murine-experimental-model-original-tumor-development-peritoneal

Murine Experimental Model of Original Tumor Development and Peritoneal Metastasis <em>via</em> Orthotopic Inoculation with Ovarian Carcinoma Cells

Epithelial ovarian carcinoma (EOC) is associated with a poor prognosis because it shows peritoneal dissemination. To improve the prognosis, it is ...

Bell Research Center for Reproductive Health and Cancer

Nagoya University Graduate School of Medicine

Reservoir cells latently infected with HIV-1 pose one of the major obstacles that hamper ultimate eradication of HIV-1 from infected patients. In this report, we showed that direct contact with MOLT-4 T cells induced HIV-1 replication in J(22)-HL-60 latently infected cells without any additional stimulus. Neutralization experiments revealed that pro-inflammatory cytokines, whose production was increased following cell-cell contact, were unlikely to be primarily involved in the induced HIV-1 replication. Cell-cell contact, but not soluble components in the culture supernatant, caused a rapid phosphorylation and degradation of IkappaBalpha, which led to elevated NF-kappaB DNA binding activity in J(22)-HL-60 cells. Furthermore, forced expression of a super-repressor form of IkappaBalpha or pretreatment with ritonavir efficiently blocked the activation of NF-kappaB and HIV-1 replication in J(22)-HL-60 cells co-cultured with MOLT-4 T cells. Moreover, either resting or PHA stimulated primary CD4(+) T cells induced HIV-1 replication in J(22)-HL-60 cells in a similar way with that of MOLT-4 cells. These results indicated that direct contact with CD4(+) T cells induced HIV-1 replication in latently infected cells and provide insight into the molecular mechanism of virus release from myeloid progenitor cells latently infected with HIV-1.

Efficient induction of HIV-1 replication in latently infected cells through contact with CD4+ T cells: involvement of NF-kappaB activation.

Cervical cancer is a major global public health care concern and the second most commonly diagnosed malignancy among females worldwide. B7-H4 is an immunoregulatory protein that has been shown to be overexpressed in several types of cancer and is often associated with more advanced disease and poor prognosis. We investigated whether B7-H4 is a prognostic maker for cervical cancer by detecting its expression in cervical cancer specimens. Formalin-fixed, paraffin-embedded tissue blocks from cervical cancer were evaluated for B7-H4 expression by immunohistochemistry with free R software analysis. The intensity of B7-H4 immunoexpression was evaluated according to age, histological type, International Federation of Gynecology and Obstetrics (FIGO) stage, lymphovascular space invasion (LVSI) and lymph node status. We investigated the distribution and expression of B7-H4 in 102 cervical cancer specimens and determined the association between its expression and clinicopathological characteristics, including patient outcomes. Of the 102 specimens, 31 were found to be negative for B7-H4 immunoexpression, whereas 71 were B7-H4-positive. When classified by negative vs. positive expression, B7-H4 was not found to be associated with any of the clinicopathological parameters investigated. A positive B7-H4 expression significantly predicted poor overall survival (OS) when compared to negative expression (P<0.05). In the multivariate analysis, positive B7-H4 expression was identified as an independent prognostic factor for OS (P<0.05). Our data suggested that positive B7-H4 expression may be a useful biomarker in patients with cervical cancer likely to have an unfavorable clinical outcome.

B7-H4 overexpression correlates with a poor prognosis for cervical cancer patients.

Glypican-3 (GPC3) is specifically expressed in ovarian clear cell carcinoma (OCCC), hepatocellular carci-noma (HCC), and melanoma and lung cancer. GPC3 is being explored as a potential candidate for OCCC and HCC immunotherapy. As a tumor-associated antigen, induction of immune response of GPC3 in ovarian cancer remains elusive. We established a GPC3 transgenic mouse ovarian cancer cell line, OV2944-HM-1 (HM-1), and used the intraperitoneal ovarian cancer mouse model to investigate immune response in GPC3-expressing tumor. We found that GPC3 expression in the tumor increased F4/80+CD86+ macrophage (M1) proportion and caused GPC3-specific CD8+ T cell immune responses, and prolonged mouse survival. Our results demonstrated that GPC3 expression induced T cell-mediated immune response in this mouse ovarian cancer model and also provided supportive evidence that GPC3 is an ideal target for ovarian cancer immunotherapy.

Article	Year
Efficient induction of HIV-1 replication in latently infected cells through contact with CD4+ T cells: involvement of NF-kappaB activation. Virology\| PubMed ID: 17222438	2007
B7-H4 overexpression correlates with a poor prognosis for cervical cancer patients. Molecular and clinical oncology\| PubMed ID: 24649336	2014
GPC3 expression in mouse ovarian cancer induces GPC3‑specific T cell-mediated immune response through M1 macrophages and suppresses tumor growth. Oncology reports\| PubMed ID: 24992906	2014

Yoshihiro Koya

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