Unraveling the Role of EV-Derived miR-150-5p in Prostate Cancer Metastasis and Its Association with High-Grade Gleason Scores: Implications for Diagnosis.

Metastasis remains the leading cause of mortality in prostate cancer patients. The presence of tumor cells in lymph nodes is an established prognostic indicator for several cancer types, such as melanoma, breast, oral, pancreatic, and cervical cancers. Emerging evidence highlights the role of microRNAs enclosed within extracellular vesicles as facilitators of molecular communication between tumors and metastatic sites in the lymph nodes. This study aims to investigate the potential diagnostic utility of EV-derived microRNAs in liquid biopsies for prostate cancer. By employing microarrays on paraffin-embedded samples, we characterized the microRNA expression profiles in metastatic lymph nodes, non-metastatic lymph nodes, and primary tumor tissues of prostate cancer. Differential expression of microRNAs was observed in metastatic lymph nodes compared to prostate tumors and non-metastatic lymph node tissues. Three microRNAs (miR-140-3p, miR-150-5p, and miR-23b-3p) were identified as differentially expressed between tissue and plasma samples. Furthermore, we evaluated the expression of these microRNAs in exosomes derived from prostate cancer cells and plasma samples. Intriguingly, high Gleason score samples exhibited the lowest expression of miR-150-5p compared to control samples. Pathway analysis suggested a potential regulatory role for miR-150-5p in the Wnt pathway and bone metastasis. Our findings suggest EV-derived miR-150-5p as a promising diagnostic marker for identifying patients with high-grade Gleason scores and detecting metastasis at an early stage.

Transcriptome-Wide Analysis of Low-Concentration Exposure to Bisphenol A, S, and F in Prostate Cancer Cells.

Bisphenol A (BPA) is a ubiquitous synthetic compound used as a monomer in the production of polycarbonate plastics and epoxy resins. Even at low doses, BPA has been associated with the molecular progression of diseases such as obesity, metabolic syndrome, and hormone-regulated cancers due to its activity as an endocrine-disrupting chemical (EDC). Consequently, the use of BPA has been regulated worldwide by different health agencies. BPA structural analogs such as bisphenol S and bisphenol F (BPS and BPF) have emerged as industrial alternatives, but their biological activity in the molecular progression of cancer remains unclear. Prostate cancer (PCa) is a hormone-dependent cancer, and the role of BPA structural analogs in PCa progression is still undescribed. In this work, we use an in vitro model to characterize the transcriptomic effect of low-concentration exposure to bisphenol A, S, or F in the two main stages of the disease: androgen dependency (LNCaP) and resistance (PC-3). Our findings demonstrated that the low concentration exposure to each bisphenol induced a differential effect over PCa cell lines, which marks the relevance of studying the effect of EDC compounds through all the stages of the disease.

SFRP1 induces a stem cell phenotype in prostate cancer cells.

Prostate cancer (PCa) ranks second in incidence and sixth in deaths globally. The treatment of patients with castration-resistant prostate cancer (CRPC) continues to be a significant clinical problem. Emerging evidence suggests that prostate cancer progression toward castration resistance is associated with paracrine signals from the stroma. SFRP1 is one of the extracellular proteins that modulate the WNT pathway, and it has been identified as a mediator of stromal epithelium communication. The WNT pathway is involved in processes such as cell proliferation, differentiation, cell anchoring, apoptosis, and cell cycle regulation as well as the regulation of stem cell populations in the prostatic epithelium. In the present study, we explored the role of exogenous SFRP1 on the stem cell phenotype in prostate cancer. The results reveal that cancer stem cell markers are significantly increased by exogenous SFRP1 treatments, as well as the downstream target genes of the Wnt/-catenin pathway. The pluripotent transcription factors SOX2, NANOG, and OCT4 were also up-regulated. Furthermore, SFRP1 promoted prostate cancer stem cell (PCSC) properties in vitro, including tumorsphere formation, migration, bicalutamide resistance, and decreased apoptosis. Taken together, our results indicate that SFRP1 participates in the paracrine signaling of epithelial cells, influencing them and positively regulating the stem cell phenotype through deregulation of the WNT/ß-catenin pathway, which could contribute to disease progression and therapeutic failure. This research increases our molecular understanding of how CRPC progresses, which could help us find new ways to diagnose and treat the disease.

