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1.
Ann Hematol ; 100(4): 995-1002, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33651193

RESUMO

Waldenstrom macroglobulinemia (WM) is a rare type of non-Hodgkin lymphoma with great heterogeneity, and the data of peripheral blood T-lymphocyte subsets in WM are limited. This study aimed to investigate the clinical correlation and distribution of circulating T-lymphocyte subsets in newly diagnosed WM patients. We retrospectively searched medical records for 86 newly diagnosed WM patients. Comparisons of the absolute CD3+ T-lymphocyte count (ACD3C), CD4+ T-lymphocyte count (ACD4C), CD8+ T-lymphocyte count (ACD8C), and CD4+/CD8+ T-lymphocyte ratio (CD4+/CD8+) as continuous parameters in different groups were calculated. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). Young patients (<65 years) had lower ACD8C levels and a higher CD4+/CD8+ ratio. And the lower level of ß2-microglobulin (<3 mg/L) was associated with a higher CD4+/CD8+ ratio. With a median follow-up of 25 months, the univariate survival analysis showed that CD4+/CD8+ ratio inversion (CD4+/CD8+<1.5) was associated with shorter OS and PFS, and multivariate analysis confirmed that inverted CD4+/CD8+ ratio could be an independent adverse prognostic factor for OS and PFS. Additionally, initial treatment with rituximab or bortezomib significantly improved the PFS and OS of CD4+/CD8+ inversion patients but did not affect normal CD4+/CD8+ patients. We show that low circulating CD4+/CD8+ ratio at diagnosis is an adverse prognostic factor in WM patients and that first-line therapy which included rituximab or bortezomib significantly improved PFS and OS for patients with CD4+/CD8+ ratio less than 1.5.


Assuntos
Relação CD4-CD8 , Macroglobulinemia de Waldenstrom/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Alquilantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/mortalidade , Microglobulina beta-2/análise
2.
Medicine (Baltimore) ; 100(3): e24273, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546048

RESUMO

ABSTRACT: The exact dose of cytarabine still remain controversial for the management of patients with acute myeloid leukemia (AML) after complete remission (CR), but recent studies favor lower doses. This study aimed to investigate the toxic effects of single-intermediate dose (ID) cytarabine in patients with AML after achieving CR, compared with standard-dose cytarabine.In this retrospective study, AML patients who achieved CR after consolidation therapy before enrollment between 07/2008 and 05/2019 were included. All patients were divided into single-ID cytarabine and standard-dose cytarabine. The Kaplan-Meier method was used to compare overall survival (OS) and relapse-free time (RFS). Cox regression models were used to assess factors independently associated with OS and RFS. The toxic side effects of hematology and non-hematology were observed.52 patients were enrolled. There were 33 in ID group, 19 in Standard dose group. The 3-year RFS rate (40.4% vs 22.2%, P = .031) was better in the ID group than in the standard-dose group, while the 3-year OS rate was not different between the 2 groups (50.2% vs 27.8%, P = .074). Treatment stratage of ID cytarabine chemotherapy significantly improve the prognosis of AML regardless of patient age, risk grade, WBC count. There were no significant differences between the 2 groups in grade 3 to 4 bone marrow suppression, gastrointestinal symptoms, blood transfusion, infections.Patients with AML receiving ID cytarabine showed better survival and similar toxicity profiles compared with patients who received standard-dose cytarabine.


Assuntos
Quimioterapia de Consolidação/normas , Citarabina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Indução de Remissão/métodos , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Quimioterapia de Consolidação/métodos , Quimioterapia de Consolidação/estatística & dados numéricos , Citarabina/farmacologia , Citarabina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida
3.
Ann Hematol ; 100(4): 979-986, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33608849

