Papers by Benjamin Vesper
Journal of Archaeological Science, 2015
Bone collagen is the required substrate for a variety of archaeometric analyses, including radioc... more Bone collagen is the required substrate for a variety of archaeometric analyses, including radiocarbon dating, stable isotope analysis, proteomics, and ancient DNA. Sampling of bone for such analyses is, however, a destructive process, and biomolecular extraction is a time-, labor-, and capital-intensive process. As such, the ability to pre-screen bone for potential collagen level in the field (or in remote museums, storage repositories, or other deployed and austere environments) for archaeological and forensic purposes is highly desirable. Building on previous assessments of hand-held spectroscopic tools and several recent bench top Raman studies, and using a robust selection of well-characterized ancient bone samples, it is demonstrated here that rapid (30 s), non-destructive assessment by means of 1064 nm Raman spectroscopy can provide a field-deployable means by which to quantify bone collagen content. Specifically, it was found that the 1450 cm À1 to 960 cm À1 peak height ratio can provide quantitative estimates of bone collagen content with an error of ±2.8 wt%, and those samples with ratios of greater than 0.1 are uniformly suitable for analysis. Hand-held Raman spectroscopic technology has therefore evolved to the point where field deployment by archaeologists and forensic scientists would be both justified and worthwhile.
HPV and Cancer, 2012
ABSTRACT This chapter presents a brief historical background of the human papillomavirus (HPV), i... more ABSTRACT This chapter presents a brief historical background of the human papillomavirus (HPV), including a discussion of the discovery of the virus, various papillomavirus classification groups currently used to describe HPV, and the structure of the virus. Genotypic differences are found among the different HPV classes (alpha, beta, gamma, mu, nu); the role that these genotypic differences play in contributing to cancers and other diseases is also explored herein.
Bioconjugate Chemistry, 2010
Magnetic resonance imaging (MRI) has long been used clinically and experimentally as a diagnostic... more Magnetic resonance imaging (MRI) has long been used clinically and experimentally as a diagnostic tool to obtain three-dimensional, high-resolution images of deep tissues. These images are enhanced by the administration of contrast agents such as paramagnetic Gd(III) complexes. Herein, we describe the preparation of a series of multimodal imaging agents in which paramagnetic Gd(III) complexes are conjugated to a fluorescent tetrapyrrole, namely, a porphyrazine (pz). Zinc metalated pzs conjugated to one, four, or eight paramagnetic Gd(III) complexes are reported. Among these conjugates, Zn-Pz-8Gd(III) exhibits an ionic relaxivity four times that of the monomeric Gd(III) agent, presumably because of increased molecular weight and a molecular relaxivity that is approximately thirty times larger, while retaining the intense electronic absorption and emission of the unmodified pz. Unlike current clinical MR agents, Zn-Pz-1Gd(III) is taken up by cells. This probe demonstrates intracellular fluorescence by confocal microscopy and provides significant contrast enhancement in MR images, as well as marked phototoxicity in assays of cellular viability. These results suggest that pz agents possess a new potential for use in cancer imaging by both MRI and near-infrared (NIR) fluorescence, while acting as a platform for photodynamic therapy.
Journal of the Chemical Society, Dalton Transactions, 2001
... Antonio Garrido Montalbana, Sarah LJ Michelb, Sven M. Bauma, Benjamin J. Vesperb, Andrew JP W... more ... Antonio Garrido Montalbana, Sarah LJ Michelb, Sven M. Bauma, Benjamin J. Vesperb, Andrew JP Whitea, David J. Williamsa, Anthony GM Barrett*a and Brian M. Hoffman*b. ... 5, M. Moussavi, AD Cian, J. Fischer and R. Weiss, Inorg. ...
Oral Oncology Supplement, 2009
diagnosis of oral cancer. The objective of this survey is to evaluate the knowledge of the aspect... more diagnosis of oral cancer. The objective of this survey is to evaluate the knowledge of the aspects related to oral cancer in the Barretos region (Brazil).
