Brenda Laster | Ben Gurion University of the Negev (original) (raw)

Papers by Brenda Laster

Journal of cancer research and clinical oncology, 2015

Telomerase activation and an alternative lengthening of telomeres (ALT) mechanism are two telomer... more Telomerase activation and an alternative lengthening of telomeres (ALT) mechanism are two telomere-lengthening cancer cell survival mechanisms elicited by both chemo- and/or radiotherapy. Telomere lengthening interferes with cell lethality and results in the immortalization of cancer cells. To counteract these mechanisms, we developed a drug delivery system (DDS) consisting of a polymeric implant that is inserted directly into tumors. The DDS releases, continuously and gradually, a cationic porphyrin (PdTMPyP4) for >30 days after a single application, and inhibits telomerase activation. The PdTMPyP4 porphyrin is incorporated into a poly(co-glycolic lactic)acid (PLGA) polymer, solidified and cut into small rods. PdTMPyP4 release from the rods was measured spectrophotometrically over time. Uptake of Pd in the DNA of in L428 Hodgkins lymphoma cells was measured by ICP-MS, and telomerase activation by the TRAP assay. The rods were placed into the growth medium of cells whose growth r...

Brachytherapy, 2009

In photon activation therapy (PAT), energy deposition at critical sites within a tumor can be inc... more In photon activation therapy (PAT), energy deposition at critical sites within a tumor can be increased by complexing the DNA with higher Z atoms, and provoking the emission of Auger electrons after inducing a photoelectric effect. This in vivo study evaluates the hypothesis using X-rays from palladium-103 seeds to excite the L-edge of platinum (Pt) atoms bound to the DNA of cancerous cells. Pt (II) tetrakis(N-methyl-4-pyridyl) porphyrin chloride was used to locate Pt atoms adjacent to the DNA of the KHJJ murine mammary carcinoma; a 2.3-mCi palladium-103 seed was implanted in the tumor. The tumor periphery received subtherapeutic doses. The rate of tumor growth in mice treated with PAT was slower than in mice treated with brachytherapy only. The tumor growth delay for PAT-treated mice is attributed to Auger emission from Pt atoms that produced substantial local damage. However, other co-existing mechanisms cannot be ruled out.

Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]

Several chemical methods are available for the solubilization of boronated porphyrins. We have pr... more Several chemical methods are available for the solubilization of boronated porphyrins. We have previously reported the tumor localization of nido carboranyl porphyrins in which the icosahedral carborane cages have been opened to give B/sub 9/C/sub 2/ anions. One of these species has shown tumor boron levels of nearly 50 ..mu..g B/g when delivered by week-long subcutaneous infusions. We report here recent in vivo experiments with a new, highly water-soluble porphyrin based on the hematoporphyrin-type of compound in which aqueous solubility is achieved using the two propionic acid side chains of the ''natural'' porphyrin frame. 7 refs.

The resurgence of interest in boron neutron capture therapy (BNCT) as a treatment for malignant l... more The resurgence of interest in boron neutron capture therapy (BNCT) as a treatment for malignant lesions has resulted in the synthesis of numerous boron compounds as candidates for clinical use. The model presented provides a rapid, quantitative, and cost-effective approach to the evaluation of the biological efficacy of these drugs.

Boronated compounds are currently being studied for possible use in Boron Neutron Capture Therapy... more Boronated compounds are currently being studied for possible use in Boron Neutron Capture Therapy (BNCT). We found that one of these agents, BOPP (tetrakis-carborane-carboxylate, esters of 2,4-bis (a,bdihydroxyethyl) deuteroporphyrin IX), could also be labeled with indium (In-BOPP) and, therefore, could also be used potentially to transport high Z atoms into tumor cell DNA for AET (Auger Electron Therapy). In order to assess the uptake of these agents into cells, the role of the LDL receptor in the intracellular accumulation of BOPP and In-BOPP was investigated.

Ultrasound in Medicine & Biology, 2016

Previous studies have found that cancer cells whose metastatic potential is low are more vulnerab... more Previous studies have found that cancer cells whose metastatic potential is low are more vulnerable to mechanical stress-induced trauma to their cytoskeleton compared with benign cells. Because ultrasound induces mechanical stresses on cells and tissues, it is postulated that there may be a way to apply ultrasound to tumors to reduce their ability to metastasize. The difference between low-malignant-potential cancer cells and benign cells could be a result of their different responses to the mechanical stress insonation induced. This hypothesis was tested in vitro and in vivo. Low-malignant-potential cells were found to be more sensitive to insonation, resulting in a significantly higher mortality rate compared with that of benign cells, 89% versus 21%, respectively. This effect can be controlled by varying ultrasound parameters: intensity, duration, and duty cycle. Thus, the results presented in this study suggest the application of ultrasound to discriminate between benign and malignant cells.

The utilization of an epithermal neutron beam for neutron capture therapy (NCT) is desirable beca... more The utilization of an epithermal neutron beam for neutron capture therapy (NCT) is desirable because of the increased tissue penetration relative to a thermal neutron beam. Over the past few years, modifications have been and continue to be made at the Brookhaven Medical Research Reactor (BMRR) by changing its filter components to produce an optimal epithermal beam. An optimal epithermal beam should contain a low fast neutron contamination and no thermal neutrons in the incident beam. Recently a new moderator for the epithermal beam has been installed at the epithermal port of the BMRR and has accomplished this task. This new moderator is a combination of alumina (AlâOâ) bricks and aluminum (Al) plates. A 0.51 mm thick cadmium (Cd) sheet has reduced the thermal neutron intensity drastically. Furthermore, an 11.5 cm thick bismuth (Bi) plate installed at the port surface has reduced the gamma dose component to negligible levels. Foil activation techniques have been employed by using b...

