Publications by authors named "M Carmen de la Fuente"

744 Publications

The Postnatal Leptin Surge Supports Immune Cell Function in Rats.

Immunol Invest 2021 Jun 14:1-17. Epub 2021 Jun 14.

Department of Genetics, Physiology and Microbiology (Unit of Animal Physiology). Faculty of Biology, Complutense University of Madrid, Madrid, Spain.

: Leptin plays an important role in the regulation of the immune response. There is a physiological surge of leptin in rodents during the neonatal period, which has mainly been studied in the context of brain development. However, little is known about the effects of this neonatal leptin surge on immunity. Therefore, we investigated whether blocking this leptin surge could affect several immune functions.: Male and female rats were injected subcutaneously with 5 mg/Kg/day of rat pegylated super leptin antagonist during the neonatal period (PND5-9). On the peripubertal period, relevant functions as well as cytokine release by spleen leukocytes were studied in these animals.: The results showed that the animals significantly display an impaired anti-tumor NK activity and chemotactic and proliferation capacity of lymphocytes in response to mitogens. In addition, several cytokine concentrations, released under mitogen-stimulated conditions, were also altered.: In conclusion, the neonatal leptin surge seems to be involved in the establishment of an adequate immune response and cytokine profile, which are crucial for the maintenance of a healthy life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08820139.2021.1940199DOI Listing
June 2021

Vorasidenib, a dual inhibitor of mutant IDH1/2, in recurrent or progressive glioma; Results of a first-in-human Phase I trial.

Clin Cancer Res 2021 Jun 2. Epub 2021 Jun 2.

Center For Neuro-Oncology, Dana-Farber Cancer Institute.

Purpose: Lower-grade gliomas (LGGs) are malignant tumors in young adults. Current therapy is associated with short- and long-term toxicity. Progression to higher tumor grade is associated with contrast enhancement on MRI. The majority of LGGs harbor mutations in the genes encoding isocitrate dehydrogenase 1 or 2 (). Vorasidenib (AG-881) is a first-in-class, brain-penetrant, dual inhibitor of the mutant IDH1 and mutant IDH2 enzymes.

Experimental Design: We conducted a multicenter, open-label, phase I, dose escalation study of vorasidenib in 93 patients with mutant (m) solid tumors, including 52 patients with glioma that had recurred or progressed following standard therapy. Vorasidenib was administered orally, once daily, in 28-day cycles until progression or unacceptable toxicity. Enrollment is complete; this trial is registered with ClinicalTrials.gov, NCT02481154 Results: Vorasidenib showed a favorable safety profile in the glioma cohort. Dose-limiting toxicities of elevated transaminases occurred at doses >100 mg and were reversible. The protocol-defined objective response rate per Response Assessment in Neuro-Oncology criteria for LGG (RANO-LGG) in patients with nonenhancing glioma was 18% (one partial response, three minor responses). The median progression-free survival was 36.8 months [95% confidence interval (CI), 11.2-40.8] for patients with nonenhancing glioma and 3.6 months (95% CI, 1.8-6.5) for patients with enhancing glioma. Exploratory evaluation of tumor volumes in patients with nonenhancing glioma showed sustained tumor shrinkage in multiple patients.

Conclusions: Vorasidenib was well tolerated and showed preliminary antitumor activity in patients with recurrent or progressive nonenhancing m LGG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-21-0611DOI Listing
June 2021

Trichinella spiralis in a cougar (Puma concolor) hunted by poachers in Chile.

Rev Bras Parasitol Vet 2021 24;30(3):e002821. Epub 2021 May 24.

Facultad de Ciencias Veterinarias, Universidad de Concepción, Chillán, Ñuble, Chile.

