Scorpion venoms and associated toxins as anticancer agents: update on their application and mechanism of action

Cancer remains one of the deadliest non-infectious diseases of the 21^st century, causing millions of mortalities per year worldwide. Analyses of conventional treatments, such as radiotherapy and chemotherapy, have shown not only a lower therapeutic efficiency rate but also plethora of side-effects. Considering the desperate need to identify promising anticancer agents, researchers are in quest to design and develop new tumoricidal drugs from natural sources. Over the past few years, scorpion venoms have shown exemplary roles as pivotal anticancer agents. Scorpion venoms associated metabolites, particularly toxins demonstrated in vitro anticancer attributes against diversified cell lines by inhibiting the growth and progression of the cell cycle, inhibiting metastasis by blocking ion channels such as K⁺ and Cl⁻, and/or inducing apoptosis by intrinsic and extrinsic pathways. This review sheds light not only on in vitro anticancer properties of distinct scorpion venoms and their toxins, but also on their mechanism of action for designing and developing new therapeutic drugs in future.     

Duodenum-preserving pancreatic head resection in solid pseudopapillary neoplasm—Report of a case

INTRODUCTION

Solid pseudopapillary neoplasm (SPPN) was first characterized by Virginia Frantz in 1959. The duodenum-preserving pancreatic head resection (DPPHR) has been described as treatment for low-grade malignant tumors of the head of the pancreas including eight cases of SPPN.PRESENTATION OF CASE: A 16-year-old white female patient presented with abdominal pain and dyspepsia. Computed tomography scan of abdomen showed a 10 × 9 × 10 cm³ lesion on the pancreatic head. After radiological diagnosis of SPPN the patient was submitted to DPPHR. Resection was achieved with clear margins. Immunohistochemical study demonstrated positivity for progesterone receptor, β-catenin, cytoplasmic paranuclear dot-like CD99, negativity for chromogranin and S100 protein and Ki 67 index of 1%.

DISCUSSION

A large encapsulated pancreatic mass with well-defined borders that contains areas of calcifications and intratumoral hemorrhage on CT scan in a young female is virtually diagnostic of an SPPN. A particular dot-like intracytoplasmic expression of CD99 appears to be highly unique for SPPN

CONCLUSION

DPPHR should be considered in cases of SPPN in the pancreas head if there is no compromise with oncologic radicality.     

Neurotrophic factors in women with crack cocaine dependence during early abstinence: the role of early life stress

Background

Neurotrophic factors have been investigated in the pathophysiology of alcohol and drug dependence and have been related to early life stress driving developmental programming of neuroendocrine systems.

Methods

We conducted a follow-up study that aimed to assess the plasma levels of glial cell line–derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT3) and neurotrophin-4/5 (NT4/5) in crack users during 3 weeks of early abstinence in comparison with healthy controls. We performed a comprehensive clinical assessment in female inpatients with crack cocaine dependence (separated into 2 groups: participants with (CSA+) and without (CSA−) a history of childhood sexual abuse) and a group of nonuser control participants.

Results

Our sample included 104 women with crack cocaine dependence and 22 controls; of the women who used crack cocaine, 22 had a history of childhood sexual abuse and 82 did not. The GDNF plasma levels in the CSA+ group increased dramatically during 3 weeks of detoxification. In contrast, those in the CSA− group showed lower and stable levels of GDNF under the same conditions. Compared with the control group, BDNF plasma levels remained elevated and NGF levels were reduced during early abstinence. We found no differences in NT3 and NT4/5 between the patients and controls. However, within-group analyses showed that the CSA+ group exhibited higher levels of NT4/5 than the CSA− group at the end of detoxification.

Limitations

Some of the participants were using neuroleptics, mood stabilizers or antidepressants; our sample included only women; memory bias could not be controlled; and we did not investigate the possible confounding effects of other forms of stress during childhood.

Conclusion

This study supports the association between early life stress and peripheral neurotrophic factor levels in crack cocaine users. During early abstinence, plasmastic GDNF and NT4/5 were the only factors to show changes associated with a history of childhood sexual abuse.     

Evidence for a direct effect of captopril on early steps of insulin action in BC3H-1 myocytes

Captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been reported to improve insulin sensitivity. However, despite extensive investigation, the mechanisms responsible for this effect are not fully understood. Reduction of plasma angiotensin II and inhibition of kininase II have been suggested to contribute to improve insulin sensitivity. Insulin binding was measured at tracer insulin concentration in intact cells with or without captopril treatment. Specific binding, expressed as percent of total insulin added, was not different in control and captopril-treated cells. However, captopril treatment caused an increase in insulin-induced insulin receptor substrate-1 (IRS-1) phosphorylation accompanied by an increased association of IRS-1 with phosphoinositide-3 kinase (PI-3 kinase), despite no change on insulin receptor (IR) autophosphorylation. There was also an increased threonine kinase B (AKT) phosphorylation in captopril-treated cells followed by enhanced basal and insulin-stimulated glucose uptake. These results indicate that captopril treatment has a direct effect on early phosphorylation events induced by insulin in BC3H-1 myocytes.