RESUMO
Metastases are the cause of the vast majority of cancer deaths. In the metastatic process, cells migrate to the vasculature, intravasate, extravasate, and establish metastatic colonies. This pattern of spread requires the cancer cells to change shape and to navigate tissue barriers. Approaches that block this mechanical program represent new therapeutic avenues. We show that 4-hydroxyacetophenone (4-HAP) inhibits colon cancer cell adhesion, invasion, and migration in vitro and reduces the metastatic burden in an in vivo model of colon cancer metastasis to the liver. Treatment with 4-HAP activates nonmuscle myosin-2C (NM2C) (MYH14) to alter actin organization, inhibiting the mechanical program of metastasis. We identify NM2C as a specific therapeutic target. Pharmacological control of myosin isoforms is a promising approach to address metastatic disease, one that may be readily combined with other therapeutic strategies.
Assuntos
Acetofenonas/farmacologia , Actomiosina/metabolismo , Citoesqueleto , Metástase Neoplásica/fisiopatologia , Actinas/metabolismo , Animais , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Feminino , Células HCT116 , Humanos , Camundongos , Camundongos NusRESUMO
Two substituted phosphonium tetrahydoxidohexaoxidopentaborate(1-) salts, [iPrPPh3][B5O6(OH)4]·3.5H2O (1) and [MePPh3][B5O6(OH)4]·B(OH)3·0.5H2O (2), were prepared by templated self-assembly processes with good yields by crystallization from basic methanolic aqueous solutions primed with B(OH)3 and the appropriate phosphonium cation. Salts 1 and 2 were characterized by spectroscopic (NMR and IR) and thermal (TGA/DSC) analysis. Salts 1 and 2 were thermally decomposed in air at 800 °C to glassy solids via the anhydrous phosphonium polyborates that are formed at lower temperatures (<300 °C). BET analysis of the anhydrous and pyrolysed materials indicated they were non-porous with surface areas of 0.2-2.75 m2/g. Rhe recrystallization of 1 and 2 from aqueous solution afforded crystals suitable for single-crystal XRD analyses. The structure of 1 comprises alternating cationic/anionic layers with the H2O/pentaborate(1-) planes held together by H-bonds. The cationic planes have offset face-to-face (off) and vertex-to-face (vf) aromatic ring interactions with the iPr groups oriented towards the pentaborate(1-)/H2O layers. The anionic lattice in 2 is expanded by the inclusion of B(OH)3 molecules to accommodate the large cations; this results in the formation of a stacked pentaborate(1-)/B(OH)3 structure with channels occupied by the cations. The cations within the channels have vf, ef (edge-to-face), and off phenyl embraces. Both H-bonding and phenyl embrace interactions are important in stabilizing these two solid-state structures.
RESUMO
The synthesis and characterization of six new substituted guanidium tetrahydroxidohexaoxidopentaborate(1-) salts are reported: [C(NH2)2(NHMe)][B5O6(OH)4]·H2O (1), [C(NH2)2(NH{NH2})][B5O6(OH)4] (2), [C(NH2)2(NMe2)][B5O6(OH)4] (3), [C(NH2)(NMe2)2][B5O6(OH)4] (4), [C(NHMe)(NMe2)2][B5O6(OH)4]·B(OH)3 (5), and [TBDH][B5O6(OH)4] (6) (TBD = 1,5,7-triazabicyclo [4.4.0]dec-5-ene). Compounds 1-6 were prepared as crystalline salts from basic aqueous solution via self-assembly processes from B(OH)3 and the appropriate substituted cation. Compounds 1-6 were characterized by spectroscopic (NMR and IR) and by single-crystal XRD studies. A thermal (TGA) analysis on compounds 1-3 and 6 demonstrated that they thermally decomposed via a multistage process to B2O3 at >650 °C. The low temperature stage (<250 °C) was endothermic and corresponded to a loss of H2O. Reactant stoichiometry, solid-state packing, and H-bonding interactions are all important in assembling these structures. An analysis of H-bonding motifs in known unsubstituted guanidinium salts [C(NH2)3]2[B4O5(OH)4]·2H2O, [C(NH2)3][B5O6(OH)4]·H2O, and [C(NH2)3]3[B9O12(OH)6] and in compounds 1-6 revealed that two important H-bonding R22(8) motifs competed to stabilize the observed structures. The guanidinium cation formed charge-assisted pincer cation-anion H-bonded rings as a major motif in [C(NH2)3]2[B4O5(OH)4]·2H2O and [C(NH2)3]3[B9O12(OH)6], whereas the anion-anion ring motif was dominant in [C(NH2)3][B5O6(OH)4]·H2O and in compounds 1-6. This behaviour was consistent with the stoichiometry of the salt and packing effects also strongly influencing their solid-state structures.
