Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience.

AIM: 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. METHOD: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. FINDINGS: 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%). DISCUSSION: 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.

Tendency of cancer patients and their relatives to use internet for health-related searches: Turkish Oncology Group (TOG) Study.

PURPOSE: This study aimed to reveal the habits of using internet by cancer patients and their relatives to access health-related information and services in Turkey. METHODS: An 18-item questionnaire survey was applied in cancer patients and their relatives. RESULTS: A total of 1106 patients (male, 37.3%, and female, 62.7%) and their relatives were included in the study. The responders had been using internet to obtain health information about oncological diseases, once a month (34.2%), 1-2 times a week (27.4%) or 2-3 times a month (21.9%). After diagnosis of cancer was made, participants more frequently (64.4%) investigated health-related issues, while 64.9% of them considered internet as an important search tool, and 16.7% of them had thought to give up cancer therapy under the influence of internet information. Some (33.1%) participants had used herbal medicine, and 16.7% of them had learnt these herbal products from internet. Still 12.7% of them had not questioned the accuracy of internet information, while 26.9% of them indicated that they had not shared the internet information about cancer with their physicians, and 13 % of them searched information in internet without asking their physicians. CONCLUSION: Cancer patients and their relatives showed a higher tendency to use health-related internet information which may mislead them, and can result in treatment incompliance. Health professionals should offer evidence-based information to the patients and their relatives through internet.

Genomic large rearrangement screening of BRCA1 and BRCA2 genes in high-risk Turkish breast/ovarian cancer patients by using multiplex ligation-dependent probe amplification assay.

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.

Bevacizumab plus irinotecan-based therapy in metastatic colorectal cancer patients previously treated with oxaliplatin-based regimens.

BACKGROUND: Treatment of patients with metastatic colorectal cancer (MCRC) previously exposed to oxaliplatin-based regimen is challenging. Efficacy and toxicity of bevacizumab plus irinotecan-based regimens were assessed in the second-line treatment of MCRC patients. PATIENTS AND METHODS: Forty patients with a median age of 53 years (range, 31-75) were retrospectively evaluated. Patients progressing or relapsing after treatment with oxaliplatin-based regimens were given bevacizumab 5 mg/kg every 2 weeks in combination with irinotecan-based regimens. All patients had previously received oxaliplatin either in the adjuvant setting (n = 8) or for metastatic disease (n = 32). RESULTS: Three patients achieved a complete response (7.5%), 5 partial responses (12.5%) and 14 (35%) stable disease resulting in an overall response rate of 20%. Median progression-free survival was 6 months (95% CI, 4.0-8.0) with a median overall survival of 14 months (95% CI, 10.2-17.8). One-year survival rate was 55.9%. Grade 3-4 toxicities were as follows: neutropenia (n = 15, 37.5%), febrile neutropenia (n = 2, 5%), diarrhea (n = 11, 27.5%), nausea and vomiting (n = 3, 7.5%), gastrointestinal perforation (n = 2, 5%), and thromboembolism (n = 2, 5%). CONCLUSION: Bevacizumab plus irinotecan-based combination chemotherapy is an active and safe treatment option in patients failing oxaliplatin-based therapy.

Peritumoral lymphatic microvessel density associated with tumor progression and poor prognosis in gastric carcinoma.

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.

Does a Secure Attachment Style Predict High Psychological Resilience in Patients With Cancer Receiving Chemotherapy?

Introduction To investigate the level of psychological resilience and the impact of attachment styles on the degree of resilience to distress in patients with cancer receiving chemotherapy. Methods Patients with cancer receiving chemotherapy were included in the study. Participants were requested to complete the Relationship Scales Questionnaire (RSQ), Resilience Scale for Adults (RSA), and a personal information form during the data collection phase. One-way analysis of variance (ANOVA) was used to compare that parameter among the attachment styles. Logistic regression analysis was carried out to identify independent factors affecting resilience. Results A total of 384 individuals were included in this study (mean age 53.5 ± 12.1, 27.1 % male). The RSQ results showed that the attachment styles of 190 (49.5%) participants were secure, whereas 194 (50.5%) subjects had an insecure attachment. The median RSA score of participants with a secure attachment was significantly higher than that of patients with insecure attachment (133.15 ± 16.6 vs. 127.0 ± 20.0, p=0.001). Patients with the RSA score of >130 were more educated, were in better economic condition, had better perceived social support, and had a higher frequency of secure attachment than those defined as low resilient. Logistic regression analysis revealed that poor and medium perceived social support and insecure attachment style independently predicted low resilience (RSA≤130). Conclusion This study demonstrates that the secure attachment style in patients with cancer improves stress resilience as compared to the insecure attachment style. Our findings also show that insufficient perceived social support is likely a negative factor in resilience.

