Latest News on Tumour Necrosis: Feb 2021

Latest News on Tumour Necrosis: Feb 2021

Tumour necrosis factor and cancer

Tumour necrosis factor (TNF) is a major inflammatory cytokine that was first identified for its ability to induce rapid haemorrhagic necrosis of experimental cancers. When efforts to harness this anti-tumour activity in cancer treatments were underway, a paradoxical tumour-promoting role of TNF became apparent. Now that links between inflammation and cancer are appreciated, is TNF a target or a therapeutic in malignant disease — or both? [1]

Macrophage-induced angiogenesis is mediated by tumour necrosis factor-α

Macrophages are important in the induction of new blood vessel growth during wound repair, inflammation and tumour growth1–4. We show here that tumour necrosis factor-α (TNF-α), a secretory product of activated macrophages that is believed to mediate tumour cytotoxicity5–9, is a potent inducer of new blood vessel growth (angiogenesis). In vivo, TNF-α induces capillary blood vessel formation in the rat cornea and the developing chick chorioallantoic membrane at very low doses. In vitro, TNF-α stimulates chemotaxis of bovine adrenal capillary endothelial cells and induces cultures of these cells grown on type-1 collagen gels to form capillary-tube-like structures. The angiogenic activity produced by activated murine peritoneal macrophages is completely neutralized by a polyclonal antibody to TNF-α, suggesting immunological features are common to TNF-α and the protein responsible for macrophage-derived angiogenic activity. In inflammation and wound repair, TNF-α could augment repair by stimulating new blood vessel growth; in tumours, TNF-α might both stimulate tumour development by promoting vessel growth and participate in tumour destruction by direct cytotoxicity10–12. [2]

Tumour necrosis factor-α as a tumour promoter

It is becoming more evident that many aspects of tumour promotion arise from persistent and unresolving inflammation. One of the key molecules mediating the inflammatory processes in tumour promotion is the cytokine, tumour necrosis factor-α (TNF-α). Clinically, elevated serum concentrations and increased expression of TNF-α are present in various pre-neoplastic and malignant diseases, compared with serum and tissue from healthy individuals. Although over the last few decades high-dose administration of TNF-α has been used as a cytotoxic agent, recent pre-clinical cancer models have provided critical evidence to support the link between chronic, low level TNF-α exposure and the acquisition of pro-malignant phenotype (i.e., increased growth, invasion and metastasis). Furthermore, sophisticated cellular systems are being utilised to dissect the crucial role TNF-α plays in the communication of stromal/inflammatory cells and tumour cells. Understanding the intricate roles of TNF-α in the process of tumour promotion will assist in the development of novel cancer therapeutics. [3]

The Safety and Effectiveness of Single and Repeat Dosing of Intra-Articular Anti-Tumour Necrosis Factor Treatment after Failure of Intra-Articular Steroids

Objectives: To determine if intra-articular (ia) anti-tumour necrosis factor (TNF) yielded benefit in patients failing ia steroid injections and determine the safety and durability of single and repeated ia anti-TNF treatment in inflammatory arthritis.
Methods: Patients with inflammatory arthritis having one or two active joints, and having failed previous ia steroids were injected with ia adalimumab or ia etanercept mixed with triamcinolone and lidocaine via a retrospective chart audit.
Results: Twenty-six patients were followed: 18 received ia adalimumab, 12 received ia etanercept and 4 received both. Twenty-five knees, 17 ankles, 1 wrist and 1 PIP were injected of whom 6 had repeated injections to a joint. Nine were on concomitant systemic anti-TNF therapy. Fifteen had RA, 4 had a seronegativearthropathy, 3 had psoriatic arthritis, and 4 had other arthritis. When determining a response to ia anti-TNF for > 2 months in patients with sufficient follow up 13 of 18 receiving iaadalimumab and 6/7 with ia etanercept had benefit. There were no serious adverse events (SAEs) and only one AE in a wrist post ia adalimumab, with rebound inflammation after 6 weeks of marked relief. Two were able to cancel or postpone joint surgery(knee and ankle)and one cancelled an yttrium injection.
Conclusions: There were no SAEs and prolonged benefit was found with ia anti-TNF and steroids and lidocaine compared to previous ia steroids with lidocaine in the majority (20/27). Although not approved for ia administration, ia anti-TNFs may be cost effective in persistent synovitis of one or two joints recalcitrant to ia steroids. [4]

Changes in Lipid Peroxidation, Free Radical Scavengers and Tumour Necrosis Factor-alpha in Serum of Wistar Rats with Induced Thyroid Dysfunction

Aim: To assess the changes in lipid peroxidation, free radical scavengers and tumour necrosis factor-alpha in serum of Wistar rats with induced thyroid dysfunction.

