The clinical importance of serum galectin-3 levels in breast cancer patients with and without metastasis.

OBJECTIVE: Studies have investigated expression status of galectin-3 (Gal-3), but very little is known about the importance of circulating Gal-3 in patients with breast cancer (BC). The purpose of the study was to investigate the clinical significance and potential diagnostic value of plasma Gal-3 levels in patients with BC. MATERIALS AND METHODS: Fifty-two patients with BC and 35 age-matched healthy controls were enrolled. Levels of Gal-3 were investigated in BC patients and healthy controls. Gal-3 levels were determined using ELISA method. RESULTS: Serum Gal-3 levels were significantly higher in BC patients than in controls (P = 0.002). Gal-3 levels did not significantly differ according to patients' statuses of lymph node involvement, hormone receptor, lymphovascular invasion, e-cadherin, menopausal, stage, serum hemostatic markers (prothrombin time, partial thromboplastin time, and international normalized ratio), platelet counts, mean platelet volume, lactate dehydrogenase, carcinoembryonic antigen, and carbohydrate antigen 15-3 values (P > 0.05 for all). A cut-off value of Gal-3 to predict BC was determined at ≥3.17 ng/ml with a sensitivity of 75.0%, a specificity of 65.71%, a positive and negative predictive values of 76.5 and 63.9%, respectively (area under the curve: 0.705 [95% confidence interval, 0.598-0.798], P = 0.0002). CONCLUSION: Serum Gal-3 levels were significantly higher in BC patients and did not significantly differ according to clinical and tumoral characteristics of patients. Furthermore, there was no difference in Gal-3 levels between BC patients with and without metastatic disease. Serum Gal-3 levels can be used as an adjunct to other diagnostic or screening tests for BC regardless of clinical and tumoral characteristics of patients.

The clinical importance of serum urokinase plasminogen activator receptor and carbonic anhydrase IX levels and the effect of anthracycline-based adjuvant chemotherapy on these biomarkers in breast cancer.

INTRODUCTION: Breast cancer mortality rates after metastasis is high. Urokinase plasminogen activator receptor (uPAR) and carbonic anhydrase IX (CAIX) play very important roles during tumor cell invasion and metastasis. The purpose of this study was to evaluate plasma levels of uPAR and CAIX and the effect of anthracycline-based chemotherapy on these biomarkers in patients with operable breast cancer. MATERIALS AND METHODS: Sixty-five patients and 25 age-matched healthy controls were enrolled. Levels of uPAR and CAIX were investigated before and after adjuvant chemotherapy. Basal (prechemotherapy) uPAR and CAIX levels in patients were compared with those in healthy controls and in patients after 3 cycles of chemotherapy. Levels of uPAR and CAIX were determined using the ELISA method. RESULTS: uPAR and CAIX levels were significantly higher in patients (P: 0.02 and P: 0.03, respectively). Postchemotherapy uPAR and CAIX levels were higher than basal levels (P: 0.645 and P < 0.001, respectively). A cut-off value of 27.99 pg/mL for uPAR was associated with 45.31% sensitivity and 84.62% specificity, and with a positive predictive value (PPV) of 87.9% and a negative predictive value (NPV) of 38.6%. A cut-off value of 777.84 pg/mL for CAIX was associated with 90.62% sensitivity and 30.77% specificity, and with a PPV of 76.3% and an NPV of 57.1%. CONCLUSION: We determined that uPAR and CAIX levels were higher in the fluorouracil, epirubicin, and cyclophosphamide (FEC) chemotherapy group than in the control group, but there was no difference between the FEC and epirubicin/adriamycin chemotherapy groups in terms of basal and postchemotherapy uPAR, CAIX levels. Furthermore, uPAR is more specific, and CAIX is more sensitive in the diagnosis of breast cancer.

Elevated Serum Levels of SCUBE1, a Marker for Coagulation, in Patients with Breast Cancer.

