다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

CA : A Cancer Journal for Clinicians

2458 Despite dramatic improvements in treatment over the past 40 years, acute lymphoblastic leukemia (ALL) remains one of the most common causes of death from disease in childhood. Glucocorticoids are among the most effective agents used in the treatment of lymphoid malignancies, and patient response to treatment is an important determinant of long-term outcome in childhood ALL. In spite of its clinical significance, the molecular basis of glucocorticoid resistance is still poorly understood. The aim of this study was to develop an experimental model system to define clinically relevant mechanisms of glucocorticoid resistance in childhood ALL. An in vivo model of childhood ALL has been developed in our laboratory, using patient biopsies established as xenografts in immune-deficient nonobese diabetic severe-combined immunodeficient (NOD/SCID) mice. This model is highly representative of the human disease (Lock et al., Blood, 99: 4100-4108, 2002). The in vivo responses of these xenografts to the glucocorticoid dexamethasone (DEX) correlated significantly with patient outcome (p 1 μM) in xenografts from six patients, five of whom died of their disease. In contrast, four DEX-sensitive xenografts (IC50 values 2-fold in sensitive xenografts within 8 hours of treatment. In contrast, Bim induction was dramatically attenuated in DEX-resistant xenografts. These results have identified a clinically significant and novel mechanism of glucocorticoid resistance in childhood ALL, which occurs downstream of receptor-ligand interactions, but upstream of the signalling pathway resulting in Bim induction and apoptosis.

Novel mechanisms of glucocorticoid resistance in childhood acute lymphoblastic leukemia.

Purpose Recent studies suggest that tumor-infiltrating lymphocytes (TILs) are associated with disease-free (DFS) and overall survival (OS) in operable triple-negative breast cancer (TNBC). We seek to validate the prognostic impact of TILs in primary TNBCs in two adjuvant phase III trials conducted by the Eastern Cooperative Oncology Group (ECOG). Patients and methods Full-face hematoxylin and eosin–stained sections of 506 tumors from ECOG trials E2197 and E1199 were evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments (sTILs). Patient cases of TNBC from E2197 and E1199 were randomly selected based on availability of sections. For the primary end point of DFS, association with TIL scores was determined by fitting proportional hazards models stratified on study. Secondary end points were OS and distant recurrence–free interval (DRFI). Reporting recommendations for tumor marker prognostic studies criteria were followed, and all analyses were prespecified. Results The majority of 481 evaluable cancers had TILs (sTILs, 80%; iTILs, 15%). With a median follow-up of 10.6 years, higher sTIL scores were associated with better prognosis; for every 10% increase in sTILs, a 14% reduction of risk of recurrence or death (P = .02), 18% reduction of risk of distant recurrence (P = .04), and 19% reduction of risk of death (P = .01) were observed. Multivariable analysis confirmed sTILs to be an independent prognostic marker of DFS, DRFI, and OS. Conclusion In two national randomized clinical trials using contemporary adjuvant chemotherapy, we confirm that stromal lymphocytic infiltration constitutes a robust prognostic factor in TNBCs. Studies assessing outcomes and therapeutic efficacies should consider stratification for this parameter.

Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199

Developmental fate decisions are dictated by master transcription factors (TFs) that interact with cis-regulatory elements to direct transcriptional programs. Certain malignant tumors may also depend on cellular hierarchies reminiscent of normal development but superimposed on underlying genetic aberrations. In glioblastoma (GBM), a subset of stem-like tumor-propagating cells (TPCs) appears to drive tumor progression and underlie therapeutic resistance yet remain poorly understood. Here, we identify a core set of neurodevelopmental TFs (POU3F2, SOX2, SALL2, and OLIG2) essential for GBM propagation. These TFs coordinately bind and activate TPC-specific regulatory elements and are sufficient to fully reprogram differentiated GBM cells to "induced" TPCs, recapitulating the epigenetic landscape and phenotype of native TPCs. We reconstruct a network model that highlights critical interactions and identifies candidate therapeutic targets for eliminating TPCs. Our study establishes the epigenetic basis of a developmental hierarchy in GBM, provides detailed insight into underlying gene regulatory programs, and suggests attendant therapeutic strategies. PAPERCLIP:

