Cancer research is research into cancer to identify causes and develop strategies for prevention, diagnosis, treatment, and cure.
Cancer research ranges from epidemiology, molecular bioscience to the performance of clinical trials to evaluate and compare applications of the various cancer treatments. These applications include surgery, radiation therapy, chemotherapy, hormone therapy, immunotherapy
and combined treatment modalities such as chemo-radiotherapy. Starting
in the mid-1990s, the emphasis in clinical cancer research shifted
towards therapies derived from biotechnology research, such as cancer immunotherapy and gene therapy.
Cancer research is done in academia, research institutes, and corporate environments, and is largely government funded.
History
Sidney Farber is regarded as the father of modern chemotherapy.
Cancer research has been ongoing for centuries. Early research focused on the causes of cancer. Percivall Pott
identified the first environmental trigger (chimney soot) for cancer in
1775 and cigarette smoking was identified as a cause of lung cancer in
1950. Early cancer treatment focused on improving surgical techniques
for removing tumors. Radiation therapy took hold in the 1900s.
Chemotherapeutics were developed and refined throughout the 20th
century.
The U.S. declared a "War on Cancer" in the 1970s, and increased the funding and support for cancer research.
Seminal papers
Some of the most highly cited and most influential research reports include:
The Hallmarks of Cancer, published in 2000, and Hallmarks of Cancer: The Next Generation, published in 2011, by Douglas Hanahan and Robert Weinberg. Together, these articles have been cited in over 30,000 published papers.
Types of research
Cancer
research encompasses a variety of types and interdisciplinary areas of
research. Scientists involved in cancer research may be trained in areas
such as chemistry, biochemistry, molecular biology, physiology, medical physics, epidemiology, and biomedical engineering. Research performed on a foundational level is referred to as basic research and is intended to clarify scientific principles and mechanisms. Translational research
aims to elucidate mechanisms of cancer development and progression and
transform basic scientific findings into concepts that can be applicable
to the treatment and prevention of cancer. Clinical research
is devoted to the development of pharmaceuticals, surgical procedures,
and medical technologies for the eventual treatment of patients.
However, one 2015 study suggested that between ~70% and ~90% of
cancers are due to environmental factors and therefore potentially
preventable.
Furthermore, it is estimated that with further research cancer death
rates could be reduced by 70% around the world even without the
development of any new therapies. Cancer prevention research receives only 2–9% of global cancer research funding,
albeit many of the options for prevention are already well-known
without further cancer-specific research but are not reflected in
economics and policy. Mutational signatures of various cancers, for example, could reveal further causes of cancer and support causal attribution.
Prompt detection of cancer is important, since it is usually more
difficult to treat in later stages. Accurate detection of cancer is
also important because false positives can cause harm from unnecessary
medical procedures. Some screening protocols are currently not accurate
(such as prostate-specific antigen testing). Others such as a colonoscopy or mammogram
are unpleasant and as a result some patients may opt out. Active
research is underway to address all these problems, to develop novel
ways of cancer screening and to increase detection rates.
Scientists work on identifying and measurability of novel biomarkers or sets of such to detect cancer early, such as tumor-associated mycobiomes and bacterial microbiomes
Numerous cell signaling pathways are disrupted in the development of cancer.
Research into the cause of cancer involves many different disciplines
including genetics, diet, environmental factors (i.e. chemical carcinogens).
In regard to investigation of causes and potential targets for
therapy, the route used starts with data obtained from clinical
observations, enters basic research, and, once convincing and
independently confirmed results are obtained, proceeds with clinical
research, involving appropriately designed trials on consenting human
subjects, with the aim to test safety and efficiency of the therapeutic
intervention method.
An important part of basic research is characterization of the potential
mechanisms of carcinogenesis, in regard to the types of genetic and
epigenetic changes that are associated with cancer development. The
mouse is often used as a mammalian model for manipulation of the
function of genes that play a role in tumor formation, while basic
aspects of tumor initiation, such as mutagenesis, are assayed on
cultures of bacteria and mammalian cells.
The goal of oncogenomics is to identify new oncogenes or tumor suppressor genes
that may provide new insights into cancer diagnosis, predicting
clinical outcome of cancers, and new targets for cancer therapies. As
the Cancer Genome Project
stated in a 2004 review article, "a central aim of cancer research has
been to identify the mutated genes that are causally implicated in
oncogenesis (cancer genes)." The Cancer Genome Atlas project is a related effort investigating the genomic changes associated with cancer, while the COSMIC cancer database documents acquired genetic mutations from hundreds of thousands of human cancer samples.
These large scale projects, involving about 350 different types of cancer, have identified ~130,000 mutations in ~3000 genes
that have been mutated in the tumors. The majority occurred in 319
genes, of which 286 were tumor suppressor genes and 33 oncogenes.
