José Luis Rodríguez Peralto’s research while affiliated with Hospital 12 de Octubre and other places

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Publications (70)


Mogamulizumab‐induced alopecia. Multicentric case series: Clinical, trichoscopic and histological characterization
  • Article

February 2025

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9 Reads

Journal of the European Academy of Dermatology and Venereology

Raquel Cavestany Rodríguez

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Daniel Falkenhain López

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Pablo L. Ortiz‐Romero

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[...]

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Virginia Velasco‐Tamariz

Figure SN1. Optical tweezing (OT)-indentation implemented in horizontal geometry. a Schematics of the experimental OT setup for lateral cell forcing in a trapping anvil with four fixing
Antibodies for western blot
Primers for ChIP
ELOVL6 as a Therapeutic Target: Disrupting c-MYC-Driven Lipid Metabolism to Enhance Chemotherapy in Pancreatic Cancer
  • Preprint
  • File available

November 2024

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20 Reads

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, marked by a survival rate of only 12%. Consequently, the exploration of novel therapeutic strategies becomes a critical clinical imperative. Among the genetic alterations contributing to PDAC, c-MYC overexpression arises due to upstream mutations, amplifications, and copy number alterations. c-MYC serves as a key regulator in the tumor's metabolic reprogramming, playing a pivotal role in proliferation, migration, and metastasis. This study delves into the investigation of the role of the elongase ELOVL6 in c-MYC-induced cell transformation and its potential as a therapeutic target in PDAC. Here, we demonstrate that c-MYC regulates lipid elongation to promote cell transformation, offering a new avenue for therapeutic intervention. Initially, we show the direct regulation of ELOVLs expression by c-MYC in various PDAC mouse models and cell lines, elucidating its upregulation during transformation and tumor progression. Genetic or chemical inhibition of ELOVL6 results in decreased proliferation and migration, accompanied by alterations in fatty acid elongation. These changes in fatty acid composition led to modifications in membrane rigidity, permeability, and thickness, which collectively affect micropinocytosis and macropinocytosis. Importantly, we observe an increase in Abraxane uptake and a synergistic effect when combined with ELOVL6 interference in vitro. In vivo validation demonstrates that ELOVL6 inhibition significantly reduces tumor growth and enhances the response to Abraxane, thereby increasing overall survival. Altogether, these results position ELOVL6 as a promising therapeutic target in the treatment of PDAC

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Fig. 4. Association between NRAS/BRAF status and TERT mRNA expression levels. Means±standard deviation (SD) comparison of TERT mRNA expression levels between melanoma tumors with BRAF mutated (n = 48), NRAS mutated (n = 22), or wild-type (WT) for both genes (n = 8). Variance analysis by ANOVA one way unpaired test with P-value = 0.0007. Multiple comparisons test: NRAS mutated vs BRAF mutated (P-value = 0.046); BRAF mutated vs WT for both genes (P-value = 0.031), and NRAS mutated vs WT for both genes (P-value = 0.0001). P value style GP: *P < 0.050, **P < 0.010, ***P < 0.001, and ****P < 0.0001.
Univariate Cox Regression Analyses in 53 melanoma patients. Ten variables (3 clinical and 7 molecular) were studied separately for each analysis (PFS and OS).
pTERT C250T mutation: A potential biomarker of poor prognosis in metastatic melanoma

August 2023

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56 Reads

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6 Citations

Heliyon

Melanoma is the most aggressive form of skin cancer and the leading cause of death from cutaneous tumors. Several studies have associated alterations in the TERT promoter region (pTERT) with gene overexpression, aggressiveness and poor prognosis of the disease. The aim of this study was to clarify the role of pTERT molecular status in paired samples of primary melanoma and metastasis using tissue and plasma to establish a correlation with disease progression and survival.A total of 88 FFPE tissue samples from 53 patients with advanced melanoma were analyzed. Of these, 35 had paired samples. We also examined cfDNA samples from plasma of 25 patients. We detected a good correlation between primary tumors and metastases in pTERT mutation and methylation status. We were also able to identify pTERT mutations in plasma samples that correlated with mutational status in tissue samples. Interestingly, the C250T mutation was associated with worse survival and higher TERT mRNA expression, compared to the other most common mutation: C228T. In addition, hyper-methylation of the promoter region seems to be related to the progression of pTERT wild type (WT) patients. These results suggest that TERT gene alterations plays an important role during tumor progression, with the detection of the C250T mutation in tissue and plasma as a potential biomarker of poor prognosis in patients with advanced melanoma.



