A 63 element 1.75 dimensional ultrasound phased array for the treatment of benign prostatic hyperplasia

BACKGROUND: Prostate cancer and benign prostatic hyperplasia are very common diseases in older American men, thus having a reliable treatment modality for both diseases is of great importance. The currently used treating options, mainly surgical ones, have numerous complications, which include the many side effects that accompany such procedures, besides the invasive nature of such techniques. Focused ultrasound is a relatively new treating modality that is showing promising results in treating prostate cancer and benign prostatic hyperplasia. Thus this technique is gaining more attention in the past decade as a non-invasive method to treat both diseases. METHODS: In this paper, the design, construction and evaluation of a 1.75 dimensional ultrasound phased array to be used for treating prostate cancer and benign prostatic hyperplasia is presented. With this array, the position of the focus can be controlled by changing the electrical power and phase to the individual elements for electronically focusing and steering in a three dimensional volume. The array was designed with a maximum steering angle of ± 13.5° in the transverse direction and a maximum depth of penetration of 11 cm, which allows the treatment of large prostates. The transducer piezoelectric ceramic, matching layers and cable impedance have been designed for maximum power transfer to tissue. RESULTS: To verify the capability of the transducer for focusing and steering, exposimetry was performed and the results correlated well with the calculated field. Ex vivo experiments using bovine tissue were performed with various lesion sizes and indicated the capability of the transducer to ablate tissue using short sonications. CONCLUSION: A 1.75 dimensional array, that overcame the drawbacks associated with one-dimensional arrays, has been designed, built and successfully tested. Design issues, such as cable and ceramic capacitances, were taken into account when designing this array. The final prototype overcame also the problem of generating grating lobes at unwanted locations by tapering the array elements

Derivation of a Triple Mosaic Adenovirus for Cancer Gene Therapy

A safe and efficacious cancer medicine is necessary due to the increasing population of cancer patients whose particular diseases cannot be cured by the currently available treatment. Adenoviral (Ad) vectors represent a promising therapeutic medicine for human cancer therapy. However, several improvements are needed in order for Ad vectors to be effective cancer therapeutics, which include, but are not limited to, improvement of cellular uptake, enhanced cancer cell killing activity, and the capability of vector visualization and tracking once injected into the patients. To this end, we attempted to develop an Ad as a multifunctional platform incorporating targeting, imaging, and therapeutic motifs. In this study, we explored the utility of this proposed platform by generating an Ad vector containing the poly-lysine (pK), the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK), and the monomeric red fluorescent protein (mRFP1) as targeting, tumor cell killing, and imaging motifs, respectively. Our study herein demonstrates the generation of the triple mosaic Ad vector with pK, HSV-1 TK, and mRFP1 at the carboxyl termini of Ad minor capsid protein IX (pIX). In addition, the functionalities of pK, HSV-1 TK, and mRFP1 proteins on the Ad vector were retained as confirmed by corresponding functional assays, indicating the potential multifunctional application of this new Ad vector for cancer gene therapy. The validation of the triple mosaic Ad vectors also argues for the ability of pIX modification as a base for the development of multifunctional Ad vectors

