ABSTRACT
BACKGROUND: Cancer cell-derived extracellular vesicles (EVs) have previously been shown to contribute to pre-metastatic niche formation. Specifically, aggressive tumors secrete pro-metastatic EVs that travel in the circulation to distant organs to modulate the microenvironment for future metastatic spread. Previous studies have focused on the interface between pro-metastatic EVs and epithelial/endothelial cells in the pre-metastatic niche. However, EV interactions with circulating components such as low-density lipoprotein (LDL) have been overlooked. RESULTS: This study demonstrates that EVs derived from brain metastases cells (Br-EVs) and corresponding regular cancer cells (Reg-EVs) display different interactions with LDL. Specifically, Br-EVs trigger LDL aggregation, and the presence of LDL accelerates Br-EV uptake by monocytes, which are key components in the brain metastatic niche. CONCLUSIONS: Collectively, these data are the first to demonstrate that pro-metastatic EVs display distinct interactions with LDL, which impacts monocyte internalization of EVs.
Subject(s)
Brain Neoplasms/metabolism , Extracellular Vesicles/metabolism , Lipoproteins, LDL/metabolism , Brain Neoplasms/pathology , Breast Neoplasms , Cell Line, Tumor , Endothelial Cells , Humans , Macrophages , Monocytes , THP-1 Cells , Tumor MicroenvironmentABSTRACT
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer and has the highest propensity to manifest as metastatic disease. Recent characterizations of the genetic signature of ccRCC have revealed several factors correlated with tumor cell migration and invasion; however, the specific events driving malignancy are not well defined. Furthermore, there remains a lack of targeted therapies that result in long-term, sustainable response in patients with metastatic disease. We show here that neuronal pentraxin 2 (NPTX2) is overexpressed specifically in ccRCC primary tumors and metastases, and that it contributes to tumor cell viability and promotes cell migration through its interaction with the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR4. We propose NPTX2 as a novel molecular target for therapy for patients with ccRCC diagnosed with or at risk of developing metastatic disease.
Subject(s)
C-Reactive Protein/genetics , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Nerve Tissue Proteins/genetics , Receptors, AMPA/genetics , C-Reactive Protein/metabolism , Carcinoma, Renal Cell/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Survival/genetics , Humans , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Neoplasm Metastasis/genetics , Neoplasm Metastasis/pathology , Nerve Tissue Proteins/metabolism , Receptors, AMPA/metabolism , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolismABSTRACT
A case of a 79-year-old female with rupture of the spleen due to primary angiosarcoma is presented. Symptoms were non-specific. Diagnosis was based on histology postoperatively. Primary angiosarcoma of the spleen is a very rare and aggressive neoplasm with a high metastatic rate and almost uniformly fatal. Due to small number of reported cases, there are no guidelines concerning adjuvant or palliative treatment or any beneficial protocols of chemotherapy or radiotherapy up to date. Splenectomy prior to rupture seems to have a positive impact on long-term survival.
Subject(s)
Hemangiosarcoma/complications , Splenic Neoplasms/complications , Splenic Rupture/etiology , Aged , Female , Hemangiosarcoma/diagnosis , Hemangiosarcoma/surgery , Humans , Splenic Neoplasms/diagnosis , Splenic Neoplasms/surgery , Splenic Rupture/diagnosis , Splenic Rupture/surgery , Tomography, X-Ray ComputedABSTRACT
We report the case of a 17-year-old male with a rupture into the biliary tract. The patient was urgently admitted to the surgical department with the clinical diagnosis of cholangitis. Modern imaging techniques and specific serologic tests established the diagnosis of intrabiliary rupture of a liver hydatid cyst due to E. granulosus. Despite the fact that surgery remains the cornerstone of treatment, conservative management was preferred, due to the location of the echinococcal cyst in the right lobe of the liver adjacent to the inferior vena cava and the age of the patient. Endoscopic sphincterotomy was performed with subsequent evacuation of the biliary tree, followed by a sixcycle treatment with albendazole. At one-year follow-up, the patient is in good health, with no radiologic or serologic evidence of relapse.
Subject(s)
Albendazole/therapeutic use , Anticestodal Agents/therapeutic use , Biliary Tract Diseases/etiology , Biliary Tract Diseases/therapy , Echinococcosis, Hepatic/complications , Echinococcosis, Hepatic/therapy , Sphincterotomy, Endoscopic , Adolescent , Biliary Tract Diseases/parasitology , Combined Modality Therapy , Humans , Male , Rupture, SpontaneousABSTRACT
To determine if reducing the intensity of the mobilizing chemotherapy protocol used would alter the number and/or quality of the progenitors mobilized in patients with chronic myelogenous leukaemia (CML), we undertook a pilot study. 36 consecutive CML patients previously treated only with hydroxyurea were given mobilization therapy within 12 months of diagnosis. 17 patients were treated by the ICE protocol and 19 patients received the mini-ICE protocol. The leukapheresis product collected from 22/36 patients (62%) was entirely Ph-negative. The cytogenetic results between ICE and mini-ICE-treated protocols were not significant, although the reduction in median days of hospitalization required for the mini-ICE versus the ICE protocol was highly significant (P < 0.0001). There was no significant difference in the yield of CD34+ cells and CFU-GM collected. No patient in the mini-ICE protocol experienced high-grade oral mucositis and GI toxicity whereas three such cases occurred with the ICE protocol. No patient died of the mobilization procedure in either group.
