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At least 1,225 records · Page 68

Reparative neurogenesis after cerebral ischemia: Clinical application prospects

At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die before reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors.

60 APPLIED LIFE SCIENCES↗

Matrigel immobilization on the shish-kebab structured poly(ε-caprolactone) nanofibers for skin tissue engineering

Surface properties of tissue engineering scaffolds such as topography, hydrophilicity, and functional groups play a vital role in cell adhesion, migration, proliferation, and apoptosis. First, poly(ε-caprolactone) (PCL) shish-kebab scaffolds (PCL-SK), which feature a three-dimensional structure comprised of electrospun PCL nanofibers covered by periodic, self-induced PCL crystal lamellae on the surface, was created to mimic the nanotopography of native collagen fibrils in the extracellular matrix (ECM). Second, matrigel was covalently immobilized on the surface of alkaline hydrolyzed PCL-SK scaffolds to enhance their hydrophilicity. This combined approach not only mimics the nanotopography of native collagen fibrils, but also simulates the surface features of collagen fibrils for cell growth. To investigate the viability of such scaffolds, HEF1 fibroblast cell assays were conducted and the results revealed that the nanotopography of the PCL-SK scaffolds facilitated cell adhesion and proliferation. The matrigel functionalization on PCL-SK scaffolds further enhanced cellular response, which suggested elevated biocompatibility and greater potential for skin tissue engineering applications.

60 APPLIED LIFE SCIENCES↗

Porous composite materials ZrO{sub 2}(MgO)-MgO for osteoimplantology

The pore structure and phase composition of ceramic composite material ZrO{sub 2}(Mg)-MgO at different sintering temperatures were studied. The main mechanical characteristics of the material were determined and it was shown that they are close to the characteristics of natural bone tissues. It was shown that material structure has a positive effect on the pre-osteoblast cells proliferation. In-vitro studies of pre-osteoblast cells, cultivation on material surface showed a good cell adhesion, proliferation and differentiation of MMSC by osteogenic type.

36 MATERIALS SCIENCE↗

Peripheral blood hematology, plasma biochemistry, and the optimization of an in vitro immune-based assay in the brown watersnake ( Nerodia taxispilota )

Reptiles represent a phylogenetic lineage that provides a unique link between ectothermic anamniotes and endothermic amniotes. Compared to mammalian and avian species, our understanding of the reptilian immune system is greatly lacking. This gap in knowledge is largely due to an absence of established immune-based assays or specific reagents for these species. In the present study, brown watersnakes (Nerodia taxispilota) were live-captured in the wild, sexed, weighed, measured, bled via the caudal vein and released. At 24 hr post-collection, peripheral blood leukocytes were enriched and evaluated with an established mammalian in-vitro lymphocyte proliferation assay. Snake peripheral blood leukocyte enrichment yielded > 90% lymphocytes with viabilities averaging 81.5%. Baseline physiologic data for N. taxispilota, including hematology and total solids, leukocyte differentials, cell recovery and plasma biochemistry, were also collected. Cells cultured with Concanavalin A exhibited significantly increased proliferation at both 72 and 96 hr. Furthermore, these preliminary results show that enriched peripheral blood from wild-caught N. taxispilota provides a sufficient yield of leukocytes that can be cultured and functionally evaluated using a standard mammalian in-vitro immune-based assay.

59 BASIC BIOLOGICAL SCIENCES↗

Delineating transcriptional networks of prognostic gene signatures refines treatment recommendations for lymph node-negative breast cancer patients

The majority of women diagnosed with lymph node-negative breast cancer are unnecessarily treated with damaging chemotherapeutics after surgical resection. This highlights the importance of understanding and more accurately predicting patient prognosis. We define the transcriptional networks regulating well-established prognostic gene expression signatures. We find that the same set of transcriptional regulators consistently lie upstream of both ‘prognosis’ and ‘proliferation’ gene signatures, suggesting that a central transcriptional network underpins a shared phenotype within these signatures. Strikingly, the master transcriptional regulators within this network predict recurrence risk for lymph node-negative breast cancer better than currently used multigene prognostic assays, particularly in estrogen receptor-positive patients. Simultaneous examination of p16 INK4A expression, which predicts tumours that have bypassed cellular senescence, revealed that intermediate levels of p16 INK4A correlate with an intact pRB pathway and improved survival. A combination of these master transcriptional regulators and p16 INK4A , termed the OncoMasTR score, stratifies tumours based on their proliferative and senescence capacity, facilitating a clearer delineation of lymph node-negative breast cancer patients at high risk of recurrence, and thus requiring chemotherapy. Furthermore, OncoMasTR accurately classifies over 60% of patients as ‘low risk’, an improvement on existing prognostic assays, which has the potential to reduce overtreatment in early-stage patients. Taken together, the present study provides new insights into the transcriptional regulation of cellular proliferation in breast cancer and provides an opportunity to enhance and streamline methods of predicting breast cancer prognosis.

