Utility of serum and urine uPAR levels for diagnosis of breast cancer.

Malignant tumors have a capacity to degrade the extracellular matrix by controlled proteolysis. One system involved in these processes is the urokinase-type plasminogen activator (uPA) system. uPAR levels are elevated in tumors from several types of cancer. Our study was planned to investigate serum and urine levels of uPAR in breast cancer patients (n=180) and healthy controls (n=60) by ELISA. Serum (p<0.001) and urine (p<0.001) uPAR values in the patients were both significantly elevated. High serum and urine levels of uPAR can be used as diagnostic tools in lymph node positive patients.

Evaluation of glutathione S-transferase P1 polymorphisms (Ile105Val and Ala114Val) in patients with small cell lung cancer.

AIMS: Glutathione S-transferase P1 (GSTP1) plays an important role in cellular protection against oxidative stress and toxic chemicals. Polymorphisms within GSTP1 are associated with alterations in enzyme activity, which may lead to development of lung disease and cancer. In this study, we aimed to investigate the GSTP1 Ile105Val and Ala114Val polymorphisms in patients with small cell lung cancer (SCLC). PATIENTS/METHODS: GSTP1 Ile105Val polymorphism in exon 5 and GSTP1 Ala114Val polymorphism in exon 6 were determined by using polymerase chain reaction-restriction fragment length polymorphism techniques in 89 patients with SCLC and 108 control patients with chronic obstructive pulmonary disease (COPD). Genotype frequencies and cigarette smoking intensities were compared among SCLC and COPD patients. RESULTS: There were significantly less SCLC patients with variant exon 6 genotypes than COPD patients (7.9% vs. 20.4%, p=0.007), while the number of patients with variant exon 5 genotypes were comparable among groups. SCLC and COPD patients with variant exon 6 genotype showed trends toward exhibiting reduced cigarette consumption. CONCLUSIONS: The variant GSTP1 exon 6 genotype might be conferring protection against SCLC development. Whether this effect is associated with exposure to cigarette smoking needs to be clarified.

Intraglomerular crescentic metastases of malignant melanoma.

We describe here a patient with a metastatic malignant melanoma displaying crescentic lesions in the glomeruli. A 64-year-old woman was referred to our hospital because of a sudden increase of serum creatinine. Clinical diagnosis suggested rapidly progressive glomerulonephritis. Renal biopsy revealed diffuse crescentic lesions containing metastatic melanoma cells. These cells were also seen in the glomerular capillary lumina and tubules, and a few scattered tumor cells were also present in the interstitium. Glomerular metastasis is a very rare entity. To the best of our knowledge, this patient is the first to be described in the English language literature showing intraglomerular metastasis of malignant melanoma as demonstrated by needle biopsy and is only the second patient with intraglomerular metastasis presenting with acute renal failure.

Effect of kefir on the quality of life of patients being treated for colorectal cancer.

PURPOSE/OBJECTIVES: To determine kefir's effect on the prevention of gastrointestinal complaints and quality of life (QOL) in patients being treated for colorectal cancer. DESIGN: Randomized, controlled, prospective, interventional study. SETTING: Istanbul University Oncology Institute in Turkey. SAMPLE: 40 patients, 20 of whom were randomized to the experimental (kefir) arm and 20 who were randomized to the control arm. METHODS: Informed consent to participate in the study was obtained. Before treatment began, demographics, illness-related characteristics, complaints, and QOL of participants were evaluated. During treatment, side effects were evaluated one week after every cycle of therapy. QOL was evaluated after the third and sixth cycles of treatment. MAIN RESEARCH VARIABLES: The effect of kefir on the prevention of gastrointestinal complaints and QOL in patients being treated for colorectal cancer. FINDINGS: Following chemotherapy, the experimental (kefir) group had more treatment-related gastrointestinal complaints but a decrease in sleep disturbance. No difference was found between the two groups for QOL. CONCLUSIONS: Kefir does not prevent or decrease gastrointestinal complaints in patients undergoing chemotherapy for colorectal cancer. Kefir did decrease sleep disturbances in the experimental group. IMPLICATIONS FOR NURSING: Many patients use complementary and alternative medicine during cancer therapy. This study may provide information about the effectiveness of kefir in patients with cancer.

Serum levels of interleukin-6 and interleukin-10 in Turkish patients with aggressive non-Hodgkin's lymphoma.