IRE1α–XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity

Tumours evade immune control by creating hostile microenvironments that perturb T cell metabolism and effector function 1?4 . However, it remains unclear how intra-tumoral T cells integrate and interpret metabolic stress signals. Here we report that ovarian cancer?an aggressive malignancy that is refractory to standard treatments and current immunotherapies 5?8 ?induces endoplasmic reticulum stress and activates the IRE1α?XBP1 arm of the unfolded protein response 9,10 in T cells to control their mitochondrial respiration and anti-tumour function. In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression. Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α?XBP1 activation that suppressed mitochondrial activity and IFNγ production. Mechanistically, induction of XBP1 regulated the abundance of glutamine carriers and thus limited the influx of glutamine that is necessary to sustain mitochondrial respiration in T cells under glucose-deprived conditions. Restoring N-linked protein glycosylation, abrogating IRE1α?XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites. XBP1-deficient T cells in the metastatic ovarian cancer milieu exhibited global transcriptional reprogramming and improved effector capacity. Accordingly, mice that bear ovarian cancer and lack XBP1 selectively in T cells demonstrate superior anti-tumour immunity, delayed malignant progression and increased overall survival. Controlling endoplasmic reticulum stress or targeting IRE1α?XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.Fil: Song, Minkyung. Weill Cornell Medicine; Estados UnidosFil: Sandoval, Tito A.. Weill Cornell Medicine; Estados UnidosFil: Chae, Chang-Suk. Weill Cornell Medicine; Estados UnidosFil: Chopra, Sahil. Weill Cornell Medicine; Estados UnidosFil: Tan, Chen. Weill Cornell Medicine; Estados UnidosFil: Rutkowski, Melanie R.. University of Virginia; Estados UnidosFil: Raundhal, Mahesh. Dana Farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados UnidosFil: Chaurio, Ricardo A.. H. Lee Moffitt Cancer Center & Research Institute; Estados UnidosFil: Payne, Kyle K.. H. Lee Moffitt Cancer Center & Research Institute; Estados UnidosFil: Konrad, Csaba. Weill Cornell Medicine; Estados UnidosFil: Bettigole, Sarah E.. Quentis Therapeutics Inc.; Estados UnidosFil: Shin, Hee Rae. Quentis Therapeutics Inc.; Estados UnidosFil: Crowley, Michael J. P.. Weill Cornell Graduate School of Medical Sciences; Estados UnidosFil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Kossenkov, Andrew V.. The Wistar Institute; Estados UnidosFil: Motorykin, Ievgen. Weill Cornell Medicine,; Estados UnidosFil: Zhang, Sheng. Weill Cornell Medicine,; Estados UnidosFil: Manfredi, Giovanni. Weill Cornell Medicine,; Estados UnidosFil: Zamarin, Dmitriy. Memorial Sloan Kettering Cancer Center; Estados UnidosFil: Holcomb, Kevin. Weill Cornell Medicine,; Estados UnidosFil: Rodriguez, Paulo C.. H. Lee Moffitt Cancer Center & Research Institute; Estados UnidosFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Conejo Garcia, Jose R.. H. Lee Moffitt Cancer Center & Research Institute; Estados UnidosFil: Glimcher, Laurie H.. Dana Farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados UnidosFil: Cubillos-Ruiz, Juan R.. Weill Graduate School Of Medical Sciences; Estados Unidos. Weill Graduate School Of Medical Sciences; Estados Unido

Spatiotemporal variation of the epifaunal assemblages associated to Sargassum muticum on the NW Atlantic coast of Morocco

Epifaunal assemblages inhabiting the non-indigenous macroalga Sargassum muticum (Yendo) Fensholt were investigated on two physically distinct intertidal rocky (S1) and sandy (S2) sites along the Atlantic coast of Morocco. The objective of this study was to test whether the habitat-forming marine alga S. muticum invasive in these sites supported different epifaunal assemblages under different environmental conditions and through time. The gastropods Steromphala umbilicalis, S. pennanti, and Rissoa parva and the isopod Dynamene bidentata were the most contributive species to the dissimilarity of epifaunal assemblage structure between both sites throughout seasons. SIMPER analysis showed a dissimilarity of 58.3-78.5% in the associated species composition of S. muticum between study sites with respect to sampling season. Species diversity and total abundance were significantly higher at the rocky site compared to the sandy site. PERMANOVA analyses showed significant differences of associated epifaunal assemblage structure for the season and site interaction. Accordingly, site and season were determinant factors conditioning the role of habitat in structuring epifaunal assemblages.info:eu-repo/semantics/publishedVersio

Identification and manipulation of tumor associated macrophages in human cancers

Evading immune destruction and tumor promoting inflammation are important hallmarks in the development of cancer. Macrophages are present in most human tumors and are often associated with bad prognosis. Tumor associated macrophages come in many functional flavors ranging from what is known as classically activated macrophages (M1) associated with acute inflammation and T-cell immunity to immune suppressive macrophages (M2) associated with the promotion of tumor growth. The role of these functionally different myeloid cells is extensively studied in mice tumor models but dissimilarities in markers and receptors make the direct translation to human cancer difficult. This review focuses on recent reports discriminating the type of infiltrating macrophages in human tumors and the environmental cues present that steer their differentiation. Finally, immunotherapeutic approaches to interfere in this process are discussed

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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