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170-453: Radiation therapy is commonly applied to the cancerous tumor because of its ability to control cell growth. Ionizing radiation works by damaging the DNA of cancerous tissue leading to cellular death . To spare normal tissues (such as skin or organs which radiation must pass through to treat the tumor), shaped radiation beams are aimed from several angles of exposure to intersect at the tumor, providing

340-485: A MEK inhibitor trametinib . In February 2024, the Food and Drug Administration approved the first cancer treatment that uses tumor-infiltrating lymphocytes, also called TIL therapy, specifically for melanomas that have not improved with other treatments. Additionally, scientists are testing a vaccine designed to match the unique genetic details of a patient's cancer in an advanced clinical trial. Currently, surgical excision

510-523: A mole that has changed in size, shape, color, has irregular edges, has more than one color, is itchy or bleeds. More than 90% of cases are caused by exposure to ultraviolet radiation from the Sun . This exposure increases the risk of all three main types of skin cancer. Exposure has increased, partly due to a thinner ozone layer . Tanning beds are another common source of ultraviolet radiation. For melanomas and basal-cell cancers, exposure during childhood

680-449: A UV-signature mutation indicating that these cancers are caused by UVB radiation via direct DNA damage. However malignant melanoma is predominantly caused by UVA radiation via indirect DNA damage. The indirect DNA damage is caused by free radicals and reactive oxygen species. Research indicates that the absorption of three sunscreen ingredients into the skin, combined with a 60-minute exposure to UV, leads to an increase of free radicals in

850-472: A break of three months followed by another phase of three gray of radiation for five days. Radiation therapy works by damaging the DNA of cancer cells and can cause them to undergo mitotic catastrophe . This DNA damage is caused by one of two types of energy, photon or charged particle . This damage is either direct or indirect ionization of the atoms which make up the DNA chain. Indirect ionization happens as

1020-445: A buffer to recruit or titrate ions or antibiotics. Extracellular DNA acts as a functional extracellular matrix component in the biofilms of several bacterial species. It may act as a recognition factor to regulate the attachment and dispersal of specific cell types in the biofilm; it may contribute to biofilm formation; and it may contribute to the biofilm's physical strength and resistance to biological stress. Cell-free fetal DNA

1190-481: A cancer to radiation is described by its radiosensitivity. Highly radiosensitive cancer cells are rapidly killed by modest doses of radiation. These include leukemias , most lymphomas , and germ cell tumors . The majority of epithelial cancers are only moderately radiosensitive, and require a significantly higher dose of radiation (60–70 Gy) to achieve a radical cure. Some types of cancer are notably radioresistant, that is, much higher doses are required to produce

1360-413: A cell makes up its genome ; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes. The information carried by DNA is held in the sequence of pieces of DNA called genes . Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into

1530-450: A chain by covalent bonds (known as the phosphodiester linkage ) between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone . The nitrogenous bases of the two separate polynucleotide strands are bound together, according to base pairing rules (A with T and C with G), with hydrogen bonds to make double-stranded DNA. The complementary nitrogenous bases are divided into two groups,

1700-445: A complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation , which depends on the same interaction between RNA nucleotides. In an alternative fashion, a cell may copy its genetic information in a process called DNA replication . The details of these functions are covered in other articles; here

1870-559: A cyst or another type of cancer. Ultraviolet radiation from sun exposure is the primary environmental cause of skin cancer. This can occur in professions such as farming. Other risk factors that play a role include: UV-irradiation of skin cells causes damage to DNA through photochemical reactions . Cyclobutane pyrimidine dimers formed by adjacent thymine bases, or by adjacent cytosine bases, are frequent types of DNA damage induced by UV. Human skin cells are capable of repairing most UV-induced damage by nucleotide excision repair ,

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2040-432: A dose, including whether the patient is receiving chemotherapy, patient comorbidities, whether radiation therapy is being administered before or after surgery, and the degree of success of surgery. Delivery parameters of a prescribed dose are determined during treatment planning (part of dosimetry ). Treatment planning is generally performed on dedicated computers using specialized treatment planning software. Depending on

2210-492: A double helix can thus be pulled apart like a zipper, either by a mechanical force or high temperature . As a result of this base pair complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. This reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in organisms. Most DNA molecules are actually two polymer strands, bound together in

2380-495: A few. There is insufficient evidence either for or against screening for skin cancers. Vitamin supplements and antioxidant supplements have not been found to have an effect in prevention. Evidence for reducing melanoma risk from dietary measures is tentative, with some supportive epidemiological evidence, but no clinical trials. Zinc oxide and titanium oxide are often used in sunscreen to provide broad protection from UVA and UVB ranges. Eating certain foods may decrease

2550-428: A full set of the mitochondrial genes. Each human mitochondrion contains, on average, approximately 5 such mtDNA molecules. Each human cell contains approximately 100 mitochondria, giving a total number of mtDNA molecules per human cell of approximately 500. However, the amount of mitochondria per cell also varies by cell type, and an egg cell can contain 100,000 mitochondria, corresponding to up to 1,500,000 copies of

2720-439: A helical fashion by noncovalent bonds; this double-stranded (dsDNA) structure is maintained largely by the intrastrand base stacking interactions, which are strongest for G,C stacks. The two strands can come apart—a process known as melting—to form two single-stranded DNA (ssDNA) molecules. Melting occurs at high temperatures, low salt and high pH (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH

2890-571: A higher number is also possible but this would be against the natural principle of least effort . The phosphate groups of DNA give it similar acidic properties to phosphoric acid and it can be considered as a strong acid . It will be fully ionized at a normal cellular pH, releasing protons which leave behind negative charges on the phosphate groups. These negative charges protect DNA from breakdown by hydrolysis by repelling nucleophiles which could hydrolyze it. Pure DNA extracted from cells forms white, stringy clumps. The expression of genes

3060-407: A linear accelerator in appearance, but used a sealed radioactive source like the one shown above. 2DXRT mainly consists of a single beam of radiation delivered to the patient from several directions: often front or back, and both sides. Conventional refers to the way the treatment is planned or simulated on a specially calibrated diagnostic X-ray machine known as a simulator because it recreates

3230-406: A linear scar. If the repair is made along a natural skin fold or wrinkle line, the scar will be hardly visible. Larger defects may require repair with a skin graft, local skin flap, pedicled skin flap, or a microvascular free flap. Skin grafts and local skin flaps are by far more common than the other listed choices. Skin grafting is patching of a defect with skin that is removed from another site in

3400-667: A long-standing puzzle known as the " C-value enigma ". However, some DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression . Some noncoding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes but are important for the function and stability of chromosomes. An abundant form of noncoding DNA in humans are pseudogenes , which are copies of genes that have been disabled by mutation. These sequences are usually just molecular fossils , although they can occasionally serve as raw genetic material for

3570-418: A method of closing defects with tissue that closely matches the defect in color and quality. Skin from the periphery of the defect site is mobilized and repositioned to fill the deficit. Various forms of local flaps can be designed to minimize disruption to surrounding tissues and maximize cosmetic outcome of the reconstruction. Pedicled skin flaps are a method of transferring skin with an intact blood supply from

