Cytogenetics of pineoblastoma: four new cases and a literature review

Pineoblastoma represents a class of primitive neuroectodermal tumors (PNET) with poorly differentiated neuroepithelial cells that are histologically indistinguishable from medulloblastomas. It is a rare tumor, typically arising in childhood, and to date only a few cytogenetic cases have been published. We report four new cases in which conventional cytogenetics demonstrated the presence of an abnormal clone. The tumors showed a variety of ploidy levels, from hypodiploid to hypertetraploid. Both structural and numerical aberrations were frequent, and in three out of the four cases a large degree of cell-to-cell variation was observed. The most frequently involved chromosome in structural rearrangements was chromosome 1, observed in three of the four cases. The short arm was involved in two of the three cases; in the third case, the anomaly was in the long arm. Two cases showed unbalanced gain of chromosome 17q, one of them showing i(17)(q10). Together, the four cases illustrate the complex karyotypic nature of this tumor type and represent a step toward determining whether a nonrandom cytogenetic picture exists and how this may be related to other associated tumor types.     

Antibody levels against tetanus and diphtheria after polychemotherapy for childhood sarcoma: a report from the Late Effects Surveillance System

Background

It is known that antineoplastic treatment may induce secondary immunodeficiency, but studies after childhood sarcoma are rare. Since 1998, the Late Effects Surveillance System (LESS) of the German Society for Paediatric Oncology and Haematology (GPOH) prospectively registers late effects in soft tissue-, osteo- and Ewing's sarcoma patients treated within the therapy trials EICESS-92/EURO-E.W.I.N.G.-99, CWS-96/CWS-2002P, COSS-96 in Austria, Germany and Switzerland.

Patients and methods

Antibody levels (AL) against diphtheria and tetanus were used as markers for immunity and classified according to established guidelines for protective AL values. There were 47 eligible relapse-free patients < 21 years of age (31 males; 10 osteosarcoma, 12 Ewing's and 25 soft tissue sarcoma patients). Median age at diagnosis was 9.6 (interquartile range: 4.4-14.7) years.

Results

A median 7.2 (3.7-12.2) months after end of antineoplastic therapy, in 28% (13/47; 95% CI 16-43%) of patients there were no protective AL (<0.1 IU/ml) against diphtheria and/or tetanus. Diphtheria and tetanus AL were positively correlated (r = 0.39; p = 0.007). In multivariable analysis, the type of treatment had no effect on AL, similar to tumour type and time of examination after treatment end. Younger patients had significantly lower AL against tetanus (p = 0.009) and girls had significantly lower AL against diphtheria than boys (p = 0.015).

Conclusion

Lack of protective AL against tetanus and/or diphtheria is frequent after childhood sarcoma treatment. Prospective surveillance of immunity and, if indicated, re-immunization is warranted in patients treated for childhood cancer.     

Spatial clustering of childhood cancers in Switzerland: a nationwide study

Purpose

Childhood cancers are rare and little is known about their etiology. Potential risk factors include environmental exposures that might implicate spatial variation of cancer risk. Previous studies of spatial clustering have mainly focused on childhood leukemia. We investigated spatial clustering of different childhood cancers in Switzerland using exact geocodes of place of residence.

Methods

We included 6,034 cancer cases diagnosed at age 0–15 years during 1985–2015 from the Swiss Childhood Cancer Registry. Age and sex-matched controls (10 per case) were randomly sampled from the national censuses (1990, 2000, 2010). Geocodes of place of residence were available at birth and diagnosis for both cases and controls. We used the difference in k-functions and Cuzick–Edwards test to assess global clustering and Kulldorff’s circular scan to detect individual clusters. We also carefully adjusted for multiple testing.

Results

After adjusting for multiple testing, we found no evidence of spatial clustering of childhood cancers neither at birth (p?=?0.43) nor diagnosis (p?=?0.13). Disregarding multiple testing, results of individual tests indicated spatial clustering of all childhood cancers combined (p?<?0.01), childhood lymphoma (p?=?0.01), due to Hodgkin lymphoma (HL) (p?=?0.02) at diagnosis, and embryonal tumors of the central nervous system (CNS) at birth and diagnosis, respectively (p?=?0.05 and p?=?0.02).

