Possible association between cerebral white matter atrophy and impaired performance of activities of daily living in patients with Parkinson's disease.

INTRODUCTION: The contribution of brain abnormalities in patients with Parkinson's disease (PD) to impaired functional status remains uncertain. Our study assessed whether global and regional brain structural abnormalities are associated with impaired performance of activities of daily living (ADL) in PD patients. MATERIAL AND METHODS: A retrospective analysis was conducted of 46 patients with PD, recruited prospectively from a movement disorder clinic. Motor impairment and disability were assessed using the Hoehn and Yahr (H-Y) scale and Unified Parkinson's Disease Rating Scale Part III (UPDRS-III). Cognitive status was evaluated with Montreal Cognitive Assessment (MoCA). The performance of ADL was indexed by the sum score of the Physical Self-Maintenance Scale (PSMS) and Lawton Instrumental ADL scale. Brain magnetic resonance imaging (MRI) was performed to assess white matter hyperintensities and medial temporal lobe atrophy (MTLA). Global brain atrophy, indexed by the relative grey matter volume (RGM), relative white matter volume (RWM) and average cortical thickness of the whole brain, was quantified by voxel-based morphometry (VBM). RESULTS: The ADL score (where higher scores indicate poorer performance) negatively correlated with RWM (where greater volume indicates less severe atrophy; r = -0.41, p = 0.004) and RGM (where greater volume indicates less severe atrophy; r = -0.43, p = 0.003) but not with the average cortical thickness ( r = -0.16, p = 0.29). With ADL score as the dependent variable in a linear regression model, H-Y stage and RWM significantly correlated with the ADL score after adjusting for age and MoCA score, and together accounted for 51% of the variance therein. RGM was not significantly correlated with the ADL score after adjusting for age and MoCA score. CONCLUSIONS: Cerebral white matter atrophy may be associated with the performance of ADL in patients with PD, indicating an important role of white matter impairment in their functional status.

Quantitative CT evaluation after two cycles of induction chemotherapy to predict prognosis of patients with locally advanced oesophageal squamous cell carcinoma before undergoing definitive chemoradiotherapy/radiotherapy.

OBJECTIVE: To investigate the performance of quantitative CT analysis in predicting the prognosis of patients with locally advanced oesophageal squamous cell carcinoma (ESCC) after two cycles of induction chemotherapy before definitive chemoradiotherapy/radiotherapy. METHODS: A total of 110 patients with locally advanced ESCC were retrospectively analysed. Baseline chest CT and CT after two cycles of induction chemotherapy were analysed. A multivariate Cox proportional-hazard regression model was used to identify independent prognostic markers for survival analysis. Then, a CT scoring system was established. Time-dependent receiver operating characteristic (ROC) curve analysis and the Kaplan-Meier method were employed for analysing the prognostic value of the CT scoring system. RESULTS: Body mass index, treatment strategy, change ratios of thickness (ΔTHmax), CT value of the primary tumour (ΔCTVaxial) and the short diameter (ΔSD-LN), and the presence of an enlarged small lymph node (ESLN) after two cycles of chemotherapy were noted as independent factors for predicting overall survival (OS). The specificity of the presence of ESLN for death after 12 months was up to 100%. Areas under the curve value of the CT scoring system for predicting OS and progression-free survival (PFS) were higher than that of the RECIST (p < 0.05). Responders had significantly longer OS and PFS than non-responders. CONCLUSION: Quantitative CT analysis after two cycles of induction chemotherapy could predict the outcome of locally advanced ESCC patients treated with definitive chemoradiotherapy/radiotherapy. The CT scoring system could contribute to the development of an appropriate strategy for patients with locally advanced ESCC. KEY POINTS: • Quantitative CT evaluation after two cycles of induction chemotherapy can predict the long-term outcome of locally advanced oesophageal cancer treated with definitive chemoradiotherapy/radiotherapy. • A CT scoring system provides valuable imaging support for indicating the prognosis at the early stage of therapy. • Quantitative CT evaluation can assist clinicians in personalising treatment plans.

Clinical and imaging associations for non-ketotic hyperglycemic chorea: a case-control study.

