Immunopathological effects of Agaricus blazei Murill polysaccharides against Schistosoma mansoni infection by Th1 and NK1 cells differentiation.

In this study, we examined the ability of A. blazei Murill polysaccharides (AB-PS) to activate the immune system in vivo and the protective activity exhibited against parasitic S. mansoni in the murine model. AB-PS treatment significantly reduced the worm and egg burden in infected BALB/c and C57BL/6 mice with dose- and time-dependent manners. Additionally, a dose- and time-dependent expression of IL-2, INF-γ, and TNF-α cytokines was also observed in both strains of mice treatments. Using T1/T2 doubly transgenic mice, we demonstrated that AB-PS-treated mice splenocytes initiated early differentiation of Th1 and NK1 cells, which was consistent with the reduction course of Schistosoma infection. Although AB-PS treatment enhanced the Th1 response, it did not suppress Th2 cell activity in treated mice. Histopathological data of the livers showed AB-PS treatment significantly attenuated the liver fibrosis induced by S. mansoni eggs. AB-PS augmented type-1 responses by inducing Th1 and NK1 cell differentiation to effectively decrease the infection rate of S. mansoni. Furthermore, AB-PS treatment may not only inhibit the schistosome infection, but also improving the pathological effects of granulomas formation. This study provides evidence for a novel therapeutic potential, by which A. blazei Murill may be used to treat or prevent schistosome infection.

Unique clustering genes in the bacterial chromosome affecting the type-III secretion of enterohaemorrhagic Escherichia coli.

Bioinformatics analysis was used to search for unknown genes that might influence the phenotypic presentations of enterohaemorrhagic Escherichia coli (EHEC). By so doing and using the known genomic data from EHEC O157 : H7 and K-12, it has been deduced that genes Z4863 to Z4866 of EHEC do not exist in K-12 strains. These four gene sequences have low degrees of homology (18-40 % amino acid identities) to a set of genes in K-12, which have been known to encode fatty acid biosynthesis enzymes. We referred these four consecutive genes as a fasyn cluster and found that deletion of fasyn from EHEC resulted in a defective type-III secretion (T3S). This deletion apparently did not decrease the amounts of the T3S proteins ectopically expressed from plasmids. Examination of the corresponding mRNAs by real-time PCR revealed that the mRNAs readily decreased in the fasyn-deleted mutant and this suppressive effect on the mRNA levels appeared to spread across all lee operons. Complementation with fasyn reverted the T3S-deficient phenotype. Furthermore, this reversion was also seen when the mutant was supplemented with locus of enterocyte effacement activators (Ler or GrlA). Thus, these unique clustering genes located apart from locus of enterocyte effacement on the bacterial chromosome also play a role in affecting T3S of EHEC.

Combined IL-12 Plasmid and Recombinant SjGST Enhance the Protective and Anti-pathology Effect of SjGST DNA Vaccine Against Schistosoma japonicum.

Schistosomiasis is listed as one of most important tropical diseases and more than 200 million people are estimated to be infected. Development of a vaccine is thought to be the most effective way to control this disease. Recombinant 26-kDa glutathione S-transferase (rSjGST) has previously been reported to achieve a worm reduction rate of 42-44%. To improve the efficiency of the vaccine against Schistosoma japonicum, we immunized mice with a combination of pcDNA vector-encoded 26-kDa SjGST (pcDNA/SjGST), IL-12 expressing-plasmid (pIL-12), and rSjGST. Co-vaccination with pcDNA/SjGST, pIL-12, and rSjGST led to a reduction in worm burden, hepatic egg burden, and the size of liver tissue granulomas than that in the untreated infection controls. In addition, we detected high levels of specific IgG, IgG1, and IgG2a against the rSjGST antigen in infected mice vaccinated with this combination of pcDNA/SjGST, pIL-12, and rSjGST. Moreover, high expression levels of Th2 cytokines, including IL-4 and IL-10, were also detected in this group, without diminished levels of IL-12, INF-γ, and TNF-α cytokines that are related to parasite killing. In conclusion, we have developed a new vaccination regimen against S. japonicum infection and shown that co-immunization with pcDNA/SjGST vaccine, pIL-12, and rSjGST has significant anti-parasite, anti-hepatic egg and anti-pathology effects in mice. The efficacy of this vaccination method should be further validated in large animals such as water buffalo. This method may help to reduce the transmission of zoonotic schistosomiasis japonica.