There exists strong evidence that tumor growth can be actively controlled by the host immune system and interleukins are known to play a significant role in immune response regulation. Inflammatory cytokines play important roles in the pathogenesis of lymphomas. This study was conducted to investigate the serum levels of IL-6 and IL-10 in patients with aggressive non-Hodgkin's lymphoma (A-NHL) and the relationships with prognostic parameters and therapy. These serum factors were measured in 46 A-NHL patients pathologically verified before and after chemotherapy in comparison with 21 healthy controls using enzyme-linked immunosorbent assays (ELISAs). There were significant differences in the serum IL-10 and IL-6 levels between A-NHL patients and controls (p= 0.038 and p<0.001, respectively). None of the prognostic parameters analyzed was significantly correlated with the serum IL-6 concentrations. This was also true for serum IL-10 values, except for LDH and bone marrow involvement. Serum IL-10 levels were elevated in the group of patients with high level LDH compared with the group of patients with a normal level (p= 0.017). Also, serum IL-10 levels were significantly different in the presence or absence of bone marrow involvement (p= 0.016). In addition, we found a significant relationship between the serum levels of serum levels of IL-6 and IL-10 in patients with A-NHL (r= 0.47, p<0.001). We found that serum IL-10 levels decreased due to chemotherapy effect independent of the chemotherapy response (p= 0.027). However, serum IL-6 levels were not changed. In conclusion, our data suggest that higher serum IL-6 and IL-10 levels can be useful for diagnosis of A-NHL. However, our sample size is small, and larger scale research is needed in this field to provide new knowledge.

Serum levels of angiogenic factors in early breast cancer remain close to normal.

The study which we performed was to determine serum concentrations of angiogenic factors including VEGF, angiogenin and TGF-beta 1 in early stage breast cancer patients. These parameters were measured by ELISA in sera of 90 patients with breast cancer and 75 healthy controls. The mean serum VEGF concentration in patients compared to controls was not significantly different (0.33ng/mL vs 0.43ng/mL, respectively; p=0.156). Likewise, the insignificant change in mean values in patients vs controls was also observed for serum TGF-beta 1 (0.19ng/mL vs 0.19ng/mL, respectively; p=0.215) and serum angiogenin (243.24ng/mL vs 244.5ng/mL, respectively; p=0.976). Statistically significant correlation was found only between the tests, such as VEGF and angiogenin in patients who were included in the study (p<0.001). In conclusion, we couldn't find any diagnostic value between the early stage breast cancer and the three angiogenic parameters.

Chemotherapy with pegylated liposomal doxorubicin and cisplatin in recurrent platinum-sensitive epithelial ovarian cancer.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is the only nonplatinum agent to significantly improve survival in patients with platinum-sensitive recurrent ovarian cancer. The present study was designed to assess the efficacy and safety of PLD plus cisplatin combination therapy in these patients. METHODS: Twenty-two women (median age, 57 years) with ovarian cancer that recurred 6 months or more after standard carboplatin and paclitaxel therapy were eligible for enrollment. Cisplatin was administered intravenously as a 60-min infusion on day 1, at a single dose of 60 mg/m(2), and PLD was given intravenously as a 1-h infusion on day 2, at a dose of 50 mg/m(2). Treatment cycles were repeated on an outpatient basis every 28 days. RESULTS: Hematological toxicity was mainly leucopenia/neutropenia, and this was the principal dose-limiting toxicity. Severe (grade III-IV) leucopenia/neutropenia was observed in 7 (32%) and 9 (41%) patients, respectively. Only 2 (9%) patients were complicated by febrile neutropenia. Grade III-IV anemia occurred in only 4 (18%) patients. Severe thrombocytopenia was not noted; only 5 patients (23%) had grade I-II toxicity. NO toxicity in biochemical parameters was noted. Several severe nonhematological adverse effects were managed according to standard protocols and were transient, as well as being well-tolerated. Twenty-one patients were evaluated for response. The overall response rate was 62% (13 of 21; 95% confidence interval [CI], 38%-82%), with four (19%) complete and nine (43%) partial responses. At the time of last follow-up, all of the 22 patients were alive. The median follow-up period was 8.5 months (range, 2 to 22 months). CONCLUSION: PLD combined with cisplatin at the schedule and dosage used in this study is an active and safe second-line chemotherapy regimen with acceptable and easily manageable toxicities in women with platinum-sensitive recurrent ovarian cancer.

Lower level of MAPK expression is associated with anthracycline resistance and decreased survival in patients with hormone receptor negative breast cancer.

