Targeted attenuation of elevated histone marks at SNCA alleviates α-synuclein in Parkinson's disease.

Epigenetic deregulation of α-synuclein plays a key role in Parkinson's disease (PD). Analysis of the SNCA promoter using the ENCODE database revealed the presence of important histone post-translational modifications (PTMs) including transcription-promoting marks, H3K4me3 and H3K27ac, and repressive mark, H3K27me3. We investigated these histone marks in post-mortem brains of controls and PD patients and observed that only H3K4me3 was significantly elevated at the SNCA promoter of the substantia nigra (SN) of PD patients both in punch biopsy and in NeuN-positive neuronal nuclei samples.

Malignant Hidradenocarcinoma in the Lower Extremity: A Case Report of a Rare Tumor.

Malignant hidradenocarcinomas are rare soft tissue tumors of sweat gland origin. We present the case of a soft tissue, fungating tumor of 15 years' duration of the medial ankle in an 85-year-old male that exhibited malignant features clinically and radiographically. Subsequent punch biopsy revealed a diagnosis of malignant hidradenocarcinoma.

Impact of tumor-derived CCL2 on T cell effector function.

To study the effects of tumor-derived monocyte chemoattractant protein-1 (MCP-1, CCL2) on the anti-tumor immune response we used the 4T1 murine mammary carcinoma which constitutively expresses CCL2. We generated 4T1 that do not express detectable levels of CCL2 and found that the T cell response to the tumors were altered. Lymph nodes draining the CCL2- tumor contained CD62Llo cells that produced greater levels of INF-gamma in response to the tumor than CD62Llo cells from lymph nodes draining a tumor that produced CCL2.

A dual role for tumor-derived chemokine RANTES (CCL5).

To investigate the role of tumor-derived CCL5 (regulated upon activation, normal T cell expressed and secreted, RANTES) in tumor immunity we compared the T cell response to tumors derived from the 4T1 murine mammary carcinoma cell line that express different levels of CCL5. Tumors that expressed low levels of CCL5 exhibited a decrease in the in vivo, but not the in vitro, growth rate. In conjunction with the decreased growth rate the tumors that produced lower levels of CCL5 contained a greater number of tumor infiltrating lymphocytes compared to tumors that express normal levels of CCL5.

Altered chemokine receptor sensitivity in FVBN202 rat neu transgenic mice.

We report here that breast cancer cells from spontaneous tumors that arise in rat neu transgenic mice produce several chemokines capable of acting upon cells of the immune system. Moreover, mice bearing these spontaneous tumors possess splenic T cells as well as CD11c+, CD11b+ and CD19+ cells with an altered sensitivity to recombinant chemokines compared to naïve mice. A comparison between T-cell migration and the level of chemokines produced by the tumor cells revealed that the altered chemotactic activity was not a direct consequence of tumor-derived chemokines.