Radioprotective effects of Antrodia cinnamomea are enhanced on immune cells and inhibited on cancer cells.

UNLABELLED: Abstract Purpose: The radioprotective effects of Antrodia cinnamomea (AC) were investigated for understanding the potential usefulness of AC as an adjunct treatment for reducing radiation side-effects. MATERIALS AND METHODS: In this study, we determined the ability of AC extracts (AC539) to reduce radiation side-effects by analyzing cellular viability in normal mouse spleen immune cells and human cancer cells with different radiosensitivity. We further detected the effect of AC on radiation-induced changes in cytokine- and inflammatory-related gene expressions. Furthermore, apoptosis assay was performed to determine whether AC could inhibit radiation-induced cytotoxicity. RESULTS: We found that an AC dose of 100-150 µg/ml in a time-dependent manner was the most effective in blocking radiation-induced cytotoxicity, in vitro. Radiation-induced cytotoxicity was inhibited in spleen immune cells by 37-56%; however, pretreatment of human colorectal cancer cell line HT-29 with AC did not have any effect on radiation-induced cytotoxicity, while pretreatment of radiosensitive human breast cancer cell lines BT-474 with AC caused a moderate enhancement of radiation-induced damage. Furthermore, AC pretreatment differentially regulated the mRNA expression of several important immunomodulatory genes in response to irradiation in normal and cancer cells. CONCLUSIONS: Our data indicate that AC may inhibit important immunoregulatory signaling which could be vital in the avoidance of an over-activated cytotoxic and inflammatory response of the immune system caused by radiation-induced tissue damage. Additionally, AC does not provide a radioprotective effect to tumor cells but instead enhances radiation-induced inflammation and cytotoxicity in cancer.

Protein interactions and regulation of EscA in enterohemorrhagic E. coli.

Infections caused by enterohemorrhagic Escherichia coli (EHEC) can lead to diarrhea with abdominal cramps and sometimes are complicated by severe hemolytic uremic syndrome. EHEC secretes effector proteins into host cells through a type III secretion system that is composed of proteins encoded by a chromosomal island, locus for the enterocyte effacement (LEE). EspA is the major component of the filamentous structure connecting the bacteria and the host's cells. Synthesis and secretion of EspA must be carefully controlled since the protein is prone to polymerize. CesAB, CesA2, and EscL have been identified as being able to interact with EspA. Furthermore, the intracellular level of EspA declines when cesAB, cesA2, and escL are individually deleted. Here, we report a LEE gene named l0033, which also affects the intracellular level of EspA. We renamed l0033 as escA since its counterpart in enteropathogenic E. coli has been recently described. Similar to CesAB, EscL, and CesA2, EscA interacts with EspA and enhances the protein stability of EspA. However, EscA is also able to interact with inner membrane-associated EscL, CesA2, and EscN, but not with cytoplasmic CesAB. In terms of gene organizations, escA locates in LEE3. Expression of EscA is faithfully regulated via Mpc, the first gene product of LEE3. Since Mpc is tightly regulated to low level, we suggest that EscA is highly synchronized and critical to the process of escorting EspA to its final destination.

SitA contributes to the virulence of Klebsiella pneumoniae in a mouse infection model.

Klebsiella pneumoniae is an opportunistic pathogen, which causes a wide range of nosocomial infections. Recently, antibiotic resistance makes K. pneumoniae infection difficult to deal with. Investigation on virulence determinants of K. pneumoniae can provide more information about pathogenesis and unveil new targets for treatment or vaccine development. In this study, SitA, a Fur-regulated divalent cation transporter, was found significantly increased when K. pneumoniae was cultured in a nutrient-limited condition. A sitA-deletion strain (ΔsitA) was created to characterize the importance of SitA in virulence. ΔsitA showed higher sensitivity toward hydroperoxide than its parental strain. In a mouse intraperitoneal infection model, the survival rate of mice infected with ΔsitA strain increased greatly when compared with that of mice infected with the parental strain, suggesting that sitA deletion attenuates the bacterial virulence in vivo. To test whether ΔsitA strain is a potential vaccine candidate, mice were immunized with inactivated bacteria and then challenged with the wild-type strain. The results showed that using ΔsitA mutant protected mice better than using the wild-type strain or the capsule-negative congenic bacteria. In summary, SitA was found being important for the growth of K. pneumoniae in vivo and deleting sitA might be a potential approach to generate vaccines against K. pneumoniae.

