Prevalence and coprevalence of modifiable risk factors for upper digestive tract cancer among residents aged 40-69 years in Yangzhong city, China: a cross-sectional study.

OBJECTIVES: To describe the prevalence of modifiable risk factors for upper digestive tract cancer (UDTC) and its coprevalence, and investigate relevant influencing factors of modifiable UDTC risk factors coprevalence among residents aged 40-69 years in Yangzhong city, China. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 21 175 participants aged 40-69 years were enrolled in the study. 1962 subjects were excluded due to missing age, marital status or some other selected information. Eventually, 19 213 participants were available for the present analysis. MAIN OUTCOMES MEASURES: Prevalence and coprevalence of eight modifiable UDTC risk factors (overweight or obesity, current smoking, excessive alcohol consumption, insufficient vegetables intake, insufficient fruit intake and the consumption of pickled, fried and hot food) were analysed. RESULTS: The prevalence of overweight/obesity, current smoking, excessive alcohol consumption, insufficient vegetables intake, insufficient fruit intake and the consumption of pickled, fried and hot food in this study was 45.3%, 24.1%, 16.2%, 66.1%, 94.5%, 68.1%, 36.0% and 88.4%, respectively. Nearly all (99.9%) participants showed one or more UDTC risk factors, 98.6% of the participants showed at least two risk factors, 92.2% of the participants had at least three risk factors and 69.7% of the participants had four or more risk factors. Multivariate logistic regression analysis revealed that men, younger age, single, higher education, higher annual family income and smaller household size were more likely to present modifiable UDTC risk factors coprevalence. CONCLUSIONS: The prevalence and coprevalence of modifiable UDTC risk factors are high among participants in Yangzhong city. Extra attention must be paid to these groups who are susceptible to risk factors coprevalence during screening progress. Relative departments also need to make significant public health programmes that aim to decrease modifiable UDTC risk factors coprevalence among residents aged 40-69 years from high-risk areas of UDTC.

Optimizing cancer pain management in resource-limited settings.

PURPOSE: Adequate cancer pain management (CPM) is challenging in resource-limited settings, where current international guideline recommendations are difficult to implement owing to constraints such as inadequate availability and accessibility of opioids, limited awareness of appropriate opioid use among patients and clinicians, and lack of guidance on how to translate the best evidence into clinical practice. The multinational and multidisciplinary CAncer Pain managEment in Resource-limited settings (CAPER) Working Group proposes a two-step initiative to bridge clinical practice gaps in CPM in resource-limited settings. METHODS: A thorough review of the literature, a steering committee meeting in February 2017, and post-meeting teleconference discussions contributed to the development of this initiative. As a first step, we developed practical evidence-based CPM algorithms to support healthcare providers (HCPs) in tailoring treatment according to availability of and access to resources. The second part of the initiative proposes a framework to support an effective implementation of the CPM algorithms that includes an educational program, a pilot implementation, and an advocacy plan. RESULTS: We developed CPM algorithms for first-line use, breakthrough cancer pain, opioid rotation, and refractory cancer pain based on the National Comprehensive Cancer Network guidelines and expert consensus. Our proposed educational program emphasizes the practical elements and illustrates how HCPs can provide optimal CPM according to evidence-based guidelines despite varied resource limitations. Pilot studies are proposed to demonstrate the effectiveness of the algorithms and the educational program, as well as for providing evidence to support a draft advocacy document, to lobby policymakers to improve availability and accessibility of analgesics in resource-limited settings. CONCLUSIONS: These practical evidence-informed algorithms and the implementation framework represent the first multinational step towards achieving optimal CPM in resource-limited settings.

Managing Pain in Patients With Cancer: The Chinese Good Pain Management Experience.

