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1.
Rinsho Ketsueki ; 65(1): 18-23, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311384

RESUMO

Aggressive types of adult T-cell leukemia-lymphoma (ATL), namely, the acute type, lymphoma type, and chronic type with poor prognostic factors, have a poor prognosis. Although allogeneic hematopoietic stem cell transplantation (HSCT) may improve prognosis, relapse is common. In June 2021, tucidinostat was approved for relapsed or refractory ATL in Japan. We report a case of a 62-year-old man with relapsed ATL after allogeneic HSCT. In March 2017, he was diagnosed with ATL (acute type) and received two courses of mLSG-15 therapy. ATL cells reappeared in his peripheral blood, so he underwent allogeneic bone marrow transplantation in September 2017. In June 2021, his soluble interleukin-2 receptor (sIL-2R) level increased, and he began experiencing sensory abnormalities in his face and legs. In September, he developed respiratory failure and was diagnosed with relapse of ATL. He was again treated with mLSG-15. His sIL-2R normalized and the sensory abnormalities decreased, but sIL-2R rose again in February 2022. After tucidinostat treatment was initiated, sIL-2R normalized and the patient's general condition improved. Tucidinostat shows promise as an effective treatment for ATL that has relapsed after allogeneic HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Resultado do Tratamento , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Recidiva , Receptores de Interleucina-2
2.
Rinsho Ketsueki ; 65(1): 30-34, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311386

RESUMO

A 47-year-old woman presented with subcutaneous hemorrhage. Blood tests revealed leukoerythroblastosis, anemia, and thrombocytopenia. Bone marrow biopsy led to a diagnosis of primary myelofibrosis (aaDIPSS, DIPSS-plus: intermediate-II risk). JAK2, CALR, and MPL mutations were not detected in peripheral blood, but targeted sequencing of bone marrow specimens revealed a double mutation (Q157R, S34F) in U2AF1. Allo-PBSCT was performed using an HLA-matched related donor, and post-transplantation bone marrow examination showed complete donor chimerism on day 55. Two years after allogeneic transplantation, the patient remains relapse-free. Although U2AF1 gene abnormality is known as a poor prognostic factor in primary myelofibrosis, this patient had a favorable long-term prognosis due to prompt transplantation therapy. This case highlights the importance of detailed gene mutation analysis in patients with triple-negative MF.


Assuntos
Mielofibrose Primária , Feminino , Humanos , Pessoa de Meia-Idade , Mielofibrose Primária/genética , Mielofibrose Primária/terapia , Mielofibrose Primária/diagnóstico , Fator de Processamento U2AF/genética , Mutação , Medula Óssea/patologia , Transplante Homólogo , Janus Quinase 2/genética , Calreticulina/genética
3.
Rinsho Ketsueki ; 65(1): 35-40, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311387

RESUMO

A 64-year-old woman presented with fine motor impairment in both hands. MRI revealed a contrast-enhanced lesion in the medulla oblongata. Lymphoid cells with abnormal blebs were observed and a CD4+/CD8+ double positive (DP) T cell population was detected by flow cytometry (FCM) in the bone marrow (BM) and the peripheral blood (PB). CLEC16A::IL2 fusion gene was identified by whole exome sequencing with DNA prepared from DP T cells. Clonal rearrangement of the T-cell receptor gene and expression of TCL1A protein were detected. This led to a diagnosis of T-cell prolymphocytic leukemia (T-PLL) with central nervous system (CNS) infiltration. Abnormal cells in BM and PB became undetectable on microscopy and FCM, and the CNS lesion disappeared on MRI after second-line therapy with alemtuzumab. Meanwhile, the CLEC16A::IL2 fusion mRNA remained detectable in PB. Allogeneic hematopoietic stem-cell transplantation was performed, and the fusion mRNA has now been undetectable for more than 5 years since transplantation. This is the first report of a T-PLL case with a CLEC16A::IL2 fusion gene.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Prolinfocítica de Células T , Feminino , Humanos , Pessoa de Meia-Idade , Leucemia Prolinfocítica de Células T/genética , Leucemia Prolinfocítica de Células T/metabolismo , Leucemia Prolinfocítica de Células T/terapia , Interleucina-2/metabolismo , Alemtuzumab , RNA Mensageiro , Proteínas de Transporte de Monossacarídeos , Lectinas Tipo C/genética
4.
Rinsho Ketsueki ; 65(1): 41-46, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311388