Several hereditary factors can increase the chance of
cancer-causing mutations, including the activation of oncogenes or the
inhibition of tumor suppressor genes. The functions of various onco- and
tumor suppressor genes can be disrupted at different stages of tumor
progression. Mutations in such genes can be used to classify the
malignancy of a tumor.
In later stages, tumors can develop a resistance to cancer
treatment. The identification of oncogenes and tumor suppressor genes is
important to understand tumor progression and treatment success. The
role of a given gene in cancer progression may vary tremendously,
depending on the stage and type of cancer involved.
Cancer epigenetics
Cancer epigenetics is the study of epigenetic modifications to the DNA of cancer cells
that do not involve a change in the nucleotide sequence, but instead
involve a change in the way the genetic code is expressed. Epigenetic
mechanisms are necessary to maintain normal sequences of tissue specific
gene expression and are crucial for normal development. They may be just as important, if not even more important, than genetic mutations in a cell's transformation to cancer. The disturbance of epigenetic processes in cancers, can lead to a loss of expression of genes that occurs about 10 times more frequently by transcription silencing (caused by epigenetic promoter hypermethylation of CpG islands)
than by mutations. As Vogelstein et al. points out, in a colorectal
cancer there are usually about 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations.
However, in colon tumors compared to adjacent normal-appearing colonic
mucosa, there are about 600 to 800 heavily methylated CpG islands in the
promoters of genes in the tumors while these CpG islands are not
methylated in the adjacent mucosa. Manipulation of epigenetic alterations holds great promise for cancer prevention, detection, and therapy. In different types of cancer, a variety of epigenetic mechanisms can be perturbed, such as the silencing of tumor suppressor genes and activation of oncogenes by altered CpG islandmethylation patterns, histone modifications, and dysregulation of DNA binding proteins. There are several medications which have epigenetic impact, that are now used in a number of these diseases.
Diet and cancer
Advertisement suggesting that a healthy diet helps prevent cancer.
Many dietary recommendations have been proposed to reduce the risk of
cancer, few have significant supporting scientific evidence. Obesity and drinking alcohol have been correlated with the incidence and progression of some cancers. Lowering the consumption of sweetened beverages is recommended as a measure to address obesity.
Some specific foods are linked to specific cancers. There is strong evidence that processed meat and red meat intake increases risk of colorectal cancer. Aflatoxin B1, a frequent food contaminant, increases risk of liver cancer, while drinking coffee is associated with a reduced risk. Betel nut chewing causes oral cancer. Stomach cancer is more common in Japan due to its high-salt diet.
Dietary recommendations for cancer prevention typically include weight management and eating a healthy diet,
consisting mainly of "vegetables, fruit, whole grains and fish, and a
reduced intake of red meat, animal fat, and refined sugar." A healthy dietary pattern may lower cancer risk by 10–20%. There is no clinical evidence that diets or specific foods can cure cancer.
Periods of intermittent fasting (time-restricted feeding which may not include caloric restriction)
is investigated for potential usefulness in cancer prevention and
treatment and as of 2021 additional trials are needed to elucidate the
risks and benefits.
In some cases, "caloric restrictions could hinder both cancer growth
and progression, besides enhancing the efficacy of chemotherapy and
radiation therapy". Caloric restriction mimetics, including some present in foods like spermidine, are also investigated for these or similar reasons. Such and similar dietary supplements may contribute to prevention or treatment, with candidate substances including apigenin, berberine, jiaogulan, and rhodiola rosea.
Cancer research is funded by government grants, charitable foundations and pharmaceutical and biotechnology companies.
In the early 2000s, most funding for cancer research came from
taxpayers and charities, rather than from corporations. In the US, less
than 30% of all cancer research was funded by commercial researchers
such as pharmaceutical companies.
Per capita, public spending on cancer research by taxpayers and
charities in the US was five times as much in 2002–03 as public spending
by taxpayers and charities in the 15 countries that were full members
of the European Union.
As a percentage of GDP, the non-commercial funding of cancer research
in the US was four times the amount dedicated to cancer research in
Europe. Half of Europe's non-commercial cancer research is funded by charitable organizations.
The National Cancer Institute is the major funding institution in the United States. In the 2023 fiscal year, the NCI funded $7.1 billion in cancer research.
Difficulties
Difficulties inherent to cancer research are shared with many types of biomedical research.
Cancer research processes have been criticised. These include,
especially in the US, for the financial resources and positions required
to conduct research. Other consequences of competition for research
resources appear to be a substantial number of research publications
whose results cannot be replicated.
Replicability
Results
from The Reproducibility Project: Cancer Biology suggest most studies
of the cancer research sector may not be replicable.
