Observational studies have reported an inverse relationship between selenium status (blood or toenail) and the risk of laryngeal cancer; however, the impact of low serum selenium level on survival ...has not been evaluated.
We conducted a prospective study of 296 patients diagnosed with laryngeal cancer in Szczecin, Poland. Serum selenium was measured at diagnosis and prior to treatment. Patients were followed from the date of diagnosis to death at five years. Vital status was obtained by linkage to the Polish National Death Registry.
The five-year survival after diagnosis was 82.0% (95% CI: 68% to 91%) for individuals in the highest quartile of serum selenium (> 66.8 μg/L) and was 28.6% (95% CI 19% to 42%) for individuals in the lowest quartile (<50.0 μg/L). In an age- and sex-adjusted analysis, the hazard ratio (HR) for death from all causes was 7.01 (95% CI 3.81 to 12.9) for patients in the lowest quartile of serum selenium, compared to those in the highest quartile. The corresponding multivariate HR was 3.07 (95% CI 1.59 to 5.94).
This study suggests that a selenium level in excess of 70 μg/L is associated with improved outcome among patients undergoing treatment for laryngeal cancer. Further studies are needed to evaluate if selenium supplementation to achieve this level might improve overall prognosis.
Selenium (Se) is an antioxidant nutrient whose deficiency can influence adverse outcomes of pregnancy. The aim of this study is to determine whether serum Se level in early healthy pregnancy may be a ...risk marker for pregnancy induced hypertension. We obtained data from our prospective study in which we recruited healthy women in weeks 10-14 of a single pregnancy. In this analysis, we examined 121 women who subsequently developed pregnancy-induced hypertension and matched 363 women who remained normotensive. We measured Se levels (using the ICP-MS technique) in the serum in weeks 10-14 of the pregnancy. The odds ratios of pregnancy-induced hypertension (95% confidence intervals) were calculated using multivariate logistic regression. We found that the mean Se level was lower in the case group compared to the control (57.51 vs. 62.89 μg/L;
= 2.6 × 10
). Excessive body mass index (BMI) and smoking influenced the estimated odds ratios. In the subgroup of women who had never smoked with normal pre-pregnancy BMI, the adjusted odds ratio (AOR) of pregnancy-induced hypertension was 15.34 (95% CI: 2.73-86.31,
= 0.002) for Se levels in the lowest quartile (≤57.68 µg/L), as compared to the highest quartile (>66.60 µg/L), after adjusting for all the accepted confounders. In the whole cohort, the prognostic value of Se by logistic regression showed that the area under curve (AUC) = 0.814. In our study, one can consider the role of Se as a risk marker of pregnancy-induced hypertension.
It has not yet been established, whether or not the maternal serum selenium (Se) in early pregnancy may be a risk marker of small-for-gestational age (SGA) birth weight. Selenium is important for ...human health and is involved in oxidative balance, a key element in the development of the placenta and fetus. This innovative study was nested in a prospective cohort of 750 women recruited in the 10-14th week of a single pregnancy, all of whom were healthy during recruitment. We examined mothers delivering SGA infants (with birth weight <10th percentile) (
= 48) and matched mothers delivering appropriate-for-gestational age (AGA) infants (between 10-90th percentile) (
= 192). We measured the maternal microelement concentrations in the serum from the 10-14th gestational week, using the inductively coupled plasma mass spectrometry (ICP-MS). The odds ratios of SGA (and 95% confidence intervals) were assessed in logistic regression. The mean maternal Se concentrations were lower in mothers in the SGA group compared to the AGA group (59.60 vs. 62.54 µg/L;
= 0.020). Women in the lowest Q
quartile of Se (≤56.60 µg/L) have about three times higher risk of SGA compared to women in the higher quartiles (Q
or Q
); the odds ratio of SGA was OR = 3.02 (
= 0.019) for Q
vs. Q
quartile. The risk profile graph confirms the results. We found that excessive pre-pregnancy BMI (body mass index) affected the estimated SGA odds ratios. Early pregnancy maternal serum selenium status can be a risk marker of SGA newborns and more research is needed in larger groups.
