Substantial gene expression shifts during larval transitions in the pearl oyster Pinctada margaritifera.

Early development stages in marine bivalve are critical periods where larvae transition from pelagic free-life to sessile mature individuals. The successive metamorphosis requires the expression of key genes, the functions of which might be under high selective pressure, hence understanding larval development represents key knowledge for both fundamental and applied research. Phenotypic larvae development is well known, but the underlying molecular mechanisms such as associated gene expression dynamic and molecular cross-talks remains poorly described for several nonmodel species, such as P. margaritifera. We designed a whole transcriptome RNA-sequencing analysis to describe such gene expression dynamics following four larval developmental stages:  d-shape, Veliger, Umbo and Eye-spot. Larval gene expression and annotated functions drastically diverge. Metabolic function (gene expression related to lipid, amino acid and carbohydrate use) is highly upregulated in the first development stages, with increasing demand from  d-shape to umbo. Morphogenesis and larval transition are partly ordered by Thyroid hormones and Wnt signaling. While larvae shells show some similar characteristic to adult shells, the cause of initialization of biomineralization differ from the one found in adults. The present study provides a global overview of Pinctada margaritifera larval stages transitioning through gene expression dynamics, molecular mechanisms and ontogeny of biomineralization, immune system, and sensory perception processes.

Association between post-operative hPG80 (circulating progastrin) detectable level and worse prognosis in glioblastoma.

BACKGROUND: Patients with glioblastomas have a dismal prognosis, and there is no circulating predictive or prognostic biomarker. Circulating progastrin, hPG80, is a tumor-promoting peptide present in the blood of patients with various cancers that has been shown to have prognostic value. We evaluated the prognostic value of plasma hPG80 in patients with isocitrate dehydrogenase-wild type glioblastoma after surgery. PATIENTS AND METHODS: A multicentric retrospective study in glioblastoma patients treated with standard radio-chemotherapy was conducted. The hPG80 levels were measured in plasma EDTA samples collected after surgery with an ELISA DxPG80.lab kit (Biodena Care, Montpellier, France), which has a detection threshold of 1.2 pM. The relationship between post-operative hPG80 plasma levels, in combination with other known prognostic factors, and patients' progression-free survival (PFS) and overall survival (OS) was evaluated. RESULTS: Sixty-nine patients were assessable. Plasma samples were collected after tumor biopsy (B), partial resection (PR), and complete resection (CR) for 22, 25, and 22 patients, respectively. At a median concentration of 5.37 pM (interquartile range 0.00-13.90 pM), hPG80 was detected in 48 (70%) patients (hPG80+). CR was associated with significant lower values of hPG80 levels: the median value was 0.7 versus 9.1 pM for PR (P = 0.02) and 8.3 pM for B (P = 0.004). The hPG80 detection rate was also significantly lower: 50% (CR) versus 72% (PR) versus 86% (B) (P = 0.005). The median follow-up was 39 months [22.4 months-not reached]. hPG80 post-operative detection was associated with numerically shorter PFS (6.4 versus 9.4 months, P = 0.13) and OS (14.5 versus 20.9 months, P = 0.11). In multivariate analysis, hPG80 was a prognostic factor for OS (P = 0.034). CONCLUSIONS: Circulating hPG80 could serve as a new prognostic biomarker after surgery in patients with glioblastoma treated with radio-chemotherapy.

Whole transcriptome sequencing and biomineralization gene architecture associated with cultured pearl quality traits in the pearl oyster, Pinctada margaritifera.

BACKGROUND: Cultured pearls are unique gems produced by living organisms, mainly molluscs of the Pinctada genus, through the biomineralization properties of pearl sac tissue. Improvement of P. margaritifera pearl quality is one of the biggest challenges that Polynesian research has faced to date. To achieve this goal, a better understanding of the complex mechanisms related to nacre and pearl formation is essential and can now be approached through the use of massive parallel sequencing technologies. The aim of this study was to use RNA-seq to compare whole transcriptome expression of pearl sacs that had producing pearls with high and low quality. For this purpose, a comprehensive reference transcriptome of P. margaritifera was built based on multi-tissue sampling (mantle, gonad, whole animal), including different living stages (juvenile, adults) and phenotypes (colour morphotypes, sex). RESULTS: Strikingly, few genes were found to be up-regulated for high quality pearls (n = 16) compared to the up-regulated genes in low quality pearls (n = 246). Biomineralization genes up-regulated in low quality pearls were specific to prismatic and prism-nacre layers. Alternative splicing was further identified in several key biomineralization genes based on a recent P. margaritifera draft genome. CONCLUSION: This study lifts the veil on the multi-level regulation of biomineralization genes associated with pearl quality determination.

