Antitumor Activity and Mechanism of Action of Hormonotoxin, an LHRH Analog Conjugated to Dermaseptin-B2, a Multifunctional Antimicrobial Peptide.

Prostate cancer is the most common cancer in men. For patients with advanced or metastatic prostate cancer, available treatments can slow down its progression but cannot cure it. The development of innovative drugs resulting from the exploration of biodiversity could open new therapeutic alternatives. Dermaseptin-B2, a natural multifunctional antimicrobial peptide isolated from Amazonian frog skin, has been reported to possess antitumor activity. To improve its pharmacological properties and to decrease its peripheral toxicity and lethality we developed a hormonotoxin molecule composed of dermaseptin-B2 combined with d-Lys6-LHRH to target the LHRH receptor. This hormonotoxin has a significant antiproliferative effect on the PC3 tumor cell line, with an IC50 value close to that of dermaseptin-B2. Its antitumor activity has been confirmed in vivo in a xenograft mouse model with PC3 tumors and appears to be better tolerated than dermaseptin-B2. Biophysical experiments showed that the addition of LHRH to dermaseptin-B2 did not alter its secondary structure or biological activity. The combination of different experimental approaches indicated that this hormonotoxin induces cell death by an apoptotic mechanism instead of necrosis, as observed for dermaseptin-B2. These results could explain the lower toxicity observed for this hormonotoxin compared to dermaseptin-B2 and may represent a promising targeting approach for cancer therapy.

Post-chemotherapy retroperitoneal teratoma in nonseminomatous germ cell tumors: Do predictive factors exist? Results from a national multicenter study.

BACKGROUND AND OBJECTIVES: To identify predictive preoperative factors of the presence of teratoma in retroperitoneal lymph node dissection specimens. METHODS: We performed a 20 years multicenter retrospective analysis of all patients who underwent retroperitoneal lymph node dissection for residual masses after chemotherapy (PC-RPLND). Patients had undergone PC-RPLND after chemotherapy for advanced testicular cancer. The histologic components of the primary tumor were compared with those of the residual masses using logistic regression. RESULTS: A total of 469 NSGCT patients underwent PC-RPLND (complete data available for 211). By PC-RPLND, necrosis was found in 84 cases, teratoma in 102 cases, and viable tumor in 25 cases. The univariate and multivariate analyses showed that teratoma (P = 0.001 and P = 0.002, respectively) and yolk sac tumor (P = 0.009 and P = 0.035, respectively) in orchiectomy specimens were statistically significant predictors of the presence of teratoma in retroperitoneal lymph nodes. CONCLUSIONS: PC-RPLND is the standard treatment for any supracentimetric residual lesion. This procedure is associated with a high morbidity, and almost half patients are overtreated. The presence of teratoma and yolk sac tumor in the orchiectomy specimen were independent significant predictors of teratoma in retroperitoneal masses. J. Surg. Oncol. 2016;114:992-996. © 2016 Wiley Periodicals, Inc.

Atypical Presentation of Testicular Adrenal Rest Tumor (TART) Leading to Bilateral Partial Orchiectomy in a 31-Year-Old Adult Revealing Primary Adrenal Insufficiency with CYP11A1 Deficiency.

Adrenogenital syndrome is commonly associated with a deficiency in 21-hydroxylase but can be present in other rare enzymatic blocks. We report here the case of a 31-year-old man who presented with bilateral painful testicle lesions leading to bilateral partial orchiectomy as they were suspected for malignancy. These lesions were finally identified as benign testicle adrenal rest tumors (TARTs), and the patient was actually belatedly diagnosed with primary adrenal insufficiency due to 2 mutations of the CYP11A1 gene encoding the cholesterol side-chain cleavage enzyme (P450scc); the mutations were 940G > A (p.Glu314Lys) and c.1393C > T (p.Arg465Trp). The same mutations were found in his 29-year-old sister, who was then also diagnosed for primary adrenal insufficiency. Deficiency in P450scc is an extremely rare genetic autosomal recessive disorder with around 40 described families in the literature and 30 different mutations. As the diagnosis of delayed onset of P450Scc mutation is difficult, this case illustrates the need for a systematic endocrinological assessment in any case of bilateral testicle lesions, thus avoiding unnecessary surgery.

