Breast Cancer
Mary J. Marian, Gerard E. Mullin in Integrating Nutrition Into Practice, 2017
Carcinogenesis is a multistage process consisting of several phases including initiation, promotion, and progression (Figure 9.2). Initiation occurs when the cell has been exposed to an agent that results in the first genetic mutation, but by itself initiation is not sufficient for a cancer to develop. Instead, the initiated cell must be activated by a promoting agent that causes cellular proliferation—that is, the process called promotion. Initiated and promoted cells eventually form a tumor mass during the process of progression. At the end of the carcinogenesis process, the cell will have some or all of the characteristics of a cancer cell: growth signal autonomy, insensitivity to antigrowth signals, limitless replicative potential, evasion of apoptosis, sustained angiogenesis, tissue invasion, and metastasis. Diet, including whole foods (vegetables, whole grains, teas, etc.) and bioactive constitutive compounds within foods, can influence cancer development at various stages. In 2007, a joint panel of the World Cancer Research Fund (WCRF) and American Institute for Cancer Research published its findings on the role of food, nutrition, and physical activity in cancer prevention. These evidence-based reviews are updated periodically on the website at http://www.dietandcancerreport.org/cup/. In their 2010 updated review breast cancer report, the panel members judged the weight of the evidence for the role of nutrition and lifestyle factors in the etiology of breast cancer (http://www.dietandcancerreport.org/cancer_resource_center/downloads/cu/Breast-Cancer-2010-Report). Premenopausal and postmenopausal breast cancers were considered separately in the report. Premenopausal cancers are thought to be mainly genetically driven, with the environment and nutrition playing smaller roles in their genesis.
Nutraceutical’s Role in Proliferation and Prevention of Colorectal Cancer
Sheeba Varghese Gupta, Yashwant V. Pathak in Advances in Nutraceutical Applications in Cancer, 2019
Cancer rates are tolling high constantly worldwide. High life expectancy, environmental changes, urbanization, and changing lifestyles have been vital contributive factors for the hike in carcinogenesis. Carcinogenesis is a complex process that involves numerous pathways that bring oncogenetic transformation in the normal cells and render them unassailably viable. The cancer cells undergo unlimited replication due to growth signal autonomy, evasion of growth and inhibitory signals, evasion of apoptosis, invasion, metastasis, and sustained angiogenesis [1]. The fact that cancer cells are very similar to the normal human cells makes them a very difficult target. In spite of extensive research and development in the field of oncology, it still remains a big challenge to prevent, treat, or mitigate this disease. Among several cancer subtypes, one of the highly incidental and preventive cancer is the colorectal cancer (CRC). As per American Cancer Society’s (ACS) statistical data, CRC is the third most common cancer worldwide. CRC is one of the most lethal cancers contributing to about 7,000,000 annual cancer-related deaths [2]. The ACS has estimated an astounding statistics that claims 97,220 new cases of colon and 43,030 new cases of rectal cancer present every year. Their extrapolated estimates for 2018 presented a lifetime risk of about 1 in 22 men and 1 in 24 women to be suffering from CRC. The global burden of CRC is expected to increase by 60 % till 2030; expecting about 2.2 million new cases and about 1.1 million deaths. Out of several risk factors that are believed to contribute to the pathogenesis of this lethal disease, diet and lifestyle have been realized to have a principal role.
