[Situation and Problems of Activities for Cancer Cooperative Treatment in Kumamoto].

The Consultation Support and Information Providing Committee, which is a subsidiary organization of the Kumamoto Cancer Medical Cooperation Council, created a critical path called"my medical chart,"which is used in Kumamoto prefecture jointly. The path was implemented in 2009 at designated cancer hospitals. For promoting cancer consultation support centers and nurturing cancer counselors, the Cancer Special Counselor Working Group was formed, and activities were initiated. These activities of the Committee resulted in an increased number of patients visiting the designated cancer hospitals. The number of medical cooperations using"my medical chart"exceeded 4,800. A disparity was also observed in cancer treatment, such as surgery, radiotherapy, and chemotherapy. We investigate the situation of cancer treatment and report current problems and future issues.

Achromatic wave plate in THz frequency region based on parallel metal plate waveguides with a pillar array.

We demonstrated an achromatic wave plate based on parallel metal plate waveguides in the high THz frequency region. The metal plates have periodic rough structures on the surface, which allow slow transverse magnetic wave propagation and fast transverse electric wave propagation. A numerical simulation showed that the height of the periodic roughness is important for optimizing the birefringence. We fabricated stacked metal plates containing two types of structures by chemical etching. An array of small pillars on the metal plates allows higher frequency optimization. We experimentally demonstrated an achromatic quarter-wave plate in the frequency region from 2.0 to 3.1 THz.

Achromatic THz wave plate composed of stacked parallel metal plates.

We propose a simple achromatic terahertz wave plate composed of stacked parallel metal plates with a hole array. It consists of an ensemble of designed parallel plate waveguides; the high and low propagation speeds of waves in TE and TM waveguide modes with the same group velocity cause a constant phase difference over a wide frequency region. Using that wave plate, we obtained intense single- and multi-cycle THz pulses with circular polarization.

Mutual contribution of Pten and estrogen to endometrial carcinogenesis in a PtenloxP/loxP mouse model.

OBJECTIVE: An association between estrogen and the risk of type 1 endometrial carcinoma, which shows frequent mutations in the Pten tumor suppressor gene, has consistently been found in many studies. However, such tumors usually arise in perimenopausal or postmenopausal women with decreased serum estrogen levels. This study aimed to reveal the contributions of estrogen to endometrial carcinogenesis in a mouse model of endometrial carcinoma initiated by conditional targeting of Pten. METHODS: The Cre-loxP system was used to achieve Pten inactivation within mouse endometrial epithelium. We delivered a recombinant adenovirus vector expressing Cre recombinase to the endometrial cavity of the Pten mice that had been ovariectomized at 10 weeks old. Mice were subcutaneously injected with 17ß-estradiol (E2) or vehicle, followed by injection of the adenovirus. Two weeks after adenovirus injection, the entire endometrium was analyzed. RESULTS: Mice that did not receive E2 injection notably developed endometrial neoplasia, complex atypical hyperplasia, or carcinoma (7/8, 87.5%). In contrast, hyperplastic but nonneoplastic endometrium was observed in E2-treated mice. In these E2-treated mice, immunohistochemistry revealed that Pten-null glandular epithelial cells clonally proliferate among the hyperplastic endometrium. CONCLUSIONS: The results of this study suggest that estrogen clonally proliferates Pten-null epithelial cells together with surrounding cells, and depletion of estrogen induces predominant growth of Pten-null cells with estrogen-independent capabilities, resulting in abnormal structure of the glandular cells and subsequent neoplasia. This phenomenon might explain why the incidence of human endometrial carcinoma increases with perimenopausal or postmenopausal status, which represents declining ovarian function. Our model mice have partially resolved the issue of endometrial Pten- and estrogen-related carcinogenesis and have potential to represent a valuable tool for developing novel therapies against this carcinoma.

Long-term oncological outcomes of ovarian serous carcinomas with psammoma bodies: a novel insight into the molecular pathogenesis of ovarian epithelial carcinoma.

