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1.
Lancet Haematol ; 7(12): e861-e873, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33242443

RESUMO

BACKGROUND: The phase 3 GIMEMA-MMY-3006 trial, which compared bortezomib, thalidomide, and dexamethasone (VTD) combination therapy with thalidomide and dexamethasone (TD) as induction therapy before and consolidation therapy after double autologous haematopoietic stem-cell transplantation (HSCT) for newly diagnosed multiple myeloma, showed the superiority of the triplet regimen over the doublet in terms of increased complete response rate and improved progression-free survival. We report the results from the final analysis of the study. METHODS: In this randomised, open-label, phase 3 study, patients aged 18-65 years with previously untreated symptomatic multiple myeloma and a Karnofsky Performance Status of 60% or higher were enrolled at 73 centres in Italy. Patients were randomised (1:1) by a web-based system to receive three 21-day cycles of thalidomide (100 mg daily orally for the first 14 days and 200 mg daily thereafter) plus dexamethasone (total 320 mg per cycle; 40 mg on days 1-2, 4-5, 8-9, and 11-12 in the VTD regimen, and 40 mg on days 1-4 and 9-12 in the TD regimen), either alone (TD group) or with bortezomib (1·3 mg/m2 intravenously on days 1, 4, 8, and 11; VTD group). After double autologous HSCT, patients received two 35-day cycles of either the VTD or TD regimen, according to random assignment, as consolidation therapy. The primary outcome was the rate of complete response and near complete response after induction (already reported). In this updated analysis we assessed long-term progression-free survival and overall survival (secondary endpoints of the study) with an extended 10-year median follow-up, and analysed the variables influencing survival. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, NCT01134484. FINDINGS: Between May 10, 2006, and April 30, 2008, 480 patients were enrolled and randomly assigned to receive VTD (241 patients) or TD (239 patients). Six patients withdrew consent before start of treatment. 236 (99 [42%] women) in the VTD group and 238 (102 [43%] women) in the TD group were included in the intention-to-treat analysis. The data cutoff date for this analysis was May 31, 2018. Median follow-up for surviving patients was 124·1 months (IQR 117·2-131·7). The 10-year progression-free survival estimate for patients in the VTD group was 34% (95% CI 28-41) compared with 17% (13-23) for the TD group (hazard ratio [HR] 0·62 [95% CI 0·50-0·77]; p<0·0001). 60% (95% CI 54-67) of patients in the VTD group were alive at 10 years versus 46% (40-54) of patients in the TD group (HR 0·68 [95% CI 0·51-0·90]; p=0·0068). VTD was an independent predictor of improved progression-free survival (HR 0·60 [95% CI 0·48-0·76]; p<0·0001) and overall survival (HR 0·68 [0·50-0·91]; p=0·010). The incidence of second primary malignancies per 100 person-years was 0·87 (95% CI 0·49-1·44) in the VTD group compared with 1·41 (0·88-2·13) in the TD group. INTERPRETATION: Incorporation of VTD into double autologous HSCT resulted in clinically meaningful improvements in long-term progression-free survival and overall survival, confirming that a regimen including bortezomib and an immunomodulatory drug is the gold standard treatment for patients with newly diagnosed myeloma who are fit for high-dose chemotherapy. FUNDING: Seràgnoli Institute of Haematology, University of Bologna, and BolognAIL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Talidomida/uso terapêutico , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Bortezomib/farmacologia , Dexametasona/farmacologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Talidomida/farmacologia , Adulto Jovem
2.
Medicine (Baltimore) ; 99(43): e22832, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120810

RESUMO

BACKGROUND: Anterior cruciate ligament rupture is a common motor system injury, and the most effective treatment is anterior cruciate ligament reconstruction (ACLR). Choosing the right graft is an important factor to ensure the success of the surgery. Current research shows that the clinical effect of autologous ligaments is better than that of allogeneic ligaments and artificial ligaments. However, there are differences between the autogenous ligaments, and how to choose them is still controversial. This study evaluated the published systematic reviews on the efficacy of different autologous ligament grafts in ACLR, and based on this, conducted a network meta-analysis of related randomized controlled trials. METHODS: We searched 8 international and Chinese databases including PubMed, Embase, Web of Science, and Cochrane Library. The methodological quality of systematic reviews will be evaluated by Assessing the Methodological Quality of Systematic Reviews-2 (AMSTAR2) measurement tool. Cochrane's risk of bias tool will be used to assess the risk of bias of included randomized controlled trials, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will be used to evaluate the evidence quality. Network meta-analysis will be applied to evaluate the therapeutic effect of different autologous grafts. The main outcome measures are IKDC score, clinical failure rate, Lachman test, Lysholm score, and the incidence of complications. Odds ratio and its 95% confidence interval will be used to synthesize the dichotomy results, while the mean difference and 95% confidence interval of continuous variables will be used for continuous variables. RESULTS: This study will provide comprehensive evidence for the application of autologous grafts in ACLR. CONCLUSION: The results of this study will help clinicians make appropriate decisions. PROTOCOL REGISTRATION NUMBER: INPLASY202090061.


