Yuji Aiyoshi

Gene expression profiling identifies platelet-derived growth factor as a diagnostic molecular marker for papillary thyroid carcinoma

Purpose: Cancer diagnostics and therapeutics are often based on clinically relevant markers that are expressed specifically in a malignant tissue at levels higher than in normal tissue. We examined potential markers for papillary thyroid carcinoma (PTC) by monitoring PTC-specific gene expression using cDNA microarray. Experimental Design: Gene expression profiles for PTC tissue, normal thyroid tissue, and healthy peripheral blood cells were compared by use of a human 4000-gene cDNA microarray. Protein expressions of the up-regulated genes in PTC were examined in thyroid tissues by immunohistochemistry. Results: Sixty-four genes were overexpressed in PTC tissue relative to normal thyroid tissue and healthy peripheral blood cells. The genes that were up-regulated in PTC were involved in cell cycle regulation, DNA damage response, angiogenesis, and oncogenesis. Among these genes, basic fibroblast growth factor and platelet-derived growth factor were identified by immunochemical methods as proteins that are specifically expressed at high levels in thyroid neoplasms. Basic fibroblast growth factor, which has been identified as a biomarker for PTC, was overexpressed in 54% of PTC cases, 67% of follicular thyroid carcinomas, and 36% of benign thyroid neoplasms. Platelet-derived growth factor was overexpressed in 81% of PTC cases and 100% of follicular carcinomas, but was immunonegative in normal thyroid tissues and benign thyroid neoplasms. Conclusions: Platelet-derived growth factor may be a potential biomarker for PTC and follicular carcinoma. Expression profile analysis using a microarray followed by immunohistochemical study can be used to facilitate the development of molecular biomarkers for cancer.

Effects of α2-adrenergic action on cyclic AMP levels in canine thyroid slices

Abstract The elevation of cyclic AMP levels induced by TSH in canine thyroid slices was markedly inhibited by norepinephrine. Yohimbine (100 μM), an α 2 -adrenergic blocker, completely abolished the inhibitory effect of norepinephrine. The inhibition by yohimbine was dose-related. Phentolamine, a mixed α-adrenergic blocker, showed similar effects, while prazosin, an α 1 -adrenergic blocker exhibited no such effects. These results indicate that there exist α 2 -adrenergic receptors in canine thyroid glands, which may be involved in thyroid gland functions.

Effects of substance P on thyroidal cyclic AMP levels and thyroid hormone release from canine thyroid slices

A neuropeptide, substance P (1-50 microM) caused a prompt but transient rise in tissue cyclic AMP levels and also increased the release of thyroid hormones from canine thyroid slices. While norepinephrine markedly inhibited the stimulation by TSH of such parameters as reported previously, substance P had no effect. These results suggest that substance P may play a regulatory role in thyroid gland functions in a manner different from norepinephrine.

Interferometric X-Ray Imaging of Breast Cancer Specimens at 51 keV X-Ray Energy

The feasibility of the interferometric X-ray imaging technique is examined for revealing the features of breast cancer specimens. The interferometric X-ray imaging system consisted of an asymmetrically cut silicon crystal, a monolithic X-ray interferometer, a phase-shifter, an object cell, and an X-ray CCD camera. Ten 10-mm-thick formalin-fixed breast cancer specimens were imaged at 51 keV, and these images were compared with absorption-contrast X-ray images obtained at 18 keV monochromatic synchrotron X-ray. The interferometric X-ray images clearly depicted the essential features of the breast cancer such as microcalcification down to a size of 0.036 mm, spiculation, and detailed inner soft tissue structures closely matched with histopathological morphology, while the absorption-contrast X-ray images obtained using nearly the same X-ray dose only resolved microcalcification down to a size of 0.108 mm and spiculation. The interferometric X-ray imaging technique can be considered to be an innovative technique for the early and accurate diagnosis of breast cancer using an extremely low X-ray dose.

A case of metastasis from gastric cancer to the thyroid gland

Metastatic tumors in the thyroid gland are rarely seen in clinical practice. This report describes a case of metastasis from gastric cancer to the thyroid, found five years after removal of the primary gastric lesion. The patient had a large thyroid mass extending to the mediastinum, but there were no obvious metastatic lesions anywhere except in the thyroid. Subtotal thyroidectomy was performed and histological examination revealed the same findings as those of the original gastric cancer. Of additional interest are the findings that led us to believe this metastatic tumor produced alpha-fetoprotein. Seven months following the operation, the patient died suddenly and, although it is difficult to say whether the patient’s survival was prolonged, we believe that the thyroid surgery gave him considerable palliation.

Altered expression patterns of heterogeneous nuclear ribonucleoproteins A2 and B1 in the adrenal cortex.

