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PURPOSE: To compare the oncological safety of nipple-sparing breast-conserving surgery (BCS) versus central lumpectomy for centrally located breast cancer (CLBC). METHODS: Patients who underwent BCS for CLBC at Asan Medical Center from 2007 to 2018 were reviewed retrospectively. The oncological outcomes of nipple-sparing BCS (NS-BCS) and central lumpectomy were compared using univariate and multivariate Cox regression analyses and compared again after 1:1 propensity score matching (PSM). RESULTS: The study included 306 patients who underwent NS-BCS and 106 patients who underwent central lumpectomy (median follow-up: 111 months). On multivariate analysis, central lumpectomy had a lower risk of local recurrence compared to NS-BCS, albeit without statistical significance (HR 0.14, 95% CI 0.02-1.24; p = 0.077). There was no significant difference in the risk of death (HR 0.14, 95% CI 0.01-1.68, p = 0.12). After PSM, each group had 106 patients. The 5-year and 10-year local recurrence-free survival rates were 94.2% and 92.9% for NS-BCS, and 99.1% and 99.1% for central lumpectomy, respectively (p = 0.031). There were no significant differences in overall survival, regional recurrence-free survival, or distant recurrence-free survival. Fifteen patients (4.9%) who underwent NS-BCS had ipsilateral breast tumor recurrence (IBTR), of which 40% were in the nipple-areolar complex and previous surgical sites. One patient (0.9%) who underwent central lumpectomy experienced an IBTR in a different quadrant. CONCLUSION: NS-BCS showed more local recurrence than central lumpectomy. When deciding whether to spare the nipple during BCS in CLBC, patients should be sufficiently informed about the risk of IBTR.
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Neoplasias de la Mama , Mastectomía Segmentaria , Recurrencia Local de Neoplasia , Pezones , Puntaje de Propensión , Humanos , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Femenino , Persona de Mediana Edad , Pezones/cirugía , Mastectomía Segmentaria/métodos , Estudios Retrospectivos , Adulto , Anciano , Resultado del Tratamiento , Tratamientos Conservadores del Órgano/métodos , Estudios de SeguimientoRESUMEN
The formation of red blood cells begins with the differentiation of multipotent haematopoietic progenitors. Reconstructing the steps of this differentiation represents a general challenge in stem-cell biology. Here we used single-cell transcriptomics, fate assays and a theory that allows the prediction of cell fates from population snapshots to demonstrate that mouse haematopoietic progenitors differentiate through a continuous, hierarchical structure into seven blood lineages. We uncovered coupling between the erythroid and the basophil or mast cell fates, a global haematopoietic response to erythroid stress and novel growth factor receptors that regulate erythropoiesis. We defined a flow cytometry sorting strategy to purify early stages of erythroid differentiation, completely isolating classically defined burst-forming and colony-forming progenitors. We also found that the cell cycle is progressively remodelled during erythroid development and during a sharp transcriptional switch that ends the colony-forming progenitor stage and activates terminal differentiation. Our work showcases the utility of linking transcriptomic data to predictive fate models, and provides insights into lineage development in vivo.
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Eritrocitos/citología , Células Precursoras Eritroides/citología , Eritropoyesis , Animales , Basófilos/citología , Ciclo Celular/genética , Ciclo Celular/fisiología , Linaje de la Célula/efectos de los fármacos , Linaje de la Célula/genética , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Células Precursoras Eritroides/efectos de los fármacos , Células Precursoras Eritroides/metabolismo , Eritropoyesis/efectos de los fármacos , Femenino , Citometría de Flujo , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/farmacología , Mastocitos/citología , Ratones , Proteínas Proto-Oncogénicas c-kit/metabolismo , ARN Citoplasmático Pequeño/análisis , ARN Citoplasmático Pequeño/genética , Análisis de la Célula Individual , TranscriptomaRESUMEN
PURPOSE: Relapsing polychondritis (RP) is a rare systemic autoimmune disease affecting cartilaginous and non-cartilaginous structures. Neurological involvement is rarer but results in profound disability. Early identification and treatment of underlying RP may promote neurological recovery. CASE REPORT: We illustrated a 53-year-old man diagnosed with dementia. Neuroimaging and cerebrospinal fluid studies disclosed meningoencephalitis. "Prominent ear sign" was evident on diffusion-weight magnetic resonance imaging. After glucocortisone administration, the improvement of clinical manifestations was closely correlated subsequent neuroimaging findings. CONCLUSION: The importance of better understanding of this disease in terms of the prevention of further tissue damage in patients with RP cannot be overemphasized.
