Cancer chemoprevention with natural agents: Where we are now?

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Sanjay Gupta ◽  
Karishma Gupta ◽  
Jeniece Montellano
Keyword(s):  
Cellular Proliferation ◽  
Precancerous Lesions ◽  
Cancer Control ◽  
Cancer Chemoprevention ◽  
Intraepithelial Neoplasia ◽  
Malignant Cell ◽  
Genetic Alterations ◽  
Clinical Cancer ◽  
Natural Agents ◽  
Initiation Stage

Chemoprevention is defined as a means of cancer control in which the occurrence of clinical cancer can be prevented, slowed or reversed by the administration of one or more synthetic or naturally occurring biologic compounds [1-5]. In contrast to cancer treatment, the goal of chemoprevention is to reduce the incidence of clinical cancer. Preventing the onset of clinical cancer is desirable because therapy for established cancer is not uniformly effective. Chemoprevention also implies the prevention of precancerous lesions, which are called pre-invasive neoplasia, dysplasia, or intraepithelial neoplasia, depending on the organ system [5, 6]. The process of carcinogenesis involves the accumulation of multiple sequential genetic alterations and mutations that transforms a normal cell to a malignant cell capable of stromal invasion and ultimately metastasis. Carcinogenesis is traditionally separated into three phases: initiation, promotion and progression [6]. The initiation stage is relatively rapid and involves carcinogen binding and damage to DNA. The promotion phase is reversible, as tumor promoters act as mitogens to induce clones of initiated cells to expand. The promotion phase is a consequence of the functional loss of regulatory proteins and cellular checkpoints important for cellular proliferation and apoptosis. Progression is a stage in which phenotypically and genotypically altered cells develop irreversible macroscopic and microscopic changes. Because initiation and progression are irreversible, the promotion phase of carcinogenesis may be the best target for chemoprevention.

scholarly journals Breast Cancer Chemoprevention: Old and New Approaches

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Massimiliano Cazzaniga ◽  
Bernardo Bonanni
Keyword(s):  
Breast Cancer ◽  
Precancerous Lesions ◽  
Molecular Targets ◽  
Cancer Chemoprevention ◽  
New Approaches ◽  
Estrogen Receptor Modulators ◽  
Natural Agents ◽  
Breast Cancer Chemoprevention ◽  
Er Positive ◽  
High Risk Populations

In 1976, Sporn has defined chemoprevention as “the use of pharmacologic or natural agents that inhibit the development of invasive breast cancer either by blocking the DNA damage that initiates carcinogenesis, or by arresting or reversing the progression of premalignant cells in which such damage has already occurred.” Although the precise mechanism or mechanisms that promote a breast cancer are not completely established, the success of several recent clinical trials in preventive settings in selected high-risk populations suggests that chemoprevention is a rational and an appealing strategy. Breast cancer chemoprevention has focused heavily on endocrine intervention using selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). Achieving much success in this particular setting and new approaches as low-dose administration are actually under investigations in several topics. Unfortunately, these drugs are active in prevention of endocrine responsive lesions only and have no effect in reducing the risk of estrogen-negative breast cancer. Thus, recently new pathways, biomarkers, and agents likely are to be effective in this subgroup of cancers and were put under investigation. Moreover, the identification of new potential molecular targets and the development of agents aimed at these targets within cancer have already had a significant impact on advanced cancer therapy and provide a wealth of opportunities for chemoprevention. This paper will highlight current clinical research in both ER-positive and ER-negative breast cancer chemoprevention, explaining the biologic effect of the various agents on carcinogenesis and precancerous lesions, and finally presenting an excursus on the state-of-the-art about new molecular targets under investigations in breast cancer settings.

