Carlos Pérez‐Plasencia

Autonomous University of Tlaxcala

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César López‐Camarillo

Universidad Autónoma de la Ciudad de México

David Cantú de León

CHI Health

Nadia Jacobo‐Herrera

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Alma D. Campos-Parra

Universidad Veracruzana

Eduardo López–Urrutia

Autonomous University of Tlaxcala

Oliver Millán-Catalán

Instituto Nacional de Cancerología

Miriam Rodríguez‐Sosa

Autonomous University of Tlaxcala

Laurence A. Marchat

Instituto Politécnico Nacional

Oscar Peralta‐Zaragoza

Instituto Nacional de Salud Pública

Luis A. Herrera

Instituto Nacional de Cancerología

Cooperative Institutions

Universidad Nacional Autónoma de México

236

Instituto Nacional de Cancerología

222

Instituto Politécnico Nacional

103

Center for Research and Advanced Studies of the National Polytechnic Institute

Autonomous University of Tlaxcala

Instituto Nacional de Cancerología

National Institute of Genomic Medicine

Mexican Social Security Institute

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Universidad Autónoma de la Ciudad de México

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Factors Associated with Parametrial Involvement in Endometrial Carcinoma in Patients Treated with Radical Hysterectomy

International Journal of Surgical Pathology (2024)

Salim Barquet-Muñoz Antonio Bandala-Jacques Ma Delia Perez-Montiel Diddier Prada Marithe Martínez-Flores

Introduction Describe factors associated with parametrial involvement, and how these factors modify the prognosis of patients with endometrial carcinoma treated with radical hysterectomy. Methods Observational study in which categorized patients according to those with and without parametrial involvement. A descriptive analysis and comparative analysis were performed for associations between parametrial spread and clinical, surgical, and pathology variables. Results We analyzed 85 patients, which 18 (21%) had parametrial involvement. Pathology factors associated with parametrial involvement were the endometrioid subtype, grade 3, and variants of poor prognosis (odds ratio (OR) 3.41, 95% CI 1.09-10.64; P = 0.035), myometrial invasion of over 50% (OR 7.76, 95% CI 1.65-36.44; P = 0.009), serosal involvement (OR 17.07, 95% CI 3.87-75.35; P < 0.001), ovarian metastasis (OR 5.15, 95% CI 1.36-19.46; P = 0.016), positive peritoneal cytology (OR 3.9, 95% CI 1.04-14.77; P = 0.044), and lymph node metastasis (OR 3.4; 95% CI 1.16-9.97; P = 0.026). Five-year disease-free survival was 74% (95% CI 57.4-85.4) for the group without parametrial spread and 50.8% (95% CI 22.7-73.4) for the group with parametrial spread ( P = 0.001). Similarly, 5-year overall survival was 85.2% (95% CI 67.9-93.6) for the group without parametrial spread and 47.5% (95% CI 8.1-80.2) for the group with parametrial spread ( P = 0.002). Conclusion Factors associated with parametrial involvement were histologies of poor prognosis, tumors affecting uterine serosa, cervix, or spread beyond the uterus. Additionally, parametrial involvement directly affects prognosis by reducing overall survival, disease-free survival and increasing odds for recurrence.

Parametrial

10.1177/10668969231225773

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Tumor–Stromal Interactions in a Co-Culture Model of Human Pancreatic Adenocarcinoma Cells and Fibroblasts and Their Connection with Tumor Spread

Biomedicines (2021)

Elena Prieto‐García C. Vanesa Díaz-García Alba Agudo-López Virginia Pardo Inés García‐Consuegra

One key feature of pancreatic ductal adenocarcinoma (PDAC) is a dense desmoplastic reaction that has been recognized as playing important roles in metastasis and therapeutic resistance. We aim to study tumor–stromal interactions in an in vitro coculture model between human PDAC cells (Capan-1 or PL-45) and fibroblasts (LC5). Confocal immunofluorescence, Enzyme-Linked Immunosorbent Assay (ELISA), and Western blotting were used to evaluate the expressions of activation markers; cytokines arrays were performed to identify secretome profiles associated with migratory and invasive properties of tumor cells; extracellular vesicle production was examined by ELISA and transmission electron microscopy. Coculture conditions increased FGF-7 secretion and α-SMA expression, characterized by fibroblast activation and decreased epithelial marker E-cadherin in tumor cells. Interestingly, tumor cells and fibroblasts migrate together, with tumor cells in forming a center surrounded by fibroblasts, maximizing the contact between cells. We show a different mechanism for tumor spread through a cooperative migration between tumor cells and activated fibroblasts. Furthermore, IL-6 levels change significantly in coculture conditions, and this could affect the invasive and migratory capacities of cells. Targeting the interaction between tumor cells and the tumor microenvironment might represent a novel therapeutic approach to advanced PDAC.

