Radiotherapy plus anti-PD1 versus radiotherapy for hepatic toxicity in patients with hepatocellular carcinoma.

PURPOSE: In this study, we aimed to compare the radiation-induced hepatic toxicity (RIHT) outcomes of radiotherapy (RT) plus antibodies against programmed cell death protein 1 (anti-PD1) versus RT alone in patients with hepatocellular carcinoma (HCC), evaluate prognostic factors of non-classic radiation-induced liver disease (ncRILD), and establish a nomogram for predicting the probability of ncRILD. PATIENTS AND METHODS: Patients with unresectable HCC treated with RT and anti-PD1 (RT + PD1, n = 30) or RT alone (n = 66) were enrolled retrospectively. Patients (n = 30) in each group were placed in a matched cohort using propensity score matching (PSM). Treatment-related hepatotoxicity was evaluated and analyzed before and after PSM. The prognostic factors affecting ncRILD were identified by univariable logistic analysis and Spearman's rank test in the matched cohort to generate a nomogram. RESULTS: There were no differences in RIHT except for increased aspartate aminotransferase (AST) ≥ grade 1 and increased total bilirubin ≥ grade 1 between the two groups before PSM. After PSM, AST ≥ grade 1 occurred more frequently in the RT + PD1 group (p = 0.020), and there were no significant differences in other hepatotoxicity metrics between the two groups. In the matched cohort, V25, tumor number, age, and prothrombin time (PT) were the optimal prognostic factors for ncRILD modeling. A nomogram revealed a good predictive performance (area under the curve = 0.82). CONCLUSIONS: The incidence of RIHT in patients with HCC treated with RT + PD1 was acceptable and similar to that of RT treatment. The nomogram based on V25, tumor number, age, and PT robustly predicted the probability of ncRILD.

Design, synthesis, and evaluation of antitumor activity of novel C-6 sulfhydryl-substituted and 20-substituted derivatives of celastrol.

Celastrol has been identified as a potential candidate for anticancer drug development. In this study, 28 novel celastrol derivatives with C-6 sulfhydryl substitution and 20-substitution were designed and synthesized, and their antiproliferative activity against human cancer cells and non-malignant human cells was evaluated, with cisplatin and celastrol being used as controls. The results showed that most of the derivatives had enhanced in vitro anticancer activity compared to the parent compound celastrol. Specifically, derivative 2f demonstrated the most potent inhibitory potential and selectivity against HOS with an IC50 value of 0.82 µM. Our study provides new insights into the structure-activity relationship of celastrol and suggests that compound 2f may be a promising drug candidate for the treatment of osteosarcoma.

Proteomics and liquid biopsy characterization of human EMT-related metastasis in colorectal cancer.

Tumor cells undergo epithelial-mesenchymal transition (EMT), however, there is a room of disagreement in role of EMT heterogeneity to colorectal cancer metastasis (mCRC) evolution. To uncover new EMT-related metastasis proteins and pathways, we addressed the EMT status in colorectal cancer liver metastasis patient-derived CTCs to identify proteins that promote their distant metastasis. And then, we performed a comparative proteomic analysis in matched pairs of primary tumor tissues, adjacent mucosa tissues and liver metastatic tissues. By integrative analysis we show that, unstable Epithelial/Mesenchymal (E/M)-type CTCs had the strongest liver metastases formation ability and the proportion of E/M-type CTCs correlated with distant metastases. Using an optimized proteomic workflow including data independent acquisition (DIA) and parallel reaction monitoring (PRM), we identified novel EMT-related protein cluster (GNG2, COL6A1, COL6A2, DCN, COL6A3, LAMB2, TNXB, CAVIN1) and well-described (ERBB2) core protein level changes in EMT-related metastasis progression, and the proteomic data indicate ERBB2, COL6A1 and CAVIN1 are promising EMT-related metastatic biomarker candidates. This study contributes to our understanding of the role that EMT plays in CRC metastasis and identifies heterogeneous EMT phenotypes as a key piece for tumor progression and prognosis. We further propose that therapies targeting this aggressive subset (E/M-type) of CTCs and related protein may be worthy of exploration as potential suppressors of metastatic evolution.

Association of systemic inflammation and low performance status with reduced survival outcome in older adults with cancer.

