Small cell lung cancer (SCLC) is a highly malignant tumor with a very poor prognosis; therefore, more effective treatments are urgently needed for patients afflicted with the disease. In recent years, emerging molecular classifications based on key transcription factors of SCLC have provided more information on the tumor pathophysiology, metastasis, immune microenvironment, and acquired therapeutic resistance and reflected the intertumoral heterogeneity of the various SCLC phenotypes. Additionally, advances in genomics and single-cell sequencing analysis have further revealed the high intratumoral heterogeneity and plasticity of the disease. Herein, we review and summarize these recent lines of evidence and discuss the possible pathogenesis of SCLC.
Humans ; Small Cell Lung Carcinoma/genetics* ; Lung Neoplasms/genetics* ; Prognosis ; Genomics ; Phenotype ; Tumor Microenvironment

乳腺癌，骨转移，预后 乳腺癌是世界范围内女性最常见的恶性肿瘤，高达75%的患者最终会发生骨转移。骨转移发生风险与肿瘤分子分 型、组织病理和患者生理阶段等密切相关，骨转移合并其他部位转移、发生骨相关事件、骨转移灶的特点等都可影响患者的预后。 目前临床广泛应用的骨转移治疗方法包括全身应用抗肿瘤药物和骨改良药物、局部行骨转移灶放疗和骨转移灶手术。除抗肿瘤 药物外的其他治疗手段都有望改善患者预后。近年来发展的骨转移治疗新手段，如对乳腺癌原发灶的处理、放射性物质镭、骨转 移关键信号分子抑制剂和某些新技术应用在提高患者生存方面都有良好的前景。本文就乳腺癌骨转移患者的预后相关因素作 简要综述。

Objective To explore the long-term outcomes and complications of patients with hematological malignancies (HM) after haploidentical donor transplantation (HDT) or siblingidentical donor transplantation (SDT).Methods From June,2011 to July,2016,89 patients with HM receiving allo-HSCT were retrospectively analyzed,including 57 patients undergoing HDT and 32 cases undergoing SDT.Results The median time to achieve neutrophil engraftment was 2 days shorter after HDT than SDT,whereas that of platelet engraftment was 3 days longer after HDT than SDT.The cumulative incidence for 3 to 4 grade acute graft-versus-host disease (GVHD) was not obviously different between HDT and SDT (8.77％ versus 12.5％ respectively;x2 =0.313,P =0.576).The cumulative incidence for chronic GVHD was not significantly different between HDT and SDT (45.6％ versus 37.5％;~ =0.551,P =0.458).Cytomegalovirus (CMV) reactivity was significantly higher in patients after HDT (77.19％) than those after SDT (21.88％) (x2 =25.633,P＜0.001).The occurrence of hemorrhagic cystitis was also obviously higher in patients after HDT (26.32％)than those after SDT (3.85％) (x2 =5.340,P =0.021).The 1-,2-,and 3-year relapse-free survival rate of patients receiving HDT and SDT was 63.9％,55.4％,44.3％ and 71.2％,58.3％,51.8％,respectively (P =0.541).The 1-,2-,and 3-year overall survival rate of patients receiving HDT and SDT was 75.3％,65.3％,52.3％ and 76.9％,62.9％,62.9％,respectively (P =0.777).Conclusion Considering similar incidence of severe GVHD and long-term outcomes,haploidentical donors should be recommended as a potential alternative donor source when an identical donor is lacking for patients with HM.

Objective To study the immune re-constitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematological malignancies.Methods From June 2011 to May 2015,65 patients with hematological malignancies were analyzed retrospectively.Lymphocyte subsets were determined by flow cytometry (FCM),including total T lymphocytes (CD3+),helper T cells (CD3+ CD4+),cytotoxic T cells (CD3+ CD8+),CD4/CD8 ratio,nature killer (NK) cells (CD3-CD56+),NKT cells (CD3+ CD56+),B lymphocytes (CD19+),naive T cells (CD3+ HLA-DR+),static T cells (CD3+ HLA-DR-),and regulatory T cells (CD4+ CD25high Foxp3+) on the day 14,28 and 42,and on the month 2,3,6,9,12,15,18 and 24 after allo-HSCT.Results The percentage of CD3+ T cells located normal range after hematological recovery,and its absolute number recovered to normal range at + 15 months.The percentage of CD3+ CD4+ T cells recovered to normal range at + 24 months.However,the absolute number of CD3+ CD4+ T cells did not recover to normal range until 24 months after allo-HSCT.The percentage of CD3+ CD8+ T cells was higher than normal range at + 42 day,and its absolute number was greater than normal range at + 3 months.Hence,low CD4/CD8 ratio was observed for a long period.The re-constitution time points of the percentage and absolute number of CD3+ HLA-DR+ T cells were + 3 months and + 24 months respectively.The re-constitution time points of the percentage and absolute number of CD3 + HLA-DR-T cells were + 2 months and + 15 months respectively.The re-constitution time points of the percentage and absolute number of regulatory T cells were + 12 months and + 15 months respectively.The percentage of NKT cells located in normal range after hematological recovery,and its absolute number retumed to normal range at + 12 months.The re-constitution time points of the percentage and absolute number of B cells were + 9 months and + 18 months respectively.The percentage of NK cells located in normal range after hematological recovery,and its absolute number returned nearly to normal range at + 3 months.Conditioning regimen containing ATG,source of stem cells,CD34+ cell number,GVHD,and CMV reactivation were all associated with immune re-constitution after allo-HSCT.Conclusion Different immune cells showed different re-constitution models after allo-HSCT,and the percentage recovered faster than absolute number for a certain kind of immune cells.Studying immune re-constitution and its associated factors may offer beneficial information for insight into transplantation immunology and improve the management of allo-HSCT.

In recent years, epidermal growth factor receptor tyrosine kinase inhibitors have been recommended by many guidelines as first-line drugs for advanced non-small cell lung cancer (NSCLC) with EGFR gene mutations and no resistance. However, with the prolongation of medication time, most appear acquired resistance. In recent years, breakthroughs in inhibitors of programmed death-1 (PD-1) and its ligand (PD1 ligand, PD-L1) have rapidly changed the therapeutic model of NSCLC. Recent studies have shown that the efficacy of immune checkpoint inhibitors in EGFR-mutant NSCLC patients is not satisfactory, which might be caused by low PD-L1 expression, inhibitory immune microenvironment and low tumor mutation load. This review will elaborate the immune microenvironment of NSCLC patients with EGFR mutation, the latest study progression of immune checkpoint inhibitors and its combined with TKI, expecting to bring new hopes for the treatment of EGFR-mutant NSCLC patients.
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Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; immunology ; ErbB Receptors ; genetics ; Humans ; Immune System ; drug effects ; immunology ; Lung Neoplasms ; drug therapy ; genetics ; immunology ; Molecular Targeted Therapy ; methods ; Mutation