Combined Therapy with Rituximab Plus Cyclophosphamide/Vincristine/Prednisone for Sjogren’s Syndrome-Associated B-Cell Non-Hodgkin’s Lymphoma

Sjogren’s syndrome (SS) is characterized by an increased risk of developing non-Hodgkin’s lymphoma (NHL). Optimal treatment for NHL-complicating SS is not clearly established. NHL, which expresses the CD20 antigen on tumor cell surfaces, is a disease entity candidate to treatment with anti-CD20 monoclonal antibodies. We report clinical and immunological data of a patient with SS and NHL who was treated with a regimen consisting of cyclophosphamide/vincristine/prednisone (CVP) plus rituximab. A 68-year-old women had a 26-year history of SS and autoimmune thyroiditis. The clinical course of SS was complicated with severe splenomegaly. An increased percentage of CD19+ B cells (up to 30%) was detected in peripheral blood during follow-up. Clonal rearrangement of immunoglobulin heavy chain was detected. Low-grade B marginal zone lymphoma was diagnosed (peripheral blood immunophenotype: CD19 + CD20 + CD23 + sIg + Kappa; bone marrow immunophenotype: 25% lymphocytes; CD19 + CD20 + CD79A/BCL2+). She received a total of six cycles of CVP plus rituximab (375 mg/m²). Therapy was well tolerated, and B lymphocytes were depleted from the peripheral blood. Splenomegaly normalized. No evidence of neoplastic infiltration was detected in bone marrow after completion of therapy, while certain symptoms of SS (sicca and arthralgia) improved with treatment. CVP plus rituximab proved effective in a patient with SS with NHL.     

The new international staging system for lung cancer. Evolution of the system and concerned remarks

The rationale of the Staging System of Lung Cancer is discussed from his presentation (Mountain, 1985) to the recent revision and proposals of new classifications. Survival rates offered a strong statistical support to the latest revision in 1997. Stage Group have become 7 out of Stage 0 (Tis). In the New Lymph Node Map, station 4 is confirmed as mediastinal (N2). The improved definition of Stage Grouping requires a golden standard of staging and a worldwide consensus on the surgical approach to mediastinal lymphadenectomy. IASLC, the International Association for the Study of Lung Cancer, is now moving to collect a new largest database with the aim to offer the next expected Revision.     

Bupropion. Effects on cerebral monoamines in rat and on blood pressure in dog

Intravenous injections of bupropion into the femoral vein of dogs did not change cardiovascular peripheric responses because it did not affect significantly either arterial pressure or heart rate. In acute experiments bupropion increased the levels of DA, NA and 5-HT in the brain of rats. There was a remarkable correlation between the levels of monoamines and the hypermotility.     

Stem cells therapy in acute myocardial infarction: a new era?

Clinical and Experimental Medicine - Stem cells transplantation after acute myocardial infarction (AMI) has been claimed to restore cardiac function. However, this therapy is still restricted to...     

The Effect of LKB1 Activity on the Sensitivity to PI3K/mTOR Inhibition in Non–Small Cell Lung Cancer

IntroductionLiver kinase B1 (LKB1), also called serine/threonine kinase 11 (STK11), is a tumor suppressor that functions as master regulator of cell growth, metabolism, survival, and polarity. Approximately 30% to 35% of patients with NSCLC possess inactivated liver kinase B1 gene (LKB1), and these patients respond poorly to anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy. Therefore, novel therapies targeting NSCLC with LKB1 loss are needed.MethodsWe used a new in silico signaling analysis method to identify the potential therapeutic targets and reposition drugs by integrating gene expression data with the Kyoto Encyclopedia of Genes and Genomes signaling pathways. LKB1 wild-type and LKB1-deficient NSCLC cell lines, including knockout clones generated by clustered regularly interspaced short pallindromic repeats–Cas9, were treated with inhibitors of mechanistic target of rapamycin kinase (mTOR) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and a dual inhibitor.ResultsIn silico experiments showed that inhibition of both mTOR and PI3K can be synergistically effective in LKB1-deficient NSCLC. In vitro and in vivo experiments showed the synergistic effect of mTOR inhibition and PI3K inhibition in LKB1-mutant NSCLC cell lines. The sensitivity to dual inhibition of mTOR and PI3K is higher in LKB1-mutant cell lines than in wild-type cell lines. A higher compensatory increase in Akt phosphorylation after rapamycin treatment of LKB1-deficient cells than after rapamycin treatment of LKB1 wild-type cells is responsible for the synergistic effect of mTOR and PI3K inhibition. Dual inhibition of mTOR and PI3K resulted in a greater decrease in protein expression of cell cycle–regulating proteins in LKB1 knockout cells than in LKB1 wild-type cells.ConclusionDual molecular targeted therapy for mTOR and PI3K may be a promising therapeutic strategy in the specific population of patients with lung cancer with LKB1 loss.     

Pathologic Considerations and Standardization in Mesothelioma Clinical Trials

The accurate diagnosis of mesothelioma is critical for the appropriate clinical management of this cancer. Many issues complicate making the diagnosis of mesothelioma including the presence of reactive mesothelial cells in benign pleural effusions, the heterogeneity of mesothelioma histopathology, the relatively high incidence of other epithelial malignancies that metastasize to the pleura, and primary sarcomas that arise within the pleura. Given the rapidly evolving field of molecular profiling and the need for translational correlates in mesothelioma clinical trials, the National Cancer Institute (NCI)–International Association for the Study of Lung Cancer–Mesothelioma Applied Research Foundation Clinical Trials Planning Meeting was convened in March 2017 to develop a consensus on standard pathology guidelines for future NCI-sponsored clinical trials in mesothelioma. This consensus statement covers recommendations for specimen handling, pathologic classification and diagnosis, biobanking, and tissue correlative studies.