Angiotensin II receptor blockers, steroids and radiotherapy in glioblastoma-a randomised multicentre trial (ASTER trial). An ANOCEF study.

BACKGROUND: Glioblastomas (GBMs) induce a peritumoural vasogenic oedema impairing functional status and quality of life. Steroids reduce brain tumour-related oedema but are associated with numerous side-effects. It was reported in a retrospective series that angiotensin receptor blockers might be associated with reduced peritumoural oedema. The ASTER study is a randomised, placebo-controlled trial to assess whether or not the addition of Losartan to standard of care (SOC) can reduce steroid requirement during radiotherapy (RT) in patients with newly diagnosed GBM. PATIENTS AND METHODS: Patients with a histologically confirmed GBM after biopsy or partial surgical resection were randomised between Losartan or placebo in addition to SOC with RT and temozolomide (TMZ). The primary objective was to investigate the steroid dosage required to control brain oedema on the last day of RT in each arm. The secondary outcomes were steroids dosage 1 month after the end of RT, assessment of cerebral oedema on magnetic resonance imaging, tolerance and survival. RESULTS: Seventy-five patients were randomly assigned to receive Losartan (37 patients) or placebo (38 patients). No difference in the steroid dosage required to control brain oedema on the last day of RT, or one month after completion of RT, was seen between both arms. The incidence of adverse events was similar in both arms. Median overall survival was similar in both arms. CONCLUSIONS: Losartan, although well tolerated, does not reduce the steroid requirement in newly diagnosed GBM patients treated with concomitant RT and TMZ. Trial registration number NCT01805453 with ClinicalTrials.gov.

Bioactive extracellular compounds produced by the dinoflagellate Alexandrium minutum are highly detrimental for oysters.

Blooms of the dinoflagellate Alexandrium spp., known as producers of paralytic shellfish toxins (PSTs), are regularly detected on the French coastline. PSTs accumulate into harvested shellfish species, such as the Pacific oyster Crassostrea gigas, and can cause strong disorders to consumers at high doses. The impacts of Alexandrium minutum on C. gigas have often been attributed to its production of PSTs without testing separately the effects of the bioactive extracellular compounds (BECs) with allelopathic, hemolytic, cytotoxic or ichthyotoxic properties, which can also be produced by these algae. The BECs, still uncharacterized, are excreted within the environment thereby impacting not only phytoplankton, zooplankton but also marine invertebrates and fishes, without implicating any PST. The aim of this work was to compare the effects of three strains of A. minutum producing either only PSTs, only BECs, or both PSTs and BECs, on the oyster C. gigas. Behavioral and physiological responses of oysters exposed during 4 days were monitored and showed contrasted behavioral and physiological responses in oysters supposedly depending on produced bioactive substances. The non-PST extracellular-compound-producing strain primarily strongly modified valve-activity behavior of C. gigas and induced hemocyte mobilization within the gills, whereas the PST-producing strain caused inflammatory responses within the digestive gland and disrupted the daily biological rhythm of valve activity behavior. BECs may therefore have a significant harmful effect on the gills, which is one of the first organ in contact with the extracellular substances released in the water by A. minutum. Conversely, the PSTs impact the digestive gland, where they are released and mainly accumulated, after degradation of algal cells during digestion process of bivalves. This study provides a better understanding of the toxicity of A. minutum on oyster and highlights the significant role of BECs in this toxicity calling for further chemical characterization of these substances.

A concurrent ultra-fractionated radiation therapy and temozolomide treatment: A promising therapy for newly diagnosed, inoperable glioblastoma.