INTRODUCTION: Hormone receptor negative breast cancer is encountered in about 30% of all patients with breast cancer and is considered as a prognostically unfavorable subset. The aim of this study is to evaluate the prognostic impact of various molecular markers in patients with receptor negative breast cancer. METHODS: Tumor specimens from 140 patients with receptor negative (ER, PR) breast cancer were analyzed for MAPK, Her-2/neu, EGFR and PI3K expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables were determined with respect to disease-free and overall survival. RESULTS: Nineteen (13.6%), 45 (32.1%), 16 (11.4%) and 47 (33.5%) patients had positive staining for EGFR, PI3K, Her-2/neu and MAPK, respectively. Twenty-three patients with positive MAPK (16.4%) had a high level of expression (score 4-7) and 24 (17.1%) had a low score (1-3). A lower percentage of MAPK expression was significantly associated with a poorer OS (p = 0.03) and a tendency for shorter DFS (p = 0.08) among those who were positive for MAPK. Anthracycline resistance remained the only independent significant variable for OS by Cox regression analysis (p = 0.001, HR:26.1). In patients with recurrent disease, median survival after initial relapse was 16.8 months. MAPK was determined as the only prognostic factor for this endpoint. Patients with higher level of MAPK staining showed significantly shorter survival following initial recurrence (p = 0.04). CONCLUSION: MAPK expression is a significant prognostic factor for non-metastatic patients with hormone receptor breast cancer. A lower level of staining is shown to be associated with with antracycline resistance and oveall survival, whereas a higher expression level is correlated with shorter survival following initial relapse, suggesting possible role of different molecular mechanisms pertaining to tumor progression once recurrence occurs. Further translational research is required to elucidate molecular mechanisms of the cross-talk between intracellular signaling and molecular pathways leading to drug resistance in patients with receptor negative breast cancer.

A pilot study evaluating the efficacy and toxicity of biweekly gemcitabine and pegylated liposomal doxorubicin in recurrent platinum-resistant epithelial ovarian cancer.

BACKGROUND: Both gemcitabine and pegylated liposomal doxorubicin (PLD) are antineoplastic drugs with clinical activity in patients with platinum-resistant ovarian cancer. The present study was designed to assess the efficacy and safety of biweekly scheduled gemcitabine and PLD combination therapy in such patients. METHODS: Eighteen women with ovarian cancer that had recurred within 6 months after standard carboplatin and paclitaxel therapy were eligible for enrollment. Gemcitabine 2000 mg/m(2) and PLD 20 mg/m(2) were administered intravenously on days 1 and 15 of a 28-day cycle. RESULTS: Hematological toxicity was mild. No severe (grade III/IV) leucopenia/neutropenia or thrombocytopenia was observed. Severe anemia was seen in only 3 (17%) patients. Several other severe nonhematological adverse effects were well tolerated and easily managed. The overall response rate was 28% (5 of 18; 95% confidence interval [CI], 10%-54%) with 2 (11%) complete and 3 (17%) partial responses. The median overall survival time was 17 months (range, 1 to 25 months). The median survival for patients with clinical benefit including disease response or stabilization was 17 months (range, 3 to 26 months) compared to that of patients with progressive disease, which was 2 months (range, 1 to 11 months; P = 0.04). CONCLUSION: A biweekly schedule of gemcitabine combined with PLD is an active and safe chemotherapy regimen with acceptable and easily manageable toxicities in women with recurrent platinum-resistant ovarian cancer.

Ovarian carcinoma with simultaneous breast and rectum metastases.

BACKGROUND: Metastatic involvement of the breast and the rectum from ovarian carcinoma are very rare events. CASE REPORT: We report a case of ovarian carcinoma with metastasis to the breast and rectum simultaneously, 6 years after initial diagnosis. RESULTS: Morphologic and immunohistochemical findings from pathologic samples of all involved sites confirmed the ovarian origin, which spared the patient unnecessary breast and rectal surgery. To our knowledge, this is the first case of ovarian carcinoma with simultaneous metastases to the breast and rectum reported to date. CONCLUSION: Accurate differential diagnosis from primary breast and rectal carcinoma is very important because the prognosis and treatment differ significantly.

Biweekly administration of gemcitabine and cisplatin chemotherapy in patients with anthracycline and taxane-pretreated metastatic breast cancer.

