Metastasis
Classification and external resources
Cut surface of a liver showing multiple metastatic nodules originating from pancreatic cancer
DiseasesDB	28954
MedlinePlus	002260

Metastasis, or metastatic disease (sometimes abbreviated mets), is the spread of a disease from one organ or part to another non-adjacent organ or part.^[1][2] It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research.^[3] In origin metastasis is a Greek word meaning "displacement", from μετά, meta, "next", and στάσις, stasis, "placement". The plural is metastases.

Cancer occurs after a single cell in a tissue is progressively genetically damaged to produce a cancer stem cell possessing a malignant phenotype. These cancer stem cells are able to undergo uncontrolled abnormal mitosis, which serves to increase the total number of cancer cells at that location. When the area of cancer cells at the originating site becomes clinically detectable, it is called a primary tumor. Some cancer cells also acquire the ability to penetrate and infiltrate surrounding normal tissues in the local area, forming a new tumor. The newly formed "daughter" tumor in the adjacent site within the tissue is called a local metastasis.

Some cancer cells acquire the ability to penetrate the walls of lymphatic and/or blood vessels, after which they are able to circulate through the bloodstream (circulating tumor cells) to other sites and tissues in the body. This process is known (respectively) as lymphatic or hematogeneous spread.

After the tumor cells come to rest at another site, they re-penetrate the vessel or walls and continue to multiply, eventually forming another clinically detectable tumor. This new tumor is known as a metastatic (or secondary) tumor. Metastasis is one of three hallmarks of malignancy (contrast benign tumors).^[4] Most tumors and other neoplasms can metastasize, although in varying degrees (e.g., basal cell carcinoma rarely metastasize).^[4]

When tumor cells metastasize, the new tumor is called a secondary or metastatic tumor, and its cells are similar to those in the original tumor. This means, for example, that, if breast cancer metastasizes to the lungs, the secondary tumor is made up of abnormal breast cells, not of abnormal lung cells. The tumor in the lung is then called metastatic breast cancer, not lung cancer.

Signs and symptoms[link]

Symptoms of cancer metastasis depend location of the tumor.

The symptoms of metastasis varies with location of the tumors.

Initially, nearby lymph nodes are struck early.^[5] Lungs, bones, liver, and brain are the most common metastasis locations from solid tumors.^[5]

• In lymph nodes, a common symptom is lymphadenopathy
• Lungs: cough, hemoptysis and dyspnea^[5] (shortness of breath)
• Liver: hepatomegaly (enlarged liver), nausea^[5] and jaundice^[5]
• Bones: bone pain,^[5] fracture of affected bones^[5]
• Brain: neurological symptoms such as headaches,^[5] seizures,^[5] and vertigo.^[5]

Although advanced cancer may cause pain, it is often not the first symptom.

Some patients, however, don't show any symptoms.^[5]

Pathophysiology[link]

Metastatic tumours are very common in the late stages of cancer. The spread of metastases may occur via the blood or the lymphatics or through both routes. The most common places for the metastases to occur are the lungs, liver, brain, and the bones.^[6]

Factors involved[link]

Metastasis is a complex series of steps in which cancer cells leave the original tumor site and migrate to other parts of the body via the bloodstream or the lymphatic system. To do so, malignant cells break away from the primary tumor and attach to and degrade proteins that make up the surrounding extracellular matrix (ECM), which separates the tumor from adjoining tissue. By degrading these proteins, cancer cells are able to breach the ECM and escape. When oral cancers metastasize, they commonly travel through the lymph system to the lymph nodes in the neck. The body resists metastasis by a variety of mechanisms through the actions of a class of proteins known as metastasis suppressors, of which about a dozen are known.^[7]

Cancer researchers studying the conditions necessary for cancer metastasis have discovered that one of the critical events required is the growth of a new network of blood vessels, called tumor angiogenesis.^[8] It has been found that angiogenesis inhibitors would therefore prevent the growth of metastases.^[4]

