Although oncological treatments are improving, the prognosis of non-small-cell lung cancer (NSCLC) patients has not. Several biomarkers related to prognosis have been evaluated, and M30 and M65 have ...been reported to be higher in patients with NSCLC than in healthy people. In the current study, we evaluated the clinical importance of the change in serum M30 and M65 values after chemotherapy in patients with NSCLC. Serum M30 and M65 values were measured before and 48 h after chemotherapy in thirty-two patients with advanced NSCLC. The importance of the change in the levels of these markers after chemotherapy was analyzed by univariate analysis. The median serum M65 and M30 values increased significantly after chemotherapy (
p
< 0.001). The median M30 value after chemotherapy was an important prognostic factor for both overall survival (OS) (
p
= 0.002) and progression-free survival (PFS) (
p
= 0.002). Stage and histopathological type were significant both for PFS and OS. Multivariate analysis showed that the median M30 value after chemotherapy was the only independent prognostic factor for PFS (
p
= 0.04, HR 5.4) and OS (
p
= 0.02, HR 11.49). Our results indicated that both serum M30 and M65 values increased after chemotherapy in patients with advanced NSCLC, and an elevated serum M30 value was an independent prognostic factor for both PFS and OS.
After total (TG) or distal subtotal gastrectomy (DG), patients are at high risk of vitamin B^sub 12^ (vit-B^sub 12^) deficiency, which results in elevation of homocysteine levels. The changing of ...serum vit-B^sub 12^ and homocysteine levels in patients with gastric cancer is not well known. Seventy-two patients with gastric cancer who had undergone currative gastrectomy and 50 healthy controls were included. Serum vit-B^sub 12^ and homocysteine levels were analyzed in gastric cancer patients. In addition, these parameters were compared with those of healthy control subjects. While serum vit-B^sub 12^ levels in gastrectomized patients were significantly lower than that of healthy controls (221.8±125.6 pg/mL vs. 309.9±174.3 pg/mL, p=0.002), homocysteine levels were significantly higher in patients with gastric cancer (14.2±6.7 mumol/L vs. 12.5±6.1 mumol/L, p=0.016). Mean serum folate level was found to be high in healthy controls (7.3 ng/mL) compared to patients (9.2 ng/mL, p=0.027). Out of 72 patients, 40 patients (55.6 %) with gastric cancer developed vit-B^sub 12^ deficiency after gastrectomy. Vit-B^sub 12^ deficiency was found to be related with gastrectomy type (p=0.02) and homocysteine levels (p=0.014). In patients who underwent TG, the incidence of vit-B^sub 12^ deficiency was significantly higher compared with those with DG (67.5 vs. 32.5 %). In addition, serum vit-B^sub 12^ level in patients with DG was significantly higher than that of patients with TG (248.3±122.0 pg/mL vs. 200.8±126.7 pg/mL, p=0.041), whereas homocysteine levels were significantly lower in DG group compared with TG group (12.1±6.1 mumol/L vs. 15.8±6.9 mumol/L, p=0.014). A logistic regression analysis showed that the extent of gastrectomy was found to be an independent factor for predicting the occurrence of vit-B^sub 12^ deficiency (p<0.001, odds ratio 1.38). Our results showed that cumulative vit-B^sub 12^ deficiency rate was significantly higher after TG compared with that after DG, while homocysteine levels were significantly higher in TG group compared with DG group. The extent of gastrectomy was found to be an independent factor for predicting the occurrence of vit-B^sub 12^ deficiency. Vit-B^sub 12^ deficiency and hyperhomocysteinemia are imperious clinical situation for patients with gastric cancer after surgery. Hence, both preoperative and regular postoperative monitoring of vit-B^sub 12^ and homocysteine levels for all gastrectomized patients with gastric cancer are important and necessary for early detection and prevention of vit-B^sub 12^ deficiency and hyperhomocysteinemia as a risk factor for cardiovascular diseases.
Background
M30 and M65 are derivatives of cytokeratin 18 and released from the epithelial cell during cell death. These markers can be used to evaluate prognosis and chemotherapy response in several ...tumours. We evaluated serum M30 and M65 values in patients with advanced non-small-cell lung cancer (NSCLC) compared with those in a healthy group.
Material and methods
Thirty-two patients with advanced NSCLC and thirty-two healthy people were included in the study. Serum M30 and M65 values were measured by quantitative ELISA method. The best cut-off value for serum M65 was calculated by ROC analysis and then univariate analysis was performed to determine the importance of M65 value in predicting progression-free survival (PFS).