RESUMO
Crystalline materials containing hybrid inorganic-organic metal borates (complexes with oxidoborate ligands) display a variety of novel framework building blocks. The structural aspects of these hybrid metallaoxidoborates containing Cd(II), Co(II), Cu(II), Ga(III), In(III), Mn(II), Ni(II) or Zn(II) metal centers are discussed in this review. The review describes synthetic approaches to these hybrid materials, their physical properties, their spectroscopic properties and their potential applications.
RESUMO
The synthesis of a number of pentaborate(1-) salts from cations arising from N-substituted α,α-, α,ß-, and α,γ-diaminoalkanes has been attempted in aqueous solution from B(OH)3 and the appropriate diammine in a 10:1 ratio. Despite relatively mild work-up conditions the pentaborate(1-) salts prepared were not always as anticipated and the following compounds were isolated in good yield: [Me2NH(CH2)2NHMe2][B5O6(OH)4]2 (1), [Et2NH(CH2)2NHEt2][B5O6(OH)4]2 (2), [Et2NH2][B5O6(OH)4] (3), [Me2NH2][B5O6(OH)4] (4), [Me2NH(CH2)3NHMe2][B5O6(OH)4]2 (5), [Et2NH(CH2)3NHEt2][B5O6(OH)4]2 (6), [Me3NCH2CH=CH2][B5O6(OH)4] (7), and [Me3N(CH2)3NMe3] [B5O6(OH)4]2.0.5H2O (8). The tetraborate(2-) salt, [Me3N(CH2)2NMe3][B4O5(OH)4].2B(OH)3.2H2O (9) was obtained in moderate yield (41%) from a 3:1 reaction of B(OH)3 with [Me3N(CH2)2NMe3](OH)2. All compounds were characterized by spectroscopy (1H, 11B, 13C NMR and IR) and thermal gravimetric analysis (TGA). BET analysis on materials derived thermally from selected samples (1, 2, 6, 7) all had porosities of < 1 m2/g, demonstrating that they were non-porous. Single-crystal XRD structures were obtained for 2, 3, 7, 8 and 9 and all contain extensive H-bonded polyborate lattices.
Assuntos
Compostos de Amônio/química , Boratos/química , Sais/química , Cátions/química , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Cloreto de Sódio/química , Água/químicaRESUMO
The synthesis and X-ray diffraction structure of [Co(en)3][B5O6(OH)4][B8O10(OH)6]·5H2O (1) are reported. Compound 1 arises through a selective-templating process from a Dynamic Combinatorial Library of polyborate anions. Compound 1 contains two different polyborate species, with [B8O10(OH)6](2-) being particularly novel. It is comprised of fused tetraborate and pentaborate anions with a 4-coordinate B atom and a 3-coordinate O atom in common.
RESUMO
Local failures following radiation therapy are multifactorial, and the contributions of the tumor and the host are complex. Current models of tumor equilibrium suggest that a balance exists between cell birth and cell death due to insufficient angiogenesis, immune effects, or intrinsic cellular factors. We investigated whether host immune responses contribute to radiation-induced tumor equilibrium in animal models. We report an essential role for immune cells and their cytokines in suppressing tumor cell regrowth in two experimental animal model systems. Depletion of T cells or neutralization of IFN-γ reversed radiation-induced equilibrium, leading to tumor regrowth. We also demonstrate that PD-L1 blockade augments T cell responses, leading to rejection of tumors in radiation-induced equilibrium. We identify an active interplay between tumor cells and immune cells that occurs in radiation-induced tumor equilibrium and suggest a potential role for disruption of the PD-L1/PD-1 axis in increasing local tumor control.
