Mouse avatars of human cancers: the temporality of translation in precision oncology.

Patient-derived xenografts (PDXs) are currently promoted as new translational models in precision oncology. PDXs are immunodeficient mice with human tumors that are used as surrogate models to represent specific types of cancer. By accounting for the genetic heterogeneity of cancer tumors, PDXs are hoped to provide more clinically relevant results in preclinical research. Further, in the function of so-called "mouse avatars", PDXs are hoped to allow for patient-specific drug testing in real-time (in parallel to treatment of the corresponding cancer patient). This paper examines the circulation of knowledge and bodily material across the species boundary of human and personalized mouse model, historically as well as in contemporary practices. PDXs raise interesting questions about the relation between animal model and human patient, and about the capacity of hybrid or interspecies models to close existing translational gaps. We highlight that the translational potential of PDXs not only depends on representational matching of model and target, but also on temporal alignment between model development and practical uses. Aside from the importance of ensuring temporal stability of human tumors in a murine body, the mouse avatar concept rests on the possibility of aligning the temporal horizons of the clinic and the lab. We examine strategies to address temporal challenges, including cryopreservation and biobanking, as well as attempts to speed up translation through modification and use of faster developing organisms. We discuss how featured model virtues change with precision oncology, and contend that temporality is a model feature that deserves more philosophical attention.

Long-term outcomes after plaque incision and grafting for Peyronie's disease: comparison of porcine dermal and bovine pericardium grafts.

BACKGROUND: Plaque incision and grafting (PEG) is one of the mainstays in surgical therapy for severe penile curvature in Peyronie's disease (PD). Different kinds of grafts are available for covering albugineal defects during PEG, both allografts and xenografts. However, to date, none of these proved superior to others. OBJECTIVES: To compare two different types of xenograft, porcine dermal matrix and bovine pericardium matrix in PEG for PD. MATERIALS AND METHODS: From 2010 to 2019, 63 patients with PD underwent PEG, using porcine dermal (n = 25; Group 1) and bovine pericardium (n = 38; Group 2) grafts. Long-term outcomes were evaluated through multi-disciplinary questionnaires administration by phone interview. The following items were considered: correction of penile bending, quality of erection, intercourse ability, penile shortening, and sensitiveness. Overall satisfaction and impact of surgery on sexual activity and quality of life were also investigated. RESULTS: Plaque median (IQR) size was 29 (22-33) mm and was smaller in Group 1 (27.5 vs. 31 mm; P = .03). Complete follow-up data were available for 53 patients (84%). Considering post-operative outcomes, no differences were found when considering ED rates, penile shortening, sensitiveness, complications, and penile straightening (all P > .1). Patients in Group 2 were more likely to have palpable penile nodules at follow-up (20.6 vs. 0%; P = .03). However, patient's post-operative sexual life satisfaction was consistent between the two groups, with just 1 (5.3) and 8 (23.5) patients in Group 1 and 2 respectively referring a worsening in sexual life satisfaction (P = 0.2). At follow-up, 84.9% of patients that would still undergo surgery for PD, with no statistical difference between the two groups (P = .4). CONCLUSIONS: Corporoplasty with PEG is an effective treatment for men with PD. Porcine dermal and bovine pericardium xenografts seem to have similar long-term outcomes.

Acceptance of organ xenotransplantation among Latin American immigrants resident in the United States.

BACKGROUND: Making xenotransplantation socially acceptable is the first step in working toward the promotion of this potential therapy option for providing transplant organs. OBJECTIVE: To analyze the attitude toward xenotransplantation among the Latin American population resident in Florida (the USA), and to determine the variables affecting this attitude. METHODS: A sample of Latin American residents in the state of Florida was randomized and stratified according to nationality, age, and sex (n = 1524). Attitude was assessed using a validated questionnaire (PCID-XenoTx Rios) which was self-completed anonymously. STATISTICAL ANALYSIS: descriptive analysis, Student's t-test, the chi-square test, and a logistic regression analysis. RESULTS: The questionnaire completion rate was 95% (n = 1450). If it was assumed that xenotransplanted organs functioned as well as human ones, 10% (n = 147) would be in favor, 73% (n = 1092) against, and 17% (n = 246) undecided. If the results were worse, only 2% (n = 35) would be in favor. This favorable attitude was related to country of origin (Honduras and Guatemala; P < 0.001); age (P < 0.001); sex (women; P < 0.001); marital status (married; P < 0.001); descendents (yes; P < 0.001); level of formal education (secondary education and university; P < 0.001); participation in voluntary prosocial activities (yes; P < 0.001); having spoken about donation and transplantation within the family (yes; P < 0.001); a partner's favorable attitude toward transplantation (P = 0.040); religion (catholic; P < 0.001); knowing the attitude of one's religion toward donation (yes; P < 0.001); previous experience of donation and/or transplantation (yes; P < 0.001); a belief that one might need a transplant in the future (yes; P < 0.001); and a favorable attitude toward human donation (yes; P < 0.001). The following were associated with attitude in the multivariate analysis: age (≥40 yrs; OR = 1.152); marital status (married; OR = 500); prosocial activities (yes, I participate in them; OR = 9.196. No, but I would like to; OR = 332.538); religion (catholic; OR = 2000); attitude toward deceased organ donation (in favor; OR = 2000); and previous experience of donation and/or transplantation (yes; OR = 500). CONCLUSIONS: The attitude of Latin Americans resident in Florida toward xenotransplantation is very negative, and is determined by many psychosocial factors, mainly related to their prior attitude toward the different kinds of human organ donation.