Median raphe cysts: A clinico‐pathologic and immunohistochemical study of 52 cases

November 2022

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13 Reads

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3 Citations

Journal of Cutaneous Pathology

Background: Median raphe cysts (MRC) are epithelial-lined cystic lesions of the genital area that do not communicate with the urethra or the overlying epidermis. Immunohistochemically, MRC show positivity for cytokeratin (CK) 5-6, CK 7, carcinoembryonic antigen (CEA), p63 and uroplakin III (URO III). GATA 3 and human milk fat globulin 1 (HMFG1) are immunohistochemical markers that have been not previously studied in MRC. Methods: We conducted a study of 52 patients diagnosed with MRC in Dermatology and Pathology Departments of eight hospitals between 1990 and 2016. The monoclonal antibodies used were CK5-6, CK7, CK20, URO III, p63, GATA3 and HMFG1. HMFG1 was studied in five cases of apocrine hidrocystomas and compared with five cases of MRC from our series. Results: CK 5-6, CK7 and p63 expression showed strong positivity in the urothelial epithelium of 48 cases. CK20 was focally positive in areas of mucinous differentiation in three cases. GATA3 showed intense nuclear staining in 30 cases. HMFG1 was positive in three cases of MRC and in three cases of apocrine hidrocystoma. Conclusion: Positivity of GATA3 and CK7 in MRC supports the urothelial origin of these cysts. We found no differences in HMFG1 expression between MRC and apocrine hidrocystomas.


(A) Erythematous annular scaly papules and plaques on the face. (B,C) Dermoscopy showed thin arborizing vessels, big yellow dots, white scales, and erythema. (D) RCM at the level of the spinous layer: epidermal disarray with loss of the honeycomb pattern and exocytosis of inflammatory cells (yellow asterisks). (E) RCM at the level of the superficial dermis: dilated adnexal infundibulum with follicular hyperkeratosis (red circles), periadnexal inflammatory cell infiltrate and sparse inflammatory cells (red arrows) and degenerated collagen bundles (red asterisk). (F) Histology (Hematoxylin–Eosin stain ×30) revealed dense perivascular superficial lymphocytic infiltrate located in epidermis and hair follicles, vacuolar degeneration of the basal layer. (G) CD123 immunostaining showing many CD123⁺ plasmacytoid dendritic cells.
Subacute cutaneous lupus erythematosus induced by Capecitabine: Confocal microscopy and dermoscopy findings

July 2022

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31 Reads

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3 Citations


Activity and safety of topical pimecrolimus in patients with early stage mycosis fungoides (PimTo-MF): a single-arm, multicentre, phase 2 trial