Several proteins implicated in hormonogenesis of the adrenal cortex have alternatively spliced isoforms, which respond differently to adrenocorticotropic hormone (ACTH). Heterogeneous nuclear ribonucleoproteins A2 and B1 are among the abundant pre-mRNA-binding proteins involved in alternative splicing. We examined the expression of A2 and B1 in normal adrenal cortex and tumors. B1 was variably expressed in the zona fasciculata-reticularis, although A2 was diffusely expressed in the three zones. B1 was more abundant in compact cells than clear cells, and B1 expression was frequent in the zona reticularis, which consists mainly of compact cells. In three kinds of cortical adenomas autonomously producing hormones, B1 was generally overexpressed and there were no significant differences among them. In cortisol-producing tumors, non-tumor parts of the cortex, which were generally atrophic due to low ACTH, had less B1 protein than normal adrenals. These results suggested a correlation between B1 expression and the hormonal activity responding to ACTH. In vitro ACTH stimulation induced a biphasic expression of B1 in an H295R cortical carcinoma cell line, and it paralleled hormonogenesis. Conclusively, B1 expression varied in relation to the hormonal activity responding to the ACTH, and it may provide a key to elucidating the splicing mechanisms involved in hormonogenesis.

The biological characteristics and chemosensitivity of anaplastic thyroid carcinoma transplanted into nude mice

Three xenografts established from three patients with anaplastic thyroid carcinoma were investigated for their biological characteristics and chemosensitivity. The histological and immunohistochemical findings of these tumors were almost the same as those of the original tumors. Although the growth rate of each xenograft was constant, the tumor doubling time varied from 4.8 per 9.0 days, and the labeling indexes, determined using bromodeoxyuridine pulse labeling, varied from 11.4 to 25.1 per cent. The chemosensitivity tests were performed according to the Battle Columbus Laboratories Protocol, with adriamycin, cyclophosphamide, cisplatin, mitomycin C and tegafur administered intraperitoneally to tumor-bearing nude mice in maximum tolerable doses. Tumors with slower growth rates tended to be sensitive to more drugs. Furthermore, cyclophosphamide showed antitumor effects against all the tumors tested. Althouth previous treatments of the original tumors may have affected the results, our results suggest that a more suitable chemotherapy for anaplastic thyroid carcinoma could be developed.

Interventricular methotrexate therapy for carcinomatous meningitis due to breast cancer: a case with leukoencephalopathy

A 46-year-old woman presented with paraplegia and severe lumbago. She had had a radical mastectomy for left breast cancer 10 years earlier, and 6 months prior to presentation she completed CMF chemotherapy for treatment of retroperitoneal metastasis. CT and MRI to identify potential causes of the paraplegia and lumbago showed leptomeningeal carcinomatosis due to dissemination from invasive recurrence of the retroperitoneal tumor. An Ommaya reservoir was inserted, and infusion of intrathecal methotrexate (MTX; 5 mg twice weekly) began. Her clinical symptoms improved after receiving 53 mg MTX. However, after receiving 83 mg MTX, the patient became dizzy from leukoencephalopathy. Although administration of prednisolone mostly resolved her symptom, the patient died 9 months after the diagnosis of carcinomatous meningitis.

Non-invasive lobular carcinoma within a fibroadenoma, a preoperatively diagnosed case

Breast cancer within a fibroadenoma is rare and usually diagnosed postoperatively from pathological specimens. This paper reports a 54-year-old female with non-invasive carcinoma within a fibroadenoma, diagnosed preoperatively. She underwent a medical examination and mastopathy was suspected. On physical examination a mass 2 cm in diameter was palpated in the left breast. Ultrasonography showed a mass with smooth margins and uniform internal echoes, but cytology showed malignancy. Mammography showed a round mass with distinct margins and no calcification. As fibroadenoma, diagnosed by ultrasonography and mammography, and breast cancer, diagnosed by cytology, were not consistent results several core biopsies were performed. Needle biopsy showed proliferation of atypical epithelial cells; breast cancer within a fibroadenoma was diagnosed. MRI showed a circular mass with distinct, smooth margins and in a dynamic study, the mass showed irregular staining and the presence of early staining. Left lumpectomy and dissection of the left axillary lymph nodes was performed. Histological examination showed non-invasive lobular carcinoma occurring within a fibroadenoma

Mass Screening of Breast Cancer by Ultrasound Transmission Technique–Theoretical Considerations

A method of mass screening for breast cancer by ultrasound transmission technique is proposed. The method uses pulsed ultrasound waves that pass through the pressed breast. Distribution of mean velocity of transmission subtracted by a constant, e.g., velocity of ultrasound in water, should be displayed in an image. The feasibility of the method is theoretically discussed with the affirmative results. In this discussion, the thickness of the pressed breast is assumed to be 5×10-2 m, that of a malignant tumour to be 5×10-3 m. The velocity of ultrasound in normal tissue is assumed to be 1430 m/s, that in a tumour to be 1471 m/s.