Breast cancer (BC) is the most common cancer among women and a major cause of death. Signal Peptide-Cub-Epidermal growth factor domain-containing protein-1 (SCUBE1) is secreted under hypoxia and inflammatory conditions from platelet alpha granules. Its biological function is uncertain, although it may be a procoagulant substance in cancer patients. SCUBE1 is useful for identifying thrombotic diseases, including cancers and acute coronary syndromes. D-dimer reflects the relationship between coagulation activation and fibrinolysis; namely, thrombosis and D-dimer levels are closely linked. This is the first investigation of the potential diagnostic and prognostic value of SCUBE1 levels in patients with BC. Fifty patients and 33 age-matched and body mass index-matched healthy controls were enrolled. Blood samples were collected before chemotherapy regimens commenced. Serum SCUBE1 and D-dimer levels were measured before adjuvant chemotherapy and were compared to the healthy controls. SCUBE1 levels were determined using an enzyme-linked immunosorbent assay (ELISA) method. SCUBE1 and D-dimer levels were significantly higher in patients than in the controls (p = 0.03 and p < 0.001, respectively). A cut-off value of 1.55 ng/mL for SCUBE1 was associated with 62% sensitivity and 72.7% specificity and with positive predictive value of 77.5% and negative predictive value of 55.8%. Two patients with high SCUBE1 and D-dimer levels also developed pulmonary embolism. SCUBE1 may indicate hypercoagulability in patients with BC and thus help identify patients at greater risk of thrombosis and requiring anti-thrombosis treatment. SCUBE1 may also be used as an assistant test for identifying patients at risk of BC.

The effect of adjuvant chemotherapy on plasma TAT and F 1+2 levels in patients with breast cancer.

INTRODUCTION: Increased thromboembolic disorders and chemotherapy-induced thromboembolic events are well known phenomena in patients with breast cancer. Antithrombin III (AT III) inactivates thrombin, resulting in increased thrombin-antithrombin (TAT) levels. Activated factor X cleaves prothrombin and thrombin, resulting in increased levels of prothrombin fragment 1+2 (F 1+2). Increased TAT and F 1+2 levels show coagulation activation. The aim of this study was to examine plasma levels of TAT and F 1+2 and the effect of anthracycline-based chemotherapy on plasma TAT and F 1+2 in patients with operable breast cancer. MATERIALS AND METHODS: Seventy patients and 30 age-matched healthy controls were enrolled. Levels of TAT and F 1+2 were investigated before and after adjuvant chemotherapy. Basal levels (pre-chemotherapy) of TAT and F 1+2 in patients were compared with those in healthy controls and patient levels after 3 cycles of chemotherapy. Levels of TAT and F 1+2 were determined using the ELISA method. RESULTS: TAT and d-dimer levels were significantly higher in patients, (P: 0.02 and P<0.001, respectively). Post-chemotherapy F 1+2 levels were higher than basal levels (P: 0.02). F 1+2 levels were higher in patients, although the difference was not statistically significant (P: 0.52). There was no difference between basal and post-chemotherapy TAT levels. DISCUSSION: In conclusion, while higher post-chemotherapy F 1+2 levels suggest that the cumulative effect of chemotherapy increases the risk of thrombosis, TAT and d-dimer levels indicate that the effect of the cancer further increases the risk of thrombosis in patients with operable breast cancer.

Clinicopathological Characteristics of Triple-negative Breast Cancers in the Northeast Region of Turkey.

BACKGROUND: Triple-negative (TN) breast cancer is a subtype of breast cancer characterised by a loss of estrogen receptor (ER), progesterone receptor (PR) expression, and the absence of human epidermal growth factor (HER2) overexpression. AIMS: To identify the relationships between clinicopathological characteristics of TN breast cancers in the northeast region of Turkey and disease free survival (DFS) and overall survival (OS). STUDY DESIGN: Retrospective clinical study. METHODS: Seven hundred and eighty non-metastatic breast cancer patients were enrolled in this study. The relationships between TN breast cancer and other breast cancers with respect to clinicopathological characteristics, as well as DFS and OS, were studied. RESULTS: The triple-negative phenotype was detected in 204 patients (27.1%). Patients with triple-negative breast cancer had more grade 2-3 tumours compared to those with other types of breast cancer (92.5% versus 84.3%, p=0.004). Invasive ductal carcinoma histology, on the other hand, was less prevalent in patients with TN breast cancer (77% versus 84.5%, p=0.016). No significant differences were identified between the groups in other clinicopathological variables. Relapse and mortality rates were higher in the TN group during the follow-up of both groups [57 (27.9%) versus 89 (16.2%), p<0.001 for relapse; 27 (13.2%) versus 37 (6.8%), p=0.005 for mortality]. The univariate analysis demonstrated shorter DFS and OS for patients with TN breast cancer compared to those with other types of breast cancer. In the multivariate analysis, patients with TN breast cancer were 2.21 times more likely to develop relapse, while the likelihood of death increased 3.21-fold (p<0.001 and p<0.001). CONCLUSION: Triple-negative breast cancers demonstrate a more aggressive clinical course compared to other breast cancers. More effective strategies should be developed for the treatment of this subgroup of breast cancer.

