It is already well known that the efficacy of CDDP as well as its side effects vary in distinct patients with HNSCC, and single nucleotide variants (SNVs) in genes that act in CDDP metabolism constitute a plausible explanation for this finding.</div></div><div><h3>Objectives</h3><div>To investigate the roles of SNVs GSTM1, GSTT1, GSTP1 c.313A>G, XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C, ERCC1 c.354C>T, MLH1 c.93G>A, MSH2 c.211+9C>G, MSH3 c.3133A>G, EXO1 c.1765G>A, TP53 c.215G>C, CASP3 c.-1191A>G and c.-182-247G>T, FAS c.-1378G>A and c.-671A>G, and FASL c.-844C>T SNVs on kidney function outcomes in HNSCC patients undergoing CDDP treatment.</div></div><div><h3>Materials and Methods</h3><div>A total of 109 patients with locally advanced HNSCC treated with CDDP were included in the study. Genotypes were determined using polymerase chain reaction (PCR). Renal function was assessed by calculating estimating glomerular filtration rate (eGFR) using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, before treatment initiation and 30 days post-treatment. The percentage variation in kidney function was calculated by determining the difference between baseline (pre-chemotherapy) and follow-up (post-chemotherapy) values for eGFR divided by the pre-chemotherapy value and represented as ΔeGFR.</div></div><div><h3>Results</h3><div>Patients with the GSTT1 present and ERCC1 c.354CT or TT isolated genotypes presented a decline in kidney function of 4.94% and 8.94%, respectively. A decline of 17.67% in renal function post-CDDP treatment was observed in patients with the GSTT1 present combined with TP53 c.215CC genotype. Patients with the GSTP1 c.313AG or GG and ERCC1 c.354CT or TTC>T (17.57%), MLH1 c.93GA or A (12.49%), or MSH3 c.3133AG or GG (12.19%) combined genotypes showed a reduction in renal function after CDDP treatment. Renal function declines of 18.85% and 13.38% were observed in patients with ERCC1 c.354CT or TT and MLH1 c.93GA or AA or MSH3 c.3133AG or GG combined genotypes, respectively.</div></div><div><h3>Conclusion</h3><div>Our data indicates, for the first time, preliminary evidence that combined inherited abnormalities, SNVs that act in CDDP metabolism, act as independent factors for nephrotoxicity in HNSCC patients and can be used to select patients for personalized treatments that promote renal protection and reduced nephrotoxicity.</div></div><div><h3>Acknowledgements</h3><div>The study was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (grant number 88887","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103767"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829748","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}
Marcelo Moreira da Silva , Carla Lima Santos Viviani , Andre Meluzzi dos Reis , Renato Ramos Barra , Mario Olimpio De Menezes
{"title":"PAPEL DO PET/CT COM 18F- FDG NA AVALIAÇÃO DO COLANGIOCARCINOMA: UM ESTUDO RETROSPECTIVO","authors":"Marcelo Moreira da Silva , Carla Lima Santos Viviani , Andre Meluzzi dos Reis , Renato Ramos Barra , Mario Olimpio De Menezes","doi":"10.1016/j.htct.2025.103805","DOIUrl":"10.1016/j.htct.2025.103805","url":null,"abstract":"<div><h3>Introdução/Justificativa</h3><div>O colangiocarcinoma é uma neoplasia maligna do trato biliar com prognóstico geralmente desfavorável. O diagnóstico precoce e o estadiamento preciso são cruciais para o manejo adequado desses pacientes. A tomografia por emissão de pósitrons/tomografia computadorizada (PET/CT) com 18F-fluordesoxiglicose (FDG) tem se mostrado uma ferramenta promissora na avaliação dessa doença, porém seu papel ainda não está completamente estabelecido.</div></div><div><h3>Objetivos</h3><div>Este estudo visa avaliar o impacto do PET/CT com 18F- FDG no estadiamento do colangiocarcinoma, com foco na detecção de envolvimento linfonodal regional e doença metastática à distância.