The distribution of boron in mice bearing transplanted Harding-Passey melanomas after rapid and s... more The distribution of boron in mice bearing transplanted Harding-Passey melanomas after rapid and slow administration of monomer were studied. Thin layer chromatographic analysis of the corresponding infusion solution revealed a slow-moving principal band that was later shown to correspond to Na/sub 4/B/sub 24/H/sub 22/S/sub 2/, the dimer of Na/sub 2/B/sub 12/H/sub 11/SH. It was found that while monomer and chemically synthesized dimer yielded similar boron concentrations when they were given rapidly intraperitoneally to mice, the dimer yielded higher boron concentrations in mouse melanoma and higher melanoma-blood boron concentration when each was infused slowly intraperitoneally for 8 to 9 days. Studies have been started on the uptake of dimer into an intracerebrally implanted rat glioma. Boron levels in the rat glioma and in the mouse melanoma from slow intraperitoneal infusion of proportionately comparable amounts of dimer, are similar. However, after these slow infusions boron le...

The present invention covers a new radiation source, samarium-145, with radiation energies slight... more The present invention covers a new radiation source, samarium-145, with radiation energies slightly above those of I-125 and a half-life of 340 days. The samarium-145 source is produced by neutron irradiation of SM-144. This new source is useful as the implanted radiation source in photon activation therapy of malignant tumors to activate the stable I-127 contained in the IdUrd accumulated in the tumor, causing radiation sensitization and Auger cascades that irreperably damage the tumor cells. This new source is also useful as a brachytherapy source.

Clinical Cancer Research, 2015

Basic life sciences, 1989

Physics Today

A new twist on the quantum vacuum Physics Today 72, 74 (2019); https://doi.

ACS Applied Materials & Interfaces

There is widespread and increasing interest in the preparation of organoboron compounds for their... more There is widespread and increasing interest in the preparation of organoboron compounds for their potential medical application for neutron capture therapy (NCT). The authors approach was to synthesize a boron-containing pyrimidine nucleoside,5-dihydroxyboryl-2'-deoxyuridine (DBDU), which could act as a sensitizing agent in boron neutron-capture reactions. Irradiation of tumor cells that have incorporated boron nucleoside with neutrons would, therefore, principally destroy only tumor tissue. Since the nucleoside would be localized primarily in the nucleus, the greater biological efficacy would permit utilization of lower boron concentrations. Synthetic procedures to novel boron nucleosides and pyrimidines that could be of potential utility for NCT have been worked out. These include the synthesis of 2-thio-5-dihydroxyboryluracil and 2,4-dithio-5-dihydroxyboryluracil, which may be taken up selectively in melanoma cells as analogues of 2-thiouracil; and 6-dihydroxyborylpurine-2&#3...

Treatment planning for clinical trials with boron neutron capture therapy (BNCT) is complicated s... more Treatment planning for clinical trials with boron neutron capture therapy (BNCT) is complicated substantially by the fact that the radiation field generated by the activating external neutron beam is composed of several different types of radiation, i.e., fast neutrons, recoil protons from elastic collisions with hydrogen, gamma rays from the reactor and from neutron capture by body hydrogen, protons from nitrogen capture, and the products of the NCT interaction. Furthermore, the relative contribution of each type of radiation varies with depth in tissue. Because each of these radiations has its own RBE, and the RBE of the fast neutron component will not be constant as the neutron spectrum changes with depth, the problem of predicting the severity of the biological effect, in depth, becomes complex indeed. In order to attack this problem, Monte Carlo calculations of dose, checked against benchmark measurements, are employed. Two approaches are then used to assess the severity of the...

The possibility of using a boronated analog of thymidine for Neutron Capture Therapy (NCT) is int... more The possibility of using a boronated analog of thymidine for Neutron Capture Therapy (NCT) is intriguing, as the boron is targeted to the cell's most sensitive location. Such an analog has been synthesized in the form of dihydroxyboryldeoxyuridine (DBDU). Data are presented indicating that DBDU is indeed incorporated in the nucleus, and that significant radiosensitization is produced in cell cultures as a consequence of this uptake. The results demonstrate that cells exposed to DBDU for 1 cell cycle incorporate an amount of boron such that the resultant biological effect is equivalent to a boron concentration of 6 ..mu..g /sup 10/B/g cell. Other studies have shown that it should be possible to effect successful BNCT with a boron concentration of approx.15 ..mu..g /sup 10/B/g cell (with an epithermal neutron beam; thermal beams would require more; reference 1). Thus it would appear that DBDU is capable of delivering boron concentrations approaching that which should be useful for...

It was found that the energy deposited in the cell from each 10B(n,α) reaction is 2.3 MeV. This r... more It was found that the energy deposited in the cell from each 10B(n,α) reaction is 2.3 MeV. This represents the total kinetic energy of the alpha particle and the Li ion. The energy deposited in the cell from each 157Gd(n,γ)158Gd reaction is 0.045 MeV, due to the Auger electrons. It was found that ~6 10B(n,α) 7Li reactions were needed at dose of 3.3 MW × Minutes to damage the cells to the 10% level of survival. (The dose is expressed in MW-Min units, i.e. reactor power multiplied by irradiation time in minutes, to avoid using various unknown values of RBE.) Because of the high Gd(n,γ) cross section, this same level of survival was obtained at 1.8 MW-Min, with 68 157Gd(n,γ)158Gd reactions