Aptamers as Theragnostic Tools in Prostate Cancer.

Despite of the capacity that several drugs have for specific inhibition of the androgen receptor (AR), in most cases, PCa progresses to an androgen-independent stage. In this context, the development of new targeted therapies for prostate cancer (PCa) has remained as a challenge. To overcome this issue, new tools, based on nucleic acids technology, have been developed. Aptamers are small oligonucleotides with a three-dimensional structure capable of interacting with practically any desired target, even large targets such as mammalian cells or viruses. Recently, aptamers have been studied for treatment and detection of many diseases including cancer. In PCa, numerous works have reported their use in the development of new approaches in diagnostics and treatment strategies. Aptamers have been joined with drugs or other specific molecules such as silencing RNAs (aptamer-siRNA chimeras) to specifically reduce the expression of oncogenes in PCa cells. Even though these studies have shown good results in the early stages, more research is still needed to demonstrate the clinical value of aptamers in PCa. The aim of this review was to compile the existing scientific literature regarding the use of aptamers in PCa in both diagnosis and treatment studies. Since Prostate-Specific Membrane Antigen (PSMA) aptamers are the most studied type of aptamers in this field, special emphasis was given to these aptamers.

Deciphering the Code between Air Pollution and Disease: The Effect of Particulate Matter on Cancer Hallmarks.

Air pollution has been recognized as a global health problem, causing around 7 million deaths worldwide and representing one of the highest environmental crises that we are now facing. Close to 30% of new lung cancer cases are associated with air pollution, and the impact is more evident in major cities. In this review, we summarize and discuss the evidence regarding the effect of particulate matter (PM) and its impact in carcinogenesis, considering the "hallmarks of cancer" described by Hanahan and Weinberg in 2000 and 2011 as a guide to describing the findings that support the impact of particulate matter during the cancer continuum.

Cytoplasmic p21(CIP1/WAF1), ERK1/2 activation, and cytoskeletal remodeling are associated with the senescence-like phenotype after airborne particulate matter (PM(10)) exposure in lung cells.

The exposure to particulate matter with a mean aerodynamic diameter ≤10 µm (PM10) from urban zones is considered to be a risk factor in the development of cancer. The aim of this work was to determine if PM10 exposure induces factors related to the acquisition of a neoplastic phenotype, such as cytoskeletal remodeling, changes in the subcellular localization of p21(CIP1/WAF1), an increase in ß-galactosidase activity and changes in cell cycle. To test our hypothesis, PM10 from an industrial zone (IZ) and a commercial zone (CZ) were collected, and human adenocarcinoma lung cell cultures (A549) were exposed to a sublethal PM10 concentration (10 µg/cm(2)) for 24 h and 48 h. The results showed that PM10 exposure induced an increase in F-actin stress fibers and caused the cytoplasmic stabilization of p21(CIP1/WAF1) via phosphorylation at Thr(145) and Ser(146) and the phosphorylation of ERK1/2 on Thr(202). Changes in the cell cycle or apoptosis were not observed, but an increase in ß-galactosidase activity was detected. The PM10 from CZ caused more dramatic effects in lung cells. We conclude that PM10 exposure induced cytoplasmic p21(CIP1/WAF1) retention, ERK1/2 activation, cytoskeleton remodeling and the acquisition of a senescence-like phenotype in lung cells. These alterations could have mechanistic implications regarding the carcinogenic potential of PM10.

Follicular neoplasms of the thyroid: importance of clinical and cytological correlation.

