Enhanced antitumor effect of L-buthionine sulfoximine or ionizing radiation by copper complexes with 2,2´-biquinoline and sulfonamides on A549 2D and 3D lung cancer cell models.

Two ternary copper(II) complexes with 2,2'-biquinoline (BQ) and with sulfonamides: sulfamethazine (SMT) or sulfaquinoxaline (SDQ) whose formulae are Cu(SMT)(BQ)Cl and Cu(SDQ)(BQ)Cl·CH3OH, in what follows SMTCu and SDQCu, respectively, induced oxidative stress by increasing ROS level from 1.0 µM and the reduction potential of the couple GSSG/GSH2. The co-treatment with L-buthionine sulfoximine (BSO), which inhibits the production of GSH, enhanced the effect of copper complexes on tumor cell viability and on oxidative damage. Both complexes generated DNA strand breaks given by-at least partially-the oxidation of pyrimidine bases, which caused the arrest of the cell cycle in the G2/M phase. These phenomena triggered processes of apoptosis proven by activation of caspase 3 and externalization of phosphatidylserine and loss of cell integrity from 1.0 µM. The combination with BSO induced a marked increase in the apoptotic population. On the other hand, an improved cell proliferation effect was observed when combining SDQCu with a radiation dose of 2 Gy from 1.0 µM or with 6 Gy from 1.5 µM. Finally, studies in multicellular spheroids demonstrated that even though copper(II) complexes did not inhibit cell invasion in collagen gels up to 48 h of treatment at the higher concentrations, multicellular resistance outperformed several drugs currently used in cancer treatment. Overall, our results reveal an antitumor effect of both complexes in monolayer and multicellular spheroids and an improvement with the addition of BSO. However, only SDQCu was the best adjuvant of ionizing radiation treatment.

Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in 413 cases of newly diagnosed acute promyelocytic leukemia. The European APL Group.

All trans-retinoic acid (ATRA) syndrome is a life-threatening complication of uncertain pathogenesis that can occur during the treatment of acute promyelocytic leukemia (APL) by ATRA. Since its initial description, however, no large series of ATRA syndrome has been reported in detail. We analyzed cases of ATRA syndrome observed in an ongoing European trial of treatment of newly diagnosed APL. In this trial, patients 65 years of age or less with an initial white blood cell count (WBC) less than 5,000/microL were initially randomized between ATRA followed by chemotherapy (CT) (ATRA-->CT group) or ATRA with CT started on day 3; patients with WBC greater than 5,000/microL received ATRA and CT from day 1; patients aged 66 to 75 received ATRA-->CT. In patients with initial WBC less than 5, 000/microL and allocated to ATRA-->CT, CT was rapidly added if WBC was greater than 6,000, 10,000, 15,000/microL by days 5, 10, and 15 of ATRA treatment. A total of 64 (15%) of the 413 patients included in this trial experienced ATRA syndrome during induction treatment. Clinical signs developed after a median of 7 days (range, 0 to 35 days). In two of them, they were in fact present before the onset of ATRA. In 11 patients, they occurred upon recovery from the phase of aplasia due to the addition of CT. Respiratory distress (89% of the patients), fever (81%), pulmonary infiltrates (81%), weight gain (50%), pleural effusion (47%), renal failure (39%), pericardial effusion (19%), cardiac failure (17%), and hypotension (12%) were the main clinical signs, and 63 of the 64 patients had at least three of them. Thirteen patients required mechanical ventilation and two dialysis. A total of 60 patients received CT in addition to ATRA as per protocol or based on increasing WBC; 58 also received high dose dexamethasone (DXM); ATRA was stopped when clinical signs developed in 30 patients. A total of 55 patients (86%) who experienced ATRA syndrome achieved complete remission (CR), as compared with 94% of patients who had no ATRA syndrome (P = .07) and nine (14%) died of ATRA syndrome (5 cases), sepsis (2 cases), leukemic resistance (1 patient), and central nervous system (CNS) bleeding (1 patient). None of the patients who achieved CR and received ATRA for maintenance had ATRA syndrome recurrence. No significant predictive factors of ATRA syndrome, including pretreatment WBC, could be found. Kaplan Meier estimates of relapse, event-free survival (EFS), and survival at 2 years were 32% +/- 10%, 63% +/- 8%, and 68% +/- 7% in patients who had ATRA syndrome as compared with 15% +/- 3%, 77% +/- 2%, and 80% +/- 2% in patients who had no ATRA syndrome (P = .05, P = .003, and P = .03), respectively. In a stepwise Cox model that also included pretreatment prognostic variables, ATRA syndrome remained predictive for EFS and survival. In conclusion, in this multicenter trial where CT was rapidly added to ATRA in case of high or increasing WBC counts and DXM generally also used at the earliest clinical sign, the incidence of ATRA syndrome was 15%, but ATRA syndrome was responsible for death in only 1.2% of the total number of patients treated. However, occurrence of ATRA syndrome was associated with lower EFS and survival.

[Monoclonal gammopathy and primary hyperparathyroidism. Apropos of 2 cases and review of the literature]. / Gammapathie monoclonale et hyperparathyroïdie primitive. A propos de deux observations et revue de la littérature.

Frequency of primary hyperparathyroidism (HP) is increased in neoplasia. Though uncommon, both HP and monoclonal gammopathy are not exceptionally associated as seen in a literature review reporting 24 observations. The mechanism of this association remains unclear but does not seems coincidental. Association of hypercalcemia with gammopathy does not suggest systematically malignant hypercalcemia and implies the search for hyperparathyroidism. The authors report two patients presenting respectively a multiple IgD myeloma and an monoclonal gammopathy of undetermined signification associated with a parathyroid adenoma.

Depigmenting procedures and drugs employed by melanoderm populations.

The "fashion" of lightening the skin represents a very serious problem because it involves the melanoderm populations, not only in Africa, but in the world, undermining their physical integrity and psychological equilibrium. The diffusion of the skin-whitening practice is much more intense in the areas where there are inter-relations between Blacks and Whites. Among the drugs used, mercury prevails under the form of biioduro salts in aseptic soaps; hydroquinone taken in form of per os pills, and cortisoides. The resource of using traditional skin-bleaching plants seems frequent, but the information we tried to gather from informants has been very scarce.

Various uses of the castor oil plant (Ricinus communis L.). A review.

The ancient and modern medicinal uses of the castor bean plant, Ricinus communis L. (Euphorbiaceae), in about fifty countries worldwide, has been surveyed. The different medicinal uses are grouped separately in relation to their pharmacological action, whether real or presumed, within the various medical specialties. The results show an extensive use of this plant throughout the world and the authors suggest that further research should be carried out to determine the active principles present in the various parts of the plant.