Tumor progression

Cancer-Associated Fibroblasts

Immunofluorescence

10.3390/biomedicines9040364

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Citations (14)

Differential protein expression profile in skin biopsies from patients with hand-foot syndrome who have benefited from topical heparin treatment.

Journal of Clinical Oncology (2013)

Analia Rodríguez Garzotto Isabel Ruppen M. Pilar Ximenez de Embun L. Iglesias Cristina Grávalos

9641 Background: Hand-foot syndrome (HFS) is a dose-limiting toxicity of capecitabine (CAP), leading to significant morbidity in patients receiving this agent. Interruption or dose reduction of CAP is the only effective strategy. The purpose of our study is to define the pathophysiology and risk factors predictors of CAP-induced HFS. Previously, we had conducted a clinical trial in patients who developed HFS secondary to CAP. Topical heparin was administered in palms and soles of patients four times/day for three weeks (w), evidencing clinical improvement in 99% of patients. Methods: Paired-skin biopsies of palms at baseline and after 3w from 21 patients were obtained. An iTRAQ (isobaric tags for relative and absolute quantitation) proteomics approach was performed to identify molecular pathways associated with HFS reversion. Results: Comparative analysis between baseline and post-treatment skin samples identified 1876 proteins with high confidence (> 99%). The involvement of the identified proteins in biological networks served to characterize molecular pathways associated with HFS reversion. Conclusions: Several proteins identified in this study have a close relationship with keratinocyte terminal differentiation and keratinocyte intercellular strength. Also, we describe differential expression among proteins involved in inflammatory processes, skin immunity and cell death. In summary, our study not only served to uncover molecular mechanisms associated with HFS reversion, but also to reveal the biomarker role of several proteins in this syndrome. [Table: see text]

S100A8

Pathophysiology

10.1200/jco.2013.31.15_suppl.9641

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Anti-inflammatory and Antitumor Activity of a Triple Therapy for a Colitis-Related Colorectal Cancer

Journal of Cancer (2016)

Gabriela Figueroa‐González Verónica García-Castillo Jossimar Coronel-Hernández Eduardo López–Urrutia Sonia León‐Cabrera

Colorectal cancer (CRC) is an important health issue worldwide, accounting for the third place of cancer incidence.Chronic inflammation, as seen in Crohn's disease and ulcerative colitis, is the most important risk factor for developing CRC, as it favours neoplastic transformation by enhancing epithelial cell turnover in the colonic mucosa.Treatments for CRC need to be improved; currently they are not specific and have several secondary effects in patients.The main objective of this work was to evaluate a new therapeutic strategy against a colitis-related colorectal cancer in vivo and in vitro by targeting mTOR-signaling and lactate dehydrogenase A. Together, these mechanisms directly affect tumor energetics.In this study we evaluated a better and more efficient triple therapy against a chronic inflammation-associated CRC in vivo and in vitro.After the development of tumors, mice were treated intraperitoneally during a forty-day period with single drugs or different combinations of Metformin, Sodium Oxamate and Doxorubicin.Targeted inhibition of the mTOR pathway, lactate dehydrogenase A and the concurrent use of Doxorubicin (called in this work as triple therapy), leaded to a notable reduction in the number and size of tumors in mice, and, a significant pro-inflammatory cytokines reduction Besides, we showed that treated cells were induced to early autophagy, and apoptosis cell death.Our results represent a novel and robust therapeutic strategy for overcoming CRC by means of targeting central molecular pathways in cancer by the combination of Metformin, Oxamate, and Doxorubicin leading to a rapid tumor growth inhibition and a dramatic colorectal crypt restoration.Besides, drug combination resulted in a notable reduction of anti-inflammatory cytokines.

