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Depigmenting Agents
Published in Vineet Relhan, Vijay Kumar Garg, Sneha Ghunawat, Khushbu Mahajan, Comprehensive Textbook on Vitiligo, 2020
Vaccines using melanoma-associated antigen were reported by many authors to produce depigmentation by eliciting an autoimmune response directed against malignant but also normal melanocytes. 4-(p-hydroxyphenyl)-2-butanone and 4-n-butylresorcinol not only inhibit tyrosinase but also act as cytotoxic agents as they are oxidized to their quinonic forms, leading to a double effect. Hydroquinone in higher concentrations of more than 4%, IFN-gamma, and alkylating agent busulfan should be further investigated as topical depigmenting agents for use in human beings with vitiligo universalis. Some compounds like N-acetyl-4-S-cysteaminylphenol, N-2,4-acetoxyphenyl thioethyl acetamide, and N-hydroxycinnamoyl-phenalkylamides have been proposed as anti-melanoma drugs as well as for use as hypopigmenting agents. Ethanolic extracts of Myrica rubra dried leaves have shown good depigmenting effects in vitro and pseudo superoxide dismutase activity. They contain quercetin, myricetin, and some 3-O-rhamnoside derivatives. In vivo studies have been recommended to evaluate their potential use as depigmenting agents [39]. Taking into consideration recent findings on the possible role of immune adjuvants such as imiquimod, CpG oligonucleotides, and heat shock proteins in melanocyte destruction, supplementing the depigmenting effect of MBEH with such adjuvants has been suggested [40].
Clinical Studies In Oncology
Published in Siegfried Matzku, Rolf A. Stahel, Antibodies in Diagnosis and Therapy, 2019
Jan Schmielau, Wolff Schmiegel
The high molecular weight melanoma associated antigen (HMW-MAA) is expressed in a high degree on melanoma lesions with restricted distribution in normal tissue. This tumor associated antigen served as a target for antibodies, which have been used in clinical studies for idiotype vaccination. Mittelman et al. (1990) applied the murine anti-HMW-MAA monoclonal antibody MF 11-30 in two consecutive studies to patients with metastatic melanoma. The antibody was injected subcutaneously at an amount of 0.5, 1, and 3 mg at day 0, 7, and 28 and up to 10 times to achieve a detectable immunization. Registrating a dose dependent anti-idiotypic antibody level with escalating single doses of up to 4 mg, and three minor responses, the authors conducted a second trial with 2mg subcutaneously administered MF 11-3 with the same time schedule and a maximum of 12 injections in 19 evaluable patients (Mittelman et al., 1990). Separating the 16 patients, which developed detectable Ab3, into two groups according to their Ab3 level, a significantly prolonged average survival time of 55 weeks compared to 19 weeks was noted with Ab3 levels of 1 :8 and more. One CR was obtained.
Predominantly Immature Interstitial and Intra-alveolar Fibrosis
Published in Philip T. Cagle, Timothy C. Allen, Mary Beth Beasley, Diagnostic Pulmonary Pathology, 2008
Proliferating fibroblasts are immunopositive for vimentin and sometimes for smooth muscle actin antibodies, indicating myofibroblastic differentiation, but they are generally negative for desmin. Immunohistochemical stains, though usually not necessary, can be useful in differentiating immature smooth muscle proliferation in lymphangioleimyomatosis (LAM), which is additionally positive for desmin, HMB-45, and melanoma-associated antigen recognized by T cells 1 (MART1) in addition to vimentin and smooth muscle actin. CD1a and S100 protein stains help to detect Langerhans cell collections in LCH cases. In small biopsies, inflammatory myofibroblastic tumor (IMT), also known as inflammatory pseudotumor and plasma cell granuloma, may mimic BOOP. IMT shows a spectrum of fibroblastic and myofibroblastic cellular proliferations that contain variable amount of inflammatory cells including plasma cells, lymphocytes, macrophages, and occasional eosinophils. IMT typically presents as a solitary, well-demarcated and lobulated mass on radiological study, which replaces the underlying lung tissue, in contrast to BOOP that has preserved underlying alveolar architecture (Fig. 7). In small biopsies, distinction can be difficult. Besides, IMT may show BOOP reaction at the periphery. A subset of IMT cases, especially in patients younger than 30 years of age, show strong anaplastic lymphoma kinase 1 (ALK-1) positivity, which would be also helpful (Fig. 8). An algorithm for histopathological differential diagnosis of immature fibrosis is summarized in 1 and 2.
