Taxol chemotherapy in breast cancer

Cancer scientists at Georgetown University Medical Center have taken a step towards understanding how and why a widely used chemotherapy drug works in breast cancer patients. In laboratory studies, the scientists isolated a protein, caveolin-1, showing that in breast cancer cells this protein can enhance cell death in response to the use of Taxol, one of two taxane chemotherapy drugs used to treat advanced breast and ovary cancer. But in order to work, they found the protein needs to be "switched on," or phosphorylated. The results were published in the current (February 23) issue of the Journal of Biological Chemistry. Their finding suggests it may eventually be possible to test individual patients with breast cancer for the status of such molecular markers as caveolin-1 in their tumors to determine the efficacy-to-toxicity ratio for Taxol, said the studys first author, postdoctoral fellow Ayesha Shajahan, Ph.D., of Lombardi Comprehensive Cancer Center at Georgetown. "Because breast tumors are not all the same, it is important to know the cancers molecular makeup in order to increase the efficiency, and lower the toxicity, of chemotherapy drugs, and this work takes us some steps forward in this goal," she said. "It also offers insights into why some breast cancer cells can become resistant to therapeutic drugs". Additionally, the study identifies caveolin-1 as a new molecular target for increasing the efficacy of taxanes, as per the studys lead investigator, Robert Clarke, Ph.D., D.Sc., a Professor of Oncology and Physiology & Biophysics. "This is important because the taxanes are active drugs in breast cancer, so now that we know caveolin-1 is a new mechanism to explain how these drugs kill breast cancer cells, we can potentially take advantage of that fact to improve these agents". The taxanes are Taxol (also known as paclitaxel) and Taxotere (docetaxel). Taxol was originally derived from the Pacific yew tree, and Taxotere is a semi-synthetic version of Taxol with slight chemical changes. These drugs stabilize a cells "microtubules," the road-like protein structures that send chemical signals to all parts of the cell, and which must be flexible if a cell is to divide. Taxanes lock these structures into place, not allowing them to change when the cell begins to divide - which is necessary for tumor growth. Research has also indicated that the drugs induce programmed cell death (apoptosis) in cancer cells by inactivating an "apoptosis stopping protein" called BCL2, thus stopping it from inhibiting cell death. Caveolin-1 is a protein that is found in most cells under normal conditions and it is involved in an array of cellular events that ranges from vesicle trafficking to cell migration. It is, therefore, as a key regulator of multiple events within the cell. In cancer, the expression level of caveolin-1 can vary depending on cell type. However, the precise role of caveolin-1 in cancer has been controversial: whether it acts as a suppressor or facilitator of tumor formation depends on the cell type. In human breast cancer, caveolin-1 has been known to act as a tumor suppressor since caveolin-1 expression is down-regulated during the primary stages of breast cancer. More recent studies indicate that that caveolin-1 expression is increased in more aggressive types of breast cancer. Under the mentorship of Clarke, Shajahan sought to determine factors that regulate expression and function of caveolin-1 in the breast. In this study, the scientists show that in their breast cancer cell model that phosphorylated caveolin-1 increased cell death by activating other key regulators vital to both breast cancer progression and cell death, including BCL2, the same protein that Taxol works on; p21, which controls cell cycle progression; and the tumor suppressor p53. If caveolin-1 isnt phosphorylated, breast cancer cells appear to be resistant to Taxol therapy, the scientists conclude. "Thus, this study opens an area of investigation in our lab that will concentrate on understanding how this multi-tasking protein can serve as a marker for chemotherapeutic drug efficacy," Shajahan said.