RESUMO

The patient was a 21-year-old man who had been diagnosed with Crohn's disease and received infliximab and azathioprine six years earlier. He was admitted with fever and fatigue. Peripheral blood examination showed LDH 2,473 U/l and thrombocytopenia, and contrast-enhanced computed tomography (CT) showed hepatosplenomegaly. Bone marrow biopsy and liver biopsy showed CD4+CD56+TCRγδ+CD8- atypical cells, leading to a diagnosis of hepatosplenic T-cell lymphoma (HSTCL). The patient was refractory to CHOP and DA-EPOCH, and therefore received cord blood transplantation with myeloablative conditioning. CT showed reduced in hepatosplenomegaly and peripheral blood examination showed LDH 165 U/l and plt 180,000/µl, so the patient was discharged on day117. HSTCL is a tumor of immature γδT cells with a Vδ1 mutation in the spleen, and immunodeficiency has been implicated in its pathogenesis. Patients with inflammatory bowel disease treated with azathioprine are known to have an increased risk of lymphoproliferative disease. In this case, use of immunosuppressive drugs for Crohn's disease may have caused malignant transformation of γδ cells in the intestinal epithelium. Although the patient was refractory to chemotherapy, he was able to achieve remission with early cord blood transplantation and long-term survival is expected.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença de Crohn , Neoplasias Hepáticas , Linfoma de Células T , Neoplasias Esplênicas , Masculino , Humanos , Adulto Jovem , Adulto , Doença de Crohn/induzido quimicamente , Doença de Crohn/tratamento farmacológico , Azatioprina/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Imunossupressores/uso terapêutico , Linfoma de Células T/etiologia , Linfoma de Células T/terapia , Linfoma de Células T/diagnóstico , Neoplasias Esplênicas/etiologia
5.
Rinsho Ketsueki ; 65(1): 1-6, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311382

RESUMO

A 66-year-old man was diagnosed with symptomatic IgG-λ multiple myeloma based on the presence of anemia, thrombocytopenia, renal dysfunction, and a tumor on the right sixth rib. Bone marrow aspiration yielded a dry tap and biopsy revealed myelofibrosis grade 2. Partial response was achieved with Bd (bortezomib and dexamethasone) and VRd (bortezomib, lenalidomide, and dexamethasone). The patient received autologous stem cell transplantation, but the myeloma relapsed 3 months later, and liver tumors developed as well. DKd (daratumumab, carfilzomib, and dexamethasone) was administered, but the patient died due to disease progression. Autopsy revealed multiple extramedullary lesions in the liver, spleen, gallbladder, adrenal glands, kidneys, and multiple lymph nodes, as well as ascites.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Mielofibrose Primária , Masculino , Humanos , Idoso , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Bortezomib/uso terapêutico , Mielofibrose Primária/complicações , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/terapia , Dexametasona/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia , Transplante Autólogo
6.
Rinsho Ketsueki ; 65(1): 7-12, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311391

RESUMO

An 18-year-old man underwent allogenic bone marrow transplantation (BMT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Ph+ALL relapsed 3 months after the first BMT, and the patient underwent a second BMT. However, Ph+ALL relapsed 4 months after the second BMT, and he received a haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) from his father. Molecular complete remission was confirmed 29 days after haplo-PBSCT. However, the patient needed dialysis for end-stage renal disease due to thrombotic microangiopathy 3 years and 2 months after haplo-PBSCT. He received a kidney transplantation from his father 7 years and 10 months after haplo-PBSCT, and got off dialysis after the kidney transplantation. Immunosuppressive therapy with methylprednisolone, tacrolimus, and mycophenolate mofetil was started for kidney transplantation, but the dose of immunosuppressive agents was reduced successfully without rejection soon after kidney transplantation. The patient has maintained long-term remission since the haplo-PBSCT, and his kidney function was restored by the kidney transplantation from his father.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Falência Renal Crônica , Transplante de Rim , Leucemia-Linfoma Linfoblástico de Células Precursoras , Masculino , Humanos , Adolescente , Cromossomo Filadélfia , Transplante Homólogo , Transplante de Medula Óssea , Doença Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
7.
Radiother Oncol ; 193: 110118, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38316192

RESUMO

In 2023, the Common Sense Oncology (CSO) movement was launched with the goal of recalibrating cancer care to focus on outcomes that matter to patients. We extend the three CSO pillars - evidence generation, interpretation and communication - to radiation oncology and advocate for better evidence demonstrating the value of our modality.