BACKGROUND: Inflammation is involved in the progression and prognosis of cancer because it can affect the physical status and prognosis of patients. Among numerous systemic inflammatory markers, the optimal prognostic indicator of older adults with cancer is still unclear. We aimed to identify an ideal inflammatory immune marker in older adults with cancer and assess the survival outcome combined with eastern cooperative oncology group performance status (ECOG PS). METHODS: We included 1767 older adults with cancer (66.2% males, 70.97 ± 5.49 years old) from a prospective cohort study. Fifteen systemic inflammatory biomarkers were compared to identify the optimal biomarker using prognostic area under the curve (AUC) and concordance index (C-index) analysis. The prognostic value of the clinical parameters was elucidated by performing uni- and multivariate analyses. RESULTS: The AUC, C-index, and the subgroup survival analysis of ECOG PS groups showed that the lymphocyte-C reactive protein ratio (LCR) and C-reactive protein/albumin ratio (CAR) were more accurate in reflecting patient prognosis than the other 13 inflammatory markers. Compared with patients in the high LCR group, those in the low LCR group had worse survival (hazard ratio (HR) 1.64, 95% confidence interval (95%CI) 1.42-1.91, p < 0.001). Compared with patients in the low CAR group, those in the high CAR group had worse survival (HR 1.65, 95% CI 1.43-1.91, p < 0.001). Older adults with cancer with an ECOG PS score of 2 or 3-4 and a high inflammation (low LCR, 13.3 months and 9.2 months, respectively; or high CAR, 9.6 months and 9.6 months, respectively) had shorter median survival time compared to those with an ECOG PS score of 0/1 and a low inflammation (high LCR, 77.4 months; or low CAR, 77.0 months). CONCLUSION: LCR and CAR might be the better predictive immune inflammatory factors for OS, which improved the survival prediction of different ECOG PS groups in older adults with cancer. High ECOG PS (≥2) and high inflammation increased the risk of death in older adults with cancer.

MTUS1 is a promising diagnostic and prognostic biomarker for colorectal cancer.

BACKGROUND: The morbidity and mortality of colorectal cancer (CRC) remain high, posing a serious threat to human life and health. The early diagnosis and prognostic evaluation of CRC are two major challenges in clinical practice. MTUS1 is considered a tumour suppressor and can play an important role in inhibiting cell proliferation, migration, and tumour growth. Moreover, the expression of MTUS1 is decreased in different human cancers, including CRC. However, the biological functions and molecular mechanisms of MTUS1 in CRC remain unclear. METHODS: In the present study, data from The Cancer Genome Atlas (TCGA) database were analysed using R statistical software (version 3.6.3.) to evaluate the expression of MTUS1 in tumour tissues and adjacent normal tissues using public databases such as the TIMER and Oncomine databases. Then, 38 clinical samples were collected, and qPCR was performed to verify MTUS1 expression. We also investigated the relationship between MTUS1 expression and clinicopathological characteristics and elucidated the diagnostic and prognostic value of MTUS1 in CRC. In addition, the correlation between MTUS1 expression and immune infiltration levels was identified using the TIMER and GEPIA databases. Furthermore, we constructed and analysed a PPI network and coexpression modules of MTUS1 to explore its molecular functions and mechanisms. RESULTS: CRC tissues exhibited lower levels of MTUS1 than normal tissues. The logistic regression analysis indicated that the expression of MTUS1 was associated with N stage, TNM stage, and neoplasm type. Moreover, CRC patients with low MTUS1 expression had poor overall survival (OS). Multivariate analysis revealed that the downregulation of MTUS1 was an independent prognostic factor and was correlated with poor OS in CRC patients. MTUS1 expression had good diagnostic value based on ROC analysis. Furthermore, we identified a group of potential MTUS1-interacting proteins and coexpressed genes. GO and KEGG enrichment analyses showed that MTUS1 was involved in multiple cancer-related signalling pathways. Moreover, the expression of MTUS1 was significantly related to the infiltration levels of multiple cells. Finally, MTUS1 expression was strongly correlated with various immune marker sets. CONCLUSIONS: Our results indicated that MTUS1 is a promising biomarker for predicting the diagnosis and prognosis of CRC patients. MTUS1 can also become a new molecular target for tumour immunotherapy.

Clinical implications and biological features of a novel postoperative recurrent HCC classification: A multi-centre study.

