Correlation of Caveolin-1 Expression with Prognosis in Patients with Gastric Cancer after Gastrectomy.

BACKGROUND: Upregulation of caveolin-1 (Cav-1) expression is correlated with histopathological grade and poor prognosis in several human cancers. However, in gastric cancer, its clinical utility as a useful prognostic molecular marker remains unclear. METHODS: The prognostic importance of Cav-1 expression was retrospectively analyzed by immunohistochemistry in 148 patients with gastric cancer who had undergone radical gastrectomy. RESULTS: Cav-1 expression was positive in 23 (15.5%) patients and negative in 125 (84.5%) patients. Tumor location, tumor grade, lymph node involvement, pT stage, pTNM stage, and the presence of recurrence were found to be significantly associated with Cav-1 expression. The median disease-free survival (DFS) of patients with negative Cav-1 expression was significantly better than that of patients with positive Cav-1 expression (not reached vs. 10.2 months, p < 0.001). Moreover, patients with positive Cav-1 expression had a worse median overall survival (OS) compared to patients with negative Cav-1 expression (14.2 vs. 40.3 months, p = 0.004). In the multivariate analysis, Cav-1 expression (positive vs. negative) was an independent prognostic factor for DFS (p < 0.001, hazard ratio (HR) 2.58) and OS (p = 0.031, HR 1.87), as was lymph node metastasis. CONCLUSION: Our results suggest that positive Cav-1 expression is associated with progression and poor prognosis in gastric cancer patients after radical gastrectomy. Targeting Cav-1 would be a potential option for future gastric cancer treatment.

20 THz-bandwidth continuous-wave fiber optical parametric amplifier operating at 1 µm using a dispersion-stabilized photonic crystal fiber.

We report the experimental demonstration of a continuous-wave all-fiber optical parametric amplifier in the 1 µm band with a record bandwidth of more than 20 THz and a peak gain of almost 40 dB. This is achieved by using a photonic crystal fiber with a high figure of merit and strongly reduced longitudinal dispersion fluctuations. Due to their unique bandwidth and gain characteristics, fiber parametric amplifiers at 1 µm provide an interesting alternative to solid-state or ytterbium-doped fiber amplifiers for ultrafast optical pulse and signal processing.

Phase-matched third-harmonic generation in highly germanium-doped fiber.

Phase-matched third-harmonic generation is demonstrated in a germanium-doped optical fiber. Green light at 514.4 nm is generated in an LP(03) mode when a pump field at ~1543.3 nm is launched into the fiber in the fundamental LP(01) mode. The phase matching is achieved for a particular combination of the germanium doping concentration and the fiber core diameter.

Frequency-selective excitation of guided acoustic modes in a photonic crystal fiber.

We present experimental and numerical results demonstrating the simultaneous frequency-selective excitation of several guided acoustic Brillouin modes in a photonic crystal fiber with a multi-scale structure design. These guided acoustic modes are identified by using a full vector finite-element model to result from elastic radial vibrations confined by the wavelength-scale air-silica microstructure. We further show the strong impact of structural irregularities of the fiber on the frequency and modal shape of these acoustic resonances.

Slow light propagation in a ring erbium-doped fiber.

Slow light propagation is demonstrated by implementing Coherent Population Oscillations in a silica fiber doped with erbium ions in a ring surrounding the single mode core. Though only the wings of the mode interact with erbium ions, group velocities around 1360 m/s are obtained without any spatial distortion of the propagating mode.

White-light cw-pumped supercontinuum generation in highly GeO(2)-doped-core photonic crystal fibers.

GeO(2)-doped-core photonic crystal fibers show greatly enhanced Kerr and Raman responses with respect to pure silica without any significant modification of the group-velocity dispersion curve. We show that such fibers allow a significant improvement of cw-pumped supercontinuum generation. We report for the first time to our knowledge the generation of a white-light cw-pumped supercontinuum spanning from 470 nm to more than 1750 nm.

Self-oscillations in a cascaded Raman laser made with a highly nonlinear photonic crystal fiber.

