Autophagy is usually a pro-survival mechanism in cancer cells, especially in the course of chemotherapy, thus autophagy inhibition may enhance the chemotherapy-mediated anti-cancer effect. However, ...since autophagy is strongly involved in the immunogenicity of cell death by promoting ATP release, its inhibition may reduce the immune response against tumors, negatively influencing the overall outcome of chemotherapy. In this study, we evaluated the in vitro and in vivo anti-cancer effect of curcumin (CUR) against Her2/neu overexpressing breast cancer cells (TUBO) in the presence or in the absence of the autophagy inhibitor chloroquine (CQ). We found that TUBO cell death induced by CUR was increased in vitro by CQ and slightly in vivo in nude mice. Conversely, CQ counteracted the Cur cytotoxic effect in immune competent mice, as demonstrated by the lack of in vivo tumor regression and the reduction of overall mice survival as compared with CUR-treated mice. Immunohistochemistry analysis revealed the presence of a remarkable FoxP3 T cell infiltrate within the tumors in CUR/CQ treated mice and a reduction of T cytotoxic cells, as compared with single CUR treatment. These findings suggest that autophagy is important to elicit anti-tumor immune response and that autophagy inhibition by CQ reduces such response also by recruiting T regulatory (Treg) cells in the tumor microenvironment that may be pro-tumorigenic and might counteract CUR-mediated anti-cancer effects.
An innovative hyaluronan-based nano-delivery system is proposed for the active targeting towards ER+ breast cancer. Hyaluronic acid (HA), an endogenous and bioactive anionic polysaccharide, is ...functionalized with estradiol (ES), a sexual hormone involved in the development of some hormone-dependent tumors, to give an amphiphilic derivative (HA-ES) able to spontaneously self-assemble in water to form soft nanoparticles or nanogels (NHs). The synthetic strategy used to obtain the polymer derivatives and the physico-chemical properties of the obtained nanogels (ES-NHs) are reported. ES-NHs ability to entrap hydrophobic molecules has also been investigated, by loading curcumin (CUR) and docetaxel (DTX), both able to inhibit the growth of ER+ breast cancer. The formulations are studied for their capability to inhibit the growth of the MCF-7 cell line, thus evaluating their efficacy and potential as a selective drug delivery systems. Our results demonstrate that ES-NHs have not toxic effects on the cell line, and that both ES-NHs/CUR and ES-NHs/DTX treatments inhibit MCF-7 cell growth, with ES-NHs/DTX effect higher than that of free DTX. Our findings support the use of ES-NHs to deliver drugs to ER+ breast cancer cells, assuming a receptor-dependent targeting.
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BACKGROUND AND AIMS: Monitoring of canopy vigour is an important tool in vineyard management to obtain balanced vines (vegetative vs reproductive organs). Leaf area index is the main parameter ...representing canopy vigour. Our aim was to test an automated computational method to obtain leaf area index and canopy vigour parameters from grapevines with digital photography and video analysis using MATLAB programming techniques for rapid data uptake and gap size analysis. METHODS AND RESULTS: The proposed method was tested against allometry at a Chilean experimental site planted with cv. Merlot. A temporal and spatial assessment of the method was also tested in a drought and drought/recovery experiment with cv. Chardonnay in the Riverland, South Australia. These data were geo‐referenced and compared to the normalised difference vegetation index extracted from the WorldView‐2 satellite images at a 2 m² per pixel resolution. CONCLUSIONS: The maximum leaf area index data obtained with cover digital photography and video analysis are an accurate, cost‐effective and easy‐to‐use method to estimate spatial and temporal canopy LAI and structure when compared to standard measurements (allometry and plant canopy analyser). SIGNIFICANCE OF THE STUDY: This study has demonstrated that the method proposed is an accurate and inexpensive tool for application in experiments and by the industry to monitor spatio‐temporal distribution of vigour.
