FOLFCIS Treatment and Genomic Correlates of Response in Advanced Anal Squamous Cell Cancer

Background

Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.

The prognostic value of cytogenetic analyses in patients with acute nonlymphocytic leukemia treated with the same intensive chemotherapy.

BACKGROUND. Some specific chromosome abnormalities for the leukemias have been proven to be associated with the prognosis of acute nonlymphocytic leukemia (ANLL). However, most of these reports included patients treated with different protocols. Therefore, some bias has been involved in the evaluation of the prognostic factors in such reports. METHODS. The authors studied the morphologic, cytogenetic, and clinical features of 136 patients (86 males and 50 females) with de novo ANLL treated with the same protocol of intensive induction chemotherapy using multivariate analyses. RESULTS. Chromosome abnormalities were detected in 62.5% of the patients. The overall complete remission (CR) rate of disease was 85.5% in these patients. More than 90% of the patients with t(8;21) and pseudodiploid abnormalities achieved experienced CR. However, CR rates in the patients with abnormalities of chromosome 5 or 7 were 50%. With multivariate analyses by the type of karyotypic abnormality, CR duration and survival time of the patients with t(8;21) were longer than those of patients with normal karyotype and abnormalities of chromosome 5 or 7. Abnormalities of chromosome 5 or 7 and hyperdiploid were associated with poor prognosis. Older age and lower platelet counts also were factors contributing to shorter survival times. With the analysis with French-American-British (FAB) classification, only hypoplastic leukemia was a poor prognostic factor. CONCLUSIONS. These data suggest that cytogenetic analyses plays an important role in estimating the prognosis of patients treated with intensive induction chemotherapy.     

Transmission disequilibrium tests confirm the link between DRD4 gene polymorphism and infant attachment.

Following up the results of a previous population association study (Lakatos et al. [2000: Mol Psychiatry 5:633-637; Lakatos et al. [2002: Mol Psychiatry 7:27-31]) by analyses based on parental genetic data confirmed the link between infant attachment and the dopamine D4 receptor (DRD4) gene. Extended transmission disequilibrium tests (ETDT) were performed to determine whether biased transmission of exon III 48 basepair repeat alleles occurred to infants displaying disorganized and secure attachment behavior with their mothers. The overall allele-wise TDTs were significant for both groups (P = 0.038 and 0.020, respectively): a trend for preferential transmission of the seven-repeat allele to disorganized infants was observed (TDT(chi)(2) = 3.27, df = 1, P = 0.071), and there was a significant non-transmission of the same allele to securely attached infants (TDT(chi)(2) = 6.00, df = 1, P = 0.014). Analysis of haplotypes of the exon III repeat and the -521 C/T promoter polymorphisms in family trios showed that the transmission bias in the larger secure group was due to the low-rate transmission of the T.7 haplotype containing both the seven-repeat and the -521 T alleles (TDT(chi)(2) = 4.46, df = 1, P = 0.035). This suggests that not carrying the T.7 haplotype of the DRD4 gene may act as a resilience factor in the optimal development of early attachment.     

Attachment and temperament revisited: infant distress,attachment disorganisation and the serotonin transporter polymorphism

Objective: This study’s aim was to evaluate whether infant disorganised attachment and infant proneness to distress exhibited differential relations to infant genetic factors as indexed by the serotonin transporter polymorphism. Background: The role of the short allele of the serotonin transporter polymorphism (5-HTTLPR) in enhancing sensitivity to fearful and negative affect has been well-established. In the current study, we used this known property of the short allele to provide a test of an important postulate of attachment theory, namely that infant attachment security or disorganisation is not a function of the infant’s proneness to distress. Methods: Participants were 39 parents and infants assessed between 12 and 18 months in the Strange Situation Procedure. Genotype categories for the 5-HTTLPR (and rs25531) were created by both the original and the reclassified grouping system; infant proneness to distress was assessed directly in the Strange Situation Procedure. We also assessed maternal behaviour at 18 months to evaluate whether any observed genetic effect indicated a passive effect through the mother. Results: Consistent with previous findings, the 5-HTTLPR short allele was significantly related to the infant’s wariness and distress, but was not related to attachment security or attachment disorganisation. In addition, maternal disrupted interaction with the infant was not related to infant genotype or infant distress. Conclusion: Results support the concept that infant proneness to distress is associated with serotonergic factors while infant attachment security or disorganisation is not a function of either 5-HTTLPR or behaviourally rated proneness to distress.     

Myrica rubra leaves as a potential source of a dual 5-LOX/COX inhibitor

Myrica rubra Sieb. et Zucc. is a valuable fruit tree that is used in Chinese, Japanese and Taiwanese traditional medicine. We investigated the anti-inflammatory activity of M. rubra leaves extracted with four different solvents. Total phenolics were determined using the Folin–Ciocalteu method. Extracts were investigated for their inhibitory activity toward the pro-inflammatory enzymes cyclooxygenase-1 and -2 (COX-1, COX-2) and 5-lipoxygenase (5-LOX). The ethanol extract of M. rubra leaves demonstrated a strong inhibition of prostaglandin E₂ (PGE₂) biosynthesis catalyzed by both COX-1 (93.42%) and COX-2 (75.71%) and leukotriene B₄ (LTB₄) formation catalyzed by 5-LOX (82.72%). Further we identified selective COX-1 inhibition by the n-butanol and aqueous fractions of the ethanol extract (with an IC₅₀ for COX-1 inhibition of 1.07 and 0.71?µg?mL^?1 _, respectively) and dual 5-LOX/COX inhibition by the ethyl acetate fraction (with an IC₅₀ of 3.29 for COX-1, 2.54 for COX-2 and 8.30?µg?mL^?1 for 5-LOX).