In a 2012 paper, C. Glenn Begley, a biotech consultant working at Amgen,
and Lee Ellis, a medical researcher at the University of Texas, found
that only 11% of 53 pre-clinical cancer studies had replications that
could confirm conclusions from the original studies.
In late 2021, The Reproducibility Project: Cancer Biology examined 53
top papers about cancer published between 2010 and 2012 and showed that
among studies that provided sufficient information to be redone, the
effect sizes were 85% smaller on average than the original findings. A survey of cancer researchers found that half of them had been unable to reproduce a published result.
Another report estimated that almost half of randomized controlled
trials contained flawed data (based on the analysis of anonymized
individual participant data (IPD) from more than 150 trials).
Members of the public can also join clinical trials as healthy control subjects or for methods of cancer detection.
There could be software and data-related procedures that increase
participation in trials and make them faster and less expensive. One open source platform matches genomically profiled cancer patients to precision medicine drug trials.
Supporters of different types of cancer have adopted different colored awareness ribbons and promote months of the year as being dedicated to the support of specific types of cancer. The American Cancer Society began promoting October as Breast Cancer Awareness Month
in the United States in the 1980s. Pink products are sold to both
generate awareness and raise money to be donated for research purposes.
This has led to pinkwashing, or the selling of ordinary products turned pink as a promotion for the company.
Oncology is a branch of medicine that deals with the study, treatment, diagnosis, and prevention of cancer. A medical professional who practices oncology is an oncologist. The name's etymological origin is the Greek word ὄγκος (ónkos), meaning "tumor", "volume" or "mass".
An oncologist typically focuses on a specialty area for how cancer is treated, such as for surgery, radiation, gynecological, geriatrics, pediatrics, and numerous disciplines based on individual organ systems (breast, brain, liver, among others).
The expertise of an oncologist is obtained when a person suspects
having cancer, is diagnosed with having cancer, or is being treated for
cancer.
Diagnosis
Medical
histories remain an important screening tool for an oncologist to
assess the character of the concerns and nonspecific symptoms in the
person with cancer (such as fatigue, weight loss, unexplained anemia, fever of unknown origin, paraneoplastic phenomena and other signs) may warrant further investigation for malignancy.
Diagnostic methods in oncology may involve a biopsy or resection;
these are methods by which suspicious neoplastic growths can be removed
in part or in whole, and evaluated by a pathologist to determine
malignancy. This is currently the gold standard for the diagnosis of
cancer and is crucial in guiding the next step in management (active
surveillance, surgery, radiation therapy, chemotherapy, or a combination
of these)
Apart from diagnoses, these modalities (especially imaging by CT scanning) are often used to determine operability, i.e., whether it is surgically possible to remove a tumor in its entirety.
A tissue diagnosis (from a biopsy) by a pathologist is essential for the proper classification of cancer
and to guide the next step of treatment. On extremely rare instances
when this is not possible, "empirical therapy" (without an exact
diagnosis) may be considered, based on the available evidence (e.g.
history, x-rays and scans.)
Immunohistochemical markers often give a strong indication of the primary malignancy. This situation is referred to as "malignancy of unknown primary", and again, treatment is empirically based on past experience of the most likely origin.
Therapy
Depending
upon the cancer identified, follow-up and palliative care will be
administered at that time. Certain disorders (such as ALL or AML) will require immediate admission and chemotherapy, while others will be followed up with regular physical examination and blood tests.
Often, surgery is attempted to remove a tumor
entirely. This is only feasible when there is some degree of certainty
that the tumor can in fact be removed. When it is certain that parts
will remain, curative surgery is often impossible, e.g. when there are metastases,
or when the tumor has invaded a structure that cannot be operated upon
without risking the patient's life. Occasionally surgery can improve
survival even if not all tumour tissue has been removed; the procedure
is referred to as "debulking" (i.e. reducing the overall amount of
tumour tissue). Surgery is also used for the palliative
treatment of some cancers, e.g. to relieve biliary obstruction, or to
relieve the problems associated with some cerebral tumors. The risks of
surgery must be weighed against the benefits.
Chemotherapy and radiotherapy are used as a first-line radical therapy in several malignancies. They are also used for adjuvant
therapy, i.e. when the macroscopic tumor has already been completely
removed surgically but there is a reasonable statistical risk that it
will recur. Chemotherapy and radiotherapy are commonly used for
palliation, where disease is clearly incurable: in this situation the
aim is to improve the quality of life and to prolong it.
Hormone manipulation is well established, particularly in the treatment of breast and prostate cancer.