June 2022

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94 Reads

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10 Citations

The Lancet Haematology

Background The calcineurin pathway is often activated in mycosis fungoides. We aimed to assess the activity and safety of topical pimecrolimus, a calcineurin inhibitor, in patients with early mycosis fungoides. Methods PimTo-MF was a single-arm, multicentre, phase 2 trial done at six medical centres in Spain. Patients (aged ≥18 years) had histologically confirmed early mycosis fungoides (stages IA–IIA) and an Eastern Cooperative Oncology Group performance status of 0–1. Key exclusion criteria included the use of concurrent treatments for mycosis fungoides, including sunbathing, topical or systemic corticosteroids, and other calcineurin inhibitors. Patients applied topical pimecrolimus 1% cream on their skin lesions twice daily for 16 weeks (1 g per 2% of body surface), with subsequent follow-up of 12 months. Dosage modifications were not allowed. To evaluate adherence to the treatment, patients were instructed to return all empty tubes to the hospital (as per drug accountability protocols). The primary endpoint was the overall response ratein the intention-to-treat population. PimTo-MF is registered with EudraCT, 2014-001377-14, and is complete. Findings Between March 1, 2015, and Sept 30, 2016, 39 patients were enrolled. All patients were assessable, with a median age of 51·5 years (IQR 45–62), and the population was predominantly male (24 male [62%], 15 female [38%]). Median follow-up after baseline was 5·7 years (IQR 5·7–6·2). 22 (56%) of 39 patients had an overall response (one complete response, 21 partial responses). Responses were observed across IA (14 [54%] of 26 patients) and IB (eight [73%] of 11 patients) clinical stages, but not IIA. Topical pimecrolimus was well tolerated and no patient required a dose reduction or discontinued treatment because of unacceptable drug-related toxicity. No patients were lost to follow-up or discontinued treatment. 13 (33%) of 39 patients reported adverse events; transitory mild burning or pruritus (grade 1) was the most common, seen in eight (21%) patients. In three (8%) of these patients, the burning or pruritus was considered related to treatment. No grade 4 or 5 adverse events were observed. Interpretation Pimecrolimus 1% cream seems active and safe in patients with early stage mycosis fungoides. Our findings should be taken with caution until long-term follow-up data are obtained that confirm the safety of this treatment. Further controlled clinical trials are warranted to confirm these results. Funding Instituto de Salud Carlos III and the European Regional Development Fund. Translation For the Spanish translation of the abstract see Supplementary Materials section.


Histopathology of Dermatologic Complications of Tattoos

May 2022

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96 Reads

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3 Citations

American Journal of Dermatopathology

Tattoos are characterized by the introduction of exogenous pigments into the dermis. Tattoos usually serve cosmetic purposes, although they may have other causes, such as traumatic pigment implants in accidents or medical-related tattoos in the context of radiotherapy. Dermatologic adverse reactions are relatively uncommon, and they include infections, immune-mediated reactions, cutaneous lesions secondary to the Koebner phenomenon, exacerbation of preexisting dermatosis, benign and malignant neoplasms, and a miscellaneous group of dermatologic conditions that may appear in a preexisting tattoo. The aim of this study is to review the types of histopathologic reactions that may appear in a preexisting permanent tattoo.


Citations (33)


... While such proximity between cell division and centriole amplification may appear risky, 1 this cell cycle variant-marked by the association of centriole amplification with low CDK activitycould be an efficient barrier to avoid DNA replication and cell division in cells with amplified centrioles. Supporting this ''failsafe'' hypothesis, several medical reports reveal the existence of MCCs in cysts that have been found in a wide variety of normally non-multiciliated organs (2,202 occurrences of the term ''ciliated cyst'' in the PubMed database, e.g., in Ferná ndez Figueras et al., 43 Rubio et al., 44 and Hughes et al. 45 ). Such potential for multiciliation in a progenitor cell could also underpin the observed formation of MCCs along the lumen of non-MCC fluid-producing tissues (kidney, urethra) in pathological situations, where they could contribute to restore fluid flow. ...

Reference:

Cyclin switch tailors a cell cycle variant to orchestrate multiciliogenesis
Principales tipos de quistes en dermatopatología: Parte 2
  • Citing Article
  • March 2024

Revista Española de Patología

... Several studies have demonstrated that TERT mRNA levels in tumors are potential diagnostic and prognostic markers [39][40][41][42]. In colorectal cancer [43,44] and metastatic melanoma [45], tissue and plasma TERT mRNA levels were found to be independent markers of therapeutical response and, therefore, were prognostic of disease progression. ...

pTERT C250T mutation: A potential biomarker of poor prognosis in metastatic melanoma

Heliyon

... Although physical and radiological assessment suggests the cyst type, histopathological confirmation is needed. Four types have been identified: urethral, epidermoid, glandular, and mixed (5,19). According to the lining, pseudostratified columnar epithelium, stratified squamous epithelium, urothelium, glandular epithelium and coexisting mixed epithelium, respectively. ...

