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Biomedical subjects

P Ledakis

Publications and source records attributed to P Ledakis.

9 recordsLinked to original sources
PubMed2001

Weekly docetaxel and estramustine in patients with hormone-refractory prostate cancer.

The combination of docetaxel and estramustine has exhibited synergistic activity both in prostate cancer cell lines and in patients with hormone-refractory prostate cancer (HRPC). Based on these promising preclinical and phase I/II data, we conducted a study of weekly docetaxel and estramustine in patients with metastatic HRPC and a poor performance status. A total of 30 patients received (1) a 3-day course of oral estramustine during weeks 1 and 2 of each 3-week cycle plus (2) docetaxel, 35 mg/m(2) intravenously on day 2 of weeks 1 and 2. The median number of cycles per patient was 5, ranging from 1 to 22. The median patient age was 74 years (range, 61 to 90 years), and the median baseline Karnofsky performance status was 60% (range, 50% to 80%). Twenty-three patients (76%) had a > or =50% decrease in serum prostate-specific antigen (PSA); 17 (56%) of these patients had a > or =75% decrease in PSA. Pain scores and performance status likewise improved in 70% of patients. Three complete responses and four partial responses were observed among 12 patients with measurable disease. Toxicities were primarily nonhematologic in nature, with the most common being grade 1 through 3 nausea, asthenia, diarrhea, and edema. Given the activity and tolerability of weekly docetaxel and estramustine in this study, this regimen appears to be more suitable than previously studied docetaxel/estramustine administration schedules for treating metastatic HRPC in elderly patients with a poor performance status.

Adenocarcinoma↗
PubMed2001

Squamous cell carcinoma of the colon with an elevated serum squamous cell carcinoma antigen responding to combination chemotherapy.

Primary squamous cell colorectal carcinomas are uncommon, and their characteristics are not well known. They seem to occur most commonly in the fifth decade of life with a slight predominance for men. The most commonly reported anatomic locations are the rectum and the proximal colon. Clinical features and common diagnostic methods do not easily differentiate squamous cell colorectal carcinomas from adenocarcinomas. Because of their extremely rare occurrence, it is difficult to study their natural course, clinical behavior, and response to therapy. This report presents the case of a pure squamous cell colorectal cancer and provides a brief review of the literature, which includes 60 previously published cases. The case of a patient with T3N2M0 primary squamous cell carcinoma of the rectosigmoid colon, which was initially treated with abdominoperineal resection followed by adjuvant chemotherapy and radiation, is presented. During the follow-up, an elevated squamous cell carcinoma antigen (SCC Ag) level led to restaging computed tomography scans, which confirmed recurrent metastatic disease in the liver. Response to chemotherapy with a decrease in tumor size correlated with a decrease in the serum SCC Ag level. Although SCC Ag has been used as a tumor marker for squamous cell cancers of the lung, head and neck, uterine cervix, and esophagus, this is the first reported case of a squamous cell colon carcinoma presenting with an elevated SCC Ag at the time of recurrence. In addition, this patient showed an objective partial response to combination chemotherapy, with a decrease in the serum level of this tumor marker.

Antigens, Neoplasm↗
PubMed2001

An adverse interaction between warfarin and capecitabine: a case report and review of the literature.

Warfarin is one of the most commonly used oral anticoagulants in the clinic. It is well established that a wide range of antineoplastic drugs interact with warfarin, resulting in altered coagulation parameters and/or bleeding sequelae. While altered coagulation parameters have been observed in patients taking the oral 5-fluorouracil prodrug, capecitabine, in combination with warfarin, no report to date has described clinically overt evidence of bleeding. Herein, we report 2 cancer patients who presented with bleeding episodes that most likely resulted from an adverse interaction between capecitabine and warfarin after 6 weeks of concomitant therapy. In each case, there was a marked elevation in both the prothrombin time and international normalized ratio (> 10), with subsequent gastrointestinal bleeding. The exact mechanism of this interaction is yet unknown, but it is possible that capecitabine might, in some manner, reduce the hepatic metabolism of warfarin. Close monitoring of coagulation parameters is recommended for all patients receiving concomitant warfarin and capecitabine, with appropriate adjustment of warfarin dosage. The nature and extent of this interaction requires further investigation.

Aged↗
PubMed1998

Limitations of differential display.

Since its original description, differential display PCR (DD-PCR) has been extensively used in attempts to identify novel genes under a variety of circumstances. Despite its widespread use, however, few novel genes of interest have been identified. In the present study we describe a set of experiments examining reasons for failure of differential display. Evidence is presented that aberrant priming at both the 5' and 3' ends results in competition in the PCR, precluding detection of messages other than those which are abundantly expressed. Appropriate calculations are discussed which indicate this was predictable and unlikely to be overcome. While DD may be successfully applied in some settings, the evidence indicates that only abundantly expressed messages can be detected. This limitation is emphasized.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Cathepsins D, B, and L in malignant human lung tissue.

The levels of cathepsins in malignant and surrounding nonmalignant lung tissue were determined in 17 non-small cell lung cancer specimens. Cathepsin (Cat) D activity was assayed using hemoglobin, whereas Cat B and Cat L activities were assayed using fluorimetric substrates, benzoylcarbonyl-Ala-Arg-Arg-7-amino-4-methylcoumarine and benzoylcarbonyl-Phe-Arg-7-amino-4-methylcoumarine, respectively. Cat protein concentrations were determined using ELISAs. In malignant tissues, the activities of Cat B and Cat L were significantly higher than the activities in nonmalignant tissues (P < 0.0012 and P < 0.0003, respectively), whereas Cat D concentration was not. There was also a 5.6-fold increase in median Cat B protein (P < 0.054) and a 2.2-fold increase in Cat L protein (P < 0.069). By contrast, the aspartic proteinase, Cat D protein, was not significantly increased in tumors versus control lung tissues. Moderate but significant correlation (r = 0.5, P < 0.045) between Cat B and Cat L expression was observed, but neither correlated with Cat D. The relative increase in median Cat L activity (P < 0.037) and protein (P < 0.0005) was greater in poorly differentiated tumors than in moderate ones. Cat L activity (P < 0.003) and protein (P < 0. 005) increases were higher in adenocarcinoma than in squamous cell carcinoma. We conclude that in lung cancers the three lysosomal enzymes are regulated in a noncoordinate manner and that there is specific induction of cysteine cathepsins. Whether Cat B and/or Cat L would be of diagnostic and/or prognostic value requires further study in a larger patient population.

Adult↗