RESUMO

High-dose methotrexate (HD-MTX) at 3 g/m2 is one of the strategies for central nervous system (CNS) prophylaxis in the first-line treatment of aggressive lymphomas, especially in diffuse large B cell lymphoma patients with high-risk CNS-International Prognostic Index. The objective of our study was to retrospectively analyze the safety of 2 cycles of systemic HD-MTX administered as an ambulatory regimen. Between January 2013 and December 2016, 103 patients were carefully selected on 6 criteria, including age < 60, albumin > 34, performance status 0 or 1, normal renal and hepatic functions, good understanding of practical medical guidance, and no loss of weight. Strict procedures of HD-MTX infusion were observed including alkalinization, urine pH monitoring, and leucovorin rescue. Renal and hepatic functions were monitored at days 2 and 7. MTX clearance was not monitored. Toxicities and grades of toxicity were collected according to the NCI-CTCAE (version 4.0). Among the 103 selected patients, 92 (89%) patients successfully completed the planned 2 cycles of HD-MTX on an outpatient basis. Eleven patients completed only 1 cycle, 3 because of lymphoma progression and 8 because of toxicity including 3 grade II hepatotoxicity, 2 grade I/II renal toxicity, 1 grade III neutropenia, 1 active herpetic infection, and 1 grade III ileus reflex. Reported adverse events (AE) included 92 (84%) grade I/II and 18 (16%) grade III/IV. Grade III hepatotoxicity, mostly cytolysis, was the most frequent AE observed with 8 (8%) events. Grade III/IV hematologic toxicities concerned 9 patients with 8 grade III/IV neutropenia and 1 thrombocytopenia. Renal toxicity was rare, mild, and transient, observed with 4 (4%) grade I/II events. Ambulatory administration of HD-MTX at 3 g/m2 without MTX clearance monitoring is safe with strict medical guidance. It requires careful selection of patients before administration, and a renal and hepatic monitoring after the administration.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Sistema Nervoso Central/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Metotrexato/uso terapêutico , Adolescente , Adulto , Assistência Ambulatorial , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Infusões Intravenosas , Nefropatias/induzido quimicamente , Testes de Função Renal , Leucovorina/uso terapêutico , Testes de Função Hepática , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/patologia , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Invasividade Neoplásica , Ambulatório Hospitalar , Prednisona/administração & dosagem , Estudos Retrospectivos , Rituximab/administração & dosagem , Vincristina/administração & dosagem , Vindesina/administração & dosagem , Adulto Jovem
4.
Medicine (Baltimore) ; 100(6): e24703, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578607

RESUMO

RATIONALE: The abnormal expression of B-cell lymphoma-2 (Bcl-2) family members is often associated with the progression of the disease. Bcl-2 inhibitors (eg, venetoclax) were first reported to inhibit the proliferation of malignant lymphocytes and have a significant effect on patients with chronic lymphoblastic leukemia, but research on myeloid tumors is relatively delayed. Venetoclax was approved in 2018 for the treatment of acute myeloid leukemia (AML) patients who were not suitable for high-dose chemotherapy. The approval of venetoclax is an advance in the treatment of hematological tumors. PATIENT CONCERNS: Here we report a 64-year-old male with an increased white blood cell (WBC) count (39.0 × 109/L) and lymphocyte count (30.6 × 109/L) on physical examination in July 2014. The patients were diagnosed with chronic lymphocytic leukemia (CLL) through bone marrow (BM) smears and immunophenotyping without any cytogenetic or molecular abnormalities. Chlorambucil was prescribed, WBC was stable between 15 × 109/L and 25 × 109/L in the past 6 years. He came to the hospital again in May 2020 and complained of fatigue for 2 weeks. WBC (16.7 × 109/L) and lymphocyte (14.76 × 109/L) counts were increased, hemoglobin (HGB) and platelet (PLT) were decreased in peripheral blood, which indicated the progression of the disease. DIAGNOSES: The patient was diagnosed as secondary AML after CLL based on the clinical and laboratory findings. INTERVENTIONS: He achieved a morphological complete remission in both AML and CLL without any adverse reactions after one course of venetoclax monotherapy. OUTCOMES: He received standard daunorubicin and cytarabine combined with venetoclax as consolidation therapy and is now ready for allogeneic-hematopoietic stem cell transplantation. LESSONS: Our case presents a challenge to traditional treatment. New drugs such as venetoclax have shown outstanding effects in this respect. High expression of Bcl-2 can identify the responders of venetoclax. These findings should be validated in future clinical trials. We fully believe that in the near future, the comprehensive use of targeted drugs with different mechanisms will not only improve the quality of life of patients, but also completely change the prognosis of patients with recurrent and refractory hematological malignancies.


Assuntos
Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/etiologia , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Daunorrubicina/administração & dosagem , Daunorrubicina/uso terapêutico , Progressão da Doença , Transplante de Células-Tronco Hematopoéticas/normas , Humanos , Imunofenotipagem/métodos , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Mieloide Aguda/patologia , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Resultado do Tratamento
5.
BMJ Case Rep ; 14(1)2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414115

RESUMO

Symptomatic drug-induced liver injury (DILI) is an uncommon problem. Direct DILI is dose-related, predictable with short latency (hour to days) and is generally associated with transient and reversible transaminitis without jaundice. Antimetabolites including methotrexate are a common cause for direct DILI. Hepatotoxicity associated with high-dose methotrexate (HD-MTX) is generally transient and includes reversible elevation of transaminase in up to 60% and associated hyperbilirubinaemia (≤grade 2) in 25% of courses and therefore is of no clinical significance. Severe grades of DILI with HD-MTX (grade ≥4) are extremely rare. We describe an adolescent with Burkitt leukaemia who had reversible grade 4 DILI including hyperbilirubinaemia postfirst course of HD-MTX. Rechallenge with two-third dose of HD-MTX in subsequent chemotherapeutic cycle did not cause recurrence of DILI.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Linfoma de Burkitt/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Hiperbilirrubinemia/induzido quimicamente , Metotrexato/efeitos adversos , Antimetabólitos Antineoplásicos/administração & dosagem , Criança , Relação Dose-Resposta a Droga , Humanos , Masculino , Metotrexato/administração & dosagem , Índice de Gravidade de Doença
6.
Medicine (Baltimore) ; 99(51): e23719, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371122