Cyclooxygenase-2 expression and its association with angiogenesis, Helicobacter pylori, and clinicopathologic characteristics of gastric carcinoma.

Cyclooxygenase-2 (COX-2) is upregulated in gastric carcinoma, and its increased levels were found to have a prognostic significance in some studies. Both angiogenesis and Helicobacter pylori infection have been reported to be associated with COX-2 expression of gastric cancer in recent studies. In this study, COX-2 expression and its association with CD31 staining, H.-pylori infection, and well-known clinicopathological factors were investigated in 65 gastric cancer patients. COX-2 and CD31 expression assessment was done by immunohistochemical methods. Whartin Starry stain was performed for H.-pylori infection. Of 65 patients, 32 (49%) revealed intense COX-2 immunostaining. Among various clinicopathologic characteristics, COX-2 expression was inversely correlated with tumor size, TNM stage, and lymph node status. Thirty-two (49%) patients revealed intense CD31 immunostaining. Among various clinicopathologic characteristics, CD31 expression was associated only with lymph node metastasis. COX-2 expression was not correlated with CD31 staining and H.-pylori infection. Both COX-2 and CD31 staining had no prognostic significance. In conclusion, we found that COX-2 expression was significantly higher in earlier stages of gastric cancer. It can be suggested that COX-2 expression may be important in the initial development of gastric cancer but not in progression of the disease. Other factors which may be associated with COX-2 in gastric cancer, including angiogenesis and H.-pylori infection, should be investigated in further studies.

Coexistence of gastrointestinal stromal tumor (GIST) of the rectum and adenocarcinoma of the prostate in a patient with familial GIST.

BACKGROUND: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal system. The rectum is a rare location for GIST. Prostate adenocarcinoma is the most common malignancy in geriatric men. Rarely, rectal GIST mimics prostate pathologies. CASE REPORT: We describe a 58-year-old male patient who was admitted with signs and symptoms of prostatism. A presumptive diagnosis of primary prostate sarcoma was made based on imaging studies and a trucut biopsy. Removal of the mass compressing both the prostate and the rectum revealed the final diagnosis of synchronous prostate adenocarcinoma and high-grade GIST originating from the rectum. The patient also had a family history of GIST. CONCLUSION: According to our knowledge, there are 5 more reported cases of rectal GIST, which were misdiagnosed as prostate malignancy. Rectal GIST may simulate prostate carcinoma clinically, and should always be kept in mind in the differential diagnosis of prostate pathologies.

Temozolomide in newly diagnosed malignant gliomas: administered concomitantly with radiotherapy, and thereafter as consolidation treatment.

BACKGROUND: Surgical resection followed by radiotherapy used to be the standard treatment in malignant gliomas. Recently, temozolomide has become a cornerstone in the treatment of these patients. We evaluated retrospectively the efficacy and the toxicity of temozolomide which was administered concomitantly with radiotherapy, and thereafter as consolidation treatment. PATIENTS AND METHODS: Medical records of 64 patients with malignant glioma were reviewed. Postoperatively, temozolomide was given at a dose of 75 mg/m(2)/day concomitantly with cranial radiotherapy. After 4 weeks of rest, patients were treated with temozolomide 200 mg/m(2) on days 1-5 every 28 days for 6 cycles. RESULTS: 62 patients were evaluable for response and toxicity. Objective response rate was 38.7% including 7 (11.3%) complete responses, and 17 (27.4%) partial responses. Median progression-free survival, and overall survival have not yet been reached in the grade III astrocytoma group at a median follow-up of 19 months. In the glioblastoma multiforme group, median progression-free survival, and median overall survival were 10 and 19 months, respectively. 2-year survival rates were 80% and 19% for the grade III astrocytoma, and for the glioblastoma multiforme groups, respectively. Toxicity was mild to moderate with rare grade 4 toxicities. CONCLUSION: Our data suggest that temozolomide is an active regimen for malignant gliomas. It was more effective in younger patients with better performance status.

