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Serious Cerebral Perforators: Anatomical Submitting as well as Clinical Symptoms: A synopsis.
Subsequent target validation in NRP2 knockout and knockdown models revealed secreted phosphoprotein 1 (SPP1/OPN/Osteopontin) as a downstream target positively regulated by NRP2. Copyright © 2020 Schulz, Gorodetska, Behrendt, Fuessel, Erdmann, Foerster, Datta, Mayr, Dubrovska and Muders.To date, PDAC remains the cancer having the worst prognosis with mortality rates constantly on the rise. Efficient cures are still absent, despite all attempts to understand the aggressive physiopathology underlying this disease. A major stumbling block is the outdated preclinical modeling strategies applied in assessing effectiveness of novel anticancer therapeutics. Current in vitro preclinical models have a low fidelity to mimic the exact architectural and functional complexity of PDAC tumor found in human set, due to the lack of major components such as immune system and tumor microenvironment with its associated chemical and mechanical signals. The existing PDAC preclinical platforms are still far from being reliable and trustworthy to guarantee the success of a drug in clinical trials. Therefore, there is an urgent demand to innovate novel in vitro preclinical models that mirrors with precision tumor-microenvironment interface, pressure of immune system, and molecular and morphological aspects of the PDAC normally experienced within the living organ. This review outlines the traditional preclinical models of PDAC namely 2D cell lines, genetically engineered mice, and xenografts, and describing the present famous approach of 3D organoids. We offer a detailed narration of the pros and cons of each model system. Finally, we suggest the incorporation of two off-center newly born techniques named 3D bio-printing and organs-on-chip and discuss the potentials of swine models and in silico tools, as powerful new tools able to transform PDAC preclinical modeling to a whole new level and open new gates in personalized medicine. Copyright © 2020 Swayden, Soubeyran and Iovanna.In recent years, immunotherapies have been clinically investigated in AML and other myeloid malignancies. While most of these are focused on stimulating the adaptive immune system (including T cell checkpoint inhibitors), several key approaches targeting the innate immune system have been identified. Macrophages are a key cell type in the innate immune response with CD47 being identified as a dominant macrophage checkpoint. CD47 is a "do not eat me" signal, overexpressed in myeloid malignancies that leads to tumor evasion of phagocytosis by macrophages. Blockade of CD47 leads to engulfment of leukemic cells and therapeutic elimination. Pre-clinical data has demonstrated robust anti-cancer activity in multiple hematologic malignancies including AML and myelodysplastic syndrome (MDS). In addition, clinical studies have been underway with CD47 targeting agents in both AML and MDS as monotherapy and in combination. learn more This review will describe the role of CD47 in myeloid malignancies and pre-clinical data supporting CD47 targeting. In addition, initial clinical data of CD47 targeting in AML/MDS will be reviewed, and including the first-in-class anti-CD47 antibody magrolimab. Copyright © 2020 Chao, Takimoto, Feng, McKenna, Gip, Liu, Volkmer, Weissman and Majeti.Emerging details of the gene expression and mutational features of canine lymphoma and leukemia demonstrate areas of similarities and differences between disease subsets in the humans and dogs. Many features of canine diffuse large B-cell lymphoma resemble the ABC form of human DLBCL, including constitutive activation of the NF-kB pathway, and almost universal presence of double expressing MYC/BCL2 lymphomas. Frequent TRAF3 mutations and absence of BCL6 expression are differences with the human disease that need further exploration. Canine peripheral T-cell lymphoma is more common in dogs than in people and behaves in a similarly aggressive manner. Common features of canine and human PTCL include activation of the PI3 kinase pathways, loss of PTEN, and the tumor suppressor CDKN2. There is insufficient data available yet to determine if canine PTCL exhibits the GATA3-TBX21 dichotomy seen in people. Common to all forms of canine lymphoproliferative disease are breed-specific predilections for subsets of disease. This is particularly striking in PTCL, with the Boxer breed being dramatically overrepresented. Breed-specific diseases provide an opportunity for uncovering genetic and environmental risk factors that can aid early diagnosis and prevention. Copyright © 2020 Avery.Cyclic hormonal stimulation of the breast tissue plays a significant role in breast carcinogenesis. Current risk factor models do not include direct measures of cycle characteristics although the effects of possible surrogates of cycle activity such as age at menarche and menopause, parity, and nursing time have been investigated. Future risk models should also include menstrual cycle length, regularity, number of cycles before first full-term pregnancy, and life-time number of cycles. New risk factor models for pre- and postmenopausal breast cancer are proposed here. Furthermore, there is a need for more long-term, prospective studies investigating menstrual cycle characteristics as data currently available are primarily retrospective and collected at one time-point only. Copyright © 2020 Olsson and Olsson.Background Osteoradionecrosis (ORN) of the cervical spine is a serious complication after radiotherapy (RT), which may show increased radiotracer uptake on a bone scan (BS) and be mistaken as metastasis. We aimed to assess the value of magnetic resonance imaging (MRI) in the differentiation of cervical spine ORN from bone metastasis after RT detected by BS in nasopharyngeal carcinoma (NPC). Methods In this retrospective study, 35 NPC patients who had undergone RT were enrolled, of whom 21 patients showed cervical spine ORN and 14 showed bone metastasis. New areas of increased radiotracer uptake in the cervical spine on a BS were noted in all patients, following which the patients underwent neck MRI for further assessment. Two radiologists independently reviewed two sets of images including a BS set and an MRI set (MRI with BS) and reached a consensus. The diagnostic sensitivity, specificity, and accuracy for ORN detection were calculated, and interobserver agreement was evaluated using the kappa test. Results A total of 75 cervical spine lesions were identified (44, ORN; 31 metastases).
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