Abnormal uterine cavity: differential diagnosis with MR imaging

The objective of the study was to assess the usefulness of magnetic resonance (MR) imaging in distinguishing malignant from benign conditions in patients with an abnormal uterine cavity. Fifty-four patients that were suspected of having abnormal uterine cavities were retrospectively evaluated by using MR imaging. The diagnosis of an abnormal uterine cavity included a thickened endometrium, and/or a endometrial mass, and/or a submucosal mass. Threshold values to classify the uterine cavity as abnormal on sagittal T₂-weighted images were >10 mm for premenopausal women and >5 mm for postmenopausal women. Malignancy was diagnosed when lesions invaded the myometrial/junctional zone, and/or lesion enhancement was lower than that of the adjacent myometrium. The results found that histology confirmed 18 malignant and 37 benign lesions. Twelve of 15 endometrial carcinomas and 3 malignant mixed mesodermal tumors (MMMT) were correctly characterized as malignant on enhanced T₁-weighted images; whereas 6 of 15 endometrial carcinomas and 3 MMMT were correctly characterized on T₂-weighted images. Thirty-four of 37 benign cases were correctly characterized as not malignant on enhanced T₁-weighted images. One of 14 submucosal leiomyomas, one endometrial stromal metaplasia, and one of ten pathologically normal endometria were misdiagnosed on enhanced T₁-weighted images but were correctly diagnosed on T₂-weighted images. The overall sensitivity, specificity, and accuracy for distinguishing malignant from benign central uterine masses were 83%, 92%, and 89% for enhanced T₁-weighted image, and 50%, 97%, and 82% for T₂-weighted image, respectively. We came to the conclusion that in diagnosing patients with abnormal uterine cavity, MR imaging may help differentiate malignant from benign disorders.     

Delivery of triptolide with reduction-sensitive polymer nanoparticles for liver cancer therapy on patient-derived xenografts models

Hepatocellular carcinoma (HCC) has become the fourth predominant cause of cancer-related deaths worldwide, and HCC is still one of the worst prognoses for survival as it is poorly responsive to both chemotherapy and surgical treatment due to drug resistance and great toxic effects. Triptolide (TP), a key ingredient from the traditional Chinese medical herb, has been utilized to treat inflammation and antitumor for centuries. However, investigations of this potent agent have been met with only limited success due to the severe systemic toxicities in patients and low water solubility as well as its high toxicity over the past two decades. Herein, we reported the development of a reduction-responsive drug delivery system loaded with TP for glutathione (GSH)-triggered drug release for cancer therapy. With the GSH-sensitive TP loaded nanoparticles, the remarkable increases in tumor accumulation and amelioration of drug toxicity in animals are demonstrated, which is likely due to sustained stepwise release of active TP within cancer cells. Moreover, in a patient-derived tumor xenograft model of liver cancer, administration of tritolide nanoparticles enhances the antitumor efficacy relative to administration of free TP. These findings indicate that GSH-sensitive release of TP may be a promising strategy for cancer treatment.     

Two new anthraquinone derivatives and one new triarylbenzophenone analog from Selaginella tamariscina

Abstract

Two new anthraquinone derivatives, selaginones A (1) and B (2), and one new triarylbenzophenone analog, selagibenzophenone B (3), were isolated from Selaginella tamariscina (Beauv.) Spring. Their structures were established by 1D-, 2D-NMR and HR-ESI-MS data. Compounds 1 and 2 represent the uncommon examples of aryl substituted anthraquinone derivatives. Especially, compound 2 is a unique anthranone with exceptional structural feature, in which a p-hydroxyphenyl moiety is attached to the C-10 position. Compound 3 is the second naturally occurring triarylbenzophenone and showed moderate activity against SMCC-7721 and MHCC97-H cell lines with IC₅₀ values of 39.8, 51.5 μM respectively.     

