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Showing posts with label Tumors. Show all posts
Showing posts with label Tumors. Show all posts

Antiangiogenic therapy


Angiogenesis is the creation of new blood vessels. The term comes from 2 Greek words: angio, meaning "blood vessel," and genesis, meaning "beginning."

Normally, this is a healthy process. As the human body grows and develops, it needs to make new blood vessels to get blood to all of its cells. As adults, we don't have quite the same need for making new blood vessels, but there are times when angiogenesis is still important. New blood vessels, for instance, help the body heal wounds and repair damaged body tissues.



But in a person with cancer, this same process creates new, very small blood vessels that provide a tumor with its own blood supply and allow it to grow.

Anti-angiogenesis is a form of targeted therapy that uses drugs or other substances to stop tumors from making new blood vessels. Without a blood supply, tumors can't grow.

Tumor Destruction

A Tumor or tumour (via Old French tumour from Latin tumor "swelling")originally meant an abnormal swelling of the flesh. In contemporary English, tumor has evolved to become synonymous with neoplasia , all other forms being called swelling . This tendency has also become common in medical literature. The noun tumefaction, derived from the adjective tumefied, is the current medical term for non-neoplastic tumors .


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Tumors and/or swellings can be caused by:
Other forms of swelling are part of the normal functions of the body and may or may not be included as causes of tumor. Examples include enlargement of the uterus in pregnancy and erection of the penis.


  • Neoplasia, an abnormal proliferation of tissues. Most (not all) neoplasms cause a tumor. Neoplasms (or tumors) may be benign or malignant (cancer).
  • Non-neoplastic causes :
  1. Inflammation, by far the most common cause; tumor is one of the classic signs of inflammation. The lump following a blow on the head is a typical example. Infection is another common cause of inflammation.
  2. Edema, the accumulation of an excessive amount of fluid in the tissues, either with or without inflammation.
  3. Malformation, a congenital anomaly in the architecture of a tissue. A typical example is an epidermal nevus.
  4. Cyst, the accumulation of fluid in a closed structure. Breast cysts are a typical example.
  5. Hemorrhage in a closed structure.

Green Fluorescent Protein(GFP)

Green florescent protein (GFP) has revolutionized research in medicine and biology, enabling scientist to get a visual fix on how organs function on the spread of disease and the response of infected cells to treatment,
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In 2008 Nobel Chemsitry prize was announced to Osamu Shimomura of Japan and American duo Martin chalfie and Roger Tsien for deriving Florescent protein from a jellyfish Aequorea Victoria.
The GFP is composed of 238 amino acids; it is isolated from jellyfish Aequorea Victoria that fluoresces green when exposed to blue light.It was discovered
GFP has a typical beta barrel structure, consisting of one β-sheet with a alpha helix containing the fluorophore running through the center, while the tightly packed barrel shell protects the flurophore from quenching by the surrounding microenviornment,the inward facing side chains of the barrel induce specific cyclization reactions on the tripeptide Ser65-Tyr66-Gly67 that lead to fluorophore formation. This occurs in a series of discrete steps with distinct excitation and emission properties.
GFP has functioned has a guiding star for bichemist, biologist and medical scientist, The gene to make GFP is inserted into the DNA of lab animals, bacteria or other cells, where it is switched on by other genes, the glow becomes apparent under ultraviolet light, The telltale protein gives researchers an instant way of monitoring process that were previously invisible.
By targeting nerve cells in Alzheimer’s disease person scientist can follow the, destruction caused by disease, Tumour progression can be followed by adding GFP to cancer cells, By adding GFP to a growing mouse embryo, they can see how the pancreas generates insulin-producing beta cells. Today GFP is a standard tool for thousands of researchers all over the world
GFP derivatives
Due to the potential for widespread usage and the evolving needs of researchers, many different mutants of GFP have been engineered. The first major improvement was a single point mutation (S65T) reported in 1995 in Nature by Roger Tsien This mutation dramatically improved the spectral characteristics of GFP, resulting in increased fluorescence, photostability and a shift of the major excitation peak to 488nm with the peak emission kept at 509 nm. This matched the spectral characteristics of commonly available FITC filter sets, increasing the practicality of use by the general researcher. The addition of the 37 °C folding efficiency (F64L) point mutant to this scaffold yielded enhanced GFP (EGFP). EGFP has an extinction coefficient (denoted ε), also known as its optical cross section of 9.13×10−21 m²/molecule, also quoted as 55,000 M−1cm−1. The quantum yield (QY) of EGFP is 0.60. The relative brightness, expressed as ε•QY, is 33,000 M−1cm−1. Superfolder GFP, a series of mutations that allow GFP to rapidly fold and mature even when fused to poorly folding peptides, was reported in 2006.

