The roles of antiapoptotic sphingosine kinase-1 and glucosylceramide genes in drug induced cell death of MCF-7 breast cancer cells.

PURPOSE: Sphingolipids are important signaling molecules mediating cell survival, proliferation, cell cycle regulation and apoptosis. Ceramide is the most vital sphingolipid which induces growth arrest, senescence, and apoptosis. In this study, we aimed to determine the roles of sphingosine kinase-1 (SK-1) and glucosylceramide synthase (GCS) genes in paclitaxel, doxorubicin, tamoxifen, cyclophosphamide and docetaxel induced apoptosis in human MCF-7 breast cancer cells. METHODS: IC50 values (drug concentration inhibiting cell growth by 50%) of the anticancer agents were calculated using XTT cell proliferation assay. Changes in mitochondrial membrane potential (MMP) were determined using JC-1 assay kit. Changes in the mRNA levels of SK-1 and GCS genes were measured by using RT-PCR technique. RESULTS: The results demonstrated significant decrease in cellular proliferation and increase in loss of MMP in a dose-dependent manner. Paclitaxel, doxorubicin, tamoxifen, cyclophosphamide and docetaxel application downregulated SK-1 expression while paclitaxel, tamoxifen, cyclophosphamide and docetaxel but not doxorubicin downregulated GCS comparing to untreated control cells. CONCLUSION: These results show for the first time that these agents induce apoptosis in MCF-7 cells by downregulating the antiapoptotic SK-1 and GCS genes that may result in accumulation of apoptotic ceramides.

Primary thyroid lymphoma: case series with literature review.

Non Hodgkin's lymphomas (NHL) of the thyroid are rare thyroid neoplasms. The majority of histopathologic types are extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type and, diffuse large B-cell lymphoma (DLBCL). Most of them arise in a background of Hashimoto's thyroiditis and patients mostly present with a rapidly enlarging thyroid mass and with pressure symptoms. Treatment depends on the histological subtype and stage of the disease and includes radiotherapy and chemotherapy. The prognosis usually is favorable with proper treatment. Herein, we discuss the clinical diagnosis and treatment of thyroid lymphoma.

Multiple myeloma presenting as massive ascites.

Ascites is a rare complication of multiple myeloma and may occur either at presentation or more often during the disease course. Most reported cases have been associated with IgA type of myeloma. When it occurs, it is usually associated with extensive liver infiltration with plasma cells, infectious peritonitis or myelomatous peritoneal infiltration. Herein, we describe a case of IgG type multiple myeloma diagnosed by further examinations due to the presence of plasma cells in ascitic fluid.

A patient with diffuse large B-cell non-Hodgkin's lymphoma and AA type amyloidosis.

AA-type amyloidosis is a consequence of a long-standing systemic inflammation and is not associated with a monoclonal protein or clonal bone marrow plasma cells. Proinflammatory cytokines such as interleukin (IL)1, IL-6, and tumor necrosis factor (TNF) stimulate the synthesis of serum amyloid A during inflammation. Although the association of non-Hodgkin's lymphoma (NHL) with AL-type amyloidosis is well known and patients with Hodgkin's lymphoma with AA amyloidosis have been described, AA-type amyloidosis with NHL is extremely infrequent. We report a case of amyloidosis associated with NHL that subsided during R-CHOP chemotherapy.

The development of metachronous prostate cancer and chronic myeloid leukemia in a patient with metastatic rectal cancer.

We report herein an unusual case of metachronous triple cancers (rectum, prostate and Philadelphia(+) [Ph(+)] chronic myeloid leukemia [CML]). A metastatic rectal cancer was diagnosed in a 76-year-old male patient, who was treated with transanal tumor resection and chemotherapy. Thirty months from the initial rectal cancer diagnosis, prostate cancer was diagnosed and the patient was administered maximal androgen blockade and received palliative radiotherapy to the lumbar spine because of painful bone metastases. Thirty months after the diagnosis of rectal cancer and 12 months after the diagnosis of prostate cancer the patient developed Ph(+) CML and imatinib treatment was started. After one-year period in remission, CML evolved into accelerated phase and the patient died of intracranial hemorrhage.

