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Biomedical subjects

A Soto

Publications and source records attributed to A Soto.

6 recordsLinked to original sources

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the first-line therapy for high-grade non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence due to immune evasion. We identify HLA-E and NKG2A as mediators of adaptive resistance involving chronic activation of NK and T cells in BCG-unresponsive tumors. Prolonged IFN-γ exposure enhances HLA-E and PD-L1 expression on recurrent tumors, accompanied by the accumulation of NKG2A+ NK and CD8 T cells. HLA-Ehigh tumor cells preferentially cluster near CXCL12-rich stromal regions with dense effector cell presence, underscoring a spatially segregated tumor architecture. Although cytotoxic lymphocytes retain effector potential, their activity is restrained by HLA-E/NKG2A and PD-L1/PD-1 pathways located in their immediate neighborhood within the bladder tumor microenvironment. These data reveal a spatially organized immune escape program that limits anti-tumor immunity. Our findings support dually targeting NKG2A and PD-L1 checkpoint blockade as a rational, bladder-sparing strategy for patients with BCG-unresponsive NMIBC.

BCG-unresponsive

Classification of coryneform bacteria associated with human urinary tract infection (group D2) as Corynebacterium urealyticum sp. nov.

Urealytic strains of coryneform bacteria that are designated Corynebacterium group D2 and are isolated from human urine are a cause of urinary tract infections. Cell wall and lipid analyses confirmed that these organisms are members of the genus Corynebacterium but can be separated from other species in the genus on the basis of DNA base composition and DNA-DNA hybridization values. Biochemically, strains in this taxon can be distinguished from other Corynebacterium spp. by their failure to produce acid from carbohydrates, by their failure to reduce nitrates, and by their ability to hydrolyze urea. We regard these bacteria as a new species of the genus Corynebacterium and propose the name Corynebacterium urealyticum. The type strain is strain NCTC 12011 (= ATCC 43042).

Base Composition

A numerical analysis of ribosomal RNA gene patterns for typing clinical isolates of Corynebacterium group D2.

Restriction digest fragments of DNA from 46 clinical isolates identified as Corynebacterium group D2, were separated by electrophoresis, Southern blotted onto nylon membranes and hybridized to a ribosomal RNA gene probe. The resulting band patterns were subjected to unweighed pair-group cluster analysis. Representative strains from the main clusters were compared with similarly prepared band patterns from type strains of human Corynebacterium species. The results indicate that strains identified as Corynebacterium group D2 represent a unique taxon and that computer-assisted analysis of rRNA gene restriction fragment polymorphism (ribotyping) could be a useful technique in epidemiological studies of these bacteria.

Bacterial Typing Techniques

Electrocardiographic changes after adriamycin chemotherapy.

The electrocardiograms of 146 patients with metastatic carcinoma of the breast were reviewed before, during, and after the patients received Adriamycin (Doxorubicin) chemotherapy (AD). The most significant electrocardiographic change occurred in the amplitude of the QRS voltage. Seven patients developed cardiomyopathy after AD and showed a significant decrease in QRS voltage. This decrease, however, was more severe at the onset of congestive heart failure that at conclusion of Adriamycin. In 35 patients with pleural effusion, there was an inverse relation between the extent of the effusion and the amplitude of QRS voltage in the absence of congestive heart failure. These results indicate that 1) the sudden and relatively severe decrease in QRS voltage with the onset of CHF limits the value of this ECG criterion for predicting early Adriamycin toxicity, and 2) caution should be exercised in the interpretation of QRS voltage changes in patients with significant pleural effusion.

Breast Neoplasms

Acute cardiac toxicity of antineoplastic agents as the first manifestation of pheochromocytoma.

A 47-year-old male with histiocytic lymphoma and no previous history of heart disease developed significant fluctuations of blood pressure, electrocardiographic evidence of myocardial ischemia, and life-threatening arrhythmia after the first dose of BACOP (bleomycin, adriamycin, cyclophosphamide, Oncovin, and prednisone) chemotherapy. The presence of pheochromocytoma was suspected, and it was demonstrated by elevated urinary metanephrines, catecholamines, and vanillylmandelic acid, and finally confirmed on autopsy. The possible role of chemotherapeutic agents in stimulating excessive catecholamine release, thus causing transient cardiac injury, is suggested.

Adrenal Gland Neoplasms