Many other mutations have been made, including color mutants; in particular blue fluorescent protein(EBFP, EBFP2, Azurite, mKalama1), cyan fluorescent protein (ECFP, Cerulean, CyPet) and yellow fluorescent protein derivatives (YFP, Citrine, Venus, YPet). BFP derivatives (except mKalama1) contain the Y66H substitution. The critical mutation in cyan derivatives is the Y66W substitution, which causes the chromophore to form with an indole rather than phenol component. Several additional compensatory mutations in the surrounding barrel are required to restore brightness to this modified chromophore due to the increased bulk of the indole group. The red-shifted wavelength of the YFP derivatives is accomplished by the T203Y mutation and is due to π-electron stacking interactions between the substituted tyrosine residue and the chromophore.These two classes of spectral variants are often employed for fluorescence resonance energy transfer (FRET) experiments. Genetically-encoded FRET reporters sensitive to cell signaling molecules, such as calcium or glutamate, protein phosphorylation state, protein complementation, receptor dimerization and other processes provide highly specific optical readouts of cell activity in real time.
Semirational mutagenesis of a number of residues led to pH-sensitve mutants known as pHluorins, and later super-ecliptic pHluorins. By exploiting the rapid change in pH upon synaptic vesicle fusion, pHluorins tagged to synaptobrevin have been used to visualize synaptic activity in neurons.
The nomenclature of modified GFPs is often confusing due to overlapping mapping of several GFP versions onto a single name. For example,mGFP often refers to a GFP with an N-terminal palmitoylation that causes the GFP to bind to cell membranes. However, the same term is also used to refer to monomeric GFP, which is often achieved by the dimer interface breaking A206K mutation. Wild-type GFP has a weakdimerization tendency at concentrations above 5 mg/mL. mGFP also stands for "modified GFP" which has been optimized through amino acid exchange for stable expression in plant cells.
Use
The availability of GFP and its derivatives has thoroughly redefined fluorescence microscopy and the way it is used in cell biology and other biological disciplines. While most small fluorescent molecules such as FITC (fluorescein isothiocyanate) are strongly phototoxic when used in live cells, fluorescent proteins such as GFP are usually much less harmful when illuminated in living cells. This has triggered the development of highly automated live cell fluorescence microscopy systems which can be used to observe cells over time expressing one or more proteins tagged with fluorescent proteins. Analysis of such time lapse movies has redefined the understanding of many biological processes including protein folding, protein transport, and RNA dynamics, which in the past had been studied using fixed (i.e. dead) material.
Another powerful use of GFP is to express the protein in small sets of specific cells. This allows researchers to optically detect specific types of cells in vitro (in a dish), or even in vivo (in the living organism).

Benign Fibroadenoma Tumors

Definition

Fibroadenoma of the breast is a benign (noncancerous) tumor.

Causes, incidence, and risk factors

Fibroadenoma is the most common benign tumor of the breast and the most common breast tumor in women less than 30 years of age. Fibroadenomas are usually found as solitary lumps, but about 10-15% of women have multiple lumps that may affect both breasts.

Black women tend to develop fibroadenomas more frequently and at an earlier age than white women. The cause of fibroadenoma is not known.


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Symptoms



Lumps may be moveable, painless, firm, or rubbery, with well-defined borders
May grow in size, especially during pregnancy
Often get smaller after menopause (if not taking hormones)

Signs and tests

The following may be performed to gain information about a breast lump:

Physical examination
Mammogram
Breast Ultrasound
Fine needle aspiration
Biopsy (needle or open)
Treatment

A biopsy is needed to get a definitive diagnosis. Women in their teens or early 20s may not need a biopsy if the lump goes away on its own.
If a biopsy indicates that the lump is a fibroadenoma, the lump may be left in place or removed, depending on the patient and the lump. If left in place, it may be watched over time with physical examinations, mammograms, and ultrasounds.
The lump may be surgically removed at the time of an open biopsy (this is called an excisional biopsy). The decision depends on the features of the lump and the patient's preferences.
Alternative treatments include removing the lump with a needle, and destroying the lump without removing it (such as by freezing, in a process called cryoablation).
Expectations (prognosis)

The outlook is excellent, although patients with fibroadenoma have a slightly higher risk of breast cancer later. Lumps that are not removed should be periodically monitored by physical examinations and imaging, following the recommendations of the doctor.

Complications

If the lump is left in place for observation, removal may be needed at a later time if the lump changes, grows, or persists.
Cancer may be found in the lump (very rare) and require further treatment.
Biopsy or removal may result in bleeding or scarring.
Calling your health care provider

Patients should contact their health care provider if they feel a new breast lump, if a known lump changes, or if they note changes in the breast that aren’t affected by the menstrual cycle. Women should perform regular breast self exam and undergo breast screening as recommended by their health care provider.