Both metachronous and synchronous tumors pose a diagnostic and clinical challenge, more so when one of the specimens demonstrates the rare neuroendocrine histology. We describe a patient with sarcoidosis who was treated for endometrial and ovarian neoplasm, recurred with two separate histologies (adenocarcinoma and high grade neuroendocrine), both associated with microsatellite instability (MSI)-high status. Targeted next-generation sequencing of tumor with synonymous somatic alterations pointed to a common ancestry of all three tumors and patient was successfully treated with a tailored immunotherapy regimen. Her sarcoidosis worsened only slightly, and immunotherapy did not need to be discontinued. This case highlights the importance of molecular testing for the optimal therapy of complex synchronous tumors and the need for communication between surgical and medical oncologists in patients with MSI-high cancer. KEY POINTS The case of a patient with a recurrent gynecological cancer presenting as microsatellite instability (MSI)-high endometrial adenocarcinoma and MSI-high neuroendocrine tumor is reported. This case demonstrated a common genetic lineage with good response to checkpoint inhibition without clinical worsening of autoimmune disease. This article adds to the literature, suggesting tumor evolution with neuroendocrine differentiation in some cancers, and argues that a molecular-based approach to treatment might achieve better understanding and possibly superior treatment outcomes.Adenovirus (AdV) infection is a common complication in bone marrow/hematopoietic stem cell transplant and solid organ transplant recipients. AdV infection usually presents as hemorrhagic cystitis, but sometimes it can progress to acute kidney injury showing AdV nephritis (AdVN). We present the case of a 52-year-old Japanese female who had received a living kidney transplantation (KT) from her husband. At 21 months post-KT, the patient presented with a fever, but no renal dysfunction and no abnormal urine findings. A contrast-enhanced computed tomography (CT) scan revealed a few mass lesions with hypoperfusion in the transplanted kidney. An enhanced CT-guided biopsy targeting one of these lesions revealed a necrotizing tubulointerstitial nephritis suggesting AdVN. https://www.selleckchem.com/products/a-196.html The polymerase chain reaction tests for ADV were negative in a urine sample but positive in the sera and the frozen kidney biopsy samples. AdVN can manifest as an unusual pattern of acute lobar nephritis/acute focal bacterial nephritis-like localization without symptoms of acute kidney injury or urinary tract infection. Enhanced CT can provide clues for clinical diagnosis.
The relationship between circulating exosomal circular RNA (circRNA) and prognosis of patients with nasopharyngeal carcinoma (NPC) remain unknown. This study focused on the expression of exosomal circMYC and its relationship with the recurrence and prognosis of patients with NPC.

The circulating exosomes were obtained from 210 patients with NPC. Quantitative polymerase chain reaction, 5-ethynyl-2'-deoxyuridine (EdU) staining, colony formation, and bioinformatic analysis were performed.

Circulating exosomal circMYC was significantly increased in patients with NPC and was associated with tumor size, lymph node metastasis, TNM stage, survival rate, and disease recurrence. Gain-functional and loss-functional experiments revealed that overexpression of circMYC promoted cell proliferation and reduce radiosensitivity, while knockdown of circMYC inhibited cell proliferation and enhanced radiotherapy.