The role of immunohistochemistry in the diagnosis of cervical intraepithelial neoplasia of different severity

2016 ◽  
pp. 138-140
Author(s):  
S.I. Zhuk ◽  
◽  
O.A. Taran ◽  
A.N. Koshmienskaya ◽  
T.V. Lobastova ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cervical Intraepithelial Neoplasia ◽  
Precancerous Lesions ◽  
Molecular Genetic ◽  
Intraepithelial Neoplasia ◽  
Reproductive Age ◽  
Moderate Degree ◽  
Ki 67 ◽  
The Third ◽  
Diagnosis And Prognosis

The objective: the finding of protein expression of apoptosis regulator BCL-2, Smooth Muscule Actin and the antigen Ki-67 in cervical intraepithelial neoplasia of different severity to optimize the diagnosis and prognosis of the disease. Patients and methods. The study involved 42 women of reproductive age with cervical intraepithelial the neoplasia of the cervix varying degrees applied to the doctor of cervical pathology Zhitomir regional oncologic dispensary. All women (n=42) were divided into groups. The first group included 15 patients (35.7%) with cervical intraepithelial neoplasia with mild. The second group included 13 women (31%) with cervical intraepithelial neoplasia a moderate degree. The third group was represented by patients with cervical intraepithelial neoplasia with severe – 14 respondents (33.3 per cent). Results. Marker BCL-2 in patients of the first group was positive in 7 patients (46.7%), Smooth Muscule Actin was positive in 9 patients (60%) and Ki-67 was diagnosed in 8 of the surveyed women (53.3%). In the second group of BCL-2 was positive in 8 patients (61.5%), Clone 124, Smooth Muscule Actin, Clone 1A4 was positive in 9 patients (69.2%), and Ki-67 was diagnosed in 12 of the surveyed women (92.3%). Marker BCL-2 in patients of the third group was positive in 12 patients (85.7%), Smooth Muscule Actin was positive in 10 patients (71.4%) and Ki-67 was diagnosed in 13 of the surveyed women (92.9% ). Conclusion. Carcinogenesis is associated with molecular genetic damage to the cervix. Some of the products of this process can be used as prognostic and diagnostic markers of tumor progression. Determination of protein expression of apoptosis regulator BCL-2, Smooth Muscule Actin and the antigen Ki-67 in cervical intraepithelial neoplasia makes it possible to accurately verify the diagnosis and to predict the course of pathological changes in the flat epithelium of the cervix. Key words: cervical intraepithelial neoplasia, cervical cancer, morphological diagnostics of precancerous lesions, BCL-2, Smooth Muscule Actin, Ki-67.

scholarly journals Multicentre Evaluation of Hepika Test Clinical Accuracy in Diagnosing HPV-Induced Cancer and Precancerous Lesions of the Uterine Cervix

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 619
Author(s):  
Daniela Gustinucci ◽  
Lucia Ciccocioppo ◽  
Luigi Coppola ◽  
Giovanni Negri ◽  
Gianfranco Zannoni ◽  
...  
Keyword(s):  
Uterine Cervix ◽  
Protein Complexes ◽  
Precancerous Lesions ◽  
Intraepithelial Neoplasia ◽  
Population Based ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lower Sensitivity ◽  
Adenocarcinoma In Situ ◽  
Clinical Accuracy ◽  
Grade 3

Objective: To evaluate the clinical accuracy of Hepika test to identify cancer/precancerous lesions of the uterine cervix. Materials and Methods: A multicentre retrospective study was carried out in 2018 and included 330 liquid-based cytology samples from three Italian centres of women aged 25–64 who had been tested for the human papillomavirus (HPV) and whose histology or follow-up outcome was known. Hepika is an enzyme-linked immunosorbent assay (ELISA) targeting the protein complexes E6#p53 and E7#pRb. After excluding samples without sufficient residual material, the clinical accuracy of Hepika test was evaluated in 274 samples: adenocarcinoma (ADC) (4), squamous cell carcinoma (SCC) (7), adenocarcinoma in situ (AIS) (1), cervical intraepithelial neoplasia (CIN) grade 3 (60), CIN2 (51), CIN1 (34), and negative histology (117). Association, sensitivity, and specificity for carcinoma, CIN3+ and CIN2+ are reported. Results: Positive Hepika test was associated with a high probability of carcinoma (odds ratio (DOR) = 33.68, 95% confidence interval (CI) 7.0–163.1); sensitivity was 81.8%, specificity, 88.2%. A positive Hepika test showed a weaker association with CIN3+ lesions (DOR = 3.5; 95% CI 1.75–6.99) and lower sensitivity (27.8%). Conclusion: The Hepika test was found to be an accurate biomarker for HPV-induced cervical carcinoma. Population-based prospective studies are needed to confirm the clinical usefulness of the Hepika test in the differential diagnosis of HPV-induced invasive lesions.

