Novel missense mutation of the DNA topoisomerase I gene in SN-38-resistant DLD-1 cells

Irinotecan hydrochloride, a camptothecin derivative, is one of the most effective drugs for colorectal cancer, and SN-38 is its main active metabolite. Development of resistance is a major obstacle to the clinical application of this drug. We established an SN-38-resistant subline from DLD-1 human colon cancer cells by continuous exposure to SN-38 and studied the mechanisms of resistance. The resistant subline (designated as DLDSNR6) had 10- to 100-fold higher resistance to camptothecin derivatives but showed no cross-resistance to doxorubicin, mitomycin C, and etoposide. DLDSNR6 cells carried a missense mutation in one allele of the DNA topoisomerase I gene that substituted glycine for serine at amino acid residue 365 accompanied by loss of the latter part of the remaining wild-type allele. Topoisomerase I expression was equal in DLDSNR6 and DLD-1 cells, but the nuclear extract of DLDSNR6 cells showed lower topoisomerase I catalytic activity. Moreover, exposure to camptothecin caused less accumulation of topoisomerase I-DNA complexes in DLDSNR6 cells than in DLD-1 cells. These findings suggest that the mutation interfered with both the catalytic activity of topoisomerase I and the stability of the ternary complex between topoisomerase I, DNA, and SN-38. This SN-38-resistant DLDSNR6 cell line may be useful for understanding the mechanisms of topoisomerase I function and drug-enzyme interactions.     

Effect of thermocycling on interfacial gap-formation in Class V cavities and mechanical properties of spherical silica filler addition to resin-modified glass ionomer restorations

The effects of thermocycling at 20,000 cycles and addition of silanized spherical silica filler (SF) on resin-modified glass ionomer cement (RMGIC) restorations were investigated. A RMGIC added with an untreated spherical silica filler (UF) was used as a comparison. Marginal gaps in Class V tooth cavities, compressive strength, diametral tensile strength, flexural strength, and shear bond strengths to enamel and dentin were examined. All thermocycled samples showed decreased frequency of marginal gap formation as compared to the 24-hour samples, with reduction of 73% to 95%. At the immediate condition, after 24 hours, and after thermocycling, the addition of 10 wt% SF yielded the most favorable results in terms of marginal gap formation in Class V cavities, compressive strength, flexural strength, and shear bond strength to enamel. Diametral tensile strength and flexural strength were also increased significantly by the addition of 5 wt% SF. Further, shear bond strength tests showed that the addition of SF had no effect on bonding capability to enamel and dentin.     

A case of Reye syndrome with rotavirus infection accompanied with high cytokines

We report on a 23-month-old boy with a rare complication of rotavirus gastroenteritis. He was diagnosed as acute encephalopathy with DIC accompanied with high levels of cytokines. The liver pathology also revealed mild infiltration and fatty changes. He was suspected to be suffering from a cytokine storm followed by Reye syndrome.     

Primary biomarkers in cerebral spinal fluid obtained from patients with influenza-associated encephalopathy analyzed by metabolomics

In order to search for the specific biomarkers of patients with influenza-associated encephalopathy this article analyzed all metabolites in cerebrospinal fluid (CSF) by using metabolome analysis. In all metabolites, the peaks of two molecular weights, 246.0092 and 204.0611, were significantly higher than those in other diseases including influenza without convulsion (p < .05). The peak of a molecular weight 228.0247 in all of the patients except one was less than that in other patients. These results indicate that the new metabolites detected in CSF would be primary markers for the diagnosis of influenza-associated encephalopathy.     

Relationship between plasma concentrations of cytokines, ratio of CD4 and CD8, lymphocyte proliferative responses, and depressive and anxiety state in bulimia nervosa

OBJECTIVE: Immunological dysfunction in participants with bulimia nervosa (BN) might be due to not only chaotic eating behavior but also psychological state, such as depression and anxiety, because studies have found a close relationship between depression, anxiety, and immunological dysfunction. METHOD: Participants included 20 females with BN and 14 control females. In eight BN participants, immune function was measured twice, before and after inpatient treatment. Cytokines [interleukin (IL)-1 receptor antagonist, IL-2 soluble receptor alpha, IL-6 soluble receptor (sIL-6r), and tumor necrosis factor soluble receptor II (sTNF-rII)], lymphocyte subsets (CD4 and CD8), and lymphocyte proliferative responses were measured. RESULTS: There were no differences in plasma cytokine levels or lymphocyte subsets between the BN participants and the controls. Conversely, lymphocyte proliferative responses were significantly lower in BN participants than in the controls. Lymphocyte proliferative responses negatively correlated with anxiety trait and improved with an improvement of bulimic state. CONCLUSION: The comorbid nonspecific anxiety trait significantly contributes to suppressing lymphocyte proliferative responses in BN participants.     

Recent advances in video‐assisted thoracoscopic surgery for lung cancer

As a result of increased use of CT in both screening and daily practice, the number of early lung cancers has increased enormously. Surgeons pursue both curativity and reduced invasiveness in treating patients with early stage lung cancer; therefore, minimally invasive operations, such as video‐assisted thoracoscopic surgery (VATS) lobectomy are now being routinely performed. Most previous reports have shown that there is no difference in mortality and local recurrence between open surgery and VATS in stage I patients. However, surgeons' improved technical experience and patients' demands could soon make VATS lobectomy the operative method of choice for early stage lung cancer. Moreover, the indications for VATS are expanding to encompass complex procedures such as segmentectomy or sleeve resection. Training and dissemination of the technique and the monitoring of outcomes are necessary.     

Estrogen Receptor α Induction by Mitoxantrone Increases Abcg2 Expression in Placental Trophoblast Cells

Substrate‐induced upregulation of ATP‐binding cassette subfamily G member 2 (ABCG2) has been well studied in cancer cells, but it is also important to understand whether ABCG2 is upregulated by its substrates in tissues in which it is constitutively expressed. In the present study, we aimed to clarify the regulatory mechanism of Abcg2 expression by its substrate, mitoxantrone, in placental cells. Abcg2 mRNA expression in rat placental TR‐TBT 18d‐1 cells treated with 10 μM mitoxantrone for 24 h was increased, compared with that in nontreated cells, whereas 10 μM pheophorbide‐a had no effect. Methylated CpG level in the promoter region of the Abcg2 gene was low and was not altered by mitoxantrone. On the contrary, mitoxantrone markedly increased the expression of estrogen receptor (ER) α and progesterone receptor (PR) B. Fulvestrant, an ER antagonist, attenuated the mitoxantrone‐induced increase of Abcg2 mRNA expression, whereas mifepristone, a PR antagonist, had little effect. 17β‐estradiol, an ER ligand, positively regulated the mitoxantrone‐induced increase of Abcg2 expression. DNA demethylation by 5‐aza‐2‐deoxycytidine treatment increased ERα expression, but mitoxantrone failed to facilitate the demethylation of ERα promoter in TR‐TBT 18d‐1 cells. In conclusion, Abcg2 expression is induced by mitoxantrone via the induction of ERα in TR‐TBT 18d‐1 cells.