8.
J Imaging Inform Med ; 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38343225

RESUMO

Accurate delineation of the clinical target volume (CTV) is a crucial prerequisite for safe and effective radiotherapy characterized. This study addresses the integration of magnetic resonance (MR) images to aid in target delineation on computed tomography (CT) images. However, obtaining MR images directly can be challenging. Therefore, we employ AI-based image generation techniques to "intelligentially generate" MR images from CT images to improve CTV delineation based on CT images. To generate high-quality MR images, we propose an attention-guided single-loop image generation model. The model can yield higher-quality images by introducing an attention mechanism in feature extraction and enhancing the loss function. Based on the generated MR images, we propose a CTV segmentation model fusing multi-scale features through image fusion and a hollow space pyramid module to enhance segmentation accuracy. The image generation model used in this study improves the peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM) from 14.87 and 0.58 to 16.72 and 0.67, respectively, and improves the feature distribution distance and learning-perception image similarity from 180.86 and 0.28 to 110.98 and 0.22, achieving higher quality image generation. The proposed segmentation method demonstrates high accuracy, compared with the FCN method, the intersection over union ratio and the Dice coefficient are improved from 0.8360 and 0.8998 to 0.9043 and 0.9473, respectively. Hausdorff distance and mean surface distance decreased from 5.5573 mm and 2.3269 mm to 4.7204 mm and 0.9397 mm, respectively, achieving clinically acceptable segmentation accuracy. Our method might reduce physicians' manual workload and accelerate the diagnosis and treatment process while decreasing inter-observer variability in identifying anatomical structures.

9.
Cureus ; 16(2): e53931, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38343705

RESUMO

When a malignant tumor infiltrates the psoas muscle, it is termed malignant psoas syndrome (MPS). We are reporting this case because the malignancy led to atrophy of the psoas muscle, and the clinical course differed from the typical presentation of MPS. A 72-year-old Japanese female with advanced sigmoid colon cancer and multiple metastases had been undergoing systemic chemotherapy for four years. She complained of severe back pain on a numeric rating scale (NRS) of 4-5, left groin pain, and hip flexion weakness. Although she could stand up, she started experiencing difficulties while walking and became reliant on a wheelchair. At the time of referral to our department, her performance status was 2. On examination, she was capable of hip adduction and abduction, and flexion was impossible on the left side and possible on the right side. Imaging revealed metastases to the 11th and 12th thoracic vertebrae, extending to the upper portion of the first lumbar vertebra, leading to atrophy of the left psoas major muscle and impairment of hip flexion. She received palliative radiation therapy (RT) of 30 Gy in 10 fractions over a period of 2 weeks. Following RT, she had grade 1 skin inflammation but no severe complications. Two weeks after RT, her pain improved (NRS 0-1) and she regained hip flexion. When hip flexion failure occurs in patients with malignant tumors, it is important to recognize that it may be caused by a tumor located near the lower thoracic or upper lumbar spine, even if the psoas muscle itself is not directly infiltrated by the tumor.

10.
Head Neck ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38344931

RESUMO

BACKGROUND: New patient referrals are often processed by practice coordinators with little-to-no medical background. Treatment delays due to incorrect referral processing, however, have detrimental consequences. Identifying variables that are associated with a higher likelihood of surgical oncological resection may improve patient referral processing and expedite the time to treatment. The study objective is to develop a supervised machine learning (ML) platform that identifies relevant variables associated with head and neck surgical resection. METHODS: A retrospective cohort study was conducted on 64 222 patient datapoints from the SEER database. RESULTS: The random forest ML model correctly classified patients who were offered head and neck surgery with an 81% accuracy rate. The sensitivity and specificity rates were 86% and 71%. The positive and negative predictive values were 85% and 73%. CONCLUSIONS: ML modeling accurately predicts head and neck cancer surgery recommendations based on patient and cancer information from a large population-based dataset. ML adjuncts for referral processing may decrease the time to treatment for patients with cancer.

