ABSTRACT
Non-Hodgkin lymphoma (NHL) that primarily involves the colon is rare and should be distinguished from the more common systemic nodal lymphoma. It has unique clinical expectations and management consideration. Different histologic subtypes of NHL involve the colon, which varies in the clinical behavior and likelihood of obtaining durable remissions with treatment. This article will review the current understanding of the different histologic subtypes of primary colorectal lymphoma and propose management algorithms.
ABSTRACT
Invadosomes are F-actin-based structures involved in extracellular matrix degradation, cell invasion, and metastasis formation. Analyzing their proteome is crucial to decipher their molecular composition, to understand their mechanisms, and to find specific elements to target them. However, the specific analysis of invadosomes is challenging, because it is difficult to maintain their integrity during isolation. In addition, classical purification methods often suffer from contaminations, which may impair data validation. To ensure the specific identification of invadosome components, we here develop a method that combines laser microdissection and mass spectrometry, enabling the analysis of subcellular structures in their native state based on low amounts of input material. Using this combinatorial method, we show that invadosomes contain specific components of the translational machinery, in addition to known marker proteins. Moreover, functional validation reveals that protein translation activity is an inherent property of invadosomes, which is required to maintain invadosome structure and activity.
Subject(s)
Podosomes/metabolism , Protein Biosynthesis , Proteomics/methods , RNA, Messenger/metabolism , Actins/metabolism , Animals , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Chromatography, High Pressure Liquid/methods , Extracellular Matrix/metabolism , Humans , Laser Capture Microdissection/methods , Mice , NIH 3T3 Cells , Neoplasms/diagnosis , Neoplasms/pathology , Podosomes/pathology , Tandem Mass Spectrometry/methodsABSTRACT
High-grade B cell lymphoma with MYC and BCL2 rearrangements (double hit) has a poor prognosis with standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). We report here a treatment algorithm of DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab) followed by BEAM (carmustine, etoposide, cytarabine, melphalan) autologous transplant in 36 cases of previously untreated double hit lymphoma (DHL) from 2010 to 2015. A high risk International Prognostic Index (IPI) was present in 42% of cases. At median follow-up of 38 months, the 2-year progression free survival (PFS) and overall survival (OS) were 69% (95% CI 54-84%) and 71% (95% CI 56-86%). Eight cases were refractory to induction with 1-year OS 20%, and no factors were predictive for primary refractory disease. Of 28 responders, 17 proceeded to transplant while 11 were observed, primarily due to age and co-morbidities. By 24-week landmark analysis after diagnosis, the 2-year PFS and OS were both 94% (95% CI 83-100%) vs 79% (95% CI 52-100%) for transplant vs observation (p = .59 for both PFS and OS). There was no significant benefit to consolidative transplant in our series, and primary refractory DHL needs novel approaches.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Lymphoma, Large B-Cell, Diffuse/therapy , Aged , Carmustine/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Gene Rearrangement , Humans , Lymphoma, Large B-Cell, Diffuse/genetics , Melphalan/administration & dosage , Middle Aged , Prednisone/administration & dosage , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-myc/genetics , Rituximab/administration & dosage , Transplantation, Autologous , Treatment Outcome , Vincristine/administration & dosageSubject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Adult , Aged , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , Disease-Free Survival , Humans , Middle Aged , Neutropenia/chemically induced , Pneumonia/chemically induced , Treatment OutcomeABSTRACT
Nivolumab is a humanized immunoglobulin gamma-4 kappa anti-programmed cell death 1 monoclonal antibody that is currently approved in the treatment of several solid tumors and recently gained accelerated approval in classical Hodgkin lymphoma (cHL) that has relapsed or progressed following autologous hematopoietic stem-cell transplantation and post-transplantation brentuximab vedotin. The purpose of this article is to review the immunophysiologic basis, clinical efficacy, and toxicity of nivolumab in the treatment of cHL. In addition, we will review ongoing clinical trials and potential future directions of checkpoint inhibition in the treatment of cHL.