Augmentation of 3‐methylcholanthrene‐induced bioactivation in the human hepatoma cell line HepG2 by the calcium channel blocker nicardipine

(Cancer Sci 2010; 101: 652–657) The abilities of the dihydropyridine calcium channel blocker nicardipine (Nic) to induce cytochrome P450 1 family enzymes (CYP1s) and to enhance the 3‐methylcholanthrene (MC)‐mediated induction of CYP1s and formation of MC‐DNA adduct were examined in the human hepatoma cell line HepG2. The results from real time RT‐PCR analysis demonstrated that Nic could induce CYP1 mRNAs and enhance the MC‐mediated induction of the CYP1 mRNAs. The luciferase‐reporter gene assay using the HepG2‐A10 cell line, which has been previously established for the screening of aryl hydrocarbon receptor (AhR) activators, also indicated the augmentation of MC‐mediated activation of AhR (induction of luciferase) by Nic, although Nic showed limited capacity for the activation of AhR. Furthermore, the results from the Western blot analysis of CYP1s, the enzyme activity assay, and the assay for MC‐DNA adduct formation indicated that Nic could enhance the MC‐mediated induction of CYP1s, especially CYP1A1. Furthermore, the intracellular accumulation level of [³H]MC after treatment of HepG2 cells with [³H]MC significantly increased in the presence of Nic. The present findings demonstrate that Nic can enhance the MC‐mediated induction of CYP1s, especially CYP1A1, and the formation of MC‐DNA adduct in HepG2 cells. Furthermore, the augmentation of the MC‐mediated bioactivation by Nic is demonstrated to occur mainly through an increase in intracellular accumulation of MC.     

The roles of <Superscript>18</Superscript>F-FDG-PET/CT and US-guided FNAC in assessment of axillary nodal metastases in breast cancer patients

Background

There is a need for less invasive techniques for preoperative identification of axillary lymph node (ALN) metastases.

Method

Patients underwent ultrasonography (US) and ¹⁸F-fluorodeoxyglucose-positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT), and then US-guided fine needle aspiration cytology (FNAC) and/or sentinel lymph node (SLN) biopsy were performed based on the US findings of the ALNs. Subsequently, patients with positive FNAC as well as those with positive SLN underwent axillary lymph node dissection (ALND). Postoperatively, removed SLNs and ALNs were examined histologically.

Results

Fifty (85 %) of 59 patients with positive ¹⁸F-FDG uptake in the axilla had axillary metastases, but ¹⁸F-FDG uptake results were false-positive in 9 (15 %) cases. On the other hand, 29 patients with positive FNAC underwent ALND without the need for SLN biopsy, while the remaining 20 patients with negative FNAC as well as 249 patients with negative US findings underwent SLN biopsy. Subsequently, 68 patients with positive SLN underwent ALND.

Conclusions

Positive FDG uptake in the axilla does not always indicate axillary metastasis. US-guided FNAC is useful to avoid unnecessary ALND in patients with positive ¹⁸F-FDG uptake. However, SLN biopsy is needed in patients with negative US findings of the ALNs and those with negative FNAC.

     

Transplantation of cardiac progenitor cells ameliorates cardiac dysfunction after myocardial infarction in mice

Cardiac progenitor cells are a potential source of cell therapy for heart failure. Although recent studies have shown that transplantation of cardiac stem/progenitor cells improves function of infarcted hearts, the precise mechanisms of the improvement in function remain poorly understood. The present study demonstrates that transplantation of sheets of clonally expanded stem cell antigen 1–positive (Sca-1–positive) cells (CPCs) ameliorates cardiac dysfunction after myocardial infarction in mice. CPC efficiently differentiated into cardiomyocytes and secreted various cytokines, including soluble VCAM-1 (sVCAM-1). Secreted sVCAM-1 induced migration of endothelial cells and CPCs and prevented cardiomyocyte death from oxidative stress through activation of Akt, ERK, and p38 MAPK. Treatment with antibodies specific for very late antigen-4 (VLA-4), a receptor of sVCAM-1, abolished the effects of CPC-derived conditioned medium on cardiomyocytes and CPCs in vitro and inhibited angiogenesis, CPC migration, and survival in vivo, which led to attenuation of improved cardiac function following transplantation of CPC sheets. These results suggest that CPC transplantation improves cardiac function after myocardial infarction through cardiomyocyte differentiation and paracrine mechanisms mediated via the sVCAM-1/VLA-4 signaling pathway.     

PRIMARY MUCIN-PRODUCING ADENOSQUAMOUS CARCINOMA OF THE THYROID GLAND

A rare case of mucin-producing adenosquamous carcinoma of the thyroid gland is reported in a 57-year-old woman. Light microscopically, much of the tumor showed a feature of mucin-producing adenosquamous carcinoma; squamous cells and mucous signet ring cells. In the lower portion of the tumor, a calcified area containing small foci of follicular carcinoma and its squamous cell metaplasia was accompanied. Histochemically, neutral, non-sulphated and sulphated acid mucins were found in the mucous cells, and no thyroglobulin or calcitonin was detected in the tumor cells. Electron microscopically, some tonofibrils and mucin production were observed concomitantly in the tumor cells. These findings suggested the possibility that this mucin-producing adenosquamous carcinoma originated from squamous cell metaplasia of pre-existing follicular carcinoma. ACTA PATHOL. JPN. 37: 1157 -1164, 1987.     

The relationship of p53 Protein and lymph node metastases in invasive breast cancer

The p53 expression in invasive breast cancers from 106 patients was correlated with clinicopathological variables to ascertain its usefulness for estimating prognosis. The p53 expression was significantly associated with the number of axillary lymph node metastases and the presence of internal mammary lymph node metastases; however, it was not associated with age, menopausal status, histologic type, or tumor size. Although p53 expression was a significant prognostic factor according to univariate analysis, it did not appear to be an independent prognostic factor according to multivariate analysis. Thus, the prognostic power of p53 expression is likely to be weak and therefore probably of limited clinical value. Nevertheless, the number of patients in our study was small, and we believe that an investigation of a larger series of patients is indicated.     

Adenolipoma of the thyroid gland

A rare case of adenolipoma (thyrolipoma) of the thyroid gland is reported. Previously reported cases are reviewed and the pathogenesis of this unusual thyroid lesion is discussed.     

A retrospective study on the efficacy of cervical lymph node dissection in well-differentiated carcinoma of the thyroid

The management of cervical lymph node metastases in well-differentiated carcinoma of the thyroid is controversial. In our department, from 1963 to 1972, node plucking was performed only in patients with cervical lymphadenopathy whereas, from 1973 to 1983, modified radical neck dissection was therapeutically or electively performed. In order to determine whether the more extensive dissection is adequate, a retrospective analysis was performed using two groups of patients who were managed differently with regard to the treatment of cervical lymph node metastases. From this series of 206 patients with more than five years follow-up, it was found that the rates of survival and lymph node recurrence did not differ between the two groups. However, since the well-differentiated carcinoma of the thyroid has relatively indolent biological behaviour, further long-term follow-up seems to be necessary for demonstrating the efficacy of neck dissection.