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A number of new agents are being looked at in clinical trials that focus on pathways involved in pancreatic cancer purchase 20gm diclofenac gel with mastercard. Targeted nanoparticles coated with material that hone in on tumor cells and deliver drugs to kill them are being tested in animal models as treatment for metastatic neuroendocrine tumors discount diclofenac gel 20 gm on line. The main advantage would be reducing the toxicity of the drugs to the normal tissues of the body generic diclofenac gel 20gm line. The future treat- ment of pancreatic cancer will involve a personalized approach purchase diclofenac gel 20 gm on-line, i. Biomarkers of Pancreatic Cancer Unlike screenings for other conditions such as colon, breast and prostate cancers, there is no routine way to see whether a patient has a tumor in the pancreas. Current research is focused on finding biomarkers of pancreatic cancer so that a simple blood or urine test could be developed. Because of the complex pathophysiology of Universal Free E-Book Store Personalized Management of Cancers of Various Organs 359 pancreatic cancer, sensitive and specific biomarkers are also required. Extensive genomics/transcriptomics and proteomics studies are being carried out to find can- didate biomarkers and contribute to high-throughput systems for large cohort screening. Among numerous biomarkers histone modifications are promising indi- cators of prognosis and response to therapy. Histone Modifications Predict Treatment Response in Pancreatic Cancer Measuring levels of specific histone modifications within cells has previously shown that low cellular levels of particular histones could determine which prostate cancer patients were more likely to suffer a recurrence and which patients with lung and kidney cancers would experience poorer survival rates. An assay to detect histone modifications can now be used to predict prognosis and response to treatment in subsets of patients with pancreatic cancer (Manuyakorn et al. Immunohistochemistry was performed for histone H3 lysine 4 dimethylation (H3K4me2), histone H3 lysine 9 dimethylation (H3K9me2), and histone H3 lysine 18 acetylation (H3K18ac). Positive tumor cell staining for each histone modification was used to classify patients into low- and high-staining groups, which were related to clinicopathological parameters and clinical outcome measures. Low cellular levels of H3K4me2, H3K9me2, or H3K18ac were each sig- nificant and independent predictors of poor survival. Combined low levels of H3K4me2 and/or H3K18ac were the most significant predictor of overall survival. Further research in cell lines and animal models will determine what, if any, role the histone modifications have in causing the development of aggressive forms of pancreatic cancer. Uncovering the mechanism of how the histone modifications are associated with cancer develop- ment and/or progression may facilitate design of strategies to interfere with that process and form the basis for a targeted therapy or chemoprevention. Personalized Management of Prostate Cancer Prostate cancer is the most common type of cancer found in American men, other than skin cancer, and is the second leading cause of cancer deaths, according to the American Cancer Society. Research is aimed at finding gene variants associated with sus- ceptibility to cancer. Synthetic associations at genome-wide signals could therefore account for a proportion of the missing herita- bility of complex diseases such as cancer. Such findings are useful for understand- ing some of the biological underpinnings of prostate cancer risk, but there is possibility of finding other situations involving synthetic associations between com- mon and rare variants influencing specific traits or conditions. Now oncologists can customize “targeted” cancer treatments for each patient based on the molecular make-up of their tumors. These “smart drugs” selectively stop the growth of tumor cells with the molecular abnormality. Therefore, the experimental drug could potentially help about 60,000 prostate cancer patients a year, if the laboratory results are confirmed in clinical trials, which are ongoing. Prostate Px (Aureon Laboratories), integrates histology, molecular biology and clinical information and applies bioinformatics to stratify patients as high or low risk for disease recurrence post-prostatectomy. Results are provided as the Prostate Px score (0–100), which reports the likelihood of recurrence of the prostate cancer. In a prospective study, integration of clinicopathological variables with imaging and biomarker data (systems pathology) resulted in a highly accurate tool for predicting clinical failure within 5 years after prostatectomy (Donovan et al. The data support a role for androgen receptor signaling in clinical progression and duration of response to androgen deprivation therapy. The anticancer agent docetaxel and thalidomide shows significant inter- individual variation in their pharmacokinetic and toxicity profiles as well as wide pharmacological variations. Genetic poly- morphisms were analyzed for associations with clinical response and toxicity.