A study of immunomodulatory genes responses to macrophages of Schistosoma japonicum infection during different stages by microarray analysis.

Macrophages initiate, modulate, and also serve as final effector cells in immune responses during the course of schistosomal infections. In this study, we investigated the gene expression profile and functional changes of macrophages in immune responses against the Schistosoma japonicum by microarray analysis. Hierarchical clustering analysis demonstrated that a significant switch in gene transformation associated with a type-1 response and linked with a type-2 cytokine phenotype occurs between 4.5 and 8 weeks post-infection. Moreover, the gene profiles at 3 later time-points following egg challenge were similar in complexity and magnitude. The data also showed that there were mostly inhibition of gene expression related TLR, IFN, MHC and TNFrsf at the switch between 4.5 and 8 weeks post-infection, It is suggested that these immunomodulatory genes may be down-regulated in defense against S. japonicum eggs and granuloma pathology. The induction of alternatively activated macrophage (AAMϕ) was important for dampening the inflammation in hepatic granulomas and contributing to a decrease in cytotoxicity. The gene expressions involved in repair/remodeling during liver fibrosis were also observed after egg production. Understanding the immune mechanisms associated with parasitic resistance, pathology of parasite infection, and parasite growth will provide useful insight on host-schistosome interactions and for the control of schistosomiasis.

Therapy-related acute lymphoblastic leukemia with t(4;11)(q21;q23) masqueraded as marrow lymphocytosis in a patient with breast cancer.

Therapy-related acute leukemia develops in patients after chemotherapy and/or radiotherapy for a prior cancer, and most cases are acute myeloid leukemia with a much lower frequency of acute lymphoblastic leukemia (ALL). One unique feature of these therapy-related ALL (t-ALL) is an increased incidence of chromosome band 11q23 aberrations as compared with de novo ALL. In adult female patients, breast cancer is the most common primary cancer. Herein, we report the case of a 49-year-old Taiwanese lady who developed t-ALL with t(4;11)(q21;q23) 16 months after cyclophosphamide, epirubicin, and 5-fluorouracil chemotherapy for her breast cancer. The unusual feature is that the t-ALL was heralded 4 months ago by marrow lymphocytosis comprising atypical small lymphocytes with condensed chromatin mimicking a B-cell chronic lymphoproliferative disorder. Retrospective studies using additional antibodies for immunophenotyping and PCR-based clonality study for immunoglobulin gene rearrangement showed that these atypical small lymphocytes shared similar features with the leukemic blasts at the frank leukemic stage. Our results suggest that these atypical small lymphocytes are lymphoblasts in disguise and that the clinicopathological correlations with ancillary pathological studies are important to reach a definitive diagnosis of such an unusual case.

Hairy cell leukemia and variant in Taiwan: report of a variant case and literature review.

Hairy cell leukemia (HCL) is characterized by leukemic cells with abundant "hairy" cytoplasm, strong cytoplasmic positivity for tartrate-resistant acid phosphatase (TRAP), characteristic immunophenotype and sensitivity to treatment with purine nucleoside analogs. HCL-variant (HCL-v) encompasses chronic B-cell leukemias resembling classical HCL but exhibiting variant cytomorphology, variant immunophenotype and resistance to conventional HCL therapy. We present the case of a 67-year-old Taiwanese male with HCL-v who had leukocytosis and splenomegaly. His hairy leukemic cells were weakly positive for TRAP and expressed CDllc and CD103 but not CD25. He received oral chemotherapy with chlorambucil and in complete hematological remission in 9 months but relapsed 2 months later. Literature review revealed 9 cases of HCL and 3 cases of HCL-v including current case from Taiwan. All patients were adults with splenomegaly. The HCL patients had a significantly higher frequency of leukopenia (p = 0.024) and monocytopenia (p = 0.008) and a lower frequency of leukocytosis (p = 0.018) than HCL-v patients. All 8 HCL patients responded favorably to 2-chlorodeoxyadenosine with or without splenectomy. The 3 HCL-v patients had leukocytosis and received chemotherapy with variable outcome. HCL and HCL-v are rare in Taiwan and their pathological and immunophenotypical features were not fully characterized. A multimodality approach incorporating hematological findings, cytomorphology, histopathology, cytochemistry, complete immunophenotyping and clinical features is needed to identify and characterize such cases in Taiwan.

