Tumor antigens for cancer immunotherapy: therapeutic potential of xenogeneic DNA vaccines

Preclinical animal studies have convincingly demonstrated that tumor immunity to self antigens can be actively induced and can translate into an effective anti-tumor response. Several of these observations are being tested in clinical trials. Immunization with xenogeneic DNA is an attractive approach to treat cancer since it generates T cell and antibody responses. When working in concert, these mechanisms may improve the efficacy of vaccines. The use of xenogeneic DNA in overcoming immune tolerance has been promising not only in inbred mice with transplanted tumors but also in outbred canines, which present with spontaneous tumors, as in the case of human. Use of this strategy also overcomes limitations seen in other types of cancer vaccines. Immunization against defined tumor antigens using a xenogeneic DNA vaccine is currently being tested in early phase clinical trials for the treatment of melanoma and prostate cancers, with proposed trials for breast cancer and Non-Hodgkin's Lymphoma

AVO Analysis of a Weak BSR on the Hikurangi Margin, New Zealand

Gas hydrates occur in deep, cold areas on the Hikurangi margin, New Zealand, generally at water depths of ≥ 600m and ≤ 8oC temperature. In these areas elevated hydrostatic pressures and low temperatures create stable conditions for hydrate formation. The occurrence of Bottom-Simulating Reflections (BSRs) is known to indicate the Base of the Gas Hydrate Stability (BGHS) zone, below which solid hydrates cannot exist due to increasing temperatures of sediments. BSRs in most settings worldwide are thought to be largely caused by free gas at the base of the gas hydrate stability zone. They are characterized by a large negative reflection coefficient due to significant decrease in P-wave velocity attributed to the presence of gas below the BSR. On the Hikurangi margin however, many BSRs appear relatively weak. This study presents the results of Amplitude Variation with Offset (AVO) analysis of a weak BSR beneath Puke Ridge, a thrust ridge on the accretionary wedge east of Gisborne, North Island. Rock-physics modelling is used to interpret the findings. The 05CM04 seismic line has been processed by preserving the amplitude and care has been taken to not bias the variation of reflectivity coefficient with offset. The zero-offset reflection coefficient or AVO intercept (A) is in the range of -0.008 to - 0.015 and the AVO gradient (B) is between -0.015 and -0.03. Rock-physics modelling was employed to determine the possible concentrations of gas and hydrate that can yield the observed reflection coefficients. Negligible hydrate saturation above with a patchy gas distribution of 3% saturation beneath the BSR might explain this pattern. An alternative end-member estimation of 13% saturation of hydrate in a frame-supporting model with no gas beneath it could generate the observed reflection coefficient but it is geologically unlikely. Synthetic modelling reveals that the low reflectivity of the BSR could also be due to the presence of thin layers of more concentrated or evenly distributed gas but this scenario is considered to be geologically unlikely. BSRs beneath some thrust ridges in the southern Hikurangi margin, appear as a series of clearly separated bright spots, which indicate free gas accumulations which when connected mimic the geometry of the seafloor. The most likely lithologic explanation for these high amplitude patches within weak BSRs, is the concept of segmented BSRs which is also seen in the Gulf of Mexico. The bright ―gas‖ anomalies are inferred to correlate with sand-rich high permeability layers while the weak BSR could be due to low saturations of gas in clay-rich low permeability layers. The weak BSR beneath the Puke Ridge is indicative of low and patchy gas saturations in low-permeability reservoir rocks while high amplitude patches found in this area may indicate high-permeability sands that may be attractive reservoir rocks for future gas hydrate production

