Somatic Mutations in Latin American Breast Cancer Patients: A Systematic Review and Meta-Analysis.

(1) Background: Somatic mutations may be connected to the exposome, potentially playing a role in breast cancer's development and clinical outcomes. There needs to be information regarding Latin American women specifically, as they are underrepresented in clinical trials and have limited access to somatic analysis in their countries. This study aims to systematically investigate somatic mutations in breast cancer patients from Latin America to gain a better understanding of tumor biology in the region. (2) Methods: We realize a systematic review of studies on breast cancer in 21 Latin American countries using various databases such as PubMed, Google Scholar, Web of Science, RedAlyc, Dianlet, and Biblioteca Virtual en Salud. Of 392 articles that fit the criteria, 10 studies have clinical data which can be used to create a database containing clinical and genetic information. We compared mutation frequencies across different breast cancer subtypes using statistical analyses and meta-analyses of proportions. Furthermore, we identified overexpressed biological processes and canonical pathways through functional enrichment analysis. (3) Results: 342 mutations were found in six Latin American countries, with the TP53 and PIK3CA genes being the most studied mutations. The most common PIK3CA mutation was H1047R. Functional analysis provided insights into tumor biology and potential therapies. (4) Conclusion: evaluating specific somatic mutations in the Latin American population is crucial for understanding tumor biology and determining appropriate treatment options. Combining targeted therapies may improve clinical outcomes in breast cancer. Moreover, implementing healthy lifestyle strategies in Latin America could enhance therapy effectiveness and clinical outcomes.

Preterm Delivery in Obese Mothers Predicts Tumor Necrosis Factor-α Levels in Breast Milk.

Background: Breast milk (BM) is a nutritive fluid that is rich in bioactive components such as hormones and cytokines that can shape the newborn's feeding habits and program the newborn's immature immune system. BM components can change under different scenarios that include maternal body mass index (BMI) and premature birth. This study aimed to study the interaction of premature status or maternal obesity on the hormonal and cytokine profile in BM according to the sex of the offspring. Materials and Methods: We recruited 31 women with preterm births from the Centro de Alta Especialidad Dr. Rafael Lucio in Mexico. Luminex multiplexing assay was used for quantifying cytokine profile of monocyte chemoattractant protein-1, tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)1-ß, IL-2, IL-4, IL-6, IL-7, and hormones insulin, ghrelin, leptin, and glucagon in mature BM samples. Biological modeling was performed to predict the interaction between cytokines and hormones, maternal BMI status, infant birth sex, parity, and gestational age. Results: BM multiplex analysis showed positive correlations for TNF-α and increasing prematurity and for higher maternal BMI and IL-2, IL-4, and IL-6 cytokines. Multiple regression models identified an interaction between maternal BMI and gestational weeks in male infants that is associated to TNF-α accumulation in BM. Biological modeling predicts that preterm delivery in mothers with obesity modulates TNF- α levels in mature BM of women with male offspring. Conclusion: Prematurity and obesity modify BM's immune profile. TNF- α expression increases as prematurity increases, and maternal BMI correlates positively with increases in IL-2, IL-6, and IL-4. Our multiple regression model also shows that maternal BMI and gestational weeks in male infants predict TNF-α.

NUSAP1 and PCLAF (KIA0101) Downregulation by Neoadjuvant Therapy is Associated with Better Therapeutic Outcomes and Survival in Breast Cancer.

Purpose: To evaluate whether changes in genomic expression that occur beginning with breast cancer (BC) diagnosis and through to tumor resection after neoadjuvant chemotherapy (NCT) reveal biomarkers that can help predict therapeutic response and survival. Materials and Methods: We determined gene expression profiles based on microarrays in tumor samples from 39 BC patients who showed pathologic complete response (pCR) or therapeutic failure (non-pCR) after NCT (cyclophosphamide-doxorubicin/epirubicin). Based on unsupervised clustering of gene expression, together with functional enrichment analyses of differentially expressed genes, we selected NUSAP1, PCLAF, MME, and DST. We evaluated the NCT response and the expression of these four genes in BC histologic subtypes. In addition, we study the presence of tumor-infiltrating lymphocytes. Finally, we analyze the correlation between NUSAP1 and PCLAF against disease-free survival (DFS) and overall survival (OS). Results: A signature of 43 differentially expressed genes discriminated pCR from non-pCR patients (|fold change >2|, false discovery rate <0.05) only in biopsies taken after surgery. Patients achieving pCR showed downregulation of NUSAP1 and PCLAF in tumor tissues and increased DFS and OS, while overexpression of these genes correlated with poor therapeutic response and OS. These genes are involved in the regulation of mitotic division. Conclusions: The downregulation of NUSAP1 and PCLAF after NCT is associated with the tumor response to chemotherapy and patient survival.

