Midline cutaneous anomalies of the craniospinal axis.

Patients with midline cutaneous anomalies of the craniospinal axis can be indicative of underlying embryonic defects, such as neural tube defects. Lack of familiarity with these midline aberrant skin findings may lead to misdiagnosis and delayed treatment. In this review, midline cutaneous anomalies of the craniospinal axis including aplasia cutis congenita, cranial and spinal dysraphism, and other developmental anomalies are explored in detail with emphasis on cutaneous clues to the diagnosis and appropriate workup.

Tumor targeting nanoparticle E749-57-HSP110-RGD elicits potent anti-tumor immune response in a CD8-dependent manner in cervical cancer-bearing mouse model.

Our previous research verified that HSP (heat shock protein) 110 could enhance the anti-tumor effect of HPV16 E749-57 epitope. In this study, to optimize the immunotherapy of this vaccine type, we developed and evaluated the anti-tumor immunity of a nanoparticle vaccine format assembling with E749-57-HSP110 fusion expression plasmid and RGD-GGG-K18 polypeptide. The nanoparticle vaccine was self-assembled from positively charged RGD-GGG-K18 polypeptide and negatively charged fusion expression plasmid pIRES2-3נE7-HSP110-EGFP. The particle size, stability, expression of E749-57-HSP110 fusion protein and the target ability of nanoparticle were determined, respectively. Specific CTL responses were determined by E7 tetramer staining and cytotoxicity assay in TC-1 tumor-bearing mice (CD4/CD8 knockout). The preventive and therapeutic experiments of nanoparticle vaccine were investigated in TC-1 tumor-bearing mice. Results showed that the RGD-GGG-K18 polypeptide and pIRES2-3נE7-HSP110-EGFP plasmid self-assembled nanoparticles about 100 nanometers in diameter when the charge ratios of peptide/plasmid were 2. The nanoparticles effectively entered TC-1 cells directed by RGD target-peptide, and correctly expressed the E7-HSP110 fusion protein. The HSP110 effectively facilitated nanoparticles activating CD8+T cells than nanoparticles without HSP110, including the CD8+ T cell number and the IFN-γ level; in contrast, the CD4+T cells immune response remained indiscriminate among the mice groups. This nanoparticle formulation inhibited tumor growth and prolonged the survival duration in the prophylactic and therapeutic mouse models. Therefore, the RGD-based tumor-targeting nanoparticle expressing E749-57-HSP110 fusion protein can efficiently evoke anti-tumor activity and thus suggests it might be a favorable candidate for cervical cancer immunotherapy.

Systemic Epstein-Barr virus-positive T-cell lymphoma of childhood.

We report a case of a 7-year-old Chinese boy who presented with acute fever, multiple oral ulcers, and skin nodules. A diagnosis of systemic Epstein-Barr virus (EBV)-positive T-cell lymphoma of childhood was established using systemic laboratory examination, imaging studies, bone marrow and skin biopsy with immunohistochemistry, and in situ hybridization for EBV-encoded RNA (EBER) and gene rearrangements. Notable features of this case include the absence of pancytopenia and hemophagocytic syndrome as well as spontaneous resolution without chemotherapy for several months; however, the condition relapsed, and the patient died.

Heat shock protein 110 improves the antitumor effects of the cytotoxic T lymphocyte epitope E7(49-57) in mice.

Several strategies have been used to enhance the vaccine-induced immunity of peptide vaccines and effective therapeutic benefits, including the utilization of heat shock proteins (HSP), especially the HSP70 family. HSP110 exhibits a higher binding affinity with protein and is capable of enhancing the immunogenicity of protein antigens; however, whether HSP110 can also increase the efficiency of peptide vaccine remains unclear. Here, we investigated mHSP110 as a chaperone immunoadjuvant to enhance the immune response to HPV16 oncoprotein E7-derived CTL epitope E7(49-57) in a mouse model. We developed the HSP110-E7(49-57) complex and demonstrated that mHSP110 could form complexes with peptide E7(49-57) using FITC-labeled E7(49-57) as the tracer. Inoculation of the mHSP110-E7(49-57) complex was capable of priming strong epitope-specific immune response as determined by its ability to elicit an epitope-specific splenocytes proliferation and a cytotoxic T cell response, and IFNgamma production in splenocytes. Results also showed that immunization with the mHSP110-E7(49-57) complex completely protected mice against subsequent challenge with tumor cells. More importantly, immunization of this complex also significantly inhibited the growth of established tumors and prolonged the survival time of the tumor-bearing animals. Thus, mHSP110-E7(49-57) complex vaccine represents a potentially powerful approach for use in the immunotherapy of cervical cancer associated with HPV16 infection. More importantly, the multi-epitopes derived from E7 and other E proteins can be applied to the strategy described in this study to form a multi-antigenic vaccine to induce an improved antitumor immune response to cervical cancer in the future.