Trichinellosis is a zoonosis caused by nematodes of the Trichinella genus, of which 10 species have been described. Species identification when larvae is found is only possible using molecular tools. Meat from pigs and game animals not subjected to veterinary inspection are the main sources of human infections. The hunting of native carnivores is prohibited in Chile due to conservation issues and the fact that those animals favor pest control. The illegal hunting of a cougar (Puma concolor) occurred in September 2020. Herein, the molecular identification of Trichinella larvae, by analyzing nuclear (expansion segment V) and mitochondrial (cytochrome C oxidase subunit I) sequences are described. Both the amplification of the expansion segment V region and the phylogenetic analysis of a segment of a fragment of the cytochrome c-oxidase subunit I sequence confirmed that the larvae belonged to T. spiralis. The case described herein represents the first evidence of illegal hunting of a protected mammal infected with Trichinella in Chile, highlighting the 'One Health' perspective to face this disease in the rural-sylvatic interphase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/S1984-29612021033DOI Listing
May 2021

Estimated Effect of COVID-19 Lockdown on Skin Tumor Size and Survival: An Exponential Growth Model.

Actas Dermosifiliogr 2020 Oct 20;111(8):629-638. Epub 2020 Sep 20.

Servicio de Dermatología, Instituto Valenciano de Oncología, Valencia, Spain.

Background And Objectives: Spain is in a situation of indefinite lockdown due to the ongoing coronavirus disease 2019 (COVID-19) pandemic. One of the consequences of this lockdown is delays in medical and surgical procedures for common diseases. The aim of this study was to model the impact on survival of tumor growth caused by such delays in patients with squamous cell carcinoma (SCC) and melanoma.

Material And Methods: Multicenter, retrospective, observational cohort study. We constructed an exponential growth model for both SCC and melanoma to estimate tumor growth between patient-reported onset and surgical excision at different time points.

Results: Data from 200 patients with SCC of the head and neck and 1000 patients with cutaneous melanoma were included. An exponential growth curve was calculated for each tumor type and we estimated tumor size after 1, 2, and 3 months of potential surgical delay. The proportion of patients with T3 SCC (diameter > 4 cm or thickness > 6 mm) increased from 41.5% (83 patients) in the initial study group to an estimated 58.5%, 70.5%, and 72% after 1, 2, and 3 months of delay. Disease-specific survival at 2, 5, and 10 years in patients whose surgery was delayed by 3 months decreased by 6.2%, 8.2%, and 5.2%, respectively. The proportion of patients with ultrathick melanoma (> 6 mm) increased from 6.9% in the initial study group to 21.9%, 30.2%, and 30.2% at 1, 2, and 3 months. Five- and 10-year disease-specific survival both decreased by 14.4% in patients treated after a potential delay of 3 months.

Conclusions: In the absence of adequate diagnosis and treatment of SCC and melanoma in the current lockdown situation in Spain, we can expect to see to a considerable increase in large and thick SCCs and melanomas. Efforts must be taken to encourage self-examination and facilitate access to dermatologists in order to prevent further delays.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.adengl.2020.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502279PMC
October 2020

The Immunity Clock.

J Gerontol A Biol Sci Med Sci 2021 May 12. Epub 2021 May 12.

Department of Genetics, Physiology and Microbiology (Unity of Animal Physiology), Faculty of Biology, Complutense University of Madrid (UCM), Madrid, Spain.

The immune system has been for long considered a marker of health. The age-related decline in its function results in a greater incidence of infections, autoimmune diseases and cancer. Nevertheless, it is still not known if immune function can be used to accurately estimate the rate of aging of an individual. A set of 14 immune function variables were measured in 214 healthy individuals ranging from 19 to 88 years old. All immune variables were selected as independent variables for the prediction of age by multiple linear regression (MLR). The Immunity Clock was constructed including the following 5 immune variables: natural killer activity, phagocytosis and chemotaxis of neutrophils and chemotaxis and proliferative capacity of lymphocytes reaching an adjusted R 2 of 80.3% and a standard error of the estimate of 4.74 years. The Immunity Clock was validated in a different group of healthy individuals (N=106) obtaining a Pearson´s correlation coefficient of 0.898 (p < 0.001) between chronological age and the age estimated by the Immunity Clock, the ImmunolAge. Moreover, we demonstrate that women with anxiety (N=10) show a higher ImmunolAge than their chronological age whereas healthy centenarians (N=8) show a lower one. In addition, the Immunity Clock provided here proves to be useful for monitoring the effectiveness of a nutritional intervention lasting one month, by detecting a diminished ImmunolAge in the same individuals. Further research will be needed to ascertain if the Immunity Clock is a passive marker of the aging process or it plays an active role in it.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gerona/glab136DOI Listing
May 2021