The document discusses various cancer treatment methods including surgery, radiotherapy, immunotherapy, hormone therapy, chemotherapy, and combination/adjuvant chemotherapy. It provides details on each method such as how surgery is used for diagnosis and removal of tumors, how different types of radiation are used in radiotherapy, and how chemotherapy works by destroying cancer cells. The document also covers natural compounds that can induce apoptosis in cancer cells, including plant extracts, flavonoids, and curcumin which suppresses prostaglandin formation through COX-2 inhibition. Nanoparticles are also discussed as a means of targeted drug delivery to cancer cells to reduce side effects.

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Cancer treatment
1. Surgery
 It is used for both diagnosis and therapy.
 To obtain a sample for diagnosis surgery is
usually required.
 The removal of a suspected neoplasm or a portion of it for diagnostic
purposes is termed “biopsy”.
 Surgical removal of cancer is the oldest and most classical method of
treatment.
 Curative surgery is performed on a primary neoplastic lesion, whether it
is benign or malignant.
 If metastatic lesion are present, surgery may be carried out to remove
the tumor(s) in order to reduce the amount of cancer in body, this if
surgery is followed by other modification (radiotherapy and
chemotherapy).
 It is also carried out in order to remove the bulks of tumors that may
obstruct or press on vital organs and passages.
2. Radiotherapy
 It is very effective whether used after surgery or alone with
chemotherapy.
 Different types of radiation are used.
 Their mechanism depends on damaging the dividing cells, but it also
affects normal tissue.
 Malignant lymphomas, leukemias and most carcinomas are relatively
sensitive to radiation.
 Sarcomas are more resistant.

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3. Immunotherapy
 It depends on the stimulation of the host’s own immune defense or, the
treatment of the host with antibodies specific for the tumor, especially
after treatment with drugs.
4. Hormone therapy
 It depends on:
(a) lowering the plasma hormones,
(b) blocking the action of circulating hormones
through blocking certain receptors (e.g. tamoxifen)
and
(c) additive hormone therapies (used mainly in
breast cancers).
5. Chemotherapy
 Once metastasis occurs, surgical and most
probably radiation therapy are not curative.
 Although complete cure is difficult in this stage, chemotherapy, is used
for increasing the useful life-time of many patients.
 There are some cancers in advanced stages that respond well to
chemotherapy
- e.g. acute lymphocytic leukemia, Hodgkin’s disease (a lymphoma),
Burkitt’s lymphoma, Ewing’s sarcoma of bone, and Wilm’s tumer of
the kidney.
- All these tumors are characterized by rapid growth.
 Successive chemotherapy is related to the growth fraction of the
tumor, that is, the percentage of cells undergoing cell division at any
one time.
 Rapidly growing cancers have large growth fractions; therefore, the
drugs affect greater proportion of the cell population.
 The search for and development of new drugs is very difficult and takes
a long time.

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 A drug goes through several stages such as;
- selection of the compound
- screening its effectiveness in animals
- study how the body handles it, and
- finally trials on patients.
6. Combination chemotherapy
 Is used to improve the results of treating cancer patients.
 Each drug is chosen for its ability to attack cells at a certain point in
their life cycle.
 When properly combined, several drugs (2-6) may be more effective
in treating a particular cancer than 1single drug.
7. Adjuvant chemotherapy
 Doctors sometimes use chemotherapy as a precautionary measure when
they are uncertain if a cancer has spread.
 This use of drugs is called ‘adjuvant chemotherapy’.
 The drugs are intended to destroy cancerous cells that may be alive but
undetected, in the body.
 Adjuvant chemotherapy is commonly used when cancer has been
discovered in several lymph nodes.

