Myricetin and Naringenin Inhibit Human Squamous Cell Carcinoma Proliferation and Migration In Vitro

In this study the potential anticancer effect of 2 flavonoids, myiricetin (MYR) and naringenin (NAR) has been evaluated on an oral squamous cell carcinoma (OSCC) cell line, SCC-25, and HaCaT cells. Both the flavonoids inhibited SCC-25 cell growth, although NAR selectively affected cancer cells without impairing HaCaT cell growth. The cell proliferation inhibition by MYR and NAR was not related to apoptosis induction, but on cell cycle impairment, because a G₀/G₁ and a G₂/M blockage was highlighted following 24 h of treatment in SCC-25 and HaCaT cells, respectively. Western blot analysis showed that MYR induced a decrease of Cyclin D₁ in SCC-25 and of Cyclin B₁ in HaCaT cells, while NAR negatively modulated Cyclin D₁ expression in SCC-25 cells. Wound-healing and cell invasion assays demonstrated that both the flavonoids were able to reduce motility on both SCC-25 and HaCaT cells. In conclusion the results of the present study show the anticancer potential of NAR and MYR on OSCC because they exert cytostatic effect by the impairment of cell cycle progression. Moreover both the flavonoids inhibit cell migration, thus highlighting their potential effect as antimetastatic agents. Therefore, MYR and NAR appear as promising candidate as oral cancer chemopreventive agents.     

Prospective study of erythropoietin use on quality of life and cost effectiveness in acute myeloid leukemia and allogeneic hematopoietic stem cell transplantation patients

BACKGROUND:

Despite frequent anemia and multiple transfusions in patients undergoing chemotherapy and allogeneic hematopoietic stem cell transplantation (allo‐HSCT) for acute myeloid leukemia , recommendations for use of erythropoiesis‐stimulating agents (ESAs) in these populations are still missing. The primary objective was the effect of ESA administration on patient's quality of life (QoL). Secondary objectives were hemoglobin (Hb) recovery, red blood cell (RBC) transfusions, overall survival, and event‐free survival.

METHODS:

Adult patients with Hb ≤ 11 g/dL after consolidation chemotherapy for acute myeloid leukemia (group 1), or after allo‐HSCT for any hematological diseases (group 2), were prospectively included. ESA was administered subcutaneously once per week during a maximum period of 6 months and was stopped when Hb level reached 12 g/dL. A paired‐matched analysis using a historical control group was performed for secondary endpoints. Fifty‐two patients were included in group 1, and 55 patients were in group 2.

RESULTS:

For the global population, a significant improvement of QoL was noticed with ESA use; 83% (group 1) and 71% (group 2) of patients achieved an Hb level ≥ 12 g/dL without transfusion requirement. The pair‐matched analysis showed a reduction of 4 RBC units per patient in group 1 (P = .0002) and 3 RBC units per patient in group 2 (P = .04). No significant difference in terms of thromboembolic events, overall survival, and event‐free survival was observed between ESA and control groups. A RBC transfusion median savings of €1712 per patient was estimated in each group.

CONCLUSIONS:

ESAs have a clinical and economic benefit on Hb recovery, could improve a patient's QoL, and lead to a significant reduction in number of RBC transfusions with no effect on survival. Cancer 2013. © 2012 American Cancer Society.     

Tumor markers in colorectal cancer,gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update

Biomarkers currently play an important role in the detection and management of patients with several different types of gastrointestinal cancer, especially colorectal, gastric, gastro‐oesophageal junction (GOJ) adenocarcinomas and gastrointestinal stromal tumors (GISTs). The aim of this article is to provide updated and evidence‐based guidelines for the use of biomarkers in the different gastrointestinal malignancies. Recommended biomarkers for colorectal cancer include an immunochemical‐based fecal occult blood test in screening asymptomatic subjects ≥50 years of age for neoplasia, serial CEA levels in postoperative surveillance of stage II and III patients who may be candidates for surgical resection or systemic therapy in the event of distant metastasis occurring, K‐RAS mutation status for identifying patients with advanced disease likely to benefit from anti‐EGFR therapeutic antibodies and microsatellite instability testing as a first‐line screen for subjects with Lynch syndrome. In advanced gastric or GOJ cancers, measurement of HER2 is recommended in selecting patients for treatment with trastuzumab. For patients with suspected GIST, determination of KIT protein should be used as a diagnostic aid, while KIT mutational analysis may be used for treatment planning in patients with diagnosed GISTs.     

