bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of lithogeochemistry to gold exploration in the St Ives goldfield, Western Australia
Authors: Prendergast Kylie 
Published: April 2007

Lithogeochemistry is being routinely applied to gold exploration programmes at St Ives, Kambalda. Sampling of fresh rock for multi-element analysis is undertaken in all ongoing exploration drilling, and supplementary sampling of archived drill hole pulp samples has also been implemented. Samples are digested by a four-acid digest (hydrofluoric, nitric, perchloric and hydrochloric acids) in Teflon tubes using a specially designed microprocessor controlled digester and analysed by ICP-MS/OES for 36 elements (Ag, As, Ba, Bi, Ce, Cs, Hf, La, Li, Mo, Nb, Pb, Rb, Sb, Ta, Te, Th, W, Zr, Al, Ca, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, P, S, Sc, Sr, Ti, V, Zn). Multi-element results undergo two stages of assessment: (a) utilization of trace elements to characterize lithological and stratigraphic domains, and (b) utilization of major and pathfinder elements to characterize samples that are altered or enriched above background levels.
Bi-plots of trace elements are used to constrain rock type and stratigraphy. Diagnostic inter-element ratios are apparent, which enable clear differentiation of Kambalda Komatiite, Devon Consols Basalt and Paringa Basalt. Condenser Dolerite can be differentiated from other mafic units except Lunnon Basalt. Fractionated dolerite sills are highly prospective host rocks for gold mineralization in the St Ives field. In all cases the fractionated portion of dolerite sills is readily identified by a Ti concentration greater than 6000 ppm.
Unaltered and altered ultramafic, mafic, felsic–intermediate rocks have been assessed using molar Na/Al and K/Al alteration indices to define areas of sodic, potassic and strong potassic alteration. The distribution of potassic and sodic altered samples favourably correlates with the distribution of observed biotite and albite alteration and known gold mineralization.
Pathfinder elements (As, Bi, Sb, W, Mo) have been assessed at the scale of the whole field. Antimony is decoupled from Mo and Bi. Bismuth displays good association with existing gold deposits and areas of known intrusions. Areas of As enrichment correlate spatially with Sb although they are not as widely distributed. Tungsten is the most constrained of the pathfinders and displays excellent correlation with major structures and existing gold deposits.
TIP30 Mutant Derived from Hepatocellular Carcinoma Specimens Promotes Growth of HepG2 Cells through Up-Regulation of N-cadherin
Authors: Jiang Chao , Pecha Jill , Hoshino Isamu , Ankrapp David , Xiao Hua 
Published: April 2007

Abstract
TIP30 is a tumor suppressor whose expression is altered in human liver, prostate, lung, colon, and breast cancers. Mice lacking TIP30 spontaneously developed hepatocellular carcinomas (HCC) and other tumors at a higher incidence than wild-type mice. Somatic missense mutations in the TIP30 gene were identified in human HCC tissue specimens, which resulted in instability or abnormal cellular distribution of TIP30 protein in cells. Here, we show that TIP30 mutants are able to promote cell growth and invasion and inhibit cisplatin-induced apoptosis in the HCC cell line HepG2 negative for endogenous TIP30. Moreover, one of the TIP30 mutants can dramatically accelerate tumor formation in immunodeficient mice. Analysis of gene expression in HepG2 cells, ectopically expressing either wild-type TIP30 or mutant TIP30, by Affymetrix GeneChip array, real-time quantitative PCR, and Western blotting assays reveals that TIP30 mutants can alter expression of genes involved in the regulation of tumorigenesis. This includes up-regulation of expression of N-cadherin and c-MYC and down-regulation of expression of p53 and E-cadherin. N-cadherin knockdown with small interfering RNA in HepG2 cells expressing mutant TIP30 resulted in a profound reduction in cell viability. Taken together, our data indicate that somatic mutations in the TIP30 gene may abolish its native tumor-suppressor activity and gain oncogenic activities partially through up-regulation of N-cadherin, thereby potentiating the pathogenesis of HCC in patients. [Cancer Res 2007;67(8):1–9]
Monocyte Chemotactic Protein-1 Mediates Prostate Cancer–Induced Bone Resorption
Authors: Lu Yi , Cai Zhong , Xiao Guozhi , Keller Evan T. , Mizokami Atsushi , Yao Zhi , Roodman G. David , Zhang Jian 
Published: April 2007

