[DEFERRED NEPHRECTOMY IN A PATIENT WITH METASTATIC RENAL CELL CARCINOMA AFTER A NEAR-COMPLETE RESPONSE TO IMMUNOTHERAPY].

INTRODUCTION: The treatment of newly diagnosed metastatic renal cell carcinoma (mRCC) evolved dramatically with the approval of immune checkpoint inhibitors (ICI) such as nivolumab, ipilimumab, and pembrolizumab for this indication. Herein, we describe the case of a 52-year old male patient, without chronic diseases and with a 30-pack-year smoking history, who was diagnosed with mRCC (clear cell carcinoma) including enlarged lymph nodes in the mediastinum, a mass in the pleura, and numerous metastases in both lungs. The patient was treated with a combination of nivolumab and ipilimumab, followed by nivolumab monotherapy, which is still ongoing (as of December 2021). The patient had a near-complete response (near resolution of the metastatic lesions) and did not experience adverse events. After 13 months of treatment, and in light of the near-complete response, the patient underwent a radical laparoscopic nephrectomy. The postoperative period was uneventful and the patient was discharged from the hospital 3 days after surgery. Examining the excised kidney revealed no residual tumor, connective tissue, signs of inflammation and necrosis. As of December 2021 (approximately 23 months from immunotherapy initiation) the patient had no evidence of disease. This case report demonstrates a treatment approach involving deferred nephrectomy after (and during) ICI treatment. The response of the patient described herein to a combination of nivolumab and ipilimumab is consistent with the available data supporting the efficacy of this combination as a first-line therapy in mRCC. Currently, the evidence supporting deferred nephrectomy (after ICI) vs upfront nephrectomy and then ICI, or ICI alone without nephrectomy is limited to a few retrospective studies. Thus, prospective randomized studies are needed to elucidate the role of deferred nephrectomy in mRCC. Two phase 3 studies (PROBE and NORDIC-SUN) that were designed to address this issue are currently enrolling patients and their results are expected within several years.

Stability and antioxidant activity of gossypol derivative immobilized on N-polyvinylpyrrolidone.

The objective of this study is analysis of stability and antioxidant and antiradical activities of the gossypol derivative - megosin conjugated with N-polyvinylpyrrolidone (PVP). The results of study have shown the greater stability of megosin+PVP than megosin in aqueous solution of wide range of pH. Here we also demonstrated that megosin+PVP, named rometin, possess high antioxidant activity in the same range as well known antioxidant trolox as determined by its ability to scavenge free ABTS(+) and DPPH radicals in vitro. In addition, megosin+PVP was able to prevent accumulation of products of lipid peroxidation (thiobarbituric acid reactive substances and diene conjugates) and lysophospholipids formation in mitochondria membranes caused by CCl(4)-induced oxidative stress in rat liver in vivo. Furthermore, megosin+PVP rescued mitochondrial functions, such as respiration and oxidative phosphorylation, which declined after CCl(4) administration. Thus we present that the conjugation of megosin to PVP increase its stability and remain antioxidant activity in vivo and in vitro.

The interaction of PVP complexes of gossypol and its derivatives with an artificial membrane lipid matrix.

In this paper, we present the results of a study on the membrane-active properties of gossypol, its derivatives and their polyvinylpyrrolidone complexes as assessed by differential scanning calorimetry and by the fluorescent probe method. The latter revealed the change in polarization of the incident radiation caused by the action of the polyphenol on the artificial membrane lipid matrix.

The immobilization of gossypol derivative on N-polyvinylpyrrolidone increases its water solubility and modifies membrane-active properties.

The conjugate of the gossypol derivative megosin (1) with N-polyvinylpyrrolidone named rometin (2) was synthesized. The effects of 1 and 2 on the structure and permeability of human erythrocytes and rat liver mitochondria were compared. Compound 1 induced dose-dependent erythrocyte hemolysis and increased mitochondrial permeability, with concomitant changes in membrane structure as determined by ESR and fluorescence anisotropy methods. Immobilization of 1 on N-polyvinylpyrrolidone (compound 2) increased its water solubility and reduced the intensity of its effects on erythrocyte membrane integrity and mitochondrial permeability, which correlated with a decrease in the membranes structural changes induced by the compound. Although the same concentrations of free and N-polyvinylpyrrolidone bound 1 were used, far less (14)C-labeled 1 was incorporated into the membranes from complex than free 1. The increase in water solubility and the reduction of membrane-active properties of 1 after immobilization on N-polyvinylpyrrolidone could explain our previous observation of the decreased toxicity of 1.