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1.
Int J Hematol ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619657

RESUMO

We report a rare case of spontaneous regression (SR) in an elderly untreated patient with multiple solitary plasmacytoma (MSP). Diagnosis of MSP was confirmed through surgical resection of the left nasal cavity mass and subsequent biopsy of the right humerus. The patient was considered ineligible for chemotherapy due to poor performance status. At 3-month post-diagnosis, the patient's condition worsened with deteriorating bone lesions and emergence of a new serum monoclonal protein. However, these clinical findings completely disappeared at 6 months, and positron emission tomography-computed tomography at 1 year confirmed complete metabolic remission. Notably, peripheral blood lymphocyte counts were inversely correlated with tumor progression and remission. Pathological re-evaluation of the initial biopsy specimens revealed programmed cell death protein 1 (PD-1) expression in tumor-infiltrating CD8+ T cells. In addition, tumor cells were infected with Epstein-Barr virus (EBV) but were negative for programmed cell death ligand 1 (PD-L1) expression, which is the most potent immune escape mechanism in tumor cells. While the mechanism underlying SR remains unclear, our findings suggest that host immune response as well as EBV infection may contribute to SR. Further studies are needed to elucidate the clinicopathologic mechanisms of tumor regression in plasma cell neoplasms.

2.
Int J Hematol ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519820

RESUMO

Response determined by 18[F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)-CT after induction therapy can predict progression-free survival (PFS) in follicular lymphoma (FL). However, little prospective research has examined the significance of PET after second-line therapy. We conducted a prospective multicenter phase II trial (W-JHS NHL01) of bendamustine plus rituximab (BR) without rituximab maintenance for FL in first relapse. This study aimed to evaluate the usefulness of end-of-treatment (EOT)-PET for predicting PFS in FL patients in first relapse. EOT-PET examinations were performed between 6 and 8 weeks from the start of the last BR cycle. The primary endpoint was 1-year PFS. Key secondary endpoints were overall response rate (ORR), complete response rate (CRR), and 1-year overall survival (OS). Seventy-five patients were enrolled, and 8 were excluded from analysis. ORR was 86.6% and CRR was 59.7%. One-year PFS was 88.9% (95% confidence interval [CI] 80.7-94.3%) and 1-year OS in 75 patients was 97.3% (95% CI 89.6-99.3%). One-year PFS was significantly inferior in EOT-PET-positive patients (n = 9) compared with PET-negative patients (n = 58) (77.8% vs. 93.1%; p = 0.02). We confirmed that EOT-PET after second-line BR therapy could predict early progression in FL patients in first relapse.

3.
Eur J Cardiothorac Surg ; 65(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38489836

RESUMO

OBJECTIVES: After staged reconstruction for hypoplastic left heart syndrome, the neoaortic root tends to dilate, and the incidence of significant neoaortic valve insufficiency increases with time. This study aimed to evaluate the mid-term outcomes of the neoaortic root geometries and valve function after chimney reconstruction in the Norwood procedure. METHODS: Between 2013 and 2021, 20 consecutive patients who underwent chimney reconstruction during the Norwood procedure for hypoplastic left heart syndrome and its variants in our institution were enrolled. The actual diameters of the following points were measured, and Z-scores were calculated based on the normal aortic root geometries using the long axis view of echocardiography at the pre-Norwood stage and the lateral view of angiography at pre-Glenn, pre-Fontan, post-Fontan and follow-up (age 5-6 years) stages: neoaortic valve annulus; sinus of Valsalva; sinotubular junction; and ascending aorta just proximal to the anastomosis to the aortic arch. The degree of neoaortic valve regurgitation was evaluated by echocardiography at each stage. RESULTS: The median follow-up period was 3.9 years. Neoaortic roots after chimney reconstruction were spared from progressive dilation over time. With growth, the conical configuration of the neoaortic roots was preserved without geometrical distortion. The Z-scores of the annulus, sinus of Valsalva, sinotubular junction and ascending aorta ranged roughly from 4 to 6, 4 to 6, 2 to 4 and 0 to 2, respectively. All neoaortic valves at each stage had mild or no regurgitation. CONCLUSIONS: Chimney reconstruction prevented neoaortic root dilation and avoided significant neoaortic valve regurgitation in the mid-term. These neoaortic dimensions with smooth flow profiles in the neoaorta after chimney reconstruction may have contributed to the current results. Further studies are needed to clarify the long-term outcomes.