11.
Am J Gastroenterol ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38345215

RESUMO

OBJECTIVES: To verify the value of the pathological criteria for additional treatment in locally resected pT1 colorectal carcinoma (CRC) which have been used in the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines since 2009. METHODS: We enrolled 4719 patients with pT1 CRC treated at 27 institutions between July 2009 and December 2016 (1259 patients with local resection alone [Group A], 1508 patients with additional surgery after local resection [Group B], and 1952 patients with surgery alone [Group C]). All five factors of the JSCCR guidelines (submucosal resection margin, tumor histologic grade, submucosal invasion depth, lymphovascular invasion, and tumor budding) for lymph node metastasis (LNM) had been diagnosed prospectively. RESULTS: Any of the risk factors were present in 3801 patients. The LNM incidence was 10.3% (95% confidence interval [95% CI] 9.3-11.4) in Group B/C patients with risk factors, whereas it was 1.8% (95% CI 0.4-5.2) in those without risk factors (P<0.01). In Group A, the incidence of recurrence was 3.4% in patients with risk factors, but it was only 0.1% in patients without risk factors (P<0.01). The disease-free survival (DFS) rate of Group A patients classified as risk-positive was significantly worse than those of Groups B and C patients. However, the 5-year DFS rate in Group A patients with no risk was 99.2%. CONCLUSIONS: Our large-scale real-world multicenter study demonstrated the validity of the JSCCR criteria for pT1 CRC after local resection, especially regarding favorable outcomes in patients with low risk of LNM.

12.
J Mater Chem B ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38345341

RESUMO

Leukemia is a type of clonal disorder of hematopoietic stem and progenitor cells characterized by bone marrow failure, differentiation arrest, and lineage skewing. Despite leukemia being a complex disease and it being difficult to identify a single driving force, redox homeostasis, the balance between reactive oxygen species (ROS) producers and cellular antioxidant systems, is normally impaired during leukemogenesis. In this context, the modulation of ROS in leukemia cells can be harnessed for therapeutic purposes. Nanozymes are functional nanomaterials with enzyme-like characteristics, which address the intrinsic limitations of natural enzymes and exhibit great potential in synergistic antitumor therapy. Nanozymes possess catalytic activities (e.g., peroxidase-like activity, catalase-like activity, superoxide dismutase-like activity, and oxidase-like activity) to regulate ROS levels in vitro and in vivo, making them promising for leukemia therapy. On account of the rapid development of nanozymes recently, their application potentials in leukemia therapy are gradually being explored. To highlight the achievements of nanozymes in the leukemia field, this review summarizes the recent studies of nanozymes with anti-leukemia efficacy and the underlying mechanism. In addition, the challenges and prospects of nanozyme research in leukemia therapy are discussed.

13.
Cir Esp (Engl Ed) ; 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38346559

RESUMO

INTRODUCTION: Surgery is the only potentially curative treatment for colorectal cancer liver metastases (LMCRC) and its indication and results have varied in the last 30 years. METHODS: All patients operated on for LMCRC in our centre from 1990 to 2021 were prospectively collected, establishing 3 subgroups based on the year of the first surgery: group A 1990-1999, group B 2000-2010, group C 2011-2021. Clinical characteristics and the results of survival, recurrence and prognostic factors were compared. RESULTS: 1736 hepatectomies were included (Group A n = 208; Group B n = 770; Group C n = 758). Patients in group C had better survival at 5 and 10 years (A 40.5%/28.2%; B 45.9%/32.2%; C 51.6%/33.1%, p = 0.013), although there were no differences between groups in overall recurrence at 5 and 10 years (A 73%/75.7%; B 67.6%/69.2%, and C 63.9%/66%, p = 0.524), nor in liver recurrence (A 46.4%/48.2%; B 45.8%/48.2%; and C 44.4%/48.4%, p = 0.899). An improvement was observed in median survival after recurrence, being 19 months, 23 months, and 31 months (groups A, B and C respectively). Prognostic factors of long-term survival changed over the 3 study periods. The only ones that remained relevant in the last decade were the presence of >4 liver metastasis, extrahepatic disease at the time of hepatectomy, and intraoperative blood transfusion. CONCLUSIONS: Survival after surgery for LMCRC has improved significantly, although this cannot be explained by a reduction in overall and hepatic recurrence, but rather by an improvement in post-recurrence survival. Involvement of the resection margin has lost prognostic value in the last decade.