There are several different cell types critical to tumour growth. In particular endothelial progenitor cells are a very important cell population in tumour blood vessel growth. This finding was demonstrated in the high impact factor journals of Science (2008) and Genes and Development (2007) which also showed that endothelial progenitor cells are critical for metastasis and angiogenesis.^[9][10] This importance of endothelial progenitor cells in tumour growth, angiogenesis and metastasis has been confirmed by a recent publication in Cancer Research (August 2010). This seminal paper has demonstrated that endothelial progenitor cells can be marked using the Inhibitor of DNA Binding 1 (ID1). This novel finding meant that investigators were able to track endothelial progenitor cells from the bone marrow to the blood to the tumour-stroma and even incorporated in tumour vasculature. This finding of endothelial progenitor cells incorporated in tumour vasculature proves the importance of this cell type in blood vessel development in a tumour setting and metastasis. Furthermore, ablation of the endothelial progenitor cells in the bone marrow lead to a significant decrease in tumour growth and vasculature development. Therefore endothelial progenitor cells are very important in tumour biology and present novel therapeutic targets.^[11]

Routes of metastasis[link]

Main sites of metastases for some common cancer types. Primary cancers are denoted by "...cancer" and their main metastasis sites are denoted by "...metastases".^[12]

Metastasis occurs by four routes:

1. Transcoelomic[link]

The spread into body cavities occurs by the seeding surface of the peritoneal, pleural, pericardial or subarachnoid spaces. For example, ovarian tumours spreads transperitoneally to the surface of the liver. Mesothelioma can spread through the pleural cavity.^[13]

2. Lymphatic spread[link]

Invasion into the lymphatic system is followed by the transport of tumor cells to regional lymph nodes and ultimately to other parts of the body. This is the most common route of metastasis for carcinomas.

3. Haematogenous spread[link]

This is typical of all sarcomas but it is the favored route in certain carcinomas (e.g. those originating in kidneys). Because of their thinner walls veins are more frequently invaded than arteries and metastasis follows the pattern of the venous flows.

4. Transplantation or implantation[link]

Mechanical carriage of fragments of tumor cells by surgical instruments during operation or the use of needles during diagnostic procedures.

Cancer cells may spread to lymph nodes (regional lymph nodes) near the primary tumor. This is called nodal involvement, positive nodes, or regional disease. ("Positive nodes" is a term that would be used by medical specialists to describe a patient's condition, meaning that the patient's lymph nodes near the primary tumor tested positive for malignancy. It is common medical practice to test by biopsy at least two lymph nodes near a tumor site when doing surgery to examine or remove a tumor.) Localized spread to regional lymph nodes near the primary tumor is not normally counted as metastasis, although this is a sign of worse prognosis. Transport through lymphatics is the most common pathway for the initial dissemination of carcinomas.^[4]

Organ-specific targets[link]

There is a propensity for certain tumors to seed in particular organs. This was first discussed as the "seed and soil" theory by Stephen Paget over a century ago in 1889. For example, prostate cancer usually metastasizes to the bones. In a similar manner, colon cancer has a tendency to metastasize to the liver. Stomach cancer often metastasises to the ovary in women, then it is called a Krukenberg tumor.

According to the "seed and soil" theory, it is difficult for cancer cells to survive outside their region of origin, so in order to metastasize they must find a location with similar characteristics.^[14] For example, breast tumor cells, which gather calcium ions from breast milk, metastasize to bone tissue, where they can gather calcium ions from bone. Malignant melanoma spreads to the brain, presumably because neural tissue and melanocytes arise from the same cell line in the embryo.^[15]

In 1928 James Ewing challenged the "seed and soil" theory and proposed that metastasis occurs purely by anatomic and mechanical routes.

Metastasis and primary cancer[link]

It is theorized that metastasis always coincides with a primary cancer, and, as such, is a tumor that started from a cancer cell or cells in another part of the body. However, over 10% of patients presenting to oncology units will have metastases without a primary tumor found. In these cases, doctors refer to the primary tumor as "unknown" or "occult," and the patient is said to have cancer of unknown primary origin (CUP) or unknown primary tumors (UPT). It is estimated that 3% of all cancers are of unknown primary origin.^[16] Studies have shown that, if simple questioning does not reveal the cancer's source (coughing up blood—"probably lung", urinating blood—"probably bladder"), complex imaging will not either.^[16] In some of these cases a primary tumor may appear later.