The results of three different treatment modalities in patients with locally advanced nasopharyngeal carcinoma.

The aim of the study was to evaluate the toxicity and efficacy of 62 patients with locally advanced nasopharyngeal carcinoma (NPC) (stage III, IVA, IVB) treated by three different modalities. Cisplatin was given weekly 35 mg/m(2)/day or every 3 weeks 100 mg/m(2)/day during radiotherapy (RT) in all patients. Patients were classified into following three groups: The patients in the group 1 (n=23) were treated only with concurrent chemoradiotherapy (CCRT). In the group 2 (n=15), before the CCRT, neoadjuvant chemotherapy, consisting of intravenous cisplatin and docetaxel on day 1, every 3 weeks treatment cycles was administered. In the group 3 (n=24), adjuvant chemotherapy, consisting of cisplatin on day 1 and 5-fluorouracil on day 1 to 5 every 3 weeks was used after CCRT. Three arms were treated with the same RT technique and dose. There was no difference for age, sex, and stage among the groups. Radiotherapy was administered in planned dose for all patients. A total of 82% patients completed planned chemotherapy concurrent with RT. The treatment related adverse effects were mild or moderate in intensity. There was no statistical difference between the groups regarding the treatment responses. Complete response rate of RT was 73.9%, 86.7%, and 87.5%, respectively. Median progression free survival (PFS) and overall survival (OS) were 13, 12, 9 months and 22, 20, 15 months for groups 1, 2, 3, respectively. No difference was observed in median OS and PFS among three groups. In our study, the efficacy and toxicity of neoadjuvant and/or adjuvant chemotherapy with CCRT and CCRT alone were found similar.

Single agent gemcitabine in the second-line treatment of advanced non-small cell lung cancer after treatment with taxane + platinum regimens.

In this study, we investigated the activity of single agent gemcitabine in the second-line setting of non-small cell lung cancer (NSCLC). File records of 21 patients treated with single agent gemcitabine in advanced NSCLC who received one prior chemotherapy including a taxane and platinum combination were retrospectively evaluated. Treatment consisted of IV gemcitabine 1,250 mg/m2 on days 1 and 8, followed by a 1-week rest repeated every 3 weeks. A partial response was achieved in four (19%) patients. The median response duration was 16 (range, 12-32) weeks. Six (29%) patients had a SD more than 3 months. The median time to progression was 16 (range, 8-32) weeks. No complete response was observed. Median overall survival was 36 weeks for second-line gemcitabine in all patients (95%: CI 5-13 months). Hematological toxicity (all grades) was reported by 9 (42.9%) patients. One (4.75%) patient experienced grade 3/4 neutropenia. Grade 3/4 nausea and vomiting and mucositis were reported in one (4.75%) patient. In conclusion, this study shows that single agent gemcitabine is active and well tolerated as a second-line therapy for advanced NSCLC.

Carboplatin and oral cyclophosphamide combination after temozolomide failure in malignant gliomas.

BACKGROUND: Temozolomide is a novel cytotoxic agent for malignant gliomas. However, treatment failure occurs approximately in half of patients, and the optimal regimen in this setting has yet to be defined. In the present study, we assessed retrospectively the efficacy and toxicity of the combination of carboplatin and oral cyclophosphamide in temozolomide-resistant patients. METHODS: We evaluated the medical records of 30 patients with malignant gliomas. After failure of temozolomide therapy, patients were treated with a combination of carboplatin and oral cyclophosphamide. Treatment consisted of intravenous carboplatin AUC 6 (based on the Calvert Formula) on day 1 and oral cyclophosphamide 75 mg/m2 daily on days 1 to 14, followed by 14 days of rest, with the treatment repeated every 4 weeks. RESULTS: All patients were evaluated for response and toxicity. The objective response rate was 30%, including 9 partial responses. Median time to disease progression and median overall survival was 7 months and 8 months, respectively. Clinically responsive patients had statistically significant longer progression-free survival and overall survival than unresponsive patients. Hematological side effects were commonly observed toxicities, with neutropenia the most frequent. CONCLUSIONS: Our data suggest that carboplatin and oral cyclophosphamide therapy is a convenient regimen after failure of temozolomide therapy in patients with malignant gliomas because of its activity, feasibility and tolerability. Further prospective studies are needed in this setting.

