Personalized Medicine Applied to Forensic Sciences: New Advances and Perspectives for a Tailored Forensic Approach

Santurro, Alessandro; Vullo, Anna Maria; Borro, Marina; Gentile, Giovanna; Russa, Raffaele La; Simmaco, Maurizio; Frati, Paola; Fineschi, Vittorio

doi:10.2174/1389201018666170207141525

Cited by 30 publications

(22 citation statements)

References 70 publications

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“…1 The Precision Medicine Initiative is an innovative approach to health care, in which cancer treatment is a major concern. 2,3 However, clinical translation is difficult, in that many experiments and preclinical trials are needed for approval, which requires tremendous costs. Meanwhile, drug discovery has slowed, and only a small proportion of proposed medications are successfully translated into prescriptive and approved therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Folate-receptor-targeted laser-activable poly(lactide-<em>co</em>-glycolic acid) nanoparticles loaded with paclitaxel/indocyanine green for photoacoustic/ultrasound imaging and chemo/photothermal therapy

Liu

Chen

et al. 2018

IJN

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BackgroundCancer is one of the most serious threats to human health. Precision medicine is an innovative approach to treatment, as part of which theranostic nanomedicine has been studied extensively. However, the required biocompatibility and substantial cost for the approval of nanomedicines hinder their clinical translation.PurposeWe designed a novel type of theranostic nanoparticle (NP) folate-receptor-targeted laser-activatable poly(lactide-co-glycolic acid) (PLGA) NPs loaded with paclitaxel (Ptx)/indo-cyanine green (ICG)-folic acid-polyethylene glycol (PEG)-PLGA-Ptx@ICG-perfluorohexane (Pfh)- using safe and approved materials and drugs, which would facilitate clinical translation. With laser irradiation, highly efficient photothermal therapy can be achieved. Additionally, targeted NPs can be activated by near-infrared laser irradiation at a specific region, which leads to the sharp release of Ptx at areas of high folate-receptor expression and ensures a higher Ptx concentration within the tumor region, thereby leading to chemo/photothermal synergistic antitumor efficacy. Meanwhile, the NPs can be used as a dual-modality contrast agent for photoacoustic and ultrasound imaging.Materials and methodsFA-PEG-PLGA-Ptx@ICG-Pfh NPs were prepared by sonification method and characterized for physicochemical properties. Cytotoxicity and in vivo biocompatibility were evaluated respectively by CCK8 assay and blood analysis. NPs as dual-modality contrast agents were evaluated by photoacoustic/ultrasound imaging system in vitro and in vivo. In vitro anticancer effect and in vivo anticancer therapy was evaluated by CCK8 assay and MDA-MB231 tumor-bearing mice model.ResultsFA-PEG-PLGA-Ptx@ICG-Pfh NPs were in the size of 308±5.82 nm with negative zeta potential and showed excellent photothermal effect. The NPs could be triggered sharp release of Ptx by laser irradiation, and showed the good biocompatibility in vitro and in vivo. Through photoacoustic/ultrasound imaging, the NPs showed an excellent ability as dual-modality contrast agents in vitro and in vivo. FA-PEG-PLGA-Ptx@ICG-Pfh NPs with laser irradiation showed the best anticancer efficacy in vitro and in vivo.ConclusionSuch a biocompatible and novel theranostic NP is expected to integrate dual-modality imaging with improved therapeutic efficacy and provide a promising paradigm for cancer therapy.

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Section: Introductionmentioning

confidence: 99%

Folate-receptor-targeted laser-activable poly(lactide-<em>co</em>-glycolic acid) nanoparticles loaded with paclitaxel/indocyanine green for photoacoustic/ultrasound imaging and chemo/photothermal therapy

Liu

Chen

et al. 2018

IJN

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“…[ 33 – 35 ] However, despite the extensive use of the method, the interpretation of the results is complex in relation to the presence of confounding factors including the state of conservation of the biological matrix and the increase in the levels of tryptase in other conditions different from anaphylaxis. [ 36 , 37 ]…”

Section: Discussionmentioning

confidence: 99%

Mast cells activation and high blood tryptase levels due to paclitaxel administration. Is Cremophor EL the culprit?