Assuntos
Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Transplante Autólogo/métodos , Humanos , Metanálise em Rede , Revisões Sistemáticas como Assunto
3.
Nat Commun ; 11(1): 5173, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33057068

RESUMO

In ovarian cancer (OC), IL-17-producing T cells (Th17s) predict improved survival, whereas regulatory T cells predict poorer survival. We previously developed a vaccine whereby patient-derived dendritic cells (DCs) are programmed to induce Th17 responses to the OC antigen folate receptor alpha (FRα). Here we report the results of a single-arm open-label phase I clinical trial designed to determine vaccine safety and tolerability (primary outcomes) and recurrence-free survival (secondary outcome). Immunogenicity is also evaluated. Recruitment is complete with a total of 19 Stage IIIC-IV OC patients in first remission after conventional therapy. DCs are generated using our Th17-inducing protocol and are pulsed with HLA class II epitopes from FRα. Mature antigen-loaded DCs are injected intradermally. All patients have completed study-related interventions. No grade 3 or higher adverse events are seen. Vaccination results in the development of Th1, Th17, and antibody responses to FRα in the majority of patients. Th1 and antibody responses are associated with prolonged recurrence-free survival. Antibody-dependent cell-mediated cytotoxic activity against FRα is also associated with prolonged RFS. Of 18 patients evaluable for efficacy, 39% (7/18) remain recurrence-free at the time of data censoring, with a median follow-up of 49.2 months. Thus, vaccination with Th17-inducing FRα-loaded DCs is safe, induces antigen-specific immunity, and is associated with prolonged remission.


Assuntos
Vacinas Anticâncer/administração & dosagem , Células Dendríticas/transplante , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Ovarianas/terapia , Células Th17/imunologia , Idoso , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/imunologia , Intervalo Livre de Doença , Feminino , Receptor 1 de Folato/imunologia , Humanos , Imunidade Humoral , Injeções Intradérmicas , Interferon gama/metabolismo , Interleucina-17/metabolismo , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/mortalidade , Células Th17/metabolismo , Transplante Autólogo/efeitos adversos , Transplante Autólogo/métodos
4.
Medicine (Baltimore) ; 99(44): e22931, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126356

RESUMO

RATIONALE: Synchronous development of both anaplastic large cell lymphoma (ALCL) and multiple myeloma (MM) in a patient is rare. To our knowledge, until now only one case has been reported. Treatment needs to cover both and is a challenge. Here we reported another case and discussed the diagnosis and treatment. PATIENT CONCERNS: This is a 63-year old woman who presented with a mass in upper abdominal skin. Positron emission tomography/computed tomography (PET/CT) showed the high metabolism in left abdominal skin and left axillary lymph nodes. Histopathologic and immunohistochemical evaluation identified the cutaneous mass as an ALK-negative ALCL. Bone marrow smear showed increased plasma cells which expressed CD38, CD138, and cLambda concomitantly. The increased monoclonal immunoglobulin IgD λ was detected by immunofixation electrophoresis. DIAGNOSES: Diagnosis of both ALCL and MM was confirmed. INTERVENTIONS: The patient successively received 6 cycles of B-CHOD regimen, one cycle of ID regimen, 2 cycles of DHAX regimen, one cycle of L-DA-EPOCH and autologous stem cell transplantation (ASCT). Then lenalidomide was performed as a maintenance therapy. OUTCOMES: Both ALCL and MM achieved complete remission. LESSONS: We reported a very rare case with synchronous development of ALCL and MM, in whom a good therapeutic response to chemotherapies followed by ASCT has been observed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Lenalidomida/administração & dosagem , Linfoma Anaplásico de Células Grandes , Mieloma Múltiplo , Neoplasias Cutâneas , Parede Abdominal/patologia , Bleomicina/administração & dosagem , Exame de Medula Óssea/métodos , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Imuno-Histoquímica , Linfoma Anaplásico de Células Grandes/imunologia , Linfoma Anaplásico de Células Grandes/patologia , Linfoma Anaplásico de Células Grandes/terapia , Quimioterapia de Manutenção/métodos , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/terapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Prednisona/administração & dosagem , Indução de Remissão , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Transplante Autólogo/métodos , Vincristina/administração & dosagem
5.
Medicine (Baltimore) ; 99(40): e22535, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019460

RESUMO

RATIONALE: Adolescent wrist trauma can cause epiphyseal dysplasia and even distal radius deformity malunion. At present, there is no uniform treatment standard for the malunion of the distal radius of adolescents. Osteotomy and autologous bone grafting are currently one of the effective ways to treat the disease. We treated an adolescent patient with distal radius deformity malunion, and used this surgical method to treat the patient and achieved satisfactory results. PATIENT CONCERNS: A 16-year-old boy suffered from a serious distal radius deformity after trauma of the left wrist 8 years ago. DIAGNOSES: Physical examination, X-rays examination, high-resolution computed tomography scan, and 3-dimensional reconstruction images of the affected limb helped us diagnose the distal radius fracture malunion. INTERVENTIONS: The fracture malunion was treated by osteotomy and autologous iliac bone grafting. OUTCOMES: At the 2-year follow-up, wrist flexion returned to 68°, wrist dorsiflexion to 55°, radial deviation to 14°, ulnar deviation to 12°, forearm pronation to 75°, supination to 67°. Grip strength increased to 35.1 kg after 2 years of operation, recovered to 87% of the uninjured side. Quick DASH score at 2-year follow-up was 9. No complication, such as nonunion or infection, was observed. LESSONS: This rare case provides valuable insights for hand surgeons. High-resolution computed tomography scan and 3-dimensional reconstruction can help us effectively diagnose wrist diseases. Small lesions on the articular surface of the distal radius will change the position and function of the wrist joint, and cause traumatic arthritis of the wrist joint. Therefore, it is very important to reconstruct the normal structure of the distal radius articular surface. Osteotomy and autologous iliac bone grafting are effective treatments for serious distal radius fracture malunion in the adolescent patient. During the operation, care should be taken to protect the osteoepiphysis to avoid bone dysplasia.


