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Cimetidine for recurrent respiratory papillomatosis in pregnancy as an alternative adjuvant treatment

Tan SH, Ghauth S, Liew YT, Abu Bakar Z

Eur Arch Otorhinolaryngol, 2024 Feb;281(2):1053-1055.
PMID: 38078971 DOI: 10.1007/s00405-023-08364-4

BACKGROUND: We report the first case of cimetidine as an alternative adjuvant therapy in a pregnant woman with recurrent respiratory papillomatosis (RRP). A 40 year old woman at 19 week gestation presented with progressive hoarseness and shortness of breath for 1 month. Flexible nasopharyngolaryngoscopy revealed multiple papillomatous lesions over both vocal cords and subglottic area obstructing 60% of her airway. She had previously been diagnosed with juvenile onset RRP at the age of 5 and underwent endoscopic clearance regularly every 6 months.
METHOD: The patient was started on a trial of oral cimetidine at a dose of 30 mg/kg and responded well, eventually requiring endoscopic excision only after 2 years. Subsequently, she underwent in vitro fertilisation treatment and stopped taking her cimetidine. After undergoing endoscopic clearance of her papillomata under general anaesthesia, she restarted on cimetidine during her 2nd and 3rd trimester.
RESULTS: Ensuing follow-up demonstrated stable minimal papillomata lesions on her right inferior surface of her vocal cord with no recurrence on her left vocal cord and subglottic area.
CONCLUSION: Cimetidine is generally safe and not known to be associated with any major teratogenic risks during pregnancy. RRP is postulated to worsen in pregnant women due to the increase in oestrogen levels during pregnancy. Hence, adjuvant therapy was imperative for our patient to reduce recurrent papillomata formation during her pregnancy. Larger scale studies are warranted to assess the use of long-term high-dose cimetidine in terms of efficacy and safety in pregnancy.

Matched MeSH terms: Adjuvants, Immunologic/therapeutic use
The Immunomodulatory Potential of Selected Bioactive Plant-Based Compounds in Breast Cancer: A Review

Baraya YS, Wong KK, Yaacob NS

Anticancer Agents Med Chem, 2017;17(6):770-783.
PMID: 27539316 DOI: 10.2174/1871520616666160817111242

Breast cancer has continued to cause high cancer death rates among women worldwide. The use of plants' natural products in breast cancer treatment has received more attention in recent years due to their potentially wider safety margin and the potential to complement conventional chemotherapeutic drugs. Plantbased products have demonstrated anticancer potential through different biological pathways including modulation of the immune system. Immunomodulatory properties of medicinal plants have been shown to mitigate breast cancer cell growth. Different immune cell types participate in this process especially cytotoxic T cells and natural killer cells, and cytokines including chemokines and tumor necrosis factor-α. Medicinal plants such as Glycyrrhiza glabra, Uncaria tomentosa, Camellia sinensis, Panax ginseng, Prunus armenaica (apricot), Allium sativum, Arctium lappa and Curcuma longa were reported to hold strong potential in breast cancer treatment in various parts of the world. Interestingly, research findings have shown that these plants possess bioactive immunomodulators as their main constituents producing the anticancer effects. These immunomodulatory compounds include ajoene, arctigenin, β-carotene, curcumin, epigallocatechin-3-gallate, ginsan, glabridin and quinic acid. In this review, we discussed the ability of these eight immunomodulators in regulating the immune system potentially applicable in breast cancer treatment via anti-inflammatory (curcumin, arctigenin, glabridin and ajoene) and lymphocytes activation (β-carotene, epigallocatechin-3-gallate, quinic acid and ginsan) properties, as well as future research direction in their use for breast cancer treatment.

Matched MeSH terms: Adjuvants, Immunologic/therapeutic use*
Fulltext Gut Immune System and the Implications of Oral-Administered Immunoprophylaxis in Finfish Aquaculture

Lee PT, Yamamoto FY, Low CF, Loh JY, Chong CM

Front Immunol, 2021;12:773193.
PMID: 34975860 DOI: 10.3389/fimmu.2021.773193

The gastrointestinal immune system plays an important role in immune homeostasis regulation. It regulates the symbiotic host-microbiome interactions by training and developing the host's innate and adaptive immunity. This interaction plays a vital role in host defence mechanisms and at the same time, balancing the endogenous perturbations of the host immune homeostasis. The fish gastrointestinal immune system is armed with intricate diffused gut-associated lymphoid tissues (GALTs) that establish tolerance toward the enormous commensal gut microbiome while preserving immune responses against the intrusion of enteric pathogens. A comprehensive understanding of the intestinal immune system is a prerequisite for developing an oral vaccine and immunostimulants in aquaculture, particularly in cultured fish species. In this review, we outline the remarkable features of gut immunity and the essential components of gut-associated lymphoid tissue. The mechanistic principles underlying the antigen absorption and uptake through the intestinal epithelial, and the subsequent immune activation through a series of molecular events are reviewed. The emphasis is on the significance of gut immunity in oral administration of immunoprophylactics, and the different potential adjuvants that circumvent intestinal immune tolerance. Comprehension of the intestinal immune system is pivotal for developing effective fish vaccines that can be delivered orally, which is less labour-intensive and could improve fish health and facilitate disease management in the aquaculture industry.