A two-tier system in which ovarian epithelial carcinomas are subdivided into type I and type II tumors has been proposed on the basis of recent molecular pathogenesis findings. Type I tumors, unrelated to tumor protein p53 (TP53) mutations, show favorable prognosis in a slow step-wise process, whereas type II tumors, related to TP53 mutations, contribute to poor prognosis. Ovarian serous carcinomas with excessive psammoma bodies behave like type I tumors. However, their etiology and prognostic significance remain obscure. The objective of the present study was to evaluate the characteristic features and potential relevance of psammoma bodies to the clinical outcome of 44 patients with serous carcinomas with long-term follow-up. The 5- and 10-year survival rates were significantly different between the serous carcinomas with less than 5% area of psammoma bodies and those at least 5% area (P < 0.01). All tumors with at least 5% area were both diploid and immunohistochemically negative for TP53 mutations. All patients with these tumors, including eight with International Federation of Gynecology and Obstetrics (FIGO) stages III or IV disease, survived more than 5 years and their 10-year survival rate was 76%. In multivariate analysis using clinical parameters, the apparent existence of psammoma bodies was an indication to view serous carcinomas as type I tumors with long-term survival. Our results suggested that the formation of psammoma bodies is associated with increased apoptotic tumor cell death related to normal TP53 function. The pathological findings of psammoma bodies might contribute to the consideration of pathogenesis and to the development of prognostic prediction rules for serous carcinomas.

Involvement of M2-polarized macrophages in the ascites from advanced epithelial ovarian carcinoma in tumor progression via Stat3 activation.

Ascites macrophages in advanced epithelial ovarian cancer (AdEOC) are involved in cancer metastasis and progression by modifying the tumor microenvironment. However, the precise mechanisms of cell-to-cell interaction between macrophages and tumor cells are still unclear. This study focused on the activation of signal transducer and activator of transcription 3 (Stat3) which is a critical signal transduction molecule at a point of convergence for numerous oncogenic signaling pathways as well as controlling the M2-poralization of macrophages. AdEOC ascites, in which high concentration of interleukin (IL)-6, IL-10, growth-related oncogene-alpha and vascular endothelial growth factor were detected, stimulated the proliferation of SKOV3 cells, a human ovarian cancer cell line. The simultaneous blocking of IL-6 and IL-10 by neutralizing antibodies suppressed ascites-induced tumor cell proliferation. Stat3 activation in SKOV3 cells was induced by co-culture with macrophages especially with macrophage colony stimulating factor-primed M2 macrophages but lesser extent with granulocyte-macrophage colony stimulating factor-primed immature macrophages. Cyclin-D1 expression in SKOV3 cells was also significantly induced by co-culture with macrophages. Blocking of Stat3 in macrophages by small interfering RNA inhibited the production of IL-6 and IL-10 by macrophages, and suppressed Stat3 activation and cyclin-D1 induction in co-cultured SKOV3 cells. Stat3 activation in SKOV3 cells was abrogated by simultaneous neutralization of IL-6 and IL-10. These results indicate that Stat3 activation by IL-6 and IL-10 plays an important role in cell-to-cell interaction between tumor cells and macrophages in the ascites of AdEOC.

Broadband and high power terahertz pulse generation beyond excitation bandwidth limitation via chi2 cascaded processes in LiNbO3.

We proposed a novel THz generation technique beyond the limitation of the input optical pulse width, based on phase modulation via cascaded chi((2)) process. When intense THz electric field generated by optical rectification lies in electro-optic (EO) crystal, emitted THz field gives phase modulation to the optical excitation pulse. The phase modulation causes excitation pulse narrowing and consequently gives rise to the enhancement of conversion efficiency and THz wave bandwidth broadening. We experimentally realize this generation technique with high chi((2)) EO crystal LiNbO(3) and with subpicosecond pulse from Yb-doped fiber laser. It opens new concept of THz technologies.

High-resolution time-of-flight terahertz tomography using a femtosecond fiber laser.

