It is commonly argued that Liu Zongzhou was dissatisfied with the fact that some followers of Wang Yangming in the late Ming Dynasty paid insufficient attention to self-cultivation practices (gongfu工夫), so he deliberately emphasized the difficulty and importance of personal cultivation which is often misunderstood as some kind of strict inner spiritual cultivation. This essay will argue that with the gradual deepening in the studies on Liu Zongzhou's thought as a whole, there are more dimensions to be recovered in our understanding of his self-cultivation theory. Liu Zongzhou's holistic self-cultivation theory is based on the unity of body and heartmind, and theory and practice, where each person is a node of relations, and is an unbounded narrative in the world. On this basis, self-cultivation is not simply an inward vector that relates to inner spiritual practice, but has an important and often overlooked relational and social dimension.
Abstract Frequent tumor relapse in hepatocellular carcinoma (HCC) has been commonly attributed to the failure to completely eradicate cancer stem cells (CSCs) in the tumor residues by conventional treatments. We have previously reported that the tumor growth of HCC is fuelled, at least in part, by a small subset of CSCs marked by the CD133 surface phenotype. Our present study aims 1) to delineate the molecular mechanism by which CD133+ liver CSCs mediate HCC tumor formation and progression; and 2) to develop a novel diagnostic / prognostic biomarker and targeted therapy for HCC detection and treatment. RNA-Seq profiling was employed to compare the gene expression profiles between sorted CD133+ and CD133- subsets isolated from HCC cell lines Huh7 and PLC8024. Annexin A3 (ANXA3) was identified as the most significantly up-regulated secretory protein in the CD133+ subset. Validation in additional HCC cell lines and clinical samples likewise showed ANXA3 to be preferentially expressed in the CD133+ subset. Up-regulation of ANXA3 in both endogenous and secretory forms was tightly associated with advanced tumor stages. In addition, quantification of serum ANXA3 provides a novel biomarker with high specificity and sensitivity for HCC diagnosis. Functional studies involving lentiviral-based knockdown and overexpression approaches found ANXA3 to regulate cancer and stem cell-like properties including tumor initiation, migration, invasion, angiogenesis, self-renewal and resistance to chemotherapy and apoptosis. Subsequent gene expression profiling by cDNA microarray found ANXA3 to be functionally involved in driving CD133+ CSCs via a deregulated JNK/AP-1 pathway. In light of the functional significance and clinical relevance of ANXA3 in HCC, we subsequently developed a novel neutralizing monoclonal antibody specific against ANXA3 and tested for its application as a therapeutic treatment against HCC. In vitro functional studies showed that ANXA3 neutralizing antibody treatment dramatically reduced cell proliferation, sphere formation, migration, invasion, angiogenesis, and sensitized cells to apoptosis and cisplatin treatment in vitro. This observation was further confirmed in vivo where neutralizing antibody treatment attenuated tumor growth, concomitant with a reduced CD133+ subset in the residual xenografts. Mechanistically, treatment of HCC cells with ANXA3 neutralizing antibody in vitro and in vivo, similarly led to a suppressed JNK pathway. Taken together, ANXA3 confers both cancer and stem cell-like properties in CD133+ liver CSCs via JNK pathway. ANXA3 neutralizing antibody possesses therapeutic effect in HCC by eliminating CD133+ liver CSCs. We believe that ANXA3 could serve as a potential therapeutic target to attain complete eradication of HCC. Citation Format: Man Tong, Chun Ming Fung, Xin Yuan Guan, Stephanie Ma. Annexin A3 is a therapeutic target for CD133+ liver cancer stem cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 221. doi:10.1158/1538-7445.AM2014-221
<p>PDF file, 720K, Detection of DNA copy number change of Rab25 by dual-color fluorescent in situ hybridization (FISH) in ESCC cell lines KYSE520, EC109 and formalin-fixed paraffin-embedded ESCC clinical tissue specimens (#1 and #2) with no or low Rab25 expression. BAC probe to Rab25 and the control reference probe to the centromere of chromosome 1 are represented by red and green signals, respectively. Magnification at 1000x.</p>
<p>The total mRNA levels of AZIN1 (left panel) and FLNB (right panel) in 69 matched pairs of ESCC and NT specimens in Cohort 1 (Paired Student's t test).</p>
<div>Abstract<p>A poor prognosis in head and neck squamous cell carcinoma (HNSCC) patients is commonly associated with the presence of regional metastasis. Cisplatin-based chemotherapy concurrent with radiation therapy is commonly used in the treatment of locally advanced HNSCC. However, the result is dismal due to common acquisition of chemoresistance and radioresistance. Epidemiologic studies have shown the importance of dietary substances in the prevention of HNSCC. Here, we found that lupeol, a triterpene found in fruits and vegetables, selectively induced substantial HNSCC cell death but exhibited only a minimal effect on a normal tongue fibroblast cell line <i>in vitro</i>. Down-regulation of NF-κB was identified as the major mechanism of the anticancer properties of lupeol against HNSCC. Lupeol alone was not only found to suppress tumor growth but also to impair HNSCC cell invasion by reversal of the NF-κB–dependent epithelial-to-mesenchymal transition. Lupeol exerted a synergistic effect with cisplatin, resulting in chemosensitization of HNSCC cell lines with high NF-κB activity <i>in vitro</i>. In <i>in vivo</i> studies, using an orthotopic metastatic nude mouse model of oral tongue squamous cell carcinoma, lupeol at a dose of 2 mg/animal dramatically decreased tumor volume and suppressed local metastasis, which was more effective than cisplatin alone. Lupeol exerted a significant synergistic cytotoxic effect when combined with low-dose cisplatin without side effects. Our results suggest that lupeol may be an effective agent either alone or in combination for treatment of advanced tumors. [Cancer Res 2007;67(18):8800–9]</p></div>
Supplementary Figure 2 from Lupeol Suppresses Cisplatin-Induced Nuclear Factor-κB Activation in Head and Neck Squamous Cell Carcinoma and Inhibits Local Invasion and Nodal Metastasis in an Orthotopic Nude Mouse Model
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