AbstractProstate cancer preferentially metastasizes to bone, resulting in high mortality. Strategies to inhibit prostate cancer metastasis include targeting both tumor-induced osteoblastic lesions and underlying osteoclastic activities. We and others have previously shown that blocking receptor activator of nuclear factor-κB ligand (RANKL) partially blocks tumor establishment and progression in bone in murine models. However, levels of RANKL in the cell lines used in these studies were very low, suggesting that soluble factors other than RANKL may mediate the cancer-induced osteoclast activity. To identify these factors, a human cytokine antibody array was used to measure cytokine expression in conditioned medium collected from primary prostate epithelial cells (PrEC), prostate cancer LNCaP and its derivative C4-2B, and PC3 cells. All prostate cancer cells produced high amounts of monocyte chemotactic protein-1 (MCP-1) compared with PrEC cells. Furthermore, levels of interleukin (IL)-6, IL-8, GROα, ENA-78, and CXCL-16 were higher in PC3 than LNCaP. These results were confirmed by ELISA. Finally, human bone marrow mononuclear cells (HBMC) were cultured with PC3 conditioned medium. Although both recombinant human MCP-1 and IL-8 directly stimulated HBMC differentiation into osteoclast-like cells, IL-8, but not MCP-1, induced bone resorption on dentin slices with 21 days of culture in the absence of RANKL. However, the conditioned medium–induced bone resorption was inhibited by MCP-1 neutralizing antibody and was further synergistically inhibited with IL-8 antibody, indicating that MCP-1, in addition to IL-8, mediates tumor-induced osteoclastogenesis and bone resorption. MCP-1 may promote preosteoclast cell fusion, forming multinucleated tartrate-resistant acid phosphatase–positive osteoclast-like cells. This study may provide novel therapeutic targets for treatment of prostate cancer skeletal metastasis. [Cancer Res 2007;67(8):3646–53]
Modulation of Angiogenic Phenotype Alters Tumorigenicity in Rat Ovarian Epithelial Cells
Authors: Schumacher Jennifer J. , Dings Ruud P.M. , Cosin Jonathan , Subramanian Indira V. , Auersperg Nelly , Ramakrishnan Sundaram 
Published: April 2007

Abstract
Vascular endothelial growth factor (VEGF) expression correlates with microvessel density, stage, malignant ascites, metastasis, and survival in ovarian cancer. By transducing VEGF165 into a nontumorigenic rat ovarian surface epithelial cell line (ROSE199), we investigated the direct effect of an angiogenic phenotype on tumor development. The neu oncogene, which is overexpressed in &gt;30% of ovarian cancers, was used in comparison. Neu-transfected ROSE199 cells showed phenotypic characteristics of transformation in vitro with an abundance of focus-forming units in monolayer cultures and anchorage-independent growth in soft agar. In contrast, VEGF-secreting ROSE199 cells (VR) retained normal morphology and in vitro growth characteristics (e.g., proliferation rate) compared with parental ROSE199 cells. Interestingly, injection of VR cells into athymic mice formed malignant ascites in 100% of the animals when injected into the peritoneum and developed vascularized tumors in 85% of the mice when injected s.c. Furthermore, blocking VEGF-mediated signaling by the Flk-1/KDR receptor kinase inhibitor SU5416 significantly inhibited the growth of VR tumors. To validate that the proangiogenic switch is responsible for tumor development, the angiogenic phenotype was balanced by the inducible coexpression of endostatin under the control of Tet-activated promoter. Coexpression of endostatin along with VEGF reversed the tumorigenic phenotype of VR cells. These studies show that alterations in the angiogenic characteristics of ovarian surface epithelium may play an important role in the etiology of ovarian cancer, and that inhibition of angiogenesis can be effective in the treatment of epithelial ovarian cancer. [Cancer Res 2007;67(8):3683–90]
Sanguinarine-Dependent Induction of Apoptosis in Primary Effusion Lymphoma Cells
Authors: Hussain Azhar R. , Al-Jomah Naif A. , Siraj Abdul K. , Manogaran Pulicat , Al-Hussein Khalid , Abubaker Jehad , Platanias Leonidas C. , Al-Kuraya Khawla S. , Uddin Shahab 
Published: April 2007