BACKGROUND: Thyroid cancer presents as nodules. Thyroid nodules are frequent, but only 5-30% are malignant. Fine needle aspiration biopsy (FNAB) is useful for initial evaluation; nevertheless, malignancy is uncertain when follicular neoplasm is reported. Some factors can be associated with malignancy. Therefore, we analyzed our follicular neoplasms in order to identify those factors associated with a higher risk of malignancy. METHODS: We analyzed the clinical files of consecutive patients with cytological diagnoses of follicular neoplasm. RESULTS: From 1,005 cases of thyroid nodules, 121 were follicular neoplasms according to cytology. Of these, 75 were surgically treated. Definitive report showed 45 benign (60%) and 30 malignant (40%) cases. Benign cases included 29 goiters, 11 follicular adenomas, and 5 cases of thyroiditis. Malignant cases were comprised of 12 papillary carcinomas, 4 follicular carcinomas, 3 papillary carcinomas-follicular variant, 1 lymphoma, 1 teratoma, 5 medullary carcinomas, 2 insular carcinomas, 1 anaplastic carcinoma and 1 metastatic breast carcinoma. Tumor size of benign lesions was 3.43 ± 2.04 cm, and 4.67 ± 2.78 (p = 0.049) for malignant lesions. Age was 46.95 ± 15.39 years for benign lesions and 48.67 ± 17.28 for malignant lesions (p = 0.66). Fifty percent of males showed malignancy vs. 37.7% of females (p < 0.005). CONCLUSIONS: Our results suggest that size and gender, but not age, are associated with cytological pattern. Ultrasonographic characteristics may be useful discriminating patients with a higher risk of malignancy. FNAB is a useful tool for initial evaluation of thyroid nodules, but clinical evaluation can enhance predictive value.

Prospective evaluation of oral mucositis in acute leukemia patients receiving chemotherapy.

PURPOSE: Knowledge of oral mucositis (OM) in patients with acute leukemia (AL) and chemotherapy (CT) has remained limited. Thus, a prospective, longitudinal study was undertaken to characterize clinical features, associated risk factors, and behavior of OM in a cohort of AL patients starting CT. METHODS: Prospective and longitudinal study. A cohort of patients, older than 15 years of age with AL, scheduled to receive CT, was followed from March 2006 to October 2007. At baseline and three times per week, for 21 days, patients had an oral examination performed using the Oral Mucositis Assessment Scale (OMAS); also, oral pain and difficulty to swallow were recorded using a visual analog scale. Weekly, salivary flow measurements (Schirmer's test modified version) were done. RESULTS: A cohort of 29 AL patients was followed for a median time of 21 (range, 14-53) days; 12 (41.4%) developed OM, with a mean OMAS score of 0.181 (SD +/- 0.56) and a mean peak OMAS score of 1.8 (SD +/- 0.56). The OM onset mean time was 9.8 (range, 2-20, SD +/- 6.09) days, with a mean duration of 7 (range, 3-14, SD +/- 4.15) days. OM was significantly correlated with salivary flow [rs = 0.420 (P = 0.0051)], oral pain [rs = 0.47 (P < 0.0001)], ability to swallow [rs = 0.36 (P = 0.0001)], and type of food intake [rs = 0.38 (P < 0.0001)]. CONCLUSIONS: OM is a frequent and early side effect of CT closely correlated with oral pain, difficulty to swallow, and impairment in food intake.

HIV-related oral lesions, demographic factors, clinical staging and anti-retroviral use.

