[Evaluation of Patient Adherence to Anastrozole Therapy for Breast Cancer].

PURPOSE: There are many reports that describe the effectiveness of aromatase inhibitors as endocrine therapy after breast cancer surgery. However, there are few detailed evaluations of patient adherence to anastrozole(ANA)therapy. Here, we evaluated the adherence to ANA therapy in postoperative patients with primary breast cancer. METHODS: We investigated 102 postoperative patients with primary breast cancer without distant metastasis, who received ANA at JCHO Kyusyu Hospital. We calculated the medication continuation rate and disease-free survival at 5 years from the initiation of medication. The reasons for medication discontinuation and alternative drug therapy after ANA therapy discontinuation were also investigated. Re- sults: The 5-year continuation rate of ANA treatment alone was 79%(81/102). The rate of all patients who continued ANA treatment, including 9 who changed to other drugs, was 88%(90/102). The most frequent ANA discontinuation reasons were progressive disease(8 cases), arthritis(5 cases), and nausea(3 cases). The disease-free survival rate was 92%(94/102), and the overall survival rate was 97%(99/102). CONCLUSION: ANA showed a high continuation rate. Adherence of ANA in postoperative patients with breast cancer was well maintained, even when the treatment was changed to other drugs due to adverse events.

Minimum of the order parameter fluctuations of seismicity before major earthquakes in Japan.

It has been shown that some dynamic features hidden in the time series of complex systems can be uncovered if we analyze them in a time domain called natural time χ. The order parameter of seismicity introduced in this time domain is the variance of χ weighted for normalized energy of each earthquake. Here, we analyze the Japan seismic catalog in natural time from January 1, 1984 to March 11, 2011, the day of the M9 Tohoku earthquake, by considering a sliding natural time window of fixed length comprised of the number of events that would occur in a few months. We find that the fluctuations of the order parameter of seismicity exhibit distinct minima a few months before all of the shallow earthquakes of magnitude 7.6 or larger that occurred during this 27-y period in the Japanese area. Among the minima, the minimum before the M9 Tohoku earthquake was the deepest. It appears that there are two kinds of minima, namely precursory and nonprecursory, to large earthquakes.

[Mediastinal Hemangioma with Literature Review;Report of a Case].

A 58-year-old woman visited a local physician for evaluation of collagen disease and screening computed tomography (CT) showed a posterior mediastinal tumor. After referral to our hospital, CT and magnetic resonance imaging (MRI) showed a mass, approximately 2 cm in diameter, located on the right of the 1st thoracic vertebra. Since a neurogenic tumor was suspected, thoracoscopic excision was performed. Surgical findings revealed a tumor between the 1st and 2nd ribs in the close vicinity of the right brachiocephalic vein. We severed blood vessels flowing into the tumor and removed it. The tumor, 25 mm in maximal diameter, was diagnosed as hemangioma by histological examinations. The prevalence of a hemangioma is less than 0.5% of all mediastinal tumors. Since it lacks specific imaging findings, its preoperative diagnosis is quite difficult to establish. Although a hemangioma in the mediastinum is quite rare, it should be included in the differential diagnoses of mediastinal tumors.

The characteristic structure of anti-HIV actinohivin in complex with three HMTG D1 chains of HIV-gp120.