Early identification of women at risk of developing pregnancy-induced hypertension (PIH) is very important. The involvement of copper (Cu) and zinc (Zn) in the oxidative balance suggests the ...possibility of their association with this disease, in which oxidative stress plays a key role. However, it has not been established so far whether the microelement levels in early pregnancy may be risk markers of the disease, as prospective studies are limited in number. In our innovative single-center study, we identified from a prospective cohort of healthy women in the 10-14th week of a single pregnancy: women subsequently developing pregnancy-induced hypertension (
= 121) and matched women remaining normotensive (
= 363). We measured the concentrations of microelements in the serum from 10-14 week, using the inductively coupled plasma mass spectrometry (ICP-MS). The odds ratios of the disease (and 95% confidence intervals) were assessed in logistic regression. In the whole cohort, the odds ratio (OR) of PIH was 1.52 (
= 0.174) for women in the lowest (Q1) quartile of Cu (≤1540.58 µg/L) compared with women in the highest (Q4) quartile (>1937.46 µg/L), but adjusted odds ratio (AOR) was 2.17 (
= 0.019) after adjusted for pre-pregnancy body mass index (BMI) and gestational age at recruitment. The higher levels of Cu in the subgroup of BMI ≥ 25 kg/m
compared to normal BMI were found (1847.64 vs. 1673.36 µg/L;
< 0.0001). In the subgroup of women with the normal pre-pregnancy BMI, the adjusted odds ratio of PIH was AOR = 2.95 (
= 0.040) for Q1 vs. Q4 quartile. Our results suggest that lower Cu levels in early pregnancy may be connected with higher risk of PIH, but BMI affected estimated odds ratios. Zinc levels had no effect on the risk.
To estimate the rate of pathologic complete response (pCR) to neoadjuvant chemotherapy in BRCA1 mutation carriers according to chemotherapy regimen.
From a registry of 6,903 patients, we identified ...102 women who carried a BRCA1 founder mutation and who had been treated for breast cancer with neoadjuvant chemotherapy. Pathologic complete response was evaluated using standard criteria.
Twenty-four (24%) of the 102 BRCA1 mutation carriers experienced a pCR. The response rate varied widely with treatment: a pCR was observed in one (7%) of 14 women treated with cyclophosphamide, methotrexate, and fluorouracil (CMF); in two (8%) of 25 women treated with doxorubicin and docetaxel (AT); in 11 (22%) of 51 women treated with doxorubicin and cyclophosphamide (AC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC), and in 10 (83%) of 12 women treated with cisplatin.
A low rate of pCR was observed in women with breast cancer and a BRCA1 mutation who were treated with AT or CMF. A high rate of pCR was seen after treatment with cisplatin. An intermediate rate of PCR was associated with AC or FAC. The relative benefits of AC and platinum therapy need to be confirmed through follow-up of this and other cohorts.
Selective tumor cell cytotoxicity can be achieved through a synthetic lethal strategy using poly(ADP)-ribose polymerase (PARP) inhibitor therapy in BRCA1/2 mutation carriers in whom tumor cells have ...defective homologous recombination (HR) DNA repair. Platinum-based chemotherapy responses correlate with HR DNA repair capacity. Olaparib is a potent, oral PARP inhibitor that is well tolerated, with antitumor activity in BRCA1/2 mutation carriers.
Patients with BRCA1/2-mutated ovarian cancer were treated with olaparib within a dose-escalation and single-stage expansion of a phase I trial. Antitumor activity was subsequently correlated with platinum sensitivity.
