维生素C联合维生素K3抗肿瘤作用的研究进展

维生素C（vC）和维生素K3（VK3）在抗氧化、提高机体免疫力和止血等方面被广泛应用.20世纪40年代,人们发现它们也具有抗肿瘤作用.研究表明,VC与VK3联合给药比例为100：1时,具有最佳的协同抗肿瘤作用,并能大幅降低剂量,不会增加机体的不良反应.能够对乳腺癌、卵巢癌、前列腺癌、膀胱癌、白血病等多种肿瘤细胞产生杀伤作用.这种组合已被申请了专利并进行了Ⅰ/ⅡA期临床试验,试验结果表明其能延长晚期癌症患者的生存时间,不良反应轻,具有广阔的应用前景.文章就VC联合VK3的协同抗肿瘤作用进行综述.     

Incidentally discovered tumors of the endocrine glands

Clinically inapparent masses, or 'incidentalomas' of the endocrine glands are increasingly common owing to continued advancements in medical imaging. Incidentalomas of the adrenal glands have received substantial attention in the literature, whereas lesions of the thyroid and endocrine pancreas, though frequently encountered in the clinic, have received relatively little attention. We review the detection and subsequent management of incidentalomas of the thyroid, adrenal and pancreas, with specific attention paid to the mode of detection and risk stratification of lesions.     

Hormonal function of the thymus gland in melanoma of the skin: relation to functional disorders of other endocrine glands

The analysis of correlations between levels of epiphyseal, hypophyseal, adrenocortical and gonadal hormones suggested functional disorders developing in these glands to be interdependent and account for dysfunction of the thymus and immune system in patients suffering malignant melanoma. The degree of relationship between pituitary-adrenal system and thymus function disorders increased with tumor size; it was more pronounced in males. The rationale for application of pineal gland preparations in melanoma patients aimed at combatting neuroendocrine disorders is discussed.     

维生素K2与骨质疏松症的研究进展

骨质疏松症是一种骨量降低,骨组织微结构破坏,以骨脆性增加,骨强度下降,骨折风险增加为特征的全身骨骼系统疾病。近年来,随着老龄化人数的增加,骨质疏松症已经严重威胁了中老年人身体健康,成为人类社会共同关注的重要健康问题。据一项全国性流行病学调查显示,50岁以上男性骨质疏松症患病率为14．4％,女性升高到20．7％,60岁以上人群的患病率进一步升高。     

Transplantable murine salivary gland carcinoma (myoepithelioma). I. Biologic behavior and ultrastructural features.

Three salivary gland adenocarcinomas that arose spontaneously in female BALB/c mice, originally being maintained for plasmacytoma (MOPC) investigations, were studied; only one of the original hosts was MOPC-bearing. The initial carcinomas clearly originated from the salivary gland, not the breast, and did not resemble plasma cell lesions. The submandibular gland was the site of origin in each instance. Lesions were identical to those described previously in strains A and C mice as myoepitheliomas, with intracellular fibrils positive by phosphotungstic acid-hematoxylin (PTAH) stain. Each cell line (A, B, and C) of the salivary gland carcinomas was serially transplanted for 28, 29 and 14 generations, respecitvely. The lesion was easily transplanted, achieved almost 100% takes, and uniformly killed the host in 6-12 weeks, with metastasis to the peritoneum and liver. A myeloproliferative reaction characterized by leukemoid changes regularly occurred during the growth of the tumors. Each transplant generation was identical to its original salivary gland precursor by light and electron microscopy. In their growth pattern, the tumors resembled sarcomas with large areas of spindle cells. Ultrastructurally, the neoplastic cells contained the organelles of acinar and possibly ductal cells and exhibited varying degrees of synthetic and secretory activity, characterized by abundant free ribosomes and granular ergastoplasm, with prominent canaliculi containing abundant secretory material. Numerous desmosomes were seen, as well as coarse filaments and fine fibrils in most tumors cells, particularly in cells exhibiting lesser degrees of secretion. The filaments most likely represented the PTAH-positive intracellular fibrils observed by light microscopy. All tumors had numerous cells with resting features.     

Effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) treatment on human tumor cell growth in vitro. I. Synergism of combined vitamin C and K3 action

The effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) administered separately or in combination on the in vitro cultured human neoplastic cell lines MCF-7 (breast carcinoma), KB (oral epidermoid carcinoma), and AN3-CA (endometrial adenocarcinoma) have been examined. When given separately, vitamin C or K3 had a growth inhibiting action only at high concentrations (5.10(3) mumol/1 and 10(5) nmol/l, respectively). Combined administration of both vitamins demonstrated a synergistic inhibition of cell growth at 10 to 50 times lower concentrations. At this level separately given vitamins are not toxic. The sensitivity to this treatment was somewhat different in the three cell lines, being slightly higher for KB line. This tumor cell growth inhibitory effect was completely suppressed by the addition of catalase to the culture medium containing vitamins C and K3, suggesting an excessive production of hydrogen peroxide as being implied in mechanisms responsible for the above-mentioned effects.     