The anti-HIV lectin actinohivin (AH) specifically interacts with HMTG (high-mannose-type glycan), which is attached to the glycoprotein gp120 of HIV-1 in a process in which the three branched mannotriose chains (D1, D2, and D3) of HMTG exhibit different binding affinities, it being estimated that that of D1 is the strongest, that of D3 is weaker, and that of D2 is undetectable. These properties have been ascribed to the stereochemical differences in linkages between the second and the third mannose residues of the three chains. In order to clarify the interaction geometry between AH and the major target D1, an X-ray determination of the crystal structure of AH in complex with D1-which is α(1,2)mannotriose composed of three mannose (Man) residues linked together only by α(1,2) bonding-has been performed. In each of the three D1-binding pockets of AH, two Man residues of D1 are accommodated at zones 1 and 2 in the pocket, in the same way as those found in the α(1,2)mannobiose-bound AH crystals. However, an OMIT map shows poor densities at both ends of the two residues. This suggests the existence of positional disorder of D1 in the pocket: the two zones are each occupied by two Man residues in two different modes, with mode A involving the Man1 and Man2 residues and mode B the Man2 and Man3 residues. In each mode, D1 is stabilized by adopting a double-bracket-shaped conformation through CH⋅⋅⋅O interactions. In mode B, however, the Man1 residue, which is the most sensitive residue to AH binding, protrudes wholly into the solvent region without contacts with AH. In mode A, in contrast, the Man3 residue interacts with the essential hydrophobic amino acid residues (Tyr and Leu conserved between the three pockets) of AH. Therefore, mode A is likely to be the one that occurs when whole HMTG is bound. In this mode, the two hydroxy groups (O3 and O4) of the Man2 residue are anchored in zone 2 by four hydrogen bonds with Asp, Asn, and Tyr residues of AH. In addition, it has been found that an isolated water molecule buried in the hydrophobic long loop bridges between Asp of AH and the hydroxy group of Man2 through hydrogen bonds. The most interesting feature is found in the interaction of the Man1 and Man3 residues with AH. All eight hydroxy groups of the two residues are completely exposed in the solvent region, whereas their hydrophobic parts make contacts with a Leu residue and two Tyr residues so that the shape of D1 and the surface of AH fit well over a wide area. These structural characteristics are potentially useful for development of AH to produce more effective antiretroviral drugs to suppress the infectious expansion of HIV/AIDS and to help expedite an end to the HIV/AIDS pandemic in the near future.

Peculiarity in crystal packing of anti-HIV lectin actinohivin in complex with α(1-2)mannobiose.

Previously, the anti-HIV lectin actinohivin (AH) was cocrystallized with the target α(1-2)mannobiose (MB) in the apparent space group P213. However, three MB-bound AH rotamers generated by ±120° rotations around the molecular pseudo-threefold rotation axis are packed randomly in the unit cell according to P212121 symmetry [Hoque et al. (2012). Acta Cryst. D68, 1671-1679]. It was found that the AH used for crystallization contains short peptides attached to the N-terminus [Suzuki et al. (2012). Acta Cryst. F68, 1060-1063], which cause packing disorder. In the present study, the fully mature homogeneous AH has been cocrystallized with MB into two new crystal forms at different pH. X-ray analyses of the two forms reveal that they have peculiar character in that the space groups are the same, P22121, and the unit-cell parameters are almost the same with the exception of the length of the a axis, which is doubled in one form. The use of homogeneous AH resulted in the absence of disorder in both crystals and an improvement in the resolution, thereby establishing the basis for AH binding to the target MB. In addition, the two crystal structures clarify the interaction modes between AH molecules, which is important knowledge for understanding the multiple binding effect generated when two AH molecules are linked together with a short peptide [Takahashi et al. (2011). J. Antibiot. 64, 551-557].

Inhibition of infection and transmission of HIV-1 and lack of significant impact on the vaginal commensal lactobacilli by carbohydrate-binding agents.

