Oral squamous cell carcinoma (OSCC), an epithelial malignancy affecting a variety of subsites in the oral cavity, is prevalent in Asia. The survival rate of OSCC patients has not improved over the past decades due to its heterogeneous etiology, genetic aberrations, and treatment outcomes. Improvement in therapeutic strategies and tailored treatment options is an unmet need. To unveil the mutational spectrum, whole-exome sequencing of 120 OSCC from male individuals in Taiwan was conducted. Analyzing the contributions of the five mutational signatures extracted from the dataset of somatic variations identified four groups of tumors that were significantly associated with demographic and clinical features. In addition, known (TP53, FAT1, EPHA2, CDKN2A, NOTCH1, CASP8, HRAS, RASA1, and PIK3CA) and novel (CHUK and ELAVL1) genes that were significantly and frequently mutated in OSCC were discovered. Further analyses of gene alteration status with clinical parameters revealed that the tumors of the tongue were enriched with copy-number alterations in several gene clusters containing CCND1 and MAP4K2. Through defining the catalog of targetable genomic alterations, 58% of the tumors were found to carry at least one aberrant event potentially targeted by US Food and Drug Administration (FDA)-approved agents. Strikingly, if targeting the p53-cell cycle pathway (TP53 and CCND1) by the drugs studied in phase I-III clinical trials, those possibly actionable tumors are predominantly located in the tongue, suggesting a better prediction of sensitivity to current targeted therapies. Our work revealed molecular OSCC subgroups that reflect etiological and prognostic correlation as well as defined the landscape of major altered events in the coding regions of OSCC genomes. These findings provide clues for the design of clinical trials for targeted therapies and stratification of OSCC patients with differential therapeutic efficacy.

Renal transplantation (RTx) recipients have a high incidence of cancer, including transitional cell carcinoma (TCC). Posttransplantation urologic malignancies still present a challenge for transplant surgeons. Using the Dialysis and Transplant Registry of Taichung Veterans General Hospital, a total of 55 cancers were diagnosed in 52 RTx recipients between May 1983 and September 2001. Of these, 24 RTx recipients developing TCC were identified and presented the distinctly high percentage (43.6%) of TCC that were malignancies after RTx in Taiwan. The mean time between transplantation and initial diagnosis was 46 months in our series. Painless hematuria with pyuria is the most common mode of presentation. Transitional cell carcinoma of RTx recipients had multiple foci. Moreover, synchronous TCC in bilateral upper urinary tracts were confirmed in 9 (41%) recipients. The pathologic status of disease is invasive at diagnosis (pTa: 2, pT1: 7, pT2: 4, pT3: 6, pT4: 2, graft metastasis: 1 and distant metastasis: 2). Disseminated metastasis occurred in 6 recipients, all of whom died of their disease within 16 months. Five recipients received adjuvant chemotherapy and retained stable renal function. We conclude that RTx recipients have a markedly increased incidence of TCC in Taiwan, and that prophylactic bilateral nephroureterectomy of native kidneys with bladder cuff excision can be performed simultaneously in RTx recipients with TCC.

Evidence suggests that curcumin, the phytochemical agent in the spice turmeric, might be a potential therapy for Alzheimer's disease (AD). Its antioxidant, anti-inflammatory properties have been investigated extensively. Studies have also shown that curcumin can reduce amyloid pathology in AD. The underlying mechanism, however, is complex and is still being explored. In this study, we used the APPswe/PS1dE9 double transgenic mice, an AD model, to investigate the effects and mechanisms of curcumin in the prevention and treatment of AD. The water maze test indicated that curcumin can improve spatial learning and memory ability in mice. Immunohistochemical staining and Western blot analysis were used to test major proteins in β-amyloid aggregation, β-amyloid production, and β-amyloid clearance. Data showed that, 3 months after administration, curcumin treatment reduced Aβ40 , Aβ42 , and aggregation of Aβ-derived diffusible ligands in the mouse hippocampal CA1 area; reduced the expression of the γ-secretase component presenilin-2; and increased the expression of β-amyloid-degrading enzymes, including insulin-degrading enzymes and neprilysin. This evidence suggests that curcumin, as a potential AD therapeutic method, can reduce β-amyloid pathological aggregation, possibly through mechanisms that prevent its production by inhibiting presenilin-2 and/or by accelerating its clearance by increasing degrading enzymes such as insulin-degrading enzyme and neprilysin.