Targeted Therapy

10.7150/jca.13123

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Citations (20)

Mechanistic added value of a trans-Sulfonamide-Platinum-Complex in human melanoma cell lines and synergism with cis-Platin

Molecular Cancer (2017)

Alba Agudo-López Elena Prieto‐García José Alemán Carlos Pérez‐Plasencia C. Vanesa Díaz-García

Cisplatin is a potent antitumor agent. However, toxicity and primary and secondary resistance are major limitations of cisplatin-based chemotherapy, leading to therapeutic failure. We have previously reported that mono-sulfonamide platinum complexes have good antitumor activity against different tumoral cell lines and with a different and better cytotoxic profile than cisplatin. Besides, N-sulfonamides have been used extensively in medicinal chemistry as bactericides, anticonvulsant, inhibitors of the carbonic anhydrase, inhibitors of histone deacetylases, and inhibitors of microtubule polymerization, among others. We aimed to compare the cytotoxic effects of cisplatin and a trans-sulfonamide-platinum-complex (TSPC), in two human melanoma cell lines that differ in their TP53 status: SK-MEL-5, TP53 wild type, and SK-MEL-28, TP53 mutated. We performed cytotoxicity assays with both drugs, alone and in combination, cell cycle analyses, western blotting and immunoprecipitation, and fluorescence immunocytochemistry. TSPC had similar antiproliferative activity than cisplatin against SK-MEL-5 (3.24 ± 1.08 vs 2.89 ± 1.12 μM) and higher against SK-MEL-28 cells (5.83 ± 1.06 vs 10.17 ± 1.29 μM). Combination of both drugs inhibited proliferation in both cell lines, being especially important in SK-MEL-28, and showing a synergistic effect. In contrast to cisplatin, TSPC caused G1 instead G2/M arrest in both cell lines. Our present findings indicate that the G1 arrest is associated with the induction of CDKN1A and CDKN1B proteins, and that this response is also present in melanoma cells containing TP53 mutated. Also, strong accumulation of CDKN1A and CDKN1B in cells nuclei was seen upon TSPC treatment in both cell lines. Overall, these findings provide a new promising TSPC compound with in vitro antitumor activity against melanoma cell lines, and with a different mechanism of action from that of cisplatin. Besides, TSPC synergism with cisplatin facilitates its potential use for co-treatment to reduce toxicity and resistance against cisplatin. TSPC remains a promising lead compound for the generation of novel antineoplastic agent and to explore its synergism with other DNA damaging agents.

10.1186/s12943-017-0618-7

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Citations (13)

P-314 mIR-26A and mIR-335-5p as clinical biomarkers in Latin American patients with colon cancer: Preliminary results

Annals of Oncology (2023)

B. Carbajal-López G. Calderillo-Ruiz Eduardo Madrigal‐Santillán J. Coronel Herández A. Martínez Gutiérrez

Clinical Significance

10.1016/j.annonc.2023.04.370

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DNA methylation data for identification of epigenetic targets of resveratrol in triple negative breast cancer cells

Data in Brief (2017)

Rubiceli Medina‐Aguilar Carlos Pérez‐Plasencia Patricio Gariglio Laurence A. Marchat Ali Flores‐Pérez

Previous studies revealed that some bioactive food components have anti-cancer effects. However epigenetic effects of dietary compound resveratrol are largely unknown in breast cancer cells (M.A. Dawson, T. Kouzarides, 2012) [1]. Here we provide novel data and comparisons of DNA methylation status of promoter gene regions in response to resveratrol treatment at 24 h and 48 h versus untreated MDA-MB-231 breast cancer cells. DNA methylation changes were measured using Array-PRIMES method (aPRIMES) followed by whole-genome hybridization using human DNA methylation promoter microarray NimbleGen HG18 Refseq Promoter 3×720 K array. Our data were associated to corresponding changes in mRNA expression in a set of cancer-related genes. Using gene ontology analysis we also identify cancer-related cellular processes and pathways that can be epigenetically reprogramed by resveratrol. Data in this article are associated to the research articles "Methylation Landscape of Human Breast Cancer Cells in Response to Dietary Compound Resveratrol". Medina Aguilar et al., PLoS ONE 11(6): e0157866. doi:10.1371/journal.pone.0157866 2016 (A.R. Medina, P.C. Pérez, L.A. Marchat, P. Gariglio, M.J. García, C.S. Rodríguez, G.E. Ruíz, et al., 2016) [2]; and "Resveratrol inhibits cell cycle progression by targeting Aurora kinase A and Polo-like kinase 1 in breast cancer cells" in Oncology Reports. Medina Aguilar et al., 2016 Jun; 35(6):3696-704. doi: 10.3892/or.2016.4728 (A.R. Medina, P. Gariglio, M.J. García, O.E. Arechaga, S.N. Villegas, C.M. Martínez et al., 2016) [3].