A role of ygfZ in the Escherichia coli response to plumbagin challenge.

Plumbagin is found in many herbal plants and inhibits the growth of various bacteria. Escherichia coli strains are relatively resistant to this drug. The mechanism of resistance is not clear. Previous findings showed that plumbagin treatment triggered up-regulation of many genes in E. coli including ahpC, mdaB, nfnB, nfo, sodA, yggX and ygfZ. By analyzing minimal inhibition concentration and inhibition zones of plumbagin in various gene-disruption mutants, ygfZ and sodA were found critical for the bacteria to resist plumbagin toxicity. We also found that the roles of YgfZ and SodA in detoxifying plumbagin are independent of each other. This is because of the fact that ectopically expressed SodA reduced the superoxide stress but not restore the resistance of bacteria when encountering plumbagin at the absence of ygfZ. On the other hand, an ectopically expressed YgfZ was unable to complement and failed to rescue the plumbagin resistance when sodA was perturbed. Furthermore, mutagenesis analysis showed that residue Cys228 within YgfZ fingerprint region was critical for the resistance of E. coli to plumbagin. By solvent extraction and HPLC analysis to follow the fate of the chemical, it was found that plumbagin vanished apparently from the culture of YgfZ-expressing E. coli. A less toxic form, methylated plumbagin, which may represent one of the YgfZ-dependent metabolites, was found in the culture supernatant of the wild type E. coli but not in the ΔygfZ mutant. Our results showed that the presence of ygfZ is not only critical for the E coli resistance to plumbagin but also facilitates the plumbagin degradation.

A putative lytic transglycosylase tightly regulated and critical for the EHEC type three secretion.

Open reading frame l0045 in the pathogenic island of enterohemorrhagic Escherichia coli O157:H7 has been predicted to encode a lytic transglycosylase that is homologous to two different gene products encoded by the same bacteria at loci away from the island. To deduce the necessity of the presence in the island, we created an l0045-deleted strain of EHEC and observed that both the level of cytosolic EspA and that of the other type III secreted proteins in the media were affected. In a complementation assay, a low level-expressing L0045 appeared to recover efficiently the type III secretion (TTS). On the other hand, when l0045 was driven to express robustly, the intracellular levels of representative TTS proteins were severely suppressed. This suppression is apparently caused by the protein of L0045 per se since introducing an early translational termination codon abolished the suppression. Intriguingly, the authentic L0045 was hardly detected in all lysates of EHEC differently prepared while the same construct was expectedly expressed in the K-12 strain. A unique network must exist in EHEC to tightly regulate the presence of L0045, and we found that a LEE regulator (GrlA) is critically involved in this regulation.

Primary urothelial carcinoma of the upper tract: important clinicopathological factors predicting bladder recurrence after surgical resection.

The aim of the present study was to further characterize potential clinicopathological predictors for urinary bladder recurrence-free survival (UBRFS) in patients with primary urothelial carcinoma of the upper urinary tract (UUT-UC). The present series included 385 cases of surgically treated primary localized UUT-UC without previous or concurrent urothelial carcinoma of the urinary bladder. Among the 374 patients with follow-up information, clinicopathological features and therapeutic information including whether they received a laparoscopy-assisted nephroureterectomy (LNU) and adjuvant chemotherapy were correlated with UBRFS. After a median follow up of 69 months, 86 patients (23%) developed urinary bladder recurrence. The median time to develop urinary bladder recurrence was 12 months. At the univariate level, an increment in histological grade (P= 0.0321), a prominent papillary configuration (P= 0.0004), LNU (P= 0.0397) and male gender (P= 0.0401) significantly predicted an inferior UBRFS. At the multivariate level, increase of histological grade (P < 0.0001, relative risk (RR) = 3.776), prominent papillary configuration (P < 0.0001, RR = 3.244), and male gender (P= 0.0463, RR = 1.444) independently predicted UBRFS. In conclusion, male patients and those with high-grade and papillary UUT-UC, and who received LNU had higher risks of urinary bladder recurrence. Accordingly, for these patients, more intensive follow up coupled with postoperative intravesical adjuvant therapy to prevent urinary bladder recurrence should also be considered.

