Intravenous MSC-Treatment Improves Impaired Brain Functions in the R6/2 Mouse Model of Huntington's Disease via Recovered Hepatic Pathological Changes.

Huntington's disease (HD), a congenital neurodegenerative disorder, extends its pathological damages beyond the nervous system. The systematic manifestation of HD has been extensively described in numerous studies, including dysfunction in peripheral organs and peripheral inflammation. Gut dysbiosis and the gut-liver-brain axis have garnered greater emphasis in neurodegenerative research, and increased plasma levels of pro-inflammatory cytokines have been identified in HD patients and various in vivo models, correlating with disease progression.

Blocking TGF-β- and Epithelial-to-Mesenchymal Transition (EMT)-mediated activation of vessel-associated mural cells in glioblastoma impacts tumor angiogenesis.

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. GBM displays excessive and unfunctional vascularization which may, among others, be a reason for its devastating prognosis. Pericytes have been identified as the major component of the irregular vessel structure in GBM.

Development of an optimized, non-stem cell line for intranasal delivery of therapeutic cargo to the central nervous system.

Neural stem cells (NSCs) are considered to be valuable candidates for delivering a variety of anti-cancer agents, including oncolytic viruses, to brain tumors. However, owing to the previously reported tumorigenic potential of NSC cell lines after intranasal administration (INA), here we identified the human hepatic stellate cell line LX-2 as a cell type capable of longer resistance to replication of oncolytic adenoviruses (OAVs) as a therapeutic cargo, and that is non-tumorigenic after INA. Our data show that LX-2 cells can longer withstand the OAV XVir-N-31 replication and oncolysis than NSCs.

Intranasal Delivery of Oncolytic Adenovirus XVir-N-31 via Optimized Shuttle Cells Significantly Extends Survival of Glioblastoma-Bearing Mice.

A glioblastoma (GBM) is an aggressive and lethal primary brain tumor with restricted treatment options and a dismal prognosis. Oncolytic virotherapy (OVT) has developed as a promising approach for GBM treatment. However, reaching invasive GBM cells may be hindered by tumor-surrounding, non-neoplastic cells when the oncolytic virus (OV) is applied intratumorally.

TGF-Beta Modulates the Integrity of the Blood Brain Barrier In Vitro, and Is Associated with Metabolic Alterations in Pericytes.

The blood-brain barrier (BBB) is a selectively permeable boundary that separates the circulating blood from the extracellular fluid of the brain and is an essential component for brain homeostasis. In glioblastoma (GBM), the BBB of peritumoral vessels is often disrupted. Pericytes, being important to maintaining BBB integrity, can be functionally modified by GBM cells which induce proliferation and cell motility via the TGF-β-mediated induction of central epithelial to mesenchymal transition (EMT) factors.

The Oncolytic Adenovirus XVir-N-31, in Combination with the Blockade of the PD-1/PD-L1 Axis, Conveys Abscopal Effects in a Humanized Glioblastoma Mouse Model.

Glioblastoma (GBM) is an obligatory lethal brain tumor with a median survival, even with the best standard of care therapy, of less than 20 months. In light of this fact, the evaluation of new GBM treatment approaches such as oncolytic virotherapy (OVT) is urgently needed. Based on our preliminary preclinical data, the YB-1 dependent oncolytic adenovirus (OAV) XVir-N-31 represents a promising therapeutic agent to treat, in particular, therapy resistant GBM.

The Combination of Curaxin CBL0137 and Histone Deacetylase Inhibitor Panobinostat Delays KMT2A-Rearranged Leukemia Progression.

Rearrangements of the () gene are present in approximately 10% of acute leukemias and characteristically define disease with poor outcome. Driven by the unmet need to develop better therapies for KMT2A-rearranged leukemia, we previously discovered that the novel anti-cancer agent, curaxin CBL0137, induces decondensation of chromatin in cancer cells, delays leukemia progression and potentiates standard of care chemotherapies in preclinical KMT2A-rearranged leukemia models. Based on the promising potential of histone deacetylase (HDAC) inhibitors as targeted anti-cancer agents for KMT2A-rearranged leukemia and the fact that HDAC inhibitors also decondense chromatin an alternate mechanism, we investigated whether CBL0137 could potentiate the efficacy of the HDAC inhibitor panobinostat in KMT2A-rearranged leukemia models.

