Other articles by Charles A. Kunos on PubMed

• Migration of Implanted Free Radioactive Seeds for Adenocarcinoma of the Prostate Using a Mick Applicator Brachytherapy. 2004  |   Pubmed ID: 15374538 This study investigates the rate of free seed migration and associated seed-related sequelae after using a radioimmunoguided Mick applicator technique to place radioactive seeds within the prostate.
• Comparison of Helical Tomotherapy Versus Conventional Radiation to Deliver Craniospinal Radiation Technology in Cancer Research & Treatment. Jun, 2008  |   Pubmed ID: 18473494 The purpose of this study was to investigate whether helical tomotherapy would better dose-limit growing vertebral ring apophyses during craniospinal radiation as compared to conventional techniques. Four pediatric patients with M0 medulloblastoma received tomotherapy craniospinal radiation (23.4 Gy, 1.8 Gy/fx) by continuous helical delivery of 6 MV photons. Weekly blood counts were monitored. For comparison, conventional craniospinal radiation plans were generated. To assist in tomotherapy planning, a cross-sectional growth study of 52 children and young adults was completed to evaluate spine growth and maturation. Vertebral ring apophyses first fused along the posterolateral body-pedicle synostosis, proceeding circumferentially toward the anterior vertebral body such that the cervical and lumbar vertebrae fused early and mid-thoracic vertebrae fused late. For the four pediatric patients, tomotherapy resulted between 2% and 14% vertebral volume exceeding 23 Gy. Conventional craniospinal radiation predicted between 33% and 44% exceeding 23 Gy. Cumulative body radiation doses exceeding 4 Gy were between 50% and 57% for tomotherapy and between 25% and 37% for conventional craniospinal radiation. Tomotherapy radiation reduced neutrophil, platelet, and erythrocyte hemoglobin levels during treatment. Tomotherapy provides improved dose avoidance to growing vertebrae as compared to conventional craniospinal radiation. However, the long-term effects of tomotherapy dose avoidance on spine growth and large volume low dose radiation in children are not yet known.
• Radiation Therapy in Addition to Gross Total Resection of Retroperitoneal Sarcoma Results in Prolonged Survival: Results from a Single Institutional Study Journal of Oncology. 2008  |   Pubmed ID: 19277103 Purpose. Typical treatment of retroperitoneal sarcomas (RPSs) is surgery with or without radiation therapy for localized disease. With surgery alone, local failure rates are as high as 90%; this led to radiation therapy playing an important role in the treatment of RPSs. Methods. Thirty-one patients with retroperitoneal sarcoma treated with gross total resection and radiation therapy make up this retrospective analysis. Nineteen were treated preoperatively and 12 postoperatively (median dose, 59.4 Gy)-sixteen also received intraoperative radiation therapy (IORT) (median dose, 11 Gy). Patients were followed with stringent regimens, including frequent CT scans of the chest, abdomen, and pelvis. Results. With a median follow-up of 19 months (range 1-66 months), the 2-year overall survival (OS) rate is 70% (median, 52 months). The 2-year locoregional control (LRC) rate is 77% (median, 61.6 months). The 2-year distant disease free survival (DDFS) rate is 70% (median not reached). There were no differences in radiation-related acute and late toxicities among patients treated pre- versus postoperatively, whether with or without IORT. Conclusions. Compared to surgery alone, neoadjuvant or adjuvant radiation therapy offers patients with RPS an excellent chance for long-term LRC, DDS, and OS. The integration of modern treatment planning for external beam radiation therapy and IORT allows for higher doses to be delivered with acceptable toxicities.