RESUMO

ABSTRACT: Maintenance treatment after first-line chemotherapy for patients with metastatic colorectal cancer (mCRC) is a priority strategy. However, which medicine is chosen is controversial. This study aimed to determine the efficacy and safety of maintenance treatment with metronomic capecitabine vs observation.In this randomized controlled trial, patients who completed 18 weeks of induction chemotherapy with XELOX and achieved disease control were randomly assigned centrally (1:1) to receive maintenance therapy with metronomic chemotherapy or observation until disease progression. The primary endpoint was progression-free survival from randomization; secondary endpoints included overall survival and safety. Analyses were performed by intention to treat.Between January 1st, 2017 and December 31th 2018, 48 patients were enrolled and randomly assigned to receive maintenance treatment with metronomic capecitabine (n = 25) or only observation (n = 23). The median progression-free survival in the metronomic capecitabine group was 5.66 (95% confidence interval [CI] 5.25-6.07) months vs 3.98 (95%CI 3.71-4.24) months in the observation group (hazard ratio 0.11, 95% [CI] 0.04-0.26, P = .000). There was no statistically significant difference in median overall survival: 23.82 (95% CI 22.38-25.25) months in the metronomic capecitabine group vs 21.81 (95% CI 20.23-23.38) months in the observation group (hazard ratio 0.49, 95% CI 0.21-1.11, P = .087). Subgroup analyses were generally consistent with the primary finding. Similar safety profiles were observed in both arms. The most frequent adverse events in metronomic capecitabine group included neutropenia, diarrhea, hand-foot skin reaction, and mucositis.Maintenance therapy with metronomic capecitabine can be considered an alternative option following first-line chemotherapy of XELOX in patients with metastatic colorectal cancer with controlled toxicities.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Oxaloacetatos/uso terapêutico , Administração Metronômica , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Neoplasias Colorretais/patologia , Feminino , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Oxaloacetatos/administração & dosagem , Oxaloacetatos/efeitos adversos , Intervalo Livre de Progressão
7.
Medicine (Baltimore) ; 99(50): e23606, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327329

RESUMO

INTRODUCTION: Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative neoplasm of early childhood characterized by excessive proliferation of myelomonocytic cells and an aggressive clinical course. Allogenic hematopoietic stem cell transplantation (HSCT) is a firmly established treatment, but patients without fully matched donors have poor prognoses. Disease recurrence is the main cause of treatment failure. Meanwhile, most cases with splenomegaly present with platelet transfusion refractoriness, but splenectomy remains controversial. DNA hypermethylation correlates with poor prognosis in JMML; however, hypomethylating therapy alone does not eradicate leukemic clones. Thus, a suitable treatment with a good success rate remains elusive. PATIENT CONCERNS: Here, we report our experience with a patient who suffered from recurrent fever, pallor, abdominal distention, leukocytosis, and thrombocytopenia with a silent past history and family history of somatic KRAS mutation. The patient was treated with decitabine as a bridging therapy before haploidentical HSCT. Decitabine was also used prophylactically after transplantation. DIAGNOSIS: We arrived at a JMML diagnosis after observing leukocytosis, less than 20% blast cells in the peripheral blood and bone marrow, increased monocyte counts, negativity for the BCR-ABL fusion gene, positivity for somatic KRAS mutation, and massive splenomegaly. INTERVENTIONS: The patient accepted splenectomy before HSCT, and haploidentical HSCT was applied after treatment with a DNA-hypomethylating agent. The hypomethylating agent was administered for 1 year after HSCT to prevent disease recurrence. OUTCOMES: The patient presented with complete remission of the disease and mild graft versus host disease for 26 months after treatment with decitabine and HSCT. LESSONS: Combining haploidentical HSCT and DNA-hypomethylating agents may improve the prognosis of JMML. Meanwhile, splenectomy could be an effective option in cases with massive splenomegaly and platelet transfusion refractoriness.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Decitabina/uso terapêutico , Leucemia Mielomonocítica Juvenil/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Antimetabólitos Antineoplásicos/administração & dosagem , Terapia Combinada , Decitabina/administração & dosagem , Diagnóstico Diferencial , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Leucemia Mielomonocítica Juvenil/terapia , Masculino , Recidiva Local de Neoplasia/terapia
8.
Medicine (Baltimore) ; 99(50): e23615, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327333

