Search

Dysfunction of p53 and resistance to cancer drugs can arise through mutually exclusive overexpression of MDM2 or MDM4. Cisplatin-resistant cells, however, can demonstrate increased binding of both MDM2 and MDM4 to p53 but in absence of cellular overexpression. Whether MDM2 inhibitors alone can activate p53 in these resistant cells was investigated with the goal to establish the mechanism for potential synergy with cisplatin. Thus, growth inhibition by individual drugs and combinations was assessed by a colorimetric assay. Drug-treated parental A2780 and resistant tumor cells were also examined for protein expression using immunoblot and reverse phase protein array (RPPA) and then subjected to Ingenuity Pathway Analysis (IPA). Gene expression was assessed by real-time polymerase chain reaction, DNA damage by confocal microscopy, cell cycle by flow cytometry, and homologous recombination (HR) by a GFP reporter assay. Our results demonstrate that Nutlin-3 but not RITA (reactivation of p53 and induction of tumor cell apoptosis) effectively disrupted the p53-MDM2-MDM4 complex to activate p53, which increased robustly with cisplatin/Nutlin-3 combination and enhanced antitumor effects more than either agent alone. RPPA, IPA, and confocal microscopy provided evidence for an “apparent” increase in DNA damage resulting from HR inhibition by cisplatin/Nutlin-3. Molecularly, the specific HR protein Rad51 was severely downregulated by the combination via two mechanisms: p53-dependent transrepression and p53/MDM2-mediated proteasomal degradation. In conclusion, Nutlin-3 fully destabilizes the p53-MDM2-MDM4 complex and synergizes with cisplatin to intensify p53 function, which then downregulates Rad51 through a bimodal mechanism. As a result, HR is inhibited and antitumor activity enhanced in otherwise HR-proficient sensitive and resistant tumor cells.SIGNIFICANCE STATEMENTRad51 downregulation by the combination of cisplatin and Nutlin-3 inhibits homologous recombination (HR), which leads to persistence in DNA damage but not an increase. Thus, inhibition of HR enhances antitumor activity in otherwise HR-proficient sensitive and resistant tumor cells.

Reported here are new platinum(IV) (Pt(IV)) complexes bearing ferrocene (Fc) moieties. These systems differ from one another only by the nature of the functional group (ester vs amide) connecting the linker to the Fc subunits. This minor structural variation (one atom difference) leads to major differences in solubility, stability, and antiproliferative activity against lung (A549) cancer cells. The host–guest chemistry of these complexes was investigated in an aqueous medium in the presence of β-cyclodextrins (β-CD), either free or in the form of a covalently linked Fc-Pt-β-CD hybrid. An inclusion complex between Fc and β-CD is formed in aqueous media, presumably as a result of hydrophobic interactions involving the Fc and the inner β-CD cavity. Consequently, it proved possible to use a β-CD-based strategy to purify the Pt-Fc conjugates in this study under aqueous conditions (by means of C18 silica gel columns). The use of a β-CD adjuvant also allowed dimethyl sulfoxide (DMSO) to be avoided as an organic cosolvent in cell studies. The amide version reported here (2) proved to be more soluble, more stable, and more active than the ester analogue (11) in A549 cells. The use of a β-CD functionalized with a fluorescent probe allowed intracellular Pt-Fc localization to be visualized by confocal fluorescence microscopy.