The use of immunohistochemistry has permitted pathologists to give an identity to many of these metastases. However, imaging of the indicated area only occasionally reveals a primary. In rare cases (e.g., of melanoma), no primary tumor is found, even on autopsy. It is therefore thought that some primary tumors can regress completely, but leave their metastases behind.

Common sites of origin[link]

This unreferenced section requires citations to ensure verifiability.

• Lung
• Breast
• Skin: melanoma (other skin tumors rarely metastasize)
• Colon
• Kidney
• Prostate
• Pancreas
• Cervix

Diagnosis[link]

The cells in a metastatic tumor resemble those in the primary tumor. Once the cancerous tissue is examined under a microscope to determine the cell type, a doctor can usually tell whether that type of cell is normally found in the part of the body from which the tissue sample was taken.

For instance, breast cancer cells look the same whether they are found in the breast or have spread to another part of the body. So, if a tissue sample taken from a tumor in the lung contains cells that look like breast cells, the doctor determines that the lung tumor is a secondary tumor. Still, the determination of the primary tumor can often be very difficult, and the pathologist may have to use several adjuvant techniques, such as immunohistochemistry, FISH (fluorescent in situ hybridization), and others. Despite the use of techniques, in some cases the primary tumor remains unidentified.

Metastatic cancers may be found at the same time as the primary tumor, or months or years later. When a second tumor is found in a patient that has been treated for cancer in the past, it is more often a metastasis than another primary tumor.

It was previously thought that most cancer cells have a low metastatic potential and that there are rare cells that develop the ability to metastasize through the development of somatic mutations.^[17] According to this theory, diagnosis of metastatic cancers is only possible after the event of metastasis. Traditional means of diagnosing cancer (e.g. a biopsy) would only investigate a subpopulation of the cancer cells and would very likely not sample from the subpopulation with metastatic potential.^[18]

The somatic mutation theory of metastasis development has not been substantiated in human cancers. Rather, it seems that the genetic state of the primary tumor reflects the ability of that cancer to metastasize.^[18] Research comparing gene expression between primary and metastatic adenocarcinomas identified a subset of genes whose expression could distinguish primary tumors from metastatic tumors, dubbed a "metastatic signature."^[18] Up-regulated genes in the signature include: SNRPF, HNRPAB, DHPS and securin. Actin, myosin and MHC class II down-regulation was also associated with the signature. Additionally, the metastatic-associated expression of these genes was also observed in some primary tumors, indicating that cells with the potential to metastasize could be identified concurrently with diagnosis of the primary tumor.^[19]

Expression of this metastatic signature has been correlated with a poor prognosis and has been shown to be consistent in several types of cancer. Prognosis was shown to be worse for individuals whose primary tumors expressed the metastatic signature.^[18] Additionally, the expression of these metastatic-associated genes was shown to apply to other cancer types in addition to adenocarcinoma. Metastases of breast cancer, medulloblastoma and prostate cancer all had similar expression patterns of these metastasis-associated genes.^[18]

The identification of this metastasis-associated signature provides promise for identifying cells with metastatic potential within the primary tumor and hope for improving the prognosis of these metastatic-associated cancers. Additionally, by identifying the genes whose expression is changed in metastasis offers potential targets to inhibit metastasis.^[18]

• 

  Cut surface of a humerus sawn lengthwise, showing a large cancerous metastasis (the whitish tumor between the head and the shaft of the bone)

• 

  Micrograph of thyroid cancer (papillary thyroid carcinoma) in a lymph node of the neck. H&E stain

• 

  CT image of multiple liver metastases

• 

  CT image of a lung metastasis

• 

  Metastasis proven by liver biopsy (tumor (adenocarcinoma) - lower two-thirds of image). H&E stain.