We report the observation of self-oscillations of the output power in a cascaded Raman fiber laser delivering two Stokes components. Our cascaded Raman fiber laser is made with a highly nonlinear photonic crystal fiber and it oscillates within a Perot-Fabry cavity formed by weak Fresnel reflections from the fiber ends. From our experimental and theoretical study, we identify stimulated Raman scattering as being the physical effect dominant in the emergence of unstable behaviors inside the Perot-Fabry cavity. Mechanisms of laser destabilization are thus found to be very different from polarization mechanisms previously identified as being responsible for unstable behaviors in conventional one-stage Raman fiber lasers [14, 15].

Grating-free Raman laser using highly nonlinear photonic crystal fiber.

We demonstrate a Raman laser made from a grating-free highly-nonlinear photonic crystal fiber. The laser threshold power is lower than 600 mW and laser power characteristics recorded in experiments are accurately described from the usual simplest model dealing only with stationary evolutions of total optical powers [J. Opt. Soc. Am. 69, 803-807 (1979)]. In our theoretical treatment, reflectivity coefficients are fixed parameters, in strong contrast with procedures usually implemented to describe Raman fiber lasers made with fiber Bragg gratings. Experimental investigations of the spectral properties of our grating-free Raman fiber laser evidence that the shape of the Stokes power spectrum remains remarkably Gaussian whatever the incident pump power. Increasing the incident pump power induces a drift of the Stokes wavelength together with a broadening of the Stokes optical spectrum. Investigations on the role of light polarization on laser characteristics show that our grating-free Raman fiber laser behaves as a Raman laser made with a standard polarization maintaining fiber.

Efficient Bragg gratings in phosphosilicate and germanosilicate photonic crystal fiber.

We present ArF laser-induced dynamics of Bragg grating (BG) growths in phosphosilicate-doped or germanosilicate-doped core photonic crystal fibers (PCFs). To this end, we have adapted the technique of H2 loading, usually used in conventional fiber, to the case of microstructured fiber, allowing both the concentration of hydrogen in the PCFs to be kept nearly constant for the time of the exposure and the BG spectra to be easily recorded. We compared the characteristics of BG growths in the two types of PCF to those in conventional step-index fibers. We then conducted a study of the thermal stability of the BGs in PCFs through 30 min of isochronal annealing. At the same time we discuss the role played by the microstructuration and the doping with regard to the grating contrast and the Bragg wavelength stability.

Light transmission in multiple or single subwavelength trefoil channels of microstructured fibers.

We evaluate the trefoil channels present between the holes of microstructured fibers as a potential dense array of small waveguides. In channels with an inner radius of 330nm, calculations indicate possible propagation with a mode waist of ~350nm at lambda=670nm, near to the diffraction limit. Actual measurements have been performed on a 1-meter fiber section, with injection by a microlensed fiber and mapping of output by near-field scanning optical microscopy. They show that light can be output in individual channels or in several of them, depending on the injection. The observed waist is ~500nm, possibly due to experimental widening. Estimated propagation losses are <20dB/m. Since each channel occupies only 2microm2, this structure opens a way to dense parallel optical processing.

Modeling of electron-cyclotron-resonance-heated plasmas

This article describes the behavior of electron-cyclotron-resonance-heated plasmas, with particular attention paid to mirror-confined plasmas, which are of great interest in plasma processing and in highly charged ion production. Using a one-dimensional (in velocity) description of the electron distribution function, we calculate the electron density and confinement time. The theoretical results are compared with experiments, and it is shown that a maximum critical density can be achieved in such plasmas.

Pericallosal lipoma extending through the choroidal fissure: US/CT/MRI correlation.

Choroid plexus lipomas (CPL) are known to be associated with pericallosal lipomas (lipomas of the corpus callosum--LCC). Twenty-six cases have previously been reported. Approximately half of these lipomas are connected via the choroidal fissure (LCC-CPL); this connection is almost always bilateral. We present an unusual unilaterally connected LCC-CPL in a neonate.

Protein synthesis in skeletal muscle of uremic patients: effect of low-protein diet and supplementation with ketoacids.