• Modulating Radiation Resistance by Inhibiting Ribonucleotide Reductase in Cancers with Virally or Mutationally Silenced P53 Protein Radiation Research. Dec, 2009  |   Pubmed ID: 19929413 Therapeutic ionizing radiation damages DNA, increasing p53-regulated ribonucleotide reductase (RNR) activity required for de novo synthesis of the deoxyribonucleotide triphosphates used during DNA repair. This study investigated the pharmacological inhibition of RNR in cells of virally or mutationally silenced p53 cancer cell lines using 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine(R), NSC #663249), a chemotherapeutic radiosensitizer that equally inhibits RNR M2 and p53R2 small subunits. The effects of 3-AP on RNR inhibition and resulting radiosensitization were evaluated in cervical (CaSki, HeLa and C33-a) and colon (RKO, RKO-E6) cancer cells. 3-AP treatment significantly enhanced radiation-related cytotoxicity in cervical and colon cancer cells. 3-AP treatment significantly decreased RNR activity, caused prolonged radiation-induced DNA damage, and resulted in an extended G(1)/S-phase cell cycle arrest in all cell lines. Similar effects were observed in both RKO and RKO-E6 cells, suggesting a p53-independent mechanism of radiosensitization. We conclude that inhibition of ribonucleotide reductase by 3-AP enhances radiation-mediated cytotoxicity independent of p53 regulation by impairing repair processes that rely on deoxyribonucleotide production, thereby substantially increasing the radiation sensitivity of human cancers.
• Phase I Trial of Pelvic Radiation, Weekly Cisplatin, and 3-aminopyridine-2-carboxaldehyde Thiosemicarbazone (3-AP, NSC #663249) for Locally Advanced Cervical Cancer Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Feb, 2010  |   Pubmed ID: 20145183 This study assessed the safety/tolerability, pharmacokinetics, and clinical activity of three times weekly i.v. 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in combination with once-weekly i.v. cisplatin and daily pelvic radiation in patients with gynecologic malignancies. 3-AP is a novel small-molecule inhibitor of ribonucleotide reductase (RNR) and is being tested as a potential radiosensitizer and chemosensitizer.
• Ribonucleotide Reductase Inhibition Enhances Chemoradiosensitivity of Human Cervical Cancers Radiation Research. Nov, 2010  |   Pubmed ID: 20954859 For repair of damaged DNA, cells increase de novo synthesis of deoxyribonucleotide triphosphates through the rate-limiting, p53-regulated ribonucleotide reductase (RNR) enzyme. In this study we investigated whether pharmacological inhibition of RNR by 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) enhanced chemoradiation sensitivity through a mechanism involving sustained DNA damage. RNR inactivation by 3-AP and resulting chemoradiosensitization were evaluated in human cervical (CaSki, C33-a) cancer cells through study of DNA damage (γ-H2AX signal) by flow cytometry, RNR subunit p53R2 and p21 protein steady-state levels by Western blot analysis and laser scanning imaging cytometry, and cell survival by colony formation assays. 3-AP treatment led to sustained radiation- and cisplatin-induced DNA damage (i.e. increased γ-H2AX signal) in both cell lines through a mechanism of inhibited RNR activity. Radiation, cisplatin and 3-AP exposure resulted in significantly elevated numbers and persistence of γ-H2AX foci that were associated with reduced clonogenic survival. DNA damage was associated with a rise in p53R2 but not p21 protein levels 6 h after treatment with radiation and/or cisplatin plus 3-AP. We conclude that blockage of RNR activity by 3-AP impairs DNA damage responses that rely on deoxyribonucleotide production and thereby may substantially increase chemoradiosensitivity of human cervical cancers.
• Adherence to Vaginal Dilation Following High Dose Rate Brachytherapy for Endometrial Cancer International Journal of Radiation Oncology, Biology, Physics. Jul, 2011  |   Pubmed ID: 20619551 We report demographic, clinical, and psychosocial factors associated with adherence to vaginal dilation and describe the sexual and marital or nonmarital dyadic functioning of women following high dose rate (HDR) brachytherapy for endometrial cancer.
• Low-dose Abdominal Radiation As a Docetaxel Chemosensitizer for Recurrent Epithelial Ovarian Cancer: a Phase I Study of the Gynecologic Oncology Group Gynecologic Oncology. Feb, 2011  |   Pubmed ID: 21075438 The aim of this study was to determine the maximum tolerated dose and dose-limiting toxicity (DLT) of whole abdomen radiation as a chemosensitizer of weekly docetaxel for women with recurrent epithelial ovarian fallopian tube, or peritoneal cancers.