</div></div><div><h3>Materiais e Métodos</h3><div>Realizamos um estudo retrospectivo utilizando um programa de busca de expressões no laudo RIS, com as palavras-chave \"CID 10 C22\" e \"colangiocarcinoma\", no período de 01/01/2019 a 01/01/2023. Inicialmente, 176 exames foram identificados, resultando em 71 exames após remoção de duplicidades. Excluímos ainda 5 exames que utilizaram outros traçadores, além de 2 pacientes por apresentarem colangiocarcinoma como tumor sincrônico durante avaliação de outro câncer primário, totalizando 64 exames elegíveis. Os exames foram classificados de acordo com suas indicações: ● Estadiamento: 27 exames ● Reavaliação: 31 exames ● Diagnóstico diferencial de lesão hepática: 4 exames ● Outros tumores hepáticos: 2 exames Focamos nossa análise nos 27 exames realizados para estadiamento, avaliando o impacto do PET/CT na detecção de envolvimento linfonodal e metastático.</div></div><div><h3>Resultados</h3><div>Avaliação Linfonodal Regional: ● Exames positivos: 11 pacientes (40,7%) ● Exames negativos: 16 pacientes (59,3%) Os sítios de linfonodos regionais que apareceram nos estudos foram: ducto hilar, cístico, ducto biliar comum, artéria hepática, pancreaticoduodenal posterior e linfonodos da veia porta. Avaliação Metastática: ● Exames positivos: 14 pacientes (51,9%) ● Exames negativos: 13 pacientes (48,1%) Distribuição dos Sítios Metastáticos: 1. Pulmão: 5 pacientes (35,7%) 2. Osso: 5 pacientes (35,7%) 3. Linfonodos abdominais: 8 pacientes (57,1%) 4. Carcinomatose peritoneal: 2 pacientes (14,3%) 5. Linfonodos torácicos: 1 paciente (7,1%) 6. Adrenal: 1 paciente (7,1%).</div></div><div><h3>Conclusão</h3><div>O PET/CT com 18F-FDG demonstrou ser uma ferramenta valiosa no estadiamento do colangiocarcinoma, detectando envolvimento linfonodal regional em 40,7% dos casos e doença metastática em 51,9% dos pacientes. A técnica foi particularmente útil na identificação de metástases em diversos sítios, com destaque para linfonodos abdominais, pulmão e ossos. Esses achados sugerem que o PET/CT com 18F-FDG pode ter um impacto significativo no manejo clínico desses pacientes, potencialmente alterando a estratégia terapêutica em casos onde a doença metastática não era previamente suspeitada.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103805"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829767","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}
Samara Mendes Matos, Nathali Ricardo Barbosa de Lima, Luciana Carvalheira
{"title":"EFEITO DA ATIVAÇÃO NEUTRÔNICA NO COPOLÍMERO PLA-PEG ASSOCIADO À NANOPARTÍCULAS DE OURO","authors":"Samara Mendes Matos, Nathali Ricardo Barbosa de Lima, Luciana Carvalheira","doi":"10.1016/j.htct.2025.103778","DOIUrl":"10.1016/j.htct.2025.103778","url":null,"abstract":"<div><h3>Introdução/Justificativa</h3><div>Nos últimos anos, vários estudos têm sido dedicados à compreensão dos efeitos da radiação ionizante sobre moléculas orgânicas, especialmente aquelas com potencial para aplicações médicas e farmacológicas. Devido à sua variedade, versatilidade e propriedades, os materiais poliméricos são a classe de materiais mais investigada no desenvolvimento de sistemas para aplicação na medicina. O polietilenoglicol (PEG) é um polímero quimicamente estável, regularmente utilizado em cosméticos e como carga em produtos farmacêuticos, pois o organismo o elimina sem metabolizá-lo. Além disso, as partículas de PEG escapam do reconhecimento e captura por células fagocíticas após a administração in vivo, permanecendo por um período prolongado na circulação sistêmica. Já o ácido polilático (PLA) é um poliéster alifático biocompatível e biodegradável, sintetizado a partir de recursos renováveis, como amido de milho ou cana-de-açúcar. Devido às sua taxa de degradação lenta e baixa toxicidade, o PLA tem sido amplamente utilizado em sistemas de liberação de fármacos. A combinação de PEG e PLA como copolímero (PLA-PEG) oferece um efeito sinérgico ao combinar a hidrofilicidade do PEG com a biodegradabilidade do PLA. O uso deste copolímero na área médica tem ocorrido de diversas formas, sendo de interesse principal estudar sua associação com nanopartículas de ouro (AuNPs) e a aplicação desses nanossistemas tanto para exames de imagem quanto para terapia. A utilização do copolímero PLA-PEG para a funcionalização superficial das AuNPs pode otimizar ainda mais o desempenho deste nanossistema, melhorando a estabilidade e permitindo um encapsulamento e liberação mais eficiente dos fármacos de interesse. A alta energia emitida por fontes radioativas causa a formação de radicais livres que podem se recombinar, levando a um rearranjo das cadeias poliméricas. Esse processo pode resultar em reticulação ou degradação do material irradiado.