AVO Analysis of a Weak BSR on the Hikurangi Margin, New Zealand

Gas hydrates occur in deep, cold areas on the Hikurangi margin, New Zealand, generally at water depths of ≥ 600m and ≤ 8oC temperature. In these areas elevated hydrostatic pressures and low temperatures create stable conditions for hydrate formation. The occurrence of Bottom-Simulating Reflections (BSRs) is known to indicate the Base of the Gas Hydrate Stability (BGHS) zone, below which solid hydrates cannot exist due to increasing temperatures of sediments. BSRs in most settings worldwide are thought to be largely caused by free gas at the base of the gas hydrate stability zone. They are characterized by a large negative reflection coefficient due to significant decrease in P-wave velocity attributed to the presence of gas below the BSR. On the Hikurangi margin however, many BSRs appear relatively weak. This study presents the results of Amplitude Variation with Offset (AVO) analysis of a weak BSR beneath Puke Ridge, a thrust ridge on the accretionary wedge east of Gisborne, North Island. Rock-physics modelling is used to interpret the findings. The 05CM04 seismic line has been processed by preserving the amplitude and care has been taken to not bias the variation of reflectivity coefficient with offset. The zero-offset reflection coefficient or AVO intercept (A) is in the range of -0.008 to - 0.015 and the AVO gradient (B) is between -0.015 and -0.03. Rock-physics modelling was employed to determine the possible concentrations of gas and hydrate that can yield the observed reflection coefficients. Negligible hydrate saturation above with a patchy gas distribution of 3% saturation beneath the BSR might explain this pattern. An alternative end-member estimation of 13% saturation of hydrate in a frame-supporting model with no gas beneath it could generate the observed reflection coefficient but it is geologically unlikely. Synthetic modelling reveals that the low reflectivity of the BSR could also be due to the presence of thin layers of more concentrated or evenly distributed gas but this scenario is considered to be geologically unlikely. BSRs beneath some thrust ridges in the southern Hikurangi margin, appear as a series of clearly separated bright spots, which indicate free gas accumulations which when connected mimic the geometry of the seafloor. The most likely lithologic explanation for these high amplitude patches within weak BSRs, is the concept of segmented BSRs which is also seen in the Gulf of Mexico. The bright ―gas‖ anomalies are inferred to correlate with sand-rich high permeability layers while the weak BSR could be due to low saturations of gas in clay-rich low permeability layers. The weak BSR beneath the Puke Ridge is indicative of low and patchy gas saturations in low-permeability reservoir rocks while high amplitude patches found in this area may indicate high-permeability sands that may be attractive reservoir rocks for future gas hydrate production

Apolipoprotein A1 as a potential biomarker in the ascitic fluid for the differentiation of advanced ovarian cancers

Context: Primary ovarian cancer and ovarian metastasis from non-ovarian cancers in advanced stage are closely mimicking conditions whose therapeutics and prognosis are different. Objective: To identify biomarkers that can differentiate the two variants of advanced ovarian cancers. Methods: Gel-based proteomics and antibody-based assays were used to study the differentially expressed proteins in the ascitic fluid of fourteen patients with advanced ovarian cancers. Results: Programmed Cell Death 1-Ligand 2, apolipoprotein A1, apolipoprotein A4 and anti-human fas antibody are differentially expressed proteins. Conclusions: Apolipoprotein A1 with a 61.8?ng/ml cut-off is a potential biomarker with the best differentiating statistical parameters

Harnessing genomics to improve outcomes for women with cancer in India : key priorities for research

Cumulatively, breast, cervical, ovarian, and uterine cancer account for more than 70% of cancers in women in India. Distinct differences in the clinical presentation of women with cancer suggest underlying differences in cancer biology and genetics. The peak age of onset of breast and ovarian cancer appears to be a decade earlier in India (age 45–50 years) than in high-income countries (age >60 years). Understanding these differences through research to develop diagnosis, screening, prevention, and treatment frameworks that ar e specific to the Indian population are critical and essential to improving women's health in India. Since the sequencing of the human genome in 2001, applications of advanced technologies, such as massively parallel sequencing, have transformed the understanding of the genetic and environmental drivers of cancer. How can advanced technologies be harnessed to provide health-care solutions at a scale and to a budget suitable for a country of 1·2 billion people? What research programmes are necessary to answer questions specific to India, and to build capacity for innovative solutions using these technologies? In order to answer these questions, we convened a workshop with key stakeholders to address these issues. In this Series paper, we highlight challenges in tackling the growing cancer burden in India, discuss ongoing genomics research and developments in infrastructure, and suggest key priorities for future research in cancer in India