OBJECTIVES: A selection of carbohydrate-binding agents (CBAs) with different glycan specificities were evaluated for their inhibitory effect against HIV infection and transmission, and their interaction with vaginal commensal bacteria. METHODS: Several assays were used for the antiviral evaluation: (i) cell-free virus infection of human CD4+ T lymphocyte C8166 cells; (ii) syncytium formation in co-cultures of persistently HIV-1-infected HUT-78/HIV-1 and non-infected CD4+ SupT1 cells; (iii) DC-SIGN-directed capture of HIV-1 particles; and (iv) transmission of DC-SIGN-captured HIV-1 particles to uninfected CD4+ C8166 cells. CBAs were also examined for their interaction with vaginal commensal lactobacilli using several viability, proliferation and adhesion assays. RESULTS: The CBAs showed efficient inhibitory activity in the nanomolar to low-micromolar range against four events that play a crucial role in HIV-1 infection and transmission: cell-free virus infection, fusion between HIV-1-infected and non-infected cells, HIV-1 capture by DC-SIGN and transmission of DC-SIGN-captured virus to T cells. As candidate microbicides should not interfere with the normal human microbiota, we examined the effect of CBAs against Lactobacillus strains, including a variety of vaginal strains, a gastrointestinal strain and several non-human isolates. None of the CBAs included in our studies inhibited the growth of these bacteria in several media, affected their viability or had any significant impact on their adhesion to HeLa cell monolayers. CONCLUSIONS: The CBAs in this study were inhibitory to HIV-1 in several in vitro infection and transmission models, and may therefore qualify as potential microbicide candidates. The lack of significant impact on commensal vaginal lactobacilli is an important property of these CBAs in view of their potential microbicidal use.

The Application of Sulfur Influences Microbiome of Soybean Rhizosphere and Nutrient-Mobilizing Bacteria in Andosol.

This study aimed to determine the effect of sulfur (S) application on a root-associated microbial community resulting in a rhizosphere microbiome with better nutrient mobilizing capacity. Soybean plants were cultivated with or without S application, the organic acids secreted from the roots were compared. High-throughput sequencing of 16S rRNA was used to analyze the effect of S on microbial community structure of the soybean rhizosphere. Several plant growth-promoting bacteria (PGPB) isolated from the rhizosphere were identified that can be harnessed for crop productivity. The amount of malic acid secreted from the soybean roots was significantly induced by S application. According to the microbiota analysis, the relative abundance of Polaromonas, identified to have positive association with malic acid, and arylsulfatase-producing Pseudomonas, were increased in S-applied soil. Burkholderia sp. JSA5, obtained from S-applied soil, showed multiple nutrient-mobilizing traits among the isolates. In this study, S application affected the soybean rhizosphere bacterial community structure, suggesting the contribution of changing plant conditions such as in the increase in organic acid secretion. Not only the shift of the microbiota but also isolated strains from S-fertilized soil showed PGPB activity, as well as isolated bacteria that have the potential to be harnessed for crop productivity.

Structural insights into the specific anti-HIV property of actinohivin: structure of its complex with the α(1-2)mannobiose moiety of gp120.

Actinohivin (AH) is an actinomycete lectin with a potent specific anti-HIV activity. In order to clarify the structural evidence for its specific binding to the α(1-2)mannobiose (MB) moiety of the D1 chains of high-mannose-type glycans (HMTGs) attached to HIV-1 gp120, the crystal structure of AH in complex with MB has been determined. The AH molecule is composed of three identical structural modules, each of which has a pocket in which an MB molecule is bound adopting a bracket-shaped conformation. This conformation is stabilized through two weak C-H...O hydrogen bonds facilitated by the α(1-2) linkage. The binding features in the three pockets are quite similar to each other, in accordance with the molecular pseudo-threefold symmetry generated from the three tandem repeats in the amino-acid sequence. The shape of the pocket can accept two neighbouring hydroxyl groups of the O(3) and O(4) atoms of the equatorial configuration of the second mannose residue. To recognize these atoms through hydrogen bonds, an Asp residue is located at the bottom of each pocket. Tyr and Leu residues seem to block the movement of the MB molecules. Furthermore, the O(1) atom of the axial configuration of the second mannose residue protrudes from each pocket into an open space surrounded by the conserved hydrophobic residues, suggesting an additional binding site for the third mannose residue of the branched D1 chain of HMTGs. These structural features provide strong evidence indicating that AH is only highly specific for MB and would facilitate the highly specific affinity of AH for any glycoprotein carrying many HMTGs, such as HIV-1 gp120.

