Genetic citizenship: DNA testing and the Israeli Law of Return.

The Israeli State recently announced that it may begin to use genetic tests to determine whether potential immigrants are Jewish or not. This development would demand a rethinking of Israeli law on the issue of the definition of Jewishness. In this article, we discuss the historical and legal context of secular and religious definitions of Jewishness and rights to immigration in the State of Israel. We give a brief overview of different ways in which genes have been regarded as Jewish, and we discuss the relationship between this new use of genetics and the society with which it is co-produced. In conclusion, we raise several questions about future potential impacts of Jewish genetics on Israeli law and society.

Comparison of carboplatin-paclitaxel to docetaxel-cisplatin-5-flurouracil induction chemotherapy followed by concurrent chemoradiation for locally advanced head and neck cancer.

OBJECTIVES: In head and neck squamous cell carcinoma (HNSCC), docetaxel, cisplatin and 5-fluorouracil (TPF) has become an accepted induction chemotherapy regimen. However, carboplatin-paclitaxel (CT) regimens have shown comparable outcomes. Here, we compared the outcomes of patients treated with either TPF or CT as induction chemotherapy followed by definitive chemoradiation. PATIENTS AND METHODS: We performed a single-institution retrospective analysis of patients with Stage III-IV HNSCC. From a database of 803 patients, we identified 143 patients treated with TPF or CT induction chemotherapy between 1999 and 2012. RESULTS: 53 patients and 90 patients received TPF or CT induction chemotherapy, respectively. The median follow-up was 18.9 months. The 1 year locoregional control was 80.5% for CT compared to 55.5% for TPF (HR 0.32, P=.0002). The 1 year progression free survival was 73.2% for CT compared to 60.7% for TPF (HR 0.57; P=.02). On multivariable analysis, CT remained significant for LRC (HR 0.28; P=0.04). TPF induction chemotherapy was associated with worse renal toxicity as measured by peak creatinine increases during induction chemotherapy (P=0.001). TPF was also associated with a trend toward more chemotherapy dose reductions or changes in systemic agents during concurrent chemoradiation (43.4% for TPF vs. 27.8% for CT; P=0.06). CONCLUSIONS: Compared to TPF induction chemotherapy, CT induction chemotherapy had at least similar if not better LRC and PFS in patients while having less renal toxicity. Thus, CT induction chemotherapy may benefit patients with locally advanced HNSCC by facilitating adequate chemoradiation regimens that enhanced disease control.

Molecular consequences of genetic variations in the glutathione peroxidase 1 selenoenzyme.

Accumulating data have implicated the selenium-containing cytosolic glutathione peroxidase, GPx-1, as a determinant of cancer risk and a mediator of the chemopreventive properties of selenium. Genetic variants of GPx-1 have been shown to be associated with cancer risk for several types of malignancies. To investigate the relationship between GPx-1 enzyme activity and genotype, we measured GPx-1 enzyme activity and protein levels in human lymphocytes as a function of the presence of two common variations: a leucine/proline polymorphism at codon 198 and a variable number of alanine-repeat codons. Differences in GPx activity among these cell lines, as well as in the response to the low-level supplementation of the media with selenium, indicated that factors other than just genotype are significant in determining activity. To restrict the study to genotypic effects, human MCF-7 cells were engineered to exclusively express allelic variants representing a combination of either a codon 198 leucine or proline and either 5 or 7 alanine-repeat codons following transfection of GPx-1 expression constructs. Transfectants were selected and analyzed for GPx-1 enzyme activity and protein levels. GPx-1 with 5 alanines and a leucine at codon 198 showed a significantly higher induction when cells were incubated with selenium and showed a distinct pattern of thermal denaturation as compared with GPx-1 encoded by the other examined alleles. The collective data obtained using both lymphocytes and MCF-7 indicate that both intrinsic and extrinsic factors cooperate to ultimately determine the levels of this enzyme available to protect cells against DNA damage and mutagenesis.

Validation of temporal optimization effects for a single fraction of radiation in vitro.

PURPOSE: To experimentally validate how temporal modification of the applied dose pattern within a single fraction of radiation therapy affects cell survival. METHOD AND MATERIALS: Using the linear-quadratic model, we have previously demonstrated that the greatest difference in cell survival results from comparing a temporal dose pattern delivering the highest doses during the middle of a fraction and the lowest at the beginning and end ("Triangle") to one with the lowest doses at the middle and the highest at the beginning and end ("V-shaped"). Also, these differences would be greatest in situations with low alpha/beta and large dose/fraction and fraction length. Two low (WiDr, PC-3) and one high (SQ-20B) alpha/beta cell lines were irradiated in six-well plates with 900 cGy over 20 min (900 cGy/20 min), one each with a Triangle and V-shaped dose pattern. WiDr cells were subjected to the same experiments with first 180 cGy/20 min, then 900 cGy/5 min. Cell survival was assessed using the clonogenic assay. RESULTS: At 900 cGy/20 min, irradiation with a V-shaped pattern resulted in an increased survival compared with use of a Triangle pattern of 21.2% for WiDr (p < 0.01), 18.6% for PC-3 (p < 0.025), and 4.7% for SQ-20B cells (p > 0.05). For WiDr cells at 180 cGy/20 min, this increase reduced to 2.7% (p > 0.05) and to -0.8% (p > 0.05) at 900 cGy/5 min. CONCLUSIONS: These results verify the assertions of the modeling study in vitro, and imply that the temporal pattern of applied dose should be considered in treatment planning and delivery.