PURPOSE: The number of cancer cases in China has increased rapidly from 2.1 million in 2000 to 4.3 million in 2015. As a consequence, pain management as an integral part of cancer treatment became an important health care issue. In March 2011, the Good Pain Management (GPM) program was launched to standardize the treatment of cancer pain and improve the quality of life for patients with cancer. With this work, we will describe the GPM program, its implementation experience, and highlight key lessons that can improve pain management for patients with cancer. METHODS: We describe procedures for the selection, implementation, and assessment procedures for model cancer wards. We analyzed published results in areas of staff training and patient education, pain management in practice, analgesic drugs administration, and patient follow-up and satisfaction. RESULTS: Pain management training enabled medical staff to accurately assess the level of pain and to provide effective pain relief through timely dispensation of medication. Patients with good knowledge of treatment of pain were able to overcome their aversion to opioid drugs and cooperate with nursing staff on pain assessment to achieve effective drug dose titration. Consumption of strong opioid drugs increased significantly; however, there was no change for weaker opioids. Higher pain remission rates were achieved for patients with moderate-to-severe pain levels. Proper patient follow-up after discharge enabled improved outcomes to be maintained. CONCLUSION: The GPM program has instituted a consistent and high standard of care for pain management at cancer wards and improved the quality of life for patients with cancer.

S-1 plus cisplatin versus fluorouracil plus cisplatin in advanced gastric or gastro-esophageal junction adenocarcinoma patients: a pilot study.

The safety and efficacy of S-1 plus cisplatin in Chinese advanced gastric cancer patients in first line setting is unknown. In this pilot study, patients with advanced gastric or gastro-esophageal junction adenocarcinoma were enrolled and randomly assigned in a 1:1 ratio to receive S-1 plus cisplatin (CS group) or 5-FU plus cisplatin (CF group). The primary endpoint was time to progression (TTP). Secondary end points included overall survival (OS) and safety. This study was registered on ClinicalTrials. Gov, number NCT01198392. A total of 236 patients were enrolled. Median TTP was 5.51 months in CS group compared with 4.62 months in CF group [hazard ratio (HR) 1.028, 95% confidential interval (CI) 0.758-1.394, p = 0.859]. Median OS was 10.00 months and 10.46 months in CS and CF groups (HR 1.046, 95%CI 0.709-1.543, p = 0.820), respectively. The most common adverse events in both groups were anemia, leukopenia, neutropenia, nausea, thrombocytopenia, vomiting, anorexia and diarrhea. We find that S-1 plus cisplatin is an effective and tolerable option for advanced gastric or gastro-esophageal junction adenocarcinoma patients in China.

Overexpression of SLC38A1 is associated with poorer prognosis in Chinese patients with gastric cancer.

BACKGROUND: Current literature has demonstrated that host glutamine depletion facilitates tumorigenesis. Likewise, the glutamine transporter SLC38A1 is putatively associated with malignant transformation and tumor progression. Taken together, this forms the premise for undertaking the current study. The twofold aim of this study was to provide insight into whether or not a variance in the expression of SLC38A1 exists between human gastric cancer and healthy human tissues, and to determine how silencing the SLC38A1 gene could affect the proliferation, viability, migration, and invasion of gastric cancer cells. METHODS: Immunohistochemical staining was used to analyze the expression of SLC38A1 in gastric cancer tissues and adjacent healthy mucosa in 896 patients with pathologically confirmed gastric cancer who had underwent R0 resection. SH-10-TC cells (a gastric cancer cell line) were used to examine whether silencing SLC38A1 with siRNA could affect cell viability, migration and invasion. RESULTS: The SLC38A1 protein was very low or undetectable in healthy gastric mucosa. In contrast, strong staining of SLC38A1 protein was found in the cytoplasm in 495 out of the 896 gastric cancer samples. More pronounced SLC38A1 expression in gastric cancer tissues was significantly associated with age, differentiation status, lymph node metastasis, TNM stage and PCNA (proliferating cell nuclear antigen) expression. Upon univariate survival analysis, SLC38A1 expression was correlated with poor survival. Multivariate survival analysis revealed that SLC38A1 was an independent prognostic factor. CONCLUSION: SLC38A1 is overexpressed in gastric cancer, which suggests that it is contributory to tumor progression. These results encourage the exploration of SLC38A1 as a target for intervention in gastric cancer.

Association of IL-6 polymorphisms with hepatocellular carcinoma risk: evidences from a meta-analysis.