Breast cancer-resistance protein 1-expressing verapamil- sensitive side population cells were identified in human ovarian cancer cell lines and primary ascites cells from patients with ovarian cancer cheap 20gm diclofenac gel visa. In the future discount 20 gm diclofenac gel with visa, individualized therapy must incorporate analysis of the stem cell-like subpopulation of ovarian cancer cells when designing therapeutic strategies for ovarian cancer patients purchase 20 gm diclofenac gel otc. Intratumoral heterogeneity occurs in nearly all solid cancers 20 gm diclofenac gel free shipping, including ovarian can- cer, contributing to the development of resistance mechanisms. Multiple metastatic lesions from individual patients were analyzed along with 22 paired pretreatment and posttreatment samples. In the paired primary and relapse cohort, they observed a greater degree of genomic change in tumors from patients that were initially sensi- tive to chemotherapy and had longer progression-free interval compared with tumors from patients that were resistant to primary chemotherapy. Mapping the mechanisms that confer resistance may enable prediction of whether some women are likely to respond to a certain drug or not, and find ways of reversing resistance. Pathway Targeted Therapies for Ovarian Cancer Mouse ovarian epithelial tumor cell lines that contain various combinations of genetic alterations in the p53, c-myc, K-ras and Akt genes have been used as model for the molecular characterization of pathway-targeted therapy. Response to a par- ticular anticancer drug can be related to the signaling pathway involved. Rapamycin effectively inhibits the growth of tumors that rely on Akt signaling for proliferation, whereas tumors in which Akt signaling is not the driving force in proliferation are resistant to rapamycin. The introduction of activated Akt to the rapamycin-resistant cells does not render the cells susceptible to rapamycin if they can use alternative pathways for survival and proliferation. Therefore, the rapamycin-sensitive tumors develop resistance to rapamycin when presented with alternative survival pathways, such as the mitogen-activated extracellular kinase signaling pathway. These findings indicate that mammalian target of rapamycin inhibitors may be effective in a subset of tumors that depend on Akt activity for survival but not effective in all tumors that exhibit Akt activation. Tumors with alternative survival pathways may require the inactiva- tion of multiple individual pathways for successful treatment. These results have significant implications for the use of pathway-targeted therapy in advanced human ovarian cancers, which typically display numerous genetic alterations that are likely to require impairment of multiple molecular pathways for successful treatment. Universal Free E-Book Store Personalized Management of Cancers of Various Organs 323 Interruption of multiple specific biochemical pathways may be a promising therapeutic strategy in ovarian carcinomas that exhibit resistance to an individual targeted therapy. This strategy may be useful for developing personalized therapies for ovarian cancer. Resistance to platinum therapy is a major obstacle that needs to be overcome in the treatment of ovarian cancer patients. These findings indicate that targeting the Notch pathway significantly increases tumor sensitivity to platinum therapy. Both platinum-resistant and platinum-sensitive relapses may benefit from such an approach as clinical data suggest that all relapses after platinum therapy are increas- ingly platinum resistant. A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients’ lives. Overall, these discoveries set the stage for approaches to the treatment of high-grade serous ovarian cancer in which aberrant genes or networks are detected and targeted with therapies selected to be effective against these specific aberrations. Targeting Hematogenous Metastasis of Ovarian Cancer Ovarian cancer has a clear predilection for metastasis to the omentum, but the underlying mechanisms involved in ovarian cancer spread were not well under- stood. These results highlight hematogenous spread as an important mode of ovarian cancer metastases and use of this knowledge to design better strategies for prevention and treatment. An estimated 80 % of platinum-resistant ovarian cancer patients have been found to have folate receptor-positive disease, and ~40 % express the receptor, as detected by etarfola- tide, in all of their target tumor lesions. Compared to patients who do not express folate receptors on their tumors, folate receptor-positive patients have been shown to have a poorer overall prognosis. Vintafolide is a conjugate of folic acid (vitamin B9) linked to an anticancer agent, the potent vinca alkaloid desacetylvinblastine hydrazide. Since cancer cells Universal Free E-Book Store Personalized Management of Cancers of Various Organs 325 generally consume higher levels of folate than normal cells to fuel their growth, some cancer cell types, including ovarian, have high concentrations of the folate receptor on their surface. Vintafolide is designed to selectively target the folate receptor to deliver the anti-cancer agent to the cancerous tissue. Tumors that have high concentrations of the folate receptor are identified by etarfolatide, a non- invasive imaging diagnostic agent. Intravenous folic acid is used with 99m Tc- etarfolatide for the enhancement of image quality.