Diagnostic and prognostic significance of CA IX and suPAR in gastric cancer.

This study was intended to evaluate the prognostic and diagnostic significance of carbonic anhydrase IX (CA IX) and soluble urokinase plasminogen activator receptor (suPAR) levels in gastric cancer patients. CA IX and suPAR were analyzed from serum and plasma samples of gastric cancer patients. Fifty patients and 34 controls were enrolled. CA IX and suPAR levels were statistically significantly higher in the patient group (patient; 182.5 ± 212.4, control; 47.3 ± 32, P = 0.0001 and patient; 5.74 ± 5.3, control; 2.27 ± 0.77, P = 0.0001, respectively). CA IX and suPAR levels were higher in metastatic subjects (metastatic; 227.1 ± 273.5, non-metastatic; 147.4 ± 144.1, P > 0.05). Prognosis was worse in the patient group with elevated suPAR. CA IX and especially suPAR are correlated with the presence and stage of the disease. High suPAR levels indicate a poorer prognosis in gastric cancer patients.

Thrombin activatable fibrinolysis inhibitor and thrombin-antithrombin-III-complex levels in patients with gastric cancer.

The relation between cancer and coagulation is the subject of investigation since a relation between tumor and thrombosis has been determined. Antithrombin III is an important thrombin inhibitor, and increased thrombin-antithrombin (TAT) complex levels activate coagulation. Activated thrombin activatable fibrinolysis inhibitor (TAFI) inhibits the conversion of plasminogen to plasmin. In addition, it directly inactivates plasmin. Defective fibrinolysis increases the risk of thrombosis. In this study, we evaluated homeostatic parameters, TAFI, and TAT levels in patients with gastric cancer applying to the medical oncology outpatient clinic. Fifty-two patients and 35 healthy controls were included. ELISA was used to measure TAFI and TAT complex levels. These were statistically higher in the patient group (p < 0.05 and p = 0.001, respectively). D-dimer levels were higher in stage IV (p = 0.05). Correlations between lymph nodes and TAFI and TAT levels were examined. Weak but positive correlation between lymph nodes and TAFI was detected (R = 0.452, p = 0.027). TAFI and TAT levels were evaluated using relative operating characteristic analysis to differentiate the disease. TAT was more specific than TAFI according to this analysis (TAFI area under curve (AUC), 0.676; TAT AUC, 0.874). Thrombotic events and bleeding disorders need to be borne in mind in gastric cancer. This situation is due to the impairment of the balance between coagulation and fibrinolysis. Further studies are now needed to evaluate the effects of TAFI and TAT on survey and prognosis as well as the potential of these parameters as tumor markers for gastric cancer.

Effects of zoledronic acid and ibandronic acid on renal functions and calcium, phosphorus and alkaline phosphatase levels in breast cancer patients with bone metastases: a retrospective analysis.

AIM OF THE STUDY: Bone is a common site of metastasis in patients with breast cancer. Skeletal complications associated with bone metastasis are commonly treated with bisphosphonates. However, there are a number of side-effects associated with these, such as renal failure, hypocalcemia and osteonecrosis of the jaw. We aimed to determine the effects of ibandronic and zoledronic acid on serum creatinine (SCr), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP) and estimated glomerular filtration rates (eGFR). The objective was to determine the safety of these bisphosphonates, especially zoledronic acid. MATERIAL AND METHODS: Forty-one patients diagnosed with breast cancer (all with bone metastasis) were enrolled. We retrospectively evaluated bisphosphonate type, duration of treatment, infusion time and the parameters SCr, Ca, P, ALP and eGFR. RESULTS: Nineteen patients were included in the zoledronic acid group and 22 in the ibandronic acid group. Mean age in the ibandronic acid group was 53.27 ±11.01, and 53.26 ±9.98 in the zoledronic acid group. Median duration of administration in the ibandronic acid group was 11 (7-37) months, and 10 (7-57) months in the zoledronic acid group. SCr levels did not change significantly during the study period. Pre- and post-treatment Ca levels were also unchanged, but serum ALP levels in the ibandronic acid group and P levels in the zoledronic acid decreased after the final administration; eGFR was unchanged by the end of the study. CONCLUSIONS: Zoledronic and ibandronic acid are safe modalities in the treatment of skeletal events in breast cancer patients with bone metastasis.

Penile metastasis from adenocarcinoma of the prostate in a patient with colorectal carcinoma.