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♦ Conditions that limit the effectiveness of chemotherapy:
 Normal cells, like cancerous cells, are killed during chemotherapy.
 If a patient suffers severe side effects from the death of normal cells,
his program of chemotherapy must be adjusted.
 Since most cancer drugs disrupt cell division, side effects tend to occur
in those parts of the body comprised of frequently dividing cells-the
stomach, anus, the hair follicles and the bone marrow.
♣ Drug resistance:
 Resistance to a chemotherapeutic agent may be considered under two
main headings: primary and acquired, which together constitute the
major problem in cancer chemotherapy.
 The experimental approach in man has largely been directed against the
problem of acquired resistance, and the systems involved have been
found to be highly complex.
 Several mechanisms may be operative, such as selective killing of
sensitive population leaving resistant cells or an adaptive change by the
tumor cell.

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Natural inducers of apoptosis
Implication for cancer therapy and prevention
♦ Need for apoptotic inducers
 The accepted modality for cancer treatment involves surgery,
radiation and drugs, singly or in combination.
 Cancer chemotherapeutic agents can often provide temporary relief
from symptoms, prolongation of life and occasionally, cures.
 A successful anticancer drug should kill or incapacitate cancer cells
without causing excessive damage to normal cells.
 This ideal situation is achievable by inducing apoptosis in cancer
cells.
 The life span of both normal and cancer cells is significantly affected
by the rate of apoptosis.
 Thus, modulating apoptosis may be useful in the management and
therapy or prevention of cancer.
 Significantly, natural products are providing such templates.
 Recent studies on tumor inhibitory compounds of plant origin have
yielded an impressive array of novel structures.
 Besides, epidemiological studies suggest that consumption of diets
containing fruits and vegetables, major sources of phytochemicals
and micronutrients, may reduce the risk of developing cancer.
 Certain products from plants are known to induce apoptosis in
neoplastic cells but not in normal cells.

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◘ Types of natural products used to induce apoptosis :
 PPlant extracts.
 Flavonoids.
 henolic compounds.
 Tea polyphenols.
 Alkaloids.
 Polysaccharides and glycoproteins.
 Lectins.
 Tannins and lignins.
 Isoprenoids.
 Quinones.
◘ Mode of action of some natural products
♣ Auto-oxidative and Cyclooxygenase-2 catalyzed transformation of the
dietary chemopreventive agent Curcumin

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 The yellow plant phenolic pigment curcumin shows a remarkable
ability to affect a wide variety of signaling pathways that are
dysregulated during tumorigenesis, including proliferation, invasion
apoptosis, and cell-cycle checkpoints.
 Altogether more than one hundred molecular targets of curcumin
have been identified using in vitro cell culture-based assays.
 The diversity of biological effects of curcumin has been attributed to
its ability to act as an antioxidant, anti-inflammatory and anti-viral
agent.
 As a consequence of promising in vitro results, several clinical trials
have been initiated to investigate the effect of dietary curcumin in the
prevention of inflammatory bowel disease, colon and pancreatic
cancer, and Alzheimer’s, among others.
 One of the suggested chemopreventive mechanisms of curcumin is
the suppression of prostaglandin formation by the COX-2 enzyme.
 Induction of COX-2 is hallmarks in the development of many
cancers, best studied in the case of colon carcinogenesis.
 Suppression of COX-2 activity by selective or non-selective
inhibitors of the cyclooxygenase enzymes leads to a significant
reduction of colon cancer in animal models and in human populations
with a genetically elevated cancer risk.
 The interactions of curcumin with arachidonic acid metabolism and
prostaglandin biosynthesis are remarkably complex:
- curcumin has been shown to downregulate the expression of COX-2
mRNA and protein and also to directly inhibit the enzymatic
activities of COX-2.
- In addition, curcumin has been shown to inhibit the enzymatic
activity lipoxygenase, the enzyme that initiates biosynthesis of
leukotrienes from arachidonic acid.

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◘ Nanotechnology
 Has an advantage in cancer therapy.
 Nanoparticles (size in nanometer range) provide a new mode of cancer
drug delivery functioning as a carrier for entry through fenestrations in
tumor vasculature allowing direct cell access.
 These particles allow exquisite modification for binding to cancer cell
membranes, the microenvironment, or to cytoplasmic or nuclear
receptor sites.
 This results in delivery of high drug concentrations to the targeted
cancer cell, with reduced toxicity of normal tissue.
 Several such engineered drugs are in clinical practice, including
liposomal doxorubicin and albumin conjugate paclitaxel.
 This new technology provides many exciting therapeutic approaches for
targeted high concentration drug delivery to cancer cells with reduced
injury of normal cells.