RESUMO

RATIONALE: Myeloid sarcomas (MS) are defined as rare extramedullary masses composed of immature myeloid cells. MS mostly develops in patients with acute myeloid leukemia (AML), and involves primarily the skin, soft tissues, bones, and lymph nodes. Pleura and pericardium involvement of MS are extremely uncommon. Polyserositis is also a very rare extramedullary presentation of acute myeloid leukemia (AML). PATIENT CONCERNS: A 30-year-old woman with a complaint of right neck mass combined with coughing for 2 months as well as fever and systemic edema for the last 10 days, was admitted to our center on July 11, 2019. Initial positron emission tomography (PET) scan indicated systemic lymphadenopathy, bilateral pleural effusion, and pericardial effusion. DIAGNOSIS: The initial pathological diagnosis of lymph nodes was MS. Subsequent bone marrow analysis confirmed AML. INTERVENTIONS: Conventional IA induction regimen followed by high-dose cytarabine (HiDAC) regimen. OUTCOMES: Complete absorption of pericardial and pleural effusion after the first cycle of IA induction chemotherapy. LESSONS: Polyserositis can be an extramedullary presentation of AML. Patients with polyserositis should undergo routine flow cytometric analysis. For AML with extamedullary infiltration, systemic chemotherapy should be administered in all confirmed cases.


Assuntos
Leucemia Mieloide Aguda/diagnóstico , Sarcoma Mieloide/diagnóstico , Adulto , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Derrame Pericárdico/etiologia , Derrame Pleural/etiologia , Tomografia por Emissão de Pósitrons , Sarcoma Mieloide/complicações , Sarcoma Mieloide/diagnóstico por imagem , Sarcoma Mieloide/tratamento farmacológico , Tomografia Computadorizada por Raios X
9.
N Engl J Med ; 383(26): 2526-2537, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33369355

RESUMO

BACKGROUND: Although induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor. METHODS: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of the oral formulation of azacitidine (CC-486, a hypomethylating agent that is not bioequivalent to injectable azacitidine), as maintenance therapy in patients with AML who were in first remission after intensive chemotherapy. Patients who were 55 years of age or older, were in complete remission with or without complete blood count recovery, and were not candidates for hematopoietic stem-cell transplantation were randomly assigned to receive CC-486 (300 mg) or placebo once daily for 14 days per 28-day cycle. The primary end point was overall survival. Secondary end points included relapse-free survival and health-related quality of life. RESULTS: A total of 472 patients underwent randomization; 238 were assigned to the CC-486 group and 234 were assigned to the placebo group. The median age was 68 years (range, 55 to 86). Median overall survival from the time of randomization was significantly longer with CC-486 than with placebo (24.7 months and 14.8 months, respectively; P<0.001). Median relapse-free survival was also significantly longer with CC-486 than with placebo (10.2 months and 4.8 months, respectively; P<0.001). Benefits of CC-486 with respect to overall and relapse-free survival were shown in most subgroups defined according to baseline characteristics. The most common adverse events in both groups were grade 1 or 2 gastrointestinal events. Common grade 3 or 4 adverse events were neutropenia (in 41% of patients in the CC-486 group and 24% of patients in the placebo group) and thrombocytopenia (in 22% and 21%, respectively). Overall health-related quality of life was preserved during CC-486 treatment. CONCLUSIONS: CC-486 maintenance therapy was associated with significantly longer overall and relapse-free survival than placebo among older patients with AML who were in remission after chemotherapy. Side effects were mainly gastrointestinal symptoms and neutropenia. Quality-of-life measures were maintained throughout treatment. (Supported by Celgene; QUAZAR AML-001 ClinicalTrials.gov number, NCT01757535.).


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Quimioterapia de Manutenção , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Quimioterapia de Manutenção/efeitos adversos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Qualidade de Vida , Indução de Remissão , Análise de Sobrevida
10.
Medicine (Baltimore) ; 99(43): e22923, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120845

