Clinicopathological risk factors for local recurrence in oral squamous cell carcinoma.

Local recurrence of oral squamous cell carcinoma (OSCC) after primary surgery has been considered to be a poor prognostic entity in terms of survival rate. The purpose of this study is to evaluate the incidence of local recurrence and to identify significant risk factors for the local recurrence in OSCC. The authors retrospectively reviewed records for 187 patients who underwent radical surgery for OSCC. The local recurrence rate was 16.0% (30/187 patients) in this study. The survival rate of patients with local recurrence was 33.3%, which was significantly lower than that (94.3%) of patients without local recurrence. Pattern of invasion (POI), neoadjuvant chemotherapy (NAC), and the status of the surgical margin were identified as factors influencing local recurrence. In particular, NAC and the status of the surgical margin were independent risk factors by multivariate analysis. The deep margin was resected at a close site in many NAC-treated patients, suggesting that NAC may lead to local recurrence and poor outcomes. No efficacy of NAC was observed, suggesting that the standard treatment of oral cancers is surgery alone.

RNAi-mediated down-regulation of alpha-actinin-4 decreases invasion potential in oral squamous cell carcinoma.

alpha-actinin-4, originally identified as an actin-binding protein associated with cell motility, invasion, and metastasis of cancer cells, appears to be overexpressed in various human epithelial carcinomas, including colorectal, breast, esophageal, ovarian, and non-small cell lung carcinomas. The authors evaluated whether alpha-actinin-4 might be appropriate as a molecular target for cancer gene therapy. In 64 primary oral squamous cell carcinomas (OSCCs) and 10 normal oral mucosal specimens, and in seven human OSCC cell lines, alpha-actinin-4 expression was evaluated immunologically and correlations with clinicopathologic factors were examined. Overexpression of alpha-actinin-4 was detected in 38 of 64 oral squamous cell carcinomas (70%); significantly more frequently than in normal oral mucosa. The expression of alpha-actinin-4 was significantly associated with invasion potential defined by the Matrigel invasion assay. Cancer cell lines with higher alpha-actinin-4 expression had greater invasive potential. An RNAi-mediated decrease in alpha-actinin-4 expression reduced the invasion potential. These results indicated that the overexpression of alpha-actinin-4 was associated with an aggressive phenotype of OSCC. The study indicated that alpha-actinin-4 could be a potential molecular target for gene therapy by RNAi targeting for OSCC.

Overexpression of metastasis-associated MTA1 in oral squamous cell carcinomas: correlation with metastasis and invasion.

Metastasis-associated protein 1 (MTA1) is physiologically expressed at low levels in human tissues. Its expression is associated with progression of solid cancers and is common in cancer cell lines. This study investigated whether MTA1 was expressed in squamous cell carcinoma (SCC) and would be a useful metastatic marker. Specimens from 38 patients with oral SCC were stained using the avidin-biotin-peroxidase technique with polyclonal antibodies against MTA1. Human SCC cell lines SAS, HSC2, OSC19 and OSC20 were analysed for MTA1 mRNA expression. MTA1 expression in control tissues was significantly lower than in carcinomas. MTA1 protein expression was detected in 33 of 38 SCC tissues from patients. Histologically, MTA1 protein production was strongly associated with cancer cell invasion, and clinically there was a correlation between lymph node metastasis and MTA1 protein production. Among the cancer cell lines, HSC2 showed the lowest mRNA expression, and OSC20 showed the highest MTA1 mRNA expression. In the Matrigel invasion assay, the HSC2 cell line showed the lowest invasion and the OSC20 cell line showed the highest invasion. RNAi-mediated MTA1 silencing in the OSC20 cells decreased the invasion index. MTA1 expression in oral SCC may be associated with increased invasive ability, which may cause lymph node metastasis.

[Total aortic root replacement exclusively with full-thickness suturing].