</div></div><div><h3>Objetivos</h3><div>O objetivo deste estudo é avaliar os efeitos da ativação neutrônica do complexo formado por AuNPs-SH-PEG-PLA, observando se ocorre radiólise desses polímeros ou alguma degradação nesse sistema. Este estudo também nos fornecerá informações sobre a dose mínima necessária para a ativação desse complexo, o que é de extrema importância não apenas para os pacientes, mas também para a proteção radiológica de todos os profissionais envolvidos no processo.</div></div><div><h3>Materiais e Métodos</h3><div>A obtenção do nanossistema AuNPs-SH-PEG-PLA foi baseada na metodologia de Reena et al. (2017). O nanosistema foi irradiado no canal J9 com um fluxo de nêutrons de 10⁸ n.cm⁻²·s⁻¹ no reator Argonauta, com um tempo de irradiação de 2h para cada amostra. Foram obtidas 2 amostras, cada uma contendo uma alíquota de 3 ml do nanosistema. As amostras foram divididas de acordo com a dose aplicada, sendo que a primeira amostra não recebeu nenhum tipo de irradiação e as outras receberam 2,","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103778"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828171","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}
Diego Samuel Rodrigues , Letícia Fernanda Alves , João Frederico da Costa Azevedo Meyer , Moníze Valéria Ramos da Silva , Natália Barreto , Catarina Raposo
{"title":"IN VITRO POPULATION GROWTH OF HUMAN GLIOBLASTOMAS: REAL PATIENTS AND CURVE FITTING","authors":"Diego Samuel Rodrigues , Letícia Fernanda Alves , João Frederico da Costa Azevedo Meyer , Moníze Valéria Ramos da Silva , Natália Barreto , Catarina Raposo","doi":"10.1016/j.htct.2025.103807","DOIUrl":"10.1016/j.htct.2025.103807","url":null,"abstract":"<div><h3>Introduction/Justification</h3><div>For more than a century, a variety of ordinary differential equation growth models have been used to describe and predict the proliferation of human malignancies. Indeed, in the field of mathematical oncology, the growth of cell populations over time is typically represented by sigmoidal functions, such as logistic or Gompertz curves and their generalizations. These models are particularly focused on understanding and predicting the proliferation of cancer cells, including those from human glioblastomas, which can be very aggressive brain tumors with a survival rate of less than two years.</div></div><div><h3>Objectives</h3><div>This research examines in vitro cell cultures of five lines of human glioblastoma using curve fitting and numerical parameter estimation of real datasets to separately describe the growth profile of all these cell populations lineages over time.</div></div><div><h3>Materials and Methods</h3><div>Cell culture experiments were performed in the Advanced Therapeutics Laboratory at FCF-UNICAMP. These included a well-established human glioblastoma cell line (NG97) and four other glioblastoma cell lines derived from clinical patients designated N07, C03, L09 and J01. Twelve repeated time series of experiments were collected for each cell line. Cell counting was performed daily on days 1 to 6. The drda R package was used for curve fitting of the measured data aiming to determine the intrinsic growth rate and other parameters for each of the five cell lines. The 5-parameter generalized logistic curve was used, and all the resulting models were analyzed under statistical criteria such as the Akaike Information Criterion (AIC) and the Bayesian Information Criterion (BIC).