Five-year study assessing the clinical utility of anti-Müllerian hormone measurements in reproductive-age women with cancer.

RESEARCH QUESTION: An important discussion point before chemotherapy is ovarian toxicity, a side-effect that profoundly affects young women with cancer. Their quality of life after successful treatment, including the ability to conceive, is a major concern. We asked whether serum anti-Müllerian hormone (AMH) measurements before chemotherapy for two most common malignancies are predictive of long-term changes in ovarian reserve? DESIGN: A prospective cohort study measured serum AMH in 66 young women with lymphoma and breast cancer, before and at 1 year and 5 years after chemotherapy, compared with 124 healthy volunteers of the same age range (18-43 years). Contemporaneously, patients reported their menses and live births during 5-year follow-up. RESULTS: After adjustment for age, serum AMH was 1.4 times higher (95% CI 1.1 to 1.9; P < 0.02) in healthy volunteers than in cancer patients before chemotherapy. A strong correlation was observed between baseline and 5-year AMH in the breast cancer group (P < 0.001, regression coefficient = 0.58, 95% CI 0.29 to 0.89). No significant association was found between presence of menses at 5 years and serum AMH at baseline (likelihood ratio test from logistics regression analysis). CONCLUSIONS: Reproductive-age women with malignancy have lower serum AMH than healthy controls even before starting chemotherapy. Pre-chemotherapy AMH was significantly associated with long-term ovarian function in women with breast cancer. At key time points, AMH measurements could be used as a reproductive health advisory tool for young women with cancer. Our results highlight the unsuitability of return of menstruation as a clinical indicator of ovarian reserve after chemotherapy.

Functionalized magnetic nanoparticles as vehicles for the delivery of the antitumor drug gemcitabine to tumor cells. Physicochemical in vitro evaluation.

Gemcitabine is a chemotherapy drug used in different carcinomas, although because it displays a short biological half-life, its plasmatic levels can quickly drop below the effective threshold. Nanoparticle-based drug delivery systems can provide an alternative approach for regulating the bioavailability of this and most other anticancer drugs. In this work we describe a new model of composite nanoparticles consisting of a core of magnetite nanoparticles, coated with successive layers of high molecular weight poly(acrylic acid) and chitosan, and a final layer of folic acid. The possibility of using these self-assembled nanostructures for gemcitabine vehiculization is explored. First, the surface charge of the composite particles is studied by means of electrophoretic mobility measurements as a function of pH for poly(acrylic acid) (carbopol) of different molecular weights. The adsorption of folic acid, aimed at increasing the chances of the particles to pass the cell membrane, is followed up by optical absorbance measurements, which were also employed for drug adsorption determinations. As a main result, it is shown that gemcitabine adsorbs onto the surface of chitosan/carbopol-coated magnetite nanoparticles. In vitro experiments show that the functionalized magnetic nanoparticles are able to deliver the drug to the nuclei of liver, colon and breast tumor cells.