Heat shock protein 90 overexpression independently predicts inferior disease-free survival with differential expression of the alpha and beta isoforms in gastrointestinal stromal tumors.

PURPOSE: Most gastrointestinal stromal tumors harbor a mutated KIT or PDGFRA receptor tyrosine kinase (RTK). Heat shock protein 90 (Hsp90) is a chaperone mediating the folding and stabilization of many oncoproteins, including KIT. An Hsp90 inhibitor, 17-AAG, can attenuate KIT activation and proliferation of gastrointestinal stromal tumor cell lines. We further evaluated Hsp90 immunoexpression and the difference between alpha and beta isoforms in gastrointestinal stromal tumor specimens. EXPERIMENTAL DESIGN: Hsp90 immunostain was assessable in 306 cases on tissue microarrays of primary gastrointestinal stromal tumors and correlated with various variables and disease-free survival (DFS). RTK mutation variants, confirmed in 142 cases by sequencing with or without precedent denaturing high pressure liquid chromatography screening, were dichotomized into two prognostically different groups. Differential expression of transcript and protein isoforms was measured by real-time reverse transcription-PCR and Western blotting in 16 and 6 cases, respectively. RESULTS: Hsp90 overexpression (55%) significantly correlated with larger size, nongastric location, higher mitotic count and NIH risk level, Ki-67 overexpression (all P < or = 0.001), and unfavorable RTK genotypes (P = 0.020). It strongly portended inferior DFS univariately (P < 0.0001) and remained independent in multivariate analysis (P = 0.031; risk ratio, 2.44), along with high-risk category, Ki-67 overexpression, and old age. For both mRNA and protein, Hsp90beta was more abundant than Hsp90alpha, whereas the latter was significantly higher in high-risk cases. CONCLUSIONS: Hsp90 overexpression represents a poor prognosticator that correlates with several adverse parameters, highlighting its role in disease progression and alternative therapy for high-risk, imatinib-resistant gastrointestinal stromal tumors. Hsp90alpha seems more relevant to the intrinsic aggressiveness of gastrointestinal stromal tumors, albeit less abundant than Hsp90beta.

Immunohistochemical and biogenetic features of diffuse-type tenosynovial giant cell tumors: the potential roles of cyclin A, P53, and deletion of 15q in sarcomatous transformation.

PURPOSE: Diffuse-type tenosynovial giant cell tumor (D-TSGCT) is an aggressive proliferation of synovial-like mononuclear cells with inflammatory infiltrates. Despite the COL6A3-CSF1 gene fusion discovered in benign lesions, molecular aberrations of malignant D-TSGCTs remain unidentified. EXPERIMENTAL DESIGN: We used fluorescent in situ hybridization and in situ hybridization to evaluate CSF1 translocation and mRNA expression in six malignant D-TSGCTs, which were further immunohistochemically compared with 24 benign cases for cell cycle regulators involving G(1) phase and G(1)-S transition. Comparative genomic hybridization, real-time reverse transcription-PCR, and a combination of laser microdissection and sequencing were adopted to assess chromosomal imbalances, cyclin A expression, and TP53 gene, respectively. RESULTS: Five of six malignant D-TSGCTs displayed CSF1 mRNA expression by in situ hybridization, despite only one having CSF1 translocation. Cyclin A (P = 0.008) and P53 (P < 0.001) could distinguish malignant from benign lesions without overlaps in labeling indices. Cyclin A transcripts were more abundant in malignant D-TSGCTs (P < 0.001). All malignant cases revealed a wild-type TP53 gene, which was validated by an antibody specifically against wild-type P53 protein. Chromosomal imbalances were only detected in malignant D-TSGCTs, with DNA losses predominating over gains. Notably, -15q was recurrently identified in five malignant D-TSGCTs, four of which showed a minimal overlapping deletion at 15q22-24. CONCLUSIONS: Deregulated CFS1 overexpression is frequent in malignant D-TSGCTs. The sarcomatous transformation involves aberrations of cyclin A, P53, and chromosome arm 15q. Cyclin A mRNA is up-regulated in malignant D-TSGCTs. Non-random losses at 15q22-24 suggest candidate tumor suppressor gene(s) in this region. However, P53 overexpression is likely caused by alternative mechanisms rather than mutations in hotspot exons.

