In vitro regeneration ability of diploid and autotetraploid plants of Cichorium intybus L.

Polyploidy has played a significant role in the evolutionary history of plants and is a valuable tool for obtaining useful characteristics. Because of the novelty of polyploids, comparison of their in vitro culture responses with diploids would be notable. In this study, leaf explants from diploid, autotetraploid and mixoploid plants of Cichorium intybus L. were cultured in vitro on the similar media and under same conditions. The ploidy level of the obtained calluses and regenerants were determined by flow cytometry analysis. The callogenic response of leaf explants cultured on the callus induction medium did not depend on the ploidy level of their parental plants. According to the flow cytometry analysis, the increased ploidy levels (4x) and (8x) were observed in the callus cultures with diploid and tetraploid origin, respectively. A considerable difference was observed between the ploidy level of mixoploid plants and their calluses, indicating the dominance of diploid cells in the callus tissue. The results showed that polyploidy led to the loss of organogenic potential as the tetraploid origin calluses failed to regenerate, while the diploid origin calluses successfully regenerated to whole plants.Полиплоидия сыграла значительную роль в эволюционной истории растений как ценный инструмент получения полезных признаков. В настоящей работе приведено сравнение культурального ответа in vitro полиплоидов с диплоидами. Листовые экспланты диплоидных, автотетраплоидных и миксоплоидных растений Cichorium intybus L. культивировали на одних и тех же средах в одинаковых условиях. Уровень плоидности индуцированных каллусов и регенерантов определяли с помощью жидкостной цитометрии. Способность листовых эксплантов к каллусообра-зованию на среде для индукции каллуса не зависела от уровня плоидности исходных растений. По данным жидкостной цитометрии в каллусных культурах диплоидного и тетраплоидного происхождения на блюдалось увеличение уровней плоидности (4x и 8x соответственно). Значительные отличия в уровнях плоидности обнаружены у миксоплоидных растений и их каллусов, при этом в каллусной ткани доминировали диплоидные клетки. Показано, что поли плоидия приводила к потере органогенного потенциала, так как тетраплоидные каллусы не были способны к регенерации, а в каллусах диплоидного происхождения успешно происходила регенерация растений

Comparing Blood Sugar Levels Measured by the Glucometer in Healthy and Crushed Fingers to Predict Gangrene in Tehran, Iran

Background: Crushed fingers are one of the most common reasons that patients visit the emergency centers for hand surgery, and based on the level of injury, it can cause many disabilities for patients. It is difficult to decide the treatment strategies (amputation, aggressive revascularization, immediate or delayed complex reconstruction and immediate conservative treatment) for crushed fingers. Objectives: The current study aimed to compare the blood sugar (BS) levels measured by the glucometer in healthy and crushed fingers to predict gangrene in patients referred to 15 Khordad Hospital in Tehran, Iran. Methods: This cohort study was conducted on 265 patients with crushed fingers referred to the emergency center of 15 Khordad hospital in Tehran, Iran, from March 2015 to March 2016. Blood glucose levels were measured by glucometer in the crushed fingers and in the finger of the opposite side at the same time and measurements were recorded. Data were analyzed using t-test and chi-square test with SPSS software version 22. Results: The results showed that 317 crushed fingers of 265 patients were ischemic based on the color, temperature, capillary refill time and pulse oximetry and accordingly the vascular reconstruction was not possible. Of 317 crushed fingers, 61 (19.24%) became gangrene (all with sugar levels lower than 37). The mean BS levels of the amputated and non-amputated fingers were 33.5 ± 1.52 and 111.04 ± 15.27 mg/dL, respectively. Therefore, there was a significant difference in the mean BS level between the patients with amputated and non-amputated fingers (P < 0.001). Conclusions: The lower levels of sugar in crushed fingers compared to healthy fingers can help to diagnose gangrene in crushed finger

Commentaire

Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver-operating characteristic curves (AUCs) to quantify our ability to predict therapeutic resistance in individual patients, where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in UK Medical Research Council/National Cancer Research Institute, Dutch–Belgian Cooperative Trial Group for Hematology/Oncology/Swiss Group for Clinical Cancer Research, US cooperative group SWOG and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death (‘primary refractoriness’). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival, was even more difficult. Our limited ability to forecast resistance based on routinely available pretreatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and posttreatment data to optimize resistance prediction in AML

The blind men and the AML elephant:can we feel the progress?

The pharmacological therapy of non-promyelocytic acute myeloid leukemia (AML) has remained unchanged for over 40 years with an anthracycline–cytarabine combination forming the backbone of induction treatments. Nevertheless, the survival of younger patients has increased due to improved management of the toxicity of therapies including stem cell transplantation. Older patients and those with infirmity that precludes treatment-intensification have, however, not benefited from improvements in supportive care and continue to experience poor outcomes. An increased understanding of the genomic heterogeneity of AML raises the possibility of treatment-stratification to improve prognosis. Thus, efforts to identify agents with non-conventional anti-leukemic effects have paralleled those aiming to optimize leukemia cell-kill with conventional chemotherapy, resulting in a number of randomized controlled trials (RCT). In the last 18 months, RCTs investigating the effects of vosaroxin, azacitidine and gemtuzumab ozogamycin and daunorubicin dose have been reported with some studies indicating a statistically significant survival benefit with the investigational agent compared with standard therapy and potentially, a new era in AML therapeutics. Given the increasing costs of cancer care, a review of these studies, with particular attention to the magnitude of clinical benefit with the newer agents would be useful, especially for physicians treating patients in single-payer health systems