Approximately 50% of all cancer cases in the Western world can be treated to remission
with radical treatment. For pediatric patients, that number is much
higher. A large number of cancer patients will die from the disease, and
a significant proportion of patients with incurable cancer will die of
other causes. There may be ongoing issues with symptom control
associated with progressive cancer, and also with the treatment of the
disease. These problems may include pain, nausea, anorexia, fatigue, immobility, and depression. Not all issues are strictly physical: personal dignity may be affected. Moral and spiritual issues are also important.
While many of these problems fall within the remit of the oncologist, palliative care
has matured into a separate, closely allied specialty to address the
problems associated with advanced disease. Palliative care is an
essential part of the multidisciplinary cancer care team. Palliative
care services may be less hospital-based than oncology, with nurses and
doctors who are able to visit the patient at home.
Ethical issues
There are a number of recurring ethical questions and dilemmas in oncological practice. These include:
What information to give the patient regarding disease extent/progression/prognosis.
These issues are closely related to the patient's personality,
religion, culture, and family life. Though these issues are complex and
emotional, the answers are often achieved by the patient seeking counsel
from trusted personal friends and advisors. It requires a degree of
sensitivity and very good communication on the part of the oncology team
to address these problems properly.
Progress and research
There
is a tremendous amount of research being conducted on all frontiers of
oncology, ranging from cancer cell biology, and radiation therapy to chemotherapy treatment regimens and optimal palliative care and pain relief. Next-generation sequencing and whole-genome sequencing
have completely changed the understanding of cancers. Identification of
novel genetic/molecular markers will change the methods of diagnosis
and treatment, paving the way for personalized medicine.
Digestion is the breakdown of large insoluble food compounds into small water-soluble components so that they can be absorbed into the blood plasma. In certain organisms, these smaller substances are absorbed through the small intestine into the blood stream. Digestion is a form of catabolism that is often divided into two processes based on how food is broken down: mechanical and chemical digestion. The term mechanical digestion refers to the physical breakdown of large pieces of food into smaller pieces which can subsequently be accessed by digestive enzymes. Mechanical digestion takes place in the mouth through mastication and in the small intestine through segmentation contractions. In chemical digestion, enzymes break down food into the small compounds that the body can use.
In the human digestive system,
food enters the mouth and mechanical digestion of the food starts by
the action of mastication (chewing), a form of mechanical digestion, and
the wetting contact of saliva. Saliva, a liquid secreted by the salivary glands, contains salivary amylase, an enzyme which starts the digestion of starch in the food. The saliva also contains mucus, which lubricates the food; the electrolyte hydrogencarbonate (HCO−3), which provides the ideal conditions of pH for amylase to work; and other electrolytes (Na+, K+, Cl−). About 30% of starch is hydrolyzed into disaccharide
in the oral cavity (mouth). After undergoing mastication and starch
digestion, the food will be in the form of a small, round slurry mass
called a bolus. It will then travel down the esophagus and into the stomach by the action of peristalsis. Gastric juice in the stomach starts protein digestion. Gastric juice mainly contains hydrochloric acid and pepsin. In infants and toddlers, gastric juice also contains rennin
to digest milk proteins. As the first two chemicals may damage the
stomach wall, mucus and bicarbonates are secreted by the stomach. They
provide a slimy layer that acts as a shield against the damaging effects
of chemicals like concentrated hydrochloric acid while also aiding
lubrication.
Hydrochloric acid provides acidic pH for pepsin. At the same time
protein digestion is occurring, mechanical mixing occurs by peristalsis,
which is waves of muscular contractions that move along the stomach
wall. This allows the mass of food to further mix with the digestive
enzymes. Pepsin breaks down proteins into peptides or proteoses, which is further broken down into dipeptides and amino acids
by enzymes in the small intestine. Studies suggest that increasing the
number of chews per bite increases relevant gut hormones and may
decrease self-reported hunger and food intake.
When the pyloric sphincter valve opens, partially digested food (chyme) enters the duodenum where it mixes with digestive enzymes from the pancreas and bile juice from the liver
and then passes through the small intestine, in which digestion
continues. When the chyme is fully digested, it is absorbed into the
blood. 95% of nutrient absorption occurs in the small intestine. Water
and minerals are reabsorbed back into the blood in the colon (large intestine) where the pH is slightly acidic (about 5.6 ~ 6.9). Some vitamins, such as biotin and vitamin K (K2MK7)
produced by bacteria in the colon are also absorbed into the blood in
the colon. Absorption of water, simple sugar and alcohol also takes
place in stomach. Waste material (feces) is eliminated from the rectum during defecation.
Digestive system
Digestive systems take many forms. There is a fundamental distinction
between internal and external digestion. External digestion developed
earlier in evolutionary history, and most fungi still rely on it. In this process, enzymes are secreted into the environment surrounding the organism, where they break down an organic material, and some of the products diffuse back to the organism. Animals have a tube (gastrointestinal tract)
in which internal digestion occurs, which is more efficient because
more of the broken down products can be captured, and the internal
chemical environment can be more efficiently controlled.
