De-differentiation associated with drop metastasis of a recurrent intracranial solitary fibrous tumor: a case report and literature review.

BACKGROUND: Central nervous system is a rare occurring location of solitary fibrous tumors (SFTs). SFTs have a potential for recurrence, which is the leading cause of death in patients with these disease entities. De-differentiation phenomenon combined with cerebrospinal fluid (CSF) dissemination through drop metastasis of STFs from intracranial to intraspinal has only been reported in extremely limited cases. CASE DESCRIPTION: Herein, we present a case of SFT in a 54-year old male. MRI showed characteristic of mixed high and low signal with 6.3 cm × 6.5 cm × 5.9 cm. After radical surgical resection, the pathology indicated benign SFT. However, MRI re-examination of 22 months later detected local recurrence, concomitant with spreading of intracranial and intraspinal through CSF dissemination. And interestingly, the second pathology found de-differentiation phenomenon and malignance of SFT, in which some areas transformed to rhabdomyosarcoma. CONCLUSION: This is the first case report of recurrent intracranial SFT de-differentiating to rhabdomyosarcoma concurrent with CSF pathway drop metastasis. Benign intracranial SFTs have the potential of de-differentiation, which may play an important role in its distant metastasis. The underlying molecular biological and pathological mechanisms of benign SFT malignance transformation still warrant further exploration.

Intracranial solitary fibrous tumor/hemangiopericytomas: a clinical analysis of a series of 17 patients.

OBJECTIVE: Solitary fibrous tumors (SFTs) and haemangiopericytomas (HPCs) are rare mesenchymal tumors in central nervous system (CNS). Although progressed recognition to the diagnosis and treatment of SFT/HPCs, it still remains many confusions regarding on its occurrence, aggressive evolution, malignant transformation, dedifferentiation phenomenon, distant metastasis and unpredictable propensity. PATIENTS AND METHODS: Seventeen cases of CNS SFT/HPCs who underwent surgical treatment from January 2010 to December 2020 were collected in the authors' institute. Clinical, radiological, pathological data and followup details were reviewed in all cases. RESULTS: The age of this series was 41-73 years old. Seven cases located subtentorially, five cases originated from middle skull base and four in supratentorial. MRI shows iso-signal intensity on T1WI, and heterogeneous slightly long/short signal on T2WI. There is significant contrast after gadolinium-enhancement. It is easy to be misdiagnosed before surgery. The positive rate of nuclear STAT6 is 94.12%, higher than CD34 (87.5%). Eight patients were grade I, eight grade II and one in grade III. Five cases developed tumor relapse, in which two cases had local intracranial recurrence combined with dissemination and metastasis of cerebrospinal fluid in the spinal canal, accompanied by pathological malignant transformation, and another one occurred blood metastasis. CONCLUSIONS: CNS SFT/HPCs are rare intracranial tumors with unpredictable propensity. Gross total resection is critical to its overall clinical prognosis. Given its potential recurrence and malignant transition, adjuvant radiotherapies are recommended when necessary, and long-term follow-up is indispensable. The underlying molecular biological mechanisms are still needed to be further exploration.

Knockdown of asparagine synthetase by RNAi suppresses cell growth in human melanoma cells and epidermoid carcinoma cells.

Melanoma, the most aggressive form of skin cancer, causes more than 40,000 deaths each year worldwide. And epidermoid carcinoma is another major form of skin cancer, which could be studied together with melanoma in several aspects. Asparagine synthetase (ASNS) gene encodes an enzyme that catalyzes the glutamine- and ATP-dependent conversion of aspartic acid to asparagine, and its expression is associated with the chemotherapy resistance and prognosis in several human cancers. The present study aims to explore the potential role of ASNS in melanoma cells A375 and human epidermoid carcinoma cell line A431. We applied a lentivirus-mediated RNA interference (RNAi) system to study its function in cell growth of both cells. The results revealed that inhibition of ASNS expression by RNAi significantly suppressed the growth of melanoma cells and epidermoid carcinoma cells, and induced a G0/G1 cell cycle arrest in melanoma cells. Knockdown of ASNS in A375 cells remarkably downregulated the expression levels of CDK4, CDK6, and Cyclin D1, and upregulated the expression of p21. Therefore, our study provides evidence that ASNS may represent a potential therapeutic target for the treatment of melanoma.

TSC2 nonsense mutation in angiomyolipoma with epithelial cysts: a case report and literature review.