BACKGROUND & AIMS: The multiplicity of hepatocellular carcinoma (HCC) recurrence patterns is the most important determinant of patients' postsurgical survival. A systematic HCC recurrence classification is needed to help prevent and treat postoperative HCC recurrence in the era of precision medicine. METHODS: A total of 1319 patients with recurrent HCC from four hospitals were enrolled and divided into a development cohort (n = 916), internal validation cohort (n = 225) and external validation cohort (n = 178). A comprehensive study of patients' clinicopathological factors and biological features was conducted. RESULTS: Four subtypes of recurrence were identified, which integrated recurrence features, survival, effects on systemic and liver function and potential therapeutics after recurrence: type I (solitary-intrahepatic oligorecurrence); type II (multi-intrahepatic oligorecurrence); type III (progression recurrence) and type IV (hyper-progression recurrence). Type III~IV recurrence indicated exceptionally poor prognosis. Subsequently, two nomogram models were established for type III~IV recurrence prediction, and both demonstrated excellent predictive performance and applicability of pre and postoperative strategy formulation. Multiple biological analyses revealed that HCC cases with type III~IV recurrence were characterized by enrichment in p53 mutations, CCND1 amplification, high proliferation/metastasis potential, inactive metabolism and immune exhaustion features. Over-expression of high mobility group protein 2 (HMGA2) enhanced the highly malignant behaviour of HCC through multiple molecular pathways, making it a potential prognostic predictor and therapeutic target. CONCLUSIONS: This 'recurrent HCC classification' has important potential value in identifying patients with surgical benefit, predicting postsurgical survival and guiding treatment strategies. Multidimensional biological insights also increased knowledge of factors associated with HCC recurrence.

Microwave ablation versus laparoscopic resection as first-line therapy for solitary 3-5-cm HCC.

BACKGROUND AND AIMS: The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time. APPROACH AND RESULTS: From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008-2019 (n = 335 in each group) and 2014-2019 (n = 257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65-1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05-1.75, p = 0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95% CI 0.56-1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98-1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0-cm HCCs (HR 0.88, 95% CI 0.53-1.47, p = 0.630) and 4.1-5.0-cm HCCs (HR 0.77, 95% CI 0.37-1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001). CONCLUSIONS: MWA might be a first-line alternative to LLR for solitary 3-5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.

Huaier granule prevents the recurrence of early-stage hepatocellular carcinoma after thermal ablation: A cohort study.

ETHNOPHARMACOLOGICAL RELEVANCE: Clinical trials have demonstrated that Trametes robinophila Murr (Huaier granule) can inhibit recurrence and metastasis after hepatocellular carcinoma (HCC) resection, but its efficacy as an adjuvant therapy after thermal ablation of early HCC is unknown. AIM OF THE STUDY: To analyze the prognostic value and side effects of Huaier granules in HCC patients undergoing thermal ablation. MATERIALS AND METHODS: Clinical information from 340 eligible subjects with early-stage HCC who were admitted to our department from September 1, 2008 to January 1, 2019 was extracted from the electronic medical record database. They were divided into the thermal ablation + TCM group and the thermal ablation group. Differences in their overall survival (OS), progression-free survival (PFS), extrahepatic metastatic rate (EMR), and therapeutic side effects (TSEs) between the two groups were compared. Beneficiaries of the integrated treatment and adequate treatment length were predicted. RESULTS: The median follow-up was 32.5 months (range 2-122 months). The 1-year, 3-year and 5-year OS rates in the integrated treatment group and the control group were 93.2% vs. 92.6%, 54.5% vs. 51.4%, 23.5% vs. 19.7% (p = 0.110, HR 0.76(0.54-1.07)). The 1-year, 3-year and 5-year PFS rates were 78.8% vs. 69.4%, 50.6% vs. 40.6%, 35.3% vs. 26.5%, respectively (p = 0.020, HR 0.67(0.48-0.94)). The median OS (35 vs. 31 months) and PFS (24 vs. 12.5 months) were longer in the integrated treatment group. The EMR in the integrated treatment group was significantly lower than that in the control group (p = 0.018, HR 0.49 (0.27-0.89)). Patients with any two of the following three factors might be predicted to be beneficiaries of the integrated treatment, including younger than 65 years (p =0.039, HR 0.70 (0.50-0.98)), single tumor (p = 0.035, HR 0.70 (0.50-0.98), and tumor size ≤3 cm (p = 0.029, HR 0.69 (0.50-0.96). Patients with continuous oral administration of TCM following ablation had a lower probability of recurrence and metastasis within 2 years (p = 0.015, HR 0.67 (0.49-0.93)). Although the integrated treatment group reported a higher incidence of nausea and emesis, there were no significant differences between the two groups. CONCLUSION: TCM following ablation may prolong PFS and suppress recurrence in patients with HCC, with continuous oral administration for more than 2 years maybe experience a greater benefit. The TSEs of the treatment are mild and can be tolerated.

