MicroRNAs and cancer resistance: A new molecular plot.

The most common cause of cancer relapse is drug resistance, acquired or intrinsic, which strongly limits the efficacy of both conventional and new targeted chemotherapy. MicroRNAs (miRNAs) are a growing, large family of short noncoding RNAs frequently dysregulated in malignancies. Although the mechanism of miRNA-mediated drug resistance is not fully understood, an increasing amount of evidence suggests their involvement in the acquisition of tumor cell drug resistance, pointing towards the need for novel and more innovative therapeutic approaches. Use of antagomiRs or mimics can modulate specific miRNAs in order to restore gene networks and signaling pathways, perhaps optimizing chemotherapies by increasing cancer cell sensitivity to drugs. The aim of this review is to provide a state-of-the-art scenario with regard to the most recent discoveries in the field of miRNAs involved in the process of resistance to cancer therapy.

Pro- and anti-oxidant parameters in rat liver after short-term exposure to hexachlorobenzene.

The association between an in vivo oxidative stress condition of the liver and hepatic porphyria during HCB intoxication is postulated. After 30 days of treatment, HCB (25 mg/kg b.w.) promotes an induction of microsomal cytochrome P450 system, increase in microsomal superoxide anion generation accompanied by increased levels of liver lipid peroxidation, as measured by the production of thiobarbituric acid reactants and by spontaneous visible chemiluminescence. Concomitantly, liver antioxidant defenses are slightly modified, with decreased activity of glutathione peroxidase, superoxide dismutase and glucose-6-phosphate dehydrogenase contributing to an oxidative stress condition of the liver. These liver biochemical alterations are closely related to increased levels of urinary coproporphyrin, plasma AST and ALT activities and to the onset of liver morphological lesions.

A hemodynamic approach to clinical results in the TRAM flap after selective delay.

The delay phenomenon in the transverse rectus abdominis myocutaneous (TRAM) flap was studied by means of a laser-Doppler flowmeter and an echo color-flow Doppler device. Twenty-eight patients who underwent breast reconstruction with a TRAM flap in our hospitals were analyzed. Eighteen of them underwent selective delay 1 month before the major surgical procedure, and of them, 15 completed the reconstructive procedure. Ten patients were used as a control group and underwent TRAM flap breast reconstruction without selective delay. Cutaneous blood flow in the TRAM flaps was measured in 20 patients with a laser-Doppler flowmeter, and measurements were taken before, during, and after the surgical procedure, following a standardized protocol, as in Tuominen's original scheme. Variations in the cutaneous blood flow in the standard TRAM flap (10 patients) confirmed data obtained from the literature, i.e., an increase when elevating the cutaneous and subcutaneous parts of the flap and a decrease when ligating the deep inferior and superficial epigastric vessels. Compared with the standard TRAM flap, blood flow in the delayed flaps (10 patients) seemed to be more stable, without falling under the baseline. When elevating the cutaneous and subcutaneous parts of the flap (phase 3), blood flow values reached 120.2 percent (SEM 46.8 percent) on the random side and 131.6 percent (p < 0.009, SEM 9.58 percent, standard deviation 30.3 percent) on the axial side. During phase 4 (cutting the rectus muscles), blood flow values reached 115.0 percent (SEM 40.5 percent) on the random side and 102.8 percent (SEM 1.2 percent, standard deviation 3.8 percent, p < 0.049) on the axial side. In order to obtain further hemodynamic data, 10 patients who underwent selective vascular delay 1 month prior to breast reconstruction with a delayed TRAM flap in our hospitals were then studied by means of an echo color-flow Doppler device. Two of these patients also had been studied with the laser-Doppler flowmeter. Superior epigastric artery diameter (in millimeters) and resistivity (expressed as Pourcelot's index) were measured before and after selective delay of the deep and superficial inferior epigastric vessels, following a standardized protocol. Measurements were taken with 7.5- and 10-MHz linear probes at a point located after the origin of the costomarginal artery. In every patient an increase in the superior epigastric artery diameter and a decrease in the resistivity index were observed, and this was statistically significant. In the nonirradiated patients, the increase in the average diameter of the superior epigastric artery was 98.1 percent, and the average resistivity index decrease was 14.1 percent. In the irradiated patients, the increase in the average diameter of the superior epigastric artery was 35.5 percent, and the average resistivity index decrease was 29.8 percent. In conclusion, laser-Doppler flowmeter evaluations show that cutaneous blood flow in the delayed flap is more constant and undergoes fewer variations than that in the standard TRAM flap. In addition, echo color-flow Doppler indicates that the basis for the increase in the vascular territory of the superior epigastric artery caused by the delay maneuver is an increase in the superior epigastric artery diameter, always accompanied by a decrease in the resistivity index. Two different mechanisms seem to us to be related to these modifications in the blood circulation. In the nonirradiated patients, superior epigastric artery dilation prevails, whereas in the irradiated patients, a decrease in the resistivity index is the dominant mechanism of compensation. These hemodynamic findings well support the decrease in flap necrosis reported in our series (standard TRAM: 30 percent; delayed TRAM: 7.1 percent).