Ultrastructural damage in lung tissues in rats treated with doxorubicin and paclitaxel.

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.

Serum YKL-40 levels as a prognostic factor in patients with locally advanced breast cancer.

INTRODUCTION: YKL-40 is a growth factor for connective tissue cells; it also stimulates the migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum levels have been associated with poorer prognosis in metastatic breast cancer. In the present study we evaluated the prognostic role of serum YKL-40 levels in patients with locally advanced breast cancer. METHODS: YKL-40 levels were measured using ELISA in serum samples obtained from 45 breast cancer patients prior to surgery and chemotherapy. The median follow-up time was 46 months (range, 10-96 months). All patients underwent surgery after chemotherapy. During the follow-up period, 21 patients relapsed and there were 17 deaths. RESULTS: The median serum YKL-40 concentration in patients with locally advanced breast cancer was 149.5 mug/l (range, 25.0-1021.3 microg/l). This was higher than levels observed in healthy female controls but the difference was not significant (P=0.44). Serum YKL-40 levels were also higher in patients with tumour size >2 cm and node-positive disease but again the differences were not significant (P>0.05). Tumour volume was correlated with serum YKL-40 levels (r=0.308, P=0.039). High serum YKL-40 levels were associated with shorter disease-free and overall survival although this trend failed to reach significance (P>0.05). Multivariate analysis including tumour size, lymph node status, oestrogen and progesterone receptor status, tumour grade, and serum YKL-40 levels indicated that serum YKL-40 levels were an independent prognostic variable for overall survival (hazard ratio, 1.004; 95% confidence intervals: 1.00, 1.07; P=0.027). Tumour size, lymph node status and oestrogen receptor status were also independent prognostic variables for overall survival (P<0.05). CONCLUSION: Our results show that serum levels of the growth factor YKL-40 may be a useful prognostic indicator of outcome for patients with locally advanced breast cancer. Further studies are required to fully elucidate the biological function of YKL-40 in breast cancer.

Gemcitabine plus capecitabine combination in metastatic breast cancer patients previously treated with anthracyclines and taxanes.

BACKGROUND: Treatment of patients with metastatic breast cancer (MBC) exposed to anthracyclines and taxanes is challenging. Effective and well-tolerated regimens are required. Gemcitabine plus capecitabine combination was assessed in MBC patients pretreated with anthracyclines and taxanes. PATIENTS AND METHODS: A total of 31 patients treated between November 2004 and September 2005 were retrospectively evaluated in 4 institutions. The median age was 48 years (range 29-77). The patients were given gemcitabine 1,000 mg/m(2) on days 1 and 8, and capecitabine 1,500 mg/m(2) twice daily on days 1-14 every 3 weeks. RESULTS: A total of 160 cycles of chemotherapy were administered with a median of 5 cycles per patient (range 2-12). Three patients achieved a partial response (10%) and 8 patients (26%) stable disease. The median time to disease progression was 6 months (95% CI 5-7), with a median survival of 18 months (95% CI 15-21) at a median follow-up of 16 months (range 2-28). One-year and 2-year survival rates were 67 and 28%, respectively. Grade 3-4 toxicities were as follows: neutropenia (n = 11, 35%), nausea and vomiting (n = 4, 13%), hand-foot syndrome (n = 2, 6%), anemia (n = 2, 6%), thrombocytopenia (n = 2, 6%) and asthenia (n = 1, 3%). CONCLUSION: The combination of gemcitabine plus capecitabine was a tolerable regimen with a mild but comparable survival efficacy to similar regimens in patients with MBC after anthracyclines and taxanes.

Can core biopsy be used instead of surgical biopsy in the diagnosis and prognostic factor analysis of breast carcinoma?