The purpose of this study was to investigate the modifications of muscle protein synthesis activity in uremic patients fed a low-protein diet and a low-protein diet supplemented with a keto acid-amino acid mixture. The protein synthesis activity was evaluated in vitro on isolated muscle ribosomes incubated in a cell-free medium with tritiated leucine. Simultaneously, nitrogen kinetics and amino acid patterns were examined. Protein synthesis activity is correlated with the protein content of the diet in uremic patients. The keto acid-amino acid supplementation enhances protein synthesis. Variations of protein synthesis can be correlated with the variations of nitrogen balance which implies a major role of protein synthesis activity in muscle protein metabolism. Variations in plasma levels of the essential amino acids, mainly leucine and valine, can be correlated with the variations of protein synthesis activity, and these amino acids seem therefore to be mediators of the dietary effects on protein synthesis in uremia.

Interleukin-2 and lymphokine activated killer (LAK) cells in the treatment of malignant glioma: clinical and experimental studies.

The phenomenon of glioma killing by lymphokine activated killer cells (LAK) was studied. We demonstrate that LAK cells generated by culturing the lymphokine interleukin-2 (IL-2) with peripheral blood lymphocytes from brain tumour patients destroys autologous glioma. The rat 9L glioma model was used to show that LAK killing was tumour-selective as glioma but not syngeneic normal brain tissue was destroyed. The susceptibility of both human and 9L rat glioma to LAK cell killing was markedly diminished by pretreating glioma cells with trypsin or chymotrypsin, but was unaffected by pretreatment with neuraminidase, glycosidases, sodium periodate or hydrocortisone. These results suggest that the cell surface determinant on glioma cells responsible for its tumour selective lysis by LAK is a protein sensitive to trypsin and chymotrypsin. The tumour-selective killing of glioma by LAK in vitro prompted the initiation of a Phase I study in which ten patients with malignant glioma have been treated with direct intracerebral injection of IL-2 or LAK without evidence of systemic or brain toxicity.

Lymphokine activated killer (LAK) cell-mediated lysis of murine glioma: trypsin-chymotrypsin-sensitive glioma protein is responsible for tumor-selective recognition by LAK cells.

The killing of Fischer rat 9L glioma in vitro by lymphokine-activated killer (LAK) cells was studied. LAK cells generated by culturing Fischer spleen cells with recombinant interleukin 2 markedly lysed glioma cells but did not kill syngeneic normal brain tissue in a chromium release microcytotoxicity assay. Susceptibility of glioma to lysis by LAK cells was markedly diminished by pretreating the glioma cells with trypsin or chymotrypsin but was unaffected by pretreatment with neuraminidase, glycosidases, or sodium periodate. These results suggest that LAK cell killing of glioma is probably tumor-selective and that a crucial cell surface determinant on glioma cells responsible for its tumor-selective lysis by LAK is a protein sensitive to trypsin and chymotrypsin.

Interleukin 2-activated cytotoxic lymphocytes in cancer therapy.

LAK are cytolytic lymphocytes with the unique capacity for killing NK-resistant fresh human tumor cells in short-term assays. LAK kill autologous as well as allogeneic tumors with complete cross-reactivity. Initial studies on the classification of LAK conclude that LAK are distinct from the classical NK and T lymphocyte systems, based on a number of criteria including surface phenotype, activation conditions, and a spectrum of susceptible target cells. LAK kill ras oncogene-transfected fibroblasts like they kill fresh tumors. As yet, the target cell determinant responsible for susceptibility to LAK lysis is unknown. Activation of LAK requires only IL 2 and is blocked by monoclonal antibodies to the IL 2 receptor. Because only IL 2 alone is sufficient for LAK activation, we have done in vitro testing to determine whether fresh PBL could be activated in the presence of tumor, as might be desirable in vivo. LAK were activated sufficiently to mediate significant destruction of fresh tumor. We also tested whether LAK could be maintained in the presence of large tumors, providing IL 2 was added. Again, results were positive, suggesting that LAK either recycle or are a self-renewing population that depend on IL 2 for continued functions. Because of these and other findings, we have initiated a clinical protocol to test whether LAK made from the PBL of patients with brain tumor could eliminate residual glioma tumor cells. Autologous LAK plus rIL 2 to maintain lytic ability are injected during surgery. Preclinical studies in a rat glioma model have shown this approach to be safe, and previous in vivo murine studies have concluded that LAK kill tumors in Winn-type lung colony formation tests (Kedar et al. 1982). Much work is needed before we can understand the LAK phenomenon and determine its usefulness in cancer therapy, as well as its inherent biologic role. We hope that this chapter will stimulate both interest and the basic research needed to realize LAK potential.