RESUMO

RATIONALE: Most acute promyelocytic leukemia (APL) patients respond to all-trans-retinoic acid (ATRA)and have a good prognosis. However, variants APL who carry PLZF/RARа, STAT5B/RARа, and STAT3/RARа are insensitive to ATRA and have poor prognoses. The standard treatment for variants APL is still unclear due to the small sample size. PATIENT CONCERNS: Here we reported a Chinese male who was admitted to our hospital with the complaint of rib pain, dyspnea, and fever (37.5°C). Blood tests showed leukopenia (1.83 × 10/L), anemia (hemoglobin 73 g/L), and thrombocytopenia (54 × 10/L). Prothrombin time and activated partial thromboplastin time were normal. DIAGNOSES: The patient was diagnosed as STAT5b-RARa-positive APL based on the clinical and laboratory findings. INTERVENTIONS: ATRA was used immediately for induction treatment, then he was treated with ATRA + arsenic trioxide and got the severe cardiac insufficiency. Subsequently, consolidation chemotherapy was added with ATRA + Huangdai tablets + idarubicin and decitabine, cytarabine, aclamycin (DCAG). OUTCOMES: The patient relapsed soon after his first molecular complete remission (CRm), fortunately, he got a second CRm with DCAG. He has survived for more than 9 months and remains CRm, now he is looking for a suitable donor to prepare for hematopoietic stem cell transplantation (HSCT). LESSONS: APL patients with STAT5B-RARa is not only resistant to ATRA, but also to conventional combination chemotherapy such as daunorubicin and cytarabine/idarubicin and cytarabine or other regimens. Relapse and extramedullary infiltration is common, HSCT is a effective treatment, and the best time for HSCT is after the first CR. It should be noted that this patient got CRm with DCAG after relapse, so the role of decitabine in APL with STAT5B-RARa needs to be considered.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Decitabina/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Adolescente , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Trióxido de Arsênio/administração & dosagem , Trióxido de Arsênio/uso terapêutico , Grupo com Ancestrais do Continente Asiático/genética , Quimioterapia de Consolidação , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Decitabina/administração & dosagem , Quimioterapia Combinada , Feminino , Hospitalização , Humanos , Idarubicina/administração & dosagem , Idarubicina/uso terapêutico , Leucemia Promielocítica Aguda/genética , Masculino , Pessoa de Meia-Idade , Recidiva , Receptor alfa de Ácido Retinoico/metabolismo , Fator de Transcrição STAT5/metabolismo , Resultado do Tratamento , Tretinoína/efeitos adversos , Tretinoína/uso terapêutico
11.
Anticancer Res ; 40(9): 4869-4874, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878774

RESUMO

BACKGROUND/AIM: In the present study, we evaluated the efficacy of adjuvant administration of oral recombinant methioninase (o-rMETase) against recurrence and metastasis in a 4T1 murine breast-cancer syngeneic model. MATERIALS AND METHODS: 4T1 cells were orthotopically implanted into the 2nd mammary fat pad of BALB/c mice. The 4T1 orthotopic syngeneic models were randomized into 2 groups after primary tumor resection: untreated control and o-rMETase (100 units, oral, daily, 2 weeks). RESULTS: The frequency and extent of local recurrence were reduced by o-rMETase. The number of individual cancer cells and metastatic nodules on the lung surface was significantly lower in the o-rMETase-treated mice than the untreated control mice. CONCLUSION: Adjuvant o-rMETase inhibited local recurrence and lung metastasis after primary tumor resection.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Liases de Carbono-Enxofre/administração & dosagem , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Neoplasias Mamárias Experimentais/tratamento farmacológico , Administração Oral , Animais , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Esquema de Medicação , Feminino , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/cirurgia , Camundongos , Camundongos Endogâmicos BALB C , Recidiva Local de Neoplasia/prevenção & controle , Proteínas Recombinantes/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Medicine (Baltimore) ; 99(39): e22335, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991445

RESUMO

INTRODUCTION: Plasmablastic lymphoma (PBL) is an uncommon and aggressive large B-cell lymphoma commonly diagnosed in human immunodeficiency viruses -positive patients. Oral cavity is the most commonly PBL affected site. Most oral PBLs presented as asymptomatic swellings, frequently associated with ulcerations and bleeding. Most cases lacked B-symptoms, suggesting a more local involvement of the disease. No standard treatment is yet for oral PBL. Five-year survival rate recorded no more than 33.5%. PATIENT CONCERNS: A 39-year-old male presented to Dental Clinic with 1 month swelling of the oral cavity, in absence of any other symptoms or signs. He followed antibiotic therapy just on suspicion of an oral abscess and later oral surgical treatment on suspicion of bone neoplasm. DIAGNOSIS: Surgical specimen analysis highlighted a diffuse infiltrate of large-sized atypical cells with plasmablastic appearance and plasma cell phenotype. Oral cavity PBL was diagnosed. Blood tests recorded mild lymphopenia and positive human immunodeficiency viruses serology. INTERVENTIONS: Patient underwent chemotherapy including intrathecal methotrexate prophylaxis, in addition to a highly active antiretroviral therapy. OUTCOMES: At 12 months from diagnosis, patient recorded complete hematological remission. CONCLUSIONS: Oral PBL diagnosis requires a high level of suspicion and awareness both by physicians and pathologists. They should be aware of the extent of such disease which is often mistaken as oral abscess or infected tooth, thus leading to delay the most appropriate diagnostic evaluation. As PBL is an aggressive non-Hodgkin lymphoma, a delayed diagnosis might negatively impact on both treatment and survival.


