Real­world evidence of advanced non­small cell lung carcinoma treated with an immune checkpoint inhibitor plus chemotherapy.

Immunotherapy is an effective treatment strategy for patients with advanced non-small cell lung cancer (NSCLC). Although clinical trials on immunotherapy have provided promising results, real-world research in clinical practice is needed to assess the effectiveness and safety of immunotherapy. The present study aimed to characterize real-world outcomes in patients with advanced NSCLC treated with immune checkpoint inhibitor (ICI)-based regimens. The medical records of patients with advanced NSCLC, who were treated with programmed cell death protein-1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) inhibitors, were reviewed for data collection. The primary objectives were to evaluate progression-free survival (PFS) and overall survival (OS). Therefore, multiple Cox regression models were used to investigate the predictive factors for survival outcomes. Furthermore, survival curves for PFS and OS were created using Kaplan-Meier estimates and compared using the log-rank test. The present study included a total of 133 patients with advanced NSCLC who received therapy with ICIs between January 1, 2019 and December 31, 2022. The final follow-up date was August 24, 2023. The median PFS and OS times were 9.8 and 27.2 months, respectively. Univariate Cox regression analysis demonstrated that sex, clinical stage, PD-L1 status, previous systemic therapy, and brain and liver metastases were associated with PFS, while Eastern Cooperative Oncology Group (ECOG) status, clinical stage, PD-L1 status and brain metastasis were associated with OS. Furthermore, multivariate Cox regression analysis demonstrated that a PD-L1 tumor proportion score (TPS) of ≥50% was an indicator of favorable PFS and OS. An ECOG performance status score of ≥1 was also associated with poor OS but not with PFS. Furthermore, brain metastasis was an indicator for poor PFS and OS, while liver metastasis was only associated with a poor PFS. Finally, the results of the present study demonstrated that PD-L1 status was an independent predictor for PFS and OS in patients with advanced NSCLC, especially adenocarcinoma, who were treated with ICIs plus chemotherapy. The results also suggested that patients with a PD-L1 TPS of ≥50% could benefit when the aforementioned regimens were administrated as a first-line or later-line therapy.

Investigating the Influence of Diverse Functionalized Carbon Nanotubes as Conductive Fibers on Paper-Based Sulfur Cathodes in Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are expected to be one of the next generations of high-energy-density battery systems due to their high theoretical energy density of 2600 Wh kg-1. Embracing the trends toward flexibility, lightweight design, and cost-effectiveness, paper-based electrodes offer a promising alternative to traditional coated cathodes in Li-S batteries. Within paper-based electrodes, conductive fibers such as carbon nanotubes (CNTs) play a crucial role. They help to form a three-dimensional network within the paper matrix to ensure structural integrity over extended cycling while mitigating the shuttle effect by confining sulfur within the cathode. Herein, we explore how variously functionalized CNTs, serving as conductive fibers, impact the physical and electrochemical characteristics of paper-based sulfur cathodes in Li-S batteries. Specifically, graphitized hydroxylated carbon nanotubes (G-CNTs) exhibit remarkable capacity at low currents owing to their excellent conductivity and interaction with lithium polysulfide (LiPS), achieving the highest initial specific capacity of 1033 mAh g-1 at 0.25 C (1.1 mA cm-2). Aminated multi-walled carbon nanotubes (NH2-CNTs) demonstrate an enhanced affinity for LiPS due to the -NH2 groups. However, the uneven distribution of these fibers may induce electrode surface passivation during charge-discharge cycles. Notably, hydroxylated multi-walled carbon nanotubes (OH-CNTs) can establish a uniform and stable 3D network with plant fibers, showcasing superior mechanical properties and helping to mitigate Li2S agglomeration while preserving the electrode porosity. The paper-based electrode integrated with OH-CNTs even retains a specific capacity of approximately 800 mAh g-1 at about 1.25 C (5 mA cm-2), demonstrating good sulfur utilization and rate capacity compared to other CNT variants.

The 2023 MANCTRA Acute Biliary Pancreatitis Care Bundle: A Joint Effort Between Human Knowledge and Artificial Intelligence (ChatGPT) to Optimize the Care of Patients With Acute Biliary Pancreatitis in Western Countries.

