Pavel Jandik

THE PERIPHERAL BLOOD LEUKOCYTE PHENOTYPE IN PATIENTS WITH BREAST CANCER: EFFECT OF DOXORUBICIN/PACLITAXEL COMBINATION CHEMOTHERAPY

Presence of functional immune system is critical for any attempt aimed at improving survival of breast cancer patients by strategies based on immune system manipulation. We evaluated by flow cytometry the phenotype of peripheral blood leukocyte of 43 breast cancer patients. In 11 patients, the phenotype was evaluated before and during the chemotherapy by combination of doxorubicin and paclitaxel (AT). Compared with controls breast cancer patients had significantly higher relative and absolute numbers of CD3−HLADR+, CD3−CD69+ and CD14+CD16−, and significantly lower percentages of CD3− and CD8−CD28+ cells. After one cycle of AT, the absolute numbers of CD3+, CD3−CD4−, CD3+CD8+ and CD8−CD28+ cells increased significantly. Present data show a presence of T-cell activation in breast cancer patients. Administration of AT may lead to an increase in functional T-cells in peripheral blood, indicating a potential for combining chemotherapy with immunotherapy in the treatment of breast cancer patients.

The association between specific nutritional antioxidants and manifestation of colorectal cancer

Determination of specific antioxidants for examination of oxidative balance and immune responses may be of value in the early diagnosis of colorectal cancer. In the present report, we investigated urinary excretion of zinc, copper, and neopterin and serum levels of vitamins A, C, and E in 30 patients (age = 64 +/- 12 y) with colorectal cancer at the time of diagnosis and in 30 control subjects (age = 61 +/- 11 y) with benign disorders not associated with a systemic inflammatory response. Urinary excretion of zinc, copper, and neopterin was significantly elevated, and serum concentration of vitamin A was decreased in patients with colorectal cancer; these changes are characteristics of systemic immune activation. These phenomena may be of use for the detection of tumor progression and immune response to neoplasm.

Pegylated Liposomal Doxorubicin in Combination with Hyperthermia for Treatment of Skin Metastases of Breast Carcinoma: A Case Report

Background: Incorporation of doxorubicin hydrochloride into pegylated liposomes (PLD) may decrease chemotherapy side effects and increase the activity. Hyperthermia could further potentiate its effectiveness. Case Report: A patient with skin metastases of breast carcinoma was treated with intravenous infusion of PLD (Caelyx®) in combination with ultrasound hyperthermia. Each cycle consisted of infusion of 40 mg PLD absolute dose, followed by 2 fractions of hyperthermia 41–43 °C for 45 min 1 and 48 h after infusion. A complete remission was observed after the combination treatment with no significant toxicity. Conclusion: Present observations suggest that the combination of PLD with hyperthermia of skin metastases of breast carcinoma may be an active and well tolerated treatment.

Increased urinary zinc excretion in cancer patients is linked to immune activation and renal tubular cell dysfunction

Urinary zinc excretion is known to be increased in cancer patients, but the pathogenesis of this phenomenon remains uncertain. Both skeletal muscle catabolism and renal tubular cell dysfunction have been proposed to explain this observation. We have investigated urinary zinc and N-acetyl-β-d-glucosaminidase (NAG), an indicator of renal tubular cell dysfunction, as well as serum neopterin, an index of systemic immune activation, in 22 patients with cancer and seven controls. Both serum neopterin and urinary zinc were significantly elevated in cancer patients (15.8 ± 12.7 versus 7.3 ± 2.3 nmol l−1 and 1.77 ± 0.80 versus 1.21 ± 0.41 mmol mol−1 creatinine, P < 0 and P < 0.05, respectively), while NAG was similar in cancer patients and the controls (13.58 ± 13.80 versus 13.68 ± 12.19 μkat mol−1 creatinine). A significant correlation was observed between serum neopterin and urine zinc (rs = 0.5119, P < 0.02), serum neopterin and urine NAG (rs = 0.6761, P < 0.002), and urinary zinc and NAG (rs = 0.6348, P < 0.002). In conclusion, the present data indicate a link between urinary zinc excretion and immune activation as well as renal tubular cell dysfunction. In addition, renal tubular cell dysfunction appears to be linked to immune activation.