OX40 as a novel target for the reversal of immune escape in colorectal cancer.

First-generation immunological checkpoint inhibitors, such as CTLA-4, PD-L1 and PD-1 exhibit significant advantages over conventional cytotoxic drugs, such as oxaliplatin and 5-FU, for the treatment of colorectal cancer. However, these inhibitors are not ideal due to their low objective response rate and the vulnerability of these treatment methods when faced with emerging drug resistant cancers. This study summarizes the immunological characteristics of colorectal cancer treatment, and analyzes the ways in which OX40 may improve the efficacy of these treatments. Activation of the OX40 signaling pathway can enhance the activity of CD4+/CD8+ T cells and inhibit the function of Treg. Simultaneously, OX40 can directly inhibit the expression of Foxp3, affect the inhibitory function of Treg, and inhibit the immunosuppressive factors in the tumor microenvironment so as to reverse immune escape and reverse drug resistance. Therefore, OX40 is an important target for treating colorectal cancer in "cold tumors" with less immunogenicity.

Retrospective study of preoperative chemoradiotherapy with capecitabine versus capecitabine plus oxaliplatin for locally advanced rectal cancer.

This study aimed to evaluate whether the addition of oxaliplatin to a neoadjuvant chemoradiotherapy (CRT) regimen could improve survival benefit in locally advanced rectal cancer (LARC) patients. We retrospectively analysed 73 LARC patients (cT2-4 and/or cN1-2) who received preoperative CRT with capecitabine followed by surgery (arm A, 43 patients) or capecitabine plus oxaliplatin followed by surgery (arm B, 30 patients). The main endpoints of the study were pathologic complete response (pCR) rate, overall survival (OS) and disease-free survival (DFS). The secondary endpoints included the sphincter preservation rate and safety. The pCR for arms A and B were 28% and 17% (P = 0.267). In arms A and B, the mean OS was 84.287 months (95% CI 68.413-100.160) and 106.333 months (95% CI 99.281-113.386) (P = 0.185); the mean DFS was 72.812 months (95% CI 56.271-89.353) and 95.073 months (95% CI 83.392-106.754) (P = 0.310); and the sphincter preservation rates were 72% and 67%, respectively (P = 0.619). The incidence of grade 3 toxicity was much higher in arm B than in arm A (57% vs. 21%, P = 0.002). Adding oxaliplatin to a preoperative CRT regimen for LARC did not improve the survival benefits of patients or increase toxicity.

A nomogram for preoperative prediction of lymphatic infiltration in colorectal cancer: A personalized approach to clinical decision making.

Lymphatic infiltration (LI) is a key factor affecting the treatment of patients with colorectal cancer (CRC). Thus, the aim of this study was to develop and validate a nomogram for individual preoperative prediction of LI in patients with CRC.We conducted a retrospective analysis of 664 patients who received their initial diagnosis of CRC at our center. Those patients were allocated to a training dataset (n = 468) and a validation dataset (n = 196). The least absolute shrinkage and selection operator regression model was used for data dimension reduction and feature selection. The nomogram was constructed from the training dataset and internally verified using the concordance index (C-index), calibration, area under the receiver operating characteristic curve and decision curve analysis (DCA).The enhancement computed tomography reported N1/N2 classification, preoperative tumor differentiation, elevated carcinoembryonic antigen, and carbohydrate antigen19-9 level were selected as variables for the prediction nomogram. Encouragingly, the nomogram showed favorable calibration with C-index 0.757 in the training cohort and 0.725 in validation cohort. The DCA signified that the nomogram was clinically useful. The Kaplan-Meier survival curve showed that patients with LI had a worse prognosis and could benefit from postoperative adjuvant chemotherapy.Use common clinicopathologic factors, a non-invasive scale for individualized preoperative forecasting of LI was established conveniently. LI prediction has great significance for risk stratification of prognosis and treatment of resectable CRC.