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3740-724: A mild to moderate sun burn. The fatigue often sets in during the middle of a course of treatment and can last for weeks after treatment ends. The irritated skin will heal, but may not be as elastic as it was before. Late side effects occur months to years after treatment and are generally limited to the area that has been treated. They are often due to damage of blood vessels and connective tissue cells. Many late effects are reduced by fractionating treatment into smaller parts. Cumulative effects from this process should not be confused with long-term effects – when short-term effects have disappeared and long-term effects are subclinical, reirradiation can still be problematic. These doses are calculated by

3910-589: A much larger absorbed dose there than in the surrounding healthy tissue. Besides the tumor itself, the radiation fields may also include the draining lymph nodes if they are clinically or radiologically involved with the tumor, or if there is thought to be a risk of subclinical malignant spread. It is necessary to include a margin of normal tissue around the tumor to allow for uncertainties in daily set-up and internal tumor motion. These uncertainties can be caused by internal movement (for example, respiration and bladder filling) and movement of external skin marks relative to

4080-409: A narrower, deeper major groove. The A form occurs under non-physiological conditions in partly dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, and in enzyme-DNA complexes. Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form . Here, the strands turn about

4250-450: A nearby region of the body. An example of such reconstruction is a pedicled forehead flap for the repair of a large nasal skin defect. Once the flap develops a source of blood supply form its new bed, the vascular pedicle can be detached. The mortality rate of basal-cell and squamous-cell carcinoma is around 0.3%, causing 2000 deaths per year in the US. In comparison, the mortality rate of melanoma

4420-425: A neurosurgeon for tumors in the brain or spine. There are two types of stereotactic radiation. Stereotactic radiosurgery (SRS) is when doctors use a single or several stereotactic radiation treatments of the brain or spine. Stereotactic body radiation therapy (SBRT) refers to one or several stereotactic radiation treatments with the body, such as the lungs. Some doctors say an advantage to stereotactic treatments

4590-519: A normal oxygen environment. Much research has been devoted to overcoming hypoxia including the use of high pressure oxygen tanks, hyperthermia therapy (heat therapy which dilates blood vessels to the tumor site), blood substitutes that carry increased oxygen, hypoxic cell radiosensitizer drugs such as misonidazole and metronidazole , and hypoxic cytotoxins (tissue poisons), such as tirapazamine . Newer research approaches are currently being studied, including preclinical and clinical investigations into

4760-556: A number of measures including decreasing indoor tanning and mid-day sun exposure, increasing the use of sunscreen , and avoiding the use of tobacco products . It is important to limit sun exposure and to avoid tanning beds, because they both involve UV light. UV light is known to damage skin cells by mutating their DNA. The mutated DNA can cause tumors and other growths to form on the skin. Further, there are other risk factors beside just UV exposure. Fair skin, prolonged history of sunburns, moles, and family history of skin cancer are just

4930-429: A period of two weeks. In a full thickness skin graft, a segment of skin is totally removed and the donor site needs to be sutured closed. Split thickness grafts can be used to repair larger defects, but the grafts are inferior in their cosmetic appearance. Full thickness skin grafts are more acceptable cosmetically. However, full thickness grafts can only be used for small or moderate sized defects. Local skin flaps are

5100-412: A process that protects against skin cancer, but may be inadequate at high levels of exposure. A malignant epithelial tumor that primarily originates in the epidermis, in squamous mucosa or in areas of squamous metaplasia is referred to as a squamous-cell carcinoma. Macroscopically, the tumor is often elevated, fungating , or may be ulcerated with irregular borders. Microscopically, tumor cells destroy

5270-405: A radical cure than may be safe in clinical practice. Renal cell cancer and melanoma are generally considered to be radioresistant but radiation therapy is still a palliative option for many patients with metastatic melanoma. Combining radiation therapy with immunotherapy is an active area of investigation and has shown some promise for melanoma and other cancers. It is important to distinguish

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5440-442: A radius of 10 Å (1.0 nm). According to another study, when measured in a different solution, the DNA chain measured 22–26 Å (2.2–2.6 nm) wide, and one nucleotide unit measured 3.3 Å (0.33 nm) long. The buoyant density of most DNA is 1.7g/cm . DNA does not usually exist as a single strand, but instead as a pair of strands that are held tightly together. These two long strands coil around each other, in

5610-476: A result of the ionization of water, forming free radicals , notably hydroxyl radicals, which then damage the DNA. In photon therapy, most of the radiation effect is through free radicals. Cells have mechanisms for repairing single-strand DNA damage and double-stranded DNA damage. However, double-stranded DNA breaks are much more difficult to repair, and can lead to dramatic chromosomal abnormalities and genetic deletions. Targeting double-stranded breaks increases

5780-416: A second protein when read in the opposite direction along the other strand. In bacteria , this overlap may be involved in the regulation of gene transcription, while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome. DNA can be twisted like a rope in a process called DNA supercoiling . With DNA in its "relaxed" state, a strand usually circles

5950-445: A simple TTAGGG sequence. These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases, known as a guanine tetrad , form a flat plate. These flat four-base units then stack on top of each other to form a stable G-quadruplex structure. These structures are stabilized by hydrogen bonding between

6120-639: A single treatment is best to improve patient comfort. One fractionation schedule that is increasingly being used and continues to be studied is hypofractionation. This is a radiation treatment in which the total dose of radiation is divided into large doses. Typical doses vary significantly by cancer type, from 2.2 Gy/fraction to 20 Gy/fraction, the latter being typical of stereotactic treatments (stereotactic ablative body radiotherapy, or SABR – also known as SBRT, or stereotactic body radiotherapy) for subcranial lesions, or SRS (stereotactic radiosurgery) for intracranial lesions. The rationale of hypofractionation

6290-444: A vaccine that stimulates the production of a protein critical to the skin's antioxidant network could reinforce people's defenses against skin cancer. Treatment is dependent on the specific type of cancer, location of the cancer, age of the person, and whether the cancer is primary or a recurrence. For a small basal-cell cancer in a young person, the treatment with the best cure rate ( Mohs surgery or CCPDMA ) might be indicated. In

6460-404: A very high failure rate, e.g. women who have received radiation for breast cancer develop late effect chest wall tissue fibrosis and hypovascularity, making successful reconstruction and healing difficult, if not impossible. There are rigorous procedures in place to minimise the risk of accidental overexposure of radiation therapy to patients. However, mistakes do occasionally occur; for example,

6630-468: A year as of 2010, 49,000 of which are due to melanoma and 31,000 of which are due to non-melanoma skin cancers. This is up from 51,000 in 1990. More than 3.5 million cases of skin cancer are diagnosed annually in the United States, which makes it the most common form of cancer in that country. One in five Americans will develop skin cancer at some point of their lives. The most common form of skin cancer

6800-435: Is 15–20% and it causes 6500 deaths per year. Even though it is much less common, malignant melanoma is responsible for 75% of all skin cancer-related deaths. The survival rate for people with melanoma depends upon when they start treatment. The cure rate is very high when melanoma is detected in early stages, when it can easily be removed surgically. The prognosis is less favorable if the melanoma has spread to other parts of

6970-413: Is a polymer composed of two polynucleotide chains that coil around each other to form a double helix . The polymer carries genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses . DNA and ribonucleic acid (RNA) are nucleic acids . Alongside proteins , lipids and complex carbohydrates ( polysaccharides ), nucleic acids are one of

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7140-504: Is a rough estimate; good statistics are not kept. Of nonmelanoma skin cancers, about 80% are basal-cell cancers and 20% squamous-cell skin cancers. Basal-cell and squamous-cell skin cancers rarely result in death. In the United States, they were the cause of less than 0.1% of all cancer deaths. Globally in 2012, melanoma occurred in 232,000 people and resulted in 55,000 deaths. White people in Australia , New Zealand and South Africa have