We report on a phase II clinical trial to determine the effect of a concurrent ultra-fractionated radiotherapy and temozolomide treatment in inoperable glioblastoma patients. A phase II study opened; patients over 18 years of age who were able to give informed consent and had histologically proven, newly diagnosed inoperable diagnosed and supratentorial glioblastoma were eligible. Three doses of 0.75 Gy spaced apart by at least 4 hr were delivered daily, 5 days a week for six consecutive weeks for a total of 67.5 Gy. Chemotherapy was administered during the same period, which consisted of temozolomide given at a dose of 75 mg/m(2) for 7 days a week. After a 4-week break, chemotherapy was resumed for up to six cycles of adjuvant temozolomide treatment, given every 28 days, according to the standard 5-day regimen. Tolerance and toxicity were the primary endpoints; survival and progression-free survival were the secondary endpoints. In total, 40 patients were enrolled in this study, 29 men and 11 women. The median age was 58 years, and the median Karnofsky performance status was 80. The concomitant ultra-fractionated radiotherapy and temozolomide treatment was well tolerated. Complete responses were seen in four patients, and partial responses were reported in seven patients. The median survival from the initial diagnosis was 16 months. Several long-term survivors were noted. Concurrent ultra-fractionated radiation therapy and temozolomide treatment are well accepted by the patients. The results showed encouraging survival rates for these unfavorable patients.

Association among growth, food consumption-related traits and amylase gene polymorphism in the Pacific oyster Crassostrea gigas.

To examine further a previously reported association between amylase gene polymorphism and growth in the Pacific oyster Crassostrea gigas, ecophysiological parameters and biochemical and molecular expression levels of alpha-amylase were studied in Pacific oysters of different amylase genotypes. Genotypes that previously displayed significantly different growth were found to be significantly different for ingestion and absorption efficiency. These estimated parameters, used in a dynamic energy budget model, showed that observed ingestion rates (unlike absorption efficiencies) allowed an accurate prediction of growth potential in these genotypes. The observed association between growth and amylase gene polymorphism is therefore more likely to be related to ingestion than to absorption efficiency. Additionally, relative mRNA levels of the two amylase cDNAs were also strongly associated with amylase gene polymorphism, possibly reflecting variation in an undefined regulatory region, although no corresponding variation was observed in specific amylase activity. Amylase gene sequences were determined for each genotype, showing the existence of only synonymous or functionally equivalent non-synonymous polymorphisms. The observed associations among growth, food consumption-related traits and amylase gene polymorphism are therefore more likely to be related to variation in the level of amylase gene expression than to functional enzymatic variants.

[Protein S100 beta and Melanoma Inhibitory Activity (MIA): a prospective study of their clinical value for the early detection of metastasis in malignant melanoma]. / Protéine S100 Béta et Melanoma Inhibitory Activity (MIA) sériques: étude prospective de leur valeur pour la détection précoce de métastases dans le mélanome.

BACKGROUND: We examined whether serum values for proteins S100B and MIA could allow early and reliable screening of metastatic growth in melanoma. PATIENTS AND METHODS: We carried out a prospective study from 1998 to 2005 in patients presenting non-metastatic melanomas with a Breslow score>0.75 mm. Four PS00B and MIA measurements per patient were performed at regular intervals over 1 to 2 years. Blood samples were analysed for PS100B and MIA using an ELISA technique. RESULTS: Fifty patients were analysed. The maximum interval between collection of samples was 8 months. Metastatic development was noted in 15 patients. Where melanoma progressed to stage III, sensitivity was 33% for PS100B and 25% for MIA. Where it progressed to stage IV, sensitivity was 50% for PS100B and 30% for MIA. A rise in these values preceded discovery of metastasis in 3 cases for PS100B and of MIA in 1 case. Specificity of the assays was 100% for PS100B and 91% for MIA. DISCUSSION: Sensitivity and specificity were better for PS100B than for MIA regarding detection of metastasis during follow-up of thick melanomas. The ELISA technique used in our study seemed to increase the specificity of the assay but not its sensitivity compared to other techniques used previously. We may thus confirm the benefits of PS100B assay for early detection of metastasis in melanomas. However, this laboratory surveillance method is not an acceptable substitute for regular clinical follow-up due to its low sensitivity.

Thymidine kinase as a proliferative marker: clinical relevance in 1,692 primary breast cancer patients.