Effective targeting of NAMPT in patient-derived xenograft models of high-risk pediatric acute lymphoblastic leukemia.

The prognosis for children diagnosed with high-risk acute lymphoblastic leukemia (ALL) remains suboptimal, and more potent and less toxic treatments are urgently needed. We investigated the efficacy of a novel nicotinamide phosphoribosyltransferase inhibitor, OT-82, against a panel of patient-derived xenografts (PDXs) established from high-risk and poor outcome pediatric ALL cases. OT-82 was well-tolerated and demonstrated impressive single agent in vivo efficacy, achieving significant leukemia growth delay in 95% (20/21) and disease regression in 86% (18/21) of PDXs.

Potent antileukemic activity of curaxin CBL0137 against MLL-rearranged leukemia.

Around 10% of acute leukemias harbor a rearrangement of the MLL/KMT2A gene, and the presence of this translocation results in a highly aggressive, therapy-resistant leukemia subtype with survival rates below 50%. There is a high unmet need to identify safer and more potent therapies for MLL-rearranged (MLL-r) leukemia that can be combined with established chemotherapeutics to decrease treatment-related toxicities. The curaxin, CBL0137, has demonstrated nongenotoxic anticancer and chemopotentiating effects in a number of preclinical cancer models and is currently in adult Phase I clinical trials for solid tumors and hematological malignancies.

About a rare disease misdiagnosed as malignant lymphoma or tuberculosis: Kikuchi-Fujimoto's disease.

Kikuchi-Fujimoto's disease KFD is a rare and benign cause of cervical lymphadenopathy. It is an anatomoclinical entity of unknown etiology. The confirmation of the diagnosis is always provided by histological lymph node study.

[Rhinoscleroma of the cavum with expression in cervical lymph nodes: about a case].

Rhinoscleroma is a specific granulomatous and chronic disorder with insidious evolution. It is causes by pathogen Klebsiella rhinoscleromatis. It mainly occurs in the nasal cavities and positive diagnosis is sometimes problematic.

Extra-corporeal normothermic machine perfusion of the porcine kidney: working towards future utilization in Australasia.

Background: The ongoing supply-demand gap with respect to donor kidneys for transplantation necessitates the increased use of higher kidney donor profile index and/or donation after circulatory death (DCD) kidneys. Machine perfusion (MP) preservation has become increasingly popular as a means to preserve such organs. Human data regarding normothermic kidney MP (NMP) is in its infancy, and such a system has not been established in the Australasian clinical setting.

Role of plasma cells in Waldenström macroglobulinaemia.

Waldenström macroglobulinaemia (WM) is an indolent mature B cell lymphoma characterised by an infiltrate of heterogeneous B cells and hypersecretion of IgM. There are two distinct cellular populations that can be distinguished on morphology and immunophenotyping within the bone marrow. The predominant lymphoplasmacytic compartment arises at an earlier stage in ontogeny, and is responsible for the cytopenias noted during the symptomatic phase of the disease.

A case of Kartagener syndrome with rhinolalia clausa.

Kartagener syndrome is an autosomal recessive genetic ciliary disorder comprising of a classic triad of sinusitis, situs inversus and bronchiectasis. It's the one of primary ciliary dyskinesia disorders with manifestations present from childhood. Most patients of PCD have situs inversus.

Cervical lymph node metastasis in chromophobe renal cell carcinoma: a case report and review of the literature.

The metastasis of chromophobe renal cell carcinoma to head and neck region, described herein, has never been reported before to our knowledge. A 56-year-old woman with a history of nephrectomy, that revealed chromophobe renal cell carcinoma six years before, presented left cervical mass. Imaging showed with left cervical lymphadenopathies and thyroid nodule.