Cáncer colorrectal. Variantes génicas en la vía de señalización BMP y ancestría en población mexicana / Colorectal cancer. Genetic variants in BMP signaling pathway and ancestry in the Mexican population

Resumen Introducción: Variantes génicas relacionadas con la vía de señalización de las proteínas morfogenéticas óseas (BMP2, BMP4, GREM1, SMAD7) se han asociado a cáncer colorrectal, principalmente en poblaciones caucásicas. Objetivo: Describir la asociación de variantes en miembros de la vía BMP en población mexicana, caracterizada por su ancestría indoamericana y caucásica. Métodos: Se realizó el genotipado de 1000 casos de cáncer colorrectal y 1043 individuos de control reclutados en la Ciudad de México, Monterrey y Torreón mediante la plataforma Sequenom. Con análisis univariados y multivariados se estudiaron las asociaciones entre cáncer colorrectal y variantes. Resultados: Las variantes rs4444235, rs12953717 y rs4939827 replicaron la asociación con la neoplasia (p ≤ 0.05). La ascendencia caucásica mostró asociación con el tumor. Conclusiones: El estudio mostró las asociaciones entre cáncer colorrectal y las variantes SMAD7 y BMP4, así como con el componente caucásico de la mezcla étnica.

Abstract Introduction: Genetic variants related to bone morphogenetic proteins (BMP2, BMP4, GREM1, SMAD7) signaling pathway have been associated with colorectal cancer, mainly in Caucasian populations. Objective: To describe the association of variants in members of the BMP signaling pathway in a Mexican population, characterized by its indigenous American and Caucasian ancestry. Methods: Genotyping of 1,000 colorectal cancer cases and 1,043 control individuals recruited in Mexico City, Monterrey, and Torreón was carried out using the Sequenom platform. Associations between colorectal cancer and variants were studied with univariate and multivariate analyses. Results: Variants rs4444235, rs12953717 and rs4939827 replicated the association with the neoplasm (p ≤ 0.05). Caucasian ancestry showed association with the tumor. Conclusions: The study replicated the associations between colorectal cancer and SMAD7 and BMP4 variants, with an association being observed with the Caucasian component of the ethnic mix.

Concordance between Ki-67 index in invasive breast cancer and molecular signatures: EndoPredict and MammaPrint.

Identifying patients with hormone receptor-positive (HR+) early invasive breast cancer (EIBC) who benefit from adjuvant chemotherapy has improved with molecular signature tests. However, due to high cost and limited availability, alternative tests are used. The present study sought to evaluate the performance of the proliferation marker Ki-67 to identify these patients and explore its association with molecular signatures and risk stratification markers. From the San José TecSalud Hospital in Monterrey México, patients with HR+ EIBC as tested with EndoPredict or MammaPrint and Ki-67 index were identified. They were categorized into two groups: Group 1 (June 2016-August 2018) was evaluated using EndoPredict and Group 2 (June 2016-August 2018) with MammaPrint. A ≥20% Ki67 index cutoff was utilized to identify highly proliferative EIBC and an area under the receiver-operating characteristic curve and κ concordance were utilized to evaluate the performance of Ki-67 index compared to molecular signature tests. In the EndoPredict group, 54/96 patients were considered high-risk based on their EPclin score, while 57/96 patients had Ki-67 index ≥20%. However, there was no significant overall concordance between them (59.37%, κ=0.168, P=0.09), while the given risk of distant recurrence given in percentage by EPclin had a positive association with the Ki67 index (P=0.04). In the MammaPrint group, 21/70 patients were considered high-risk and 36/70 patients presented with a Ki-67 index ≥20% with a significant overall concordance (67.14%, κ=0.35, P<0.001). In addition, high Ki-67 index was associated with the Nottingham histological grade in both groups. In conclusion, there was a concordance between Ki-67 and MammaPrint risk stratification of HR+ EIBC and no concordance with the EndoPredict molecular signature, but a positive association with the given percentage of recurrence and the median Ki-67 index as the cutoff at our center. Cost-effectiveness analyses of these tests in developing countries are required; until then, the use of Ki-67 appears reasonable to aid clinical decisions, together with the other established clinicopathological variables.

