Whole brain radiotherapy (WBRT) for leptomeningeal metastasis from NSCLC in the era of targeted therapy: a retrospective study.

BACKGROUND AND PURPOSE: Leptomeningeal metastasis (LM) is a rare but detrimental complication in patients with non-small cell lung cancer (NSCLC). Although whole brain radiotherapy (WBRT) is used to eliminating cancer cells or microscopic foci, it is becoming less favorable due to the concerns over neurocognitive toxicity. This study aimed to re-evaluate the role of WBRT in the setting of modern targeted therapy. MATERIALS AND METHODS: From December 2014 to March 2019, 80 NSCLC patients with cytologically and/or radiologically proven LM diagnosis were retrospectively analyzed. RESULTS: The median OS (mOS) after diagnosis of LM was 8.0 (95%CI: 4.4 to 11.6) months, and the one-year OS was 39.4%. The mOS for EGFR-mutated LM patients was 12.6 (3.0 to 22.2) months versus only 4.1 (2.8 to 5.4) for patients with wild-type EGFR (P < 0.001). Younger patients (< 53.5 yrs.) appeared to have a better OS than older patients (≥53.5 yrs.) (12.6 vs. 6.1, P = 0.041). No survival benefits were found in EGFR-mutated patients who received WBRT (P = 0.490). In contrast, mOS was significantly prolonged in wild-type EGFR patients with WBRT versus non-WBRT (mOS: 8.0 vs. 2.1, P = 0.002). Multivariate analysis indicated that WBRT (P = 0.025) and younger age (P = 0.048) were independent prognostic factors that predicted prolonged survival for wild-type EGFR LM patients from NSCLC. CONCLUSION: Our study demonstrated that WBRT has clear survival advantages for patients with wild-type EGFR, and molecular biological stratification of LM patients for WBRT is highly recommended.

Evaluation of Red Cell Distribution Width to Lymphocyte Ratio as Potential Biomarker for Detection of Colorectal Cancer.

BACKGROUND AND AIM: Colorectal cancer (CRC) is the third most lethal cancer globally. This study sought to determine the feasibility of using red cell distribution width-to-lymphocyte ratio (RLR) as a tool to facilitate CRC detection. METHODS: Seventy-eight healthy controls, 162 patients diagnosed with CRC, and 94 patients with colorectal polyps (CP) from June 2017 to October 2018 were retrospectively reviewed. Clinical data were obtained to analyze preoperative RLR level, and receiver operating characteristic (ROC) curve analysis was performed to estimate the potential role of RLR as a CRC biomarker. RESULTS: RLR was higher in patients with CRC than in healthy participants (P < 0.05). ROC analysis indicated that combined detection of RLR and CEA appears to be a more effective marker to distinguish among controls, CP, and CRC patients, yielding 56% sensitivity and 90% specificity. RLR levels were significantly greater in those who had more advanced TNM stages (P < 0.05) and patients with distant metastasis stages (P < 0.05). CONCLUSIONS: RLR might serve as a potential biomarker for CRC diagnosis.

Effect of Modified Wuzi Yanzong Pill () on Tip60-Mediated Apoptosis in Testis of Male Rats after Microwave Radiation.

OBJECTIVE: To investigate the effect of a modified Wuzi Yanzong Pill (, WZYZP) on the male rats' testis after microwave radiation, as well as its potential mechanism. METHODS: Forty-five male rats were randomly assigned to three groups: the control group, the radiation group, and the WZYZP group. The rats in the radiation group and WZYZP group were exposed to microwave radiation for 15 min once, while the rats in the control group were not exposed to any radiation. The rats in the WZYZP group were given a modified of WZYZP by gavage daily for 7 days. Apoptosis in the testis was evaluated using terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay. Histopathological alterations of the testis were observed by haematoxylin-eosin (HE) staining. Tat-interactive protein, 60kD (Tip60) and p53 expressions were determined by Western blotting. RESULTS: The apoptosis index (AI) in the radiation group was higher than that of the WZYZP group and control group on day 1 (D1), day 7 (D7) day 14 (D14) after radiation (P<0.05). The seminiferous tubules were of normal morphology in the control group. In the radiation group, the partial seminiferous tubules were collapsed, basement membranes of the seminiferous epithelia became detached. WZYZP could restore the morphological changes. There was no expression of Tip60 among the three groups on D7 and D14. The expression of p53 was higher in the radiation group than in the control group (P<0.05). WZYZP could down-regulate the rising p53 induced by radiation on D7 and D14 (P<0.05). CONCLUSION: A modified WZYZP may affect germ cells, and its protective effects may partly result from its ability to intervene in Tip60 mediated apoptosis.

