An Embryonic Diapause-like Adaptation with Suppressed Myc Activity Enables Tumor Treatment Persistence

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卡培他滨中有机残留溶剂的检测

目的建立气相色谱法测定卡培他滨原料药中二氯甲烷、乙醇、甲醇和乙酸乙酯4种有机溶剂。方法采用DB-624毛细管柱,FID检测器,以DMSO为溶剂。结果各有机溶剂的平均加样回收率为93.7%～97.6%,RSD为2.5%～3.7%。结论该方法稳定准确,可用于卡培他滨中有机溶剂残留的检测。     

Immunohistochemical Detection of Post-Therapy Residual Testicular Lymphoblasts in Childhood Acute Lymphoblastic Leukemia (All)

The aim of this study was to evaluate the diagnostic value of immunohistochemistry with monoclonal antibodies (MoAbs) in detecting residual blast cells in testicular biopsies from children with acute lymphoblastic leukemia (ALL). In a prospective study of 26 patients, testicular biopsies were performed after completion of therapy, and the average follow-up after biopsies was 29 months. After immunostaining, seven patients with negative biopsies on routine histology showed scattered, strongly calla-positive cells as well as cells reacting with anti-B (CD22) MoAb. Among these seven patients with residual blast cells, four had relapsed either in testes (n = 1), bone marrow and testes (n = 1), or in the bone marrow (n = 2). In contrast, among the 15 patients without residual blast cells, all but 1 remained in complete remission. In four other cases no definite conclusion was possible after immunohistochemical study. Four testicular biopsies from patients with occult infiltration were used as positive controls. Negative controls consisted of testicular biopsies from children with testicular ectopia and postmortem testicular tissue specimens. Results suggest that the risk of relapse is significantly higher in patients with positive immunohistochemical findings indicating persistent residual blast cells. However, the predictive value of these findings requires confirmation on a larger number of cases to have therapeutic implications.     

Will new drugs change the standard of care for patients with mantle cell lymphoma?

Mantle Cell lymphoma is a heterogeneous malignancy that has different subtypes with variable levels of aggressiveness. Research on the pathobiology of this disease is helping us understand the etiology for this heterogeneity and has the potential to guide future therapeutic options. The availability of the Ki67 proliferation index and the use of the MIPI score can help determine which of the numerous therapeutic options might be utilized. Minimal Residual Disease testing can act as a guide as to the potential benefit of maintenance therapy. This article discusses the current standard of care for Mantle Cell lymphoma and our current understanding of the pathobiology of the disease leading to strategies to improve patient outcomes with some of the newer targeted agents.     

Wilms Tumor 1 gene expression levels improve risk stratification in AML patients. Results of a multicentre study within the Spanish Group for Molecular Biology in Haematology

Histone deacetylase inhibitors (HDACi) had emerged as promising drugs in leukaemia, but their toxicity due to lack of specificity limited their use. Therefore, there is a need to elucidate the role of HDACs in specific settings. The study of HDAC expression in childhood leukaemia could help to choose more specific HDACi for selected candidates in a personalized approach. We analysed HDAC1‐11, SIRT1, SIRT7, MEF2C and MEF2D mRNA expression in 211 paediatric patients diagnosed with acute leukaemia. There was a global overexpression of HDACs, while specific HDACs correlated with clinical and biological features, and some even predicted outcome. Thus, some HDAC and MEF2C profiles probably reflected the lineage and the maturation of the blasts and some profiles identified specific oncogenic pathways active in the leukaemic cells. Specifically, we identified a distinctive signature for patients with KMT2A (MLL) rearrangement, with high HDAC9 and MEF2D expression, regardless of age, KMT2A partner and lineage. Moreover, we observed an adverse prognostic value of HDAC9 overexpression, regardless of KMT2A rearrangement. Our results provide useful knowledge on the complex picture of HDAC expression in childhood leukaemia and support the directed use of specific HDACi to selected paediatric patients with acute leukaemia.     

Prognostic significance of flow‐cytometry evaluation of minimal residual disease in children with acute myeloid leukaemia treated according to the AIEOP‐AML 2002/01 study protocol

In children with acute myeloid leukaemia (AML ), assessment of initial treatment response is an essential prognostic factor; methods more sensitive than morphology are still under evaluation. We report on the measurement of minimal residual disease (MRD ), by multicolour flow‐cytometry in one centralized laboratory, in 142 children with newly diagnosed AML enrolled in the Associazione Italiana di EmatoOncologia Pediatrica‐AML 2002/01 trial. At the end of the first induction course, MRD was <0·1% in 69, 0·1–1% in 16 and >1% in 51 patients. The 8‐year disease‐free survival (DFS ) of 125 children in morphological complete remission and with MRD <0·1%, 0·1–1% and ≥1% was 73·1 ± 5·6%, 37·8 ± 12·1% and 34·1 ± 8·8%, respectively (P  < 0·01). MRD was also available after the second induction course in 92/142 patients. MRD was ≥0·1% at the end of the first induction course in 36 patients; 13 reached an MRD <0·1% after the second one and their DFS was 45·4 ± 16·7% vs. 22·8 ± 8·9% in patients with persisting MRD ≥0·1% (P  = 0·037). Multivariate analysis demonstrated that MRD ≥0·1% after first induction course was, together with a monosomal karyotype, an independent adverse prognostic factor for DFS . Our results show that MRD detected by flow‐cytometry after induction therapy predicts outcome in patients with childhood AML and can help stratifying post‐remission treatment.     

Toward liquid biopsies in cancer treatment: application of circulating tumor DNA

Circulating tumor DNA (ctDNA) refers to the fraction of cell‐free DNA in a patient's blood originating from tumor cells. Increased knowledge about tumor genomics, improvements in targeted therapies, and accompanying advances in DNA‐sequencing technologies have increased the interest in using ctDNA as a minimally invasive tool in cancer diagnostics and treatment. Especially, early tumor detection including identification of minimal residual disease and stratification of adjuvant therapy are promising approaches. Also, ctDNA showed to be reliable in treatment monitoring and can be used to assess therapy resistance due to the broad variety of tumor subclones captured in ctDNA. Therefore, using ctDNA in the clinical setting has the potential to improve therapeutic outcomes. In the present review, we summarize the status of ctDNA in oncology with focus of being an alternative to tissue biopsies in early detection and treatment monitoring.     

The Effect of Corneal Higher Order Aberrations on Postoperative Residual Astigmatism after Toric IOL Implantation

Background: To demonstrate the effect of preoperative higher order aberrations (HOAs) on postoperative residual astigmatism in toric intraocular lens (IOL) implantation.

Methods: A retrospective, controlled, comparative study that involved patients who underwent toric IOL implantation. Patients were divided into two groups according to the difference between the estimated residual astigmatism and actual postoperative astigmatism [difference ≤0.5 diopters (D), Group A; difference >0.5 D, Group B]. Corneal astigmatisms with axis, and various aberration values were compared between the two groups.

Results: Total RMS and HOA RMS values in Group B were significantly higher than those in Group A (p < .001, = 0.003). The vertical coma value, and its absolute value, in Group B were significantly higher than those in Group A (p < .001, = 0.002). The total RMS and absolute value of the vertical coma showed a positive linear correlation with the degree of residual postoperative astigmatism (R-square = 0.139, 0.131; p = .027, 0.036).

Conclusions: If the residual astigmatism after insertion of the toric IOL was greater than expected, corneal aberrations, shown by total RMS and HOA RMS values before surgery, especially of the vertical coma, tended to be high.