Sphingolipids and Lymphomas: A Double-Edged Sword.

Lymphomas are a highly heterogeneous group of hematological neoplasms. Given their ethiopathogenic complexity, their classification and management can become difficult tasks; therefore, new approaches are continuously being sought. Metabolic reprogramming at the lipid level is a hot topic in cancer research, and sphingolipidomics has gained particular focus in this area due to the bioactive nature of molecules such as sphingoid bases, sphingosine-1-phosphate, ceramides, sphingomyelin, cerebrosides, globosides, and gangliosides. Sphingolipid metabolism has become especially exciting because they are involved in virtually every cellular process through an extremely intricate metabolic web; in fact, no two sphingolipids share the same fate. Unsurprisingly, a disruption at this level is a recurrent mechanism in lymphomagenesis, dissemination, and chemoresistance, which means potential biomarkers and therapeutical targets might be hiding within these pathways. Many comprehensive reviews describing their role in cancer exist, but because most research has been conducted in solid malignancies, evidence in lymphomagenesis is somewhat limited. In this review, we summarize key aspects of sphingolipid biochemistry and discuss their known impact in cancer biology, with a particular focus on lymphomas and possible therapeutical strategies against them.

Transcriptional Profile of HCV Replicon Cells after Treatment with Acetylsalicylic Acid.

OBJECTIVE: It has been demonstrated in vitro that acetylsalicylic acid (ASA) treatment halves hepatitis C virus (HCV) expression in hepatocarcinoma cells. However, the signaling pathway that promotes this ASA-induced antiviral effect has not yet been identified. AIM: The aim of this work was to identify alterations in the transcriptional profile of Huh-7-HCV-subgenomic replicon cells with vs. without ASA treatment. This comparison sheds light onto the signaling pathways and molecular mechanisms involved in the antiviral effects of ASA. METHODS: Human hepatocellular carcinoma (Huh-7) cells that express non-structural HCV proteins (Huh-7-HCV-replicon cells) were exposed to 4 mM ASA for 0, 24, 48, and 72 hours. Total RNA was isolated, and cDNA was synthesized. Transcripts were then tagged with biotin and purified. Thereafter, they were fragmented and hybridized on HG-U133 Plus 2 Gene Expression chips. Hybridization signals were captured using a GeneChip 3000 7G Scanner and analyzed via Expression Console and dChip Software. RESULTS: When exposed to ASA, hepatocarcinoma cells with non-structural HCV proteins were found to differentially regulate genes with oxidative roles in the cell. The most upregulated genes were interleukin 8 (IL-8), cytochrome P450 (CYP450), and metallothioneins (MTs), while the most downregulated genes were ribonucleotide reductases (RRs). CONCLUSION: These results show that ASA modulates the expression of genes with antioxidant functions. This suggests that ASA induces a remodeling of the antioxidant microenvironment, which may in turn interfere with the replication of HCV.

Germline Variants in Cancer Genes from Young Breast Cancer Mexican Patients.

Breast cancer (BC) is one of the most frequent cancer types in women worldwide. About 7% is diagnosed in young women (YBC) less than 40 years old. In Mexico, however, YBC reaches 15% suggesting a higher genetic susceptibility. There have been some reports of germline variants in YBC across the world. However, there is only one report from a Mexican population, which is not restricted by age and limited to a panel of 143 genes resulting in 15% of patients carrying putatively pathogenic variants. Nevertheless, expanding the analysis to whole exome involves using more complex tools to determine which genes and variants could be pathogenic. We used germline whole exome sequencing combined with the PeCanPie tool to analyze exome variants in 115 YBC patients. Our results showed that we were able to identify 49 high likely pathogenic variants involving 40 genes on 34% of patients. We noted many genes already reported in BC and YBC worldwide, such as BRCA1, BRCA2, ATM, CHEK2, PALB2, and POLQ, but also others not commonly reported in YBC in Latin America, such as CLTCL1, DDX3X, ERCC6, FANCE, and NFKBIE. We show further supporting and controversial evidence for some of these genes. We conclude that exome sequencing combined with robust annotation tools and further analysis, can identify more genes and more patients affected by germline mutations in cancer.