Single-nucleotide polymorphisms in the coding region of a disintegrin and metalloproteinase with thrombospondin motifs 4 and hepatocellular carcinoma: A retrospective case-control study.

Previous studies have shown that single-nucleotide polymorphisms (SNPs) of a disintegrin and metalloproteinase with thrombospondin type 1 motif 4 (ADAMTS4) may involve in the pathogenesis of some diseases. However, it is not clear whether they are associated with hepatocellular carcinoma (HCC). A hospital-based case-control study, including 862 cases with HCC and 1120 controls, was conducted to assess the effects of 258 SNPs in the coding regions of ADAMTS4 on HCC risk and prognosis. We found that six SNPs in ADAMTS4 were differential distribution between cases and controls via the primary screening analyses; however, only rs538321148 and rs1014509103 polymorphisms were further identified to modify the risk of HCC (odds ratio: 2.73 and 2.95; 95% confidence interval, 2.28-3.29 and 2.43-3.58; P-value, 5.73 × 10-27 and 1.36 × 10-27 , respectively). Significant interaction between these two SNPs and two known causes of hepatitis B virus and aflatoxin B1 were also observed. Furthermore, rs538321148 and rs1014509103 polymorphisms were associated not only with clinicopathological features of tumor such as tumor stage and grade, microvessel density, and vessel metastasis, but with poor overall survival. Additionally, these SNPs significantly downregulated ADATMS4 expression in tumor tissues. These data suggest that SNPs in the coding region of ADAMTS4, such as rs538321148 and rs1014509103, may be potential biomarkers for predicting HCC risk and prognosis.

Targeting snoRNAs as an emerging method of therapeutic development for cancer.

The relevance of the dysregulation of snoRNAs in human cancer has been widely investigated and has challenged the view that snoRNAs merely function as house-keeping genes for the posttranscriptional modification of rRNAs. Accumulating evidence has shown the intimate connection between snoRNAs and proliferation, apoptosis, invasion and migration of tumor cells via manual intervention patterns of snoRNA expression. In this review, we focused on how snoRNAs are dysregulated and its regulation of the formation and development of cancer. We summarized the non-classical functions of snoRNAs in the context of their regulations of the signaling pathways involving PI3K-AKT and K-Ras and p53-dependant manner. Under these novel functions and characteristics, snoRNAs can act as potential and feasible biomarkers for diagnosis. Simultaneously, these promising therapeutic strategies should be considered to counteract the perturbations of snoRNAs.

Radiofrequency-Sensitive Longitudinal Relaxation Tuning Strategy Enabling the Visualization of Radiofrequency Ablation Intensified by Magnetic Composite.

As a minimally invasive heat source, radiofrequency (RF) ablation still encounters potential damages to the surrounding normal tissues because of heat diffusion, high power, and long time. With a comprehensive understanding of the current state of the art on RF ablation, a magnetic composite using porous hollow iron oxide nanoparticles (HIONs) as carriers to load dl-menthol (DLM) has been engineered. This composite involves two protocols for enhancing RF ablation, that is, HION-mediated magnetothermal conversion in RF field and RF solidoid vaporation (RSV)-augmented inertial cavitation, respectively. A combined effect based on two protocols is found to improve energy transformation, and further, along with hydrophobic DLM-impeded heat diffusion, improve the energy utilization efficiency and significantly facilitate ex vivo and in vivo RF ablation. More significantly, in vitro and in vivo RSV processes and RSV-augmented inertial cavitation for RF ablation can be monitored by T1-weighted magnetic resonance imaging (MRI) via an RF-sensitive longitudinal relaxation tuning strategy because the RSV process can deplete DLM and make HION carriers permeable to water molecules, consequently improving the longitudinal relaxation rate of HIONs and enhancing T1-weighted MRI. Therefore, this RF-sensitive magnetic composite holds a great potential in lowering the power and time of RF ablation and improving its therapeutic safety.

Prolonging Gastrointestinal-Stromal-Tumor-free life, an optimal suggestion of imatinib intervention ahead of operation.

