Dual Inhibition of mTORC1/2 Reduces Migration of Cholangiocarcinoma Cells by Regulation of Matrixmetalloproteinases

Cholangiocarcinoma (CCA) is a rare but highly aggressive tumor entity for which systemic therapies only showed limited efficacy so far. As OSI-027—a dual kinase inhibitor targeting both mTOR complexes, mTORC1 and mTORC2 - showed improved anti-cancer effects, we sought to evaluate its impact on the migratory and metastatic capacity of CCA cells in vitro. We found that treatment with OSI-027 leads to reduced cell mobility and migration as well as a reduced surviving fraction in colony-forming ability. While neither cell viability nor proliferation rate was affected, OSI-027 decreased the expression of MMP2 and MMP9. Moreover, survival as well as anti-apoptotic signaling was impaired upon the use of OSI-027 as determined by AKT and MAPK blotting. Dual targeting of mTORC1/2 might therefore be a viable option for anti-neoplastic therapy in CCA.

Primitive neuroectodermal tumor of ulnar nerve: A rare case

Primitive neuroectodermal tumor (PNET) is a highly aggressive tumor and mostly develops in children and young adults. PNETs of peripheral nerves are uncommon. Ulnar nerve, in particular, is an extremely peculiar origin for PNET and to the best of our knowledge only few well-documented cases have been yet reported.

TRP channel expression correlates with the epithelial–mesenchymal transition and high-risk endometrial carcinoma

Transient receptor potential (TRP) channels excel in cellular sensing as they allow rapid ion influx across the plasma membrane in response to a variety of extracellular cues. Recently, a distinct TRP mRNA expression signature was observed in stromal cells (ESC) and epithelial cells (EEC) of the endometrium, a tissue in which cell phenotypic plasticity is essential for normal functioning. However, it is unknown whether TRP channel mRNA expression is subject to the phenotypic switching that occurs during epithelial to mesenchymal transition (EMT) and mesenchymal to epithelial transition (MET), and whether TRP channel mRNA expression is associated with aggressive phenotypes in endometrial cancer (EC). Here, we induced EMT and MET in vitro using in primary EEC and ESC, respectively, and analyzed expression and functionality of TRP channels using RT-qPCR and intracellular Ca2+ imaging. The outcome of these experiments showed a strong association between TRPV2 and TRPC1 mRNA expression and the mesenchymal phenotype, whereas TRPM4 mRNA expression correlated with the epithelial phenotype. In line herewith, increased TRPV2 and TRPC1 mRNA expression levels were observed in both primary and metastatic EC biopsies and in primary EC cells with a high EMT status, indicating an association with an aggressive tumor phenotype. Remarkably, TRPV2 mRNA expression in primary EC biopsies was associated with tumor invasiveness and cancer stage. In contrast, increased TRPM4 mRNA expression was observed in EC biopsies with a low EMT status and less aggressive tumor phenotypes. Taken together, this dataset proved for the first time that TRP channel mRNA expression is strongly linked to cellular phenotypes of the endometrium, and that phenotypic transitions caused by either experimental manipulation or malignancy could alter this expression in a predictable manner. These results implicate that TRP channels are viable biomarkers to identify high-risk EC, and potential targets for EC treatment.

CHARACTERISTIC OF AMELOBLASTOMA IN ORAL AND MAXILLOFACIAL SURGERY AT HASAN SADIKIN HOSPITAL : 2 YEARS RETROSPECTIVE STUDY

ABSTRACTBackground: Ameloblastoma is the most common odontogenic tumor. Ameloblastoma is a borderline tumor because it is a benign but locally aggressive tumor with a high recurrence rate if the excision is not complete. The principle of treatment for ameloblastoma is excision all the tumor. This article aimed to conduct a retrospective study to analyze the characteristics of ameloblastoma in patients at Oral and Maxillofacial Surgery Hasan Sadikin Hospital Oral Surgery between the period of January 2018-December 2019Method: This is a retrospective study with 37 patients diagnosed with ameloblastoma during 2018-2019. We took data from each patient such as gender, age, radiological features, histopathological diagnosis of the location of ameloblastoma, management, defects, reconstruction. Result: A total of 22 patients were diagnosed with plexiform ameloblastoma, 12 cases of follicular ameloblastoma, 3 cases of mixed plexiform and follicular ameloblastoma. 31 patients were treated radically, while 6 patients were treated conservatively. Radical treatment is more often used to reduce recurrence rates, whereas conservative measures are indicated in children and adolescents, as well as adult patients with unilocular ameloblastoma types. Conclusion: The most characteristic of ameloblastoma is plexiform ameloblastoma in the mandible. Ameloblastoma is usually performed radically and reconstructed with an AO plate.

