Pancreatic cancer cells are resistant to the growth-inhibitory and apoptosis-inducing effects of conventional chemotherapeutic agents. There are multiple genetic and epigenetic events during the process of carcinogenesis that enable the cancer cells to avoid normal growth constraints and apoptosis. Investigation of the mechanisms involved has led to multiple strategies that encourage cell death and apoptosis to occur. The pathways involved are summarized in this review, together with some recently developed strategies to promote cell death in this cancer and with a particular focus on the frondoside A, a novel triterpenoid glycoside isolated from the Atlantic sea cucumber, Cucumaria frondosa. Frondoside A inhibited proliferation of AsPC-1 human pancreatic cancer cells in a concentration- and time-dependent manner, as measured by (3)H-thymidine incorporation and cell counting. In concert with inhibition of cell growth, frondoside A induced significant morphological changes consistent with apoptosis. Propidium iodide DNA staining showed an increase of sub-G0/G1 cell population of apoptotic cells induced by frondoside A. Frondoside A-induced apoptosis was confirmed by annexin V binding and TUNEL assay. Furthermore, western blotting showed a decrease in expression of Bcl-2 and Mcl-1, an increase in Bax expression, activation of caspases 3, 7, and 9, and an increase in the expression of the cyclin-dependent kinase inhibitor, p21. These findings show that frondoside A induced apoptosis in human pancreatic cancer cells through the mitochondrial pathway and activation of the caspase cascade. Finally, a very low concentration of frondoside A (10 mug/kg/day) inhibited growth of AsPC-1 xenografts in athymic mice. In conclusion, new chemotherapeutic agents are desperately needed for pancreatic cancer because of the poor responsiveness to currently available treatment options. Frondoside A has potent growth inhibitory effects on human pancreatic cancer cells, and the inhibition of proliferation is accompanied by marked apoptosis. Frondoside A may be valuable for the treatment or chemoprevention of this devastating disease.
analgesic mixture did not affect the MTC needed to elicit contractions in women who received epidurally placed catheters (P = 0.731). The baseline MTC for the 1 patient who received an intrathecal catheter was 1.2 mA, but an adequate test was not determined as the MTC exceeded the protocol limit of 2 mA once the analgesic mixture was administered.This study showed that injecting a low dose of bupivacaine/fentanyl intrathecally does not impact the MTC for catheters that are placed in the epidural space, supporting the idea that the EST acts at the spinal nerve. However, the same level of bupivacaine did affect the MTC when the catheter was placed intrathecally. The level of increase in MTC was impossible to determine, as the protocol limited the applied current to 2 mA. Further study will be needed to confirm the site of action for EST. This technique was also successful in determining the catheter position for epidurals before the test dose was injected.
Abstract:We have studied the purity of entangled photon-pairs generated in a dispersionshifted fiber at various temperatures. Two-photon interference with visibility > 98% is observed at 77K, without subtraction of the background Raman photons. For many quantum information processing applications it is desirable to produce entangled photon-pairs at telecom wavelengths directly in the fiber by use of the fiber's Kerr nonlinearity. Our previous works [1] have pointed out that spontaneous Raman scattering, which gives rise to majority of background photons, prevents one from achieving two-photon interference with unit visibility. In this paper we report on measurements of true coincident counts due to correlated photon-pairs and accidental coincident counts due to the background Raman photons in a dispersion-shifted fiber (DSF) at various temperatures (room, 300 K; dry ice, 195 K; and liquid nitrogen, 77 K). Figure 1(a) depicts our experimental setup. Pump pulses of τ p ≃ 6 ps duration and λ p = 1538.7 nm wavelength arrive at 75.3 MHz rate. A 300m piece of DSF with λ 0 = 1538.7 nm is used. The signal (idler) photons of 1543.5 nm (1533.9 nm) wavelength are detected with total detection efficiency of 9% (7%). With the uncooled and cooled fibers we record coincidence and accidental-coincidence counts for varying pump powers. After subtracting dark counts of detectors we plot the ratio between coincidence and accidental-coincidence counts vs. single counts/pulse as shown in Fig. 1(b). Ratios as high as 111:1 at 77 K (60:1 at 195 K) are obtained compared to 28:1 at room temperature. At 77 K, the maximum ratio is obtained for ≃ 75 µW of pump power, corresponding to signal-idler photon-pair production rate of ≃ 0.01/pulse. A horizontally-polarized pump pulse is split into P H and P V by the half-wave plate (HWP1) placed in front of a polarization beam splitter (PBS1). The clockwise and counter-clockwise pump pulses scatter signal-idler photon-pairs, which are then coherently superimposed through the same PBS1, thus creating the two-photon polarization-entangled state |H i |H s + |V i |V s at the output of PBS1. We record two-photon coincidence counts while varying the relative polarization angles of signal and idler channels. At 77 K we observe two-photon interference with visibility > 98% without subtraction of the accidental counts caused by the background Raman photons, as shown in the inset of Fig. 1(b). The observed high visibility is attributed to the suppression of spontaneous Raman scattering at lower temperatures. The observed visibility is about 95% (91%) at 195 K (300 K).
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