Skin metastasis secondary to cancer of the prostate is rare and the prognosis is poor. A 65-year-old male patient diagnosed with metastatic colon carcinoma presented with polyuria and subcutaneous nodular mass on dorsal side of the corpus penis. The serum prostate specific antigen (PSA) level was 111.1 ng/mL and therefore the patient underwent transperineal prostate biopsy. Pathology reported adenocarcinoma of the prostate. The subcutaneous nodular lesion on the penis was totally excised and removed. Immunohistochemical examination of the excised mass was carcinoembryonic antigen (CEA) negative and PSA positive. Taking all these findings into consideration, the patient was diagnosed with prostate cancer that had metastasized to the penis. FOLFOX-4 chemotherapy regime in addition to bicalutamide and goserelin acetate was administered to the patient who also had metastatic colon cancer.

Fifty-one Kaposi sarcoma patients.

INTRODUCTION: Kaposi sarcoma (KS) is a mesenchymal tumor originating from lymphatic endothelial cells. Immunosuppressive patients have higher risk for KS. HHV-8 has a role in immunopathogenesis of KS. Aim Evaluation of demographical properties with tumor characteristics and treatment modalities of KS. MATERIAL AND METHOD: Histopathologically documented KS patients were evaluated retrospectively. Anti-HIV seroprevalence was also evaluated with patient and tumor characteristics besides treatment regimens. RESULTS: Fifty-one patients were included between September 1998 and February 2009. Male/female ratio was 3.25 (39/12). Median age was 68 (31-94). Lower extremity was the most common site whereas excisional biopsy was the most common diagnostic procedure. Smoking rate was 42.8%. Twenty percent had family history for cancer. Anti- HIV seropositivity rate was 1.9%. Thirty eight percent had local monotherapy, and radiotherapy was most common (26%). Multidisciplinary approach rate was 44%. Most of them had surgery and radiotherapy combination. Two-third of the patients had radiotherapy alone or with other modalities. Rates were as 12% for chemotherapy and 6% for interferon. Vincristine-bleomycin-doxorubicin combination was the most preferred regimen (60%). CONCLUSION: Male patients in the sixth decade seem to have higher risk for KS. Smoking rate was almost as high. Local therapy might be sufficient in most of the patients. However, we may also consider systemic chemotherapy for selected patients, including vincristine, bleomycin and doxorubicin.

The expression of MCM-2 in invasive breast carcinoma: a stereologic approach.

OBJECTIVES: The aim of this study is to examine the expression of MCM-2 and conventional proliferation marker Ki-67 in breast carcinoma by stereologic technique and to compare it with various clinicopathologic parameters. METHODS: The expression of MCM-2 and Ki-67 on paraffin-embedded tumor tissue sections of patients with invasive breast carcinoma was analyzed immunohistochemically. Stereologic method was used for evaluation of the percentage of positively stained tumor cells. RESULTS: Significant positive correlation was found between the expression of MCM-2 and that of Ki-67 (r = 0.74, p < 0.001). MCM-2 and Ki-67 expression was significantly associated with histologic grade (p < 0.05), and negative correlation was observed between MCM-2 or Ki-67 expression and estrogen status (p < 0.05). No significant association was observed between MCM-2 or Ki-67 expression and patient age, tumor size, lymph node status, clinical stage and menopausal status. CONCLUSION: Our results suggest that MCM-2 expression is significantly associated with histologic grade of breast carcinoma and with cell proliferation capacity (Ki-67 labelling index). Additional studies are required using the stereologic method to compare and understand the utility of Ki-67 and MCM-2 expression in invasive breast carcinoma (Tab. 1, Fig. 4, Ref. 34). Full Text (Free, PDF) www.bmj.sk.

Laryngeal squamous cell carcinoma with knee and heel skin metastases: a case report.

Distant metastases from laryngeal carcinoma are frequently seen in the lung, bone and liver, while skin metastases are rarely observed. In these cases presented as case reports in the literature, the supradiaphragmatic region is usually involved. Skin metastasis in lower extremity has only been reported in a few cases. While being an indicator of poor prognosis, skin metastasis is also considered as a messenger of distant organ metastasis. Survival is very short after development of skin metastasis. In our case, nodular skin metastasis was found both in the superior-lateral margin of the left patella and in the right heel. This is the first case reported in the literature on laryngeal carcinoma metastasizing to these localizations.

Clear cell hidradenoma of the gluteal region: a case report.