Management[link]

Treatment and survival is determined by whether or not a cancer is local or has spread to other locations. If the cancer spreads to other tissues and organs, it may decrease a patient's likelihood of survival. However, there are some cancers (i.e., some forms of leukemia, a cancer of the blood) that can kill without spreading at all.

When cancer has metastasized, it may be treated with radiosurgery, chemotherapy, radiation therapy, biological therapy, hormone therapy, surgery or a combination of these. The choice of treatment generally depends on the type of primary cancer, the size and location of the metastasis, the patient's age and general health, and the types of treatments used previously. In patients diagnosed with CUP, it is still possible to treat the disease even when the primary tumor cannot be located.

The treatment options currently available are rarely able to cure metastatic cancer, though some tumors, such as testicular cancer and thyroid cancer, are usually still curable.

See also[link]

• Disseminated disease
• Brown-Sequard Syndrome (Sections on Cavernous malformation, Germinoma, Renal cell carcinoma and Lung Cancer)
• Brain metastasis

References[link]

External links[link]

Look up metastasis in Wiktionary, the free dictionary.

Medical information about metastatic cancer

• Q&A: Metastatic Cancer – from the National Cancer Institute
• Invasion and Metastases – from Cancer Medicine e.5
• How Cancer Grows and Spreads – an interactive Flash presentation that explores the progression of a carcinoma from a single cell to metastasis; from Children's Hospital Boston

Charities and advocacy groups dealing with metastatic cancer

• The MetaCancer Foundation – resources and support for metastatic cancer survivors and their caregivers
• Metastatic Breast Cancer Network
• Children's Cancer Research Charity for Metastatic Cancer in Kids

Iannis Xenakis in his studio in Paris, c. 1970 (photograph by Michèle Daniel).

Iannis Xenakis (Greek pronunciation: [ˈʝanis kseˈnakis], Greek: Γιάννης Ξενάκης) (May 29, 1922 – February 4, 2001) was a Greek composer, music theorist, and architect-engineer. After 1947, he fled Greece, becoming a naturalized citizen of France. He is commonly recognized as one of the most important post-war avant-garde composers.^[1][2] Xenakis pioneered the use of mathematical models in music such as applications of set theory, stochastic processes and game theory and was also an important influence on the development of electronic music. He integrated music with architecture, designing music for pre-existing spaces, and designing spaces to be integrated with specific music compositions and performances.

Among his most important works are Metastaseis (1953–4) for orchestra, which introduced independent parts for every musician of the orchestra; percussion works such as Psappha (1975) and Pléïades (1979); compositions that introduced spatialization by dispersing musicians among the audience, such as Terretektorh (1966); electronic works created using Xenakis's UPIC system; and the massive multimedia performances Xenakis called polytopes. Among the numerous theoretical writings he authored, the book Formalized Music: Thought and Mathematics in Composition (1971) is regarded as one of his most important. As an architect, Xenakis is primarily known for his early work under Le Corbusier: the Sainte Marie de La Tourette, on which the two architects collaborated, and the Philips Pavilion at Expo 58, which Xenakis designed alone.

Life[link]

1922–1947: Early years in Greece[link]

Xenakis was born in Brăila, Romania. He was the eldest son of Klearchos Xenakis, a Greek businessman from Euboea, and Fotini Pavlou from Lemnos. His parents were both interested in music, and it was Fotini who introduced the young Xenakis to music. Her early death, when the boy was only five years old, was a traumatic experience that, in his own words, "deeply scarred" the future composer.^[3] He was subsequently educated by a series of governesses, and then, in 1932, sent to a boarding school on the Aegean island of Spetsai, Greece. He sang at the school's boys' choir, where the repertoire included works by Palestrina, and Mozart's Requiem, which Xenakis memorized in its entirety.^[4] It was also at the Spetsai school that Xenakis studied notation and solfège, and became enamored with Greek traditional and sacred music.^[4]

