118-449: 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
236-480: A glycopeptide isolated from Streptomyces verticillus , also intercalates DNA, but produces free radicals that damage DNA. This occurs when bleomycin binds to a metal ion , becomes chemically reduced and reacts with oxygen . Mitomycin is a cytotoxic antibiotic with the ability to alkylate DNA. Most chemotherapy is delivered intravenously , although a number of agents can be administered orally (e.g., melphalan , busulfan , capecitabine ). According to
354-459: A nucleobase , a sugar and a phosphate group . The nucleobases are divided into purines ( guanine and adenine ) and pyrimidines ( cytosine , thymine and uracil ). Anti-metabolites resemble either nucleobases or nucleosides (a nucleotide without the phosphate group), but have altered chemical groups . These drugs exert their effect by either blocking the enzymes required for DNA synthesis or becoming incorporated into DNA or RNA. By inhibiting
472-414: A certain dose, the effect plateaus and proportionally no more cell death occurs with increased doses. Subtypes of the anti-metabolites are the anti-folates , fluoropyrimidines, deoxynucleoside analogues and thiopurines . The anti-folates include methotrexate and pemetrexed . Methotrexate inhibits dihydrofolate reductase (DHFR), an enzyme that regenerates tetrahydrofolate from dihydrofolate . When
590-531: A chemical that stops movement of other cells in the affected area, thus preventing the intruder from using the sponge's internal transport systems. If the intrusion persists, the grey cells concentrate in the area and release toxins that kill all cells in the area. The "immune" system can stay in this activated state for up to three weeks. Sponges have three asexual methods of reproduction: after fragmentation, by budding , and by producing gemmules . Fragments of sponges may be detached by currents or waves. They use
708-564: A context fear conditioning event. The blockage of memory consolidation was proposed to be due to the inhibition by Ara-CTP of the DNA non-homologous end joining pathway. Thus transient DNA breakage followed by non-homologous end joining appear to be necessary steps in the formation of a long-term memory of an event. Isolation of arabinose-containing nucleotides from the Caribbean sponge Cryptotheca crypta (now Tectitethya crypta ) together with
826-445: A few carnivorous sponges have lost these water flow systems and the choanocytes. All known living sponges can remold their bodies, as most types of their cells can move within their bodies and a few can change from one type to another. Even if a few sponges are able to produce mucus – which acts as a microbial barrier in all other animals – no sponge with the ability to secrete a functional mucus layer has been recorded. Without such
944-444: A high index of suspicion and the use of CT scanning, nonoperative treatment for uncomplicated cases, and sometimes elective right hemicolectomy to prevent recurrence. Nausea , vomiting , anorexia , diarrhea , abdominal cramps, and constipation are common side-effects of chemotherapeutic medications that kill fast-dividing cells. Malnutrition and dehydration can result when the recipient does not eat or drink enough, or when
1062-546: A large extent, chemotherapy can be thought of as a way to damage or stress cells, which may then lead to cell death if apoptosis is initiated. Many of the side effects of chemotherapy can be traced to damage to normal cells that divide rapidly and are thus sensitive to anti-mitotic drugs: cells in the bone marrow , digestive tract and hair follicles . This results in the most common side-effects of chemotherapy: myelosuppression (decreased production of blood cells, hence that also immunosuppression ), mucositis (inflammation of
1180-423: A mucus layer their living tissue is covered by a layer of microbial symbionts, which can contribute up to 40–50% of the sponge wet mass. This inability to prevent microbes from penetrating their porous tissue could be a major reason why they have never evolved a more complex anatomy. Like cnidarians (jellyfish, etc.) and ctenophores (comb jellies), and unlike all other known metazoans, sponges' bodies consist of
1298-542: A non-living jelly-like mass ( mesohyl ) sandwiched between two main layers of cells. Cnidarians and ctenophores have simple nervous systems, and their cell layers are bound by internal connections and by being mounted on a basement membrane (thin fibrous mat, also known as " basal lamina "). Sponges do not have a nervous system similar to that of vertebrates but may have one that is quite different. Their middle jelly-like layers have large and varied populations of cells, and some types of cells in their outer layers may move into
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#17327930804091416-417: A number of strategies in the administration of chemotherapeutic drugs used today. Chemotherapy may be given with a curative intent or it may aim to prolong life or to palliate symptoms . All chemotherapy regimens require that the recipient be capable of undergoing the treatment. Performance status is often used as a measure to determine whether a person can receive chemotherapy, or whether dose reduction
1534-767: A preventative and treatment effect of diarrhoea related to chemotherapy alone and with radiotherapy. However, a high index of suspicion is appropriate, since diarrhoea and bloating are also symptoms of typhlitis , a very serious and potentially life-threatening medical emergency that requires immediate treatment. Anemia can be a combined outcome caused by myelosuppressive chemotherapy, and possible cancer-related causes such as bleeding , blood cell destruction ( hemolysis ), hereditary disease, kidney dysfunction, nutritional deficiencies or anemia of chronic disease . Treatments to mitigate anemia include hormones to boost blood production ( erythropoietin ), iron supplements , and blood transfusions . Myelosuppressive therapy can cause
1652-601: A recent (2016) systematic review, oral therapies present additional challenges for patients and care teams to maintain and support adherence to treatment plans. There are many intravenous methods of drug delivery, known as vascular access devices. These include the winged infusion device , peripheral venous catheter , midline catheter, peripherally inserted central catheter (PICC), central venous catheter and implantable port . The devices have different applications regarding duration of chemotherapy treatment, method of delivery and types of chemotherapeutic agent. Depending on
1770-876: A root-like base. Sponges are more abundant but less diverse in temperate waters than in tropical waters, possibly because organisms that prey on sponges are more abundant in tropical waters. Glass sponges are the most common in polar waters and in the depths of temperate and tropical seas, as their very porous construction enables them to extract food from these resource-poor waters with the minimum of effort. Demosponges and calcareous sponges are abundant and diverse in shallower non-polar waters. The different classes of sponge live in different ranges of habitat: Sponges with photosynthesizing endosymbionts produce up to three times more oxygen than they consume, as well as more organic matter than they consume. Such contributions to their habitats' resources are significant along Australia's Great Barrier Reef but relatively minor in