OBJECTIVE: To generate an up-to-date bundle to manage acute biliary pancreatitis using an evidence-based, artificial intelligence (AI)-assisted GRADE method. BACKGROUND: A care bundle is a set of core elements of care that are distilled from the most solid evidence-based practice guidelines and recommendations. METHODS: The research questions were addressed in this bundle following the PICO criteria. The working group summarized the effects of interventions with the strength of recommendation and quality of evidence applying the GRADE methodology. ChatGPT AI system was used to independently assess the quality of evidence of each element in the bundle, together with the strength of the recommendations. RESULTS: The 7 elements of the bundle discourage antibiotic prophylaxis in patients with acute biliary pancreatitis, support the use of a full-solid diet in patients with mild to moderately severe acute biliary pancreatitis, and recommend early enteral nutrition in patients unable to feed by mouth. The bundle states that endoscopic retrograde cholangiopancreatography should be performed within the first 48 to 72 hours of hospital admission in patients with cholangitis. Early laparoscopic cholecystectomy should be performed in patients with mild acute biliary pancreatitis. When operative intervention is needed for necrotizing pancreatitis, this should start with the endoscopic step-up approach. CONCLUSIONS: We have developed a new care bundle with 7 key elements for managing patients with acute biliary pancreatitis. This new bundle, whose scientific strength has been increased thanks to the alliance between human knowledge and AI from the new ChatGPT software, should be introduced to emergency departments, wards, and intensive care units.

Endoscopic retrograde appendicitis therapy versus appendectomy or antibiotics in the modern approach to uncomplicated acute appendicitis: A systematic review and meta-analysis.

INTRODUCTION: Endoscopic retrograde appendicitis therapy has been proposed as an alternative strategy for treating appendicitis, but debate exists on its role compared with conventional treatment. METHODS: This systematic review was performed on MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE. The last search was in April of 2023. The risk ratio with a 95% confidence interval was calculated for dichotomous variables, and the mean difference with a 95% confidence interval for continuous variables. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool (randomized controlled trials) and the Risk of Bias in Non-Randomized Studies of Intervention tool (non-randomized controlled trials). RESULTS: Six studies met the eligibility criteria. Four studies compared endoscopic retrograde appendicitis therapy (n = 236 patients) and appendectomy (n = 339) and found no differences in technical success during index admission (risk ratio 0.97, 95% confidence interval [0.92,1.02]). Appendectomy showed superior outcomes for recurrence at 1-year follow-up (risk ratio 11.28, 95% confidence interval [2.61,48.73]). Endoscopic retrograde appendicitis therapy required shorter procedural time (mean difference -14.38, 95% confidence interval [-20.17, -8.59]) and length of hospital stay (mean difference -1.19, 95% confidence interval [-2.37, -0.01]), with lower post-intervention abdominal pain (risk ratio 0.21, 95% confidence interval [0.14,0.32]). Two studies compared endoscopic retrograde appendicitis therapy (n = 269) and antibiotic treatment (n = 280). Technical success during admission (risk ratio 1.11, 95% confidence interval [0.91,1.35]) and appendicitis recurrence (risk ratio 1.07, 95% confidence interval [0.08,14.87]) did not differ, but endoscopic retrograde appendicitis therapy decreased the length of hospitalization (mean difference -1.91, 95% confidence interval [-3.18, -0.64]). CONCLUSION: This meta-analysis did not identify significant differences between endoscopic retrograde appendicitis therapy and appendectomy or antibiotics regarding technical success during index admission and treatment efficacy at 1-year follow-up. However, a high risk of imprecision limits these results. The advantages of endoscopic retrograde appendicitis therapy in terms of reduced procedural times and shorter lengths of stay must be balanced against the increased risk of having an appendicitis recurrence at one year.

Do high soil geochemical backgrounds of selenium and associated heavy metals affect human hepatic and renal health? Evidence from Enshi County, China.

