Wilms’ Tumor-1 Transcript in Peripheral Blood Helps Diagnose Acute Myeloid Leukemia and Myelodysplastic Syndrome in Patients With Pancytopenia.

Wilms’ tumor-1 transcript in peripheral blood helps diagnose acute myeloid leukemia and myelodysplastic syndrome in patients with pancytopenia.

Filed under: Drug and Alcohol Rehabilitation

Anticancer Res. 2012 Oct; 32(10): 4479-83
Yamauchi T, Matsuda Y, Takai M, Tasaki T, Hosono N, Negoro E, Ikegaya S, Takagi K, Kishi S, Yoshida A, Urasaki Y, Ueda T

Background/Aim: Pancytopenia is caused by acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), aplastic anemia (AA), or by non-hematological diseases. Because Wilms’ tumor-1 (WT1) is overexpressed in patients with AML and MDS, its expression level may be helpful for diagnosing these hematological malignancies.We retrospectively investigated the WT1 transcripts in peripheral blood (PB) from 47 patients with decreased blood cell counts.The final diagnoses included AML, MDS, AA, drug poisoning, and non-hematological diseases. PB WT1 mRNA was overexpressed in AML and MDS, whereas the patients with other diseases mostly tested negatively for the transcript. The patients with MDS with higher marrow blast counts had higher PB WT1 mRNA levels. The sensitivity of the PB WT1 transcript in detecting AML and MDS was 78%, and the specificity was 90%.The WT1 mRNA level in PB may help diagnose AML and MDS in patients with pancytopenia.
HubMed – drug

Combination Chemotherapy of Alternating Etoposide and Carboplatin with Weekly Administration of Irinotecan and Cisplatin in Extensive-stage Small-cell Lung Cancer.

Filed under: Drug and Alcohol Rehabilitation

Anticancer Res. 2012 Oct; 32(10): 4473-4478
Yoshimura A, Noro R, Miyanaga A, Mizutani H, Kosaihira S, Minegishi Y, Seike M, Hino M, Ando M, Nomura K, Okano T, Kobayashi K, Gemma A,

BACKGROUND: A phase II study was conducted to determine the tumor efficacy and tolerance of alternating chemotherapy in extensive-stage small-cell lung cancer (ED-SCLC). PATIENTS AND METHODS: Thirty-six patients with previously untreated ED-SCLC were enrolled in the study. At least four courses of chemotherapy consisting of alternation of two drug combinations were given: alternating cycles of etoposide and carboplatin (EC) with weekly administration of irinotecan and cisplatin (IP) at 3- or 4-week intervals. RESULTS: The overall response rate was 81.8%. The median duration of survival and progression-free survival were 314 days and 144 days, respectively. Hematological toxicity was the main adverse event. Grade 3 or 4 neutropenia, thrombocytopenia and anemia were observed in 69.2, 25.6 and 23.1% of the patients, respectively. Severe diarrhea (10.8%) was remarkable during the IP regimen. CONCLUSION: This novel alternating chemotherapy for patients with ED-SCLC showed moderate tumor efficacy and an acceptable safety profile.
HubMed – drug

Functional Profiling to Select Chemotherapy in Untreated, Advanced or Metastatic Non-small Cell Lung Cancer.

Filed under: Drug and Alcohol Rehabilitation

Anticancer Res. 2012 Oct; 32(10): 4453-60
Nagourney RA, Blitzer JB, Shuman RL, Asciuto TJ, Deo EA, Paulsen M, Newcomb RL, Evans SS

Background/Aim: To assess the impact of drug selection upon the treatment of advanced and metastatic non-small cell lung cancer (NSCLC), we applied a functional platform that measures drug-induced cell death in human tumor primary-culture micro-spheroids isolated from surgical specimens.At diagnosis, microspheroids isolated by mechanical and enzymatic disaggregation were examined for drug-induced cell-death by morphology and staining characteristics. Drugs were administered using standard protocols. Thirty-one patients, who received at least one cycle of therapy, were evaluable. All patients signed informed consent.Twenty out of 31 patients responded (64.5%), 1 completely and 19 partially, providing a two-fold improvement over historical control of 30% (p=0.00015), a median time-to-progression of 8.5 months and a median overall survival of 21.3 months.This functional platform is feasible and provides a favorable objective response rate, time-to-progression and survival in advanced, metastatic, untreated NSCLC, and warrants further evaluation.
HubMed – drug

Decitabine, a DNA Methyltransferase Inhibitor, Reduces P-Glycoprotein mRNA and Protein Expressions and Increases Drug Sensitivity in Drug-resistant MOLT4 and Jurkat Cell Lines.

Filed under: Drug and Alcohol Rehabilitation

Anticancer Res. 2012 Oct; 32(10): 4439-44
Onda K, Suzuki R, Tanaka S, Oga H, Oka K, Hirano T

Multidrug resistance (MDR) is a major clinical obstacle in the treatment of several cancers including hematological malignancies and solid tumors. The ATP-binding cassette transporter B1 (ABCB1) gene and its product, P-glycoprotein (P-gp), is one molecule that is involved in drug resistance. Here we report on the effect of decitabine (5-aza-2′-deoxycytidine), an inhibitor of DNA methyltransferase, on ABCB1 mRNA and P-gp expressions in drug-resistant MOLT4 and Jurkat cells. We found that decitabine treatment reduced ABCB1 mRNA and P-gp expressions in MOLT4/daunorubicin-resistant and Jurkat/doxorubicin-resistant cells. The decrease in the expression of ABCB1 mRNA and P-gp was accompanied by increased sensitivity to anticancer drugs in both drug-resistant cell lines. Our data suggest that DNA methylation is one of the mechanisms underlying ABCB1/P-gp overexpression in drug-resistant hematopoietic cell lines. The modulation of ABCB1/P-gp by DNA methylation inhibitors may be an effective strategy to overcome P-gp-related drug resistance.
HubMed – drug

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