Tailoring of chitosan through the involvement of its amino, acetamido, and hydroxy groups can give derivatives of enhanced solubility and remarkable anticancer activity. The general mechanism of such activity is associated with the disturbances in normal functioning of cell cycle, interference to the central dogma of biological system from DNA to RNA to protein or enzymatic synthesis, and the disruption of hormonal path to biosynthesis to inhibit the growth of cancer cells. Both chitosan and its various derivatives have been reported to selectively permeate through the cancer cell membranes and show anticancer activity through the cellular enzymatic, antiangiogenic, immunoenhancing, antioxidant defense mechanism, and apoptotic pathways. They get sequestered from noncancer cells and provide their enhanced bioavailability in cancer cells in a sustained release manner. This review presents the putative mechanisms of anticancer activity of chitosan and mechanistic approaches of structure activity relation upon the modification of chitosan through functionalization, complex formation, and graft copolymerization to give different derivatives.

/pdf/anticancer-activity-of-chitosan-chitosan-derivatives-and-4lngxn1b1v.pdf

Anticancer Activity of Chitosan, Chitosan Derivatives, and Their Mechanism of Action

Purpose
Although various types of immunotherapy have been used to improve the prognosis of patients with advanced renal cell carcinoma (RCC), adoptive immunotherapy using gamma-delta (γδ) T cells has not yet been tried. In this study, we designed a pilot study of adoptive immunotherapy using in vitro activated γδ T cells against advanced RCC to evaluate the safety profile and possible anti-tumor effects of this study.

Safety profile and anti-tumor effects of adoptive immunotherapy using gamma-delta T cells against advanced renal cell carcinoma: a pilot study.

Cells of the macrophage lineage are considered to be of special importance in the defense of the host against tumor development and spread. Immunotherapeutic strategies to stimulate macrophage (MAC) tumor cytotoxicity make use of activating compounds such as gamma-interferon which are given systemically. However, there are several lines of evidence that in malignant disease the generation of cytotoxic effector MACs is impaired. Both defective cell maturation and loss of responsiveness to activation are described. Here, a first clinical phase I trial of adoptive immunotherapy in cancer patients using autologous MACs generated in vitro from blood monocytes (MOs) is reported. Mononuclear cells were isolated by cytapheresis and density centrifugation and cultured in hydrophobic Teflon bags for 7 days with 2% autologous serum and recombinant human gamma-interferon being present for the last 18 h. Cytotoxic MO-derived MACs were then purified by countercurrent elutriation and reinfused into the patient. A total of 72 therapies have been performed with patients being treated i.v. (n = 8) and i.p. (n = 7). In vitro generated MACs proved to be mature as judged by the expression of maturation-associated surface molecules (MAX antigens, CD16, CD51, CD71), were cytotoxic to U937 tumor cells, and were efficient secretory cells. Cell dose escalation was performed in the first patients beginning with 10(8) MACs to finally infuse the total number of cells recovered from one single cycle of isolation and culture. MAC yield varied from 1 to 17 x 10(8) representing 13-79% of MOs initially seeded. Adoptive MAc transfer was well tolerated. Side effects observed were low-grade fever (less than 38.5 degrees C), induction of the coagulation cascade, and abdominal discomfort after i.p. application. The procoagulant activity of MAC autografts was cell dose dependent and demonstrated by detection of circulating fibrin monomers and thrombin-antithrombin complexes. Biological responses observed included elevated serum neopterin levels and the appearance of interleukin-6 in sera and ascitic fluids. Indication of a possible therapeutic effect was only observed in i.p.-treated patients and consisted of disappearance of malignant ascites in 2 of 7 patients.

https://cancerres.aacrjournals.org/content/canres/50/23/7450.full.pdf

Adoptive Transfer of Tumor Cytotoxic Macrophages Generated in Vitro from Circulating Blood Monocytes: A New Approach to Cancer Immunotherapy

Tumour necrosis factor alpha (TNFα) and interferon gamma (IFNγ) were originally found to be produced by inflammatory cells and play important roles in the immune system and surveillance of tumour growth. By activating distinct signalling pathways of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and JAK/STAT, TNFα and IFNγ were reported to effectively trigger cell death and perform powerful anti-cancer effects. In this review, we will discuss the new advancements of TNFα and IFNγ in anti-cancer therapy.