7310-449: Is also related to its size. Due to complex radiobiology , very large tumors are affected less by radiation compared to smaller tumors or microscopic disease. Various strategies are used to overcome this effect. The most common technique is surgical resection prior to radiation therapy. This is most commonly seen in the treatment of breast cancer with wide local excision or mastectomy followed by adjuvant radiation therapy . Another method

7480-516: Is as safe as possible. Radiation therapy is used to treat early stage Dupuytren's disease and Ledderhose disease . When Dupuytren's disease is at the nodules and cords stage or fingers are at a minimal deformation stage of less than 10 degrees, then radiation therapy is used to prevent further progress of the disease. Radiation therapy is also used post surgery in some cases to prevent the disease continuing to progress. Low doses of radiation are used typically three gray of radiation for five days, with

7650-447: Is called intercalation . Most intercalators are aromatic and planar molecules; examples include ethidium bromide , acridines , daunomycin , and doxorubicin . For an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations. As a result, DNA intercalators may be carcinogens , and in

7820-435: Is called a polynucleotide . The backbone of the DNA strand is made from alternating phosphate and sugar groups. The sugar in DNA is 2-deoxyribose , which is a pentose (five- carbon ) sugar. The sugars are joined by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These are known as the 3′-end (three prime end), and 5′-end (five prime end) carbons,

7990-600: Is commonly a red, scaling, thickened patch on sun-exposed skin. Some are firm hard nodules and dome shaped like keratoacanthomas . Ulceration and bleeding may occur. When SCC is not treated, it may develop into a large mass. Squamous-cell is the second most common skin cancer. It is dangerous, but not nearly as dangerous as a melanoma. Most melanoma consist of various colours from shades of brown to black. A small number of melanoma are pink, red or fleshy in colour; these are called amelanotic melanoma and tend to be more aggressive. Warning signs of malignant melanoma include change in

8160-417: Is crucial at this stage as the patient will have to be placed in an identical position during each treatment. Many patient positioning devices have been developed for this purpose, including masks and cushions which can be molded to the patient. Image-guided radiation therapy is a method that uses imaging to correct for positional errors of each treatment session. The response of a tumor to radiation therapy

8330-434: Is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high GC -content have more strongly interacting strands, while short helices with high AT content have more weakly interacting strands. In biology, parts of

8500-443: Is found in the blood of the mother, and can be sequenced to determine a great deal of information about the developing fetus. Skin neoplasm Skin cancers are cancers that arise from the skin . They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. It occurs when skin cells grow uncontrollably, forming malignant tumors. The primary cause of skin cancer

8670-546: Is fractionated (spread out over time) for several important reasons. Fractionation allows normal cells time to recover, while tumor cells are generally less efficient in repair between fractions. Fractionation also allows tumor cells that were in a relatively radio-resistant phase of the cell cycle during one treatment to cycle into a sensitive phase of the cycle before the next fraction is given. Similarly, tumor cells that were chronically or acutely hypoxic (and therefore more radioresistant) may reoxygenate between fractions, improving

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8840-411: Is influenced by how the DNA is packaged in chromosomes, in a structure called chromatin . Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of methylation of cytosine bases. DNA packaging and its influence on gene expression can also occur by covalent modifications of the histone protein core around which DNA is wrapped in

9010-432: Is introduced by enzymes called topoisomerases . These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication . DNA exists in many possible conformations that include A-DNA , B-DNA , and Z-DNA forms, although only B-DNA and Z-DNA have been directly observed in functional organisms. The conformation that DNA adopts depends on

9180-553: Is limited, such as the face. Cure rates are equivalent to wide excision. Special training is required to perform this technique. An alternative method is CCPDMA and can be performed by a pathologist not familiar with Mohs surgery . In the case of disease that has spread (metastasized), further surgical procedures or chemotherapy may be required. Treatments for metastatic melanoma include biologic immunotherapy agents ipilimumab , pembrolizumab , nivolumab , cemiplimab ; BRAF inhibitors , such as vemurafenib and dabrafenib ; and

9350-449: Is measured in grays (Gy), and varies depending on the type and stage of cancer being treated. For curative cases, the typical dose for a solid epithelial tumor ranges from 60 to 80 Gy, while lymphomas are treated with 20 to 40 Gy. Preventive (adjuvant) doses are typically around 45–60 Gy in 1.8–2 Gy fractions (for breast, head, and neck cancers.) Many other factors are considered by radiation oncologists when selecting

9520-471: Is needed to support this. Computer-assisted diagnosis devices have been developed that analyze images from a dermatoscope or spectroscopy and can be used by a diagnostician to aid in the detection of skin cancer. CAD systems have been found to be highly sensitive in the detection of melanoma, but have a high false-positive rate. There is not yet enough evidence to recommend CAD as compared to traditional diagnostic methods. High-frequency ultrasound (HFUS)

9690-436: Is not clear if sunscreen affects the risk of basal-cell cancer. Nonmelanoma skin cancer is usually curable. Treatment is generally by surgical removal but may, less commonly, involve radiation therapy or topical medications such as fluorouracil . Treatment of melanoma may involve some combination of surgery, chemotherapy , radiation therapy and targeted therapy . In those people whose disease has spread to other areas of

9860-422: Is nothing special about the four natural nucleobases that evolved on Earth. On the other hand, DNA is tightly related to RNA which does not only act as a transcript of DNA but also performs as molecular machines many tasks in cells. For this purpose it has to fold into a structure. It has been shown that to allow to create all possible structures at least four bases are required for the corresponding RNA , while

10030-768: Is of unclear usefulness in the diagnosis of skin cancer. There is insufficient evidence for reflectance confocal microscopy to diagnose basal cell or squamous cell carcinoma or any other skin cancers. Sunscreen is effective and thus recommended to prevent melanoma and squamous-cell carcinoma. There is little evidence that it is effective in preventing basal-cell carcinoma. Other advice to reduce rates of skin cancer includes avoiding sunburn, wearing protective clothing, sunglasses and hats, and attempting to avoid sun exposure or periods of peak exposure. The U.S. Preventive Services Task Force recommends that people between 9 and 25 years of age be advised to avoid ultraviolet light. The risk of developing skin cancer can be reduced through

10200-432: Is one of four types of nucleobases (or bases ). It is the sequence of these four nucleobases along the backbone that encodes genetic information. RNA strands are created using DNA strands as a template in a process called transcription , where DNA bases are exchanged for their corresponding bases except in the case of thymine (T), for which RNA substitutes uracil (U). Under the genetic code , these RNA strands specify

10370-497: Is particularly harmful. For squamous-cell skin cancers, total exposure, irrespective of when it occurs, is more important. Between 20% and 30% of melanomas develop from moles. People with lighter skin are at higher risk as are those with poor immune function such as from medications or HIV/AIDS . Diagnosis is by biopsy . Decreasing exposure to ultraviolet radiation and the use of sunscreen appear to be effective methods of preventing melanoma and squamous-cell skin cancer. It

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10540-538: Is poorly responsive to radiation or chemotherapy. For low-risk disease, radiation therapy ( external beam radiotherapy or brachytherapy ), topical chemotherapy ( imiquimod or 5-fluorouracil) and cryotherapy (freezing the cancer off) can provide adequate control of the disease; all of them, however, may have lower overall cure rates than certain type of surgery. Other modalities of treatment such as photodynamic therapy, epidermal radioisotope therapy , topical chemotherapy, electrodesiccation and curettage can be found in