59 BASIC BIOLOGICAL SCIENCES↗

Increased Expression of DNAJC12 is Associated with Aggressive Phenotype of Gastric Cancer

Background: Identification of gastric cancer-related molecules is necessary to elucidate the pathological mechanisms of this heterogeneous disease. The purpose of this study was to identify novel genes associated with aggressive phenotypes of gastric cancer. Methods: Global expression profiling was conducted using tissues from four patients with metastatic gastric cancer to identify genes overexpressed in gastric cancer. Fifteen gastric cell lines and 262 pairs of surgically resected gastric tissues were subjected to mRNA expression analysis. The contribution of the candidate gene on gastric cancer cell proliferation, invasion, adhesion, and migration were evaluated using small interfering RNA. Results: DnaJ heat shock protein family (Hsp40) member C12 (DNAJC12) was identified as a candidate gene by transcriptome analysis. In clinical samples, DNAJC12 mRNA levels were higher in gastric cancer tissues compared with normal adjacent tissues. Patients with high DNAJC12 expression showed significantly shorter overall survival in our cohort and in the extra-validation cohort analyzed by a published microarray dataset. High DNAJC12 expression in gastric cancer tissues was significantly associated with lymphatic involvement, infiltrative growth type, lymph node metastasis, and advanced stage and was identified as an independent prognostic factor for overall survival in multivariable analysis. Increased expression of DNAJC12 was found in 12 of 14 examined gastric cancer cell lines. Knockdown of DNAJC12 expression significantly decreased the proliferation and invasion abilities of gastric cancer cells. Conclusions: Our findings support DNAJC12 as a candidate gene associated with aggressive phenotypes of gastric cancer.

60 APPLIED LIFE SCIENCES↗

Methylprednisolone Inhibits Tumor Growth and Peritoneal Seeding Induced by Surgical Stress and Postoperative Complications

Background: Surgery often introduce inflammatory response, which may promote tumor growth and metastasis of residual cancer cells. We investigated the impacts of methylprednisolone on the tumor growth and peritoneal seedings in mice treated with lipopolysaccharide (LPS), which mimics systemic inflammation induced by surgical stress and postoperative complications. Methods: The serum interleukin-6 (IL-6) levels, tumor volume, tumor weight, and the number of peritoneal nodules were investigated in tumor growth model and peritoneal seeding model using BALB/c mice and murine CT26 cancer cell lines in vivo. We conducted functional analyses of IL-6 in Western blotting and proliferation assays in vitro. We also investigated whether preoperative administration of methylprednisolone decreased postoperative serum IL-6 levels in cancer patients in a randomized clinical study. Results: In the in vivo study, methylprednisolone inhibited the LPS-induced increase of serum IL-6 levels (mean, 33,756 pg/ml vs. 5917 pg/ml; P < 0.001), tumor volume (mean, 397 mm{sup 3} vs. 274 mm{sup 3}; P = 0.019), tumor weight (mean, 0.38 g vs. 0.15 g; P = 0.020), and the number of peritoneal nodules (mean, 112 vs. 47; P = 0.002). In the in vitro study, IL-6 enhanced JAK/STAT signaling and increased the cell proliferation, and IL-6R-neutralizing antibody attenuated these effects. In the clinical study, serum IL-6 levels were significantly decreased by methylprednisolone (median, 97.5 pg/ml vs. 18.0 pg/ml; P = 0.030). Conclusions: Surgical stress and postoperative complications may enhance tumor growth due to the increase of IL-6. However, methylprednisolone can decrease serum IL-6 levels, thus inhibiting tumor growth and peritoneal seeding.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Commercial Nuclear Reprocessing in the United States

The short presentation outline: Reprocessing Overview; Events leading up to Carter’s Policy; Results of the decision; Policy since Nuclear Nonproliferation Act. Conclusions reached: Reprocessing ban has become an easy and visible fix to the public concern about proliferation, but has not completely stopped proliferation; and, Reprocessing needs to become detached from political considerations, so technical research can continue, regardless of the policy decisions we decide to take.