Background: The non-ketotic hyperglycemic chorea (NKHC) was a rare complication for patients with diabetes mellitus, but not been well studied. In the present research, we aimed to investigate the clinical and imaging characteristics of NKHC and explore the potential association. Methods: We performed a case-control study with patients diagnosed as NKHC. The patients with group of NKHC were retrospectively recruited, while the matched group were set to screened patients with diabetes mellitus but no NKHC at a 1:3 ratio. The clinical and imaging data were collected for all the participants of the two groups. Firstly, Correlation analysis was conducted to test the difference of all the variables between the NKHC group and matched group. Then, the putative associated factors for NKHC were further identified. Results: Eleven men and 9 women with NKHC and 60 matched participants were analyzed. The mean age of the NKHC group was 68.5 ± 14.9 years. Participants with NKHC were more likely to have a higher glycosylated hemoglobin (HbA1c) level (13 ± 2.82 vs. 10.57 ± 2.71, P<0.001), and a higher frequency of renal dysfunction (estimated glomerular filtration rates <60 ml/min/1.73m2) (55% vs. 20%, P=0.005). Logistic regression analyses showed that both higher HbA1c and renal dysfunction were significantly correlated with NKHC. Conclusion: A higher value of HbA1c and renal dysfunction may be associated with the occurrence of NKHC.

Quantitative CT analysis to predict esophageal fistula in patients with advanced esophageal cancer treated by chemotherapy or chemoradiotherapy.

BACKGROUND: Esophageal fistula is one of the most serious complications of chemotherapy or chemoradiotherapy (CRT) for advanced esophageal cancer. This study aimed to evaluate the performance of quantitative computed tomography (CT) analysis and to establish a practical imaging model for predicting esophageal fistula in esophageal cancer patients treated with chemotherapy or chemoradiotherapy. METHODS: This study retrospectively enrolled 204 esophageal cancer patients (54 patients with fistula, 150 patients without fistula) and all patients were allocated to the primary and validation cohorts according to the time of inclusion in a 1:1 ratio. Ulcer depth, tumor thickness and length, and minimum and maximum enhanced CT values of esophageal cancer were measured in pretreatment CT imaging. Logistic regression analysis was used to evaluate the associations of CT quantitative measurements with esophageal fistula. Receiver operating characteristic curve (ROC) analysis was also used. RESULTS: Logistic regression analysis showed that independent predictors of esophageal fistula included tumor thickness [odds ratio (OR) = 1.167; p = 0.037], the ratio of ulcer depth to adjacent tumor thickness (OR = 164.947; p < 0.001), and the ratio of minimum to maximum enhanced CT value (OR = 0.006; p = 0.039) in the primary cohort at baseline CT imaging. These predictors were used to establish a predictive model for predicting esophageal fistula, with areas under the receiver operating characteristic curves (AUCs) of 0.946 and 0.841 in the primary and validation cohorts, respectively. The quantitative analysis combined with T stage for predicting esophageal fistula had AUCs of 0.953 and 0.917 in primary and validation cohorts, respectively. CONCLUSION: Quantitative pretreatment CT analysis has excellent performance for predicting fistula formation in esophageal cancer patients who treated by chemotherapy or chemoradiotherapy.

Right Cortical Infarction and a Reduction in Putamen Volume May Be Correlated with Empathy in Patients after Subacute Ischemic Stroke-A Multimodal Magnetic Resonance Imaging Study.