Clear cell hidradenoma is a rare skin appendage tumor. A 41-year-old female presented with right gluteal mass. Excisional biopsy of the mass was performed. Under the epidermis, an eosinophilic-cytoplasm, uniform-appearance, oval-round-nucleus, benign tumor with cystic and solid components was detected. These results were consistent with clear cell hidradenoma. The patient had not been given postoperative adjuvant treatment and has been under follow up free from disease for 2 years.

Association of gastrointestinal stromal tumor and acute myeloid leukemia preceded by myelodysplastic syndrome with refractory anemia.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. GISTs are believed to be related to mutational activation of receptor tyrosine kinases, KIT, or platelet-derived growth factor receptor-alpha. The coexistence of GISTs with other neoplasms has been extensively addressed in the literature. The most common second neoplasms are colorectal cancer, prostate cancer, and neoplasms derived from lymphoid tissue. In this case report, we describe a patient affected by GIST and acute myeloid leukemia preceded by myelodysplastic syndrome with refractory anemia. The clinicopathological characteristics of the patient are discussed and the literature is reviewed.

The effects of melatonin on human hepatoma (Hep G2) cell line.

BACKGROUND: Melatonin has been suggested to have antiproliferative effects on cancer cells. These effects can be attributed to immunomodulation, growth factor inhibition, induction of apoptosis and prooxidant properties. Melatonin is considered as a safe drug with minimal adverse effects. OBJECTIVES: We planned to investigate the effects of melatonin in hepatoma (Hep G2) cell line. In this study, different concentrations of melatonin were studied to assess its effects on human hepatoma (Hep G2) cell line in vitro. METHODS: In this study, different doses (5 x 10(-5) M, 5 x 10(-4) M, 10(-3) M) of melatonin were administered into hepatocellular carcinoma cell line in vitro. After an incubation period of 72 hours, the studied and control groups were evaluated for cell cycle, morphology, proliferating index and apoptosis percentage. RESULTS: A significant decrease in percentage of phase G0/G1 cells was found in high-dose melatonin group (10(-3) M) compared to control group. Melatonin increased the cell counts in S phase of cell cycle at high doses as well. However, phase G2/M cell percentage did not change with the administration of melatonin. Cell proliferation was increased in all melatonin groups, but the only statistically significant difference was found between the high-dose and control groups. There was a significant increase in proliferative index between the control group and high-dose melatonin group. CONCLUSION: High dose of melatonin increases the cell count in S phase and shows an antiproliferative effect on hepatoma cells. This indicates that melatonin can be considered a promising drug when used along with other antineoplastic agents for the treatment of hepatoma.However, it has no effect on apoptosis and colony counts (Tab. 1, Fig. 2, Ref. 19). Full Text (Free, PDF) www.bmj.sk.

Effect of the farnesyl transferase inhibitor L-744,832 on the colon cancer cell line DLD-1 and its combined use with radiation and 5-FU.

BACKGROUND: Ras oncogenes are found in 25% of human tumors and they significantly affect prognosis. One of the major fields studied to improve anticancer drugs is blockade of the oncogenic ras protein function. One of the mechanisms to block the function of these proteins is to block farnesylation using a farnesyl transferase inhibitor (FTI) and thus to prevent the ras from anchoring to the cell membrane. METHODS: In this study, we investigated the effects of FTI L-744,832 either alone or in combination with 5-fluorouracil (5-FU; 1 microM/l) and radiotherapy (2, 6, and 10 Gy) on the colon cancer cell line DLD-1 with mutations in K-, N- and H-ras, c-myb, c-myc, p53, fos, sis and DNA repair genes. Drugs were added 3 h after cultivation. Radiotherapy was performed on the 3rd day of the study. On the 3rd day, medium and drugs were changed. Evaluations were performed on the 6th day. RESULTS: Administration of L-744,832, neither alone nor its combination with 5-FU and radiation, affected the number of DLD-1 cells and apoptosis rates. Regarding its effects on the cell cycle, L-744,832 was shown to lead to G(0)/G(1) and G(2)/M accumulation in a dose-dependent manner when administered alone. However, in combination with 5-FU, only a G(0)/G(1) accumulation was observed. CONCLUSION: Our study showed that FTI L-744,832 does not effect the cell number and apoptosis rate of DLD-1 cells and it cannot overcome 5-FU and radiation resistance, although it is able to modify some phases of the cell cycle.

Hodgkin's disease and autoimmune hemolytic anemia: a case report.