PURPOSE: To assess the prognostic value of thymidine kinase (TK), an enzyme involved in the DNA synthesis salvage pathway, relative to other prognostic factors in primary breast cancer. PATIENTS AND METHODS: This retrospective study involved 1,692 patients with operable breast cancer treated in six institutions (median follow-up, 82 months). Among the 857 node-negative patients, 135 received adjuvant chemotherapy (fluorouracil, doxorubicin, cyclophosphamide [FAC] or fluorouracil, etoposide, and cisplatin [FEC]). TK was assayed in cytosol with a quantitative radioenzymatic technique. Disease-specific survival (DSS), local recurrence-free interval (LRI), and distant-relapse-free interval (DRI) were investigated. RESULTS: High TK levels were associated with large tumor size, high histologic grade, and steroid hormone receptor negativity. Univariate analysis of the entire data set showed that high TK levels were related to shorter DSS (P < 10(-5)), LRI (P < 10(-3)), and DRI (P < 10(-5)). In time-dependent Cox models, high TK levels remained an independent predictor of the three outcomes, both in the overall population and in node-negative patients, although its prognostic value decreased over time. In node-negative patients, the introduction of an interaction term in multivariate analysis suggested that chemotherapy was more efficacious for patients who had tumors with high TK contents. In node-positive patients, high TK levels were related only to an increased risk of LRI. CONCLUSION: High TK values are an important risk factor in node-negative patients and seem to be associated with a beneficial effect of adjuvant FAC or FEC in patients who received adjuvant chemotherapy. The rationale of chemotherapy for patients with slowly proliferating tumors has to be discussed from a risk-benefit point of view.

Biodistribution of 111indium-labeled macrophages infused intravenously in patients with renal carcinoma.

PURPOSE: We have previously reported a clinical trial on the intravenous injection of autologous activated macrophages (AAM) in 15 patients with renal carcinoma. The present paper concerns scintigraphic investigations performed in 11 of these patients after injection of 111indium oxinate-radiolabeled AAM. METHODS: AAM were prepared from mononuclear cells (MNC) collected by apheresis from patients treated simultaneously with granulocyte-macrophage colony-stimulating factor (GM-CSF). MNC were cultured for 6 days in the presence of GM-CSF and exposed for 18 h to gamma-interferon, the AAM were then separated by elutriation and injected. RESULTS: After intravenous infusion, radiolabeled AAM were transiently retained in the lungs, where they predominated in the first hour. Later on, radioactivity accumulated in liver and spleen and then decreased from the first and second day, respectively. In one patient, two foci of radioactivity were detected in the lungs 1 h after injection, and persisted thereafter. Their association with tumor lesions was uncertain. This observation possibly resulted from the presence of granulocytes in the radiolabeled AAM populations of this patient. It seems that MNC collected from GM-CSF-treated patients and cultured in the presence of GM-CSF enables the differentiation of granulocytes. CONCLUSIONS: A series of 11 investigations confirms the previously reported distribution pattern of intravenously injected AAM. It is possible that in patients treated with hematopoietic cell-mobilizing agents, granulocytes develop in cultures designed to produce monocyte-derived antigen-presenting cells.

[Standards, options and recommendations for tumor markers in colorectal cancer]. / Standards, Options et Recommandations: marqueurs tumoraux sériques dans les cancers du côlon.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the French National Federation of Comprehensive Cancer Centers (FNCLCC), the 20 French Cancer Centers and specialists from French Public University or General Hospitals, and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome of cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To define, according to the definitions of the Standards, Options and Recommendations project, the characteristics of the main tumor markers in colorectal cancer and their potential role in the management of patients with this malignancy. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 117 independent reviewers, and to the medical committees of the 20 French Cancer Centers. RESULTS: The main recommendations for the tumor markers in colorectal cancer are: 1) The carcinoembryonic antigen (CEA) is the reference serum marker (standard). 2) All the analyses for a given patient must be performed in the same laboratory, using the same technique (standard, expert agreement). 3) CEA or CA 19-9 should not be used for screening or diagnosis (standard, level of evidence B2). 4) High initial serum concentration of CEA is of bad predictive value (standard, level of evidence C). CEA is an independent prognostic factor of survival in colorectal cancers with lymph node metastases (standard, level of evidence B2). 5) CEA is the most sensitive biological parameter for the screening of hepatic metastases (standard, level of evidence B2). 6) CEA serum concentration before palliative chemotherapy is an independent prognostic factor of survival (standard, level of evidence B2). The combination of CEA assay with imagery techniques and clinical examination can help monitor the response to palliative chemotherapy (standard), in particular in non measurable disease (standard, expert agreement). 7) In 65% of the cases, CEA is the first indicator of relapse (standard, level of evidence B2). CEA is the choice marker for monitoring patients with colorectal cancer (standard, level of evidence B2). 8) A sustained biological follow-up including CEA assay can be used to predict the operability of recurring tumors (standard, level of evidence B2). Nevertheless, no survival advantage has been shown (standard).

