The pleiotrophin-ALK axis is required for tumorigenicity of glioblastoma stem cells.

Increasing evidence suggests that brain tumors arise from the transformation of neural stem/precursor/progenitor cells. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma. Here we show that anaplastic lymphoma kinase (ALK) and its ligand pleiotrophin are required for the self-renewal and tumorigenicity of glioblastoma stem cells (GSCs). Furthermore, we demonstrate that pleiotrophin is transactivated directly by SOX2, a transcription factor essential for the maintenance of both neural stem cells and GSCs. We speculate that the pleiotrophin-ALK axis may be a promising target for the therapy of glioblastoma.

The critical role of cyclin D2 in cell cycle progression and tumorigenicity of glioblastoma stem cells.

Cancer stem cells are believed to be responsible for tumor initiation and development. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma stem cells (GSCs). However, little is known about the molecular mechanisms of cell cycle regulation that discriminate between GSCs and differentiated glioblastoma cells. Here we show that cyclin D2 is the cyclin that is predominantly expressed in GSCs and suppression of its expression by RNA interference causes G1 arrest in vitro and growth retardation of GSCs xenografted into immunocompromised mice in vivo. We also demonstrate that the expression of cyclin D2 is suppressed upon serum-induced differentiation similar to what was observed for the cancer stem cell marker CD133. Taken together, our results demonstrate that cyclin D2 has a critical role in cell cycle progression and the tumorigenicity of GSCs.

Development of a real-time hand dose monitor for personnel in interventional radiology.

Medical procedures denoted as interventional radiology require operation near an X ray beam, which brings high dose exposures to the operators' hands. For the effectual control of their extremity doses, a prototype of a real-time wrist dosemeter has been developed, hand dose monitor (HDM), based on a single silicon detector. Experiments were performed to test its response to diagnostic X rays. The HDM was highly sensitive and showed a linear response down to doses of a few tens of microsieverts. Though dose rate, energy and angular dependence of the response were observed in some extreme conditions, the HDM was proved to be of practical use if it was appropriately calibrated. Since an HDM enables personnel to check their hand doses on a real-time basis, it would enable medical staff to control the exposure themselves.

Granular cell tumor of the breast: report of a case.

A case of granular cell tumor of the breast in a 43-year-old woman is described. The patient presented with a painless mass in the upper-outer quadrant of her right breast. Mammography showed a spiculated tumor and ultrasonography demonstrated a hypoechoic mass with an irregular border. Magnetic resonance (MR) mammography revealed a homogeneous enhanced mass in T1-weighted images using Gd-DTPA and a ringed high-intensity area around the mass in T2-weighted images. Fine-needle aspiration cytology failed to show any malignant cells. A partial resection of the breast was performed and histological examination revealed a granular cell tumor. Granular cell tumors are generally always benign, but they may be misdiagnosed as malignant tumors because of their mammographic and ultrasonographic findings. MR mammography did not reveal a typical breast cancer in either T1- or T2-weighted images in the present case. This case illustrates the need for care in preoperative examinations in order to avoid overdiagnosis of breast cancer.

Malignant phyllodes tumor of the breast with hypoglycemia: report of a case.

A surgically resected case of giant malignant phyllodes tumor of the breast associated with a hypoglycemic attack is reported. A 54-year-old woman was referred to our hospital with loss of consciousness and a huge chest wall tumor. She was diagnosed as having a malignant phyllodes tumor by core needle biopsy and underwent palliative simple mastectomy because lung metastasis was detected on computed tomography and by other imaging modalities on admission. The preoperative laboratory data revealed a very low fasting blood sugar level of 37 mg/dl. After removal of the tumor, the blood sugar level gradually normalized (90-100 mg/dl) and the plasma insulin-like growth factor-II (IGF-II) level promptly decreased. The IGF-II level of tumor extracts was high (2500 ng/g wet weight) and the majority of atypical cells stained positively for IGF-II immunohistochemically. These findings suggested that the patient's hypoglycemia was associated with IGF-II produced by a giant malignant phyllodes tumor that consumed glucose.

Early Breast Cancer Following Treatment of Myelodysplastic Syndrome: Report of a Case.