BACKGROUND: The aim of the present study was to compare the prevalence of HIV-related oral lesions (HIV-OL) between two health centers for HIV in Mexico City and to analyze the factors that, in addition to combined antiretroviral therapy (CART) and low CD4(+), may be associated with possible differences in prevalence. METHODS: A cross-sectional observational study was performed between January 2000 and February 2003 at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), a specialized referral center for HIV/AIDS patients and the Clínica Especializada Condesa (CEC), a primary care center for HIV-infected individuals without social security insurance. A consecutive sample of HIV-infected individuals had an oral examination based on established clinical criteria. Demographic, clinical and laboratory data were obtained. Independent association of each factor with specific HIV-OL was assessed by logistic regression modeling. RESULTS: Eight hundred fifty individuals were examined (INCMNSZ: 479; CEC: 371). Hairy leukoplakia (HL), periodontal disease (PD) and Kaposi's sarcoma (KS) were independently associated with the study site [odds ratio (OR) = 1.7 (95% confidence interval (CI): 1.1-2.4), OR = 4.2 (95% CI: 1.3-13), OR = 10.1 (95% CI: 2.7-38.2), respectively], being more frequent in CEC patients. HL was independently associated with men having sex with men OR = 1.7 (95% CI: 1.1-2.8). All HIV-OL were independently associated with CD4(+) counts and, with the exception of PD and KS, with time under CART. CONCLUSIONS: The present comparative study showed that several factors were associated with a difference in prevalence of oral lesions found in two AIDS clinics located in Mexico City. Severe immune suppression, CART duration and the study site were associated with HIV-OL. Further investigation into factors such as socioeconomic determinants associated with HIV-OL is warranted.

Ulcera lingual como signo único de infección recurrente por micobacteria en un paciente con VIH/SIDA / Lingual ulcer as the only sign of recurrent mycobacterial infection in an HIV/AIDS-infected patient

Se describe un paciente con VIH/SIDA en el que se identificó una infección por micobacteria en la mucosa bucal, probablemente tuberculosis, en un centro de referencia para VIH/SIDA de la Ciudad de México. El propósito del presente informe es describir los hallazgos clínicos e histológicos en un paciente con VIH/SIDA, quien después de haber sido tratado exitosamente para tuberculosis ganglionar 4 años antes, presentó una úlcera lingual como único signo que sugirió recurrencia de infección por micobacteria, probablemente tuberculosis. Hombre de 39 años de edad, atendido desde 1991 en el Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, por el diagnóstico de infección con VIH. En 1999, el paciente presentó tuberculosis ganglionar, recibiendo tratamiento antifímico con involución de las adenopatías y desaparición de los síntomas sistémicos. En mayo del 2003 acudió a consulta por presentar una úlcera superficial en lengua, dolorosa, de 4 meses de evolución, de 0.7 cm. de diámetro, bien circunscrita, crateriforme, con bordes ligeramente elevados, irregulares e indurados. El estudio histopatológico mostró inflamación granulomatosa crónica con células gigantes multinucleadas sugestivas de infección por micobacteria, lo cual hizo pensar en recurrencia de tuberculosis, por lo que se indicó rifampicina, pirazinamida, etambutol y estreptomicina. En junio del 2003 el paciente inició TARAA, que incluyó dos ITRAN y un ITRNN. La lesión lingual evolucionó favorablemente, con cicatrización parcial a la primera semana y remisión total a los 45 días del inicio del tratamiento antifímico; a los 7 meses de seguimiento permanece sin lesión. El presente caso tiene la particularidad de que la úlcera lingual fue la única manifestación de infección por micobacteria, sugestiva de tuberculosis, en un paciente con VIH/SIDA, que pudo ocurrir como resultado de la recurrencia del episodio previo de TB ganglionar

The report describes an HIV/AIDS patient seen at a referral center in Mexico City, in whom a mycobacterial infection in the oral mucosa, probably tuberculosis (TB) was identified. The purpose is to describe the clinical and histological findings in an HIV-infected patient, who after being treated successfully for tuberculous lymphangitis 4 years ago, presented with a lingual ulcer as the only suggestive sign of recurrence of mycobacterial infection, probably M. tuberculosis. A 39-year-old man seen inthe HIV clinic of the Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” in Mexico City since 1991 for HIV infection. In 1999 the patient developed tuberculous lymphangitis; he was managed with a 4-drug regimen for 12 months, with improvement of local and systemic symptoms. In May of 2003, the patient presented a painful superficial lingual ulcer, 0.7 cm in diameter, well circumscribed, crateriform with slightly elevated, irregular and indurated borders, of 4 months duration. The histopathological examination showed chronic granulomatous inflammation with giant multinucleated cells, suggestive of mycobacterial infection, and recurrence of TB was considered. Rifampin, isoniazide, pyrazinamide, ethambutol and streptomycin were administered. The lingual lesion improved with partial healing at the first week and total remission at 45 days after the beginning of the antituberculous treatment. In June, 2003, the patient began highly active antiretroviral therapy (HAART) that included two NRTIs and one NNRTI. At 7 months of follow-up, the patient remains free of lingual lesions. The particularity of the present case is that the lingual ulcer was the only sign of infection by mycobacteria, suggestive of TB, in an HIV/AIDS patient that probably represented a recurrence of a previous episode