1888-401: A state of assembly and disassembly. Vinca alkaloids and taxanes are the two main groups of anti-microtubule agents, and although both of these groups of drugs cause microtubule dysfunction, their mechanisms of action are completely opposite: Vinca alkaloids prevent the assembly of microtubules, whereas taxanes prevent their disassembly. By doing so, they can induce mitotic catastrophe in
2006-644: A study in 2007 found no evidence of this and concluded that they extract bacteria and other micro-organisms from water very efficiently (about 79%) and process suspended sediment grains to extract such prey. Collar bodies digest food and distribute it wrapped in vesicles that are transported by dynein "motor" molecules along bundles of microtubules that run throughout the syncytium . Sponges' cells absorb oxygen by diffusion from water into cells as water flows through body, into which carbon dioxide and other soluble waste products such as ammonia also diffuse. Archeocytes remove mineral particles that threaten to block
2124-568: A tendency to bleed easily, leading to anemia. Medications that kill rapidly dividing cells or blood cells can reduce the number of platelets in the blood, which can result in bruises and bleeding . Extremely low platelet counts may be temporarily boosted through platelet transfusions and new drugs to increase platelet counts during chemotherapy are being developed. Sometimes, chemotherapy treatments are postponed to allow platelet counts to recover. Sponge Parazoa /Ahistozoa ( sans Placozoa ) Sponges or sea sponges are members of
2242-471: A third of the total mass of living tissue in some sponges, and some sponges gain 48% to 80% of their energy supply from these micro-organisms. In 2008, a University of Stuttgart team reported that spicules made of silica conduct light into the mesohyl , where the photosynthesizing endosymbionts live. Sponges that host photosynthesizing organisms are most common in waters with relatively poor supplies of food particles and often have leafy shapes that maximize
2360-738: Is biomineralized . The mesohyl functions as an endoskeleton in most sponges, and is the only skeleton in soft sponges that encrust hard surfaces such as rocks. More commonly the mesohyl is stiffened by mineral spicules , by spongin fibers or both. Spicules, which are present in most but not all species, may be made of silica or calcium carbonate, and vary in shape from simple rods to three-dimensional "stars" with up to six rays. Spicules are produced by sclerocyte cells, and may be separate, connected by joints, or fused. Some sponges also secrete exoskeletons that lie completely outside their organic components. For example, sclerosponges ("hard sponges") have massive calcium carbonate exoskeletons over which
2478-484: Is systemic therapy for cancer: they are introduced into the blood stream (the system) and therefore can treat cancer anywhere in the body. Systemic therapy is often used with other, local therapy (treatments that work only where they are applied), such as radiation , surgery , and hyperthermia . Traditional chemotherapeutic agents are cytotoxic by means of interfering with cell division (mitosis) but cancer cells vary widely in their susceptibility to these agents. To
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#17327930804092596-572: Is a neuter plural of the Modern Latin term porifer , which comes from the roots porus meaning "pore, opening", and -fer meaning "bearing or carrying". Sponges are similar to other animals in that they are multicellular , heterotrophic , lack cell walls and produce sperm cells . Unlike other animals, they lack true tissues and organs . Some of them are radially symmetrical, but most are asymmetrical. The shapes of their bodies are adapted for maximal efficiency of water flow through
2714-479: Is a "life-threatening gastrointestinal complication of chemotherapy." Typhlitis is an intestinal infection which may manifest itself through symptoms including nausea , vomiting , diarrhea , a distended abdomen , fever , chills , or abdominal pain and tenderness. Typhlitis is a medical emergency . It has a very poor prognosis and is often fatal unless promptly recognized and aggressively treated. Successful treatment hinges on early diagnosis provided by
2832-1054: Is a nucleobase analogue that is metabolised in cells to form at least two active products; 5-fluourouridine monophosphate (FUMP) and 5-fluoro-2'-deoxyuridine 5'-phosphate (fdUMP). FUMP becomes incorporated into RNA and fdUMP inhibits the enzyme thymidylate synthase; both of which lead to cell death. Capecitabine is a prodrug of 5-fluorouracil that is broken down in cells to produce the active drug. The deoxynucleoside analogues include cytarabine , gemcitabine , decitabine , azacitidine , fludarabine , nelarabine , cladribine , clofarabine , and pentostatin . The thiopurines include thioguanine and mercaptopurine . Anti-microtubule agents are plant -derived chemicals that block cell division by preventing microtubule function. Microtubules are an important cellular structure composed of two proteins, α-tubulin and β-tubulin . They are hollow, rod-shaped structures that are required for cell division, among other cellular functions. Microtubules are dynamic structures, which means that they are permanently in
2950-568: Is an important factor in achieving better treatment outcomes. Similar results were found in a study involving people with colorectal cancer who have been treated with the popular FOLFOX regimen. The incidence of serious diarrhea was reduced from 12% in the BSA-dosed group of patients to 1.7% in the dose-adjusted group, and the incidence of severe mucositis was reduced from 15% to 0.8%. The FOLFOX study also demonstrated an improvement in treatment outcomes. Positive response increased from 46% in
3068-500: Is an independent prognostic predictor of survival in various cancer types. Alkylating agents are the oldest group of chemotherapeutics in use today. Originally derived from mustard gas used in World War I , there are now many types of alkylating agents in use. They are so named because of their ability to alkylate many molecules, including proteins , RNA and DNA . This ability to bind covalently to DNA via their alkyl group
3186-402: Is constant, specimens 1 m (3.3 ft) wide must be about 5,000 years old. Some sponges start sexual reproduction when only a few weeks old, while others wait until they are several years old. Adult sponges lack neurons or any other kind of nervous tissue . However, most species have the ability to perform movements that are coordinated all over their bodies, mainly contractions of
3304-431: Is easiest. The fragile glass sponges , with " scaffolding " of silica spicules, are restricted to polar regions and the ocean depths where predators are rare. Fossils of all of these types have been found in rocks dated from 580 million years ago . In addition Archaeocyathids , whose fossils are common in rocks from 530 to 490 million years ago , are now regarded as a type of sponge. Although most of
3422-504: Is known about how they actually capture prey, although some species are thought to use either sticky threads or hooked spicules . Most carnivorous sponges live in deep waters, up to 8,840 m (5.49 mi), and the development of deep-ocean exploration techniques is expected to lead to the discovery of several more. However, one species has been found in Mediterranean caves at depths of 17–23 m (56–75 ft), alongside