Taxol chemotherapy in breast cancer

Cancer scientists at Georgetown University Medical Center have taken a step towards understanding how and why a widely used chemotherapy drug works in breast cancer patients. In laboratory studies, the scientists isolated a protein, caveolin-1, showing that in breast cancer cells this protein can enhance cell death in response to the use of Taxol, one of two taxane chemotherapy drugs used to treat advanced breast and ovary cancer. But in order to work, they found the protein needs to be "switched on," or phosphorylated. The results were published in the current (February 23) issue of the Journal of Biological Chemistry. Their finding suggests it may eventually be possible to test individual patients with breast cancer for the status of such molecular markers as caveolin-1 in their tumors to determine the efficacy-to-toxicity ratio for Taxol, said the studys first author, postdoctoral fellow Ayesha Shajahan, Ph.D., of Lombardi Comprehensive Cancer Center at Georgetown. "Because breast tumors are not all the same, it is important to know the cancers molecular makeup in order to increase the efficiency, and lower the toxicity, of chemotherapy drugs, and this work takes us some steps forward in this goal," she said. "It also offers insights into why some breast cancer cells can become resistant to therapeutic drugs". Additionally, the study identifies caveolin-1 as a new molecular target for increasing the efficacy of taxanes, as per the studys lead investigator, Robert Clarke, Ph.D., D.Sc., a Professor of Oncology and Physiology & Biophysics. "This is important because the taxanes are active drugs in breast cancer, so now that we know caveolin-1 is a new mechanism to explain how these drugs kill breast cancer cells, we can potentially take advantage of that fact to improve these agents". The taxanes are Taxol (also known as paclitaxel) and Taxotere (docetaxel). Taxol was originally derived from the Pacific yew tree, and Taxotere is a semi-synthetic version of Taxol with slight chemical changes. These drugs stabilize a cells "microtubules," the road-like protein structures that send chemical signals to all parts of the cell, and which must be flexible if a cell is to divide. Taxanes lock these structures into place, not allowing them to change when the cell begins to divide - which is necessary for tumor growth. Research has also indicated that the drugs induce programmed cell death (apoptosis) in cancer cells by inactivating an "apoptosis stopping protein" called BCL2, thus stopping it from inhibiting cell death. Caveolin-1 is a protein that is found in most cells under normal conditions and it is involved in an array of cellular events that ranges from vesicle trafficking to cell migration. It is, therefore, as a key regulator of multiple events within the cell. In cancer, the expression level of caveolin-1 can vary depending on cell type. However, the precise role of caveolin-1 in cancer has been controversial: whether it acts as a suppressor or facilitator of tumor formation depends on the cell type. In human breast cancer, caveolin-1 has been known to act as a tumor suppressor since caveolin-1 expression is down-regulated during the primary stages of breast cancer. More recent studies indicate that that caveolin-1 expression is increased in more aggressive types of breast cancer. Under the mentorship of Clarke, Shajahan sought to determine factors that regulate expression and function of caveolin-1 in the breast. In this study, the scientists show that in their breast cancer cell model that phosphorylated caveolin-1 increased cell death by activating other key regulators vital to both breast cancer progression and cell death, including BCL2, the same protein that Taxol works on; p21, which controls cell cycle progression; and the tumor suppressor p53. If caveolin-1 isnt phosphorylated, breast cancer cells appear to be resistant to Taxol therapy, the scientists conclude. "Thus, this study opens an area of investigation in our lab that will concentrate on understanding how this multi-tasking protein can serve as a marker for chemotherapeutic drug efficacy," Shajahan said.

