Search

Maspin, a 42 kDa protein produced in normal breast cells, has been shown to inhibit the invasion and metastasis of breast cancer in an animal model. Ingestion of acetylsalicylic acid (aspirin) by breast cancer patients has been reported to restore the systemic synthesis of maspin through the stimulation of systemic nitric oxide production. Studies were carried out to determine the effect of aspirin on the incidence of breast cancer metastasis, which is reported to occur in 50% of patients who have previously received chemotherapy, radiation, and/or surgery. Thirty-five female patients (aged 41-65 years) with breast cancer who had previously received these therapies took one 75 mg/70 kg body weight enteric-coated aspirin tablet every 24 h, after an adequate meal, for 3 years. Their plasma nitric oxide and maspin levels were measured. The occurrence of metastasis was ascertained monthly by a qualified oncologist, and confirmed, if necessary, by biopsy. Daily ingestion of aspirin by participants resulted in an increase in maspin levels from 0.95 ± 0.04 to 4.63 ± 0.05 nM after 24 h. These levels were maintained for 3 years. These studies suggest that daily ingestion of aspirin might significantly reduce the incidence of breast cancer metastasis in patients who have previously received anticancer therapies.

SUMMARY Background: More than 90% of all hypertensive persons are reported to have essential hypertension (EH), a particular form of elevated blood pressure, for which no diagnostic test is currently available. The level of plasma renal (R) cortexin (PRC), a hypotensive protein produced in the kidney cortex cells, was reported to be reduced from 218 nM in the plasma of normotensive persons (NP) to 0 nM in the plasma of patients with EH. The feasibility of using the determination of PRC by enzyme-linked immunosorbent assay (ELISA) as a diagnostic test for EH was investigated. Methods: The PRC was determined by ELISA using electrophoretically pure cortexin as the antigen. A total of 344 persons (male and female) with EH, with or without diabetes mellitus (DM), and receiving or not receiving any anti-hypertensive and/or anti-diabetic medication at presentation, as well as an equal number of age- and gender-matched NP participated in the study. Results: All persons with EH, with or without co-existing DM, were found to have 0 nM PRC, regardless of whether they were receiving anti-hypertensive and anti-diabetic drugs, including those who had been taking these medications over an extended period of time (3 months). Conclusions: The determination of PRC as a marker protein by ELISA, a rapid method that can be carried out in any diagnostic laboratory, was shown to be suitable for the diagnosis of EH, even in those subjects who had co-existing DM and were receiving both anti-hypertensive and anti-diabetic medication. (Clin. Lab. 2013;59:xx-xx. DOI: 10.7754/Clin.Lab.2012.120633)

Because kidney tissue damage is associated with both hypertension and impaired nitric oxide (NO) production, we investigated the possibility whether the kidney tissue contains any activator of endothelial NO synthase (eNOS) that could be important in essential hypertension. An activator protein of M(r) 43000 Da for eNOS from the goat kidney cortex homogenate was purified to homogeneity by chromatographic techniques. This activator trivially, called "cortexin," was determined by enzyme-linked immunosorbent assay using anticortexin antibody. NO was determined by the formation of methemoglobin. Injection of 0.5 nmol cortexin/kg body weight to rabbit pretreated with l-epinephrine that increased the systolic and diastolic pressures to 195 +/- 3.40 mm Hg and 98.14 +/- 6.64 mm Hg, respectively, reduced and kept the elevated pressures at normal ranges of 133.57 +/- 12.14 (systolic) and 51.03 +/- 3.21 (diastolic) for 45 hours with simultaneous increase of plasma NO level. The inhibition of cortexin-induced NO synthesis nullified the antihypertensive effect of cortexin. The plasma cortexin level in newly diagnosed persons with essential hypertension was 0 pmol/mL (median), which contrasted with 218.94 pmol cortexin/mL (median), in normotensive persons (P.0005; n = 25). We concluded that the impaired production of cortexin in the cortex of kidney might lead to essential hypertension.