circMYC is an oncogene in NPC cells and can enhance the radiotherapy resistance of NPC cells. Circulating exosomal circMYC can be used as a potential therapeutic target for NPC.
circMYC is an oncogene in NPC cells and can enhance the radiotherapy resistance of NPC cells. Circulating exosomal circMYC can be used as a potential therapeutic target for NPC.The ability of Salmonella to survive and replicate within mammalian host cells involves the generation of a membranous compartment known as the Salmonella-containing vacuole (SCV). Salmonella employs a number of effector proteins that are injected into host cells for SCV formation using its type-3 secretion systems encoded in SPI-1 and SPI-2 (T3SS-1 and T3SS-2, respectively). Recently, we reported that S. Typhimurium requires T3SS-1 and T3SS-2 to survive in the model amoeba Dictyostelium discoideum. Despite these findings, the involved effector proteins have not been identified yet. Therefore, we evaluated the role of two major S. Typhimurium effectors SopB and SifA during D. discoideum intracellular niche formation. First, we established that S. Typhimurium resides in a vacuolar compartment within D. discoideum. Next, we isolated SCVs from amoebae infected with wild type or the ΔsopB and ΔsifA mutant strains of S. Typhimurium, and we characterised the composition of this compartment by quantitative proteomics. This comparative analysis suggests that S. Typhimurium requires SopB and SifA to modify the SCV proteome in order to generate a suitable intracellular niche in D. discoideum. Accordingly, we observed that SopB and SifA are needed for intracellular survival of S. Typhimurium in this organism. Thus, our results provide insight into the mechanisms employed by Salmonella to survive intracellularly in phagocytic amoebae.
Exosomes present essential roles for intercellular interaction via extracellular pathways during systemic dysfunctions, including preeclampsia (PE). Here, we assessed the specific mechanism of mesenchymal stem cells (MSC)-originated exosomes in PE.

The effects of exosomes on trophoblasts were studied by EdU, wound healing, Transwell and TUNEL assays. By microarray analysis, we found that exosomes enhanced the microRNA-139-5p (miR-139-5p) in trophoblasts, and confirmed the target gene of miR-139-5p by bioinformatics prediction and dual-luciferase reporter gene assay. At the same time, ERK/MMP-2 pathway-related biomolecules were assessed through Western blot analysis. The pathway inhibitor was used for rescue experiments. Finally, the effect of exosomes on the pathology of PE rats was verified by in vivo experiments.