Assuntos
Citotoxicidade Imunológica , Neoplasias/imunologia , Linfócitos T/imunologia , Animais , Antígeno B7-H1 , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Proliferação de Células , Modelos Animais de Doenças , Humanos , Imunoterapia , Interferon gama/imunologia , Interferon gama/metabolismo , Camundongos , Metástase Neoplásica , Neoplasias/patologia , Neoplasias/cirurgia , Receptor de Morte Celular Programada 1 , Radiocirurgia , Carga Tumoral/imunologia , Carga Tumoral/efeitos da radiaçãoRESUMO
A series of mono/bimetallic isostructural hybrid tetraborates of the general formula [ZnxCo(1-x)(1,3-dap)B4O7] has been prepared using a solvothermal method. Their adsorption/desorption curves for H2O and D2O demonstrate that these materials have a stronger affinity for H2O than for D2O and enrich the D2O content of D2O/H2O mixtures.
RESUMO
The mucin 1 (MUC1) oncoprotein is aberrantly overexpressed in human breast cancers. Although MUC1 modulates the activity of estrogen receptor alpha (ER), there is no information regarding the effects of MUC1 on global gene expression patterns and the potential role of MUC1-induced genes in predicting outcome for breast cancer patients. We have developed an experimental model of MUC1-induced transformation that has identified the activation of genes involved in cholesterol and fatty acid metabolism. A 38-gene set of experimentally derived MUC1-induced genes associated with lipid metabolism was applied to the analysis of ER(+) breast cancer patients treated with tamoxifen. The results obtained from 2 independent databases demonstrate that patients overexpressing MUC1 and the lipid metabolic pathways are at significantly higher risk for death and recurrence/distant metastasis. By contrast, these genes were not predictive in untreated patients. Furthermore, a positive correlation was found between expression of the 38-gene set and the ER signaling pathway. These findings indicate that (i) MUC1 regulates cholesterol and fatty acid metabolism, and (ii) activation of these pathways in ER(+) breast cancers predicts failure to tamoxifen treatment.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Redes Reguladoras de Genes , Metabolismo dos Lipídeos/genética , Mucina-1/fisiologia , Valor Preditivo dos Testes , Colesterol/metabolismo , Receptor alfa de Estrogênio , Feminino , Humanos , Metástase Neoplásica , Proteínas de Neoplasias , Prognóstico , Recidiva , Taxa de Sobrevida , Ativação TranscricionalRESUMO
The nonmetal cation polyborate salt of stoichiometry [H(2)en](2)[B(11)O(18)(OH)]·7H(2)O is obtained from the reaction of 1,2-diaminoethane and boric acid (1:5 ratio) in H(2)O/MeOH. An X-ray crystallographic study of the product reveals that the polyborate moiety is composed of two isolated hydrated polyborate anions: [B(4)O(5)(OH)(4)](2-) and [B(7)O(9)(OH)(5)](2-). The structure is templated by the cations with the anions forming a supramolecular H-bonded network, augmented by additional H-bonds involving the waters of crystallization and the cations.
RESUMO
Ad.Egr-TNF is a radioinducible adenovector currently in phase 3 trials for inoperable pancreatic cancer. The combination of Ad.Egr-TNF and ionizing radiation (IR) contributes to local tumor control through the production of tumor necrosis factor-alpha (TNFalpha) in the tumor microenvironment. Moreover, clinical and preclinical studies with Ad.Egr-TNF/IR have suggested that this local approach suppresses the growth of distant metastatic disease; however, the mechanisms responsible for this effect remain unclear. These studies have been performed in wild-type (WT) and TNFR1,2(-/-) mice to assess the role of TNFalpha-induced signaling in the suppression of draining lymph node (DLN) metastases. The results demonstrate that production of TNFalpha in the tumor microenvironment induces expression of interferon (IFNbeta). In turn, IFNbeta stimulates the production of chemokines that recruit CD8(+) T cells to the tumor. The results further demonstrate that activation of tumor antigen-specific CD8(+) CTLs contributes to local antitumor activity and suppression of DLN metastases. These findings support a model in which treatment of tumors with Ad.Egr-TNF and IR is mediated by local and distant immune-mediated antitumor effects that suppress the development of metastases.