Assuntos
Insuficiência da Valva Aórtica , Síndrome do Coração Esquerdo Hipoplásico , Procedimentos de Norwood , Humanos , Pré-Escolar , Criança , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Resultado do Tratamento , Procedimentos de Norwood/efeitos adversos , Aorta/cirurgia , Ecocardiografia , Insuficiência da Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/etiologia , Seguimentos , Estudos Retrospectivos
5.
J Clin Exp Hematop ; 64(1): 59-64, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38417872

RESUMO

We report a case of therapy-related myelodysplastic syndrome (MDS), which developed 9 years after autologous peripheral blood stem cell transplantation (PBSCT) for peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). A 65-year-old male was diagnosed with PTCL-NOS. After 6 cycles of the CHOP (cyclophosphamide [CPA], doxorubicin, vincristine, and prednisone) regimen, he achieved a first complete response (CR). He relapsed 33 months later and received salvage chemotherapy, which consisted of the CHASE regimen (CPA, high-dose cytarabine, dexamethasone, and etoposide). During the recovery phase of the first cycle of CHASE, his peripheral blood stem cells (PBSCs) were harvested and frozen in 2 bags. After 2 courses of CHASE, he underwent autologous PBSCT, which involved the use of the LEED preconditioning regimen (melphalan, CPA, etoposide, and dexamethasone) and one of the frozen bags. This resulted in a second CR. At 39 months after PBSCT, he relapsed with a tumor in his right arm. After it was resected, he received eight cycles of brentuximab vedotin and 45 Gy of involved-field irradiation concurrently and achieved a third CR. Nine years after autologous PBSCT, he was diagnosed with MDS with excess blasts 2 (MDS-EB-2). His disease progressed to acute myeloid leukemia after 2 courses of azacitidine therapy. He successfully underwent a second autologous PBSCT involving the busulfan and melphalan preconditioning regimen and the other frozen bag, which had been stored for 9 years. He has been in complete cytogenetic remission for 1 year since the second autologous PBSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Linfoma de Células T Periférico , Síndromes Mielodisplásicas , Masculino , Humanos , Idoso , Linfoma de Células T Periférico/terapia , Linfoma de Células T Periférico/tratamento farmacológico , Etoposídeo , Melfalan/uso terapêutico , Transplante Autólogo/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida , Dexametasona/uso terapêutico , Síndromes Mielodisplásicas/etiologia , Síndromes Mielodisplásicas/terapia , Resultado do Tratamento , Terapia Combinada
6.
Transfusion ; 64(4): 674-684, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38419458

RESUMO

BACKGROUND: In patients with relapsed or refractory B cell acute lymphoblastic leukemia or B cell non-Hodgkin lymphoma (r/r B-ALL/B-NHL) with low CD3+ cells in the peripheral blood (PB), sufficient CD3+ cell yield in a single day may not be obtained with normal-volume leukapheresis (NVL). Large-volume leukapheresis (LVL) refers to the processing of more than three times the total blood volume (TBV) in a single session for PB apheresis; however, the efficiency and safety of LVL for manufacturing of tisagenlecleucel (tisa-cel) remain unclear. This study aimed to investigate the tolerability of LVL. STUDY DESIGN AND METHODS: We retrospectively collected data on LVL (≥3-fold TBV) and NVL (<3-fold TBV) performed for patients with r/r B-ALL/B-NHL in our institution during November 2019 and September 2023. All procedures were performed using a continuous mononuclear cell collection (cMNC) protocol with the Spectra Optia. RESULTS: Although pre-apheresis CD3+ cells in the PB were significantly lower in LVL procedures (900 vs. 348/µL, p < .01), all patients could obtain sufficient CD3+ cell yield in a single day with a comparably successful rate of final products (including out-of-specification) between the two groups (97.2% vs. 100.0%, p = 1.00). The incidence and severity of citrate toxicity (no patients with grade ≥ 3) during procedures was not significantly different between the two groups (22.2% vs. 26.1%, p = .43) and no patient discontinued leukapheresis due to any complications. CONCLUSION: LVL procedures using Spectra Optia cMNC protocol was well tolerated and did not affect the manufacturing of tisa-cel.