3540-433: Is much greater than that of the canals, water flow through chambers slows to 3.6 cm per hour , making it easy for choanocytes to capture food. All the water is expelled through a single osculum at about 8.5 cm per second , fast enough to carry waste products some distance away. In zoology a skeleton is any fairly rigid structure of an animal, irrespective of whether it has joints and irrespective of whether it
3658-536: Is obtained from the Chinese ornamental tree Camptotheca acuminata . Drugs that target topoisomerase II can be divided into two groups. The topoisomerase II poisons cause increased levels enzymes bound to DNA. This prevents DNA replication and transcription, causes DNA strand breaks, and leads to programmed cell death ( apoptosis ). These agents include etoposide , doxorubicin , mitoxantrone and teniposide . The second group, catalytic inhibitors, are drugs that block
Cytarabine - Misplaced Pages Continue
3776-901: Is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer , which is called medical oncology . The term chemotherapy now means the non-specific use of intracellular poisons to inhibit mitosis (cell division) or to induce DNA damage (so that DNA repair can augment chemotherapy). This meaning excludes the more-selective agents that block extracellular signals ( signal transduction ). Therapies with specific molecular or genetic targets, which inhibit growth-promoting signals from classic endocrine hormones (primarily estrogens for breast cancer and androgens for prostate cancer), are now called hormonal therapies . Other inhibitions of growth-signals, such as those associated with receptor tyrosine kinases , are targeted therapy . The use of drugs (whether chemotherapy, hormonal therapy, or targeted therapy)
3894-434: Is probably most common, where larvae with vertically transmitted symbionts also acquire others horizontally). There are four types of larvae, but all are lecithotrophic (non-feeding) balls of cells with an outer layer of cells whose flagella or cilia enable the larvae to move. After swimming for a few days the larvae sink and crawl until they find a place to settle. Most of the cells transform into archeocytes and then into
4012-668: Is required. Because only a fraction of the cells in a tumor die with each treatment ( fractional kill ), repeated doses must be administered to continue to reduce the size of the tumor. Current chemotherapy regimens apply drug treatment in cycles, with the frequency and duration of treatments limited by toxicity. The effectiveness of chemotherapy depends on the type of cancer and the stage. The overall effectiveness ranges from being curative for some cancers, such as some leukemias , to being ineffective, such as in some brain tumors , to being needless in others, like most non-melanoma skin cancers . Dosage of chemotherapy can be difficult: If
4130-594: Is similar enough to human deoxycytosine to be incorporated into human DNA, but different enough that it kills the cell. Cytosine arabinoside interferes with the synthesis of DNA. Its mode of action is due to its rapid conversion into cytosine arabinoside triphosphate , which damages DNA when the cell cycle holds in the S phase (synthesis of DNA). Rapidly dividing cells, which require DNA replication for mitosis , are therefore most affected. Cytosine arabinoside also inhibits both DNA and RNA polymerases and nucleotide reductase enzymes needed for DNA synthesis. Cytarabine
4248-444: Is similar to that of vinca alkaloids in that they bind to tubulin, inhibiting microtubule formation. Podophyllotoxin is used to produce two other drugs with different mechanisms of action: etoposide and teniposide . Topoisomerase inhibitors are drugs that affect the activity of two enzymes: topoisomerase I and topoisomerase II . When the DNA double-strand helix is unwound, during DNA replication or transcription , for example,
4366-426: Is that they interrupt cell division . The most important subgroup is the anthracyclines and the bleomycins ; other prominent examples include mitomycin C and actinomycin . Among the anthracyclines, doxorubicin and daunorubicin were the first, and were obtained from the bacterium Streptomyces peucetius . Derivatives of these compounds include epirubicin and idarubicin . Other clinically used drugs in
4484-463: Is the active metabolite being incorporated into DNA during DNA synthesis. Several mechanisms of resistance have been reported. Cytarabine is rapidly deaminated by cytidine deaminase in the serum into the inactive uracil derivative. Cytarabine-5´-monophosphate is deaminated by deoxycytidylate deaminase, leading to the inactive uridine-5´-monophosphate analog. Cytarabine-5´-triphosphate is a substrate for SAMHD1 . Furthermore, SAMHD1 has been shown to limit
4602-463: Is the first of a series of cancer drugs that altered the sugar component of nucleosides . Other cancer drugs modify the base. Cytarabine is often given by continuous intravenous infusion, which follows a biphasic elimination – initial fast clearance rate followed by a slower rate of the analog. Cytarabine is transported into the cell primarily by hENT-1. It is then monophosphorylated by deoxycytidine kinase and eventually cytarabine-5´-triphosphate, which
4720-601: Is the only skeleton in soft sponges that encrust such hard surfaces as rocks. More commonly, the mesohyl is stiffened by mineral spicules , by spongin fibers, or both. 90% of all known sponge species that have the widest range of habitats including all freshwater ones are demosponges that use spongin; many species have silica spicules, whereas some species have calcium carbonate exoskeletons . Calcareous sponges have calcium carbonate spicules and, in some species, calcium carbonate exoskeletons, are restricted to relatively shallow marine waters where production of calcium carbonate
4838-455: Is the primary cause for their anti-cancer effects. DNA is made of two strands and the molecules may either bind twice to one strand of DNA (intrastrand crosslink) or may bind once to both strands (interstrand crosslink). If the cell tries to replicate crosslinked DNA during cell division , or tries to repair it, the DNA strands can break. This leads to a form of programmed cell death called apoptosis . Alkylating agents will work at any point in
Cytarabine - Misplaced Pages Continue
4956-832: The PICC line . These have a lower infection risk, are much less prone to phlebitis or extravasation , and eliminate the need for repeated insertion of peripheral cannulae. Isolated limb perfusion (often used in melanoma ), or isolated infusion of chemotherapy into the liver or the lung have been used to treat some tumors. The main purpose of these approaches is to deliver a very high dose of chemotherapy to tumor sites without causing overwhelming systemic damage. These approaches can help control solitary or limited metastases, but they are by definition not systemic, and, therefore, do not treat distributed metastases or micrometastases . Topical chemotherapies, such as 5-fluorouracil , are used to treat some cases of non-melanoma skin cancer . If
5074-399: The amino , carboxyl , sulfhydryl , and phosphate groups in biologically important molecules. Non-classical alkylating agents include procarbazine and hexamethylmelamine. Anti-metabolites are a group of molecules that impede DNA and RNA synthesis. Many of them have a similar structure to the building blocks of DNA and RNA. The building blocks are nucleotides ; a molecule comprising