Assuntos
Linfócitos T CD8-Positivos/metabolismo , Metástase Neoplásica/prevenção & controle , Metástase Neoplásica/terapia , Radiação Ionizante , Fator de Necrose Tumoral alfa/metabolismo , Adenoviridae/genética , Animais , Proliferação de Células , Vetores Genéticos/genética , Humanos , Interferon beta/metabolismo , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Mutantes , Metástase Neoplásica/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/genéticaRESUMO
The title compound, C(36)H(30)NP(2) (+)·I(-), was obtained accidently from crystallization of a reaction mixture containing [(Ph(3)P)(2)N]OH and B(OH)(3), which was contaminated with MeI. There are two independent [(Ph(3)P)(2)N](+) cations and two I(-) anions within the asymmetric unit. The central PNP angles are non-linear [137.6â (2) and 134.4â (2)°] and the phenyl substituents on P centres adopt different conformations within these two cations.
RESUMO
The structure of the title salt, C(24)H(20)P(+)·H(8)B(3) (-), at 120â (2)â K has triclinic (P1) symmetry with an unusual Z = 5, although there is pseudosymmetry observed with the tetraphenylphosphonium cations exhibiting I symmetry. One of the anions is disordered over two sets of sites with refined occupancies of 0.478â (11) and 0.522â (11).
RESUMO
Dendritic cells (DC) play an essential role in innate immunity and radiation-elicited immune responses. LGP2 is a RIG-I-like receptor involved in cytoplasmic RNA recognition and antiviral responses. Although LGP2 has also been linked to cell survival of both tumor cells and T cells, the role of LGP2 in mediating DC function and antitumor immunity elicited by radiotherapy remains unclear. Here, we report that tumor DCs are linked to the clinical outcome of patients with breast cancer who received radiotherapy, and the presence of DC correlates with gene expression of LGP2 in the tumor microenvironment. In preclinical models, host LGP2 was essential for optimal antitumor control by ionizing radiation (IR). The absence of LGP2 in DC dampened type I IFN production and the priming capacity of DC. In the absence of LGP2, MDA5-mediated activation of type I IFN signaling was abrogated. The MDA5/LGP2 agonist high molecular weight poly I:C improved the antitumor effect of IR. This study reveals a previously undefined role of LGP2 in host immunity and provides a new strategy to improve the efficacy of radiotherapy. SIGNIFICANCE: These findings reveal an essential role of LGP2 in promoting antitumor immunity after radiotherapy and provide a new strategy to enhance radiotherapy.
Assuntos
Células Dendríticas/patologia , RNA Helicases/genética , Neoplasias de Mama Triplo Negativas/radioterapia , Animais , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Proteína DEAD-box 58/genética , Proteína DEAD-box 58/metabolismo , Células Dendríticas/efeitos da radiação , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Helicase IFIH1 Induzida por Interferon/genética , Helicase IFIH1 Induzida por Interferon/metabolismo , Interferon gama/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Poli I-C/farmacologia , RNA Helicases/metabolismo , Radiação Ionizante , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidadeRESUMO
BACKGROUND: The Signal Transducer and Activator of Transcription 1 (STAT1) has traditionally been regarded as a transmitter of interferon signaling and a pro-apoptotic tumour suppressor. Recent data have identified new functions of STAT1 associated with tumourigenesis and resistance to genotoxic stress, including ionizing radiation (IR) and chemotherapy. To investigate the mechanisms contributing to the tumourigenic functions of STAT1, we performed a combined transcriptomic-proteomic expressional analysis and found that STAT1 is associated with regulation of energy metabolism with potential implication in the Warburg effect. METHODS: We generated a stable knockdown of STAT1 in the SCC61 human squamous cell carcinoma cell line, established tumour xenografts in athymic mice, and compared transcriptomic and proteomic profiles of STAT1 