It is unclear whether the United States Environmental Protection Agency (US EPA) method can accurately assess heavy metal risks in high-Se areas. Herein, a black shale outcropping in Enshi County, China, was taken as the study area, and a carbonate outcropping in Lichuan County was the control area. Selenium and associated heavy metal concentrations in rock, soil, rice, human blood and urine samples and human sensitive hepatic and renal biomarkers were measured. The results showed that the contents of selenium, cadmium, molybdenum and copper in the study area were 3.68 ± 2.72 µg/g, 2.65 ± 1.42 µg/g, 16.3 ± 15.5 µg/g, and 57.3 ± 17.6 µg/g, respectively, in soil (n = 47) and 1.072 ± 0.924 µg/g, 0.252 ± 0.310 µg/g, 2.800 ± 2.167 µg/g, and 10.91 ± 27.42 µg/g, respectively, in rice (n = 47). The daily adult intake levels of selenium, cadmium and molybdenum from rice consumption in the study area (exposure group) exceed the recommended tolerance values in China. According to the US EPA method, these environmental media pose a significant risk to human health. However, in the exposure group (n = 111), the median levels of the sensitive hepatic biomarkers alanine aminotransferase (18 U/L), aspartate aminotransferase (28 U/L) and total bilirubin (10.9 µmol/L) and the sensitive renal biomarkers serum creatinine (70.1 µmol/L), urinary nitrogen (5.73 mmol/L) and uric acid (303.80 µmol/L) were within reference ranges and had values equivalent to those of the control group (P > 0.05). The elements tended to differentiate during migration from one medium to another. Due to the complex interaction between selenium and heavy metals, a survey of human health indicators is indispensable when the US EPA method is used to assess the heavy metal risks in high-Se areas. The recommended molybdenum tolerable intake in the U.S. (2000 µg/d) is reasonable based on a comparison.

Ion recognition properties of 2,2'-bibenzimidazole regulated by ammonium-modified pillar[5]arenes.

With the increasing issues of environmental degradation and health problem, the selective detection of toxic ions has attracted considerable attention from researchers. Chemical fluorescent sensors with the advantages of facile operation, high sensitivity, rapid response, and easy visualization are emerging as powerful detection tools towards ions. However, the selective recognition of ions is always hindered by the presence of other interfering substances. Herein, we show that supramolecular host-guest interaction based on a pillar[5]arene provides a new opportunity to regulate the ionic recognition properties of guest molecules. A pillar[5]arene-based host-guest complex HG was constructed through the host-guest interaction between ammonium functionalized pillar[5]arene (HAP5) and 2,2'-bibenzimidazole (G). The host-gust complex HG can realize the successive, highly selective, and sensitive detection of specific ions. It was found that only in the presence of HAP5, the sensitivity towards cations was evidently enhanced, and selective successive recognition for I- and HSO4- was achieved. Those results indicate that the introduction of HAP5 can effectively improve the ion recognition performance of 2,2'-bibenzimidazole, so it is a feasible strategy using supramolecular host-guest interaction to regulate the ionic recognition properties of guest molecules.

Are laparoscopic cholecystectomy and natural orifice transluminal endoscopic surgery gallbladder preserving cholecystolithotomy truly comparable? A propensity matched study.