• Radiosensitization of Human Cervical Cancer Cells by Inhibiting Ribonucleotide Reductase: Enhanced Radiation Response at Low-dose Rates International Journal of Radiation Oncology, Biology, Physics. Jul, 2011  |   Pubmed ID: 21470790 To test whether pharmacologic inhibition of ribonucleotide reductase (RNR) by 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) enhances radiation sensitivity during low-dose-rate ionizing radiation provided by a novel purpose-built iridium-192 cell irradiator.
• Deoxynucleoside Salvage Facilitates DNA Repair During Ribonucleotide Reductase Blockade in Human Cervical Cancers Radiation Research. Oct, 2011  |   Pubmed ID: 21756082 Cells generate 2'-deoxyribonucleoside triphosphates (dNTPs) for both replication and repair of damaged DNA predominantly through de novo reduction of intracellular ribonucleotides by ribonucleotide reductase (RNR). Cells can also salvage deoxynucleosides by deoxycytidine kinase/thymidine kinase 1 in the cytosol or by deoxyguanosine kinase/thymidine kinase 2 in mitochondria. In this study we investigated whether the salvage dNTP supply pathway facilitates DNA damage repair, promoting cell survival, when pharmacological inhibition of RNR by 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC no. 663249) impairs the de novo pathway. Human cervical cancer cells were subjected to radiation with or without 3-AP under medium deoxynucleoside concentrations of 0, 0.05, 0.5 and 5.0 µM. Efficacy of DNA damage repair was assessed by γ-H2AX flow cytometry and focus counts, by single cell electrophoresis (Comet assay), and by caspase 3 cleavage assay as a marker of treatment-induced apoptosis. Cell survival was assessed by colony formation. We found that deoxyribonucleotide salvage facilitates DNA repair during RNR inhibition by 3-AP and that salvage reduces the radiochemosensitivity of human cervical cancer cells.
• Chemotherapy Plus Radiation in Advanced-stage Endometrial Cancer International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. Dec, 2011  |   Pubmed ID: 21897269 We hypothesize that adjuvant radiation and chemotherapy improve the clinical benefit from treatment of advanced-stage endometrial adenocarcinoma.
• Robotic Surgery in Gynecologic Oncology Obstetrics and Gynecology International. 2011  |   Pubmed ID: 22190946 Robotic surgery for the management of gynecologic cancers allows for minimally invasive surgical removal of cancer-bearing organs and tissues using sophisticated surgeon-manipulated, robotic surgical instrumentation. Early on, gynecologic oncologists recognized that minimally invasive surgery was associated with less surgical morbidity and that it shortened postoperative recovery. Now, robotic surgery represents an effective alternative to conventional laparotomy. Since its widespread adoption, minimally invasive surgery has become an option not only for the morbidly obese but for women with gynecologic malignancy where conventional laparotomy has been associated with significant morbidity. As such, this paper considers indications for robotic surgery, reflects on outcomes from initial robotic surgical outcomes data, reviews cost efficacy and implications in surgical training, and discusses new roles for robotic surgery in gynecologic cancer management.
• Molecular Strategies of Deoxynucleotide Triphosphate Supply Inhibition Used in the Treatment of Gynecologic Malignancies Gynecology & Obstetrics (Sunnyvale, Calif.). Dec, 2011  |   Pubmed ID: 25392744 Chemotherapies targeting deoxynucleotide triphosphate synthesis are of high medical interest in the treatment of gynecologic malignancies. In this article, we focus on targeted inhibitors of ribonucleotide reductase, an enzyme in charge of ribonucleotide reduction to their corresponding deoxyribonucleotide to be used as the building blocks of DNA. We also discuss human clinical trials have utilized ribonucleotide reductase subunit-specific inhibitors, particularly trials for women with cervical cancer.