Some organisms, including nearly all spiders,
secrete biotoxins and digestive chemicals (e.g., enzymes) into the
extracellular environment prior to ingestion of the consequent "soup".
In others, once potential nutrients or food is inside the organism, digestion can be conducted to a vesicle
or a sac-like structure, through a tube, or through several specialized
organs aimed at making the absorption of nutrients more efficient.
Schematic drawing of bacterial conjugation. 1- Donor cell produces pilus. 2- Pilus attaches to recipient cell, bringing the two cells together. 3- The mobile plasmid is nicked and a single strand of DNA is transferred to the recipient cell. 4- Both cells recircularize their plasmids, synthesize second strands, and reproduce pili; both cells are now viable donors.
Bacteria use several systems to obtain nutrients from other organisms in the environments.
Channel transport system
In a channel transport system, several proteins form a contiguous
channel traversing the inner and outer membranes of the bacteria. It is a
simple system, which consists of only three protein subunits: the ABC protein, membrane fusion protein (MFP), and outer membrane protein.
This secretion system transports various chemical species, from ions,
drugs, to proteins of various sizes (20–900 kDa). The chemical species
secreted vary in size from the small Escherichia coli peptide colicin V, (10 kDa) to the Pseudomonas fluorescens cell adhesion protein LapA of 900 kDa.
Molecular syringe
A type III secretion system means that a molecular syringe is used through which a bacterium (e.g. certain types of Salmonella, Shigella, Yersinia) can inject nutrients into protist cells. One such mechanism was first discovered in Y. pestis
and showed that toxins could be injected directly from the bacterial
cytoplasm into the cytoplasm of its host's cells rather than be secreted
into the extracellular medium.
Conjugation machinery
The conjugation machinery of some bacteria (and archaeal flagella) is capable of transporting both DNA and proteins. It was discovered in Agrobacterium tumefaciens, which uses this system to introduce the Ti plasmid and proteins into the host, which develops the crown gall (tumor). The VirB complex of Agrobacterium tumefaciens is the prototypic system.
In the nitrogen-fixingRhizobia, conjugative elements naturally engage in inter-kingdom conjugation. Such elements as the Agrobacterium
Ti or Ri plasmids contain elements that can transfer to plant cells.
Transferred genes enter the plant cell nucleus and effectively transform
the plant cells into factories for the production of opines, which the bacteria use as carbon and energy sources. Infected plant cells form crown gall or root tumors. The Ti and Ri plasmids are thus endosymbionts of the bacteria, which are in turn endosymbionts (or parasites) of the infected plant.
The Ti and Ri plasmids are themselves conjugative. Ti and Ri transfer between bacteria uses an independent system (the tra, or transfer, operon) from that for inter-kingdom transfer (the vir, or virulence, operon). Such transfer creates virulent strains from previously avirulent Agrobacteria.
Release of outer membrane vesicles
In addition to the use of the multiprotein complexes listed above, gram-negative bacteria possess another method for release of material: the formation of outer membrane vesicles.
Portions of the outer membrane pinch off, forming spherical structures
made of a lipid bilayer enclosing periplasmic materials. Vesicles from
a number of bacterial species have been found to contain virulence
factors, some have immunomodulatory effects, and some can directly
adhere to and intoxicate host cells. While release of vesicles has been
demonstrated as a general response to stress conditions, the process of
loading cargo proteins seems to be selective.
Venus Flytrap (Dionaea muscipula) leaf
Gastrovascular cavity
The gastrovascular cavity
functions as a stomach in both digestion and the distribution of
nutrients to all parts of the body. Extracellular digestion takes place
within this central cavity, which is lined with the gastrodermis, the
internal layer of epithelium. This cavity has only one opening to the outside that functions as both a mouth and an anus: waste and undigested matter is excreted through the mouth/anus, which can be described as an incomplete gut.
In a plant such as the Venus flytrap
that can make its own food through photosynthesis, it does not eat and
digest its prey for the traditional objectives of harvesting energy and
carbon, but mines prey primarily for essential nutrients (nitrogen and
phosphorus in particular) that are in short supply in its boggy, acidic
habitat.
Trophozoites of Entamoeba histolytica with ingested erythrocytes
Birds have bony beaks that are specialised according to the bird's ecological niche. For example, macaws
primarily eat seeds, nuts, and fruit, using their beaks to open even
the toughest seed. First they scratch a thin line with the sharp point
of the beak, then they shear the seed open with the sides of the beak.
The mouth of the squid is equipped with a sharp horny beak mainly made of cross-linked proteins.