et al. 2020

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Rationale: Although the cancer incidence continues to rise, cancer mortality has declined over the past decade, in large part due to more efficacious chemotherapeutic regimens thus, the ability to use first-line chemotherapeutic agents in the treatment of patients with cancer is crucial. Antineoplastic agents can potentially cause toxic and/or hypersensitivity reactions, that can have serious consequences. Anaphylaxis is a big pitfall in oncological patients; the most important aspect in diagnosing anaphylaxis is to precisely identify the offending agent to prevent future events. Paclitaxel (Taxol) is widely used as antitumor medication in the ovarian, breast, non-small-cell lung, and other cancers. Paclitaxel hypersensitivity reactions are frequently described in the literature, but fatalities are rarely reported. Due to the low solubility of paclitaxel, the compound requires dissolution in Cremophor EL, a derivative of castor oil. Patient concerns: A 79-year-old man was affected by high-grade non-papillary urothelial carcinoma and underwent a radical cystectomy and prostatectomy with locoregional lymphadenectomy. Diagnosis: Eight months later, relapse was detected, and penis amputation and left nephrostomy were performed. Multiple metastases to lymph nodes were detected. Interventions: Palliative chemotherapy was started with Paclitaxel (110 mg) infused at a rate of 50 mL/h. Despite premedication with cetirizine dihydrochloride, dexamethasone, ondansetron, ranitidine, 20 min after Paclitaxel infusion starts, the patient developed general distress, followed by cardiac arrest. Outcomes: The mechanism of fatal paclitaxel-associated hypersensitivity reaction is uncertain and its solvent vehicle Cremophor EL may be involved. Several mechanisms have been postulated: an IgE-mediated mast cell degranulation induced by paclitaxel or Cremophor EL, a non-IgE-mediated idiosyncratic mast cell degranulation by paclitaxel or by Cremophor EL, and complement activation. Severe hypersensitivity reactions with fatal outcome are considered rare. Lessons: The unpredictability and often dramatic reactions of Taxol cause substantial anxiety for doctors and caretakers. They also represent a significant logistic and financial burden on hospitals. Despite premedication, skin testing, and desensitization protocols administration of taxane-based, chemotherapy cannot be considered safe and severe to fatal hypersensitivity reactions cannot be prevented.

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“…The application of new technologies as -omics (genomic, transcriptomics, epigenetics/imprintomics, proteomic and metabolomics) promises to dramatically impact on forensic sciences [ 42 ]. Relevant information may help in the so-called “molecular autopsy”, as a complementary tool to the classical autopsy.…”

Section: Discussionmentioning

confidence: 99%

Proteomics in Deaths by Drowning: Diagnostic Efficacy of Apolipoprotein A1 and α-1 Antitrypsin, Pilot Study

et al. 2020

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Drowning is one of the leading causes of death worldwide. The pathophysiology of drowning is complex and, sometimes, interpretation of the circumstances of death in the autopsy becomes the main source of information in its diagnosis. New advances in medical research, such as proteomics, especially in forensic pathology, are still in the development. We proposed to investigate the application of Mass Spectrometry-based technologies, to identify differentially expressed proteins that may act as potential biomarkers in the postmortem diagnosis of drowning. We performed a pilot proteomic experiment with the inclusion of two drowned and two control forensic cases. After applying restrictive parameters, we identified apolipoprotein A1 (ApoA1) and α-1 antitrypsin as differentially expressed between the two diagnostic groups. A validation experiment, with the determination of both proteins in 25 forensic cases (16 drowned and 9 controls) was performed, and we corroborated ApoA1 higher values in the drowning group, whereas α-1 antitrypsin showed lower levels. After adjusting by confounder factors, both remained as predictive independent factors for diagnosis of drowning (p = 0.010 and p = 0.022, respectively). We constructed ROC curves for biomarkers’ levels attending at the origin of death and established an ApoA1 cut-off point of 100 mg/dL. Correct classification based on the diagnosis criteria was reached for 73.9% of the cases in a discriminant analysis. We propose apolipoprotein A1 (with our cutoff value for correct classification) and α-1 antitrypsin as valuable biomarkers of drowning. Our study, based on forensic cases, reveals our proteomic approach as a new complementary tool in the forensic diagnosis of drowning and, perhaps, in clinical future implications in drowned patients. However, this is a pilot approach, and future studies are necessary to consolidate our promising preliminary data.

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Personalized Medicine Applied to Forensic Sciences: New Advances and Perspectives for a Tailored Forensic Approach

Cited by 30 publications

References 70 publications

Folate-receptor-targeted laser-activable poly(lactide-<em>co</em>-glycolic acid) nanoparticles loaded with paclitaxel/indocyanine green for photoacoustic/ultrasound imaging and chemo/photothermal therapy

Folate-receptor-targeted laser-activable poly(lactide-<em>co</em>-glycolic acid) nanoparticles loaded with paclitaxel/indocyanine green for photoacoustic/ultrasound imaging and chemo/photothermal therapy

Mast cells activation and high blood tryptase levels due to paclitaxel administration. Is Cremophor EL the culprit?

Proteomics in Deaths by Drowning: Diagnostic Efficacy of Apolipoprotein A1 and α-1 Antitrypsin, Pilot Study

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