14.
BJU Int ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38346924

RESUMO

OBJECTIVE: To investigate whether combination treatment of prostate-specific membrane antigen (PSMA)-based radioguided surgery (RGS) with short-term androgen deprivation therapy (ADT) improves oncological outcomes in men with oligorecurrent prostate cancer (PCa) as compared to treatment with short-term ADT only. METHODS: The TRACE-II study is an investigator-initiated, prospective, randomised controlled clinical trial. Patients (aged >18 years) with hormone-sensitive recurrent PCa after radical prostatectomy or radiotherapy (brachytherapy or external beam radiotherapy), with involvement of ≤2 lymph nodes or local oligorecurrent disease within the pelvis as determined by PSMA positron emission tomography (PET)/computed tomography (CT) are randomly assigned in a 1:1 ratio between 6-month ADT (Arm A) or 6-month ADT plus RGS (Arm B). The primary objective is to determine clinical progression-free survival (CPFS) at 24 months. After PSMA-RGS, CPFS is defined as the time between the start of treatment and the appearance of a re-recurrence (any N1 or M1) as suggested by PSMA-PET/CT or symptoms related to progressive PCa, or death from any cause. The secondary objectives include metastasis-free survival at 2, 5 and 10 years, biochemical progression-free survival at 2 years, and patient-reported quality of life at 2, 5 and 10 years. A total of 60 patients, 30 per arm, will be included. The trial is powered (80%) to detect at least a 30% absolute difference in CPFS between the two study arms in the period 2 years after randomisation. We expect to enrol the required participants in 3 years. The study has an expected duration of 5 years in total. CONCLUSIONS: Combining RGS with short-term ADT might be oncologically beneficial for patients with oligorecurrent PCa. In this first randomised controlled trial, we are investigating the potential oncological benefits of this combined treatment, while also focusing on maintaining quality of life.

15.
Biochem Genet ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347290

RESUMO

Fanconi anemia (FA) is the predominant hereditary syndrome of bone marrow failure (BMF), distinguished by impairments in DNA repair mechanisms. The deficiency in the FANC pathway, which governs DNA repair and replication rescue, results in aberrant responses to DNA damage in individuals with FA. The objective of this study is to examine the involvement of the FANC core complex in BMF and ascertain nucleolar homeostasis-related genes by conducting transcriptome analysis on primary hematopoietic stem cells obtained from FA patients with FANCA and FANCC variants. In the present study, we analyzed scRNA-seq data obtained from both healthy donors and individuals diagnosed with FA in order to investigate the phenomenon of cell-cell communication. Through the implementation of trajectory analysis, the differentiation pathways of several progenitor cell types, such as HSC cells transitioning into LMPP, N, M, B-prog, and E cells, were elucidated. Moreover, by scrutinizing the inferred interactions, notable disparities in cell-cell communication were observed between FA patients and their healthy counterparts. Our analysis has unveiled heightened interactions involving TNFSF13B, MIF, IL16, and COL4A2 in patients with FA. Furthermore, we have developed a prognostic model for predicting the outcome of acute myeloid leukemia (AML) which has exhibited remarkable predictive precision, with an AUC exceeding 0.83 at the 3- and 5-year intervals following the baseline assessment. In summary, the prognostic model that has been developed provides a valuable instrument for forecasting outcomes of AML by utilizing the genes identified through both single-cell and bulk transcriptome analyses.

