Development of a Robust and Quantitative High-Throughput Screening Method for Antibiotic Production in Bacterial Libraries.

Over the past 30 years, there has been a dramatic rise in the number of infections caused by multidrug-resistant bacteria, which have proliferated due to the misuse and overuse of antibiotics. Over this same time period, however, there has also been a decline in the number of antibiotics with novel mechanisms of action coming to market. Therefore, there is a growing need for an increase in the speed at which new antibiotics are discovered and developed. Natural products produced by bacteria have been and continue to be a robust source of novel antibiotics; however, new and complementary methods for screening large bacterial libraries for novel antibiotic production are needed due to the current agar methods being limited in scope, time consuming, and prone to error. Herein, we describe a rapid, robust, and quantitative high-throughput liquid culture screening method for antibiotic production by bacteria. This method has the ability to screen both mono- and coculture mixtures of bacteria in vitro and be adapted to other phenotypic natural product analyses. Over 260 bacterial species were screened in monoculture, and 38 and 34% were found to produce antibiotics capable of inhibition of Staphylococcus aureus or Escherichia coli, respectively, with 8 and 4% being classified as strong producers (≥30% growth inhibition), respectively. Bacteria found to not produce antibiotics in monoculture were also screened in coculture using an adaptation of this method. Of the more than 270 cocultures screened, 14 and 30% were found to produce antibiotics capable of inhibition of S. aureus or E. coli, respectively. Of those bacteria found to produce antibiotics in monoculture, 43 bacteria were subjected to 16S rRNA sequencing and found to be majority Pseudomonas (37%), Serratia (19%), and Bacillus (14%) bacteria, but two novel producers, Herbaspirillum and Kluyvera, were also found.

Neutron versus photon radiotherapy for local control in inoperable breast cancer.

BACKGROUND AND PURPOSE: By virtue of their high linear energy transfer (LET) characteristics the biologic effectiveness of neutrons is less dependent on tissue oxygenation tension and cell cycle phase as compared to that with photons. Hence, an improved clinical benefit is to be expected predominantly in large, hypoxic and slowly growing tumors. Since a short course of radiotherapy is required for clinical reasons, it prompted the authors to initiate a randomly controlled trial on locally advanced breast cancer. PATIENTS AND METHODS: Between 1996 and 1999, 27 patients with locally advanced breast cancer were irradiated with photons (60 Gy, 30 fractions; 8 MV, (60)Co) or neutrons (18 Gy, twelve fractions; 66 MeV(p-->Be)). The mean tumor diameters were 699 +/- 399 ml for the photon group and 1,097 +/- 831 ml in the neutron group. RESULTS: After a mean follow-up period of 21.5 months tumor involution was evaluated in 22 patients. Partial and complete remissions were registered in 6/10 patients of the photon group and 5/12 patients of the neutron group. Late grade 3-4 morbidity according to RTOG definition was scored in 5/10 patients in the photon group and in 6/12 patients in the neutron group. With regard to tumor control and late radiation morbidity no differences between the two treatment arms were observed. CONCLUSION: The underlying data indicate that no benefit is to be expected from neutron therapy in breast cancer.

Medical and radiation oncology for breast cancer in developing countries with particular reference to locally advanced breast cancer.

The first part of this review outlines the extent of the problem of breast cancer in developing countries, with particular reference to the difficulties surrounding breast cancer treatment in these countries. The second part is devoted to discussion of chemotherapy, hormonal therapy, and radiotherapy treatments suitable for developing countries. The goals of the review are to show how treatment strategies can be adapted in poorer countries and how oncologists from the developed world can play a role in developing countries. This review should be relevant to the developing world in general, but as the author comes from South Africa, many of the examples are from that country which has features of the developed and developing world.