Fifty patients were treated: 48 had germline BRCA1/2 mutations; one had a BRCA2 germline sequence change of unknown significance, and another had a strong family history of BRCA1/2-associated cancers who declined mutation testing. Of the 50 patients, 13 had platinum-sensitive disease, 24 had platinum-resistant disease, and 13 had platinum-refractory disease (according to platinum-free interval). Twenty (40%; 95% CI, 26% to 55%) achieved Response Evaluation Criteria in Solid Tumors (RECIST) complete or partial responses and/or tumor marker (CA125) responses, and three (6.0%) maintained RECIST disease stabilization for more than 4 months, giving an overall clinical benefit rate of 46% (95% CI, 32% to 61%). Median response duration was 28 weeks. There was a significant association between the clinical benefit rate and platinum-free interval across the platinum-sensitive, resistant, and refractory subgroups (69%, 45%, and 23%, respectively). Post hoc analyses indicated associations between platinum sensitivity and extent of olaparib response (radiologic change, P = .001; CA125 change, P = .002).
Olaparib has antitumor activity in BRCA1/2 mutation ovarian cancer, which is associated with platinum sensitivity.
The aim of this study was to assess the relationship between serum iron concentrations in early healthy pregnancy and the risk of pregnancy-induced hypertension. The data comes from our prospective ...cohort study in which we recruited healthy women in week 10-14 of single pregnancy. We examined a study group (
= 121) consisting of women subsequently developing pregnancy-induced hypertension and a control group (
= 363) of matched women remaining normotensive. We measured iron concentrations in the serum collected in 10-14 gestational week, using the ICP-MS technique (mass spectrometry with inductively coupled plasma). The odds ratios of the disease (95% confidence intervals) for iron concentrations were assessed in multivariate logistic regression. We found that the mean microelement concentration was lower in the case group compared to normotensive controls (
= 0.011). Women in the lowest quartile of iron (≤801.20 µg/L) had a 2.19-fold increase in pregnancy-induced hypertension risk compared with women in the highest quartile (>1211.75 µg/L) (odds ratio (OR) = 2.19; 95% CI: 1.24-3.88;
= 0.007). This result was sustained after adjusted for all the accepted confounders. Women in the higher Q
quartile (801.20-982.33 µg/L) had a 17% lower risk, compared with those in the highest quartile (OR = 0.83; 95% CI: 0.65-2.32;
= 0.519).
Olaparib (AZD2281), an orally active poly (ADP-ribose) polymerase inhibitor that induces synthetic lethality in BRCA1- or BRCA2-deficient cells, has shown promising clinical efficacy in nonrandomized ...phase II trials in patients with ovarian cancer with BRCA1 or BRCA2 deficiency. We assessed the comparative efficacy and safety of olaparib and pegylated liposomal doxorubicin (PLD) in this patient population.
In this multicenter, open-label, randomized, phase II study, patients with ovarian cancer that recurred within 12 months of prior platinum therapy and with confirmed germline BRCA1 or BRCA2 mutations were enrolled. Patients were assigned in a 1:1:1 ratio to olaparib 200 mg twice per day or 400 mg twice per day continuously or PLD 50 mg/m(2) intravenously every 28 days. The primary efficacy end point was Response Evaluation Criteria in Solid Tumors (RECIST) -assessed progression-free survival (PFS). Secondary end points included objective response rate (ORR) and safety.
Ninety-seven patients were randomly assigned. Median PFS was 6.5 months (95% CI, 5.5 to 10.1 months), 8.8 months (95% CI, 5.4 to 9.2 months), and 7.1 months (95% CI, 3.7 to 10.7 months) for the olaparib 200 mg, olaparib 400 mg, and PLD groups, respectively. There was no statistically significant difference in PFS (hazard ratio, 0.88; 95% CI, 0.51 to 1.56; P = .66) for combined olaparib doses versus PLD. RECIST-assessed ORRs were 25%, 31%, and 18% for olaparib 200 mg, olaparib 400 mg, and PLD, respectively; differences were not statistically significant. Tolerability of both treatments was as expected based on previous trials.
The efficacy of olaparib was consistent with previous studies. However, the efficacy of PLD was greater than expected. Olaparib 400 mg twice per day is a suitable dose to explore in further studies in this patient population.