• (18)FDG-PET/CT Definition of Clinical Target Volume for Robotic Stereotactic Body Radiosurgery Treatment of Metastatic Gynecologic Malignancies Journal of Nuclear Medicine & Radiation Therapy. Dec, 2011  |   Pubmed ID: 25506042 The objective of the current article was to evaluate 2-[(18)F]fluoro-2-deoxy-D-glucose (18)F-FDG) as measured by positron emission tomography for delineation of abdominopelvic gross tumor volumes (GTV) for stereotactic body radiosurgery treatment (SBRT) of metastatic gynecologic cancers. A retrospective review of SBRT was conducted in 27 women with stage IV gynecologic cancers recurring in para-aortic lymph nodes. Robotic SBRT involved 2400 cGy in 3 consecutive 800 cGy daily fractions prescribed to a 3.0 mm expanded planning tumor volume (PTV) defined by both CT-based and (18)F-FDG-based GTVs. In this study, (18)F-FDG-based GTVs led to significantly larger PTVs in all 27 women, than if they had been based on CT GTVs alone (P < 0.001). Enlarged PTVs may have resulted from the breathing-induced target motion during the time of (18)F-FDG image acquisition smearing (18)F-FDG signal over a greater anatomic dimension. Ultimately, SBRT-target local control, based on the RECIST 1.1 criteria, was 96% (26 of 27), and associated with minor reversible toxicity. The use of (18)F-FDG to define SBRT target volumes warrants further interrogation in SBRT clinical trials.
• On Model Ensemble Analyses of Nonmonotonic Data Nucleosides, Nucleotides & Nucleic Acids. 2012  |   Pubmed ID: 22303993 Mammalian ribonucleotide reductase (RNR) activity has been reported to be nonmonotonic in ATP. If many nonlinear models are to be fitted to such data automatically as part of a model search process, use of the same initial parameter values across all models can lead to too many poor fitting, monotonic least squares fits, i.e., false model rejections. We propose that such fits can be rescued by using as initial parameter estimates the final estimates of neighboring models that do have nonmonotonic fits; here models are neighbors if complexes that they represent differ by at most one ligand. We use this approach to show that troughs in RNR activity versus ATP can be fitted similarly well by models that do or do not demand a third ATP binding site.
• Management of 3-aminopyridine-2-carboxaldehyde Thiosemicarbazone-induced Methemoglobinemia Future Oncology (London, England). Feb, 2012  |   Pubmed ID: 22335579 The anticancer agent 3-aminopyridine-2-carboxaldehyde thiosemicarbazone is a ribonucleotide reductase inhibitor. It inactivates ribonucleotide reductase by disrupting an iron-stabilized radical in ribonucleotide reductase's small subunits, M2 and M2b (p53R2). Unfortunately, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone also alters iron II (Fe(2+)) in hemoglobin. This creates Fe(3+) methemoglobin that does not deliver oxygen. Fe(2+) in hemoglobin normally auto-oxidizes to inactive Fe(3+) methemoglobin at a rate of nearly 3% per day and this is counterbalanced by a reductase system that normally limits methemoglobin concentrations to less than 1% of hemoglobin. This balance may be perturbed by symptomatic toxicity levels during 3-aminopyridine-2-carboxaldehyde thiosemicarbazone therapy. Indications of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone sequelae attributable to methemoglobinemia include resting dyspnea, headaches and altered cognition. Management of methemoglobinemia includes supplemental oxygen, ascorbate and, most importantly, intravenously administered methylene blue as a therapeutic antidote.
• Hematological Toxicity After Robotic Stereotactic Body Radiosurgery for Treatment of Metastatic Gynecologic Malignancies International Journal of Radiation Oncology, Biology, Physics. Sep, 2012  |   Pubmed ID: 22543208 To evaluate hematological toxicity after robotic stereotactic body radiosurgery (SBRT) for treatment of women with metastatic abdominopelvic gynecologic malignancies.