The associations between IL-6 gene single nucleotide polymorphisms (SNPs) and risk of hepatocellular carcinoma (HCC) are controversial. We performed a meta-analysis to provide more credible evidence. We searched for relevant studies published up to 2013 by performing an efficient searching strategy. Odds ratios (OR) with 95% confidence interval (95% CI) was used to estimate the strength of the associations between IL-6 polymorphisms and HCC risk. We identified eight case-control studies involving 1,448 HCC cases and 3,160 controls. Our estimation specifically focused on two SNPs of the IL-6 gene, -174 G/C and -572 G/C. The combined results showed that association between IL-6-174 G/C polymorphism and risk of HCC was significant under additive model (CC vs. GG: OR 0.36; 95% CI, 0.16, 0.85) and recessive model (GG+CG vs. CC: OR 2.82; 95% CI 1.26, 6.28). However, the IL-6-572 G/C polymorphism was not associated with HCC risk. In conclusion, IL-6-174 G/C, but not -572 G/C polymorphism could be a candidate for susceptibility to HCC. However, the results should be cautiously interpreted due to the limited number of the included studies.

[Trastuzumab in combination with chemotherapy versus chemotherapy alone for first-line treatment of HER2-positive advanced gastric or gastroesophageal junction cancer: a Phase III, multi-center, randomized controlled trial, Chinese subreport].

OBJECTIVE: To evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer. METHODS: Fifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival. RESULTS: Eighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively. CONCLUSIONS: Addition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.

Expression of group IIA phospholipase A2 is an independent predictor of favorable outcome for patients with gastric cancer.

Growing evidence suggests that phospholipase A2 (PLA2) plays a pivotal role in tumorigenesis in human gastrointestinal cancer. One of the well-studied isoforms of PLA2, group IIA PLA2 (PLA2G2A), appears to exert its protumorigenic or antitumorigenic effects in a tissue-specific manner. The present study was designed to determine the expression profile and prognostic value of PLA2G2A in gastric cancer in a large Chinese cohort. By using real-time polymerase chain reaction, the amount of PLA2G2A messenger RNA in 60 pairs of fresh gastric tumors and adjacent noncancerous mucosa was measured. The immunostaining of PLA2G2A in 866 gastric cancers with paired noncancerous tissues was assayed. No expression of PLA2G2A was found in normal gastric mucosa, and focal expression of PLA2G2A was noticed in intestinal metaplasia, whereas significantly increased expression of PLA2G2A was observed in the cytoplasm of gastric cancer cells. Furthermore, the extent of PLA2G2A expression was associated with tumor size (P < .001), tumor differentiation (P = .001), T class (P < .001), N class (P < .001), and TNM stage (P < .001) of gastric cancer. Multivariate analysis showed that PLA2G2A expression was an independent predictor of survival for patients with gastric cancer (P = .024). Expression of PLA2G2A seems to be protective for patients with gastric cancer (hazard ratio, 1.423; 95% confidence interval, 1.047-1.935), and it may be a target for achieving better treatment outcomes.

Reduced group IVA phospholipase A2 expression is associated with unfavorable outcome for patients with gastric cancer.

Arachidonic acid metabolic pathway has been implicated in the inflammation-associated tumorigenesis of gastrointestinal cancers. As the rate-limiting enzyme of arachidonic acid production, group IVA phospholipase A2 (PLA2G4A) is hypothesized to play a fundamental role in gastric tumorigenesis as well as cyclooxygenase-2 (COX-2). However, little is known about the expression and role of PLA2G4A in gastric cancer, and the association of PLA2G4A with COX-2 remains to be elucidated. In this study, the mRNA expression of PLA2G4A and COX-2 in 60 pairs of fresh gastric tumors and corresponding adjacent non-cancerous mucosa was detected by using real-time quantitative PCR and the immunostaining of the both proteins in paired samples from 866 gastric cancer patients were assessed by using immunohistochemistry method. The clinicopathological and the prognostic relevance of PLA2G4A and COX-2 expression were determined. The results revealed a significantly reduced expression of PLA2G4A in gastric tumors compared to in non-cancerous tissues, as opposite to the increased expression of COX-2. PLA2G4A was significantly associated with tumor size (P = 0.003), tumor grade (P < 0.001), intestinal type (P = 0.003), T classification (P < 0.001), N classification (P < 0.001), and thereby TNM stage (P < 0.001). PLA2G4A and COX-2 expression were both identified as independent prognostic factors in multivariate Cox model analysis (P = 0.024 for PLA2G4A and P < 0.001 for COX-2). Moreover, the reduced PLA2G4A and increased COX-2 expression was both associated with unfavorable survival for patients with gastric cancer. PLA2G4A might serve as a promising target for future therapeutic approaches to gastric cancer combined with COX-2 inhibitors.