Assuntos
Remoção de Componentes Sanguíneos , Leucaférese , Receptores de Antígenos de Linfócitos T , Humanos , Leucaférese/métodos , Estudos Retrospectivos , Antígenos CD34 , Remoção de Componentes Sanguíneos/métodos
7.
Intern Med ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38403772

RESUMO

Nuclear protein of the testis carcinoma (NUTC) is a rare and aggressive malignancy. We herein report a case of NUTC in the lung characterized by a bronchial lesion and elevated alpha-fetoprotein levels. A 35-year-old Japanese man presented to our institution with suspected advanced lung cancer based on a histological examination. Subsequently, next-generation sequencing (NGS) yielded a positive BRD4-NUTM1 fusion. In addition, positive NUT immunostaining of the lung biopsy specimen confirmed NUTC in the lungs. Systemic chemotherapy and radiotherapy showed a temporary response, with decreased serum alpha-fetoprotein levels. We highlight this case of a prompt diagnosis by NGS of NUTC in a young individual with a rapidly progressing tumor.

8.
Int J Hematol ; 119(4): 459-464, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38349446

RESUMO

Although chimeric antigen receptor T-cell (CAR-T) therapies have dramatically improved the outcomes of relapsed/refractory B-cell malignancies, recipients suffer from severe humoral immunodeficiencies. Furthermore, patients with coronavirus disease 2019 (COVID-19) have a poor prognosis, as noted in several case reports of recipients who had COVID-19 before the infusion. We report the case of a 70-year-old woman who developed COVID-19 immediately before CAR-T therapy for high-grade B-cell lymphoma. She received Tixagevimab-Cilgavimab chemotherapy and radiation therapy but never achieved remission. She was transferred to our hospital for CAR-T therapy, but developed COVID-19. Her symptoms were mild and she was treated with long-term molnupiravir. On day 28 post-infection, lymphodepleting chemotherapy was restarted after a negative polymerase chain reaction (PCR) test was confirmed. The patient did not experience recurrence of COVID-19 symptoms or severe cytokine release syndrome. Based on the analysis and comparison of the previous reports with this case, we believe that CAR-T therapy should be postponed until a negative PCR test is confirmed. In addition, Tixagevimab-Cilgavimab and long term direct-acting antiviral agent treatment can be effective prophylaxis for severe COVID-19 and shortening the duration of infection.


Assuntos
COVID-19 , Hepatite C Crônica , Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Humanos , Feminino , Idoso , Antivirais , Imunoterapia Adotiva , Terapia Baseada em Transplante de Células e Tecidos , Antígenos CD19
9.
Int J Prosthodont ; 37(1): 27-33, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381983

RESUMO

PURPOSE: To determine the influence of partial edentulous distal extension and the use of removable partial dental prostheses in partially edentulous areas on the force exerted on the anterior teeth. MATERIALS AND METHODS: A total of 83 volunteer patients participated in this study. The occlusal force was measured using an occlusal force measuring sheet in the patient's mouth. The occlusal forces and ratios were compared using the Wilcoxon signed-rank test (P < .05). RESULTS: The force exerted on the anterior teeth increased significantly as the number of remaining teeth decreased in an edentulous distal extension. The force exerted on the anterior teeth decreased significantly with the use of a removable partial dental prosthesis. CONCLUSIONS: In a clinical setting, when the number of remaining teeth in a partial edentulous distal extension decreases, the burden on the anterior teeth increases. Our findings suggest that, for patients with partial edentulous distal extension, using a removable partial dental prosthesis is effective in preserving the residual anterior teeth by reducing excessive force.