The Open Lung Cancer Journal, 2009
The free radical nitric oxide (NO) is known to play an important role in the biology of human can... more The free radical nitric oxide (NO) is known to play an important role in the biology of human cancers, including lung cancer. However, it is still not clear how elevated amounts of nitric oxide affect tumor development and propagation. Herein we develop an in vitro model system to study these effects in lung tumor cells. Two cell lines-one human lung adenocarcinoma (A549) and one mouse adenocarcinoma (LP07) cell line-were adaptively grown in increasing concentrations of the NO donor DETA-NONOate over several months. Both cell lines were successfully adapted to high levels of NO (HNO). Experiments validated the adaptation occurred as a result of the exogenous NO produced by the DETA-NONOate, and was not merely a response to the chemical composition of DETA-NONOate. No morphological differences were observed between cells that were adapted to the HNO and cells which did not undergo the adaptation process (i.e., "parent cells"). Parent cells were unable to survive when placed directly in media containing high levels of DETA-NONOate, suggesting that the adapted cells underwent a biological change enabling them to survive and grow in a HNO environment. The adapted cells were found to grow faster than the parent cells under both normal growth conditions and stressful growth conditions (serum-less media, growth on soft agar) even when the DETA-NONOate was removed from the HNO culture media. These adapted cell lines can serve as a novel tool for use in future experiments designed to better understand the role nitric oxide plays in lung cancer.
Photochemistry and photobiology
We report the preparation of chiral oxygen atom-appended porphyrazines (pzs) as biomedical optica... more We report the preparation of chiral oxygen atom-appended porphyrazines (pzs) as biomedical optical agents that absorb and emit in the near-IR wavelength range. These pzs take the form M[pz(A(4-n)B(n))], where "A" and "B" represent moieties appended to the pz's pyrrole entities, A = (2R,3R) 2,3-dimethyl-2,3-dimethoxy-1,4-diox-2-ene, B = beta,beta'-di-isopropoxybenzo, M is the incorporated metal ion (M = H(2), Zn), and n = 0, 1, 2 (-cis/-trans) and 3 (Scheme 1). When dissolved in polar media, H(2)[pz(trans-A(2)B(2))] 5a does not fluoresce and has a negligible quantum yield for singlet oxygen generation (capital EF, Cyrillic(Delta) = 0.074 +/- 0.001, methanol), as measured by the photo-oxidation of DMA. However, when sequestered in the nonpolar environment of a liposome, it displays strong NIR emission (lambda(max) = 705 nm, capital EF, Cyrillic(f) = 0.087) and an extremely high singlet oxygen quantum yield (capital EF, Cyrillic(Delta)-->1). Of this serie...
ChemMedChem, 2008
Gastroesophageal reflux disease (GERD) affects both men and women worldwide, with the most common... more Gastroesophageal reflux disease (GERD) affects both men and women worldwide, with the most common symptom of GERD being frequent heartburn. If left untreated, more serious diseases including esophagitis and/or esophageal cancer may result. GERD has been commonly held to be the result of gastric acid refluxing into the esophagus. Recent work, however, has shown that there are acid-producing cells in the upper aerodigestive tract. In addition, acid-producing bacteria located within the upper gastrointestinal tract and oral cavity may also be a contributing factor in the onset of GERD. Proton pump inhibitors (PPIs) are commonly prescribed for treating GERD; these drugs are designed to stop the production of gastric acid by shutting down the H(+)/K(+)-ATPase enzyme located in parietal cells. PPI treatment is systemic and therefore significantly different than traditional antacids. Although a popular treatment choice, PPIs exhibit substantial interpatient variability and commonly fail to...
European Journal of Cancer Supplements, 2007
Tumor Biology, 2013
Mitochondria combine hydrogen and oxygen to produce heat and adenosine triphosphate (ATP). As a t... more Mitochondria combine hydrogen and oxygen to produce heat and adenosine triphosphate (ATP). As a toxic by-product of oxidative phosphorylation (OXPHOS), mitochondria generate reactive oxygen species (ROS). These free radicals may cause damage to mitochondrial DNA (mtDNA) and other molecules in the cell. Nitric oxide (NO) plays an important role in the biology of human cancers, including
Tumor Biology, 2010
Nitric oxide (NO), a free radical, has been implicated in the biology of human cancers, including... more Nitric oxide (NO), a free radical, has been implicated in the biology of human cancers, including breast cancer, yet it is still unclear how NO affects tumor development and propagation. We herein gradually adapted four human breast adenocarcinoma cell lines (BT-20, Hs578T, T-47D, and MCF-7) to increasing concentrations of the NO donor DETA-NONOate up to 600 muM. The resulting model system consisted of a set of fully adapted high nitric oxide ("HNO") cell lines that are biologically different from the "parent" cell lines from which they originated. Although each of the four parent and HNO cell lines had identical morphologic appearance, the HNO cells grew faster than their corresponding parent cells and were resistant to both nitrogen- and oxygen-based free radicals. These cell lines serve as a novel tool to study the role of NO in breast cancer progression and potentially can be used to predict the therapeutic response leading to more efficient therapeutic regimens.