Assuntos
Fraturas Mal-Unidas/cirurgia , Osteotomia/métodos , Fraturas do Rádio/complicações , Transplante Autólogo/métodos , Adolescente , Assistência ao Convalescente , Transplante Ósseo/métodos , Fraturas Mal-Unidas/diagnóstico por imagem , Humanos , Ílio/transplante , Processamento de Imagem Assistida por Computador/instrumentação , Masculino , Radiografia/métodos , Amplitude de Movimento Articular , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Articulação do Punho/fisiologia
6.
Medicine (Baltimore) ; 99(40): e22642, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019490

RESUMO

RATIONALE: Reactivation of hepatitis B virus (HBV) after treatment with bortezomib-based regimens in HBV-positive patients with multiple myeloma (MM) has been reported in the past few years. Nevertheless, there is evidence of inhibition of HBV replication by bortezomib in transgenic mice. However, there is still no clinical evidence that bortezomib inhibits HBV. PATIENT CONCERNS: A 55-year-old MM patient with a family history of MM, who was also a chronic HBV carrier, achieved HBV clearance after treatment with a bortezomib-based regimen in combination with anti-HBV drugs. DIAGNOSES: The diagnosis was MM with chronic carrier of HBV. INTERVENTIONS: He received bortezomib-based regimen for MM as well as entecavir as a prophylaxis to prevent HBV reactivation. OUTCOMES: This patient achieved HBsAg and HBV-DNA clearance after 2 months and the remission was maintained during the next 2 years. He also achieved complete remission of MM and underwent consolidation therapy with autologous hematopoietic stem cell transplantation. LESSONS: This is the first case of MM with HBV clearance after receiving a bortezomib-based regimen combined with anti-HBV drug. Research on related mechanisms might provide new suggestions and hope for better management of HBV positive patients with MM and for the treatment of HBV patients.


Assuntos
Antineoplásicos/uso terapêutico , Antivirais/uso terapêutico , Bortezomib/uso terapêutico , Guanina/análogos & derivados , Mieloma Múltiplo/tratamento farmacológico , Protocolos Clínicos , Quimioterapia Combinada , Guanina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Antígenos de Superfície da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Autólogo/métodos , Resultado do Tratamento
7.
Anticancer Res ; 40(10): 5687-5700, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988894

RESUMO

BACKGROUND: We previously developed a novel technique for expanding highly activated and purified natural killer (NK) cells able to maximize the theoretical activation potential of NK cells; thus, we named this cell population zenithal-NK (ZNK). AIM: To evaluate the safety, feasibility, and preliminary efficacy of autologous ZNK cells in patients with different types of advanced cancer with measurable solid lesions. PATIENTS AND METHODS: In this phase I/IIb first-in-human, open-label, dose-escalation study (trial registration ID: UMIN-000011555), eligible patients received ZNK cells intravenously starting from 106 to 108 cells/patient/dose at 2-week dosing intervals. A maximum of six cycles were allowed. Safety and survival analyses were also carried out for cases that were excluded and never administered ZNK cells. RESULTS: As of April 20, 2017, a total of nine patients were enrolled in this study, with one recruited twice. Overall, neither grade 2 or higher toxicities (Common Terminology Criteria for Adverse Events v5.0) caused by cell administration, nor adverse events causing discontinuation of protocol treatment were found. In four cases, the number of administered ZNK cells was increased to 108 cells/body/dose without any serious dose-limiting toxicity; the maximally tolerated dose was therefore considered to be at least 108 cells. The overall response rate was 40.0% in 10 net cases, one of partial response and three of stable disease, and the patient with partial response is still alive after 4 year's observation. CONCLUSION: These results demonstrate that autologous ZNK cells are safe and well-tolerated in patients with different types of advanced solid tumors. Clinical studies using similarly active ZNK cells from human leukocyte antigen/killer cell immunoglobulin-like receptor-mismatched healthy donors under Good Manufacturing Practice-compliant manufacturing, and with modified treatment regimen, i.e. doses and frequencies, are warranted for further investigation to show the potential of ZNK cells in such patients.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Células Matadoras Naturais/transplante , Neoplasias/terapia , Transplante Autólogo/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células/genética , Relação Dose-Resposta Imunológica , Feminino , Humanos , Células Matadoras Naturais/imunologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/patologia
8.
Medicine (Baltimore) ; 99(31): e21431, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756151

RESUMO

RATIONALE: The use of autologous hematopoietic stem cell transplantation (AHSCT) for autoimmune diseases has become the first indication for transplant in nonmalignant disease. Mucormycosis is a rare invasive infection with increasing incidence in patients treated with AHSCT. We report the first case of pulmonary mucormycosis following AHSCT for systemic sclerosis (SSc). PATIENT CONCERNS: A 24-year-old woman with rapidly progressive diffuse cutaneous SSc presented with an acute respiratory distress syndrome 6 days after AHSCT. DIAGNOSES: The results of clinical and computed tomography scan were consistent with pulmonary mucormycosis and the diagnosis was confirmed by a positive Mucorales Polymerase Chain Reaction on a peripheral blood sample. INTERVENTIONS AND OUTCOMES: Early antifungal therapy by intravenous amphotericin B provided rapid improvement within 4 days and sustained recovery after 2 years of follow-up. LESSONS: With the progressively increasing use of AHSCT and other stem cell therapy for treatment of severe SSc and other autoimmune diseases, the potential onset of rare post-transplant fungal infections, such as mucormycosis, requires careful patient monitoring and better awareness of early initiation of adequate therapy.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Mucormicose/etiologia , Esclerodermia Difusa/etiologia , Escleroderma Sistêmico/terapia , Transplante Autólogo/efeitos adversos , Doença Aguda , Administração Intravenosa , Assistência ao Convalescente , Anfotericina B/administração & dosagem , Anfotericina B/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Pneumopatias Fúngicas/diagnóstico por imagem , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/patologia , Mucorales/genética , Esclerodermia Difusa/patologia , Transplante Autólogo/métodos , Resultado do Tratamento , Adulto Jovem
9.
Nat Commun ; 11(1): 3778, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32728076