[Serum S100B protein and stage of cutaneous melanoma: a prospective study]. / Protéine S100B sérique et stade du mélanome cutané: étude prospective.

OBJECTIVE: We searched for a correlation between serum S100B protein and cutaneous malignant melanoma stage, according to the American Joint Committee on Cancer staging system, and between elevation of serum S100B protein and development of metastasis. PATIENTS AND METHODS: We conducted a prospective bicentric study for 20 months in 122 patients with malignant melanoma. LIA-mat(R) assay was used to determine serum S100B at each examination. The optimal cut-off value was determined from the ROC curve. RESULTS: The optimal cut-off value to discriminate patients with metastases from patients in remission was 0.09 microg/l. Sensitivity was 46 p. 100 in patients with stage III and 86 p. 100 in patients with stage IV disease. The positive predictive value for stage III/IV was 77 p. 100 and the negative predictive value was 89 p. 100. Serial measurements were made in 56 patients. The serum S100B protein level was elevated in 69 p. 100 of the patients disclosing disease progression (9/13). In 44 p. 100 of the patients (4/9), serum S100B protein level rose within a delay of 3 months before new metastases were detected. DISCUSSION: Our study confirms that serum S100B protein is a tumor marker for melanoma staging and follow-up. A rise in S100B protein precedes or reveals metastasis.

Prognostic value of uPA and p53 accumulation measured by quantitative biochemical assays in 1245 primary breast cancer patients: a multicentre study.

The purpose of this retrospective multicentre study was to assess the prognostic value of urokinase plasminogen activator (uPA) and p53 levels in a large series of primary breast cancer, using an automatic quantitative luminometric method. Samples of 1245 operable breast tumours were collected from seven French institutions and patients were followed for a median of 75 months. The median uPA and p53 levels assayed in cytosols by means of the immunoluminometric technique (LIA) were 0.31 and 0.20 ng mg(-1) of protein respectively. In univariate analysis, high levels of uPA and p53 were associated with shorter disease-specific survival, disease-free interval, and distant recurrence-free interval. The 5-year survival rates were 95.5% among patients with uPA values below the 20th percentile, and 77.5% in those with values above the 80th percentile. The 5-year survival rates were 91.0% in patients with p53 values below the 20th percentile, and 77.6% in those with values above the 80th percentile. In multivariate analysis, the risk of disease-related death increased with uPA levels after adjustment for tumour size, histological grade, lymph node involvement, and estrogen receptor status. A high level of uPA was also related to a shorter disease-free interval and distant recurrence-free interval. In node-negative patients, a high level of uPA remained strongly related to the three outcomes. When adjusted for other prognostic factors, p53 was no longer significantly related to the outcomes. Given its rapidity and simple application to routinely prepared cytosols, this LIA may be useful for evaluating the prognostic impact of uPA in primary breast cancer, particularly in node-negative patients. According to our results, the prognostic value of p53 accumulation is limited when uPA is included in multivariate analysis.

Comparison of Cyfra 21-1, TPA and SCC tumor markers in esophageal squamous cell carcinoma.

The tumor markers Cyfra 21-1, TPA and SCC were assayed in a series of 96 patients with squamous cell carcinoma of the esophagus. Sensitivity was 42% for Cyfra 21-1, 40% for TPA and 37% for SCC. Combining Cyfra 21-1 and SCC gave a 56% sensitivity and combining TPA and SCC a 58% sensitivity. Sensitivity varied with disease stage and was particularly good in stage IV disease. Tumor markers did not vary with tumor differentiation. SCC levels were higher in tumors in the upper third of the esophagus. Pre-treatment levels of Cyfra 21-1 correlated with histological response. Cyfra 21-1 was also the only marker which distinguished significantly different survival curves. In multivariate analysis, however, treatment was the only independent factor predictive of survival.

[Gene therapy of cerebral glioblastoma by adenovirus vector. Experimental model in the rat]. / Thérapie génique du glioblastome cérébral par vecteur adénoviral. Modèle expérimental chez le rat.

