Gemcitabine is a pyrimidine nucleoside analog that becomes triphosphorylated intracellularly where it competitively inhibits cytidine incorporation into DNA strands. Another mechanism-of-action of gemcitabine (diphosp...Gemcitabine is a pyrimidine nucleoside analog that becomes triphosphorylated intracellularly where it competitively inhibits cytidine incorporation into DNA strands. Another mechanism-of-action of gemcitabine (diphosphorylated form) involves irreversible inhibition of the enzyme ribonucleotide reductase thereby preventing deoxyribonucleotide synthesis. Functioning as a potent chemotherapeutic gemcitabine promote decreases in neoplastic cell proliferation and apoptosis which is frequently found to be effective for the treatment of several leukemias and a wide spectrum of carcinomas. A brief plasma half-life in part due to rapid deamination and chemotherapeutic-resistance restricts the utility of gemcitabine in clinical oncology. Selective “targeted” delivery of gemcitabine represents a potential molecular strategy for simultaneously prolonging its plasma half-life and minimizing innocient tissues and organ systems exposure to chemotherapy. The molecular design and an organic chemistry based synthesis reaction is described that initially generates a UV-photoactivated gemcitabine intermediate. In a subsequent phase of the synthesis method the UV-photoactivated gemcitabine intermediate is covalently bonded to a monoclonal immunoglobulin yielding an end-product in the form of gemcitabine-(C4-amide)-[anti-HER2/neu]. Analysis by SDS-PAGE/chemiluminescent auto-radiography did not detect evidence of gemcitabine-(C4-amide)-[anti-HER2/neu] polymerization or degradative fragmentation while cell-ELISA demonstrated retained binding-avidity for HER2/neu trophic membrane receptor complexes highly over-expressed by chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3). Compared to chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3), the covalent immunochemotherapeutic, gemcitabine-(C4-amide)-[anti-HER2/neu] is anticipated to exert greater levels of cytotoxic anti-neoplastic potency against other neoplastic cell types like pancreatic carcinoma, small-cell lung carcinoma, neuroblastoma, glioblastoma, oral squamous cell carcinoma, cervical epitheliod carcinoma, or leukemia/lymphoid neoplastic cell types based on their reported sensitivity to gemcitabine and gemcitabine covalent conjugates.展开更多
Background We have discovered an unexpected phenomenon that patients with malignant tumor （MT） were commonly associated with type I Brugada-like wave on electrocardiogram（ECG）. Methods For a retro- spective study,...Background We have discovered an unexpected phenomenon that patients with malignant tumor （MT） were commonly associated with type I Brugada-like wave on electrocardiogram（ECG）. Methods For a retro- spective study, we collected the clinical history, demographic data, laboratory examinations, imaging docu- ments and medication information of 22 patients with type I Brugada-like wave. Results Of 22 patients with type I Brugada-like wave, five suffered from MT, accounting for 22.7%. Of the 5 MT patients, two had nor- mal ECG when diagnosis was made, displayed Brugada-like wave during the chemotherapy of anti-neoplastic drug. After appearing, Brugada-like wave would continuously exist during the course of chemotherapy. The longest existing time of Brugada-like wave lasted over five years. The two patients had no compression of right ventricular outflow tract（RVOT）, no electrolyte abnormality and no use of the known drugs being able to in- duce Brugada-like wave, such as class I anti-arrhythmic drugs. Conclusion Anti-neoplastic drug is a new factor being able to induce Brugada-like wave.展开更多
文摘Gemcitabine is a pyrimidine nucleoside analog that becomes triphosphorylated intracellularly where it competitively inhibits cytidine incorporation into DNA strands. Another mechanism-of-action of gemcitabine (diphosphorylated form) involves irreversible inhibition of the enzyme ribonucleotide reductase thereby preventing deoxyribonucleotide synthesis. Functioning as a potent chemotherapeutic gemcitabine promote decreases in neoplastic cell proliferation and apoptosis which is frequently found to be effective for the treatment of several leukemias and a wide spectrum of carcinomas. A brief plasma half-life in part due to rapid deamination and chemotherapeutic-resistance restricts the utility of gemcitabine in clinical oncology. Selective “targeted” delivery of gemcitabine represents a potential molecular strategy for simultaneously prolonging its plasma half-life and minimizing innocient tissues and organ systems exposure to chemotherapy. The molecular design and an organic chemistry based synthesis reaction is described that initially generates a UV-photoactivated gemcitabine intermediate. In a subsequent phase of the synthesis method the UV-photoactivated gemcitabine intermediate is covalently bonded to a monoclonal immunoglobulin yielding an end-product in the form of gemcitabine-(C4-amide)-[anti-HER2/neu]. Analysis by SDS-PAGE/chemiluminescent auto-radiography did not detect evidence of gemcitabine-(C4-amide)-[anti-HER2/neu] polymerization or degradative fragmentation while cell-ELISA demonstrated retained binding-avidity for HER2/neu trophic membrane receptor complexes highly over-expressed by chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3). Compared to chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3), the covalent immunochemotherapeutic, gemcitabine-(C4-amide)-[anti-HER2/neu] is anticipated to exert greater levels of cytotoxic anti-neoplastic potency against other neoplastic cell types like pancreatic carcinoma, small-cell lung carcinoma, neuroblastoma, glioblastoma, oral squamous cell carcinoma, cervical epitheliod carcinoma, or leukemia/lymphoid neoplastic cell types based on their reported sensitivity to gemcitabine and gemcitabine covalent conjugates.
文摘Background We have discovered an unexpected phenomenon that patients with malignant tumor （MT） were commonly associated with type I Brugada-like wave on electrocardiogram（ECG）. Methods For a retro- spective study, we collected the clinical history, demographic data, laboratory examinations, imaging docu- ments and medication information of 22 patients with type I Brugada-like wave. Results Of 22 patients with type I Brugada-like wave, five suffered from MT, accounting for 22.7%. Of the 5 MT patients, two had nor- mal ECG when diagnosis was made, displayed Brugada-like wave during the chemotherapy of anti-neoplastic drug. After appearing, Brugada-like wave would continuously exist during the course of chemotherapy. The longest existing time of Brugada-like wave lasted over five years. The two patients had no compression of right ventricular outflow tract（RVOT）, no electrolyte abnormality and no use of the known drugs being able to in- duce Brugada-like wave, such as class I anti-arrhythmic drugs. Conclusion Anti-neoplastic drug is a new factor being able to induce Brugada-like wave.