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Mechanism of apoptosis proposed for some phenolics
♦ AKBA inhibits cancerous cells proliferation
1. Although there is increasing evidence showing that boswellic acid might be a
potential anticancer agent, the mechanisms involved in its action are unclear.
2. In the present study, we showed that acetyl-keto-β-boswellic acid (AKBA)
inhibited cellular growth in several colon cancer cell lines.
- Cell cycle analysis by flow cytometry showed that cells were arrested at the
G1 phase after AKBA treatment.
3. Further analysis showed that cyclin D1 and E, CDK 2 and 4 and phosphorylated
Rb were decreased in AKBA-treated cells while p21 expression was increased.

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4. The growth inhibitory effect of AKBA was dependent on p21 but not p53.
- HCT-116 p53 cells were sensitized to the apoptotic effect of AKBA,
suggesting that p21 may have protected cells against apoptosis by inducing a
G1 arrest.
5. In conclusion, we have demonstrated that AKBA inhibited cellular growth in
colon cancer cells.
- These findings may have implications to the use of boswellic acids as
potential anticancer agents in colon cancer.

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AUTOXIDATIVE AND CYCLOOXYGENASE-2 CATALYZED
TRANSFORMATION OF THE
DIETARY CHEMOPREVENTIVE AGENT CURCUMIN
 The diversity of biological effects of curcumin has been attributed to its ability to
act as an antioxidant, anti-inflammatory and anti-viral agent.
 Prior to the more recent interest in its chemopreventive properties, curcumin was
being considered as a food coloring agent but its chemical and photochemical
instability prevented widespread application.
 Light-induced degradation of curcumin in organic solvents results in cleavage of
the heptadienone chain, and the most abundant products have been identified as
vanillin, ferulic aldehyde, ferulic acid, and feruloylmethane.
 Chemopreventive mechanisms of curcumin is the suppression of prostaglandin
formation by the COX-2 enzyme.
Conclusion
 Apoptosis or programmed cell death is a series of genetically controlled
events that result in the removal of unwanted cells.
 Apoptosis is an important method of cellular control and any disruption
of this process leads to abnormal growth – cancer.
 Apoptotic cells show a very characteristic morphology as well as
specific molecular features.
 Induction of apoptosis in cancer cells or malignant tissues is recognized
as an efficient strategy for cancer chemotherapy.
 Apoptosis also seems to be a reliable marker for the evaluation of
potential agents for cancer prevention.
 A wide variety of natural compounds appear to possess significant
cytotoxic as well as chemopreventive activity.

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 Many of these agents act via apoptosis.
 Extracts of plants used in traditional medicine also have a similar
property.
 Many more screening studies are necessary using plant extracts and
compounds isolated from them.
 Potential apoptotic inducers should not be cytotoxic to normal tissues
and the immune cell system.
 Naturally occurring compounds that are included in the diet are non-
toxic and may partially regulate programmed cell death in several
tissues and organs.
 Elaborate studies with such compounds with respect to their abilities to
induce apoptosis and understanding their mechanism of action may
provide valuable information for their possible application in cancer
therapy and prevention.
‫ا‬‫ل‬Diagrams‫ا‬‫ل‬‫ل‬‫ي‬‫ح‬‫و‬‫ا‬‫ل‬‫ي‬‫ه‬‫ا‬‫ا‬‫ط‬‫ا‬‫ر‬‫ا‬‫س‬‫و‬‫د‬‫ه‬‫ي‬‫ا‬‫ل‬‫ل‬‫ي‬‫ع‬‫ل‬‫ي‬‫ن‬‫ا‬‫غ‬‫ي‬‫ر‬‫ك‬‫د‬‫ا‬‫ل‬‫ل‬‫ت‬‫و‬‫ض‬‫ي‬‫ح‬☺