Three-dimensional conformal vs. intensity-modulated radiotherapy in head-and-neck cancer patients: comparative analysis of dosimetric and technical parameters

BACKGROUND AND PURPOSE: The use of intensity-modulated radiotherapy (IMRT) is now widely advocated for the treatment of head-and-neck cancers, to increase the therapeutic ratio of radiotherapy used as sole modality of treatment or in combination with chemotherapy. This report aims to summarize the technical and dosimetric factors to be taken into consideration to assess the respective advantages of the various high conformality treatments in radiotherapy, especially in the framework of quality assurance procedures. MATERIALS AND METHODS: Twenty-six head-and-neck cancer patients were irradiated following a feasibility internal protocol with IMRT. Treatments were performed with either the static step-and-shoot (20) or the dynamic sliding window (6) techniques on a 6 MV Varian Clinac equipped with a multileaf collimator with 80 leaves. Dose plans were computed using commercial treatment planning systems: MDS-Nordion Helax-TMS for static cases and Varian Eclipse for dynamic cases. Dose plans were evaluated in terms of physical quantities based on dose-volume histograms and isodose distributions. Each IMRT plan was also compared to a reference 3D conformal therapy plan (3DCRT). RESULTS: Elective target volumes ranged from 530 to 1151 cm(3) with a mean of 780 +/- 141 cm(3). Boost volumes ranged from 248 to 832 cm(3) with a mean of 537 +/- 165 cm(3). Thirty-two dose plans were generated with static technique and 10 with dynamic. In the static mode, 6.8 +/- 3.4 fields were applied on average with 12.5 +/- 1.3 segments per field. In the static mode, 264 +/- 56 MU per Gy were erogated, whereas in the dynamic mode, 387 +/- 126 MU per Gy were erogated, to be compared to 147 +/- 20 computed for reference 3DCRT plans. For all target volumes in general, conformity was improved compared to 3DCRT (e.g. V(95) increased from 85% to 93% with p < 0.001, or equivalent uniform dose normalized to prescribed dose increased from 0.86 to 0.96 with p = 0.002). Irradiation of parotid glands or spinal cord improved, as well: For parotids, D(2/3V) reduced from 59 Gy to 41 Gy (p < 0.001). For spinal cord, D(max) reduced from about 40 Gy to about 30 Gy (p < 0.001).     

Role of transjugular liver biopsy in the diagnostic and therapeutic management of patients with severe liver disease

Purpose. This study sought to assess the diagnostic yield, the impact on treatment and the safety of transjugular liver biopsy

Materials and methods. We reviewed the medical records of 72 patients with severely impaired liver function who underwent transjugular biopsy at our department. Contraindications to percutaneous liver biopsy included thrombocytopenia, severe coagulopathy, marked ascites or a combination of the above. Patients were divided into four groups based on the clinically suspected cause of liver disease. Group 1 included 44 patients (58%) with acute abnormalities of liver function, whereas groups 2, 3 and 4 included patients with chronic abnormalities suspected to be due to infectious cirrhosis (12 patients, 16%), alcoholic cirrhosis (seven patients, 9%) and cirrhosis of unknown origin (13 patients, 17%), respectively. A Quick-Core (Cook, ProAct Ltd., State College, Pennsylvania, USA) needle allowing automated tissue sampling was used for all biopsies

Results. Biopsy specimens were diagnostic in 69 out of 72 patients (91%). Biopsy findings influenced treatment in 34 out of 69 patients (49%). The most significant results were obtained in group 1, where the histological diagnosis differed from clinical suspicion in 25/39 patients. There was only one major complication and four minor complications. The major complication was an arteriovenous and arteriobiliary fistula with haemorrhage and anaemia, which was successfully embolised by the same team of interventional radiologists

Conclusions. Transjugular liver biopsy proved to be a safe procedure that provided important information for the clinical and therapeutic management of patients in whom treatment would have been either empirical or unfeasible

     