PURPOSE: The aim of this article was to investigate the efficacy of ultrasonography-guided core needle biopsy and prognostic factor analysis of breast cancer to plan overall treatment strategy. PATIENTS AND METHODS: A consecutive series of nonpalpable and palpable breast cancers constituted our study group (n= 201 lesions; mean size, 20.4 mm) Mean number of core samples was 3.4. Malignant lesions diagnosed with core biopsy underwent therapeutic surgical excision. Core biopsy and surgical excisions were compared for histologic type, grade, estrogen receptors (ERs), progesterone receptors (PgRs), and c-erbB2 levels. Cutoff values for ER, PgR, and c-erbB2 affecting the management strategy were selected as 10%, 10%, and 50%, respectively. RESULTS: Eighty-five lesions (42.3%) were malignant in core biopsy (mean size, 18.4 mm). Among these, 11 were inoperable and 13 were surgically excised at other institutions. In 61 lesions, core and surgical excision specimens were evaluated in the same institution (mean tumor size, 18.6 mm; range 6-60 mm). Concordance between the 2 biopsy methods was 85.2% (52 of 61) for histologic type of tumor, 68.8% (33 of 48) for tumor grade, 90% (27 of 30) for ER, 86.7% (26 of 30) for PgR, and 79.3% (23 of 29) for c-erbB2 levels. Appropriate site selection for sampling was indicated to be of paramount importance, especially in determining reliable ER, PgR, and c-erbB2 levels. CONCLUSION: Core needle biopsy of breast cancer is equally effective compared with surgical biopsy and can be used in overall treatment planning. However, appropriate site selection for sampling should be guaranteed using ultrasonographic guidance.

Capecitabine plus oxaliplatin (xelox) in the treatment of chemotherapy-naive patients with metastatic colorectal cancer.

BACKGROUND: Capecitabine and oxaliplatin are both synergistically active against metastatic colorectal cancer (MCRC). We evaluated our experience at two centers with capecitabine and oxaliplatin combination (XELOX) in previously untreated patients with MCRC. PATIENTS AND METHODS: We reviewed medical records of 85 previously untreated patients with MCRC who received first-line XELOX regimen. Oxaliplatin was given at a dose of 130 mg/m2 on day 1 in combination with capecitabine 1500 mg/m2/day on days 1-14 every 3 weeks. RESULTS: Seventy-six of 85 patients were evaluated for response and toxicity. Patients with a follow up of less than 6 months were excluded from the study. Objective response rate was 46% including 8 complete responses (10.5%) and 27 partial responses (35.5%). Additionally, 20 patients (26.3%) had disease stabilization at least 3 months after the treatment. The patients were followed for a median 12.5 months (range 2-32). Median time to disease progression (TTP) was 11 months (range 2-27 months). Median overall survival (OS) time has not yet been reached. One-year survival rate was 66%. Toxicity was modest with infrequent grade 3-4 adverse effects. CONCLUSION: XELOX is an active regimen against MCRC in the first-line setting with favorable toxicity profile. Our results appear to be comparable, if not superior, to the results of other reports of first-line XELOX therapy in respect to objective response rates, survival data, and safety profile. Convenience with oral administration of every 3-week schedule makes XELOX regimen a compelling therapeutic option in the treatment of first-line MCRC.

Ultrastructural damage in vascular endothelium in rats treated with paclitaxel and doxorubicin.

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.

Prognostic importance of COX-2 expression in patients with colorectal cancer.

A relationship between cyclooxygenase-2 (COX-2) expression and the pathogenesis of colorectal cancer has been reported in recent studies. Moreover, it has been indicated that COX-2 expression may have a prognostic role in colorectal cancer patients. In this study, we investigated the prognostic significance of COX-2 expression in 83 patients with colorectal cancer. COX-2 expression was assessed using immunohistochemical methods and was evaluated by grading both staining intensity and staining extension. The relationships between COX-2 expression and clinicopathological features of the patients and patient survival were evaluated. There was no relationships between COX-2 expression and tumor size (tm < 3 cm or tm > or = 3 cm), tumor histopathological differentiation (poorly differentiated or moderately + well differentiated), number of metastatic lymph nodes (< 4 or 3 > or = 4), histopathology of the tumor, localization of the tumor (colon or rectum), distant metastasis, and vascular invasion of the tumor. In the multivariate analysis, COX-2 expression was not found as an independent prognostic factor. We demonstrated that COX-2 expression was not correlated with clinicopathological characteristics of colon carcinoma and disease outcome.

Prognostic implication of nm23-H1 expression in colorectal carcinomas.

AIMS: 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. METHODS: Immunostaining was performed on 185 colorectal carcinomas using a polyclonal anti-nm23-H1 antibody. RESULTS: 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 (chi2 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). CONCLUSIONS: 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.