5192-451: The epithelia of more complex animals, they are not bound tightly by cell-to-cell connections or a basal lamina (thin fibrous sheet underneath). The flexibility of these layers and re-modeling of the mesohyl by lophocytes allow the animals to adjust their shapes throughout their lives to take maximum advantage of local water currents. The simplest body structure in sponges is a tube or vase shape known as "asconoid", but this severely limits
5310-456: The genus Chondrocladia uses a highly modified water flow system to inflate balloon-like structures that are used for capturing prey. Freshwater sponges often host green algae as endosymbionts within archaeocytes and other cells and benefit from nutrients produced by the algae. Many marine species host other photosynthesizing organisms, most commonly cyanobacteria but in some cases dinoflagellates . Symbiotic cyanobacteria may form
5428-521: The immune system , often by paralysing the bone marrow and leading to a decrease of white blood cells , red blood cells , and platelets . Anemia and thrombocytopenia may require blood transfusion . Neutropenia (a decrease of the neutrophil granulocyte count below 0.5 x 10 / litre ) can be improved with synthetic G-CSF ( granulocyte -colony-stimulating factor, e.g., filgrastim , lenograstim , efbemalenograstim alfa ). In very severe myelosuppression , which occurs in some regimens, almost all
5546-470: The mesohyl and form spermatic cysts while eggs are formed by transformation of archeocytes , or of choanocytes in some species. Each egg generally acquires a yolk by consuming "nurse cells". During spawning, sperm burst out of their cysts and are expelled via the osculum . If they contact another sponge of the same species, the water flow carries them to choanocytes that engulf them but, instead of digesting them, metamorphose to an ameboid form and carry
5664-728: The metazoan phylum Porifera ( / p ə ˈ r ɪ f ər ə ˌ p ɔː -/ pər- IF -ər-ə, por- ; meaning 'pore bearer'), a basal animal clade and a sister taxon of the diploblasts . They are sessile filter feeders that are bound to the seabed , and are one of the most ancient members of macrobenthos , with many historical species being important reef -building organisms. Sponges are multicellular organisms consisting of jelly-like mesohyl sandwiched between two thin layers of cells , and usually have tube-like bodies full of pores and channels that allow water to circulate through them. They have unspecialized cells that can transform into other types and that often migrate between
5782-463: The pinacocytes , squeezing the water channels and thus expelling excess sediment and other substances that may cause blockages. Some species can contract the osculum independently of the rest of the body. Sponges may also contract in order to reduce the area that is vulnerable to attack by predators. In cases where two sponges are fused, for example if there is a large but still unseparated bud, these contraction waves slowly become coordinated in both of
5900-455: The " Siamese twins ". The coordinating mechanism is unknown, but may involve chemicals similar to neurotransmitters . However, glass sponges rapidly transmit electrical impulses through all parts of the syncytium , and use this to halt the motion of their flagella if the incoming water contains toxins or excessive sediment. Myocytes are thought to be responsible for closing the osculum and for transmitting signals between different parts of
6018-611: The 1950s, though, these had been overfished so heavily that the industry almost collapsed, and most sponge-like materials are now synthetic. Sponges and their microscopic endosymbionts are now being researched as possible sources of medicines for treating a wide range of diseases. Dolphins have been observed using sponges as tools while foraging . Sponges constitute the phylum Porifera, and have been defined as sessile metazoans (multicelled immobile animals) that have water intake and outlet openings connected by chambers lined with choanocytes , cells with whip-like flagella. However,
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#17327930804096136-468: The 5-FU clinical study cited above, people whose dose was adjusted to achieve a pre-determined target exposure realized an 84% improvement in treatment response rate and a six-month improvement in overall survival (OS) compared with those dosed by BSA. In the same study, investigators compared the incidence of common 5-FU-associated grade 3/4 toxicities between the dose-adjusted people and people dosed per BSA. The incidence of debilitating grades of diarrhea
6254-597: The BSA-dosed group to 70% in the dose-adjusted group. Median progression free survival (PFS) and overall survival (OS) both improved by six months in the dose adjusted group. One approach that can help clinicians individualize chemotherapy dosing is to measure the drug levels in blood plasma over time and adjust dose according to a formula or algorithm to achieve optimal exposure. With an established target exposure for optimized treatment effectiveness with minimized toxicities, dosing can be personalized to achieve target exposure and optimal results for each person. Such an algorithm
6372-617: The US by Upjohn under the brand name Cytosar-U. It is also known as ara-C (arabinofuranosyl cytidine). Chemotherapy medication Chemotherapy (often abbreviated chemo , sometimes CTX and CTx ) is the type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents ) in a standard regimen . Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs), or it may aim only to prolong life or to reduce symptoms ( palliative chemotherapy). Chemotherapy
6490-410: The activity of topoisomerase II, and therefore prevent DNA synthesis and translation because the DNA cannot unwind properly. This group includes novobiocin , merbarone, and aclarubicin , which also have other significant mechanisms of action. The cytotoxic antibiotics are a varied group of drugs that have various mechanisms of action. The common theme that they share in their chemotherapy indication
6608-560: The adjacent unopened DNA winds tighter (supercoils), like opening the middle of a twisted rope. The stress caused by this effect is in part aided by the topoisomerase enzymes. They produce single- or double-strand breaks into DNA, reducing the tension in the DNA strand. This allows the normal unwinding of DNA to occur during replication or transcription. Inhibition of topoisomerase I or II interferes with both of these processes. Two topoisomerase I inhibitors, irinotecan and topotecan , are semi-synthetically derived from camptothecin , which
6726-475: The amount of sunlight they collect. A recently discovered carnivorous sponge that lives near hydrothermal vents hosts methane-eating bacteria and digests some of them. Sponges do not have the complex immune systems of most other animals. However, they reject grafts from other species but accept them from other members of their own species. In a few marine species, gray cells play the leading role in rejection of foreign material. When invaded, they produce
