Clinical features suggesting the presence of PVOD, number of evaluable cells, and Golde score.

<p>6-MWD: 6-minute walking distance. mPAP: mean pulmonary artery pressure. CI: cardiac index. PVR: pulmonary vascular resistance. WU: Wood units. PAWP: pulmonary artery wedge pressure. DLCO: diffusion capacity. PaO₂: partial pressure of oxygen in arterial blood.</p><p>Clinical features suggesting the presence of PVOD, number of evaluable cells, and Golde score.</p

Description of the Golde score calculation in sputum macrophages.

<p>Description of the Golde score calculation in sputum macrophages.</p

Haemosiderin-laden macrophages are significantly (<i>P</i><0.05) more present in sputum from PVOD patients as compared to the others (IPAH, CTEPH and SAPH, respectively).

<p>Haemosiderin-laden macrophages are significantly (<i>P</i><0.05) more present in sputum from PVOD patients as compared to the others (IPAH, CTEPH and SAPH, respectively).</p

Histologic specimen from a patient suffering from PVOD who underwent lung transplantation.

<p>Intimal thickening and fibrous obstruction of septal veins and preseptal venules (asterixis) as well as features of pulmonary capillary hemangiomatosis with proliferation of dilated and congested capillaries as well as dilated lymphatic (left upper and right lower part of the figure; arrowhead). Alveoli with haemosiderin-laden macrophages of Golde score 3–4 (arrow) are clearly visible. Haemosiderin-negativ macrophages are difficult to be identified. Golde score from the tissue was 304, as compared to 252 in the sputum.</p

Clinical characteristics of the four patient groups.

<p>Clinical characteristics of the four patient groups.</p

Change in patient PSA in response to gene therapy.

PSA doubling time (PSADT) for all the patients were estimated before gene therapy (PSADT.PRE) and after adenoviral injections (PSADT.POST). Mean, median, minimum, and maximum PSADT are tabulated (A; years). Median and IQR of pre- and post-gene therapy PSADT is plotted in B. Statistical mean, median, minimum, and maximum PSADT for patients that were injected with low-dose of adenovirus (cohorts #1–3) and from patients from high-dose (cohorts #4–5) were estimated and plotted in C. A plot of mean, median, minimum, maximum and IQR for both the groups is shown to the right (D). Absolute PSA count (pg/mL) for patient #12 (E) and #13 (F) over time is plotted. Red dotted line indicates the day of Ad5-IL-12 adenoviral injection. Blue arrows indicate date of androgen suppression therapy (AST).</p

Treatment schema.

Subjects underwent a series of pretreatment evaluations and met all the eligibility criteria before enrolled in the study. Subjects received a single intraprostatic injection of the Ad5-yCD/mutTKSR39rep-hIL-12 adenovirus at one of five dose levels (see Table 1) on day 1. Two days later (day 3), subjects received a one-week (7 day) course of 5-FC (150 mg/kg/day) + vGCV (1,800 mg/day) prodrug therapy. Toxicity assessments occurred twice a week during the first two weeks and then at every scheduled follow-up visit. The primary endpoint was toxicity through day 30.</p

An estimation of peripheral blood mononuclear cells (PBMCs) for all cohorts.

An estimation of peripheral blood mononuclear cells (PBMCs) for all cohorts.</p

Patient baseline characteristics and adenoviral injection.

Each cohort had 3 patients that were injected with an increasing Ad5-IL-12 dose.</p

Changes in serum IL-12, IFNγ, and CXCL10 levels in each cohort.

Patient blood was drawn within 30 days of the Ad5-IL-12 adenoviral injection or on the day of adenovirus injection prior to the procedure (day 0) and on the days as described in the clinical protocol (up to day 24). Cytokines were measured by ELISA based on cytokine specific standard curves (IL-12 0–500 pg/mL; CXCL10 and IFNγ 0–1,000 pg/mL). The peak cytokine value for each patient was estimated (pg/mL; as presented in Table 3). A mathematical mean value for each cytokine for all the patients within a cohort was estimated and plotted using MS Excel. The mean serum IL-12 (A), IFNγ (B), and CXCL10 (C) with errors (standard error of the mean; SEM) is shown for each cohort along with goodness of fit (R2) and significance (p). P values from Jonckheere-Terpstra test is also provided (p*).</p