The high affinity folate binding protein (FBP) is overexpressed in ovarian cancers. However, its role in the pathogenesis and biological behaviour of these neoplasms is not clearly understood. Using the monoclonal antibody (MAb) MOv 18 and cytofluorimetric analysis, we investigated FBP expression in frozen neoplastic tissues from 136 patients diagnosed with epithelial ovarian cancer. FBP values were compared with clinico‐pathological characteristics (age, stage, histologic grade, histologic type, DNA ploidy, percentage of S‐phase cells, and previous chemotherapeutic treatment). Some amount of FBP overexpression was observed in 122 of the 136 tumours examined. The overall mean value of FBP fluorescence index (FBP FI) was 5.6 (median 2.7; min 0.8 − max, 78.9). By univariate analysis, FBP FI was overexpressed to a higher degree in ovarian neoplasms with high histologic grade, advanced stage, serous histology, aneuploid status, and high percentage of cells in S‐phase. Of the total number (136) of cases, 106 had all the parameters assessed and were thus selected for stepwise selection procedure. The only significant independent variable was the percentage of S‐phase cells, which accounted for about 31% of variance of FBP FI. Our results indicate that FBP is associated with parameters of biological aggressiveness in ovarian cancers. Int. J. Cancer 74:193‐198, 1997. © 1997 Wiley‐Liss, Inc.

Purpose: UGT1A1*28 polymorphism has been associated with decreased glucuronidation of SN38, the active metabolite of irinotecan. This could increase toxicity with this agent.Patients and Methods: In a prospective study, 250 metastatic colorectal cancer patients were treated with irinotecan, fluorouracil, and leucovorin as first-line treatment. UGT1A1*28 polymorphism was investigated with respect to the distribution of hematologic and nonhematologic toxicity, objective response rate, and survival. Pharmacokinetics was investigated in a subgroup of patients (71 of 250) who had been analyzed with respect to toxicity and efficacy.Results: UGT1A1*28 polymorphism was associated with a higher risk of grade 3 to 4 hematologic toxicity (odds ratio [OR], 8.63; 95% CI, 1.31 to 56.55), which was only relevant for the first cycle, and was not seen throughout the whole treatment period for patients with both variant alleles TA₇/TA₇compared with wild-type TA₆/TA₆. The response rate was also higher in TA₇/TA₇patients (OR, 0.32; 95% CI, 0.12 to 0.86) compared with TA₆/TA₆. A nonsignificant survival advantage was observed for TA₇/TA₇when compared with TA₆/TA₆patients (hazard ratio, 0.81; 95% CI, 0.45 to 1.44). Higher response rates were explained by a different pharmacokinetics with higher biliary index [irinotecan area under the curve (AUC)×(SN38 AUC/SN38G AUC)] and lower glucuronidation ratio (SN38G AUC/SN38 AUC) associated with the TA₇/TA₇genotype and a higher response rate, indicating that the polymorphism is functionally relevant.Conclusion: The results indicate that UGT1A1*28 polymorphism is of some relevance to toxicity; however, it is less important than discussed in previous smaller trials. In particular, the possibility of a dose reduction for irinotecan in patients with a UGT1A1*28 polymorphism is not supported by the result of this analysis.

Aim: To demonstrate that exosomes (exo) could increase the therapeutic index of doxorubicin (DOX). Materials & methods: Exosomes were characterized by nanoparticle tracking analysis and western blot. Tissue toxicity was evaluated by histopathological analysis and drug efficacy by measuring tumor volume. DOX biodistribution was analyzed by MS. Results: Exosomal doxorubicin (exoDOX) avoids heart toxicity by partially limiting the crossing of DOX through the myocardial endothelial cells. For this reason, mice can be treated with higher concentration of exoDOX thus increasing the efficacy of DOX as demonstrated in breast and ovarian mouse tumors. Conclusion: ExoDOX is safer and more effective than free DOX. Importantly, the first spontaneous transformed syngeneic model of high-grade serous ovarian cancer was utilized for providing a new therapeutic opportunity.

Inorganic nanoparticles (NPs) including those derived from metals (e.g., gold, silver), semiconductors (e.g., quantum dots), carbon dots, carbon nanotubes, or oxides (e.g., iron oxide), have been deeply investigated recently for diagnostic and therapeutic purposes in oncology. Compared to organic nanomaterials, inorganic NPs have advanced advantages and unique characteristics for better imaging and drug delivery. Still, only a limited number of inorganic NPs are translated into clinical practice. In this review, we discuss the progression of inorganic NPs for cancer therapy and imaging, focusing our attention on opportunities, limitations and challenges for the main constituting nanomaterials, including metallic and magnetic NPs. In particular, the pre-clinical and clinical trials from the bench toward clinic are here investigated.

The application of nanotechnology in the medical field is called nanomedicine. Nowadays, this new branch of science is a point of interest for many investigators due to the important advances in which we assisted in the lasts decades, in particular for cancer treatment. Cancer nanomedicine has been applied in different fields such as drug delivery, nanoformulation and nanoanalytical contrast reagents. The application of nanotechnology to pharmaceutical science allowed to build up nanosystems based on at least two stage vectors (drug/nanomaterial), which often shown a better pharmacokinetics (PK), bioavailability and biodistribution. As result of these advantages, the nanomaterials accumulate passively in the tumor (enhanced permeability and retention, EPR) decreasing side effects of free drug. In the last decades, many new drug formulations have been translated from the bench to the bedside. In this review, we describe the main drug nanoformulations based on different types of organic nanoparticles (NPs), the advantages that the new formulations have over to their free drug counterparts and how nanodrugs have improved the clinical care.