10710-414: Is preferably completed within a certain amount of time. For children, a typical fraction size may be 1.5 to 1.8 Gy per day, as smaller fraction sizes are associated with reduced incidence and severity of late-onset side effects in normal tissues. In some cases, two fractions per day are used near the end of a course of treatment. This schedule, known as a concomitant boost regimen or hyperfractionation,

10880-440: Is prolonged exposure to ultraviolet (UV) radiation from the sun or tanning devices. Skin cancer is the most commonly diagnosed form of cancer in humans. There are three main types of skin cancers: basal-cell skin cancer (BCC), squamous-cell skin cancer (SCC) and melanoma . The first two, along with a number of less common skin cancers, are known as nonmelanoma skin cancer (NMSC). Basal-cell cancer grows slowly and can damage

11050-514: Is rarely used). The stability of the dsDNA form depends not only on the GC -content (% G,C basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the melting temperature (also called T m value), which is the temperature at which 50% of the double-strand molecules are converted to single-strand molecules; melting temperature

11220-428: Is recreated by an enzyme called DNA polymerase . This enzyme makes the complementary strand by finding the correct base through complementary base pairing and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5′ to 3′ direction, different mechanisms are used to copy the antiparallel strands of the double helix. In this way, the base on the old strand dictates which base appears on

11390-442: Is that they deliver the right amount of radiation to the cancer in a shorter amount of time than traditional treatments, which can often take 6 to 11 weeks. Plus treatments are given with extreme accuracy, which should limit the effect of the radiation on healthy tissues. One problem with stereotactic treatments is that they are only suitable for certain small tumors. Stereotactic treatments can be confusing because many hospitals call

11560-516: Is the largest human chromosome with approximately 220 million base pairs , and would be 85 mm long if straightened. In eukaryotes , in addition to nuclear DNA , there is also mitochondrial DNA (mtDNA) which encodes certain proteins used by the mitochondria. The mtDNA is usually relatively small in comparison to the nuclear DNA. For example, the human mitochondrial DNA forms closed circular molecules, each of which contains 16,569 DNA base pairs, with each such molecule normally containing

11730-563: Is the most common form of treatment for skin cancers. The goal of reconstructive surgery is the restoration of normal appearance and function. The choice of technique in reconstruction is dictated by the size and location of the defect. Excision and reconstruction of facial skin cancers are generally more challenging due to the presence of highly visible and functional anatomic structures in the face. When skin defects are small in size, most can be repaired with simple repair where skin edges are approximated and closed with sutures. This will result in

11900-475: Is the most common type of cancer in people between 15 and 44 years in both countries. The incidence of skin cancer has been increasing. The incidence of melanoma among Auckland residents of European descent in 1995 was 77.7 cases per 100,000 people per year, and was predicted to increase in the 21st century because of "the effect of local stratospheric ozone depletion and the time lag from sun exposure to melanoma development." Skin cancers result in 80,000 deaths

12070-441: Is to allow the cell to replicate chromosome ends using the enzyme telomerase , as the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes. These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected. In human cells , telomeres are usually lengths of single-stranded DNA containing several thousand repeats of

12240-547: Is to reduce the probability of local recurrence by denying clonogenic cells the time they require to reproduce and also to exploit the radiosensitivity of some tumors. In particular, stereotactic treatments are intended to destroy clonogenic cells by a process of ablation, i.e., the delivery of a dose intended to destroy clonogenic cells directly, rather than to interrupt the process of clonogenic cell division repeatedly (apoptosis), as in routine radiotherapy. Different cancer types have different radiation sensitivity. While predicting

12410-501: Is to shrink the tumor with neoadjuvant chemotherapy prior to radical radiation therapy. A third technique is to enhance the radiosensitivity of the cancer by giving certain drugs during a course of radiation therapy. Examples of radiosensitizing drugs include cisplatin , nimorazole , and cetuximab . The impact of radiotherapy varies between different types of cancer and different groups. For example, for breast cancer after breast-conserving surgery , radiotherapy has been found to halve

12580-438: Is under treatment. Side effects are dose-dependent; for example, higher doses of head and neck radiation can be associated with cardiovascular complications, thyroid dysfunction, and pituitary axis dysfunction. Modern radiation therapy aims to reduce side effects to a minimum and to help the patient understand and deal with side effects that are unavoidable. The main side effects reported are fatigue and skin irritation, like

12750-442: Is used on tumors that regenerate more quickly when they are smaller. In particular, tumors in the head-and-neck demonstrate this behavior. Patients receiving palliative radiation to treat uncomplicated painful bone metastasis should not receive more than a single fraction of radiation. A single treatment gives comparable pain relief and morbidity outcomes to multiple-fraction treatments, and for patients with limited life expectancy,

12920-657: The DNA sequence . Mutagens include oxidizing agents , alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and X-rays . The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine dimers , which are cross-links between pyrimidine bases. On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks. A typical human cell contains about 150,000 bases that have suffered oxidative damage. Of these oxidative lesions,

13090-406: The amino-acid sequences of proteins is determined by the rules of translation , known collectively as the genetic code . The genetic code consists of three-letter 'words' called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT). In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase . This RNA copy is then decoded by a ribosome that reads

13260-420: The basement membrane and form sheets or compact masses which invade the subjacent connective tissue (dermis). In well differentiated carcinomas, tumor cells are pleomorphic /atypical, but resembling normal keratinocytes from prickle layer (large, polygonal, with abundant eosinophilic (pink) cytoplasm and central nucleus). Their disposal tends to be similar to that of normal epidermis: immature/basal cells at

13430-494: The body . As of 2003 the overall five-year cure rate with Mohs' micrographic surgery was around 95 percent for recurrent basal cell carcinoma. Australia and New Zealand exhibit one of the highest rates of skin cancer incidence in the world, almost four times the rates registered in the United States, the UK and Canada . Around 434,000 people receive treatment for non-melanoma skin cancers and 10,300 are treated for melanoma. Melanoma

13600-469: The cell nucleus as nuclear DNA , and some in the mitochondria as mitochondrial DNA or in chloroplasts as chloroplast DNA . In contrast, prokaryotes ( bacteria and archaea ) store their DNA only in the cytoplasm , in circular chromosomes . Within eukaryotic chromosomes, chromatin proteins, such as histones , compact and organize DNA. These compacting structures guide the interactions between DNA and other proteins, helping control which parts of

13770-421: The skin that do not heal, ulcering in the skin, discolored skin, and changes in existing moles , such as jagged edges to the mole, enlargement of the mole, changes in color, the way it feels or if it bleeds. Other common signs of skin cancer can be painful lesion that itches or burns and large brownish spot with darker speckles. Basal-cell skin cancer (BCC) usually presents as a raised, smooth, pearly bump on

13940-419: The 3′ and 5′ carbons along the sugar-phosphate backbone confers directionality (sometimes called polarity) to each DNA strand. In a nucleic acid double helix , the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel . The asymmetric ends of DNA strands are said to have a directionality of five prime end (5′ ), and three prime end (3′), with