• Therapeutic Mechanisms of Treatment in Cervical and Vaginal Cancer Oncology & Hematology Review. 2012  |   Pubmed ID: 22943045 Cervical and vaginal cancers remain serious health problems. Worldwide, more than 530,000 women annually are diagnosed with these diseases, with most new incident cases occurring in nations with limited health resources and underdeveloped screening programs. For women whose disease is too bulky or widespread for surgery, radiochemotherapy should be looked upon as the standard of care. Randomized clinical trials have indicated that radiochemotherapy strategies that disrupt the repair of damaged DNA are key to the management of advanced stage cervical and vaginal cancers. Here, from a viewpoint of cancer cell molecular biology, treatments for advanced stage cervical and vaginal cancers are discussed.
• Elevated Ribonucleotide Reductase Levels Associate with Suppressed Radiochemotherapy Response in Human Cervical Cancers International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. Nov, 2012  |   Pubmed ID: 23051959 Ribonucleotide reductase (RNR) supplies deoxyribonucleotide diphosphates demanded by cells to repair radiation-induced DNA damage. Here, we investigate the impact of pretherapy RNR M1, M2, and M2b (p53R3) subunit level upon human cervical cancer radiochemosensitivity.
• DNTP Supply Gene Expression Patterns After P53 Loss Cancers. Nov, 2012  |   Pubmed ID: 23205301 Loss of the transcription factor p53 implies mRNA losses of target genes such as the p53R2 subunit of human ribonucleotide reductase (RNR). We hypothesized that other genes in the dNTP supply system would compensate for such p53R2 losses and looked for this in our own data and in data of the Gene Expression Omnibus (GEO). We found that the de novo dNTP supply system compensates for p53R2 losses with increases in RNR subunit R1, R2, or both. We also found compensatory increases in cytosolic deoxycytidine kinase (dCK) and thymidine kinase 1 (TK1) and in mitochondrial deoxyguanosine kinase (dGK), all of the salvage dNTP supply system; in contrast, the remaining mitochondrial salvage enzyme thymidine kinase 2 (TK2) decreased with p53 loss. Thus, TK2 may be more dedicated to meeting mitochondrial dNTP demands than dGK which may be more obligated to assist cytosolic dNTP supply in meeting nuclear DNA dNTP demands.
• Phase II Clinical Trial of Robotic Stereotactic Body Radiosurgery for Metastatic Gynecologic Malignancies Frontiers in Oncology. 2012  |   Pubmed ID: 23227452 Recurrent gynecologic cancers are often difficult to manage without significant morbidity. We conducted a phase II study to assess the safety and the efficacy of ablative robotic stereotactic body radiosurgery (SBRT) in women with metastatic gynecologic cancers.
• Ribonucleotide Reductase Expression in Cervical Cancer: a Radiation Therapy Oncology Group Translational Science Analysis International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. May, 2013  |   Pubmed ID: 23552804 To evaluate pretherapy ribonucleotide reductase (RNR) expression and its effect on radiochemotherapeutic outcome in women with cervical cancer.
• Emerging Role of Stereotactic Body Radiotherapy in the Treatment of Pancreatic Cancer Expert Review of Anticancer Therapy. Apr, 2013  |   Pubmed ID: 23560842 The management of pancreatic cancer continues to be challenging. Despite surgical, genetic and molecular advances, its overall prognosis remains poor. Surgical resection is the only modality that offers a chance for a cure, with an overall survival rate of 10-20% at 5 years. However, only 20% of the patients are surgical candidates because of locally advanced disease or systemic stage at presentation. Conventional radiotherapy, with or without chemotherapy, has been used to treat patients with advanced-stage pancreatic cancer, an approach with high rates of local recurrence. Stereotactic body radiation therapy, also known as stereotactic ablative radiotherapy has emerged as a treatment modality that allows the precise delivery of a large ablative radiation dose to a tumor volume while sparing surrounding organs and tissues. Phase I and II studies have shown good rates of local control of the disease but rates of distant metastasis remain significant. Strategies to combine novel systemic therapy and stereotactic body radiation therapy are to be explored.
