Background Lymphangiogenesis and angiogenesis are critical processes for tumor growth, invasion, and metastasis, and are crucial for therapeutic strategies. The aim of the present study was to ...evaluate the clinical significance of lymphangiogenesis and its regulation in gastric carcinomas. Methods The lymphatic vessel density (LVD) in 65 gastric carcinoma cases was investigated by immunohistochemistry using D2-40 antibody, and evaluated with prognostic parameters. The intratumoral microvessel density (MVD), using CD31 antibody, was assessed and correlated with LVD. Results D2-40 identified peritumoral lymphatics in all cases, and lymphatic vessel density (LVD) ranged from 3 to 19 (median, 5; mean ± SD, 7.69 ± 4.67). The peritumoral LVD significantly correlated with large tumor size ( P = 0.0001), lymph node metastasis ( P = 0.004), visceral organ metastasis ( P = 0.0001), and TNM stage ( P = 0.001). Survival was also significantly lower in patients with high LVD tumors than in patients with low LVD tumors ( P = 0.04). Among various clinicopathologic characteristics, CD31 expression was associated only with lymph node metastasis ( P = 0.001). However, there was no significant correlation between CD31 and D2-40. Conclusion Our study showed that lymphangiogenesis plays an important role in the progression of gastric carcinoma. Therefore, D2-40, as an indicator for tumor lymphangiogenesis, may serve as a prognostic marker in gastric carcinoma.
The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment.
Retrospective analysis of ...T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey.
Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%).
The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Introduction
The aim of this study was to determine the ultrastructural effects of doxorubicin (Adriblastina®; Pharmacia and Upjohn, Milan, Italy), paclitaxel (Taxol®; BMS, Princeton, NJ), Cremophor® ...EL (a diluent of paclitaxel) and doxorubicin/paclitaxel combinations on normal lung tissues.
Methods
In the experimental protocol, 50 Wistar albino rats were used, divided into five different groups: the control group (
n
=10), the doxorubicin group (1 mg/kg) (
n
=10), the paclitaxel group (2 mg/kg) (
n
=10), the Cremophor EL group (150 mg/kg) (
n
=10) and the paclitaxel/doxorubicin group (2 mg/kg+ 1 mg/kg) (
n
=10). The drugs were administered weekly to rats via intraperitoneal injections for 14 weeks. After 3 weeks of observation, the rats were killed with thiopental sodium (30 mg/kg) and their left median lung tissues were removed and examined with a Carl Zeiss EM 900 transmission electron microscope.
Results
Our experiments showed doxorubicin to cause an increase in collagen fibre content of the alveolar wall, and paclitaxel to cause degenerations in cellular organelles. In the group in which the two agents were administered together, both effects were observed, although the effects of paclitaxel were seen to be dominant. Ultrastructural appearance was similar in the Cremophor EL group compared to the control group.
Conclusion
It was detected that doxorubicin and paclitaxel caused ultrastructural degenerations in normal lung tissues and Cremophor EL seemed to be unaccountable for these degenerations.
Expression of nm23 has been identified as a potential metastatic suppressor. In this study, nm23-H1 expression, clinicopathological parameters and influences on clinical outcomes were investigated in ...colorectal carcinoma patients.
Immunostaining was performed on 185 colorectal carcinomas using a polyclonal anti-nm23-H1 antibody.
The nm23-H1 immunoreactivity was weak in 31 (17%), moderate in 48 (26%) and strong in 106 (57%) cases. The well differentiated adenocarcinomas showed significantly strong staining for nm23-H1 compared with the moderately and poorly differentiated adenocarcinomas (χ2 test, P<0.001). Advanced tumour stages were associated with reduced nm23-H1 expression (P<0.001). There was an inverse correlation with angiolymphatic invasion, nodal metastasis and liver metastasis (univariate logistic regression analysis, P<0.001). In univariate analysis, patients with reduced expression of nm23-H1 had significantly shorter overall and disease-free survival than the strong expression group (log-rank test for trend, P=0.002 and P=0.003, respectively).