</div></div><div><h3>Results</h3><div>Curve fitting analysis revealed significant diversity in the population growth of different cell lines. The drda R package proved to be highly effective in capturing these different behaviors and the unique sigmoidal shapes associated with them. Notably, the population growth of NG97 cells showed the least variability over time, with the narrowest confidence intervals for the fitted curves and their associated parameters. This consistency can be attributed to the fact that NG97 is a well-established cell lineage. In contrast, the new patient-derived cell lines showed a greater degree of uncertainty, particularly when their confidence intervals were extrapolated beyond the last day of measurement. This observation highlights the need for additional time points in in vitro experiments with newly derived human patient cells.</div></div><div><h3>Conclusion</h3><div>According to the numerical and graphical results, to AIC and BIC metrics, and also to the respective levels of provided uncertainty, the fitted models present a reasonable growth description of all the studied lineages of glioblastoma, regardless of cell line being well-established (NG97) or newly originated from human patients","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103807"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829769","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}
Matheus Yung Perin, Vivian Naomi Horita, Daniel Naves Araújo Teixeira, Joyce Gruenwaldt, Eduardo Baldon Pereira, Carlos Takahiro Chone, Gustavo Jacob Lourenço, Ligia Traldi Macedo, Carmen Silvia Passos Lima
{"title":"INDUCTION CHEMOTHERAPY IN ADVANCED HEAD AND NECK SQUAMOUS CELL CARCINOMA: A REAL-WORLD DATA STUDY","authors":"Matheus Yung Perin, Vivian Naomi Horita, Daniel Naves Araújo Teixeira, Joyce Gruenwaldt, Eduardo Baldon Pereira, Carlos Takahiro Chone, Gustavo Jacob Lourenço, Ligia Traldi Macedo, Carmen Silvia Passos Lima","doi":"10.1016/j.htct.2025.103773","DOIUrl":"10.1016/j.htct.2025.103773","url":null,"abstract":"<div><h3>Introduction/Justification</h3><div>Approximately 60% of HNSCC patients are diagnosed at a locally or locoregionally advanced stage. Patients with locally or locoregionally advanced stage and not amenable to surgical resection receive chemoradiotherapy (CTRT) as definitive treatment, or induction chemotherapy (ICT) followed or not by CTR. In the last scenery, docetaxel plus cisplatin (TP) and docetaxel plus cisplatin plus 5-fluorouracil (TPF) followed by CTRT were first described as effective ICTs regimens with acceptable safety profile. Despite the superiority of TPF over TP in response rate, loco-regional control, and survival of patients with advanced HNSCC, unequivocal disadvantages have been attributed to the regimen, as grade 3 or above adverse events, and the need of infusion devices or inpatient beds for continuous 5-fluorouracil infusion, which clearly increases the costs of treatment.</div></div><div><h3>Objectives</h3><div>The current study aimed to analyze patients with locoregionally advanced HNSCC treated with TPF or TP followed by CTRT at the General Hospital of the University of Campinas, with the purpose of developing an ICT protocol applicable to services with limited resources.</div></div><div><h3>Materials and Methods</h3><div>Patients with HNSCC at stage III or IVA-B (T4 and/or N2b, N2c or N3) treated with ICT using TPF or TP followed by CTRT from January 14 th, 2015, to November 24 th, 2021, were included in the study. The choice between TPF and TP as induction chemotherapy (ICT) was based on the clinical judgment of the responsible oncologist, considering patient-specific factors such as performance status, comorbidities, and tolerance to intensive regimens. Additionally, the availability of a hospital bed for the continuous intravenous infusion of 5-fluorouracil was a practical determinant. Toxicity, response rate, and event-free survival (EFS) and overall survival (OS) were evaluated in patients of both groups. Event-free survival (EFS) and overall survival (OS) were assessed using the Kaplan-Meier curves and the log-rank test. The impact of clinicopathological characteristics on patients’ survival was assessed through univariate and multivariate Cox regression.