98 NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL P↗

Systems Biology Model of Interactions between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFβ and ATM Signaling

The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently, the transforming growth factor β (TGFβ) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses, and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low-dose responses and cross-talk between the ATM and TGFβ pathways initiated by low- and high-LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to crosstalk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental approaches to apply to these problems using confocal microscopy and flow cytometry to detail changes at low dose/dose-rate in order to understand individual cell responses, and will establish our mathematical models based on the experimental findings resulting from changes in DNA repair, apoptosis and proliferation.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

Investigation of Imaging Spent Nuclear Fuel Dry Casks using Cosmic Ray Muons

Recently, the use of cosmic ray muons for cargo scanning applications has been demonstrated and muons have been shown to have the potential to allow for nondestructive assessment of nuclear material accountancy. Relativistic muons have the ability to penetrate dense materials and monitoring the subsequent scattering of muons can provide information about the structure and composition of materials stored in cargo containers. The suitability of cosmic muons for a number of monitoring and imaging applications has been investigated over the years and includes applications to archaeology, volcano imaging, material identification and medical diagnosis. Novel applications of cosmic ray muons have been proposed for examination of comatose patients towards bone density monitoring and also for determination of the molten nuclear fuel location in nuclear reactors having suffered from the effects of a severe accident similar to the one happened in Fukushima. There is a need to develop a capability to monitor nuclear waste and investigate whether the stored content agrees with facility declarations to allow proliferation detection and international treaty verification. Monitoring nuclear waste and controlling nuclear material at its source is one of the main strategies to minimize the risks of nuclear proliferation and reduce potential homeland threats. Since the early 1950's, when the first nuclear power plant began to produce electricity, approximately 65,000 metric tons of spent nuclear fuel have been generated, 25% of which are under dry storage conditions. After the spent nuclear fuel has been placed inside the dry cask, the cask is welded, not allowing for visual inspection. During the long storage life of the cask, intermediate handling and transportation activities take place which does create concerns regarding fuel integrity. Accidents and natural disasters also contribute to this concern. Previous work on spent nuclear fuel dry cask monitoring using muons has shown that the muon scattering distributions are adequately separated and a and a decision rule derived from Bayes' Theorem rendering the classification of different dry casks feasible. Muons present significant advantages over the existing imaging techniques such as the utilization of the passive nature of muons, the lack of radiological sources and consequently the absence of any artificial radiological dose. In the present work, a methodology is developed to demonstrate the applicability of muons for imaging of spent nuclear fuel dry casks. Purpose is to use muons to differentiate between spent nuclear fuel dry casks with different amounts of loading. Monte Carlo simulations of dry casks with different spent nuclear fuel loading are performed to simulate the passage of polyenergetic muons having energies in the range of 1-60 GeV through matter. A 'Muon Generator' is developed to generate muons that follow the actual sea level energy distribution. The 'Muon Generator' is validated against a series of actual spectrum measurements and then coupled with the Monte Carlo particle transport code GEANT4. The accumulated dataset of scattering angles were processed with the Point-of- the-Closest-Approach (PoCA) imaging algorithm and the obtained images demonstrate that an empty dry cask can be clearly distinguished from a half-loaded or a fully loaded one. The apparent separation of the images demonstrates that the muon scattering can be used as a feature for imaging spent nuclear fuel dry casks. (authors)

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

The Role of Titania Surface Coating by Atomic Layer Deposition in Improving Osteogenic Differentiation and Hard Tissue Formation of Dental Pulp Stem Cells

Recent studies have focused on modifying implant surface properties to improve bone regeneration and osseointegration. Herein, the role of titania surface coating in enabling dental pulp stem cells (DPSCs) differentiation and hard tissue formation is studied. Atomic layer deposition is applied at lower temperature to coat a nanolayer of titania onto hard and soft polybutadiene substrates without altering their moduli, to probe the effects of surface chemistry and substrate modulus. In the absence of titania, DPSCs prefer to attach and proliferate on the hard substrate, where particle-like biomineralization is present after 28 days in culture, whereas no biomineralization is observed on the soft substrate. Applying titania surface coating results in the improvement of adhesion and proliferation, regardless of substrate modulus, whereas cell and substrate moduli remain the same as control without titania coating. Furthermore, templated biomineralization is observed given the bone-like tissue composition by Raman analysis, in consistent with real time-polymerase chain reaction (RT-PCR) results showing upregulation of osteopontin (OPN) and bone sialoprotein (BSP), representing osteogenic differentiation. Furthermore, the results indicate that titania surface coating improved the ability to nucleate banded collagen fibers which in turn templated mineral deposits, and further induced the osteogenesis of DPSCs, regardless of its substrate modulus.

