RESUMO
The bacille Calmette-Guérin (BCG) vaccine is administered in many countries as part of their vaccination schedules. Epidemiologic studies have suggested a possible benefit of this vaccine in the context of the COVID-19 pandemic and other respiratory infections. We aimed to assess the safety of this intervention in BCG-primed adults. Adult health care workers (n = 451) received a single intradermal application of the BCG vaccine (Tokyo 172 strain) in the deltoid region of the right arm. Follow-up (30 days) calls and clinical inspections were guided using a standardized data sheet to assess local and systemic reactions. Early local reactions were common at 24 h and 7 days, such as erythema (74.9%, 69.2%), induration (55.7%, 59%), a papule (53.4%, 47.7%), and edema (48.3%, 38.1). Local symptoms (pruritus 44.8%, heat 16.2%, and pain 34.8%) were less frequent at day 7. Late expected reactions (14 and 30 days) included the formation of crusts (39.6% and 63.9%), a pustule (36.6% and 17%), or ulcers (28.8% and 17.7%). Severe reactions were limited to subcutaneous abscesses (2%) and lymphadenitis (<1%).
Assuntos
COVID-19 , Exantema , Adulto , Humanos , Imunização Secundária , COVID-19/prevenção & controle , Vacina BCG , Pandemias/prevenção & controleRESUMO
Cancer is a worldwide health problem. Nevertheless, new technologies in the immunotherapy field have emerged. Chimeric antigen receptor (CAR) technology is a novel biological form to treat cancer; CAR-T cell genetic engineering has positively revolutionized cancer immunotherapy. In this paper, we review the latest developments in CAR-T in cancer treatment. We present the structure of the different generations and variants of CAR-T cells including TRUCK (T cells redirected for universal cytokine killing. We explain the approaches of the CAR-T cells manufactured ex vivo and in vivo. Moreover, we describe the limitations and areas of opportunity for this immunotherapy and the current challenges of treating hematological and solid cancer using CAR-T technology as well as its constraints and engineering approaches. We summarize other immune cells that have been using CAR technology, such as natural killer (NK), macrophages (M), and dendritic cells (DC). We conclude that CAR-T cells have the potential to treat not only cancer but other chronic diseases.
Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/genética , Imunoterapia Adotiva , Linfócitos T , Neoplasias/genética , Terapia Baseada em Transplante de Células e TecidosRESUMO
Cancer is a disease that causes millions of deaths per year worldwide because conventional treatments have disadvantages such as unspecific tumor selectivity and unwanted toxicity. Most human solid tumors present hypoxic microenvironments and this promotes multidrug resistance. In this study, we present "Magnetogene nanoparticle vector" which takes advantage of the hypoxic microenvironment of solid tumors to increase selective gene expression in tumor cells and reduce unwanted toxicity in healthy cells; this vector was guided by a magnet to the tumor tissue. Magnetic nanoparticles (MNPs), chitosan (CS), and the pHRE-Luc plasmid with a hypoxia-inducible promoter were used to synthesize the vector called "Magnetogene nanoparticles" by ionic gelation. The hypoxic functionality of Magnetogene vector nanoparticles was confirmed in the B16F10 cell line by measuring the expression of the luciferase reporter gene under hypoxic and normoxic conditions. Also, the efficiency of the Magnetogene vector was confirmed in vivo. Magnetogene was administered by intravenous injection (IV) in the tail vein and directed through an external magnetic field at the site of tumor growth in C57Bl/6 mice. A Magnetogene vector with a size of 50 to 70 nm was directed and retained at the tumor area and gene expression was higher at the tumor site than in the others tissues, confirming the selectivity of this vector towards hypoxic tumor areas. This nanosystem, that we called the "Magnetogene vector" for systemic delivery and specific gene expression in hypoxic tumors controlled by an external magnetic designed to target hypoxic regions of tumors, can be used for cancer-specific gene therapies.
