The development of novel interventions to assist the leaders of cancer support groups

Purpose

The literature on cancer support groups supports the provision of ongoing education and training for cancer support group leaders, with evidence suggesting that more skilled and experienced leaders create better outcomes for group members. To address support and training needs reported by leaders, three novel interventions were developed and pilot-tested. These included a leaders' website and discussion forum, DVD and manual, and a 2-day training workshop.

Methods

The interventions were developed using a combination of literature review, expert consensus, and consumer feedback. A convenience sample of ten leaders pilot-tested the Website and discussion forum. Using a mixed-method approach, evaluation of the workshop and the DVD and manual was conducted with 35 leaders.

Results

Overall, satisfaction with all aspects of the Website and discussion forum was high. Analysis of the quantitative data revealed extremely high satisfaction with the workshop and DVD and manual. The qualitative responses of workshop participants further supported the quantitative findings with enhanced knowledge, understanding, and confidence reported by leaders.

Conclusions

All three interventions exhibited a high degree of user acceptance, regardless of the skill or experience of the cancer support group leader. The overall positive findings from the evaluation of the leader Website and discussion forum, the DVD and manual, and the workshop for cancer support group leaders provides evidence to support more rigorous evaluation of these resources in a randomized controlled trial.     

Improved immune function with donor B-cell infusion after semi-allogeneic bone marrow transplantation in mice

BACKGROUND: Regeneration of the immune system after bone marrow transplantation (BMT) is a slow process, often prolonged by the development and treatment of graft vs. host disease (GVHD). Donor lymphocyte infusion using allogeneic T-cells is widely applied for the induction of GVHD, which is associated with the desired graft vs. leukemia effect. Due to the slow immune recovery, our objective was to accelerate the immune recovery post-BMT by B-cell injections. METHODS: T-cell-depleted stem cells obtained from female C57BL/6 (B6) mice were transplanted into lethally irradiated (Balb/c x C57BL/6) F-1 female mice. Seven days post-transplantation, murine B-cells of male C57BL/6 origin were infused into the T-cell-depleted chimeras. Thirty and 60 days post-transplantation, PCR analysis of the Y-chromosome was carried out to detect male B-cells in the transplant recipients. In order to evaluate the specific antibody response, the donors were immunized by specific T-cell-dependent and -independent antigens. RESULTS: None of the T-cell-depleted transplanted mice developed GVHD during a follow-up period of 650 days, whereas all non-T-cell-depleted recipients died. At 60 days post-transplantation, significantly higher levels of immunoglobulins (IgA, IgG1, IgG3 isotypes) were seen in chimeras supplemented with male B-cells than in chimeras reconstituted with T-cell-depleted stem cells alone. CONCLUSIONS: Our data document the feasibility of administering B-cell therapy post-allogeneic BMT to improve recovery of the humeral arm of the immune system while avoiding GVHD. Furthermore, post-transplant B-cell administration may have an important impact as an alternative to IV immunoglobulin infusions.     

Novel prodrugs of tegafur that display improved anticancer activity and antiangiogenic properties

New and more potent prodrugs of the 5-fluorouracyl family derived by hydroxymethylation or acyloxymethylation of 5-fluoro-1-(tetrahydro-2-furanyl)-2,4(1H,3H)-pyrimidinedione (tegafur, 1) are described. The anticancer activity of the butyroyloxymethyl-tegafur derivative 3 and not that of tegafur was attenuated by the antioxidant N-acetylcysteine, suggesting that the increased activity of the prodrug is in part mediated by an increase of reactive oxygen species. Compound 3 in an in vitro matrigel assay was found to be a more potent antiangiogenic agent than tegafur. In vivo 3 was significantly more potent than tegafur in inhibiting 4T1 breast carcinoma lung metastases and growth of HT-29 human colon carcinoma tumors in a mouse xenograft. In summary, the multifunctional prodrugs of tegafur display selectivity toward cancer cells, antiangiogenic activity, and anticancer activities in vitro and in vivo, superior to those of tegafur. 5-fluoro-1-(tetrahydro-2-furanyl)-2,4(1 H,3 H)-pyrimidinedione (tegafur, 1), the oral prodrug of 5-FU, has been widely used for treatment of gastrointestinal malignancies with modest efficacy. The aim of this study was to develop and characterize new and more potent prodrugs of the 5-FU family derived by hydroxymethylation or acyloxymethylation of tegafur. Comparison between the effect of tegafur and the new prodrugs on the viability of a variety of cancer cell lines showed that the IC50 and IC90 values of the novel prodrugs were 5-10-fold lower than those of tegafur. While significant differences between the IC50 values of tegafur were observed between the sensitive HT-29 and the resistant LS-1034 colon cancer cell lines, the prodrugs affected them to a similar degree, suggesting that they overcame drug resistance. The increased potency of the prodrugs could be attributed to the antiproliferative contribution imparted by formaldehyde and butyric acid, released upon metabolic degradation. The anticancer activity of the butyroyloxymethyl-tegafur derivative 3 and not that of tegafur was attenuated by the antioxidant N-acetylcysteine, suggesting that the increased activity of the prodrug is in part mediated by an increase of reactive oxygen species. Compound 3 in an in vitro matrigel assay was found to be a more potent antiangiogenic agent than tegafur. In vivo 3 was significantly more potent than tegafur in inhibiting 4T1 breast carcinoma lung metastases and growth of HT-29 human colon carcinoma tumors in a mouse xenograft. In summary, the multifunctional prodrugs of tegafur display selectivity toward cancer cells, antiangiogenic activity and anticancer activities in vitro and in vivo, superior to those of tegafur.     

