Role of Genetic Ancestry in Oropharyngeal Squamous-Cell Carcinoma: A Cross-Sectional Study in Brazil

Background: HPV infection represents an important etiologic factor for Oropharyngeal Squamous Cell Carcinoma (OPSCC). The different ethnic backgrounds could be related to different susceptibility to Human Papillomavirus (HPV). The aim of our study was to assess the whole of genetic ancestry in HPV status in OPSCC patients. Methods: We conducted a cross-sectional study on patients with OPSCC admitted to the Barretos Cancer Hospital, Brazil from 2014 to 2019. Of these, DNA extraction was performed on 40 patients and genetic ancestry was assessed using a specific panel of 46 informative ancestry markers. Results: We observed a predominance of European ancestry (63%), followed by African (18%), Amerindian (9%) and Asian (8%) both in the OPSCC HPV-positive and HPV-negative group. We did not find any statistically significant differences between the HPV-positive and HPV-negative OPSCC groups in relation to European (p = 0.499), African (p = 0.448), Asian (p = 0.275) or Amerindian (p = 0.836) ancestry. Conclusions: We found a predominance of European ancestry, both in the HPV-positive and HPV-negative groups. In our study, we did not find statistically significant differences between HPV-positive or HPV-negative groups in relation to ancestry.

Serrated pathway in colorectal carcinogenesis

Serrated adenocarcinoma is a recently described subset of colorectal cancer(CRC),which account for about10%of all CRCs and follows an alternative pathway in which serrated polyps replace the traditional adenoma as the precursor lesion to CRC.Serrated polyps form a heterogeneous group of colorectal lesions that includes hyperplastic polyps(HPs),sessile serrated adenoma(SSA),traditional serrated adenoma(TSA)and mixed polyps.HPs are the most common serrated polyp followed by SSA and TSA.This distinct histogenesis is believed to have a major influence in prevention strategies,patient prognosis and therapeutic impact.Genetically,serrated polyps exhibited also a distinct pattern,with KRAS and BRAF having an important contribution to its development.Two other molecular changes that have been implicated in the serrated pathway include microsatellite instability and the CpG island methylator phenotype.In the present review we will address the current knowledge of serrated polyps,clinical pathological features and will update the most recent findings of its molecular pathways.The understanding of their biology and malignancy potential is imperative to implement a surveillance approach in order to prevent colorectal cancer development.

Characterization of monocarboxylate transporter activity in hepatocellular carcinoma

AIM: To assess the immunoexpression of hypoxia-related markers in samples from cirrhosis and primary and metastatic hepatocellular carcinoma (HCC).

Role of endoglin and VEGF family expression in colorectal cancer prognosis and anti-angiogenic therapies

Colorectal cancer(CRC)is one of the cancer models and most of the carcinogenic steps are presently well understood.Therefore,successful preventive measures are currently used in medical practice.However,CRC is still an important public health problem as it is the third most common cancer and the fourth most frequent cause of cancer death worldwide.Nowadays,pathologic stage is a unique and well-recognized prognostic indicator,however,more accurate indicators of the biologic behavior of CRC are expected to improve the specificity of medical treatment.Angiogenesis plays an important role in the growth and progression of cancer but its role as a prognostic factor is still controversial.Probably the most important clinical implication of tumor angiogenesis is the development of anti-angiogenic therapy.The goal of this review is to critically evaluate the role of angiogenic markers,assessed by either endoglin-related microvessel density or expression of vascular endothelial growth factor family members in the CRC setting and discuss the role of these angiogenic markers in antiangiogenic therapies.

Relationship between Fusobacterium nucleatum,inflammatory mediators and microRNAs in colorectal carcinogenesis

AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4.

