Skin Cancer Pill
The choice of treatment for basal cell carcinoma includes surgical removal of the affected area by excision, cryosurgery or radiation therapy. The contemporary method of treatment introduced is through the administration of skin cancer pills called as Erivedge approved by United States food and drug administration society. Erivedge pills are designed to treat advanced levels of basal cell carcinoma. This drug was designed to prevent surgical or radiation associated intervention in sensitive areas such as the nose regions of the face where the carcinoma predominantly occurs.
Erivedge the revolutionary pill for the treatment of advanced basal carcinoma is chemically known as vismodegib. This oral medicine is associated with the prevention of overactive signaling of the Hedgehog pathway by binding to a trans membrane protein occurring in basal cell carcinoma. The continuum of the Hedgehog pathway may result in the metastases of the carcinoma.
Vismodegib (erivedge) is highly permeable and has low aqueous solubility. The plasma protein binding in patients is very high. It binds to albumin and alpha- 1acid glycoprotein. The metabolic pathways associated are oxidation, glucouronidation and also pyridine ring cleavage. The excretion of the drug predominantly happens through the hepatic route. The absorption and retention of the drug occurs in feces and urine.
Dosage and administration
The recommended dosage of erivedge is 150mg taken orally once a day. The duration of medication has to continue until the complete prophylaxis of the disease. Discontinuation of erivedge is only advisable under the incidence of drug toxicity. Additional doses of erivedge are not recommended in case of missing a dose; the next dose has to be resumed. Erivedge intake does not depend upon food intake.
Contraindications and adverse effects
Erivedge is considered as teratogenic, embryo toxic and fetotoxic drug and hence it is not recommended for pregnant women. If administered, the effects include severe birth defects such as craniofacial anomalies, absent or fused digits and also open perineum. Erivedge is also not advisable for nursing mothers as it may be excreted in the milk.
Erivedge consuming patients are advised not to donate blood for a period of seven months. Many adverse effects were reported in the clinical trials conducted on erivedge some of which are muscle spasms, arthralgia, fatigue, diarrhea, weight loss, alopecia, constipation and also decreased appetite. Erivedge intervenes with other drugs such as clarithromycin etc. in leading to adverse reactions. Erivedge usage is not recommended in children as it intervenes in the epiphyseal growth plate affecting the bones; causing damage to the teeth by necrosis, cysts in the dental pulp and also ossification of the root canal.
Geriatric use of erivedge is also not recommended. The other conditions under which the use of erivedge is not recommended is in patients having hepatic and renal impairments.
The process of localizing proteins in cells of a tissue section using the principle of antigens in tissue binding to their respective antibodies is known as Immunohistochemistry (IHC). This technique is widely used for the diagnosis of cancer. The antibodies are tagged with color-producing dyes to make them easily visible. Horseradish peroxidase and phosphatase are the two commonly used color-producing tags. Different fluorophores like FITC are also used to tag the antibodies as an alternate method. This method is widely used in confocal laser scanning microscopy to visualize two interacting protein molecules. Adinocarcinomas, Hodgkin's disease, yolk sac tumors and hepatocellular carcinoma, Gastrointestinal Stromal Tumors (GIST) and prostate cancer are diagnosed by conducting immunohistochemistry using various antigens like Carcinoembryonic antigen, CD 15 & CD30 or Alpha fetoprotein or CD117 or prostate specific antigen accordingly. Direct and indirect methods are the two methods used for the immunohistochemical staining of antigens.
In the direct method, one labelled antibody is used for staining. The antibody directly binds to the antigen which is being stained. Involving only one labeled antibody (FITC conjugated antiserum), this direct method is also known as one-step staining method. Though this method is quick since it uses only one antibody, it is rarely used after the indirect method was introduced.
In the indirect method of immuno-histochemical staining, one antibody is used against the antigen which is being examined and a second labelled antibody is used against the first. The unlabelled primary antibody or the first layer reacts with tissue antigen and the second layer or the labelled secondary antibody reacts with the primary antibody. This indirect method is considered more sensitive, since there is good signal amplification noticed through many secondary antibody reactions with various antigenic sites on the primary antibody.
Progressive Massive Fibrosis
Progressive massive fibrosis is a lung disease that is predominantly reported in people who work in mines. Hence it is also called Coal worker's Pneumoconiosis. Fibrosis is a nodular formation in different regions of the body. Often lungs are the most vulnerable. This is because of aerosol initiation, which has a faster chance of nodule formation causing tissue damage.
Most conditions associated with massive fibrosis are coherent to silicosis and pneumoconiosis. Lesions are caused due to tissue necrosis, which leads to hardening of the tissue forming nodular structures. In case of progressive fibrosis, massive scars are noticed because of dense agglomeration of the thickened nodules. These nodules predominantly appear in the upper lobes causing respiratory difficulties.
The onset of this disease is triggered by macrophage proliferation in the respective regions. The macrophages engulf the inhaled silicon particles causing the production of interleukin -I which facilitates the chemical mediation for tissue necrosis. Silica is commonly found in these necrotic nodules. The adverse effects of these silica particles are the onset of Pulmonary Alveolar Proteinosis (PAP) causing the accumulation of large particles, which can be noticed as spaces on radiological examination. Along with the affected upper lobe, the interstitial zones of the lower lobe are also obstructed and bronchial regions are damaged with the infiltration of the nodules. Honeycomb lung or asbestos bodies are common references for progressive massive fibrosis as both these conditions have giant cells upon pathological examination. Bronchogenic carcinoma and mesothelioma are the associated adverse conditions of progressive massive fibrosis.
The evaluation of patients suffering progressive massive fibrosis includes the understanding of the type of chemical or particle inhaled as it enables the physicians to rule out diagnostic errors. In cases such as pleural plaques, calcified regions of the lungs are noticed which is another cause of asbestosis. The lower region of the lungs are predominantly affected. In case of interstitial fibrosis, the bronchus and alveoli are affected with characteristic nodules of the upper and mid region. The evaluation is based on the type of chemical and the respective interleukins it releases. Most patients associated with these conditions are miners, shipyard workers, automobile mechanics and petrochemical employees.
Diagnosis and Treatment
Most diagnostic evaluations are radiological in origin as the MRI provides detailed description about the zones of the fibrosis and the size of each nodule. Histopathological analysis studies the intensity of the necrosis, giant cell presence and the macrophagic proliferation patterns. The treatment pattern is based on symptomatic analysis. Since the condition includes both lower and upper lobes, any associated mycobacterial infection has to be treated. Oxygen is given as a critical care measure in patients with hypoxemia. Surgical interventions are applicable in case of intense and irreversible tissue necrosis. Patients with progressive massive fibrosis are advised to quit smoking if as it causes intense damage.
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Bibliography / Reference
Collection of Pages - Last revised Date: July 1, 2020