Background/Objectives:Obesity (body mass index (BMI)⩾30 kg m−2) is associated with an increased risk of estrogen-dependent breast cancer after menopause. Levels of aromatase, the rate-limiting enzyme in estrogen biosynthesis, are elevated in breast tissue of obese women. Recently, the regulation of aromatase by the p53-hypoxia-inducible factor-1α (HIF1α)/pyruvate kinase M2 (PKM2) axis was characterized in adipose stromal cells (ASCs) of women with Li–Fraumeni Syndrome, a hereditary cancer syndrome that predisposes to estrogen-dependent breast cancer. The current study aimed to determine whether stimulation of aromatase by obesity-associated adipokine leptin involves the regulation of the p53-HIF1α/PKM2 axis.Subjects/Methods:Human breast ASCs were used to characterize the p53-HIF1α/PKM2-aromatase axis in response to leptin. The effect of pharmacological or genetic modulation of protein kinase C (PKC), mitogen-activated protein kinase (MAPK), p53, Aha1, Hsp90, HIF1α and PKM2 on aromatase promoter activity, expression and enzyme activity was examined. Semiquantitative immunofluorescence and confocal imaging were used to assess ASC-specific protein expression in formalin-fixed paraffin-embedded tissue sections of breast of women and mammary tissue of mice following a low-fat (LF) or high-fat (HF) diet for 17 weeks.Results:Leptin-mediated induction of aromatase was dependent on PKC/MAPK signaling and the suppression of p53. This, in turn, was associated with an increase in Aha1 protein expression, activation of Hsp90 and the stabilization of HIF1α and PKM2, known stimulators of aromatase expression. Consistent with these findings, ASC-specific immunoreactivity for p53 was inversely associated with BMI in breast tissue, while HIF1α, PKM2 and aromatase were positively correlated with BMI. In mice, HF feeding was associated with significantly lower p53 ASC-specific immunoreactivity compared with LF feeding, while immunoreactivity for HIF1α, PKM2 and aromatase were significantly higher.Conclusions:Overall, findings demonstrate a novel mechanism for the obesity-associated increase in aromatase in ASCs of the breast and support the study of lifestyle interventions, including weight management, which may reduce breast cancer risk via effects on this pathway.

Advances in diagnostic modalities have improved the understanding of the pathophysiology of neuropathic pain involving head and face. Recent updates in nomenclature of cranial neuralgias and facial pain have rationalized accurate diagnosis. Clear diagnosis and localization of pain generators are paramount, leading to better use of medical and targeted surgical treatments.

Report on the meeting: Frontiers in Cell Biology and Medicine, University of York, UK, 26-29 September 2010

Designers and manufacturers of modern complex systems have to account for both explicit and implicit customer requirements. Although, the voice of customer (VOC) provides adequate information for a new design, its integration with complex socio-technical systems are vital for the completeness of the design, where the product quality is judged by the extent to which the VOC is addressed. This dictates the product designer to effectively translate and balance the requirements from all the stakeholders. This paper presents bottom-up integration of quality through the hierarchy of new product development steps using a synergy of design for Six Sigma (DFSS) and Systems Engineering (SE) approaches. Thereby covering the quality aspects through DFSS and systems concept through SE. Embedding of SE approach to DFSS’s identify, design, optimise and validate (IDOV) methodology can result in an effective translation of the voice of all stake holders, and hence better coverage of quality.

Incorporation of Cr into ZnO lattice as a dopant in hollow core nanostructures has been achieved by coprecipitation in highly alkaline medium near room temperature. Energy dispersive spectroscopy and X-ray diffraction studies confirm the presence of Cr in the ZnO lattice and X-ray photoelectron spectroscopy (XPS) identified the dopant state to be Cr3+. Room temperature ferromagnetism in ZnO:Cr3+along with structural investigations suggest an intrinsic nature of ferromagnetism in hollow core nanospheres. Unpaired spin in Cr3+in zinc substitutional sites could create spin ordering and long-range ferromagnetic coupling. Higher Cr3+concentration leads to the formation of hollow parallelepipeds and superparamagnetism. Photoluminescence studies reveal a sharp blue emission explicitly arising due to Cr doping. Such blue emitting magnetic nanocapsules can have immense potential as biocarriers and also in spintronics.

Our knowledge of autoimmune characteristics of chronic idiopathic urticaria (CIU) is limited.

