Static polarizability of molecular materials: environmental and vibrational contributions

Modeling the dielectric behavior of molecular materials made up of large pi-conjugated molecules is an interesting and complex task. Here we address linear polarizabilities, and the related dielectric constant, of molecular crystals and aggregates made up of closed-shell pi-conjugated molecules with either a non-polar or largely polar ground-state, and also examine the behavior of mixed-valence (or charge-transfer) organic salts. We recognize important collective phenomena due to supramolecular interactions in materials with large molecular polarizabilities, and underline large vibrational contributions to the polarizability in materials with largely delocalized electrons.Comment: 18 pages, including 9 figure

SURGERY IN PATIENTS WITH TESTICULAR MALIGNANT GERM CELL TUMORS: COMPLIANCE TO SURGICAL GUIDELINES AND RESULTS IN THE ITALIAN COOPERATIVE STUDY

Purpose: Surgery represents a main and often the only treatment in patients with testicular Malignant Germ Cell Tumors (MGCT). We analyzed the compliance to surgical guidelines and the results in a series of patients with testicular MGCT -/+ retroperitoneal node involvement, without distant metastases. Method: 42 patients, observed in 15 Centers were enrolled in the Italian Cooperative Study on MGCT (January2004–December2010). 14/42 were younger than 2 y. of age, 28/42 between 13–18 y. Treatment was delivered according to COG-Staging-System: St.I patients (complete excision with inguinal orchifunicolectomy+decrease of markers, +hemiscrotectomy if scrotal involvement) did not receive further treatment; St.II patients (scrotal involvement after hemiscrotectomy and/or retroperitoneal node (RPN) enlargement:2 cm) had RPN Dissection if residuals were suspected after PEBx3or4. Results: St.I: 26 patients. 3/26 had a scrotal approach due to suspected testicular torsion: 1/3 underwent hemiscrotectomy, 2 did not receive further therapy after decrease of alphaFP, due to patient’s or physician’s decision respectively. 3/26 were successfully treated for RPN relapse, occurred at 3,6,9 months after adequate surgery (2 adolescents, 1 infant). St.II: in 4 patients CTwas delivered due to slight enlargement of RPN (+persistent alphaFP in 1). St.III: 12 patients received CT and RPND (bilateral in 1). Histology was negative in 11/12. All patients are alive without disease, 39 in 1stCR, 3 in 2ndCR (f.u 9–86 m.:med.48). 1 St.1 patient suffered from postoperative scrotal hematoma. Among patients younger than 2 y, 10/14 had a pure YST, 12/14 had St.I disease; among those between 13–18 y, 27/28 had a mixed histology, 14/28 were St.II or St.III. In 3 adolescents a testicular prosthesis was positioned during primary operation. Conclusion: Outcome was excellent. Regional relapses, observed only in St.I patients, were cured. Surgical guidelines were followed in 40/42 cases. Scrotal approach did not worsen the outcome of patients who did not receive further treatment

Chemotherapy-related damage to ovarian reserve in childhood cancer survivors : interpreting the evidence

Chemotherapy during childhood damages ovarian reserve and can affect future fertility. However, recent large epidemiological studies showed that the detrimental impact on fertility is less severe if women seek for pregnancy at a younger age. To explain this observation, we hypothesize that the detrimental effects of previous chemotherapy on the ovarian reserve may be attenuated in young adults for two main reasons. Firstly, recent evidence showed that the amount of ovarian reserve is not a critical factor for effective natural conceptions. Provided that the residual ovarian reserve allows regular ovulatory cycles, the chances of pregnancy are similar in women with intact or reduced ovarian reserve. Secondly, ovarian reserve depletion appears to be a phenomenon that is inversely related to the residual ovarian reserve rather than to age. From a mathematical perspective, this kind of regulation intrinsically attenuates the effects of an early loss of a significant amount of primordial follicles. In conclusion, the detrimental effects of chemotherapy on natural fertility may be less severe if women with a history of chemotherapy during childhood seek for pregnancy early. This information should be part of the counseling

Dual inhibition of CDK4/6 and PI3K/AKT/mTOR signaling impairs energy metabolism in MPM cancer cells

Background: Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated to asbestos exposure. One of the most frequent genetic alteration in MPM patients is CDKN2A/ARF loss, leading to aberrant activation of the Rb pathway. In MPM cells, we previously demonstrated the therapeutic efficacy of targeting this signaling with the CDK4/6 inhibitor palbociclib in combination with PI3K/mTOR inhibitors. Here, we investigated whether such combination may have an impact on cell energy metabolism. Methods: The study was performed in MPM cells of different histotypes; metabolic analyses were conducted by measuring GLUT-1 expression and glucose uptake/consumption, and by SeaHorse technologies. Results: MPM cell models differed for their ability to adapt to metabolic stress conditions, such as glucose starvation and hypoxia. Independently of these differences, combined treatments with palbociclib and PI3K/mTOR inhibitors inhibited cell proliferation more efficaciously than single agents. The drugs alone reduced glucose uptake/consumption as well as glycolysis, and their combination further enhanced these effects under both normoxic and hypoxic conditions. Moreover, the drug combinations significantly impaired mitochondrial respiration as compared with individual treatments. These metabolic effects were mediated by the concomitant inhibition of Rb/E2F/c-myc and PI3K/AKT/mTOR signaling. Conclusions: Dual blockade of glycolysis and respiration contributes to the anti-tumor efficacy of palbociclib-PI3K/mTOR inhibitors combination

