Papers by María Lourdes Garza-rodríguez
Interleukin-6 as a biomarker of hypersensitivity reactions in chemotherapeutics and monoclonal antibodies
Journal of Oncology Pharmacy Practice, Oct 9, 2023

Research Square (Research Square), Mar 28, 2024
Background: Hereditary predisposition to breast and ovarian cancer syndrome (HBOC) is a pathologi... more Background: Hereditary predisposition to breast and ovarian cancer syndrome (HBOC) is a pathological condition with increased cancer risk, including breast (BC), ovarian cancer (OC), and others. HBOC pathogenesis is caused mainly by germline pathogenic variants (GPV) in BRCA1 and BRCA2 genes. However, other relevant genes are related to this syndrome diagnosis, prognosis, and treatment, including TP53, PALB2, CHEK2, ATM, etc. This study aimed to identify the prevalence of non-BRCA genes in HBOC patients of Northeast Mexico. Methods: This multicentric study included 1285 patients with HBOC diagnosis from four oncologic centers in northeast Mexico from 2016 to 2023. Genomic and clinical data were analyzed based on multigene panel results and electronic records of the medical geneticist consultation. For the data analysis of qualitative and quantitative variants JASP statistical software (version 0.18.1) was used, taking p<0.05 as a signi cant results. Results: We found that 32.7% of the patients had at least one GPV in non-BRCA genes. The ve most frequent non-BRCA genes were CHEK2, PALB2, MUTYH, CDKN2A, and ATM. Among the group of non-BRCA genes, six are involved in the homologous repair pathway (HR), and three are related to DNA damage repair (DDR) pathways. In the analysis of GPVs in molecular pathways, DDR GPVs had a higher risk of developing BC and having cancer between 41-50 years. Conclusion: Multi-gene testing implementation improves the detection of often overlooked genes related to HBOC pathogenesis and treatment. Non-BRCA GPVs in Northern Mexico correspond to one-third of the HBOC cases, including HR and DDR pathways genes that would be misdiagnosed if not tested. HR patient carriers are potential targets of iPARP therapies. The optimal approach to cancer treatment for non-BRCA mutation carriers warrants further investigation to develop newer therapies.

Oncology Letters, May 16, 2018
Metalloproteinase matrix 11 (MMP11) is a member of the matrix metalloproteinase family, which are... more Metalloproteinase matrix 11 (MMP11) is a member of the matrix metalloproteinase family, which are able to degrade extracellular matrix components, and may serve a central function in the enhancement of tumor-induced angiogenesis, cell migration, proliferation, apoptosis and connective tissue degradation. In the present study, MMP11 gene expression was investigated using the reverse transcription-polymerase chain reaction in 68 cases of type I endometrial carcinoma, and all data were analyzed in association with clinical characteristics. Overexpression of MMP11 was demonstrated in 75%, and sub-expression was demonstrated in 25%, of endometrial cancer cases. Sub-expression cases were associated with good histological parameters, including low histological grade (G1 and G2), early pathological stage, and absence of vascular invasion, metastasis and recurrence. In total, 76.4% of endometrial cancer cases with sub-expression were identified as early stage 1A and B; however, 23.6% of cases were identified as stage 2, with vascular invasion present in 29.4% of cases. On the other hand, cases which demonstrated overexpression with high ranges (>10 times more than control) were associated with adverse histopathological characteristics, including high grade tumor (G3) and vascular invasion. In conclusion, the increased expression of MMP11 may be used as a prognostic biomarker in patients with type 1 endometrial cancer.