14110-588: The 5′ end having a terminal phosphate group and the 3′ end a terminal hydroxyl group. One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the related pentose sugar ribose in RNA. The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among aromatic nucleobases. The four bases found in DNA are adenine ( A ), cytosine ( C ), guanine ( G ) and thymine ( T ). These four bases are attached to

14280-435: The DNA are transcribed. DNA is a long polymer made from repeating units called nucleotides . The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes. In all species it is composed of two helical chains, bound to each other by hydrogen bonds . Both chains are coiled around the same axis, and have the same pitch of 34 ångströms (3.4  nm ). The pair of chains have

14450-453: The DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters , tend to have a high AT content, making the strands easier to pull apart. In the laboratory, the strength of this interaction can be measured by finding the melting temperature T m necessary to break half of the hydrogen bonds. When all the base pairs in a DNA double helix melt,

14620-401: The RNA sequence by base-pairing the messenger RNA to transfer RNA , which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (4  combinations). These encode the twenty standard amino acids , giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are

14790-488: The TAG, TAA, and TGA codons, (UAG, UAA, and UGA on the mRNA). Cell division is essential for an organism to grow, but, when a cell divides, it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for DNA replication . Here, the two strands are separated and then each strand's complementary DNA sequence

14960-558: The ability to delineate tumors and adjacent normal structures in three dimensions using specialized CT and/or MRI scanners and planning software. Virtual simulation, the most basic form of planning, allows more accurate placement of radiation beams than is possible using conventional X-rays, where soft-tissue structures are often difficult to assess and normal tissues difficult to protect. DNA Deoxyribonucleic acid ( / d iː ˈ ɒ k s ɪ ˌ r aɪ b oʊ nj uː ˌ k l iː ɪ k , - ˌ k l eɪ -/ ; DNA )

15130-442: The axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound. If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that

15300-495: The body, palliative care may be used to improve quality of life. Melanoma has one of the higher survival rates among cancers, with over 86% of people in the UK and more than 90% in the United States surviving more than 5 years . Skin cancer is the most common form of cancer, globally accounting for at least 40% of cancer cases. The most common type is nonmelanoma skin cancer, which occurs in at least 2–3 million people per year. This

15470-422: The body, brachytherapy uses sealed radioactive sources placed precisely in the area under treatment, and systemic radioisotopes are given by infusion or oral ingestion. Brachytherapy can use temporary or permanent placement of radioactive sources. The temporary sources are usually placed by a technique called afterloading. In afterloading a hollow tube or applicator is placed surgically in the organ to be treated, and

15640-403: The body. The skin graft is sutured to the edges of the defect, and a bolster dressing is placed atop the graft for seven to ten days, to immobilize the graft as it heals in place. There are two forms of skin grafting: split thickness and full thickness. In a split thickness skin graft, a shaver is used to shave a layer of skin from the abdomen or thigh. The donor site regenerates skin and heals over

15810-407: The canonical bases plus uracil. Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site . As the strands are not symmetrically located with respect to each other, the grooves are unequally sized. The major groove is 22 ångströms (2.2 nm) wide, while

15980-459: The case of an elderly frail man with multiple complicating medical problems, a difficult to excise basal-cell cancer of the nose might warrant radiation therapy (slightly lower cure rate) or no treatment at all. Topical chemotherapy might be indicated for large superficial basal-cell carcinoma for good cosmetic outcome, whereas it might be inadequate for invasive nodular basal-cell carcinoma or invasive squamous-cell carcinoma . In general, melanoma

16150-467: The case of thalidomide, a teratogen . Others such as benzo[ a ]pyrene diol epoxide and aflatoxin form DNA adducts that induce errors in replication. Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in chemotherapy to inhibit rapidly growing cancer cells. DNA usually occurs as linear chromosomes in eukaryotes , and circular chromosomes in prokaryotes . The set of chromosomes in

16320-581: The cell (see below) , but the major and minor grooves are always named to reflect the differences in width that would be seen if the DNA was twisted back into the ordinary B form . In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called complementary base pairing . Purines form hydrogen bonds to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across

16490-427: The charged particle radiation source and the tumor and sets a finite range for tissue damage after the tumor has been reached. In contrast, IMRT's use of uncharged particles causes its energy to damage healthy cells when it exits the body. This exiting damage is not therapeutic, can increase treatment side effects, and increases the probability of secondary cancer induction. This difference is very important in cases where

16660-619: The chromatin structure or else by remodeling carried out by chromatin remodeling complexes (see Chromatin remodeling ). There is, further, crosstalk between DNA methylation and histone modification, so they can coordinately affect chromatin and gene expression. For one example, cytosine methylation produces 5-methylcytosine , which is important for X-inactivation of chromosomes. The average level of methylation varies between organisms—the worm Caenorhabditis elegans lacks cytosine methylation, while vertebrates have higher levels, with up to 1% of their DNA containing 5-methylcytosine. Despite

16830-418: The close proximity of other organs makes any stray ionization very damaging (example: head and neck cancers ). This X-ray exposure is especially bad for children, due to their growing bodies, and while depending on a multitude of factors, they are around 10 times more sensitive to developing secondary malignancies after radiotherapy as compared to adults. The amount of radiation used in photon radiation therapy

17000-476: The conditions found in cells, it is not a well-defined conformation but a family of related DNA conformations that occur at the high hydration levels present in cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder. Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and

17170-405: The creation of new genes through the process of gene duplication and divergence . A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and

17340-449: The cytoplasm called the nucleoid . The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype . A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, and regulatory sequences such as promoters and enhancers , which control transcription of

17510-444: The discussions of basal-cell carcinoma and squamous-cell carcinoma . Mohs' micrographic surgery ( Mohs surgery ) is a technique used to remove the cancer with the least amount of surrounding tissue and the edges are checked immediately to see if tumor is found. This provides the opportunity to remove the least amount of tissue and provide the best cosmetically favorable results. This is especially important for areas where excess skin

17680-448: The disease process is mutation in gene PTCH1 that plays an important role in the Sonic hedgehog signaling pathway. Diagnosis is by biopsy and histopathological examination . Non-invasive skin cancer detection methods include photography, dermatoscopy, sonography, confocal microscopy , Raman spectroscopy, fluorescence spectroscopy, terahertz spectroscopy, optical coherence tomography,

17850-405: The double helix (from six-carbon ring to six-carbon ring) is called a Watson-Crick base pair. DNA with high GC-content is more stable than DNA with low GC -content. A Hoogsteen base pair (hydrogen bonding the 6-carbon ring to the 5-carbon ring) is a rare variation of base-pairing. As hydrogen bonds are not covalent , they can be broken and rejoined relatively easily. The two strands of DNA in

18020-442: The edges of the bases and chelation of a metal ion in the centre of each four-base unit. Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure. In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here,

18190-481: The end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible. Branched DNA can be used in nanotechnology to construct geometric shapes, see

18360-445: The exception of oligometastatic disease, metastatic cancers are incurable with radiation therapy because it is not possible to treat the whole body. Modern radiation therapy relies on a CT scan to identify the tumor and surrounding normal structures and to perform dose calculations for the creation of a complex radiation treatment plan. The patient receives small skin marks to guide the placement of treatment fields. Patient positioning

18530-418: The focus is on the interactions between DNA and other molecules that mediate the function of the genome. Genomic DNA is tightly and orderly packed in the process called DNA condensation , to fit the small available volumes of the cell. In eukaryotes, DNA is located in the cell nucleus , with small amounts in mitochondria and chloroplasts . In prokaryotes, the DNA is held within an irregularly shaped body in

