Avatrombopag for the salvage treatment of platelet transfusion refractoriness.

Background: Platelet transfusion refractoriness (PTR) is a life-threatening and intractable condition in hematological patients. Thrombopoietin receptor agonists such as avatrombopag promote platelet production and modulate immune intolerance. However, its application in PTR has not been extensively studied. Objectives: We aimed to compare the platelet response (PR) as well as bleeding events and mortality rate between the best available therapies (BATs) and avatrombopag (Ava) treatments in refractory PTR patients. Design: A total of 71 refractory PTR patients were enrolled at Nanfang Hospital. Intravenous immunoglobulin, steroids, and human leucocyte antigen-matched platelet transfusions were administered to 30 patients in the BATs group. The Ava group included 41 patients. Methods: Data of refractory PTR patients were retrospectively collected. The primary endpoint was PR (defined as an increase of platelet count to ⩾50 × 109/L without platelet transfusion support for 7 consecutive days). Secondary endpoints included platelet-transfusion independence rate, cumulative platelet transfusion units, World Health Organization bleeding grades, adverse events, overall survival (OS), and bleeding event-free survival (EFS). Results: There were 75.6% and 13.3% refractory PTR patients who reached PR within 3 months in Ava and BATs groups. The median platelet counts were significantly higher in Ava group from day 7. Platelet-transfusion independence rate in Ava was higher than BATs group. The median cumulative platelet transfusion unit in Ava was lower than that of BATs group. The OS and bleeding events-free EFS rate of Ava group improved within 3 months as compared to BATs group. Cox proportional hazards regression analysis revealed that Ava therapy was a protective factor for the OS and EFS. No primary disease progression or termination of avatrombopag was observed due to intolerability. Conclusion: Our study suggests that avatrombopag is an effective and safe treatment option for refractory PTR patients.

Avatrombopag in platelet transfusion refractoriness PTR is a challenging clinical issue in patients with hematologic disorders which increases early death and hospitalization costs. Thrombopoietin receptor agonists have shown inspiring effects in treating thrombocytopenia. However, there are few studies focused on the application of these drugs in PTR patients. In this study, we investigated 71 patients with PTR in which 30 patients received the best available therapies, while 41 patients received avatrombopag treatment. We found that avatrombopag increases platelet response rate, reduces platelet transfusions dependence and occurrence of severe bleeding events, as well as improves overall survival rate and event free survival in PTR patients. Avatrombopag also exhibited good tolerance and safety. We reported for the first time that avatrombopag was an effective and safe treatment in PTR, which may also help to expand the clinical application of TPO-RAs.

[Retracted] 3­ß­Εrythrodiol isolated from Conyza canadensis inhibits MKN­45 human gastric cancer cell proliferation by inducing apoptosis, cell cycle arrest, DNA fragmentation, ROS generation and reduces tumor weight and volume in mouse xenograft model.

Following the publication of the above paper, an interested reader drew to our attention that a number of apparent anomalies existed with the data presented in the above paper; specifically, there appeared to be strikingly similar and replicated patternings of the cells within the cellular images featured in Figs. 4A­D and 5A­D (affecting all the figure parts). Secondly, Fig. 4 in the above study appeared to have been a reproduction of Fig. 3 from following paper featuring different authors, albeit Fig. 4 appeared in greyscale, and not in colour, in the above paper [Wan G, Tao J­G, Wang G­D, Liu. S­P, Zhao H­X and Liang Q­D: In vitro antitumor activity of the ethyl acetate extract of Potentilla chinensis in osteosarcoma cancer cells. Mol Med Rep 14: 3634­3640, 2016]. Following an internal enquiry, the Editor of Oncology Reports was able to verify the claims made by the interested reader; therefore, in view of the number of potential anomalies that have been identified and owing to a lack of overall confidence in the presented data, the Editorial Board have decided to retract the above paper from the publication. The Journal were also contacted independently by the authors, who wished to retract the paper on account of not being able to reproduce the results shown in Fig.. 2. The Editor apologizes to the readership of the Journal for any inconvenience caused. [the original article was published in Oncology Reports 35: 2328­2338, 2016; DOI: 10.3892/or.2016.4610].

3-ß-Εrythrodiol isolated from Conyza canadensis inhibits MKN­45 human gastric cancer cell proliferation by inducing apoptosis, cell cycle arrest, DNA fragmentation, ROS generation and reduces tumor weight and volume in mouse xenograft model.