In 1938, after graduating from the Spetsai school, Xenakis moved to Athens to prepare for entrance exams at the National Technical University of Athens. Although he intended to study architecture and engineering, he also took lessons in harmony and counterpoint with Aristotelis Koundouroff.^[5] In 1940 he successfully passed the exams, but his studies were cut short by the Greco-Italian War, which began with the Italian invasion on 28 October 1940. Although Greece eventually won the war, it was not long before the German army joined the Italians in the Battle of Greece, in April 1941. This led to the Axis occupation of Greece during World War II, which lasted until late 1944, when the Soviet Army began its drive across Romania, forcing the Axis forces to slowly withdraw. Xenakis joined the communist National Liberation Front early during the war, participating in mass protests and demonstrations, and later becoming part of armed resistance—this last step was a painful experience Xenakis refused to discuss until much later in life.^[6][7] After the Axis forces left, Churchill ordered that British forces step in to help restore the monarchy; they were opposed by the Democratic Army of Greece, and the country plunged into a civil war. In December 1944, during the period of Churchill's martial law,^[8] Xenakis (who was by then a member of the communist students' company of the left-wing Lord Byron faction of ELAS) became involved in street fighting against British tanks. He was gravely wounded when a shell hit his face; that Xenakis survived the injury has been described as a miracle.^[9] He survived seriously scarred, and lost his left eye.^[10]

The Technical University worked intermittently during these years. Despite this, and Xenakis's other activities, he was able to graduate in 1947, with a degree in civil engineering.^[11] Xenakis was then conscripted into the national armed forces. Around 1947 the new government began hunting down former resistance members and sending them to concentration camps. Xenakis, fearing for his life, deserted and went into hiding. With the help of his father and others he fled Greece through Italy. On 11 November 1947 he arrived to Paris. In a late interview, Xenakis admitted to feeling tremendous guilt at leaving his country, and that guilt was one of the sources of his later devotion to music:

For years I was tormented by guilt at having left the country for which I'd fought. I left my friends—some were in prison, others were dead, some managed to escape. I felt I was in debt to them and that I had to repay that debt. And I felt I had a mission. I had to do something important to regain the right to live. It wasn't just a question of music—it was something much more significant.^[12]

In the meantime, in Greece he was sentenced (in absentia) to death by the right-wing administration. The sentence was commuted to ten years' imprisonment in 1951, and only lifted some 23 years later, after the fall of The Regime of the Colonels in 1974.^[13]

1947–1959: Architecture and music[link]

The Philips Pavilion at the time of the exhibition. Design by Xenakis

Although he was an illegal immigrant in Paris, Xenakis was able to get a job at Le Corbusier's architectural studio. He worked as engineering assistant at first, but quickly rose to performing more important tasks, and eventually to collaborating with Le Corbusier on major projects. These included a kindergarten on the roof of an apartment block in Nantes (Rezé), parts of government buildings in Chandigarh, India, the "undulatory glass surfaces" of Sainte Marie de La Tourette, a Dominican priory in a valley near Lyon, and the Philips Pavilion at Expo 58—the latter project was completed by Xenakis alone, from a basic sketch by Le Corbusier.^[14] The experience Xenakis gained played a major role in his music: important early compositions such as Metastaseis B (1953–4, also known as Metastasis) were based directly on architectural concepts.

At the same time, while working for Le Corbusier, Xenakis was studying harmony and counterpoint, and composing. He worked long and hard, frequently far into the night,^[15] and sought guidance from a number of teachers, most of whom, however, ultimately rejected him. Such was the case with Nadia Boulanger, who was the first person Xenakis approached about lessons. He then tried studying with Arthur Honegger, whose reaction to Xenakis's music was unenthusiastic. As Xenakis recounted in a 1987 interview, Honegger dismissed a piece which included parallel fifths and octaves as "not music". Xenakis, who was by that time well acquainted with music of Debussy, Béla Bartók, and Stravinsky, all of whom used such devices and much more experimental ones, was furious and left to study with Darius Milhaud, but these lessons also proved fruitless.^[16] Then, Annette Dieudonné, a close friend of Boulanger's, recommended that Xenakis try studying with Olivier Messiaen.^[17] Xenakis approached Messiaen for advice: should he once again start studying harmony and counterpoint? Unlike Honegger and Milhaud, Messiaen immediately recognized Xenakis's talent:

