Enrique Boccardo

• MS, PhD
• Principal Investigator at University of São Paulo

Background High-risk human papillomaviruses are the causal agents of a subset of head and neck cancers. A previous transcriptomic analysis showed that cIAP2 protein, involved in cell survival and apoptosis, is upregulated in OKF6 oral cells that express HPV16 E6/E7. In addition, cIAP2 promotes radioresistance, a very important concern in HNC treatm...

Even though epidemiological studies suggest that tobacco smoking and high-risk human papillomavirus (HR-HPV) infection are mutually exclusive risk factors for developing head and neck cancer (HNC), a portion of subjects who develop this heterogeneous group of cancers are both HPV-positive and smokers. Both carcinogenic factors are associated with i...

Mycoplasma hominis can be isolated from the human urogenital tract. However, its interaction with the host remains poorly understood. In this study, we aimed to assess the effects of M. hominis infection on primary human keratinocytes (PHKs). Cells were quantified at different phases of the cell cycle. Proteins involved in cell cycle regulation and...

Infection with some mucosal human papillomavirus (HPV) types is the etiological cause of cervical cancer and of a significant fraction of vaginal, vulvar, anal, penile, and head and neck carcinomas. DNA repair machinery is essential for both HPV replication and tumor cells survival suggesting that cellular DNA repair machinery may play a dual role...

Cancer cell metabolism reprograming has been investigated for many years. What started with the idea that cancer cells had respiratory deficiencies and survived by adapting to use the glycolytic pathway, is understood today as a complex and dynamic set of changes in metabolic pathways that are influenced by intrinsic (mutations, oncogene activity)...

Epstein-Barr virus (EBV) is a herpesvirus associated with lymphoid and epithelial malignancies. Both B cells and epithelial cells are susceptible and permissive to EBV infection.However, considering that 90% of the human population is persistently EBV-infected, with a minority of them developing cancer, additional factors are necessary for tumor de...

It is suggested that HPV-18 variants from the A lineage have higher oncogenic potential compared to B variants. Some studies show uneven distribution of HPV-18 variants in cervical adenocarcinomas and squamous cell carcinomas. Regarding HPV-18 variants’ functions, the few studies reported focus on E6, and none were performed using natural host cell...

Human papillomavirus (HPV)-induced carcinogenesis comprises alterations in the expression and activity of matrix metalloproteinases (MMP) and their regulators. Reversion-inducing Cysteine-rich protein with Kazal motifs (RECK) inhibits the activation of specific metalloproteinases and its expression is frequently lost in human cancers. Here we analy...

A Correction to this paper has been published: https://doi.org/10.1038/s41419-021-03564-4

Malignant transformation involves an orchestrated rearrangement of cell cycle regulation mechanisms that must balance autonomic mitogenic impulses and deleterious oncogenic stress. Human papillomavirus (HPV) infection is highly prevalent in populations around the globe, whereas the incidence of cervical cancer is 0.15%. Since HPV infection primes c...

Introduction: The main risk factor for the development of cervical cancer (CC) is persistent infection by human papillomavirus (HPV) oncogenic types. In order to persist, HPV exhibits a plethora of immune evasion mechanisms. PI3/Elafin (Peptidase Inhibitor 3) is an endogenous serine protease inhibitor involved in epithelial protection against path...

Objectives To establish a straightforward single-cell passaging cultivation method that enables high-quality maintenance of human induced pluripotent stem cells without the appearance of karyotypic abnormalities or loss of pluripotency. Methods Cells were kept in culture for over 50 passages, following a structured chronogram of passage and monito...

A subset of oral carcinomas is etiologically related to high-risk human papillomavirus (HR-HPV) infection, with HPV16 being the most frequent HR-HPV type found in these carcinomas. The oncogenic role of HR-HPV is strongly dependent on the overexpression of E6 and E7 oncoproteins, which, in turn, induce p53 and pRb degradation, respectively. Additio...

supplementary material

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 19 (COVID-19), was declared pandemic by the World Health Organization in March 2020. SARS-CoV-2 binds its host cell receptor, angiotensin-converting enzyme 2 (ACE2), through the viral spike (S) protein. The mortality related to severe acute respiratory di...

BACKGROUND High-risk human papillomaviruses (HR-HPVs) are the etiological agents of cervical cancer. Among them, types 16 and 18 are the most prevalent worldwide. The HPV genome encodes three oncoproteins E5, E6 and E7 which have a high transformation potential in culture cells when transduced together. In the present study we analyzed how these on...