It is used to kill and tear prey into manageable pieces. The beak is
very robust, but does not contain any minerals, unlike the teeth and
jaws of many other organisms, including marine species. The beak is the only indigestible part of the squid.
The tongue is skeletal muscle on the floor of the mouth of most vertebrates, that manipulates food for chewing (mastication) and swallowing (deglutition). It is sensitive and kept moist by saliva. The underside of the tongue is covered with a smooth mucous membrane.
The tongue also has a touch sense for locating and positioning food
particles that require further chewing. The tongue is used to roll food
particles into a bolus before being transported down the esophagus through peristalsis.
The sublingual region underneath the front of the tongue is a location where the oral mucosa
is very thin, and underlain by a plexus of veins. This is an ideal
location for introducing certain medications to the body. The sublingual
route takes advantage of the highly vascular
quality of the oral cavity, and allows for the speedy application of
medication into the cardiovascular system, bypassing the
gastrointestinal tract.
Teeth (singular tooth) are small whitish structures found in the jaws
(or mouths) of many vertebrates that are used to tear, scrape, milk and
chew food. Teeth are not made of bone, but rather of tissues of varying
density and hardness, such as enamel, dentine and cementum. Human teeth
have a blood and nerve supply which enables proprioception. This is the
ability of sensation when chewing, for example if we were to bite into
something too hard for our teeth, such as a chipped plate mixed in food,
our teeth send a message to our brain and we realise that it cannot be
chewed, so we stop trying.
The shapes, sizes and numbers of types of animals' teeth are
related to their diets. For example, herbivores have a number of molars
which are used to grind plant matter, which is difficult to digest. Carnivores have canine teeth which are used to kill and tear meat.
Crop
A crop, or croup, is a thin-walled expanded portion of the alimentary tract used for the storage of food prior to digestion. In some birds it is an expanded, muscular pouch near the gullet or throat. In adult doves and pigeons, the crop can produce crop milk to feed newly hatched birds.
Certain insects may have a crop or enlarged esophagus.
Herbivores have evolved cecums (or an abomasum in the case of ruminants). Ruminants have a fore-stomach with four chambers. These are the rumen, reticulum, omasum,
and abomasum. In the first two chambers, the rumen and the reticulum,
the food is mixed with saliva and separates into layers of solid and
liquid material. Solids clump together to form the cud (or bolus). The cud is then regurgitated, chewed slowly to completely mix it with saliva and to break down the particle size.
The abomasum is the fourth and final stomach compartment in
ruminants. It is a close equivalent of a monogastric stomach (e.g.,
those in humans or pigs), and digesta is processed here in much the same
way. It serves primarily as a site for acid hydrolysis of microbial and
dietary protein, preparing these protein sources for further digestion
and absorption in the small intestine. Digesta is finally moved into
the small intestine, where the digestion and absorption of nutrients
occurs. Microbes produced in the reticulo-rumen are also digested in the
small intestine.
A flesh fly "blowing a bubble", possibly to concentrate its food by evaporating water
Specialised behaviours
Regurgitation has been mentioned above under abomasum and crop, referring to crop milk, a secretion from the lining of the crop of pigeons and doves with which the parents feed their young by regurgitation.
Many sharks
have the ability to turn their stomachs inside out and evert it out of
their mouths in order to get rid of unwanted contents (perhaps developed
as a way to reduce exposure to toxins).
Other animals, such as rabbits and rodents, practise coprophagia
behaviours – eating specialised faeces in order to re-digest food,
especially in the case of roughage. Capybara, rabbits, hamsters and
other related species do not have a complex digestive system as do, for
example, ruminants. Instead they extract more nutrition from grass by giving their food a second pass through the gut.
Soft faecal pellets of partially digested food are excreted and
generally consumed immediately. They also produce normal droppings,
which are not eaten.
Young elephants, pandas, koalas, and hippos eat the faeces of
their mother, probably to obtain the bacteria required to properly
digest vegetation. When they are born, their intestines do not contain
these bacteria (they are completely sterile). Without them, they would
be unable to get any nutritional value from many plant components.
In earthworms
An earthworm's digestive system consists of a mouth, pharynx, esophagus, crop, gizzard, and intestine.
The mouth is surrounded by strong lips, which act like a hand to grab
pieces of dead grass, leaves, and weeds, with bits of soil to help chew.
The lips break the food down into smaller pieces. In the pharynx, the
food is lubricated by mucus secretions for easier passage. The esophagus
adds calcium carbonate to neutralize the acids formed by food matter
decay. Temporary storage occurs in the crop where food and calcium
carbonate are mixed. The powerful muscles of the gizzard churn and mix
the mass of food and dirt. When the churning is complete, the glands in
the walls of the gizzard add enzymes to the thick paste, which helps
chemically breakdown the organic matter. By peristalsis,
the mixture is sent to the intestine where friendly bacteria continue
chemical breakdown. This releases carbohydrates, protein, fat, and
various vitamins and minerals for absorption into the body.