Long-term results of a randomized, double-blind, and placebo-controlled phase III trial: Endostar (rh-endostatin) versus placebo in combination with vinorelbine and cisplatin in advanced non-small cell lung cancer.

BACKGROUND: : Phase II-III trials in patients with untreated and previously treated locally advanced or non-small cell lung cancer (NSCLC) suggested that Endostar was able to enhance the effect of platinum-based chemotherapy (NP regimen) with tolerable adverse effects. METHODS: Four hundred and eighty six patients were randomized into two arms: study arm A: NP plus Endostar (n = 322; vinorelbine, cisplatin, Endostar), and study arm B: NP plus placebo (n = 164; vinorelbine, cisplatin, 0.9% sodium chloride). Patients were treated every third week for two to six cycles. RESULTS: : Overall response rates were 35.4% in arm A and 19.5% in arm B (P = 0.0003). The median time to progression was 6.3 months for arm A and 3.6 months for B, respectively (P < 0.001). The clinical benefit rates were 73.3% in arm A and 64.0% in arm B (P = 0.035). Grade 3/4 neutropenia, anemia, and nausea/vomiting were 28.5%, 3.4%, and 8.0%, respectively, in Arm A compared with 28.2%, 3.0%, and 6.6%, respectively, in Arm B (P > 0.05). There were two treatment related deaths in arm A and one in arm B (P > 0.05). The median overall survival was longer in arm A than in arm B (P < 0.0001). CONCLUSION: : Long-term follow-up revealed that the addition of Endostar to an NP regimen can result in a significant clinical and survival benefit in advanced NSCLC patients, compared with NP alone.

Expression profile and prognostic role of sex hormone receptors in gastric cancer.

BACKGROUND: Increasing interest has been devoted to the expression and possible role of sex hormone receptors in gastric cancer, but most of these findings are controversial. In the present study, the expression profile of sex hormone receptors in gastric cancer and their clinicopathological and prognostic value were determined in a large Chinese cohort. METHODS: The mRNA and protein expression of estrogen receptor alpha (ERα), estrogen receptor beta (ERß), progesterone receptor (PR), and androgen receptor (AR) in primary gastric tumors and corresponding adjacent normal tissues from 60 and 866 Chinese gastric cancer patients was detected by real-time quantitative PCR and immunohistochemistry method, respectively. The expression profile of the four receptors was compared and their associations with clinicopathological characteristics were assessed by using Chi-square test. The prognostic value of the four receptors in gastric cancer was evaluated by using univariate and multivariate Cox regression analysis. RESULTS: The presence of ERα, ERß, PR, and AR in both gastric tumors and normal tissues was confirmed but their expression levels were extremely low except for the predominance of ERß. The four receptors were expressed independently and showed a decreased expression pattern in gastric tumors compared to adjacent normal tissues. The positive expression of the four receptors all correlated with high tumor grade and intestinal type, and ERα and AR were also associated with early TNM stage and thereby a favorable outcome. However, ERα and AR were not independent prognostic factors for gastric cancer when multivariate survival analysis was performed. CONCLUSIONS: Our findings indicate that the sex hormone receptors may be partly involved in gastric carcinogenesis but their clinicopathological and prognostic significance in gastric cancer appears to be limited.

Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial.