36 MATERIALS SCIENCE↗

A Graded, Porous Composite of Natural Biopolymers and Octacalcium Phosphate Guides Osteochondral Differentiation of Stem Cells

Abstract Lesions involving the osteochondral unit are difficult to treat. Biomimetic scaffolds are previously shown as promising alternative. Such devices often lack multiple functional layers that mimic bone, cartilage, and the interface. In this study, multilayered scaffolds are developed based on the use of natural extracellular matrix (ECM)‐like biopolymers. Particular attention is paid to obtain a complex matrix that mimics the native osteochondral transition. Porous, sponge‐like chitosan‐collagen‐octacalcium phosphate (OCP) scaffolds are obtained. Collagen content increases while the amount of OCP particles decreases toward the cartilage layer. The scaffolds are bioactive as a mineral layer is deposited containing hydroxyapatite at the bony side. The scaffolds stimulate proliferation of human adipose‐derived mesenchymal stem cells, but the degree of proliferation depends on the cell seeding density. The scaffolds give rise to a zone‐specific gene expression. RUNX2, COL1A1, BGLAP, and SPP1 are upregulated in the bony layer of the scaffold. SOX9 is upregulated concomitant with COL2A1 expression in the cartilage zone. Mineralization in presence of the cells is prominent in the bone area with Ca and P steadily increasing over time. These results are encouraging for the fabrication of biomimetic scaffolds using ECM‐like materials and featuring gradients that mimic native tissues and their interface.

Amann, Elisabeth↗

LncRNA ZFAS1 promotes invasion of medullary thyroid carcinoma by enhancing EPAS1 expression via miR‐214‐3p/UCHL1 axis

Abstract lncRNA ZFAS1 was identified to facilitate thyroid cancer, but its role in medullary thyroid carcinoma (MTC) remains unknown. This study aimed to unravel the potential function of this lncRNA in MTC by investigating the involvement of the lncRNA ZFAS1 in a ceRNA network that regulates MTC invasion. Proliferation, invasion, and migration of cells were evaluated using EdU staining and Transwell assays. Immunoprecipitation (IP) assays, dual‐fluorescence reporter, and RNA IP assays were employed to examine the binding interaction among genes. Nude mice were used to explore the role of lncRNA ZFAS1 in MTC in vivo. ZFAS1 and EPAS1 were upregulated in MTC. Silencing ZFAS1 inhibited MTC cell proliferation and invasion under hypoxic conditions, which reduced EPAS1 protein levels. UCHL1 knockdown increased EPAS1 ubiquitination. ZFAS1 positively regulated UCHL1 expression by binding to miR‐214‐3p. Finally, silencing ZFAS1 significantly repressed tumor formation and metastasis in MTC. LncRNA ZFAS1 promotes invasion of MTC by upregulating EPAS1 expression via the miR‐214‐3p/UCHL1 axis.

Chen, Wenjing↗

Rhizosphere bacteria containing ACC deaminase decrease root ethylene emission and improve maize root growth with localized nutrient supply

Abstract Localized nutrient supply can enhance maize root proliferation, but also increase root ethylene production. Whether engineering ethylene signalling in the rhizosphere can further enhance root growth and nutrient uptake remains unknown. Here, field and column experiments for maize ( Zea mays . L) were designed as different nutrient treatments (broadcast or localized nutrient supply containing ammonium and phosphorus) with or without inoculation with rhizobacterium Variovorax paradoxus 5C‐2 containing the 1‐aminocyclopropane‐1‐carboxylate (ACC) deaminase. Rhizobacterial inoculation increased shoot biomass by 12% and root length density by 50% with localized nutrient supply. Meanwhile, localized nutrient supply increased root ethylene production by 54% compared with broadcast, and rhizobacterial inoculation prevented the increase in root ethylene. Reduced root ethylene production following V. paradoxus 5C‐2 inoculation was highly associated with a greater proportion of fine root proliferation under localized nutrient supply, which may account for the increased nitrogen and phosphorus uptake. Our work sheds light on the understanding of the interactions between root and microbe through taking hormone into consideration to dissect the relationship between below ground and above ground. It is useful to explore the strategy of soil–crop management by introducing rhizosphere microorganisms to regulate plant ethylene signal and then benefit sustainable agriculture.

