The effect of age on the plasma levels of amoxapine and its major metabolite in depressed patients

Twenty-eight depressed patients receiving amoxapine with ages ranging from 21 to 68 years (male 12, female 16) were studied in order to clarify the age effect on plasma levels of amoxapine and its major active metabolite, 8-OH amoxapine. Plasma amoxapine levels were determined by both radioreceptor assay (RRA) and gas liquid chromatography (GLC). Plasma levels of 8-OH amoxapine were also determined by GLC. A highly significant correlation was found for plasma levels of amoxapine determined by RRA and GLC (r = 0.88, p < 0.001). There was no significant correlation between the amoxapine daily dose (mg/kg) and its plasma levels determined either by RRA or GLC. The ratios of plasma amoxapine level by RRA and GLC to daily dose significantly increased with advancing age (p < 0.05) and a significant positive correlation was also found between the ratio of plasma level of 8–OH amoxapine to daily dose and the age of the patients (p < 0.01), suggesting that the plasma 8-OH amoxapine levels were more strongly affected by age than the parent drug. These results indicate that the metabolism of amoxapine in the liver decreases with age as well as that of other tricyclic antidepressants reported previously. The higher correlation of 8-OH amoxapine with patient's age may be mainly due to its renal excretion which may also decrease with age.     

Prognostic values of initial responses to low-dose 131I-MIBG therapy in patients with malignant pheochromocytoma and paraganglioma

Purpose

We retrospectively examined whether or not initial responses of first low-dose ¹³¹I-meta-iodo-benzyl-guanidine radiotherapy (¹³¹I-MIBG therapy) in patients with malignant pheochromocytoma and paraganglioma had prognostic values.

Materials and methods

This study included 26 patients with malignant pheochromocytoma (n = 18) and paraganglioma (n = 8) who underwent the first ¹³¹I-MIBG therapy between October 2001 and September 2007. Based on the initial subjective, hormonal, scintigraphic, and objective responses to ¹³¹I-MIBG therapy, the responses were divided into progression disease (PD) and non-PD. We examined the following factors for prognostic significance: sex, age, disease, initial diagnosis (benign or malignant pheochromocytoma), hypertension, diabetes mellitus, palpitations, symptoms related to bone metastases, and number of low-dose ¹³¹I-MIBG therapy. Univariate Cox proportional regression analysis was used to identify prognostic factors for overall survival. Overall survival was analyzed by Kaplan–Meier method and the curves were compared using the log-rank test.

Results

The median survival time was 56 months. In the follow-up period, 16 patients died from exacerbation of their diseases. Univariate analysis showed that the hormonal PD [hazard ratio (HR) 3.20, P = 0.034, confidence interval (CI) 1.09–9.93], objective PD (HR 11.89, P = 0.0068, CI 2.14–65.85), single-time ¹³¹I-MIBG therapy (HR 3.22, P = 0.020, CI 1.21–8.79), hypertension (HR 2.93, P = 0.044, CI 1.02–10.50), and symptoms related to bone metastases (HR 3.54, P = 0.023, CI 1.18–13.04) were bad prognostic factors for overall survival. Kaplan–Meier analysis demonstrated that the hormonal non-PD (P = 0.026), objective non-PD (P = 0.0002), multiple-time ¹³¹I-MIBG therapy (P = 0.013), and no symptom related to bone metastases (P = 0.024) were significantly associated with good prognosis. Overall survival rate was 70 and 50 % at 5 years from the initial diagnosis and from the first ¹³¹I-MIBG therapy, respectively.

Conclusion

The hormonal and objective responses to the first low-dose ¹³¹I-MIBG therapy as well as complication of hypertension and symptoms related to bone metastases may be prognostic factors in patients with malignant pheochromocytoma and paraganglioma.     

Fibroma of the tendon sheath that expanded into the radiocarpal joint with bony involvement

We present a 46-year-old man with a fibroma of the tendon sheath of the left radiocarpal joint and bony involvement of the scaphoid and the radial styloid. Bony involvement of a fibroma of the tendon sheath is rare and has been reported only four times to our knowledge.     

人舌癌细胞快速化疗药物敏感试验

采用ＭＴＴ法检测人舌鳞状细胞癌ＳＣＣ－２５和ＳＣＣ－９两株细胞对４种临床常用抗癌药物单一用药及联合用药方案的化疗药物敏感性。单一用药的化疗药物敏感性顺序为：顺铂，博莱霉素，氨甲喋呤，５－氟脲嘧啶，以顺铂为主的联合用药化疗方案的抗癌作用明显优于单一用药，并在较低浓度时亦能达到５０％以上的肿瘤生长抑制率，本实验结果时选择临床用有一定的指导意义，ＭＴＴ法是一种有希望的，值得进一步研究发展的临床肿瘤药物试     

Cancer stem cells in human gastrointestinal cancer

Cancer stem cells (CSCs) are thought to be responsible for tumor initiation, drug and radiation resistance, invasive growth, metastasis, and tumor relapse, which are the main causes of cancer‐related deaths. Gastrointestinal cancers are the most common malignancies and still the most frequent cause of cancer‐related mortality worldwide. Because gastrointestinal CSCs are also thought to be resistant to conventional therapies, an effective and novel cancer treatment is imperative. The first reported CSCs in a gastrointestinal tumor were found in colorectal cancer in 2007. Subsequently, CSCs were reported in other gastrointestinal cancers, such as esophagus, stomach, liver, and pancreas. Specific phenotypes could be used to distinguish CSCs from non‐CSCs. For example, gastrointestinal CSCs express unique surface markers, exist in a side‐population fraction, show high aldehyde dehydrogenase‐1 activity, form tumorspheres when cultured in non‐adherent conditions, and demonstrate high tumorigenic potential in immunocompromised mice. The signal transduction pathways in gastrointestinal CSCs are similar to those involved in normal embryonic development. Moreover, CSCs are modified by the aberrant expression of several microRNAs. Thus, it is very difficult to target gastrointestinal CSCs. This review focuses on the current research on gastrointestinal CSCs and future strategies to abolish the gastrointestinal CSC phenotype.