Human papillomavirus (HPV) infection is a well-known cause of cervical cancer. Therapeutic cancer vaccines are part of the current therapeutic options for HPV-associated cancers. Axalimogen ...filolisbac (ADXS11-001) is an immunotherapy based on live attenuated Listeria monocytogenes-listeriolysin O (Lm-LLO), designed by biological engineering to secrete an antigen-adjuvant fusion protein, composed of a truncated fragment of LLO fused to HPV. The proposed mechanism of action is that Lm-based vectors infect antigen-presenting cells (APC) and secrete HPV-LLO fusion proteins within the APC cytoplasm, these proteins are processed and presented to cytotoxic T lymphocytes (CTL), thus generating a new population of CTLs specific to HPV antigens. These HPV-specific CTLs destroy HPV infected cells. ADXS11-001 has demonstrated safety results in phase I-II studies in women with cervical cancer and is being assessed in clinical trials in patients with HPV-positive anal canal and head and neck cancers.
Worldwide breast cancer ranks first in mortality and incidence rates in women over 20 years old. Rather than one disease, breast cancer is a heterogeneous group of diseases that express distinct ...molecular profiles. Neoadjuvant chemotherapy is an important therapeutic strategy for breast cancer patients independently of their molecular subtype, with the drawback of resistance development. In addition, chemotherapy has adverse effects that combined with resistance could contribute to lower overall survival. Although great efforts have been made to find diagnostic and prognostic biomarkers for breast cancer and for response to targeted and immune therapy for this pathology, little has been explored regarding biomarkers of response to anthracyclines and taxanes based neoadjuvant chemotherapy. This work aimed to evaluate the molecular profile of patients who received neoadjuvant chemotherapy to identify differentially expressed genes (DEGs) that could be used as biomarkers of chemotherapy response and overall survival. Breast cancer patients who were candidates for neoadjuvant chemotherapy were enrolled in this study. After treatment and according to their pathological response, they were assigned as sensitive or resistant. To evaluate DEGs, Gene Ontology, Kyoto Encyclopedia Gene and Genome (KEGG), and protein–protein interactions, RNA-seq information from all patients was obtained by next-generation sequencing. A total of 1985 DEGs were found, and KEGG analysis indicated a great number of DEGs in metabolic pathways, pathways in cancer, cytokine–cytokine receptor interactions, and neuroactive ligand-receptor interactions. A selection of 73 DEGs was used further for an analysis of overall survival using the METABRIC study and the ductal carcinoma dataset of The Cancer Genome Atlas (TCGA) database. Nine DEGs correlated with overall survival, of which the subexpression of C1QTNF3, CTF1, OLFML3, PLA2R1, PODN, KRT15, HLA-A, and the overexpression of TUBB and TCP1 were found in resistant patients and related to patients with lower overall survival.
Objetivo: El cáncer de mama (CAM) es un problema de salud pública mundial. La ansiedad y depresión son las principales comorbilidades que aquejan a este sector, el programa psicoeducativo de ...navegación (PPN) se presenta como una estrategia psicosocial eficaz en hospitales públicos de México. Método: Se realizó la adaptación del PPN y la evaluación de eficacia en 47 mujeres con CAM de tres hospitales de la Zona Metropolitana de Guadalajara. El PPN integró acompañamiento emocional, educación para la salud y técnicas de relajación. Se evaluaron los síntomas y los niveles de ansiedad y depresión, pre-post intervención con la Escala Hospitalaria de Ansiedad y Depresión (HADS). Resultados: Se encontró una disminución en los síntomas de ansiedad pre-test (M= 6,79, DT= 4,01) y pos-test (M= 4,19, DT= 3,03), igual que en los síntomas de depresión antes (M= 6,02, DT= 4,07) y después (M= 4,23, DT= 3,05). Se obtuvieron diferencias estadísticamente significativas entre las evaluaciones pre y post intervención tanto en las dimensiones, como en la puntuación global (p<0,001). Conclusiones: El PPN mostró eficacia para disminuir los síntomas y los niveles de ansiedad y depresión en mujeres mexicanas con CAM. Sugerimos replicar el programa en otros contextos de atención oncológica en seguimiento a las normativas nacionales.
Breast cancer ranks first in terms of mortality and incidence rates worldwide among women. The HER2+ molecular subtype is one of the most aggressive subtypes; its treatment includes neoadjuvant ...chemotherapy and the use of a HER2 antibody. Some patients develop resistance despite positive results obtained using this therapeutic strategy. Objective. To identify prognostic markers for treatment and survival in HER2+ patients. Methods. Patients treated with neoadjuvant chemotherapy were assigned to sensitive and resistant groups based on their treatment response. Differentially expressed genes (DEGs) were identified using RNA-seq analysis. KEGG pathway, gene ontology, and interactome analyses were performed for all DEGs. An enrichment analysis Gene set enrichment analysis was performed. All DEGs were analyzed for overall (OS) and disease-free survival (DFS). Results. A total of 94 DEGs were related to treatment resistance. Survival analysis showed that 12 genes (ATF6B, DHRS13, DIRAS1, ERAL1, GRIN2B, L1CAM, IRX3, PRTFDC1, PBX2, S100B, SLC9A3R2, and TNXB) were good predictors of disease-free survival, and eight genes (GNG4, IL22RA2, MICA, S100B, SERPINF2, HLA-A, DIRAS1, and TNXB) were good predictors of overall survival (OS). Conclusion: We highlighted a molecular expression signature that can differentiate the treatment response, overall survival, and DFS of patients with HER2+ breast cancer.