Background: Imatinib has been regarded as the first successful synthetic small molecule targeting at blocking tyrosine kinase. Its high efficacy stabilized disease in above 80% of chronic myeloid leukemia (CML) patients over 10 years survival. Due to the similar canceration of gastrointestinal stromal tumor (GIST) as to CML, imatinib has been approved to be used as first-line treatment. Study design: Our retrospective study was proposed to enroll 191 GIST patients with larger tumor size (≥8 cm) who preoperative accepted imatinib from those with direct operation. Analysis included demographics, cancer specific survival and relationship of their risk factors. Results: Male patients and gastrointestinal (GI) tract location took higher proportion in total cases, detection of KIT mutant took 89.7% among all traceable genetic testing. Patients with preoperative imatinib can achieve higher cancer specific survival (CSS) after both in 1 year and 3 years duration than their counterpart. Tumor size above its threshold of 8 cm would be a hazardous factor for poor prognosis. Conclusion: In conclusion, as for regressing tumor progression and creating operative chance, preoperative imatinib should be considered for the patients with high risk, although the precise duration of this intervention needs further validation.

High pretreatment plasma D-dimer predicts poor survival of colorectal cancer: insight from a meta-analysis of observational studies.

D-dimer, one of the canonical markers of hypercoagulability, was reported to be a potential prognostic marker of colorectal cancer. However, an inconsistent conclusion existed in several published studies. Thus, we performed this meta-analysis to provide a comprehensive insight into the prognostic role for pretreatment D-dimer in colorectal cancer. Six databases (English: Pubmed, Embase and Web of Science; Chinese: CNKI, Wangfang and VIP) were utilized for the literature retrieval. Hazard ratio (HR) was pooled by Stata 12.0. A total of fifteen studies (2283 cases) corresponded to this meta-analysis and provided available data to evaluate the prognostic role of D-dimer for colorectal cancer. The pooled HR reached 2.167 (95%. CI (confidence interval): 1.672-2.809, P < 0.001) utilizing random effect model due to obvious heterogeneity among the included studies (I2: 73.3%; P < 0.001). To explore the heterogeneity among the studies, we conducted a sensitivity analysis and found a heterogeneous study. After removing it, the heterogeneity reduced substantially (I2: 0%; P = 0.549) and we obtained a more convincing result by fixed effect model (HR = 2.143, 95% CI = 1.922-2.390, P < 0.001, 14 studies with 2179 cases). In summary, high pretreatment plasma D-dimer predicts poor survival of colorectal cancer based on the current evidence. Further prospective researches are necessary to confirm the role of D-dimer in colorectal cancer.

Cyclooxygenase-2 promoter 765C increase of digestive tract cancer risk in the Chinese population: a meta-analysis.

BACKGROUND: To evaluate relationship between the cyclooxygenase-2 promoter 765G/C polymorphism and digestive cancer risk in China. MATERIALS AND METHODS: A literature search through February 2014 was performed using PubMed, Chinese Biomedical Literature Database (CBM) and China National Knowledge Infrastructure (CNKI) databases, and a meta-analysis was performed with RevMan 5.2 software for odds ratios and 95%CIs. RESULTS: In total, 9 articles with 3,263 cases and 4,858 controls were included in this meta-analysis.The pooled OR (95%CIs) in the co-dominant model (GC vs GG) was 1.56 [1.19, 2.06], and in the dominant model ((CC+GC) vs GG), the pooled OR was 1.59 [1.21, 2.09] in overall cancers. In the subgroup analysis, stratified by cancer type, significant associations were found that the-765C allele had increased pancreatic cancer and gastric risk. No significant liver cancer and colorectal cancer risk of COX-2 -765G/C polymorphism was found. CONCLUSIONS: These findings suggest that COX-2-765*C is related to cancer susceptibility and may increase gastric and pancreatic cancer risk.

S-1-based therapy versus S-1 monotherapy in advanced gastric cancer: a meta-analysis.