Jin, Kemo↗

Mercury immunotoxicity in the brown watersnake ( Nerodia taxispilota ): An in vitro study

Mercury (Hg) is a heavy metal that enters the environment through natural and anthropogenic means. Once in the environment, Hg can biomagnify in food webs and is known to cause immunotoxic effects to wildlife. Compared with other vertebrates, knowledge of the reptilian immune system is lacking, especially in snakes. Further, even less is known about the impact of environmental contaminants on snake immunity. This gap in knowledge is largely due to an absence of established immune-based assays or specific reagents for these species. In this study, brown watersnakes (Nerodia taxispilota; n = 23) were captured on the Savannah River (Augusta, Georgia, USA), weighed, measured, bled, and released. Peripheral blood leukocytes (24 h old) were enriched and evaluated with an established mammalian in vitro lymphocyte proliferation assay. Enriched leukocytes were then exposed to mercury chloride (HgCl2) at 3.75, 37.5, and 75 μM. Total mercury (THg) in whole blood was also quantified. Snake peripheral blood leukocyte enrichment yielded >90% lymphocytes with viabilities averaging >70%. Exposure to HgCl 2 resulted in significant dose-dependent suppression of proliferative responses relative to spontaneous proliferation at 37.5 and 75 μM (both p ≤ 0.01) but not 3.75 μM (p = 0.99). Mean ± 1 SE concentration of THg in whole blood was 0.127 ± 0.027 mg/kg (wet weight). Based on the in vitro findings with HgCl 2 , snakes in systems with heavy Hg pollution may be at risk of immunosuppression, but N. taxispilota at the site in this study appear to be at low risk.

59 BASIC BIOLOGICAL SCIENCES↗

Nonlinear sigma models with compact hyperbolic target spaces

We explore the phase structure of nonlinear sigma models with target spaces corresponding to compact quotients of hyperbolic space, focusing on the case of a hyperbolic genus-2 Riemann surface. The continuum theory of these models can be approximated by a lattice spin system which we simulate using Monte Carlo methods. The target space possesses interesting geometric and topological properties which are reflected in novel features of the sigma model. In particular, we observe a topological phase transition at a critical temperature, above which vortices proliferate, reminiscent of the Kosterlitz-Thouless phase transition in the O(2) model [1, 2]. Unlike in the O(2) case, there are many different types of vortices, suggesting a possible analogy to the Hagedorn treatment of statistical mechanics of a proliferating number of hadron species. Below the critical temperature the spins cluster around six special points in the target space known as Weierstrass points. In conclusion, the diversity of compact hyperbolic manifolds suggests that our model is only the simplest example of a broad class of statistical mechanical models whose main features can be understood essentially in geometric terms.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Mechanistic studies of the apoptosis induced by the macrocyclic natural product tetrandrine in MGC 803 cells

Tetrandrine (Tet) is a macrocyclic tetrahydroisoquinoline alkaloid isolated from Stephania tetrandra S. Moore along with other Chinese and Japanese herbs. It has been used extensively for the treatment of silicosis, autoimmune disorders, inflammatory diseases and cardiovascular diseases. Of late, Tet has garnered increasing attention for its anticancer activity and its efficacy to reverse chemoresistance. In this study, we evaluated the cytotoxicity of Tet on MGC 803 gastric cancer cells using the methyl thiazolyl tetrazolium (MTT) assay. In addition, apoptosis and cell cycle were analyzed through flow cytometry, mitochondrial membrane potential (MMP) was measured using fluorescence microscopy and migration of cells was determined by transwell assay. It was observed that Tet efficiently inhibited the proliferation of MGC 803 cells in a concentration-dependent and time-dependent manner and reduced the number of colonies at low concentrations. It induced apoptosis through mitochondrial dysfunction, which may be related with upregulated Bcl-2-associated X protein (Bax), and downregulated of B cell lymphoma 2 (Bcl-2). On the other hand, Tet blocked the cell cycle at Gap 2 (G2)/mitosis (M) phase, which was associated with the upregulation of p21{sup CIP1/WAF1}. Furthermore, Tet elevated the intracellular reactive oxygen species (ROS) level and suppressed the migration of MGC 803 cells. Altogether, we demonstrated that Tet inhibited the proliferation and migration of gastric cancer MGC 803 cells and thus might be a potential drug candidate for the treatment of gastric cancer.

60 APPLIED LIFE SCIENCES↗

Experimental study of the antitumor effect of aurumacryl

Gold polyacrylate (aurumacryl) belonging to a new class of compounds for oncology — metal polyacrylates — was shown to exhibit strong antitumor activity. Aurumacryl causes 80—90% growth inhibition in vivo of murine solid tumors (Lewis lung carcinoma, Ca-755 adenocarcinoma, and Acatol adenocarcinoma) compared to the control and induces cell death in vitro in 60% of MCF-7 human breast carcinoma cells. Substantial changes in proliferation kinetics of the surviving fraction of tumor cells following treatment with aurumacryl were observed, which are related to the predominant accumulation (93%) of cells in the proliferative resting phase G{sub 0} and a substantial decrease in the percentage of proliferating cells (7%). These data provide evidence that the cells that survive lose reproductive ability under treatment with aurumacryl.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