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Escherichia coli has been associated with the induction of colorectal cancer (CRC). Thus, combined therapy incorporating usnic acid (UA) and antibiotics such as ceftazidime (CAZ), co-encapsulated in liposomes, could be an alternative. Coating the liposomes with chitosan (Chi) could facilitate the oral administration of this nanocarrier. Liposomes were prepared using the lipid film hydration method, followed by sonication and chitosan coating via the drip technique. Characterization included particle size, polydispersity index, zeta potential, pH, encapsulation efficiency, and physicochemical analyses. The minimum inhibitory concentration and minimum bactericidal concentration were determined against E. coli ATCC 25922, NCTC 13846, and H10407 using the microdilution method. Antibiofilm assays were conducted using the crystal violet method. The liposomes exhibited sizes ranging from 116.5 ± 5.3 to 240.3 ± 3.5 nm and zeta potentials between +16.4 ± 0.6 and +28 ± 0.8 mV. The encapsulation efficiencies were 51.5 ± 0.2% for CAZ and 99.94 ± 0.1% for UA. Lipo-CAZ-Chi and Lipo-UA-Chi exhibited antibacterial activity, inhibited biofilm formation, and preformed biofilms of E. coli. The Lipo-CAZ-UA-Chi and Lipo-CAZ-Chi + Lipo-UA-Chi formulations showed enhanced activities, potentially due to co-encapsulation or combination effects. These findings suggest potential for in vivo oral administration in future antibacterial and antibiofilm therapies against CRC-inducing bacteria.

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Gastric cancer has been demonstrating a reduction in the number of cases over the past decades, largely attributed to advancements in public health practices and increased accessibility to educational initiatives for the general population. Nevertheless, it persists as the third leading cause of mortality globally among both men and women. These fatalities are typically associated with delayed disease detection. The current study assessed the levels of homocysteine, vitamin B12, and folic acid as a means of establishing a screening biomarker profile that could be integrated into routine testing protocols to facilitate swift diagnosis of the illness. A total of 207 control subjects and 207 individuals with gastric cancer were scrutinized, with biochemical measurements conducted using chemiluminescence for homocysteine, folic acid, and vitamin B12. The two groups were matched based on age, tumor location, subtype, tumor classification, presence of Epstein-Barr Virus infection (EBV), and Helicobacter pylori (H. pylori). Significant statistical variances were identified in the mean levels of the triad of substances among cancer patients when compared to the control group for all corresponding variables. In conclusion, our study indicated that analyzing the triad of homocysteine, vitamin B12, and folic acid holds diagnostic value for gastric cancer and could potentially serve as an effective screening marker for this type of cancer in the future.

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Thyroid hormone has been shown to have both tumor-promoting and tumor-suppressing actions, which has led to significant debate over its involvement in the development of cancer. Proliferation, apoptosis, invasiveness, and angiogenesis are all aspects of cancer that are affected by the thyroid hormones T3 and T4, according to research conducted in animal models and in vitro experiments. The effects of thyroid hormones on cancer cells are mediated by many non-genomic mechanisms, one of which involves the activation of the plasma membrane receptor integrin αvß3. Typically, abnormal amounts of thyroid hormones are linked to a higher occurrence of cancer. Both benign and malignant thyroid disorders were found to be associated with an increased risk of extra-thyroidal malignancies, specifically colon, breast, prostate, melanoma, and lung cancers. The purpose of this review was to shed light on this link to define which types of cancer are sensitive to thyroid hormones and, as a result, are anticipated to respond favorably to treatment of the thyroid hormone axis.

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BACKGROUND: Peripheral blood analysis is a non-invasive and low-cost technique of prognostic value for several diseases, including oral cancer. Considering the role of inducible nitric oxide synthase in tumor-associated inflammation, this study purposed to evaluate the influence of this enzyme on peripheral blood parameters and systemic inflammatory biomarkers during murine oral carcinogenesis. METHODS: A 50 µg/mL solution of 4-nitroquinoleine-N-oxide was provided to 15 C57BL/6J (Nos2+/+ ) and 16 B6.129P2-Nos2tm1Lau /J (Nos2-/- ) for 16 weeks. Animals were followed for 8 weeks after treatment. Blood samples and tongues were collected for hematological and histopathological analyses. Red blood cells, white blood cells, and platelet cell parameters were analyzed. The neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the systemic immune-inflammation index were also calculated. The depth of invasion of all carcinomas was measured. RESULTS: Differences were found in several blood parameters. The depth of invasion in Nos2-/- was lower than in Nos2+/+ (p = 0.009), and strong correlations were found between depth of invasion and neutrophil count (ρ = -0.68, p = 0.017), lymphocyte count (ρ = 0.72, p = 0.011), neutrophil-to-lymphocyte ratio (ρ = -0.65, p = 0.025), platelet-to-lymphocyte ratio (ρ = -0.73, p = 0.013), and systemic immune-inflammation index (ρ = -0.67, p = 0.037) in Nos2-/- mice. CONCLUSION: Inducible nitric oxide synthase seems to have an important role in OSCC invasion and progression, which might be associated to alterations in immune-inflammatory cell dynamics evidenced by peripheral blood and systemic inflammatory biomarkers.

