Gastrointestinal cancer
Michael JG Farthing, Anne B Ballinger in Drug Therapy for Gastrointestinal and Liver Diseases, 2019
Cancers of the biliary tract, including carcinoma of the gall bladder and cholangiocarcinoma, are rare, and few clinical trials have addressed their management. Patients frequently present with advanced disease that is not amenable to surgical resection, and the prognosis is poor, with a median survival of less than 6 months. Palliative chemotherapy may have a role, as suggested by a trial comparing 5-fluorouracil, leucovorin and etoposide with best supportive care alone. This demonstrated improved survival (6 versus 2.5 months; p < 0.01) and quality of life in the chemotherapy arm.40 This trial included both biliary and pancreatic cancer patients (a feature of many studies of this disease) but the benefits of treatment were seen in both tumour types. 5-Fluorouracil is the most commonly used single agent, with response rates of about 10–20%. Combination of cisplatin and 5-fluorouracil increased the response rate to 32%,64 and further addition of epirubicin (the ECF regimen) produced a 40% response rate and a 40% 1-year survival.65 An interesting agent in this disease is alpha-interferon. A regimen combining a 5-day infusion of 5-fluorouracil with alpha-interferon on Days 1, 3 and 5, repeated every 2 weeks produced a response rate of 39%, and a median survival of 1 year among 19 patients.66
New Understanding of the Nature and Causes of Major Depression
Scott Mendelson in Herbal Treatment of Major Depression, 2019
Suspicions that inflammation might be involved in MDD arose from seeing similarities between the illness and what is referred to as “sickness behavior.” The syndrome of sickness behavior includes malaise, fatigue, lack of motivation, decrease in appetite, withdrawal from the environment, and depressed mood. Ostensibly, these symptoms of illness serve to force us to rest and keep us away from dangers we may be incapable of surviving because of loss of strength and vitality. Sickness behavior is due to the effects of cytokines. One of the first cytokines to be identified was alpha-interferon. Alpha-interferon stimulates the immune system to fight off viral infection, and it was one of the first successful treatments of the viral infection hepatitis C. However, the most common and predictable side effects of interferon treatment were depressed mood, malaise, fatigue, irritability, insomnia, poor memory, and difficulty concentrating.31 Indeed, psychiatrists were often enlisted into treatment teams to help manage the sometimes severe psychiatric side effects of interferon. Individuals already suffering MDD, or those with histories of the condition, were sometimes eliminated as candidates for interferon therapy.
Viruses and Antiviral Agents
John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie in Basic Sciences Endocrine Surgery Rhinology, 2018
Interferons (IFN) were the first cytokines that demonstrated efficacy in the treatment of viral infections. They are a group of naturally occurring cytokines with important immunomodulatory and antiviral activities. Clinically, they have uses in the treatment of certain malignancies and also as antiviral agents. IFNs exert their therapeutic action both by direct cellular effects, via action on cell surface receptors leading to activation of signalling pathways, and by indirect mechanisms involving induction of host anti-tumour responses.31 Interferon as a therapeutic agent is less effective in vivo than hoped. Unpleasant adverse effects such as ‘flu-like’ symptoms and haematological complications limit its use. However, alpha-interferon is used with success in chronic hepatitis B and C infection, often in conjunction with lamivudine and ribavirin, respectively.
The immunology of SARS-CoV-2 infection, the potential antibody based treatments and vaccination strategies
Published in Expert Review of Anti-infective Therapy, 2021
Zahra Payandeh, Niloufar Mohammadkhani, Mohsen Nabi Afjadi, Saeed Khalili, Masoumeh Rajabibazl, Zahra Houjaghani, Masoomeh Dadkhah
Effective innate immune response against the viral infection is correlated to interferon type I (IFN1) and its downstream pathway controlling viral replication and induction of effective adaptive immune response [43]. The PAMPs of RNA viruses not only are recognized by either the endosomal RNA receptors or TLR3 but also identified by TLR7 or the cytosolic RNA sensor (RIG-I/MDA5). Involvement of these molecules could lead to activation of the downstream signaling cascade of NF-κB and IRF3 accompanied by their nuclear translocation and finally IFN1expression [28,43,44]. Type I IFN activates the JAK-STAT pathway via IFNAR and JAK1/TYK2 kinases phosphorylate STAT1/STAT2. The STAT1/2 complexes with IRF9 and induces the nuclear transcription of IFN-stimulated genes (ISGs) which are under the control of promoters containing IFN-stimulated response element (ISRE) [28].
Fixed duration vs. prolonged duration treatment after first line therapy in patients with systemic light chain amyloidosis
Published in Amyloid, 2022
Alfonso Rivera Duarte, Donna Reece, Xuan Li, Wei Xu, Harminder Paul, Esther Masih-Khan, Andrew Winter, Rodger Tiedemann, Anca Prica, Christine Chen, Suzanne Trudel, Vishal Kukreti
Another strategy was explored in phase 2 clinical trial that administered consolidation with bortezomib and dexamethasone for six cycles after ASCT for those patients that did not achieve a hematological CR. In this study, Landau et al. found that hematological response improved in 86% of patients and 55% had evidence of organ improvement as well [22]. Another older prospective study described results with prolonged administration of alpha interferon and dexamethasone as maintenance therapy following an induction phase. However, alpha interferon is no longer used, and toxicity was considerable [23].
Pharmacotherapy for recurrent respiratory papillomatosis (RRP): a treatment update
Published in Expert Opinion on Pharmacotherapy, 2021
The pegylated form of alpha-interferon (peg-interferon alfa-2a, Pegasys®, Roche) is thought to enhance alpha interferons activity [51]. It requires less frequent administration (once weekly) and has fewer side effects [52]. The pegylated form has been used with granulocyte monocyte colony-stimulating factor (GM-CSF) to treat AORRP patients [53]. 9/11 patients who had this treatment administered subcutaneously had no relapse during treatment. This may indicate that the effects of pegylated alpha-interferon deliver enhanced outcomes.
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