Gemcitabine and cisplatin are the active agents in metastatic breast cancer pretreated with anthracycline and/or taxane as a second line treatment. The present study was designed to assess the efficacy and safety of this regimen given biweekly schedule in these patients. Twenty-seven women, median age 57, with metastatic breast cancer previously treated with anthracycline and taxane were eligible for enrollment. Gemcitabine was administered intravenously on days 1 and 15 at a dose of 2,000 mg/m(2) and Cisplatin was given intravenously on day 1 and 15 at a dose of 50 mg/m(2). Treatment cycles were repeated on an outpatient basis every 28 days. Of all 27 evaluable patients, the overall response rate was 26% (7 of 27; 95% CI: 11-46%) with seven all partial responses. The stable diseases were found in 9 (33%) patients. At the time of last follow-up, 11 (41%) of the patients died of their disease progression. The median overall survival duration was 7.4 +/- 2.8 months. The 1-year overall survival rate was 46.9% +/- 12.3. Hematological toxicity was not found as the principal dose-limiting toxicity. Severe (grade III/IV) neutropenia was observed only one (4%) patients. No patient was complicated by febrile neutropenia and G-CSF usage was not performed. Grade III and IV anemia were seen in only 4 (15%) and thrombocytopenia was noted only one (4%) patients. Severe hepatic (n = 2) and renal toxicity (n = 1) were observed and these all recovered completely without complication. Several other severe non-hematological side effects were managed easily. Permanent dose reductions were necessary in 9 (33%) patients and chemotherapy administration was also delayed in 7 (26%) patients because of delayed both hematological and non-hematological toxicity recovery. Treatment was discontinued in one (4%) patient due to severe fatigue and deteriorating performance status. In conclusion, gemcitabine and cisplatin combination therapy with this biweekly schedule and dosage is moderately active and extremely safe in patients with metastatic breast cancer previously treated with anthracycline and taxanes.

Serum levels of intercellular adhesion molecule ICAM-1 and E-selectin in advanced stage non-small cell lung cancer.

Cell adhesion is a basic count in inter- and intra-cellular communication and plays an important role in tumor progression. This study was conducted to investigate the serum levels of intercellular adhesion molecule (ICAM-1) and E-selectin in patients with advanced stage non-small cell lung cancer (NSCLC) and the relationships with known prognostic parameters and therapy. These serum factors were measured of 57 NSCLC patients pathologically verified before and after chemotherapy in comparison with 24 healthy controls by using ELISA method. Serum levels of ICAM-1 were increased significantly in NSCLC patients compared with the healthy controls (P = 0.006). However, serum E-selectin levels were not significantly different from healthy control groups (0.643). No statistically significant relationships were found between investigated all serum parameters and various characteristics of patients, and the diseases such as stage and tumor burden. Likewise, we also found no correlation between serum ICAM-1 and E-selectin (P = 0.78). We found that serum ICAM-1 levels were decreased owing to the chemotherapy effect, independently from chemotherapy response. However, serum E-selectin levels were not changed by the chemotherapy effect. The median survival of all patients was 11.9 months and 1-year survival rate was 47.6%. We found that patients performance status (P = 0.013), age (P = 0.015), and weight loss (P = 0.007) were prognostic factors for survival. Serum E-selectin levels showed a trend (P = 0.08) related to worse prognosis, however serum ICAM-1 levels were determined as ineffective on survival (P = 0.11). Multivariate analysis revealed that only weight loss (P = 0.005) and E-selectin levels (P = 0.002) remained as an independent prognostic factor for survival in patients with advanced NSCLC. In conclusion, our data suggest that higher serum ICAM-1 can be useful for diagnosis while E-selectin levels have prognostic significance and could be a potential prognostic factor in NSCLC patients.

Serum levels of apoptosis biomarkers, survivin and TNF-alpha in nonsmall cell lung cancer.

CONTEXT: This study was conducted to investigate the prognostic role and the effects of chemotherapy on serum apoptosis biomarkers consisting of survivin and tumor necrosis factor alpha (TNF-alpha) in patients with advanced stage nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Fifty-seven patients with newly diagnosed NSCLC were enrolled into study. Performance status was 0 or 1 in 47 patients and 2 in 10 patients. Thirty-two of them were no or less than 10% weight loss. Patients were treated with platinum-based chemotherapy. Serum levels of TNF-alpha and survivin were determined by enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: While serum survivin levels in patients were not significantly different from controls (p=0.321), serum TNF-alpha levels in patients were found significantly higher than in controls (p=0.029). We found that serum TNF-alpha levels were increased (p<0.001), whereas serum levels of survivin (p=0.025) were decreased by the chemotherapy effects. The changes of the TNF-alpha and survivin serum levels due to chemotherapy effect showed a significant negative correlation (r=-0.36 p=0.007). The increase of serum TNF-alpha levels was independent from chemotherapy response; however, the reduction of serum survivin levels was found only significant in the chemoresponsive group (p=0.039). While older age, weight loss and performance status yielded prognostic value, neither TNF-alpha nor survivin levels proved to be significant for survival. CONCLUSION: Our findings suggest that the reduction in the serum survivin levels of advanced NSCLC patients after chemotherapy can be used as a predictor of response to the chemotherapy but not that of survival.

Serum IL-8 and IL-12 levels in breast cancer.

