Adjuvant chemotherapy could not bring survival benefit to HR-positive, HER2-negative, pT1b-c/N0-1/M0 invasive lobular carcinoma of the breast: a propensity score matching study based on SEER database.

BACKGROUND: The benefit of adjuvant chemotherapy in invasive lobular carcinoma (ILC) is still unclear. The objective of the current study was to elucidate the effectiveness of adjuvant chemotherapy in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1b-c/N0-1/M0 ILC. METHODS: Based on Surveillance, Epidemiology, and End-Results (SEER) database, we identified original 12,334 HR-positive, HER2-negative, pT1b-c/N0-1/M0 ILC patients, who were then divided into adjuvant chemotherapy group and control group. End-points were overall survival (OS) and breast cancer-specific mortality (BCSM). Aiming to minimize the selection bias of baseline characteristics, Propensity Score Matching (PSM) method was used. RESULTS: In a total of 12,334 patients with HR-positive, HER2-negative, pT1b-c/N0-1/M0 ILC, 1785 patients (14.5%) were allocated into adjuvant chemotherapy group and 10,549 (85.5%) into control group. Used PSM, the 1785 patients in adjuvant chemotherapy group matched to the 1785 patients in control group. By Kaplan-Meier survival analyses, we observed no beneficial effect of adjuvant chemotherapy on OS in both original samples (P = 0.639) and matched samples (P = 0.962), however, ineffective or even contrary results of adjuvant chemotherapy on BCSM both in original samples (P = 0.001) and in matched samples (P = 0.002). In both original and matched multivariate Cox models, we observed ineffectiveness of adjuvant chemotherapy on OS (hazard ratio (HR) for overall survival = 0.82, 95% confidence interval (CI) [0.62-1.09]; P = 0.172 and HR = 0.90, 95%CI [0.65-1.26]; P = 0.553, respectively), unexpectedly promoting effect of adjuvant chemotherapy on BCSM (HR = 2.33, 95%CI [1.47-3.67]; P = 0.001 and HR = 2.41, 95%CI [1.32-4.39]; P = 0.004, respectively). Standard surgery was beneficial to the survival of patients. Lymph node metastasis was detrimental to survival and radiotherapy brought survival benefit in original samples, but two issues had unobvious effect in matched samples. CONCLUSION: In this study, adjuvant chemotherapy did not improve survival for patients with HR-positive, HER2-negative pT1b-c/N0-1/M0 ILC.

Cod skin peptide reduces chemotherapy-induced toxicity in gastric cancer patients.

BACKGROUND AND OBJECTIVES: The present study was conducted to evaluate the effect of cod skin peptide (CSPE) on chemotherapy-induced toxicity in gastric cancer patients. METHODS AND STUDY DESIGN: A cohort of 60 gastric cancer patients for chemotherapy was randomly divided into two groups (n=30 per group), who were orally treated with either supplemental CSPE or placebo apart from chemotherapy. The hematologic and gastrointestinal toxicities experienced by the patients, as well as their Karnofsky Performance Status (KPS) as an index of quality of life was evaluated. RESULTS: Leukocyte counts and haemoglobin levels were significantly reduced in the group treated with peptide (p<0.05), while gastrointestinal toxicity was not affected (p>0.05). KPS consists of 11 categories of quality of life, and the score denoted in deciles ranges from 100 (asymptomatic, normal function) to 0 (death). The KPS score is used to evaluate a cancer patient's ability to function at work and home, the severity of symptoms, and the patient's need for personal and medical care. Treatment with CSPE significantly improved the quality of life of patients, as indicated by increased KPS scores (p<0.05). CONCLUSIONS: CSPE can potentially be considered as a food supplement that can be used to improve the quality of life of cancer patients.

Electronic effects of the substituent on the dioxygen-activating abilities of substituted iron tetraphenylporphyrins: a theoretical study.