Eat well, get fit, stop smoking - prevent cancer

If you wanted to start today to reduce your chances of getting cancer, what would you have to do? Lose excess weight, get more exercise, eat a healthy diet and quit smoking. Watch video Those basic behavior changes would have a tremendous impact on the occurence rate of the most prevalent types of cancer - lung, breast, prostate and colon cancer - says Graham Colditz, M.D., Dr.P.H., associate director of Prevention and Control at the Siteman Cancer Center at Washington University School of Medicine in St. Louis and Barnes-Jewish Hospital. "We estimate that more than 50 percent of cancer incidence could be prevented if we act today on what we already know," Colditz says. Every year, more than 500,000 Americans die from cancer. The National Cancer Institute estimates that on average each person who dies from cancer loses 15 years of life, and altogether cancer deaths were responsible for nearly 8.7 million person-years of life lost in 2003, the most recent year for which the data were available. "The loss of life and earning potential and the social impact of cancer are enormous," Colditz says. "Reducing risk by adopting changes in lifestyle like quitting smoking and losing weight isn't always easy, but it may help to remember that these behavior changes can also reduce your risk of heart disease, diabetes, stroke and osteoporosis." Colditz's recommendations for preventing cancer also include avoiding excess alcohol consumption, taking a multivitamin with folate and protecting yourself from too much sun and from sexually transmitted diseases. Colditz recently became leader of the Siteman Center's cancer prevention program having previously headed the Harvard Center for Cancer Prevention. Physical fitness Estimates hold that 20 to 30 percent of the most common cancers in the United States stem from being overweight or physically inactive. Research has linked weight gain to common cancers such as breast and colon cancer, as well as uterine, esophageal and renal cancers. "Women who lose weight in their adult years reduce their risk of breast cancer significantly," Colditz notes. Furthermore, he asserts that a clear connection exists between higher levels of physical activity and lower occurence rate of cancer. "For example, even after diagnosis of breast cancer, physical activity has an impact on recurrence and survival," he says. Consumption. What people breathe in, drink or eat can influence whether they get cancer. It's well known that smoking is linked to lung cancer, but less usually understood is that smokers also are more likely to get colorectal cancer as well as kidney, pancreatic, cervical and stomach cancers. "The rate at which risk drops after stopping smoking varies for different cancer sites," Colditz says. "But it's very clear that within five to 10 years there will be a 50 percent reduction in cancer risk in comparison to people who keep smoking." Eventhough some recent evidence has suggested that wine and other alcoholic beverages may contain beneficial components, other data show that overconsumption of alcohol increases the possibility of getting oral, esophageal, breast and other cancers. Eating a plant-based diet can help protect against cancer. People who eat diets rich in fruits and vegetables have a lower danger of cancers of the colon, mouth, pharynx, esophagus, stomach and lung. Diets high in red meat and animal fat increase the probability of certain cancers. "There's a strong, consistent relation between higher intake of red meat and higher risk of colon cancer," Colditz notes. High intake of folate, a B vitamin, may protect a person from cancer, and epidemiological studies suggest that low folate status may play an important role early in cancer development. Colditz says experts recommend taking a multivitamin that contains folate every day. Other factors Reducing long-term exposure to the sun and to artificial light from tanning beds, booths and sun lamps can lower the danger of getting non-melanoma skin cancer. Avoiding burns and other damage from these sources - particularly in children and teens - can reduce the chances of getting melanoma skin cancer. Certain viral infections have also been strongly associated with cancer development. Some of the most important of these are human papillomavirus (HPV), a cause of cervical cancer, hepatitis B and C viruses, major causes of liver cancer, and Helicobacter pylori, which accounts for the majority of cases of stomach cancer. HPV can be spread by sexual contact, and vaccine-conferred immunity results in a marked decrease in premalignant lesions. As with the new cervical cancer vaccine, advances in chemoprevention will likely add to the prevention potential that comes from healthy lifestyle choices. "In the future we'll be seeing a range of new preventative strategies," Colditz indicates. "For example, the National Cancer Institute has a trial looking at selenium as a supplement to prevent cancer. And research shows that antiestrogens may reduce the risk of breast cancer by 60 to 80 percent in women after menopause."

Taxotere Improves Survival in Prostate Cancer

One step forward in prostate cancer: As per a press release by Sanofi-Aventis, long-term results indicate that Taxotere (docetaxel) improves survival in patients with metastatic hormone-refractory prostate cancer. Prostate cancer is second only to non-melanoma skin cancers as the most usually diagnosed cancer in men in the U.S. The prostate is a walnut-sized gland that is located between the bladder and rectum. It is responsible for forming a component of semen. Prostate cancer is stimulated to grow by male hormones, especially testosterone. Hormone treatment, which is intended to reduce levels of male hormones available to cancer cells, is a therapy option for men diagnosed with prostate cancer. By reducing levels of male hormones, the cancer cells are deprived of their growth stimulus, causing the cancer to shrink. Unfortunately, patients ultimately stop responding to hormone treatment after receiving therapy for a period of time; they are then referred to as having hormone-refractory or androgen-independent prostate cancer.