Previous studies have demonstrated that treating cultured cells with cisplatin (CDDP) up-regulated the expression of glutathione (GSH) and its de novo rate-limiting enzyme glutamate-cysteine ligase (GCL), which consists of a catalytic (GCLC) and a modifier (GCLM) subunit. It has also been shown that many CDDP-resistant cell lines exhibit high levels of GCLC/GCLM and GSH. Because the GSH system is the major intracellular regulator of redox conditions that serve as an important detoxification cytoprotector, these results have been taken into consideration that elevated levels of GCL/GSH are responsible for the CDDP resistance. In contrast to this context, we demonstrated here that overexpression of GSH by transfection with an expression plasmid containing the GCLC cDNA conferred sensitization to CDDP through up-regulation of human copper transporter (hCtr) 1, which is also a transporter for CDDP. Depleting GSH levels in these transfected cells reversed CDDP sensitivity with concomitant reduction of hCtr1 expression. Although rates of copper transport were also up-regulated in the transfected cells, these cells exhibited biochemical signature of copper deficiency, suggesting that GSH functions as an intracellular copper-chelator and that overexpression of GSH can alter copper metabolism. More importantly, our results reveal a new role of GSH in the regulation of CDDP sensitivity. Overproduction of GSH depletes the bioavailable copper pool, leading to up-regulation of hCtr1 and sensitization of CDDP transport and cell killing. These findings also have important implications in that modulation of the intracellular copper pool may be a novel strategy for improving chemotherapeutic efficacy of platinum-based antitumor agents.

In resonant column testing (ASTM standard), the shear strain distribution along the height of a specimen is assumed linear and fixed at the base. To investigate these assumptions, specimens of dry sand, mine tailings, and cemented sand are tested at different confinement and shear strain levels. The measured mode shapes for dry sands and mine tailings are linear at low and high strain levels; however, for a stiff cemented-sand specimen the first mode shape presents slippage at the end platens. Resonant frequencies decrease up to 50 % while the damping ratios increase up to 200 % because of this slippage. The coupling between the specimen and end-platens is enhanced using three different agents: gypsum cement, portland cement, and epoxy resin. The epoxy resin produces the best coupling, whereas portland and gypsum cements are effective only at low confinements and strain levels. Even after eliminating the slippage at the end-platens, the shear wave velocity of aluminum and PVC probes decreases with the increase in specimen stiffness because of the lack of base fixidity. To correct this apparent reduction, a new model and calibration procedure based on a two-degree-of-freedom system are proposed.

Symmetrically substituted 1,1′‐dimethylferrocene‐derived pyrazine, pyridine and thiazole Schiff‐base ligands and their copper(II) complexes have been prepared. The effect of anions on the antibacterial activity of these synthesized metal(II) complexes has been determined. Copyright © 2001 John Wiley & Sons, Ltd.

Symmetrically substituted 1,1'-dimethylferrocene-derived pyrazine, pyridine and thiazole Schiff-base ligands and their copper(II) complexes have been prepared. The effect of anions on the antibacterial activity of these synthesized metal(II) complexes has been determined. Copyright © 2001 John Wiley & Sons, Ltd.

Some new asymmetric 1,1′‐disubstituted ferrocene‐derived Schiff‐bases have been prepared and used as ligands in the preparation of their Co(II), Cu(II), Ni(II) and Zn(II) metal chelates. These synthesized ligands and their metal chelates have been characterized by their physical, analytical and spectral data. These have also been used for screening against pathogenic bacterial species, e.g. Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosaand Klebsiella pneumonaeand have been found to be a novel class of organometallic‐based antibacterials. Copyright © 2001 John Wiley & Sons, Ltd.

Some new asymmetric 1,1'-disubstituted ferrocene-derived Schiff-bases have been prepared and used as ligands in the preparation of their Co(II), Cu(II), Ni(II) and Zn(II) metal chelates. These synthesized ligands and their metal chelates have been characterized by their physical, analytical and spectral data. These have also been used for screening against pathogenic bacterial species, e.g. Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumonae and have been found to be a novel class of organometallic-based antibacterials. Copyright © 2001 John Wiley & Sons, Ltd.