Renal cell carcinoma in children: A clinicopathologic study

Purpose: To identify the prognostic factors, treatment, and outcome of children affected by renal cell carcinoma (RCC). Patients and Methods: The series included 41 patients (18 males and 23 females) with a median age of 124 months observed at the 11 Italian Association for Pediatric Hematology and Oncology centers from January 1973 to January 2001. Clinical data, surgical notes, pathologic findings, and summaries of therapy were taken from the charts. Results: Seven (17%) of the 41 patients had a papillary histology, and 34 (82.4%) had nonpapillary histology. Eighteen patients (43.9%) had stage I, one patient (2.4%) had stage II, two patients (4.8%) had stage IIIA, 10 patients (24.3%) had stage IIIB, and nine patients (21.9%) had stage IV disease. One patient had a bilateral involvement at diagnosis. Seven patients experienced disease recurrence. Lung and liver were the most common distant lesions and usually were fatal. In this study, the major factor influencing the prognosis was the stage. Event-free survival at 20 years was 53.5% for all patients. Overall survival at 20 years was 54.9% for all patients. Conclusion: RCC is a rare disease in children and adolescents. This neoplasm has a different clinical presentation in children compared with adults but the same outcome. In our experience, patients with localized disease could be cured by nephrectomy alone. Prospective studies in a larger number of patients are needed to confirm radiation therapy and biologic response modifiers as effective adjunct therapy in RCC stage III. The alternative therapy seems warranted in patients with advanced disease. © 2003 by American Society of Clinical Oncology

Mature and Immature Teratoma: A Report From the Second Italian Pediatric Study

Background. Teratomas demonstrate a benign clinical behavior, however they may recur with malignant components or as teratoma, and in a small group of patients prognosis could be fatal. After the ®rst Italian study, we collected cases of teratoma, alongside the protocol for malignant germ cell tumors. Procedure. Patients with teratoma were collected from 2004 to 2014. Teratomas were classi®ed according to the WHO classi®cations, as mature and immature. Patients with pathological aFP and/or bHCG, and those with a malignant germ cell component were not included. Results. The study enrolled 219 patients (150 mature, 69 immature teratomas) with a median age at diagnosis of 42 months. The primary sites involved were: 118 gonadal and 101 extragonadal teratomas. Two females with ovarian teratoma had a positive family history. Complete and incomplete surgeries were performed in 85% and 9% of cases. Seventeen events occurred: six females had a second metachronous tumor (5 contralateral ovarian teratoma, 1 adrenal neuroblastoma) and 11 teratomas relapsed/progressed (3 mature, 8 immature teratomas). Two patients died, one of progressive immature teratoma and one of surgical complications. At a median follow up of 68 months, the event-free, relapse-free, and overall survival rates were 90.6%, 94.3%, 98.6%, respectively. Conclusions. Teratomas show a good prognosis, especially the mature ones: surgery and follow-up remain the standard approach. Incomplete surgery in immature teratoma is the group at greatest risk of relapse. Bilateral ovarian tumors are a possibility, and the rare family predisposition to ovarian mature teratoma warrants further analyses

Mature and immature teratoma: A report from the second Italian pediatric study

none16noBACKGROUND: Teratomas demonstrate a benign clinical behavior, however they may recur with malignant components or as teratoma, and in a small group of patients prognosis could be fatal. After the first Italian study, we collected cases of teratoma, alongside the protocol for malignant germ cell tumors. PROCEDURE: Patients with teratoma were collected from 2004 to 2014. Teratomas were classified according to the WHO classifications, as mature and immature. Patients with pathological aFP and/or bHCG, and those with a malignant germ cell component were not included. RESULTS: The study enrolled 219 patients (150 mature, 69 immature teratomas) with a median age at diagnosis of 42 months. The primary sites involved were: 118 gonadal and 101 extragonadal teratomas. Two females with ovarian teratoma had a positive family history. Complete and incomplete surgeries were performed in 85% and 9% of cases. Seventeen events occurred: six females had a second metachronous tumor (5 contralateral ovarian teratoma, 1 adrenal neuroblastoma) and 11 teratomas relapsed/progressed (3 mature, 8 immature teratomas). Two patients died, one of progressive immature teratoma and one of surgical complications. At a median follow up of 68 months, the event-free, relapse-free, and overall survival rates were 90.6%, 94.3%, 98.6%, respectively. CONCLUSIONS: Teratomas show a good prognosis, especially the mature ones: surgery and follow-up remain the standard approach. Incomplete surgery in immature teratoma is the group at greatest risk of relapse. Bilateral ovarian tumors are a possibility, and the rare family predisposition to ovarian mature teratoma warrants further analyses. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.noneTerenziani M;D'Angelo P;Inserra A;Boldrini R;Bisogno G;Babbo GL;Conte M;Dall' Igna P;De Pasquale MD;Indolfi P;Piva L;Riccipetitoni G;Siracusa F;Spreafico F;Tamaro P;Cecchetto GTerenziani, M; D'Angelo, P; Inserra, A; Bisogno, Gianni; Bisogno, G; Babbo, Gl; Conte, M; Dall' Igna, P; De Pasquale, Md; Indolfi, P; Piva, L; Riccipetitoni, G; Siracusa, F; Spreafico, F; Tamaro, P; Cecchetto, Giovann