RESUMO
BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) represents one of the principal tumors of the head and neck. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) are considered risk factors for the development and the clinical prognosis of LSCC. High levels of p16INK4a are suggested as a surrogate marker of HPV or EBV infection in some head and neck tumors but in LSCC is still controversial. Furthermore, pRb expression may be considered an additional biomarker but it has not been clearly defined. This work aimed to compare the expression of pRb and p16INK4a as possible biomarkers in tumor tissues with and without infection by EBV or different genotypes of HPV from patients with LSCC. METHODS: Tumor samples from 103 patients with LSCC were previously investigated for the presence and genotypes of HPV using the INNO-LiPA line probe assay and for the infection of EBV by qPCR. p16 INK4a and pRb expression was assessed by immunohistochemistry. RESULTS: Of the 103 tumor samples, expression of p16INK4a was positive in 55 (53.4%) and of this, 32 (56.1%) were positive for HPV whereas 11 (39.3%) were EBV positive but both without a significantly difference (p > 0.05). pRb expression was positive in 78 (75.7%) and a higher frequency of this expression was observed in HPV negative samples (87.0%) (p = 0.021) and in high-risk HPV negative samples (85.2%) (p = 0.010). No difference was observed when comparing pRb expression and EBV infection status (p > 0.05). CONCLUSION: Our results support the suggestion that p16INK4a is not a reliable surrogate marker for identifying HPV or EBV infection in LSCC. On the other hand, most of our samples had pRb expression, which was more frequent in tumors without HPV, suggesting that pRb could indicate HPV negativity. However, more studies with a larger number of cases are required, including controls without LSCC and evaluating other molecular markers to determine the real role of p16INK4a and pRb in LSCC.
RESUMO
INTRODUCTION: Tuberculosis (TB) is a re-emerging disease considered a public health concern. In the present study, we analyzed the epidemiology and drug resistance of Mycobacterium tuberculosis strains isolated from patients with pulmonary TB. METHODOLOGY: Mycobacterium tuberculosis isolates (n = 190) were obtained from patients with pulmonary TB admitted to Dr. José Eleuterio González University Hospital (UH). Each M. tuberculosis isolate was analyzed by spoligotyping (spacer oligonucleotide typing) and MIRU-VNTR (Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeat). Drug resistance was evaluated using the Anyplex™ II MTB/MDR/XDR assay. RESULTS: The predominant spoligotypes observed were X1 (SIT 119, n = 46), T1 (SIT 53, n = 40), H3 (SIT 50, n = 13), Beijing (SIT 1, n = 11), and EAI2-Manila (SIT 19, n = 8). MIRU-VNTR analysis showed that the locus QUB-26 had the highest allelic variability. The observed drug resistance included monoresistance to rifampicin (2.6%; n = 5), isoniazid (3.2%; n = 6), and fluoroquinolones (1.6%; n = 3) as well as multidrug resistance (5.3%; n = 10). All of the Beijing strains were susceptible. Regarding comorbidities, 13.7% (26/190) of the patients were co-infected with TB and HIV (TB+HIV+), and 31.6% (55/190) had TB along with diabetes (TB + diabetes). CONCLUSIONS: The most prevalent lineages were X1 (SIT 119; 24.3%) and T1 (SIT 53; 21%). An alarming proportion (12.6%) of M. tuberculosis isolates presented drug resistance. To effectively manage TB, continuous surveillance of regional strain dissemination, drug resistance profiles, and TB-associated comorbidities is crucial.
Assuntos
Diabetes Mellitus , Infecções por HIV , Mycobacterium tuberculosis , Tuberculose Pulmonar , Humanos , Mycobacterium tuberculosis/genética , Epidemiologia Molecular , México/epidemiologia , Centros de Atenção Terciária , Filipinas , Tuberculose Pulmonar/epidemiologia , Resistência a MedicamentosRESUMO
Plant-associated microorganisms represent a potential source of new antitumor compounds. The aim of the present study was to isolate endophytic and rhizosphere Gram-positive bacteria from Ibervillea sonorae and produce extracts with antitumor activity. Methanol and ethyl acetate extracts were obtained from 28 d bacterial fermentation, after which murine L5178Y-R lymphoma cells growth inhibition was evaluated at concentrations ranging from 15.62 µg/mL to 500 µg/mL by the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide reduction colorimetric assay. IC50 and the selectivity index (SI) were calculated and compared with healthy control human peripheral blood mononuclear cells (PBMC). Identification of the isolated strains was performed using the 16S ribosomal gene and by MALDI-TOF MS mass spectrometry. The endophytic and rhizosphere bacterial extracts from strains ISE-B22, ISE-B26, ISE-B27, ISS-A01, ISS-A06, and ISS-A16 showed significant (p < 0.05) L5178Y-R cell growth inhibition, compared with an untreated control. The rhizosphere Micromonospora echinospora isolate ISS-A16 showed the highest (90.48%) percentage of lymphoma cells growth inhibition and SI (19.1) for PBMC, whereas the Bacillus subtilis ISE-B26 isolate caused significant (p < 0.01) growth inhibition (84.32%) and a SI of 5.2. Taken together, results of the present study evidenced antitumor effects by I. sonorae endophytic and rhizosphere bacteria culture extracts. Further research will involve the elucidation of the compounds that exert the antitumor activity and their evaluation in pre-clinical studies.