High-resolution tomographic imaging is demonstrated using a reflection-type terahertz time-domain spectroscopy. To realize a practical system for general use, a robust all-fiber laser was used as the pump light source. Broadband terahertz waves were generated with the combination of optical pulses compressed to 17 fs using optical fibers and a DAST crystal. Using deconvolution signal processing, the wideband spectrum of the generated terahertz waves provided high-axial resolution leading to successful imaging of a multilayered structure containing a 2-microm-thin GaAs layer. To our knowledge, this is the first demonstration of terahertz tomographic imaging of such a thin layer.

Generation and detection of broadband coherent terahertz radiation using 17-fs ultrashort pulse fiber laser.

We describe the generation and detection of broadband terahertz radiation using an all-fiber laser. Optical pulses from a mode-locked fiber laser oscillator are compressed using nonlinear and dispersion effects induced in optical fibers, and 17-fs optical pulses with 170-kW peak power are generated at the wavelength region around 1.5 microm. By injecting these pulses into an organic crystal DAST (4-N, N-dimethylamino-4'-N"-methyl-stilbazolium tosylate), broadband terahertz field is radiated at 0.1-25 THz. The frequency region exceeding 20 THz is achieved with a fiber laser for the first time.

Structural changes and cell properties of human ovarian surface epithelium in ovarian pathophysiology.

The surface epithelial cells of the ovary, which are modified peritoneal cells, form a single, focally pseudostratified layer. The Müllerian ducts differentiate after invagination of the coelomic mesothelium over the gonadal ridges during the 6th week of embryonic life. On the basis of the embryologically putative Müllerian potential of this epithelium, endometriosis can be explained by coelomic metaplasia from the peritoneum, including ovarian surface epithelium. Some pelvic endometriosis specimens have shown that epithelial cells on the ovary or pelvis are serially changed to endometriotic gland cells. Immunohistochemistry as well as scanning electron microscopy also reinforce the light-microscopical findings. A three-dimensional culture system demonstrated that human ovarian surface epithelial cells exhibited a glandular-stromal structure when they were cocultured with endometrial stromal cells in an estrogen-rich environment. Ovarian carcinomas in the epithelial-stromal category are thought to arise from the surface epithelium and its inclusions. The ovarian surface epithelium is physiologically involved in follicular rupture, oocyte release, and the subsequent repair of follicle wall during reproductive age. Simultaneously, ovulation may cause a loss of integrity of the surface epithelium, followed by accumulation of multiple mutations. The cortical invagination, surface stromal proliferation, and Müllerian differentiation of these cells are likely not to be an early step in the cancer development. However, the inclusion cysts are closely related with carcinogenesis because they are significantly more common in ovaries contralateral to those containing epithelial cancers than in control ovaries. As an in vitro study, ovarian carcinoma cell lines were established from simian virus 40 large T antigen-transformed human surface epithelial cells of the ovary. Further investigations of these cell lines may lead to insights into the preneoplastic and early stages of carcinomas. To clarify the pathogenesis of endometriosis and epithelial ovarian cancer, specifically designed studies of ovarian surface epithelium are required.

Nondestructive analysis of structure and components of tablet coated with film by the usage of terahertz time-domain reflection spectroscopy.

Nondestructive analysis of tablet is of great importance from the aspect of productivity and safety. In terahertz (THz) region, however, the analysis of core of coated tablet has not been progressed. In this study, we have measured a flat-surface push-pull osmotic pump tablet, having no orifice, having bilayer core and a coating film layer. The bilayer core was made from the drug layer and the push layer, and acetaminophen was contained in the drug layer as a model drug. To study its structure and components, we have obtained reflection spectra from the drug layer side and the push layer side measurements using THz time-domain reflection spectroscopy (THz-TDRS). From these results, detection of the peak of acetaminophen in the spectrum from the drug layer side measurements was confirmed. We have made ridges approximated toward the peak using a general method of linear regression analysis in both spectra. Two-sample t-test was applied to their gradients, and significant difference between the drug layer and the push layer was shown. These results suggested that THz-TDRS is applicable to the analysis of structure and component of a coated tablet.

Endometrioid adenocarcinoma arising in adenomyosis: elucidation by periodic magnetic resonance imaging evaluations.