Chronic Inflammation and Radiation-Induced Cystitis: Molecular Background and Therapeutic Perspectives.

Radiation cystitis is a potential complication following the therapeutic irradiation of pelvic cancers. Its clinical management remains unclear, and few preclinical data are available on its underlying pathophysiology. The therapeutic strategy is difficult to establish because few prospective and randomized trials are available. In this review, we report on the clinical presentation and pathophysiology of radiation cystitis. Then we discuss potential therapeutic approaches, with a focus on the immunopathological processes underlying the onset of radiation cystitis, including the fibrotic process. Potential therapeutic avenues for therapeutic modulation will be highlighted, with a focus on the interaction between mesenchymal stromal cells and macrophages for the prevention and treatment of radiation cystitis.

Unusual presentation of testicular cancer with tumor thrombus extending to the inferior vena cava.

A 45-year-old man with a left testis tumor with a 25 mm para-aortic lymph node swelling, multiple bilateral pulmonary metastases, bilateral pulmonary embolism, and inferior vena cava (IVC) thrombus underwent a radical orchidectomy in our institution. The thrombus extended from the left gonadal vein to the left renal vein to the IVC. The fluorine-18 fluorodeoxyglucose (f-FDG) positron emission tomography (PET) computerized tomography (CT) demonstrated a hypermetabolic focus in the retroperitoneum and in the IVC thrombus. Before orchidectomy only lactate dehydrogenase (LDH) was high but all the serum tumor markers increased postoperatively. The tumor was staged pT1N2M1aS1, which was an intermediate prognosis, based on the International Germ Cell Cancer Collaborative Group consensus (IGCCCG). After 4 courses of bleomycin, etoposide, and cisplatin (BEP) chemotherapy the patient's tumor markers normalized and the thrombus disappeared. There was only one residual retroperitoneal lymph node M1. Retroperitoneal lymph node dissection was performed. The pathological examination revealed only necrotic tissues. The patient has been disease-free since surgery.

Malignant melanoma revealed by testicular metastasi.

We report the case of an 83 years old man supported for painless indurated and nodular lesion of the left testicle. Histological analysis identified a primary cutaneous melanoma metastasis although it has never been found on physical examination. The discovery of a testicular mass should suggest first a germ cell tumor, despite in some populations (age over 60 years), other diagnosis are more frequent, including metastasis. Due to rapid disease progression and high mortality rate within a short interval, a complete staging looking for other secondary locations must be done and a multidisciplinary care and palliative involvement must also be initiated in the context of metastatic melanoma.

A 20-Year Epidemiological Review of Testis Cancer at a French Military Hospital.

OBJECTIVES: To determine if the epidemiology of testis cancer in military service has followed worldwide trends and if the end of conscription in 2000 in France marked an epidemiologic turn. METHODS: All of the patients who had an orchiectomy for a testis germ tumor from January 1990 to January 2011 were studied. The patients were divided into two groups: orchiectomy before 2000 and after 2000. RESULTS: 289 patients were included, with a mean age of 30.8. The mean age at diagnosis increased significantly as well as the proportion of stage 1 seminomas, whereas stage 1 nonseminomatous germ cell tumors (NSGCT) slightly decreased. For stage 1 seminomas, there was an increase in the surveillance (10% vs. 31%) and in the number of chemotherapies (19% vs. 22%); for stage 1 NSGCT, surveillance also increased (53% vs. 64%). The specific 5-year survival was 98.3%. CONCLUSIONS: We noted an increase in the number of stage 1 seminomas, the surveillance of located germ tumors, and an excellent survival rate. However, the population was younger with regard to national data, and the number of stage 1 NSGCT decreased in favor of advanced metastatic tumors.