A density functional theoretical (DFT) method was applied to understand the effects of the substituent on dioxygen activation by a series of substituted iron tetraphenylporphyrins [FeT(o/p-R)PP (o = ortho-substituted, p = para-substituted; R = -H, -Cl, -NO2, -CH3, -OCH3)]. The ground states (GS) of the dioxygen adducts of the substituted iron tetraphenylporphyrins [FeT(o/p-R)PPO2] were determined at the B3LYP/6-31G(d) level without any symmetry constraints. Binding energy calculations indicated that the presence of electron-withdrawing substituents at the para position favors O2 binding. Calculations of the O-O bond length of the adsorbed dioxygen revealed that the influence of the p-substituent on the activation of dioxygen decreases in the order p-CH3 > p-Cl > p-OCH3 > -H > p-NO2, while the influence of the o-substituent decreases in the order o-NO2 > o-CH3 > o-Cl > o-OCH3 > -H. The low-lying excited states (LLES) of the FeT(o/p-R)PPO2 adducts suggest that the ability to activate dioxygen decreases in the order o-CH3 > o-OCH3 = -H > o-NO2 > o-Cl for o-substituents and p-CH3 > p-Cl > -H > p-NO2 > p-OCH3 for p-substituents. NBO charge population analysis and spin density analysis showed that substitution caused more ß-electrons to be transferred from the iron tetraphenylporphyrin to the dioxygen, which enhanced dioxygen activation. Spin density analysis confirmed that the ß-electron population at the adsorbed dioxygen is an accurate indicator of the degree of dioxygen activation. The trend observed in porphyrin catalytic activity as the substituent on the dioxygen adduct was varied is consistent with the trend in the binding energy. It is clear that substituents at the ortho and para positions in these dioxygen adducts play different roles in dioxygen activation.

CD243 gene polymorphism significantly associated with breast cancer susceptibility.

We aimed to obtain a summary risk estimate for CD243 gene polymorphism associated with breast cancer. A total of nine case-control studies, including 5,073 cancer patients and 7,498 control subjects, were pooled in our fixed effects meta-analysis of the association between CD243 gene polymorphism and risk of breast cancer. All data were analyzed by using Stata software (version 12.0). We found significant risk effects under TT vs. TC + CC genetic model [odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.01-1.18, P = 0.516], but not in other comparisons. Stratifying the pooled data by ethnicity and source of controls revealed that the association between the T allele and an increased risk of breast cancer was more pronounced among Asians (TT vs. CC: OR = 1.26, 95 % CI = 1.02-1.57, P = 0.720; TT vs. TC + CC: OR = 1.31, 95 % CI = 1.07-1.61, P = 0.708) and hospital-based studies (TT vs. CC: OR = 1.25, 95 % CI = 1.02-1.53, P = 0.877; TT vs. TC + CC: OR = 1.27, 95 % CI = 1.05-1.53, P = 0.540). No notable heterogeneity was indicated across studies. Our meta-analysis demonstrates that CD243 gene polymorphism may act as a predisposition factor for breast cancer, particularly in Asian populations.

Vascular endothelial growth factor gene polymorphism (-634G/C) and breast cancer risk.

The aim of this meta-analysis was to assess if the -634G/C polymorphism represents a predisposition factor for the risk of breast cancer. We included eight published case-control studies, in which a total of 6,175 cancer cases and 6,421 cancer-free controls were included. Pooled ORs and 95 % CIs were calculated by the fixed effects model to evaluate the association of the -634G/C polymorphism and breast cancer risk. When all studies were pooled, we did not find statistical evidence of any significant association with overall breast cancer risk (ORBB vs. bb = 1.00, 95 % CI = 0.93-1.07, P = 0.999; ORBB + Bb vs. bb = 1.00, 95 % CI = 0.95-1.05, P = 0.999; ORBB vs. Bb + bb = 1.03, 95 % CI = 0.96-1.09, P = 0.984; ORallele B vs. allele b = 1.01, 95 % CI = 0.97-1.05, P = 0.998; ORBb vs. bb = 0.99, 95 % CI = 0.92-1.06, P = 0.992). In further stratified analyses by ethnicity and control source, no significant association was revealed. This study suggests that the -634G/C polymorphism does not appear to represent a risk factor for breast cancer.

Poor metabolizers at the cytochrome P450 2C19 loci is at increased risk of developing cancer in Asian populations.