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Demencia/diagnóstico , Meningoencefalitis/diagnóstico , Policondritis Recurrente/diagnóstico , Demencia/etiología , Humanos , Imagen por Resonancia Magnética , Masculino , Meningoencefalitis/etiología , Persona de Mediana Edad , Policondritis Recurrente/complicaciones , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Purpose: Tumescent in nipple-sparing mastectomy (NSM) has been reported to increase the risk of necrosis by impairing blood flow to the skin flap and nipple-areolar complex. At our institution, we introduced a tumescent-free robotic NSM using the da Vinci single-port system (Intuitive Surgical, Inc.). Methods: We conducted a retrospective analysis of patients who underwent tumescent-free robotic NSM between October 2020 and March 2023 at Asan Medical Center (Seoul, Korea). Clinicopathological characteristics, adverse events, and operative time were evaluated. Results: During the study period, 118 patients underwent tumescent-free robotic NSM. Thirty-one patients (26.3%) experienced an adverse event. Five patients (4.2%) were classified as grade III based on the Clavien-Dindo classification and required surgery. The mean total operative time was 467 minutes for autologous tissue reconstruction (n = 49) and 252 minutes for implants (n = 69). No correlation was found between the cumulative number of surgical cases and the breast operative time (P = 0.30, 0.52, 0.59 for surgeons A, B, C) for the 3 surgeons. However, a significant linear relationship (P < 0.001) was observed, with the operative time increasing by 13 minutes for every 100-g increase in specimen weight. Conclusion: Tumescent-free robotic NSM is a safe procedure with a feasible operative time and few adverse events.
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PURPOSE: This study aimed to investigate the frequency of BRCA testing and related factors among young breast cancer patients (age < 40 years) in South Korea. MATERIALS AND METHODS: We conducted a nationwide retrospective cohort study using data from the Health Insurance Review and Assessment claims. Newly diagnosed breast cancer patients younger than 40 were included. Annual BRCA testing ratios (number of BRCA test recipients/the number of patients undergoing breast cancer surgery in each year) were analyzed by region and health care delivery system. We investigated the location of breast cancer diagnosis and BRCA testing. RESULTS: From January 2010 to December 2020, there were 25,665 newly diagnosed young breast cancer patients, of whom 12,186 (47.5%) underwent BRCA testing. The BRCA testing ratios increased gradually from 0.084 (154/1,842) in 2010 to 0.961 (1,975/2,055) in 2020. Medical aid (vs. health insurance) and undergoing surgery in metropolitan cities or others (vs. Seoul), general hospitals, and clinics (vs. tertiary hospitals) were associated with a lower likelihood of BRCA testing. While 97.8% of the patients diagnosed in Seoul underwent BRCA testing in Seoul, 22.9% and 29.2% of patients who were diagnosed in metropolitan areas and other regions moved to Seoul and underwent BRCA testing, respectively. CONCLUSION: The frequency of BRCA testing has increased over time in South Korea, with Seoul showing a particularly high rate of testing. About one-quarter of patients diagnosed with breast cancer outside of Seoul moved to Seoul and underwent BRCA testing.