Lingual ulcer as the only sign of recurrent mycobacterial infection in an HIV/AIDS-infected patient.

The report describes an HIV/AIDS patient seen at a referral center in Mexico City, in whom a mycobacterial infection in the oral mucosa, probably tuberculosis (TB) was identified. The purpose is to describe the clinical and histological findings in an HIV-infected patient, who after being treated successfully for tuberculous lymphangitis 4 years ago, presented with a lingual ulcer as the only suggestive sign of recurrence of mycobacterial infection, probably M. tuberculosis. A 39-year-old man seen in the HIV clinic of the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" in Mexico City since 1991 for HIV infection. In 1999 the patient developed tuberculous lymphangitis; he was managed with a 4-drug regimen for 12 months, with improvement of local and systemic symptoms. In May of 2003, the patient presented a painful superficial lingual ulcer, 0.7 cm in diameter, well circumscribed, crateriform with slightly elevated, irregular and indurated borders, of 4 months duration. The histopathological examination showed chronic granulomatous inflammation with giant multinucleated cells, suggestive of mycobacterial infection, and recurrence of TB was considered. Rifampin, isoniazide, pyrazinamide, ethambutol and streptomycin were administered. The lingual lesion improved with partial healing at the first week and total remission at 45 days after the beginning of the antituberculous treatment. In June, 2003, the patient began highly active antiretroviral therapy (HAART) that included two NRTIs and one NNRTI. At 7 months of follow-up, the patient remains free of lingual lesions. The particularity of the present case is that the lingual ulcer was the only sign of infection by mycobacteria, suggestive of TB, in an HIV/AIDS patient that probably represented a recurrence of a previous episode.

The Changing Clinical Spectrum of Human Immunodeficiency Virus (HIV)-Related Oral Lesions in 1,000 Consecutive Patients: A 12-Year Study in a Referral Center in Mexico.