Background: Angiomyolipoma with epithelial cysts (AMLEC) is an extremely rare subtype of kidney angiomyolipoma that contains epithelial-lined cysts. The most distinctive immunohistochemical feature of AMLEC is its immunoreactivity with melanocytic markers. AMLEC also has a distinct histological structure, which aids in its pathological diagnosis. To date 27 cases of AMLEC have been reported in 11 case series. However, the molecular biology underlying the pathogenesis of AMLEC remains unexplored. Case report: A 30-year-old female was diagnosed with AMLEC and underwent partial nephrectomy. Histologically, the cross-section of cystic tissue revealed a multilocular appearance, with some cysts containing thrombus-like material, and the wall thickness was approximately 0.2 ~ 0.3 cm. Additionally, the compact subepithelial cellular stroma showed strong and diffuse nuclear labeling for estrogen receptor, progesterone receptor, and CD10, as well as HMB45 and Melan A, which are markers of melanocytic differentiation. Furthermore, using a DNA targeted sequencing panel with next-generation sequencing, we identified a nonsense mutation in TSC Complex Subunit 2 (TSC2) gene, resulting in the formation of a premature termination codon. Moreover, the mutated genes found to be enriched in the PI3K-AKT pathway. The patient in this case had a favorable postoperative follow-up at 3 months. Conclusion: To the best of our knowledge, this study represents the first analysis of genotype mutations in AMLEC, providing valuable insights for future clinical practice. These findings have significant potential in guiding the understanding and management of AMLEC, paving the way for further research and advancements in the field.

RUNX-3-expressing CAR T cells targeting glypican-3 in patients with heavily pretreated advanced hepatocellular carcinoma: a phase I trial.

Background: Glypican-3 (GPC3) is a well-characterized hepatocellular carcinoma (HCC)-associated antigen and a promising target for HCC treatment. CT017 CAR T cells were engineered to co-express CAR-GPC3 and runt-related transcription factor 3 (RUNX3), which triggers CD8+ T-cell infiltration into the cancer microenvironment. Methods: This single-center, single-arm, open-label, phase I clinical study enrolled heavily pretreated patients with GPC3-positive HCC between August 2019 and December 2020 (NCT03980288). Patients were treated with CT017 CAR T cells at a dose of 250 × 106 cells. The primary objective was to assess the safety and tolerability of this first-in-human product. Findings: Six patients received 7 infusions (one patient received 2 infusions) at the 250 × 106 cells dose. Three patients received CT017 monotherapy, and three patients received CT017-tyrosine kinase inhibitor (TKI) combination therapy at the first infusion. One patient received CT017-TKI combination therapy at the second infusion after CT017 monotherapy. All patients experienced cytokine release syndrome (CRS), with 50% (3/6) at Grade 2, 50% (3/6) at Grade 3, and all events resolved after treatment. No immune effector cell-associated neurotoxicity syndrome was observed. Dose escalation was not performed due to the investigator's decision regarding safety. Of six evaluable patients, one achieved partial response and two had stable disease for a 16.7% objective response rate, 50% disease control rate, 3.5-month median progression-free survival, 3.2-month median duration of disease control, and 7.9-month median overall survival (OS) with 7.87-month median follow-up. The longest OS was 18.2 months after CT017 infusion. Interpretation: Current preliminary phase I data showed a manageable safety profile and promising antitumor activities of CT017 for patients with advanced HCC. These results need to be confirmed in a robust clinical trial. Funding: This study was funded by CARsgen Therapeutics Co., Ltd.

Up-regulation of GluR1 in paraventricular nucleus and greater expressions of synapse related proteins in the hypothalamus of chronic unpredictable stress-induced depressive rats.

Converging evidence indicates that abnormal glutamatergic and synaptic systems may be associated with the pathophysiology of depression. Over-activation of corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) plays a key role in the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and is a prominent feature in depression. In this study, we examined the effect of chronic unpredictable stress (CUS) in rats on the expression of AMPA subunit GluR1 protein in the hypothalamic PVN as well as on the expression of GluR1 and several synapse-related proteins in the hypothalamus. We found that CUS in rats induced CRH over-expression accompanied by significant GluR1 up-regulation in the hypothalamic PVN and GluR1 co-localized with CRH in the PVN area. The expression of GluR1 and three synapse-related proteins (PSD95, SYP and MAP2) in the hypothalamus were also increased at both mRNA and protein levels in CUS rats. Correlation analysis showed that the levels of the above proteins are directly correlated with depression-like behaviors of rats in sucrose preference test, open field test and forced swim test. These findings suggest that the augmented glutamatergic and synaptic signaling might be a potential mechanism underlying CRH over-activation in the hypothalamic PVN and contribute to CUS-induced depression-like behaviors in rats.