HEPATIC ARTERIAL INFUSION CHEMOTHERAPY IN GASTRIC CANCER: A REPORT OF FOUR CASES AND ANALYSIS OF THE LITERATURE

Aims and background Gastric cancer is associated with high mortality. Although the liver is a common site of metastases in this tumor, the experience with liver-directed therapies is limited. Methods We report a single-center experience involving four patients with liver metastases from gastric cancer treated by hepatic arterial infusion (HAI). In addition, we performed a search for reports on HAI in gastric cancer metastatic to the liver and used the studies with data on survival of individual patients for a pooled analysis. Results Among three valuable patients, one had a complete response, one had stable disease and one had progressive disease. The patient with complete response is still alive 41 months after the diagnosis of liver metastases, while the other patients died 6, 22 and 31 months after the diagnosis. Objective responses were observed in 48% of the 25 patients in the pooled analysis. Objective response and limited hepatic involvement were independent predictors of survival in these patients. Conclusions Although isolated liver involvement in metastatic gastric cancer is rare, HAI seems to be similarly effective in these patients as in patients with liver metastases from colorectal cancer. The prognosis is significantly better in gastric cancer patients who have limited hepatic involvement and attain an objective response after HAI.

Pegylated liposomal doxorubicin in combination with hyperthermia in the treatment of a case of advanced hepatocellular carcinoma.

Background Currently, there is no standard treatment of inoperable advanced hepatocellular carcinoma. Study A patient with advanced hepatocellular carcinoma was treated with intravenous infusion of pegylated liposomal doxorubicin (PLD, Caelyx) in combination with ultrasound hyperthermia of the liver. Each cycle consisted of infusion of 60 mg of PLD followed by two fractions of hyperthermia 41°C to 43°C for 45 minutes 1 and 48 hours after infusion, respectively. Results A substantial regression of the tumor was observed on computed tomography scans. No toxicity of combined treatment was noted. Conclusions This may be the first report of the combination of PLD and hyperthermia in the treatment of advanced hepatocellular carcinoma. Our observation suggests that the combination of PLD with hyperthermia is technically feasible, well tolerated, and could have synergistic potential.

Expression of Bcl-2 in Breast Cancer: Correlation with Clinicopathological Characteristics and Survival

Breast cancer is the most common malignancy in women. It is an immensely heterogeneous disease, characterised by a broad variety of clinical development. The research in recent years has focused on finding new markers of prognosis. This study investigates the role of expression of the bcl-2 protein in breast cancer. We analysed bcl-2 expression in 57 women with primary breast carcinoma who were treated with neoadjuvant (primary) chemotherapy, followed by a surgical procedure. The bcl-2 expression was correlated with other clinicopathological characteristics of the tumour - histological grade, stage, expression of hormonal receptors, proliferation rate, and with the survival of the patients. No significant association of bcl-2 expression with either overall survival or disease free survival was found.

Preoperative neoadjuvant chemoradiation for locally advanced gastric adenocarcinoma

Abstract Aims and Background To evaluate toxicity and the radical resection rate in gastric adenocarcinoma treated with preoperative neoadjuvant chemoradiation. Materials & Methods 32 patients, 22 males and 10 females with gastric adenocarcinoma, were treated with chemoradiation and hyperthermia. Results The neoadjuvant regimen was completed as planned in 19/32 (59 %) patients; in the remaining patients the intensity of chemotherapy had to be reduced because of haematological and gastrointestinal toxicity. Surgical stage was as follows: 2 patients pathologically complete response, 3 patients AJCC stage I.A, 5 patients stage I.B, 7 patients stage II, 7 patients stage III.A, 1 patient stage III.B, 7 patients stage IV. R0 resection was achieved in 19/32 (59%) patients, R1 in 2/32 (6%) patients and R2 in 11 (34%) patients. Downstaging after neoadjuvant chemoradiotherapy was achieved in 17/32 (53%) patients. At the date of evaluation (31 March 2009), 4 patients were still alive 58, 81, 86 and 98 months from the date of diagnosis. Median survival was 18 months (95% confidence interval: 13–38 months). One-year survival was 69% (95% confidence interval: 53%–85%). Four-year survival was 19% (95% C.I.: 5%–34%). Conclusions Preoperative neoadjuvant chemoradiotherapy has acceptable toxicity, and can lead to a high rate of R0 resections.

Serum Neopterin and Angiotensin-converting Enzyme In Cancer Patients

Summary An elevation of serum angiotensin-converting enzyme (ACE) has been reported in some disorders associated with immune activation, e.g. sarcoidosis, HIV infection or ulcerative colitis. Both endothelial cells and macrophages are thought to be the possible source of increased ACE levels. We have investigated serum ACE and neopterin, an indicator of macrophage activation, in 23 patients with solid tumors as well as in 8 controls. Similar ACE levels have been observed in the cancer patients and the controls (2.6 ± 2.1 vs 3.4 ± 1.1 μkat/1, while neopterin has been significantly higher in the cancer patients (15.4 ± 12.6 vs 7.2 ± 2.2 nmol/I, P<O.02). No correlation has been observed between serum ACE and neopterin. We conclude that an elevation of ACE is not present in cancer patients. Macrophage activation in cancer is not accompanied by increased ACE release.