Interleukins (ILs) are known to play a fundamental role in cancer. We investigated the serum levels of IL-8 and IL-12, in breast cancer patients, and their relationship with the prognostic parameters and therapy. Forty eight patients with pathologically verified breast carcinoma and 21 healthy controls were enrolled into the study. Serum samples were obtained at baseline and after two cycles of chemotherapy. Serum IL-8 and IL-12 levels were determined using enzyme-linked immunosorbent assay (ELISA). There was no significant difference in the baseline serum IL-8 and IL-12 levels between breast cancer patients and healthy controls (p = 0.365 and p = 0.871, respectively), no significant correlation between the prognostic parameters and the serum IL-8, IL-12 levels. However, in the subgroup consisting of metastatic breast cancer patients, baseline serum IL-8 levels were significantly higher compared with non-metastatic disease (p = 0.047). Anthracycline-based chemotherapy and the addition of taxane did not change the levels of both serum IL-8 and IL-12. Serum IL-8 level may be useful in determining metastatic breast cancer. Larger studies are needed to confirm this finding.

Addition of topotecan to standard cisplatin/etoposide combination in patients with extended stage small cell lung carcinoma.

BACKGROUND: Topotecan is an active agent for the management of untreated and recurrent extensive-disease small cell lung cancer (ED-SCLC). This study was designed to evaluate the efficacy and safety of a triplet combination with topotecan added to the standard PE regimen in previously untreated patients with ED-SCLC. MATERIALS AND METHODS: Twenty-one patients (median age 55 years, and 18 male) with chemotherapy-naive ED-SCLC were enrolled into the study. PET treatment consisted of etoposide 80mg/m(2), cisplatin 20mg/m(2) and topotecan 0.75mg/m(2) and all were given intravenously on days 1 to 3 for every 3 weeks. RESULTS: Leucopoenia and/or neutropenia and to a lesser extent thrombocytopenia were the main dose-limiting toxicities. Severe leucopenia/neutropenia were observed in 14 (67%)/12 (57%) patients, and only two (10%) developed febrile neutropenia. Severe thrombocytopenia was observed in 6 (29%) patients and one patient died due to orbital and cerebral haemorrhage. Dose reductions were required in 13 (62%) patients, delays in 8 (38%) patients and early treatment discontinuation in 3 (14%) patients. The overall response rate was 52.6% (95% CI: 28, 9-75.6) with 2 (10.5%) complete and 8 (42.1%) partial responses. The overall median survival time was 6.6 months (range 0.5-16.5 months) and the 6-month overall survival was 65.3%+/-11.7. The overall median survival time of responders was 9.7 months compared to 5.7 months in non-responders (p=0.026). CONCLUSION: Topotecan combined with PE regimen with this schedule and dosage does not seem to provide any benefit in terms of response and survival in ED-SCLC patients and does not deserve further studies.

Serum and urine survivin levels in breast cancer.

This study was conducted to investigate the serum and urine levels of survivin in patients with breast cancer and the relationships with known prognostic parameters and therapy. Forty-three patients with breast cancer and 21 healthy control subjects were investigated. Serum samples were obtained on the first admission before adjuvant and metastatic treatment were given and after two cycles of chemotherapy. Serum and urine survivin levels were determined using enzyme immunometric assay (EIA) and enzyme-linked immunosorbent assay (ELISA), respectively. There was no significant difference in the baseline serum and urine levels between patients with breast carcinoma and healthy controls (p = 0.19 and p = 0.84, respectively). None of the prognostic parameters analyzed were significantly correlated with the urine survivin concentrations. This was also true for serum survivin values, except for nodal involvement. Serum survivin levels were significantly higher in the patients with nodal involvement compared with node negatives (p = 0.043). However, serum survivin levels were not influenced by the number of involved nodes (p = 0.77). No significant correlation was found between the serum and urine levels of survivin (r = 0.15, p = 0.27). Serum and urine levels did not change significantly after chemotherapy (p = 0.59 and p = 0.50, respectively). In conclusion, the result of this study suggested that serum survivin level could be a sensitive marker for detecting metastases in lymph nodes from breast cancer patients. However, much research continues in this field, and exciting new knowledge will ultimately emerge.

Isolated skeletal muscle recurrence of the paranasal sinus lymphoma in complete remission.

Paranasal sinuses represent an unusual site for non-Hodgkin's lymphoma (NHL). Failure after treatment for paranasal sinus lymphomas is usually in non-irradiated sites and marginal sites. With this case report, we present a paranasal sinus lymphoma in complete remission with an isolated recurrence in skeletal muscle of the right lower limb for the first time in the literature.