RESUMEN
Background: There is ongoing debate regarding prostate cancer (PCa) screening in advanced age males, leading to treatment decisions often based on tumor staging and life expectancy. A critical gap in clinical evidence and tailored guidelines for the advanced age with PCa persists. This study aims to compare survival outcomes of various treatment approaches in this demographic. Methods: We analyzed data from a large urological center for advanced age patients suspected of having PCa between 2012 and 2022. We collected clinical and pathological characteristics and evaluated treatment modalities, including palliative therapy and definitive therapy. Propensity score matching (PSM) analysis was implemented to reduce bias between treatment modalities. Kaplan-Meier and multivariate Cox proportional hazard regression analyses were conducted to evaluate progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Results: Out of 4,333 suspected patients, 376 individuals aged 80 years and older underwent prostate biopsy. The overall detection rate of PCa was 78.7%, with a high prevalence of high-grade tumors [International Society of Urological Pathology (ISUP) grade ≥2]. Most patients (86.5%) received palliative therapy, while 13.5% underwent definitive therapy. Patients in the definitive therapy group had lower prostate-specific antigen (PSA) values, lower tumor stage, and Charlson Comorbidity Index (CCI), longer life expectancy, and a higher Geriatric 8 (G8) score compared to the palliative therapy group. The median OS for the entire cohort was 72.0 months, with 70.0 months for palliative therapy and 96.0 months for definitive therapy. Multivariable analyses identified lymphatic and bone metastasis, as well as definitive therapy, as independent prognostic factors for PFS, CSS, and OS. Conclusions: Advanced age patients, although a small group, have distinct characteristics, including higher PSA levels, positive biopsy rates, and pathological grading and staging. In medically fit elderly patients, especially those with localized PCa and a life expectancy of ≥5 years, definitive therapy could improve survival outcomes.
RESUMEN
AIM: To investigate whether MYC and BCL-2 coexpression has prognostic significance in primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) patients, and explore its associations with patients' clinical parameters. METHODS: Fresh and paraffin-embedded tumor tissue samples from 60 PGI-DLBCL patients who had undergone surgery at the Tianjin Medical University Cancer Institute and Hospital from January 2005 to May 2010 were obtained, and 30 lymphoid tissue samples from reactive lymph nodes of age- and sex-matched patients represented control samples. Staging and diagnostic procedures were conducted according to the Lugano staging system. All patients had been treated with three therapeutic modalities: surgery, chemotherapy, or radiotherapy. Expression of MYC and BCL-2 were detected at both protein and mRNA levels by immunohistochemistry and real-time RT-PCR. RESULTS: Positive expression levels of MYC and BCL-2 proteins were detected in 35% and 45% of patients, respectively. MYC+/BCL-2+ protein was present in 30% of patients. MYC and BCL-2 protein levels were correlated with high MYC and BCL-2 mRNA expression, respectively (both P<0.05). We found that advanced-stage disease (at IIE-IV) was associated with MYC and BCL-2 coexpression levels (P<0.05). In addition, MYC+/BCL-2+ patients had more difficulty in achieving complete remission than others (P<0.05). Presence of MYC protein expression only affected overall survival and progression-free survival (PFS) when BCL-2 protein was coexpressed. The adverse prognostic impact of MYC+/BCL-2+ protein on PFS remained significant (P<0.05) even after adjusting for age, Lugano stage, international prognostic index, and BCL-2 protein expression in a multivariable model. CONCLUSION: MYC+/BCL-2+ patients have worse chemotherapy response and poorer prognosis than patients who only express one of the two proteins, suggesting that assessment of MYC and BCL-2 expression by immunohistochemistry has clinical significance in predicting clinical outcomes of PGI-DLBCL patients.
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Gastrointestinales/química , Linfoma de Células B Grandes Difuso/química , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteínas Proto-Oncogénicas c-myc/análisis , Adulto , Anciano , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , China , Supervivencia sin Enfermedad , Femenino , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/terapia , Hospitales Universitarios , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-myc/genética , ARN Mensajero/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Solitary plasmacytoma (SP) is a rare tumor with low incidence. The aim of this study was to investigate the clinical features, treatment strategies, and relative prognostic factors of 66 patients with SP. These patients made up 10.25% of the 644 patients with plasma cell dyscrasias treated at the Tianjin Medical University Cancer Institute and Hospital over the past 12 years. SP always presented with either solitary bone plasmacytoma (SBP) or extramedullary plasmacytoma (EMP), as determined by the location of the lesions. SBP occurred most frequently in the vertebral column and EMP in the upper respiratory tract. In addition to other factors, tumor size, serum M protein level, urinary Bence Jones protein level, and disease progression toward multiple myeloma were significantly different between the two groups (P<0.05). Larger tumor size (≥5 cm) was associated with poor prognosis of local control, multiple myeloma-free survival, overall survival and progression-free survival for SBP patients. Radiotherapy and serum ß2 microglobulin <3.5 mg/L were favorable prognostic factors for local control, multiple myeloma-free survival, and progression-free survival in patients with EMP.