Flow cytometric analysis of DNA ploidy and S-phase fraction in primary localized myxofibrosarcoma: correlations with clinicopathological factors, Skp2 expression, and patient survival.

BACKGROUND: Histological assessment for prognostication of myxofibrosarcomas remains challenging. We previously reported independent prognostic value of Skp2, an oncoprotein promoting S-phase progression (Clin Cancer Res 2006;12:487-98). METHODS: We evaluated S-phase fraction (SPF) and ploidy of myxofibrosarcomas and the association between SPF and Skp2. Flow cytometric findings were analyzed for 75 cases and correlated with clinicopathological factors, Skp2 labeling index (LI), metastasis-free survival (MeFS), and overall survival (OS). RESULTS: Forty-seven and 28 cases were classified as diploid and nondiploid, respectively. High SPF (>or=20%) was detected in 32 of 61 interpretable cases. Skp2 overexpression (LI >or= 10%) was seen in 36 of 72 cases with scoring. Nondiploidy correlated with higher French Federation of Cancer Centers (FNCLCC) grades (P = .006), remarkable necrosis (P = .010), and Skp2 overexpression (P = .018). Noticeably, SPF was significantly related to Skp2 LI (P < .001, r = .458), FNCLCC grade, American Joint Committee on Cancer stage, and mitotic rate. Nondiploidy predicted shorter OS (P = .0045) and MeFS (P = .0489), whereas SPF >or= 20% was only associated with inferior MeFS (P = .0252). In multivariate analyses, nondiploidy independently correlated with both OS (P = .020, RR = 3.337) and MeFS (P = .013, RR = 5.780), together with Skp2 overexpression (P = .014 for OS; P = .017 for MeFS) and disease-positive margins (P = .004 for OS; P = .002 for MeFS). CONCLUSION: Skp2 promotes S-phase progression in myxofibrosarcomas. SPF provides no independent prognostic usefulness; it is probably overshadowed by Skp2. Nondiploidy adds another predictive value to Skp2 overexpression and disease-positive margins in prognostication.

Gene l0017 encodes a second chaperone for EspA of enterohaemorrhagic Escherichia coli O157 : H7.

Escherichia coli O157:H7 tightly associates with host cells through the formation of a pedestal structure in which cell cytoskeleton rearrangement has been observed. These pathogenic properties have been attributed to an island, known as the locus of enterocyte effacement (LEE), located on the bacterial chromosome. Gene l0017 is one of the LEE genes that has been less well characterized. To understand further the function of the gene, an l0017-deleted mutant was created. The mutant lost type III protein secretion (TTS) capacity. In terms of intracellular components, there was a substantial decrease in the level of EspA, but no apparent effect on Tir and EspB was observed. Fractionation of the bacterial proteins indicated that L0017 was part of the inner-membrane fraction. This association with the membrane is consistent with the hypothesis that L0017 may act as one of the TTS components. In addition, L0017 was found to affect regulation of EspA at a post-transcriptional level. The presence of L0017 readily stabilized EspA and the interaction between L0017 and EspA was demonstrated by their co-purification as well as by a bacterial two-hybrid system. Therefore, L0017 is a chaperone, the second chaperone identified in this system after CesAB, and escorts EspA, a protein with a great tendency to polymerize.

Sonographic appearance of angiolymphoid hyperplasia with eosinophilia in the upper arm.

Angiolymphoid hyperplasia with eosinophilia is an uncommon benign condition characterized by cutaneous nodules involving primarily the head and neck regions of young adults. We report thecase of a 49-year-old woman with such a lesion in the arm. Sonographically, the lesion exhibited a hypoechoic rim and an echogenic central portion. On color Doppler imaging, the central portion was markedly vascular.

Malignant diffuse-type tenosynovial giant cell tumors: a series of 7 cases comparing with 24 benign lesions with review of the literature.