Colorectal cancer. Genetic variants in BMP signaling pathway and ancestry in the Mexican population.

INTRODUCTION: Genetic variants related to bone morphogenetic proteins (BMP2, BMP4, GREM1, SMAD7) signaling pathway have been associated with colorectal cancer, mainly in Caucasian populations. OBJECTIVE: To describe the association of variants in members of the BMP signaling pathway in a Mexican population, characterized by its indigenous American and Caucasian ancestry. METHODS: Genotyping of 1,000 colorectal cancer cases and 1,043 control individuals recruited in Mexico City, Monterrey, and Torreón was carried out using the Sequenom platform. Associations between colorectal cancer and variants were studied with univariate and multivariate analyses. RESULTS: Variants rs4444235, rs12953717 and rs4939827 replicated the association with the neoplasm (p ≤ 0.05). Caucasian ancestry showed association with the tumor. CONCLUSIONS: The study replicated the associations between colorectal cancer and SMAD7 and BMP4 variants, with an association being observed with the Caucasian component of the ethnic mix.

INTRODUCCIÓN: Variantes génicas relacionadas con la vía de señalización de las proteínas morfogenéticas óseas (BMP2, BMP4, GREM1, SMAD7) se han asociado a cáncer colorrectal, principalmente en poblaciones caucásicas. OBJETIVO: Describir la asociación de variantes en miembros de la vía BMP en población mexicana, caracterizada por su ancestría indoamericana y caucásica. MÉTODOS: Se realizó el genotipado de 1000 casos de cáncer colorrectal y 1043 individuos de control reclutados en la Ciudad de México, Monterrey y Torreón mediante la plataforma Sequenom. Con análisis univariados y multivariados se estudiaron las asociaciones entre cáncer colorrectal y variantes. RESULTADOS: Las variantes rs4444235, rs12953717 y rs4939827 replicaron la asociación con la neoplasia (p ≤ 0.05). La ascendencia caucásica mostró asociación con el tumor. CONCLUSIONES: El estudio mostró las asociaciones entre cáncer colorrectal y las variantes SMAD7 y BMP4, así como con el componente caucásico de la mezcla étnica.

DNA Repair Genes as Drug Candidates for Early Breast Cancer Onset in Latin America: A Systematic Review.

The prevalence of breast cancer in young women (YWBC) has increased alarmingly. Significant efforts are being made to elucidate the biological mechanisms concerning the development, prognosis, and pathological response in early-onset breast cancer (BC) patients. Dysfunctional DNA repair proteins are implied in BC predisposition, progression, and therapy response, underscoring the need for further analyses on DNA repair genes. Public databases of large patient datasets such as METABRIC, TCGA, COSMIC, and cancer cell lines allow the identification of variants in DNA repair genes and possible precision drug candidates. This study aimed at identifying variants and drug candidates that may benefit Latin American (LA) YWBC. We analyzed pathogenic variants in 90 genes involved in DNA repair in public BC datasets from METABRIC, TCGA, COSMIC, CCLE, and COSMIC Cell Lines Project. Results showed that reported DNA repair germline variants in the LA dataset are underrepresented in large databases, in contrast to other populations. Additionally, only six gene repair variants in women under 50 years old from the study population were reported in BC cell lines. Therefore, there is a need for new approaches to study DNA repair variants reported in young women from LA.

Spatial interaction between breast cancer and environmental pollution in the Monterrey Metropolitan Area.

This research examines the spatial structure of a sample of breast cancer (BC) cases and their spatial interaction with contaminated areas in the Monterrey Metropolitan Area (MMA). By applying spatial statistical techniques that treat the space as a continuum, degrees of spatial concentration were determined for the different study groups, highlighting their concentration pattern. The results indicate that 65 percent of the BC sample had exposure to more than 56 points of PM10. Likewise, spatial clusters of BC cases of up to 39 cases were identified within a radius of 3.5 km, interacting spatially with environmental contamination sources, particularly with refineries, food processing plants, cement, and metals. This study can serve as a platform for other clinical research by identifying geographic clusters that can help focus health policy efforts.