In developing countries, the variations in the clinical spectrum of human immunodeficiency virus (HIV)-related oral lesions over time, and the possible effects of antiretroviral therapy, have not been described. In this study we evaluate the clinical spectrum of oral lesions in a series of HIV-infected patients when first examined at the acquired immunodeficiency syndrome (AIDS) clinic of a tertiary care institution in Mexico City, Mexico, and the changes observed over 12 years. All HIV-infected adult patients had an oral examination performed by specialists in oral pathology and medicine who used established clinical diagnostic criteria for oral lesions. Four periods were defined according to the evolving pattern of antiretroviral use: the first 2 were before the introduction of highly active antiretroviral therapy (HAART) and the last 2 were during more established use of HAART. For the statistical analysis the chi-square test for contingency tables and the chi-square test for trend were utilized. For dimensional variables, except age, the Kruskal-Wallis or Mann-Whitney rank sum tests were used when applicable and trend was tested with the Spearman correlation coefficient. Age was tested through analysis of variance (ANOVA) and linear regression analysis. Alpha value was set at p = 0.05 for each test. In the 12-year study, 1,000 HIV-infected patients were included (87.9% male). At the baseline examination, oral lesions strongly associated with HIV were present in 47.1% of HIV-infected patients. Oral candidosis (31.6%), hairy leukoplakia (22.6%), erythematous candidosis (21.0%), and pseudomembranous candidosis (15.8%) were the most frequent lesions. Oral Kaposi sarcoma (2.3%), HIV-associated periodontal disease (1.7%), and oral non-Hodgkin lymphoma (0.1%) were less frequent. HIV-related oral lesions decreased systematically-by half during the course of the 4 study periods (p < 0.001). Except for Kaposi sarcoma, all oral lesions strongly associated with HIV showed a trend to decrease significantly during the study period. No apparent variation in the occurrence of salivary gland disease or human papillomavirus-associated oral lesions was found. A significant trend to a lower prevalence was observed in the group of patients who were already taking antiretroviral therapy, non-HAART and HAART (p < 0.001 and p = 0.004, respectively). Only a discrete reduction, barely significant, was noted among untreated patients (p = 0.060). By Period IV (1999-2001), those who received HAART showed the lowest prevalence of oral lesions strongly associated with HIV (p < 0.001). Patients with oral lesions strongly associated with HIV had significantly lower median CD4+ counts and higher viral loads than those without oral lesions strongly associated with HIV (p < 0.001 and p = 0.005, respectively). When CD4+ counts were correlated with prevalence of oral candidosis, a consistently negative association was found; this association prevailed even after the study group was partitioned according to period. In this selected cohort of 1,000 patients with HIV infection, the clinical spectrum of HIV-related oral lesions has changed over the 12-year study, with a decreased prevalence of most oral lesions. Our findings probably represent improvements in medical care of HIV-infected persons, earlier detection of HIV-infected patients at the AIDS clinic, the increasing use of prophylactic drugs to prevent secondary AIDS-related opportunistic infections, and, perhaps most important, the availability of potent antiretroviral therapy in recent years, since the introduction of HAART.

[Association of oral lesions with HIV serological status]. / Asociación de lesiones bucales con el estado serológico para el VIH.

OBJECTIVE: To estimate the prevalence of oral lesions and its association with HIV serological status. MATERIAL AND METHODS: A cross-sectional descriptive study was conducted between 1998 and 1999 in Mexico City, among 512 subjects attending two information centers of Centro Nacional para la Prevención del VIH/SIDA e ITS (CONASIDA, National Center for Prevention of HIV/AIDS and Sexually Transmitted Infections) for HIV serologic testing. The oral examination was performed without knowledge of the HIV status. Statistical analysis was conducted using Student's t test, Fisher's exact test and the chi 2 test; odds ratios and 95% CI were also calculated. RESULTS: A total of 512 individuals were examined, 68 of whom were HIV-positive. HIV-related oral lesions (OL), were evident in 65% (44/68) of the HIV-positive individuals; 95% of them consisted in oral candidosis (OC) and hairy leukoplakia (HL). OC and HL were strongly associated with seropositivity to HIV. CONCLUSIONS: OC and HL were the oral lesions most strongly associated to HIV seropositivity. The English version of this paper is available at: http://www.insp.mx/salud/index.html.

Asociación de lesiones bucales con el estado serológico para el VIH / Association of oral lesions with HIV serological status

OBJECTIVE: To estimate the prevalence of oral lesions and its association with HIV serological status. MATERIAL AND METHODS: A cross-sectional descriptive study was conducted between 1998 and 1999 in Mexico City, among 512 subjects attending two information centers of Centro Nacional para la Prevención del VIH/SIDA e ITS (CONASIDA, National Center for Prevention of HIV/AIDS and Sexually Transmitted Infections) for HIV serologic testing. The oral examination was performed without knowledge of the HIV status. Statistical analysis was conducted using Student's t test, Fisher's exact test and the chi 2 test; odds ratios and 95 CI were also calculated. RESULTS: A total of 512 individuals were examined, 68 of whom were HIV-positive. HIV-related oral lesions (OL), were evident in 65 (44/68) of the HIV-positive individuals; 95 of them consisted in oral candidosis (OC) and hairy leukoplakia (HL). OC and HL were strongly associated with seropositivity to HIV. CONCLUSIONS: OC and HL were the oral lesions most strongly associated to HIV seropositivity. The English version of this paper is available at: http://www.insp.mx/salud/index.html.