Frequency of fluoropyrimidine-related toxicity in patients with colon cancer from a Mexican oncology center
Journal of Clinical Oncology, Jun 1, 2023
e15616 Background: Fluoropyrimidines are chemotherapeutic agents used in various types of cancer ... more e15616 Background: Fluoropyrimidines are chemotherapeutic agents used in various types of cancer such as colorectal, breast, gastric, etc. Approximately 30% of patients treated with fluoropyrimidines present severe toxicity, which can lead to death in around 1% of them. Reduced activity of the enzyme dihydropyrimidine dehydrogenase (DPD) can cause severe fluoropyrimidine-related toxicity. The objective of this study was to identify the frequency of fluoropyrimidine-related toxicity in patients treated at an oncology center from Northeast Mexico. Methods: Retrospective and observational study of patients treated at the Centro Universitario contra el Cáncer (CUCC) in Monterrey, Mexico. Patients older than 18 years with a diagnosis of colon cancer who were treated during 2021 with the diagnosis of colon and considered candidates for fluoropyrimidine-based chemotherapy (5-FU, capecitabine) were included. Pregnant patients were excluded. None of them had a DPYD testing performed. Results: We analyzed 88 patients, of whom 51 (58%) were men, 6 (7%) in stage I, 16 (18%) in stage II, 31 (35%) in stage III, and 35 (40%) in stage IV. The mean age was 59 years, 15 (17%) of them had a PS&gt;2, overall, 94% of patients received fluoropyrimidine-based CT, presenting up to 47 (57%) of toxicities, 26 (32%) in G1, 11 (13%) in G2, and 10 (12%) in G3; no G &gt; 4 toxicities were documented. There were 7 patients (9%) that required CT discontinuation due to toxicity at some point during their treatment (see Table 1). In the subgroup of patients in stage IV, 8 (24%) had PS&gt;2, and 6 (18%) of them had some mutational panel. Conclusions: This is one of the few descriptive studies of toxicities in a population from northeastern Mexico undergoing treatment with fluoropyrimidine-based CT, in which up to 9% of the patients discontinue treatment due to toxicity. Our findings evidence a high percentage of patients with fluoropyrimidine-related toxicity. DPYD testing has not been widely adopted in most oncology centers in Mexico, mostly because of the limited access to genome sequencing. Genetic studies in this population could identify poor metabolizers patients with a high risk of toxicity before starting treatment. [Table: see text]

Genes, Jan 11, 2018
Gynecologic cancers are among the leading causes of death worldwide, ovarian cancer being the one... more Gynecologic cancers are among the leading causes of death worldwide, ovarian cancer being the one with the highest mortality rate. Olaparib is a targeted therapy used in patients presenting mutations in and genes. The aim of this study was to describe and gene variants in Mexican patients with ovarian cancer. Sequencing of and genes from tumors of 50 Mexican patients with ovarian cancer was made in a retrospective, non-randomized, and exploratory study. We found genetic variants in 48 of 50 cases. A total of 76 polymorphic variants were found in , of which 50 (66%) had not been previously reported. Furthermore, 104 polymorphic variants were found in , of which 63 (60%) had not been reported previously. Of these polymorphisms, 5/76 (6.6%) and 4/104 (3.8%) were classified as pathogenic in and , respectively. We have described the genetic variants in and of tumors from Northeast Mexican patients with sporadic ovarian cancers. Our results showed that the use of genetic testing helps rec...
Molecular Cloning and Characterization of the Circumsporozoite Protein Gene of Plasmodium inui Isolated from Formosan Macaques (Macaca cyclopis) in Taiwan
Journal of Parasitology, 2010

Diagnostics
Neutralizing antibodies (NAs) are key immunological markers and are part of the humoral response ... more Neutralizing antibodies (NAs) are key immunological markers and are part of the humoral response of the adaptive immune system. NA assays determine the presence of functional antibodies to prevent SARS-CoV-2 infection. We performed a real-world evidence study to detect NAs that confer protection against SARS-CoV-2 after the application of five vaccines (Pfizer/BioNTech, AstraZeneca, Sinovac, Moderna, and CanSino) in the Mexican population. Side effects of COVID-19 vaccines and clinical and demographic factors associated with low immunogenicity were also evaluated. A total of 242 SARS-CoV-2-vaccinated subjects were recruited. Pfizer/BioNTech and Moderna proved the highest percentage of inhibition in a mono-vaccine scheme. Muscular pain, headache, and fatigue were the most common adverse events. None of the patients reported severe adverse events. We found an estimated contagion-free time of 207 (IQR: 182–231) and 187 (IQR: 184–189) days for Pfizer/BioNTech and CanSino in 12 cases in ...

