Acute liver failure as an initial manifestation of an infiltrative hematolymphoid malignancy.
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Adult↗
Biomedical subjects
Alyssa Krasinskas
Publications and source records attributed to Alyssa Krasinskas.
Combined antiangiogenic and immune therapy of prostate cancer.
Experimental studies of antiangiogenic or immune therapy of cancer have generated a great deal of optimism. However, the results of clinical testing of these therapies are below expectations. We hypothesized that the antitumor efficacy can be increased when immune destruction of tumor cell is combined with destruction of tumor vasculature by antiangiogenic drugs. In the present study the therapeutic efficacy of combined antiangiogenic and immune therapy has been tested against the highly aggressive, MHC class I negative murine RM1 prostate tumor. SU6668 was used as the antiangiogenic drug and recombinant murine B7.2-IgG fusion protein was used to stimulate T cell-mediated immune destruction of tumor cells. SU6668 is an inhibitor of the tyrosine kinase activity of three angiogenic receptors VEGFR2 (Flk-1/KDR), PDGFRbeta and FGFR1 that play a crucial role in tumor-induced vascularization. Our studies show that B7.2-IgG treatment of mice with established RM1 prostate tumors resulted in a significant inhibition of tumor growth. Both CD4+ and CD8+ T cells were responsible for this effect. SU6668 therapy substantially inhibited tumor vascularization and tumor growth. When tumor-bearing mice were treated with SU6668 in combination with B7.2-IgG, the antitumor effects were substantially higher than in mice treated separately with SU6668 or B7.2-IgG. Prolonged treatment of mice with SU6668 did not inhibit the immunoreactivity of T lymphocytes. On the contrary, T cells from mice treated with a combination of SU6668 and B7.2-IgG showed higher proliferative responses and cytokine production following anti-CD3 stimulation than T cells of mice treated separately with these modalities. These results indicate that antiangiogenic and immune therapies using SU6668 and B7.2-IgG are compatible and manifest complementary antitumor effects. Combined antiangiogenic and immune therapy might represent a new strategy for cancer treatment.
Angiogenesis Inhibitors↗
Performance of the revised Bethesda guidelines for identification of colorectal carcinomas with a high level of microsatellite instability.
CONTEXT: Criteria for microsatellite instability (MSI) testing to rule out hereditary nonpolyposis colorectal cancer were recently revised and include parameters such as age and specific histologic features that can be identified by the pathologist, triggering reflex MSI testing. OBJECTIVE: To review the performance of the revised Bethesda guidelines to identify MSI-positive colorectal cancers. DESIGN: Seventy-five patients with colorectal cancer were included; 68 patients younger than 50 years and 7 patients between 50 and 60 years were selected based on histopathologic criteria. Microsatellite instability testing with the National Cancer Institute--recommended panel and immunohistochemistry for hMLH1 and hMSH2 were performed. Tumors were classified into microsatellite instability high (MSI-H), low (MSI-L), or stable (MSS) categories. RESULTS: Overall, 17 (23%) of 75 colorectal cancer cases were classified as MSI-H, including 13 patients younger than 50 years and 4 patients between 50 and 60 years. Among the MSI-H tumors, 10 (59%) were characterized by loss of hMLH1 and 6 (35%) were hMSH2 negative. Histologic features suggestive of MSI-H phenotype were present in 80% of MSI-H and 35% of MSS/MSI-L tumors. The number of positive lymph nodes was higher in MSS/MSI-L adenocarcinomas (P = .04). CONCLUSIONS: By selecting for age and histologic features, we detected MSI-H tumors in approximately one quarter of colorectal cancer cases meeting the revised Bethesda guidelines and identified 17 MSI-H cases, whereas only 8 would have been recognized by the prior guidelines. These data indicate that reflex testing requested by pathologists based on the revised Bethesda guidelines increases the detection of MSI-H and potential hereditary nonpolyposis colorectal cancer cases.
Adaptor Proteins, Signal Transducing↗
Inflammatory fibroid polyps of the gastrointestinal tract: clinical, pathologic, and molecular characteristics.
Inflammatory fibroid polyp (IFP) of the gastrointestinal tract is an uncommon proliferative lesion. When sampled by biopsy, IFP can be mistaken for various lesions, from granulation tissue to high-grade sarcoma. We present an unusual case of IFP and review a large series of IFPs to characterize clinical, histologic, and molecular features of diagnostic value. A total of 42 IFPs were gathered from the pathology archives of the University of Pittsburgh Medical Center over the past 22 years. Clinical, histopathologic, and immunohistochemical features were collected. A random subset of IFPs (n = 12) underwent microdissection genotyping for a broad panel of tumor suppressor gene-associated mutations (loss of heterozygosity). IFPs occurred in both sexes (male, 17; female, 25) over a broad age range (29-85 years). IFPs varied in size from 0.2 to 8 cm. The stomach (n = 19) was the most common location, followed by large bowel (n = 13) and small bowel (n = 10). Most IFPs displayed typical morphologic features (eosinophils admixed with loose, mature fibrous tissue), and in 2 instances, sampled by biopsy, IFP was confused for sarcoma. All IFPs lacked c-kit staining. No mutations were identified in any IFPs examined. IFP is a clinically underrecognized entity with unique morphologic and immunohistochemical features. On biopsy alone, the differential diagnosis may include sarcoma and other malignancies. The absence of mutational change may help to exclude malignant lesions.
Adult↗