Conclusions

This study provides weak evidence of spatial clustering of childhood cancers. Evidence was strongest for HL and embryonal CNS tumors, adding to the current literature that these cancers cluster in space.

     

Paradoxical SR Ca2+ release in guinea-pig cardiac myocytes after β-adrenergic stimulation revealed by two-photon photolysis of caged Ca2+

In heart muscle the amplification and shaping of Ca²⁺ signals governing contraction are orchestrated by recruiting a variable number of Ca²⁺ sparks. Sparks reflect Ca²⁺ release from the sarcoplasmic reticulum (SR) via Ca²⁺ release channels (ryanodine receptors, RyRs). RyRs are activated by Ca²⁺ influx via L-type Ca²⁺ channels with a specific probability that may depend on regulatory mechanisms (e.g. β-adrenergic stimulation) or diseased states (e.g. heart failure). Changes of RyR phosphorylation may be critical for both regulation and impaired function in disease. Using UV flash photolysis of caged Ca²⁺ and short applications of caffeine in guinea-pig ventricular myocytes, we found that Ca²⁺ release signals on the cellular level were largely governed by global SR content. During β-adrenergic stimulation resting myocytes exhibited smaller SR Ca²⁺ release signals when activated by photolysis (62.3% of control), resulting from reduced SR Ca²⁺ content under these conditions (58.6% of control). In contrast, local signals triggered with diffraction limited two-photon photolysis displayed the opposite behaviour, exhibiting a larger Ca²⁺ release (164% of control) despite reduced global and local SR Ca²⁺ content. This apparent paradox implies changes of RyR open probabilities after β-adrenergic stimulation, enhancing local regenerativity and reliability of Ca²⁺ signalling. Thus, our results underscore the importance of phosphorylation of RyRs (or of a related protein), as a regulatory physiological mechanism that may also provide new therapeutic avenues to recover impaired Ca²⁺ signalling during cardiac disease.     

Loss of X chromosome in childhood acute lymphoblastic leukemia

We present six cases of childhood acute lymphoblastic leukemia (ALL) in which an acquired loss of the X chromosome was detected. The cases derive from a consecutive series of 178 childhood ALL, consisting of 80 girls and 98 boys. In five cases the presence of the TEL-AML1, t(12;21), fusion product was detected by FISH. The single negative case had an unusual t(1;19)(p13;q13). In addition, this was the only case that did not have a cytogenetically visible rearrangement involving one of the chromosome regions 6q, 9p, or 12p. The six cases showed the typical presentation features of an ALL of FAB type L1, a common ALL immunophenotype with myeloid marker co-expression, and a median presenting age of 7 years. We, therefore, conclude that loss of chromosome X may be a secondary event in older girls with TEL-AML1-positive ALL.     

微载体培养MEK和Vero细胞试制甲肝灭活疫苗

目的探索微载体培养细胞大量制备甲肝病毒抗原及其灭活疫苗的可行性。方法使用 Cytodex- 1培养恒河猴胚肾细胞和 Vero细胞制备 HAV ,经过初步纯化、甲醛灭活、吸附佐剂 ,制成甲肝灭活疫苗 ,免疫昆明种小白鼠 ,测定免疫原性。结果 HAV X株和 W株抗原滴度分别为 1∶ 2 5 6、1∶ 12 8,感染滴度 (log TCID5 0 / m l)分别为 8.5 0、8.17,与静止培养获得的滴度相当。小鼠抗 HAV抗体第 45 d达到峰值 ,滴度分别为 1∶ (96 .0± 78.4)、1∶ (12 8.0± 70 .1)。结论实验性甲肝灭活疫苗具有良好的免疫原性 ,应用微载体培养细胞制备甲肝灭活疫苗是可行的。     

中西医结合治疗输卵管阻塞的临床分析

将 32例输卵管阻塞致不孕的患者分成中药组和对照组,两组患者行输卵管疏通术后在应用抗生素治疗的同时,中药组再口服“通管方”和“灌肠 2号方”灌肠,以 1个月为一疗程,进行两组保持通畅率以及妊娠率的比较。结果保持通畅率中药组优于对照组(P<0. 05),妊娠率两组无显著性差异(P>0. 05)。