scholarly journals Senolytic elimination of Cox2-expressing senescent cells inhibits the growth of premalignant pancreatic lesions

Gut ◽  
2021 ◽  
pp. gutjnl-2020-321112
Author(s):  
Dror Kolodkin-Gal ◽  
Lior Roitman ◽  
Yossi Ovadya ◽  
Narmen Azazmeh ◽  
Benjamin Assouline ◽  
...  
Keyword(s):  
Tumour Growth ◽  
Precancerous Lesions ◽  
Intraepithelial Neoplasia ◽  
Preventive Therapy ◽  
Ductal Adenocarcinoma ◽  
Potential Contribution ◽  
Pancreatic Intraepithelial Neoplasia ◽  
Promoting Effect ◽  
Paracrine Effects ◽  
Bcl2 Family

ObjectiveCellular senescence limits tumourigenesis by blocking the proliferation of premalignant cells. Additionally, however, senescent cells can exert paracrine effects influencing tumour growth. Senescent cells are present in premalignant pancreatic intraepithelial neoplasia (PanIN) lesions, yet their effects on the disease are poorly characterised. It is currently unknown whether senolytic drugs, aimed at eliminating senescent cells from lesions, could be beneficial in blocking tumour development.DesignTo uncover the functions of senescent cells and their potential contribution to early pancreatic tumourigenesis, we isolated and characterised senescent cells from PanINs formed in a Kras-driven mouse model, and tested the consequences of their targeted elimination through senolytic treatment.ResultsWe found that senescent PanIN cells exert a tumour-promoting effect through expression of a proinflammatory signature that includes high Cox2 levels. Senolytic treatment with the Bcl2-family inhibitor ABT-737 eliminated Cox2-expressing senescent cells, and an intermittent short-duration treatment course dramatically reduced PanIN development and progression to pancreatic ductal adenocarcinoma.ConclusionsThese findings reveal that senescent PanIN cells support tumour growth and progression, and provide a first indication that elimination of senescent cells may be effective as preventive therapy for the progression of precancerous lesions.

scholarly journals Subcutaneous administration of ketoprofen delays Ehrlich solid tumor growth in mice

2014 ◽  
Vol 66 (5) ◽  
pp. 1376-1382 ◽  
Author(s):  
C.M. Souza ◽  
P.A. Auler ◽  
D.C. Reis ◽  
G.E. Lavalle ◽  
E. Ferreira ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Solid Tumor ◽  
Cellular Proliferation ◽  
Subcutaneous Administration ◽  
Physiological Saline ◽  
Malignant Cell ◽  
Control Group ◽  
Ehrlich Tumor ◽  
Anti Inflammatory

Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID) has proven to exert anti-inflammatory, anti-proliferative and anti-angiogenic activities in both neoplastic and non-neoplastic conditions. We investigated the effects of this compound on tumor development in Swiss mice previously inoculated with Ehrlich tumor cells. To carry out this study the solid tumor was obtained from cells of the ascites fluid of Ehrlich tumor re-suspended in physiological saline to give 2.5x106cells in 0.05mL. After tumor inoculation, the animals were separated into two groups (n = 10). The animals treated with ketoprofen 0.1µg/100µL/animal were injected intraperitoneally at intervals of 24h for 10 consecutive days. Animals from the control group received saline. At the end of the experiment the mice were killed and the tumor removed. We analyzed tumor growth, histomorphological and immunohistochemical characteristics for CDC47 (cellular proliferation marker) and for CD31 (blood vessel marker). Animals treated with the ketoprofen 0.1µg/100µL/animal showed lower tumor growth. The treatment did not significantly influence the size of the areas of cancer, inflammation, necrosis and hemorrhage. Moreover, lower rates of tumor cell proliferation were observed in animals treated with ketoprofen compared with the untreated control group. The participation of ketoprofen in controlling tumor malignant cell proliferation would open prospects for its use in clinical and antineoplasic therapy.