OBJECTIVE: To report a case of Hodgkin's disease presenting with immune hemolytic anemia. CLINICAL PRESENTATION AND INTERVENTION: A 47-year-old man was admitted to hospital because of weight loss, fever, and inguinal lymph node adenopathy. Biopsy of the inguinal lymph node revealed mixed-cellularity Hodgkin's disease. Three days after starting combined chemotherapy, the patient showed evidence of autoimmune hemolytic anemia, which responded well to prednisolone. CONCLUSION: This case shows that clinicians should be aware of the possibility of autoimmune hemolytic anemia in patients with Hodgkin's disease presenting with anemia, and distinguish it from the anemia of chronic disease.

Carcinoma erysipelatoides resulting from gastric adenocarcinoma: an unusual clinical presentation.

OBJECTIVE: To report a rare case of carcinoma erysipelatoides on the laryngeal skin caused by stomach adenocarcinoma. CLINICAL PRESENTATION AND INTERVENTION: A 48-year-old male, who had undergone a gastrectomy 18 months prior to admission for stage IIIA gastric adenocarcinoma, presented with a reddish induration of the cervical skin, lymphadenopathy in both supraclavicular areas and widespread subcutaneous nodules. Abdominal computerized tomography and chest radiography did not reveal any organ metastasis or peritoneal carcinomatosis. A biopsy of the induration revealed atypical epithelial cells with edema and dilatation of lymphatics. The patient was given combination chemotherapy of etoposide, adriamycin, and cisplatin, and significant improvement was observed over the cervical area after three courses. The patient tolerated the systemic chemotherapy well and has been followed for two months. CONCLUSION: We recommend combination chemotherapy in patients with cutaneous metastasis of gastric adenocarcinoma as a safe and effective treatment.

Hemostatic and fibrinolytic response to nasal desmopressin in hemodialysis patients.

OBJECTIVE: To evaluate the effect of desmopressin (DDAVP) on hemostatic parameters during dialysis and in the interval between dialysis sessions. SUBJECTS AND METHODS: Fifteen patients dialyzed twice weekly at least for 1 year and 15 healthy volunteers serving as a control group were enrolled in the study. Bleeding time, platelet count, prothrombin time, activated partial thromboplastin time, tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), euglobulin clot lysis time, protein C, protein S, fibrinogen, D-dimer, factor V, VII, VIII, IX, X and von Willebrand factor (VWF) values were studied at the beginning, at 2 and 4 h of dialysis with and without administration of DDAVP at a dose level of 2 microg/kg intranasally. RESULTS: After dialysis, bleeding time shortened, PAI-1 and fibrinogen levels were lower, while VWF and D-dimer levels were higher. After DDAVP administration, bleeding time, PAI-1 levels were significantly lower (p <0.01), while tPA, factor VIII and VWF levels increased significantly (p <0.001). CONCLUSION: The findings indicate that DDAVP can be used for patients on dialysis with serious bleeding.

Effects of dexamethasone, all-trans retinoic acid, vitamin D(3) and interferon-alpha on FO myeloma cells.

BACKGROUND: Since multiple myeloma responds poorly to conventional chemotherapy or radiotherapy, new therapeutic approaches are needed. This study investigated the effects of dexamethasone, all-trans retinoic acid (ATRA), the active metabolite of vitamin D(3) [1,25(OH)(2)D(3)] and interferon-alpha on FO mouse myeloma cells (non-immunoglobulin-secreting myeloma cell line) in single drug or drug combination groups in vitro. METHODS: Apoptosis ratio and change in cell counts in 4 single drug groups (dexamethasone, ATRA, vitamin D(3) and interferon-alpha) and 6 combination drug groups (dexamethasone + vitamin D(3,) dexamethasone + ATRA, dexamethasone + interferon-alpha, vitamin D(3) + ATRA, vitamin D(3) + interferon-alpha, interferon-alpha + ATRA) were compared with the control group. RESULTS: When treatment groups were compared with the control group, there was a significant increase in apoptosis in all, but this was most prominent in the group treated with dexamethasone alone. The apoptosis ratios were 0.10 and 6.82% in the control and dexamethasone-only groups, respectively. We also found that there was a significant decrease in cell count, particularly in the dexamethasone-only, ATRA-only, and ATRA-vitamin D(3) combination groups. CONCLUSION: ATRA, interferon-alpha, vitaminD(3) and particularly dexamethasone have significant effects on FO mouse myeloma cells resulting in a decreased cell count and an increased apoptosis ratio. This study should be repeated with human myeloma cell lines for further information.