Results
There were no differences between mean serum M30 values between patients and controls (445.44±536.17 vs. 340.56±345.07,
p
=1). The mean serum M65 values were found to be significantly higher in patients than in healthy controls (1421.30±1662.59 vs. 648.85±341.17,
p
<0.001). The best cut-off value for serum M65 predicting PFS was 1311.64 U/l (AUC 0.58, sensitivity and specificity were 45.5% and 85.7% respectively). The patients with serum M65 values ≥1311.64 U/l had worse PFS than patients with serum M65 values <1311.64 U/l,
p
=0.01). There was no correlation between serum M30 value and PFS in the patient group (
p
=0.4).
Conclusions
Our results indicated that serum M65 values elevated in advanced NSCLC compared to a healthy control group and elevated serum M65 level can predict PFS in patients.
In some studies, the prognostic and predictive significance of M30 and M65 has been reported to detect response to chemotherapy. In the present study, we aimed at determining the changes of serum M30 ...and M65 values after chemotherapy and the impact of these values on treatment response and progression-free survival (PFS) and overall survival (OS) of patients with advanced gastric cancer. A total of 31 patients with advanced gastric cancer was included. M30 and M65 values were measured by a quantitative enzyme-linked immunosorbent assay (ELISA) method in serum samples before and 48 h after the first chemotherapy cycle. Pre- and postchemotherapy values of M30 and M65 were compared. The difference between the mean values of serum M30 and M65 before and after chemotherapy was calculated and the prognostic significance of changes for survival was evaluated by univariate and multivariate analysis. Logistic regression analysis was performed to predict response to chemotherapy. Serum M30 and M65 levels were found to be increased significantly after chemotherapy (M30, 582.7 ± 111.5 U/l pre mean vs. 983.3 ± 214.1 U/l post mean,
p
= 0.01; M65, 2,061.7 ± 431.2 U/l pre mean vs. 2,646.3 ± 433.1 U/l post mean,
p
= 0.003). Means of the differences of M30 and M65 levels before and 48 h after chemotherapy were 400.5 ± 190 U/l (M30-difference M30-D) and 584.6 ± 335.4 U/l (M65-D), respectively. Patients with serum M30-D of <400.5 U/l had better median PFS and OS times than patients with M30-D >400.5 U/l (PFS, 9.9 vs. 4.3 months,
p
= 0.018 and OS, 13.6 vs. 8.1 months,
p
= 0.029). In addition, median PFS and OS intervals in patients with serum M65-D > 584.6 U/l were significantly worse than those of patients whose M65-D was lower than or equal to 584.6 U/l (4.1 vs. 11.4 months for PFS,
p
= 0.002 and 5.7 vs. 13.6 months for OS,
p
= 0.005). Patients with values above M30-D and M65-D had a better tumor response compared with patients with values below M30-D and M65-D (
p
= 0.02 and
p
= 0.006, respectively). In the logistic regression analysis, only M65-D was significantly found to be an independent factor in predicting response to chemotherapy (
p
= 0.018, OR:1.4). However, only M30 levels after chemotherapy were found to be an independent prognostic factor for PFS in the multivariate analysis. These results showed for the first time that both M30 and M65 in serum samples of patients with advanced gastric cancer were elevated 48 h after chemotherapy and these were poor prognostic factors for both PFS and OS of patients. Moreover, increased serum M65 levels after chemotherapy can be predict tumor response.
Because the mechanisms of 5-Fluorouracil (5-FU) cardiotoxicity have not yet been completely identified, prophylactic options are not available. To our knowledge, there are no published data ...investigating the use of angiotensin converting enzyme (ACE) inhibitors for 5-Fluorouracil-associated cardiotoxicity. In this study, we aimed to evaluate the influence of 5-FU administration on the diameter of the brachial artery and the levels of angiotensin II. The patients were administered bolus 5-FU/leucovorin in the study group. Angiotensin II and troponin T assays, complete blood cell counts, hepatic and renal function tests were analyzed in five consecutive blood samples in the initiation, just after termination, and on 24, 48, and 72 h after termination of the regimen. Pre- and post-treatment angiotensin II and troponin T assays, complete blood cell counts, hepatic and renal function tests were also analyzed in the control group. Brachial arterial diameters were measured and recorded in all patients before and after the treatment. A total of 59 patients were included in this study. Thirty one out of 59 patients (52.5%) were in the 5-FU study group and the remaining 28 patients (47.5%) were in the control group. Basal and post-treatment brachial artery diameters in the 5-FU study group were 0.436 ± 0.51 and 0.423 ± 0.50 cm, respectively (
P
= 0.001). The corresponding values in the controls were 0.3954 ± 0.50 and 0.3957 ± 0.49 cm, basal and post-treatment, respectively (
P
= 0.979). Angiotensin II levels were not changed significantly at serial measurements (
P
= 0.496). Moreover, the corresponding measurements were not statistically different in both two groups treated with and without 5-FU (
P
= 0.372). The pathophysiology of 5-FU-induced cardiac toxicity has not yet been elucidated. In the present study, 5-FU-associated vasoconstriction was not dependent on angiotensin II levels, thus we suggest that the prophylactic administration of ACE inhibitors cannot prevent cardiotoxicity in these patients. The underlying mechanisms of cardiotoxicity related to 5-FU might be multifactorial; nevertheless, further prospective investigation for the toxic effects of fluoropyrimidines on the coronary endothelium and myocardium are needed.