Genes
Hereditary cancer syndromes (HCS) are genetic diseases with an increased risk of developing cance... more Hereditary cancer syndromes (HCS) are genetic diseases with an increased risk of developing cancer. This research describes the implementation of a cancer prevention model, genetic counseling, and germline variants testing in an oncologic center in Mexico. A total of 315 patients received genetic counseling, genetic testing was offered, and 205 individuals were tested for HCS. In 6 years, 131 (63.90%) probands and 74 (36.09%) relatives were tested. Among the probands, we found that 85 (63.9%) had at least one germline variant. We identified founder mutations in BRCA1 and a novel variant in APC that led to the creation of an in-house detection process for the whole family. The most frequent syndrome was hereditary breast and ovarian cancer syndrome (HBOC) (41 cases with BRCA1 germline variants in most of the cases), followed by eight cases of hereditary non-polyposic cancer syndrome (HNPCC or Lynch syndrome) (with MLH1 as the primarily responsible gene), and other high cancer risk sy...
CN18 Challenges in genetic counseling in hereditary cancer syndromes in Mexican population and prevention clinic experience
Annals of Oncology
Enfoque multidisciplinario para la aplicación de nanomateriales en biomedicina

Medicina Universitaria, 2014
Medical research has greatly beneited from molecular biology and increasingly relies on tools fro... more Medical research has greatly beneited from molecular biology and increasingly relies on tools from the “omics” disciplines (mainly genomics, transcriptomics, proteomics and metabolomics). The availability of biological samples preserved with high quality standards is a sine qua non condition for such studies and their repositories are referred to as biobanks. Biobanks support the transportation, storage, preservation, and initial pathological and analytical examinations of biospecimens, as well as the protection of relevant information and the comparison of clinical and laboratory findings. A biobank facility is one of the most valuable tools the academic medicine organizations can offer to their researchers to improve the competitiveness of their current and future medical research. it acts as an essential bridge and an effective catalyst for research synergies between basic and clinical sciences, and it can be potentiated with efforts to raise funds for acquiring and maintaining c...

Analysis of interleukin-8, alpha1-antitrypsin, and tumor necrosis factor-alpha as biomarkers of breast cancer in women of northeastern Mexico
Journal of Clinical Oncology, 2012
18 Background: Genetic polymorphisms of cytokine-encoding genes are known to predispose to malign... more 18 Background: Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease and variations of protein values in plasma. Interleukin (IL)-8, alpha 1-antitrypsin (AAT) and tumor necrosis factor-alpha (TNF alpha) have been related to carcinogenesis in breast tissue. Whether polymorphisms of the genes and protein values also influence breast cancer risk is unclear. The objective was to analyze the levels and polymorphisms of biomarkers in breast cancer patients for diagnostic purposes. Methods: In this cases-controls study a total of 30 patients with breast cancer confirmed by histopathology and 21 healthy individuals were studied, both groups were of three generations born in the Northeast of Mexico. Two polymorphisms of the AAT gene (Alleles Z and S), a polymorphism of IL-8 (-251 A/T polymorphism of the IL-8 promoter), and the polymorphism of TNF-alpha [-308 G/A (TNF1/TNF2) polymorphism of the TNF-alpha promoter gene] were analyzed using PCR-RFLP. Addi...

Biological Research, 2016
Background: The olfactomedin-like domain (OLFML) is present in at least four families of proteins... more Background: The olfactomedin-like domain (OLFML) is present in at least four families of proteins, including OLFML2A and OLFML2B, which are expressed in adult rat retina cells. However, no expression of their orthologous has ever been reported in human and baboon. Objective: The aim of this study was to investigate the expression of OLFML2A and OLFML2B in ocular tissues of baboons (Papio hamadryas) and humans, as a key to elucidate OLFML function in eye physiology. Methods: OLFML2A and OLFML2B cDNA detection in ocular tissues of these species was performed by RT-PCR. The amplicons were cloned and sequenced, phylogenetically analyzed and their proteins products were confirmed by immunofluorescence assays. Results: OLFML2A and OLFML2B transcripts were found in human cornea, lens and retina and in baboon cornea, lens, iris and retina. The baboon OLFML2A and OLFML2B ORF sequences have 96% similarity with their human's orthologous. OLFML2A and OLFML2B evolution fits the hypothesis of purifying selection. Phylogenetic analysis shows clear orthology in OLFML2A genes, while OLFML2B orthology is not clear. Conclusions: Expression of OLFML2A and OLFML2B in human and baboon ocular tissues, including their high similarity, make the baboon a powerful model to deduce the physiological and/or metabolic function of these proteins in the eye.