Assuntos
Antineoplásicos/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Boca/patologia , Linfoma Plasmablástico/tratamento farmacológico , Abscesso/diagnóstico , Abscesso/tratamento farmacológico , Adulto , Assistência ao Convalescente , Antibacterianos/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Quimioterapia Combinada , Edema/etiologia , Infecções por HIV/complicações , Soropositividade para HIV/sangue , HIV-1/imunologia , Humanos , Injeções Espinhais , Linfoma não Hodgkin/patologia , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Plasmócitos/patologia , Linfoma Plasmablástico/diagnóstico por imagem , Resultado do Tratamento
13.
Int J Nanomedicine ; 15: 5417-5432, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801697

RESUMO

Introduction: Green-based materials have been increasingly studied to circumvent off-target cytotoxicity and other side-effects from conventional chemotherapy. Materials and Methods: Here, cellulose fibers (CF) were isolated from rice straw (RS) waste by using an eco-friendly alkali treatment. The CF network served as an anticancer drug carrier for 5-fluorouracil (5-FU). The physicochemical and thermal properties of CF, pure 5-FU drug, and the 5-FU-loaded CF (CF/5-FU) samples were evaluated. The samples were assessed for in vitro cytotoxicity assays using human colorectal cancer (HCT116) and normal (CCD112) cell lines, along with human nasopharyngeal cancer (HONE-1) and normal (NP 460) cell lines after 72-hours of treatment. Results: XRD and FTIR revealed the successful alkali treatment of RS to isolate CF with high purity and crystallinity. Compared to RS, the alkali-treated CF showed an almost fourfold increase in surface area and zeta potential of up to -33.61 mV. SEM images illustrated the CF network with a rod-shaped structure and comprised of ordered aggregated cellulose. TGA results proved that the thermal stability of 5-FU increased within the drug carrier. Based on UV-spectroscopy measurements for 5-FU loading into CF, drug loading encapsulation efficiency was estimated to be 83 ±0.8%. The release media at pH 7.4 and pH 1.2 showed a maximum drug release of 79% and 46%, respectively, over 24 hours. In cytotoxicity assays, CF showed almost no damage, while pure 5-FU killed most of the both normal and cancer cells. Impressively, the drug-loaded sample of CF/5-FU at a 250 µg/mL concentration demonstrated a 58% inhibition against colorectal cancer cells, but only a 23% inhibition against normal colorectal cells. Further, a 62.50 µg/mL concentration of CF/5FU eliminated 71% and 39% of nasopharyngeal carcinoma and normal nasopharyngeal cells, respectively. Discussion: This study, therefore, showed the strong potential anticancer activity of the novel CF/5-FU formulations, warranting their further investigation.


Assuntos
Celulose/química , Portadores de Fármacos/química , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Fluoruracila/farmacocinética , Células HCT116 , Humanos , Neoplasias Nasofaríngeas/tratamento farmacológico , Oryza/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Difração de Raios X
14.
Int J Nanomedicine ; 15: 5445-5458, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801699

RESUMO

5-Fluorouracil (5-FU) has become one of the most widely employed antimetabolite chemotherapeutic agents in recent decades. It is considered a first line antineoplastic agent for the treatment of colorectal cancer. Unfortunately, chemotherapy with 5-FU has several limitations, including its short half-life, high cytotoxicity and low bioavailability. In order to overcome the drawbacks of 5-FU and enhance its therapeutic efficiency, many scientific groups have focused on designing a new delivery system to successfully deliver 5-FU to tumor sites. We provide a comprehensive review on different strategies to design effective delivery systems, including nanoformulations, drug-conjugate formulations and other strategies for the delivery of 5-FU to colorectal cancer. Furthermore, co-delivery of 5-FU with other therapeutics is discussed. This review critically highlights the recent innovations in and literature on various types of carrier system for 5-FU.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Fluoruracila/administração & dosagem , Animais , Antimetabólitos Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Disponibilidade Biológica , Portadores de Fármacos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/farmacocinética , Humanos , Nanoestruturas/administração & dosagem , Nanoestruturas/química
15.
Medicine (Baltimore) ; 99(31): e21432, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756152

RESUMO

INTRODUCTION: A cesarean scar pregnancy (CSP), when combined with an arteriovenous malformation (AVM), is a rare, but potentially life-threatening condition that may be associated with uncontrolled hemorrhage. Hysterectomy is indicated when conservative treatment fails. Preservation of fertility is challenging. PATIENT CONCERNS: We reported a 33-year-old woman with a CSP combined with an AVM who failed methotrexate administration as conservative treatment. DIAGNOSES: A CSP combined with an AVM was diagnosed via three-dimensional color Doppler angiogram and magnetic resonance imaging. INTERVENTIONS: Transvaginal removal of the ectopic gestation and repair of the uterine defect was performed without incident. OUTCOMES: The fertility of the patient was preserved and hysterectomy was avoided. CONCLUSION: Transvaginal fertility-sparing surgery may be successfully performed to prevent hysterectomy when conservative treatment fails in patients with a CSP combined with an AVM.