</div></div><div><h3>Results</h3><div>Eighty-seven patients with HNSCC were treated with ICT, being 38 with TPF and 49 with TP. An excess of ECOG 0 or 1 was seen in TPF group and an excess of males in TP group, but no significant differences in age, smoking and alcohol intake, body mass index, tumor location, grade and TNM stage, toxicities grade 3 or above, treatment response, and cycles interval, were seen in patients treated with TPF and TP. The median follow-up time was 22.6 months (range: 1.2 to 93.8). The two-year and five-year EFS rates of patients of the total group were 33.8% and 25.3%, respectively. ICT regimens did not alter response to ICT, and patients’ EFS and OS. Cox multivariate analysis identified stable or progressive disease (HR: 5.56) a","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103773"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828166","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}
Pedro Corbi, Laura Barros Silva, Fernanda Van Petten V. Azevedo, Gilberto C. Franchi Jr, Carmen Silvia P. Lima
{"title":"ANTIPROLIFERATIVE ACTIVITIES IN VITRO OVER SQUAMOUS CELL CARCINOMAS OF A PALLADIUM(II) COMPLEX WITH AMANTADINE","authors":"Pedro Corbi, Laura Barros Silva, Fernanda Van Petten V. Azevedo, Gilberto C. Franchi Jr, Carmen Silvia P. Lima","doi":"10.1016/j.htct.2025.103777","DOIUrl":"10.1016/j.htct.2025.103777","url":null,"abstract":"<div><h3>Introduction/Justification</h3><div>Metal-based drugs have been used in diagnosis and treatment of different types of cancer since the discovery of cisplatin's antineoplastic properties in the 1960’s. Second-generation drugs based on the platinum(II) complex cisplatin, such as carboplatin and oxaliplatin, were developed and used for cancer treatment worldwide. However, platinum(II) drugs typically cause side effects, such as nephrotoxicity, neurotoxicity and myelosuppression, which motivates the search for new drug candidates. Since the platinum(II) and palladium(II) ions have similar characteristics and form analogous compounds, palladium(II) complexes have been also studied as potential anticancer agents. Recently, a new palladium(II) drug named padeliporfin (Tookad®Soluble) has entered the clinic for the treatment of low-risk prostate cancer, which further motivates the investigation of palladium(II) complexes as potential antineoplastic drugs. Adamantanes are a class of organic compounds that consist of a single diamond-like carbon cage. The functionalization of adamantane with an amine group lead to amantadine, which has been used in the clinic as an antiviral and anti-Parkinson drug and has also been evaluated for its anticancer activity.</div></div><div><h3>Objectives</h3><div>In this study, we report for the first time the antiproliferative studies of a palladium(II) complex with amantadine (Pd-atd) over squamous cell carcinomas</div></div><div><h3>Materials and Methods</h3><div>The Pd-atd complex was prepared following the literature protocol. Briefly, the complex was prepared by the reaction of Li2PdCl4 with amantadine hydrochloride in methanol under stirring and at room temperature. The yellowish solid obtained was collected by filtration, washed with methanol and dried. Yield 72%. The [PdCl2(C10H17N)2] composition was confirmed by chemical and spectroscopic analyses. Squamous cell carcinoma of tongue (SCC-4 and SCC-25) and of hypopharynx (Fadu), and a non-tumoral cell line (HaCat, immortalized keratinocyte) were used in this study. Cells were cultivated following the methodology previously described in the literature. Cell viability was determined by dose-response curves obtained from an MTT assay measuring the absorbance after 48h.</div></div><div><h3>Results</h3><div>The Pd-atd complex inhibited proliferation of SCC-4 cells with an IC50 of 1.87 µM and it was non-toxic to HaCat cells. Cisplatin, a standard drug, presented an IC50 of 7.02 µM and it was less selective toward HaCat cells in the same experimental conditions.</div></div><div><h3>Conclusion</h3><div>The promising results of the antiproliferative activities of the Pd-atd complex over SCC-4 cells warrant for additional studies about the potential of application of the complex as an antiproliferative agent for the treatment of squamous cell carcinomas.</div></div><div><h3>Acknowledgements</h3><div>This study was supported by grants from the Brazilian Agencies FAPESP ","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103777"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828170","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}
