Molecular status of pituitary carcinoma and atypical adenoma that contributes the effectiveness of temozolomide.

There have been several reports of temozolomide (TMZ) treatment of pituitary carcinomas and atypical adenomas. O(6)-methyl-guanine-DNA methyltransferase is not the sole molecule determining the sensitivity to TMZ in pituitary carcinomas and atypical adenomas. The Japan Society of Hypothalamic and Pituitary Tumors study suggests that MSH6, one of mismatch repair pathway enzyme, fulfills a contributory role to the efficacy of TMZ treatment for pituitary carcinomas and atypical adenomas. The preserved MSH6 function might be essential for the responsiveness to TMZ treatment in pituitary carcinomas and atypical adenomas.

Disappearance of gadolinium enhancement in a chemoresistant astrocytoma of the tectum after high-dose interferon beta.

Interferon beta 6 million units per week was administered to a patient with an aggressive astrocytoma in the tectum that was resistant to cisplatin, etoposide, vinblastine, and the oral alkylating agent temozolomide. The tumor was immunopositive for O6-methylguanine-DNA methyltransferase (MGMT). Interferon beta caused the disappearance of the gadolinium-enhanced lesion in the tectum. Interferons have apoptotic and antiangiogenic effects on tumor cells, and the lesion's disappearance may have been induced by complexes of these effects. Administration of interferon beta might have a favorable effect on tectal gliomas that are immunopositive for MGMT and resistant to chemoradiotherapy including temozolomide.

Clinicopathological and molecular histochemical review of skull base metastasis from differentiated thyroid carcinoma.

Skull base metastasis from differentiated thyroid carcinoma including follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) is a rare clinical entity. Eighteen FTC cases and 10 PTC cases showing skull base metastasis have been reported. The most common symptom of skull base metastasis from FTC and PTC is cranial nerve dysfunction. Bone destruction and local invasion to the surrounding soft tissues are common on radiological imaging. Skull base metastases can be the initial clinical presentation of FTC and PTC in the presence of silent primary sites. The possibility of skull base metastasis from FTC and PTC should be considered in patients with the clinical symptoms of cranial nerve dysfunction and radiological findings of bone destruction. A variety of genetic alterations in thyroid tumors have been identified to have a fundamental role in their tumorigenesis. Molecular histochemical studies are useful for elucidating the histopathological features of thyroid carcinoma. Recent molecular findings may provide novel molecular-based treatment strategies for thyroid carcinoma.

Co-transfection of EYFP-GH and ECFP-rab3B in an experimental pituitary GH3 cell: a role of rab3B in secretion of GH through porosome.

Recently, in order to elucidate the role of rab3B in porosome, we have observed the incorporation of rab3B in the secretion of GH through porosome under confocal laser scanning microscopy (CLSM). Transfected cells with GH-EYFP fusion protein and rab3B-ECFP fusion protein were observed under CLSM, which showed the colocalization of EYFP-GH and ECFP-rab3B in the budding configuration of secretory process. These structural and functional images of rab3B imply the incorporation of rab3B in the secretion of GH through porosome.

Long-term remission of cyclic Cushing's disease that was diagnosed and treated surgically in non-active phase.

Cyclic Cushing's disease is a rare clinical entity that is defined as a periodic excessive production of adrenocorticotropic hormone (ACTH) and cortisol. Only 42 cases with cyclic Cushing's disease have been reported in the literature. The diagnosis is very difficult because of the fluctuating secretion of ACTH and cortisol. We report a 78-year-old woman with a pituitary adenoma presenting with cyclic Cushing's disease. In the present case, several interesting issues are pointed out: 1) MRI study detected the presence of an adenoma and selective venous sampling in the cavernous sinus disclosed the hypersecretion of ACTH from a pituitary adenoma. These neuroimaging and endocrinological studies were helpful for the diagnosis, even in the remission phase. 2) The disease was in the long-term remission phase after transsphenoidal surgery despite the high recurrence rate in this clinical entity, although it recurred four years later. Even in the remission phase of cyclic Cushing's disease, meticulous endocrinological and neuroimaging examinations can reveal the presence of a pituitary adenoma, which should be treated surgically.

Peptide-loaded dendritic-cell vaccination followed by treatment interruption for chronic HIV-1 infection: a phase 1 trial.

Immune response enhanced by therapeutic HIV-1 vaccine may control viral proliferation after discontinuation of highly active antiretroviral therapy (HAART). Although which strategies for therapeutic vaccination are feasible remains controversial, application of dendritic cells (DCs) as a vaccine adjuvant represents a promising approach to improving deteriorated immune function in HIV-1-infected individuals. The safety and efficacy of DC-based vaccine loaded with HIV-1-derived cytotoxic T lymphocytes (CTL) peptides were thus investigated in this study. Autologous DCs loaded with seven CTL peptides with HLA-A*2402 restriction were immunized to four HIV-1-infected individuals under HAART. In terms of safety, peptide-loaded DCs were well tolerated, and only mild local and general symptoms were observed during vaccine administration. ELISPOT assays to detect IFN-gamma production in CD8(+) lymphocytes revealed a limited breadth of responses to immunized peptides in two of four participants, but no response in the remaining two participants. Differences in immunological response might be attributable to the fact that responders displayed higher nadir CD4 counts before starting HAART and were immunized with a larger number of DCs per reactive peptide than non-responders. Discontinuation of HAART after vaccination failed to lower viral set points compared to those before starting HAART. This early outcome warrants further exploration to elucidate the therapeutic value of vaccination with DCs in HIV-1 infection.