RESUMO

Targeted genome editing has a great therapeutic potential to treat disorders that require protein replacement therapy. To develop a platform independent of specific patient mutations, therapeutic transgenes can be inserted in a safe and highly transcribed locus to maximize protein expression. Here, we describe an ex vivo editing approach to achieve efficient gene targeting in human hematopoietic stem/progenitor cells (HSPCs) and robust expression of clinically relevant proteins by the erythroid lineage. Using CRISPR-Cas9, we integrate different transgenes under the transcriptional control of the endogenous α-globin promoter, recapitulating its high and erythroid-specific expression. Erythroblasts derived from targeted HSPCs secrete different therapeutic proteins, which retain enzymatic activity and cross-correct patients' cells. Moreover, modified HSPCs maintain long-term repopulation and multilineage differentiation potential in transplanted mice. Overall, we establish a safe and versatile CRISPR-Cas9-based HSPC platform for different therapeutic applications, including hemophilia and inherited metabolic disorders.


Assuntos
Engenharia Celular/métodos , Edição de Genes , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/metabolismo , Animais , Sistemas CRISPR-Cas/genética , Linhagem Celular , Feminino , Regulação da Expressão Gênica , Hemofilia A/terapia , Humanos , Doenças Metabólicas/terapia , Camundongos , Regiões Promotoras Genéticas/genética , Transplante Autólogo/métodos , Transplante Heterólogo , alfa-Globinas/genética , alfa-Globinas/metabolismo
10.
Nat Commun ; 11(1): 3549, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669548

RESUMO

Refractory metastatic rhabdomyosarcoma is largely incurable. Here we analyze the response of a child with refractory bone marrow metastatic rhabdomyosarcoma to autologous HER2 CAR T cells. Three cycles of HER2 CAR T cells given after lymphodepleting chemotherapy induces remission which is consolidated with four more CAR T-cell infusions without lymphodepletion. Longitudinal immune-monitoring reveals remodeling of the T-cell receptor repertoire with immunodominant clones and serum autoantibodies reactive to oncogenic signaling pathway proteins. The disease relapses in the bone marrow at six months off-therapy. A second remission is achieved after one cycle of lymphodepletion and HER2 CAR T cells. Response consolidation with additional CAR T-cell infusions includes pembrolizumab to improve their efficacy. The patient described here is a participant in an ongoing phase I trial (NCT00902044; active, not recruiting), and is 20 months off T-cell infusions with no detectable disease at the time of this report.


Assuntos
Imunoterapia Adotiva/métodos , Neoplasias Musculares/terapia , Recidiva Local de Neoplasia/terapia , Receptor ErbB-2/imunologia , Rabdomiossarcoma/terapia , Linfócitos T/transplante , Biópsia , Medula Óssea/patologia , Criança , Ensaios Clínicos Fase I como Assunto , Humanos , Masculino , Neoplasias Musculares/imunologia , Neoplasias Musculares/patologia , Recidiva Local de Neoplasia/imunologia , Receptores de Antígenos Quiméricos/imunologia , Indução de Remissão/métodos , Rabdomiossarcoma/imunologia , Rabdomiossarcoma/secundário , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transplante Autólogo/métodos , Resultado do Tratamento
11.
Medicine (Baltimore) ; 99(28): e20886, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664081

RESUMO

Due to the great difficulty in being preserved in site for the variable positions, the inferior parathyroid glands were advised to being routinely autotransplanted to prevent permanent hypoparathyroidism. The aim of this study was to compare the performance in the function of the superior parathyroid glands preserved in site with that of the inferior parathyroid glands preserved in site.We conducted a retrospective study including patients who underwent thyroid surgery for papillary thyroid carcinoma at our department between January 2014 and June 2018. According to the number and original position of the autoplastic parathyroid gland(s), patients were divided into group 1 (1 superior parathyroid gland), group 2 (1 inferior parathyroid glands), group 3 (1 superior parathyroid gland and 1 inferior parathyroid gland) and group 4 (2 inferior parathyroid glands). The postoperative complications and serum parathyroid hormone and calcium were analyzed.A total of 368 patients were included in the study, among them 27, 243, 40, and 58 patients were divided into group 1, group 2, group 3, and group 4, respectively. Compared with those in group 2, the serum parathyroid hormones were higher at 1 week (2.98 ±â€Š1.52 vs 2.42 ±â€Š0.89, P = .049) and 2 weeks (3.49 ±â€Š1.42 vs 2.8 ±â€Š0.81, P = .019) postoperatively in group 1. There was also significantly different in the serum parathyroid hormone at 2 weeks postoperatively between group 3 and group 4 (2.95 ±â€Š0.98 vs 2.58 ±â€Š0.82, P = .047).The inferior parathyroid glands preserved in site recover faster than the superior parathyroid glands preserved in site.