Crystallographic study of the interaction of the anti-HIV lectin actinohivin with the α(1-2)mannobiose moiety of gp120 HMTG.

Actinohivin (AH) is a new potent anti-HIV lectin of microbial origin. In order to modify it to produce a more efficient drug, its three-dimensional structure has previously been determined with and without the target α(1-2)mannobiose moiety of the high-mannose-type glycan (HMTG) attached to HIV-1 gp120. However, ambiguity remained in the structures owing to packing disorder that was possibly associated with peptide fragments attached at the N-terminus. To resolve these problems, the duration of cultivation of the AH-producing strain was examined and it was found that in a sample obtained from a 20 d culture the heterogeneous fragments were completely removed to produce mature AH with high homogeneity. In addition, the purification procedures were simplified in order to increase the yield of AH and the addition of solvents was also examined in order to increase the solubility of AH. AH thus obtained was successfully crystallized with high reproducibility in a different form to the previously obtained crystals. The crystal diffracted well to beyond 1.90 Å resolution and the crystallographic data suggested that it contained no packing disorder.

Mechanism by which the lectin actinohivin blocks HIV infection of target cells.

Various lectins have attracted attention as potential microbicides to prevent HIV transmission. Their capacity to bind glycoproteins has been suggested as a means to block HIV binding and entry into susceptible cells. The previously undescribed lectin actinohivin (AH), isolated by us from an actinomycete, exhibits potent in vitro anti-HIV activity by binding to high-mannose (Man) type glycans (HMTGs) of gp120, an envelope glycoprotein of HIV. AH contains 114 aa and consists of three segments, all of which need to show high affinity to gp120 for the anti-HIV characteristic. To generate the needed mechanistic understanding of AH binding to HIV in anticipation of seeking approval for human testing as a microbicide, we have used multiple molecular tools to characterize it. AH showed a weak affinity to Man alpha(1-2)Man, Man alpha(1-2)Man alpha(1-2)Man, of HMTG (Man8 or Man9) or RNase B (which has a single HMTG), but exhibited a strong and highly specific affinity (K(d) = 3.4 x 10(-8) M) to gp120 of HIV, which contains multiple Man8 and/or Man9 units. We have compared AH to an alternative lectin, cyanovirin-N, which did not display similar levels of discrimination between high- and low-density HMTGs. X-ray crystal analysis of AH revealed a 3D structure containing three sugar-binding pockets. Thus, the strong specific affinity of AH to gp120 is considered to be due to multivalent interaction of the three sugar-binding pockets with three HMTGs of gp120 via the "cluster effect" of lectin. Thus, AH is a good candidate for investigation as a safe microbicide to help prevent HIV transmission.

Semi-quantitative evaluation of CD44(+) /CD24(-) tumor cell distribution in breast cancer tissue using a newly developed fluorescence immunohistochemical staining method.

CD44(+) /CD24(-) tumor cells are reported to contain cancer stem cells in breast cancer. The main purpose of the present study is to develop an immunohistofluorescence method that can quantitatively analyze CD44(+) /CD24(-) tumor cell distribution in breast cancer tissue and help better define the role of CD44(+) /CD24(-) tumor cells in breast cancer. The samples used were from 21 primary breast cancer patients who underwent neoadjuvant chemotherapy and 17 cases with sentinel lymph nodes that had lymph node micrometastasis. CD44(+) /CD24(-) tumor cells were distinguished at a single cell level using improved triple-staining immunohistofluorescence and a simulated laser capture microdissection method. The percentage of CD44(+) /CD24(-) cells significantly increased following neoadjuvant chemotherapy treatment (0.93% and 2.78%, before and after, respectively, P = 0.0043). The percentage of CD44(+) /CD24(-) cells was also significantly high in micrometastatic sentinel lymph nodes (0.49% and 1.91%, primary tumors and lymph nodes, respectively, P = 0.0246). The CD44(+) /CD24(-) tumor cell distribution was heterogeneous in both breast cancer tissue and lymph node metastasis. In a xenograft model using immunodeficient mice, the hedgehog signaling inhibitor cyclopamine repressed the tumorigenicity of CD44(+) /CD24(-) cells. Our results suggest that this semi-quantitative immunohistochemical analysis is valuable for detecting a small population of cells in cancer tissues and that the hedgehog signaling pathway inhibitor cyclopamine is useful for regulating the CD44(+) /CD24(-) tumor cells in breast cancer.