Assuntos
Prótese Parcial Removível , Arcada Parcialmente Edêntula , Boca Edêntula , Humanos , Face , Força de Mordida
10.
Artigo em Inglês | MEDLINE | ID: mdl-38394439

RESUMO

PURPOSE: The purpose of this study was to examine the mechanical influence of edentulous mandibular morphology on peri-implant bone in implant prosthetics by finite element analysis. MATERIALS AND METHODS: Computed tomographic data from 25 patients with edentulous mandibles were selected and the radius of mandibular curvature and the height of the mandible at the midline were measured in order to clarify the morphological characteristics of the mandible. From the measurement, two patients with the smallest and largest radii of the mandible were selected. Two types of three-dimensional finite element models consisting of the edentulous mandible (small and large radius), superstructure (a cantilever bridge), implants, and abutments were created. Four implants were inserted between the right and left mental foramina. The upper surface of the mandibular condyle was constrained, and a vertical load of 100 N was applied on the occlusal surface of the right first molar. Three-dimensional finite element analysis of each model was performed to examine the mechanical influence of the edentulous mandibular morphology on the peri-implant bone. RESULTS: Measurement of mandibular morphology in CT images indicated that the lower the mandibular height was, the larger was the radius of the anterior mandibular curvature. Finite element analysis revealed that a higher equivalent stress was generated in the peri-implant bone of the model with a larger radius of curvature than that of the model with a smaller radius of curvature. The highest equivalent stress in the mandible was generated in the distal margin of the peri-implant bone posterior to the loaded side of the large radius of curvature model. CONCLUSIONS: The mandibular morphology had a mechanical influence on the peri-implant bone.

11.
Cancer Sci ; 115(4): 1317-1332, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38279512

RESUMO

T-cell acute leukemia and lymphoma have a poor prognosis. Although new therapeutic agents have been developed, their therapeutic effects are suboptimal. α-Pinene, a monoterpene compound, has an antitumor effect on solid tumors; however, few comprehensive investigations have been conducted on its impact on hematologic malignancies. This report provides a comprehensive analysis of the potential benefits of using α-pinene as an antitumor agent for the treatment of T-cell tumors. We found that α-pinene inhibited the proliferation of hematologic malignancies, especially in T-cell tumor cell lines EL-4 and Molt-4, induced mitochondrial dysfunction and reactive oxygen species accumulation, and inhibited NF-κB p65 translocation into the nucleus, leading to robust apoptosis in EL-4 cells. Collectively, these findings suggest that α-pinene has potential as a therapeutic agent for T-cell malignancies, and further investigation is warranted.


Assuntos
Monoterpenos Bicíclicos , Neoplasias Hematológicas , Neoplasias , Humanos , NF-kappa B/metabolismo , Linfócitos T/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células
12.
Int J Cancer ; 154(9): 1607-1615, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38196128

RESUMO

The relationships between the therapeutic effects of immune checkpoint inhibitors (ICIs) and the intestinal flora have attracted increasing attention. However, the effects of oral probiotics on the efficacies of ICIs used to treat non-small-cell lung cancer (NSCLC) remain unclear. We investigated the effects of probiotics on the efficacies of ICIs in patients treated with and without chemotherapy. We investigated patients with advanced NSCLC on ICI monotherapy or combination ICI and chemotherapy using the Okayama Lung Cancer Study Group Immunotherapy Database (OLCSG-ID) and the Okayama Lung Cancer Study Group Immunochemotherapy Database (OLCSG-ICD). In total, 927 patients (482 on ICI monotherapy, 445 on an ICI + chemotherapy) were enrolled. Most were male, of good performance status, smokers, and without epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutations. Probiotics were administered to 19% of patients on ICI monotherapies and 17% of those on ICIs + chemotherapy. Of the former patients, progression-free survival (PFS) and overall survival (OS) were significantly better in the probiotics group (PFS 7.9 vs. 2.9 months, hazard ratio [HR] 0.54, p < .001; OS not attained vs. 13.1 months, HR 0.45, p < .001). Among patients receiving ICI and chemotherapy, there were no significant differences in PFS between those on probiotics and not but OS was significantly better in the probiotics group (PFS 8.8 vs. 8.6 months, HR 0.89, p = .43; OS not attained vs. 22.6 months, HR 0.61, p = .03). Patients on probiotics experienced better outcomes following ICI treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Probióticos , Humanos , Masculino , Feminino , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Bases de Dados Factuais , Probióticos/uso terapêutico
14.
Cytopathology ; 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38050704