Empathy has not been well studied in patients following ischemic stroke. We aimed to evaluate the relationships of multimodal neuroimaging parameters with the impairment of empathy in patients who had experienced subacute ischemic stroke. Patients who had experienced a first-event acute ischemic stroke were recruited, and we assessed their empathy using the Chinese version of the Empathy Quotient (EQ) 3 months after the index stroke. Multimodal magnetic resonance imaging (MRI) was conducted in all the participants to identify acute infarction and assess brain volumes, white matter integrity, and other preexisting abnormalities. We quantified the brain volumes of various subcortical structures, the ventricles, and cortical lobar atrophy. The microstructural integrity of the white matter was reflected in the mean fractional anisotropy (FA) and mean diffusivity (MD), and the regional mean values of FA and MD were quantified after mapping using the ICBM_DTI_81 Atlas. Twenty-three (56.1%) men and 18 (43.9%) women (mean age: 61.73 years, range: 41-77 years) were included. The median National Institutes of Health Stroke Scale (NIHSS) score at discharge was 1 (range: 0-4). On univariate analysis, the EQ was correlated with right cortical infarction (r = -0.39, p = 0.012), putamen volume (r = 0.382, p = 0.014), right putamen volume (r = 0.338, p = 0.031), and the FA value of the right sagittal stratum. EQ did not correlated with the MD value in any region of interest or pre-existing brain abnormalities. Multiple stepwise linear regression models were used to identify factors associated with EQ. After adjusting for age and the NIHSS score on admission, the frequency of right cortical infarcts negatively correlated with EQ (standardized ß = -0.358, 95% confidence interval =-0.708 to -0.076, p = 0.016), and the putamen volume positively correlated with EQ (standardized ß = 0.328, 95% confidence interval =0.044 to 0.676, p = 0.027). In conclusion, in patients who have experienced subacute ischemic stroke, right cortical infarction and a smaller putamen volume are associated with the impairment of empathy.

Corn oligopeptides inhibit Akt/NF-κB signaling pathway and inflammatory factors to ameliorate CCl4 -induced hepatic fibrosis in mice.

In this study, the effect of corn oligopeptides (COPs) with liver protection activity on mice with hepatic fibrosis (HF) induced by carbon tetrachloride (CCl4 ) was studied. It was proved that COPs can ameliorate the liver injury and inflammation caused by CCl4 by histopathology and enzyme-linked immunosorbent assay in mice. The expression of Akt/NF-κB inflammatory pathway was determined by real-time polymerase chain reaction (RT-PCR) and western blotting (WB). The results showed that COPs inhibited the expression of key proteins in the inflammatory pathway. In conclusion, the results of this study suggested that COPs could improve CCl4 -induced HF by improving liver injury, reducing the expression of inflammatory factors, and inhibiting the expression of inflammatory signaling pathways. PRACTICAL APPLICATIONS: The corns around the world are mainly used as animal feed, and the liver protective activity of corn oligopeptides (COPs) is rarely applied to the market. The development of COPs liver protective food can prevent the occurrence of liver-related diseases such as hepatic fibrosis to a certain extent. Developing COPs liver protecting food can improve the utilization value of corn. It is hoped that this study can provide experimental support for the application of COPs in liver protection food.

Synergistic regulation of nonbinary molecular switches by protonation and light.

We report a molecular switching ensemble whose states may be regulated in synergistic fashion by both protonation and photoirradiation. This allows hierarchical control in both a kinetic and thermodynamic sense. These pseudorotaxane-based molecular devices exploit the so-called Texas-sized molecular box (cyclo[2]-(2,6-di(1H-imidazol-1-yl)pyridine)[2](1,4-dimethylenebenzene); 14+, studied as its tetrakis-PF6- salt) as the wheel component. Anions of azobenzene-4,4'-dicarboxylic acid (2H+•2) or 4,4'-stilbenedicarboxylic acid (2H+•3) serve as the threading rod elements. The various forms of 2 and 3 (neutral, monoprotonated, and diprotonated) interact differently with 14+, as do the photoinduced cis or trans forms of these classic photoactive guests. The net result is a multimodal molecular switch that can be regulated in synergistic fashion through protonation/deprotonation and photoirradiation. The degree of guest protonation is the dominating control factor, with light acting as a secondary regulatory stimulus. The present dual input strategy provides a complement to more traditional orthogonal stimulus-based approaches to molecular switching and allows for the creation of nonbinary stimulus-responsive functional materials.

Identification of a delayed leaf greening gene from a mutation of pummelo.