The efficacy and safety of bevacizumab with modified irinotecan, leucovorin bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan (125 mg/m(2)), leucovorin (20 mg/m(2)) bolus, and 5-fluorouracil intravenous infusion (500 mg/m(2)) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-month PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-healing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.

Effect of sunitinib combined with ionizing radiation on endothelial cells.

The aims of present study were to evaluate the efficacy of combining sunitinib with ionizing radiation (IR) on endothelial cells in vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) were exposed to IR with or without sunitinib pretreatment. Apoptosis assay and cell cycle distribution were analyzed by flow cytometry. Clonogenic survival assay at 3 Gy dose with or without sunitinib was performed. The activity of phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway was detected by Western immunoblot. Lewis lung carcinoma mouse model was built to examine the effect of combination therapy on endothelial cells in vivo. Microvasculature changes were detected by immunohistochemistry using anti-CD31 antibody. Our results showed combination therapy of sunitinib and IR significantly increased apoptosis of endothelial cells and inhibited colony formation compared to sunitinib or radiotherapy alone. It also resulted in cell cycle redistribution (decreasing cells in S phase and increasing cells in G2/M phase). The activity of PI3K/Akt signal pathway was inhibited, which could be the potential mechanisms that account for the enhanced radiation response induced by sunitinib. In vivo analysis showed that combination therapy significantly decreased microvasculature formation. The results demonstrated that combination therapy of sunitinib and IR has the potential to increase the cytotoxic effects on endothelial cells.

A metabonomic approach to chemosensitivity prediction of cisplatin plus 5-fluorouracil in a human xenograft model of gastric cancer.

The prediction of chemosensitivity is a challenging problem in the management of cancer. In the present study, a metabonomic approach was proposed to assess the feasibility of chemosensitivity prediction in a human xenograft model of gastric cancer. BALB/c-nu/nu mice were transplanted with MKN-45 cell line to establish the xenograft model. The mice were then randomized into treatment group (cisplatin and 5-fluorouracil) and control group (0.9% sodium chloride), and their plasma were collected before treatment. Metabolic profiles of all plasma samples were acquired by using high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer (HPLC/Q-TOF-MS). Based on the data of metabolic profiles and k-Nearest Neighbor algorithm, a prediction model for chemosensitivity was developed and an average accuracy of 90.4% was achieved. In addition, a series of endogenous metabolites, including 1-acyl-lysophosphatidycholines, polyunsaturated fatty acids and their derivatives, were determined as potential indicators of chemosensitivity. In conclusion, our results suggest that the proposed metabonomic approach allows effective chemosensitivity prediction in human xenograft model of gastric cancer. The approach presents a new concept in the chemosensitivtiy prediction of cancer and is expected to be developed as a powerful tool in the personalized cancer therapy.

The p300/CBP associated factor is frequently downregulated in intestinal-type gastric carcinoma and constitutes a biomarker for clinical outcome.

OBJECTIVES: To investigate the expression of P300/CBP-associated factor (PCAF) protein in intestinal type gastric cancer (ITGC); analyze the relationship between the expression of PCAF protein and the clinical pathological characteristics of patients; explore the effects of PCAF protein on biological behaviors of ITGC. RESULTS: The expression of PCAF was markedly down-regulated in GC cell lines and ITGC tissues. PCAF was able to suppress tumorigenicity of GC cells both in vitro and in vivo, including colony formation in soft agar and tumor formation in nude mice. PCAF could also inhibit GC cells entering S phase from G1 phase. Statistical analysis displayed a significant correlation in PCAF expression with the gastric wall invasion, tumor size, TNM stage, p21, pRb (P<0.001) and PCNA (P<0.01) in ITGC specimens. A reduced PCAF protein expression correlated significantly with a mutant type p53 protein expression (P<0.01). Univariate analysis indicated that the patients demonstrating the high-PCAF/wild type p53 expression have a significantly (P<0.0001) better overall survival (OS), while multivariate analysis indicated that the location, lymph node metastasis, PCAF/p53 (P<0.0001), gastric wall invasion (P=0.001) and PCNA (P=0.018) are independently significant prognostic factors for OS. METHODS: Immunohistochemistry was performed to evaluate the expression of PCAF in a large subset containing 406 ITGC samples. Eukaryotic expression plasmid pcDNA3.1/PCAF was constructed and transfected into the human gastric cancer cell line SGC-7901 and protein expression was detected by Western blot. The proliferation and cell cycle of gastric cancer cells were evaluated by MTT assay and flow cytometry. Tumor growth in nude mice was used to access the tumorigenicity of gastric cancer cells. Apoptosis cells were detected by TUNEL staining. CONCLUSION: Reduced expression of PCAF plays an important role in the development of ITGC and correlates with a poor clinical outcome.