RESUMO

The Yokohama System for Reporting Endometrial Cytology (TYS) has been proposed by an expert meeting under the auspices of the International Academy of Cytology (IAC) in May 2016 at the IAC in Yokohama. Since its introduction, the TYS has been receiving worldwide acceptance, and this review aims to assess its global impact. The adoption of endometrial cytology as a diagnostic procedure has been hampered in the past by difficulties arising in interpreting the cellular findings due to a number of factors (such as excess blood, cellular overlapping and the complex physiology of endometrium). Recently, the use of liquid-based cytology (LBC), with its ability to remove blood and mucus and to distribute cells uniformly in a thin layer on the slide, has provided an opportunity to re-evaluate the role of endometrial cytology. LBC is a useful tool in the cytologic diagnosis and follow-up of endometrial abnormalities, which remains complementary to the emerging molecular diagnostic cytopathology. The study of LBC from endometrial cytology could be challenging since it is affected by numerous look-alikes and diagnostic pitfalls. This review discusses these various entities and takes into consideration the ancillary techniques that may be useful in the diagnostic procedure. In conclusion, our review of the published data suggests that the TYS is a valid classification scheme that has been widely accepted by cytopathologists globally, is highly reproducible and makes a valuable contribution to clinical therapeutic management. At present, molecular cytopathology is a rapidly evolving field of modern cytopathology, which underlines the effective interplay between genomics and cytology. This review aims to provide a comprehensive review of the drawbacks of endometrial cytopathology, particularly in terms of endometrial cancer diagnosis and molecular testing.

15.
J Palliat Care ; : 8258597231221924, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38115751

RESUMO

Objective: Corticosteroids are commonly used for symptom relief in patients with terminal cancer, but their use may have an impact on patient survival. We compared the survival of patients with terminal cancer who did and did not receive corticosteroid treatment for symptom relief, stratified by their predicted prognosis. Methods: We retrospectively reviewed consecutive patients with cancer who received corticosteroid treatment for symptom relief in a single palliative care unit. We stratified the patients according to their predicted prognosis using the palliative prognostic (PaP) score either before starting the corticosteroid treatment or at admission for control patients who did not receive a corticosteroid treatment. The 2 groups were compared for survival based on the PaP Scores. Results: We analyzed 204 patients treated with a corticosteroid during the study period and 139 control patients who did not receive corticosteroids during their treatment. No difference was observed in the survival between the treatment and control groups. Conclusion: Corticosteroid treatment for symptom relief in patients with terminal cancer did not affect survival time.

16.
J Clin Exp Hematop ; 63(4): 246-250, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38148014

RESUMO

Cold agglutinin disease (CAD) is a rare form of acquired autoimmune hemolytic anemia driven mainly by antibodies that activate the classical complement pathway. Several patients with CAD experience its development or exacerbation of hemolysis after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or after receiving the SARS-CoV-2 mRNA vaccine. Therefore, these patients cannot receive an additional SARS-CoV-2 mRNA vaccination and have a higher risk of severe SARS-CoV-2 infection. Sutimlimab is a monoclonal antibody that inhibits the classical complement pathway of the C1s protein and shows rapid and sustained inhibition of hemolysis in patients with CAD. However, whether sutimlimab could also inhibit hemolysis caused by SARS-CoV-2 mRNA vaccination is uncertain. Here, we present the case of a 70-year-old man with CAD who repeatedly experienced a hemolytic crisis after receiving SARS-CoV-2 mRNA vaccines. The patient eventually underwent SARS-CoV-2 mRNA vaccination safely, without hemolytic attack, under classical pathway inhibition therapy with sutimlimab. This report suggests that appropriate sutimlimab administration can suppress SARS-CoV-2 mRNA vaccination-induced CAD exacerbation, and that it could be a preventive strategy to minimize hemolytic attacks in susceptible populations.


