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Abstract: Purpose: Bone marrow metastasis of cancer is a sign of extensively hematogenous spreading of cancer and may be a terminal event of those patients. With the improvement of systemic chemotherapy for malignant disease, some patients may have longer survival. We plan to find out the clinical hematologic presentation and prognostic factors in cancer patients with bone marrow metastasis. Materials & Methods: In this retrospective study, we reviewed the results of 162 bone marrow examination carried out in adult malignancy patients (colon, lung, gastric, breast and prostate cancers) between January 2002 and December 2012 in Changhua Christian Hospital. The indication for bone marrow study for those patients with hematologic disorders included: leukoerythroblastosis, microangiopathic hemolytic anemia, unknown etiology of anemia, thrombocytopenia, bicytopenia and pancytopenia. Statistics analysis used SPSS 18.0 and overall survival was analyzed with the use of Kaplan–Meier curves and the log-rank test. Results: Thirty-four patients (20.9%) had evidence of involvement of the bone marrow by a solid tumor, most common cancers were prostate and lung. At the time of diagnosis, the most common hematologic disorders were leukoerythroblastosis and microangiopathic hemolytic anemia. Median survival after the diagnosis of bone marrow metastasis with supportive care only compared with definite treatments was 0.3 months and 20.6 months (p<0.0001). Patients with visceral organ metastasis (0.4 months vs 6.4 months, respectively; p <0.002) and anemia (2.1 months vs 6.4 months, p=0.031) had inferior survival. Patents without any cytopenia had better survival (12.5 months vs 4.1 months, p=0.029). Initial level of thrombocyte and neutrophil, bone marrow infiltration type (focal or diffuse) and disease status were not significant prognostic factor. Conclusions: Visceral metastasis and anemia are most poor prognostic factors in solid cancers with bone marrow metastasis. Since the improvement of the diagnosis and treatment for cancers during the recent decades, a portion of patients can be had better disease control after definite treatment especially in breast and prostate cancers with bone marrow metastasis. Keywords: Bone marrow metastasis, leukoerythroblastosis, microangiopathic hemolytic anemia, bone marrow involvement, adenocarcinoma.Download Full Article |
Editor’s Choice : Pathological Complete Response Induced by the Combination Therapy of Gemcitabine and 24-h Infusion of Cisplatin in Two Cases Initially Diagnosed as Node-Positive Advanced Urothelial Carcinomas
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Abstract: We report on two patients, successfully treated by the combination therapy of gemcitabine and 24-h intravenous infusion of cisplatin, who were initially diagnosed with node-positive advanced urothelial cancer. Each patient had a very good clinical response and underwent curative radical surgery after gemcitabine/cisplatin chemotherapy. A microscopically detailed examination of surgically obtained specimens showed the complete disappearance of malignant cells in the two cases. As a pilot study, we have used the regimen of gemcitabine plus 24-h continuous infusion of cisplatin, instead of bolus injection, for the treatment of 20 patients with node-positive or metastatic urothelial cancer. The clinical response rate in this regimen was 75% (complete response 7/20; 35%, partial response 8/20; 40%). The median overall survival was 665 days. As for the adverse effects, the incidences of severe neutropenia and thrombocytopenia (grade 3-4) were 20% and 15%, which might be less toxic than conventional gemcitabine plus cisplatin therapy. The 24-h infusion of cisplatin combined with gemcitabine can be highly recommended as neoadjuvant chemotherapy for locally advanced urothelial cancer. Keywords: Urothelial carcinoma, cisplatin, gemcitabine, pathological complete response.Download Full Article |
Editor’s Choice : Acetylation of 1,2,5,8-tetrahydroxy-9,10-anthraquinone Improves Binding to DNA and Shows Enhanced Superoxide Formation that Explains Better Cytotoxicity on JURKAT T Lymphocyte Cells
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Abstract: Background: Hydroxy-9,10-anthraquinones form the core unit of anthracycline anticancer drugs and are close structural analogues to these drugs. Although they show close resemblance to anthracyclines in physicochemical characteristics and electrochemical behavior their biophysical interactions are somewhat weaker than anthracyclines which is a disadvantage. One reason is the formation of anionic species by hydroxy-9,10-anthraquinones. Hence if formation of anionic species is prevented there could be a possibility hydroxy-9,10-anthraquinones would bind DNA better. Procedure: For this 1, 2, 5, 8-tetrahydroxy-9,10-anthraquinone (THAQ) was acetylated to obtain a tetra-acetylated derivative (THAQ-ace) whose interaction with calf thymus DNA was studied using UV-Vis spectroscopy at different pH.