/pdf/anti-cancer-therapy-with-tnfa-and-ifng-a-comprehensive-ow5p29dhe0.pdf

Anti-cancer therapy with TNFα and IFNγ: A comprehensive review.

Because of its immunomodulatory and anticancer activities, IFNgamma has been used as an anticancer drug in several clinical studies, unfortunately with modest results. Attempts to increase the response by increasing the dose or by repeated continuous injection often resulted in lower efficacy, likely due to counterregulatory effects. We show here that targeted delivery of low doses of IFNgamma to CD13, a marker of angiogenic vessels, can overcome major counterregulatory mechanisms and delay tumor growth in two murine models that respond poorly to IFNgamma. Tumor vascular targeting was achieved by coupling IFNgamma to GCNGRC, a CD13 ligand, by genetic engineering technology. The dose-response curve was bell-shaped. Maximal effects were induced with a dose of 0.005 microg/kg, about 500-fold lower than the dose used in patients. Nontargeted IFNgamma induced little or no effects over a range of 0.003 to 250 microg/kg. Studies on the mechanism of action showed that low doses of targeted IFNgamma could activate tumor necrosis factor (TNF)-dependent antitumor mechanisms, whereas high doses of either targeted or nontargeted IFNgamma induced soluble TNF-receptor shedding in circulation, a known counterregulatory mechanism of TNF activity. These findings suggest that antitumor activity and counterregulatory mechanisms could be uncoupled by tumor vascular targeting with extremely low doses of IFNgamma.

https://cancerres.aacrjournals.org/content/canres/65/7/2906.full.pdf

Targeted Delivery of IFNγ to Tumor Vessels Uncouples Antitumor from Counterregulatory Mechanisms

We tested the clinical efficacy of a biologically active dose (BAD) of interferon (IFN)-gamma for treatment of progressive renal cell carcinoma (RCC). Twenty-two RCC patients with disease progression subsequent to nephrectomy were entered on a phase II clinical trial. During an initial dose-finding phase, biochemical responses to repeated once-weekly subcutaneous injections of 10, 100, or 500 micrograms of recombinant IFN-gamma were tested in 16 patients. Results indicated that 100 micrograms IFN-gamma applied once weekly was biologically active with induction of serum beta 2-microglobulin and neopterin. Such a dose induced a nearly maximum response of both markers lasting more than 4 days. This dose was also associated with minimal side effects. A dose of 100 micrograms IFN-gamma given once weekly was, therefore, subsequently given weekly for long-term treatment. During a median time of therapy of 10 months (range, 2 to 32 months) two complete (CR; 20+, 20+ months) and four partial tumor responses (PR; 6...

Successful treatment of metastatic renal cell carcinoma with a biologically active dose of recombinant interferon-gamma.

Interferon-γ for the Treatment of Metastatic Renal Cancer: Dose-Dependent Stimulation and Downregulation of Beta-2 Microglobulin and Neopterin Responses

Das Nierenzellkarzinom (NZK) ist ein Tumor, der gegen Chemotherapie resistent ist. Die berichtete durchschnittliche Uberlebensrate bei Patienten mit metastatischer Krankheit betragt ungefahr 10 Monate (Maldazys u. de Kernion 1986). Vor kurzem wurden jedoch experimentelle und klinische Beweise dafur erbracht, das das NZK gegenuber verschiedenen Formen der Immuntherapie, einschlieslich der IL-2-Behandlung mit oder ohne adopti-vem Transfer von lymphokinaktivierten Killerzellen (LAK-Zellen) oder Interferon (IFN)-γ verhaltnismasig sensibel ist (Graham 1989). In diesem Bericht prasentieren wir vorklinische Daten und revidieren unsere jungsten Erfahrungen mit der Entwicklung einer effektiven Immuntherapie fur Patienten mit fortgeschrittenem NZK unter Verwendung von IFN-y.

Immuntherapie des metastasierten Nierenzellkarzinoms mit rekombinantem Interferon-γ

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

W.E. Aulitzky

Author Tools

Chat about Author

Papers

Successful treatment of metastatic renal cell carcinoma with a biologically active dose of recombinant interferon-gamma.

Interferon-γ for the Treatment of Metastatic Renal Cancer: Dose-Dependent Stimulation and Downregulation of Beta-2 Microglobulin and Neopterin Responses

Immuntherapie des metastasierten Nierenzellkarzinoms mit rekombinantem Interferon-γ