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Proteína BRCA1 , Proteína BRCA2 , Neoplasias de la Mama , Pruebas Genéticas , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/diagnóstico , República de Corea/epidemiología , Adulto , Pruebas Genéticas/estadística & datos numéricos , Pruebas Genéticas/métodos , Estudios Retrospectivos , Proteína BRCA1/genética , Proteína BRCA2/genética , Adulto Joven , Predisposición Genética a la EnfermedadRESUMEN
Early erythroid progenitors were originally defined by their colony-forming potential in vitro and classified into burst-forming and colony-forming "units" known as BFU-e and CFU-e. Until recently, methods for the direct prospective and complete isolation of pure BFU-e and CFU-e progenitors from freshly isolated adult mouse bone marrow were not available. To address this gap, a single-cell RNA-seq (scRNAseq) dataset of mouse bone marrow was analyzed for the expression of genes coding for cell surface markers. This analysis was combined with cell fate assays, allowing the development of a novel flow cytometric approach that identifies and allows the isolation of complete and pure subsets of BFU-e and CFU-e progenitors in mouse bone marrow or spleen. This approach also identifies other progenitor subsets, including subsets enriched for basophil/mast cell and megakaryocytic potentials. The method consists of labeling fresh bone marrow or spleen cells with antibodies directed at Kit and CD55. Progenitors that express both these markers are then subdivided into five principal populations. Population 1 (P1 or CFU-e, Kit+ CD55+ CD49fmed/low CD105med/high CD71med/high) contains all of the CFU-e progenitors and may be further subdivided into P1-low (CD71med CD150high) and P1-hi (CD71high CD150low), corresponding to early and late CFU-e, respectively; Population 2 (P2 or BFU-e, Kit+ CD55+ CD49fmed/low CD105med/high CD71low CD150high) contains all of the BFU-e progenitors; Population P3 (P3, Kit+ CD55+ CD49fmed/high CD105med/low CD150low CD41low) is enriched for basophil/mast cell progenitors; Population 4 (P4, Kit+ CD55+ CD49fmed/high CD105med/low CD150high CD41+) is enriched for megakaryocytic progenitors; and Population 5 (P5, Kit+ CD55+ CD49fmed/high CD105med/low CD150high CD41-) contains progenitors with erythroid, basophil/mast cell, and megakaryocytic potential (EBMP) and erythroid/ megakaryocytic/ basophil-biased multipotential progenitors (MPPs). This novel approach allows greater precision when analyzing erythroid and other hematopoietic progenitors and also allows for reference to transcriptome information for each flow cytometrically defined population.
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Células Precursoras Eritroides , Células Madre , Ratones , Animales , Citometría de Flujo , Integrina alfa6 , Estudios ProspectivosRESUMEN
Essentially all cell cycling in multicellular organisms in vivo takes place in the context of lineage differentiation. This notwithstanding, the regulation of the cell cycle is often assumed to be generic, independent of tissue or developmental stage. Here we review developmental-stage-specific cell cycle adaptations that may influence developmental decisions, in mammalian erythropoiesis and in other lineages. The length of the cell cycle influences the balance between self-renewal and differentiation in multiple tissues, and may determine lineage fate. Shorter cycles contribute to the efficiency of reprogramming somatic cells into induced pluripotency stem cells and help maintain the pluripotent state. While the plasticity of G1 length is well established, the speed of S phase is emerging as a novel regulated parameter that may influence cell fate transitions in the erythroid lineage, in neural tissue and in embryonic stem cells. A slow S phase may stabilize the self-renewal state, whereas S phase shortening may favor a cell fate change. In the erythroid lineage, functional approaches and single-cell RNA-sequencing show that a key transcriptional switch, at the transition from self-renewal to differentiation, is synchronized with and dependent on S phase. This specific S phase is shorter, as a result of a genome-wide increase in the speed of replication forks. Furthermore, there is progressive shortening in G1 in the period preceding this switch. Together these studies suggest an integrated regulatory landscape of the cycle and differentiation programs, where cell cycle adaptations are controlled by, and in turn feed back on, the propagation of developmental trajectories. This article is categorized under: Congenital Diseases > Stem Cells and Development.