18700-461: The four major types of macromolecules that are essential for all known forms of life . The two DNA strands are known as polynucleotides as they are composed of simpler monomeric units called nucleotides . Each nucleotide is composed of one of four nitrogen-containing nucleobases ( cytosine [C], guanine [G], adenine [A] or thymine [T]), a sugar called deoxyribose , and a phosphate group . The nucleotides are joined to one another in

18870-448: The functions of these RNAs are not entirely clear. One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing. A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses , blur the distinction between sense and antisense strands by having overlapping genes . In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and

19040-506: The general health of the patient. Total body irradiation (TBI) is a radiation therapy technique used to prepare the body to receive a bone marrow transplant . Brachytherapy , in which a radioactive source is placed inside or next to the area requiring treatment, is another form of radiation therapy that minimizes exposure to healthy tissue during procedures to treat cancers of the breast, prostate, and other organs. Radiation therapy has several applications in non-malignant conditions, such as

19210-448: The helical axis in a left-handed spiral, the opposite of the more common B form. These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription. For many years, exobiologists have proposed the existence of a shadow biosphere , a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of

19380-459: The highest rates of melanoma in the world. The three main types of skin cancer have become more common in the last 20 to 40 years, especially regions where the population is predominantly White. There are three main types of skin cancer: basal-cell skin cancer (basal-cell carcinoma) (BCC), squamous-cell skin cancer (squamous-cell carcinoma) (SCC) and malignant melanoma . Basal-cell carcinomas are most commonly present on sun-exposed areas of

19550-448: The hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions , and the presence of polyamines in solution. The first published reports of A-DNA X-ray diffraction patterns —and also B-DNA—used analyses based on Patterson functions that provided only a limited amount of structural information for oriented fibers of DNA. An alternative analysis

19720-427: The hydrolytic activities of cellular water, etc., also occur frequently. Although most of these damages are repaired, in any cell some DNA damage may remain despite the action of repair processes. These remaining DNA damages accumulate with age in mammalian postmitotic tissues. This accumulation appears to be an important underlying cause of aging. Many mutagens fit into the space between two adjacent base pairs, this

19890-412: The importance of 5-methylcytosine, it can deaminate to leave a thymine base, so methylated cytosines are particularly prone to mutations . Other base modifications include adenine methylation in bacteria, the presence of 5-hydroxymethylcytosine in the brain , and the glycosylation of uracil to produce the "J-base" in kinetoplastids . DNA can be damaged by many sorts of mutagens , which change

20060-431: The least common among people with radiation-induced hypopituitarism. Changes in prolactin -secretion is usually mild, and vasopressin deficiency appears to be very rare as a consequence of radiation. Delayed tissue injury with impaired wound healing capability often develops after receiving doses in excess of 65 Gy. A diffuse injury pattern due to the external beam radiotherapy 's holographic isodosing occurs. While

20230-498: The least frequent of the three common skin cancers. They frequently metastasize, and can cause death once they spread. Less common skin cancers include: Merkel cell carcinoma , Paget's disease of the breast , atypical fibroxanthoma, porocarcinoma , spindle cell tumors, sebaceous carcinomas , microcystic adnexal carcinoma , keratoacanthoma , and skin sarcomas , such as angiosarcoma , dermatofibrosarcoma protuberans , Kaposi's sarcoma , leiomyosarcoma . BCC and SCC often carry

20400-451: The linear accelerator actions (or sometimes by eye), and to the usually well-established arrangements of the radiation beams to achieve a desired plan . The aim of simulation is to accurately target or localize the volume which is to be treated. This technique is well established and is generally quick and reliable. The worry is that some high-dose treatments may be limited by the radiation toxicity capacity of healthy tissues which lie close to

20570-457: The major limitations of photon radiation therapy is that the cells of solid tumors become deficient in oxygen . Solid tumors can outgrow their blood supply, causing a low-oxygen state known as hypoxia . Oxygen is a potent radiosensitizer , increasing the effectiveness of a given dose of radiation by forming DNA-damaging free radicals. Tumor cells in a hypoxic environment may be as much as 2 to 3 times more resistant to radiation damage than those in

20740-441: The minor groove is 12 Å (1.2 nm) in width. Due to the larger width of the major groove, the edges of the bases are more accessible in the major groove than in the minor groove. As a result, proteins such as transcription factors that can bind to specific sequences in double-stranded DNA usually make contact with the sides of the bases exposed in the major groove. This situation varies in unusual conformations of DNA within

20910-516: The mitochondrial genome (constituting up to 90% of the DNA of the cell). A DNA sequence is called a "sense" sequence if it is the same as that of a messenger RNA copy that is translated into protein. The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands can contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but

21080-477: The most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations , insertions , deletions from the DNA sequence, and chromosomal translocations . These mutations can cause cancer . Because of inherent limits in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer. DNA damages that are naturally occurring , due to normal cellular processes that produce reactive oxygen species,

21250-421: The multispectral imaging technique, thermography, electrical bio-impedance, tape stripping and computer-aided analysis. Dermatoscopy may be useful in diagnosing basal cell carcinoma in addition to skin inspection. There is insufficient evidence that optical coherence tomography (OCT) is useful in diagnosing melanoma or squamous cell carcinoma. OCT may have a role in diagnosing basal cell carcinoma but more data

21420-464: The new strand, and the cell ends up with a perfect copy of its DNA. Naked extracellular DNA (eDNA), most of it released by cell death, is nearly ubiquitous in the environment. Its concentration in soil may be as high as 2 μg/L, and its concentration in natural aquatic environments may be as high at 88 μg/L. Various possible functions have been proposed for eDNA: it may be involved in horizontal gene transfer ; it may provide nutrients; and it may act as

21590-800: The offspring. In males previously having undergone radiotherapy, there appears to be no increase in genetic defects or congenital malformations in their children conceived after therapy. However, the use of assisted reproductive technologies and micromanipulation techniques might increase this risk. Hypopituitarism commonly develops after radiation therapy for sellar and parasellar neoplasms, extrasellar brain tumors, head and neck tumors, and following whole body irradiation for systemic malignancies. 40–50% of children treated for childhood cancer develop some endocrine side effect. Radiation-induced hypopituitarism mainly affects growth hormone and gonadal hormones . In contrast, adrenocorticotrophic hormone (ACTH) and thyroid stimulating hormone (TSH) deficiencies are

21760-454: The open reading frame. In many species , only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons , with over 50% of human DNA consisting of non-coding repetitive sequences . The reasons for the presence of so much noncoding DNA in eukaryotic genomes and the extraordinary differences in genome size , or C-value , among species, represent

21930-408: The patient. Serious radiation complications may occur in 5% of RT cases. Acute (near immediate) or sub-acute (2 to 3 months post RT) radiation side effects may develop after 50 Gy RT dosing. Late or delayed radiation injury (6 months to decades) may develop after 65 Gy. Most side effects are predictable and expected. Side effects from radiation are usually limited to the area of the patient's body that

22100-457: The periphery, becoming more mature to the centre of the tumor masses. Tumor cells transform into keratinized squamous cells and form round nodules with concentric, laminated layers, called "cell nests" or "epithelial/keratinous pearls". The surrounding stroma is reduced and contains inflammatory infiltrate (lymphocytes). Poorly differentiated squamous carcinomas contain more pleomorphic cells and no keratinization . A molecular factor involved in