[Inhibition of angiogenesis of LCI-D20 hepatocellular carcinoma by metronomic chemotherapy of S-1].

OBJECTIVE: To investigate the role of metronomic chemotherapy of S-1 on angiogenesis of hepatocellular carcinoma in animal model. METHOD: S-1 was dissolved in a 0.5% (w/v) HPMC solution. 30 LCI-D20 were randomly devided into five groups: control group(O), 10 mg * kg(-1) * d(-1) S-1 group (A), 1 mg * kg(-1) * d(-1) S-1 group (B), 0.5 mg * kg(-1) * d(-1) S-1 group (C) and 0.25 mg * kg(-1) * d S-1 group (D). 28 days after the treatment with 0.5% (w/v) HPMC solution, tumors in LCI-D20 mice were moved out. Tumor mass was measured and microvessel density (MVD) was used to evaluate angiogenesis in tumor. The cellular apoptosis was determined using flow cytometry. The expression of VEGF, bFGF and TSP-1 was measured by RT-PCR. RESULTS: The mean tumor mass was 2.01, 0.38, 1.12, 1.38, 2.27 g in O, A, B, C, D group, respectively. The mean MVD was 39.57, 19.90, 5.93, 17.10, 29.53 in O, A, B, C, D respectively. The mean tumor cellular apoptosis rate was 4.08%, 44.37%, 31.73%, 19.83%, and 8.25% in O, A, B, C, D respectively. The expression of VEGF and bFGF in O group was highest, and A was slightly low, and C and D taked the third place, and B was the lowst; The expression of TSP-1 in B was highest, and C and D were slightly low, and A taked the third place, and O was the lowst. CONCLUSION: Metronomic chemotherapy of S-1 destabilizes pre-existing tumor vasculature and inhibits ongoing angiogenesis.

Overexpression of Grb2/HER2 signaling in Chinese gastric cancer: their relationship with clinicopathological parameters and prognostic significance.

PURPOSE: Growth factor receptor-bound 2 (Grb2)-mediated HER2 signaling is thought to play a critical role in gastric cancer development, progression and metastasis. However, little is known about their expression in gastric cancer. In this study, we try to explore their relationship with clinicopathological parameters and prognostic significance in gastric cancer patients. MATERIALS AND METHODS: We examined the expression of Grb2 and HER2 in normal gastric mucosa, primary gastric cancers, and lymph node metastases using immunohistochemical analysis of tissue microarrays containing specimens obtained from 1,143 patients with gastric cancer. RESULTS: Grb2 was overexpressed in 48% (553/1,143) of primary tumors and 59% (155/262) of lymph node metastases. We observed significant differences in Grb2 expression between the primary tumors and the lymph node metastases (P < 0.01). Also, HER2 was overexpressed in 28% (321/1,143) of the primary tumors and 30% (79/262) of the lymph node metastases. Overexpression of Grb2 and Her2 was associated with age (>60 years), tumor location (cardia of stomach), adenocarcinoma, and high/moderate differentiation. A significant relationship was found between Grb2 and HER2 expression using Chi-Square Tests and Spearman Correlation. Overexpression of Grb2 correlated significantly with poor survival rates in both univariate and multivariate analysis. CONCLUSIONS: Our data demonstrated a progressive amplification of Grb2 and HER2 expression in gastric carcinogenesis, suggesting the importance of Grb2 and HER2 as positive biomarkers for gastric cancer development and progression.