Three metalloproteases belonging to the AAA superfamily (Yme1p, Afg3p and Rca1p) are involved in protein turnover and respiratory chain complex assembly in the yeast inner mitochondrial membrane. Analysis of the completed genome sequences of Caenorhabditis elegansand Drosophila melanogasterindicates that this gene family typically comprises 3–4 members in metazoans. Phylogenetic analysis reveals three main branches represented, respectively, by Saccharomyces cerevisiae YME1, human SPG7(paraplegin) and S. cerevisiae AFG3and RCA1. mt‐AAA metalloproteases are weak candidates for several previously studied Drosophilamutants. A full elucidation of the cellular and physiological roles of mt‐AAA metalloproteases in metazoans will require the creation of targeted mutations.

In yeast, three AAA superfamily metalloproteases (Yme1p, Afg3p and Rca1p) are localized to the mitochondrial inner membrane where they perform roles in the assembly and turnover of the respiratory chain complexes. We have investigated the function of the proposed human orthologue of yeast Yme1p, encoded by the YME1Lgene on chromosome 10p. Transfection of both HEK‐293EBNA and yeast cells with a green fluorescent protein‐tagged YME1L cDNA confirmed mitochondrial targeting. When expressed in a yme1disruptant yeast strain, YME1Lrestored growth on glycerol at 37°C. We propose that YME1Lplays a phylogenetically conserved role in mitochondrial protein metabolism and could be involved in mitochondrial pathologies.

Symmetric 1,1′‐dimethylferrocene derived Schiff‐base ligands have been prepared by the condensation reaction of 1,1′‐diacetylferrocene with 2‐aminopyrazine, 2‐aminopyridine and 2‐aminothiazole respectively. Their transition metal chelates, of the type [M(L)]Cl2[M = Cu(II)] and [M(L)(Cl2)] [M = Co(II), Ni(II) and Zn(II)] have been prepared. The synthesized Schiff‐base ligands and their metal(II) chelates have been characterized by their physical, analytical and spectral data. Copyright © 2000 John Wiley & Sons, Ltd.

Symmetric 1,1'-dimethylferrocene derived Schiff-base ligands have been prepared by the condensation reaction of 1,1'-diacetylferrocene with 2-aminopyrazine, 2-aminopyridine and 2-aminothiazole respectively. Their transition metal chelates, of the type [M(L)]Cl2 [M = Cu(II)] and [M(L)(Cl2)] [M = Co(II), Ni(II) and Zn(II)] have been prepared. The synthesized Schiff-base ligands and their metal(II) chelates have been characterized by their physical, analytical and spectral data. Copyright © 2000 John Wiley & Sons, Ltd.

Recent animal studies on the mechanism of migraine show that intracranial pain is accompanied by increased periorbital skin sensitivity. These findings suggest that the pathophysiology of migraine involves not only irritation of meningeal perivascular pain fibers but also a transient increase in the responsiveness (ie, sensitization) of central pain neurons that process information arising from intracranial structures and skin. The purpose of this study was to determine whether the increased skin sensitivity observed in animal also develops in humans during migraine attacks. Repeated measurements of mechanical and thermal pain thresholds of periorbital and forearm skin areas in the absence of, and during, migraine attacks enabled us to determine the occurrence of cutaneous allodynia during migraine. Cutaneous allodynia is pain resulting from a nonnoxious stimulus to normal skin. In 79% of the patients, migraine was associated with cutaneous allodynia as defined, and in 21% of the patients it was not. The cutaneous allodynia occurred either solely within the referred pain area on the ipsilateral head, or within and outside the ipsilateral head. Cutaneous allodynia in certain well‐defined regions of the skin during migraine is an as yet unreported neurological finding that points to hyperexcitability of a specific central pain pathway that subserves intracranial sensation. Ann Neurol 2000;47:614–624