Study Design: An experimental animal study was conducted in which Wistar rats with induced thyroid dysfunction were studied.

Place and Duration of Study: Animal House, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto and Department of Chemical Pathology, Faculty of Medical Laboratory Sciences, Usmanu Danfodiyo University, Sokoto, between June, 2016 and December, 2016.

Methodology: Twenty-one (21) male Wistar rats weighing 140 – 180 grams were randomly divided into three groups. Therefore, each group consists of 7 rats. Euthyroid (control): untreated receiving daily intraperitoneal injection of 0.9% normal saline solution; hypothyroid:  treated with daily oral administration of 6-propyl-2-thiouracil (5 mg/100 g) and hyperthyroid: treated with daily intraperitoneal injection of L-thyroxine (0.1 µg/g). At the end of the 30 days treatment,  rats were fasted for 12 hours and blood samples were collected under chloroform anaesthesia for the estimation of serum total triidothyronine (tT3), total tetraiodothyronine (tT4), thyroid stimulating hormone (TSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), malondialdehyde (MDA) and tumour necrosis-alpha (TNF-α) using standard techniques. The rats were then scarified by cervical decapitation and slices of liver tissue were made for histological examination.

Results: The result indicated that final body weight, and serum tT3, tT4, SOD, CAT and GPX were significantly (P<0.05; P< 0.001) lower in hypothyroid and hyperthyroid rats while, serum MDA and TNF-α were significantly (P<0.05; P< 0.001) higher in hypothyroid and hyperthyroid compared with euthyroid rats. Serum TSH was significantly (P< 0.001) higher in hypothyroid compared with euthyroid and hyperthyroid rats. Histological examination of the hepatocellular tissue of euthyroid rat revealed normochromic and normocytic cellular architecture. There was polymorphocytic infiltration with mild inflammation and hypochromatic liver in hypothyroid rats while, conspicuous infiltrations of polymorphs in all fields were observed in hyperthyroid rats.

Conclusion: In this study, serum MDA and TNF-α were significantly higher, and SOD, CAT and GPX activities were lower in experimental hypothyroid and hyperthyroid rats. The result therefore suggests that a decreased antioxidant capacity coupled with increased oxidative stress and TNF-α may play an important role in the pathogenesis of hepatic injury due to thyroid dysfunction and underscores the role of antioxidants in reducing oxidative stress associated with thyroid dysfunction. [5]


[1] Balkwill, F., 2009. Tumour necrosis factor and cancer. Nature reviews cancer9(5), pp.361-371.

[2] Leibovich, S.J., Polverini, P.J., Shepard, H.M., Wiseman, D.M., Shively, V. and Nuseir, N., 1987. Macrophage-induced angiogenesis is mediated by tumour necrosis factor-α. Nature329(6140), pp.630-632.

[3] Szlosarek, P., Charles, K.A. and Balkwill, F.R., 2006. Tumour necrosis factor-α as a tumour promoter. European journal of cancer42(6), pp.745-750.

[4] Chia, J. and Pope, J. (2011) “The Safety and Effectiveness of Single and Repeat Dosing of Intra-Articular Anti-Tumour Necrosis Factor Treatment after Failure of Intra-Articular Steroids”, Journal of Advances in Medicine and Medical Research, 2(1), pp. 39-53. doi: 10.9734/BJMMR/2012/805.

[5] Yeldu, M.H. and Ishaq, S., 2017. Changes in Lipid Peroxidation, Free Radical Scavengers and Tumour Necrosis Factor-alpha in Serum of Wistar Rats with Induced Thyroid Dysfunction. Annual Research & Review in Biology, pp.1-14.

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