Adiponectin is a peptide hormone secreted from the adipose tissue, affecting the proliferation and insulin sensitivity in different cell types. The levels of adiponectin have been found to be ...decreased in hyperinsulinemia and insulin resistant states, such as obesity. The previous studies have suggested that plasma adiponectin levels are decreased in patients with endometrial and breast cancer. In our study, the relationship among serum adiponectin levels, demographic features and histopathological variables was evaluated in gastric cancer patients. Forty consecutive patients with gastric cancer who underwent gastrectomy with standard lymph node dissection were included and 43 healthy controls were included in this study. The serum levels of glucose, insulin, C-peptide, HbA1c and adiponectin were measured in both groups. We analyzed the correlation among these parameters and patients’ demographic features, such as age, gender, body mass index (BMI) and histopathological variables such as tumor localization, stage, nodal status, histological grade, vascular and lymphatic invasion. The mean age was 60.05 + 9.72 in patients, while it was 38.6 + 12.73 in controls. The mean serum adiponectin levels were 12.62 + 7.9 and 10.07 + 6.72 ng/ml, respectively, in groups. There was no different in terms of adiponectin, C-peptide, HOMA-R level in both groups. On the other hand, BMI, glucose and insulin levels were significantly different in gastric cancer patients in comparison with the controls. There was no correlation among the levels of adiponectin, BMI, insulin and c-peptide levels in patient group (
P
> 0.05). The adiponectin levels of woman were significantly lower than male patients (
P
= 0.002). No relations were detected among tumor stage, tumor localization, nodal status, lymphatic and vascular invasion, and the levels of serum adiponectin (
P
> 0.05). Interestingly, a positive correlation was found between tumor grade and plasma adiponectin levels (
r
= 0.372;
P
= 0.018). Our results suggest that plasma adiponectin levels were similar in both patients with gastric cancer and the controls. In addition, no correlation was found between adiponectin levels and demographic features and histopathological variables of patients. But, in undifferentiated tumors, plasma adiponectin level was significantly higher than well-differentiated grade tumors.
Biochemical changes of iron deficiency anemia (IDA) are extremely similar to chronicle illness anemia (CIA). Here, we investigated a new marker, soluble transferrin receptor (sTfR) and a new index, ...sTfR/ferritin in differential diagnosis of these two types of anemias.
Hemoglobin, MCV, MCH, hsCRP, iron, total iron binding capacity, percent transferrin saturation, ferritin, ESR levels were determined in patients attending our hospital's hematology department with symptoms and signs of anemia. 56 patients were diagnosed as IDA and 26 as CIA (14 with rheumatoid arthritia and 12 with non-hematologic malignancy). A third group who has IDA with positive rheumatologic inflammation parameters (hsCRP and ESR) is constituted (IDA
+
CIA). 30 healthy volunteers made up the control group. sTfR levels were determined of whole individuals and sTfR/ferritin indices were calculated as sTfR/log Ferritin. sTfR assay were performed on COBAS Integra 400 analyser (Roche Diagnostics, Germany), immunoturbidimetrically.
sTfR values of 4 groups ( IDA, CIA, IDA
+
CIA and healthy controls) were 10.91
±
4.03; 3.36
±
1.14; 7.70
±
1.66; 2.66
±
0.76 mg/L respectively (ANOVA
p
<
0.001). IDA and IDA
+
CIA group showed statistically significant differences compared with controls (
p
<
0.0001 and
p
<
0.001, respectively) sTfR/ferritin indices of 4 groups were 23.59
±
19.68; 1.43
±
0.64; 5.69
±
1.35; 1.57
±
0.55, respectively (ANOVA
p
<
0.001). IDA and IDA
+
CIA group showed statistically significant differences compared with controls (
p
<
0.0001 and
p
<
0.001, respectively).
sTfR values were different in IDA and CIA patients. sTfR/ferritin index was found to be more effective than sTfR in the diagnosis of iron deficiency anemia. These tests can be very useful in conditions where serum iron measurement is insufficient or inflammation exists.