Hedgehog signaling pathway mediates the progression of non-invasive breast cancer to invasive breast cancer.

The purpose of this study is to clarify the contribution of the Hedgehog signaling pathway (Hh pathway) to the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). A total of 149 surgically resected mammary disease specimens and 12 sentinel lymph nodes with micro-metastasis (Ly-met) were studied. The degree of Hh pathway activation was estimated from the Gli1 nuclear staining ratio (%Gli1 nuclear translocation) in cancer cells. The invasiveness of breast cancer cells was determined using Matrigel assays. A serial increase of %Gli1 nuclear translocation to IDC from non-neoplastic diseases was confirmed. In tumor specimens, %Gli1 nuclear translocation correlated with the invasiveness of each type of mammary disease and also correlated with invasion-related histopathological parameters. The %Gli1 nuclear translocation in lymph nodes with micro-metastasis was similar to that in primary sites and higher than that in DCIS with microinvasion and DCIS. Blockade of the Hh pathway decreased the invasiveness of breast cancer cells. In IDC, %Gli1 nuclear translocation correlated with the expression of estrogen receptor-α. Estrogen increased %Gli1 nuclear translocation and the invasiveness of estrogen receptor-α-positive cells. The Hh pathway mediates progression from a non-invasive phenotype to an invasive phenotype and %Gli1 nuclear translocation may be useful as a predictive marker for evaluating the ability of invasiveness.

VEGFR2 is selectively expressed by FOXP3high CD4+ Treg.

CD25+ FOXP3+CD4+ T cells (Treg) have been considered to play an important role in immune tolerance against several tumor antigens. It has also been indicated that high-level expression of FOXP3 (FOXP3high) is sufficient to confer suppressive activity to normal non-Treg. Here, we showed for the first time that vascular endothelial growth factor receptor 2 (VEGFR2) is selectively expressed by FOXP3high but not FOXP3low Treg. Such VEGFR2+ Treg exist in several tissues including PBMC and malignant effusion-derived lymphocytes. In conclusion, VEGFR2 may be a novel target for controlling Treg with highly suppressive function.

Actinohivin, a broadly neutralizing prokaryotic lectin, inhibits HIV-1 infection by specifically targeting high-mannose-type glycans on the gp120 envelope.

The lectin actinohivin (AH) is a monomeric carbohydrate-binding agent (CBA) with three carbohydrate-binding sites. AH strongly interacts with gp120 derived from different X4 and R5 human immunodeficiency virus (HIV) strains, simian immunodeficiency virus (SIV) gp130, and HIV type 1 (HIV-1) gp41 with affinity constants (KD) in the lower nM range. The gp120 and gp41 binding of AH is selectively reversed by (alpha1,2-mannose)3 oligosaccharide but not by alpha1,3/alpha1,6-mannose- or GlcNAc-based oligosaccharides. AH binding to gp120 prevents binding of alpha1,2-mannose-specific monoclonal antibody 2G12, and AH covers a broader epitope on gp120 than 2G12. Prolonged exposure of HIV-1-infected CEM T-cell cultures with escalating AH concentrations selects for mutant virus strains containing N-glycosylation site deletions (predominantly affecting high-mannose-type glycans) in gp120. In contrast to 2G12, AH has a high genetic barrier, since several concomitant N-glycosylation site deletions in gp120 are required to afford significant phenotypic drug resistance. AH is endowed with broadly neutralizing activity against laboratory-adapted HIV strains and a variety of X4 and/or R5 HIV-1 clinical clade isolates and blocks viral entry within a narrow concentration window of variation (approximately 5-fold). In contrast, the neutralizing activity of 2G12 varied up to 1,000-fold, depending on the virus strain. Since AH efficiently prevents syncytium formation in cocultures of persistently HIV-1-infected HuT-78 cells and uninfected CD4+ T lymphocytes, inhibits dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin-mediated capture of HIV-1 and subsequent virus transmission to CD4+ T lymphocytes, does not upregulate cellular activation markers, lacks mitogenic activity, and does not induce cytokines/chemokines in peripheral blood mononuclear cell cultures, it should be considered a potential candidate drug for microbicidal use.