RESUMEN
OBJECTIVE: To explore the role of c-Myc in mesenchymal stromal cell-mediated drug resistance and elucidate the molecular mechanism of acute myeloid leukemia (AML) from the version of tumor microenvironment. METHODS: AML cell lines U937 and KG1a were co-cultured with mesenchymal stromal cells (MSC) from bone marrow of healthy donors between January to March 2012. The AML cell lines plated alone was cultured as controls. Apoptosis induced by mitoxantrone was measured by flow cytometry and Annexin V/PI double and 4'-6-diamidino-2-phenylindole (DAPI) staining. And c-Myc protein was detected by Western blot under both culturing conditions. After a pre-treatment of c-Myc inhibitor 10058-F4, the apoptosis of AML cell was also evaluated. RESULTS: Apoptosis of AML cells (U937 and KG1a) significantly decreased during co-culturing with MSC (9.88% ± 1.53% vs 42.83% ± 2.03%, P = 0.004;20.60% ± 2.87% vs 42.53% ± 5.29%, P = 0.030). Drug resistance was implicated. The co-culturing of AML cells with MSC significantly induced an up-regulation of c-Myc. The inhibition of c-Myc with 10058-F4 could induce apoptosis of AML cells. After an addition of 10058-F4 into the co-culture system, the apoptotic rate of KG1a cells significantly increased from 23.87% ± 1.55% to 57.23% ± 3.88% (P = 0.009). Similarly the apoptotic rates spiked from 16.07% ± 2.11% to 53.47% ± 4.08% in U937 cells (P = 0.004) to overcome the stromal cell-mediated drug resistance. CONCLUSIONS: The co-culturing of AML cells and MSC induces an up-regulation of c-Myc protein so as to cause the emergence of chemoresistance. Therefore targeting c-Myc protein may provide a novel therapeutic strategy of AML.
Asunto(s)
Resistencia a Antineoplásicos , Leucemia Mieloide Aguda/metabolismo , Células Madre Mesenquimatosas/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Adulto , Apoptosis , Línea Celular Tumoral , Femenino , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Adulto JovenRESUMEN
OBJECTIVE: This article aimed to review the biological characteristics of enhancer of zests homolog 2 (EZH2), and the transcriptional repression mechanism of action of EZH2 in tumors, particularly in the progression of lymphoma. DATA SOURCES: The data cited in this review were mainly obtained from the articles listed in PubMed and HighWare that were published from March 2004 to April 2012. The search terms were "enhancer of zests homolog 2", "polycomb group", and "lymphoma". STUDY SELECTION: Articles regarding the mechanism of EZH2 in post-transcriptional modification, functions of polycomb group proteins, and the roles of EZH2 in lymphoma were selected. RESULTS: EZH2 acts as oncogene and involved in many kinds of tumors. Moreover, it plays an important role in tumorigenesis and lymphomagenesis by promoting the proliferation and aggressiveness of neoplastic cells, facilitating malignant tumor cell diffusion, and mediating transcriptional silencing. CONCLUSION: EZH2 mediated transcriptional repression through its methyltransferase activity at the chromatin level has certain influence on lymphoma, and there might exist a therapeutic window for the development of new agents and identification of novel diagnostic markers based on EZH2.
Asunto(s)
Linfoma/etiología , Complejo Represivo Polycomb 2/fisiología , Progresión de la Enfermedad , Proteína Potenciadora del Homólogo Zeste 2 , Epigénesis Genética , Histonas/metabolismo , Humanos , Linfoma/genética , Metilación , Mutación , Complejo Represivo Polycomb 2/genéticaRESUMEN
The effects of conventional treatment for myelodysplastic syndrome (MDS) are not remarkable to date, while only a minority of patients was eligible for allogeneic stem cell transplantation. As epigenetics plays a significant role during the occurrence and development of MDS, and histone deacetylase inhibitors (HDACI), a class of gene expression modulating drugs, are currently being developed for therapy of several types of solid tumor, more attention is paying to HDACI as potential therapy of MDS. This review summarizes briefly the rationale for HDACI use in MDS, the common mechanism of HDACI, the present state of the clinical efficiency, and future development in this field.
Asunto(s)
Inhibidores de Histona Desacetilasas/uso terapéutico , Síndromes Mielodisplásicos/tratamiento farmacológico , Epigénesis Genética , Humanos , Síndromes Mielodisplásicos/genéticaRESUMEN
Lymphomas encompass a group of malignancies that originate in the lymph nodes or other lymphoid tissues. Epigenetic modification, especially by histone deacetylase (HDACs), plays a key role during the occurrence and development of lymphomas. Consequently, HDAC inhibitors (HDACIs), a class of gene expression-modulating drugs, have emerged as promising mechanism-based agents for the treatment of lymphomas. This review presents the rationale of HDAC inhibition, describes the epigenetic-based mechanisms of action of HDACIs, discusses their clinical efficiency, and summarizes the current and future developments in this field.