Overview of vertebrate digestion
In most vertebrates,
digestion is a multistage process in the digestive system, starting
from ingestion of raw materials, most often other organisms. Ingestion
usually involves some type of mechanical and chemical processing.
Digestion is separated into four steps:
Ingestion: placing food into the mouth (entry of food in the digestive system),
Mechanical and chemical breakdown: mastication and the mixing of the resulting bolus with water, acids, bile and enzymes in the stomach and intestine to break down complex chemical species into simple structures,
Absorption: of nutrients from the digestive system to the circulatory and lymphatic capillaries through osmosis, active transport, and diffusion, and
Egestion (Excretion): Removal of undigested materials from the digestive tract through defecation.
Underlying the process is muscle movement throughout the system through swallowing and peristalsis.
Each step in digestion requires energy, and thus imposes an "overhead
charge" on the energy made available from absorbed substances.
Differences in that overhead cost are important influences on lifestyle,
behavior, and even physical structures. Examples may be seen in humans,
who differ considerably from other hominids (lack of hair, smaller jaws
and musculature, different dentition, length of intestines, cooking,
etc.).
The major part of digestion takes place in the small intestine.
The large intestine primarily serves as a site for fermentation of
indigestible matter by gut bacteria and for resorption of water from digests before excretion.
In mammals, preparation for digestion begins with the cephalic phase in which saliva is produced in the mouth and digestive enzymes are produced in the stomach. Mechanical and chemical digestion begin in the mouth where food is chewed, and mixed with saliva to begin enzymatic processing of starches.
The stomach continues to break food down mechanically and chemically
through churning and mixing with both acids and enzymes. Absorption occurs in the stomach and gastrointestinal tract, and the process finishes with defecation.
The human gastrointestinal tract
is around 9 metres (30 feet) long. Food digestion physiology varies
between individuals and upon other factors such as the characteristics
of the food and size of the meal, and the process of digestion normally
takes between 24 and 72 hours.
Digestion begins in the mouth with the secretion of saliva and its digestive enzymes. Food is formed into a bolus by the mechanical mastication and swallowed into the esophagus from where it enters the stomach through the action of peristalsis. Gastric juice contains hydrochloric acid and pepsin which could damage the stomach lining, but mucus
and bicarbonates are secreted for protection. In the stomach further
release of enzymes break down the food further and this is combined with
the churning action of the stomach. Mainly proteins are digested in
stomach. The partially digested food enters the duodenum as a thick semi-liquid chyme. In the small intestine, the larger part of digestion takes place and this is helped by the secretions of bile, pancreatic juice and intestinal juice. The intestinal walls are lined with villi, and their epithelial cells are covered with numerous microvilli to improve the absorption of nutrients by increasing the surface area of the intestine. Bile helps in emulsification of fats and also activates lipases.
In the large intestine, the passage of food is slower to enable fermentation by the gut flora to take place. Here, water is absorbed and waste material stored as feces to be removed by defecation via the anal canal and anus.
The cephalic phase occurs at the sight, thought and smell of food, which stimulate the cerebral cortex. Taste and smell stimuli are sent to the hypothalamus and medulla oblongata. After this it is routed through the vagus nerve
and release of acetylcholine. Gastric secretion at this phase rises to
40% of maximum rate. Acidity in the stomach is not buffered by food at
this point and thus acts to inhibit parietal (secretes acid) and G cell (secretes gastrin) activity via D cell secretion of somatostatin.
The gastric phase takes 3 to 4 hours. It is stimulated by distension of the stomach, presence of food in stomach and decrease in pH. Distention activates long and myenteric reflexes. This activates the release of acetylcholine, which stimulates the release of more gastric juices. As protein enters the stomach, it binds to hydrogen ions, which raises the pH of the stomach. Inhibition of gastrin and gastric acid secretion is lifted. This triggers G cells to release gastrin, which in turn stimulates parietal cells to secrete gastric acid. Gastric acid is about 0.5% hydrochloric acid, which lowers the pH to the desired pH of 1–3. Acid release is also triggered by acetylcholine and histamine.
The intestinal phase has two parts, the excitatory and the inhibitory. Partially digested food fills the duodenum. This triggers intestinal gastrin to be released. Enterogastric reflex inhibits vagal nuclei, activating sympathetic fibers causing the pyloric sphincter to tighten to prevent more food from entering, and inhibits local reflexes.