Abstract The repertoire of autoantibodies found in cancer patients partly overlaps with that typical of patients with autoimmune diseases. Beside the biochemical and immunological properties of the ...target antigens and their altered expression in tumor tissues, the intratumoral inflammatory context can play a key role in the induction of autoimmune disease-associated autoantibodies in cancer patients. Furthermore, the impact of such antibodies on cancer growth and progression can be deeply influenced by the interplay with inflammation. The characterization of the spontaneous humoral responses occurring in cancer patients, of the mechanisms that trigger and sustain the autoantibody response and of the biological effects of such autoantibodies may help the rational design of anti-cancer immunotherapeutic protocols.
•Carbohydrate analysis of plants allow to understand the physiology and phenology of the crop.•Near infrared (NIR) spectroscopy was collected from grapevine trunk and leaf tissues.•NIR could predict ...starch and TNC concentration in grapevine trunk and leaf tissues.
Carbohydrate assays are commonly used in crops and plant research to understand the way in which carbohydrates are allocated within the vine and to assess its influence on the physiology and phenology of the plant. Total non-structural carbohydrate (TNC) concentration is normally assessed by wet chemistry methods which are time consuming and costly, especially when studying carbohydrate dynamics over seasons. Near infrared (NIR) spectroscopy is a fast and easy technique that has lately gained wide acceptance for the analysis of the chemical composition of grain, food, wine, pharmaceutical products, among others. Near infrared is the region of the electromagnetic spectrum between 750nm and 2500nm and it is used to gather information on the relative proportions of CH, NH and OH bonds of the organic molecules. This study collected NIR spectra from grapevine trunk and leaf tissues, measured TNC concentration of the same samples using a wet chemical method and compared the results using multivariate data analysis to develop a rapid procedure for the estimation of TNC concentration in grapevine tissues. Results showed that NIR spectroscopy could be used to predict starch and TNC concentration in freeze-dried and ground grapevine trunk and leaf tissues. Moreover, it has been demonstrated that a robust universal model could be applied to the prediction of TNC in both leaves and trunks. Therefore, this method could be used as a practical tool for a rapid screening of TNC concentration for high temporal and spatial assessment of grapevine tissues at given phenological stages. The main advantages of this technique over traditional methods are the rapidity and the ease-of-use protocol in routine analysis, which allows a considerable reduction of costs and time.
Background and Aims
Old vineyards are often suggested to be superior to younger ones, a claim that has scarcely been investigated scientifically. The aim of this study was to investigate if vineyard ...age influences vine performance.
Methods and Results
Five commercial Shiraz vineyards in the Barossa Valley, SA, were selected; each site contained younger vines, which had been vegetatively propagated from older vines on the same site. Measurements of vegetative growth and reproductive development were obtained over three seasons. Results show that the effect of vine age is difficult to measure and separate from seasonal and site interactions. Vine age was strongly correlated with trunk circumference. Vines aged 49 years showed more similarities with older vines (93–168 years old) than with younger vines (6–28 years old).
Conclusions
Vine age had an impact on grapevine reproductive performance. Older vines produced a yield greater than that of younger vines. Greater vine size, measured by increase in trunk circumference over time, may be a key determining factor in increased reproductive capacity.
Significance of the Study
Vine age is commonly attributed to superior vine performance, as a precursor to fruit and wine quality. Our findings suggest that increasing vine age had a positive effect on reproductive performance in terms of yield, contrary to popular belief. This establishes a starting point for future studies that are underway to quantify if these findings have an effect on fruit and wine composition and sensory attributes.