• Radiochemotherapy Plus 3-aminopyridine-2-carboxaldehyde Thiosemicarbazone (3-AP, NSC #663249) in Advanced-stage Cervical and Vaginal Cancers Gynecologic Oncology. Jul, 2013  |   Pubmed ID: 23603372 Cervical and vaginal cancers have virally-mediated or mutated defects in DNA damage repair responses, making these cancers sensible targets for ribonucleotide reductase inhibition during radiochemotherapy.
• Radiation Quality, Like Art, Consists in Drawing the Line Somewhere Frontiers in Oncology. 2013  |   Pubmed ID: 23882449 The architects of phase I radiochemotherapy development programs impose a semblance of structured radiation "intensity" and adverse event predictability upon radiation-anticancer agent interactions whose natural complexity and improper mixing would otherwise lead to dire health consequences. It is incumbent upon radiation oncology investigators to pledge radiation quality and safety to the participants of radiochemotherapy trials. Measures of radiation quality and safety may be tools to scrutinize radiation-anticancer agent dose and schedule, as well as, radiation field design among diverse radiation delivery platforms. In this article, the merits and demerits of phase I radiochemotherapy quality and safety policies are critiqued considering the current era of rapidly evolving radiation technologies.
• Role of Stereotactic Radiosurgery in Gynecologic Cancer Current Opinion in Oncology. Sep, 2013  |   Pubmed ID: 23942297 This current work offers an opinion on the evidence accumulated in humans regarding stereotactic ablative radiation (SABR) therapy, a favorable option for the treatment of persistent or recurrent metastatic gynecologic cancers.
• Cabazitaxel-induced Stabilization of Microtubules Enhances Radiosensitivity in Ovarian Cancer Cells Frontiers in Oncology. 2013  |   Pubmed ID: 24066277 Up to 40% of women with ovarian cancer have short disease-free intervals due to molecular mechanisms of chemotherapy resistance. New therapeutic strategies are sought. Ovarian cancers are sensitive to radiochemotherapy. The taxane cabazitaxel (XRP6258, Jevtana) promotes tubulin assembly and stabilizes microtubules against depolymerization in cells, acting similarly in mechanism to paclitaxel. Here, sequences of cabazitaxel-radiation co-administration are tested for drug-alone cytotoxicity and optimal radiosensitization.
• Lymphovascular Space Invasion (LVSI) is an Isolated Poor Prognostic Factor for Recurrence and Survival Among Women with Intermediate- to High-risk Early-stage Endometrioid Endometrial Cancer International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. Oct, 2013  |   Pubmed ID: 24257558 Whereas previous studies have shown that lymphovascular space invasion (LVSI) is associated with an increased risk for recurrent endometrioid endometrial cancer and worse survival, the magnitude of this risk in relationship to the other high-risk features is poorly understood. Our aim was to study the impact of LVSI in comparison with the other high-risk features in recurrence and survival.
• Acute Gastrointestinal Toxicity After Robotic Stereotactic Ablative Radiotherapy for Treatment of Metastatic Gynecological Malignancies Future Oncology (London, England). Feb, 2014  |   Pubmed ID: 24490610 The aim of this study was to assess acute and subacacute gastrointestinal toxicity after fractionated stereotactic ablative radiotherapy (SABR) in women having recurrent gynecological cancers in the upper abdomen.
• Novel Biological Radiochemotherapy Approaches in Locally Advanced-stage Cervical Cancer Management Discovery Medicine. Apr, 2014  |   Pubmed ID: 24759622 Biological anticancer agents that enhance radiochemotherapeutic effect are appealing in the modern medical treatment of uterine cervix cancer. In this concise review, the focus is on three classes of biological anticancer agents. The first class is ribonucleotide reductase inhibitors. These biological anticancer agents impede deoxyribonucleotide payout and stop new synthesis of DNA molecule building blocks. By disrupting deoxyribonucleotide supply and demand economics, ribonucleotide reductase inhibitors disrupt the repair of radiation- and chemotherapy-induced DNA damage and enhance cancer cell death. Angiogenesis inhibitors represent a second class of biological anticancer agents. Angiogenesis inhibitors are conceptually thought to normalize cancer tumor vasculature and modulate vascular endothelial growth factor signals. Consequences of normalized tumor vessel permeability are better oxygen supply for radiosensitization and improved tumor fluid dynamics imparting chemosensitization. A third class, cytolytic T-cell immune modulators, edits human immune system responses to cancer cell antigens. These biological anticancer agents exploit molecular signaling involved in immune detection and in immune eradication. Completed and planned clinical trials utilizing these agents are discussed relative to the future radiochemotherapeutic management of uterine cervix cancer.