16.
Int J Surg ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38348896

RESUMO

OBJECTIVE: To conduct a meta-analysis to provide the latest evidence of nonsurgical local salvage options in the first-line radiotherapy failure setting for localized prostate cancer patients. BACKGROUND: Recurrence of localized prostate cancer after primary radiotherapy (RT) remains a clinical challenge. There is no consensus on optimal nonsurgical local salvage therapies, which mainly consist of cryotherapy (CRYO), high-intensity focused ultrasound (HIFU), high/low-dose-rate brachytherapy (HDR/LDR), and stereotactic body radiotherapy (SBRT). METHODS: Our study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We systematically searched PubMed, Web of Science, Cochrane Library and ClinicalTrials.gov up to September 2023 to identify potentially relevant studies. The risk of bias was assessed using the European Association of Urology (EAU) items. Biochemical recurrence-free survival (bRFS) and genitourinary/gastrointestinal toxicities were the outcomes of interest. Pooled rates with 95% confidence intervals (CIs) were evaluated. RESULTS: A total of 99 studies comprising 8440 patients were included. The pooled rate of 1-year biochemical control (BC) was highest for LDR (0.88, 95%CI 0.72-0.95) and lowest for SBRT (0.68, 95%CI 0.49-0.83). The pooled rate of 5-year BC was highest for CRYO (0.52, 95%CI 0.33-0.69) and lowest for HDR (0.23, 95%CI 0.08-0.51). HIFU presented the worst outcome of grade ≥3 genitourinary toxicities (GU3), with a rate of 0.22 (95%CI 0.12-0.3). Conversely, CRYO (0.09, 95%CI 0.04-0.14), HDR (0.05, 95%CI 0.02-0.07), LDR (0.10, 95%CI 0.06-0.14) and SBRT (0.06, 95%CI 0.03-0.09) presented low rates of GU3. All subgroups induced a quite low incidence of grade ≥3 gastrointestinal toxicities (GI3). CONCLUSIONS: Nonsurgical salvage therapies are promising modalities for prostate cancer in the local radiorecurrence setting. Based on the preliminary evidence from this study, CRYO and SBRT might present a relatively steady efficacy of BC with acceptable treatment-related toxicities.

17.
J Clin Invest ; 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349740

RESUMO

Radiotherapy (RT) is considered immunogenic, but clinical data demonstrating RT-induced T-cell priming are scarce. Here, we show in a mouse tumor model representative of human lymphocyte-depleted cancer that RT enhances spontaneous priming of thymus-derived (FOXP3+ Helios+) regulatory T-cells (Tregs) by the tumor. These Tregs acquire an effector phenotype, populate the tumor and impede tumor control by a simultaneous, RT-induced CD8+ cytotoxic T-cell (CTL) response. Combination of RT with CTLA-4 or PD-1 blockade, which enables CD28 costimulation, further increased this Treg response and failed to improve tumor control. We discovered that upon RT, CD28-ligands CD86 and CD80 differentially affected the Treg response. CD86, but not CD80, blockade prevented the effector (e)Treg response, enriched the tumor-draining lymph node for PD-L1+CD80+ migratory, conventional dendritic cells (cDCs) and promoted CTL priming. Blockade of CD86 alone or in combination with PD-1, enhanced intra-tumoral CTL accumulation and the combination significantly increased RT-induced tumor regression and overall survival. We advise that combining RT with PD-1 and/or CTLA-4 blockade may be counterproductive in lymphocyte-depleted cancers, since they drive Treg responses in this context. However, combining RT with CD86 blockade may promote control of such tumors by enabling a CTL response.

18.
Artigo em Inglês | MEDLINE | ID: mdl-38336504

RESUMO

AIMS: This study describes nationwide primary radiotherapy utilisation trends for non-metastasised rectal cancer in the Netherlands between 2008 and 2021. In 2014, both colorectal cancer screening and a new guideline specifying prognostic risk groups for neoadjuvant treatment were implemented. MATERIALS AND METHODS: Patients with non-metastasised rectal cancer in 2008-2021 (n = 37 510) were selected from the Netherlands Cancer Registry and classified into prognostic risk groups. Treatment was studied over time and age. Multilevel logistic regression analyses were carried out to identify factors associated with (i) radiotherapy versus chemoradiotherapy use for intermediate rectal cancer and (ii) chemoradiotherapy without versus with surgery for locally advanced rectal cancer. RESULTS: For early rectal cancer, the use of neoadjuvant radiotherapy decreased (15% to 5% between 2008 and 2021), whereas the use of endoscopic resections increased (8% in 2015, 17% in 2021). In intermediate-risk rectal cancer, neoadjuvant chemoradiotherapy (43% until 2011, 25% in 2015) shifted to radiotherapy (42% in 2008, 50% in 2015), the latter being most often applied in older patients. In locally advanced rectal cancer, the use of chemoradiotherapy without surgery increased (2-4% in 2008-2013, 17% in 2019-2021). Both neoadjuvant treatment in intermediate disease and omission of surgery following chemoradiotherapy in locally advanced disease varied with increasing age (odds ratio>75vs<50: 2.17, 95% confidence interval 1.54-3.06) and treatment region (Southwest and Northwest odds ratio 0.63, 95% confidence interval 0.42-0.93 and odds ratio 0.65, 95% confidence interval 0.44-0.95, respectively, compared with the North). CONCLUSION: Treatment patterns in non-metastasised rectal cancer significantly changed over time. Effects of both the national screening programme and the new treatment guideline were apparent, as well as a paradigm shift towards organ preservation (watch-and-wait). Observed regional variations may indicate adoption differences regarding new treatment strategies.

