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1.
Int J Surg Pathol ; 32(3): 570-577, 2024 May.
Article in English | MEDLINE | ID: mdl-37461831

ABSTRACT

Neuroendocrine tumors (NETs) are only exceptionally primary to the kidney. At present, scant information is known regarding the behavior and prognosis of renal NETs, especially according to the assessment of grading parameters used for NETs originating from other more commonplace sites such as the pancreas and lungs. There are only rare reports of grade assessment in renal NETs, with most of these reports relying upon now antiquated World Health Organization gastroenteropancreatic and lung/thymus criteria. As an additional prognostic factor, positive CA9 staining in NETs may correlate with elevated grade, stage and risk of metastasis while serving as a potential target of chemotherapy and immunotherapy and indicator of Von Hippel-Lindau Syndrome. Rarer still are descriptions of renal NETs presenting with renal cell carcinoma in the ipsilateral or contralateral kidney. Thus, we present a patient with a primary renal NET of the right kidney with regional lymphovascular invasion and distant metastasis with an emphasis on grading criteria concordant with the World Health Organization 2022 gastroenteropancreatic and lung/thymus systems. In addition, we discuss unusual staining for CA9 in the patient's tumor and a concomitant left kidney clear cell renal cell carcinoma that may act as a clinicopathologic mimic of Von Hippel-Lindau Syndrome.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Neuroendocrine Tumors , Pancreatic Neoplasms , von Hippel-Lindau Disease , Humans , Neuroendocrine Tumors/pathology , Carbonic Anhydrase IX , von Hippel-Lindau Disease/complications , von Hippel-Lindau Disease/pathology , Kidney Neoplasms/pathology , Carcinoma, Renal Cell/pathology , Kidney/pathology , Pancreatic Neoplasms/pathology , Neoplasm Grading
2.
Front Cell Infect Microbiol ; 13: 1191806, 2023.
Article in English | MEDLINE | ID: mdl-37424774

ABSTRACT

Pseudomonas aeruginosa is a common cause of hospital-acquired infections, including central line-associated bloodstream infections and ventilator-associated pneumonia. Unfortunately, effective control of these infections can be difficult, in part due to the prevalence of multi-drug resistant strains of P. aeruginosa. There remains a need for novel therapeutic interventions against P. aeruginosa, and the use of monoclonal antibodies (mAb) is a promising alternative strategy to current standard of care treatments such as antibiotics. To develop mAbs against P. aeruginosa, we utilized ammonium metavanadate, which induces cell envelope stress responses and upregulates polysaccharide expression. Mice were immunized with P. aeruginosa grown with ammonium metavanadate and we developed two IgG2b mAbs, WVDC-0357 and WVDC-0496, directed against the O-antigen lipopolysaccharide of P. aeruginosa. Functional assays revealed that WVDC-0357 and WVDC-0496 directly reduced the viability of P. aeruginosa and mediated bacterial agglutination. In a lethal sepsis model of infection, prophylactic treatment of mice with WVDC-0357 and WVDC-0496 at doses as low as 15 mg/kg conferred 100% survival against challenge. In both sepsis and acute pneumonia models of infection, treatment with WVDC-0357 and WVDC-0496 significantly reduced bacterial burden and inflammatory cytokine production post-challenge. Furthermore, histopathological examination of the lungs revealed that WVDC-0357 and WVDC-0496 reduced inflammatory cell infiltration. Overall, our results indicate that mAbs directed against lipopolysaccharide are a promising therapy for the treatment and prevention of P. aeruginosa infections.


Subject(s)
Antibodies, Bacterial , Antibodies, Monoclonal , Lipopolysaccharides , Pseudomonas Infections , Pseudomonas aeruginosa , Animals , Female , Mice , Antibodies, Bacterial/immunology , Antibodies, Monoclonal/immunology , Bacterial Adhesion , Bacterial Load/immunology , Convalescence , Inflammation Mediators/immunology , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/immunology , Pneumonia, Bacterial/immunology , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/prevention & control , Pseudomonas aeruginosa/immunology , Pseudomonas Infections/immunology , Pseudomonas Infections/microbiology , Pseudomonas Infections/prevention & control , Sepsis/immunology , Sepsis/microbiology , Sepsis/prevention & control
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