The exosomes originated from hucMSC fostered the trophoblast cell migration, invasion and proliferation and obstructed apoptosis. Moreover, miR-139-5p could be transmitted to trophoblasts through hucMSC-secreted exosomes.
Both metachronous and synchronous tumors pose a diagnostic and clinical challenge, more so when one of the specimens demonstrates the rare neuroendocrine histology. We describe a patient with sarcoidosis who was treated for endometrial and ovarian neoplasm, recurred with two separate histologies (adenocarcinoma and high grade neuroendocrine), both associated with microsatellite instability (MSI)-high status. Targeted next-generation sequencing of tumor with synonymous somatic alterations pointed to a common ancestry of all three tumors and patient was successfully treated with a tailored immunotherapy regimen. Her sarcoidosis worsened only slightly, and immunotherapy did not need to be discontinued. This case highlights the importance of molecular testing for the optimal therapy of complex synchronous tumors and the need for communication between surgical and medical oncologists in patients with MSI-high cancer. KEY POINTS The case of a patient with a recurrent gynecological cancer presenting as microsatellite instability (MSI)-high endometrial adenocarcinoma and MSI-high neuroendocrine tumor is reported. This case demonstrated a common genetic lineage with good response to checkpoint inhibition without clinical worsening of autoimmune disease. This article adds to the literature, suggesting tumor evolution with neuroendocrine differentiation in some cancers, and argues that a molecular-based approach to treatment might achieve better understanding and possibly superior treatment outcomes.Adenovirus (AdV) infection is a common complication in bone marrow/hematopoietic stem cell transplant and solid organ transplant recipients. AdV infection usually presents as hemorrhagic cystitis, but sometimes it can progress to acute kidney injury showing AdV nephritis (AdVN). We present the case of a 52-year-old Japanese female who had received a living kidney transplantation (KT) from her husband. At 21 months post-KT, the patient presented with a fever, but no renal dysfunction and no abnormal urine findings. A contrast-enhanced computed tomography (CT) scan revealed a few mass lesions with hypoperfusion in the transplanted kidney. An enhanced CT-guided biopsy targeting one of these lesions revealed a necrotizing tubulointerstitial nephritis suggesting AdVN. https://www.selleckchem.com/products/a-196.html The polymerase chain reaction tests for ADV were negative in a urine sample but positive in the sera and the frozen kidney biopsy samples. AdVN can manifest as an unusual pattern of acute lobar nephritis/acute focal bacterial nephritis-like localization without symptoms of acute kidney injury or urinary tract infection. Enhanced CT can provide clues for clinical diagnosis. The relationship between circulating exosomal circular RNA (circRNA) and prognosis of patients with nasopharyngeal carcinoma (NPC) remain unknown. This study focused on the expression of exosomal circMYC and its relationship with the recurrence and prognosis of patients with NPC. The circulating exosomes were obtained from 210 patients with NPC. Quantitative polymerase chain reaction, 5-ethynyl-2'-deoxyuridine (EdU) staining, colony formation, and bioinformatic analysis were performed. Circulating exosomal circMYC was significantly increased in patients with NPC and was associated with tumor size, lymph node metastasis, TNM stage, survival rate, and disease recurrence. Gain-functional and loss-functional experiments revealed that overexpression of circMYC promoted cell proliferation and reduce radiosensitivity, while knockdown of circMYC inhibited cell proliferation and enhanced radiotherapy. circMYC is an oncogene in NPC cells and can enhance the radiotherapy resistance of NPC cells. Circulating exosomal circMYC can be used as a potential therapeutic target for NPC. circMYC is an oncogene in NPC cells and can enhance the radiotherapy resistance of NPC cells. Circulating exosomal circMYC can be used as a potential therapeutic target for NPC.The ability of Salmonella to survive and replicate within mammalian host cells involves the generation of a membranous compartment known as the Salmonella-containing vacuole (SCV). Salmonella employs a number of effector proteins that are injected into host cells for SCV formation using its type-3 secretion systems encoded in SPI-1 and SPI-2 (T3SS-1 and T3SS-2, respectively). Recently, we reported that S. Typhimurium requires T3SS-1 and T3SS-2 to survive in the model amoeba Dictyostelium discoideum. Despite these findings, the involved effector proteins have not been identified yet. Therefore, we evaluated the role of two major S. Typhimurium effectors SopB and SifA during D. discoideum intracellular niche formation. First, we established that S. Typhimurium resides in a vacuolar compartment within D. discoideum. Next, we isolated SCVs from amoebae infected with wild type or the ΔsopB and ΔsifA mutant strains of S. Typhimurium, and we characterised the composition of this compartment by quantitative proteomics. This comparative analysis suggests that S. Typhimurium requires SopB and SifA to modify the SCV proteome in order to generate a suitable intracellular niche in D. discoideum. Accordingly, we observed that SopB and SifA are needed for intracellular survival of S. Typhimurium in this organism. Thus, our results provide insight into the mechanisms employed by Salmonella to survive intracellularly in phagocytic amoebae. Exosomes present essential roles for intercellular interaction via extracellular pathways during systemic dysfunctions, including preeclampsia (PE). Here, we assessed the specific mechanism of mesenchymal stem cells (MSC)-originated exosomes in PE. The effects of exosomes on trophoblasts were studied by EdU, wound healing, Transwell and TUNEL assays. By microarray analysis, we found that exosomes enhanced the microRNA-139-5p (miR-139-5p) in trophoblasts, and confirmed the target gene of miR-139-5p by bioinformatics prediction and dual-luciferase reporter gene assay. At the same time, ERK/MMP-2 pathway-related biomolecules were assessed through Western blot analysis. The pathway inhibitor was used for rescue experiments. Finally, the effect of exosomes on the pathology of PE rats was verified by in vivo experiments. The exosomes originated from hucMSC fostered the trophoblast cell migration, invasion and proliferation and obstructed apoptosis. Moreover, miR-139-5p could be transmitted to trophoblasts through hucMSC-secreted exosomes.
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