Assuntos
Anemia Hemolítica Autoimune , COVID-19 , Masculino , Humanos , Idoso , Anemia Hemolítica Autoimune/etiologia , SARS-CoV-2 , Vacinas de mRNA , Vacinas contra COVID-19/efeitos adversos , Hemólise , RNA Mensageiro
17.
Transplantation ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38012835

RESUMO

BACKGROUND: Pegfilgrastim, a long-acting form of granulocyte-colony stimulating factor, with a convenient single-injection dosage, is being investigated for peripheral blood stem cell (PBSC) mobilization in healthy volunteers. However, data on the adequate dose of pegfilgrastim for PBSC mobilization are limited. This phase 2, single-arm study evaluated the efficacy and safety of pegfilgrastim for PBSC mobilization in healthy volunteers. METHODS: The study comprised 2 phases: pilot (steps 1-3, dose escalation, a single subcutaneous dose of 3.6, 7.2, and 10.8 mg pegfilgrastim, respectively) and evaluation (step 4, efficacy and safety assessments). The primary endpoint was the proportion of subjects who achieved mobilization of ≥20 × 106/L cluster of differentiation 34 positive (CD34+) cells. RESULTS: Thirty-five subjects (6 each in steps 1 and 2 and 23 in step 4) were included. In the pilot phase, step 3 with a 10.8 mg dose was not conducted due to favorable outcomes in step 2 (desired CD34+ cell count), at 7.2 mg pegfilgrastim, which was identified as the optimal dose for the evaluation phase. In the evaluation phase, successful CD34+ mobilization was achieved in all 23 subjects. The mean peripheral blood CD34+ cells count peaked on day 5. Back pain, thrombocytopenia, transient elevations of alkaline phosphatase, and lactate dehydrogenase were the most common adverse events. All adverse events were mild, and none led to study discontinuation. CONCLUSIONS: A single-dose pegfilgrastim successfully mobilized an optimal number of CD34+ cells and was well tolerated. Pegfilgrastim could be an alternative option for PBSC mobilization in healthy volunteers. The trial was registered at www.clinicaltrials.gov (NCT03993639).

18.
Transl Lung Cancer Res ; 12(10): 2098-2112, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-38025818

RESUMO

Background: Epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion and exon 21 L858R, are driver oncogenes of non-small cell lung cancer (NSCLC), with EGFR tyrosine kinase inhibitors (TKIs) being effective against EGFR-mutant NSCLC. However, the efficacy of EGFR-TKIs is transient and eventually leads to acquired resistance. Herein, we focused on the significance of cell cycle factors as a mechanism to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC before the emergence of acquired resistance. Methods: Using several EGFR-mutant cell lines, we investigated the significance of cell cycle factors to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC. Results: In several EGFR-mutant cell lines, certain cancer cells continued to proliferate without EGFR signaling, and the cell cycle regulator retinoblastoma protein (RB) was not completely dephosphorylated. Further inhibition of phosphorylated RB with cyclin-dependent kinase (CDK) 4/6 inhibitors, combined with the EGFR-TKI osimertinib, enhanced G0/G1 cell cycle accumulation and growth inhibition of the EGFR-mutant NSCLC in both in vitro and in vivo models. Furthermore, residual RB phosphorylation without EGFR signaling was maintained by extracellular signal-regulated kinase (ERK) signaling, and the ERK inhibition pathway showed further RB dephosphorylation. Conclusions: Our study demonstrated that the CDK4/6-RB signal axis, maintained by the MAPK pathway, attenuates the efficacy of EGFR-TKIs in EGFR-mutant NSCLC, and targeting CDK4/6 enhances this efficacy. Thus, combining CDK4/6 inhibitors and EGFR-TKI could be a novel treatment strategy for TKI-naïve EGFR-mutant NSCLC.

