We report that humanleukocyte interferon preparations increase theexpression of82-microglobulin by 100-200% onthesurface ofnormal fibroblast andmelanoma cell lines sensitive tointerferon. This increase inexpression canbe correlated with anincrease inHLAsynthesis asmeasured byin- corporation of(3S)methionine inthese antigens. This enhanced HLAsynthesis, which is5-to17-fold, istime dependent anddose related. Synchronized cells intheGO/GI phase ofthecell cycle appear tobemoresensitive tothis interferon action. Neither an increase insurface expression norinHLAsynthesis isobserved inamelanoma cell line resistant totheantiviral andantigrowth effects ofinterferon. Furthermore, there appears tobeastronger correlation between this increased HLAsynthesis andtheantiviral function thanbetween itandtheantiproliferative action of interferon. Interferons areglycoproteins that have antiviral, immunoreg- ulatory, andantiproliferativ e functions. Previously, human leu- kocyte interferon hasbeen shown toenhance theexpression of surface major histocompatibility antigens, HLA-Aand-Band

Interferon increases HLA synthesis inmelanoma cells: Interferon-resis tant and-sensitive cell lines

Sarcomas are heterogeneous malignant tumors of mesenchymal origin characterized by more than 100 distinct subtypes. Unfortunately, 25–50% of patients treated with initial curative intent will develop metastatic disease. In the metastatic setting, chemotherapy rarely leads to complete and durable responses; therefore, there is a dire need for more effective therapies. Exploring immunotherapeutic strategies may be warranted. In the past, agents that stimulate the immune system such as interferon and interleukin-2 have been explored and there has been evidence of some clinical activity in selected patients. In addition, many cancer vaccines have been explored with suggestion of benefit in some patients. Building on the advancements made in other solid tumors as well as a better understanding of cancer immunology provides hope for the development of new and exciting therapies in the treatment of sarcoma. There remains promise with immunologic checkpoint blockade antibodies. Further, building on the success of autologous cell transfer in hematologic malignancies, designing chimeric antigen receptors that target antigens that are over-expressed in sarcoma provides a great deal of optimism. Exploring these avenues has the potential to make immunotherapy a real therapeutic option in this orphan disease.

https://downloads.hindawi.com/journals/sarcoma/2014/391967.pdf

Sarcoma immunotherapy: past approaches and future directions.

Purpose: This three-arm randomized study compares response rates and overall survival of patients with metastatic renal cell cancer (RCC) receiving high-dose or one of two low-dose interleukin-2 (IL-2) regimens. Patients and Methods: Patients with measurable metastatic RCC and a good performance status were randomized to receive either 720,000 U/kg (high-dose [HD]) or 72,000 U/kg (low-dose [LD]), both given by intravenous (IV) bolus every 8 hours. After randomly assigning 117 patients, a third arm of low-dose daily subcutaneous IL-2 was added, and an additional 283 patients were randomly assigned. Results: A total of 156 patients were randomly assigned to HD IV IL-2, and 150 patients to LD IV IL-2. Toxicities were less frequent with LD IV IL-2 (especially hypotension), but there were no IL-2-related deaths in any arm. There was a higher response proportion with HD IV IL-2 (21%) versus LD IV IL-2 (13%; P = .048) but no overall survival difference. The response rate of subcutaneous IL-2 (10%, partial response and complete response) was similar to that of LD IV IL-2, differing from HD IV (P = .033). Response durability and survival in completely responding patients was superior with HD IV compared with LD IV therapy (P = .04). Conclusion: Major tumor regressions, as well as complete responses, were seen with all regimens tested. IL-2 was more clinically active at maximal doses, although this did not produce an overall survival benefit. The immunological factors which constrain the curative potential of IL-2 to only a small percentage of patients need to be further elucidated.

Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer

Parallel evolution of polymer chemistry and immunology: Integrating mechanistic biology with materials design.

The Noni fruit, or scientifically known as Morinda citrifolia can be found in various parts of the world, especially in the pacific region. It is a small evergreen bushy-like tree originated from the Rubiaceae family. The plant has been used by polynesians as a medicinal herb for more than 2000 years. A substantial amount of phytochemicals can be found in the roots of this plant. Among all, damnacanthal has been found to be the most interesting, versatile and potent compound. Damnacanthal or chemically known as,3- hydroxy-1-methoxyanthraquinone-2-caboxaldehyde (C16H10O5), appears as pale yellow crystals with a melting point of 210-211 °C. This compound is of particular interest due to its striking pharmacological properties. Damnacanthal was shown to inhibit the oncogene Ras, p56lck tyrosine kinase, NF-KB pathway and induce apoptosis in vitro. This review aims to discuss the biological properties of damnacanthal, specifically on its anti-cancer activity that has been reported.

/pdf/damnacanthal-a-promising-compound-as-a-medicinal-fkkxqqots8.pdf

Damnacanthal: A Promising Compound as a Medicinal Anthraquinone

Cytokines are molecular mediators of intercellular signaling that function to regulate homeostasis of the immune system. There are five families of cytokines classified by their receptor usage. The effects of individual cytokines on immunity depend on several factors, including the local cytokine concentration, the pattern of cytokine receptor expression, and the integration of multiple signaling pathways in responding immune cells. Cytokines have shown therapeutic potential for the initiation and potentiation of antitumor immunity. Interferon-α and interleukin-2 (IL-2) have been approved as single agents for the treatment of metastatic melanoma and renal cell carcinoma, and several other cytokines have shown promise in preclinical tumor models. New strategies for improving the therapeutic benefit of cytokines are in development and include cytokine-antibody fusion molecules, delivery in recombinant viral vectors, expression by irradiated whole tumor cells, PEGylation, DNA vaccination, and ex vivo exposure to immune effector cells.

Cytokines in the Treatment of Cancer

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Cytokines in the Treatment of Cancer