Delayed greening of young leaves is an unusual phenomenon of plants in nature. Citrus are mostly evergreen tree species. Here, a natural mutant of "Guanxi" pummelo (Citrus maxima), which shows yellow leaves at the young stage, was characterized to identify the genes underlying the trait of delayed leaf greening in plants. A segregating population with this mutant as the seed parent and a normal genotype as the pollen parent was generated. Two DNA pools respectively from the leaves of segregating seedlings with extreme phenotypes of normal leaf greening and delayed leaf greening were collected for sequencing. Bulked segregant analysis (BSA) and InDel marker analysis demonstrated that the delayed leaf greening trait is governed by a 0.3 Mb candidate region on chromosome 6. Gene expression analysis further identified a key candidate gene (Citrus Delayed Greening gene 1, CDG1) in the 0.3 Mb region, which showed significantly differential expression between the genotypes with delayed and normal leaf greening phenotypes. There was a 67 bp InDel region difference in the CDG1 promoter and the InDel region contains a TATA-box element. Confocal laser-scanning microscopy revealed that the CDG1-GFP fusion protein signals were co-localized with the chloroplast signals in the protoplasts. Overexpression of CDG1 in tobacco and Arabidopsis led to the phenotype of delayed leaf greening. These results suggest that the CDG1 gene is involved in controlling the delayed leaf greening phenotype with important functions in chloroplast development.

Global cortical atrophy may be associated with fatigue in patients with parkinson's disease.

PURPOSE: Fatigue has been recognized as a common non-motor problem in patients with Parkinson's disease (PD). The determination of the clinical correlates of fatigue in PD patients is necessary. The purpose of this study was to explore the risk factors related to the severity of fatigue in PD. PATIENTS AND METHODS: In this study, 141 patients with PD were recruited. All patients were evaluated comprehensively, including motor function, fatigue severity scale (FSS), cognition and psychiatric status. Brain magnetic resonance imaging (MRI) examinations were performed to assess the severity of white matter hyperintensities, and the presence of silent lacunes, medial temporal lobe atrophy (MTLA), and global cortical atrophy (GCA). The crude associations of variables with FSS were examined using Pearson (nor-mally distributed) or Spearman correlation (categorical or non-normal distributed) analyses. Multiple linear regression analysis was performed to find the correlates of fatigue severity in PD patients. RESULTS: In the whole sample, with FSS as the dependent variable in a linear regression model, Hamilton Depression Rating Scale (HAM-D), GCA, female sex were significant correlates of FSS, accounting for 24% of the variance of it. When subjects with depression (HAM-D ≥ 35) were excluded, HAM-D, GCA, female sex remained significant correlates of FSS, accounting for 22% of the variance of FSS. There is no correlation between white matter hyperintensities and FSS. CONCLUSION: GCA may be an important correlate of the fatigue severity commonly observed in PD patients.

Multiple hypointense vessels on susceptibility-weighted imaging predict early neurological deterioration in acute ischaemic stroke patients with severe intracranial large artery stenosis or occlusion receiving intravenous thrombolysis.

BACKGROUND AND PURPOSE: Early neurological deterioration (END) is a common feature in patients with acute ischaemic stroke (AIS) receiving thrombolysis. This study aimed to investigate whether the presence of multiple hypointense vessels (MHVs) on susceptibility-weighted imaging (SWI) could predict END in patients with the anterior circulation AIS treated with recombinant tissue plasminogen activator (r-tPA). METHODS: This was a retrospective study focusing on AIS patients suffering from symptomatic stenosis or occlusion of the middle cerebral artery or internal carotid artery with r-tPA treatment. We collected clinical variables and initial haematological and neuroimaging findings. MHVs were measured on SWI performed after intravenous thrombosis and were defined as the presence of a greater number of veins or veins of a larger diameter with greater signal loss on SWI than those of the contralesional haemisphere. The degree of hyperintensity of MHVs was classified into four grades: none, subtle, moderate and extensive. END was defined as an increase in the National Institutes of Health Stroke Scale score by 2 points during the first 48 hours after the onset of symptoms. Multivariate logistic regressions were conducted to investigate the predictors of END. RESULTS: The study included 61 patients (51 males and 10 females) with a mean age of 62.4±12.6 years. Thirty-five (57.4%) patients presented with MHVs: 8 (13.1%) were graded as subtle MHVs, while 23 (37.7%) and 4 (6.6%) were graded as moderate or extensive MHVs, respectively. Twenty patients (32.8%) presented with END. Logistic regression analysis showed that compared with patients without MHVs, moderate MHVs (adjusted OR 5.446, 95% CI 1.360 to 21.800; p=0.017) and extensive MHVs (adjusted OR 15.240, 95% CI 1.200 to 193.544; p=0.036) were significantly associated with END. CONCLUSIONS: MHVs might be a useful predictor of END in AIS patients with symptomatic large artery stenosis or occlusion after r-tPA treatment.