22270-428: The place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. In addition to RNA and DNA, many artificial nucleic acid analogues have been created to study the properties of nucleic acids, or for use in biotechnology. Modified bases occur in DNA. The first of these recognized was 5-methylcytosine , which was found in the genome of Mycobacterium tuberculosis in 1925. The reason for

22440-530: The presence of these noncanonical bases in bacterial viruses ( bacteriophages ) is to avoid the restriction enzymes present in bacteria. This enzyme system acts at least in part as a molecular immune system protecting bacteria from infection by viruses. Modifications of the bases cytosine and adenine, the more common and modified DNA bases, play vital roles in the epigenetic control of gene expression in plants and animals. A number of noncanonical bases are known to occur in DNA. Most of these are modifications of

22610-412: The prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a glycosidic bond . Therefore, any DNA strand normally has one end at which there is a phosphate group attached to the 5′ carbon of a ribose (the 5′ phosphoryl) and another end at which there is a free hydroxyl group attached to the 3′ carbon of a ribose (the 3′ hydroxyl). The orientation of

22780-414: The probability that cells will undergo cell death . Cancer cells are generally less differentiated and more stem cell -like; they reproduce more than most healthy differentiated cells, and have a diminished ability to repair sub-lethal damage. Single-strand DNA damage is then passed on through cell division; damage to the cancer cells' DNA accumulates, causing them to die or reproduce more slowly. One of

22950-466: The proposals was the existence of lifeforms that use arsenic instead of phosphorus in DNA . A report in 2010 of the possibility in the bacterium GFAJ-1 was announced, though the research was disputed, and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules. At the ends of the linear chromosomes are specialized regions of DNA called telomeres . The main function of these regions

23120-401: The radiation delivery method, several angles or sources may be used to sum to the total necessary dose. The planner will try to design a plan that delivers a uniform prescription dose to the tumor and minimizes dose to surrounding healthy tissues. In radiation therapy, three-dimensional dose distributions may be evaluated using the dosimetry technique known as gel dosimetry . The total dose

23290-401: The radiation oncologist and many factors are taken into account before the subsequent radiation takes place. During the first two weeks after fertilization , radiation therapy is lethal but not teratogenic . High doses of radiation during pregnancy induce anomalies , impaired growth and intellectual disability , and there may be an increased risk of childhood leukemia and other tumors in

23460-579: The radiation therapy machine Therac-25 was responsible for at least six accidents between 1985 and 1987, where patients were given up to one hundred times the intended dose; two people were killed directly by the radiation overdoses. From 2005 to 2010, a hospital in Missouri overexposed 76 patients (most with brain cancer) during a five-year period because new radiation equipment had been set up incorrectly. Although medical errors are exceptionally rare, radiation oncologists, medical physicists and other members of

23630-511: The radiation therapy treatment team are working to eliminate them. In 2010 the American Society for Radiation Oncology (ASTRO) launched a safety initiative called Target Safely that, among other things, aimed to record errors nationwide so that doctors can learn from each and every mistake and prevent them from recurring. ASTRO also publishes a list of questions for patients to ask their doctors about radiation safety to ensure every treatment

23800-694: The radiosensitivity of a particular tumor, which to some extent is a laboratory measure, from the radiation "curability" of a cancer in actual clinical practice. For example, leukemias are not generally curable with radiation therapy, because they are disseminated through the body. Lymphoma may be radically curable if it is localized to one area of the body. Similarly, many of the common, moderately radioresponsive tumors are routinely treated with curative doses of radiation therapy if they are at an early stage. For example, non-melanoma skin cancer , head and neck cancer , breast cancer , non-small cell lung cancer , cervical cancer , anal cancer , and prostate cancer . With

23970-419: The rate at which the disease recurs. In pancreatic cancer, radiotherapy has increased survival times for inoperable tumors. Radiation therapy (RT) is in itself painless. Many low-dose palliative treatments (for example, radiation therapy to bony metastases ) cause minimal or no side effects, although short-term pain flare-up can be experienced in the days following treatment due to oedema compressing nerves in

24140-526: The risk of sunburns but this is much less than the protection provided by sunscreen. A meta-analysis of skin cancer prevention in high risk individuals found evidence that topical application of T4N5 liposome lotion reduced the rate of appearance of basal cell carcinomas in people with xeroderma pigmentosum , and that acitretin taken by mouth may have a skin protective benefit in people following kidney transplant . A paper published in January 2022 showed that

24310-432: The section on uses in technology below. Several artificial nucleobases have been synthesized, and successfully incorporated in the eight-base DNA analogue named Hachimoji DNA . Dubbed S, B, P, and Z, these artificial bases are capable of bonding with each other in a predictable way (S–B and P–Z), maintain the double helix structure of DNA, and be transcribed to RNA. Their existence could be seen as an indication that there

24480-678: The sensitivity based on genomic or proteomic analyses of biopsy samples has proven challenging, the predictions of radiation effect on individual patients from genomic signatures of intrinsic cellular radiosensitivity have been shown to associate with clinical outcome. An alternative approach to genomics and proteomics was offered by the discovery that radiation protection in microbes is offered by non-enzymatic complexes of manganese and small organic metabolites. The content and variation of manganese (measurable by electron paramagnetic resonance) were found to be good predictors of radiosensitivity , and this finding extends also to human cells. An association

24650-431: The sequence of amino acids within proteins in a process called translation . Within eukaryotic cells, DNA is organized into long structures called chromosomes . Before typical cell division , these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. Eukaryotic organisms ( animals , plants , fungi and protists ) store most of their DNA inside

24820-473: The shape of a double helix . The nucleotide contains both a segment of the backbone of the molecule (which holds the chain together) and a nucleobase (which interacts with the other DNA strand in the helix). A nucleobase linked to a sugar is called a nucleoside , and a base linked to a sugar and to one or more phosphate groups is called a nucleotide . A biopolymer comprising multiple linked nucleotides (as in DNA)

24990-552: The single-ringed pyrimidines and the double-ringed purines . In DNA, the pyrimidines are thymine and cytosine; the purines are adenine and guanine. Both strands of double-stranded DNA store the same biological information . This information is replicated when the two strands separate. A large part of DNA (more than 98% for humans) is non-coding , meaning that these sections do not serve as patterns for protein sequences . The two strands of DNA run in opposite directions to each other and are thus antiparallel . Attached to each sugar

25160-498: The single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins. At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop . In DNA, fraying occurs when non-complementary regions exist at

25330-590: The size, shape, color or elevation of a mole. Other signs are the appearance of a new mole during adulthood or pain, itching, ulceration, redness around the site, or bleeding at the site. An often-used mnemonic is "ABCDE", where A is for "asymmetrical", B for "borders" (irregular: "Coast of Maine sign"), C for "color" (variegated), D for "diameter" (larger than 6 mm – the size of a pencil eraser) and E for "evolving." Merkel cell carcinomas are most often rapidly growing, non-tender red, purple or skin colored bumps that are not painful or itchy. They may be mistaken for

25500-406: The skin, especially the face. They rarely metastasize and rarely cause death. They are easily treated with surgery or radiation. Squamous-cell skin cancers are also common, but much less common than basal-cell cancers. They metastasize more frequently than BCCs. Even then, the metastasis rate is quite low, with the exception of SCC of the lip or ear, and in people who are immunosuppressed. Melanoma are

