scholarly journals Quimioprevenção e câncer no contexto brasileiro: Da higidez ao diagnóstico

2021 ◽  
Vol 10 (8) ◽  
pp. e44610817448
Author(s):  
Mariane Minussi Baptistella ◽  
Carolina Sales de Oliveira ◽  
Raphaela Rebeca Silveira Assunção ◽  
Pollyanna Francielli de Oliveira
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
Lung Cancer ◽  
Cancer Chemoprevention ◽  
National Library ◽  
Cancer Breast ◽  
Non Melanoma Skin Cancer ◽  
Melanoma Skin

O câncer representa um dos maiores problemas de saúde pública do mundo. Apesar dos avanços crescentes e de alguns sucessos ocasionais, pacientes e profissionais da saúde permanecem enfrentando diversos contratempos procedentes da terapia oncológica. Nesse sentido, a quimioprevenção é interessante, pois implica evitar o sofrimento causado pelo câncer, tendo potencial efeito antes do diagnóstico, no prognóstico e, também, no tratamento. Nesta revisão, teve-se como objetivo elencar as principais abordagens quimiopreventivas, a nível primário, secundário e terciário, para os tumores mais frequentes no Brasil e que possuem correlação com hábitos cotidianos adotados. Para isso, foi realizado um levantamento bibliográfico das publicações disponíveis nas bases da National Library of Medicine (NIH – PubMed) e Scholar Google dos últimos 20 anos. Utilizou-se os descritores: “chemoprevention”, “cancer chemoprevention” “non melanoma skin cancer”, “lung cancer”, “breast cancer”, e “colorectal cancer”. São notáveis os resultados obtidos por diversos estudos in vitro e in vivo, tal qual as histórias de sucesso clínico. Não obstante, os desafios ainda são muitos devido, sobretudo, às variáveis encontradas nas respostas individuais dos pacientes, as quais podem ser influenciadas por especificidades do quadro clínico, e entre outros fatores, como também as limitações de investimento e adesão. Futuras pesquisas e investimento em educação e conscientização do público em geral e de profissionais da saúde, a respeito dos benefícios por trás da quimioprevenção do câncer, possibilitariam a ampla aplicação da quimioprevenção e beneficiariam diversos âmbitos da saúde.

Mutational analysis of rare insertions and deletions in exon 18 and 19 of HER2 in Chinese patients with different cancer types.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3069-3069
Author(s):  
Jianwen Qin ◽  
Dongsheng Shi ◽  
Lijie Song ◽  
Yan Yin ◽  
Bin Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
Lung Cancer ◽  
Drug Response ◽  
Chinese Patients ◽  
Driver Mutations ◽  
Wild Type ◽  
Cancer Types ◽  
Exon 20

3069 Background: HER2 belongs to the same family with EGFR and is known as an important cancer driver gene. Kinase domain insertions and deletions (KD indels) are frequent driver mutations in both EGFR and HER2. The most common HER2 KD indels are the exon 20 insertions while others are rarely reported. Our study aimed to investigate the role of less common HER2 KD indels in solid tumors. Methods: This study was performed in 63,267 Chinese patients including 53,591 patients with lung cancer, 5,888 patients with colorectal cancer, 3,774 patients with breast cancer and 14 patients with renal pelvis cancer. Tissue or plasma samples from the patients were subjected to capture-based targeted sequencing covering HER2 and other cancer related genes. The sequencing data of each patient were retrospectively collected and analyzed. The HER2 exon 18/19 indels identified in our study were compared with data from COSMIC and MSKCC. In vitro analysis in Ba/F3 cell lines was performed to assess drug response of different HER2 exon 18/19 indels. Results: We identified recurrent HER2 KD indels in exon 18 and 19, with a frequency of 0.04% (25/63,267). The data from COSMIC and MSKCC reported the prevalence of HER2 exon 18/19 indels ranging from 0.04% to 0.23% among breast, cervical, and pancreatic cancers. In our study, HER2 exon 18/19 indels were identified in 20 patients with lung cancer (0.037%), two with colorectal cancer (0.034%), two with breast cancer (0.053%) and one with renal pelvis cancer (7.143%). Only two patients (8%) harbored concurrent actionable driver mutations including EGFR mutation and MET amplification. Meanwhile, high level of normalized allelic frequency of HER2 exon 18/19 indels was presented in most patients (22/25, 88%). In lung cancer, the presence of EGFR driver mutation was less common in patients with HER2 exon 18/19 indels than wild type HER2 (5% vs. 47.4%, p < 0.01). The rates of concurrent driver mutations in lung cancer were comparable between HER2 exon 18/19 indels and the two established HER2 drivers, exon 20 insertions and S310 mutations. The in vitro proliferation assay demonstrated that E698_P699insLL mutation in HER2 exon 18 and L755_E757delinsPQ mutation in HER2 exon 19 both conferred a survival advantage to Ba/F3 cells. Dose-response curves showed inhibitory effects on cell viability of several HER2 tyrosine kinase inhibitors including neratinib, lapatinib, poziotinib and afatinib. In particular, lapatinib, poziotinib and afatinib demonstrated comparable or stronger inhibitory ability toward the two HER2 mutants than wild type HER2 in terms of IC50. Conclusions: Our study revealed a novel class of HER2 KD indels in exon 18/19 that may act as driver mutations in several cancer types. The drug response observed in vitro indicated the potential to use anti- HER2 targeted therapies for HER2 exon 18/19 indels. Further studies on this rare type of HER2 mutation are warranted.