Asymmetrical cortical vessel sign predicts prognosis after acute ischemic stroke.

INTRODUCTION: To assess whether the asymmetrical cortical vessel sign (ACVS) on susceptibility-weighted imaging (SWI) could predict 90-day poor outcomes in anterior circulation acute ischemic stroke (AIS) patients treated with recombinant tissue plasminogen activator (r-tPA). METHODS: Clinical data of consecutive patients with anterior circulation AIS treated with r-tPA were retrospectively analyzed. Clinical variables included age, sex, vascular risk factors, NIHSS score, onset to treatment time, and initial hematologic and neuroimaging findings. Follow-up was performed 90 days after onset. Poor outcome was defined as a modified Rankin scale (mRS) ≥3 at 90 days. RESULTS: A total of 145 patients were included, 35 (24.1%) patients presented with ACVS (≥Grade 1) on SWI. Fifty-three (36.6%) patients had a poor outcome at 90 days. ACVS (≥Grade 1) occurred in 21 (39.6%) patients with poor outcome compared with 14 (15.2%) patients with favorable outcome (p = .001). Univariate analysis indicated that age, NIHSS score on admission, previous stroke, hemorrhagic transformation, severe intracranial large artery stenosis or occlusion (SILASO), and ACVS were associated with 90-day poor outcome (p < .05). Since SILASO and ACVS were highly correlated and ACVS had different grades, we used three logistic regression models. Results from the three models showed that ACVS was associated with 90-day poor outcome. CONCLUSIONS: In r-tPA-treated patients with anterior circulation AIS, ACVS might be a helpful neuroimaging predictor for poor outcome at 90 days.

Time-dependent solid-state molecular motion and colour tuning of host-guest systems by organic solvents.

Host-guest complex solid state molecular motion is a critical but underexplored phenomenon. In principle, it can be used to control molecular machines that function in the solid state. Here we describe a solid state system that operates on the basis of complexation between an all-hydrocarbon macrocycle, D4d-CDMB-8, and perylene. Molecular motion in this solid state machine is induced by exposure to organic solvents or grinding and gives rise to different co-crystalline, mixed crystalline, or amorphous forms. Distinct time-dependent emissive responses are seen for different organic solvents as their respective vapours or when the solid forms are subject to grinding. This temporal feature allows the present D4d-CDMB-8⊃perylene-based system to be used as a time-dependent, colour-based 4th dimension response element in pattern-based information codes. This work highlights how dynamic control over solid-state host-guest molecular motion may be used to induce a tuneable temporal response and provide materials with information storage capability.

Preexisting Cerebral Abnormalities and Functional Outcomes After Acute Ischemic Stroke.

PURPOSE: The aim of this study was to investigate the association between preexisting cerebral abnormalities in patients with acute ischemic stroke upon their functional outcomes. METHODS: We recruited 272 patients with first-ever acute ischemic stroke. Cerebral abnormalities on magnetic resonance imaging included infarction, silent brain infarcts (SBI), enlarged perivascular spaces, white matter lesions (WMLs), global brain atrophy, and medial temporal lobe atrophy (MTLA). Functional outcomes were assessed using the instrumental activities of daily living (IADL) scale and basic activities of daily living (BADL) scale, at 3 and 6 months after the index stroke. RESULTS: Two hundred and fifty patients completed the 3-month follow-up and 246 patients completed the 6-month follow-up. Univariate analyses showed that patients with poor IADL and BADL were older, more likely to be men, had higher National Institutes of Health Stroke Scale (NIHSS) score on admission, more frequent atrial fibrillation, and large artery atherosclerosis subtypes. They also had more frequent cortical infarcts, subcortical infarcts, infratentorial infarcts, larger infarct volume, more frequent presence of SBI, severe WMLs, and MTLA. In multiple regression analyses, NIHSS on admission, subcortical region infarct and MTLA were significant predictors of poor IADL at 3 months. National Institutes of Health Stroke Scale on admission, SBI and MTLA were significant predictors of poor IADL at 6 months. National Institutes of Health Stroke Scale on admission and MTLA were significant predictors of poor BADL at 3 months. National Institutes of Health Stroke Scale on admission and SBI were significant predictors of poor BADL at 6 months. CONCLUSIONS: In patients with acute ischemic stroke, the presence of SBI, and severe MTLA represent significant predictors of poorer functional outcomes, thus highlighting the importance of preexisting cerebral abnormalities.