The objective of the present study was to investigate the in vitro and in vivo anticancer and apoptotic effects of 3-ß-erythrodiol, a plant-derived triterpene against MKN-45 human gastric cancer cells. In addition, effects on cellular morphology, cell cycle phase distribution, DNA fragmentation, and ROS generation were also elucidated in the current research work. Cytotoxic activity of 3-ß-erythrodiol was demonstrated by MTT cell viability and LDH assay. Cellular morphological study was carried out using phase contrast, fluorescence and scanning electron microscopy. Cell cycle analysis was evaluated by flow cytometry and gel electrophoresis was used to evaluate DNA fragmentation pattern. The results of the present study revealed that 3-ß-erythrodiol induced dose-dependent as well as time-dependent anticancer effects in MKN-45 gastric cancer cells. Cellular morphological changes in MKN-45 cells as indicated by fluorescence and scanning electron microscopy were induced by 3-ß-erythrodiol. This triterpene induced both early and late apoptotic features in these cancer cells. 3-ß-Erythrodiol treatment led to sub-G1 cell cycle arrest with a corresponding decrease in S-phase cells and an increase in G2/M phase cells. DNA fragments were evident in gel electrophoresis experiment following 3-ß-erythrodiol treatment. It was observed that 0.50 and 1.0 µg/g 3-ß-erythrodiol injection reduced the tumor weight from 1.4 g in PBS-treated group (control) to 0.61 and 0.22 g, respectively. Similarly, 0.50 and 1.0 µg/g 3-ß-erythrodiol injection reduced the tumor volume from 1.5 cm3 in PBS-treated group (control) to 0.91 and 0.31 cm3, respectively. The present investigation indicates that 3-ß-erythrodiol exerts anti-proliferative effects in human gastric cancer by inducing early and late apoptosis, cell cycle arrest, and ROS generation. It also decreased the tumor volume and tumor weight in male Balb/c nude mice.

Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation.

Colon cancer is one of the leading causes of cancer-related death worldwide, and the therapeutic application of 5-fluorouracil (5-FU) is limited due to its nonspecificity, low bioavailability, and overdose. The present study is an attempt to improve the chemotherapeutic efficacy of 5-FU in colon cancers. Therefore, we have prepared 5-FU-loaded hyaluronic acid (HA)-conjugated silica nanoparticles (SiNPs) to target to colon cancer cells. In this study, we have showed the specific binding and intracellular accumulation of targeted nanoparticles based on HA surface modifications in colon carcinoma cells. The particles had spherical shapes with sizes of approximately 130 nm. HA-conjugated nanoparticles showed a sustained release pattern for 5-FU and continuously released for 120 hours. We have further investigated the cytotoxicity potential of targeted and nontargeted nanoparticles in colo-205 cancer cells. IC50 value of 5-FU/hyaluronic acid-conjugated silica nanoparticles (HSNP) was 0.65 µg/mL compared with ~2.8 µg/mL for 5-FU/SNP after 24 hours of incubation. The result clearly showed that HA-conjugated NP was more effective in inducing apoptosis in cancer cells than nontargeted NP. The 5-FU/HSNP showed ~45% of cell apoptosis (early and late apoptosis stage) compared with only 20% for 5-FU/silica nanoparticles (SNP)-treated group. The HA-conjugated nanoparticles provide the possibility of efficient drug transport into tumors that could effectively reduce the side effects in the normal tissues. 5-FU/HSNP was highly efficient in suppressing the tumor growth in xenograft tumor model. The proportion of Ki67 in 5-FU/HSNP-treated group was significantly lower than that of either free drug or nontargeted SiNPs. Altogether, we have showed that conjugation of HA to SiNPs could result in enhanced uptake of 5-FU through CD44-mediated endocytosis uptake and could result in significant antitumor efficacy. Thus, 5-FU/HSNP could be a promising drug delivery system for colon cancer therapy.

Contribution of the Rgg transcription regulator to metabolism and virulence of Streptococcus suis serotype 2.

The Rgg-like regulators, a family of transcription factors commonly found in many Gram-positive bacteria, play multiple roles, especially in the control of pathogen virulence. Here, we report an rgg homologue from a Chinese isolate, 05ZYH33, of Streptococcus suis serotype 2 (SS2). Deletion of the rgg gene in SS2 increased its adhesion to Hep-2 cells and hemolytic activity in vitro. Significantly, inactivation of the rgg gene attenuated SS2 virulence in an experimental piglet infection model. Using DNA microarrays and quantitative reverse transcription-PCR, we found that the Rgg regulator affects the transcriptional profile of 15.87% (n = 345) of all of the annotated chromosomal genes, including those involved in nonglucose carbohydrate metabolism, DNA recombination, protein biosynthesis, bacterial defense mechanisms, and others. It was experimentally verified that the deletion of rgg in SS2 reduced the utilization of nonglucose carbohydrates, such as lactose and maltose. In addition, the rgg gene was found to be associated with changes in the bacterial microscopic phenotype and growth curve. These data suggested that Rgg in SS2 is a global transcriptional regulator that plays an important role in promoting SS2 bacterial survival during pathogen-host interaction.