Influence of some experimental factors on metal toxicity to Selenastrum capricornutum

Toxic effects of Cd⁺⁺, Cu⁺⁺, and Zn⁺⁺ on Selenastrum capricornutum were evaluated in various experimental conditions in order to determine the influence of the composition of the test medium and of the concentration of the algal biomass on the toxicity of metals to algae. Four media recommended in different standard methods (International Standards Organisation, U.S. Environmental Protection Agency, Organisation for Economic Cooperation and Development, AFNOR) were compared. Results of algal bioassays showed that the sensitivity of algae during the exponential growth phase was not influenced by the concentration of macronutrients in the medium. On the contrary, the numeration of the algal suspensions tested appeared determinant as the toxicity decreased when the quantity of algal inoculum was increased: with inocula of nearly 3 × 10⁴, 2.5 × 10⁵, 6 × 10⁵, and 3 × 10⁶ cells/mL at t = 0, the corresponding EC₅₀ were 46, 80, 110, and up to 300 μg/L for cadmium, 10, 65, 105, and 280 μg/L for copper, and 90, 163, 225, and 365 μg/L for zinc. Modifications in the speciation forms of the metal induced by a rapid increase of the pH could be responsible for part of this decreased toxicity.     

A systematic assessment of common genetic variation in CYP11A and risk of breast cancer

CYP11A catalyzes the rate-limiting step in the biosynthesis of sex-steroid hormones. In this study, we employed a systematic approach that involved gene resequencing and a haplotype-based analysis to investigate the relationship between common variation in CYP11A and breast cancer risk among African-Americans, Latinas, Japanese-Americans, Native Hawaiians, and Whites in the Multiethnic Cohort Study. Resequencing in a multiethnic panel of 95 advanced breast cancer cases revealed no common missense variant (> or =5% frequency). Common haplotype patterns were assessed by genotyping 36 densely spaced single nucleotide polymorphisms (SNPs) spanning 67 kb of the CYP11A locus in a multiethnic panel of subjects (n = 349; 1 SNP/1.86 kb on average). We identified one to two regions of strong linkage disequilibrium in these populations. Twelve tagging SNPs were selected to predict the common haplotypes (> or =5% frequency) in these regions with high probability (average R(h)(2) = 0.94) and were examined in a breast cancer case-control study in the Multiethnic Cohort Study (1,615 cases and 1,962 controls). A global test for differences in risk according to common haplotypes over the locus was statistically significant (P = 0.006), as were associations with haplotypes in each block (block 1 global test, P = 0.008; haplotype 1D, effect per haplotype copy, odds ratios, 1.23; 95% confidence interval, 1.03-1.48) and block 2 (global test, P = 0.016; haplotype 2F odds ratios, 1.52; 95% confidence interval, 1.15-2.01). These haplotypes were most common in Japanese-Americans and Native Hawaiians, followed by Whites then Latinas, and were rare in African-Americans (<5% frequency); the haplotype effects on risk across each group were homogeneous. Based on these findings, CYP11A deserves further consideration as a candidate breast cancer susceptibility gene.     

Prenatally diagnosed sacrococcygeal teratoma: a prognostic classification

Purpose

The objective of this study is to describe a prognostic classification for prenatally diagnosed sacrococcygeal teratoma (SCT).

Methods

Charts from 44 fetuses were reviewed. Three groups were defined as follows: group A—tumor diameter less than 10 cm, absent or mild vascularity and slow growth; group B—diameter 10 cm or greater, pronounced vascularity or high-output cardiac failure and fast growth; group C—diameter 10 cm or greater, predominantly cystic lesion with absent or mild vascularity and slow growth.

Results

Size at diagnosis, growth rate, and vascularity were higher in group B. Gestational age at delivery was lower in group B. Eleven of 21 died in the perinatal period in group B and none in groups A and C. In group C, drainage or shunting of the SCT has been performed in 6 of 10 cases.

Conclusions

Group A is associated to good maternal and perinatal outcome, as well as group C, although shunting or drainage of the SCT could be necessary. Large fast-growing SCT with rich vascularity is associated with a higher perinatal mortality and morbidity than smaller lesions with mild vascularity.     