Breakdown into nutrients
Protein digestion
Protein digestion occurs in the stomach and duodenum in which 3 main enzymes, pepsin secreted by the stomach and trypsin and chymotrypsin secreted by the pancreas, break down food proteins into polypeptides that are then broken down by various exopeptidases and dipeptidases into amino acids. The digestive enzymes however are mostly secreted as their inactive precursors, the zymogens. For example, trypsin is secreted by pancreas in the form of trypsinogen, which is activated in the duodenum by enterokinase to form trypsin. Trypsin then cleaves proteins to smaller polypeptides.
Digestion of some fats can begin in the mouth where lingual lipase breaks down some short chain lipids into diglycerides. However fats are mainly digested in the small intestine. The presence of fat in the small intestine produces hormones that stimulate the release of pancreatic lipase from the pancreas and bile from the liver which helps in the emulsification of fats for absorption of fatty acids. Complete digestion of one molecule of fat (a triglyceride) results a mixture of fatty acids, mono- and di-glycerides, but no glycerol.
In humans, dietary starches are composed of glucose units arranged in long chains called amylose, a polysaccharide. During digestion, bonds between glucose molecules are broken by salivary and pancreatic amylase, resulting in progressively smaller chains of glucose. This results in simple sugars glucose and maltose (2 glucose molecules) that can be absorbed by the small intestine.
Lactase is an enzyme that breaks down the disaccharidelactose to its component parts, glucose and galactose.
Glucose and galactose can be absorbed by the small intestine.
Approximately 65 percent of the adult population produce only small
amounts of lactase and are unable to eat unfermented milk-based foods. This is commonly known as lactose intolerance.
Lactose intolerance varies widely by genetic heritage; more than 90
percent of peoples of east Asian descent are lactose intolerant, in
contrast to about 5 percent of people of northern European descent.
Sucrase is an enzyme that breaks down the disaccharide sucrose, commonly known as table sugar, cane sugar, or beet sugar. Sucrose digestion yields the sugars fructose and glucose which are readily absorbed by the small intestine.
Some nutrients are complex molecules (for example vitamin B12) which would be destroyed if they were broken down into their functional groups. To digest vitamin B12 non-destructively, haptocorrin in saliva strongly binds and protects the B12 molecules from stomach acid as they enter the stomach and are cleaved from their protein complexes.
After the B12-haptocorrin complexes pass from the stomach via the pylorus to the duodenum, pancreatic proteases cleave haptocorrin from the B12 molecules which rebind to intrinsic factor (IF). These B12-IF complexes travel to the ileum portion of the small intestine where cubilin receptors enable assimilation and circulation of B12-IF complexes in the blood.
Digestive hormones
Action of the major digestive hormones
There are at least five hormones that aid and regulate the digestive
system in mammals. There are variations across the vertebrates, as for
instance in birds. Arrangements are complex and additional details are
regularly discovered. Connections to metabolic control (largely the
glucose-insulin system) have been uncovered.
Gastrin – is in the stomach and stimulates the gastric glands to secrete pepsinogen (an inactive form of the enzyme pepsin) and hydrochloric acid. Secretion of gastrin is stimulated by food arriving in stomach. The secretion is inhibited by low pH.
Secretin – is in the duodenum and signals the secretion of sodium bicarbonate in the pancreas and it stimulates the bile secretion in the liver. This hormone responds to the acidity of the chyme.
Cholecystokinin
(CCK) – is in the duodenum and stimulates the release of digestive
enzymes in the pancreas and stimulates the emptying of bile in the gall bladder. This hormone is secreted in response to fat in chyme.
Gastric inhibitory peptide
(GIP) – is in the duodenum and decreases the stomach churning in turn
slowing the emptying in the stomach. Another function is to induce insulin secretion.
Motilin – is in the duodenum and increases the migrating myoelectric complex component of gastrointestinal motility and stimulates the production of pepsin.
Significance of pH
Digestion is a complex process controlled by several factors. pH
plays a crucial role in a normally functioning digestive tract. In the
mouth, pharynx and esophagus, pH is typically about 6.8, very weakly
acidic. Saliva controls pH in this region of the digestive tract. Salivary amylase is contained in saliva and starts the breakdown of carbohydrates into monosaccharides. Most digestive enzymes are sensitive to pH and will denature in a high or low pH environment.
The stomach's high acidity inhibits the breakdown of carbohydrates within it. This acidity confers two benefits: it denatures proteins for further digestion in the small intestines, and provides non-specific immunity, damaging or eliminating various pathogens.
In the small intestines, the duodenum provides critical pH
balancing to activate digestive enzymes. The liver secretes bile into
the duodenum to neutralize the acidic conditions from the stomach, and
the pancreatic duct empties into the duodenum, adding bicarbonate
to neutralize the acidic chyme, thus creating a neutral environment.
The mucosal tissue of the small intestines is alkaline with a pH of
about 8.5.
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