Charles A. Kunos

Bio: Charles A. Kunos is an academic researcher from Case Western Reserve University. The author has contributed to research in topics: Radiation therapy & Cervical cancer. The author has an hindex of 26, co-authored 101 publications receiving 2001 citations. Previous affiliations of Charles A. Kunos include Cleveland Museum of Natural History & University Hospitals of Cleveland.

Comparison and Consensus Guidelines for Delineation of Clinical Target Volume for CT- and MR-Based Brachytherapy in Locally Advanced Cervical Cancer

Abstract: Objective 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. Methods and Materials Twenty-three experts in gynecologic radiation oncology contoured the same 3 cervical cancer brachytherapy cases: 1 stage IIB near-complete response (CR) case with a tandem and ovoid, 1 stage IIB partial response (PR) case with tandem and ovoid with needles, and 1 stage IB2 CR case with a tandem and ring applicator. The CT contours were completed before the MRI contours. These were analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with κ statistics as a measure of agreement between participants. The conformity index was calculated for each of the 6 data sets. Dice coefficients were generated to compare the CT and MR contours of the same case. Results For all 3 cases, the mean tumor volume was smaller on MR than on CT ( P Conclusion In a comparison of MR-contoured with CT-contoured CTV volumes, the higher level of agreement on CT may be due to the more distinct contrast medium visible on the images at the time of brachytherapy. MR at the time of brachytherapy may be of greatest benefit in patients with large tumors with parametrial extension that have a partial or complete response to external beam. On the basis of these results, a 95% consensus volume was generated for CT and for MR. Online contouring atlases are available for instruction at http://www.nrgoncology.org/Resources/ContouringAtlases/GYNCervicalBrachytherapy.aspx.

Phase I trial of pelvic radiation, weekly cisplatin, and 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) for locally advanced cervical cancer.

Abstract: Purpose: 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. Experimental Design: Patients with stage IB2 to IVB cervical cancer ( n = 10) or recurrent uterine sarcoma ( n = 1) were assigned to dose-finding cohorts of 2-hour 3-AP infusions during 5 weeks of cisplatin chemoradiation. Pharmacokinetic and methemoglobin samples and tumor biopsy for RNR activity were obtained on day 1 and day 10. Clinical response was assessed. Results: The maximum tolerated 3-AP dose was 25 mg/m 2 given three times weekly during cisplatin and pelvic radiation. Two patients experienced manageable 3-AP–related grade 3 or 4 electrolyte abnormalities. 3-AP pharmacokinetics showed a 2-hour half-life, with median peak plasma concentrations of 277 ng/mL (25 mg/m 2 ) and 467 ng/mL (50 mg/m 2 ). Median methemoglobin levels peaked at 1% (25 mg/m 2 ) and 6% (50 mg/m 2 ) at 4 hours after initiating 3-AP infusions. No change in RNR activity was found on day 1 versus day 10 in six early complete responders, whereas elevated RNR activity was seen on day 10 as compared with day 1 in four late complete responders ( P = 0.02). Ten (100%) patients with stage IB2 to IVB cervical cancer achieved complete clinical response and remained without disease relapse with a median 18 months of follow-up (6-32 months). Conclusions: 3-AP was well tolerated at a three times weekly i.v. 25 mg/m 2 dose during cisplatin and pelvic radiation. Clin Cancer Res; 16(4); 1298–306

First rib metamorphosis: its possible utility for human age-at-death estimation.

Abstract: Human first ribs demonstrate predictable, sequential changes in shape, size, and texture with increasing age, and thus, can be used as an indicator of age at death. Metamorphosis of the first rib's head, tubercle, and costal face was documented in a cross-sectional sample of preadult and adult first ribs of known age at death from the Hamann-Todd skeletal collection (Cleveland Museum of Natural History, Cleveland, Ohio). Blind tests of the usefulness of the first rib as an age indicator were conducted, including tabulation of intraobserver and interobserver inaccuracies and biases. First rib age estimates show inaccuracies and biases by decade comparable to those generated by other aging techniques. Indeed, the first rib method is useful as an isolated age indicator. When used in conjunction with other age indicators, the first rib improves the quality of summary age assessments.

Linear systems

Abstract: Most of the signal processing that we will study in this course involves local operations on a signal, namely transforming the signal by applying linear combinations of values in the neighborhood of each sample point. You are familiar with such operations from Calculus, namely, taking derivatives and you are also familiar with this from optics namely blurring a signal. We will be looking at sampled signals only. Let's start with a few basic examples. Local difference Suppose we have a 1D image and we take the local difference of intensities, DI(x) = 1 2 (I(x + 1) − I(x − 1)) which give a discrete approximation to a partial derivative. (We compute this for each x in the image.) What is the effect of such a transformation? One key idea is that such a derivative would be useful for marking positions where the intensity changes. Such a change is called an edge. It is important to detect edges in images because they often mark locations at which object properties change. These can include changes in illumination along a surface due to a shadow boundary, or a material (pigment) change, or a change in depth as when one object ends and another begins. The computational problem of finding intensity edges in images is called edge detection. We could look for positions at which DI(x) has a large negative or positive value. Large positive values indicate an edge that goes from low to high intensity, and large negative values indicate an edge that goes from high to low intensity. Example Suppose the image consists of a single (slightly sloped) edge:

Iron and cancer: more ore to be mined

Abstract: Iron is an essential nutrient that facilitates cell proliferation and growth. However, iron also has the capacity to engage in redox cycling and free radical formation. Therefore, iron can contribute to both tumour initiation and tumour growth; recent work has also shown that iron has a role in the tumour microenvironment and in metastasis. Pathways of iron acquisition, efflux, storage and regulation are all perturbed in cancer, suggesting that reprogramming of iron metabolism is a central aspect of tumour cell survival. Signalling through hypoxia-inducible factor (HIF) and WNT pathways may contribute to altered iron metabolism in cancer. Targeting iron metabolic pathways may provide new tools for cancer prognosis and therapy.