Median raphe cysts: A clinico‐pathologic and immunohistochemical study of 52 cases
  • Citing Article
  • November 2022

Journal of Cutaneous Pathology

... Out of which, SCLE was seen in 11 patients. [5][6][7] Systemic lupus erythematosus was seen in 2 cases [5,8] and discoid lupus erythematosus was seen in 3 cases. [5,9,10] Most of the cutaneous lesions occurred after 2 cycles of capecitabine. ...

Subacute cutaneous lupus erythematosus induced by Capecitabine: Confocal microscopy and dermoscopy findings

... It was well tolerated and no patient required a dose reduction or discontinued treatment due to drug-related toxicity. [18] There is only one case report of the successful use of tacrolimus ointment 0.1% in the treatment of MF. [19] The NCCN guidelines suggest that TCI may be considered as a steroid-sparing treatment for lesions in the perioral and periorbital regions in patients with early-stage MF. [2] In contrast, the EORTC guidelines acknowledge that while the results are promising, they should be interpreted with caution, and no recommendation can currently be made regarding the use of TCI in MF. [1] ...

Activity and safety of topical pimecrolimus in patients with early stage mycosis fungoides (PimTo-MF): a single-arm, multicentre, phase 2 trial
  • Citing Article
  • June 2022

The Lancet Haematology

... MYC interacts with BPTF to induce MDR in cancer cells through upregulation of ABC transporters [376]. BPTF is a cofactor that alters chromatin structure to increase transcription activation and recruitment of c-MYC to ABC-transporter promoters, elevating their expression and contributing to gemcitabine (drug) resistance [377,378]. ...

Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR)

... Aliuminio hidroksidas ir aliuminio fosfatas yra dažniausiai naudojami adjuvantai vakcinose. Nėra dokumentuota adjuvantų sukeltų anafilaksijų atvejų, tačiau dėl vakcinų, kurių sudėtyje yra aliuminio, gali išryškėti kontaktinė alergija, mažos granulomos, mazgeliai bei dilgėlinė [15]. ...

Contact allergy to aluminum following vaccination: A report of 3 cases
  • Citing Article
  • October 2021

Actas Dermo-Sifiliográficas (English Edition)

... Biopsy samples from individuals with paucibacillary leprosy commonly exhibit the tuberculoid pattern, showcasing granulomatous inflammation characterized by well-organized clusters of epithelioid histiocytes, multinucleated giant cells, and lymphocytes; the infiltrate commonly exhibits a "sausage shape" as it progresses along the pathways of nerves and appendages [20,28]. The presence of organisms is minimal, and if detected, they can be demonstrated only with acid-fast dyes like the Fite method [20] [ Figure 7]. ...

Granulomas in Dermatopathology: Principal Diagnoses — Part 2
  • Citing Article
  • July 2021

Actas Dermo-Sifiliográficas (English Edition)

... The underlying disorder appears to be a reduction in vascular tone with a tendency towards excessive vasodilation triggered by factors such as abrupt changes from cold to heat, exposure to the sun and UV-A radiation, alcohol, very hot or spicy foods, and stressors. Other possible causes include immune system activation and infestation by skin mite Demodex folliculorum, which is known to live within the sebaceous unit (1,3,5). Rosacea is suspected to be related to infection with Helicobacter pylori bacteria, but the theory remains controversial. ...

Granulomas en Dermatopatología: principales entidades. Parte I
  • Citing Article
  • April 2021

Actas Dermo-Sifiliográficas (English Edition)

... In the literature, we found 30 cases of AGEP associated with COVID-19. Nevertheless, 26 of those were drug-related, with hydroxychloroquine implicated in 21 cases (Table 1), [2,3,6,7,[9][10][11][12][13][14][15]. The association between hydroxychloroquine and AGEP is well documented. ...

Hydroxychloroquine‐induced acute generalized exanthematous pustulosis: an adverse reaction to keep in mind during COVID‐19 pandemic

Journal der Deutschen Dermatologischen Gesellschaft