Vulvar intraepithelial neoplasia (VIN) is associated with human papillomavirus (HPV) infection. Curcumin is a natural bioactive compound with antineoplastic properties. The use of nanoparticles containing curcumin could allow a better performance of this compound in therapies. So, VIN biopsies were collected and HPV DNA detection was performed by P...

Background Human papillomavirus (HPV) infection is the central factor for cervical cancer, whereas epithelial immune mechanisms contribute to the progression of HPV infection and its associated lesions. The authors evaluated the expression of indoleamine 2,3‐dioxygenase (IDO) and tryptophan 2,3‐dioxygenase (TDO) in cervicovaginal samples from women...

Actinic cheilitis (AC) is considered a precancerous lesion of the lip.1 Renal transplant recipients (RTR) have a higher susceptibility to human papillomavirus (HPV) infections and lip squamous cell carcinoma (SCC). 2 Over 200 HPV types were described and most cluster within the α‐, β‐ and γ‐HPV genera. 3 Merkel Cell Polyomavirus (MCPyV) and several...

Cervical cancer, caused by high oncogenic risk Human Papillomavirus (HPV) infection, continues to be a public health problem, mainly in developing countries. Using peptide phage display as a tool to identify potential molecular targets in HPV associated tumors, we identified α-mannosidase, among other enriched sequences. This enzyme is expressed in...

Example of T cell proliferation assays and frequency of myeloid cells in SW treated naïve mice. A. Example of T cell proliferation assay. Cell Dye labeled T cells were incubated with 10 ng/ml PMA and 1 μg/ml Ionomycin for 4 days, harvested, labeled with anti-CD4 and anti-CD8 and analyzed by flow cytometry. B. Frequency of myeloid cells in the splee...

Enrichment of CD11b+ splenocytes and macrophage gating strategy. A. Enrichment of CD11b+ splenocytes. Left side, example of pre and post sort. Right side. Average enrichment of CD11b+ cells from spleens of each experimental group. B. Gating strategy to identify TAM. After harvesting, tumors were digested with 1mg/ml Collagenase I and IV and single...

SW treatment changes lectin binding to the surface of tumor cells and leukocytes. A. TC-1 cells and bone marrow and spleen single cell suspensions were treated with 1 or 2 μg/ml SW for 48 hours, before harvesting. Cells were then incubated with 0.3 μg/ml biotinylated tomato lectin, washed and then incubated with phycoerythrin conjugated streptavidi...

Cervical cancer continues to be a public health problem in developing countries. Previous studies have shown that cervical cancer cells display markers of aerobic glycolysis, indicating that these tumors are likely to secrete lactate. Mostly, lactate is recognized as a molecule capable of suppressing immune responses, through inhibition of T cells,...

Alterations in specific DNA damage repair mechanisms in the presence of human papillomavirus (HPV) infection have been described in different experimental models. However, the global effect of HPV on the expression of genes involved in these pathways has not been analyzed in detail. In the present study, we compared the expression profile of 135 ge...

Persistent infection with high-risk human papilloma virus (HR-HPV) is the main risk factor for the development of invasive cervical cancer although is not sufficient to cause cervical cancer. Several host and environmental factors play a key role in cancer initiation/progression, including cytokines and other immune-response mediators. Here, we cha...

High-risk human papillomavirus (HR-HPV) infection is not a sufficient condition for cervical cancer development because most infections are benign and naturally cleared. Epidemiological studies revealed that tobacco smoking is a cofactor with HR-HPV for cervical cancer initiation and progression, even though the mechanism by which tobacco smoke coo...

CSC exposure increases CYP1B1, E6 and E7 expression levels in cervical cell lines. (A) CYP1B1 mRNA was evaluated through RT-qPCR after CSC treatment in CaSki cells. (B,C) E6 and E7 mRNA levels were evaluated in SiHa cells at different times of CSC exposure using RT-qPCR. ∗p< 0.05, n.s: non-significant.

Treatment with cigarette smoke components induce changes in the cell phenotype. (A) CaSki cells were treated with 10 μg/mL CSC or DMSO for different periods of time using cycloheximide as a translation inhibitor. The protein extracts were used for immunoblotting with antibodies directed against p53 and pRB. (B) Soft agar from SiHa cells exposed to...

Cigarette smoke components induce c-Jun phosphorylation in SiHa cells. Confocal microscopy for c-JunS73 and c-FosT232 in SiHa cells treated 2 h with DMSO and CSC, using a secondary antibody conjugated to the Texas Red fluorophore. DAPI: fluorescent DNA marker, Rhodamine: fluorescent marker of cytoskeleton of actin. The images are representative of...