Tumor Biology, 2011
The free radical nitric oxide (NO) is over-expressed in many tumors, including head and neck squa... more The free radical nitric oxide (NO) is over-expressed in many tumors, including head and neck squamous cell carcinomas (HNSCC). However, the role NO plays in tumor pathophysiology is still not well understood. We herein report the development of an in vitro model system which can be used to probe the role of NO in the carcinogenesis of HNSCC. Five HNSCC cell lines were adapted to a high NO (HNO) environment by gradually introducing increasing concentrations of DETA-NONOate, a nitrogen-based NO donor, to cell media. The adaptation process was carried out until a sufficiently high enough donor concentration was reached which enabled the HNO cells to survive and grow, but which was lethal to the original, unadapted ("parent") cells. The adapted HNO cells exhibited analogous morphology to the parent cells, but grew better than their corresponding parent cells in normal media, on soft agar, and in the presence of hydrogen peroxide, an oxygen-based free radical donor. These results indicate the HNO cell lines are unique and possess biologically different properties than the parent cell lines from which they originated. The HNO/parent cell lines developed herein may be used as a model system to better understand the role NO plays in HNSCC carcinogenesis.
Tumor Biology, 2012
Previously, we demonstrated that A549, a human lung cancer cell line, could be adapted to the fre... more Previously, we demonstrated that A549, a human lung cancer cell line, could be adapted to the free radical nitric oxide (NO • ). NO • is known to be over expressed in human tumors. The original cell line, A549 (parent), and the newly adapted A549-HNO (which has a more aggressive phenotype) serve as a useful model system to study the biology of NO • . To see if tumor cells can similarly be adapted to any free radical with the same outcome, herein we successfully adapted A549 cells to high levels of hydrogen peroxide (HHP). A549-HHP, the resulting cell line, was more resistant and grew better then the parent cell line, and showed the following characteristics: (1) resistance to hydrogen peroxide, (2) resistance to NO • , (3) growth with and without hydrogen peroxide, and (4) resistance to doxorubicin. Gene chip analysis was used to determine the global gene expression changes between A549-parent and A549-HHP and revealed significant changes in the expression of over 1,700 genes. This gene profile was markedly different from that obtained from the A549-HNO cell line. The mitochondrial DNA content of the A549-HHP line determined by quantitative PCR favored a change for a more anaerobic metabolic profile. Our findings suggest that any free radical can induce resistance to other free radicals; this is especially important given that radiation therapy and many chemotherapeutic agents exert their effect via free radicals. Utilizing this model system to better understand the role of free radicals in tumor biology will help to develop new therapeutic approaches to treat lung cancer.
Tetrahedron, 2005
The syntheses of a variety of substituted diaminomaleonitriles, with variable nitrogen substituen... more The syntheses of a variety of substituted diaminomaleonitriles, with variable nitrogen substituents, were undertaken. Linstead macrocyclization of the resulting diaminomaleonitriles gave access to a wide range of functionalized porphyrazine-...
