ADC is useful for differentiation of some human brain tumors, particularly DNT, malignant lymphomas versus glioblastomas and metastatic tumors, and ependymomas versus PNETs.

Balanced and restored structural sections across the far-eastem Nepal Himalaya have been constructed in order to determine the structure and evolution of the Himalayan orogenic wedge and the amount of tectonic shortening the region has undergone since the initiation of thrusting along the Main Central Thrust (MCT). The far-eastem Nepal Himalaya is comprised of three distinct, thrust-bound tectonic packages; the Higher Himalayan (Crystalline) thrust sheet, the Lesser Himalayan (Metasediment) thrust package, and the Sub-Himalayan imbricate fan. The Higher Himalayan Crystallines, consisting of kyanite-and sillimanite-bearing gneisses intruded by the Miocene (?) Jannu leucogranites, have been thrust over the Lesser Himalayan Metasediments along the MCT for a distance of 140 rcm to 175 kin. The Lesser Himalayan Metasediments are a 12 km thick unit consisting primarily of phyllites, metaquartzites, and mylonitic augen gneisses in which garnet, biotite and chlorite metamorphic zones are exposed in progressively deeper structural levels. The Lesser Himalayan (Metasediment) thrust package is underlain by a decollement, the Main Detachment Fault (MDF), which lies at a calculated depth of between 6 and 10 km underneath the Mahabharat Lekh, and at a calculated depth of 20 to 25 km north of the Tamar Khola Dome. The Tamar Khola Dome overlies a footwall ramp along the MDF where the MDF cuts upsection through the Lesser Himalayan Metasediments. The Lesser Himalayan thrust package probably has an internal structure aproximating a hinterland-dipping duplex, with the MCT and the MDF corresponding to the roof and floor thrusts, respectively. Both the Tamar Khola Thrust, an out-of-sequence breach thrust, and the Main Boundary Thrust (MBT) are splay thrusts off of the MDF. The Sub-Himalaya, consisting of nonmetamorphosed sedimentary rocks, displays an emergent imbricate fan geometry and is underlain by the southern continuation of the MDF which lies at a depth of 5.5 km 1o 6 km beneath the Siwalik Hills. Folding and thrusting within the Lesser Himalayan thrust package and the Sub-Himalayan imbricate fan have accomodated 45 to 70 km of tectonic shortening. Total north-south shortening across the Higher, Lesser, and Sub-Himalaya of far-eastem Nepal, south of the Tibetan Plateau, has been of the order of 185 km to 245 km and has occurred at an average rate of 7.4 mm to 15.3 mm per year since the initiation of the MCT between 16 and 25 Ma.

Classification of hypothalamic hamartomas into these two categories based on MR findings resulted in a clear correlation between symptoms and the subsequent clinical course.

No abstract

Wnts are secreted ligands that consist of 19 members in humans, regulate cell proliferation, differentiation, motility and fate in many stages including the embryonic stage and tumorigenesis. Wnts bind to cell surface receptors named Frizzleds and LRPs, and transduce their signals through b-catenin-dependent and -independent intracellular pathways. Gliomas are one of the most common intracranial tumors. Gliomas exhibit a progression associated with widespread infiltration into surrounding neuronal tissues. However, the molecular mechanisms that stimulate the invasion of glioma cells are not fully understood. We established two cell lines from human glioma cases and analyzed the expression of all Wnt and Frizzled members in these cell lines and other well-known glioma cell lines by real-time PCR study. The mRNA of Wnt-5a and -7b and Frizzled-2, -6 and -7 were overexpressed in glioma cells. The elevation of Wnt-5a expression was most remarkable. Although Wnt-5a is reported to have oncogenic and antioncogenic activity in several cancers, the role of Wnt-5a signaling in human glioma cells remains unclear. Immunohistochemical study also revealed high expression of Wnt-5a in 26 (79%) of 33 human glioma cases. The positivity of Wnt-5a expression was correlated with the clinical grade. Knockdown of Wnt-5a expression suppressed migration, invasion and expression of matrix metalloproteinase-2 of glioma cells. Reciprocally, treatment with purified Wnt-5a ligand resulted in stimulation of cell migration and invasion. MMP-2 inhibitor suppressed the Wnt-5a-dependent invasion of U251 cells. These results suggested that Wnt-5a is not only a prognostic factor but also a therapeutic target molecule in gliomas for preventing tumor cell infiltration. (Cancer Sci 2011; 102: 540-548) G liomas of astrocytic, oligodendroglial and ependymal origin account for more than 70% of all brain tumors. The most frequent (65%) and most malignant histological type is glioblastoma. Despite advances in surgical and clinical neurooncology, their prognosis remains poor. In a meta-analysis of 12 randomized clinical trails, the overall survival rate of patients with glioblastomas (grade IV) and anaplastic astrocytomas (grade III) was 40% at 1 year and only slightly higher (46%) after combined radiotherapy and chemotherapy.(1) Glioblastomas may develop de novo (primary glioblastoma) or by progression from low-grade or anaplastic astrocytoma (secondary glioblastoma). Various genetic alterations were reported in glioblastoma.(2) Furthermore, glioblastomas are characterized by marked invasiveness and vascularity. Glioma tumor cells often invade beyond the main tumor mass at diagnosis and this makes surgical treatment difficult. Clarification of the molecular mechanism of invasion could be useful in understanding the pathogenesis of glioma.Wnt proteins are a large family of cysteine-rich secreted molecules consisting of at least 19 members in mammals to date. Wnt regulates cell growth, cell motility and cell fate. (3,4) There are at least three distinct i...