Carcinogenesis and Molecular Genetics
Peter G. Shields in Cancer Risk Assessment, 2005
All tissues have a rate at which cells naturally die, while other cells divide to take their place. The skin, for example, consists of large numbers of cells that are dying or dead and are constantly sloughed off, while new layers of skin regenerate by cell division beneath the cell surface. Maintaining the homeostatic balance of cell loss and cell gain is crucial to the health and survival of the tissue and organism, and so the balance is tightly regulated in all tissues throughout the body. Disturbing this balance of cell loss and cell proliferation can lead to disease. Tumor formation occurs when cell division exceeds cell death. This happens in one of two ways: either cell proliferation is increased so that it occurs faster than cell death or cell death is prevented or slowed so that it no longer keeps up with cell division. The progression of cellular changes leading to this excess growth and formation of a malignant tumor is the process known as multistage carcinogenesis. Most, if not all, of the morphological and biochemical characteristics of malignant cells have as their source either genetical or epigenetical alterations in gene expression. Therefore, the controls that usually tightly regulate the cell growth and death processes on a molecular level must be examined and manipulated in order to fully understand multistage carcinogenesis. Many factors can contribute to carcinogenesis, including viruses, chemicals, radiation, diet, hormones, and genetical predisposition. Currently, there is much attention ascribed to cancer genes that can increase or decrease an individual’s chance of getting cancer and influence a person’s prognosis after the diagnosis of cancer has been made. In addition to providing risk assessment information, knowledge of why these genes are important and how they work may yield important clues to the molecular causes of cancer. Genes that are important in cancer come in two general types, operationally defined as oncogenes and tumor suppressor genes (1). Oncogenes are genes which act to stimulate cell division or increase cell survival, when expressed in a biochemically abnormal environment which is permissive for their growth stimulatory effects. When overexpressed or expressed aberrantly, they may disrupt the division–death ratio. Tumor suppressor genes have an equally important role in tissues, but in preventing in tumor formation. Normally, they protect cells from abnormal growth in several ways and, in cancers, are often found to be mutated so that their function is either altered or lost entirely. The complex interplay between oncogenes and tumor suppressor genes can be exemplified using the ras oncogene which becomes oncogenic by expressing altered function after a single base change, and the bcl-2 gene, which codes for a mitochondrial protein that helps prevent apoptotic cell death. Overexpression of a mutant ras oncogene is actually lethal to normal cells, but in the context of a cell which has lost expression of bcl-2, mutant ras becomes promitogenic (2).
Documentation of Ultrastructural Changes in Nucleus and Microvilli by Fish Oil in Experimental Colon Carcinogenesis
Published in Ultrastructural Pathology, 2015
Gayatri Sharma, Isha Rani, Archana Bhatnagar, Navneet Agnihotri
Fish oil (FO) exerts a chemopreventive effect by regulating apoptosis in colon carcinogenesis. The present study reports the ultrastructural changes in various organelles on supplementation of FO in experimental colon carcinogenesis. The carcinogen treatment led to abnormal nuclear shape and alteration in microvilli number indicating cancer establishment. On the other hand, different ratios of FO and corn oil increased chromatin condensation along with an extensive loss of microvilli in a dose- and time-dependent manner which depicts an increase in apoptosis. The associated ultrastuctural alterations support the facilitation of apoptosis by FO as a mechanism for its beneficial effect in colon carcinogenesis.
Role of canonical Wnt signaling in endometrial carcinogenesis
Published in Expert Review of Anticancer Therapy, 2012
Thanh H Dellinger, Kestutis Planutis, Krishnansu S Tewari, Randall F Holcombe
While the role of Wnt signaling is well established in colorectal carcinogenesis, its function in gynecologic cancers has not been elucidated. Here, we describe the current state of knowledge of canonical Wnt signaling in endometrial cancer (EC), and its implications for future therapeutic targets. Deregulation of the Wnt/β-catenin signaling pathway in EC occurs by inactivating β-catenin mutations in approximately 10–45% of ECs, and via downregulation of Wnt antagonists by epigenetic silencing. The Wnt pathway is intimately involved with estrogen and progesterone, and emerging data implicate it in other important signaling pathways, such as mTOR and Hedgehog. While no therapeutic agents targeting the Wnt signaling pathway are currently in clinical trials, the preclinical data presented suggest a role for Wnt signaling in uterine carcinogenesis, with further research warranted to elucidate the mechanism of action and to proceed towards targeted cancer drug development.
Extracting biomarkers of commitment to cancer development: potential role of vibrational spectroscopy in systems biology
Published in Expert Review of Molecular Diagnostics, 2015
Georgios Theophilou, Maria Paraskevaidi, Kássio MG Lima, Maria Kyrgiou, Pierre L Martin-Hirsch, Francis L Martin
The complex processes driving cancer have so far impeded the discovery of dichotomous biomarkers associated with its initiation and progression. Reductionist approaches utilizing ‘omics’ technologies have met some success in identifying molecular alterations associated with carcinogenesis. Systems biology is an emerging science that combines high-throughput investigation techniques to define the dynamic interplay between regulatory biological systems in response to internal and external cues. Vibrational spectroscopy has the potential to play an integral role within systems biology research approaches. It is capable of examining global models of carcinogenesis by scrutinizing chemical bond alterations within molecules. The application of infrared or Raman spectroscopic approaches coupled with computational analysis under the systems biology umbrella can assist the transition of biomarker research from the molecular level to the system level. The comprehensive representation of carcinogenesis as a multilevel biological process will inevitably revolutionize cancer-related healthcare by personalizing risk prediction and prevention.
Related Knowledge Centers
- Metastasis
- Oncogene
- Cancer
- Neoplastic Processes
- Epigenetic
- Natural Selection
- Malignant Transformation