Chemosensitivity analysis and study of gene resistance on tumors and cancer stem cell isolates from patients with colorectal cancer.

Colorectal cancer (CRC) is one of the main causes of mortality. Recent studies suggest that cancer stem cells (CSCs) can survive after chemotherapy and promote tumor invasiveness and aggression. According to a higher hierarchy complexity of CSC, different protocols for isolation, expansion, and characterization have been used; however, there are no available resistance biomarkers that allow predicting the clinical response of treatment 5­fluorouracil (5FU) and oxaliplatin. Therefore, the primary aim of the present study was to analyze the expression of gene resistance on tumors and CSC­derived isolates from patients CRC. In the present study, adenocarcinomas of the colon and rectum (CRAC) were classified based on an in vitro adenosine triphosphate­based chemotherapy response assay, as sensitive and resistant and the percentage of CD24 and CD44 markers are evaluated by immunohistochemistry. To isolate resistant colon­CSC, adenocarcinoma tissues resistant to 5FU and oxaliplatin were evaluated. Finally, all samples were sequenced using a custom assay with chemoresistance­associated genes to find a candidate gene on resistance colon­CSC. Results showed that 59% of the CRC tissue analyzed was resistant and had a higher percentage of CD44 and CD24 markers. An association was found in the expression of some genes between the tumor­resistant tissue and CSC. Overall, isolates of the CSC population CD44+ resistant to 5FU and oxaliplatin demonstrated different expression profiles; however, the present study was able to identify overexpression of the KRT­18 gene, in most of the isolates. In conclusion, the results of the present study showed overexpression of KRT­18 in CD44+ cells is associated with chemoresistance to 5FU and oxaliplatin in CRAC.

miRNA signature associated with R-CHOP refractoriness in patients diagnosed with diffuse large B cell lymphoma.

Refractoriness remains as one of the challenges in patients with lymphoma under chemotherapy, and among biological regulators in cells driving this type of response are microRNAs (miRNAs). Different genes are constantly turned on or off according to the miRNAs expression profiles affecting the drug response in patients and their stability in serum and plasma makes them potential prognostic biomarkers in several diseases. Here we described a profile of miRNAs in plasma of diffuse large B cell lymphoma (DLBCL) patients. miRNA expression arrays were carried using pre-treatment plasma samples of sixteen patients, followed by a comparison between the responder and the non-responders. After six cycles of R-CHOP treatment, twelve out of sixteen patients were clinically diagnosed with complete response while in four patients no clinical response was observed. Between these groups, a signature of fifteen differential expressed miRNAs was found. The circulating miRNAs in plasma of patients with no response were related to the drug resistance in other types of cancer, by targeting genes involved in cell proliferation and apoptosis, among other cell processes.

Immunotyping of tumor-infiltrating lymphocytes in triple-negative breast cancer and genetic characterization.

Tumor-infiltrating lymphocytes (TILs) reflect the host immune response against cancer cells. Immunomodulators have been recently suggested as a novel therapeutic strategy against triple-negative breast cancer (TNBC). However, the TIL profile in TNBC has not been thoroughly investigated. In the present study, the percentage, immunophenotype and genetic profiles of TILs in pre-surgical tumor samples of patients with TNBC were evaluated prior to neoadjuvant chemotherapy (NAC). Patients diagnosed with breast cancer at Hospital San José TecSalud were consecutively and prospectively enrolled in the present study between August 2011 and August 2015. The pathological response to NAC was evaluated using the de Miller-Payne and MD Anderson Cancer Center system. TIL percentage (low, intermediate, and high) was evaluated using special hematoxylin-eosin staining on the core needle biopsies. The immunophenotype of TILs was assessed by immunohistochemistry (IHC) for CD3+, CD4+ and CD8+. In addition, the gene expression profile of CD3, CD4, CD8, CD20, CD45, forkhead box P3, interleukin 6, programmed cell death 1 and CD274 molecule was assessed in all patients. A total of 26 samples from patients with TNBC prior to NAC were included in the present study. TILs were low in 30.7%, intermediate in 38.4% and elevated in 30.7% of tumors. CD3+ and CD4+ counts were associated with the pathological response to NAC (P=0.04). Finally, an overexpression pattern of CD3, CD4, CD8, CD45 and CD20 genes was observed in patients with a partial or complete pathological response. The present results demonstrated that TILs may predict the pathological response to NAC in patients with TNBC. Furthermore, a more accurate association was identified between the high expression levels of CD3, CD4, CD8, CD45 and CD20 genes and partial and complete pathological response, compared with the association between high expression and IHC alone.