Metal-Based Drugs, 2008
The porphyrazines (pzs), a class of porphyrin analogues, are being investigated for their potenti... more The porphyrazines (pzs), a class of porphyrin analogues, are being investigated for their potential use as tumor imaging/therapeutic agents. We here examine six peripherally-functionalized M[pz(A n B 4-n )] pzs with n = 4, 3, or 2 (in a trans conformation) and M = H 2 or Zn, where A is an [S((CH 2 ) 2 O) 4 Me] 2 unit and B is a fused β, β -diisopropyloxybenzo group. Cell viability/proliferation assays and fluorescence microscopy were carried out in both tumor and normal cells. Dark toxicity studies disclosed that four of the compounds exhibited toxicity in both normal and tumor cells; one was nontoxic in both normal and tumor cells, and one was selectively toxic to normal cells. Additionally, three of the pzs showed enhanced photo-induced toxicity with these effects in some cases being observed at treatment concentrations of up to ten-fold lower than that needed for a response in Photofrin. All six compounds were preferentially absorbed by tumor cells, suggesting that they have potential as in vitro diagnostic agents and as aids in the isolation and purification of aberrant cells from pathological specimens. In particular, two promising diagnostic candidates have been identified as part of this work.
Journal of the American Chemical Society, 2004
We report the preparation of two novel H2[pz(An;B4-n)] porphyrazines (pzs) which were designed to... more We report the preparation of two novel H2[pz(An;B4-n)] porphyrazines (pzs) which were designed to position themselves quite differently when attached to a surface: one to form a standard self-assembled monolayer (SAM) roughly perpendicular to a surface, the other to lie horizontally along a surface. As the former, we synthesized a pz, 1, where one pyrrole group is functionalized with two thioethers terminated in mercaptides (SR, R ) (CH 2)3CONH(CH2)2S-), each protected as a disulfide, and -S-Me is attached to the other pyrrole sites; the latter is a pz, 2, with dialkoxybenzo groups fused to two trans-pyrroles of the pz ring, and SR groups are attached to the other pair of pyrroles. Nanostructures of 1 and 2 were successfully patterned on gold surfaces via dip-pen nanolithography, and the predicted molecular orientation of the resulting structures was confirmed by topographic AFM images. The two pzs exhibit similar reduction potentials in solution. Both show large shifts in potential upon surface binding, with the magnitude of the shift depending on the proximity/orientation of the pz to the surface. The first reduction potential of the "vertically" aligned 1 shifts by ca. +430 mV when incorporated in a binary pz/hexanethiol SAM, while that for 2, which lies flat, shifts by ca. +800 mV; the potential thus shifts by ca. +370 mV upon taking a given pz that stands atop a two-legged insulating "standoff" in a traditional SAM and "laying it down". We suggest these observed effects can be explained by image-charge energetics, and this is supported by a simple model.
Journal of Photochemistry and Photobiology B: Biology, 2006
The porphyrazines (pzs) are a class of porphyrin derivatives being studied for their use as optic... more The porphyrazines (pzs) are a class of porphyrin derivatives being studied for their use as optical imaging agents and photodynamic therapy (PDT) anti-tumor agents. A previous study revealed that the anionic pz, 18 -of the form H 2 [pz(A n ;B 4 À n )], where A is ½SðCH 2 Þ 3 CO À 2 , B is a fused b 0 ,b 0 -diisopropyloxy benzo group, with n = 2 (trans) -selectively killed tumor cells, while analogous neutral and positively charged pzs lacked this property. In this report, we compare the properties of a suite of three H 2 [pz(A n ;B 4 À n )] pzs containing the same A and B groups as 18, but differing in their values of n: pzs 4 (n = 4) and 11 (n = 3), and 18 (n = 2, trans) exhibit a progressive variation in charge due to the carboxylates, balance between hydrophobic/hydrophilic character, as well as a progressive variation in the singlet oxygen quantum yield (U D ): U D (18) > U D (11) > U D (4). The biological activity of the pzs was tested in human lung carcinoma (A549) and SV40 transformed embryonic (WI-38 VA13) cell lines. Pzs 4 and 11 exhibited significant toxicity in both tumor and normal cells, while 18 showed selective anti-tumor cell activity in a dose-dependent manner. As the number of net negative charges decreased, the compounds became less toxic to normal cells, and the killing effect observed with these compounds was light independent. These observations indicate that the toxicity may have little to do with singlet oxygen quantum yields, but rather is more dependent on the net number of negative charges a pz contains. The study reported herein presents an example of how the porphyrazines can be easily modified to vary their biological behavior and specifically suggest that anionic porphyrazines pzs with lower n (fewer carboxylates, larger hydrophobic core) are more specific tumor killers, while those with larger n (increased net negative charge) are more potent tumor killers.
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Papers by Benjamin Vesper