Interest of dynamic tests in acute ecotoxicity assessment in algae

Sorption of toxics by algae may be important and occurs very early. Thus, a decrease of the experimental toxic concentrations in the medium results in understating toxicity when tests are conducted under static conditions. In this work, two different methods of exposure of algae (Chlorella vulgaris) are studied, the static test and the pseudodynamic test. Acute effects (biological and analytical effects) of inorganic compounds (Cu²⁺, Cd²⁺, Pb²⁺, Cr⁶⁺) have been evaluated for 96 hr of exposure; in each case, IC₅₀ is much lower in the dynamic condition than in the static one. The percentage of reduction varies from 55 to 75% after 96 hr. Accumulation of metal by chlorellae is greater when testing by the pseudodynamic way, with Cu²⁺ and Pb²⁺. But in the case of Cd²⁺ and Cr⁶⁺, the concentration factors are similar in the two kinds of exposure. These results point out the advantage of the pseudodynamic test, of which the methodology is very easy, for a more realistic assessment of acute ecotoxicity in these organisms.     

Chordomas of the base of the skull and upper cervical spine. One hundred patients irradiated by a 3D conformal technique combining photon and proton beams

To define the prognostic factors for local control and overall survival among 100 consecutive patients with chordoma of the base of skull or upper cervical spine treated by fractionated irradiation combining proton and photon beams. Between December 1993 and August 2002, 100 patients (median age: 53 years [8 - 85], M/F sex ratio: 3/2) were treated by a combination of high-energy photons and protons. The proton component was delivered at the Centre de Protonthérapie d'Orsay (CPO) by a 201 MeV beam. The median total dose delivered to the tumor volume was 67 GyECo. With a median follow-up of 31 months [range: 0 - 87], 25 tumours relapsed locally. The 2- and 4-year local control rates were 86.3% (+/-3.9%) and 53.8% (+/-7.5%), respectively. According to multivariate analysis, at least 95% of the tumor volume encompassed by the 95% isodose (p = 0.048; RR: 3.4 95%CI [1.01 - 11.8]) and a minimal dose delivered into the tumor volume <56 GyECo (p = 0.042; RR: 2.3 95%CI [1.03 - 5.2]) were independent prognostic factors of local control. Ten patients died. The 2- and 5-year overall survival rates were 94.3% (+/-2.5%) and 80.5% (+/-7.2%), respectively. According to multivariate analysis, local tumor control (p = 0.005; RR: 21 95%CI [2.2 - 200]) was a prognostic factor of overall survival. For chordomas of the base of the skull and upper cervical spine treated by surgery and irradiation combining photons and protons, the quality of irradiation, reflected by homogeneity of the dose into the tumor volume, is a major factor of local control. Close attention must be paid to minimize the underdosed areas close to critical organs. The role of surgical resection remains paramount, and a trial of dose escalation would have to consider an increase in the dose to critical organs, especially as current results indicate the low toxicity of this treatment.     

Interstitial brachytherapy of periorificial skin carcinomas of the face: a retrospective study of 97 cases

PURPOSE: To analyze outcomes after interstitial brachytherapy of facial periorificial skin carcinomas. PATIENTS AND METHODS: We performed a retrospective analysis of 97 skin carcinomas (88 basal cell carcinomas, 9 squamous cell carcinomas) of the nose, periorbital areas, and ears from 40 previously untreated patients (Group 1) and 57 patients who had undergone surgery (Group 2). The average dose was 55 Gy (range, 50-65 Gy) in Group 1 and 52 Gy (range, 50-60 Gy) in Group 2 (mean implantation times: 79 and 74 hours, respectively). We calculated survival rates and assessed functional and cosmetic results de visu. RESULTS: Median age was 71 years (range, 17-97 years). There were 29 T1, 8 T2, 1 T3, and 2 Tx tumors in Group 1. Tumors were <2 cm in Group 2. Local control was 92.5% in Group 1 and 88% in Group 2 (median follow-up, 55 months; range, 6-132 months). Five-year disease-free survival was better in Group 1 (91%; range, 75-97) than in Group 2 (80%; range, 62-90; p = 0.23). Of the 34 patients whose results were reassessed, 8 presented with pruritus or epiphora; 1 Group 2 patient had an impaired eyelid aperture. Cosmetic results were better in Group 1 than in Group 2 with, respectively, 72% (8/11) vs. 52% (12/23) good results and 28 (3/11) vs. 43% (10/23) fair results. CONCLUSIONS: Brachytherapy provided a high level of local control and good cosmetic results for facial periorificial skin carcinomas that pose problems of surgical reconstruction. Results were better for untreated tumors than for incompletely excised tumors or tumors recurring after surgery.     