6844-405: The anthracycline group are pirarubicin , aclarubicin , and mitoxantrone . The mechanisms of anthracyclines include DNA intercalation (molecules insert between the two strands of DNA), generation of highly reactive free radicals that damage intercellular molecules and topoisomerase inhibition. Actinomycin is a complex molecule that intercalates DNA and prevents RNA synthesis . Bleomycin,
6962-523: The approximately 5,000–10,000 known species of sponges feed on bacteria and other microscopic food in the water, some host photosynthesizing microorganisms as endosymbionts , and these alliances often produce more food and oxygen than they consume. A few species of sponges that live in food-poor environments have evolved as carnivores that prey mainly on small crustaceans . Most sponges reproduce sexually , but they can also reproduce asexually. Sexually reproducing species release sperm cells into
7080-638: The assembly of tubulin into microtubules. The original vinca alkaloids are natural products that include vincristine and vinblastine . Following the success of these drugs, semi-synthetic vinca alkaloids were produced: vinorelbine (used in the treatment of non-small-cell lung cancer ), vindesine , and vinflunine . These drugs are cell cycle -specific. They bind to the tubulin molecules in S-phase and prevent proper microtubule formation required for M-phase . Taxanes are natural and semi-synthetic drugs. The first drug of their class, paclitaxel ,
7198-418: The body. Sponges contain genes very similar to those that contain the "recipe" for the post- synaptic density, an important signal-receiving structure in the neurons of all other animals. However, in sponges these genes are only activated in "flask cells" that appear only in larvae and may provide some sensory capability while the larvae are swimming. This raises questions about whether flask cells represent
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#17327930804097316-645: The bone marrow stem cells (cells that produce white and red blood cells ) are destroyed, meaning allogenic or autologous bone marrow cell transplants are necessary. (In autologous BMTs, cells are removed from the person before the treatment, multiplied and then re-injected afterward; in allogenic BMTs, the source is a donor.) However, some people still develop diseases because of this interference with bone marrow. Although people receiving chemotherapy are encouraged to wash their hands, avoid sick people, and take other infection-reducing steps, about 85% of infections are due to naturally occurring microorganisms in
7434-475: The cancer cells. Following this, cell cycle arrest occurs, which induces programmed cell death ( apoptosis ). These drugs can also affect blood vessel growth , an essential process that tumours utilise in order to grow and metastasise. Vinca alkaloids are derived from the Madagascar periwinkle , Catharanthus roseus , formerly known as Vinca rosea . They bind to specific sites on tubulin, inhibiting
7552-589: The cancer has central nervous system involvement, or with meningeal disease, intrathecal chemotherapy may be administered. Chemotherapeutic techniques have a range of side effects that depend on the type of medications used. The most common medications affect mainly the fast-dividing cells of the body, such as blood cells and the cells lining the mouth, stomach, and intestines. Chemotherapy-related toxicities can occur acutely after administration, within hours or days, or chronically, from weeks to years. Virtually all chemotherapeutic regimens can cause depression of
7670-933: The cell cycle and thus are known as cell cycle-independent drugs. For this reason, the effect on the cell is dose dependent; the fraction of cells that die is directly proportional to the dose of drug. The subtypes of alkylating agents are the nitrogen mustards , nitrosoureas , tetrazines , aziridines , cisplatins and derivatives, and non-classical alkylating agents. Nitrogen mustards include mechlorethamine , cyclophosphamide , melphalan , chlorambucil , ifosfamide and busulfan . Nitrosoureas include N-Nitroso-N-methylurea (MNU), carmustine (BCNU), lomustine (CCNU) and semustine (MeCCNU), fotemustine and streptozotocin . Tetrazines include dacarbazine , mitozolomide and temozolomide . Aziridines include thiotepa , mytomycin and diaziquone (AZQ). Cisplatin and derivatives include cisplatin , carboplatin and oxaliplatin . They impair cell function by forming covalent bonds with
7788-477: The center. The larvae then leave their parents' bodies. The cytological progression of porifera oogenesis and spermatogenesis ( gametogenesis ) is very similar to that of other metazoa. Most of the genes from the classic set of meiotic genes, including genes for DNA recombination and double-strand break repair, that are conserved in eukaryotes are expressed in the sponges (e.g. Geodia hentscheli and Geodia phlegraei ). Since porifera are considered to be
7906-415: The central cavity, where the water deposits nutrients and then leaves through a hole called the osculum . The single-celled choanoflagellates resemble the choanocyte cells of sponges which are used to drive their water flow systems and capture most of their food. This along with phylogenetic studies of ribosomal molecules have been used as morphological evidence to suggest sponges are the sister group to
8024-597: The cross-section area of the choanocyte-lined regions is much greater than that of the intake and outlet channels. This makes the flow slower near the choanocytes and thus makes it easier for them to trap food particles. For example, in Leuconia , a small leuconoid sponge about 10 centimetres (3.9 in) tall and 1 centimetre (0.39 in) in diameter, water enters each of more than 80,000 intake canals at 6 cm per minute . However, because Leuconia has more than 2 million flagellated chambers whose combined diameter
8142-452: The dose is too low, it will be ineffective against the tumor, whereas, at excessive doses, the toxicity ( side-effects ) will be intolerable to the person receiving it. The standard method of determining chemotherapy dosage is based on calculated body surface area (BSA). The BSA is usually calculated with a mathematical formula or a nomogram , using the recipient's weight and height, rather than by direct measurement of body area. This formula
8260-448: The earliest divergent animals, these findings indicate that the basic toolkit of meiosis including capabilities for recombination and DNA repair were present early in eukaryote evolution. Sponges in temperate regions live for at most a few years, but some tropical species and perhaps some deep-ocean ones may live for 200 years or more. Some calcified demosponges grow by only 0.2 mm (0.0079 in) per year and, if that rate
8378-457: The efficacy of cytarabine efficacy in patients. When used as an antiviral , cytarabine-5´-triphosphate functions by inhibiting viral DNA synthesis. Cytarabine is able to inhibit herpesvirus and vaccinia virus replication in cells during tissue culture. However, cytarabine treatment was only effective for herpesvirus infection in a murine model. In mice, Ara-CTP (cytarabine-5'-triphosphate) blocks memory consolidation, but not short-term memory, of
8496-622: The enzyme is inhibited by methotrexate, the cellular levels of folate coenzymes diminish. These are required for thymidylate and purine production, which are both essential for DNA synthesis and cell division. Pemetrexed is another anti-metabolite that affects purine and pyrimidine production, and therefore also inhibits DNA synthesis. It primarily inhibits the enzyme thymidylate synthase , but also has effects on DHFR, aminoimidazole carboxamide ribonucleotide formyltransferase and glycinamide ribonucleotide formyltransferase . The fluoropyrimidines include fluorouracil and capecitabine . Fluorouracil
