Vitamin E and cancer prevention: Studies with different forms of tocopherols and tocotrienols

α-Tocopherol (α-T) is the major form of vitamin E (VE) in animals and has the highest activity in carrying out the essential antioxidant functions of VE. Because of the involvement of oxidative stress in carcinogenesis, the cancer prevention activity of α-T has been studied extensively. Lower VE intake or nutritional status has been shown to be associated with increased cancer risk, and supplementation of α-T to populations with VE insufficiency has shown beneficial effects in lowering the cancer risk in some intervention studies. However, several large intervention studies with α-T conducted in North America have not demonstrated a cancer prevention effect. More recent studies have centered on the γ- and δ-forms of tocopherols and tocotrienols (T3). In comparison with α-T, these forms have much lower systemic bioavailability but have shown stronger cancer-preventive activities in many studies in animal models and cell lines. γ-T3 and δ-T3 generally have even higher activities than γ-T and δ-T. In this article, we review recent results from human and laboratory studies on the cancer-preventive activities of different forms of tocopherols and tocotrienols, at nutritional and pharmacological levels. We aim to elucidate the possible mechanisms of the preventive actions and discuss the possible application of the available information for human cancer prevention by different VE forms.     

Estrogen receptors in ductal carcinoma in situ of breast

A number of investigators have suggested treatment of precursor lesions for invasive breast cancer such as ductal carcinoma in situ with antiestrogen. However, very little information is available on the incidence of estrogen receptor in such lesions and the probability of treatment success. Fourteen formalin-fixed tissue specimens of intraductal carcinoma in situ from 14 female patients aged 40 to 66 years were evaluated for the presence of estrogen receptor by immunoperoxidase technique using estrogen receptor antibody. Eight of the 14 lesions (57%) were positive for estrogen receptor. The incidence of estrogen receptor in intraductal carcinoma in situ is very similar to that of invasive carcinoma of breast, leading to the speculation that ER-positive invasive carcinoma originates from ER-positive precursor lesions. Since only 70 per cent of positive receptor lesions are expected to respond to antiestrogens, it appears that only 40 per cent of patients with ductal carcinoma in situ of breast will benefit from endocrine therapy.     

Vitamin E succinate promotes breast cancer tumor dormancy

BACKGROUND: Vitamin E succinate (VES) is the most potent antitumor analogue of vitamin E. Despite many reports of VES's antitumor activity in vitro, there is little information about its antitumor effects in vivo. MATERIALS AND METHODS: We investigated the effect of VES on the growth of human breast cancer cells in vitro and in vivo. RESULTS: VES decreased cell viability in MDA-MB-231 and MCF-7 human breast cancer cells. Although VES increased apoptosis in MDA-MB-231 cells, it had no effect on apoptosis in MCF-7 cells. The inhibitory effect of VES on cell growth was specific for the intact molecule because a markedly reduced effect was noted when either vitamin E or succinic acid was administered alone. VES inhibited the growth of MDA-MB-231 cells in nude mice. Also, VES was found to inhibit vascular endothelial growth factor (VEGF) gene expression in MDA-MB-231 cells. CONCLUSIONS: VES inhibits the growth of breast cancer cells in vitro and in vivo. This is the first report of VES inhibition of established tumor growth in vivo. The mechanism of VES's in vivo effects may involve inhibition of tumor angiogenesis since VES inhibits VEGF gene expression.     

Different Cross-Reactivities of IgM Responses in Dengue,Zika and Tick-Borne Encephalitis Virus Infections

Flaviviruses circulate worldwide and cause a number of medically relevant human diseases, such as dengue, Zika, yellow fever, and tick-borne encephalitis (TBE). Serology plays an important role in the diagnosis of flavivirus infections, but can be impeded by antigenic cross-reactivities among flaviviruses. Therefore, serological diagnosis of a recent infection can be insufficiently specific, especially in areas where flaviviruses co-circulate and/or vaccination coverage against certain flaviviruses is high. In this study, we developed a new IgM assay format, which is well suited for the specific diagnosis of TBE, Zika and dengue virus infections. In the case of TBE and Zika, the IgM response proved to be highly specific for the infecting virus. In contrast, primary dengue virus infections induced substantial amounts of cross-reactive IgM antibodies, which is most likely explained by structural peculiarities of dengue virus particles. Despite the presence of cross-reactive IgM, the standardized nature and the quantitative read-out of the assay even allowed the serotype-specific diagnosis of recent dengue virus infections in most instances.     

Multimodality management of a polyfunctional pancreatic endocrine carcinoma with markedly elevated serum vasoactive intestinal polypeptide and calcitonin levels

We present an unusual case of a 52-year-old woman with severe, uncontrollable, refractory diarrhea attributable to pancreatic endocrine carcinoma (ECA) with markedly elevated serum vasoactive intestinal polypeptide (VIP) and calcitonin levels. After initial correction of fluid and electrolyte abnormalities, the patient was treated with high-dose octreotide. Shortly thereafter, due to the intractable nature of her diarrhea, she underwent cytoreductive hepatic surgery. The pancreatosplenectomy specimen showed a poorly differentiated ECA of the distal pancreas, immunoreactive for synaptophysin, CD56, and S100 protein, with morphologically similar hepatic and lymph node metastases. Postoperatively, her diarrhea improved, along with decline in serum VIP and calcitonin levels. Systemic chemotherapy with etoposide and cisplatin did not result in any radiographic and biochemical improvement. Having radiologically stable disease with depot-octreotide and short-acting octreotide (Sandostatin), she was subjected to peptide receptor radiotherapy with [177Lu-DOTA0,Tyr]octreotate (LuTate) that resulted in marked clinical and biochemical improvement, along with dramatic reduction in the number and size of hepatic metastases. In summary, this is a unique case of metastatic VIP- and calcitonin-secreting pancreatic ECA with dramatic sustained clinical, biochemical, and objective tumor response to peptide receptor radionuclide therapy.     

The role of cytoreductive hepatic surgery as an adjunct to the management of metastatic neuroendocrine carcinomas.

BACKGROUND: Patients with metastatic neuroendocrine cancers to the liver often present with disabling endocrinopathies and pain associated with bulky disease. Quality of life for these patients is poor and can require long-term therapy with somatostatin analogs for control of their symptoms. Alternative therapies to decrease tumor burden and subsequent hormone release have been investigated. Of these, cytoreductive surgery was found to have the most consistent and profound impact on symptom regression and overall survival. METHODS: Several cases are reported that illustrate an aggressive multimodality approach in the treatment of metastatic neuroendocrine cancers to the liver. The literature is reviewed and the role of cytoreductive surgery in the management of hepatic neuroendocrine metastases is discussed. RESULTS: Cytoreductive surgery can be performed safely with minimal morbidity and mortality. Regression of symptoms occurs in the majority of patients and survival is prolonged. CONCLUSIONS: Surgical intervention as part of an aggressive multimodality treatment plan results in improved outcomes for patients with advanced hepatic metastases of neuroendocrine origin. Future directions may include earlier surgical intervention with adjuvant therapies reserved for aggressive recurrent disease.     

Arteriovenous fistula between the hepatic artery and the hepatic vein

A patient is presented with multiple vascular anomalies in the branches of the celiac axis as well as in the portal vein and its branches. Apparently, unique in the literature is the presence of a large arteriovenous fistula between the hepatic artery and one of the hepatic veins. The anomalies are presumed to be congenital in origin.