普罗布考和抗氧化维生素不影响体外实验条件下内皮细胞的白细胞粘附

为探讨预防动脉粥样硬化的药物普罗布考,维生素C和维生素E是否抑制内皮细胞表面粘附分子表达和白细胞一内皮细胞的粘附,以及这种抑制是否通过影响核因子－kB的活性来实现的,在液体流动小室中进行细胞粘附实验。用ELISA方法测定内皮细胞粘附分子E－选择素的表达;用电泳迁移率分析测定内皮细胞核因子－kB的活性,经肿瘤坏死因子α刺激的内皮细胞核因子－B活性增加,粘附分子E－选择素的表达上调（是基础水平的3．5倍）,其表面HL60细胞的粘附增加（是基础水平的4－26倍）,而抗氧化剂PDTC使所有这些变化都受到抑制。PDTC浓度为18umol/L时对粘附分子E－选择素的表达呈最大半抑制;PDTC浓度为52umol/L时对内皮细胞表面HL60细胞的粘附呈最大半抑制,普罗布考,维生素C和维生素E对肿瘤坏死因子α诱导的粘附分子表达和HL60细胞与内皮细胞的粘附没有作用,对核因子－kB的活性没有影响,临床上常用的这三种抗氧化剂并未影响作为动脉粥样硬化始动机制之一的E－选择素介导的白细胞－内皮细胞粘附水平。     

Effect of the chronic combined administration of cisplatin and paclitaxel in a rat model of peripheral neurotoxicity

We have characterised for the first time the general and neurological side effects experienced when using a series of chronic non-lethal cisplatin + paclitaxel schedules in Wistar rats, selected according to our previous experience and the animals’ maximum tolerated dose.At the pathological level, the use of combination schedules was definitely more toxic at the kidney and sternal bone marrow level than the single-agent schedules.At the neurophysiological examination based on the assessment of the nerve conduction velocity measurement in the tail nerve, we identified only one combination schedule that was more neurotoxic than the similar schedules based on single-agent administration. This observation was confirmed by the neuropathological examination performed on the sciatic nerve, dorsal root ganglia, ventral and dorsal roots.Our study supports the hypothesis that the general and, to a lesser extent, neurological effects of a combination of cisplatin and paclitaxel are different from those of the administration of both drugs as single agents. We believe that these models may be useful for testing neuroprotective strategies.     

Impact of Structural Changes on Multifocal Electroretinography in Patients With Use of Hydroxychloroquine

PurposeTo investigate the relationship between retinal structure and macular function in eyes screened for hydroxychloroquine (HCQ) toxicity.MethodsParticipants referred for hydroxychloroquine retinopathy screening with spectral domain optical coherence tomography (SD-OCT) and multifocal electroretinogram (mfERG) testing were included in the analysis. Amplitude and implicit time of mfERG N1 and P1 responses were included in the analysis. Ring ratios were computed for amplitude values as the ratio of rings 1–3:5 (R1–3:R5). A control group of healthy participants was included for comparison of SD-OCT metrics.ResultsSixty-three eyes screened for HCQ retinopathy and 30 control eyes were analyzed. The outer nuclear layer (ONL) was significantly thinner in HCQ patients in the foveal (P = 0.008), parafoveal (P < 0.0001), and perifoveal (P < 0.0001) regions. The HCQ cohort was further divided into two subgroups according to the presence of structural clinically detectable retinopathy (i.e., structural damage as detected by multimodal imaging). HCQ eyes without retinopathy had a thinner ONL thickness in the foveal (P = 0.032), parafoveal (P < 0.0001), and perifoveal (P < 0.0001) regions and a thinner inner nuclear layer (INL) in the parafoveal region (P = 0.045 versus controls). Structural changes in HCQ patients without retinopathy were significantly associated with macular function as R2:R5 ring ratio of mfERG P1 amplitude was associated with INL (P = 0.002) and ONL (P = 0.044) thicknesses, and R3:R5 ring ratio of P1 amplitude was associated with ONL thickness (P = 0.004).ConclusionsOur results suggest that structural alterations secondary to HCQ toxicity may occur in the absence of clinically detectable retinopathy, and this may reflect in an impaired macular function.     

Kawasaki's disease with paralytic ileus. A case report

The authors report on an 18 month-old boy affected by Kawasaki's disease (KD). The diagnosis of KD was made after exclusion of conditions with similar presentation. Two days after admission the child presented vomiting, abdominal distension, meteorism and increase of scrotal swelling with edema. An abdominal X-ray showed the presence of multiple water and gas levels in the ileum and subsequent diagnosis of paralitic ileus was made. After several evacuative enema the intestinal symptomatology resolved. The patient was treated twice (2 g/kg day and after 3 days again 2 g/kg day) with intravenous immunoglobulin following which he made an uneventful recovery. The authors conclude that the presence of paralytic ileus in a febrile child may represent an unusual clinical sign of KD and justify a timely commencement of intravenous immuno-globulin therapy.