BACKGROUND: Cholecystectomy is the preferred treatment option for symptomatic gallstones. However, another option is gallbladder-preserving cholecystolithotomy which preserves the normal physiological functions of the gallbladder in patients desiring to avoid surgical resection. AIM: To compare the feasibility, safety and effectiveness of pure natural orifice transluminal endoscopic surgery (NOTES) gallbladder-preserving cholecystolithotomy vs laparoscopic cholecystectomy (LC) for symptomatic gallstones. METHODS: We adopted propensity score matching (1:1) to compare trans-rectal NOTES cholecystolithotomy and LC patients with symptomatic gallstones. We reviewed 2511 patients with symptomatic gallstones from December 2017 to December 2020; 517 patients met the matching criteria (NOTES, 110; LC, 407), yielding 86 pairs. RESULTS: The technical success rate for the NOTES group was 98.9% vs 100% for the LC group. The median procedure time was 119 min [interquartile ranges (IQRs), 95-175] with NOTES vs 60 min (IQRs, 48-90) with LC (P < 0.001). The frequency of post-operative pain was similar between NOTES and LC: 4.7% (4/85) vs 5.8% (5/95) (P = 0.740). The median duration of post-procedure fasting with NOTES was 1 d (IQRs, 1-2) vs 2 d with LC (IQRs, 1-3) (P < 0.001). The median post-operative hospital stay for NOTES was 4 d (IQRs, 3-6) vs 4 d for LC (IQRs, 3-5), (P = 0.092). During follow-up, diarrhea was significantly less with NOTES (5.8%) compared to LC (18.6%) (P = 0.011). Gallstones and cholecystitis recurrence within a median of 12 mo (range: 6-40 mo) following NOTES was 10.5% and 3.5%, respectively. Concerns regarding the presence of abdominal wall scars were present in 17.4% (n = 15/86) of patients following LC (mainly women). CONCLUSION: NOTES provides a feasible new alternative scar-free treatment for patients who are unwilling or unable to undergo cholecystectomy. This minimally invasive organ-sparing procedure both removes the gallstones and preserves the physiological function of the gallbladder. Reducing gallstone recurrence is essential to achieving widespread clinical adoption of NOTES.

Endoscopic retrograde appendicitis therapy versus laparoscopic appendectomy for uncomplicated acute appendicitis.

BACKGROUND: Endoscopic retrograde appendicitis therapy (ERAT) is a new and minimally invasive technique for the treatment of acute appendicitis. This study aimed to assess the efficacy and clinical outcomes of ERAT versus laparoscopic appendectomy for patients with uncomplicated acute appendicitis. METHODS: We adopted propensity score matching (1:1) to compare ERAT and laparoscopic appendectomy in patients with uncomplicated acute appendicitis between April 2017 and March 2020. We reviewed 2880 patients with suspected acute appendicitis, of whom 422 patients with uncomplicated acute appendicitis met the matching criteria (ERAT 79; laparoscopic appendectomy 343), yielding 78 pairs of patients. RESULTS: The rate of curative treatment within 1 year after ERAT was 92.1 % (95 % confidence interval [CI] 83.8 % to 96.3 %). The percentage of patients recording visual analog scale values of  ≤ 3 for pain at 6 hours after treatment was 94.7 % (95 %CI 87.2 % to 97.9 %) in the ERAT group, which was significantly higher than that in the laparoscopic appendectomy group (83.3 %; 95 %CI 73.5 % to 90.0 %). Median procedure time and median hospital length of stay were significantly lower in the ERAT group compared with the laparoscopic appendectomy group. At 1 year, the median recurrence time was 50 days (interquartile range 25-127) in the ERAT group. The overall adverse event rate was 24.4 % (95 %CI 14.8 % to 33.9 %) in the laparoscopic appendectomy group and 18.4 % (95 %CI 9.7 % to 27.1 %) in the ERAT group, with no significant difference between the two groups. CONCLUSION: ERAT was a technically feasible method of treating uncomplicated acute appendicitis compared with laparoscopic appendectomy.

Case Report: Squamous Cell Carcinoma of Pancreas With High PD-L1 Expression: A Rare Presentation.

Primary pancreatic squamous cell carcinoma is sporadic. The diagnosis is usually made following surgery or needle biopsy and requires a thorough workup to exclude metastatic squamous cell carcinoma. Squamous cell carcinoma of the pancreas often has a very poor prognosis. There is no treatment guideline for this type of cancer, and to date, no therapeutic regimen has been proven effective. Here, we report the effectiveness of immunotherapy in combination with chemotherapy against locally advanced squamous cell carcinoma of the pancreas with high programmed cell death ligand 1 (PD-L1) expression. Regional intra-arterial infusion chemotherapy consisting of nab-Paclitaxel followed by gemcitabine infused via gastroduodenal artery every three weeks for two cycles. This therapy resulted in the depletion of carcinoma, and the patient continues to lead a high-quality life with no symptoms for more than 16 months.