19.
Transfusion ; 63(11): 2120-2130, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37792312

RESUMO

BACKGROUND: Large-volume leukapheresis (LVL) refers to processing of more than three volumes of blood in a single session for peripheral blood stem cell collection. Recently, continuous mononuclear cell collection (cMNC) protocol has been developed using the Spectra Optia system, which is a widely used apheresis device. LVL using the novel protocol has been investigated in patients. However, the efficiency and safety of LVL in healthy donors using this protocol has not been characterized. Therefore, this study aimed to evaluate the efficiency and tolerability of CD34+ collection of LVL with the cMNC protocol in healthy donors. STUDY DESIGN AND METHODS: We retrospectively collected data on LVL (>3 total blood volume) and normal-volume leukapheresis (NVL) performed in healthy donors between October 2019 and December 2021. All procedures were performed using the cMNC protocol. RESULTS: Although pre-apheresis CD34+ cell count was lesser in LVL (23.5 vs. 58.0/µL, p < .001), CD34+ collection efficiency was comparable between LVL and NVL (61.2% vs. 61.4%, p = .966). Platelet loss was significantly higher in LVL compared to NVL (38.0% vs. 29.4%, p < .001), with no correlation between attrition of platelet and processing blood volume. Moreover, the incidence of citrate toxicity during procedures was comparable between the two groups (31.6% vs. 21.4%, p = .322). All LVL procedures could be completed without any adverse events. CONCLUSION: Allogeneic LVL procedure using Spectra Optia cMNC protocol was well tolerated by the donors and resulted in efficient collection of CD34+ cells, which was comparable to that of NVL.


Assuntos
Remoção de Componentes Sanguíneos , Células-Tronco de Sangue Periférico , Humanos , Leucaférese/métodos , Estudos Retrospectivos , Remoção de Componentes Sanguíneos/métodos , Leucócitos , Antígenos CD34 , Mobilização de Células-Tronco Hematopoéticas/métodos
20.
J Dent ; 139: 104763, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37879558

RESUMO

OBJECTIVES: Reduced occlusal support is thought to be related to a decline in masticatory performance. However, previous research in this field was based on cross-sectional studies. In this study, we conducted a 6-year longitudinal observation of older adults living in the community and examined the associations of changes in occlusal support with masticatory performance. METHODS: Of the 864 participants aged 72-74 years in the SONIC study, 488 who were followed up (median follow-up period 5.92 years) and had no missing data were included in this study. Participants were divided into three groups according to the number of occlusal support zones in the posterior area: Complete occlusion (four zones), Reduced occlusion (one to three zones), and Collapsed occlusion (no occlusal support zone). Longitudinal analysis of the relationship between occlusal support and masticatory performance was undertaken with linear mixed-effects models. RESULTS: Sex, occlusal force, number of unreplaced missing teeth, aging, and occlusal support change were significantly related to masticatory performance. Furthermore, the interaction term between change in occlusal support and aging was a significant explanatory variable for the decline in masticatory performance. The interaction was strongest in the group that changed from Complete or Reduced occlusion to Collapsed occlusion. This result indicates that the loss of occlusal support is a major factor contributing to declining masticatory performance. CONCLUSIONS: The decline of occlusal support was greatly associated with the deterioration of masticatory performance. Our results suggest that older adults need to prevent the collapse of posterior occlusal support to maintain their masticatory performance. CLINICAL SIGNIFICANCE: Occlusal support is important for preserving masticatory performance in older adults. Preventing the loss of molars and retaining occlusal support may contribute to maintaining food intake diversity and nutritional status, thereby improving quality of life. Dental professionals need to carefully examine dental status to assess the risk of occlusal collapse.


Assuntos
Mastigação , Qualidade de Vida , Humanos , Idoso , Estudos Transversais , Oclusão Dentária , Força de Mordida
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