There are several case reports of adenocarcinomas developing within adenomyosis. However, there is no report demonstrating the natural course from adenomyosis to adenocarcinoma. We report a patient (a 41-year-old Japanese woman) who was observed every 6 months after being diagnosed with adenomyosis at our University Hospital. Although she went through menopause at age 51, she occasionally complained subsequently of abnormal genital bleeding. Eleven years after the initial diagnosis, endometrial cytology revealed the presence of malignant cells. Pelvic magnetic resonance imaging (MRI) demonstrated replacement of the adenomyotic lesion by a poorly demarcated lesion, compared to the findings on prior MRI. Consequently, we performed a modified radical hysterectomy and pelvic lymph node dissection, under a presumptive diagnosis of adenocarcinoma arising in adenomyosis. Histological diagnosis revealed an endometrioid adenocarcinoma (G3) transformed from adenomyotic epithelium, which was classified, according to the International Federation of Gynecology and Obstetrics, as stage Ic, pT1cN0M0. In this patient, periodic MRI evaluations, in conjunction with pathological examination, identified the transformation from adenomyosis to adenocarcinoma.

Terahertz time-domain spectroscopy of amino acids and polypeptides.

Frequency-dependent absorption coefficients and refractive indices of amino acids (glycine and l-alanine) and polypeptides (polyglycine and poly-l-alanine) in the wavenumber region from 7 to 55 cm(-1) were measured by terahertz time-domain spectroscopy. A vibrational band was observed at 45.5 cm(-1) for polyglycine, which was assigned as an interchain mode. The reduced absorption cross sections of the amino acids and polypeptides show power-law behavior. The exponents are different between the monomers and polymers, and those of the two polypeptides suggest that the time dependences of the total dipole moments are similar in the timescale of subpico- to picoseconds.

Roles of luteinizing hormone/chorionic gonadotropin receptor in anchorage-dependent and -independent growth in human ovarian surface epithelial cell lines.

Epithelial ovarian carcinomas are thought to arise from cells of ovarian surface epithelium (OSE) covering the free surface of the human ovary. Two immortalized human cell lines, OSE2a (non-tumorigenic) and OSE2b-2 (tumorigenic), were previously established from normal OSE cells of a reproductive-age patient. In the present study, we found that expression of luteinizing hormone (LH)/chorionic gonadotropin (CG) receptor (LH/CGR) is present in OSE2a cells and absent in OSE2b-2 cells. In OSE2a cells, a low concentration (10(3) mIU/ml) of CG enhanced anchorage-dependent growth via up-regulation of insulin-like growth factor-1 (IGF1), whereas a high concentration (10(5) mIU/ml) of CG induced anchorage-independent growth and down-regulation of IGF1 expression. To investigate involvement of other genes in LH/CGR-related tumorigenicity, we compared cDNA expression arrays of OSE2a and OSE2b-2 cells, and found that the following genes had lower expression in OSE2b-2 than in OSE2a: integrin beta 1, intercellular adhesion molecule-1 (ICAM1), and Waf1/Cip1. Subsequent semiquantitative reverse transcription polymerase chain reaction using OSE2a cells showed that expression of integrin beta 1 was down-regulated by a high concentration (10(5) mIU/ml) of CG. These results suggest that LH/CGR affects anchorage-dependent and -independent growth by mediating up- and down-regulation of IGF1 and integrin beta 1. Repetitive and excessive activation of LH/CGR may cause genetic alteration of its signal transduction pathway, resulting in stimulation of growth of OSE cells, initiation of ovarian carcinogenesis, and cancer progression.

High-energy, all-solid-state, ultraviolet laser power-amplifier module design and its output-energy scaling principle.

We demonstrate that a coaxially pumped, large-aperture ultraviolet power-amplifier module with solid-state tunable laser medium Ce(3+):LiCaAlF6 has 98-mJ, 290-nm, and 3-ns output pulses with a sufficient extraction efficiency of 25%. The detailed information of design parameters, including the gain-coefficient dependence on pump condition, is successfully accumulated for further energy scaling for a terawatt-class ultraviolet chirped pulse amplification laser system or a high-pulse-energy laser system.