8614-443: The enzymes involved in DNA synthesis, they prevent mitosis because the DNA cannot duplicate itself. Also, after misincorporation of the molecules into DNA, DNA damage can occur and programmed cell death ( apoptosis ) is induced. Unlike alkylating agents, anti-metabolites are cell cycle dependent. This means that they only work during a specific part of the cell cycle, in this case S-phase (the DNA synthesis phase). For this reason, at
8732-423: The fact that growth in any direction increases the number of choanocyte chambers enables them to take a wider range of forms, for example, "encrusting" sponges whose shapes follow those of the surfaces to which they attach. All freshwater and most shallow-water marine sponges have leuconid bodies. The networks of water passages in glass sponges are similar to the leuconid structure. In all three types of structure
8850-535: The first outgroup to branch off the evolutionary tree from the last common ancestor of all animals , with fossil evidence of primitive sponges such as Otavia from as early as the Tonian period (around 800 Mya ). The branch of zoology that studies sponges is known as spongiology . The term sponge derives from the Ancient Greek word σπόγγος spóngos . The scientific name Porifera
8968-582: The formula only takes into account the individual's weight and height. Drug absorption and clearance are influenced by multiple factors, including age, sex, metabolism, disease state, organ function, drug-to-drug interactions, genetics, and obesity, which have major impacts on the actual concentration of the drug in the person's bloodstream. As a result, there is high variability in the systemic chemotherapy drug concentration in people dosed by BSA, and this variability has been demonstrated to be more than ten-fold for many drugs. In other words, if two people receive
9086-515: 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 Medicines . Cytarabine is mainly used in the treatment of acute myeloid leukaemia , acute lymphocytic leukaemia (ALL) and in lymphomas , where it is the backbone of induction chemotherapy . Cytarabine also possesses antiviral activity, and it has been used for
9204-536: The immune system is suppressed to a critically low level. In Japan , the government has approved the use of some medicinal mushrooms like Trametes versicolor , to counteract depression of the immune system in people undergoing chemotherapy. Trilaciclib is an inhibitor of cyclin-dependent kinase 4/6 approved for the prevention of myelosuppression caused by chemotherapy. The drug is given before chemotherapy to protect bone marrow function. Due to immune system suppression, neutropenic enterocolitis (typhlitis)
9322-417: The lining of the digestive tract), and alopecia (hair loss). Because of the effect on immune cells (especially lymphocytes), chemotherapy drugs often find use in a host of diseases that result from harmful overactivity of the immune system against self (so-called autoimmunity ). These include rheumatoid arthritis , systemic lupus erythematosus , multiple sclerosis , vasculitis and many others. There are
9440-412: The living tissue is suspended like a cobweb that contains most of the cell types. This tissue is a syncytium that in some ways behaves like many cells that share a single external membrane , and in others like a single cell with multiple nuclei . Most sponges work rather like chimneys : they take in water at the bottom and eject it from the osculum at the top. Since ambient currents are faster at
9558-406: The main cell layers and the mesohyl in the process. They do not have complex nervous , digestive or circulatory systems . Instead, most rely on maintaining a constant water flow through their bodies to obtain food and oxygen and to remove wastes, usually via flagella movements of the so-called " collar cells ". Believed to be some of the most basal animals alive today, sponges were possibly
9676-408: 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
9794-436: The middle layer and change their functions. A sponge's body is hollow and is held in shape by the mesohyl , a jelly-like substance made mainly of collagen and reinforced by a dense network of fibers also made of collagen. 18 distinct cell types have been identified. The inner surface is covered with choanocytes , cells with cylindrical or conical collars surrounding one flagellum per choanocyte. The wave-like motion of
9912-448: The mobility of their pinacocytes and choanocytes and reshaping of the mesohyl to re-attach themselves to a suitable surface and then rebuild themselves as small but functional sponges over the course of several days. The same capabilities enable sponges that have been squeezed through a fine cloth to regenerate. A sponge fragment can only regenerate if it contains both collencytes to produce mesohyl and archeocytes to produce all
10030-434: The more usual filter-feeding sponges. The cave-dwelling predators capture crustaceans under 1 mm (0.039 in) long by entangling them with fine threads, digest them by enveloping them with further threads over the course of a few days, and then return to their normal shape; there is no evidence that they use venom . Most known carnivorous sponges have completely lost the water flow system and choanocytes . However,
10148-442: The number of choanocytes and hence in pumping capacity enables syconoid sponges to grow up to a few centimeters in diameter. The "leuconoid" pattern boosts pumping capacity further by filling the interior almost completely with mesohyl that contains a network of chambers lined with choanocytes and connected to each other and to the water intakes and outlet by tubes. Leuconid sponges grow to over 1 m (3.3 ft) in diameter, and
10266-691: The organic matter forms a thin layer with choanocyte chambers in pits in the mineral. These exoskeletons are secreted by the pinacocytes that form the animals' skins. Although adult sponges are fundamentally sessile animals, some marine and freshwater species can move across the sea bed at speeds of 1–4 mm (0.039–0.157 in) per day, as a result of amoeba -like movements of pinacocytes and other cells. A few species can contract their whole bodies, and many can close their oscula and ostia . Juveniles drift or swim freely, while adults are stationary. Sponges do not have distinct circulatory , respiratory , digestive , and excretory systems – instead,
10384-432: The ostia, while those at the base of the animal are responsible for anchoring it. Other types of cells live and move within the mesohyl: Many larval sponges possess neuron-less eyes that are based on cryptochromes . They mediate phototaxic behavior. Glass sponges present a distinctive variation on this basic plan. Their spicules, which are made of silica , form a scaffolding -like framework between whose rods
10502-539: The ostia, transport them through the mesohyl and generally dump them into the outgoing water current, although some species incorporate them into their skeletons. In waters where the supply of food particles is very poor, some species prey on crustaceans and other small animals. So far only 137 species have been discovered. Most belong to the family Cladorhizidae , but a few members of the Guitarridae and Esperiopsidae are also carnivores. In most cases, little