Nuclear factor kappaB-activated monocytes contribute to pancreatic cancer progression through the production of Shh.

Recently, it was reported that Hh signaling is activated in tumor stromal cells but not in tumor cells themselves and that stromal cells may play a role in the proliferation of cancer cells. This suggests the possibility that stromal cells have an important role in the proliferation of tumor cells that may be mediated through Hh signaling. In this report, we present for the first time that inflammation-stimulated monocytes produce Shh through activation of the NF-kappaB signaling pathway, and that the Shh produced promotes the proliferation of pancreatic cancer cells in a paracrine manner through Hh signaling.

Lipopolysaccharide (LPS) increases the invasive ability of pancreatic cancer cells through the TLR4/MyD88 signaling pathway.

BACKGROUND: Inflammation plays a multifaceted role in cancer progression, and NF-kappaB is one of the key factors connecting inflammation with cancer progression. We have shown that lipopolysaccharide (LPS) promotes NF-kappaB activation in colon cancer cells and pancreatic cancer cells. However, it is unclear why inflammatory stimuli can induce NF-kappaB activation in cancer cells. METHODS: We used two human pancreatic cancer cells, Panc-1 and AsPC-1, as target cells. LPS was used as an inflammatory stimulus. To confirm the participation of TLR4/NF-kappaB signaling pathway, we used three different NF-kappaB inhibitors (PDTC, IkappaBalpha mutant, and NF-kappaB decoy ODN) and siRNAs (against TLR4, MyD88, and MMP-9). Effect of LPS on pancreatic cancer cell invasive ability was determined by Matrigel invasion assay. RESULTS: LPS increased the invasive ability of pancreatic cancer cells, while blockade of NF-kappaB pathway decreased the LPS-dependent increased invasive ability. Blockade of TLR4 or MyD88 by siRNA also decreased the LPS-dependent increased invasive ability. CONCLUSION: These results suggest that TLR/MyD88/NF-kappaB signaling pathway plays a significant role in connecting inflammation and cancer invasion and progression.

The Hedgehog pathway is a possible therapeutic target for patients with estrogen receptor-negative breast cancer.

Understanding the expression patterns of estrogen receptor-alpha (ERalpha) is essential for determining therapeutic strategies for patients with breast cancer. The prognosis of patients with ERalpha-negative breast cancer is still poor. We have previously shown that Hedgehog (Hh) signaling is constitutively activated in breast cancer and that Hh signaling could be a new therapeutic target. Therefore, in this study, whether or not Hh signaling could be utilized as a therapeutic target for patients with ERalpha-negative breast cancer was examined. For this purpose, three ERalpha-negative breast cancer cell lines were used in which Hh pathway-related molecules such as the ligand Patched1 and the transcriptional factor Gli1 as target cells are expressed. Cyclopamine, an inhibitor of the Hh pathway, significantly suppressed both the cell proliferation and invasion ability of these cancer cells. In addition, the knockdown of Gli1 by RNA interference in these cells also significantly reduced both cell proliferation and invasion ability. Since our previous data have shown a constitutive activation of the Hh pathway in surgically-resected ERalpha-negative breast cancer specimens, the Hh pathway, especially Gli1, may be a useful therapeutic target for patients with ERalpha-negative breast cancer.