BACKGROUND: CYP2C19 encodes a member of the cytochrome P450 superfamily of enzymes, which play a central role in activating and detoxifying many carcinogens and endogenous compounds thought to be involved in the development of cancer. In the past decade, two common polymorphisms among CYP2C19 (CYP2C19*2 and CYP2C19*3) that are responsible for the poor metabolizers (PMs) phenotype in humans and cancer susceptibility have been investigated extensively; however, these studies have yielded contradictory results. METHODS AND RESULTS: To investigate this inconsistency, we conducted a comprehensive meta-analysis of 11,554 cases and 16,592 controls from 30 case-control studies. Overall, the odds ratio (OR) of cancer was 1.52 [95% confidence interval (CI): 1.23-1.88, P<10(-4)] for CYP2C19 PMs genotypes. However, this significant association vanished when the analyses were restricted to 5 larger studies (no. of cases ≥ 500 cases). In the subgroup analysis for different cancer types, PMs genotypes had an effect of increasing the risks of esophagus cancer, gastric cancer, lung cancer and hepatocellular carcinoma as well as head neck cancer. Significant results were found in Asian populations when stratified by ethnicity; whereas no significant associations were found among Caucasians. Stratified analyses according to source of controls, significant associations were found only in hospital base controls. CONCLUSIONS: Our meta-analysis suggests that the CYP2C19 PMs genotypes most likely contributes to cancer susceptibility, particularly in the Asian populations.

Quantitative assessment of common genetic variants on chromosome 5p12 and hormone receptor status with breast cancer risk.

Several genome-wide association studies on breast cancer (BC) have reported similar findings of a new susceptibility locus, 5p12. After that, a number of studies reported that the rs10941679, rs4415084, and rs981782 polymorphism in chromosome 5p12 has been implicated in BC risk. However, the studies have yielded contradictory results. To derive a more precise estimation of the relationship, a meta-analysis of 131,983 BC cases and 200,314 controls from 24 published case-control studies was performed. Overall, significantly elevated BC risk was associated with rs10941679, rs4415084, and rs981782 risk allele when all studies were pooled into the meta-analysis. In the subgroup analysis by ethnicity, significantly increased risks were found for the rs10941679 and rs4415084 polymorphism among Caucasians and East Asians, while no significant associations were observed for the two polymorphisms in African and other ethnic populations. For 5p12-rs981782, significant associations were only detected among Caucasians. In addition, we found that rs10941679 and rs4415084 on 5p12 confer risk, exclusively for estrogen receptor (ER)-positive tumors with per-allele OR of 1.16 (95% CI: 1.11-1.21; P<10(-5)) and of 1.14 (95% CI: 1.09-1.19; P<10(-5)) respectively. Ethnicity was identified as a potential source of between-study heterogeneity. In conclusion, this meta-analysis demonstrated that common variations are a risk factor associated with increased BC susceptibility, but these associations vary in different ethnic populations.

Substituent effects on geometric and electronic properties of iron tetraphenylporphyrin: a DFT investigation.

To investigate the effects of the substituents, substituent positions and axial chloride ligand on the geometric and electronic properties of the iron tetraphenylporphyrin (FeTPP), a series of the substituented iron tetraphenylporphyrins and their chlorides, FeT(o/p-R)PP and FeT(o/p-R)PPCl (R = -H, -Cl, -NO(2), -OH, -OCH(3)), were systematically calculated without any symmetry constraint by using DFT method. For geometric structure, the substituent position and axial Cl ligand change the configuration of the iron porphyrin obviously. The ortho-substituents prefer making the phenyls perpendicular to the porphyrin ring; the axial chloride draws the central Fe ion ~0.500 Å out of the porphyrin plane toward the ligand. With regard to electronic properties, it is found that E(LUMO) could be related to the catalytic activity. The electron-withdrawing group always lowers the energies of both frontier orbitals, while the electron-donating one heightens them simultaneously, but they affect the E(HOMO) and E(LUMO) in the same sequence, -NO(2) < -Cl < -H < -OH < -OCH(3). The substituent effects on the central Fe ion were explored by calculating NBO charge distribution, spin density and natural electron configuration.