DANIELA CARNEIRO DE Lima , Alex H. Schöntal , Clóvis Orlando Pereira da Fonseca , Fabiano Reis , Carmen Silva Passos Lima , Mary Ann Foglio
{"title":"PROTOCOL OF A RANDOMIZED PILOT STUDY ON SURVIVAL IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS UNDERGOING CHEMORADIATION VERSUS COMBINED CHEMORADIATION WITH INTRANASAL PERILLYL ALCOHOL","authors":"DANIELA CARNEIRO DE Lima , Alex H. Schöntal , Clóvis Orlando Pereira da Fonseca , Fabiano Reis , Carmen Silva Passos Lima , Mary Ann Foglio","doi":"10.1016/j.htct.2025.103776","DOIUrl":"10.1016/j.htct.2025.103776","url":null,"abstract":"<div><h3>Introduction/Justification</h3><div>Glioblastoma multiforme (GBM) is a highly aggressive type of brain tumor and remains one of the most challenging cancers to treat. This tumor is characterized by rapid progression and unfavorable prognosis. After undergoing surgery, radiotherapy (RT), and chemotherapy (CT) with temozolomide (TMZ), patients generally exhibit low survival rates. Perillyl alcohol (POH) is a hydroxylated monoterpene with antitumor, anti-angiogenic, and pro-apoptotic properties, inhibiting RAS oncogene-mediated signaling. In vitro and in vivo studies showed POH's cytotoxicity to both TMZ-resistant and sensitive cells, and its effectiveness as a radiosensitizer in malignant glioma cell lines. In phase I/II trials with oral POH in advanced, refractory cancer patients, nausea and other gastrointestinal toxicities led to study discontinuation. Currently, POH is being studied as an inhaled anticancer agent, showing no toxicity and promising activity with increased survival in patients with recurrent gliomas, however, these studies were not randomized, and to date, these investigations have been conducted exclusively in patients with recurrent gliomas.</div></div><div><h3>Objectives</h3><div>This study presents a protocol from the University of Campinas, developed by experts across multiple fields, to evaluate the effects of intranasal POH in GBM patients.</div></div><div><h3>Materials and Methods</h3><div>Patient's will be recruited from the Oncology Service at the General Hospital of the University of Campinas (UNICAMP) after tumor resection, with a total of 40 participants. Adult individuals of any gender will be included. Through randomization, participants will be randomly assigned to two groups: the control group (RT+CT) and the intervention group (RT+CT+ POH inhalations). Block randomization of four patients will ensure balance between groups during recruitment. The randomization sequence was generated at www.randomization.com. The control group will undergo RT and CT with TMZ: 75 mg/m² of TMZ daily for 6 weeks during RT (2 Gy/day for 5 days a week, totaling 60 Gy), followed by 150 or 200 mg/m² of TMZ for 5 days per cycle in 28-day cycles for 6 cycles. The participants in the intervention group will receive the same treatment plus 0.3% POH inhalations (55 mg in 3 mL of water, 4 times daily, with 6-hour intervals). They will undergo 6 weeks of RT + TMZ + POH, followed by 6 cycles of TMZ + POH (5 days of TMZ + POH, followed by 23 days of POH only). Cranial MRIs will be analyzed by an expert neuroradiologist using T2/FLAIR signal intensity with perfusion, without knowledge of patient group allocation. MRIs are part of routine treatment, performed every 3-4 months in the first year, and response will be assessed using MacDonald and RANO criteria for high-grade gliomas. Toxicity assessment of standard treatment with POH will follow the NCI Common Terminology Criteria, version 5.0. Progression-free survival will be compared betw","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103776"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828169","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}