Prognostic value of the ratio of metastatic lymph nodes in gastric cancer: an analysis based on a Chinese population.

BACKGROUND AND OBJECTIVES: To determine the prognostic value of the ratio of metastatic lymph nodes (RML) for gastric cancer and compare it to the prognostic value of the number-based pN classification. METHODS: The survival of 513 patients who underwent curative resection between 2000 and 2005 was retrieved. The prognostic value of two factors for nodal status: RML classification (RML0, 0%; RML1, < or =30%; RML2, < or =50%; RML3, >50%) and pN classification (6th TNM system), was analyzed. RESULTS: Both RML and pN classifications were independent prognostic factors when considered separately in multivariate analysis (P-values < 0.05). Moreover, the proportion of explained variation (PEV) analysis showed that each classification had more prognostic value than other prognostic factors in two models respectively (P-values < 0.05). The D-measure for prognostic separation was 1.563 versus 1.383 for RML versus pN. Bootstrap results for the difference of D-measures did not show a significant difference between RML and pN in terms of prognostic power (95% CI, -0.102 to 0.175). CONCLUSIONS: RML is an independent prognostic factor for gastric cancer. However, no significant evidence is found to support the hypothesis that RML classification carries more prognostic value than pN classification.

A survey of cancer pain status in Shanghai.

This is a multicenter investigational survey conducted in 76 hospitals in Shanghai between July and August 2004. The objective was to investigate the cancer pain status and physicians' pain management capabilities in Shanghai. A total of 923 cancer patients involved in the investigation completed a questionnaire which included general condition, self-assessment of pain and questions of pain control knowledge. The study results were analyzed concerning: reason for cancer pain, type and intensity of cancer pain, treatment methods, patients' understanding of addiction, patients' request for pain treatment, and patients' and physicians' viewpoint on current cancer pain treatment.

Synergistic inhibitory activity of zoledronate and paclitaxel on bone metastasis in nude mice.

Zoledronic acid (Zometa, ZOL) and cytotoxic chemotherapy agents have been reported to have synergistic antitumor activities. However, there is limited data on the effects of combination therapies on the development of bone metastasis in animal models of lung cancer. The purpose of this study was to establish a human lung adenocarcinoma cell line with high bone metastatic potential in an immunodeficient mouse model and to evaluate the synergistic inhibitory activity of zoledronate and paclitaxel (P) on bone metastasis in nude mice. A human lung adenocarcinoma cell line with high bone metastatic potential (SPC-A1-BM) was established by 10 rounds of in vivo selection. Cells were inoculated into the cardiac ventricle of NIH-BNX mice, which were treated 8 days later with: ZOL (0.2 mg/kg s.c. twice weekly) alone, P (6.0 mg/kg every week, i.p.) alone, P + ZOL, or vehicle (10 mice per group). Tumor growth was evaluated with bone scans, X-rays and in situ immunohistochemistry. Serum n-telopeptide of type I collagen (NTX) was measured by ELISA. Survival was assessed using the Kaplan-Meier method. Bone scan, radiographic and histological assessments revealed fewer bone metastases in all treatment groups vs. vehicle, with P + ZOL significantly reducing the incidence of bone metastases detected by bone scans (P=0.020) and X-rays (P=0.036). A histological analysis revealed marginal differences in the number of bone metastases between P + ZOL and vehicle (P=0.058). There was a trend towards differences in survival between the groups (P=0.1511) and survival was significantly longer for the P + ZOL group vs. vehicle (P=0.022). Compared with vehicle and ZOL alone, cancerous cells in the bone of mice treated with P + ZOL expressed higher levels of Bax and lower levels of Bcl-2 and Bcl-xl. ZOL produced a trend towards reduced NTX levels vs. vehicle and P + ZOL produced a profound reduction in NTX vs. vehicle (P=0.022). The results of this study indicated that zoledronate enhanced the efficacy of paclitaxel synergistically, by reducing the incidence of bone metastasis from lung cancer and prolonging survival in a mouse model of non-small cell lung cancer with a high potential for metastasis to bone.