Mitochondrial genome of the critically endangered smalltooth sawfish <Emphasis Type="Italic">Pristis pectinata</Emphasis> from Veracruz,Mexico

Sawfishes, family Pristidae, occur in tropical and subtropical coastal marine, estuarine and freshwater ecosystems. The smalltooth sawfish (Pristis pectinata) has been wholly or nearly eliminated from large areas of its former range in the Atlantic Ocean by fishing pressure (trawl and inshore netting) and habitat modification. Here, we report the complete sequence of the mitochondrial genome of a specimen caught in Barra de Cazones by local fishermen, Veracruz, Mexico in 2015, where was thought to be almost extinct and compare it with the previously reported mitochondrial genome from an individual caught in Florida. The genome structure and composition of both specimens is almost identical, except for two nucleotide variations remarking the low variation between regions for this species. The mitochondrial genome has a total length of 16803 nucleotides; in average the base composition was A 32.1%, T 28.9%, C 26.0% and G 13.1%, containing 13 protein-coding genes, 2 rRNA genes; 22 tRNA genes.     

Agomelatine (S20098) modulates the expression of cytoskeletal microtubular proteins, synaptic markers and BDNF in the rat hippocampus, amygdala and PFC

Rationale

Agomelatine is described as a novel and clinical effective antidepressant drug with melatonergic (MT₁/MT₂) agonist and 5-HT_2C receptor antagonist properties. Previous studies suggest that modulation of neuronal plasticity and microtubule dynamics may be involved in the treatment of depression.

Objective

The present study investigated the effects of agomelatine on microtubular, synaptic and brain-derived neurotrophic factor (BDNF) proteins in selected rat brain regions.

Methods

Adult male rats received agomelatine (40?mg/kg?i.p.) once a day for 22?days. The pro-cognitive effect of agomelatine was tested in the novel object recognition task and antidepressant activity in the forced swimming test. Microtubule dynamics markers, microtubule-associated protein type 2 (MAP-2), phosphorylated MAP-2, synaptic markers [synaptophysin, postsynaptic density-95 (PSD-95) and spinophilin] and BDNF were measured by Western blot in the hippocampus, amygdala and prefrontal cortex (PFC).

Results

Agomelatine exerted pro-cognitive and antidepressant activity and induced molecular changes in the brain areas examined. Agomelatine enhanced microtubule dynamics in the hippocampus and to a higher magnitude in the amygdala. By contrast, in the PFC, a decrease in microtubule dynamics was observed. Spinophilin (dendritic spines marker) was decreased, and BDNF increased in the hippocampus. Synaptophysin (presynaptic) and spinophilin were increased in the PFC and amygdala, while PSD-95 (postsynaptic marker) was increased in the amygdala, consistent with the phenomena of synaptic remodelling.

Conclusions

Agomelatine modulates cytoskeletal microtubule dynamics and synaptic markers. This may play a role in its pharmacological behavioural effects and may result from the melatonergic agonist and 5-HT_2C antagonist properties of the compound.     

Risk of hematoma following needle electromyography of the paraspinal muscles

The purpose of this study was to establish the incidence of MRI-detectable hematomas following paraspinal EMG. We provide a retrospective review of patients who underwent paraspinal EMG and subsequent concordant level spine MRI. A total of 370 charts (431 MRIs) met the inclusion criteria. No paraspinal hematomas were observed. These results should further the development of evidence-based guidelines for patients who have greater-than-normal bleeding risk and support the notion that paraspinal EMG is a relatively safe procedure.     

Low and dysregulated production of follistatin in immune cells of relapsing-remitting multiple sclerosis patients

One of the mechanisms known to play a key role in neuronal and oligodendroglial fate specification of neural stem cells (NSCs) is restriction of bone morphogenic proteins (BMP) signaling by BMP antagonists. Here, we demonstrate that follistatin mRNA and protein secreted levels in peripheral blood mononuclear cells (PBMCs) of relapsing-remitting multiple sclerosis (RR-MS) patients are significantly reduced compared to healthy controls (HC). We also observed a different profile of regulation mechanisms. Follistatin was similarly expressed and secreted by T lymphocytes and monocytes among the PBMCs of HC, and follistatin upregulation of HC was subjected to stimulation with both LPS and TNF-α. Among PBMCs of RR-MS patients, however, follistatin was found to be downregulated in their monocytes and unresponsive to stimulation with either LPS or TNF-α. Our results may shed some light on the mechanisms involved in remyelination failure in MS, which may be related to the inability of RR-MS patients' immune cells to provide a sufficient pro-neurogenic and oligodendrogenic niche, by expressing and secreting follistatin, in addition to the previously described noggin reduced expression. Our results indicate that the low expression of follistatin in immune cells of patients with RR-MS is a result of the altered immunoregulation of monocytes in these patients.