Assuntos
Cucurbitaceae , Rizosfera , Animais , Bactérias , Bactérias Gram-Positivas , Humanos , Leucócitos Mononucleares , CamundongosRESUMO
Arsenic is considered a worldwide pollutant that can be present in drinking water. Arsenic exposure is associated with various diseases, including cancer. Antioxidants as selenite and α-tocopherol-succinate have been shown to modulate arsenic toxic effects. Since changes in STAT3 and PSMD10 gene expression have been associated with carcinogenesis, the aim of this study was to evaluate the effect of arsenic exposure and co-treatments with selenite or α-tocopherol-succinate on the expression of these genes, in the livers of chronically exposed Syrian golden hamsters. Animals were divided into six groups: (i) control, (ii) chronically treated with 100 ppm arsenic, (iii) treated with 6 ppm α-tocopherol-succinate (α-TOS), (iv) treated with 8.5 ppm selenite, (v) treated with arsenic + α-TOS, and (vi) treated with arsenic + selenite. Urine samples and livers were collected after 20 weeks of continuous exposure. The urine samples were analyzed for arsenic species by atomic absorption spectrophotometry, and real-time RT-qPCR analysis was performed for gene expression evaluation. A reduction in STAT3 expression was observed in the selenite-treated group. No differences in PSMD10 expression were found among groups. Histopathological analysis revealed hepatic lymphocytosis in selenite-treated animals. As a conclusion, long-term exposure to arsenic does not significantly alter the expression of STAT3 and PSMD10 oncogenes in the livers of hamsters; however, selenite down-regulates STAT3 expression and provokes lymphocytosis.
Assuntos
Antioxidantes/farmacologia , Arsênio/efeitos adversos , Fígado/efeitos dos fármacos , Linfocitose/induzido quimicamente , Fator de Transcrição STAT3/genética , Ácido Selenioso/farmacologia , Administração Oral , Animais , Antioxidantes/administração & dosagem , Arsênio/administração & dosagem , Arsênio/urina , Regulação para Baixo/efeitos dos fármacos , Estimativa de Kaplan-Meier , Fígado/patologia , Masculino , Mesocricetus , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Fator de Transcrição STAT3/metabolismo , Ácido Selenioso/administração & dosagem , Aumento de Peso/efeitos dos fármacos , alfa-Tocoferol/farmacologia , alfa-Tocoferol/uso terapêuticoRESUMO
Endophytic fungi have become potential sources of antitumor agents, particularly against antineoplastic-resistant cancer cells, with marginal or nil adverse effects for the oncological patient. Endophytic fungi were isolated from stems of the Lophocereus marginatus cactus, commonly found in Mexico. Methanol extracts were then obtained from fungus liquid cultures and their effects on tumor cell growth against murine lymphoma (L5178Y-R), human colorectal adenocarcinoma (HT-29), and human breast cancer (MCF-7) cells were evaluated at concentrations ranging from 31 µg/mL to 250 µg/mL via the colorimetric 3- [4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide reduction assay, using monkey kidney epithelial (MA-104) and human peripheral mononuclear (PBMC) cells as controls. Furthermore, we obtained the IC50 and the selectivity index (SI) was calculated from the IC50 ratio of normal and tumor cells. In addition, molecular identification of fungi showing cytotoxic activity was determined, using internal transcribed spacer molecular markers. PME-H001, PME-H002, PME-H005, PME-H007, and PME-H008 filamentous fungus strain extracts showed significant (p < 0.05) tumor cell growth inhibition. In particular, they significantly (p < 0.05) inhibited L5178Y-R cell growth, whereas the least susceptible cell line was HT-29. The endophytic strain PME-H008 of Cladosporium sp. caused the highest growth inhibition percentage against L5178Y-R and HT-29 cells with 96.6% (p < 0.01) and 42.5% (p < 0.05) respectively, and the highest SIs against L5178Y-R cells with 2.4 and 2.9 for MA-104 and PBMCs, respectively, whereas the PME-H005 extract showed SIs of 2.77 and 1.5 against MCF-7 and L5178Y-R cells, respectively, as compared with PBMCs. In addition, the endophytic strain PME-H007 of Metarhizium anisopliae caused the highest percentage of growth inhibition (p < 0.01) against MCF-7 cells with 55.8% at 250 µg/mL. We demonstrated in vitro antitumor effects of L. marginatus endophytic fungi. Further research will involve the isolation and in vivo testing of bioactive compounds.