ID7 Isolated from Bauhinia variegata Stem Inhibits Tumor Progression and Metastatic Mechanisms of Triple Negative Breast Cancer in Vivo

Background:The breast cancer has been the most common form of cancer among women.The triple negative subtype represents 20%of all breast cancer cases in the world and is standing out by affecting young women and being aggressive.The main cause of death of patients with cancer is due to metastasis,which can reach the liver and lungs.Objective:The activities of ID7 fraction of the stems of Bauhinia variegata L.on breast cancer,lung metastasis and liver inflammatory process were evaluated.Method:ID7 was characterized by mass-spectrometry.The viability of murine mammary cells(4T1)treated with ID7 was assessed by MTT,trypan blue and fluorescence assay and viability of BT-20,MDA-MB-231 and MCF-7 human breast cancer tumor lines by MTS.The cell migration,invasion using matrigel and adhesion were performed.The expression of cell death proteins was quanitified by western blot and the gelatinases by zimogram.The ID7 activity of the tumor(4T1)and metastatic progession in vivo was evaluated.Results:ID7 reduced the 4T1 and MDA-MB-231viability and increased the late apoptosis,inhibited the 4T1 migration and invasion,increased the 4T1 adhesion and decreased the secreted active gelatinases.ID7 also increased the expression of PARP,caspase-7 and caspase-8,RIP and TNF-R1.In vivo,the ID7 decreased the volume and weight of the tumors and decreased lung metastasis and inflammation in the liver.The characterization showed mainly the presence of oleic acid,myricetin,quercetin and kaempferol in ID7.Conclusion:Thus,it was found that ID7 fraction exhibits selective antitumor and on the mechanisms of breast cancer metastasis activity,preventing lung metastasis and inflammation in the liver.It is suggested that fatty acids and flavonoids are correlated with such activities.

HPV Vaccination in Young Girls from Developing Countries: What Are the Barriers for Its Implementation? A Systematic Review

Cervical cancer is the second most common cancer in women living in developing countries that account high HPV incidence and mortality rates. Vaccinating girls between 9 and 14 years old is supposed to be the most cost-effective public health approach against cervical cancer. This systematic review aims to assess the application and coverage of the HPV vaccine in developing countries and identify the main challenges for the introduction of the vaccine in these settings. Eligible studies were selected according to the defined inclusion and exclusion criteria. To determine the quality of the studies was employed the STROBE checklist. This review included seven studies, encompassing the analysis of 19 countries and 112,116 girls aged from 9 to 18 years old. The coverage of HPV vaccination ranged from 13.8% to 107.4%, with most of the programs having more than 60% of coverage, which reflects a high percentage of vaccinated girls. The main challenges were lack of knowledge and worries about the vaccine, insufficient financial resources and staff workers, lack of community involvement and dissemination of important information about HPV. In developing countries that implemented the HPV vaccine, high coverage rates were achieved, despite sociocultural, economic and political challenges. In the future, studies that analyze the coverage rates after the elimination of the barriers and the repercussions on the mortality rates should be conducted, so that more developing countries have the opportunity to efficiently implement the vaccine.

Alpha Defensins Genes and Vulvovaginal Candidiasis:A Study of Cases

Objective: To evaluate the alpha-defensin (α-DF) genes polymorphism in women with vulvovaginal candidiasis and recurrence. Methods: This observational study included clinical vaginal secretion samples collected over four years from 88 women, ranging in age from 18 to 65 years, from medical centers of Sao Paulo and Mogi das Cruzes, Brazil. Thirty-six of these women were asymptomatic (control group) and 52 presented clinical condition compatible with vulvovaginitis (38 primary or episodic as non-recurrent forms, and 14 recurrent vulvovaginal candidiasis). A portion of each sample was plated on Sabouraud dextrose agar with chloramphenicol and grown on CHROMagar Candida for presumptive characterization. The identification of the species was obtained by sequencing of the ITS1 region of rDNA. α-DF genes were amplified for subsequent evaluation of polymorphisms by endonuclease restriction assay. Results: From 88 samples were isolated 60 Candida albicans and 28 non-albicans Candida spp. Resistant C. albicans strains and non-albicans Candida spp. were more prevalent in recurrence. In all groups, the number of resistant non-albicans Candida spp. was most high than susceptible strains. α-DF1, α-DF3 and α-DF1/α-DF3 genotypes were found in 32 (36.4%), 17 (19.3%), 6 (6.8%) vaginal samples, respectively. About 33 samples were not amplified. Recurrence and severe disease were more observed in homozygous population. Conclusions: Non-albicans Candida spp. and homozygotic α-DF genotipes (α-DF1 and α-DF3) were more related with severe clinical signs and recurrence. Further studies about vulvovaginal candidiasis and α-DF genes are necessary to access the more comprehensive role of defensins in clinical manifestations.

