Prognostic value of nuclear morphometry in patients with TNM stage T1 ovarian clear cell adenocarcinoma

In 40 patients with TNM stage T1 ovarian clear cell adenocarcinoma, we used nuclear morphometry to study the relations among morphometric variables, clinical prognostic factors and outcome. The presence of one or more giant nuclear cells was positively associated with death (OR = 10.6, P = 0.02) and tended to be associated with disease recurrence (OR = 5.1, P = 0.07). Nuclear irregularity (expressed in terms of the nuclear roundness factor) was positively associated with both death (OR = 8.6, P = 0.02) and disease recurrence (OR = 8.2, P = 0.02). A combination of giant nuclear cell presence or nuclear irregularity proved to be a useful prognostic indicator, with a sensitivity and specificity of 83% and 71% in the prediction of death, and 75% and 71% in the prediction of disease recurrence. Patients' age and substage were of no prognostic value. We conclude that the nuclear morphometric characteristics, especially the presence of giant nuclear cells and nuclear irregularity, may be useful in predicting outcome in patients with early stage ovarian clear cell adenocarcinoma. © 1999 Cancer Research Campaig

Identification of Novel Therapeutic Targets in Microdissected Clear Cell Ovarian Cancers

Clear cell ovarian cancer is an epithelial ovarian cancer histotype that is less responsive to chemotherapy and carries poorer prognosis than serous and endometrioid histotypes. Despite this, patients with these tumors are treated in a similar fashion as all other ovarian cancers. Previous genomic analysis has suggested that clear cell cancers represent a unique tumor subtype. Here we generated the first whole genomic expression profiling using epithelial component of clear cell ovarian cancers and normal ovarian surface specimens isolated by laser capture microdissection. All the arrays were analyzed using BRB ArrayTools and PathwayStudio software to identify the signaling pathways. Identified pathways validated using serous, clear cell cancer cell lines and RNAi technology. In vivo validations carried out using an orthotopic mouse model and liposomal encapsulated siRNA. Patient-derived clear cell and serous ovarian tumors were grafted under the renal capsule of NOD-SCID mice to evaluate the therapeutic potential of the identified pathway. We identified major activated pathways in clear cells involving in hypoxic cell growth, angiogenesis, and glucose metabolism not seen in other histotypes. Knockdown of key genes in these pathways sensitized clear cell ovarian cancer cell lines to hypoxia/glucose deprivation. In vivo experiments using patient derived tumors demonstrate that clear cell tumors are exquisitely sensitive to antiangiogenesis therapy (i.e. sunitinib) compared with serous tumors. We generated a histotype specific, gene signature associated with clear cell ovarian cancer which identifies important activated pathways critical for their clinicopathologic characteristics. These results provide a rational basis for a radically different treatment for ovarian clear cell patients

Real-Time, Aptamer-Based Tracking of Circulating Therapeutic Agents in Living Animals

A sensor capable of continuously measuring specific molecules in the bloodstream in vivo would give clinicians a valuable window into patients’ health and their response to therapeutics. Such technology would enable truly personalized medicine, wherein therapeutic agents could be tailored with optimal doses for each patient to maximize efficacy and minimize side effects. Unfortunately, continuous, real-time measurement is currently only possible for a handful of targets, such as glucose, lactose, and oxygen, and the few existing platforms for continuous measurement are not generalizable for the monitoring of other analytes, such as small-molecule therapeutics. In response, we have developed a real-time biosensor capable of continuously tracking a wide range of circulating drugs in living subjects. Our microfluidic electrochemical detector for in vivo continuous monitoring (MEDIC) requires no exogenous reagents, operates at room temperature, and can be reconfigured to measure different target molecules by exchanging probes in a modular manner. To demonstrate the system's versatility, we measured therapeutic in vivo concentrations of doxorubicin (a chemotherapeutic) and kanamycin (an antibiotic) in live rats and in human whole blood for several hours with high sensitivity and specificity at sub-minute temporal resolution. Importantly, we show that MEDIC can also obtain pharmacokineticparameters for individual animals in real-time. Accordingly, just as continuous glucose monitoring technology is currently revolutionizing diabetes care, we believe MEDIC could be a powerful enabler for personalized medicine by ensuring delivery of optimal drug doses for individual patients based on direct detection of physiological parameters