HLA-G is a physiology and pathologic immunomodulator detrimentally related to cancer. Its gene is heavily transcriptionally and post-transcriptionally regulated by variants located in regulator ...regions like 3′UTR, being the most studied Ins/Del of 14-bp (rs66554220), which is known to influence the effects of endogen cell factors; nevertheless, the reports are discrepant and controversial. Herein, the relationship of the 14-bp Ins/Del variant (rs66554220) with breast cancer (BC) and its clinical characteristics were analyzed in 182 women with non-familial BC and 221 disease-free women as a reference group. Both groups from western Mexico and sex–age-matched (sm-RG). The rs66554220 variant was amplified by SSP-PCR and the fragments were visualized in polyacrylamide gel electrophoresis. The variant rs66554220 was not associated with BC in our population. However, we suggest the Ins allele as a possible risk factor for developing BC at clinical stage IV (OR = 3.05, 95% CI = 1.16–7.96, p = 0.01); nevertheless, given the small stratified sample size (n = 11, statistical power = 41%), this is inconclusive. In conclusion, the 14-bp Ins/Del (rs66554220) variant of HLA-G is not associated with BC in the Mexican population, but might be related to advanced breast tumors. Further studies are required.
Background
Functional variants ‐173 G > C (rs755622) and ‐794CATT5‐8 (rs5844572) MIF gene have been associated with the risk in several types of cancer, as well as with the increase of soluble levels ...of MIF and TNFα. However, in previous studies contradictory and uncertain results have been presented on the implication of MIF polymorphisms with the association in cancer, specifically in breast cancer (BC). We investigated whether the variants are associated with the susceptibility to develop BC and the soluble levels of MIF and TNFα in women with BC from western Mexico.
Materials and methods
A total of 152 women with BC and 182 control subjects (CS) were enrolled in this study. The determination of genotypes ‐173 G > C and ‐794 CATT5‐8 MIF polymorphisms was performed by PCR‐RFLP and PCR, respectively. In addition, the soluble levels of MIF and TNFα in both studied groups were quantified by ELISA and MILLIPLEX assay, respectively.
Results
The most frequent allele found in BC was the G (74.3%) and 6 (54%) in the variants ‐173G > C and ‐794 CATT5‐8, respectively, without significant differences in both groups. Nevertheless, the women with BC carriers ‐173*C and ‐794CATT7 have higher levels of MIF in comparison with CS. An increase of MIF (BC: 11.1 ng/mL vs CS: 5.2 ng/mL, P < .001) and TNFα (BC: 24.9 ng/mL vs CS: 9.9 pg/mL, P < .001) was found.
Conclusion
The functional variants of MIF are not genetic susceptibility markers for BC. Nevertheless, the alleles ‐173*C and ‐794CATT7 are associated with the increase of MIF circulating in women with BC.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Breast cancer (BC) is a health problem worldwide; there is evidence that inflammatory cytokines are increased in BC. Macrophage migration inhibitory factor (MIF) has multiple effects on immune cells, ...inflammation and cancer. Besides, in previous studies, contradictory and uncertain results have been presented on the implication of Th17 cytokine profile in BC. The aim of this study was to evaluate the plasma levels of MIF and the Th17 cytokine profile in BC and their association with their molecular subtypes and clinical stage. A total of 150 women with BC of Ella Binational Breast Cancer Study and 60 healthy women (HW) were evaluated in cross-sectional study. The molecular subtypes were identified by immunohistochemistry. The plasma levels of MIF were quantified by ELISA and Th17 cytokine profile by multiplex system. MIF and IL-17 were significantly increased in BC versus HW (11.1 vs. 5.2 ng/mL and 14.8 pg/mL vs. 2.5 pg/mL
p
< 0.001, respectively). Our analysis showed that both MIF and IL-17A were associated with increased risk of breast cancer (OR 3.85 CI 95% 1.98–7.50 and OR 4.51 95% 1.83–11.15, respectively), higher in aggressive subtypes Luminal B, HER2 and TN. Likewise, we observed positive correlation between MIF and IL-17A (
p
< 0.001). In addition, IL-17E was lower in BC versus HW (
p
<0.001). Likewise, we observed a positive correlation between MIF and IL-17A (
p
< 0.001). In conclusion, both MIF and IL-17A were associated with high risk for breast cancer and aggressive molecular subtypes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The rs2234693 and rs9340799 ESR1 polymorphisms have shown contradictory results in studies of breast cancer (BC). The purpose of this study was to determine the frequency and association of ESR1 ...polymorphisms (rs2234693 and rs9340799) in BC patients of Mexican population.
PCR was used to genotype rs2234693 and rs9340799 polymorphisms in the ESR1 gene in Mexican healthy subjects and breast cancer (BC) patients.
The frequency of cases and control groups of rs2234693 and rs9340799 polymorphisms in the ESR1 was similar, and none has shown any association with increased BC risk (p>0.05), although the association between the haplogenotypes (rs2234693 and rs9340799 polymorphisms) and BC patients with miscarriages CTAG variant, adjusted odds ratio (OR) 1.83 (95%CI 1.17-2.86);p=0.011 and tobacco consumption CCGG variant, adjusted OR 1.88 (95%CI 1.11-3.19);p=0.018 was evident. Also, the homozygous genotype TT rs2234693, OR 1.49 (95%CI 1.02-2.19);p=0.042 and GG rs9340799, OR 2.85 (95%CI 1.144-7.10);p=0.024 showed marginal association with BC, indicating that these factors may contribute significantly to the susceptibility of risk to BC. The TA haplotype was more common in controls than in CG. BC patients with a frequency around 0.71 among study groups, but without significant difference (p>0.05).
rs2234693 and rs9340799 polymorphisms in the ESR1 gene were not associated with susceptibility for BC. However, the haplogenotypes CTAG and CCGG of rs2234693 and rs9340799 polymorphisms could contribute significantly to the susceptibility of risk in BC positive at miscarriage and tobacco consumption in this sample population.
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