SERS sensing for cancer biomarker:Approaches and directions

These days,cancer is thought to be more than just one illness,with several complex subtypes that require different screening approaches.These subtypes can be distinguished by the distinct markings left by metabolites,proteins,miRNA,and DNA.Personalized illness management may be possible if cancer is categorized according to its biomarkers.In order to stop cancer from spreading and posing a significant risk to patient survival,early detection and prompt treatment are essential.Traditional cancer screening techniques are tedious,time-consuming,and require expert personnel for analysis.This has led scientists to reevaluate screening methodologies and make use of emerging technologies to achieve better results.Using time and money saving techniques,these methodologies integrate the procedures from sample preparation to detection in small devices with high accuracy and sensitivity.With its proven potential for biomedical use,surface-enhanced Raman scattering(SERS)has been widely used in biosensing applications,particularly in biomarker identification.Consideration was given especially to the potential of SERS as a portable clinical diagnostic tool.The approaches to SERS-based sensing technologies for both invasive and non-invasive samples are reviewed in this article,along with sample preparation techniques and obstacles.Aside from these significant constraints in the detection approach and techniques,the review also takes into account the complexity of biological fluids,the availability of biomarkers,and their sensitivity and selectivity,which are generally lowered.Massive ways to maintain sensing capabilities in clinical samples are being developed recently to get over this restriction.SERS is known to be a reliable diagnostic method for treatment judgments.Nonetheless,there is still room for advancement in terms of portability,creation of diagnostic apps,and interdisciplinary AI-based applications.Therefore,we will outline the current state of technological maturity for SERS-based cancer biomarker detection in this article.The review will meet the demand for reviewing various sample types(invasive and non-invasive)of cancer biomarkers and their detection using SERS.It will also shed light on the growing body of research on portable methods for clinical application and quick cancer detection.

Gastric cancer treated with pressurized intraperitoneal aerosol chemotherapy:revising an option for peritoneal carcinomatosis

Aim:Gastric cancer is the cancer with the highest rate of peritoneal metastization and this type of spread is associated with a higher death rate compared to dista nt orga n metastasis.The systemic chemotherapy has a mini mal effect in peritoneal metastasis so new types of treatment have emerged.The authors revised the main studies done in pressurized in traperit on eal aerosol chemotherapy(PIPAC)and prese nted the main con clusi ons.Methods:A PubMed search was con ducted focus ing on PIPAC in gastric can cer.The MeSH database was searched with the terms:"Gastric can cer[MeSH]and in traperit on eal aerosol chemotherapy".Results:Seve n studies were an alyzed.All the studies performed the tech nique with aerosol of doxorubic in and cisplat in.All cases were well tolerated,with minor adverse effects.Patients presented resolution of their abdominal symptoms and regression of macroscopic carcinomatosis.Cytoreductive surgery or hypertermic intraperitoneal chemotherapy could be performed in some patients with good response to PIPAC.The peritonitis caused by the chemotherapy was well tolerated.Conclusion:PIPAC can induce remission in end-stage and resistant disease with acceptable side effects,good safety levels for patients and health professionals,and quality of life improvement.