Matched MeSH terms: Adjuvants, Immunologic/therapeutic use*
Systemic anti-CTLA-4 and intravesical Bacille-Calmette-Guerin therapy in non-muscle invasive bladder cancer: Is there a rationale of synergism?

Fahmy O, Khairul-Asri MG, Stenzl A, Gakis G

Med Hypotheses, 2016 Jul;92:57-8.
PMID: 27241256 DOI: 10.1016/j.mehy.2016.04.037

Although intravesical instillation of Bacille-Calmette-Guerin (BCG) immunotherapy was approved many decades ago as a first line therapy for intermediate to high-risk non-muscle invasive bladder cancer, its long-term efficacy is still arguable as a proportion of up to 30-40% of patients will develop recurrence or progression of their disease. Based on currently available data on the clinical application of checkpoint inhibitors in solid tumors, the mucosa-associated lymphoid tissue seems to be a main target for anti-CTLA-4 antibodies. In this manuscript we hypothesize that the combination of anti-CTLA-4 therapy with BCG might enhance the immune activity in the bladder submucosal tissue, and subsequently, improve oncological outcomes of NMIBC.

Matched MeSH terms: Adjuvants, Immunologic/therapeutic use
Effects of supplementation with tocotrienol-rich fraction on immune response to tetanus toxoid immunization in normal healthy volunteers

Mahalingam D, Radhakrishnan AK, Amom Z, Ibrahim N, Nesaretnam K

Eur J Clin Nutr, 2011 Jan;65(1):63-9.
PMID: 20859299 DOI: 10.1038/ejcn.2010.184

Vitamin E is an essential fat-soluble vitamin that has been shown to induce favorable effects on animal and human immune systems. The objective of this study was to assess the effects of tocotrienol-rich fraction (TRF) supplementation on immune response following tetanus toxoid (TT) vaccine challenge in healthy female volunteers.

Matched MeSH terms: Adjuvants, Immunologic/therapeutic use*
Fulltext A randomized controlled phase 2 trial of the blood stage AMA1-C1/Alhydrogel malaria vaccine in children in Mali

Sagara I, Dicko A, Ellis RD, Fay MP, Diawara SI, Assadou MH, et al.

Vaccine, 2009 May 18;27(23):3090-8.
PMID: 19428923 DOI: 10.1016/j.vaccine.2009.03.014

A double blind, randomized, controlled Phase 2 clinical trial was conducted to assess the safety, immunogenicity, and biologic impact of the vaccine candidate Apical Membrane Antigen 1-Combination 1 (AMA1-C1), adjuvanted with Alhydrogel. Participants were healthy children 2-3 years old living in or near the village of Bancoumana, Mali. A total of 300 children received either the study vaccine or the comparator. No impact of vaccination was seen on the primary endpoint, the frequency of parasitemia measured as episodes >3000/microL/day at risk. There was a negative impact of vaccination on the hemoglobin level during clinical malaria, and mean incidence of hemoglobin <8.5 g/dL, in the direction of lower hemoglobin in the children who received AMA1-C1, although these differences were not significant after correction for multiple tests. These differences were not seen in the second year of transmission.

Matched MeSH terms: Adjuvants, Immunologic/therapeutic use
Acemannan, a polysaccharide extracted from Aloe vera, is effective in the treatment of oral aphthous ulceration

Bhalang K, Thunyakitpisal P, Rungsirisatean N

J Altern Complement Med, 2013 May;19(5):429-34.
PMID: 23240939 DOI: 10.1089/acm.2012.0164

The objective of this study was to elucidate the safety and effectiveness of acemannan, a polysaccharide extracted from Aloe vera, in the treatment of oral aphthous ulceration.

Matched MeSH terms: Adjuvants, Immunologic/therapeutic use*
Transfer factor with anti-EBV activity as an adjuvant therapy for nasopharyngeal carcinoma: a pilot study

Prasad U, bin Jalaludin MA, Rajadurai P, Pizza G, De Vinci C, Viza D, et al.

Biotherapy, 1996;9(1-3):109-15.
PMID: 8993768

Overall survival of nasopharyngeal carcinoma (NPC) at UICC stage IV still remains unsatisfactory even with combination chemotherapy (CT) and radio-therapy (RT). In view of the association of reactivation of Epstein-Barr virus (EBV) with the development and recurrence of NPC, immunotherapy in the form of transfer factor (TF) with specific activity against EBV (TF-B1) was suggested as an adjuvant to a combination of CT and RT in order to improve survival. In the present study, 6 UICC stage IV patients received TF-B1 and another 6 patients matched for disease stage were given TF prepared from peripheral blood leucocytes (TF-PBL). Results were compared with another 18 patients matched by age, sex, and stage of disease who received standard therapy without TF during the same period (C group). After a median follow up of 47.5 months, the survival for the TF-B1 group was found to be significantly better (P = < 0.05) than the PBL and C group. While the 8 patients with distant metastasis (DM), not treated with TF-B1 (6 in the control and 2 in the PBL group), died due to progressive disease (average survival being 14.3 months), both patients with DM in the TF-B1 group had complete remission: one died of tuberculosis after surviving for 3.5 years and another is still alive, disease free, after 4.2 years. Although the series involved a small number of cases, the apparent effect of adjuvant immunotherapy in the form of TF with anti-EBV activity is of considerable interest.

Matched MeSH terms: Adjuvants, Immunologic/therapeutic use*