Abstract
Primary effusion lymphoma (PEL) is an incurable, aggressive B-cell malignancy that develops rapid resistance to conventional chemotherapy. In efforts to identify novel approaches to block proliferation of PEL cells, we found that sanguinarine, a natural compound isolated from the root plant Sanguinaria canadendid, inhibits cell proliferation and induces apoptosis in a dose-dependent manner in several PEL cell lines. Our data show that sanguinarine treatment of PEL cells results in up-regulation of death receptor 5 (DR5) expression via generation of reactive oxygen species (ROS) and causes activation of caspase-8 and truncation of Bid (tBid). Subsequently, tBid translocates to the mitochondria causing conformational changes in Bax, leading to loss of mitochondrial membrane potential and release of cytochrome c to the cytosol. Sanguinarine-induced release of cytochrome c results in activation of caspase-9 and caspase-3 and poly(ADP-ribose) polymerase (PARP) cleavage, leading to induction of caspase-dependent apoptosis. In addition, we show that pretreatment of PEL cells with carbobenzoxy-Val-Ala-Asp-fluoromethylketone, a universal inhibitor of caspases, abrogates caspase and PARP activation and prevents cell death induced by sanguinarine. Moreover, treatment of PEL cells with sanguinarine down-regulates expression of inhibitor of apoptosis proteins (IAP). Finally, N-acetylcysteine, an inhibitor of ROS, inhibits sanguinarine-induced generation of ROS, up-regulation of DR5, Bax conformational changes, activation of caspase-3, and down-regulation of IAPs. Taken together, our findings suggest that sanguinarine is a potent inducer of apoptosis of PEL cells via up-regulation of DR5 and raise the possibility that this agent may be of value in the development of novel therapeutic approaches for the treatment of PEL. [Cancer Res 2007;67(8):3888–97]
An Imaging Biomarker of Early Treatment Response in Prostate Cancer that Has Metastasized to the Bone
Authors: Lee Kuei C. , Sud Sudha , Meyer Charles R. , Moffat Bradford A. , Chenevert Thomas L. , Rehemtulla Alnawaz , Pienta Kenneth J. , Ross Brian D. 
Published: April 2007

Abstract
Prostate cancer ranks as the most common lethal malignancy diagnosed and the second leading cause of cancer mortality in American men. Although high response rates are achieved using androgen blockade as first-line therapy, most men progress toward hormone-refractory prostate cancer. Systemic chemotherapies have been shown to improve clinical outcome in hormone refractory prostate cancer patients; however, they are not curative. Due to the high incidence of bone involvement in hormone-refractory prostate cancer, assessment of treatment response in metastatic prostate cancer to the bone remains a major clinical need. In this current study, we investigated the feasibility of using the functional diffusion map (fDM) as an imaging biomarker for assessing early treatment response in a preclinical model of metastatic prostate cancer. The fDM biomarker requires a pretreatment and midtreatment magnetic resonance imaging diffusion map, which is used to quantify spatially distinct therapeutic-induced changes in the Brownian motion (or diffusion) of water within tumor tissue. Because water within tumor cells is in a restricted environment relative to extracellular water, loss of cell membrane integrity and cellular density during therapy will be detected by fDM as an increase in diffusion. Regions of significantly increased diffusion values were detected early using fDM in docetaxel-treated versus untreated metastatic prostate bone tumors at 7 days post treatment initiation (P &lt; 0.05), indicating loss of tumor cell viability. Validation of fDM results was accomplished by histologic analysis of excised tissue. Results from this study show the capability of fDM as a biomarker for detection of bone cancer treatment efficacy, thus warranting clinical evaluation. [Cancer Res 2007;67(8):3524–8]
Identification of Cancer Stem Cell–Like Side Population Cells in Human Nasopharyngeal Carcinoma Cell Line
Authors: Wang Jing , Guo Li-Ping , Chen Li-Zhen , Zeng Yi-Xin , Lu Shih Hsin 
Published: April 2007