I understood straight away that he was not someone like the others. [...] He is of superior intelligence. [...] I did something horrible which I should do with no other student, for I think one should study harmony and counterpoint. But this was a man so much out of the ordinary that I said... No, you are almost thirty, you have the good fortune of being Greek, of being an architect and having studied special mathematics. Take advantage of these things. Do them in your music.^[18]

Xenakis attended Messiaen's classes regularly in 1951–53. Messiaen and his students studied music from a wide range of genres and styles, with particular attention to rhythm.^[19] Xenakis's compositions from 1949–52 were mostly inspired by Greek folk melodies, as well as Bartók, Ravel, and others; after studying with Messiaen, he discovered serialism and gained a deep understanding of contemporary music (Messiaen's other pupils at the time included, for example, Karlheinz Stockhausen and Jean Barraqué). Messiaen's modal serialism was an influence on Xenakis's first large-scale work, Anastenaria (1953–54): a triptych for choir and orchestra based on an ancient Dionysian ritual. The third part of the triptych, Metastaseis, is generally regarded as the composer's first mature piece; it was detached from the triptych to mark the beginning of the "official" Xenakis oeuvre.^[14]

In 1953 Xenakis married Françoise Xenakis (née Gargouïl), journalist and writer, whom he met in 1950.^[20] Their daughter Mâkhi, later a painter and sculptor, was born in 1956. In late 1954, with Messiaen's support, Xenakis was accepted into the Groupe de Recherches de Musique Concrète,^[21] an organization established by Pierre Schaeffer and Pierre Henry, dedicated to studying and producing electronic music of the musique concrète variety. Shortly after that Xenakis met conductor Hermann Scherchen, who was immediately impressed by the score of Metastaseis and offered his support. Although Scherchen did not premiere that particular work, he did give performances of later pieces by Xenakis, and the relationship between the conductor and the composer was of vital importance for the latter.^[22]

By late 1950s Xenakis slowly started gaining recognition in artistic circles. In 1957 he received his first composition award, from the European Cultural Foundation, and in 1958 the first official commission came through, from Service de Recherche of Radio-France.^[23] In the same year he produced a musique concrète piece, Concret PH, for the Philips Pavilion, and in 1960 Xenakis was well-known enough to receive a commission from UNESCO, for a soundtrack for a documentary film by Enrico Fulchignoni.^[24]

Later life[link]

After leaving Le Corbusier's studio in 1959, Xenakis was able to support himself by composition and teaching, and quickly became recognized as one of the most important European composers of his time. He became especially known for his musical research in the field of computer-assisted composition, for which he founded the Equipe de Mathématique et Automatique Musicales (EMAMu) in 1966 (known as CEMAMu: Centre d’Etudes de Mathématique et Automatique Musicales, since 1972). He taught at Indiana University in 1967–72 (and established a studio similar to EMAMu there), and worked as visiting professor at the Sorbonne in 1973–89.^[14] Xenakis frequently gave lectures (for instance, from 1975 to 1978 he was Professor of Music at Gresham College, London, giving free public lectures^[25]), taught composition (notable students include Pascal Dusapin, Henning Lohner, and Miguel Ángel Coria), and his works were performed at numerous festivals worldwide, including, for instance, the Shiraz Arts Festival in Iran.

In addition to composing and teaching, Xenakis also authored a number of articles and essays on music. Of these, Musiques formelles (1963) became particularly known. A collection of texts on applications of stochastic processes, game theory and computer programming in music, it was later revised, expanded and translated into English as Formalized Music: Thought and Mathematics in Composition (1971) during Xenakis's tenure at Indiana University.

