Additive QTLs on three chromosomes control flowering time in woodland strawberry (Fragaria vesca L.)

Flowering time is an important trait that affects survival, reproduction and yield in both wild and cultivated plants. Therefore, many studies have focused on the identification of flowering time quantitative trait locus (QTLs) in different crops, and molecular control of this trait has been extensively investigated in model species. Here we report the mapping of QTLs for flowering time and vegetative traits in a large woodland strawberry mapping population that was phenotyped both under field conditions and in a greenhouse after flower induction in the field. The greenhouse experiment revealed additive QTLs in three linkage groups (LG), two on both LG4 and LG7, and one on LG6 that explain about half of the flowering time variance in the population. Three of the QTLs were newly identified in this study, and one co-localized with the previously characterized FvTFL1 gene. An additional strong QTL corresponding to previously mapped PFRU was detected in both field and greenhouse experiments indicating that gene(s) in this locus can control the timing of flowering in different environments in addition to the duration of flowering and axillary bud differentiation to runners and branch crowns. Several putative flowering time genes were identified in these QTL regions that await functional validation. Our results indicate that a few major QTLs may control flowering time and axillary bud differentiation in strawberries. We suggest that the identification of causal genes in the diploid strawberry may enable fine tuning of flowering time and vegetative growth in the closely related octoploid cultivated strawberry.Peer reviewe

ПОБОЧНЫЕ ЭФФЕКТЫ СОРАФЕНИБА, СУНИТИНИБА И ТЕМСИРОЛИМУСА И ИХ ЛЕЧЕНИЕ У БОЛЬНЫХ МЕТАСТАТИЧЕСКИМ ПОЧЕЧНО-КЛЕТОЧНЫМ РАКОМ

Objective: to provide a systematic review of the adverse reactions of sorafenib, sunitinib, and temsirolimus and to outline actions for their prevention and correction.Materials and methods. To provide a description of the main methods to decrease the toxicity of these drugs, the authors made a systemat- ic review of their adverse reactions, by using the publications available in the PubMed database, monographs on the medicines, and instruc- tions for their medical use. Results. The frequency of their adverse reactions varied from < 1 to 72%. Grades III—IV side effects are noted more rarely; their incidence is < 1 to 13% for sorafenib, < 1 to 16% for sunitinib, and 1 to 20% for temsirolimus. Sinitinib causes most grades III—IV adverse reactions and sofafenib does the least. However, close comparative studies of the safety of these kinase inhibitors are still lacking. Virtually all side effects can be effectively prevented and treated.  Conclusion. The prevention, timely recognition, and treatment of the adverse reactions of these agents are of great importance, which allows avoidance of the unneeded dosage reduction that may result in worse therapeutic efficiency.   Цель исследования — представить систематический обзор побочных эффектов сорафениба, сунитиниба и темсиролимуса, а также в общих чертах описать меры по их предупреждению и коррекции. Материалы и методы. Для того чтобы представить описание основных методов, направленных на снижение токсичности этих препаратов, нами проведен систематический обзор побочных эффектов на основе публикаций в базе данных PubMed, монографий по лекарственным препаратам и инструкций по их медицинскому применению.Результаты. Частота развития побочных эффектов варьирует от < 1 до 72%. Побочные эффекты III—IV степени отмечаются реже, частота их возникновения от < 1 до 13% для сорафениба, от < 1 до 16% — для сунитиниба и от 1 до 20% — для темсиролимуса. Сунитиниб вызывает наибольшее количество побочных эффектов III—IV степени, а сорафениб — наименьшее. Однако все еще отсутствуют тщательные сравнительные клинические исследования безопасности этих ингибиторов киназ. Практически все побочные эффекты можно эффективно предупреждать и лечить.Заключение. Большое значение имеют профилактика, своевременное распознавание и лечение побочных эффектов этих препаратов, что позволяет избежать ненужного снижения дозы, грозящего ослаблением эффективности лечения.

Tyrosine kinase inhibitors reprogramming immunity in renal cell carcinoma: rethinking cancer immunotherapy

Review article[Abstract] The immune system regulates angiogenesis in cancer by way of both pro- and antiangiogenic activities. A bidirectional link between angiogenesis and the immune system has been clearly demonstrated. Most antiangiogenic molecules do not inhibit only VEGF signaling pathways but also other pathways which may affect immune system. Understanding of the role of these pathways in the regulation of immunosuppressive mechanisms by way of specific inhibitors is growing. Renal cell carcinoma (RCC) is an immunogenic tumor in which angiogenesis and immunosuppression work hand in hand, and its growth is associated with impaired antitumor immunity. Given the antitumor activity of selected TKIs in metastatic RCC (mRCC), it seems relevant to assess their effect on the immune system. The confirmation that TKIs improve cell cytokine response in mRCC provides a basis for the rational combination and sequential treatment of TKIs and immunotherapy

Enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent ZD6126

Current experimental and clinical knowledge supports the optimisation of endothelial cell targeting using a strategy combining anti-EGFR drugs with antivascular agents. The purpose of the present study was to examine the effects of the association of ZD6126, an antivascular microtubule-destabilising agent, with gefitinib and irradiation on the growth of six head and neck human cancer cell lines xenografted in nude mice and to study predictive and molecular factors responsible for antitumour effects. CAL33- and Hep-2-grafted cell lines were the most sensitive to ZD6126 treatment, with VEGF levels significantly higher (P=0.0336) in these tumour xenografts compared to Detroit 562- and CAL27-grafted cell lines with relatively low VEGF levels that were not sensitive to ZD6126. In contrast, neither IL8 levels nor EGFR expression was linked to the antitumour effects of ZD6126. ZD6126 in combination with gefitinib resulted in a synergistic cytotoxic interaction with greater antitumour effects than gefitinib alone. The synergistic interaction between ZD6126 and gefitinib was corroborated by a significant decrease in CD31 labelling. The present study may serve for future innovative clinical applications, as it suggests that VEGF tumour levels are possible predictors for ZD6126 antitumour efficacy. It also supports the notion of antitumour supra-additivity when combining gefitinib and ZD6126, and identifies neoangiogenesis as the main determinant of this synergistic combination

Control of Flowering in Strawberries

Strawberries (Fragaria sp.) are small perennial plants capable of both sexual reproduction through seeds and clonal reproduction via runners. Because vegetative and generative developmental programs are tightly connected, the control of flowering is presented here in the context of the yearly growth cycle. The rosette crown of strawberry consists of a stem with short internodes produced from the apical meristem. Each node harbors one trifoliate leaf and an axillary bud. The fate of axillary buds is dictated by environmental conditions; high temperatures and long days (LDs) promote axillary bud development into runners, whereas cool temperature and short days (SDs) favor the formation of branch crowns. SDs and cool temperature also promote flowering; under these conditions, the main shoot apical meristem is converted into a terminal inflorescence, and vegetative growth is continued from the uppermost axillary branch crown. The environmental factors that regulate vegetative and generative development in strawberries have been reasonably well characterized and are reviewed in the first two chapters. The genetic basis of the physiological responses in strawberries is much less clear. To provide a point of reference for the flowering pathways described in strawberries so far, a short review on the molecular mechanisms controlling flowering in the model plant Arabidopsis is given. The last two chapters will then describe the current knowledge on the molecular mechanisms controlling the physiological responses in strawberries.Peer reviewe

Salvage Cryotherapy for Radiation-Recurrent Prostate Cancer: Outcomes and Complications

Potentially curative salvage options for radio-recurrent prostate cancer include prostatectomy, brachytherapy, high-intensity focused ultrasound, and cryotherapy. Salvage cryoablation technology, surgical technique, oncologic outcomes, and complication rates have improved dramatically over the past few decades, shifting this treatment modality from investigational status to an established therapeutic option. In this review, we focus on the most up-to-date oncologic and functional outcomes, as well as complications of salvage cryotherapy for radiation-recurrent prostate cancer

ZD6474 – a novel inhibitor of VEGFR and EGFR tyrosine kinase activity

Angiogenesis is crucial for maintaining the supply of oxygen and nutrients required to support solid tumour growth. Inhibitors of tumour blood vessel formation are therefore being sought, in particular, inhibitors of vascular endothelial growth factor-A (VEGF)-signalling, which has a pivotal role in stimulating neovascular growth and survival. ZD6474 is an orally bioavailable inhibitor of VEGF receptor-2 tyrosine kinase activity that in preclinical studies has been shown to inhibit both VEGF-induced signalling in endothelial cells and tumour-induced angiogenesis. Consistent with inhibition of angiogenesis, once-daily oral dosing of ZD6474 produced significant broad-spectrum antitumour activity in a panel of histologically diverse human tumour xenografts. In addition to its antiangiogenic properties, ZD6474 also has activity against the epidermal growth factor receptor (EGFR) tyrosine kinase, which could impart a direct inhibitory effect on tumour cell growth and survival. This may be particularly relevant in tumours with a dependency upon EGFR signalling, for example in certain tumours harbouring activating mutations in EGFR. RET kinase has also been identified as a third target for ZD6474. This review summarises preclinical studies with this unique agent and considers its future direction in cancer treatment

HPV and cervical cancer related knowledge, awareness and testing behaviors in a community sample of female sex workers in China

BACKGROUND: Limited data suggested that the prevalence of Human Papillomavirus (HPV) among female sex workers (FSW) is much higher than in the general female population. The current study aimed to examine the HPV and cervical cancer related awareness, knowledge, and behaviors among FSW in China. METHODS: A total of 360 FSW recruited from entertainment establishments in Beijing completed a self-administered survey including demographics, HPV related knowledge, and health-seeking and cervical cancer preventive behaviors. RESULTS: Approximately 70.8% of the participants ever heard of cervical cancer, and as few as 22.1% and 13.3% ever heard of HPV and HPV vaccine, respectively. The mean score on a 7-item knowledge scale was 2.2 (SD = 2.4). Less than 10% of FSW perceived any risk of cervical cancer, and only 15.3% ever had a Pap smear. About 40.8% of FSW would accept HPV vaccine if it is free, and 21.8% would accept it even with a charge. Multivariate regression suggested that women with better knowledge of cervical cancer were more likely to have a Pap smear (aOR = 1.35); women who had tested for HIV were 11 times more likely to have a Pap smear, and women who had worked longer in commercial sex (aOR = 1.01) and had regular health check-ups (aOR = 1.95) were more likely to accept HPV vaccine. CONCLUSIONS: Our study underscores the needs for effective cervical cancer prevention programs for FSW in China and other resource-limited countries. We specifically call for cervical cancer and HPV knowledge and awareness programs and regular screening as well as HPV risk-reduction programs for these vulnerable women