A novel inhibitor, 2-cyano-3-(1-phenyl-3-(thiophen-2-yl)-pyrazol-4-yl)acrylamide linked to sulphamethoxazole,blocks anti-apoptotic proteins via molecular docking and strongly induced apoptosis of HCT116 cell line by different molecular tools

A new series of cyanoacrylamides incorporating sulphamethoxazol were prepared and confirmed by different spectral tools. Anticancer screening of the new compounds was done against three different types of carcinoma cell lines involving (A₅₄₉, HCT₁₁₆, and MDA) using MTT assay. Compound 7 among all tested derivatives achieved the best cytotoxic effect against all tested carcinoma cell lines. HCT₁₁₆ revealed the best sensitivity and cytotoxic activity toward compound 7 relative to 5-FU. The target compound offered less toxic effect when tested on normal melanocytes (HFB4). Simulation modeling studies revealed strong binding affinity toward the following domains (1dls, 2c6o, and 2wgj) and moderate binding modes toward (3eyl, 4kmp, 2w3l, and 5lab) domains with different binding energy scores. Gene expression profile outlined that caspase-3, BAX, and P53 genes were strongly upregulated relative to their control, while BCL2, MMP1, and CDK2 were effectively down regulated assuming the activation of the apoptotic pathway. Flow cytometry technique revealed that compound 7 stimulated cell cycle arrests at the G2/M phase. Other extensive molecular diagnostic tools were utilized in this report as ELISA, DPA, SEM, and TEM assays which confirmed that our target novel compound 7 was a very promising and interesting chemotherapeutic agent with less toxic effect. Also, authors herein suggested that additional sulphamethoxazole linked to 3-(1-phenyl-3-(thiophen-2-yl)-1H-pyrazol-4-yl)acrylonitrile in compound 7 was responsible for its promising cytotoxic activity against colorectal carcinoma cell line.     

Diffusion-weighted magnetic resonance imaging for early response assessment of chemoradiotherapy in patients with nasopharyngeal carcinoma

Purpose

To prospectively evaluate the feasibility of diffusion-weighted magnetic resonance imaging (DWI) for monitoring early treatment response to chemoradiotherapy (CRT) of nasopharyngeal carcinoma (NPC).

Materials and methods

Thirty-one patients with stage III and IV NPC were enrolled in this study from February 2012 to November 2012．T2-weighted and DWI sequences with diffusion factor of 0 and 800mm²/s were performed using a 3.0 T Philips Achieva TX scanner at baseline and 3 days, 20 days (after the first cycle of chemotherapy), 50 days (6 days after radiotherapy initiation) after neoadjuvant chemotherapy (NAC) initiation. The diameter of each primary lesion and target metastatic lymph node before and after the first cycle of NAC was measured and classified into stable disease (SD), partial response (PR) or completed response (CR) based on RECIST 1.1. The apparent diffusion coefficient (ADC) values and changes compared to baseline at each time point were compared between responders (CR and PR) and non-responders (SD). The rates of residual at the end of CRT were compared between these two groups.

Results

A significant increase in ADC was observed at each stage of therapy (P=.001) in lesions of primary and metastatic. The ADC values (ADC), ADC changes (ΔADC) and percentage ADC changes (Δ%ADC) of day 20 in responders were significantly higher than in non-responders for both primary lesions (p=.005, p=.006, p=.008, respectively) and metastatic lymph nodes (p=.002, p=.002, p=.003). Non-responders showed a higher rate of residual for both primary lesions (p=.008) and metastatic lymph nodes (p=.024) than responders.

Conclusions

DW MR imaging allows for detecting early treatment response of NPC. Patients with high ADC values and large ADC increase early after NAC initiation tended to respond better to CRT. Thus, accessing the curative effect of NAC in advanced NPC provides the opportunity to adjust following CRT regimen.     

Using intravoxel incoherent motion (IVIM) MR imaging to predict lipiodol uptake in patients with hepatocellular carcinoma following transcatheter arterial chemoembolization: A preliminary result

Purpose

To assess the usefulness of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) for predicting lipiodol uptake in patients with hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE).

Materials and methods

The institutional review board approved this study. 44 HCC patients underwent IVIM-DWI and Gd-EOB-DTPA-enhanced MRI prior to TACE. Using post-TACE CT as a reference standard, each HCC was classified into either lipiodol good uptake (LGU) or poor uptake (LPU) group. Apparent diffusion coefficient (ADC), true diffusion coefficient (D), perfusion coefficient (D*), and perfusion fraction (f) in HCC were calculated. Arterial enhancement ratio (AER) and IVIM parameters were compared between those two groups using the Mann-Whitney U test.

Results

Of the 51 HCCs, 37 (72.5%) were LGU group and 14 (27.5%) were LPU group. AER of HCC was significantly higher in LGU than LPU (0.99 ± 0.54 and 0.67 ± 0.45; P = .034). ADC, D, and f values were not significantly different (P = .073, .059, and .196, respectively) between these two groups. D* was significantly elevated in LGU than LPU (48.10 ± 15.33 and 26.75 ± 9.55; P = .001).