Breast cancer is a leading cancer in women and despite the benefits of the current therapies a significant number of patients with this tumor is at risk of relapse. Some of the alterations taking ...place in breast cancer cells are currently exploited by molecularly targeted drugs. Different drugs have been developed which target a single molecule but, given that the tumor originates from the dysregulation of many genes, there is the need to find new drugs that have more than one molecular target. Curcumin 1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (CUR), a polyphenolic compound found in the spice turmeric, is a pleiotropic molecule able to interact with a variety of molecular targets and has antitumor, anti-inflammatory, antioxidant, immunomodulatory and antimicrobial activities. Here we demonstrate that CUR inhibits the growth of breast cancer cell lines in a dose dependent manner, with IC50 values in the micromolar range, and induces an increase in the percentage of cells in sub-G0 phase, representing the apoptotic cell population. The activation of apoptosis was confirmed by PARP-1 cleavage and by the increased ratio between the pro-apoptotic Bax and the anti-apoptotic Bcl-2 protein. In addition, in CUR-treated cells the activity of ERK1/ERK2 MAP kinases was down-regulated. The cytotoxic effects of CUR were observed in breast cancer cells expressing either high or low levels of ErbB2/neu. The in vivo antitumor activity of CUR was tested in BALB-neuT mice transgenic for the neu oncogene, which develop atypical hyperplasia of the mammary gland at 6 weeks of age and invasive carcinoma at 16 weeks of age. CUR, administered to mice both early and in an advanced stage of mammary carcinogenesis, induced a significant prolongation of tumor-free survival and a reduction of tumor multiplicity. In addition, CUR administration was safe, since no modification of hematological and clinical chemistry parameters could be observed in BALB-neuT and BALB/c mice treated with this compound for several weeks. These findings support further studies on the therapeutic potential of CUR in combination with standard therapies in breast cancer patients.
•Significant night-time water uptake (Sn) were found for grapevine varieties.•Parabolic relationships were observed between Sn and grapevine water status.•A stress and a non-stress zone was ...characterised for each parabolic relationship.•Hydraulic and hormonal signals play a role in Sn and night-time transpiration.•Irrigation strategies could help to manage Sn and night-time transpiration.
Night-time water uptake (Sn) mainly corresponds to stem and organ rehydration and transpiration, the latter through stomata and cuticle. Nocturnal transpiration is uncoupled from photosynthesis, therefore it contributes to reduce water use efficiency (WUE). Night-time grapevine physiology was measured on field grown grapevines (cv. Shiraz) under partial root-zone drying (PRD) and deficit irrigation (Exp. 1), on potted vines (cv. Tempranillo) (Exp. 2) and on potted vines (cv. Cabernet Sauvignon) on a progressive drought treatment in the glasshouse (Exp. 3). Sap flow probes using the compensated heat pulse method (cHP) were installed in vines (Exp. 1 and 3). Night-time gas exchange measurements were performed for Exp. 3. Other vine water status monitoring methods used were: midday stem water potential (Ψs) for all experiments, and abscisic acid (ABA) concentration monitored from leaf sap for Exp. 3. Results showed that Sn was parabolically correlated to Ψs measured on the previous day for all treatments and cultivars. Two distinct zones where vines exhibit different night-time behaviour within the Ψsvs Sn parabolic relationships were identified for all experiments. The differences between the two identified areas were related to the water status conditions of the vines: (i) non-water stress conditions (0<Ψs<−1.0MPa); (ii) water stress conditions (−1.0MPa<Ψs<−2.0MPa). Furthermore, levels of water stress were negatively correlated to concentrations of leaf sap ABA, which helped to explain the parabolic curve found for cv. Cabernet Sauvignon.
The ability of vaccination with plasmids coding for the extracellular and the transmembrane domain of the product of transforming rat Her-2/neu oncogene (r-p185) to protect against r-p185(+) ...transplantable carcinoma (TUBO) cells and mammary carcinogenesis was evaluated. In normal BALB/c mice, DNA vaccination elicits anti-r-p185 Ab, but only a marginal CTL reactivity, and protects against a TUBO cell challenge. Massive reactive infiltration is associated with TUBO cell rejection. In BALB/c mice transgenic for the rat Her-2/neu gene (BALB-neuT), DNA vaccination elicits a lower anti-r-p185 Ab response, no CTL activity and only incompletely protects against TUBO cells, but markedly hampers the progression of carcinogenesis. At 33 wk of age, when control BALB-neuT mice display palpable tumors in all mammary glands, about 60% of immunized mice are tumor free, and tumor multiplicity is markedly reduced. Tumor-free mammary glands still display the atypical hyperplasia of the early stages of carcinogenesis, and a marked down-modulation of r-p185, along with a massive reactive infiltrate. However, BALB-neuT mice protected against mammary carcinogenesis fail to efficiently reject a TUBO cell challenge. This suggests that the mechanisms required for the rejection of transplantable tumors may not coincide with those that inhibit the slow progression of carcinogenesis.
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