Cigarette smoke components induce a loss of cell viability in a concentration-dependent manner. (A,B) Viability of CaSki and SiHa cells exposed to cigarette smoke condensate (range: 0–100 μg/mL) for 72 h evaluated through MTS incorporation. Data shown are mean from three independent experiments. ∗p < 0.05.

Human Phospho MAPK array. CaSki human cervical epithelial carcinoma cells were treated with DMSO, CSC or EGF for 2 h before lysis. The membranes were incubated with 200 μg of lysate according to the manufacturer’s instructions. Data shown are from a 2-min exposure to X-ray film. Each membrane contains 26 different capture antibodies printed in dupl...

Objectives: Oxidative stress results from an imbalance between the generation and elimination of oxidant species. This condition may result in DNA, RNA and protein damage, leading to the accumulation of genetic alterations that can favor malignant transformation. Persistent infection with high-risk human papillomavirus types is associated with inf...

We reported the presence in human cells of a noncoding mitochon-drial RNA that contains an inverted repeat (IR) of 815 nucleotides (nt) covalently linked to the 5 end of the mitochondrial 16S RNA (16S mtrRNA). The transcript contains a stem-loop structure and is expressed in human proliferating cells but not in resting cells. Here, we demonstrate t...

The name of the family Polyomaviridae, derives from the early observation that cells infected with murine polyomavirus induced multiple (poly) tumors (omas) in immunocompromised mice. Subsequent studies showed that many members of this family exhibit the capacity of mediating cell transformation and tumorigenesis in different experimental models. T...

Infection with human papillomaviruses is associated with a series of benign and malignant hyperproliferative diseases that impose a heavy burden on human populations. A subgroup of mucosal human papillomavirus types are associated with the majority of cervical cancers and a relevant fraction of vulvar, vaginal, anal, penile and head and neck carcin...

Infection with high oncogenic risk human papillomavirus types is the etiological factor of cervical cancer and a major cause of other epithelial malignancies, including vulvar, vaginal, anal, penile and head and neck carcinomas. These agents affect epithelial homeostasis through the expression of specific proteins that deregulate important cellular...

Background: Human Papillomavirus (HPV) infection is the main risk factor for the development and progression of cervical cancer. HPV-16 E6 and E7 expression is essential for induction and maintenance of the transformed phenotype. These oncoproteins interfere with the function of several intracellular proteins, including those controlling the PI3K/...

It is well known that persistent infection with high-risk HPV (hr-HPV), mostly HPV-16 and 18, is the main cause of cervical cancer development. Manganese superoxide dismutase (MnSOD or SOD2) are highly expressed in different neoplasia. The present study investigated SOD2 protein expression and the presence of hr-HPV types in 297 cervical samples in...

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular proces...

Cervical cancer is one of the leading causes of cancer death in women worldwide. Persistent infection with high-risk human papillomavirus (HPV) types is the main risk factor for the development of cervical cancer precursor lesions. HPV persistence and tumor development is usually characterized by innate immune system evasion. Alterations in Toll-li...

Oxidative stress reflects an imbalance in the maintenance of the intracellular redox state resulting in the accumulation of oxidant species that may contribute to tumorigenesis. The superoxide dismutase 2 protein (SOD2) contributes to cell homeostasis by catalyzing the dismutation of superoxide anion radicals in oxygen and hydrogen peroxide, preven...

Cervical cancer is one of the leading causes of cancer death in women worldwide. Persistent infection with high-risk human papillomavirus (HPV) types is the main risk factor for the development of cervical cancer precursor lesions and is usually characterized by innate immune system evasion. The innate immune system is the first line of defense aga...

Background: Some sexually transmitted infectious agents, such as Chlamydia trachomatis and Herpes simplex, cause local inflammation, and could contribute to Human Papillomavirus (HPV) and cervical lesion progression. Thus, the aim of this study was to determine any association between the presence of microorganisms of gynecological importance, sex...

The hallmark of high-risk human papillomavirus (HR-HPV)-related carcinogenesis is E6 and E7 oncogene overexpression. The aim of this work was to characterize epithelial oral and cervical cancer cells that express HR-HPV E6 and E7 oncoproteins. Transcriptomic assay using DNA microarrays revealed that PIR gene expression was detected in oral cells in...

The EGFR/MEK/ERK and PI3K/AKT pathways abrogation do not affect basal pirin levels in OKF6-Tert2

HPV-16 E6 and E7 transcripts are expressed and are functional in oral OKF6 cells stably transfected with pLXSNHPV-16E6/E7 vector

Página 1 de 2 https://royalsocietypublishing.org/toc/rsob/2017/7/11 Human papillomavirus HPV-16 E7 activity is important for inducing PIR (gene) upregulation in tumor epithelial cells. Immuno!uorescence image shown for CaSki (merged) cells transiently transfected with a siRNA for E7 silencing. See the related paper "Up-regulation of PIR gene expres...

Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes...

Loss of cell polarity is a fundamental process in cell transformation. Among polarity proteins, we focused on human Disc Large (DLG1), which is localized mainly at adherens junctions and contributes to the control of cell proliferation. We previously demonstrated that its expression is altered in HPV-associated cervical neoplastic lesions, but the...

Matrix metalloproteinases (MMPs) are important enzymes in the tumor microenvironment associated with progression of cervical intraepithelial neoplasia (CIN) towards squamous cell carcinoma (SCC) of the cervix. However, the role of MMPs in the inflammatory process associated with Chlamydia trachomatis infection concomitant with the carcinogenic proc...

Superoxide dismutase-2 (SOD2) is considered one of the most important antioxidant enzymes that regulate cellular redox state in normal and tumorigenic cells. Overexpression of this enzyme in lung, gastric, colorectal, breast cancer and cervical cancer malignant tumors has been observed. Its relationship with inguinal lymph node metastasis in penile...

Background Tumour microenvironment is a fundamental aspect of tumour behaviour, modulating important events as cancer cell migration and invasion, as well as angiogenesis and metastisation. Among other microenvironment features, hypoxia and acidity play important roles in this modulation. As the metabolic reprogramming of cancer cells induces extra...

Ameloblastoma is an odontogenic tumor characterized by local invasiveness and frequent recurrence. The surrounding stroma, composed of different cell types and extracellular matrix (ECM), may influence ameloblastoma invasive behavior. Furthermore, tumor and stromal cells secrete matrix metalloproteases (MMPs), which, in turn, can modulate the matri...

Tumors are complex structures containing different types of cells and molecules. The importance of the tumor microenvironment in tumor progression, growth, and maintenance is well-established. However, tumor effects are not restricted to the tumor microenvironment. Molecules secreted by, as well as cells that migrate from tumors, may circulate and...

The study of RNA and DNA oncogenic viruses has proved invaluable in the discovery of key cellular pathways that are rendered dysfunctional during cancer progression. An example is high risk human papillomavirus (HPV), the etiological agent of cervical cancer. The role of HPV oncogenes in cellular immortalization and transformation has been extensiv...

Background: Antisense mitochondrial ncRNAs are down-regulated during oncogenesis by unknown mechanisms. Results: High risk HPV E2 oncogene induces down-regulation of the antisense transcripts. Additionally, E6 and E7 induce expression of a new sense mitochondrial ncRNA. Conclusion: HPV oncogenes modulate expression of mitochondrial ncRNAs. Signific...

Cervical cancer is the third most common cancer in women worldwide. Persistent infection with high-risk HPV types, principally HPV16 and 18 is the main risk factor for the development of this malignancy. However, the onset of invasive tumor occurs many years after initial exposure in a minority of infected women. This suggests that other factors be...

Expression of HPV16 E6E7 oncoproteins does not affect the level and activity of MMP2, MMP9 and MT1-MMP in HFKs grown in monolayer. A, Primary HFKs cultured in monolayer were transduced with pLXSN-based retroviral vectors expressing HPV-16 E6wt and/or E7wt. Western blots were carried out to determine MMP-2, MMP-9 and MT1-MMP levels. Beta-actin was u...

The role of inflammation in human papillomavirus (HPV) infection and disease is complex since it involves responses capable of preventing initial infections, clearing those ongoing as well as promoting persistence and progression of associated lesions. Avoiding the immune response has been considered a key aspect of HPV persistence which is the mai...

Human papillomaviruses are small DNA viruses that cause hyperproliferative lesions of the mucosa and skin. Some HPV types, collectively known as high-risk types, are etiologically associated to cervical cancer and other anogenital malignancies. Infection by these HPV types has been associated to genomic instability, a hallmark of most human maligna...

Acute expression of E7 oncogene from human papillomavirus (HPV) 16 or HPV18 is sufficient to overcome tumor necrosis factor (TNF)-α cytostatic effect on primary human keratinocytes. In the present study, we investigated the molecular basis of E7-induced TNF resistance through a comparative analysis of the effect of this cytokine on the proliferatio...

We reported the presence in human cells of a noncoding mitochondrial RNA that contains an inverted repeat (IR) of 815 nucleotides (nt) covalently linked to the 5' end of the mitochondrial 16S RNA (16S mtrRNA). The transcript contains a stem-loop structure and is expressed in human proliferating cells but not in resting cells. Here, we demonstrate t...