Isolation of 4,4'-bond secalonic acid D from the marine-derived fungus Penicillium oxalicum with inhibitory property against hepatocellular carcinoma.

4,4'-bond secalonic acid D (4,4'-SAD) is a known compound isolated from the marine-derived fungus Penicillium oxalicum. No study about the antitumor effect of this compound has been reported, except for a few focusing on its bactericidal properties. Herein, we performed an in vitro biology test and found that 4,4'-SAD stimulated the apoptosis of tumor cells in the human hepatocellular carcinoma cell lines PLC/PRF/5 and HuH-7 by activating caspase-3, caspase-8, caspase-9, PARP, p53, and cyclin B1, as well as by regulating the Bax/Bcl-2 ratio. In vivo studies showed that 4,4'-SAD had antitumor efficacy in H22 cell xenograft model. Immunohistochemical analysis revealed that 4,4'-SAD could regulate Bax expression, which is a biomarker of tumor growth. In summary, 4,4'-SAD significantly inhibited tumor growth both in vivo and in vitro.

Weight loss correlates with macrophage inhibitory cytokine-1 expression and might influence outcome in patients with advanced esophageal squamous cell carcinoma.

BACKGROUND: Weight loss during chemotherapy has not been exclusively investigated. Macrophage inhibitory cytokine-1 (MIC-1) might play a role in its etiology. Here, we investigated the prognostic value of weight loss before chemotherapy and its relationship with MIC-1 concentration and its occurrence during chemotherapy in patients with advanced esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: We analyzed 157 inoperable locally advanced or metastatic ESCC patients receiving first-line chemotherapy. Serum MIC-1 concentrations were assessed before chemotherapy. Patients were assigned into two groups according to their weight loss before or during chemotherapy: >5% weight loss group and≤5% weight loss group. RESULTS: Patients with weight loss>5% before chemotherapy had shorter progression-free survival period (5.8 months vs. 8.7 months; p=0.027) and overall survival (10.8 months vs. 20.0 months; p=0.010). Patients with weight loss>5% during chemotherapy tended to have shorter progression-free survival (6.0 months vs. 8.1 months; p=0.062) and overall survival (8.6 months vs. 18.0 months; p=0.022), and if weight loss was reversed during chemotherapy, survival rates improved. Furthermore, serum MIC-1 concentration was closely related to weight loss before chemotherapy (p=0.001) CONCLUSIONS: Weight loss both before and during chemotherapy predicted poor outcome in advanced ESCC patients, and MIC-1 might be involved in the development of weight loss in such patients.

Retrospective analysis of adjuvant chemotherapy for curatively resected gastric cancer.