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Células Madre Embrionarias , Animales , Ciclo Celular , Diferenciación Celular , División Celular , Fase SRESUMEN
The erythroid terminal differentiation program couples sequential cell divisions with progressive reductions in cell size. The erythropoietin receptor (EpoR) is essential for erythroblast survival, but its other functions are not well characterized. Here we use Epor-/- mouse erythroblasts endowed with survival signaling to identify novel non-redundant EpoR functions. We find that, paradoxically, EpoR signaling increases red cell size while also increasing the number and speed of erythroblast cell cycles. EpoR-regulation of cell size is independent of established red cell size regulation by iron. High erythropoietin (Epo) increases red cell size in wild-type mice and in human volunteers. The increase in mean corpuscular volume (MCV) outlasts the duration of Epo treatment and is not the result of increased reticulocyte number. Our work shows that EpoR signaling alters the relationship between cycling and cell size. Further, diagnostic interpretations of increased MCV should now include high Epo levels and hypoxic stress.
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Ciclo Celular , Tamaño de la Célula , Eritrocitos/citología , Eritrocitos/metabolismo , Eritropoyesis , Receptores de Eritropoyetina/metabolismo , Adulto , Animales , Antígenos CD/metabolismo , Antígenos CD4/metabolismo , Diferenciación Celular , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Supervivencia Celular , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Embrión de Mamíferos/metabolismo , Eritroblastos/citología , Eritroblastos/efectos de los fármacos , Eritroblastos/metabolismo , Eritropoyetina/administración & dosificación , Eritropoyetina/farmacología , Femenino , Feto/metabolismo , Voluntarios Sanos , Humanos , Hierro/metabolismo , Hígado/embriología , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Modelos Biológicos , Proteínas Serina-Treonina Quinasas/metabolismo , Receptores de Transferrina/metabolismo , Reticulocitos/citología , Reticulocitos/efectos de los fármacos , Reticulocitos/metabolismo , Transducción de Señal , Proteína bcl-X/metabolismoRESUMEN
Cell cycle regulators are increasingly implicated in cell fate decisions, such as the acquisition or loss of pluripotency and self-renewal potential. The cell cycle mechanisms that regulate these cell fate decisions are largely unknown. We studied an S phase-dependent cell fate switch, in which murine early erythroid progenitors transition in vivo from a self-renewal state into a phase of active erythroid gene transcription and concurrent maturational cell divisions. We found that progenitors are dependent on p57KIP2-mediated slowing of replication forks for self-renewal, a novel function for cyclin-dependent kinase inhibitors. The switch to differentiation entails rapid down-regulation of p57KIP2 with a consequent global increase in replication fork speed and an abruptly shorter S phase. Our work suggests that cell cycles with specialized global DNA replication dynamics are integral to the maintenance of specific cell states and to cell fate decisions.
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Inhibidor p57 de las Quinasas Dependientes de la Ciclina/metabolismo , Replicación del ADN/fisiología , Células Eritroides/metabolismo , Fase S/fisiología , Animales , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/genética , Células Eritroides/citología , Femenino , Ratones , Ratones Mutantes , Transcripción Genética/fisiologíaRESUMEN
Baculovirus simultaneously displaying and expressing the avian influenza virus (AIV) hemagglutinin (HA) protein can induce potent anti-HA humoral and cellular immune responses. Based on the hypothesis that improving the antigen expression and presentation can further boost the AIV vaccine efficacies, we first constructed a baculoviral vector (Bac-HAW) with HA gene fused with the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) near its 3' end and expressed under the control of the hybrid CAG promoter. The WPRE fusion improved the HA expression and augmented the humoral and Th1 cellular immune responses after intramuscular administration into BALB/c mice. With Bac-HAW as the backbone, we next constructed Bac-HAMW which harbored the HA gene flanked with the signal sequence (MHCIss) and trafficking domain (MITD) of MHC class I molecule. In comparison with Bac-HAW, Bac-HAMW ameliorated the HA peptide presentation, significantly elevated the HA-specific humoral response (total IgG, IgG2a and hemagglutination inhibition titers) and favorably boosted the Th1 and IFN-γ(+)/CD8(+) T cell responses without extraneous adjuvants. These data collectively confirmed that enhancement of antigen expression and presentation by combining the WPRE and MHCIss/MITD fusion can potentiate the immunogenicity of the baculovirus-based vaccine, and implicates the potential of Bac-HAMW as an appealing AIV vaccine.