10620-661: The other cell types. A very few species reproduce by budding. Gemmules are "survival pods" which a few marine sponges and many freshwater species produce by the thousands when dying and which some, mainly freshwater species, regularly produce in autumn. Spongocytes make gemmules by wrapping shells of spongin, often reinforced with spicules, round clusters of archeocytes that are full of nutrients. Freshwater gemmules may also include photosynthesizing symbionts. The gemmules then become dormant, and in this state can survive cold, drying out, lack of oxygen and extreme variations in salinity . Freshwater gemmules often do not revive until
10738-412: The person vomits frequently, because of gastrointestinal damage. This can result in rapid weight loss, or occasionally in weight gain, if the person eats too much in an effort to allay nausea or heartburn. Weight gain can also be caused by some steroid medications. These side-effects can frequently be reduced or eliminated with antiemetic drugs. Low-certainty evidence also suggests that probiotics may have
10856-825: The person's own gastrointestinal tract (including oral cavity ) and skin. This may manifest as systemic infections, such as sepsis , or as localized outbreaks, such as Herpes simplex , shingles , or other members of the Herpesviridea . The risk of illness and death can be reduced by taking common antibiotics such as quinolones or trimethoprim/sulfamethoxazole before any fever or sign of infection appears. Quinolones show effective prophylaxis mainly with hematological cancer. However, in general, for every five people who are immunosuppressed following chemotherapy who take an antibiotic, one fever can be prevented; for every 34 who take an antibiotic, one death can be prevented. Sometimes, chemotherapy treatments are postponed because
10974-522: The person, the cancer, the stage of cancer, the type of chemotherapy, and the dosage, intravenous chemotherapy may be given on either an inpatient or an outpatient basis. For continuous, frequent or prolonged intravenous chemotherapy administration, various systems may be surgically inserted into the vasculature to maintain access. Commonly used systems are the Hickman line , the Port-a-Cath , and
11092-582: The predecessors of true neurons or are evidence that sponges' ancestors had true neurons but lost them as they adapted to a sessile lifestyle. Sponges are worldwide in their distribution, living in a wide range of ocean habitats, from the polar regions to the tropics. Most live in quiet, clear waters, because sediment stirred up by waves or currents would block their pores, making it difficult for them to feed and breathe. The greatest numbers of sponges are usually found on firm surfaces such as rocks, but some sponges can attach themselves to soft sediment by means of
11210-416: The pumping capacity that supplies food and oxygen depends on the area covered by choanocytes. Asconoid sponges seldom exceed 1 mm (0.039 in) in diameter. Some sponges overcome this limitation by adopting the "syconoid" structure, in which the body wall is pleated . The inner pockets of the pleats are lined with choanocytes, which connect to the outer pockets of the pleats by ostia. This increase in
11328-598: The realization that these compounds could act as DNA synthesis chain terminators led to exploration of these novel nucleotides as potential anticancer therapeutics. Cytarabine was first synthesized in 1959 by Richard Walwick, Walden Roberts, and Charles Dekker at the University of California, Berkeley . It was approved by the United States Food and Drug Administration in June 1969, and was initially marketed in
11446-648: The rest of animals. A great majority are marine (salt-water) species, ranging in habitat from tidal zones to depths exceeding 8,800 m (5.5 mi), though there are freshwater species. All adult sponges are sessile , meaning that they attach to an underwater surface and remain fixed in place (i.e., do not travel). While in their larval stage of life, they are motile . Many sponges have internal skeletons of spicules (skeletal-like fragments of calcium carbonate or silicon dioxide ), and/or spongin (a modified type of collagen protein). An internal gelatinous matrix called mesohyl functions as an endoskeleton , and it
11564-503: The right dose to achieve optimal treatment effectiveness with minimized toxic side effects. Some people are overdosed while others are underdosed. For example, in a randomized clinical trial, investigators found 85% of metastatic colorectal cancer patients treated with 5-fluorouracil (5-FU) did not receive the optimal therapeutic dose when dosed by the BSA standard—68% were underdosed and 17% were overdosed. There has been controversy over
11682-429: The same dose of a given drug based on BSA, the concentration of that drug in the bloodstream of one person may be 10 times higher or lower compared to that of the other person. This variability is typical with many chemotherapy drugs dosed by BSA, and, as shown below, was demonstrated in a study of 14 common chemotherapy drugs. The result of this pharmacokinetic variability among people is that many people do not receive
11800-468: The same species but different individuals can join forces to form one sponge. Some gemmules are retained within the parent sponge, and in spring it can be difficult to tell whether an old sponge has revived or been "recolonized" by its own gemmules. Most sponges are hermaphrodites (function as both sexes simultaneously), although sponges have no gonads (reproductive organs). Sperm are produced by choanocytes or entire choanocyte chambers that sink into
11918-507: The side effects and improve the therapeutic efficiency, various derivatives of these drugs (including amino acid, peptide, fatty acid and phosphates) have been evaluated, as well as different delivery systems. Cytosine arabinoside combines a cytosine base with an arabinose sugar. It is an antimetabolic agent with the chemical name of 1β-arabinofuranosylcytosine . Certain sponges , where similar compounds were originally found, use arabinoside sugars for chemical defense. Cytosine arabinoside
12036-402: The size of the animal. The body structure is characterized by a stalk-like spongocoel surrounded by a single layer of choanocytes. If it is simply scaled up, the ratio of its volume to surface area increases, because surface increases as the square of length or width while volume increases proportionally to the cube. The amount of tissue that needs food and oxygen is determined by the volume, but
12154-444: The sperm through the mesohyl to eggs, which in most cases engulf the carrier and its cargo. A few species release fertilized eggs into the water, but most retain the eggs until they hatch. By retaining the eggs, the parents can transfer symbiotic microorganisms directly to their offspring through vertical transmission , while the species who release their eggs into the water has to acquire symbionts horizontally (a combination of both