Results: Binding constant values for THAQ-ace (~105) were higher than THAQ at different pH. Increase in binding constant was attributed to anionic species not formed for THAQ-ace at physiological pH. Hence, unlike THAQ, binding constant values for THAQ-ace interacting with calf thymus DNA did not show variation with pH. In fact, it remained more or less constant. Increase in size of the acetylated form (THAQ-ace) compared to THAQ had a negative influence on binding. THAQ-ace showed enhanced superoxide formation. Both DNA binding and superoxide formation were responsible for a significant improvement in anticancer activity for THAQ-ace compared to THAQ on Jurkat T lymphocyte cells.
Conclusion: Binding constant values for THAQ-ace binding to DNA were close to that reported for some standard anthracyclines. Hence, suitable modification of the less costly hydroxy-9,10-anthraquinones could provide alternatives to anthracyclines in cancer chemotherapy. Keywords: Acetylated1,2,5,8-tetrahydroxy-9,10-anthraquinone (THAQ-ace), anthracycline, calf thymus DNA, superoxide, JURKAT T lymphocyte cells. Download Full Article |
Editor’s Choice : Evidence for the Conversion of Docetaxel into 7-Epidocetaxel in Patients Receiving Conventional Taxotere® Based Chemotherapy
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Abstract: Purpose:Epimerization at the C7atom of the baccatin moiety is a common in-vitro pathway for all taxanes, including the natural precursor 10-deacetyl baccatin III and the antineoplastic drugs paclitaxel and docetaxel. To date this in-vitro epimerization of both drugs has been elucidated completely, but epimerization of docetaxel in patients during chemotherapy has not yet described. The goal of this study was to identify the epimer of docetaxel in plasma and urine of taxotere treated patients. Patients and Methods:12 patients suffering from mamma carcinoma, lung cancer or prostate cancer were treated with various docetaxel-based schedules. Blood samples were drawn before start of infusion, at the end of infusion and 20 min thereafter, urine was collected and pooled for 6 hours. Docetaxel and its epimer epidocetaxel were quantified by solid phase extraction and reversed phase HPLC. Results:In 8 of 12 patients epidocetaxel could be quantified in plasma at the end of infusion (range 0.05 – 0.54 µg/ml). 20 minutes later concentrations were below LOQ due to rapid distribution of docetaxel into tissue. In urine, epidocetaxel has been found in 7 of 12 patients (range 0.1 – 0.5 µg/ml). Conclusion: Epidocetaxel is a distinct docetaxel metabolite in man. So our knowledge, this is the first time that quantification of epidocetaxel in blood and urine of chemotherapy patients has been reported. This finding is important for designing of new docetaxel generic drugs and the development of new chemotherapeutic schedules using docetaxel. To date the in-vivo pharmacologic and toxic properties of the epimer remain unclear. Keywords: Docetaxel, epidocetaxel, epimerization, patients, plasma, urine. Download Full Article |
Editor’s Choice : Auto-Analysis for Ki-67 Indices of Breast Cancer Using Specified Computer Software and a Virtual Microscopy
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Abstract: Ki-67 index is one of important markers that is correlated with chemotherapy response and prognosis of breast cancer patients. However, Ki-67 index is not easily provided and are limited by intra-observer error and potentially subjective decision making. We performed this study to develop an objective auto-analysis system to count Ki-67 indices. A total of185 invasive breast cancer cases were used. Immunohistochemical staining was performed using auto-stainer and MIB-1 antibody. The results were stored digitally by virtual microscopy and auto-analyzed by Genie/Aperio software (Vista, CA, USA). As for Ki-67 indices, a good correlation was observed between direct ocular observations and auto-analysis techniques (r = 0.94, p < 0.001). The index examined by auto-analysis was significantly correlated with nuclear atypia, mitotic counts, and nuclear grade of pT1 breast cancers. Auto-analysis of 5 high power fields was better correlated with nuclear grade than that of whole fields. Further, the Ki-67 index was better correlated with mitotic counts than with nuclear atypia.Auto-analysis can provide results concordant with those obtained by direct ocular observation in a short time. Auto-analysis is more likely to result in an objective observation and provide a means by which to standardize methods for immunohistochemical Ki-67 indices of breast cancer. Keywords: Breast cancer, Ki-67, auto-analysis, virtual microscopy, immunohistochemistry, prognosis, objective analysis, nuclear grade. Download Full Article |