While surgery is at the foundation of cancer treatment, its access is limited in low-income countries. Here, we describe development of a low-cost alternative therapy based on intratumoral ethanol injection suitable for resource-limited settings. Although ethanol-based tumor ablation is successful in treating hepatocellular carcinomas, the necessity for multiple treatments, injection of large fluid volumes, and decreased efficacy in treatment of non-capsulated tumors limit its applicability. To address these limitations, we investigated an enhanced ethanol ablation strategy to retain ethanol within the tumor through the addition of ethyl cellulose. This increases the viscosity of injected ethanol and forms an ethanol-based gel-phase upon exposure to the aqueous tumor environment. This technique was first optimized to maximize distribution volume, using tissue-simulating phantoms. Then, chemically-induced epithelial tumors in the hamster cheek pouch were treated. As controls, pure ethanol injections of either four times or one-fourth the tumor volume induced complete regression of 33% and 0% of tumors, respectively. In contrast, ethyl cellulose-ethanol injections of one-fourth the tumor volume induced complete regression in 100% of tumors. These results contribute to proof-of-concept for enhanced ethanol ablation as a novel and effective alternative to surgery for tumor treatment, with relevance to resource-limited settings.

Abstract.We report the development of a compact point-detection fluorescence spectroscopy system and two data analysis methods to quantify the intrinsic fluorescence redox ratio and diagnose brain cancer in an orthotopic brain tumor rat model. Our system employs one compact cw diode laser (407 nm) to excite two primary endogenous fluorophores, reduced nicotinamide adenine dinucleotide, and flavin adenine dinucleotide. The spectra were first analyzed using a spectral filtering modulation method developed previously to derive the intrinsic fluorescence redox ratio, which has the advantages of insensitivty to optical coupling and rapid data acquisition and analysis. This method represents a convenient and rapid alternative for achieving intrinsic fluorescence-based redox measurements as compared to those complicated model-based methods. It is worth noting that the method can also extract total hemoglobin concentration at the same time but only if the emission path length of fluorescence light, which depends on the illumination and collection geometry of the optical probe, is long enough so that the effect of absorption on fluorescence intensity due to hemoglobin is significant. Then a multivariate method was used to statistically classify normal tissues and tumors. Although the first method offers quantitative tissue metabolism information, the second method provides high overall classification accuracy. The two methods provide complementary capabilities for understanding cancer development and noninvasively diagnosing brain cancer. The results of our study suggest that this portable system can be potentially used to demarcate the elusive boundary between a brain tumor and the surrounding normal tissue during surgical resection. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

Summary Hsp90 inhibitors have demonstrated unusual selectivity for tumor cells despite its ubiquitous expression. This phenomenon has remained unexplained but could be influenced by ectopically expressed Hsp90 in tumors. We have synthesized novel Hsp90 inhibitors that can carry optical or radioiodinated probes via a PEG tether. We show that these tethered inhibitors selectively recognize cells expressing ectopic Hsp90 and become internalized. The internalization process is blocked by Hsp90 antibodies, suggesting that active cycling of the protein is occurring at the plasma membrane. In mice, we show exquisite accumulation of the fluor-tethered versions within breast tumors at very sensitive levels. Cell-based assays with the radiolabeled version showed picomolar detection in cells that express ectopic Hsp90. Our findings show that fluor-tethered or radiolabeled inhibitors targeting ectopic Hsp90 can be used to detect breast cancer malignancies through non-invasive imaging.

Purpose Test if oxygenation kinetics correlate with the likelihood for local tumor control following fractionated radiotherapy. Methods and Materials We used diffuse reflectance spectroscopy to noninvasively measure tumor vascular oxygenation and total hemoglobin concentration ([THb]) associated with radiotherapy of 5 daily fractions (7.5, 9 or 13.5 Gy/day) in FaDu xenografts. Spectroscopy measurements were obtained immediately before each daily radiation fraction and during the week after radiotherapy. Oxygen saturation (SO2) and [THb] were computed using an inverse Monte Carlo model. Results (1) Oxygenation kinetics during and after radiotherapy, but before tumor volumes changed, were associated with local tumor control. Locally controlled tumors exhibited significantly faster increases in oxygenation after radiotherapy (days 12-15) compared with tumors that recurred locally. (2) Within the group of tumors that recurred, faster increases in oxygenation during radiotherapy (days 3-5 interval) were correlated with earlier recurrence times. An area of 0.74 under the receiver operator curve was achieved when classifying the local control tumors from all irradiated tumors using the oxygen kinetics with a logistic regression model. (3) The rate of increase in oxygenation was radiation dose dependent. Radiation doses ≤9.5 Gy/day did not initiate an increase in oxygenation whereas 13.5 Gy/day triggered significant increases in oxygenation during and after radiotherapy. Conclusions Additional confirmation is required in other tumor models, but these results suggest that monitoring tumor oxygenation kinetics could aid in the prediction of local tumor control after radiotherapy.

As ovarian toxicity is often a safety concern for cancer therapeutics, identification of ovarian pathology is important in early stages of preclinical drug development, particularly when the intended patient population include women of child-bearing potential. Microscopic evaluation by pathologists of hematoxylin and eosin (H&E)–stained tissues is the current gold standard for the assessment of organs in toxicity studies. However, digital pathology and advanced image analysis are being explored with greater frequency and broader applicability to tissue evaluations in toxicologic pathology. Our objective in this work was to develop an automated method that rapidly enumerates rat ovarian corpora lutea on standard H&E-stained slides with comparable accuracy to the gold standard assessment by a pathologist. Herein, we describe an algorithm generated by a deep learning network and tested on 5 rat toxicity studies, which included studies that both had and had not previously been diagnosed with effects on number of ovarian corpora lutea. Our algorithm could not only enumerate corpora lutea accurately in all studies but also revealed distinct trends for studies with and without reproductive toxicity. Our method could be a widely applied tool to aid analysis in general toxicity studies.