19.
Brachytherapy ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38336557

RESUMO

PURPOSE: To provide a practical method of estimating medium-heterogeneity corrected dose without a Monte Carlo (MC) calculation in ocular brachytherapy using 125I Collaborative Ocular Melanoma Study (COMS) plaques. METHODS AND MATERIALS: Using egs_brachy, MC simulations (1) under task group-43 assumptions with fully loaded seed configurations in water (HOMO) and (2) with effects of plaque backing, insert and inter-seed interactions (HETERO) were performed for seven 125I COMS plaques (10 mm-22 mm in diameter), and homogeneous dose (DHOMO) and heterogeneous dose (DHETERO) for central-axis and off-axis points were determined. For DHOMO, 85 Gy was normalized to a depth of 5 mm. Central-axis heterogeneity correction factors (HCFs) from a depth of 0 mm (inner sclera) to 22 mm (opposite retina) were derived from a ratio of DHETERO to DHOMO. Off-axis HCFs for optic disc/macula and lens as a function of distance from optic disc/macula (DT/MT) for various basal dimensions of tumor (BD/BM) were derived from DHETERO/DHOMO. RESULTS: Central-axis HCF varied with a dose reduction of 10.3-19.8% by heterogeneity. Off-axis HCF for optic disc/macula varied significantly depending on DT/MT and BD/BM with a dose reduction of 11.3-38.3%. Off-axis HCF for lens had a dependence on MT and BM with its variation of 11.0-19.0%. A clinical example of using HCFs to estimate DHETERO was presented. CONCLUSIONS: The practical method of using depth-dependent central-axis HCF and DT/MT- and BD/BM-dependent off-axis HCF provided in this study will facilitate a heterogeneous dose estimate for 125I COMS plaques without MC calculations.

20.
Stem Cell Res Ther ; 15(1): 34, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38321524

RESUMO

Inflammation is a common and important pathological process occurring in any part of the body and relating to a variety of diseases. Effective tissue repair is critical for the survival of impaired organisms. Considering the side effects of the currently used anti-inflammatory medications, new therapeutic agents are urgently needed for the improvement of regenerative capacities of inflammatory-impaired tissues. Mesenchymal stromal stem/progenitor cells (MSCs) are characterized by the capabilities of self-renewal and multipotent differentiation and exhibit immunomodulatory capacity. Due to the ability to modulate inflammatory phenotypes and immune responses, MSCs have been considered as a potential alternative therapy for autoimmune and inflammatory diseases. Natural compounds (NCs) are complex small multiple-target molecules mostly derived from plants and microorganisms, exhibiting therapeutic effects in many disorders, such as osteoporosis, diabetes, cancer, and inflammatory/autoimmune diseases. Recently, increasing studies focused on the prominent effects of NCs on MSCs, including the regulation of cell survival and inflammatory response, as well as osteogenic/adipogenic differentiation capacities, which indicate the roles of NCs on MSC-based cytotherapy in several inflammatory diseases. Their therapeutic effects and fewer side effects in numerous physiological processes, compared to chemosynthetic drugs, made them to be a new therapeutic avenue combined with MSCs for impaired tissue regeneration. Here we summarize the current understanding of the influence of NCs on MSCs and related downstream signaling pathways, specifically in pathological inflammatory conditions. In addition, the emerging concepts through the combination of NCs and MSCs to expand the therapeutic perspectives are highlighted. A promising MSC source from oral/dental tissues is also discussed, with a remarkable potential for MSC-based therapy in future clinical applications.


Assuntos
Doenças Autoimunes , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Células-Tronco Mesenquimais/metabolismo , Inflamação/metabolismo , Diferenciação Celular , Adipogenia , Imunomodulação
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