wild-type (WT) and knockdown (KD) untreated or irradiated (IR) tumours. Transcriptional profiling was based on Affymetrix Human GeneChip(R) Gene 1.0 ST microarrays. Proteomes were determined from the tandem mass spectrometry (MS/MS) data by searching against the human subset of the UniProt database. Data were analysed using Significance Analysis of Microarrays for ribonucleic acid and Visualize software for proteins. Functional analysis was performed with Ingenuity Pathway Analysis with statistical significance measured by Fisher's exact test. RESULTS: Knockdown of STAT1 led to significant growth suppression in untreated tumours and radio sensitization of irradiated tumours. These changes were accompanied by alterations in the expression of genes and proteins of glycolysis/gluconeogenesis (GG), the citrate cycle (CC) and oxidative phosphorylation (OP). Of these pathways, GG had the most concordant changes in gene and protein expression and demonstrated a STAT1-dependent expression of genes and proteins consistent with tumour-specific glycolysis. In addition, IR drastically suppressed the GG pathway in STAT1 KD tumours without significant change in STAT1 WT tumours. CONCLUSION: Our results identify a previously uncharacterized function of STAT1 in tumours: expressional regulation of genes encoding proteins involved in glycolysis, the citrate cycle and mitochondrial oxidative phosphorylation, with predominant regulation of glycolytic genes. STAT1-dependent expressional regulation of glycolysis suggests a potential role for STAT1 as a transcriptional modulator of genes responsible for the Warburg effect.
Assuntos
Metabolismo Energético , Regulação Neoplásica da Expressão Gênica , Redes e Vias Metabólicas/genética , Neoplasias/radioterapia , Tolerância a Radiação , Fator de Transcrição STAT1/metabolismo , Animais , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Análise de Sequência com Séries de Oligonucleotídeos , Proteoma/análise , Fator de Transcrição STAT1/genética , Espectrometria de Massas em TandemRESUMO
The non-metal cation pentaborate(1-) salt [p-H2NC6H4CH2NH3][B5O6(OH)4]·1/2H2O (1) was synthesised from B(OH)3 and p-H2NC6H4CH2NH2 and crystallized from aqueous solution. Compound 1 was characterized by thermal (TGA/DSC), spectroscopic (IR, NMR) and single-crystal X-ray diffraction methods and it was found to crystallize in the non-centrosymmetric point group P21. Powder SHG measurements on 1 and some related alkylammonium pentaborate salts, [NH3CMe2(CH2OH)][B5O6(OH)4], [NH3CMe(CH2OH)2][B5O6(OH)4] and [NH3CHMeCH2OH][B5O6(OH)4], a substituted imidazolium salt, [1,2,3-Me3C3H2N2][B5O6(OH)4], a substituted piperidinium salt, [(CH2)5NH(CH2CH2OH)][B5O6(OH)4], and a substituted pyrrolidinium salt, [S-(+)-2-(HOCH2)C4H7NH2][B5O6(OH)4], were determined. Compound 1 and all compounds, except [1,2,3-Me3C3H2N2][B5O6(OH)4], showed some weak SHG activity with SHG efficiencies of 0.1-0.2 relative to that of KH2PO4 (KDP).
RESUMO
We examined the interaction between forphenicinol (FPL) and cyclophosphamide (CPA) or ionizing radiation (IR) on the growth of murine squamous cell carcinoma tumors SCCVII. Primary tumors were established in C3H mice by injecting SCCVII tumor cells subcutaneously into the right hind limb. FPL (100 mg/kg for 8 days) and/or CPA (25 mg/kg twice) were administered by intraperitoneal injection. Tumors were irradiated to a total dose of 40 Gy (eight 5-Gy fractions). SCCVII tumor growth was inhibited by FPL (P=0.054), IR (P=0.003) and CPA (P<0.001) compared with control. The combination of FPL and CPA inhibited tumor growth additively compared with either treatment alone in both small- and large-volume tumors. FPL did not significantly enhance the antitumor effects of IR, however, when CPA+FPL were combined with IR, significant tumor growth inhibition was observed compared with FPL alone (P<0.001), CPA alone (P=0.002) and IR alone (P=0.002). Due to its low toxicity profile, FPL may be combined with CPA, IR and other cytotoxic therapies to potentially enhance the therapeutic ratio.