Assuntos
Malformações Arteriovenosas/complicações , Malformações Arteriovenosas/cirurgia , Cicatriz/patologia , Preservação da Fertilidade/métodos , Adulto , Angiografia/métodos , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/tratamento farmacológico , Cesárea/efeitos adversos , Cicatriz/cirurgia , Feminino , Humanos , Imageamento Tridimensional/métodos , Imagem por Ressonância Magnética/métodos , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Gravidez , Gravidez Ectópica/cirurgia , Resultado do Tratamento , Ultrassonografia Doppler em Cores/métodos
16.
PLoS One ; 15(8): e0235503, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760083

RESUMO

PURPOSE: We evaluated the outcomes of decitabine as first-line treatment in older patients with acute myeloid leukemia (AML) and investigated the predictors, including a baseline mini nutritional assessment short form (MNA-SF) score, of response and survival. PATIENTS AND METHODS: Between 2010 and 2018, 96 AML patients aged 65 and above who received decitabine treatment at 6 centers in Korea were retrospectively evaluated. Response rates, hematologic improvements (HI), progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: The median age at diagnosis was 73.9 years, and the median number of decitabine treatments administered to the patients was 4 (range, 1-29). Of 85 patients, 15 patients (17.6%) achieved complete remission (CR) or CR with incomplete blood count recovery. Twelve patients (14.1%) showed partial remission (PR), and 18 (21.2%) demonstrated HI without an objective response. The median PFS and OS were 7.0 (95% confidence interval [CI], 4.9-9.0) and 10.6 (95% CI, 7.7-13.5%) months, respectively. In multivariate analyses, MNA-SF score ≥ 8 and the absence of peripheral blood (PB) blasts were significant predictors for improved PFS and OS. CONCLUSIONS: For older patients with newly diagnosed AML, a high MNA-SF score and the absence of PB blasts were independently associated with improved survival.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Decitabina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Indução de Remissão/métodos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Contagem de Células Sanguíneas , Medula Óssea/patologia , Decitabina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Avaliação Nutricional , Intervalo Livre de Progressão , República da Coreia/epidemiologia , Estudos Retrospectivos , Perda de Peso
17.
Surgery ; 168(3): 448-456, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32620306

RESUMO

BACKGROUND: We describe the use of pancreatic retrograde venous infusion in an orthotopic murine model of pancreatic ductal adenocarcinoma and hypothesize that pancreatic retrograde venous infusion delivery of gemcitabine will increase concentrations of gemcitabine in the tumor and the subsequent tumor response to treatment. METHODS: Murine pancreatic ductal adenocarcinoma (KPC4580P) was transplanted onto the pancreatic tail of C57BL/6J mice. Groups (n = 15) of mice were assigned to sham laparotomy and 100 mg/kg intraperitoneal infusion of gemcitabine (systemic gemcitabine), pancreatic venous isolation with pancreatic retrograde venous infusion of 100 mg/kg gemcitabine, or pancreatic retrograde venous infusion with saline infusion. Tumor pressures were recorded during pancreatic retrograde venous infusion. Mice were killed at 1 hour or 7 days after infusion. RESULTS: Baseline tumor pressures were 45 ± 8 mm Hg, and pancreatic retrograde venous infusion increased tumor pressures by 29 ± 6 mm Hg (P < .01). Pancreatic retrograde venous infusion gemcitabine mice had greater tumor gemcitabine concentrations compared with systemic gemcitabine (127 vs 19 ng/mg; P < .01) and lesser tumor volumes compared with both systemic gem and pancreatic retrograde venous infusion with saline (274 vs 857 vs 629 mm3; P < .01). CONCLUSION: Pancreatic retrograde venous infusion increased tumor pressures greater than baseline, improved gemcitabine delivery, and increased the treatment response. These findings suggest that pressurized, regional delivery overcomes the increased pressure barrier in pancreatic ductal adenocarcinoma. Additional preclinical studies with cytotoxic and immunotherapeutic agents and clinical trials using pressure-enabled drug delivery with pancreatic retrograde venous infusion devices are underway.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Infusões Intralesionais/métodos , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Antimetabólitos Antineoplásicos/farmacocinética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral/transplante , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacocinética , Modelos Animais de Doenças , Humanos , Infusões Intravenosas/métodos , Masculino , Camundongos , Pâncreas/irrigação sanguínea , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Pressão , Distribuição Tecidual
18.
Dermatol Online J ; 26(3)2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32609455