Despite ongoing trials of PARP inhibitors in the treatment of breast cancer (BC), the extent of poly(ADP-ribose)polymerase-1 (PARP-1) protein expression in BCs, which may influence treatment results, ...is not known. The purpose of this report is to assess expression of PARP-1 in BC including
BRCA1
-associated, triple negative (TN), and basal-like tumors. Immunohistochemistry with a PARP-1 antibody on tissue microarrays from 130
BRCA1
-associated and 594
BRCA1
-non-related BCs was used. The vast majority of breast carcinomas expressed high level of nuclear PARP-1 protein and a small percentage of tumors exhibited both nuclear and cytoplasmic PARP-1 expression. There was a significant difference between the mean nuclear PARP-1 quickscore in
BRCA1
-associated versus
BRCA1
-non-associated carcinomas in all tumors (
P
< 0.0001), in the basal-like group (
P
= 0.0086), TN (
P
= 0.0015), and non-basal-like groups (
P
= 0.016) but not in the non-TN group. Among
BRCA1
-associated BCs, low PARP-1 expression was found in 18.5% of all cases, 18.9% of basal-like and 21% of TN cancers. Among
BRCA1
-non-related tumors, low PARP-1 expression was found in 8.8% of all cases, 3.1% of basal-like, and 2.7% of TN cancers. PARP-1 expression is significantly associated with
BRCA1
status in basal-like and TN BCs. The assessment of PARP-1 expression in tumor samples may improve the selection of BC patients for PARP inhibitor therapy.
Microelements involved in the oxidative balance have a significant impact on human health, but their role in pregnancy are poorly studied. We examined the relationships between first trimester levels ...of selenium (Se), iron (Fe), zinc (Zn), and copper (Cu), as well as maternal characteristics and pregnancy results. The data came from a Polish prospective cohort of women in a single pregnancy without chronic diseases. A group of 563 women who had a complete set of data, including serum microelements in the 10-14th week was examined, and the following were found: 47 deliveries <37th week; 48 cases of birth weight <10th and 64 newborns >90th percentile; 13 intrauterine growth restriction (IUGR) cases; 105 gestational hypertension (GH) and 15 preeclampsia (PE) cases; and 110 gestational diabetes mellitus (GDM) cases. The microelements were quantified using mass spectrometry. The average concentrations (and ranges) of the elements were as follows: Se: 60.75 µg/L (40.91-125.54); Zn: 618.50 µg/L (394.04-3238.90); Cu: 1735.91 µg/L (883.61-3956.76); and Fe: 1018.33 µg/L (217.55-2806.24). In the multivariate logistic regression, we found that an increase in Se of 1 µg/L reduces the risk of GH by 6% (AOR = 0.94;
= 0.004), the risk of IUGR by 11% (AOR = 0.89;
= 0.013), and the risk of birth <34th week by 7% (but close to the significance) (AOR = 0.93;
= 0.061). An increase in Fe of 100 µg/L reduces the risk of PE by 27% (AOR = 0.73;
= 0.009). In the multivariable linear regression, we found negative strong associations between prepregnancy BMI, Se (β = -0.130;
= 0.002), and Fe (β = -0.164;
< 0.0001), but positive associations with Cu (β = 0.320;
< 0.000001). The relationships between Se and maternal age (β = 0.167;
< 0.0001), Se and smoking (β = -0.106;
= 0.011) and Cu, and gestational age from the 10-14th week (β = 0.142;
< 0.001) were also found. Secondary education was associated with Zn (β = 0.132;
= 0.004) and higher education was associated with Cu (β = -0.102;
= 0.023). A higher financial status was associated with Fe (β = 0.195;
= 0.005). Other relationships were statistically insignificant. Further research is needed to clarify relationships between first trimester microelements and pregnancy complications. In addition, attention should be paid to lifestyle-related and socioeconomic factors that affect microelement levels.
PDF