A series of new platinum(IV) complexes of the type [PtIV(DACH)trans(L)2Cl2] (where DACH=trans-1R,2R-diaminocyclohexane, and L=acetate, propionate, butyrate, valerate, hexanoate, or heptanoate) bearing the carboxylate groups in the axial positions have been synthesized and characterized by elemental analysis, IR, and 195Pt NMR spectroscopy. The crystal structure of the analogue [PtIV(DACH)trans(acetate)2Cl2] was determined by single crystal X-ray diffraction method. There were two crystallographically independent molecules, both of which lie on crystallographic two-fold axes. The bond lengths and bond angles of both the molecules were the same within the experimental error. The compound crystallizes in the monoclinic space group C2, with a=11.180(2) Å, b=14.736(3) Å, c=10.644(2) Å, β=112.38(3)°, Z=4 and R=0.0336, based upon a total of 1648 collected reflections. In this complex, the platinum had a slightly distorted octahedron geometry owing to the presence of a geometrically strained five-member ring. The two adjacent corners of the platinum plane were occupied by the two amino nitrogens of DACH, whereas the other two equatorial positions were occupied by two chloride ions. The remaining two axial positions were occupied by the oxygens of acetate ligands. The DACH ring was in a chair configuration. An intricate network of intermolecular hydrogen bonds held the crystal lattice together. These analogues were evaluated in vitro and demonstrated cytotoxic activity against the human ovarian 2008 tumor cell line (IC50=0.001–0.06 μM). Structure–activity study revealed that activity was highest for the analogue where L=butyrate.

The human gene RPMS12encodes a protein similar to bacterial ribosomal protein S12 and is proposed to represent the human mitochondrial orthologue. RPMS12reporter gene expression in cultured human cells supports the idea that the gene product is mitochondrial and is localized to the inner membrane. Human cells contain at least four structurally distinctRPMS12mRNAs that differ in their 5′-untranslated region (5′-UTR) as a result of alternate splicing and of 5′ end heterogeneity. All of them encode the same polypeptide. The full 5′-UTR contains two types of sequence element implicated elsewhere in translational regulation as follows: a short upstream open reading frame and an oligopyrimidine tract similar to that found at the 5′ end of mRNAs encoding other growth-regulated proteins, including those of cytosolic ribosomes. The fully spliced (short) mRNA is the predominant form in all cell types studied and is translationally down-regulated in cultured cells in response to serum starvation, even though it lacks both of the putative translational regulatory elements. By contrast, other splice variants containing one or both of these elements are not translationally regulated by growth status but are translated poorly in both growing and non-growing cells. Reporter analysis identified a 26-nucleotide tract of the 5′-UTR of the short mRNA that is essential for translational down-regulation in growth-inhibited cells. Such experiments also confirmed that the 5′-UTR of the longer mRNA variants contains negative regulatory elements for translation. Tissue representation of RPMS12mRNA is highly variable, following a typical mitochondrial pattern, but the relative levels of the different splice variants are similar in different tissues. These findings indicate a complex, multilevel regulation of RPMS12gene expression in response to signals mediating growth, tissue specialization, and probably metabolic needs.

On the basis of the spectroscopic data for some 40 alternant aromatic hydrocarbons, a simple correlation is given between the excited singlet state (pband) of such molecules and the excited lowest-energy non-Koopmans state (Aband) for their radical cations. It is shown that, with the use of this relation, the energy of the doublet state for a radical cation can be reasonably estimated if the energy of the pband for its neutral precursor is known. We have also computed the doublet state energies of the aromatic hydrocarbons using the “SDT” relations, which involve three spectroscopic quantities, viz., the excited singlet (S) and triplet (T) states of a neutral molecule and the doublet (D) state of its radical cation. The predictions of the proposed singlet-doublet state correlation are found to be far superior than those of the SDT relations.