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The growth of licorice in arid areas faces nutritional and environmental stresses. Arbuscular mycorrhizal (AM) fungi have been shown to increase the abilities of plants to develop. However, little is known regarding the role of AM fungi in licorice (Glycyrrhiza uralensis) growth. In the present study, by inoculation with two AM fungi, Glomus mosseae (Nicolson & Gerdemann) Gerd. & Trappe and Glomus veriforme (P. Karst.), the effects on licorice growth in sand were examined by measuring plant height, number of leaves, shoot and root fresh weight, and by analyzing morphological parameters of the root system in sand. The influence of the two microorganisms on the accumulation of mineral nutritions and bioactive components in licorice were also investigated. The results showed that mycorrhyzae were of the Arum-type and their colonization frequency (F %), colonization intensity (M %) and colonization intensity (m %) of AM fungi inoculation were found to be 80.0-84.6%, 49.4-60.0% and 58.4-71.9%, respectively. The inoculation significantly improved plant growth during early and late growth stages in comparison with the control. Moreover, inoculation of G. mosseae and G. versiforme, alone or in combination, improved plant phosphorus acquisition in the leaf over noninoculation plants. In addition, mycorrhiza formation enhanced the glycyrrhizin concentration in roots, but resulted in a considerable reduction of the root oxidase activity. The results indicate that the inoculation with AM fungi could be a useful approach to increase the licorice pharmic quality.

Tissue inhibitor of metalloproteinase-3 (TIMP-3), a secreted glycoprotein, plays an important role in carcinogenesis. It can bind to many proteinases to suppress their activity and thus protect the extracellular matrix from degradation. TIMP-3 may have many anticancer properties, including apoptosis induction and antiproliferative, antiangiogenic, and antimetastatic activities. This review summarizes the structure, proteinase inhibition ability, genetic and epigenetic regulation, cancer therapy potential, and contribution to cancer development of TIMP-3. Furthermore, in this review we discuss its potential as a biomarker for predicting cancer progression and the current state of drugs that target TIMP-3, either alone or in combination with clinical treatment. In conclusion, TIMP-3 can be a biomarker of cancer and a potential target for cancer therapy. This review article can serve as a basis to understand how to modulate TIMP-3 levels as a drug target of cancers.

For the production of oligosaccharides from chitosan, a chitosanase-producing bacterium, S65, was isolated from soil. On the basis of phylogenetic analysis of the 16S rDNA gene sequence and phenotypic analysis, S65 was identified as a Bacillus sp. strain. This bacterium constitutively produced chitosanase in a culture medium without chitosan as an inducer. S65 chitosanase was homogeneously purified by DEAE Sepharose fast flow anion exchange followed by Superdex 75 size exclusion, and the molecular weight was 45 kDa according to SDS−PAGE. Enzyme analysis showed that the optimum pH and temperature of S65 were 6.0 and 65 °C, respectively. Catalytic activity was stable from pH 5.5−6.5 at temperatures below 40 °C, and the pI of chitosanase was about 6.0 as determined by a test tube method. S65 chitosanase degraded carboxymethyl cellulose (CMC) at the degree of about 5.3% relative to the value of soluble chitosan, but it cannot hydrolyze colloidal chitin and crystalline cellulose. Gene encoding was cloned and sequenced. The deduced amino acid sequence of the S65 exhibited the highest homology to those of family 8 glycanase, suggesting that the enzyme belonged to family 8. Keywords: Chitosan; chitosanase; purification; characterization; gene cloning

Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) caused by an abnormal rate of apoptosis. Endogenous stem cells in the adult mammalian brain indicate an innate potential for regeneration and possible resource for neuroregeneration in PD. We previously showed that guanosine prevents apoptosis even when administered 48 hr after the toxin 1-methyl-4-phenylpyridinium (MPP(+)). Here, we induced parkinsonism in rats with a proteasome inhibitor. Guanosine treatment reduced apoptosis, increased tyrosine hydroxylase-positive dopaminergic neurons and expression of tyrosine hydroxylase in the SNc, increased cellular proliferation in the SNc and subventricular zone, and ameliorated symptoms. Proliferating cells in the subventricular zone were nestin-positive adult neural progenitor/stem cells. Fibroblast growth factor-2-expressing cells were also increased by guanosine. Thus, guanosine protected cells from apoptosis and stimulated "intrinsic" adult progenitor/stem cells to become dopaminergic neurons in rats with proteasome inhibitor-induced PD. The cellular/molecular mechanisms underlying these effects may open new avenues for development of novel therapeutics for PD.