This paper describes two cases of total aortic root replacement using a valved conduit with a side branch. The full-thickness suturing technique was exclusively used at all anastomotic sites, and some technical devices are also presented. The conduit and a Hemashield Woven Double Velour graft used to make it were found very beneficial for the operation of this kind, and our procedure will equally provide every surgeon with a good result.

[A case of double-valve replacement in a patient with idiopathic thrombocytopenic purpura].

The aortic and mitral valve replacements were successfully performed in a case with idiopathic thrombocytopenic purpura. High-dose-gamma-globulin therapy and splenectomy had been tried. Neither of them, however could increase thrombocyte. After administration of Danazol treatment, thrombocytes moderately increased. With no expectation for further increase in thrombocytes, it was decided to carry out the open heart surgery with the aid of transfusion of thrombocyte-rich fresh plasma. Haemostasis after cardiopulmonary bypass required much longer time as 3 hours than in usual cases, but being successfully controlled. It has been reported that the effectiveness rate of the high-dose-gamma-globulin therapy ranges from 80 to 90%. Therefore this strategy will be the first choice in a case with ITP requiring open heart surgery. In the event that the strategies, including splenectomy, failed, other means such as Danazol therapy and transfusion of thrombocyte-rich fresh plasma should be considered.

alpha-Fluoromethylhistidine decreases the histamine content of the rat right atrium under the influence of sympathetic activity.

alpha-Fluoromethylhistidine (alpha-FMH; 65 mg/kg, i.p.), a specific inhibitor of histidine decarboxylase, significantly decreased the histamine content of the rat right atrium in a time-dependent manner; the maximal decrease of 22.2% was observed 4 h after injection. However, alpha-FMH had no significant effect on the histamine content of the left atrium or the ventricles. The alpha-FMH-induced decrease in the right atrial histamine content was not observed in rats pretreated with 6-hydroxydopamine (25 mg/kg, i.p.). Two i.p. injections of 10 and 5 mg/kg of propranolol and the cardioselective beta 1-adrenoceptor antagonist metoprolol almost completely inhibited the alpha-FMH-induced histamine decrease. On the other hand, phentolamine (10 mg/kg, i.p.) had no influence on the histamine-decreasing action of alpha-FMH. These results suggest that in the rat right atrium there is a histamine pool where a rapid turnover of histamine is maintained by normal sympathetic activity.

Involvement of opioid and non-opioid mechanisms in footshock-induced enhancement of brain histamine turnover in mice.

Naloxone (1-10 mg/kg, i.p.) dose-dependently inhibited the footshock-induced elevation in levels of tele-methylhistamine (t-MH), a predominant metabolite of brain histamine (HA), although this compound had no effect on the HA dynamics in the non-shocked control mice. Footshock significantly enhanced the HA depletion induced by alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase. However, in mice treated with naloxone (5 mg/kg, i.p.) footshock did not significantly facilitate the alpha-fluoromethylhistidine-induced HA depletion. In mice which had been rendered morphine-tolerant following an s.c. implantation of a pellet containing 50 mg of morphine base 3 days before, footshock produced no significant elevation of the t-MH level. The treatment with alpha-methyl-p-tyrosine, p-chlorophenylalanine or atropine had no significant influence on the footshock-induced t-MH elevation. The t-MH elevation was the most marked in the midbrain. In the hypothalamus and pons-medulla oblongata, no significant change in the t-MH level was produced by footshock. These results suggest that footshock increases the HAergic activity in the mouse brain partly through activation of opioid-related mechanisms and that alterations in HA dynamics differ with region of the brain.

Brain histamine turnover enhanced by footshock.

When footshock was given to mice at 15-s intervals for 30-120 min, there was a significant increase in the brain level of tele-methyl-histamine (t-MH), a predominant metabolite of brain histamine (HA). This footshock-induced elevation of the t-MH level also occurred in mice pretreated with pargyline but not in mice pretreated with metoprine. The footshock facilitated the HA depletion induced by a-fluoromethylhistidine. These results suggest that footshock increases the brain HA turnover.