Absorption measurements on the radical cations of 3.4,8.9-dibenzotetraphene, pentaphene, 3.4-benzopentaphene, 6.7-benzopentaphene, and naphtho-(2'.3':6.7)pentaphene are made in the spectral region 7 - 5 0 kK. Electronic spectra of the cations are calculated using the Longuet- Higgins-Pople and Wasilewski type Open-Shell SCF-MO methods with limited configuration interaction. A detailed discussion of the absorption bands is given in the light of the calculations and the electronic transition energies of the cations derived from the ultraviolet photoelectron spectra of the parent hydrocarbons. The correlation between the optical and photoelectron spectra is closely examined and it is found to be excellent.

This paper presents some new relations connecting the triplet-state energy of an alternant aromatic hydrocarbon with that of its excited doublet state as well as its first ionization potential. The energy relation between the doublet and triplet states is basically a simplified version of the SDT relation but the predictive power of the proposed correlation is considerably better in spite of the drastic assumptions made in the model. Incorporation of molecular size in the doublet-triplet correlation has no appreciable effect on the predictions, but its inclusion in the ionization potential vs. triplet-state energy relation leads to a significant improvement in the results. It is explained on the basis of our new finding that the Coulomb term appearing in the expression for the ionization potential behaves in the same manner as the molecular size, which thus accounts for electron interaction in the model. The proposed correlations provide a simple but powerful means to estimate the first ionization potentials and excited doublet-state energies of polycyclic aromatic hydrocarbons directly from the knowledge of their triplet-state energies.

The pharmacokinetics of liposome-entrappedcis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum(II) (L-NDDP) and cisplatin (CDDP) were studied after i.v. and i.p. administration of an equimolar dose (11 and 5 mg/kg for L-NDDP and CDDP, respectively) in the rat. The systemic absorption following i.p. administration was faster in rats receiving CDDP than in those receiving L-NDDP. Peak serum platinum (Pt) levels were observed at 30 min and 12 h after the i.p. administration of CDDP and L-NDDP, respectively. Administration by the i.v. route did not significantly alter the serum Pt levels for either compound. However, serum Pt levels were 2–3 times greater in animals treated with L-NDDP than in those treated with CDDP. The estimated pharmacokinetic parameters for each drug were independent of the route of administration, except for the clearance (Cl) of CDDP, which increased 2-fold following i.p. administration. In addition, significant differences in pharmacokinetic parameters were observed between drug-treatment groups that were independent of the route of administration: the serum Pt area under the concentration-time curve (AUC) was higher and the volume of distribution at steady state (Vdss) was lower in rats receiving L-NDDP. Pt levels measured at 6 h in the peritoneal fluid, peritoneal tissue, and intestine of rats receiving i.p. L-NDDP were higher than those observed in rats receiving either i.v. L-NDDP or CDDP by either route. Pt levels measured in the liver and spleen of rats receiving L-NDDP were independent of the route of administration and were significantly higher than those determined in rats treated with CDDP. In contrast, kidney Pt levels were lower in rats receiving L-NDDP than in rats receiving CDDP by either route. These results suggest that the prolongation of the mean retention time of L-NDDP in the peritoneum achieved after i.p. administration without compromising the systemic distribution of the drug may result in a significant enhancement of the therapeutic efficacy of L-NDDP against malignancies confined to the peritoneal cavity as compared with that of i.p. CDDP.

We evaluated a novel system of complete hepatic venous isolation and chemofiltration (CHVI-CF) to reduce systemic drug exposure following regional hepatic infusion of doxorubicin. Rabbits bearing hepatic VX-2 tumors were given doxorubicin via either hepatic arterial infusion (HAI) or portal venous infusion (PVI). A dualballoon vena cava catheter and extracorporeal chemofilter were used to capture and filter hepatic venous blood in experimental animals. Control animals received chemotherapy without hepatic venous isolation and chemofiltration. Following a 5-min HAI of doxorubicin (3 or 5 mg/kg), control and experimental animals had similar doxorubicin levels in their livers and VX-2 tumors, but experimental animals showed a significant reduction in doxorubicin levels in systemic plasma, heart, and kidney tissue as compared with control animals (P<0.01). HAI produced a 4-fold increase in doxorubicin levels in VX-2 tumors as compared with the drug levels obtained using PVI (P<0.01). A single HAI of 3 mg/kg doxorubicin in animals treated with CHVI-CF produced marked tumor necrosis at 7 and 14 days after treatment. By increasing the total body clearance of doxorubicin, this system will allow HAI of higher doses of drug in attempts to improve the antitumor response.