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Gastric adenocarcinoma is a complex disease with diverse genetic modifications, including Anaplastic Lymphoma Kinase (ALK) gene changes. The ALK gene is located on chromosome 2p23 and encodes a receptor tyrosine kinase that plays a crucial role in embryonic development and cellular differentiation. ALK alterations can result from gene fusion, mutation, amplification, or overexpression in gastric adenocarcinoma. Fusion occurs when the ALK gene fuses with another gene, resulting in a chimeric protein with constitutive kinase activity and promoting oncogenesis. ALK mutations are less common but can also result in the activation of ALK signaling pathways. Targeted therapies for ALK variations in gastric adenocarcinoma have been developed, including ALK inhibitors that have shown promising results in pre-clinical studies. Future studies are needed to elucidate the ALK role in gastric cancer and to identify predictive biomarkers to improve patient selection for targeted therapy. Overall, ALK alterations are a relevant biomarker for gastric adenocarcinoma treatment and targeted therapies for ALK may improve patients' overall survival.

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Dioclea violacea seed mannose-binding lectin (DvL) has attracted considerable attention because of its interesting biological activities, including antitumor, antioxidant, and anti-inflammatory activities. This study evaluated the cytotoxic effect of DvL on tumor and normal cells using the mitochondrial activity reduction (MTT) assay, the carcinogenic and anti-carcinogenic activity by the epithelial tumor test (ETT) in Drosophila melanogaster, and the anti-angiogenic effect by the chick embryo chorioallantoic membrane (CAM) assay. Data demonstrated that DvL promoted strong selective cytotoxicity against tumor cell lines, especially A549 and S180 cells, whereas normal cell lines were weakly affected. Furthermore, DvL did not promote carcinogenesis in D. melanogaster at any concentration tested, but modulated DXR-induced carcinogenesis at the highest concentrations tested. In the CAM and immunohistochemical assays, DvL inhibited sarcoma 180-induced angiogenesis and promoted the reduction of VEGF and TGF-ß levels at all concentrations tested. Therefore, our results demonstrated that DvL is a potent anticancer, anti-angiogenic, and selective cytotoxic agent for tumor cells, suggesting its potential application as a prototype molecule for the development of new drugs with chemoprotective and/or antitumor effects.

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AIMS: The developmental Origins of Health and Disease (DOHaD) concept has provided the framework to assess how early life experiences can shape health and disease throughout the life course. Using a model of maternal exposure to a low protein diet (LPD; 6% protein) during the gestational and lactational periods, we demonstrated changes in the ventral prostate (VP) transcriptomic landscape in young rats exposed to maternal malnutrition. Male offspring Sprague Dawley rats were submitted to maternal malnutrition during gestation and lactation, and they were weighed, and distance anogenital was measured, followed were euthanized by an overdose of anesthesia at 21 postnatal days. Next, the blood and the ventral prostate (VP) were collected and processed by morphological analysis, biochemical and molecular analyses. RNA-seq analysis identified 411 differentially expressed genes (DEGs) in the VP of maternally malnourished offspring compared to the control group. The molecular pathways enriched by these DEGs are related to cellular development, differentiation, and tissue morphogenesis, all of them involved in both normal prostate development and carcinogenesis. Abcg1 was commonly deregulated in young and old maternally malnourished offspring rats, as well in rodent models of prostate cancer (PCa) and in PCa patients. Our results described ABCG1 as a potential DOHaD gene associated with perturbation of prostate developmental biology with long-lasting effects on carcinogenesis in old offspring rats. A better understanding of these mechanisms may help with the discussion of preventive strategies against early life origins of non-communicable chronic diseases.

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ABSTRACT Background: Recently, significant associations between non-alcoholic fatty liver disease (NAFLD) and extra-hepatic cancer have been reported. Objective: To carry out a comprehensive review of the current evidence in the literature on the association between NAFLD and extra-hepatic cancer. Methods: A narrative literature review was performed through an online search for the MeSH terms "fatty liver" and "cancer" in MEDLINE (via PubMed) and LILACS (via BVS). Original studies that described the impact of NAFLD on different types of extra-hepatic malignancies were included. Results: After careful analysis, nine prospective cohort studies, one retrospective cohort study, three case-control studies, and three cross-sectional studies were selected. Conclusion: There is consistent evidence on the association between NAFLD and extra-hepatic carcinogenesis, especially in relation to colorectal, gastric, pancreatic, breast, prostate, and bladder cancers.