scholarly journals Photodynamic Therapy for Low-grade Cervical Intraepithelial Neoplasia (CIN1): A Case Report

2020 ◽  
Vol 4 (6) ◽  
Author(s):  
Yinyin Zhang ◽  
Hong Lin ◽  
Huizhen Fan
Keyword(s):  
Photodynamic Therapy ◽  
Cervical Intraepithelial Neoplasia ◽  
Persistent Infection ◽  
Precancerous Lesions ◽  
Irradiation Time ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Cervical Canal ◽  
Low Grade ◽  
Oxygen Inhalation

As a drug-mechanical combination technology, photodynamic (PDT) can achieve accurate and targeted therapy for malignant tumors and benign diseases through the production of reactive oxygen species, oxygen free radicals or singlet oxygen by photosensitizers at specific wavelengths. Compared with traditional surgery, it has the advantages of selective killing, repeatable treatment, preserving target organ function and so on. The purpose of this study was to explore the clinical value of photodynamic therapy in cervical precancerous lesions by taking the patients with low-grade cervical intraepithelial neoplasia (CIN1) with high-risk human papillomavirus (HR-HPV) persistent infection diagnosed by "three-step diagnosis and treatment procedure" as an example. Using HiPorfin as a photosensitizer, photodynamic therapy was performed 48 hours after intravenous drip. Set laser wavelength 630nm, light dose density 137.58J/cm2, transmission efficiency 1.42, output power 2w. 3cm columnar optical fiber was placed around the 2cm in the cervical canal to cover all the lesions, and the irradiation time was 900s (600s in the cervical canal and 300s outside the cervical canal). The patients were given oxygen inhalation for 6 hours after operation, and the patients were observed for itching and other discomfort, and paid attention to avoid light. Photodynamic therapy was performed again in the same way on the second day. After two months of treatment, pathological biopsy showed chronic cervicitis, indicating that the disease had been effectively controlled. Theoretically, although the patient is not the absolute indication of photodynamic therapy (that is, meeting CIN ? or CIN ?, having fertility requirements and not undergoing surgery), this therapy can remove not only the superficial lesions inside and outside the cervix, but also the potential lesions not found under colposcopy. It can also block the persistent infection of HPV by inhibiting the expression of HPV18, E6 and E7mRNA in Hela cells. In combination with Baofukang suppository, it can block HPV infection. Increase the negative conversion rate of cervical HPV and reduce the probability of recurrence after CIN1 cure. For young female patients with persistent HR-HPV infection and fertility requirements, photodynamic therapy is an effective choice for clinical treatment of CIN1.

Endometrial Cancer: genetic, metabolic characteristics, therapeutic strategies and nanomedicine

2021 ◽  
Vol 28 ◽  
Author(s):  
Yuxuan Cai ◽  
Bei Wang ◽  
Wen Xu ◽  
Kai Liu ◽  
Yisong Gao ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Precancerous Lesions ◽  
Hypoxia Inducible Factor ◽  
The United States ◽  
Genetic Alterations ◽  
Therapeutic Strategies ◽  
Current Application ◽  
Female Population ◽  
Von Hippel Lindau ◽  
Metabolic Characteristics

Background: Endometrial cancer is the fourth most common malignancy in the female population worldwide. It was estimated that 65,620 new cases and 12,590 subsequent deaths occurred in 2020 in the United States. Patients with type II and advanced endometrial cancer do not respond well to the current treatments. Therefore, endometrial cancer should be better understood in order to develop more effective treatments. Objective: To provide an overview of genetic, metabolic characteristics, therapeutic strategies and current application of nanotechnology surrounding endometrial cancer. Method: Relevant articles were retrieved from Pubmed and were systematically reviewed. Results: Hypoxia-inducible factor-1 and Von Hippel-Lindau factor participated in oncogenesis and progression of endometrial cancer, and Nrf2 was associated with oncogenesis. Various genetic alterations were found in endometrial cancer. The examination of the abnormal X chromosome inactivation may help with the diagnosis of endometrial cancer and its precancerous lesions. Some absent tumor suppressor genes, activated oncogenes were revealed by the genetically modified mouse models. Disorders in glucose and lipid metabolism were found in endometrial cancer. Current therapeutic strategies focused on the HIF-1α pathway, the mTOR pathway as well as immunotherapy. Nanotechnology showed great potential in endometrial cancer’s early diagnosis, metastasis determination and treatment. Conclusion: Endometrial cancer has been understood in various aspects, but the underlying mechanisms still remain relatively unknown, which might be the source of novel diagnostic, prognostic and therapeutic targets. Nanomedicine in endometrial cancer is poorly studied, but the current researches showed great results in treating endometrial cancer. It needs further researching.

