Browsing by Subject "Paclitaxel"

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    Improved biotechnological production of paclitaxel in Taxus media cell cultures by the combined action of coronatine and calix[8]arenes
    (Elsevier, 2021-06) Escrich, Ainoa; Moyano, Elisabeth; Cusido, Rosa M.; Bonfill, Mercedes; Hosseini, Bahman; Palazón, Javier; Almagro Romero, Lorena; Biología Vegetal
    Paclitaxel (PTX), a widely used anticancer agent, is found in the inner bark of several Taxus species, although at such low levels that its extraction is ecologically unsustainable. Biotechnological platforms based on Taxus sp. cell cultures offer an eco-friendlier approach to PTX production, with yields that can be improved by elicitation. However, the also limited excretion of target compounds from the producer cells to the medium hampers their extraction and purification. In this context, we studied the effect of treating T. media cell cultures with the elicitor coronatine (COR) and calix[8]arenes (CAL), nanoparticles that can host lipophilic compounds within their macrocyclic scaffold. The highest taxane production (103.5 mg.L−1), achieved after treatment with COR (1 μM) and CAL (10 mg.L−1), was 15-fold greater than in the control, and PTX represented 82% of the total taxanes analyzed. Expression levels of the flux-limiting PTX biosynthetic genes, BAPT and DBTNBT, increased after the addition of COR, confirming its elicitor action, but not CAL. The CAL treatment significantly enhanced taxane excretion, especially when production levels were increased by COR; 98% of the total taxanes were found in the culture medium after COR + CAL treatment. By forming complexes with PTX, the nanoparticles facilitated its excretion to the medium, and by protecting cells from PTX toxicity, its intra-and extra-cellular degradation may have been avoided. The addition of COR and CAL to T. media cell cultures is therefore a bio-sustainable and economically viable system to improve the yield of this important anticancer compound.
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    Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE)
    (2019) T. Bachelot, E. Ciruelos; A. Schneeweiss, F. Puglisi; T. Peretz-Yablonski, I. Bondarenko; S. Paluch-Shimon, A. Wardley; J.L. Merot, Y. du Toit; V. Easton, N. Lindegger; D. Miles, PERUSE investigators; Alonso Romero, José Luis; Medicina
    Background Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. Patients and methods In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8 mg/kg loading dose, then 6 mg/kg every 3 weeks (q3w)] and pertuzumab (840 mg loading dose, then 420 mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54 years; 29% had received prior trastuzumab. Median treatment duration was 16 months for pertuzumab and trastuzumab and 4 months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months’ median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9–22.7] months overall (19.6, 23.0 and 18.1 months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%–82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). Conclusions Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile.
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    Reduced histologic neo in-stent restenosis after use of a paclitaxel-coated cutting balloon in porcine coronary arteries
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Traxler, Denise; Hemetsberger, Rayyan; Spannbauer, Andreas; Zlabinger, Katrin; Gugerell, Alfred; Lukovic, Dominika; Mandic, Ljubica; Pavo, Noemi; Winkler, Johannes; Gyöngyösi, Mariann
    The incidence of in-stent restenosis (ISR) has declined dramatically, but once it develops, no current treatment option, such as drug-eluting stents, drug-coated balloons, or cutting balloons (CBs), prevents re-narrowing of the stented atherosclerotic artery. In this preclinical study, we aimed to improve the efficacy of ISR treatment by coating CBs with paclitaxel (paclitaxel-eluting cutting balloon; PECB) and to characterize the histological features of neo-ISRs that arise after ISR treatment. ISR was induced by bare metal stent (BMS) implantation in coronary arteries in pigs. After one month of follow-up, BMS-induced ISR was treated with either CB or PECB. After another month, we performed quantitative coronary angiography, explanted the treated arteries and assessed histopathological and histomorphometric parameters. In addition, we compared histological features of neo-ISRs with pre-treatment ISRs. Injury, inflammation, fibrin deposition, and endothelialization scores were similar between the CB and PECB groups at one month after ISR treatment. Neointimal area (0.87±0.61 vs. 1.95±1.14 mm 2, p=0.02), mean neointimal thickness (0.40±0.39 vs. 0.99±0.56 mm, p=0.01), and percent area stenosis (27.3±20.4 vs. 48.3±22.9%, p=0.04) were decreased in PECB-treated coronary arteries compared to CB-treated arteries, respectively. Density of cells (predominantly smooth muscle cells; SMCs) was increased in neo-ISRs (3.51±3.05×10 3 vs. 6.35±2.57×10 3 cells/mm 2 , p<0.01),but significantly more CD68 + and CD20 + cells were found in pre-treatment ISRs. In conclusion, PECB treatment of ISRs led to better results in terms of smaller neointimal area and %area stenosis of neo-ISR. SMC density was increased in neo-ISRs in contrast with higher percentage of CD68 + and CD20 + cells in pre- treatment ISRs.
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    The role of hyperthermic intraperitoneal chemotherapy using paclitaxel in platinum-sensitive recurrent epithelial ovarian cancer patients with microscopic residual disease after cytoreduction
    (springer, 2015-03) Cascales Campos, Pedro Antonio; Gil Martínez, José; Feliciangeli, Eduardo; Gil Gómez, Elena; González Gil, Alida; López López, Víctor; Ruiz Pardo, José; Nieto Díaz, Aníbal; Parrilla Paricio, Juan José; Parrilla Paricio, Pascual; Cirugía, Pediatría y Obstetricia y Ginecología
    En este trabajo, se compararon 2 grupos homogéneos de pacientes con carcinomatosis peritoneal de origen ovárico recurrente, sensibles al platino en las que se realizó una citorreducción completa de la enfermedad: un grupo estaba formado por pacientes intervenidas antes y el otro después de inicio del programa de cirugía oncológica peritoneal. Bajo esta premisa se estudió como HIPEC había mejorado los resultados en pacientes con recurrencias platino-sensibles. Se trata de un aporte multidisciplinar en el que trabajamos conjuntamente los servicios de Cirugía, Ginecología y Oncología Médica. En los resultados, se encontró una mejoría a favor del tratamiento HIPEC en grupos comparables, sin diferencias significativas en ninguna de las variables preoperatorias estudiadas: Tras un análisis multivariante de los factores identificados en el análisis univariante, solo la presencia de tumores con histología indiferenciada (hazard ratio 2,57; IC 95 % 1,21–5,46; p < 0,05) fue un factor independiente asociado a una supervivencia libre de enfermedad reducida. La supervivencia libre de enfermedad a 1 y 3 años fue del 77 y 23 % en los pacientes del grupo I y del 77 y 45% diferencias clínicamente relevantes entre los 2 grupos, con una mejora evidente de la supervivencia a favor del grupo tratado con HIPEC. No se encontraron diferencias en cuanto a las complicaciones postoperatorias entre ambos grupos por lo que en este estudio se reforzó la idea de que HIPEC no incrementaba la morbilidad postoperatoria con su administración.