RESUMO Contexto: Recentemente, associações significativas entre a doença hepática gordurosna não-alcoólica (DHGNA) e neoplasias extra-hepáticas têm sido descritas. Objetivo: Realizar uma revisão abrangente acerca das evidências atuais na literatura sobre a associação entre DHGNA e neoplasias extra-hepáticas. Métodos: Uma revisão narrativa de literatura foi realizada através da busca on-line pelos descritores "fígado gorduroso" e "câncer" em MEDLINE (através do PubMed) e LILACS (através da BVS). Estudos originais que descreveram o impacto da DHGNA em diferentes tipos de neoplasias malignas extra-hepáticas foram incluídos. Resultados: Após análise criteriosa, nove estudos prospectivos de coorte, um coorte histórica, três estudos de caso-controle, e três estudos transversais foram selecionados. Conclusão: Existem evidências consistentes a respeito da associação entre DHGNA e a carcinogênese extra-hepática, especialmente em relação aos cânceres de cólon e reto, estômago, pâncreas, mama, próstata e bexiga.

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Abstract Objective To report the prevalence of malignant transformation of vulvar lichen sclerosus (VLS) and possible risk factors. Methods This is a cohort study with data analysis from medical records of 138 patients with histological diagnosis of VLS registered at the Vulvar Pathology Outpatient Clinic of the University Hospital, between 2007 and 2017. Predominance of risk factors was performed using logistic regression analysis. The variables studied were the length of follow-up, age, regular or irregular follow up; presence of symptoms (dyspareunia, pruritus and/or vulvar burning); histology characteristics, the presence of epithelial hyperplasia; and the presence of autoimmune diseases. Results There were 138 patients included in the study, and among them five progressed to malignant transformation. The patients had a median age of 59 years and 83% were symptomatic. The most frequent symptom was itching with 72%. Autoimmune diseases were present in 11.6%, the most prevalent being thyroid disease. All five case of malignant transformation (0.6%) had an irregular follow up. The logistic regression analysis was used among the studied variables, and no statistical significance was found among them (p ≥ 0.05). The relationship between hyperplasia and the clinical outcome of malignant transformation, in which non-significant but acceptable p value close to 0.05 was observed. Conclusion The prevalence of malignant transformation in patients with VLS was 0.6%, and common factors were the lack of adherence to medical treatments and the loss of follow-up.

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Objetivo: Describir el desarrollo de un carcinoma oral de células escamosas, en el que la irritación mecánica crónica aparenta tomar un rol protagonista en la carcinogénesis. Caso clínico: Un paciente de 41 años de edad, argen- tino, con antecedentes de fisura labio alvéolo palatina, diabe- tes mellitus, convulsiones, consumo de cocaína y marihuana, enolismo crónico y tabaquismo, acude al Servicio de Odonto- logía del Hospital Central de Mendoza para la evaluación de una úlcera dolorosa en el dorso de su lengua, de varias sema- nas de evolución, en íntima relación con un primer premolar superior derecho y una pieza supernumeraria. Se realizó una biopsia y de la anatomía patológica resultó el diagnóstico de carcinoma oral de células escamosas. Se ofreció al paciente posibles tratamientos que rechazó, por lo que se inició terapia paliativa y sintomática. Al avanzar su mal estado general, fa- lleció por complicaciones relacionadas a la deglución. Si bien no está definido el rol de la irritación mecánica crónica en la etiología de la carcinogénesis, ejerce un efecto promotor del daño causado por el tabaco y el alcohol. Si bien el paciente era fumador y bebía alcohol, se puede observar que desarrolló un carcinoma de células escamosas en evidente relación a un trauma crónico, ya que la lesión en la cara dorsal de lengua está en íntimo contacto con el factor irritante. Aun así, la evi- dencia actual disponible es limitada y discute el protagonismo del trauma crónico por lo que se necesitan más estudios para evaluar y definir la posible relación causal de la irritación me- cánica crónica en la carcinogénesis (AU)

Aim: To describe the development of an oral squamous cell carcinoma, in which chronic mechanical irritation ap- pears to play a significant role in carcinogenesis. Clinical case: A 41-year-old patient, from Argenti- na, with a history of cleft lip and palate, diabetes mellitus, seizures, cocaine and cannabis use, chronic alcoholism and smoking, comes to the Dentistry Service of the Central Hospi- tal for the evaluation of a painful ulcer on the dorsum of the tongue, which had been developing for several weeks, in close relation to an upper right first premolar and a supernumerary tooth. A biopsy was performed, and the pathological anatomy resulted in the diagnosis of oral squamous cell carcinoma. Possible treatments were offered to the patient, which he re- jected, so palliative and symptomatic therapy was initiated instead. As his poor general condition progressed, he died due to complications related to swallowing. Although the role of chronic mechanical irritation in the development of carcino- genesis is not yet fully defined, it has been shown to have a promoting effect on the damage caused by tobacco and alco- hol. Although the patient was a smoker and drank alcohol, it can be observed that he developed a squamous cell carcinoma in obvious relation to a chronic trauma, since the lesion devel- ops on the dorsal face of the tongue in close contact with the irritant factor. Still, the current evidence available is limited and discusses the role of chronic trauma, so more studies are needed to evaluate and define the possible causal relation- ship of chronic mechanical irritation in the development of carcinogenesis (AU)

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