Induction chemotherapy, cytoreductive surgery and intraoperative hyperthermic pleural irrigation in patients with stage IVA thymoma

The optimal treatment for Masaoka stage IVA thymoma remains controversial. Whilst extrapleural pneumonectomy (EPP) has been proposed, we sought to examine the results of our institutional preference for induction chemotherapy, cytoreductive surgery and intraoperative hyperthermic pleural irrigation. We undertook a retrospective study of patients undergoing surgery for Masaoka stage IVA thymoma following induction chemotherapy over a three-year period at our institution. Between February 2007 and February 2010, 42 patients underwent surgery for thymoma. Six patients underwent surgery with intent to perform cytoreductive surgery and intraoperative hyperthermic pleural irrigation. Complete cytoreductive surgery was not feasible in one patient and thymectomy only was performed. One patient had re-operation for recurrent disease 24 months after the first operation and there were therefore seven procedures undertaken in six patients during the study period. There were no in-hospital deaths. Median follow-up was 18.8 months (range 1.5-31.9 months). One patient died 14 months postoperatively from an acute cardiovascular event. The four remaining patients are alive and well with no evidence of disease recurrence. Multimodality therapy consisting of induction chemotherapy and cytoreductive surgery is a safe, feasible treatment for stage IVA thymoma. Our experience suggest that full pleurectomy is an alternative to EPP.     

Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study

Extranodal NK/T-cell lymphoma, nasal type, is a rare and highly aggressive disease with a grim prognosis. No therapeutic strategy is currently identified in relapsing patients. We report the results of a French prospective phase II trial of an L-asparaginase-containing regimen in 19 patients with relapsed or refractory disease treated in 13 centers. Eleven patients were in relapse and 8 patients were refractory to their first line of treatment. L-Asparaginase-based treatment yielded objective responses in 14 of the 18 evaluable patients after 3 cycles. Eleven patients entered complete remission (61%), and only 4 of them relapsed. The median overall survival time was 1 year, with a median response duration of 12 months. The main adverse events were hepatitis, cytopenia, and allergy. The absence of antiasparaginase antibodies and the disappearance of Epstein-Barr virus serum DNA were significantly associated with a better outcome. These data confirm the excellent activity of L-asparaginase-containing regimens in extranodal NK/T-cell lymphoma. L-Asparaginase-based treatment should thus be considered for salvage therapy, especially in patients with disseminated disease. First-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma warrants evaluation in prospective trials. This trial is registered at www.clinicaltrials.gov as #NCT00283985.     

The cancer stem cell hypothesis: failures and pitfalls

Based on the clonal evolution model and the assumption that the vast majority of tumor cells are able to propagate and drive tumor growth, the goal of cancer treatment has traditionally been to kill all cancerous cells. This theory has been challenged recently by the cancer stem cell (CSC) hypothesis, that a rare population of tumor cells, with stem cell characteristics, is responsible for tumor growth, resistance, and recurrence. Evidence for putative CSCs has been described in blood, breast, lung, prostate, colon, liver, pancreas, and brain. This new hypothesis would propose that indiscriminate killing of cancer cells would not be as effective as selective targeting of the cells that are driving long-term growth (ie, the CSCs) and that treatment failure is often the result of CSCs escaping traditional therapies.The CSC hypothesis has gained a great deal of attention because of the identification of a new target that may be responsible for poor outcomes of many aggressive cancers, including malignant glioma. As attractive as this hypothesis sounds, especially when applied to tumors that respond poorly to current treatments, we will argue in this article that the proposal of a stemlike cell that initiates and drives solid tissue cancer growth and is responsible for therapeutic failure is far from proven. We will present the point of view that for most advanced solid tissue cancers such as glioblastoma multiforme, targeting a putative rare CSC population will have little effect on patient outcomes. This review will cover problems with the CSC hypothesis, including applicability of the hierarchical model, inconsistencies with xenotransplantation data, and nonspecificity of CSC markers.