Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabine.

Ribonucleotide reductase subunits M1 (RRM1) and M2 (RRM2) are involved in the metabolism of gemcitabine (2',2'-difluorodeoxycytidine), which is used for the treatment of nonsmall cell lung cancer. The mRNA expression of RRM1 and RRM2 in tumours from lung adenocarcinoma patients treated with docetaxel/gemcitabine was assessed and the results correlated with clinical outcome. RMM1 and RMM2 mRNA levels were determined by quantitative real-time PCR in primary tumours of previously untreated patients with advanced lung adenocarcinoma who were subsequently treated with docetaxel/gemcitabine.

Gemcitabine plus oxaliplatin (GEMOX) in pretreated patients with advanced ovarian cancer: a multicenter phase II study of the Hellenic Oncology Research Group (HORG).

The aim of this study was to evaluate the safety and activity of a gemcitabine-oxaliplatin combination (GEMOX) regimen in pretreated patients with advanced ovarian cancer. Twenty-seven platinum-refractory/resistant and 14 platinum-sensitive patients received gemcitabine 1500 mg/m2 intravenously in days 1+8 and oxaliplatin 130 mg/m2 in day 8 every 21 days. Ten responses (one complete, nine partial) were observed; five in platinum-sensitive and five in platinum-resistant tumors.

Molecular detection and prognostic value of circulating cytokeratin-19 messenger RNA-positive and HER2 messenger RNA-positive cells in the peripheral blood of women with early-stage breast cancer.

Purpose: The aim of this study was to evaluate the clinical relevance of the simultaneous detection of cytokeratin (CK)-19 messenger RNA (mRNA)- and HER2 mRNA-positive cells in peripheral blood of women with early-stage breast cancer.

Patients And Methods: CK-19 mRNA- and HER2 mRNA-positive cells were detected using a real-time and a nested reverse-transcriptase polymerase chain reaction assay, respectively, in a cohort of 185 women with early-stage breast cancer before the initiation of any adjuvant systemic treatment. Detection of CK-19 mRNA- and HER2 mRNA-positive cells in the peripheral blood was correlated with clinical outcome.

Circulating tumor cells in breast cancer.

Purpose Of Review: To critically review the latest findings concerning the detection and characterization of circulating tumor cells in breast cancer.

Recent Findings: Various studies have used different methods and markers for circulating tumor cell detection in breast cancer. Data on the prognostic value of circulating tumor cell monitoring by the CellSearch system are now available in patients with measurable metastatic breast cancer receiving chemotherapy, whereas no such data are still available for adjuvant or neoadjuvant settings.

Comparison of HER2 detection methods between central and regional laboratories in Greece.

Purpose: HER2 gene amplification and overexpression is associated with aggressive breast cancer and poor prognosis. Accurate HER2 testing of patients with breast cancer before treatment is important to ensure that as many patients with HER2-positive breast cancer as possible receive the most appropriate treatment and that women with HER2-negative disease avoid a potentially toxic therapy. This study compares immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) HER2 testing at central and regional laboratories in Greece.

'Classical' but not 'other' mutations of EGFR kinase domain are associated with clinical outcome in gefitinib-treated patients with non-small cell lung cancer.

'Classical' mutations in the EGFR tyrosine kinase domain (exons 18, 19 and 21) have been associated with sensitivity to tyrosine kinase inhibitors (TKIs) in patients with NSCLC. The aim of the current study was to evaluate whether other than the classical G719X, DEL19 and L858R mutations of EGFR confer sensitivity to TKIs. Genomic DNA was extracted from microdissected formalin-fixed paraffin-embedded tumour tissue from 86 patients treated with gefitinib.

A dose escalation study of the biweekly administration of paclitaxel, oxaliplatin and capecitabine in patients with advanced solid tumors.

Purpose: To determine the dose-limiting toxicities (DLTs) and the maximum-tolerated doses of the paclitaxel, oxaliplatin (LOHP) and capecitabine combination in patients with advanced solid tumors.

Patients And Methods: Patients received escalating doses of paclitaxel (starting dose 100 mg/m2) and LOHP (starting dose 40 mg/m2) on days 1 and 15 and capecitabine (starting dose 800 mg/m2/day) on days 1-7 and 15-21 every 28 days. DLTs were evaluated in the first cycle.

A dose escalation and pharmacokinetic study of biweekly pegylated liposomal doxorubicin, paclitaxel and oxaliplatin in patients with advanced solid tumors.

Purpose: To evaluate the maximum tolerated doses (MTD) and the dose-limiting toxicities (DLT) of the combination of pegylated liposomal doxorubicin (PEG-LD), paclitaxel and oxaliplatin (L-OHP) administered every 2 weeks in patients with advanced solid tumors.

Methods: Thirty-nine pretreated patients with advanced solid tumors received escalated doses of PEG-LD (10-16 mg/m(2)), paclitaxel (100-120 mg/m(2)) and L-OHP (50-70 mg/m(2)) every 2 weeks. As one cycle of treatment was considered the administration of both drugs on days 1 and 15 of a 4-week cycle.

