Effects of Crotalus durissus collilineatus venom in the isolated rat kidney.

Ophidian accidents caused by the subspecies Crotalus durissus are responsible for high morbity and mortality rates. Acute renal failure is a common complication observed in these accidents. The aim of the present study was to investigate the renal effects promoted by the venom of C. d. collilineatus and its fractions, crotoxin and phospholipase A2. C. d. collilineatus (Cdc; 30 microg mL(-1)), crotoxin (CTX; 10 microg mL(-1)) and phospholipase A2 (PLA2; 10 microg mL(-1)) were tested in isolated rat kidney. The first 30 min of each experiment were used as an internal control and Cdc or its fractions, CTX and PLA2 were added to the system after this period. All experiments lasted 120 min. The venom of Cdc decreased perfusion pressure (PP; control120 = 110.3 +/- 3.69 mmHg; Cdc120 = 96.7+/-8.1 mmHg), renal vascular resistance (RVR; control120 = 6.42+/-0.78 mmHg mL g(-1) min(-1); Cdc120 = 4.8+/-0.56 mmHg/mL g(-1) min(-1)), urinary flow (UF; control120 = 0.19+/-0.03 mL g(-1) min(-1); Cdc120 = 0.12 +/- 0.01 mL g(-1) min(-1)), and glomerular filtration rate (GFR; control120 = 0.79 +/- 0.07 mL g(-1) min(-1); Cdc120 = 0.53 +/- 0.09 mL g(-1) min(-1)), but had no effect on the percent of sodium tubular transport (%TNa+), percent of chloride tubular transport (%TK+) and percent of potassium tubular transport (%TCl-). CTX and PLA2 reduced the GFR, while UF, PP and RVR remained stable during the full 120 min of perfusion. Crotoxin administration also diminished the %TK+ (control120 = 69.94 +/- 6.49; CTX120 = 33.28 +/- 4.78) and %TCl- (control120 = 79.53 +/- 2.67; CTX120 = 64.62 +/- 6.93). PLA2 reduced the %TK+, but exerted no effect on the %TNa+ or on that of TCl-. In conclusion, the C. d. collilineatus venom altered the renal functional parameters evaluated. We suggest that crotoxin and phospholipase A2 were involved in this process, since the renal effects observed would be due to the synergistic action of the components of the venom.     

Thyroid cancer in adolescents and young adults

In adolescents and young adults, thyroid cancer accounts for 13% of all invasive neoplasms, being three times more frequent in females, but overdiagnosis and overtreatment are common. There are two therapeutic approaches, one radical and no longer preferred in all instances, and the other conservative. Permanent complications of surgery and metabolic irradiation can affect quality of life and carry an economic burden. The overall survival rate approaches 100% for patients with differentiated thyroid cancer regardless of the extent of treatment. Medullary thyroid carcinoma is a very different entity, occurring most frequently in the context of hereditary tumor susceptibility syndromes.     

Combination anti-CD137 and anti-CD40 antibody therapy in murine myc-driven hematological cancers

In order to stimulate antigen presentation and T cell activity against cancer, we treated three different tumor models in mice with the monoclonal antibodies anti-CD40 plus anti-CD137 (BiMab). In a subcutaneous transplantable MC38 colon cancer model, there was significant enhancement in the survival of mice following BiMab treatment. Anti-CD40 has shown considerable success against lymphoma in previous studies by other investigators, and we also showed in this study that, in a model of Eμ-Myc lymphoma, there was a statistically significant enhancement of survival of mice following BiMab treatment. Following the success of the BiMab treatment in the previous two models, we wished to determine if it would be successful in a mouse model of multiple myeloma. Firstly, we tested a transplantable model of disease in which multiple myeloma cells derived from Vk*MYC mice were injected intravenously. A minor proportion of anti-CD137 and BiMab treated mice experienced prolongation of life beyond 250 days. Then we tested the therapy in a spontaneously occurring multiple myeloma model, in Vk*MYC transgenic mice. The majority of mice treated survived longer than control mice, although statistical significance was not demonstrated.     

