34 research outputs found
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Intergenerational reforms in women’s right to inheritance in India
The evolution after the Hindu Code Bill, women's property ownership in India has improved. Women's position in old custom and their evolution in modern law from the colonial period to the Hindu Code Bill are the study's main focus areas. In ancient legal codes, such as Dharmashastras, Manusmriti, and Arthashastra, women were denied property rights and she always is dependent on their father, husband, or son. As per our constitution, every human being has the right to equitable treatment. Equal property rights for men and women are important for reducing the gender gap, to empower women in order to promote social and economic development and to ensure gender and social justice within the framework of Personal Laws and inform women about the areas of legislation that are most likely to affect and enhance their lives. So the focus of the article is on women's inheritance rights in old Indian laws and their development in modern laws with help of international conventions. As the status of women in India improves economically and socially, there is a need for more development and a single or uniform property rights for every sect of Indian females
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Not AvailableDevelopment of aqueous carotenoid-rich extract (ACE) is a major challenge for the food industry looking for
natural colourants. Red capsicum an excellent source of carotenoids has been explored as a novel source for development of ACE through enzymatic liquefaction (EL). Three carbohydrases enzymes viz. viscozyme L, pectinase and cellulase were tested for their liquefaction effects and ability to recover higher carotenoids in aqueous extract. EL significantly (p \ 0.05) improved the extract yield and total soluble solids by 2.5-fold to threefold in comparison with unliquefied extract. Incremental increase in dosage of enzymes significantly (p \ 0.05) improved the extract yield, total carotenoids, phenolics, ascorbic acid content and antioxidant activity. Viscozyme and pectinase caused significantly higher recovery of carotenoids and other bioactives than cellulase. Viscozyme at dosage of 0.3 % at 60 C gave the best results. Processing residue or pomace, a spin-off from the EL, was dried to capsicum pomace powder (CPP) and developed as a functional ingredient.
The ACE and CPP had higher carotenoid content ranging from 41.72 to 279.83 mg/100 g, respectively. Valorization of capsicum through EL is a promising approach to recover concentrates as valuable food ingredient with reduced processing waste and thus providing sustainability to environment through green processing.Not Availabl
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Not AvailableIndia is one of the leading litchi (Litchi chinensis Sonn.) producing countries in the world. A leaf blight on litchi was observed in April 2012 on nursery plants at Muzaffarpur, Bihar, India. Light to dark brown necrosis starting from leaf tips resulted in complete drying of leaves. Blighting of panicles and fruits were also noticed during April–June, 2014. Panicles dried out as a result of necrosis, while necrosis of pedicels led to complete drying of the rind of developing fruits. Infected tissues collected from different sites in diseased fields were cultured on potato dextrose agar (PDA), and the pathogen was identified as Alternaria alternata (Fr.) Keissler on the basis of morphological and cultural characteristics. The fungus produced greyish-black colonies on PDA with obclavate or obpyriform conidia in chains. Conidia had 1–4 transverse and 0–3 longitudinal septa, and measured 16–40 × 4–13 μm. Morphological identification was confirmed by sequencing the internal transcribed spacer (ITS) region of rDNA using ITS1 and ITS4 primers. Pathogenicity tests indicated that A. alternata infected and caused blights of the leaves, panicles and fruit of litchi. Alternaria alternata has been reported to cause post-harvest decay of litchi fruit, but this is the first report of A. alternata causing blights of leaves, panicles and fruit in the field.Not Availabl
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Not AvailableInulin and color imparting carotenoid pigments are candidate functional ingredients for development of a low-fat functional yoghurt. The study evaluates the potential of carotenoid-rich extract from red-capsicum (5%) and different levels of inulin (4, 6 and 8%) on functional and structural properties of low-fat setyoghurt. Changes in pH, syneresis, sensory and rheological parameters were monitored for 14 days at 662C. The variations in sensory acceptability and syneresis were related to rheological properties. Hysteresis area in the flow curve
(shear stress–shear rate) increased until 10th day of storage. Inulin fortification significantly reduced syneresis by 59% over control. The time sweep and frequency sweep experiments confirmed stability of protein networks in yoghurt fortified with inulin at high levels. Consistency index of yoghurts was higher for inulin-fortified yoghurts and kept increasing up to 10 days. Results suggest promising applications of natural carotenoids in conjunction with inulin for improving quality of low-fat yoghurt.Not Availabl
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Not AvailableIndia is one of the leading litchi (Litchi chinensis Sonn.) producing countries in the world. A leaf blight on litchi was observed in April 2012 on nursery plants at Muzaffarpur, Bihar, India. Light to dark brown necrosis starting from leaf tips resulted in complete drying of leaves. Blighting of panicles and fruits were also noticed during April–June, 2014. Panicles dried out as a result of necrosis, while necrosis of pedicels led to complete drying of the rind of developing fruits. Infected tissues collected from different sites in diseased fields were cultured on potato dextrose agar (PDA), and the pathogen was identified as Alternaria alternata (Fr.) Keissler on the basis of morphological and cultural characteristics. The fungus produced greyish-black colonies on PDA with obclavate or obpyriform conidia in chains. Conidia had 1–4 transverse and 0–3 longitudinal septa, and measured 16–40 × 4–13 μm. Morphological identification was confirmed by sequencing the internal transcribed spacer (ITS) region of rDNA using ITS1 and ITS4 primers. Pathogenicity tests indicated that A. alternata infected and caused blights of the leaves, panicles and fruit of litchi. Alternaria alternata has been reported to cause post-harvest decay of litchi fruit, but this is the first report of A. alternata causing blights of leaves, panicles and fruit in the field.Not Availabl