Different prognostic value of cytokeratin-19 mRNA positive circulating tumor cells according to estrogen receptor and HER2 status in early-stage breast cancer.

Purpose: To examine the prognostic value of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in early-stage breast cancer patients focusing on clinically relevant subgroups based on estrogen receptor (ER) and HER2 expression.

Patients And Methods: CK-19 mRNA-positive CTCs were detected by real-time reverse transcriptase polymerase chain reaction in the blood of 444 consecutive, stage I-III, breast cancer patients before initiation of adjuvant chemotherapy. The association between detection of CK-19 mRNA-positive CTCs and clinical outcome was analyzed for patients with ER-positive, ER-negative, triple-negative, HER2-positive, and ER-positive/HER2-negative tumors.

A dose escalation study of biweekly oral vinorelbine and gemcitabine in patients with solid tumors.

Purpose: To determine the maximum tolerated doses (MTDs) and the dose-limiting toxicities of a biweekly administration of oral vinorelbine and gemcitabine in patients with advanced solid tumors.

Patients And Methods: Twenty-eight patients with advanced stage solid tumors were enrolled, and 12 (42.9%) of them were chemotherapy naive.

Docetaxel versus docetaxel plus gemcitabine as front-line treatment of patients with advanced non-small cell lung cancer: a randomized, multicenter phase III trial.

To compare the overall survival (OS) of patients with advanced non-small cell lung (NSCLC) treated with either docetaxel plus gemcitabine or single-agent docetaxel. Chemotherapy-naive patients with advanced/metastatic NSCLC were randomly assigned to receive either DG [n=157; gemcitabine 1100mg/m(2) on days 1 and 8], docetaxel 75mg/m(2) on day 8 or D [n=155; docetaxel 100mg/m(2) on day 1] every 3 weeks. A total of 312 patients were evaluable for toxicity and response.

Imatinib inhibits colorectal cancer cell growth and suppresses stromal-induced growth stimulation, MT1-MMP expression and pro-MMP2 activation.

Tumor progress depends on the proliferation of cancer cells, their interactions with stroma and the proteolytic action of enzymes. Colon cancer is c-kit positive and responsive to the specific tyrosine kinase inhibitor imatinib. We investigated the effect of imatinib on the proliferation of a panel of epithelial colon cancer cell lines in presence and absence of the antimetabolite 5-FU, and the effect of conditioned media (CM) derived from colon stromal fibroblasts with and without previous exposure to imatinib.

A dose escalation study of gemcitabine plus pemetrexed administered biweekly in patients with solid tumors.

Purpose: The study aimed to determine the maximum tolerated doses (MTDs) and identify the dose-limiting toxicities of the biweekly administration of pemetrexed plus gemcitabine in patients with solid tumors.

Patients And Methods: Patients with advanced malignancies were treated with escalated doses of gemcitabine and pemetrexed (starting doses 1,250 and 300 mg/m(2), respectively) both given on days 1 and 15 in cycles of 4 weeks.

Results: Forty-one patients were treated at 7 dose levels.

A dose-escalation study of pegylated liposomal Doxorubicin and oxaliplatin in patients with advanced solid tumors.

Purpose: A phase I study was conducted to determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of the pegylated liposomal doxorubicin (PLD) and oxaliplatin combination in patients with advanced solid tumors.

Patients And Methods: Forty-five patients with advanced-stage solid tumors received escalating doses of PLD 25-50 mg/m(2) as 60-min intravenous (i.v.

Vaccination of patients with advanced non-small-cell lung cancer with an optimized cryptic human telomerase reverse transcriptase peptide.

Purpose: To evaluate the immunological and clinical response as well as the safety of the optimized peptide telomerase reverse transcriptase p572Y (TERT572Y) presented by HLA-A*0201 in patients with advanced non-small-cell lung cancer (NSCLC).

Patients And Methods: Twenty-two patients with advanced NSCLC and residual (n = 8) or progressive disease (PD; n = 14) following chemotherapy and/or radiotherapy received two subcutaneous injections of the optimized TERT572Y peptide followed by four injections of the native TERT572 peptide administered every 3 weeks. Peptide-specific immune responses were monitored by enzyme-linked immunosorbent spot assay and/or TERT572Y pentamer staining.

A dose escalation and pharmacokinetic study of biweekly pegylated liposomal doxorubicin, paclitaxel and gemcitabine in patients with advanced solid tumours.

To determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of pegylated liposomal doxorubicin (PLD), paclitaxel (PCX) and gemcitabine (GEM) combination administered biweekly in patients with advanced solid tumours. Twenty-two patients with advanced-stage solid tumours were treated with escalated doses of PLD on day 1 and PCX plus GEM on day 2 (starting doses: 10, 100 and 800 mg m(-2), respectively) every 2 weeks. DLTs and pharmacokinetic (PK) parameters of all drugs were determined during the first cycle of treatment.

Front-line bevacizumab in combination with oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) in patients with metastatic colorectal cancer: a multicenter phase II study.

Purpose: To evaluate the efficacy and the toxicity of front line FOLFOX4 combined with bevacizumab in patients with metastatsic CRC (mCRC).