RESUMO

Keratoacanthomas are rapidly growing neoplasms of squamous epithelium. Despite their benign nature, they are often difficult to distinguish from squamous cell carcinoma and require excision. In cases in which excision is not successful or not desired, intralesional treatments may be considered. However, limited research exists on individual therapeutic efficacy. We present a 68-year-old man who developed multiple eruptive keratoacanthomas around the wound edge of a previous keratoacanthoma excision. Considering previous excisional failure, intralesional 5-fluorouracil was used as a treatment modality. Injections every 3-4 weeks over a course of 12 weeks induced clinical keratoacanthoma clearance with excellent cosmetic results. This case showcases that weekly intralesional 5-fluorouracil injections, as was the standard mode of treatment in previous case reports, may not be necessary. This less frequent injection strategy is more convenient for the patient and may lead to fewer treatments and less medication necessary. Although a case-by-case basis is needed for any alternative approach to keratoacanthoma treatment, this report is useful for the practicing clinician in showing that 5-fluorouracil may be efficacious in these difficult-to-treat patients.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Fluoruracila/administração & dosagem , Ceratoacantoma/tratamento farmacológico , Idoso , Braço/cirurgia , Humanos , Injeções Intralesionais , Ceratoacantoma/cirurgia , Masculino , Recidiva
19.
Oncol Rep ; 44(4): 1758-1770, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32700745

RESUMO

Breast cancer is the leading cause of cancer­-associated deaths in women. Combination immunotherapy attracts great interest as a treatment for breast cancer. However, there are no studies on the use of cytotoxic T­lymphocyte antigen 4 (CTLA­4) monoclonal antibody in combination with the melanoma­associated antigen A family (MAGE­As) co­antigen peptide (p248V9) for treating breast cancer, which should be explored. To this aim, in the present study, the samples of 115 patients with breast cancer were collected, and MAGE­As and CTLA­4 levels in breast cancer and adjacent normal tissues were assessed by immunohistochemical staining. The effect of 5­aza­2'­deoxycytidine (5DC) on the expression of MAGE­As in breast cancer cell lines was assessed by reverse transcription­quantitative PCR and western blot assay. Cytotoxic T cells (CTLs) were induced by MAGE­As co­antigen peptide. The specific lytic rate and IFN­Î³ level were examined by CCK­8 assay and ELISA, respectively. It was found that MAGE­As were highly expressed in breast cancer tissues. 5DC treatment promoted the expression of MAGE­As in breast cancer cells. The upregulation of the expression of MAGE­As specifically enhanced the ability of CTLs to kill breast cancer cells. CTLA­4 was highly expressed in breast cancer tissues and cells, and patients with breast cancer exhibiting high expression of CTLA­4 had low overall survival. CTLA­4 promoted the lytic efficiency of CTLs in breast cancer cells, and the combination of an anti­CTLA­4 antibody and 10 µM 5DC exhibited the highest cell lysis ability of CTLs. The present study demonstrated that MAGE­As co­antigen peptide­specific CTLs in combination with an anti­CTLA­4 monoclonal antibody and 5DC, have potent tumor cell­killing effects. It provides a novel theory for the development of breast cancer therapies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Antígeno CTLA-4/antagonistas & inibidores , Carcinoma Ductal de Mama/tratamento farmacológico , Antígenos Específicos de Melanoma/metabolismo , Linfócitos T Citotóxicos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Antígeno CTLA-4/imunologia , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Linhagem Celular Tumoral , Decitabina/administração & dosagem , Feminino , Seguimentos , Humanos , Metástase Linfática , Células MCF-7 , Antígenos Específicos de Melanoma/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Taxa de Sobrevida , Linfócitos T Citotóxicos/efeitos dos fármacos
20.
Medicine (Baltimore) ; 99(25): e20809, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569228

RESUMO

RATIONALE: Pyrotinib is a novel dual pan-ErbB receptor tyrosine kinase inhibitor, approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). However, there was still limited information regarding specific effect of pyrotinib on HER2-positive MBC patients with phosphoinositol-3 kinase mutation. PATIENT CONCERNS: A 63-year-old woman accidentally discovered a left breast lesion. The breast cancer was diagnosed by biopsy of breast lesion and postoperative pathological examination in March, 2017. The patient was presented with HER2-positive (3+), invasive carcinoma of the left breast with lymph nodes and lung nodules metastasis, and the clinical stage was T4N2M1. However, the lesion continued to aggressive disease progression with the treatment of trastuzumab plus multiple chemotherapy regimens and traditional Chinese medicine. DIAGNOSES: The woman was diagnosed with invasive carcinoma of the left breast and lymph nodes and lung nodules metastasis. INTERVENTIONS: The patient received 6 cycles of pyrotinib in combination with capecitabine regularly. OUTCOMES: Progression free survival was more than 6 months, and the patient's efficacy evaluation was partial remission. LESSONS: Our clinical observations demonstrated that pyrotinib may be an effective treatment for patients with HER2-positive MBC.


Assuntos
Acrilamidas/uso terapêutico , Aminoquinolinas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Acrilamidas/administração & dosagem , Aminoquinolinas/administração & dosagem , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade
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