Effects of insulin+glucose pretreatment on bupivacaine cardiotoxicity in rats.

A mistaken overdose of bupivacaine into systemic circulation may cause severe cardiovascular side effects. The aim of this study was to assess the effects of pretreatment with combined intra venous lipid emulsion (ILE) and high-dose insulin therapy against cardiotoxicity caused by bupivacaine intoxication. The rats were divided into the following three groups: Group B received a saline pretreatment plus a bupivacaine, group L received ILE pretreatment plus a bupivacaine, and in group I, insulin with glucose was infused intravenously, plus ILE pretreatment plus a bupivacaine. The electrocardiogram tracing, invasive arterial pressure, and heart rate (HR) of rats were monitored continuously. Arterial blood gas analysis was performed in all groups. Arterial blood gas analysis revealed that the baseline pH, PaO2, and PaCO2 values were similar between groups ( p > 0.05). Widening of Q, R, and S wave complex was found 46.8 ± 16.7, 92.0 ± 5.80, and 106.5 ± 17.9 s after initiation of bupivacaine infusion in groups B, L, and I, respectively. Time elapsed until 25% reduction of HR 127.3 ± 17.7, 248.4 ± 34.1, and 260.1 ± 51.3 s for groups B, L, and I, and 25% reduction of mean arterial pressure 107.6 ± 14.1, 253.2 ± 36.3, and 292 ± 57.7 s for groups B, L, and I, respectively. Arrhythmia was observed after 142.2 ± 27.5, 180.7 ± 17.8, and 190.7 ± 19.2 s for groups B, L, and I, respectively. Finally, asystole occurred after 560.1 ± 76.4, 782.4 ± 63.0, and 882.5 ± 105.1 s for groups B, L, and I, respectively. This finding indicates that the survival time of rats administered pretreatment with ILE plus insulin+glucose and those given ILE was observed to be longer.

Symptomatic hypocalcemia in a patient with latent hypoparathyroidism and breast carcinoma with bone metastasis following administration of pamidronate.

Pamidronate is an effective drug used not only in patients with tumor-associated hypercalcemia, but also in normocalcemic patients with metastatic bone disease to relieve pains. We describe a 39-year-old normocalcemic patient with subclinical hypoparathyroidism and bone metastasis due to breast carcinoma. Following parenteral administration of 60 mg pamidronate, the corrected serum level of calcium decreased from 2.12 mmol/l (=8.9 mg/dl) to 1.42 mmol/l (5.7 mg/dl), accompanied with carpal pedal spasm. The present case indicates that the hypocalcemia due to latent hypoparathyroidism was compensated by extensive osteolysis due to bone metastasis, and that overt hypocalcemia may develop after intravenous administration of pamidronate in such a patient.

Effect of Sialic Acid on Platelet Cryopreservation.

Sialic acid is a molecule which is responsible for the net negative surface charge of platelets. We investigated the effect of sialic acid on fresh and cryopreserved platelets. Platelet samples were obtained by platelet apheresis from 8 healthy donors. Platelet suspensions with different sialic acid concentrations (0, 1, 2 and 4 mg/mL) were studied for ADP and ristocetin induced platelet aggregation, basal and ADP induced P-selectin and glycoprotein- Ib/IX expression. Then platelet samples were cryopreserved in 5% DMSO with or without 4 mg/mL sialic acid. After thawing, P-selectin expression was compared with the control group. Six samples were also washed after thawing and P-selectin expression was again compared to unwashed samples. Sialic acid suppressed ADP induced platelet aggregation and P-selectin expression in a dose dependent manner. In cryopreserved samples, P-selectin expression of 4 mg/mL sialic acid containing group was found significantly higher than the control group (p< 0.001). In cryopreserved control group, P-selectin expression of thawedwashed group was significantly higher than thawed-unwashed group (p< 0.05). Our results indicate that sialic acid is not a good cryoprotective agent. Washing procedure after thawing to eliminate DMSO causes significant platelet activation.