Genetic variants in CYP2A6 and UGT1A9 genes associated with urinary nicotine metabolites in young Mexican smokers.

Nicotine is the major pharmacologically active substance in tobacco. Several studies have examined genotypes related to nicotine metabolism, but few studies have been performed in the Mexican population. The objective was to identify associations between gene variants in metabolizing enzymes and the urinary levels of nicotine metabolites among Mexican smokers. The levels of nicotine and its metabolites were determined in the urine of 88 young smokers from Mexico, and 167 variants in 24 genes associated with nicotine metabolism were genotyped by next-generation sequencing (NGS). Trans-3'-hydroxy-cotinine (3HC) and 4-hydroxy-4-(3-pyridyl)-butanoic acid were the most abundant metabolites (35 and 17%, respectively). CYP2A6*12 was associated with 3HC (p = 0.014). The rs145014075 was associated with creatinine-adjusted levels of nicotine (p = 0.035), while the rs12471326 (UGT1A9) was associated to cotinine-N-glucuronide (p = 0.030). CYP2A6 and UGT1A9 variants are associated to nicotine metabolism. 4HPBA metabolite was an abundant urinary metabolite in young Mexican smokers.

Everolimus for cardiac rhabdomyomas in children with tuberous sclerosis. The ORACLE study protocol (everOlimus for caRdiac rhAbdomyomas in tuberous sCLErosis): a randomised, multicentre, placebo-controlled, double-blind phase II trial.

INTRODUCTION: Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma. METHODS: ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure. CONCLUSIONS: ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.

Tipificación de serotipos del virus del papiloma humano de alto riesgo / Typification of high-risk human papilomavirus serotypes

Resumen: OBJETIVO: Identificar los serotipos más frecuentes de virus del papiloma humano mediante pruebas al azar en pacientes previamente diagnosticadas con cáncer cervicouterino. MATERIALES Y MÉTODOS: Estudio prospectivo y observacional, efectuado en pacientes con displasia cervical, atendidas en el Hospital Regional Materno Infantil de Alta Especialidad de Nuevo León, Monterrey, entre enero y marzo de 2016. Criterios de inclusión: pacientes mayores de 18 años, que acudieron a la unidad médica para seguimiento y control ginecológico, con reporte anormal en la prueba de Papanicolaou, confirmado por histopatología, mediante biopsia dirigida por colposcopia. Criterios de exclusión: mujeres con histerectomía total por indicación de enfermedad benigna, sin antecedente de neoplasia intracervical; mayores a 70 años después de 3 citologías cervicales negativas en la década previa; pacientes que recibieron quimioterapia, radioterapia u otros tratamientos farmacológicos y quienes acudieron a revisión médica durante su ciclo menstrual. Para el análisis de los datos se utilizó estadística descriptiva. RESULTADOS: Se registraron 30 pacientes. Las clasificaciones más frecuentes de neoplasia cervical fueron: NIC-1 (n = 15), NIC-2 (n = 9) y NIC-3 (n = 6). Todas las pacientes analizadas tuvieron, al menos, un serotipo de VPH de alto riesgo. Los serotipos identificados con mayor frecuencia fueron el 31 y 33 (n = 18). En 18 pacientes se encontraron 6 o más serotipos de VPH. De 15 pacientes con lesiones de alto grado, 8 tuvieron la asociación de serotipos 31 y 33, y en 6 se identificó un serotipo aislado (16 y 51). CONCLUSIONES: Los serotipos identificados con mayor frecuencia fueron el 31 y 33. Desafortunadamente, la vacuna nonavalente que protege contra los serotipos más frecuentes de VPH no se encuentra disponible en Latinoamérica.