Assuntos
Cactaceae , Endófitos , Animais , Fungos , Humanos , Leucócitos Mononucleares , Camundongos , Extratos Vegetais/toxicidadeRESUMO
Equine infectious anemia (EIA) is a highly infectious disease in members of the Equidae family, caused by equine infectious anemia virus (EIAV). The disease severity ranges from subclinical to acute or chronic, and causes significant economic losses in the equine industry worldwide. Serologic tests for detection of EIAV infection have some concerns given the prolonged seroconversion time. Therefore, molecular methods are needed to improve surveillance programs for this disease. We attempted detection of EIAV in 6 clinical and 42 non-clinical horses in Nuevo Leon State, Mexico, using the agar gel immunodiffusion (AGID) test for antibody detection, and nested and hemi-nested PCR for detection of proviral DNA. We found that 6 of 6, 5 of 6, and 6 of 6 clinical horses were positive by AGID, nested PCR, and hemi-nested PCR, respectively, whereas 0 of 42, 1 of 42, and 9 of 42 non-clinical horses were positive by these tests, respectively. BLAST analysis of the 203-bp 5'-LTR/tat segment of PCR product revealed 83-93% identity with EIAV isolates in GenBank and reference strains from other countries. By phylogenetic analysis, our Mexican samples were grouped in a different clade than other sequences reported worldwide, indicating that the LRT/tat region represents an important target for the detection of non-clinical horses.
Assuntos
Anemia Infecciosa Equina/diagnóstico , Vírus da Anemia Infecciosa Equina/isolamento & purificação , Animais , Anemia Infecciosa Equina/epidemiologia , Anemia Infecciosa Equina/virologia , Feminino , Cavalos , Masculino , México/epidemiologia , Filogenia , Reação em Cadeia da Polimerase/veterinária , Prevalência , Testes Sorológicos/veterináriaRESUMO
Contact with stinging spines venom from several Lepidoptera larvae may result in skin lesions. In Mexico, envenomation outbreaks caused by Megalopyge opercularis were reported between 2015 and 2016. The aim of this study was to identify the venomous caterpillars in Nuevo Leon, Mexico and evaluate several biological activities of their hemolymph (HEV) and spine setae (SSV) venoms. M. opercularis was identified by cytochrome oxidase subunit (COI) designed primers. HEV and SSV extracts cytotoxic activity was assessed on the L5178Y-R lymphoma cell line. For apoptotic cells number and apoptosis, cells were stained with acridine orange/ethidium bromide and validated by DNA fragmentation. Human peripheral blood mononuclear cells (hPBMC) cytokine response to the extracts was measured by the cytometric bead array assay. Extracts effect on pro-coagulation activity on human plasma was also evaluated. HEV and SSV extracts significantly inhibited (p < 0.01) up to 63% L5178Y-R tumor cell growth at 125-500 µg/mL, as compared with 43% of Vincristine. About 79% extracts-treated tumor cells death was caused by apoptosis. Extracts stimulated (p < 0.01) up to 60% proliferation of resident murine lymphocytes, upregulated IL-1ß, IL-6, IL-8, and TNF-α production by hPBMC, and showed potent pro-coagulant effects. The pharmacological relevance of these venoms is discussed.