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Cell Cycle of Cancer

Cancer Background

Cancer is a class of diseases in which abnormal cells divide without control and are able to invade other tissues. Cancer cells can spread to other parts of the body through the blood and lymph systems. Normally, cell proliferation is under tight control through many mechanisms. For example, DNA damage and repair mechanisms exist in order to decrease the likelihood of genetic mutation and cell transformation. Apoptosis is needed to destroy cells that represent a threat to the integrity of the organism. In addition, the immune system is ready to recognize and destroy cancerous cells. However these error-correction methods often fail in small ways, especially in environments that make errors more likely to arise and propagate. Accumulating disruptions in these control mechanisms lead to progressive error accumulation until unregulated proliferation and cancer forming.

Cell Cycle Background

The cell cycle is an ordered set of events, culminating in cell growth and division. The cell cycle of eukaryotes can be divided in two brief periods: interphase, during which the cell grows, accumulating nutrients needed for mitosis and duplicating its DNA, and the mitosis (M) phase, during which the cell splits itself into two distinct cells, often called “daughter cells”. By studying molecular events in cells, interphase is divided into three stages, G1, S, and G2. Thus the cell cycle consists of four phases: G1, S, G2, M.

G1 phase is from the end of the previous M phase until the beginning of DNA synthesis, and G stands for gap. During this phase the biosynthetic activities of the cell, which had been considerably slowed down during M phase, resume at a high rate. This phase is marked by synthesis of various enzymes that are required in S phase, mainly those needed for DNA replication. An important cell cycle control mechanism activated during this period (G1 Checkpoint) ensures that everything is ready for DNA synthesis.

DNA replication occurs during the ensuing S (synthesis) phase. To produce two similar daughter cells, the complete DNA instructions in the cell must be duplicated. Thus, during this phase, the amount of DNA in the cell has effectively doubled.

The cell then enters the G2 (gap 2) phase, which lasts until the cell enters mitosis. During the G2 phase the cell will continue to grow and produce new proteins. At the end of this gap is another control checkpoint (G2 Checkpoint) to determine if the cell can now proceed to enter M (mitosis) and divide.

After the interphase, during which the cell grows and accumulates nutrients, the cell begins mitosis. Cell growth and protein production stop, all of the cell’s energy is focused on the complex and orderly division into two similar daughter cells. As in both G1 and G2, there is a Checkpoint in the middle of mitosis (Metaphase Checkpoint) that ensures the cell is ready to complete cell division.

Nonproliferative cells in multicellular eukaryotes generally enter the quiescent G0 state from G1 and may remain quiescent for long periods of time. The G0 phase is even indefinitely for a cell that has reached an end stage of development and will no longer divide (e.g. neuron).

Early work in frog and invertebrate embryos suggested that cell cycle events are triggered by the activity of a biochemical oscillator centered on cyclin-CDK complexes. The cyclin/CDK complexes induce two processes, duplication of centrosomes and DNA during interphase, and mitosis. The roles of individual cyclins were tested by adding recombinant proteins to cyclin- biologidepleted extracts. Cyclin E supports DNA replication and centrosome duplication, cyclin A supports both of these processes and mitosis, and cyclin B supports mitosis alone. In the cell cycle, Cyclin D/CDK4, Cyclin D/CDK6, and Cyclin E/CDK2 regulate transition from G1 to S phase; Cyclin A/CDK2 is active in S phase; Cyclin B/CDK1 regulates progression from G2 to M phase.

It is widely accepted that the central cell cycle oscillator is based on cyclin/CDK complexes. However, this view of cell cycle regulation was challenged by evidence fora cyclin/CDK-independent oscillator in budding yeast. Haase SB and Reed SI. observed that oscillations of similar periodicity in cells responding to mating pheromone in the absence of G1 cyclin (Cln)- and mitotic cyclin (Clyclin B)-associated kinase activity in the budding yeast Saccharomyces cerevisiae. It is indicated that a previously unrecognized oscillator may play an integral role in regulating early cell cycle events. In addition, Orlando DA and colleagues discovered that a network of sequentially expressed transcription factors could regulate the bulk of the periodic transcription program and function as an oscillator independent of Cyclin B/CDKs.

Cancer Biomarker / Tumor Biomarker

Cancer biomarkers are present in tumor tissues or serum and encompass a wide variety of molecules, including DNA, mRNA, transcription factors, cell surface receptors, and secreted proteins. Cancer biomarkers can be used for prognosis: to predict the natural course of a tumor, indicating whether the outcome for the patient is likely to be good or poor (prognosis). They can also help doctors to decide which patients are likely to respond to a given drug (prediction) and at what dose it might be most effective (pharmacodynamics).

Sino Biological offers a comprehensive set of tools for cancer biomarker related studies, including recombinant proteins, antibodies (rabbit mAbs, mouse mAbs, rabbit pAbs), ELISA kits, and ORF cDNA clones.

Cancer Stem Cell (CSC) Marker

Sino Biological offers a comprehensive set of tools for study of cancer stem cells. These include recombinant proteins, antibodies, ELISA kits and gene cDNA clones directed towards molecules which are identified as cancer stem cell (CSC) markers or involved in CSC proliferation and differentiation pathways.

Cancer Stem Cell (CSC) Background

A cancer stem cell (CSC) is a cell within a tumor that possesses the capacity to self-renew and to generate the heterogeneous lineages of cancer cells that comprise the tumor. Bonnet and Dick isolated a subpopulation of leukaemic cells that express a specific surface marker CD34, but lack the CD38 marker. It is the first conclusive evidence for cancer stem cells. Later studies discovered that some other malignant tumors, including cancers of the: brain, breast, colon, ovary, pancreas and prostate, can also be composed of morphologically and phenotypically heterogeneous cell populations with varying self-renewal capacities, degrees of differentiation, and clonogenic and tumorigenic potentials. These observations have led to the development of the cancer stem cell theory, which points that many tumors, like physiologic tissues, can be hierarchically organized, and that cancer stem cells are essential for their propagation.