Patients And Methods: Chemotherapy-naïve patients with mCRC, received bevacizumab (5 mg/kg every 2 weeks d1), oxaliplatin (85 mg/m2 on d1), leucovorin (200 mg/m2) on days 1 and 2 and 5-Fluorouracil (400 mg/m2 as i.v.

Phosphorylation of FAK, PI-3K, and impaired actin organization in CK-positive micrometastatic breast cancer cells.

Several markers have been used to detect circulating tumor cells (CTC) in the peripheral blood of patients with breast cancer. However, analysis of activated signaling kinases in CTC implicated in cellular transformation, migration, and survival has not been addressed so far. In the present study, we focused on the phenotypic profile of micrometastatic cells in peripheral blood mononuclear cells (PBMC) preparations from 45 breast cancer patients.

Clinical relevance of circulating CK-19 mRNA-positive cells detected during the adjuvant tamoxifen treatment in patients with early breast cancer.

Background: The purpose of this study was to evaluate the effect of adjuvant treatment with tamoxifen on the CK-19 mRNA+ cells in patients with early-stage breast cancer.

Patients And Methods: CK-19 mRNA+ cells were prospectively and longitudinally detected using a specific real-time PCR assay for CK-19 mRNA in 119 patients with estrogen and/or progesterone receptor-positive tumors during the period of tamoxifen administration.

Results: Twenty-two (18.

Simultaneous expression of c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4 receptors in non-small-cell lung carcinomas: correlation with clinical outcome.

The expression of c-erbB receptors was immunohistochemically examined in paraffin embedded specimens from non-small-cell lung carcinomas. A total of 209 patients were enrolled [squamous-cell carcinomas (n=59), adenocarcinomas (n=130), large-cell carcinomas (n=15) and giant-cell carcinomas (n=5)]. The HercepTest kit scoring guidelines were used for the interpretation of positivity.

Irinotecan plus weekly 5-fluorouracil and leucovorin as salvage treatment for patients with metastatic colorectal cancer: a phase II trial.

Background: A phase II study was conducted to evaluate the toxicity and efficacy of irinotecan/5-fluorouracil/leucovorin (CPT-11/5-FU/LV (AIO schedule)) as salvage treatment in patients with metastatic colorectal cancer.

Patients And Methods: 33 patients relapsing after oxaliplatin (L-OHP)-based first-line chemotherapy were enrolled. Their median age was 69 years, 20 (61%) patients were male, and performance status (WHO) was 0, 1, and 2 in 15, 16 and 2 patients respectively; prior surgery 20 (61%) patients; adjuvant chemotherapy 11 (33%) patients, and adjuvant radiotherapy 6 (18%) patients.

Irinotecan plus weekly 5-fluorouracil and leucovorin as salvage treatment for patients with metastatic colorectal cancer: A phase II trial.

Purpose: A phase II study was conducted to evaluate the toxicity and efficacy of irinotecan (CPT-11), 5-fluorouracil/leucovorin (5-FU/LV) (AIO regimen) as salvage treatment in patients with metastatic colorectal cancer (MCC).

Patients And Methods: Thirty-three patients relapsing after oxaliplatin-based first line chemotherapy were enrolled. There were 20 males and 13 females with median age of 69 years and WHO performance status (PS) of 0, 1, and 2 in 15, 16 and 2 patients, respectively.

Circulating HER2 mRNA-positive cells in the peripheral blood of patients with stage I and II breast cancer after the administration of adjuvant chemotherapy: evaluation of their clinical relevance.

Background: The purpose of this study was to evaluate the prognostic value of circulating tumor cells (CTCs) expressing HER2 messenger RNA (mRNA) after the administration of adjuvant chemotherapy in women with operable breast cancer.

Patients And Methods: HER2 mRNA-positive CTCs were detected by nested RT-PCR in the peripheral blood of 214 patients with stage I and II breast cancer after the completion of adjuvant chemotherapy.

Results: HER2 mRNA-positive CTCs were detected in 45 (21%) patients.

ProANP and NT-proBNP levels to prospectively assess cardiac function in breast cancer patients treated with cardiotoxic chemotherapy.

Background: Cardiac function impairment is a known side effect of epirubicin-based chemotherapy. Activation of natriuretic peptides is demonstrated in patients with heart failure.

Aims: To identify prospectively the cardiotoxic profile of epirubicin-based chemotherapy in breast cancer patients and to evaluate the sensitivity of proANP and NT-proBNP as early biochemical markers of cardiac dysfunction.

An improved method for the diagnostic approach of alpha+-thalassaemia.

An improved method for the diagnostic approach of alpha(+)-thalassaemia is described. The method is based on five common parameters: absence of iron deficiency, mild morphological abnormalities of erythrocytes, normal or slightly reduced erythrocytic indices MCV and MCH, normal chromatographic findings, and presence of haemoglobin H inclusions in erythrocytes with methyl-violet stain after, but not before, incubation with oxidant agent. We studied by DNA analysis, 58 subjects fulfilling the above mentioned diagnostic criteria and we found that 50 of them (86.