The Plk3-Cdc25 circuit

Polo-like kinases (Plks) are key regulators of the cell cycle, especially in the G2 phase and mitosis. They are incorporated into signaling networks that regulate many aspects of the cell cycle, including but not limited to centrosome maturation and separation, mitotic entry, chromosome segregation, mitotic exit, and cytokinesis. The Plks have well conserved 30-amino-acid elements, designated polo boxes (PBs), located in their carboxyl-termini, which with their flanking regions constitute a functional Polo-box domain (PBD). Members of the Plk family exist in a variety of organisms including Polo in Drosophila melanogaster; Cdc5 in Saccharomyces cerevisiae; Plo1 in Schizosaccharomyces pombe; Plx1 in Xenopus laevis; and Plk1, Snk/Plk2, Fnk/Prk/Plk3, and Sak in mammals. Polo, Cdc5, and Plo1 are essential for viability. The Plks can be separated into two groups according to their functions. The first group (Polo, Cdc5, plo1, Plx1, and Plk1) primarily performs mitotic functions, whereas the second group (Plk2 and Plk3) appears to have additional functions during the G1, S, and G2 phases of the cell cycle. Several contributions to this issue will discuss different aspects of Plk involvement in cell-cycle regulation. This review, therefore, will focus on the role of Plk3 in regulating Cdc25 phosphatase function and its effect on the cell cycle.     

Trauma-associated growth of suspected dormant micrometastasis

Background  

Cancer patients may harbor micrometastases that remain dormant, clinically undetectable during a variable period of time. A traumatic event or surgery may trigger the balance towards tumor growth as a result of associated angiogenesis, cytokine and growth factors release.     

Natural products as angiogenesis modulators

Cancer remains one of the major causes of death worldwide. Anti-angiogenic therapy is one of the new approaches to anticancer therapy. Out of 22 angiogenesis inhibitors currently under clinical trials there are 11 natural products or were modeled on a natural product parent. This review shows the potential of natural products for the discovery of new anti-angiogenic leads.     

Evaluation of pain-related behavior, bone destruction and effectiveness of fentanyl, sufentanil, and morphine in a murine model of cancer pain

The present study was conducted to evaluate the pain development and bone destruction during bone cancer growth in a murine model of bone cancer pain and to evaluate the analgesic efficacy of fentanyl, sufentanil, and morphine in this model. C3H/HeNCrl mice were inoculated into the intramedullary space of the femur with osteolytic NCTC 2472 fibrosarcoma cells, and followed during a 3-week period to assess pain behaviors (spontaneous lifting and limb-use during forced ambulation on rotarod) and bone destruction (parameters indicative of bone lesions determined by microCT-scans of the tumor-bearing bones) during bone cancer growth. The results showed that in this murine model of cancer-induced bone pain, behavioural manifestations of pain emerge in parallel with the progression of bone destruction. The subcutaneous administration of fentanyl (0.025-0.64 mg/kg), sufentanil (0.005-0.04 mg/kg), and morphine (2.5-40 mg/kg) on the test days 15 and 22 post-inoculation reduced pain-related behaviors in a dose dependent manner. A complete relief from pain-related behaviors was achieved with the following doses: > or =0.16 mg/kg fentanyl, 0.02 mg/kg sufentanil, and 20 mg/kg morphine. In conclusion, the results showed a clear link between tumor growth-induced bone destruction and behavioral pain manifestations, the latter was effectively controlled by the opioids fentanyl, sufentanil, and morphine.     

Effects of sublethal doses of fipronil on the behavior of the honeybee (Apis mellifera)

Fipronil is a phenylpyrazole insecticide introduced for pest control, but it can also affect non-target insects such as honeybees. In insects, fipronil is known to block GABA receptors and to inhibit ionotropic glutamate-gated chloride channels, but the behavioral effects of low doses are not yet fully understood. We have studied the effect of sublethal doses of fipronil on the behavior of the honeybee (Apis mellifera) under controlled laboratory conditions. The drug was either administered orally or applied topically on the thorax. A significant reduction of sucrose sensitivity was observed for the dose of 1 ng/bee 1 h after a thoracic application. No significant effect on sucrose sensitivity was obtained with acute oral treatment. A lower dose of fipronil (0.5 ng/bee applied topically) impaired the olfactory learning of the honeybees. By contrast, locomotor activity was not affected. Our results suggest a particular vulnerability of the olfactory memory processes and sucrose perception to sublethal doses of fipronil in the honeybee.     

NAT2*5/*5 genotype (341T>C) is a potential risk factor for schistosomiasis-associated bladder cancer in Egyptians

Arylamine N-acetyl transferase (NAT2) displays extensive genetic polymorphisms that affect the rates of acetylation of drugs and genotoxic compounds such as amine carcinogens. To investigate whether the slow acetylator genotype is a risk factor for development of bladder cancer following schistosomal infection of the urinary tract, the authors determined the frequencies of 3 common polymorphisms in the NAT2 gene (341T>C, 590G>A, and 282C>T), which are associated with impaired acetylation activity, in control subjects (n=61; mean age 34.3+/-9.2 years) and in schistosomiasis-associated bladder cancer patients (n=55; 52+/-10.9 years) from the Egyptian population. Genotyping was carried out using rapid cycle PCR on the LightCycler, and subjects were assigned to a slow, intermediate, or rapid acetylator phenotype on the basis of the genotypes. The frequencies of the mutant alleles observed in the controls from the present study were similar to those reported previously for both the Egyptian population and other Arab populations. Patients showed a higher prevalence (78.2%) of slow acetylator phenotype than controls (67.2%), but this did not reach statistical significance (P=0.19). However, there were significantly more individuals who were carriers of 2 mutant 341T>C alleles (NAT2*5/*5 genotype) in the patient group compared with controls (odds ratio 2.6, CI 1.02-6.67, P=0.026). The alloenzyme encoded by this allele has been shown to display a large reduction in its catalytic activity. In conclusion, these data suggest that the NAT2*5/*5 genotype is a potential risk factor for development of urinary bladder cancer in patients with prior schistosomiasis infection.     

Collaborative research partnerships with disadvantaged communities: challenges and potential solutions

Community/campus research collaborations face multiple challenges. An understanding of the community's background, history, habits and traditions, values and mode of operations is required. This article narrates a 3-year experience of undertaking collaborative public health research with five disadvantaged communities in various provinces of South Africa. Based on the experience, five main challenges exist: the value systems of those collaborating in the research; the stakeholders' costs and benefits of being involved; issues of empowerment and capacity transfer; the need for multidisciplinary research approaches; and the prerequisite of the clarity of relationships and roles between researcher and community. Categorized under the five main challenges are examples of 19 interlacing 'concepts' that detailed the South African research partnership from the perspective of the processes, dealings and daily difficulties. Examples of the challenges and concepts are highlighted from the author's research experiences with disadvantaged communities. These challenges increase exponentially with the inclusion of more research sites, more stakeholders or when undertaking cluster research. Possible preventative measures or solutions to the problems are suggested. Both the 'town' and 'gown' partners are required to attend to a multitude of factors when embarking on collaborative community-based research.