Not only is finding the source of cancer cells necessary for successful treatments, but if current treatments of cancer do not properly destroy enough cancer stem cells, the tumor will reappear. Therefore, the successful elimination of a cancer requires anticancer therapy that affects the differentiated cancer cells and the potential cancer stem cell population. Indeed, cancer stem cell-targeted approaches have shown promise in preclinical models. These approaches include direct strategies, such as ablation by targeting molecular markers of cancer stem cells or cancer stem cell-specific pathways, reversal of resistance mechanisms, and differentiation therapy, and indirect strategies, such as antiangiogenic therapy, immunotherapeutic approaches, and disruption of protumorigenic interactions between cancer stem cells and their microenvironment. A number of studies have focused on identifying specific cancer stem cell markers. Pancreatic cancer stem cells express the surface markers CD44, CD24 and epithelial specific antigen (ESA). It has also been identified that liver progenitor cells share molecular markers with adult hepatocytes and fetal hepatocytes. In addition, markers frequently used to identify adult stem cells within the prostate, breast and intestine include CD44, CD133, ESA, CD69, p63, as well as some stem cell antigen, such as CD34, c-kit, Flt-3, NCAM, and Thy-1.

Growth Factor & Receptor Background

The term growth factor encompasses a complex family of polypeptide hormones, steroid hormones, or biological factors that are capable of stimulating cell growth, proliferation and differentiation. Growth factors are important for regulating a variety of cellular processes, including regulating tissue morphogenesis, angiogenesis, cell differentiation, and neurite outgrowth. Growth factors typically act as signaling molecules between cells. Activities of growth factors are mediated via binding to transmembrane receptors that often contain cytoplasmic tyrosine kinase domains. For the last two decades, growth factors have been increasingly used in the treatment of hematologic and oncologic diseases and cardiovascular diseases like: neutropenia, myelodysplastic syndrome (MDS), leukemias, aplastic anaemia, bone marrow transplantation, angiogenesis for cardiovascular diseases.

How alkalising your body helps fight cancer

The concept of alkalizing your body to fight cancer stems from the belief that an acidic environment in the body promotes the growth of cancer cells, and therefore, by making the body more alkaline, it can help inhibit cancer growth. However, it’s important to understand that the human body has a highly regulated pH balance, and organs and systems work together to maintain this balance within a narrow range.

While the direct impact of alkalizing the body on fighting cancer is still a subject of debate, there are certain potential benefits to adopting a balanced, alkaline-promoting lifestyle that may indirectly support overall health and well-being, including cancer prevention and management. Here are some potential benefits:

  • Body pH Regulation: The body tightly regulates pH levels through various mechanisms, including the respiratory system, kidneys, and buffering systems. These mechanisms maintain the blood pH around a slightly alkaline range of 7.35 to 7.45, regardless of the pH of specific body tissues or fluids.
  • Limited Impact on Tissue pH: Consuming alkaline foods or supplements is unlikely to significantly impact the pH of body tissues or fluids. The body has natural mechanisms in place to maintain pH homeostasis, and altering tissue pH through dietary means is challenging.
  • Balanced Diet: Rather than focusing on extreme pH-altering approaches, it’s more important to adopt a balanced and nutritious diet. A diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats can provide essential nutrients, antioxidants, and phytochemicals that support overall health, including the immune system.
  • Nutrient-Rich Diet: An alkaline-promoting diet often includes a variety of fruits, vegetables, whole grains, and plant-based proteins. These foods are rich in vitamins, minerals, and antioxidants that can support the body’s overall health and immune function. A well-rounded diet provides essential nutrients necessary for proper cellular function and may contribute to overall well-being.
  • Anti-inflammatory Effects: Many alkaline-promoting foods have anti-inflammatory properties. Chronic inflammation is associated with an increased risk of developing various diseases, including certain types of cancer. By consuming an alkaline diet, which is often rich in fruits and vegetables, you may help reduce inflammation in the body.
  • Weight Management: An alkaline-promoting diet often emphasizes whole, unprocessed foods and limits processed and sugary foods. This can support weight management and reduce the risk of obesity. Obesity is a known risk factor for several types of cancer, so maintaining a healthy weight may contribute to cancer prevention.
  • Healthy Lifestyle Choices: Adopting an alkaline-promoting lifestyle often involves incorporating other healthy habits such as regular exercise, stress management, and avoiding excessive alcohol consumption and tobacco use. These lifestyle choices have been linked to a lower risk of developing cancer and can improve overall well-being.
  • Increased Intake of Plant-Based Foods: Alkaline-promoting diets typically encourage the consumption of plant-based foods, which are rich in fiber and various phytochemicals. Fiber promotes digestive health, helps maintain healthy blood sugar levels, and may play a role in reducing the risk of certain cancers, particularly colorectal cancer. Phytochemicals found in plant foods have been studied for their potential anti-cancer properties.
  • Hydration: Alkaline-promoting diets often emphasize the importance of proper hydration. Staying adequately hydrated is crucial for overall health and supports optimal bodily functions, including maintaining healthy cellular activity and efficient elimination of waste products.

It’s important to note that while adopting an alkaline-promoting lifestyle may offer potential benefits, it should not be considered a standalone treatment or cure for cancer. It’s essential to consult with healthcare professionals, including oncologists and registered dietitians, for personalized guidance and to integrate evidence-based approaches into cancer prevention, treatment, and management.

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