This study aimed to derive a more precise estimate of the prognostic significance of S-1-based therapy over S-1 monotherapy in patients with advanced gastric cancer (AGC), including overall survival (OS) time, progression-free survival (PFS) time, objective response rate (ORR), and adverse events (AEs). Studies stratifying OS, PFS, ORR, and AEs in AGC patients in an S-1-based therapy versus an S-1 monotherapy setting were eligible for analysis by systematic computerized PubMed, Embase and Cochrane Library searches. Data from these studies were pooled using STATA package version 11.0. Six studies that investigated outcomes in a total of 913 AGC cases, of which 443 (48.5%) received S-1-based therapy and 470 (51.5%) received S-1 monotherapy, were included in the meta-analysis. Median OS and median PFS were significantly prolonged in AGC patients receiving S-1-based therapy compared with those receiving S-1 monotherapy (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.71-0.96, P = 0.015, and HR 0.69, 95% CI 0.60-0.80, P = 0.000, respectively). The ORR favored patients with S-1-based therapy (OR 1.65, 95% CI 1.34-2.06, P = 0.000). Higher incidence of grade 3/4 neutropenia was found in patients with S-1-based therapy (P = 0.000). For the Asian population, S-1-based therapy significantly improved OS and PFS and enhanced ORR in comparison to S-1 monotherapy. The safety profile was poorer in patients with S-1-based therapy, but could be considerable between the S-1-based therapy and S-1 monotherapy group. Our conclusion needs to be confirmed via high-quality trials and the results need to be reproduced in other regions and populations.

[Influence and significance of preoperative intraarterial infusion chemotherapy combined with radiotherapy on survivin, p53 and Bax expression in low rectal carcinoma].

BACKGROUND & OBJECTIVE: Recently, neoadjuvant therapy has attracted more attention, but the influence of preoperative intraarterial infusion chemotherapy (PRAC) combined with radiotherapy on Survivin expression in rectal carcinoma is unclear. This study was to investigate the effect of PRAC or radiotherapy on Survivin, P53, and Bax expression in low rectal cancer. METHODS: A total of 60 patients with low rectal carcinoma were randomized into 3 groups: 19 received PRAC combined with preoperative radiotherapy (radiochemotherapy group), 15 received preoperative radiotherapy alone (radiotherapy group), and 26 received operation alone (control group). PRAC was performed using Seldinger technique. Preoperative radiotherapy was performed with a total dose of 20 Gy in 5 days, and superadded 30 Gy after operation. Control group received postoperative radiotherapy with a total dose of 50 Gy. The expression of Survivin, P53, and Bax was examined by immunohistochemistry. RESULTS: After neoadjuvant therapy, there was no significant difference in the positive rates of Survivin, P53, and Bax among the 3 groups. In radiochemotherapy group, the positive rate of Survivin was reduced from 63.16% before neoadjuvant therapy to 26.32% after operation (P<0.05), and the overexpression rate of P53 was reduced from 57.89% to 26.32% (P<0.05). In radiotherapy group, the overexpression rate of Survivin was reduced from 53.33% to 13.33% (P<0.05), but there was no significant change in the positive rate of P53. The positive rate of Bax was slightly increased after operation in above 2 groups. In these 2 groups, the median survival time was significantly longer in the patients with reduced Survivin expression than in those with increased Survivin expression (50.05 months vs. 42.61 months, P<0.01). Survivin expression was not obviously related to Bax and P53 expression (P>0.05). CONCLUSION: Neoadjuvant therapy could decrease the levels of P53 and Survivin expression, might enhance the level of Bax expression, and consequently accelerate cancer cell apoptosis and achieve a better short-term curative effect on low rectal cancer.

[Expression of P33ING1, P53 and their relationship with apoptosis in anal canal carcinoma].

OBJECTIVE: To explore the expressions of P33ING1, P53 and their relationships with apoptosis in anal canal carcinoma (ACC). METHODS: The expressions of P33ING1, P53 proteins were measured by immunohistochemistry method (SP method), and apoptosis was detected in 42 cases with ACC, 36 cases with anal canal adenoma (ACA) or anal canal papilloma (ACP), and 40 cases with paraanal inflammatory mass(PAIM). RESULTS: The positive expression rates of P33ING1 and P53 proteins were 40.5% (17/42), 97.2% (35/36) and 97.5% (39/40), 50.0% (21/42), 22.2% (8/36) and 27.5% (11/40) respectively, and the average apoptosis indexes(AI) were (10.27+/- 1.23) per thousand, (42.75+/- 0.98) per thousand and (42.67+/- 1.04) per thousand respectively in ACC, ACA or ACP and PAIM. There were significant differences in the positive expression rates of P33ING1, P53 and apoptosis index between ACC and the other two groups respectively (P< 0.05). Among 21 cases of ACC with positive expression of P53 protein,there were 18 cases with P33ING1 negative expression. CONCLUSIONS: P33ING1 expression decrease in ACC, which may play an important role in the carcinogenesis and progression of ACC. P33ING1 and P53 may have an synergistic effect of suppressing cell growth and accelerating cell apoptosis.