AIM: To determine the efficacy of adjuvant chemotherapy for gastric cancer in clinical practice, a retrospective analysis was conducted in a high-volume Chinese cancer center. METHODS: Between November 1995 and June 2007, a total of 423 gastric or esophagogastric adenocarcinoma patients who did (Arm A, n = 300) or did not (Arm S, n = 123) receive radical gastrectomy followed by postoperative chemotherapy were enrolled in this retrospective analysis. In Arm A, monotherapy(fluoropyrimidines, n = 25), doublet (platinum/fluoropyrimidines, n = 164), or triplet regimens [docetaxel/cisplatin/5FU (DCF), or modified DCF, epirubicin/cisplatin/5FU (ECF) or modified ECF, etoposide/cisplatin/FU, n = 111] were administered. Disease-free survival (DFS) and overall survival (OS) were compared between the two arms. A subgroup analysis was carried out in Arm A. A multivariate analysis of prognostic factors was conducted. RESULTS: Stage I, II and III cancers accounted for 9.7%, 35.7% and 54.6% of the cases, respectively, according to the American Joint Committee on Cancer (AJCC) staging system, 7(th) edition. Only 178 (42.1%) patients had more than 15 lymph nodes harvested. Hazard ratio estimates for Arm A compared with Arm S were 0.47 (P < 0.001) for OS and 0.59 (P < 0.001) for DFS. The 5-year OS rate was 52% in Arm A vs 36% in Arm S (P = 0.01); the adverse events in Arm A were mild and easily controlled. Ultimately, 73 patients (26.5%) who received doublet or triplet regimens switched to monotherapy with fluoropyrimidines. The OS and DFS did not differ between monotherapy and the combination regimens, however, both were statistically improved in the subgroup of patients who were switched to monotherapy with fluoropyrimidines after doublet or triplet regimens as well as patients who received ≥ 8 cycles of chemotherapy. CONCLUSION: In clinical practice, platinum/fluoropyrimidines with adequate treatment duration is recommended for stage II/III gastric cancer patients according to the 7(th) edition of the AJCC staging system after curative gastrectomy even with limited lymphadenectomy.

Neutrophil count and the inflammation-based glasgow prognostic score predict survival in patients with advanced gastric cancer receiving first-line chemotherapy.

PURPOSE: To explore the value of systemic inflammatory markers as independent prognostic factors and the extent these markers improve prognostic classification for patients with inoperable advanced or metastatic gastric cancer (GC) receiving palliative chemotherapy. METHODS: We studied the prognostic value of systemic inflammatory factors such as circulating white blood cell count and its components as well as that combined to form inflammation-based prognostic scores (Glasgow Prognostic Score (GPS), Neutrophil-Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI) and Prognostic Nutritional Index (PNI)) in 384 patients with inoperable advanced or metastatic gastric cancer (GC) receiving first-line chemotherapy. Univariate and multivariate analyses were performed to examine the impact of inflammatory markers on overall survival (OS). RESULTS: Univariate analysis revealed that an elevated white blood cell, neutrophil and/or platelet count, a decreased lymphocyte count, a low serum albumin concentration, and high CRP concentration, as well as elevated NLR/PLR , GPS, PI, PNI were significant predictors of shorter OS. Multivariate analysis demonstrated that only elevated neutrophil count (HR 3.696, p=0.003) and higher GPS (HR 1.621, p=0.01) were independent predictors of poor OS. CONCLUSION: This study demonstrated elevated pretreatment neutrophil count and high GPS to be independent predictors of shorter OS in inoperable advanced or metastatic GC patients treated with first-line chemotherapy. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

[Efficacy of albumin-bound paclitaxel in advanced gastric cancer patients].

OBJECTIVE: To evaluate the safety and efficacy of albumin-bound paclitaxel in patients with advanced gastric cancer (AGC). METHODS: The patients with histopathologic or cytopathologic diagnosed advanced gastric cancer (AGC), Karnofsky performance status ≥ 60, and life expectancy >12 weeks, and with adequate organ functions of the bone marrow, liver, kidney and heart were recuited in our study. albumin-bound paclitaxel was administered alone or combined with capecitabine, TS-1, trastuzumab or cetuxizumb. The total doses of albumin-bound paclitaxel were 200-400 mg (130-260 mg/m(2)), divided on days 1, 8 or days 1,8, and 15, given intravenously during 30 minutes of a 21-day cycle. Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. The adverse events (AE) were graded according to National Cancer Institute-Common Toxicity Criteria (NCI-CTC) 3.0 version. RESULTS: From July 2009 to Octobor 2012, the total of 25 patients were treated and completed 65 cycles of chemotherapy (median: 2 cycles, and range: 0.5-7). The median age was 57 years (range: 38-79). The majority of the patients were with non-gastroesophageal junction cancers and had metastasic disease with lymph nodes and peritoneum. Eleven patients were chemotherapy naive and the others had accepted previous systemic therapy for advanced disease. 16 patients were evaluable for clinical response. No complete response was observed and partial response (PR) was achieved in 5 patients. Five patients had stable disease and 6 patients progressed. Among the chemotherapy naive patients, 8 patients were evaluable for response, 3 patients had partial response (37.5%) and 1 patient had stable disease (tumor shrink). The clinical response rate was 50%. Time to treatment failure (TTF)was 3.7 months(95% CI 2.32-5.08) and time to death (TTD)was 7.9 months (95% CI 5.17-10.63). No statistical differences in TTF and TTD were observed between the untreated and the retreated patients or the monotherapy and the combination therapy groups. All the patients were suitable for safety assessment. Most toxicities were mild with grades 1/2. Hematologic AEs were more common with leucopenia and neutropenia. Meanwhile, nausea/vomiting, fatigue, peripheral neuropathy were the most common non-hematologic AEs. No allergic reaction or treatment-related deaths were recorded. CONCLUSION: AGC patients could benefit from albumin-bound paclitaxel with lower dose level than breast cancer patients. Additional phase I/II studies of albumin-bound paclitaxel in gastric cancer are warranted.

