Dose finding and O6-alkylguanine-DNA alkyltransferase study of cisplatin combined with temozolomide in paediatric solid malignancies

Cisplatin may have additive activity with temozolomide due to ablation of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (MGMT). This phase I/II study determined recommended combination doses using the Continual Reassessment Method, toxicities and antitumour activity in paediatric patients, and evaluated MGMT in peripheral blood mononuclear cells (PBMCs) in order to correlate with haematological toxicity. In total, 39 patients with refractory or recurrent solid tumours (median age ∼13 years; 14 pretreated with high-dose chemotherapy, craniospinal irradiation, or having bone marrow involvement) were treated with cisplatin, followed the next day by oral temozolomide for 5 days every 4 weeks at dose levels 80 mg m−2/150 mg m−2 day−1, 80/200, and 100/200, respectively. A total of 38 patients receiving 113 cycles (median 2, range 1–7) were evaluable for toxicity. Dose-limiting toxicity was haematological in all but one case. Treatment-related toxicities were thrombocytopenia, neutropenia, nausea-vomiting, asthenia. Hearing loss was experienced in five patients with prior irradiation to the brain stem or posterior fossa. Partial responses were observed in two malignant glioma, one brain stem glioma, and two neuroblastoma. Median MGMT activity in PBMCs decreased after 5 days of temozolomide treatment: low MGMT activity correlated with increased severity of thrombocytopenia. Cisplatin–temozolomide combinations are well tolerated without additional toxicity to single-agent treatments; the recommended phase II dosage is 80 mg m−2 cisplatin and 150 mg m−2 × 5 temozolomide in heavily treated, and 200 mg m−2 × 5 temozolomide in less-heavily pretreated children

Preservation of Ranking Order in the Expression of Human Housekeeping Genes

Housekeeping (HK) genes fulfill the basic needs for a cell to survive and function properly. Their ubiquitous expression, originally thought to be constant, can vary from tissue to tissue, but this variation remains largely uncharacterized and it could not be explained by previously identified properties of HK genes such as short gene length and high GC content. By analyzing microarray expression data for human genes, we uncovered a previously unnoted characteristic of HK gene expression, namely that the ranking order of their expression levels tends to be preserved from one tissue to another. Further analysis by tensor product decomposition and pathway stratification identified three main factors of the observed ranking preservation, namely that, compared to those of non-HK (NHK) genes, the expression levels of HK genes show a greater degree of dispersion (less overlap), stableness (a smaller variation in expression between tissues), and correlation of expression. Our results shed light on regulatory mechanisms of HK gene expression that are probably different for different HK genes or pathways, but are consistent and coordinated in different tissues

Social change and the family: Comparative perspectives from the west, China, and South Asia

This paper examines the influence of social and economic change on family structure and relationships: How do such economic and social transformations as industrialization, urbanization, demographic change, the expansion of education, and the long-term growth of income influence the family? We take a comparative and historical approach, reviewing the experiences of three major sociocultural regions: the West, China, and South Asia. Many of the changes that have occurred in family life have been remarkably similar in the three settings—the separation of the workplace from the home, increased training of children in nonfamilial institutions, the development of living arrangements outside the family household, increased access of children to financial and other productive resources, and increased participation by children in the selection of a mate. While the similarities of family change in diverse cultural settings are striking, specific aspects of change have varied across settings because of significant pre-existing differences in family structure, residential patterns of marriage, autonomy of children, and the role of marriage within kinship systems.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45661/1/11206_2005_Article_BF01124383.pd

Marriage and inequality in Chinese society

Until now our understanding of marriage in China has been based primarily on observations made during the twentieth century. The research of ten eminent scholars presented here provides a new vision of marriage in Chinese history, exploring the complex interplay between marriage and the social, political, economic, and gender inequalities that have so characterized Chinese society