Reconstructing and Reprogramming the Tumor-Propagating Potential of Glioblastoma Stem-like Cells

Address for Correspondence/Yazışma Adresi: Chrissa SIOKA, M.D., School of Health Sciences, University Hospital of Ioannina Faculty of Medicine, Department of Nuclear Medicine, Ioannina, Greece Phone : +3

Osteoblastic Solitary Plasmacytoma of Bone

Primary bone lymphoma (PBL) is a rare neoplasm of malignant lymphoid cells presenting with one or more bone lesions without nodal or other extranodal involvement. It accounts for approximately 1% of all lymphomas and 7% of malignant primary bone tumors. Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) represents the predominant histological type and constitutes over 80% of all cases. PBL may occur at all ages with a typical diagnosis age of 45–60 years and a slight male predominance. Local bone pain, soft tissue edema, palpable mass and pathological fracture are the most common clinical features. Diagnosis of the disease, which is frequently delayed due to its non-specific clinical presentation, is based on the combination of clinical examination and imaging studies and confirmed by combined histopathological and immunohistochemical examination. PBL can develop in any part of the skeleton, although it occurs most commonly in the femur, humerus, tibia, spine and pelvis. The imaging appearance of PBL is highly variable and unspecific. In terms of the cell-of-origin, most cases of primary bone DLBCL (PB-DLBCL), NOS belong to the germinal center B-cell-like subtype and specifically originate from germinal center centrocytes. PB-DLBCL, NOS has been considered a distinct clinical entity based on its particular prognosis, histogenesis, gene expression and mutational profile and miRNA signature. PBL carries a favorable prognosis, especially when treated with combined chemoradiotherapy.

/pdf/primary-bone-lymphoma-a-review-of-the-literature-with-u56a0fqc.pdf

Primary Bone Lymphoma: A Review of the Literature with Emphasis on Histopathology and Histogenesis

Dear Editor, Tattoos and stasis dermatitis (SD) are characterized by skin discoloration due to the deposition of chromophores in the skin, which are mainly found in dermal “professional” phagocytes, especially macrophages. Here, based on the intuitive suggestion that cells with higher odds ratios (OR) to “carry pigment inclusions” are cells capable to phagocyte more strongly and deposit indigestible pigment, we applied OR calculations to quantify and compare the pigment storage capacity of different dermal cell subpopulations in tattoos and SD. The study was approved by the University Hospital of Ioannina (approval No: 7/20521/θ23). Five tissue specimens of tattoos and nine diagnostic SD biopsies (n = 14 patients) were included. Formalinfixed, paraffinembedded tissue sections were stained for vimentin, CD117 and CD34 with the streptavidin– biotin peroxidaselabelled (LSAB) and doublestained for CD11c and CD163 with the LSAB and the alkaline phosphatase/antialkaline phosphatase (APAAP) methods. Percentages of discernable cell subpopulations were determined at ×600 magnification by counting ≥1500 cells in a randomly selected array of microscopic fields that, perpendicularly to skin surface, spanned the whole dermis through a tissue region with brisk dye deposition. Odds ratios (OR) ‘to carry pigment inclusions’ were calculated for each cell subtype and compared employing ttest (comparison with OR = 1) and Wilcoxonand Mann– Whitney Utests, at p < 0.05. In both conditions intracellular pigment storage is confined to nonmast (CD117), nonendothelial (CD34), vimentinexpressing dermal cells. Compared with SD the % pigmentstoring cells was significantly lower in tattoos (mean ± SEM: 73.6 ± 1.99% vs. 81.6 ± 2.82%; p = 0.039). Table 1 and Figure 1 compile the core results of the Received: 11 January 2023 | Accepted: 8 March 2023

Alexandra Papoudou-Bai

Papers

Osteoblastic Solitary Plasmacytoma of Bone

Primary Bone Lymphoma: A Review of the Literature with Emphasis on Histopathology and Histogenesis

Evidence for differing roles of CD11c+CD163+ and CD11c−CD163+ cells in intracellular pigment storing in tattoos and stasis dermatitis