Types of cancer

discussed below are the types of cancer

Retinoblastoma

IntroductionThis is the most common primary tumor of the eye in children. It arises from the retina. .The retina is a layer of nerve tissue that coats the back of the eye, which is important for vision of person. Retinoblasts (immature cells of the retina) multiply during gestation and early life, to make enough cells to create the retina. As child grows, these cells mature & no longer differentiate. If these immature retinoblasts turn into cancer cells, retinoblastoma develops, the cause of which is unknown. The gene responsible is RB1 gene.Incidence:The annual incidence is one in 20000 children. It occurs most often in children under 4 years of age.Types:Hereditary:•Hereditary form of Retinoblastoma occurs in 40%.•May have more than one tumor•Tumor often affects both eyes•May have tumors in other parts of the body•At increased risk for other cancers later in lifeNon-hereditary:•Most children with retinoblastoma (60%) do not have the genetic form.•They develop tumor in only one eye i.e. unilateral.•These children do not have an increased risk of developing other cancers.•Their offspring have the same risk of developing retinoblastoma as other children in the population.Symptoms:•A pupil that looks white or red instead of the usual black i.e. called as white or cat’s eye reflex.•A crossed eye i.e. strabismus.•Poor vision•A red, painful eye•An enlarged pupil•Differently colored irisesInvestigations:•Examination under general anesthesia using Retcam•Ultrasound•CT (CAT) scan•MRI•CSF examination•Bone marrow studies•Bone scan in advanced disease•Chromosomal analysis (in certain cases)Management:1.Surgery to remove the eye, known as enucleation. This s done when there is no vision in eye to save further spread & life. Enucleation may also be recommended if the tumor does not respond to treatment.2.Chemotherapy is used to shrink tumors in the eye. This approach is often used in children with bilateral disease (both eyes) for saving at least one eye which has less disease. It is also used in small tumors where the eye vision is present to save the eye. in combination with other measures such as1.Photocoagulation--using laser light to destroy blood vessels supplying the tumor.2.Thermotherapy--using heat to destroy tumor cells3.Cryotherapy--using extreme cold to destroy tumor cells4.Radiation Therapy—It is used for control of local disease with preservation of vision. Radiation plaque therapy and particle beam radiotherapy are used frequently.Prognosis:The five-year survival rate for children with retinoblastoma is more than 90%.

Neuroblastoma

Introduction:It is the second most common solid tumor in children after brain tumor. It occurs in the neural crest cells, called neuroblasts, of the sympathetic nervous system. It can occur in a number of anatomical sites. The majority of tumors (65%) are located in the abdomen, often in one of the two adrenal glands. However, primary tumors can occur anywhere in the body. Other common sites are the chest, neck or pelvis. It is one of the most malignant neoplasms of children & rarely seen in adults.Incidence:Neuroblastoma represents 7.5% of all childhood cancers. It is most commonly diagnosed between 17 months and 2 years of age.Aetiology:Neuroblastoma develops when normal neuroblasts (the immature cells of the sympathetic nervous system) fail to mature into nerve cells. Instead, they continue to grow leading to mass of cancer cells.Other hypothesis is “mutations” occurring in Neuroblastoma cells.Symptoms:Symptoms of Neuroblastoma are dependent upon the site, metastatic disease or associated paraneoplastic syndromes,
Abdominal distention/constipationPain in the abdomen.Fever, bony pain, anemia, if the disease has spread to the bone marrow, causing a decrease in red blood cells.Bulging, darkening, proptosis or swelling of the eye, if the disease has spread to tissues and bone around the eyes.Persistent diarrhea, high blood pressure, palpitations, reddening of the skin, sweating, involuntary movements of eyes & limbs, if there is associated paraneoplastic syndrome
Investigations:
Complete blood countBiochemistry including serum LDH & serum ferritinBone marrow aspiration & BiopsyUrinary VMA (Vanillyl mandelic acid) and HMV (Homovanillic acid)N-myc amplificationDNA indexMIBG (131I-meta-iodobenzyl guanidine) scanChest X-RayCT Scan of primary regionMRI spine ( If neurological symptoms)Bone scanBiopsy of the tumor
Prognostic factors:
Age of the childStage of the diseaseTumor HistopathologyMyc-N StatusDNA Index (Ploidy)
Treatment:
Induction Chemotherapy: Multi-drug chemotherapy is first given to try to reduce the size of the primary and metastatic tumor(s). The drugs used are cyclophosphamide, doxorubicin, cisplatin, etoposide, Ifosphamide.
Surgery: Surgery is done to remove as much tumor as safely possible. In some locations its possible to remove whole mass
Radiation Therapy: It is usually given locally to the tumor site.
Myleoablative therapy followed by stem cell or bone marrow transplant: Intensive doses of chemotherapy to eliminate any remaining tumor cells, followed by an autologous peripheral blood stem cell transplant, or sometimes a bone marrow transplant, to restore the immune system is used in high risk disease.
Minimum residual disease therapy: Additional drugs like 13-cis-Retinoic acid, aimed at eliminating or altering minimal residual disease is given after consolidation therapy.
MIBG Therapy: It is used when surgery is not possible because of persistent bone marrow disease after induction chemotherapy.
Prognosis:
Low risk patients have a greater than 90% survival.Intermediate risk patients have a 70-90% chance of survival.High risk patients have a 30% chance of survival