Xenakis completed his last work, O-mega for percussion soloist and chamber orchestra, in 1997. His health had been getting progressively worse over the years, and by 1997 he was no longer able to work. In 1999, Xenakis was awarded the Polar Music Prize "for a long succession of forceful works, charged with sensitivity, commitment and passion, through which he has come to rank among the most central composers of our century in the realm of art music, exercising within its various fields an influence which cannot be readily overstated".^[26] After several years of serious illness, in early February 2001 the composer lapsed into a coma. He died in his Paris home several days later, on February 4, aged 78. He was survived by his wife and his daughter.^[27]

Works[link]

Specific examples of mathematics, statistics, and physics applied to music composition are the use of the statistical mechanics of gases in Pithoprakta, statistical distribution of points on a plane in Diamorphoses, minimal constraints in Achorripsis, the normal distribution in ST/10 and Atrées, Markov chains in Analogiques, game theory in Duel and Stratégie, group theory in Nomos Alpha (for Siegfried Palm), set theory in Herma and Eonta,^[28] and Brownian motion in N'Shima. At the Shirah Arts Festival in Persepolis, he designed Polytope as a composition specific to the historic site.^[29] The following year he was commissioned by Mohammad Reza Pahlavi (the Shah of Iran), to compose Nuits, which Xenakis dedicated to political prisoners in protest at the Shah’s atrocities.^[29]

By 1979, he had devised a computer system called UPIC, which could translate graphical images into musical results, wrote Andrew Hugill in 2008.^[30] "Xenakis had originally trained as an architect, so some of his drawings, which he called 'arborescences', resembled both organic forms and architectural structures." These drawings' various curves and lines that could be interpreted by UPIC as real time instructions for the sound synthesis process. The drawing is, thus, rendered into a composition. Mycenae-Alpha was the first of these pieces he created using UPIC as it was being perfected.^{[citation needed]}

Publications[link]

• Xenakis, Iannis. 2001. Formalized Music: Thought and Mathematics in Composition (Harmonologia Series No.6). Hillsdale, NY: Pendragon Press. ISBN 1-57647-079-2

Notes[link]

References[link]

• Amagali, Rosemary Tristano. 1975. "Texture as an Organizational Factor in Selected Works of Iannis Xenakis". M.M. Thesis, Indiana University.
• Ariza, Christopher. 2005. "The Xenakis Sieve as Object: A New Model and a Complete Implementation." Computer Music Journal 29(2):40-60. http://www.mitpressjournals.org/doi/pdf/10.1162/0148926054094396'
• Baltensperger, André. 1995. Iannis Xenakis und die Stochastische Musik – Komposition im Spannungsfeld von Architektur und Mathematik. Zürich. Paul Haupt.
• Bardot, Jean-Marc. 1999. "Cendrées de Xenakis ou l'émergence de la vocalité dans la pensée xenakienne." Undergraduate thesis (equivalent). Saint-Etienne: Université Jean Monnet.
• Biasi, Salvatore di. 1994. Musica e matematica negli anni 50–60: Iannis Xenakis. Bologne. Università degli Studi di Bologna.
• Clark, Philip: "The Wire Primers: A Guide To Modern Music" Xenakis, pages 191-198; Verso, 2009; ISBN 978-1-84467-427-5
• Harley, James. 2004. Xenakis: his life in music. London: Taylor & Francis Books. ISBN 0-415-97145-4
• Hoffmann, Peter. "Iannis Xenakis", Grove Music Online, ed. L. Macy (accessed 23 December 2006), grovemusic.com (subscription access).
• Mâche, François-Bernard. 2002. Portrait(s) de Iannis Xenakis Seuil. ISBN 2-7177-2178-9
• Matossian, Nouritza. 1986. Xenakis. London: Kahn and Averill. ISBN 1-871082-17-X
• Paland, Ralph / von Blumröder, Christoph (Ed.). 2009. Iannis Xenakis: Das elektroakustische Werk. Internationales Symposion. Tagungsbericht 2006. (Signale aus Köln. Beiträge zur Musik der Zeit, Volume 14) Wien. Der Apfel. ISBN 978-3-85450-414-6
• Varga, Bálint András. 1996. Conversations with Iannis Xenakis. London: Faber and Faber. ISBN 0-571-17959-2
• Xenakis, Iannis; Roberta Brown, and John Rahn (1987). "Xenakis on Xenakis". Perspectives of New Music 25 (1/2): 16–63. 

External links[link]

Wikiquote has a collection of quotations related to: Iannis Xenakis