Assuntos
Glândulas Paratireoides/fisiologia , Glândulas Paratireoides/cirurgia , Câncer Papilífero da Tireoide/cirurgia , Glândula Tireoide/patologia , Transplante Autólogo/efeitos adversos , Adulto , Cálcio/sangue , Feminino , Humanos , Hipoparatireoidismo/prevenção & controle , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/anatomia & histologia , Hormônio Paratireóideo/sangue , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Recuperação de Função Fisiológica/fisiologia , Estudos Retrospectivos , Transplante Autólogo/métodos
12.
Ann Hematol ; 99(12): 2893-2901, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32572522

RESUMO

The amount of infused CD34+ cells has been reported to be the strongest predictor of platelet recovery after autologous stem cell transplantation (ASCT). However, the timing of platelet recovery varies widely among patients even after the infusion of similar amounts of CD34+ cells. Therefore, we retrospectively assessed 99 patients who underwent their first ASCT for lymphoma or myeloma at our center. Thirteen patients (13%) did not achieve platelet engraftment, defined as a platelet count of at least 2.0 × 104/µL without transfusion, at day 28 after transplantation, whereas 58 of 60 patients (97%) who received at least 2.0 × 106/kg CD34+ cells achieved platelet engraftment within 28 days. Multivariate analysis identified the following significant risk factors for delayed platelet recovery: hemoglobin level and platelet count before stem cell harvest, body temperature of > 39 °C within 5 days after ASCT, and infusion of a small amount (< 2.0 × 106/kg) of CD34+ cells. In a subgroup analysis of 39 patients infused with < 2.0 × 106/kg CD34+ cells, a need for repeated apheresis for stem cell harvest and a body temperature of > 39 °C within 5 days after ASCT were identified as independent factors for delayed platelet recovery. In summary, platelet recovery following ASCT was affected by insufficient hematopoietic recovery at stem cell harvest, a need for repeated apheresis, and high fever early after ASCT, particularly when the amount of infused stem cells was insufficient.


Assuntos
Plaquetas/fisiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma/sangue , Linfoma/terapia , Mieloma Múltiplo/sangue , Mieloma Múltiplo/terapia , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recuperação de Função Fisiológica/fisiologia , Estudos Retrospectivos , Transplante Autólogo/métodos , Transplante Autólogo/tendências , Adulto Jovem
13.
Medicine (Baltimore) ; 99(26): e20788, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590759

RESUMO

BACKGROUND: Treatment for most patients with head and neck cancers includes ionizing radiation with or without chemotherapy. This treatment causes irreversible damage to salivary glands in the irradiation field accompanied by a loss of fluid-secreting acinar cells and a considerable decrease of saliva secretion. There is currently no adequate conventional treatment for this condition. In recent years, we developed an effective culture method to enhance the anti-inflammatory and vasculogenic phenotypes of peripheral blood mononuclear cells (PBMNCs), and such effectively conditioned PBMNC (E-MNC) therapy has shown promising improvements to the function of radiation-injured salivary glands in preclinical studies. However, the safety and effect of E-NMC therapy have yet assessed in human. The objective of this ongoing first-in-man study is to assess the safety, tolerability, and in part the efficacy of E-MNC therapy for treating radiation-induced xerostomia. METHODS/DESIGN: This phase 1 first-in-man study is an open-label, single-center, two-step dose escalation study. A total of 6 patients, who had no recurrence of head and neck cancer over 5 years following radiation therapy and suffered from radiation-induced xerostomia, will receive a transplantation of E-NMCs derived from autologous PBMNCs to a submandibular gland. The duration of the intervention will be 1 year. To analyze the recovery of salivary secretion, a gum test will be performed. To analyze the recovery of atrophic salivary glands, computed tomography (CT), and magnetic resonance imaging (MRI) of salivary glands will be conducted. The primary endpoint is the safety of the protocol. The secondary endpoints are the changes from baseline in whole saliva secretion and salivary gland atrophy. DISCUSSION: This will be the first clinical study of regenerative therapy using E-MNCs for patients with severe radiation-induced xerostomia. The results of this study are expected to contribute to developing the low-invasive cell-based therapy for radiation-induced xerostomia. TRIAL REGISTRATION: This study was registered with the Japan Registry of Clinical Trials (http://jrct.niph.go.jp) as jRCTb070190057.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Leucócitos Mononucleares/transplante , Lesões por Radiação , Glândulas Salivares , Xerostomia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Imagem por Ressonância Magnética/métodos , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Lesões por Radiação/fisiopatologia , Lesões por Radiação/terapia , Projetos de Pesquisa , Glândulas Salivares/diagnóstico por imagem , Glândulas Salivares/patologia , Glândulas Salivares/fisiopatologia , Glândulas Salivares/efeitos da radiação , Tomografia Computadorizada por Raios X/métodos , Transplante Autólogo/métodos , Resultado do Tratamento , Xerostomia/diagnóstico , Xerostomia/etiologia , Xerostomia/fisiopatologia , Xerostomia/terapia
14.
Cir. plást. ibero-latinoam ; 46(2): 151-158, abr.-jun. 2020. ilus
Artigo em Espanhol | IBECS | ID: ibc-194715

RESUMO

INTRODUCCIÓN Y OBJETIVO: El aumento de la cirugía bariátrica como alternativa al tratamiento tanto del síndrome metabólico como de la obesidad y el sobrepeso, conlleva múltiples deformidades corporales, entre las que unas de las más complejas son las alteraciones mamarias. Su tratamiento quirúrgico depende de un diagnóstico y técnica adecuados, capaces de remodelar la estética mamaria. El objetivo de esta investigación es definir la importancia del injerto de grasa como procedimiento previo a la mamoplastia en pacientes que han sufrido grandes pérdidas ponderales. MATERIAL Y MÉTODO: Realizamos un estudio retrospectivo, lineal, en 124 pacientes sometidas a 158 procedimientos quirúrgicos consecutivos entre enero de 2009 y diciembre de 2019, con rango de edad entre 18 y 72 años. Evaluamos los procedimientos para la corrección de las diversas deformidades mamarias tales como, hipotrofia o atrofia mamaria, ptosis, asimetrías, posicionamiento lateralizado del complejo areola pezón, pérdida de la proyección del polo superior, flacidez cutánea asociada a lipodistrofia corporal persistente, cirugías previas de contorno corporal, así como la edad y el índice de masa corporal (IMC). RESULTADOS: El mayor porcentaje de procedimientos correspondió a la triple interposición de colgajos (28%, 44 procedimientos), seguida del injerto de grasa mamaria (27%, 42 procedimientos) y la triple interposición de colgajos con implante de silicona (19%, 30 procedimientos). Se realizó injerto graso mamario en un 40.50% de los procedimientos realizados, con una media de volumen graso infiltrado de 450.60 ml. CONCLUSIONES: Recomendamos la realización de injertos de grasa en todas las pacientes sometidas a cirugía de remodelación mamaria secundaria a pérdida masiva de peso con el fin de recomponer volumétricamente la mama y reconstruir estructuras cutáneas, parenquimatosas y musculares, siendo la transferencia de grasa mamaria la única forma de relleno definitiva del polo superior. Los colgajos locales representan no solo una forma de aumento volumétrico de la mama sino también una posibilidad de mejorar el contorno mamario y el segmento superior del cuerpo