Assuntos
Adjuvantes Imunológicos/farmacologia , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Ciclofosfamida/farmacologia , Glicina/análogos & derivados , Glicina/farmacologia , Animais , Carcinoma de Células Escamosas/radioterapia , Terapia Combinada , Sinergismo Farmacológico , Feminino , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos C3H , Transplante de Neoplasias , Radioterapia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A replication-defective adenoviral vector, Ad.Egr-TNF.11D, was engineered by ligating the CArG (CC(A/T)6GG) elements of the Egr-1 gene promoter upstream to a cDNA encoding human tumor necrosis factor-alpha. We report here that Ad.Egr-TNF.11D is activated by the clinically important anticancer agents cisplatin, cyclophosphamide, doxorubicin, 5-fluorouracil, gemcitabine, and paclitaxel. N-acetylcysteine, a free radical scavenger, blocked induction of tumor necrosis factor-alpha by anticancer agents, supporting a role for reactive oxygen intermediates in activation of the CArG sequences. Importantly, resistance of PC-3 human prostate carcinoma and PROb rat colon carcinoma tumors to doxorubicin in vivo was reversed by combining doxorubicin with Ad.Egr-TNF and resulted in significant antitumor effects. Treatment with Ad.Egr-TNF.11D has been associated with inhibition of tumor angiogenesis. In this context, a significant decrease in tumor microvessel density was observed following combined treatment with doxorubicin and Ad.Egr-TNF.11D as compared with either agent alone. These data show that Ad.Egr-TNF.11D is activated by diverse anticancer drugs.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Terapia Genética , Neoplasias/terapia , Fator de Necrose Tumoral alfa/genética , Acetilcisteína/farmacologia , Adenoviridae/genética , Animais , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Terapia Combinada , Proteínas de Ligação a DNA/genética , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Proteína 1 de Resposta de Crescimento Precoce , Terapia Genética/métodos , Vetores Genéticos , Humanos , Proteínas Imediatamente Precoces/genética , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neovascularização Patológica/terapia , Regiões Promotoras Genéticas/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Ratos , Fatores de Transcrição/genética , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The synthesis and characterization of a series of pentaborate(1-) salts of substituted pyrrolidinium cations [C4H8NH2][B5O6(OH)4] (), [C4H8NMe2][B5O6(OH)4] () [C4H8NMeH][B5O6(OH)4] (), [(2-CH2OH)C4H7NH2][B5O6(OH)4] () is reported. All compounds were characterized by single-crystal XRD studies with (1/2CH3COCH3) and (1/2H2O) solvated. TGA/DSC analysis of the pentaborates showed that they thermally decomposed in air at 800 °C to 2.5 B2O3, in a 2 step process involving dehydration (<250 °C) and oxidative decomposition (250-600 °C). BET analysis of materials derived thermally from the pentaborates and had internal porosities of <1 m(2) g(-1), indicating they were non-porous. All compounds show extensive supramolecular H-bonded anionic lattices. H-bond interactions are described in detail and motifs found in these and in other pentaborate structures have been examined and modelled by DFT calculations. These calculations confirm that H-bonds interactions in pentaborates are moderately strong (ca. -10 to -21 kJ mol(-1)) and are likely to dominate the energetics of their templated syntheses.
RESUMO
The promising benefits of cancer gene therapy have been limited by the inability to deliver therapeutic genes homogeneously throughout the tumor mass and to control gene expression within the tumor cells. Transcriptional targeting, the use of DNA regulatory promoter sequences to localize transgene expression, has been employed as a solution to circumvent these limitations. TNF-alpha is a cytokine that exhibits potent anticancer properties, but its utility following systemic administration is limited by toxicity. We review a strategy whereby ligating TNF-alpha to segments of the chemo-inducible EGR1 or MDR1 promoters activates expression of TNF-alpha cDNA and enhances effectiveness of gene therapy and chemotherapy.