Molecular Genetics of Cancer

2012 ◽  
Author(s):  
Leif W. Ellisen
Keyword(s):  
Risk Assessment ◽  
Tumor Suppressor ◽  
Environmental Factors ◽  
Cancer Risk ◽  
Tumor Progression ◽  
Cancer Genomics ◽  
Precancerous Lesions ◽  
Expression Profiles ◽  
Genetic Alterations ◽  
Cancer Risk Assessment

The uncontrolled clonal expansion of a cell, which often leads to invasion of surrounding tissues and metastatic spread, produces cancer. A clear histologic and molecular genetic evolution from precancerous lesions to frankly malignant and invasive cancer has been defined for some tumors (e.g., colon and bladder cancers). In rare cases, mutations may occur and be passed on in the germline, resulting in genetic predisposition to cancer (i.e., familial cancer syndromes). Environmental factors are also thought to contribute to the development of cancer. Interactions between environmental factors and subtle germline genetic variations that distinguish individuals may in some cases constitute an important determinant of cancer risk within the general population. Finally, viral infection has been linked to the development of specific cancers. Oncogenes and proto-oncogenes, and germline genetic analysis and cancer risk assessment are covered. Also discussed are genetic alterations and abnormalities, tumor suppressor genes, tumor progression, genetic mechanisms of treatment sensitivity and resistance, and emerging trends in cancer genomics and risk assessment. Figures illustrate activation of proto-oncogenes, the Knudsen two-hit model of tumor initiation, allelic losses in tumors, the retinoblastoma gene (RB1) cell cycle pathway, the p53 cellular stress and DNA damage response pathway, microsatellite instability and DNA mismatch repair, multiple oncogenes and tumor suppressors, tumor progression, cellular senescence and telomerase activation, tumor angiogenesis, chemotherapy drug resistance, targeting of oncogenic proteins by imatinib mesylate, analysis of expression profiles using high-density microarrays, and the spectrum of risk alleles for breast cancer predisposition. Tables outline oncogene and tumor suppressor gene mutations. This chapter contains 119 references.

Rare forms of vaginal diseases in women after panhysterectomy

2020 ◽  
Vol 19 (5) ◽  
pp. 150-155
Author(s):  
N.V. Zarochentseva ◽  
◽  
V.I. Krasnopolskiy ◽  
О.А. Misyukevich ◽  
I.V. Barinova ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Precancerous Lesions ◽  
Cell Cancer ◽  
Intraepithelial Neoplasia ◽  
Vaginal Wall ◽  
Cytological Examination ◽  
Clinical Observations ◽  
Papillomavirus Infection ◽  
Vaginal Intraepithelial Neoplasia ◽  
History Of

The article presents clinical observations of the development of precancerous conditions of the vaginal vault, and also squamous cell cancer in women after panhysterectomy. The examination included: comprehensive vaginoscopy, cytological examination of vaginal wall smears, human papillomavirus test, histological examination of bioplates. Conclusion. Panhysterectomy does not guarantee the absence of precancerous lesions of the vagina or vaginal cancer. Therefore, routine screening (cytology, testing for high-risk human papillomavirus, vaginoscopy) should be continued in women after panhysterectomy with a history of cervical intraepithelial neoplasias for at least 20 years, even in women older than 65 years. Key words: vaginal intraepithelial neoplasia, human papillomavirus, panhysterectomy, papillomavirus infection, cervical cancer, photodynamic therapy

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