The extent of a tumor, sometimes combined with its anatomic location, can compromise the surgeon's ability to obtain clear margins of resection. Regional recurrence of a tumor in the resection bed frequently produces significant local morbidity and limits patient survival time and quality of life. A positive margin resection model was created by induction of perinephric VX-2 tumors in New Zealand white rabbits followed by unilateral nephrectomy with grossly positive margins in the retroperitoneum. Resection bed injection of a novel collagen matrix with cisplatin (CDDP) and epinephrine prevented tumor recurrence in all treated animals. In contrast, control animals treated with CDDP alone, CDDP and epinephrine alone, or the collagen matrix with epinephrine had bulky tumor recurrence in the resection bed. Resection bed tissue levels of platinum were determined by flameless absorption spectrophotometry at 1, 4, and 7 days following nephrectomy and injection of the collagen matrix, CDDP, and epinephrine or CDDP and epinephrine without the collagen matrix. Significantly higher resection bed drug levels of platinum were achieved through the use of the novel collagen matrix than through the use of CDDP and epinephrine alone (P &lt; 0.05). The results of this study indicate that tumor bed treatment with CDDP and a unique collagen matrix drug-delivery vehicle produces prolonged high resection bed levels of platinum and prevents local tumor recurrence. Copyright 1995, 1999 Academic Press

Electronic absorption spectra of the radical cations of 1.2,7.8-dibenzochrysene, 1.2,3.4-dibenzanthracene, 1.2,5.6-dibenzanthracene and 1.2,7.8-dibenzanthracene in boric acid are measured. The transition energies of the cations are calculated using the Longuet-Higgins-Pople and Wasilewski type Open-Shell-SCF-MO methods with limited CI. A comprehensive discussion of the absorption bands is given in the light of the calculations and the photoelectron spectral data for the hydrocarbons. The correspondence between the optical and photoelectron spectra is found to be extremely good with almost negligible matrix shifts, thus highlighting the role of photoelectron spectroscopy in understanding the optical spectra of the radical cations and vice versa. Finally, a correlation diagram for the observed electronic transitions for the radical cations of anthracene and its benzologs is presented from which it is inferred that the optical A-transitions have some sort of correlation with the first IP's of the respective hydrocarbons.

Effective adjunctive therapies for colorectal carcinoma are clearly needed. We evaluated the cytotoxic responses in vitro of human colon carcinoma cell lines to combined modalities: 5-fluorouracil/leucovorin (5-FU/LV), carboplatin (CP), tumor necrosis factor (TNF) and hyperthermia (HTX). Cytotoxicity was evaluated in a cell proliferation assay using crystal violet staining. 5-FU/LV was administered 2–3 days before TNF and CP, followed 1 h later by HTX. These cell lines were relatively resistant to HTX alone (42°C for 2 h), but were heterogeneous in their responses to various doses of the other single agents. This heterogeneity was also evident for combined modalities: the geneity was also evident for combined modalities: the HCT-15 cell line exhibited significant supra-additivity for selected doses of CP, TNF and 5-FU/LV, which was further enhanced by hyperthermia. In contrast, the HT-29 cell line did not demonstrate a strong pattern for supra-additivity, whereas the DLD-1 cell line had an intermediate response. Thus, our results suggest one approach to develop effective and dose-sparing multimodality therapeutic regimens for colon adenocarcinoma.