BACKGROUND: Malignant diffuse-type tenosynovial giant cell tumor (D-TSGCT), an unusual sarcoma with concurrent or previous benign D-TSGCTs, poses challenges to diagnosis and prognostication. METHODS: We described the radiologic, clinicopathologic, and immunophenotypical findings of 5 primary and 2 metachronous malignant D-TSGCTs and reviewed published cases to better delineate their morphologic spectrum and behavior. Twenty-four benign D-TSGCTs were also statically compared to analyze the diagnostic values of various variables. RESULTS: The 7 malignant cases affected 4 females and 3 males aged 45 to 78 (mean, 60.9) years, which included 1 intraarticular and 6 extra-articular lesions. These tumors were 5 to 17 cm (mean, 9.4) and located within or near the large joints of extremities. Magnetic resonance imaging revealed expansile or infiltrative masses with frequent lobulation and heterogeneous signals. Histologically, areas of benign D-TSGCTs blended abruptly or gradually with frank sarcomas composed of pleomorphic, spindle, or enlarged oval cells, forming malignant fibrous histiocytomalike (n = 4), fibrosarcomatous (n = 1), myxosarcomatous (n = 1), or giant cell tumorlike (n = 1) patterns. One patient experienced recurrences twice, and another 3 developed metastases to the lymph nodes (n = 2), lung (n = 1), or vertebrae (n = 1), with 1 dying from disseminated diseases. An older age (P = 0.003), a larger size (P = 0.036), tumor necrosis (P < 0.001), atypical mitoses (P < 0.001), and Ki-67 overexpression (P < 0.001) appeared preferentially in malignant lesions, but these parameters had overlap between few benign and malignant tumors. CONCLUSIONS: Malignant D-TSGCTs are a distinct sarcoma with considerable morphologic variability, metastatic propensity, and lethality. Altered architecture with anaplastic cells represents an important distinguishing feature, while abnormalities of other parameters should not be directly equated with malignancy.

Shiunko and acetylshikonin promote reepithelialization, angiogenesis, and granulation tissue formation in wounded skin.

Shiunko is a traditional botanic formula (ointment) used clinically for treating wounded skin. The aim of the present study was to compare the effects of Shiunko and acetylshikonin, and its active ingredient, with those of gentamicin and silver sulfadiazine ointments, two disinfectants for wound healing. Wounds were cut in the backs of Sprague-Dawley rats. Different bacterial inoculations (Pseudomonas aeruginosa and Staphylococcus aureus) and treatments (Shiunko, acetylshikonin, gentamicin, silver sulfadiazine, and vehicle ointments) were used to treat these wounds. We found that rats treated with Shiunko and acetylshikonin on both the sterilized and infected wounds showed higher rates of reepithelialization than those treated with the other ointments (p < 0.05) during a 7-day observation. In the histological study, rats treated with Shiunko and acetylshikonin on both the sterilized and infected wounds showed greater reepithelialization, angiogenesis, and granulation tissue formation than rats treated with the other ointments (p < 0.05) on day 5 after the wounds had been sutured. Differences between rats treated with Shiunko and acetylshikonin ointments were not statistically significant. In conclusion, topically applying Shiunko and acetylshikonin on wounded skin promoted wound healing. Both ointments were effective on sterilized and infected wounds.

Polysaccharides from Antrodia camphorata mycelia extracts possess immunomodulatory activity and inhibits infection of Schistosoma mansoni.

Antrodia camphorata (AC) is a commonly used fungus in folk medicine for the treatment of viral hepatitis and cancer. AC polysaccharides (AC-PS) are reported to possess anti-inflammatory, anti-hepatitis B virus, and anticancer activities. In this study, we tested the in vivo effect of AC-PS on immune function by evaluating cytokine expression; on immunomodulation, by evaluating spleen cells; and on Schistosoma mansoni infection in mice. The induction of high levels of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) mRNA was detected in BALB/c mice after 2, 4, and 6 weeks of oral AC-PS administration. After 6 weeks of oral AC-PS administration to the BALB/c mice, the number of splenic dendritic cells, macrophages, and the surface expression of CD8 alpha+ and major histocompatibility class II I-A/I-E on dendritic cells increased. The CD4+/CD8+ ratio and number of B cells among splenocytes were also augmented. By using a disease model of parasitic infection, we found that AC-PS treatment inhibited S. mansoni infection in BALB/c mice. AC-PS appears to modulate the immune system of mice and has potential for preventing S. mansoni infection.