A 45-year-old woman was admitted to our hospital complaining of a mass in herleft breast. She had previously been diagnosed with myelodysplastic syndrome(MDS), a type of refractory anemia, based on bone marrow findings and chromosome analysis. She received a preoperative transfusion of fresh packed platelets and a recombinant human granulocyte colony-stimulating factor(rhG-CSF)injection. Left partial mastectomy and axillary lymph nodes dissection were performed to treat early breast cancer. Postoperatively, prophylactic radiotherapy of the residual breast and administration of medroxyprogesterone acetate(MPA)were performed because the tumor tissue was positive for progesterone receptors. She has remained clinically stable, with no evidence of recurrence, for more than three years to date. We report a rare case of breast cancer with MDS, treated with breast-conserving therapy. The strategy of pre- or postoperative platelet transfusion, rhG-CSFinjections, and hormonal therapy (MPA) appears to be suitable treatment for progesterone receptor(PgR)-positive breast cancer patients with MDS.

Relation between estrogen receptor and malignancy of thyroid cancer.

The relationship between the histological grade of dedifferentiation of thyroid cancer and estrogen receptors (ER) was examined immunohistochemically. Thyroid cancers were from postmenopausal females of almost the same mean age (69-73 years old) and within the same period of time (1974-1983). ER immunoreactivity located in the nucleus of the epithelium was found in all 6 well differentiated papillary cancers, and 5 of them (83.3%) showed ER-immunoreactive (ER-IR) cells amounting to 20 or more per visual field (x 100) under a light microscope. Of the 6 cases of poorly differentiated papillary cancer, 5 (83.3%) had 1-19 ER-IR cells per visual field. ER-IR cells were negative in 5 out of 6 cases (83.3%) of anaplastic cancers. Thus, the number of ER-IR cells tended to decrease with the degree of atypism of thyroid cancer (P less than 0.001).

[An immunohistochemical study of estrogen receptors in thyroid carcinoma].

Estrogen receptors immunoreactivity (ER-IR) has been examined in 64 cases of human thyroid carcinomas. ER-IR was found to be located in the nucleus of cancer cells and was detected in 30 (57.7%) of 52 papillary carcinomas that were examined. Eleven cases showing a good number of ER-IR positive cancer cells revealed a lowered EORTC index of under 65, and no ER-IR was found in 12 anaplastic carcinomas. These findings indicate that ER-IR might generally bear a similar reciprocal relationship to the malignancy of a thyroid carcinoma.

Estrogen receptors in gastric adenocarcinoma: a retrospective immunohistochemical analysis.

Estrogen receptors (ER) in human gastric carcinomas were examined immunohistochemically using a specific monoclonal antibody to human ER. ER-immunoreactivity (ER-IR) was positive in 30 (27.8%) of the 108 gastric carcinomas examined. ER-IR was located in the nucleus of cancer cells. The incidence of ER-IR positive gastric carcinoma was not significantly different between male and female cases. However, the positive tumour cells were observed in 28 (39.4%) out of the 71 poorly differentiated adenocarcinoma, the incidence being significantly higher than that in well differentiated adenocarcinoma (p less than 0.01). There was no significant difference in the incidence of ER-IR between scirrhous carcinoma and non-scirrhous poorly differentiated adenocarcinoma. Synchronous expression of ER and epidermal growth factor receptor was found in 8 of the 26 scirrhous carcinomas (30.8%). Patients with ER-IR positive scirrhous gastric carcinomas showed a much worse prognosis than those with ER-IR negative scirrhous carcinomas.

Single fiber electromyography in cat extraocular muscles.

Single fiber electromyography (SFEMG) was carried out in the extraocular muscles (EOMs) of 40 adult cats, and the recordings were analyzed. The small fluctuations of the interpotential interval (IPI), so-called "jitter phenomenon", were represented quantitatively as a mean consecutive difference (MCD). The MCD and the IPI recorded from the orbital layer of the rectus muscles were similar among the 4 rectus muscles: the MCD and the mean IPI measured in 58 motor units from the 4 rectus muscles averaged 25.82 microseconds and 0.94 ms, respectively. These values were similar to those recorded from the oblique muscles. The MCD and IPI were 34.12 microseconds and 1.70 ms, respectively, in the retractor bulbi muscles and 45.54 microseconds and 1.23 ms, respectively, in the triceps muscles. The MCDs of the rectus and inferior oblique muscles were considerably smaller than those in the retractor bulbi and the skeletal muscles.