Abstract
Side population (SP) cells have been isolated from several solid tumors. They lack distinct molecular markers for cancer stem cells (CSC) and increasing evidence suggests that they may play an important role in tumorigenesis and cancer therapy. However, there are no reports about the existence and function of SP cells in nasopharyngeal carcinoma (NPC) cells thus far. In this study, we scanned SP cells from five NPC cell lines and investigated stem cell characteristics, such as proliferation, self-renewal, and differentiation, using SP cells from the widely-used CNE-2 NPC cell line. We observed a strong tumorigenesis ability of SP cells following in vivo transplantation into nonobese diabetic/severe combined immunodeficient mice. Immunofluorescence revealed that cytokine 19 was highly expressed on SP cells. SP cells were found to be more resistant to chemotherapy and radiotherapy and this was related to the ATP-binding cassette half transporter member 2 of G family protein and Smoothened protein expression, respectively. Our results not only showed that SP cells in human NPC cell line CNE-2 had stem cell characteristics in vitro but also showed that they had a strong ability to form tumors in vivo. Importantly, we found the cell marker, cytokine 19, may serve as a potential molecular marker for further characterization of CSC. Taken together, our data shed light on tumorigenesis and therapeutic-resistant mechanisms, which are helpful for developing novel targets for effective clinical treatment of NPC. [Cancer Res 2007;67(8):3716–24]
GRP78/BiP Inhibits Endoplasmic Reticulum BIK and Protects Human Breast Cancer Cells against Estrogen Starvation–Induced Apoptosis
Authors: Fu Yong , Li Jianze , Lee Amy S. 
Published: April 2007

Abstract
The recent development of hormonal therapy that blocks estrogen synthesis represents a major advance in the treatment of estrogen receptor–positive breast cancer. However, cancer cells often acquire adaptations resulting in resistance. A recent report reveals that estrogen starvation–induced apoptosis of breast cancer cells requires BIK, an apoptotic BH3-only protein located primarily at the endoplasmic reticulum (ER). Searching for novel partners that interact with BIK at the ER, we discovered that BIK selectively forms complex with the glucose-regulated protein GRP78/BiP, a major ER chaperone with prosurvival properties naturally induced in the tumor microenvironment. GRP78 overexpression decreases apoptosis of 293T cells induced by ER-targeted BIK. For estrogen-dependent MCF-7/BUS breast cancer cells, overexpression of GRP78 inhibits estrogen starvation–induced BAX activation, mitochondrial permeability transition, and consequent apoptosis. Further, knockdown of endogenous GRP78 by small interfering RNA (siRNA) sensitizes MCF-7/BUS cells to estrogen starvation–induced apoptosis. This effect was substantially reduced when the expression of BIK was also reduced by siRNA. Our results provide the first evidence that GRP78 confers resistance to estrogen starvation–induced apoptosis in human breast cancer cells via a novel mechanism mediated by BIK. These results further suggest that GRP78 expression level in the tumor cells may serve as a prognostic marker for responsiveness to hormonal therapy based on estrogen starvation and that combination therapy targeting GRP78 may enhance efficacy and reduce resistance. [Cancer Res 2007;67(8):3734–40]
Elucidating the Function of Secreted Maspin: Inhibiting Cathepsin D–Mediated Matrix Degradation
Authors: Khalkhali-Ellis Zhila , Hendrix Mary J.C. 
Published: April 2007

Abstract
Cellular interaction with the extracellular milieu plays a significant role in normal biological and pathologic processes. Excessive degradation of basement membrane matrix by proteolytic enzymes is a hallmark of tumor invasion and metastasis, and aspartyl proteinase cathepsin D is implicated as a major contributor to this process. Maspin, a non-inhibitory serpin, plays an important role in mammary gland development and remodeling. Expression of Maspin is decreased in primary tumors and lost in metastatic lesions. Maspin is mostly cytoplasmic and is partially secreted; however, the fate and function of secreted Maspin has remained mostly unexplored. We hypothesized that secreted Maspin is incorporated into the matrix deposited by normal mammary epithelial cells and thus could play a critical role in cathepsin D–mediated matrix degradation and remodeling of mammary tissue. In the absence of Maspin, as is the case with most cancer cells, matrix degradation proceeds unrestricted, thus facilitating the progression to metastasis. To test this, we employed an in vitro model where gels containing both types I and IV collagen were preconditioned with normal mammary epithelial cells to allow the incorporation of secreted Maspin. This conditioned matrix was used to examine cathepsin D–mediated collagen degradation by human breast cancer cell lines. Our results indicate that secretion of Maspin and its deposition into the extracellular milieu play an important role in matrix degradation. In this capacity, Maspin could potentially regulate mammary tissue remodeling occurring under normal and pathologic conditions. In addition, these findings could have a potential effect on future therapeutic intervention strategies for breast cancer. [Cancer Res 2007;67(8):3535–9]
GRP78 Induction in Cancer: Therapeutic and Prognostic Implications
Authors: Lee Amy S. 
Published: April 2007