Circulating tumor cells predict prognosis following secondline AZD 9291 treatment in EGFR-T790M mutant non-small cell lung cancer patients.

PURPOSE: AZD9291 has been developed as third-generation epithermal growth factor receptor (EGFR)- tyrosine kinase inhibitor (TKI) with activities against T790M mutation. This study aimed to isolate and quantify the circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) patients after first-line EGFR TKIs and investigate their role in providing prognostic information. METHODS: Enrolled patients confirmed with EGFR T790M mutation received AZD9291 80 mg orally once daily as second-line treatment. Serial blood samples were taken at baseline (CTC-d0) and on day 28 (CTC-d28) following the initiation of AZD9291 for detection of CTCs using the Cell-Search system. RESULTS: The CTC measurements were dichotomized as favorable (<5 CTCs) and unfavorable (≥5 CTCs) groups. Patients in the favorable group at baseline exhibited significantly longer median progression-free survival (PFS) compared with patients in the unfavorable group (9.3 vs. 6.5 months; p=0.0002). The PFS interval for patients in the favorable group on day 28 was 9.7 months, significantly longer than the median PFS time of 6.2 months achieved by patients in the unfavorable group (p=0.011). In univariate and multivariate analysis, CTC-d0 ≥5 vs CTC-d0=0-4 was significantly associated with poor PFS. CONCLUSIONS: This is the first report over the presence of CTCs and their prognostic role in patients with EGFR T790M-positive NSCLC following disease progression on an EGFR TKI. The use of serial CTC evaluation as a surrogate biomarker needs further validation in larger samples of patients.

The RNASEL -1385G/A polymorphism is associated with risk of prostate cancer in Africans.

The RNASEL -1385G/A (rs486907) variant has been reported to be associated with increased risk of prostate cancer. However, these associations are not consistent among studies. To address this issue, we performed a meta-analysis to evaluate the association between RNASEL -1385G/A polymorphism and prostate cancer risk. The PubMed, Embase, and Web of Science databases were searched for relevant papers published in the past 20 years from 1997 to 2017. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of associations. Based on our search for manuscripts reporting prostate cancer susceptibility related to the rs486907 polymorphism, 16 case-control studies from 13 different publications were retrieved. No significantly positive associations were found for the polymorphism and prostate cancer susceptibility in the total population. When stratified by ethnicity, the results demonstrated that the -1385G/A polymorphism was associated with a decreased cancer risk in Africans (GG vs AA: OR =0.371, 95% CI =0.176-0.783; GG/GA vs AA: OR =0.368, 95% CI =0.175-0.776). We also found that the rs486907 polymorphism was associated with a decreased cancer risk in hospital-based controls (GG vs AA: OR =0.697, 95% CI =0.488-0.996; GG + GA vs AA: OR =0.701, 95% CI =0.502-0.978). Our meta-analysis suggests that polymorphism in the RNASEL gene is a protective factor against prostate cancer in Africans. Further studies using larger sample sizes should be conducted to elucidate the role of gene polymorphism in prostate cancer risk.

Circulating Tumor Cells Predict Prognosis Following Tyrosine Kinase Inhibitor Treatment in EGFR-Mutant Non-Small Cell Lung Cancer Patients.

Epithelial growth factor receptor (EGFR) mutations are present in 10%-26% of non-small cell lung cancer (NSCLC) tumors and are associated with the response to tyrosine kinase inhibitors (TKIs). This study aimed to detect and quantify the presence of circulating tumor cells (CTCs) in EGFR-mutant NSCLC patients and investigate their possible role in providing prognostic information. Enrolled patients received erlotinib (150 mg) or gefitinib (250 mg) orally once daily as the first-line treatment. Serial blood samples were taken at baseline (CTC-d0) and on day 28 (CTC-d28) following the initiation of erlotinib/gefitinib for detection of CTCs using the CellSearch system. CTCs ≥2 were found in 47/107 (44%) and CTCs ≥5 in 17/107 (15%). The CTC measurements were dichotomized as favorable (<5 CTCs) and unfavorable (≥5 CTCs) groups. The median progression-free survival (PFS) interval for patients in the favorable group at baseline was 11.1 months, significantly longer than the median PFS time of 6.8 months achieved by patients in the unfavorable group (p = 0.009). Patients in the favorable group on day 28 exhibited significantly longer PFS compared with patients in the unfavorable group (11.6 vs. 6.3 months; p < 0.0001). In univariate analysis, CTC-d0 ≥ 5 versus CTC-d0 = 0-4 was significantly associated with poor PFS and time-to-treatment failure (TTF). CTC-d28 ≥ 5 versus CTC-d28 = 0-4 was significantly associated with a poor PFS outcome. CTC-d0 and CTC-d28 remained independent poor prognostic markers in the stepwise multivariate analysis. Our study indicates that the CTC count is a prognostic factor for PFS and TTF outcomes in patients with advanced EGFR-mutant NSCLC.