10.1016/j.dib.2017.02.006

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Metaplastic breast cancer: a comparison between the most common histologies with poor immunohistochemistry factors

BMC Cancer (2015)

Salim Barquet-Muñoz Silvia Patricia Villarreal-Colín Luis A. Herrera Ernesto Soto‐Reyes Carlos Pérez‐Plasencia

Metaplastic carcinoma of the breast (MCB) is a rare histological type of breast cancer. This study aimed to determine whether MCB exhibits shorter overall survival (OS) and disease-free survival (DFS) compared with other histologies that are considered unfavorable.We retrospectively analyzed 157 clinical file records of the Mexico City-based National Institute of Cancerology and compared the clinical characteristics and treatment of 24 patients with MCB, 37 patients with triple-negative invasive lobular carcinoma (TN-ILC), 48 patients with high-grade invasive ductal carcinoma (HG-IDC), and 48 patients with triple-negative invasive ductal carcinoma (TN-IDC), paired by clinical stage and age. We performed a comparative analysis and analyzed OS and DFS using a log-rank test.In patients with MCB, the 5-year DFS was 52.1% (mean, 48.52 months; 95%: 35.32-61.72), and the 5-year OS was 72.2% (mean, 59.77 months; 95% CI: 48.55-71.00). No differences were observed in the DFS of MCB compared with each of the other histologies (MCB vs. HG-IDC, p = 0.865; MCB vs. TN-IDC, p = 0.966, and MCB vs. TN-ILC, p = 0.132). Moreover, no differences were observed when comparing the OS of MCB with that of each of the other histologies (MCB vs. HG-IDC, p = 0.246; MCB vs. TN-IDC, p = 0.255, and MCB vs. TN-ILC, p = 0.387).Neither OS nor DFS differ between patients with MCB and those with other histologies with unfavorable immunohistochemical factors.

Surgical oncology

10.1186/s12885-015-1079-2

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Citations (19)

DNA repair as a novel therapeutic target in breast cancer

César López‐Camarillo Laurence A. Marchat Sergio Rodrı́guez-Cuevas E. Arechaga Carlos Pérez‐Plasencia

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172 Gastric-type endocervical adenocarcinoma (GAS): a comparative analysis

David Cantú de León Lenny Gallardo-Alvarado Carlos Pérez‐Plasencia MD Perez-Montiel Oliver Millán-Catalán

Objectives

Compare clinical outcomes of GAS, usual-type endocervical adenocarcinomas (UEA) and squamous cell carcinoma (SCC).

Methods

Twenty-two cases of GAS, 44 cases of UEA and 66 cases of SCC matched by age and clinical stage were assessed. Diagnosis of GAS was based on the Kojima's criteria and immunohistochemical results. Clinical parameters (age, clinical stage and clinical outcome after first-line treatment) were recorded. Descriptive and comparative analysis was conducted. Response to treatment was compared between groups. Overall Survival (OS) and Disease-Free survival (DFS) were calculated with Kaplan-Meier method, compared with Log- Rank test.

Results

Mean age at diagnosis was 51 years (range 31–76). Five cases were clinical stage IB1 (22.7%), IB2 1 (4.5%), IIB 2 (9.1%), IIIB 4 (18.2%), IVA 2 (9.1%), IVB 8 (36.4%). The median follow-up was 23 months. GAS cases showed complete response to first-line treatment in 31.1% (n=7), partial response 18.2% (n=4), 40.9% (n=9) had persistence/progression of the disease, no statistical difference was observed when compared to other histologies (p=0.2). Progression-free survival was 85.7% without significant difference (p=0.9). The overall survival was 75% at 24 months, and comparable to SCC and UEA (p=0.6).

Conclusions

GAS has clinical features that makes difficult to diagnose, most of the times being diagnosed at advance stages. Despite the review of the literature showing that this neoplasm has an aggressive clinical course and poorer response to conventional treatment, our study was not able to demonstrate this association, larger number of cases must be evaluated.

Log-rank test

10.1136/ijgc-2019-igcs.172

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