scholarly journals Lung-Cancer Chemoprevention by Induction of Synthetic Lethality in Mutant KRAS Premalignant Cells In Vitro and In Vivo

2011 ◽  
Vol 4 (5) ◽  
pp. 666-673 ◽  
Author(s):  
Shaoyi Huang ◽  
Xiaoyang Ren ◽  
Lai Wang ◽  
Ling Zhang ◽  
Xiangwei Wu
Keyword(s):  
Lung Cancer ◽  
Synthetic Lethality ◽  
Cancer Chemoprevention

scholarly journals In VivoImmunomodulation and Lipid Peroxidation Activities Contributed to Chemoprevention Effects of Fermented Mung Bean against Breast Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Swee Keong Yeap ◽  
Hamidah Mohd Yusof ◽  
Nurul Elyani Mohamad ◽  
Boon Kee Beh ◽  
Wan Yong Ho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lipid Peroxidation ◽  
Mung Bean ◽  
Interleukin 2 ◽  
Tumor Development ◽  
Cancer Chemoprevention ◽  
Mitotic Division ◽  
Tumor Formation

Mung bean has been reported to have antioxidant, cytotoxic, and immunomodulatory effectsin vitro. Fermented products are reported to have enhanced immunomodulation and cancer chemopreventive effects. In this study, fermented mung bean treatmentsin vivowere studied by monitoring tumor development, spleen immunity, serum cytokine (interleukin 2 and interferon gamma) levels, and spleen/tumor antioxidant levels after injection with low and high risk 4T1 breast cancer cells. Pretreatment with fermented mung bean was associated with delayed tumor formation in low risk mice. Furthermore, this treatment was connected with higher serum anticancer cytokine levels, spleen T cell populations, splenocyte cytotoxicity, and spleen/tumor antioxidant levels. Histopathological evaluation of fermented mung bean treated tumor revealed lower event of mitotic division. On the other hand, antioxidant and nitric oxide levels that were significantly increased in the untreated mice were inhibited in the fermented mung bean treated groups. These results suggested that fermented mung bean has potential cancer chemoprevention effects through the stimulation of immunity, lipid peroxidation, and anti-inflammation.

scholarly journals The Oncogenic Potential of the Centromeric Border Protein FAM84B of the 8q24.21 Gene Desert

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 312 ◽  
Author(s):  
Yan Gu ◽  
Xiaozeng Lin ◽  
Anil Kapoor ◽  
Mathilda Jing Chow ◽  
Yanzhi Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Catalytic Triad ◽  
Gene Desert ◽  
Oncogenic Potential ◽  
Cancer Breast ◽  
Cancer Types ◽  
Prostate Cancers ◽  
Breast Cancer Growth

FAM84B is a risk gene in breast and prostate cancers. Its upregulation is associated with poor prognosis of prostate cancer, breast cancer, and esophageal squamous cell carcinoma. FAM84B facilitates cancer cell proliferation and invasion in vitro, and xenograft growth in vivo. The FAM84B and Myc genes border a 1.2 Mb gene desert at 8q24.21. Co-amplification of both occurs in 20 cancer types. Mice deficient of a 430 Kb fragment within the 1.2 Mb gene desert have downregulated FAM84B and Myc expressions concurrent with reduced breast cancer growth. Intriguingly, Myc works in partnership with other oncogenes, including Ras. FAM84B shares similarities with the H-Ras-like suppressor (HRASLS) family over their typical LRAT (lecithin:retinal acyltransferase) domain. This domain contains a catalytic triad, H23, H35, and C113, which constitutes the phospholipase A1/2 and O-acyltransferase activities of HRASLS1-5. These enzymatic activities underlie their suppression of Ras. FAM84B conserves H23 and H35 but not C113 with both histidine residues residing within a highly conserved motif that FAM84B shares with HRASLS1-5. Deletion of this motif abolishes FAM84B oncogenic activities. These properties suggest a collaboration of FAM84B with Myc, consistent with the role of the gene desert in strengthening Myc functions. Here, we will discuss recent research on FAM84B-derived oncogenic potential.

scholarly journals Bioactive Compounds and Metabolites from Grapes and Red Wine in Breast Cancer Chemoprevention and Therapy