Abstract
Cancer cells adapt to chronic stress in the tumor microenvironment by inducing the expression of GRP78/BiP, a major endoplasmic reticulum chaperone with Ca2+-binding and antiapoptotic properties. GRP78 promotes tumor proliferation, survival, metastasis, and resistance to a wide variety of therapies. Thus, GRP78 expression may serve as a biomarker for tumor behavior and treatment response. Combination therapy suppressing GRP78 expression may represent a novel approach toward eradication of residual tumors. Furthermore, the recent discovery of GRP78 on the cell surface of cancer cells but not in normal tissues suggests that targeted therapy against cancer via surface GRP78 may be feasible. [Cancer Res 2007;67(8):3496–9]
The randomized discontinuation trial: a phase II design to assess growth-inhibitory agents
Authors: Stadler Walter M. 
Published: April 2007

Abstract
An increasing number of putative anticancer targets and drugs have been identified with many of these expected to be growth inhibitory. Clinical development of these agents in the phase II setting is challenging because tumor shrinkages, or at least tumor shrinkages that meet the standard definitions of objective response, are not expected. Time to progression end points are however problematic because expected times in the absence of therapy (the null hypothesis) cannot be predicted accurately, thus requiring trials to enroll a concurrent control group. Another problem is that the patient population that will benefit from a new drug remains poorly defined in early-phase development. The randomized discontinuation trial design addresses both of these issues. All patients are initially treated with the drug; patients with an objective response continue therapy; patients who do not progress or experience excess toxicity within a prespecified “run-in” period are then randomized to continuing or discontinuing therapy in a double-blind, placebo controlled manner. Despite certain limitations that need to be recognized, the ability of this design to “select” a cohort most likely to benefit and to rigorously evaluate the disease-stabilizing activity of an investigational agent provides multiple advantages. [Mol Cancer Ther 2007;6(4):1180–5]
Molecular mechanisms of the chemopreventive effect on hepatocellular carcinoma development in Mdr2 knockout mice
Authors: Katzenellenbogen Mark , Mizrahi Lina , Pappo Orit , Klopstock Naama , Olam Devorah , Barash Hila , Domany Eytan , Galun Eithan , Goldenberg Daniel 
Published: April 2007

Abstract
Dietary antioxidants and selenium compounds were shown to have a therapeutic effect against hepatocellular carcinoma in several mouse models. We tested the effects of tannic acid and selenomethionine on hepatocellular carcinoma development in Mdr2 knockout (Mdr2-KO) mice. Mdr2-KO and age-matched Mdr2 heterozygous control mice were fed with tannic acid or selenomethionine during the first 3 months of life. Then, several mice from each group were sacrificed, and liver tissue samples were removed for analysis. The remaining mice were fed a regular diet until the age of 16 months, at which time the number and size of liver tumors were determined. Liver tissue samples of 3-month-old mice were subjected to gene expression profiling analysis using cDNA macroarrays containing probes for 240 genes that regulate responses to oxidative stress and inflammation or lipid metabolism. Both tannic acid and selenomethionine had partial chemopreventive effect on development of hepatocellular carcinoma in Mdr2-KO mice: they reduced the incidence of large tumor nodules (diameter &gt;1 cm) at age 16 months. Both agents inhibited gene expression and reversed up-regulation of many genes that control inflammation or response to oxidative stress in Mdr2-KO livers at age 3 months. This inhibitory effect on gene expression correlated with the ability of agents to reduce incidence of large tumors: selenomethionine was more active than tannic acid in both aspects. Understanding the molecular mechanism of chemoprevention effect could improve our therapeutic modalities while using these agents. [Mol Cancer Ther 2007;6(4):1283–91]