Abnormal Methylation of Imprinted Genes and Cigarette Smoking: Assessment of Their Association With the Risk of Male Infertility.

Male infertility is a complicated disease with causes generally split into 2 broad categories: genetic factors and environmental factors. The present study was designed to investigate the association between the methylation patterns of H19 and SNRPN imprinting control region (ICR) and male infertility and to assess the gene-environment interactions between environmental factors and methylation patterns. A total of 205 DNA samples from 48 oligozoospermia (OZ), 52 asthenozoospermia (AZ), 55 teratozoospermia (TZ) patients, and 50 normozoospermia (NZ) men were analyzed. The mean methylation level of H19-ICR in OZ (80.40% ± 12.74%) and AZ patients (81.17% ± 13.18%) was significantly lower than methylation in men with NZ (88.51% ± 10.54%, P<.001, P<.001, respectively). The mean methylation level of SNRPN-ICR in AZ patients (7.74% ± 5.71%) and TZ patients (9.33% ± 5.48%) was significantly higher than in NZ men (6.32% ± 3.54%, P<.001, P<.001, respectively). Among environmental factors, smoking was correlated with OZ (odds ratio [OR] = 5.12, 95% CI: 2.05-12.83), AZ (OR = 5.65, 95% CI: 2.13-14.99), and TZ (OR = 5.54, 95% CI: 2.21-13.89). Gene-environment interaction analysis revealed that hypomethylation of H19-ICR in OZ patients and hypermethylation of SNRPN-ICR in AZ and TZ patients were significantly associated with an increased the risk of infertility in men who were smokers (OR = 15.30, 95% CI: 1.13-207.97; OR = 13.20, 95% CI: 1.21-143.57; OR = 10.59, 95% CI: 1.04-107.39, respectively). This study demonstrated that hypomethylation of H19-ICR and hypermethylation of SNRPN-ICR are associated with male infertility, and the risk is potentiated by smoking.

Hydrophobic oligopeptide-based star-block copolymers as unimolecular nanocarriers for poorly water-soluble drugs.

Hydrophobic oligopeptide (HOP)-based star-block copolymers of the form PEI-g-(HOP-b-PEG) were synthesized, characterized and evaluated as nanocarriers for poorly water-soluble drugs. The designed PEI-g-(HOP-b-PEG) polymers were composed of a hyperbranched polyethylenimine (PEI) core, a HOP [i.e., oligo(l-tryptophan), oligo(l-phenylalanine), oligo(l-leucine), oligo(γ-benzyl-l-glutamate) and oligo(ɛ-benzyloxycarbonyl-l-lysine)] inner shell and a hydrophilic poly(ethylene glycol) (PEG) outer shell. The synthesized polymers were characterized using (1)H NMR, gel permeation chromatography (GPC) and transmission electron microscopy (TEM). Their micellization behavior was investigated by the dynamic light scattering (DLS) and fluorescence spectroscopy using pyrene as a probe; the results demonstrated that these star-block copolymers predominantly resembled unimolecular micelles, particularly when shorter HOP blocks and/or elongated PEG chains were incorporated. The encapsulation properties of these unimolecular micelles were evaluated using pyrene, oil-red O (OR) and doxorubicin (DOX) as guest hydrophobic compounds, which revealed that poorly water-soluble guests can be efficiently solubilized in PEI-g-(HOP-b-PEG) with a loading capacity of up to 10%. The encapsulated DOX demonstrated sustained release from PEI-g-(HOP-b-PEG). The synthesized star-block copolymers, given their structural versatility, water solubility and biodegradability, could potentially be used as unimolecular nanocarriers for the delivery of poorly water-soluble drugs.