Anali Del Milagro Bernabe Garnique , Jorge Antonio Elias Godoy Carlos , Natalia Sudan Parducci , Mauricio Temotheo Tavares , Karoline de Barros Waitman , Keli Lima , Leticia Veras Costa-Lotufo , Roberto Parise-Filho , João Agostinho Machado-Neto
{"title":"Hybrid histone deacetylase-kinase inhibitor potentiates venetoclax-induced cell death in chronic lymphocytic leukemia","authors":"Anali Del Milagro Bernabe Garnique , Jorge Antonio Elias Godoy Carlos , Natalia Sudan Parducci , Mauricio Temotheo Tavares , Karoline de Barros Waitman , Keli Lima , Leticia Veras Costa-Lotufo , Roberto Parise-Filho , João Agostinho Machado-Neto","doi":"10.1016/j.htct.2025.103757","DOIUrl":"10.1016/j.htct.2025.103757","url":null,"abstract":"","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 2","pages":"Article 103757"},"PeriodicalIF":1.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luana Joana Barreto Cabral , Daniela Pereira Lopes , Eduardo dos Santos Martins Filho , Rubenilson Caldas Valois , Paula Christine Amarantes Justino Oliveira , Patrícia Jeanne de Souza Mendonça-Mattos
{"title":"Anti-HLA antibody formation increases the chances of platelet refractoriness in platelet-transfused patients: a systematic review with meta-analysis","authors":"Luana Joana Barreto Cabral , Daniela Pereira Lopes , Eduardo dos Santos Martins Filho , Rubenilson Caldas Valois , Paula Christine Amarantes Justino Oliveira , Patrícia Jeanne de Souza Mendonça-Mattos","doi":"10.1016/j.htct.2025.103821","DOIUrl":"10.1016/j.htct.2025.103821","url":null,"abstract":"<div><div>Platelet refractoriness caused by alloimmunization to anti-HLA antibodies remains present in daily hemotherapy: the frequent need for platelet transfusions may influence the long-term survival of treated patients. This study aimed to perform a systematic review with meta-analysis to investigate the chances of anti-HLA antibody formation triggering immune-induced platelet refractoriness in platelet transfused individuals. By adopting Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, a search was conducted of publications in online databases between 1976 and July 2022. The risk of bias in the studies was assessed according to the data quality assessment proposed by the ‘A MeaSurement Tool to Assess systematic Reviews’ (AMSTAR-2) tool. Meta-analysis was performed by evaluating the Forest and Funnel Plots. From 832 published articles, 50 were read in full with 14 studies being included in this systematic review. The forest plot showed a likely low heterogeneity (I²: 12.3%; p-value = 0.32), and high odds ratio (174.57; confidence interval: 73.23–416.16) showing platelet refractoriness is triggered by anti-HLA alloantibodies. In this study, anti-HLA antibody formation contributed to an approximate 175-fold higher chance of triggering immune-induced platelet refractoriness. Some explanations about why some statistical differences were observed are offered by studies. This study demonstrates the need for developing policies to identify and monitor anti-HLA antibodies in patients, as well as for HLA matching, and makes some suggestions for future research to promote the prevention of patient sensitization due to platelet transfusions including the development of platelet refractoriness.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 2","pages":"Article 103821"},"PeriodicalIF":1.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833684","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":"Evidence-based medicine during the COVID-19 pandemic: A hematologist's perspective","authors":"Yung Gonzaga","doi":"10.1016/j.htct.2025.103825","DOIUrl":"10.1016/j.htct.2025.103825","url":null,"abstract":"","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 2","pages":"Article 103825"},"PeriodicalIF":1.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}