BACKGRAUND AND OBJECTIVE: The increase in bariatric surgery as an alternative to the treatment of both the metabolic syndrome and obesity and overweight leads to multiple bodily deformities, among these one of the most complex are mammary alterations. The surgical treatment of these alterations depends on an adequate diagnosis and a suitable technique able to reshape the mammary aesthetics. The objective of this research is to define the importance of fat grafting as a procedure prior to breast-plasty in patients with post-weight loss. METHODS: A retrospective and linear study was performed in 124 patients, who underwent 158 consecutive procedures between January 2009 and December 2019, age range between 18 and 72 years. The evaluated procedures allowed correction of different breast deformities such as hypotrophy or breast atrophy, ptosis, asymmetries, lateral positioning of the nipple areola complex, loss of the upper pole projection, skin flaccidity associated with persistent body lipodystrophy, previous body contour surgeries, and patient's age and body mass index (BMI). RESULTS: A total of 158 procedures were performed which the highest percentage was of triple flap interposition (28%, 44 procedures), followed by breast fat grafting (27%, 42 procedures) and triple flap interposition with silicone implants (19%, 30 procedures). The fat graft to breast was performed in 40.50% of the total procedures performed, with a mean infiltrated fat volume corresponded to 450.60 ml. CONCLUSIONS: We recommend performing fat grafts in all patients undergoing breast remodeling procedures after massive weight loss in order to volumetrically recompose the breast and rebuild skin, parenchymal and muscular structures, with breast fat transfer being the only way definitive filling of the upper pole. In addition, local flaps represent not only a form of volumetric augmentation of the breast but also a possibility of improving the breast contour and upper body segment


Assuntos
Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Mamoplastia/métodos , Retalhos Cirúrgicos/cirurgia , Adipócitos/transplante , Tecido Adiposo/transplante , Mamoplastia/reabilitação , Distribuição da Gordura Corporal , Cirurgia Bariátrica , Estudos Retrospectivos , Índice de Massa Corporal , Glândulas Mamárias Humanas/cirurgia , Géis de Silicone/uso terapêutico , Transplante Autólogo/métodos , Centrifugação/métodos
15.
Rev. bras. cir. plást ; 35(2): 243-248, apr.-jun. 2020. ilus
Artigo em Inglês, Português | LILACS | ID: biblio-1103839

RESUMO

A pele de tilápia possui microbiota não infecciosa e estrutura morfológica semelhante à pele humana. Estudos clínicos fase II, ainda não publicados, mostraram resultados promissores na sua utilização para tratamento de queimaduras. Nos protocolos destes estudos, pacientes com lesões em áreas de dobras de pele, como genitais e região inguinal, foram excluídos, pois achava-se que o biomaterial não aderiria apropriadamente, resultando em um grau de cicatrização inferior. Relato de caso de paciente do sexo feminino, 18 anos, sem comorbidades, com queimaduras de segundo grau profundo em abdômen, região inguinal, parte da genitália e metade superior de ambas as coxas, envolvendo 13,5% da área total da superfície corporal. A pele de tilápia foi aplicada nas lesões levando a uma reepitelização completa com 16 dias de tratamento. Não foram observados efeitos colaterais. A pele de tilápia traz, portanto, a promessa de um produto inovador, de fácil aplicação e alta disponibilidade, que pode se tornar a primeira pele animal nacionalmente estudada e registrada pela Agência Nacional de Vigilância Sanitária, para uso no tratamento de queimaduras. Este relato de caso contribui para reduzir as limitações em relação às áreas anatômicas apropriadas para a aplicação da pele de tilápia, uma vez que, mesmo com a necessidade de reposição de pele, foram obtidos bons resultados com aplicação na genitália e região inguinal.


Tilapia skin has a non-infectious microbiota and a morphological structure similar to human skin. Phase II clinical studies, not yet published, have shown promising results in their use for the treatment of burns. In the protocols of these studies, patients with lesions in areas of skin folds, such as genitals and inguinal regions, were excluded, as it was thought that the biomaterial would not adhere properly, resulting in a lower degree of healing. Case report of a female patient, 18 years old, without comorbidities, with deep second-degree burns in the abdomen, inguinal region, part of the genitalia and upper half of both thighs, involving 13.5% of the total body surface area. Tilapia skin was applied to the lesions leading to a complete re-epithelialization with 16 days of treatment. No side effects were observed. Tilapia skin, therefore, brings the promise of an innovative product, easy to apply, and highly available, which can become the first animal skin nationally studied and registered by the Agência Nacional de Vigilância Sanitária, for use in the treatment of burns. This case report contributes to reduce the limitations concerning the anatomical areas appropriate for the application of tilapia skin, since, even with the need for skin replacement, good results were obtained with application to the genitalia and inguinal region.