Abstract: OBJECTIVE: To identify the most frequent serotypes of human papillomavirus through random testing of patients previously diagnosed with cervical cancer. MATERIALS AND METHODS: A prospective, observational study carried out in patients with cervical dysplasia, treated at the High Specialty Regional Maternal and Child Hospital of Nuevo León, Monterrey. Inclusion criteria: patients over 18 years of age, who attended the Dysplasia Clinic of the High Specialty Regional Maternal and Child Hospital for gynecological follow-up and control, with an abnormal result in the Papanicolaou test, confirmed by histopathology, by means of colposcopy-directed biopsy. Before the procedures (cervical cytology), Exclusion criteria: women with total hysterectomy due to indications of benign disease, without a history of intracervical neoplasia; older than 70 years after 3 negative cervical cytology in the previous decade; patients who received chemotherapy, radiotherapy or other pharmacological treatments and who received medical check-ups during their menstrual cycle. Descriptive statistics were used for data analysis. RESULTS: 30 patients were registered. The most frequent classification of cervical neoplasia was: CIN1 (n = 15), CIN2 (n = 9) and CIN3 (n = 6). All the patients analyzed had at least one high-risk HPV serotype. The most frequently identified serotypes were 31 and 33 (n = 18 of 30). 6 or more HPV serotypes were found in 18 patients. Of 15 patients with high-grade lesions, 8 had the association of serotypes 31 and 33, and in 6 an isolated serotype was identified (16 and 51). CONCLUSIONS: The most frequently identified serotypes were 31 and 33. Unfortunately, the nonavalent vaccine that protects against the most frequent serotypes of HPV is not available in Latin America.

Landscape of Germline Mutations in DNA Repair Genes for Breast Cancer in Latin America: Opportunities for PARP-Like Inhibitors and Immunotherapy.

Germline mutations in BRCA1 and BRCA2 (BRCA1/2) genes are present in about 50% of cases of hereditary breast cancer. Proteins encoded by these genes are key players in DNA repair by homologous recombination (HR). Advances in next generation sequencing and gene panels for breast cancer testing have generated a large amount of data on gene variants implicated in hereditary breast cancer, particularly in genes such as PALB2, ATM, CHEK2, RAD51, MSH2, and BARD1. These genes are involved in DNA repair. Most of these variants have been reported for Caucasian, Jewish, and Asian population, with few reports for other communities, like those in Latin American (LA) countries. We reviewed 81 studies from 11 LA countries published between 2000 and 2019 but most of these studies focused on BRCA1/2 genes. In addition to these genes, breast cancer-related variants have been reported for PALB2, ATM, CHEK2, BARD1, MLH1, BRIP1, MSH2, NBN, MSH6, and PMS2 genes. Some of these variants are unique to LA populations. This analysis may contribute to enhance breast cancer variant characterization, and thus to find therapies and implement precision medicine for LA communities.

The Tumor-on-Chip: Recent Advances in the Development of Microfluidic Systems to Recapitulate the Physiology of Solid Tumors.

The ideal in vitro recreation of the micro-tumor niche-although much needed for a better understanding of cancer etiology and development of better anticancer therapies-is highly challenging. Tumors are complex three-dimensional (3D) tissues that establish a dynamic cross-talk with the surrounding tissues through complex chemical signaling. An extensive body of experimental evidence has established that 3D culture systems more closely recapitulate the architecture and the physiology of human solid tumors when compared with traditional 2D systems. Moreover, conventional 3D culture systems fail to recreate the dynamics of the tumor niche. Tumor-on-chip systems, which are microfluidic devices that aim to recreate relevant features of the tumor physiology, have recently emerged as powerful tools in cancer research. In tumor-on-chip systems, the use of microfluidics adds another dimension of physiological mimicry by allowing a continuous feed of nutrients (and pharmaceutical compounds). Here, we discuss recently published literature related to the culture of solid tumor-like tissues in microfluidic systems (tumor-on-chip devices). Our aim is to provide the readers with an overview of the state of the art on this particular theme and to illustrate the toolbox available today for engineering tumor-like structures (and their environments) in microfluidic devices. The suitability of tumor-on-chip devices is increasing in many areas of cancer research, including the study of the physiology of solid tumors, the screening of novel anticancer pharmaceutical compounds before resourcing to animal models, and the development of personalized treatments. In the years to come, additive manufacturing (3D bioprinting and 3D printing), computational fluid dynamics, and medium- to high-throughput omics will become powerful enablers of a new wave of more sophisticated and effective tumor-on-chip devices.