Our aim was to test the therapeutic effects of adenovirus-mediated gene therapy in an animal brain tumor model which was obtained by stereotactic injection of 9L gliosarcoma cells into the caudate nucleus of rat brains. Seven days after the implantation of tumor cells, adenovirus vectors bearing the Escherichia coli beta-galactosidase gene (ADVbgal) or the herpes simplex virus thymidine kinase gene (ADVtk) were stereotactically injected into the tumor. Injection of the ADVbgal resulted in the expression of the marker gene in 11 animals. Transfer of the ADVtk was followed, 3 days later, by intraperitoneal injection of ganciclovir (GCV) for 10 days. A control group was treated with saline instead of GCV. We observed a significant regression of the tumors in the rats treated with ADVtk and GCV as compared with control animals. In four cases the tumor completely disappeared after treatment. These results demonstrate the potential efficacy of adenovirus-mediated transfer of the HSVtk gene following by GCV administration for the treatment of glioblastomas.

Expression of MAGE genes in esophageal squamous-cell carcinoma.

The genes MAGE-1, -2, -3 and -4 are expressed in tumors of different histological types, but not in normal tissues, with the exception of testis and placenta. Short peptides derived from MAGE-1 and MAGE-3 gene products are recognized by cytolytic T lymphocytes when presented by HLA-class-I molecules, and represent potential targets for specific immunotherapy. We have determined whether esophageal carcinoma patients should be eligible for MAGE-peptide-based vaccine therapies. The expression of genes MAGE-1, -2, -3 and -4 in tumor samples was assessed by reverse-transcription and polymerase-chain-reaction amplification. Out of the 49 esophageal squa-mous-cell carcinomas studied, 53% expressed MAGE-1, 49% MAGE-2, 47% MAGE-3 and 71% MAGE-4. Eighty-four percent of the tumors expressed one or more of the four MAGE genes. Owing to the high incidence of MAGE gene expression in esophageal squamous-cell carcinoma, a large proportion of patients could be suitable candidates for immune therapies involving tumor-specific antigens encoded by MAGE genes.

Serum anti-p53 antibodies in patients with squamous cell carcinoma of the esophagus.

Immunoassay of serum anti-p53 antibodies was performed in a series of 63 patients with squamous cell carcinoma of the esophagus. p53 alterations were also analyzed with DGGE to detect gene mutations (n=53) and by immunohistochemistry to assess overexpression of p53 (n=43). An immune response was observed in 16 sera (25%). The corresponding biopsies all had a p53 gene mutation or overexpression of protein p53. We were unable to demonstrate any significant relationship between habitual tumor parameters (localization, cell differentiation, TNM stage) and development of p53 alterations. However, none of the patients with a localized tumor developed an immune response, while some of them had a muted gene or overexpressed p53.

[Gene therapy of a model of glioblastoma in rats using adenovirus vector encoding the HSVtk gene]. / Thérapie génique d'un modèle de glioblastome chez le rat à l'aide d'adénovirus porteurs du gène HSVtk.

Our aim was to test the therapeutic effects of adenovirus-mediated gene therapy in an animal model of brain tumor which was obtained by injection of 9L gliosarcoma cells into the caudate nucleus of rat brains. Seven days after the implantation of tumor cells, adenovirus vectors bearing the Escherichia coli beta galactosidase gene (ADV beta-gal) or the herpes simplex virus thymidine kinase gene (ADVtk) were stereotactically injected in the tumor. Injection of the ADV beta gal resulted in the expression of the marker gene in 61% of the animals. Transfer of the ADVtk was followed, 3 days later, by intraperitoneal injection of ganciclovir (GCV) for 10 days. A control group was treated with saline instead of GCV. We observed a significant regression of the tumors in 50% of the rats treated with ADVtk and GCV as compared with control animals. In 4 cases out of 6, the tumor completely disappeared after treatment. These results demonstrate the potential efficacy of adenovirus-mediated transfer of the HSVtk gene following by GCV administration for the treatment of glioblastomas.

The effect of a pulsed magnetic field and that of methyl-silane triol on galactosamine induced hepatitis among rats.

Liver cell necrosis was induced in rats by a galactosamine injection. Cell death was due to an increase of Ca++ intracellular levels and was also under the control of genes. Rats were then either exposed or not to a 6 mT 100 HZ pulsed magnetic field (PMF) and they either received or not methylsilane-triol injections. Animals were sacrificed twenty-seven hours after a galactosamine injection. On the one hand it appeared from transaminase levels that the PMF increased the number of animals which were sensitized to galactosamine but decreased transaminase levels. On the other hand PMF decreased the protective effect of MST against galactosamine. We may suggest that PMF should be considered as an additional cellular signal received through genes which would determine the evolution towards or against apoptosis according to the age of the cell itself but also the Ca++ intracellular level.