Relationship between ADH2 Arg47His variation and hepatocellular carcinoma susceptibility: a meta analysis.

BACKGROUND: To further investigate the relationship between ADH2 Arg47His variation and hepatocellular carcinoma (HCC) susceptibility through a meta-analysis. METHODS: The related articles were searched in PubMed, Embase and CNKI databases. And finally 518 cases and 607 controls were included in our meta-analysis Odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the relationship between ADH2 Arg47His variation and HCC risk. A fixed-effect model or a random-effect model was applied according to the between-study heterogeneity. RESULTS: Quantitative synthesis demonstrated that no significant association was found between ADH2 Arg47His variation and HCC susceptibility (His/His vs. Arg/Arg: OR=0.99, 95% CI=0.79-1.25; His/His + Arg/His vs. Arg/Arg: OR=1.01, 95% CI=0.86-1.20; His/His vs. Arg/Arg + Arg/His: OR=0.90, 95% CI=0.74-1.11; His vs. Arg: OR=0.98, 95% CI=0.86-1.11; Arg/His vs. Arg/Arg: OR=1.05, 95% CI=0.82-1.34). CONCLUSION: Our analysis showed that ADH2 Arg47His vvariation may not be associated with HCC susceptibility.

Polymorphisms in the vitamin D receptor (VDR) genes and skin cancer risk in European population: a meta-analysis.

There have been a few epidemiological studies reporting VDR polymorphisms including Fok1, Bsm1, Apa1 and Taq1 with skin cancer incidence and, therefore, risk. The results, however, are controversial, often due to smaller sample size. Concerning most of the studies were performed on Caucasian population, we conducted this comprehensive analysis to better understand roles of the polymorphisms in skin cancer development among Caucasian population. The results showed that Fok1 polymorphism was associated with an overall significantly increased risk of skin cancer (Ff vs. FF: OR = 1.20, 95 % CI = 1.01-1.44; ff vs. FF: OR = 1.41, 95 % CI = 1.08-1.84; Ff + ff vs. FF: OR = 1.26, 95 % CI = 1.04-1.53). Besides, we found that Taq1 polymorphism could contribute to non-melanoma skin cancer susceptibility (Tt vs. TT: OR = 1.88, 95 % CI = 1.29-2.74; tt vs. TT: OR = 2.00, 95 % CI = 1.22-3.28; Tt + tt vs. TT: OR = 1.92, 95 % CI = 1.35-2.73). We also found that the Apa1 polymorphism is associated with skin cancer development (Aa vs. AA: OR = 1.27, 95 % CI = 1.05-1.53; Aa + aa vs. AA: OR = 1.23, 95 % CI = 1.04-1.47) and NMSC subgroup (Aa vs. AA: OR = 1.72, 95 % CI = 1.51-2.57; Aa + aa vs. AA: OR = 1.50, 95 % CI = 1.03-2.17). No significant association was observed between the Bsm1 polymorphism and skin cancer risk. The current meta-analysis shows that Fok1, Taq1 and Apa1 may be the susceptibility biomarker for skin cancer in Caucasians.

Current evidence on the four polymorphisms of VDR and breast cancer risk in Caucasian women.

