The extracellular matrix modulates the hallmarks of cancer

The extracellular matrix regulates tissue development and homeostasis, and its dysregulation contributes to neoplastic progression. The extracellular matrix serves not only as the scaffold upon which tissues are organized but provides critical biochemical and biomechanical cues that direct cell growth, survival, migration and differentiation and modulate vascular development and immune function. Thus, while genetic modifications in tumor cells undoubtedly initiate and drive malignancy, cancer progresses within a dynamically evolving extracellular matrix that modulates virtually every behavioral facet of the tumor cells and cancer‐associated stromal cells. Hanahan and Weinberg defined the hallmarks of cancer to encompass key biological capabilities that are acquired and essential for the development, growth and dissemination of all human cancers. These capabilities include sustained proliferation, evasion of growth suppression, death resistance, replicative immortality, induced angiogenesis, initiation of invasion, dysregulation of cellular energetics, avoidance of immune destruction and chronic inflammation. Here, we argue that biophysical and biochemical cues from the tumor‐associated extracellular matrix influence each of these cancer hallmarks and are therefore critical for malignancy. We suggest that the success of cancer prevention and therapy programs requires an intimate understanding of the reciprocal feedback between the evolving extracellular matrix, the tumor cells and its cancer‐associated cellular stroma.     

Cisplatin cytotoxicity is enhanced with zoledronic acid in A549 lung cancer cell line: preliminary results of an in vitro study

We tested whether zoledronic acid, a biphosphonate with proposed apoptotic activity, augmented the cytotoxicity of cisplatin and/or gemcitabine in A549 lung cancer cell line. This cell line was subjected to different concentrations of the above chemotherapeutic agents and zoledronic acid. Cytotoxicity was assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) assay. Particularly, zoledronic acid in 100 micromolar (microM) concentration augmented the cytotoxicity by cisplatin 1microg/ml from 25% to 70% (Z=3.22, P=0.0072). A significant portion of cells underwent apoptosis with or without zoledronic acid, but more so with the combination treatment as assessed by an Annexin V-FITC apoptosis detection kit. However, 100microM zoledronic acid showed 50% cytotoxicity on its own, but failed to improve cytotoxicity by Gemcitabine. Thus, we show for the first time in a lung cancer cell line that zoledronic acid bears cytotoxic potential on its own and in conjunction with cisplatin. The clinical potential of this finding should be further studied.     

CT诊断用于胰腺癌侵犯胰周动静脉的临床价值分析

目的：探究CT诊断对于胰腺癌侵犯胰周动静脉的临床价值。方法：随机选取在我院就诊的64例胰腺癌患者,在他们进行手术前全在距离肿瘤边缘1cm内的血管进行分期和诊断进而进行螺旋CT检查。结果：经组织学术后病理切片染色发现胰周动脉29条,静脉48条。运用外科手术探查方法发现86条胰周动脉,89条胰周静脉。在这些血管中,有23条动脉、47条静脉经外科手术证实的确是肿瘤侵犯,并且经过CT诊断,我们最终断定为有25条动脉、46条静脉处于1～4级。结论：胰周动、静脉受到侵犯时,具有不同的CT表现特征,因此在利用CT方法判断胰周动、静脉遭受侵犯时应当根据不同情况不同对待。     

Therapeutic potential of α,β‐thujone through metabolic reprogramming and caspase‐dependent apoptosis in ovarian cancer cells

The therapeutic potential of α,β‐thujone, a functional compound found in many medicinal plants of the Cupressaceae, Asteraceae, and Lamiaceae families, has been demonstrated, including in inflammation and cancers. However, its pharmacological functions and mechanisms of action in ovarian cancer remain unclear. We investigated the anticancer properties of α,β‐thujone in ES2 and OV90 human ovarian cancer cells and its effect on sensitization to cisplatin. α,β‐thujone inhibited cancer cell proliferation and induced cell death through caspase‐dependent intrinsic apoptotic pathways. Moreover, α,β‐thujone‐mediated endoplasmic reticulum stress was associated with the loss of mitochondrial functions and altered metabolic landscape of ovarian cancer cells. α,β‐Thujone attenuated blood vessel formation in transgenic zebrafish, implying it has significant antiangiogenic potential. In addition, α,β‐thujone sensitized ovarian cancer cells to cisplatin, causing synergistic pharmacological effects. Collectively, our results suggest that α,β‐thujone has therapeutic potential in human ovarian cancer and functions via regulating multiple intracellular stress‐associated metabolic reprogramming and caspase‐dependent apoptotic pathways.     

MicroRNA-221 promotes colorectal cancer cell invasion and metastasis by targeting RECK

MicroRNAs (miRNAs) have recently emerged as regulators of metastasis. We provide insight into the behavior of miR-221 in colorectal cancer (CRC) metastasis by showing that miR-221 is significantly upregulated in metastatic CRC cell lines and tissues. miR-221 overexpression enhances, whereas miR-221 depletion reduces CRC cell migration and invasion in vitro and metastasis in vivo. We identify RECK as a direct target of miR-221, reveal its expression to be inversely correlated with miR-221 in CRC samples and show that its re-introduction reverses miR-221-induced CRC invasiveness. Collectively, miR-221 is an oncogenic miRNA which may regulate CRC migration and invasion through targeting RECK.     

Oligonucleotide biological activity: Relationship to the cell cycle and nuclear transport

Previous studies suggest that oligodeoxynucleotide (ODN) cellular uptake is cell cycle-dependent which may have important implications in cancer cell targeting. To further our understanding of ODN transport and activity, this study examines the relationships between the cell cycle, ODN cellular uptake, intracellular transport, and activity. An antisense c-myc ODN 21-mer was used to study ODN cellular uptake in Rauscher erythroleukemia cells synchronized by either chemical methods or flow cytometry. ODN uptake was examined using subcellular fractionation and confocal fluorescence microscopy. Western blot analysis was used to measure ODN-mediated decreases in c-myc protein levels. Intracellular ODN distribution and extent of uptake was influenced by the phase of the cell cycle, but the mechanism of uptake was not. The relative activity of the antisense ODN was positively correlated to ODN distribution to the cytosol, but negatively correlated to total cellular uptake. Although ODN total cellular uptake is positively influenced by the cell cycle, retention of the ODN in the cytosol (presumably extra-vesicularly) appeared to be relevant in determining the activity of an antisense ODN. Novel methods to target cytosol-acting drugs to the cytoplasm may therefore be warrented.     

转酮酶在癌症中的作用及其机制研究进展

肿瘤细胞的一大重要特征是代谢水平的改变。戊糖磷酸途径作为细胞产生NADPH和五碳糖的主要通路,在肿瘤发生发展过程中发挥着重要功能。转酮酶是戊糖磷酸途径中的关键酶之一,越来越多的研究表明其与癌症病人预后具有显著相关性。作为肿瘤诊断、治疗的潜在靶标,转酮酶具有重要的研究价值。我们就目前癌症研究中对转酮酶的研究进展做简要综述。