Assuntos
Humanos , Feminino , Adolescente , História do Século XXI , Terapêutica , Transplante Autólogo , Curativos Biológicos , Queimaduras , Relatos de Casos , Condutas Terapêuticas , Tilápia , Ciclídeos , Abdome , Estudo Clínico , Genitália , Quadril , Terapêutica/métodos , Transplante Autólogo/métodos , Transplante Autólogo/reabilitação , Curativos Biológicos/normas , Queimaduras/terapia , Condutas Terapêuticas/efeitos adversos , Condutas Terapêuticas/normas , Tilápia/anatomia & histologia , Ciclídeos/anatomia & histologia , Genitália/anatomia & histologia , Abdome/anatomia & histologia , Quadril/anatomia & histologia
16.
Int J Pediatr Otorhinolaryngol ; 135: 110111, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32497909

RESUMO

INTRODUCTION: Autologous costochondral grafting is a commonly employed technique in pediatric otolaryngology for reconstructing a cartilaginous or bony structure, such as the trachea, larynx, nose or mandible by harvesting rib cartilage or bone from the same patient. Complications include infection, pneumothorax, hematoma, scarring, and pleural leak, and the literature regarding these complication rates in pediatric patients undergoing this procedure is sparse. The objective of this study was to determine the donor site complication rate associated with rib graft harvest procedures performed by pediatric otolaryngologists in infants and children and to compare this to established complication rates reported in adults. METHODS: A retrospective cohort study was performed, examing the charts of 33 patients who underwent airway, mandible, nose, or external ear reconstruction by means of autologous rib grafting between 2010 and 2018 at an urban tertiary medical center in Boston, Massachusetts. All patients were under the age of 18 years old and had undergone rib harvest and subsequent airway, mandible, nose, or external ear reconstruction by two pediatric otolaryngologists. RESULTS: Of these, 20 were female and 13 were male, with a mean age of 2.5 years at date of surgery. No patients were excluded. A total of 41 costochondral graft harvests from a total of 36 incision sites were included. Pooled donor site complication incidences were 1 intraoperative pleural leak (2.8%) and 1 incision site infection (2.8%). Drains were not utilized postoperatively; there were no incidences of postoperative hematoma or seroma. No outside specialty consults were necessary to manage these. There were 2 instances of hypertrophic scarring, both developing in patients who underwent skin excisions for skin graft harvest or scar excision from the same incision used for graft harvest (5.6%). CONCLUSIONS AND RELEVANCE: Autologous rib grafting amounts to a simple, extrapleural chest wall procedure, which may be safely performed in children by pediatric otolaryngologists with acceptably low complication rates.


Assuntos
Cartilagem Costal/transplante , Procedimentos Cirúrgicos Reconstrutivos/métodos , Transplante Autólogo/métodos , Adolescente , Autoenxertos , Criança , Pré-Escolar , Orelha Externa/cirurgia , Feminino , Humanos , Incidência , Lactente , Laringe/cirurgia , Masculino , Mandíbula/cirurgia , Nariz/cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Traqueia/cirurgia , Transplante Autólogo/efeitos adversos
17.
Cancer Immunol Immunother ; 69(12): 2589-2598, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32591862

RESUMO

BACKGROUND: Autologous monocyte-derived mRNA co-electroporated dendritic cells with mRNA encoding CD40 ligand (CD40L), CD70 and a constitutively activated TLR4 (caTLR4) (referred to as TriMixDC-MEL) have anti-tumor activity in advanced melanoma patients. We investigated the safety and activity of adjuvant TriMixDC-MEL in stage III/IV melanoma patients. MATERIALS AND METHODS: Forty-one patients were randomly assigned to treatment with TriMixDC-MEL (n = 21) and standard follow-up (n = 20). "Cross-over" was allowed at the time of non-salvageable recurrence. The primary endpoint was the percentage of patients alive and disease-free at 1-year. For a subset of patients, (formalin-fixed paraffin-embedded), tumor tissue samples were available for mRNA expression profiling and PD-L1 immunohistochemical staining. RESULTS: Baseline characteristics were well balanced. One-year after randomization, 71% of patients in the study arm were alive and free of disease compared to 35% in the control arm. After a median follow-up of 53 months (range 3-67), 23 patients experienced a non-salvageable melanoma recurrence (TriMixDC-Mel arm n = 9 and control arm n = 14).The median time to non-salvageable recurrence was superior in the TriMixDC-MEL arm (median 8 months (range 1-6) vs. not reached; log-rank p 0.044). TriMixDC-MEL-related adverse events (AE) consisted of transient local skin reactions, flu-like symptoms and post-infusion chills. No grade ≥ 3 AE's occurred. The mRNA expression profiling revealed four genes (STAT2, TPSAB1, CD9 and CSF2) as potential predictive biomarkers. CONCLUSION: TriMixDC-MEL id/iv as adjuvant therapy is tolerable and may improve the 1-year disease-free survival rate. Combination of optimized autologous monocyte-derived DC-formulations warrants further investigation in combination with currently approved adjuvant therapy options.