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3531 ◽  
Author(s):  
Danielly C. Ferraz da Costa ◽  
Luciana Pereira Rangel ◽  
Julia Quarti ◽  
Ronimara A. Santos ◽  
Jerson L. Silva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Bioactive Compounds ◽  
Molecular Mechanisms ◽  
Red Wine ◽  
Cancer Chemoprevention ◽  
Breast Cancer Chemoprevention ◽  
Structure And Metabolism

Phytochemicals and their metabolites are not considered essential nutrients in humans, although an increasing number of well-conducted studies are linking their higher intake with a lower incidence of non-communicable diseases, including cancer. This review summarizes the current findings concerning the molecular mechanisms of bioactive compounds from grapes and red wine and their metabolites on breast cancer—the most commonly occurring cancer in women—chemoprevention and treatment. Flavonoid compounds like flavonols, monomeric catechins, proanthocyanidins, anthocyanins, anthocyanidins and non-flavonoid phenolic compounds, such as resveratrol, as well as their metabolites, are discussed with respect to structure and metabolism/bioavailability. In addition, a broad discussion regarding in vitro, in vivo and clinical trials about the chemoprevention and therapy using these molecules is presented.

Cullin-3 is a potential novel target for breast cancer chemoprevention and treatment

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13070-13070 ◽  
Author(s):  
W. Miao ◽  
M. Loignon ◽  
L. Hu ◽  
M. Basik ◽  
G. Batist
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Chemoprevention ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Protein Levels

13070 Background: Nrf2 is a master transcription factor regulating multiple phase II carcinogen-detoxifying enzymes. Modulating Nrf2 is a current chemoprevention strategy under investigation. Nrf2 levels are regulated by the Keap1, which functions as a substrate adaptor protein targeting Nrf2 to the Cullin-3 (Cul3)-dependent ubiquitin E3 ligase complex. Methods: We used RT-PCR and Western blot to measure the mRNA and protein levels of Nrf2, Keap1 and Cul3 in human breast cancer cell lines. SiRNA and retrovectors were used to construct stable Cul3 silenced breast cancer cell lines. Agilent DNA microarray analysis was used to study the Cul3-slienced cells. Results: We discovered that Nrf2 protein levels in both nucleus and cytoplasm are significantly decreased in all breast cancer cell lines examined compared to normal human mammary epithelial cells (HMEC). This was confirmed with IHC analysis in 8 out of 10 breast cancer specimens containing normal mammary tissues for comparison. Since RT-PCR showed no change in Nrf2 mRNA levels in the breast cancer cell lines, we examined the degradation pathway of Nrf2, and we found that Cul3 is significantly overexpressed in all three breast cancer cell lines studied compared to HMEC. Silencing Cul3 using siRNA results in restoration of Nrf2 protein level, along with multiple carcinogen-detoxifying enzymes, such as GCS. The Cul3 silenced cells showed remarkable growth retardation compared to the wild type MCF-7 cell line both in vitro and in vivo in a mouse mammary fat pad cancer xenograft model. Microarray analyses of Cul3 siRNA-slinced cells demonstrated upregulation of several detoxifying genes, altered cell cycle markers and several upregulated tumor suppressor genes. Conclusions: Nrf2 is significantly downregulated in breast cancer cells, which is related to the overexpression of Cul3, and may represent sensitivity of these cells to carcinogenic transformation. Knocking down Cul3 constitutively upregulates the Nrf2 as well as multiple carcinogen-detoxifying genes. Moreover, it significantly suppressess the proliferation of cancer cells in vitro and growth of xenograft tumors in vivo. These data suggest that Cul-3 is a potential new target for breast cancer chemoprevention and treatment. No significant financial relationships to disclose.

scholarly journals Arthrospira Platensis – Potential in Dermatology and Beyond

2018 ◽  
Vol 6 (1) ◽  
pp. 176-180 ◽  
Author(s):  
Uwe Wollina ◽  
Cristiana Voicu ◽  
Serena Gianfaldoni ◽  
Torello Lotti ◽  
Katlein França ◽  
...  
Keyword(s):  
Arthrospira Platensis ◽  
Current Data ◽  
Resistant Bacteria ◽  
Target Cells ◽  
Non Melanoma Skin Cancer ◽  
Anti Cancer ◽  
Ancient Times ◽  
Melanoma Skin

The search for natural products with benefits for health in general and of potential for treating human disease has gained wider interest world-wide. Here, we analyse current data on the microalga Arthrospira platensis (AP), that has been used in nutrition since ancient times in Fare East and African communities, for medical purposes with a focus on dermatology. Extracts of AP have been investigated in vitro and in vivo. The alga is rich in proteins, lipopolysaccharides and gamma-linolenic acid. AP extracts, phycocyanin compounds and polysaccharide calcium spirulan (Ca-SP) have been evaluated in various models. It could be demonstrated, that AP has significant antioxidant activity, prevents viruses from entry into target cells and inhibits the colonisation of wounds by multi-resistant bacteria. Furthermore, anti-cancer activity was documented in models of oral cancer, melanoma, and UV-induced non-melanoma skin cancer.

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