[New perspectives on medical treatment of gastric cancer].

Perioperative chemotherapy for gastric cancer has made steady progress with the application of chemotherapeutic agents and conduct of relevant clinical trials. However, palliative chemotherapy has only made marginal progress, and the median survival remains between 8-10 months. An emerging understanding of tumor biology, cellular and molecular mechanisms has revealed novel targets in gastric cancer therapy, such as trastuzumab, bevacizumab, cetuximab, etc. There are still some problems in clinical practice due to the high heterogeneity of gastric cancer including optimization of perioperative chemotherapy regimen, determination of right strategy to personalize chemotherapy or target therapy for advanced gastric cancer. In order to practically achieve individualized therapy, multicenter, prospective, randomized clinical trials according specific matters of gastric cancer should be performed in China. A deeper understanding of the biological characteristics of gastric cancer, and more translational medicine research and multi-disciplinary team collaboration should be carried out to achieve personalized medicine.

[Detection of breast cancer stem cells and the expression of key molecules in Hedgehog signaling pathway].

OBJECTIVE: To isolate and identify breast cancer initiating cells (CD44(+)/CD24(-/low) cells) in breast cancer cell lines MCF-7 and MDA-MB-231, and to evaluate the activity of the Hedgehog signaling pathway in different subpopulations. METHODS: CD44+/CD24(-/low) subpopulation and non-CD44+/CD24(-/low) subpopulation from breast cancer cell lines of MCF-7 and MDA-MB-231 were separated by fluorescence-activated cell sorting (FACS). Laser Scanning Confocal Microscope was used to identify CD44+/CD24(-/low) cells. Reverse transcription-polymerase chain reaction (RT-PCR) was employed to analyze the expression of Human Patched gene (PTCH), Sonic Hedgehog (SHH), glioma-associated oncogene homoglog-1(GIi-1), smoothened homolog (SMOH) and GAPDH of CD44+/CD24(-/low) subpopulation and non-CD44+/CD24(-/low) subpopulation from MCF-7 and MDA-MB-231. RESULTS: The CD44+/CD24(-/low) subpopulation in MCF-7 and MDA-MB-231 cell lines were (1.70+/-1.43)% and (94.2+/-1.2)% respectively. The Hedgehog signaling pathways were active in CD44+/CD24(-/low) subpopulation of MCF-7 and MDA-MB-231 cell lines. The expression of transcription factor GIi-1, which was downstream components of the hedgehog pathway, was assayed and the results showed that the level of GIi-1 mRNA of CD44+/CD24(-/low) cells was much higher than that of non-CD44+/CD24(-/low) cells (P = 0.007 in MCF-7, and 0.005 in MDA-MB-231). CONCLUSION: Breast cancer initiating cells (CD44+/CD24(-/low) subpopulation) exist in MCF-7 and MDA-MB-231 cell lines. The Hedgehog signaling pathway is active in the subpopulation of MCF-7 and MDA-MB-231 cell lines.