• Long-Term Disease Control with Triapine-Based Radiochemotherapy for Patients with Stage IB2-IIIB Cervical Cancer Frontiers in Oncology. 2014  |   Pubmed ID: 25105092 National Cancer Institute phase I #7336 and phase II #8327 clinical trials explored the safety and efficacy of triapine (NSC #663249) added to cisplatin radiochemotherapy in untreated patients with advanced-stage cervical cancer. Triapine inhibits ribonucleotide reductase, the rate-limiting enzyme responsible for DNA-building deoxyribonucleotides, and thereby, enhances radiochemosensitivity by prolonging DNA repair time. Here, we report 3-year efficacy endpoints of pelvic locoregional relapse rate, disease-free, and overall survivals.
• Hydration During Breast Radiotherapy May Lower Skin Toxicity The Breast Journal. Nov-Dec, 2014  |   Pubmed ID: 25252223
• Comparison and Consensus Guidelines for Delineation of Clinical Target Volume for CT- and MR-based Brachytherapy in Locally Advanced Cervical Cancer International Journal of Radiation Oncology, Biology, Physics. Oct, 2014  |   Pubmed ID: 25304792 To create and compare consensus clinical target volume (CTV) contours for computed tomography (CT) and 3-Tesla (3-T) magnetic resonance (MR) image-based cervical-cancer brachytherapy.
• Two-step Procedure for Evaluating Experimentally Induced DNA Damage: Texas Red and Comet Assays Methods in Molecular Biology (Clifton, N.J.). 2015  |   Pubmed ID: 25348306 The technique of Texas Red immunostaining for cellular γH2AX identifies by fluorescence microscopy DNA undergoing active remodeling or repair. To fully characterize γH2AX foci, the technique of alkaline single cell electrophoresis (Comet) assay quantifiably resolves DNA double-strand breaks from other types of DNA damage. When used together, these two techniques may provide evidence for radiochemotherapy-induced DNA damage.
• Determination of Triapine, a Ribonucleotide Reductase Inhibitor, in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry Biomedical Chromatography : BMC. Feb, 2015  |   Pubmed ID: 25677991 Triapine is an inhibitor of ribonucleotide reductase (RNR). Studies have shown that triapine significantly decreases the activity of RNR and enhanced the radiation-mediated cytotoxicity in cervical and colon cancer. In this work, we have developed and validated a selective and sensitive LC-MS/MS method for the determination of triapine in human plasma. In this method, 2-[(3-fluoro-2-pyridinyl)methylene] hydrazinecarbothioamide (NSC 266749) was used as the internal standard (IS); plasma samples were prepared by deproteinization with acetonitrile; tripaine and the IS were separated on a Waters Xbridge Shield RP18 column (3.5 µm; 2.1 × 50 mm) using a mobile phase containing 25.0% methanol and 75.0% ammonium bicarbonate buffer (10.0 mm, pH 8.50; v/v); column eluate was monitored by positive turbo-ionspray tandem mass spectrometry; and quantitation of triapine was carried out in multiple-reaction-monitoring mode. The method developed had a linear calibration range of 0.250-50.0 ng/mL with correlation coefficient of 0.999 for triapine in human plasma. The IS-normalized recovery and the IS-normalized matrix factor of triapine were 101-104% and 0.89-1.05, respectively. The accuracy expressed as percentage error and precision expressed as coefficient of variation were ≤±6 and ≤8%, respectively. The validated LC-MS/MS method was applied to the measurement of triapine in patient samples from a phase I clinical trial. Copyright © 2015 John Wiley & Sons, Ltd.