Conclusion

Both AER derived from contrast enhanced MRI and D* values derived from IVIM-DWI for HCC were significantly higher in LGU than in LPU. These parameters would be helpful for predicting the lipiodol uptake.     

Doxorubicin‐Anchored Curcumin Nanoparticles for Multimode Cancer Treatment against Human Liver Carcinoma Cells

Curcumin (Curcuma longa L), a yellow‐colored Indian spice, receives immense attention for the prevention and treatment of various cancers. Despite the superlative therapeutic efficacy, its poor solubility and instability in the aqueous medium hinder the effectiveness of cancer treatment. The novel preparation of curcumin nanoparticles by mechanical grinding of curcumin crystals without any toxic organic solvents is described here for the first time. The surface of curcumin nanoparticles is modified with the negatively charged polyelectrolyte poly(sodium 4‐strynesulfonate) through hydrogen bonding, which is the key to increasing the solubility and stability in the aqueous medium. The negative surface charge is exploited to conjugate doxorubicin drug molecule on the surface of curcumin nanoparticles as evidenced by fluorescence quenching experiments. Doxorubicin‐conjugated curcumin nanoparticles have a higher solubility with an enhanced cytotoxic effect toward the human hepatocellular carcinoma cell line by a reactive‐oxygen‐species‐mediated p53‐dependent apoptotic pathway. The combination of chemotherapy and photodynamic therapy significantly enhances antitumor activity of doxorubicin‐conjugated curcumin nanoparticles, and is expected to be a promising anticancer agent with special reference to human liver carcinoma cells.     

胃癌全胃切除患者围术期两种免疫营养支持治疗的临床比较

目的 比较胃癌全胃切除患者围术期两种免疫营养支持治疗的效果。方法 将接受全胃切除的胃癌患者随机分为围术期免疫营养（PIN）组60例,术前5d 给予肠外免疫营养支持治疗,术后早期给予肠内免疫营养支持治疗1 周;术后早期肠内免疫营养（EIN）组60例,仅在术后早期给予肠内免疫营养支持治疗1 周。比较两组患者术前及术后第1、7、10 天营养指标（总蛋白、白蛋白、前清蛋白、转铁蛋白、氮平衡）、免疫功能指标（IgG、IgA、IgM、CD3+、CD4+、CD4+/CD8+）的情况及术后感染性并发症（包括肺部感染、尿路感染、切口感染）的发生率。结果 PIN 组患者术前及术后第1天在提高患者营养指标,纠正免疫功能指标等方面较EIN 组有效,差异均有统计学意义（均P＜0.05）,且PIN 组术后感染性并发症的发生率低于EIN 组（P＜0.05）。结论 胃癌全胃切除患者围术期应用免疫营养支持治疗较单纯术后早期应用,更能改善患者的营养状况,纠正免疫功能,减少术后并发症的发生。     

VEGF、EGFR 及Parkin 蛋白在 鼻咽癌中的表达及三者间的相关性研究

目的 探讨血管内皮生长因子（VEGF）、表皮生长因子受体（EGFR）及Parkin 蛋白在鼻咽癌（NPC）中的表达情况以 及三者间的相关性。方法 应用免疫组化SP 法检测48 例NPC 组织和34例正常鼻咽部上皮组织中VEGF、EGFR 及Parkin蛋白的表达,并探讨三者间的相关性。结果 NPC组织中VEGF和EGFR蛋白表达阳性率明显高于正常鼻咽部上皮组织,Parkin蛋白表达阳性率则明显下降,且均有统计学差异（均P＜0.05）。NPC组织中VEGF蛋白表达与NPC患者有无淋巴结转移及临床TNM 分期密切相关（均P＜0.05）,而与患者的年龄、性别、病理类型、T 分期均无关（均P ＞0.05）;EGFR 和Parkin 蛋白表达与NPC 患者有无淋巴结转移密切相关（均P＜0.05）,而与患者的年龄、性别、病理类型、T分期、临床TNM分期均无关（均P ＞0.05）。NPC组织中VEGF和EGFR 蛋白的表达呈正相关（P＜0.05）,Parkin和VEGF、EGFR蛋白的表达无相关性（均P＞0.05）。结论 VEGF、EGFR 及Parkin 蛋白与NPC发生、发展有关,VEGF、EGFR 及Parkin蛋白表达可作为NPC 的预后判断指标,NPC 中VEGF 和EGFR可能起协同作用,而Parkin 则可能单独发挥作用。