Our results indicated that reduced nm23-H1 expression showed poor prognosis in colorectal carcinomas. As a result, nm23-H1 expression might be a useful marker to predict outcome while planning treatment.
In this study, MLPA assay was performed for detection of large rearrangements of BRCA1 and BRCA2 genes in 16 familial, 29 early onset, 3 male breast cancer, and 2 bilateral breast/ovarian cancer high ...risk Turkish index cases. MLPA assay for all exons of both genes and for 1100delC variant of CHEK2 gene were performed. Analyses, revealed no large genomic rearrangements in both genes, and, no 1100del variant in CHEK2 gene. Our data which represents the first results for Turkish patients, suggest that, the frequency of BRCA1 and BRCA2 genes' large rearrangements is very low.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Prolonged oral etoposide has antitumor activity in a variety of solid tumors including small cell and non-small-cell lung cancer. A total of 53 patients have been treated with prolonged oral ...etoposide at a dosage of 50-100 mg/day for 5, 7,10 or 14 days in a 21 days interval. The results of these patients were retrospectively evaluated. Twelve patients had small cell lung carcinoma (SCLC), 11 patients had non-small cell lung carcinoma (NSCLC) and 30 patients had different solid tumors including gastric, breast, ovarian and prostate carcinoma. Fifty-two patients were evaluated for response analysis. Objective response rate was found to be 19,2% (1,9% complete response (CR), 17,3% partial response (PR)). Stable disease was achieved in 30,8% of the patients. Grade 3 and 4 neutropenia occurred in 9,3% of the patients. We demonstrated a modest activity of single agent oral etoposide in our heterogenous group of patients with advanced and refractory disease. Oral etoposide may be a treatment choice for patients with refractory disease which there was no other alternative without supportive care.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Endothelium is the first physiological barrier between blood and tissues and can be injured by physical or chemical stress, particularly by the drugs used in the cancer therapy. Paclitaxel and ...doxorubicin are frequently used anticancer drugs and their cardiac side effects are well observed in clinical setting. Their side effects on the endothelium are still not clear enough. There are few investigations assessing the damages elicited by the combination use of chemotherapy agents in animal experimental models. The purpose of this study was to examine and compare the side effects of doxorubicin and paclitaxel on endothelium in vivo. The drugs were administered weekly to rats via intraperitoneal injections singly or in combinations. Lastly, aorta endothelium was examined. The most familiar parts of the aorta endothelium are the nucleus, free ribosomes, Weibel-Palada granules, plasmalemmal vesicles, and clear basement membrane. Examination of the endothelium and the related structures revealed some clear degenerative findings. Notably, administration of a paclitaxel and doxorubicin combinations caused the most dramatic change in ultrastructure, which may disrupt many functions of the endothelium.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this study was to investigate the relationship between MUC1 and MUC2 mucin expressions and clinicopathologic variables in gastric carcinomas with regard to survival times. MUC1 and MUC2 ...expressions were revealed immunohistochemically in 143 gastric carcinomas. Of these 143 patients, follow-up data were available for 45 (median survival time of 30 months, ranging from 2 to 80 months). MUC1 was detected in 82 (58%), and MUC2 in 60 (42%) out of 143 cases. Papillary adenocarcinomas showed significantly higher MUC1 and MUC2 immunoreactivity than did signet-ring cell and mucinous tumors (p = 0.045 and p = 0.01, respectively). MUC1 was highly positive in intestinal-type carcinomas (p = 0.006), whereas intestinal and diffuse carcinomas did not differ in MUC2 expression. There was a positive correlation between tumor differentiation and MUC1 expression. However, no correlation was found between MUC1 and MUC2 expressions and angiolymphatic invasion. According to the TNM classification, stage 1A tumors have significantly lower rates of MUC1 reactivity compared to higher stages (p = 0.04). The patients with gastric carcinomas expressing MUC1 showed significantly poorer survival than those without MUC1 expression (p = 0.04). The present study suggests that MUC1 expression be a useful prognostic factor for predicting the outcome of gastric carcinoma patients, whereas the role of MUC2 expression is still unclear.