Functional characteristics of the endocrine glands in skin melanoma patients

TI-2NOMO skin melanoma patients revealed pronounced functional disturbances of the pineal gland and pituitary-adrenal system. The decline in functional activity of the former was manifested by a decrease in urine excretion of melatonin. Enhanced levels of blood ACTH, alpha-MSH and cortisole pointed to the activation of pituitary-adrenal system which was particularly high in males. The degree of endocrine disorders was found to be in correlation with tumor stage. As far as pathogenesis of the lesion is concerned, preparations which bring function of endocrine glands to normal should be adjuvant to available treatment modalities for melanoma.     

Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy.

PURPOSE: The aim of this study is to evaluate the neuroprotective effect of antioxidant supplementation with vitamin E in patients treated with cisplatin chemotherapy. METHODS: Between April 1999 and October 2000, forty-seven patients were randomly assigned to either group one, which received vitamin E supplementation during cisplatin chemotherapy, or to group two, which received cisplatin chemotherapy alone. Alpha-tocopherol (vitamin E; 300 mg/d) was administered orally before cisplatin chemotherapy and continued for 3 months after the suspension of treatment. For preclinical studies, nude mice carrying the human melanoma tumor were treated with cisplatin alone or in combination with vitamin E. RESULTS: Twenty-seven patients completed six cycles of cisplatin chemotherapy: 13 patients in group one and 14 patients in group two. The incidence of neurotoxicity was significantly lower in group one (30.7%) than it was in group two (85.7%; P <.01). The severity of neurotoxicity, measured with a comprehensive neurotoxicity score based on clinical and neurophysiological parameters, was significantly lower in patients who were supplemented with vitamin E than in patients who were not supplemented with vitamin E (2 v 4.7, P <.01). The results of the preclinical studies showed that when cisplatin was combined with vitamin E, no differences were observed in tumor weight inhibition, tumor growth delay, or life span as compared with treatment with cisplatin alone. CONCLUSION: Supplementation of patients receiving cisplatin chemotherapy with vitamin E decreases the incidence and severity of peripheral neurotoxicity.     

Apoptosis/differentiation-inducing effects of vitamin K2 on HL-60 cells: dichotomous nature of vitamin K2 in leukemia cells.

We originally reported that vitamin K2 (VK2) analogs, including menaquinone 4 (MK4) but not vitamin K1, effectively induce apoptosis in various types of primary cultured leukemia cells and leukemia cell lines in vitro. It has also been reported by others that VK2 showed the differentiation-inducing activity in leukemia cell lines. To investigate the discrepancy between apoptosis- and differentiation-inductions of leukemia cells by VK2 treatment, we used bcl-2 gene transfected HL-60 cells (HL-60-bcl-2) which resulted in five-fold over-expression of BCL-2 protein, and then compared the effects of MK4 to the control HL-60-neo cells. Seventy-two hours of exposure to various concentrations of MK4 resulted in growth inhibition of these cells in a dose-dependent manner (0.1-50 microM), however, HL-60-bcl-2 was less sensitive against MK4. MK4 potently induced apoptosis of HL-60-neo cells along with the depolarization of mitochondrial membrane potential and caspase-3 activation. Notably, HL-60-bcl-2 was almost completely resistant to apoptosis induction in response to MK4, although cell growth inhibition was still observed. In spite of the abrogation of apoptosis induction, about 90% of HL-60-bcl-2 cells were arrested in the G0/G1 phase within 48 h of exposure to 10 microM of MK4 accompanied by up-modulation of p27KIP1 expression. Concomitantly, HL-60-bcl-2 cells underwent monocytic differentiation. These data suggest that VK2 also shows the differentiation inducing effects on leukemia cells which are resistant against VK2-inducing apoptosis. The dichotomous nature of VK2 against leukemia cells appears to have clinical benefits for the treatment of patients with leukemias and myelodysplastic syndromes.     

C-cell disease of the thyroid gland in multiple endocrine neoplasia, type 2b.

Multiple endocrine neoplasia, type 2b (MEN 2b) is a disorder characterized by C-cell disease of the thyroid gland (medullary carcinoma or C-cell hyperplasia, or both), pheochromocytoma, ganglioneuromatosis, and skeletal and connective tissue abnormalities. The medullary thyroid carcinoma (MTC) is bilateral and multicentric; it metastasizes locally and distally, often before the disease is recognized. Histologically proven C-cell disease was present in 89 of the 107 patients (83%) reported with the condition, including 17 Mayo Clinic patients (average age at diagnosis, 19.2 years). Nineteen of the 107 patients (18%) died of MTC (average age at death, 25.3 years); 9 (8%) succumbed to pheochromocytoma, 7 of these also having metastatic MTC; 13 12%) died of other or unknown causes, but 2 of these had disseminated MTC as well; 29 (27%) survive with metastatic MTC; an additional 21 (20%) are alive, but concentrations of plasma immunoreactive calcitonin (iCT) have not been measured; 6 more (6%), 5 of whom had thyroidectomy before the age of 12 years, are alive with normal plasma concentrations of iCT; and the remaining 10 (9%) have been lost to follow-up. Survival of patients with MEN 2b after operation was reduced when compared with that of a control population -- 80% versus 99% at 5 years and 50% versus 98% at 10 years. The only effective treatment for MTC is total thyroidectomy before metastasis occurs. "Cure" of MTC in patients with MEN 2b has generally been obtained in those having total thyroidectomy before age 12. Therefore, in young patients suspected of having MEN 2b, we recommend prompt evaluation of C-cell function by measurement of stimulated concentrations of iCT and treatment by total thyroidectomy if results are abnormal.