Assuntos
Células Dendríticas/transplante , Melanoma/terapia , Recidiva Local de Neoplasia/epidemiologia , RNA Mensageiro/imunologia , Neoplasias Cutâneas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ligante CD27/genética , Ligante CD27/imunologia , Ligante de CD40/genética , Ligante de CD40/imunologia , Terapia Combinada/métodos , Células Dendríticas/metabolismo , Intervalo Livre de Doença , Eletroporação , Feminino , Seguimentos , Humanos , Imunoterapia/métodos , Masculino , Melanoma/imunologia , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , RNA Mensageiro/genética , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Procedimentos Cirúrgicos Operatórios , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia , Transplante Autólogo/métodos , Adulto Jovem
18.
J Surg Res ; 255: 33-41, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32540578

RESUMO

BACKGROUND: Parathyroidectomy (PTX) has been demonstrated as an effective treatment for patients with secondary hyperparathyroidism (SHPT) of renal origin. However, severe hypocalcemia, called hungry bone syndrome (HBS), is a common complication following PTX in these patients and can lead to poor clinical outcomes, even death. Therefore, exploring risk factors for HBS and establishing a prediction nomogram allow intensive monitoring and prompt treating this postoperative complication, which is the main purpose of this study. METHODS: From October 2016 to October 2018, PTX with autotransplantation (PTX + AT) procedures were performed in 131 patients with SHPT of renal origin by a surgeon and his team in the Thyroid and Parathyroid Surgery Center, West China Hospital, Sichuan University, China. After applying the inclusion and exclusion criteria, a total of 114 patients were enrolled for analyses in this study. Comprehensive data including preoperative, intraoperative, and postoperative variables were prospectively collected and retrospectively analyzed. The univariate and multivariate logistic regression analyses with internal validation by bootstrapping were used to confirm independent risk factors for postoperative HBS. The nomogram was developed based on the statistical analysis results. Receiver operator characteristic (ROC) curves were drawn to compare the prediction performance among different predictors. RESULTS: The occurrence of postoperative HBS was 76.3% (87 out of 114 patients) in this study. Univariate analysis showed that preoperative intact parathyroid hormone (iPTH), serum alkaline phosphatase, bone-specific alkaline phosphatase (bone-ALP) were significantly higher in HBS group than those in non-HBS group, while preoperative corrected serum calcium and albumin were significantly lower in HBS group than those in non-HBS group. Total weight of resected parathyroid glands was significantly heavier in HBS group versus non-HBS group. Multivariate logistic regression analysis with internal validation by bootstrapping demonstrated preoperative iPTH, bone-ALP, preoperative corrected serum calcium, and total weight of resected parathyroid glands were independently associated with postoperative HBS. The nomogram including the abovementioned four independent predictors was constructed and showed better prediction performance than the other four predictors in terms of postoperative HBS. CONCLUSIONS: On the basis of this study, we found higher preoperative iPTH level, higher bone-ALP level, heavier total weight of resected parathyroid glands, and lower preoperative corrected serum calcium level were independent predictors of postoperative HBS in patients with SHPT of renal origin. The nomogram can expediently, accurately, and objectively predict the risk of postoperative HBS in individual patient with SHPT of renal origin.


Assuntos
Hiperparatireoidismo Secundário/cirurgia , Hipocalcemia/epidemiologia , Nomogramas , Paratireoidectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Transplante Autólogo/efeitos adversos , Adulto , Cálcio/sangue , Feminino , Humanos , Hiperparatireoidismo Secundário/etiologia , Hipocalcemia/sangue , Hipocalcemia/diagnóstico , Hipocalcemia/etiologia , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/transplante , Hormônio Paratireóideo/sangue , Paratireoidectomia/métodos , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Período Pré-Operatório , Curva ROC , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos , Fatores de Risco , Transplante Autólogo/métodos , Resultado do Tratamento
19.
Biochim Biophys Acta Rev Cancer ; 1874(1): 188387, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32579889

RESUMO

Late detection, compromised immune system, and chemotherapy resistance underlie the poor patient prognosis for pancreatic ductal adenocarcinoma (PDAC) patients, making it the 3rd leading cause of cancer-related deaths in the United States. Cooperation between the tumor cells and the immune system leads to the immune escape and eventual establishment of the tumor. For more than 20 years, sincere efforts have been made to intercept the tumor-immune crosstalk and identify the probable therapeutic targets for breaking self-tolerance toward tumor antigens. However, the success of these studies depends on detailed examination and understanding of tumor-immune cell interactions, not only in the primary tumor but also at distant systemic niches. Innate and adaptive arms of the immune system sculpt tumor immunogenicity, where they not only aid in providing an amenable environment for their survival but also act as a driver for tumor relapse at primary or distant organ sites. This review article highlights the key events associated with tumor-immune communication and associated immunosuppression at both local and systemic microenvironments in PDAC. Furthermore, we discuss the approaches and benefits of targeting both local and systemic immunosuppression for PDAC patients. The present articles integrate data from clinical and genetic mouse model studies to provide a widespread consensus on the role of local and systemic immunosuppression in undermining the anti-tumor immune responses against PDAC.


Assuntos
Carcinoma Ductal Pancreático/terapia , Imunoterapia/métodos , Neoplasias Pancreáticas/terapia , Evasão Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/efeitos dos fármacos , Medula Óssea/imunologia , Medula Óssea/patologia , Vacinas Anticâncer/administração & dosagem , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Quimioterapia Adjuvante/métodos , Ensaios Clínicos como Assunto , Terapia Combinada/métodos , Modelos Animais de Doenças , Intervalo Livre de Doença , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Imunidade Inata/efeitos dos fármacos , Irinotecano/farmacologia , Irinotecano/uso terapêutico , Leucovorina/farmacologia , Leucovorina/uso terapêutico , Excisão de Linfonodo , Linfonodos/imunologia , Linfonodos/patologia , Linfonodos/cirurgia , Camundongos , Camundongos Transgênicos , Terapia Neoadjuvante/métodos , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Pâncreas/imunologia , Pâncreas/patologia , Pâncreas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Baço/imunologia , Baço/patologia , Baço/cirurgia , Esplenectomia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/transplante , Transplante Autólogo/métodos
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