The Hedgehog signaling pathway plays an essential role in maintaining the CD44+CD24-/low subpopulation and the side population of breast cancer cells.

The side population (SP) and the CD44(+)/CD24(-/low) population have been reported in separate studies to include more tumorigenic cells than other populations, and to have the ability to form new tumors and undergo heterogeneous differentiation in breast cancer tissue. However, the relationship between these two populations has not yet been explored in breast cancer cells. Here it is shown that the SP and the CD44(+)/CD24(-/low) populations are overlapping. Both populations were resistant to paclitaxel. Components of the Hedgehog (Hh) signaling pathway were more highly expressed in these cell populations at both the mRNA and protein levels compared with other populations. Furthermore, inhibition of Hh signaling activity suppressed the proliferation of both populations. The significance of Hh signaling activity in the proliferation of both populations was confirmed by the effect of an si-RNA against Gli1, a trans-activator of the Hh signaling pathway, on the proliferation of both populations. These data suggest that the Hh signaling pathway is essential for the proliferation of the tumorigenic population of breast cancer cells, and that this pathway might represent a new candidate for breast cancer therapy targeting cancer stem cells.

A protein-bound polysaccharide, PSK, enhances tumor suppression induced by docetaxel in a gastric cancer xenograft model.

BACKGROUND: We have reported previously that docetaxel (TXT) induces apoptosis and nuclear factor-kappaB (NF-kappaB) activation, and that blockade of NF-kappaB activation augments TXT-induced apoptosis in human gastric cancer cells. In addition, we have also shown that a protein-bound polysaccharide PSK enhances TXT-induced apoptosis through NF-kappaB inhibition in human pancreatic cancer cells. Based on these observations, in the present study the possibility that PSK could enhance TXT-mediated tumor suppression was examined in vivo and in vitro. MATERIALS AND METHODS: A gastric cancer xenograft model was used to examine the enhanced TXT-mediated tumor suppression by PSK in vivo. The effects of PSK on proliferation and apoptosis induced by TXT in gastric cancer cells were evaluated in vitro using a human gastric cancer cell line, MK-1. The effect of PSK on increased TXT-induced invasion was also measured. RESULTS: PSK enhanced TXT-mediated tumor suppression in vivo. Immunohistochemical analyses of the tumors revealed that TXT increased NF-kappaB activation in the tumors and this was suppressed by PSK. In the ex vivo experimental system, PSK enhanced the growth inhibition and apoptosis induced by TXT in the MK-1 cells and reduced the increased invasive ability induced by TXT. CONCLUSION: PSK enhanced TXT-induced tumor suppression in a gastric cancer xenograft model.

Forest understories controlled the soil organic carbon stock during the fallow period in African tropical forest: a 13C analysis.

Soil organic carbon (SOC) dynamics after slash-burn agriculture are poorly understood in African tropical forest, though recent studies have revealed C4 grass invasion as a forest understory influences SOC dynamics after deforestation. This study aimed to quantify the relative SOC contribution of C4 and C3 plants separately through the sequential fallow periods of forest (cropland, or 4-7, 20-30, or >50 years of fallow forest) in the tropical forest of eastern Cameroon. We evaluated the SOC stock and natural 13C abundance for each layer. The SOC stock was largest in 4-7 years fallow forest (136.6 ± 8.8 Mg C ha-1; 100 cm depth, and C4:C3 = 58:42), and decreased with increasing fallow period. SOC from C4 plants was larger in the 4-7 and 20-30 years fallow forests (57.2-60.4 ± 5.8 Mg C ha-1; 100 cm depth), while it clearly decreased in >50 years fallow forest (35.0 ± 4.1 Mg C ha-1; 100 cm depth), resulting in the smallest SOC in this mature forest (106.4 ± 12.9 Mg C ha-1; 100 cm depth). These findings indicate that C4 grass understories contributed to the SOC restoration during early fallow succession in the tropical forest of eastern Cameroon.