Th1 or Th2 cytokines are correlated with Tregs and T cell subsets and pregnancy outcomes in patients with autoimmune thyroid disease during early, middle, late pregnancy, and postpartum period.

Autoimmune thyroid disease (AITD) is a T lymphocytes-mediated autoimmune disorder affecting pregnant women. The current study sought to determine the correlations between T helper-1 (Th1)/T helper-2 (Th2) cytokines and regulatory T cells (Tregs) and T cell subsets and pregnancy outcomes in AITD patients during early pregnancy (T1), middle pregnancy (T2), late pregnancy (T3), and postpartum period (PP). A total of 60 patients with Graves' disease, 60 patients with Hashimoto's thyroiditis, and 30 healthy pregnant women were initially enrolled in the study. Thyroid hormones and antibodies, Th1 or Th2 cytokines, transforming growth factor-ß, Tregs, CD4+ T helper cells (CD4+), CD8+ T helper cells (CD8+) levels were determined by means of Maglumi2000 automatic chemiluminescence instrument, enzyme-linked immunosorbent assay, and flow cytometry. Our findings demonstrated higher IFN-γ and IL-2 levels, along with lower IL-4, IL-10, TGF-ß, Treg, and CD4+/CD8+ levels in AITD patients during T1, T2, T3, and PP. Furthermore, the TGF-ß, Treg, and CD4+/CD8+ levels were lower in the IFN-γ/IL-2 high expression group but higher in the IL-4/IL-10 high expression group. The IFN-γ and IL-2 levels were higher, while IL-4 and IL-10 level were lower in AITD patients with adverse pregnancy outcomes. Lastly, Th1 cytokines were higher and Th2 cytokines were lower in AITD patients and elicited correlation with Tregs and CD4+/CD8+ levels. Collectively, our findings highlighted that up-regulation of Th1 cytokines may increase the percentage of adverse pregnancy outcomes in AITD patients.

Brain Metastases of Non-Small Cell Lung Cancer: Magnetic Resonance Spectroscopy for Clinical Outcome Assessment in Patients with Stereotactic Radiotherapy.

BACKGROUND: Brain metastases (BM) are severe incidents among patients with non-small cell lung cancer (NSCLC) and have been associated with significant morbidity and decreased survival; thus, new methods are required to improve clinical management. Magnetic resonance spectroscopy (MRS) allows noninvasive measurements of biochemical information from tumor tissue, providing clinically useful imaging biomarkers. The primary aim of this study was to explore the application of MRS in the assessment of tumor prognosis after stereotactic radiotherapy in NSCLC patients with BM. PATIENTS AND METHODS: MRS was performed on NSCLC patients attending Qingdao Center Hospital with suspected BM, and 68 patients were included in the survival analysis. The qualitative and quantitative parameters of MRS metabolites, such as choline (Cho), creatine (Cr), and N-acetyl-aspartate (NAA), were recorded. To select a cutoff for MRS metabolite parameters in the tumor and to distinguish patients who had recurrence, we performed an ROC curve analysis. Univariate and multivariate Cox regression analyses were used to assess the association between MRS metabolite parameters and clinical cancer prognosis. RESULTS: The average age was 56 years. A total of 68 NSCLC patients underwent metabolic evaluation with single voxel proton MRS and were selected for retrospective analysis. According to the area under the curve (AUC) to predict recurrence, the MRS metabolite parameters were determined as Cho (AUC=0.550), Cr (AUC=0.415), NAA (AUC=0.524), NAA/Cr (AUC=0.600), Cho/Cr (AUC=0.723), and Cho/NAA (AUC=0.543). Cho and Cr predicted poor survival while Cho/Cr and NAA/Cr predicted improved survival (P<0.05). In the multivariate model with adjustment to establish the potential role of MRS metabolite parameters, Cho/Cr showed a significant association with OS (P=0.009) and PFS (P=0.006) after stereotactic radiotherapy. CONCLUSION: The positive results of this study indicate the predictive value of metabolic characteristics of BM detected with MRS for the outcome after stereotactic radiotherapy.

Stereotactic ablative radiotherapy in treatment of early-stage non-small cell lung cancer: Unsolved questions and frontiers ahead.

Stereotactic ablative radiotherapy (SABR) has been recognized as a standard alternative treatment to surgery for inoperable early stage non-small cell lung cancer (NSCLC). Guaranteed local control rates over 90% makes oncologists wonder whether SABR is qualified enough to challenge surgery in operable patients. The role of SABR for centrally located lesions would be another question because of the increased risk of severe toxic effect. Plenty of studies suggest that optimization of dose regimen and appropriate case selection would be helpful. Additionally, the effect of adjuvant therapy following SABR in selected patients is worth looking forward, given that it significantly reduced risk of recurrence after complete resection. A consensus about salvage treatment after SABR also needs, given the current diversity of options. Finally, witnessing the emergence of proton therapy and immunotherapy, we believe that the future of SABR lay behind these novel forms of treatment.

Prophylactic cranial irradiation improved the overall survival of patients with surgically resected small cell lung cancer, but not for stage I disease.