Signs of bad prognosis are persistently rising serum creatinine discount diclofenac gel 20 gm fast delivery, heavy proteinuria cheap 20 gm diclofenac gel mastercard, persistent hypertension with gross haematuria and presence of glomerular crescents in renal biopsy buy diclofenac gel 20gm low price. Renal involvement may be the dominant lesion or may be just an incidental finding purchase 20gm diclofenac gel free shipping. Generally, when the kidney is involved, the prognosis and type of treatment are changed drastically. It affects caucasian more than black and occurs more in adolescents than in elderly. Most probably the disease reflects an exaggerated response to common environmental agents in a genetically susceptible host. But, if kidney biopsies are obtained and examined thoroughly, all patients will show glomerular disease. In clinical practice lupus nephritis is responsible for more than 5% of patients presenting with glomerulonephritis. Clinical Manifestations of Lupus Nephritis: It is known that 50-90% of lupus patients will show manifestation(s) of renal disease. Many of such patients may not show any clinically apparent renal disease, but when subjected to kidney biopsy glomerular lesions will be detected. Clinical presentation of lupus nephritis patient may vary from asymptomatic urine abnormality to rapidly progressive glomerulonephritis. Furthermore, some patients show manifestations of tubulointerstitial nephritis (e. Treatment: There is no standard regimen for the treatment of lupus nephritis patient. The available treatment protocols include: (1) Prednisolone, oral, 1mg/kg/d, (2) 3-5 days pulses of methyl prednisolone 500-1000 mg each, (3) Cytoxan (cyclophosphamide) 2-3 mg/kg orally/d (4) cytoxan 0. Generally, the target of treatment is to induce remission, then to maintain it by small doses of either one drug (Prednisolone) or combined (e. The more active the disease, the more aggressive the treatment will be and vice versa. The classic type of polyarteritis nodosa may present with ischaemic renal changes, hypertension, immobilization with renal infarctions or haemorrhage related to the kidney (haematuria, peri-renal hematoma resulting from rupture of aneurysm). Treatment: Patients with active urine sediment (proteinuria, haematuria, casts), renal impairment and documented lesions in renal biopsy should be treated by immunosuppressive drugs to achieve remission. The dose and whether prednisolone alone or combined drug regimen, depend on disease activity and initial reponse to treatment. Cyclosporin A 5mg/kg/d can be used when these drugs are toxic or have no satisfactory response. Renal involvement is documented in 10-30% of the cases, but in some series, it reaches up to 90% of the cases. The primary abnormality is most probably defective handling of mucosally presented antigen. Light microscopy usually shows changes variable from minimal abnormalities, mesangial proliferation, focal mesangial proliferation with crescent formation to membranoproliferative glomerulonephritis. Immunofluorescent microscopy will show predominant IgA deposits which are mainly mesangial, and this is usually accompanied with C3, IgG and to a lesser extent IgM. Clinical features: 1- The disease usually occurs in winter, following upper respiratory infection or following exposure to allergen. Gastrointestinal manifestations including abdominal pain, bloody diarrhea and or melena. However 5-20% of cases (especially adults) may show persistence or even progression to uraemia. Signs of bad prognosis include patients with: severe disease at presentation, persistent nephrotic syndrome, severe renal impairment and crescentic G.