Journal of Mass Spectrometry, 2015
One of the initial and critical procedures for the analysis of metabolomics data using liquid chr... more One of the initial and critical procedures for the analysis of metabolomics data using liquid chromatography and mass spectrometry is feature detection. Feature detection is the process to detect boundaries of the mass surface from raw data. It consists of detected abundances arranged in a two-dimensional (2D) matrix of mass/charge and elution time. MZmine 2 is one of the leading software environments that provide a full analysis pipeline for these data. However, the feature detection algorithms provided in MZmine 2 are based mainly on the analysis of one-dimension at a time. We propose GridMass, an efficient algorithm for 2D feature detection. The algorithm is based on landing probes across the chromatographic space that are moved to find local maxima providing accurate boundary estimations. We tested GridMass on a controlled marker experiment, on plasma samples, on plant fruits, and in a proteome sample. Compared with other algorithms, GridMass is faster and may achieve comparable or better sensitivity and specificity. As a proof of concept, GridMass has been implemented in Java under the MZmine 2 environment and is available at http:// bioinformatica.mty.itesm.mx/GridMass and MASSyPup. It has also been submitted to the MZmine 2 developing community.

Journal of laboratory automation, Jan 9, 2015
Automated DNA isolation can decrease hands-on time in routine pathology. Our aim was to apply aut... more Automated DNA isolation can decrease hands-on time in routine pathology. Our aim was to apply automated DNA isolation and perform DNA methylation analyses. DNA isolation was performed manually from fresh frozen (CRC = 10, normal = 10) specimens and colonic biopsies (CRC = 10, healthy = 10) with QIAamp DNA Mini Kit and from FFPE blocks (CRC = 10, normal = 10) with QIAamp DNA FFPET Kit. Automated DNA isolation was performed with MagNA Pure DNA and Viral NA SV kit on MagNA Pure 96 system. DNA methylation of MAL, SFRP1, and SFRP2 were analyzed with methylation-specific high-resolution melting analysis. Yield of automatically isolated samples was equal in fresh frozens and significantly lower compared to manually isolated biopsy and FFPE samples. OD260/280 of fresh frozen and biopsy samples were similar after both isolations, automated isolation resulted in lower purity in FFPE samples. Both protocols resulted in similar OD260/230 from fresh frozens, automated isolation method was superi...
Journal of Medical Primatology, 2013
Background-Olfactomedin-like is a polyfunctional polymeric glycoprotein. This family has at least... more Background-Olfactomedin-like is a polyfunctional polymeric glycoprotein. This family has at least four members. One member of this family is OLFML3, which is preferentially expressed in placenta but is also detected in other adult tissues including the liver and heart. However, the orthologous rat gene is expressed in the iris, sclera, trabecular meshwork, retina, and optic nerve. Methods-OLFML3 amplification was performed by RT-PCR from human and baboon ocular tissues. The products were cloned and sequenced.
Revista Mexicana De Patologia Clinica, 2006

Animals
Prolactin (PRL) is a hormone expressed in lactotrophs cells of the pituitary gland in primates. E... more Prolactin (PRL) is a hormone expressed in lactotrophs cells of the pituitary gland in primates. Extra pituitary expression of PRL has been reported, including the eye; however, expression in the developing eye of primates is limited. The aim of the study was determining the expression of PRL and PRL receptor (PRLR) (mRNAs and proteins) in adult and fetal baboon (Papio hamadryas) ocular tissues. Methods: We analyzed PRL and PRLR in baboon eyes tissues by immunofluorescence. The mRNAs of PRL and PRLR were detected by RT-PCR, cDNA was cloned, and sequenced. Furthermore, we performed a phylogenetic analysis to identify the evolutionary forces that underlie the divergence of PRL and PRLR primate genes. Results: We observed the expression of PRL and PRLR (mRNAs and proteins) in all retinal cell lineages of fetal and adult baboon. PRL and PRLR fit the hypothesis of evolutionary purifying gene selection. Conclusions: mRNA and protein of PRL and PRLR are expressed in fetal and adult baboon r...
Additional file 1 of ADIPOQ single nucleotide polymorphisms and breast cancer in northeastern Mexican women
Additional file 1 Table S1. Clinical-pathological characteristics in the case group.
Nanopartículas y terapia génica inductora de muerte como tratamiento contra cáncer
Uploads
Papers by María Lourdes Garza-rodríguez