Mechanistic insights of radiation-induced endothelial senescence impelling glioblastoma genomic instability at relapse

Despite aggressive clinical protocol, all glioblastoma (GBM) recur at the initial site within the irradiated peritumoral microenvironment. Whereas irradiated microenvironment has been recently proposed to accelerate GBM relapse, molecular and cellular mechanisms remain unknown. Here, using relevant in vitro and in vivo models, we decipher how radiation-induced endothelial senescence drives the emergence of aggressive GBM cells. Secretome (SASP) of radiation-induced senescent (RIS) endothelium enhances genomic instability and intratumoral heterogeneity in irradiated GBM cells. In-depth molecular studies revealed that CXCL5 and CXCL8, from the SASP, activate CXCR2 receptor on tumor cells leading to increased DNA hyper-replication, micronuclei formation and aneuploidy. Importantly, through CXCL5/8-CXCR2 axis activation, this SASP increases GBM aggressiveness in vivo. Both chemokines were detected in relapsing, but not primary, GBM biopsies and positively correlated with worst patient outcome. In conclusion, we identify new molecular and preclinical insights of relapsing GBM aggressiveness where RIS vascular niches fuel aggressive tumor emergence.

Circadian Gene cry Controls Glioblastoma Tumorigenesis through Modulation of myc Expression

Glioblastoma (GB) is the most frequent malignant brain tumor among adults and currently there is no effective treatment. It is a very aggressive tumor that grows fast and spreads through the brain causing the death of patients in 15 months. GB cells mutate frequently and generate a heterogeneous population of tumoral cells genetically distinct. Thus, the contribution of genes and signaling pathways relevant for GB progression is of great relevance. We use a Drosophila model of GB that reproduces the features of human GB, and describe the upregulation of the circadian gene cry in GB patients and in a Drosophila GB model. We study the contribution of cry to the expansion of GB cells, to the neurodegeneration caused by GB, and to premature death and determine that cry is required for GB progression. Moreover, we analyze the mechanisms that regulate cry expression by the PI3K pathway. Finally, we conclude that cry is necessary and sufficient to regulate myc expression in GB. These results contribute to the understanding of the signals that impulse GB malignancy and lethality and open novel opportunities for the treatment of GB patients.

Magnetic nanoparticles in theranostics of malignant melanoma

Malignant melanoma is an aggressive tumor with a tendency to metastasize early and with an increasing incidence worldwide. Although in early stage, melanoma is well treatable by excision, the chances of cure and thus the survival rate decrease dramatically after metastatic spread. Conventional treatment options for advanced disease include surgical resection of metastases, chemotherapy, radiation, targeted therapy and immunotherapy. Today, targeted kinase inhibitors and immune checkpoint blockers have for the most part replaced less effective chemotherapies. Magnetic nanoparticles as novel agents for theranostic purposes have great potential in the treatment of metastatic melanoma. In the present review, we provide a brief overview of treatment options for malignant melanoma with different magnetic nanocarriers for theranostics. We also discuss current efforts of designing magnetic particles for combined, multimodal therapies (e.g., chemotherapy, immunotherapy) for malignant melanoma.

Exploring Solitary Bone Plasmacytoma: A Rare Case Report

The Solitary Bone Plasmacytoma (SBP) is a rare oncologic disease corresponding to less than 5% of the malignant neoplasms of the plasma cells. It is characterized as a localized aggressive tumor consequent to the accumulation of monoclonal plasma cell neoplasms and, due to the rarity of the disease, there are only few clinical studies reporting it especially regarding prognostic factors and treatment. Here, we report a fatal clinical case of SPB in Roraima, the northernmost state of Brazil. The study shows a case of solitary bone plasmacytoma on the femur, where the patient was submitted to the preconized radiotherapy cycles. However, over approximately four-years following the diagnose, the patient required multi-modal approach to guarantee quality of life during the survival time. Finally, this study explores SBP-related issues and examines the challenges physicians face when managing the care of patients with SBP.