Fractional Kill
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Fractional Kill
In oncology, the fact that one round of chemotherapy does not kill all the cells in a tumor is a poorly understood phenomenon called fractional kill, or fractional cell kill. The fractional kill hypothesis states that a defined chemotherapy concentration, applied for a defined time period, will kill a constant fraction of the cells in a population, independent of the absolute number of cells.Chabner, B. and D. L. Longo (2006). Cancer Chemotherapy and Biotherapy: Principles and Practice. Philadelphia, Lippincott Willians & Wilkins. In solid tumors, poor access of the tumor to the drug can limit the fraction of tumor cells killed, but the validity of the fractional kill hypothesis has also been established in animal models of leukemia, as well as in human leukemia and lymphoma, where drug access is less of an issue. Because only a fraction of the cells die with each treatment, repeated doses must be administered to continue to reduce the size of the tumor. Current chemotherapy regim ...
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Oncology
Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''ónkos''), meaning "tumor", "volume" or "mass". Oncology is concerned with: * The diagnosis of any cancer in a person (pathology) * Therapy (e.g. surgery, chemotherapy, radiotherapy and other modalities) * Follow-up of cancer patients after successful treatment * Palliative care of patients with terminal malignancies * Ethical questions surrounding cancer care * Screening efforts: ** of populations, or ** of the relatives of patients (in types of cancer that are thought to have a hereditary basis, such as breast cancer) Diagnosis Medical histories remain an important screening tool: the character of the complaints and nonspecific symptoms (such as fatigue, weight loss, unexplained anemia, fever of unknown origin, paraneoplasti ...
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Chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs) or it may aim to prolong life or to reduce symptoms ( palliative chemotherapy). Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called ''medical oncology''. The term ''chemotherapy'' has come to connote non-specific usage of intracellular poisons to inhibit mitosis (cell division) or induce DNA damage, which is why inhibition of DNA repair can augment chemotherapy. The connotation of the word chemotherapy excludes more selective agents that block extracellular signals ( signal transduction). The development of therapies with specific molecular or genetic targ ...
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Cell (biology)
The cell is the basic structural and functional unit of life forms. Every cell consists of a cytoplasm enclosed within a membrane, and contains many biomolecules such as proteins, DNA and RNA, as well as many small molecules of nutrients and metabolites.Cell Movements and the Shaping of the Vertebrate Body
in Chapter 21 of
Molecular Biology of the Cell
'' fourth edition, edited by Bruce Alberts (2002) published by Garland Science. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos. It is also common to describe small molecules such as ...
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Tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, when it may be called a tumor. ICD-10 classifies neoplasms into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers and are the focus of oncology. Prior to the abnormal growth of tissue, as neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia. However, metaplasia or dysplasia does not always progress to neoplasia and can occur in other conditions as well. The word is from Ancient Greek 'new' and 'formation, creation'. Types A neoplasm can be benign, potentially m ...
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Cell Cycle
The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subsequently the partitioning of its cytoplasm, chromosomes and other components into two daughter cells in a process called cell division. In cells with nuclei ( eukaryotes, i.e., animal, plant, fungal, and protist cells), the cell cycle is divided into two main stages: interphase and the mitotic (M) phase (including mitosis and cytokinesis). During interphase, the cell grows, accumulating nutrients needed for mitosis, and replicates its DNA and some of its organelles. During the mitotic phase, the replicated chromosomes, organelles, and cytoplasm separate into two new daughter cells. To ensure the proper replication of cellular components and division, there are control mechanisms known as cell cycle checkpoints after each of the key s ...
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Cytarabine
Cytarabine, also known as cytosine arabinoside (ara-C), is a chemotherapy medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin's lymphoma. It is given by injection into a vein, under the skin, or into the cerebrospinal fluid. There is a liposomal formulation for which there is tentative evidence of better outcomes in lymphoma involving the meninges. Common side effects include bone marrow suppression, vomiting, diarrhea, liver problems, rash, ulcer formation in the mouth, and bleeding. Other serious side effects include loss of consciousness, lung disease, and allergic reactions. Use during pregnancy may harm the baby. Cytarabine is in the antimetabolite and nucleoside analog families of medication. It works by blocking the function of DNA polymerase. Cytarabine was patented in 1960 and approved for medical use in 1969. It is on the World Health Organization's List of Essential Medicin ...
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S Phase
S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during S-phase are tightly regulated and widely conserved. Regulation Entry into S-phase is controlled by the G1 restriction point (R), which commits cells to the remainder of the cell-cycle if there is adequate nutrients and growth signaling. This transition is essentially irreversible; after passing the restriction point, the cell will progress through S-phase even if environmental conditions become unfavorable. Accordingly, entry into S-phase is controlled by molecular pathways that facilitate a rapid, unidirectional shift in cell state. In yeast, for instance, cell growth induces accumulation of Cln3 cyclin, which complexes with the cyclin dependent kinase CDK2. The Cln3-CDK2 complex promotes transcription of S-phase genes by inactivating ...
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Apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old, approximately twenty to thirty billion cells die per day. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apop ...
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Flow Cytometry
Flow cytometry (FC) is a technique used to detect and measure physical and chemical characteristics of a population of cells or particles. In this process, a sample containing cells or particles is suspended in a fluid and injected into the flow cytometer instrument. The sample is focused to ideally flow one cell at a time through a laser beam, where the light scattered is characteristic to the cells and their components. Cells are often labeled with fluorescent markers so light is absorbed and then emitted in a band of wavelengths. Tens of thousands of cells can be quickly examined and the data gathered are processed by a computer. Flow cytometry is routinely used in basic research, clinical practice, and clinical trials. Uses for flow cytometry include: * Cell counting * Cell sorting * Determining cell characteristics and function * Detecting microorganisms * Biomarker detection * Protein engineering detection * Diagnosis of health disorders such as blood cancers * Measuring ...
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Actinomycin D1
Dactinomycin, also known as actinomycin D, is a chemotherapy medication used to treat a number of types of cancer. This includes Wilms tumor, rhabdomyosarcoma, Ewing's sarcoma, trophoblastic neoplasm, testicular cancer, and certain types of ovarian cancer. It is given by intravenous, injection into a vein. Most people develop side effects. Common side effects include bone marrow suppression, vomiting, mouth ulcers, hair loss, liver problems, infections, and muscle pains. Other serious side effects include future cancers, allergic reactions, and necrosis, tissue death at the site of injection. Use in pregnancy may harm the baby. Dactinomycin is in the cytotoxic antibiotic family of medications. It is believed to work by blocking the creation of RNA. Dactinomycin was approved for medical use in the United States in 1964. It is on the WHO Model List of Essential Medicines, World Health Organization's List of Essential Medicines. Medical use Actinomycin is a clear, yellowish liq ...
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