12272-504: The sponges, for example as temperatures drop, many freshwater species and a few marine ones produce gemmules , "survival pods" of unspecialized cells that remain dormant until conditions improve; they then either form completely new sponges or recolonize the skeletons of their parents. The few species of demosponge that have entirely soft fibrous skeletons with no hard elements have been used by humans over thousands of years for several purposes, including as padding and as cleaning tools. By
12390-399: The temperature drops, stays cold for a few months and then reaches a near-"normal" level. When a gemmule germinates, the archeocytes round the outside of the cluster transform into pinacocytes , a membrane over a pore in the shell bursts, the cluster of cells slowly emerges, and most of the remaining archeocytes transform into other cell types needed to make a functioning sponge. Gemmules from
12508-409: The top, the suction effect that they produce by Bernoulli's principle does some of the work for free. Sponges can control the water flow by various combinations of wholly or partially closing the osculum and ostia (the intake pores) and varying the beat of the flagella, and may shut it down if there is a lot of sand or silt in the water. Although the layers of pinacocytes and choanocytes resemble
12626-478: The treatment of generalised herpesvirus infection. However, cytarabine is not very selective in this setting and causes bone marrow suppression and other severe side effects. Therefore, ara-C is not a useful antiviral agent in humans because of its toxic profile. Cytarabine is also used in the study of the nervous system to control the proliferation of glial cells in cultures, the amount of glial cells having an important impact on neurons . Recently, cytarabine
12744-489: The types appropriate for their locations in a miniature adult sponge. Glass sponge embryos start by dividing into separate cells, but once 32 cells have formed they rapidly transform into larvae that externally are ovoid with a band of cilia round the middle that they use for movement, but internally have the typical glass sponge structure of spicules with a cobweb-like main syncitium draped around and between them and choanosyncytia with multiple collar bodies in
12862-473: The use of BSA to calculate chemotherapy doses for people who are obese . Because of their higher BSA, clinicians often arbitrarily reduce the dose prescribed by the BSA formula for fear of overdosing . In many cases, this can result in sub-optimal treatment. Several clinical studies have demonstrated that when chemotherapy dosing is individualized to achieve optimal systemic drug exposure, treatment outcomes are improved and toxic side effects are reduced. In
12980-670: The walls of the ostia. Bacteria-sized particles, below 0.5 micrometers, pass through the ostia and are caught and consumed by choanocytes . Since the smallest particles are by far the most common, choanocytes typically capture 80% of a sponge's food supply. Archaeocytes transport food packaged in vesicles from cells that directly digest food to those that do not. At least one species of sponge has internal fibers that function as tracks for use by nutrient-carrying archaeocytes, and these tracks also move inert objects. It used to be claimed that glass sponges could live on nutrients dissolved in sea water and were very averse to silt. However,
13098-493: The water flow system supports all these functions. They filter food particles out of the water flowing through them. Particles larger than 50 micrometers cannot enter the ostia and pinacocytes consume them by phagocytosis (engulfing and intracellular digestion). Particles from 0.5 μm to 50 μm are trapped in the ostia, which taper from the outer to inner ends. These particles are consumed by pinacocytes or by archaeocytes which partially extrude themselves through
13216-402: The water to fertilize ova released or retained by its mate or "mother"; the fertilized eggs develop into larvae which swim off in search of places to settle. Sponges are known for regenerating from fragments that are broken off, although this only works if the fragments include the right types of cells. Some species reproduce by budding. When environmental conditions become less hospitable to
13334-458: The whip-like flagella drives water through the sponge's body. All sponges have ostia , channels leading to the interior through the mesohyl, and in most sponges these are controlled by tube-like porocytes that form closable inlet valves. Pinacocytes , plate-like cells, form a single-layered external skin over all other parts of the mesohyl that are not covered by choanocytes, and the pinacocytes also digest food particles that are too large to enter
13452-438: Was originally derived in a 1916 study and attempted to translate medicinal doses established with laboratory animals to equivalent doses for humans. The study only included nine human subjects. When chemotherapy was introduced in the 1950s, the BSA formula was adopted as the official standard for chemotherapy dosing for lack of a better option. The validity of this method in calculating uniform doses has been questioned because
13570-570: Was originally extracted from Taxus brevifolia , the Pacific yew. Now this drug and another in this class, docetaxel , are produced semi-synthetically from a chemical found in the bark of another yew tree, Taxus baccata . Podophyllotoxin is an antineoplastic lignan obtained primarily from the American mayapple ( Podophyllum peltatum ) and Himalayan mayapple ( Sinopodophyllum hexandrum ). It has anti-microtubule activity, and its mechanism
13688-412: Was reduced from 18% in the BSA-dosed group to 4% in the dose-adjusted group and serious hematologic side effects were eliminated. Because of the reduced toxicity, dose-adjusted patients were able to be treated for longer periods of time. BSA-dosed people were treated for a total of 680 months while people in the dose-adjusted group were treated for a total of 791 months. Completing the course of treatment
13806-1119: Was reported to promote robust and persistent neuronal differentiation in NSC-34 motor neuron-like cell line. Cytarabine is permissive, dispensable, and mostly irreversible in priming NSC-34 cells for neurite initiation and regeneration after mechanical dislodgement. One of the unique toxicities of cytarabine is cerebellar toxicity when given in high doses, which may lead to ataxia . Cytarabine may cause granulocytopenia and other impaired body defenses, which may lead to infection, and thrombocytopenia , which may lead to hemorrhage . Toxicity: pancreatitis , leukopenia , thrombocytopenia, anemia , GI disturbances, stomatitis , conjunctivitis , pneumonitis , fever , and dermatitis , palmar-plantar erythrodysesthesia . Rarely, myelopathy has been reported after high dose or frequent intrathecal Ara-C administration. When used in protocols designated as high dose, cytarabine can cause cerebral and cerebellar dysfunction, ocular toxicity, pulmonary toxicity, severe GI ulceration and peripheral neuropathy (rare). To prevent
13924-508: Was used in the clinical trials cited above and resulted in significantly improved treatment outcomes. Oncologists are already individualizing dosing of some cancer drugs based on exposure. Carboplatin and busulfan dosing rely upon results from blood tests to calculate the optimal dose for each person. Simple blood tests are also available for dose optimization of methotrexate , 5-FU, paclitaxel , and docetaxel . The serum albumin level immediately prior to chemotherapy administration
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