Thursday, 15 December 2016

Cancer is a group of diseases

Cancer is a group of diseases

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Cancer is a genetic disease:

– Inherited cancer
– Sporadic cancer
• Cancer typically involves a change in gene
– Qualitative change
– Quantitative change
• Any cancer causing genetic alteration typically results in
loss of cell growth control

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What is Cancer?
Malignant Vs. Benign growth
• Benign: called a tumor
– Well circumscribed, slow growing, non invasive, non metastatic.
• Malignant: called a cancer
– Not well organized, irregularly shaped, fast growing, infiltrative
growth, metastatic.
• Initial stages of malignant cancer may typically show
benign growth;
– further accumulation of mutations may make it malignant.

• Cancer arises from a loss of
normal growth control.
• In normal tissues, the rates of
new cell growth and old cell death
are kept in balance.
• In cancer, this balance is
disrupted. This disruption can
result from uncontrolled cell
growth or loss of a cell's ability to
undergo "apoptosis."
• Apoptosis, or "cell suicide," is the
mechanism by which old or
damaged cells normally selfdestruct
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Properties of Cancer Cells
• Cancer cells exhibit several characteristics that are distinct from
normal cells.
• Multiple changes are involved in the conversion of a normal cell
to a cancer cell:
– Autocrine stimulation; grow in the absence of growth factors
– Lack of gap junctions;
– lack of contact inhibition
– Resistance to cell death; persistent telomerase activity
– Rapid growth; overtake population, invade other tissues.
– Angiogenesis
– Clonal nature of cancer
– Genomic Instability: Accumulation of successive mutations
• A germline mutation causes a hereditary cancer.
• A somatic mutation causes a sporadic cancer.

Properties of Cancer Cells:
Changes that produce a potential for immortality
• Loss of limitations on the number of cell divisions
• Ability to grow in culture – normal cells do not grow well in culture
• Restoration of telomerase activity
Properties of Cancer Cells:
 Changes that enable tumor to disrupt local tissue and invade
distant tissues

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Ability to metastasize
• Angiogenesis – secrete substances that cause blood vessels to
grow toward tumor
• Evasion of immune surveillance
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  • Most cancers result from exposures to mutagens
  •  • If one sib or twin gets cancer, other usually does not
    1. • Populations that migrate – profile of cancer becomes more like people
    2. indigenous to new location
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    Sporadic Vs. Familial Cancer
    • Familial:
    • inherited form. The family has a predisposition through a
    germline mutation.
    – Increases the probability that further mutations will occur.
    – Sometimes the initial germline mutation may be responsible
    for different cancers:
    • e.g. same family may have individuals with breast, bone, lung, ovarian
    cancer because of a single inherited germline mutation:

    • Sporadic cancers:
    • new mutations arising in somatic cells of the body.
    – Could result in any type of cancer, depending on the where the
    mutation occurs.

    Inheritance of a mutation in a "cancer protection" gene in a germ
    cell (egg or sperm). The offspring will have both a faulty copy and a
    correct copy of the "cancer protection" gene in all the cells of their
    body, and will be predisposed to develop cancer.

    Genes and Cancer
    • Two classes of genes are mutated frequently in cancer:
    – Tumor suppressor genes: loss of function mutations.
    • Normal function is to prevent cell proliferation.
    • So-called “cancer protection” genes
    – Protooncogenes: gain of function mutations.
    • quantitative change in expression of these genes common in cancer
    • Normal function is to promote cell proliferation.

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    – dominant
    • Mutant tumorsuppressor
    – recessive

    Multistep Nature of Cancer
    • Cancer develops progressively as mutations accumulate.
    • Experimental evidence in mice with either the ras OR the myc
    protooncogenes mutated: fewer tumors develop than when BOTH
    genes are mutated.
    • Mice with only one allele of the tumor suppressor p53 mutated are
    not as cancer prone as when both alleles are mutated.
    • Hereditary adenomatous polyposis or Familial adenomatous
    polyposis (FAP):
    – a typical example of the multi-step pathway for cancer.

    Multistep Nature of Cancer

    The Multi-Step Model
    Genomic Approaches to Cancer
    Diagnostics and Therapies
    • Cancer Diagnostics Goal:
    • Properly classify the type of cancer
    • To properly treat that specific type
    • Usually done by morphology,
    • Certain tumor surface markers,
    • and Identification of translocations
    • Now, genomic approaches can help
    • Determine the gene expression array of the tumor
    • Compare to tumors with known patient outcome
    • Gene profiling
    •Example: Non-Hodgkin Lymphoma, DLBCL

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