Significance of Persistent Cytogenetic Abnormalities on Myeloablative Allogeneic Stem Cell Transplantation in First Complete Remission

AbstractRisk stratification is important to identify patients with acute myelogenous leukemia (AML) who might benefit from allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission. We retrospectively studied 150 patients with AML and diagnostic cytogenetic abnormalities who underwent myeloablative allo-HSCT while in first complete remission to evaluate the prognostic impact of persistent cytogenetic abnormalities at allo-HSCT. Three risk groups were identified. Patients with favorable/intermediate cytogenetics at diagnosis (n = 49) and patients with unfavorable cytogenetics at diagnosis but without a persistent abnormal clone at allo-HSCT (n = 83) had a similar 3-year leukemia-free survival of 58%-60% despite the higher 3-year relapse incidence (RI) in the latter group (32.3%, versus 16.8% in the former group). A third group of patients with unfavorable cytogenetics at diagnosis and a persistent abnormal clone at allo-HSCT (n = 15) had the worst prognosis, with a 3-year RI of 57.5% and 3-year leukemia-free survival of only 29.2%. These data suggest that patients with AML and unfavorable cytogenetics at diagnosis and a persistent abnormal clone at allo-HSCT are at high risk for relapse after allo-HSCT. These patients should be considered for clinical trials designed to optimize conditioning regimens and/or to use preemptive strategies in the posttransplantion setting aimed at decreasing RI

Experiences of men with breast cancer: an exploratory focus group study

Management and care of men with breast cancer is based on that developed for women. Our study reports that men have specific issues regarding certain aspects of their breast cancer experience, including diagnosis, disclosure, support and gender-specific information, and offers suggestions for improved patient care

The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia

CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML

Oncolytic measles viruses encoding interferon β and the thyroidal sodium iodide symporter gene for mesothelioma virotherapy

Mesothelioma usually leads to death within 8–14 months of diagnosis. To increase the potency of oncolytic measles viruses (MVs) for mesothelioma therapy, we inserted the interferon β (IFNβ) gene alone or with the human thyroidal sodium iodide symporter (NIS) gene into attenuated MV of the Edmonston lineage. The corresponding mouse IFNβ (mIFNβ) viruses, MV-mIFNβ and MV-mIFNβ-NIS, successfully propagated in human mesothelioma cells, leading to intercellular fusion and cell death. High levels of mIFNβ were detected in the supernatants of the infected cells, and radioiodine uptake was substantial in the cells infected with MV-mIFNβ-NIS. MV with mIFNβ expression triggered CD68-positive immune cell infiltration 2–4 times higher than MV-GFP injected into the tumor site. The numbers of CD31-positive vascular endothelial cells within the tumor were decreased at day 7 after intratumoral injection of MV-mIFNβ or MV-mIFNβ-NIS, but not after MV-GFP and PBS administration. Immunohistochemical analysis showed that MV-mIFNβ changed the microenvironment of the mesothelioma by increasing innate immune cell infiltration and inhibiting tumor angiogenesis. Oncolytic MVs coding for IFNβ effectively retarded growth of human mesotheliomas and prolonged survival time in several mesothelioma tumor models. The results suggest that oncolytic MVs that code for IFNβ and NIS will be potent and versatile agents for the treatment of human mesothelioma

Combinatorial epigenetic therapy in diffuse large B cell lymphoma pre-clinical models and patients

BACKGROUND: Refractory and/or relapsed diffuse large B cell lymphoma (RR-DLBCL) patients are incurable with conventional chemotherapy due to the aggressiveness and the chemorefractory state of these tumors. DNA hypermethylation and histone deacetylation are two major epigenetic modifications by which aggressive DLBCL maintain their oncogenic state. We have previously reported that DNA methyltransferase inhibitors (DNMTI) affect RR-DLBCL growth and improve chemosensitivity. Here, we hypothesized that the combination of DNMTI with histone deacetylase inhibitor (HDI) would be an active and feasible therapeutic strategy in RR-DLBCL. Thus, we evaluated the anti-lymphoma activity of the HDI vorinostat (VST) in combination with the DNMTI azacitidine (AZA) or decitabine (DAC) in pre-clinical models of RR-DLBCL, and we determined the feasibility of the combination by conducting a phase Ib trial in RR-DLBCL patients. RESULTS: Concurrent combination of DNMTI and HDI resulted in synergistic anti-lymphoma effect toward RR-DLBCL cells in vitro and in vivo, with no significant toxicity increase. In a phase Ib trial, a total of 18 patients with a median of three prior therapies were treated with four different dose levels of AZA and VST. The most common toxicities were hematological, followed by gastrointestinal and metabolic. The clinical benefit was low as only one subject had a partial response and three subjects had stable disease. Interestingly, two of the seven patients that received additional chemotherapy post-study achieved a complete response and three others had a significant clinical benefit. These observations suggested that the combination might have a delayed chemosensitization effect that we were able to confirm by using in vitro and in vivo models. These studies also demonstrated that the addition of VST does not improve the chemosensitizing effect of DAC alone. CONCLUSIONS: Our data supports the strategy of epigenetic priming by employing DNMTI in RR-DLBCL patients in order to overcome resistance and improve their outcomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-016-0245-y) contains supplementary material, which is available to authorized users