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  • Original Article

    Immunological Characteristics between αβ TDC and γδ TDC Cells in the Spleen of Breast Cancer-Induced Mice

    Rev Bras Ginecol Obstet. 2021;43(5):368-373

    Summary

    Original Article

    Immunological Characteristics between αβ TDC and γδ TDC Cells in the Spleen of Breast Cancer-Induced Mice

    Rev Bras Ginecol Obstet. 2021;43(5):368-373

    DOI 10.1055/s-0041-1730286

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    Abstract

    Objective

    To evaluate the antitumoral role of γδ TDC cells and αβ TDC cells in an experimental model of breast cancer.

    Methods

    Thirty female Balb/c mice were divided into 2 groups: control group (n=15) and induced-4T1 group (n=15), in which the mice received 2 x 105 4T1 mammary tumor cell line. Following the 28-day experimental period, immune cells were collected from the spleen and analyzed by flow cytometry for comparison of αβ TDC (TCRαβ+ CD11c+MHCII+) and γδ TDC (TCRγδ+CD11c+MHCII+) cells regarding surface markers (CD4+ and C8+) and cytokines (IFN-γ, TNF-α, IL-12 and IL-17).

    Results

    A total of 26.53% of γδ TDC- control group (p<0.0001) - the proportion of αβ TDC was lower in splenic cells than γδ TDC; however, these 2 cell types were reduced in tumor conditions (p<0.0001), and the proportion of IFN-γ, TNF-α, IL-12 and IL-17 cytokines produced by γδ TDC was higher than those produced by αβ TDC, but it decreased under conditions of tumor-related immune system response (p<0.0001).

    Conclusion

    Healthy mice engrafted with malignant cells 4T1 breast tumor presented TDC with γδ TCR repertoire. These cells express cytotoxic molecules of lymphocytes T, producing anti-tumor proinflammatory cytokines.

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    Immunological Characteristics between αβ TDC and γδ TDC Cells in the Spleen of Breast Cancer-Induced Mice
  • Original Article

    Loss of Ovarian Function Results in Increased Loss of Skeletal Muscle in Arthritic Rats

    Rev Bras Ginecol Obstet. 2016;38(2):56-64

    Summary

    Original Article

    Loss of Ovarian Function Results in Increased Loss of Skeletal Muscle in Arthritic Rats

    Rev Bras Ginecol Obstet. 2016;38(2):56-64

    DOI 10.1055/s-0035-1571265

    Views3

    Objective

    We studied the effects of loss of ovarian function (ovariectomy) onmuscle mass of gastrocnemius and themRNA levels of IGF-1, atrogin-1, MuRF-1, andmyostatin in an experimental model of rheumatoid arthritis in rats.

    Methods

    We randomly allocated 24 female Wistar rats (9 weeks, 195.3±17.4 grams) into four groups: control (CT-Sham; n = 6); rheumatoid arthritis (RA; n = 6); ovariectomy without rheumatoid arthritis (OV; n = 6); ovariectomy with rheumatoid arthritis (RAOV; n = 6). We performed the ovariectomy (OV and RAOV) or Sham (CTSham or RA) procedures at the same time, fifteen days before the rheumatoid arthritis induction. The RA and RAOV groups were immunized and then were injected with Met- BSA in the tibiotarsal joint. After 15 days of intra-articular injections the animals were euthanized. We evaluated the external manifestations of rheumatoid arthritis (perimeter joint) as well as animal weight, and food intake throughout the study. We also analyzed the cross-sectional areas (CSA) of gastrocnemius muscle fibers in 200 fibers (H&E method). In the gastrocnemius muscle, we analyzed mRNA expression by quantitative real time PCR followed by the Livak method (ΔΔCT).

    Results

    The rheumatoid arthritis induced reduction in CSA of gastrocnemius muscle fibers. The RAOV group showed a lower CSA of gastrocnemius muscle fibers compared to RA and CT-Sham groups. Skeletal muscle IGF-1 mRNA increased in arthritics and ovariectomized rats. The increased IGF-1 mRNA was higher in OV groups than in the RA and RAOV groups. Antrogin-1 mRNA also increased in the gastrocnemius muscle of arthritic and ovariectomized rats. However, the increased atrogin-1 mRNA was higher in RAOV groups than in the RA and OV groups. Gastrocnemius muscle MuRF-1 mRNA increased in the OVand RAOVgroups, but not in the RA and Shamgroups. However, the RAOV group showed higher MuRF-1 mRNA than the OV group. The myostatin gene expression was similar in all groups.

    Conclusion

    Loss of ovarian function results in increased loss of skeletal musclerelated ubiquitin ligases atrogin-1 and MuRF-1 in arthritic rats.

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    Loss of Ovarian Function Results in Increased Loss of Skeletal Muscle in Arthritic Rats
  • Original Article

    Pathways of IFN-alpha Activation in Patients with Cervical Intraepithelial Neoplasia (CIN)

    Rev Bras Ginecol Obstet. 2021;43(9):682-689

    Summary

    Original Article

    Pathways of IFN-alpha Activation in Patients with Cervical Intraepithelial Neoplasia (CIN)

    Rev Bras Ginecol Obstet. 2021;43(9):682-689

    DOI 10.1055/s-0041-1735301

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    Abstract

    Objective

    The aim of the present study was to compare the local and systemic expression of the factors linked to the interferon alpha (IFN-α) activation pathway in different degrees of cervical intraepithelial neoplasia (CIN) and cervical cancer.

    Methods

    A total of 128 patients with CIN I, CIN II, CIN III and cervical cancer was evaluated. The real-time polymerase chain reaction (RT-PCR) technique was used to evaluate the gene expression of IFNR1, IFNR2, IFN-α, oligoadenylate synthase (2’5′OAS), cytokine signal suppressor 1 (SOCS) 1, SOCS3, signal transducer and transcription activator 1 (STAT1), and IRF9 from 128 biopsies. A total of 46 out of 128 samples were evaluated by flow cytometry for IFNAR1, IFNAR2, STAT1, IRF7 and IFN-α in peripheral blood cells.

    Results

    Patients with CIN II and III (63 samples) had a low local expression of IFNR1, but not IFNR2. Patients with some degree of injury showed high expression of SOCS1 and SOCS3. Systemically, patients with CIN II and III (20 samples) had a significant increase in IFNR1, IFNR2, STAT1, IRF7, and IFN-α in helper, cytotoxic T lymphocytes, and in monocytes.

    Conclusion

    Patients with high-grade lesions have increased systemic expression of IFN-α and its activation pathways in helper and cytotoxic T lymphocytes, as well as in monocytes due to an exacerbation of the immune response in these patients. This phenomenon is not accompanied by resolution of the lesion due to a defect in the IFN-α activation pathway that revealed by low local IFNAR1 expression and high local expression of SOCS1 and SOCS3.

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    Pathways of IFN-alpha Activation in Patients with Cervical Intraepithelial Neoplasia (CIN)

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