25670-428: The skin, if applied in too little quantity and too infrequently. However, the researchers add that newer creams often do not contain these specific compounds, and that the combination of other ingredients tends to retain the compounds on the surface of the skin. They also add that frequent re-application reduces the risk of radical formation. There are a variety of different skin cancer symptoms. These include changes in

25840-451: The sources are loaded into the applicator after the applicator is implanted. This minimizes radiation exposure to health care personnel. Particle therapy is a special case of external beam radiation therapy where the particles are protons or heavier ions . A review of radiation therapy randomised clinical trials from 2018 to 2021 found many practice-changing data and new concepts that emerge from RCTs, identifying techniques that improve

26010-402: The standard treatment for almost all tumor sites. More recently other forms of imaging are used including MRI, PET, SPECT and Ultrasound. Stereotactic radiation is a specialized type of external beam radiation therapy. It uses focused radiation beams targeting a well-defined tumor using extremely detailed imaging scans. Radiation oncologists perform stereotactic treatments, often with the help of

26180-518: The strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single common shape, but some conformations are more stable than others. In humans, the total female diploid nuclear genome per cell extends for 6.37 Gigabase pairs (Gbp), is 208.23 cm long and weighs 6.51 picograms (pg). Male values are 6.27 Gbp, 205.00 cm, 6.41 pg. Each DNA polymer can contain hundreds of millions of nucleotides, such as in chromosome 1 . Chromosome 1

26350-469: The sugar-phosphate to form the complete nucleotide, as shown for adenosine monophosphate . Adenine pairs with thymine and guanine pairs with cytosine, forming A-T and G-C base pairs . The nucleobases are classified into two types: the purines , A and G , which are fused five- and six-membered heterocyclic compounds , and the pyrimidines , the six-membered rings C and T . A fifth pyrimidine nucleobase, uracil ( U ), usually takes

26520-438: The sun-exposed skin of the head , neck , torso or shoulders . Sometimes small blood vessels (called telangiectasia ) can be seen within the tumor. Crusting and bleeding in the center of the tumor frequently develops. It is often mistaken for a sore that does not heal. This form of skin cancer is the least deadly, and with proper treatment can be eliminated, often without significant scarring. Squamous-cell skin cancer (SCC)

26690-557: The target tumor volume. An example of this problem is seen in radiation of the prostate gland, where the sensitivity of the adjacent rectum limited the dose which could be safely prescribed using 2DXRT planning to such an extent that tumor control may not be easily achievable. Prior to the invention of the CT, physicians and physicists had limited knowledge about the true radiation dosage delivered to both cancerous and healthy tissue. For this reason, 3-dimensional conformal radiation therapy has become

26860-473: The targeted tumor receives the majority of radiation, healthy tissue at incremental distances from the center of the tumor are also irradiated in a diffuse pattern due to beam divergence. These wounds demonstrate progressive, proliferative endarteritis , inflamed arterial linings that disrupt the tissue's blood supply. Such tissue ends up chronically hypoxic , fibrotic , and without an adequate nutrient and oxygen supply. Surgery of previously irradiated tissue has

27030-483: The therapeutic ratio, techniques that lead to more tailored treatments, stressing the importance of patient satisfaction, and identifying areas that require further study. The following three sections refer to treatment using X-rays. Historically conventional external beam radiation therapy (2DXRT) was delivered via two-dimensional beams using kilovoltage therapy X-ray units, medical linear accelerators that generate high-energy X-rays, or with machines that were similar to

27200-430: The therapy has survival benefit and can be curative). It is also common to combine radiation therapy with surgery , chemotherapy, hormone therapy , immunotherapy or some mixture of the four. Most common cancer types can be treated with radiation therapy in some way. The precise treatment intent (curative, adjuvant, neoadjuvant therapeutic , or palliative) will depend on the tumor type, location, and stage , as well as

27370-429: The tissue around it but is unlikely to spread to distant areas or result in death. It often appears as a painless raised area of skin that may be shiny with small blood vessels running over it or may present as a raised area with an ulcer . Squamous-cell skin cancer is more likely to spread. It usually presents as a hard lump with a scaly top but may also form an ulcer. Melanomas are the most aggressive. Signs include

27540-459: The tissue – the beam does not broaden much, stays focused on the tumor shape, and delivers small dose side-effects to surrounding tissue. They also more precisely target the tumor using the Bragg peak effect. See proton therapy for a good example of the different effects of intensity-modulated radiation therapy (IMRT) vs. charged particle therapy . This procedure reduces damage to healthy tissue between

27710-414: The treated area. Higher doses can cause varying side effects during treatment (acute side effects), in the months or years following treatment (long-term side effects), or after re-treatment (cumulative side effects). The nature, severity, and longevity of side effects depends on the organs that receive the radiation, the treatment itself (type of radiation, dose, fractionation , concurrent chemotherapy), and

27880-590: The treatment of trigeminal neuralgia , acoustic neuromas , severe thyroid eye disease , pterygium , pigmented villonodular synovitis , and prevention of keloid scar growth, vascular restenosis , and heterotopic ossification . The use of radiation therapy in non-malignant conditions is limited partly by worries about the risk of radiation-induced cancers. It is estimated that half of the US' 1.2M invasive cancer cases diagnosed in 2022 received radiation therapy in their treatment program. Different cancers respond to radiation therapy in different ways. The response of

28050-424: The treatments by the name of the manufacturer rather than calling it SRS or SBRT. Brand names for these treatments include Axesse, Cyberknife , Gamma Knife , Novalis, Primatom, Synergy, X-Knife , TomoTherapy , Trilogy and Truebeam . This list changes as equipment manufacturers continue to develop new, specialized technologies to treat cancers. The planning of radiation therapy treatment has been revolutionized by

28220-507: The tumor cell kill. Fractionation regimens are individualised between different radiation therapy centers and even between individual doctors. In North America, Australia, and Europe, the typical fractionation schedule for adults is 1.8 to 2 Gy per day, five days a week. In some cancer types, prolongation of the fraction schedule over too long can allow for the tumor to begin repopulating, and for these tumor types, including head-and-neck and cervical squamous cell cancers, radiation treatment

28390-470: The tumor position. Radiation oncology is the medical specialty concerned with prescribing radiation, and is distinct from radiology , the use of radiation in medical imaging and diagnosis . Radiation may be prescribed by a radiation oncologist with intent to cure or for adjuvant therapy. It may also be used as palliative treatment (where cure is not possible and the aim is for local disease control or symptomatic relief) or as therapeutic treatment (where

28560-550: The use of an oxygen diffusion-enhancing compound such as trans sodium crocetinate as a radiosensitizer. Charged particles such as protons and boron , carbon , and neon ions can cause direct damage to cancer cell DNA through high-LET ( linear energy transfer ) and have an antitumor effect independent of tumor oxygen supply because these particles act mostly via direct energy transfer usually causing double-stranded DNA breaks. Due to their relatively large mass, protons and other charged particles have little lateral side scatter in

28730-401: Was confirmed between total cellular manganese contents and their variation, and clinically inferred radioresponsiveness in different tumor cells, a finding that may be useful for more precise radiodosages and improved treatment of cancer patients. Historically, the three main divisions of radiation therapy are: The differences relate to the position of the radiation source; external is outside

28900-517: Was proposed by Wilkins et al. in 1953 for the in vivo B-DNA X-ray diffraction-scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions . In the same journal, James Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double helix. Although the B-DNA form is most common under

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