[Mammary reconstruction after subcutaneous mammectomy and simple mastectomy: our technical orientation]. / La ricostruzione mammaria dopo mammectomia sottocutanea e mastectomia simplex: il nostro orientamento tecnico.

The authors present their technical guidelines about the operative procedure for high risk benign breast lesions. Various reconstructive managements, conditioned by aesthetical-oncological evaluations, are proposed.

[82 mammary reconstructions immediately after subcutaneous mammectomy or after simple mastectomy. Critical evaluation of results]. / 82 Ricostruzioni mammarie immediate dopo mammectomia sottocutanea e dopo mastectomia simplex. Valutazione critica dei risultati.

The authors review their experience on 25 patients subjected to bilateral subcutaneous mastectomy and 16 patients subjected to bilateral simple mastectomy with immediate submuscular insertion of prosthesis for high risk benign breast lesions. The best aesthetic results were observed with subcutaneous mastectomy (and immediate reconstruction by prosthesis) in patients with small-middle non ptotic breasts. In addition, the authors believe that high risk lesions in large breast are better treated with simple mastectomy and immediate reconstruction by tissue expander.

[Immediate breast reconstruction. A retrospective analysis of 7 years' experience]. / La ricostruzione mammaria immediata. Analisi retrospettiva su 7 anni di esperienza.

The collaboration between oncological and plastic surgeons proved to be essential in the multifaceted treatment of the neoplasms and high-risk lesions of the breast. It guarantees psychological advantages, and improves the quality of life of the patient, who is a candidate for demolition surgery. The authors analyse the results obtained over a 7-year period, through their experiences of 98 immediate breast reconstructions performed after subcutaneous simplex, Patey or Halsted mastectomies. They assessed the validity of this approach due to the brilliant esthetic results obtained, the minimal surgical time, and the low morbidity.

[Postmastectomy breast reconstruction using myocutaneous rectus abdominalis flap. Our experience]. / La ricostruzione mammaria dopo mastectomia con lembo miocutaneo di retto addominale. Nostra esperienza.

The paper compares the results of 34 patients undergoing reconstructive surgery following radical mastectomy using a TRAM flap with those reported in the literature. The parameters taken into consideration in this study were indications for reconstructive surgery, morbidity and the results of reconstruction. The monopedicle flap offered good cosmetic results and a low rate of complications if correctly and selectively used. This selection should exclude high-risk patients. The bipedicle flap is an effective alternative and the morbidity rate was no higher among the abdominal donor.

[Immediate reconstructive approach in neoplastic pathology and "high risk" of the breast]. / L'approccio ricostruttivo immediato nella patologia neoplastica ed "a rischio" della mammella.

One of the most important aims in oncology should be the quality of life, even in the cases of limited life expectancy. With this objective, the Authors report their experience of immediate breast reconstruction after surgical treatment for neoplasms and "high risk" lesions. In 76 cases they analyzed aesthetic results and morbidity. In immediate reconstruction after Patey mastectomies, the tissue expanders offered good cosmetic results with an acceptable complication rate in comparison with more complex methods as myocutaneous flaps. These flaps represent the alternative in selected cases of Halsted mastectomies, where the mutilation is not acceptable to the patient. In "high risk" lesions surgical approach, namely subcutaneous mastectomy, may be proposed in selected cases only. The Authors emphasize that subcutaneous mastectomy with an immediate submuscular reconstruction offer good aesthetic results especially in small size breasts with mild ptosis. The capsular contracture is however significant in 25% of the patients treated with these techniques.