There have been a few epidemiological studies reporting VDR polymorphisms including Fok1, Bsm1, Apa1 and Taq1with breast cancer incidence and therefore risk. The results however are controversial, often due to smaller sample size. Concerning most of the studies were performed on Caucasian women, we conducted this comprehensive meta-analysis encompassing 38,151 cases and 47,546 controls (Fok1: 13,152 cases, 17,443 controls; Bsm1: 14,755 cases, 18,633 controls; Apa1: 3080 cases, 3412 controls; Taq1: 7164 cases, 8068 controls) to better understand roles of the polymorphisms in breast cancer development among Caucasian population. We did not find any association of the most controversial genotype Fok1 with breast cancer risk in Caucasian women (ff vs. FF: OR = 1.05, 95% CI = 0.95-1.22, P = 0.32 for heterogeneity; ff vs. Ff: OR = 1.05, 95% CI = 0.94-1.17, P = 0.40; ff vs. Ff + FF: OR = 1.07, 95% CI = 0.95-1.14, P = 0.37 and ff + Ff vs. FF: OR = 1.04, 95% CI = 0.99-1.09, P = 0.23). For Bsm1, Apa1 and Taq1, no significant association was also not found in the homozygote comparison, heterozygote comparison, recessive and dominant models respectively. In conclusion, the current analysis suggested that the four polymorphisms (Fok1, Bsm1, Apa1 and Taq1) of VDR may be not associated with breast cancer risk in Caucasian women.

The association between TP53 Arg72pro polymorphism and non-melanoma skin cancer risk: a meta-analysis including 7,107 subjects.

BACKGROUND: The p53 gene is a critical molecular in the protection of cells from DNA damage due to Ultraviolet (UV) exposure, and TP53 mutation is very common in non-melanoma skin cancer. OBJECTIVES: To assess the association between the TP53 Arg72Pro polymorphism and non-melanoma skin cancer (NMSC) risk. METHODS: We performed this meta-analysis with 13 case-control studies involving 3,520 cases and 3,587 controls. RESULTS: Our meta-analysis showed that TP53 Arg72Pro polymorphism was not associated with non-melanoma skin cancer susceptibility in overall population.(for Arg/Arg vs. Pro/Pro: OR 0.98, 95% CI 0.80-1.19; for Arg/Pro vs. Pro/Pro: OR 0.99, 95% CI 0.84-1.17; for the recessive model Arg/Arg vs. Arg/Pro + Pro/Pro: OR 1.10, 95% CI 0.89-1.35; for the dominant model Arg/Arg + Arg/Pro vs. Pro/Pro: OR 1.00, 95% CI 0.85-1.18). We also detected no effect of this polymorphism on any subtype of non-melanoma skin cancer, such as squamous cell carcinoma (SCC), and basal cell carcinoma (BCC). Furthermore, no significant association in any subgroup was detected in stratified analyses according to ethnicity. However, in the stratified analysis by sample collection resources, Arg/Arg carriers from tumor tissue subgroup had 3.42 times risk of cancer (95% CI, 1.19 to 9.84) as compared with the variant type Pro/Pro in NMSC. CONCLUSIONS: TP53 Arg72Pro polymorphism may have little involvement in the pathogenesis of NMSC, regardless of type, including SCC, and BCC.

IDO⁺ DCs and signalling pathways.

Dendritic cells (DCs) have traditionally been viewed as constituting an 'information management' system that functions solely to integrate a diverse array of incoming signals, in order to induce immune reactivity. In recent years, however, there has been a shift towards viewing these cells as key regulators in the orchestration of immunological tolerance, with increasing recognition that they are capable of suppressing T-cell responses depending on signalling processes and localised biochemical conditions. Indoleamine 2,3-dioxygenase (IDO) competent (IDO⁺) DCs are a subset of human DCs which are programmed to a tolerogenic state and play a vital role in establishing and maintaining a tumour-suppressing milieu. The expression of IDO in these DCs represents a key mechanism responsible for inducing the tolerogenic state. However, the mechanisms by which IDO becomes dysregulated in this subset of DCs have not yet been described. In this review, the function of IDO⁺ DCs within the cancer-tolerogenic milieu, as well as the signals responsible for expression of IDO in this subset, will be discussed.