Paraaortic sentinel lymph node detection in intermediate and high-risk endometrial cancer by transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR)

ObjectiveWe aimed to evaluate the accuracy of sentinel lymph node (SLN) mapping with transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) to detect lymph node (LN) metastases, in patients with intermediate and high-risk endometrial cancer (EC), focusing on its performance to detect paraaortic involvement.MethodsProspective study including women with preoperative intermediate or high-risk EC, according to ESMO-ESGO-ESTRO consensus, who underwent SLN mapping using the TUMIR approach. SLNs were preoperatively localized by planar and single photon emission computed tomography/computed tomography images, and intraoperatively by gamma-probe. Immediately after SLN excision, all women underwent systematic pelvic and paraaortic lymphadenectomy by laparoscopy.ResultsThe study included 102 patients. The intraoperative SLN detection rate was 79.4% (81/102). Pelvic and paraaortic drainage was observed in 92.6% (75/81) and 45.7% (37/81) women, respectively, being exclusively paraaortic in 7.4% (6/81). After systematic lymphadenectomy, LN metastases were identified in 19.6% (20/102) patients, with 45.0% (9/20) showing paraaortic involvement, which was exclusive in 15.0% (3/20). The overall sensitivity and negative predictive value (NPV) of SLNs by the TUMIR approach to detect lymphatic involvement were 87.5% and 97.0%, respectively; and 83.3% and 96.9%, for paraaortic metastases. After applying the MSKCC SLN mapping algorithm, the sensitivity and NPV were 93.8% and 98.5%, respectively.ConclusionThe TUMIR method provides valuable information of endometrial drainage in patients at higher risk of paraaortic LN involvement. The TUMIR approach showed a detection rate of paraaortic SLNs greater than 45% and a high sensitivity and NPV for paraaortic metastases in women with intermediate and high-risk EC.     

Survival in primary congenital pulmonary lymphangiectasia with hydrops fetalis

The recent advances in neonatal and pediatric intensive care have changed the outcome of patients with congenital pulmonary lymphangiectasia of different types, including those cases with early neonatal symptoms. However, the patients who present the most severe form of the disease, manifested by in utero hydrops (including those treated by in utero thoracoamniotic shunting to relieve the mediastinal compression), have had an unvaryingly fatal ending in all published reports, with most cases dying before birth, and the few born alive dying during the first days of life. We present a patient with primary congenital pulmonary lymphangiectasia complicated by hydrops fetalis, who was treated in utero, survived the neonatal period after intensive medical and surgical support, and was discharged home at the age of 2 months. She is currently 6 months old, and has minimal signs or symptoms of chronic lung disease. The different aspects of the management of congenital pulmonary lymphangiectasia are discussed in this report, together with a review of the literature.     

Assessment of expression of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor (LH/hCGR) and hCG protein in ovarian cancer tissues

OBJECTIVES: Ovarian cancers still remain a significant worldwide epidemiological problem. The vast majority of newly diagnosed cases are in advanced clinical stages, and the five-year survival rate in all clinical stages amounts up to less than fifty percent. A better understanding of the biology of ovarian cancer can bring us closer to successful treatment and recovery. The aim of this study was to evaluate the expression of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor (LH/hCGR) and the expression of hCG protein in the ovarian cancer tissue. MATERIALS: Histologically proven primary ovarian cancer samples (n=20) were obtained from women undergoing gynecologic surgery. Frozen sections of ovarian cancer tissues were evaluated by means of indirect immunofluorescence. RESULTS: The expression of hCG protein was ubiquitous throughout all samples, while LH/hCGR was detected in only sixty percent of samples. Co-expression of LH/hCGR and hCG protein was detected in some individual cells in tumor tissue. Some cancer cells expressed only hCG protein, but not LH/hCGR. CONCLUSIONS: Expression of LH/hCG receptor is a characteristic feature of various histological types of ovarian cancer. Co-expression of LH/hCGR and hCG protein in individual cancer cells may point to an autocrine or paracrine mechanism of _hCG activity in the tumor microenvironment. Further studies are needed to evaluate LH/hCGR and hCG protein function in the course of neoplastic development.     

DNA adducts in human female genital organs

DNA adducts, one of genetic damages markers, precede and finally can lead to oncogenic mutations. They appear in genome as a result of DNA bases damages caused by various and numerous environmental factors eg. ultraviolet light, ionic radiation, toxins and also endogenic substances, for example estrogens. It is believed that the creation of DNA adducts is a necessary but insufficient process for the neoplastic transformation of the cell. The following review presents concise knowledge about the DNA adducts creation and their sequels served in healthy and cancerous tissues of the female genital organs, on the base of the available data.