Identification and validation of a novel prognostic circadian rhythm-related gene signature for stomach adenocarcinoma
Published in Chronobiology International, 2023
Lei Qian, Xiaochen Ding, Xiaoyan Fan, Shisen Li, Yihuan Qiao, Xiaoqun Zhang, Jipeng Li
The melanoma-associated antigen family comprises the melanoma antigen D1 (MAGED1), which is abundant in healthy human tissues and critical for controlling apoptosis, gene transcription, and osteogenesis, as well as the cell cycle, circadian rhythm, and sleep (Bertrand et al. 2008; Wang et al. 2011). Recently, it was demonstrated that MAGED1 is intimately associated to the emergence of malignant tumors, such as breast and esophageal cancer (Du et al. 2009; Tian et al. 2005; Yang et al. 2014). In addition, MAGED1 has the capacity to affect Bmal1, Rev-erbα, and other genes by altering the transcriptional activity of RORα proteins, thus transmitting external cues that will coordinate physiological processes and circadian rhythms. MAGED1 is, therefore, necessary for circadian clock stability (Wang et al. 2010).
Systemic T-cell and humoral responses against cancer testis antigens in hepatocellular carcinoma patients
Published in OncoImmunology, 2022
Lisanne Noordam, Monique T.A. de Beijer, Shanta Mancham, Isabel Vogler, Patrick P.C. Boor, Valeska de Ruiter, Robbie Luijten, Jan N.M. IJzermans, Ugur Sahin, Marco J. Bruno, Dave Sprengers, Sonja I. Buschow, Jaap Kwekkeboom
An important prerequisite for clinical efficacy of vaccines is antigen immunogenicity in the target patient population. Yet, immunogenicity is largely unknown for our panel of CTAs in HCC patients. To determine whether these CTAs are immunogenic in HCC patients, we analyzed systemic CD4+ and CD8+ T-cell responses as well as IgG-responses against six CTAs of our panel (melanoma-associated antigen 1 [MAGEA1], melanoma-associated antigen 9 [MAGEA9], melanoma-associated antigen B2 [MAGEB2], melanoma-associated antigen C1 [MAGEC1], melanoma associated antigen C2 [MAGEC2], P antigen family member 1 [PAGE1]) in HCC patients. We also included synovial sarcoma, X breakpoint 2 (SSX2), a thoroughly studied tumor-restricted and immunogenic CTA with known expression in HCC.23–25 Because systemic T-cell responses against TAAs may be transiently enhanced after local tumor ablation in HCC patients,26,27 we analyzed these immunological responses before and at several time points after RFA or TACE.
Discovery of a potential biomarker for immunotherapy of melanoma: PLAC1 as an emerging target
Published in Immunopharmacology and Immunotoxicology, 2020
Ahmad-Reza Mahmoudi, Roya Ghods, Azadeh Rakhshan, Zahra Madjd, Mohammad-Reza Bolouri, Jafar Mahmoudian, Shaghayegh Rahdan, Mohammad-Reza Shokri, Shima Dorafshan, Mehdi Shekarabi, Amir-Hassan Zarnani
Interferons (IFNs), cytokines with immunomodulatory effects, have also been tested in melanoma for their ability to enhance antigen presentation to T cells [8,9] and pegylated interferon α-2β is among FDA-approved therapeutic modalities for surgically treated melanoma patients [10,11]. Apart from cytokine therapies, check point inhibitors have also been tested in patients with melanoma, for example monoclonal antibodies against immune-checkpoint molecules such as programmed cell death protein 1 (PD-1), are approved for treatment of patients with advanced melanoma [12–14]. In addition anti-CTLA-4 antibody therapy is among such immunotherapic approaches for the treatment of unresectable melanoma; but poor response rates are often seen in anti-CTLA-4 antibody therapies [15,16]. To obtain immunological responses directed against melanoma cancer cells, several candidate antigens such as melanoma antigen-1 (MAGE1), melanoma-associated antigen recognized by T cells (MART-1), and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) have been targeted in clinical trials in patients with advanced or nonresectable melanoma as well as patients with surgically resected melanoma [17]. Collectively, available results show clinical outcomes which are modest at best.