OBJECTIVES: We conducted a retrospective study to evaluate the role of prophylactic cranial irradiation (PCI) on patients with surgically resected small cell lung cancer (SCLC). PATIENTS AND METHODS: Between January 2003 and December 2009, the records of completely resected patients who were diagnosed with SCLC and definitive pTNM stage on the basis of histological proof were reviewed. According to the therapy modality, patients were allocated to PCI group and non-PCI group. RESULTS: A total of 193 patients were finally included, 67 patients in PCI group and 126 in non-PCI group. The OS rates at 2-year and 5-year in PCI group were 92.5%, and 54.9%, respectively, and those of non-PCI were 63.2% and 47.8%, respectively (p=0.005). The BMFS rate at 2-year and 5-year in PCI group was significantly better than those of non-PCI group (96.8%, 76.6% and 79.4%, 75.5%, respectively, p = 0.014). But PCI could not confer survival benefit in the patients with p-stage I. Multivariate analysis revealed that PCI (HR = 2.339; p = 0.001) was an independent prognostic factor of the overall survival. CONCLUSIONS: PCI could improve the OS of patients with surgically resected SCLC, but not for p-stage I patients.

Increased population of CD4(+)CD25(high), regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients.

PURPOSE: Regulatory T cells (T-reg) that control harmful autoimmune T cells in the periphery may also suppress the immune response against cancer. In this study we investigated the possible involvement of CD4(+)CD25(high) T-reg in the immune impairment of patients with acute myeloid leukemia (AML). EXPERIMENTAL DESIGN: The frequencies and phenotypes of CD4(+)CD25(high) T cells in the peripheral blood of AML patients were determined by flow cytometry. To assess the functional activity of CD4(+)CD25(high) T cells, CD4(+)CD25(high), and CD4(+)CD25(-) T cells were sorted from peripheral blood mononuclear cells with FACS Vantage. The immunoregulatory properties of CD4(+)CD25(high) and CD4(+)CD25(-) T cells were characterized by proliferation assays and cytokine production assays. In addition, the frequency of apoptotic and proliferating cells in CD4(+)CD25(high) T cells were respectively evaluated by 7AAD and ki67 binding cells using flow cytometry. RESULTS: Compared with healthy controls, AML patients had a higher proportion of CD4(+)CD25(high) T cells in peripheral blood. These cells were CD45-RA(-), CD69(-), CD45-RO(+), CD95(+), and intercellular CTLA-4(+), and secreted low levels of TNF-alpha and IL-10, but no IL-2, IL-4, IL-5, and IFN-gamma. They inhibited the proliferation and cytokine production (IL-2, IFN-gamma) of CD4(+)CD25(-) T cells, but improved IL-10 production under the co-culture of both subsets with stimulation, thus behaving as T-reg. Notably, CD4(+)CD25(high) T cells in AML patients presented significantly higher apoptosis and proliferation than that of healthy individuals. CONCLUSIONS: The frequency of CD4(+)CD25(high) T-reg in peripheral blood in AML patients is significantly higher when compared with healthy individuals, likely due to the increasing proliferation of CD4(+)CD25(high) T cells.

[Correlation of immunophenotype to cytogenetics and clinical features of adult acute myeloid leukemia].

BACKGROUND & OBJECTIVE: New WHO classification has been rapidly used in diagnosis of leukemia. Based on coexpression and correlation of lineage-associated antigens, multiparameter high-resolution flow cytometry has been developed to precisely identify lineage characteristics of leukemia. Some immunophenotypes correlate with cytogenetic abnormality and prognosis. This study was to analyze immunophenotype of naive acute myeloid leukemia (AML), and explore its correlations to cytogenetics, clinical features, and FAB subtype of AML. METHODS: Multiparameter high-resolution flow cytometry with a panel of 25 different monoclonal antibodies was used to analyze the surface and cytoplasmic antigens expressions of 96 adults with AML; G-binding technique was used to analyze karyotype of 73 of the 96 patients. RESULTS: In these AML patients, some antigens were correlated with FAB subtypes:expression of CD2 was enhanced in AML-M3; HLA-DR, CD34, and CD56 were absent in AML-M3; expression of CD19 was increased in AML-M2; expressions of CD14 and CD56 were enhanced in AML-M5; MPO was absent in AML-M0. Karyotype abnormality was detected in 40(54.8%) patients. CD22, CD56, and TdT expressions were correlated with karyotype abnormality. t(8; 21) was only detected in 10 AML-M2 patients with high expressions of CD15, CD19, CD34, and CD56; no lymphoid lineage antigens were detected in 7 AML-M3 patients with t (15; 17). Expressions of CD4 and TdT were positively correlated with patient's age; expressions of CD7 and CD14 were positively correlated with high white blood cell count; expressions of CD4, CD14, and CD56 were positively correlated with high platelet count. CONCLUSIONS: The abnormal antigen expression of AML is tightly linked with karyotype abnormality. Detection of immunophenotype may help to diagnose and classify AML.

[Immunophenotypes in 115 patients with acute myeloid leukemia by multi-color flow cytometry].

Immunophenotyping has become common in the diagnosis and classification of leukemia. To evaluate the immunophenotype of acute myeloid leukemia (AML), multiparameter flow cytometry and CD45/SSC gating were used to analyze the surface and cytoplasmic antigen expressions in 115 cases of AML. The results were compared with the French-American-British (FAB) Cooperative Group classification to help define the best use and role of multiparameter flow cytometry in the diagnosis and proper classification of AML. The results showed that CD38, CD38 and CD13 were the most commonly expressed antigen (94.8%, 91.3% and 89.6%, respectively). CD7 was the most commonly expressed lymphoid antigen (20.2%), followed by CD19 (16.5%) and CD2 (15%). Some immunophenotypes correlated with FAB type, including increased frequency of CD2 in M(3); lack of HLA-DR, CD34 and CD56 expression in M(3); increased frequency of CD19 in M(2), CD14 and CD56 in M(5) and lack of MPO in M(0). In conclusion, multiparameter flow cytometry is a reliable technique in the diagnosis of AML, and some immunophenotypes correlate with FAB type.