Objective: Somatotropinomae are classified as densely and sparsely granulated adenomae, which typically exhibit a perinuclear pattern (PP) and a dot pattern (DP) in cytokeratin (CK) immunostaining respectively. Some exhibit a mixed pattern (MP). We studied the relationship between these somatotropinoma subtypes and their clinico-pathological features. Methods: The study population consisted of 141 Japanese acromegalic patients. We evaluated their clinical presentation and their response to provocation tests with TRH and LHRH and to suppression (octreotide) test. Tumour tissues were subjected to immunostaining for CAM-5.2, MIB-1, CD34, E-cadherin (CDH1) and p53 (TP53). In 43 cases (30 non-DP and 13 DP), we analysed gsp mutations (constitutively activating mutations of the G s a protein that is encoded by GNAS gene). Results: The 141 adenomae were categorised into three subtypes based on their CK staining patterns; 30 (21.3%) exhibited DP, 83 (58.9%) exhibited PP, and 28 (19.9%) exhibited MP. Compared with the other subtypes, DP adenomae were significantly larger, and their E-cadherin expression and response to TRH, LHRH and octreotide challenge were lower. The postoperative cure rate tended to be lower in DP adenomae. gsp mutations were detected in 25 of 43 cases examined (58.1%); 20 of the 30 non-DP (66.7%) and 5 of the 13 DP tumours (38.5%) were affected by the mutation. Conclusion: DP somatotropinomae exhibit characteristic features. Compared with the non-DP subtypes, DP adenomae manifested a larger tumour size, a lower incidence of abnormal responses to TRH and LHRH challenge, a poor response to octreotide test and a lower expression of E-cadherin. gsp mutation was not exclusive for non-DP somatotropinomae.

In the course of 4 years, the size of the incidentalomas increased in 40% of 42 patients and became symptomatic in 20%. During the 5-year follow up, pituitary apoplexy developed in 9.5%. These findings may justify early intervention, especially in young individuals with incidentally found macroadenoma.

Tumor-associated macrophages (TAMs) are frequently found in glioblastomas and a high degree of macrophage infiltration is associated with a poor prognosis for glioblastoma patients. However, it is unclear whether TAMs in glioblastomas promote tumor growth. In this study, we found that folate receptor beta (FR beta) was expressed on macrophages in human glioblastomas and a rat C6 glioma implanted subcutaneously in nude mice. To target FR beta-expressing TAMs, we produced a recombinant immunotoxin consisting of immunoglobulin heavy and light chain Fv portions of an anti-mouse FR beta monoclonal antibody and Pseudomonas exotoxin A. Injection of the immunotoxin into C6 glioma xenografts in nude mice significantly depleted TAMs and reduced tumor growth. The immunotoxin targeting FR beta-expressing macrophages will provide a therapeutic tool for human glioblastomas.