Reinforced cytotoxicity of lymphokine-activated killer cells toward glioma cells by transfection with the tumor necrosis factor-α gene

1993 ◽  
Vol 78 (2) ◽  
pp. 252-256 ◽  
Author(s):  
Takashi Tashiro ◽  
Jun Yoshida ◽  
Masaaki Mizuno ◽  
Kenichiro Sugita
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Intrathecal Injection ◽  
Malignant Gliomas ◽  
Interleukin 2 ◽  
Human Tumor ◽  
Lak Cells ◽  
Lymphokine Activated Killer Cells ◽  
Tnf Α ◽  
Necrosis Factor

✓ Lymphokine-activated killer (LAK) cells generated from peripheral blood lymphocytes incubated with recombinant interleukin-2 were transfected with the human tumor necrosis factor (TNF)-α gene by means of novel liposomes with a positive change on their surface. The cells secreted significant amounts of TNF-α into the culture medium and exhibited reinforcement of cytotoxicity toward a human glioma cell line (U251-SP), being three times more cytotoxic than nontransfected LAK cells. The mechanism for the reinforcement of cytotoxicity is considered to involve not only an increase in TNF-α secretion from LAK cells but also its expression on their surface. Intratumoral or intrathecal injection of LAK cells transfected with the TNF-α gene may be useful for the treatment of patients with malignant gliomas.

scholarly journals Paclitaxel-activated astrocytes produce mechanical allodynia in mice by releasing tumor necrosis factor-α and stromal-derived cell factor 1

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Xiaojuan Liu ◽  
Raquel Tonello ◽  
Yuejuan Ling ◽  
Yong-Jing Gao ◽  
Temugin Berta
Keyword(s):  
Tumor Necrosis Factor ◽  
Acute Pain ◽  
Mechanical Allodynia ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Intrathecal Injection ◽  
Pain Syndrome ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background Paclitaxel is a widely used and potent chemotherapeutic agent for the treatment of cancer. However, patients receiving paclitaxel often develop an acute pain syndrome for which there are few treatment options. Astrocytes play an important role in the pathogenesis of pain in multiple preclinical models, as well as in paclitaxel-treated rodents. However, it is still unclear what the exact contribution of astrocytes may be in paclitaxel-associated acute pain syndrome (P-APS). Methods P-APS was modeled by a single systemic or intrathecal injection of paclitaxel and astrocyte contribution tested by immunohistochemical, pharmacological, and behavioral approaches. Cell cultures were also prepared to assess whether paclitaxel treatment directly activates astrocytes and whether intrathecal injection of paclitaxel-treated astrocytes produces pain that is reminiscent of P-APS. Results Systemic injection of paclitaxel resulted in increased expression of glial fibrillary acidic protein (a common marker of astrocytic activation), as well as both systemic or intrathecal injection of paclitaxel induced pain hypersensitivity indicated by the development of mechanical allodynia, which was significantly reversed by the astrocytic inhibitor L-α-AA. Cultured astrocytes were activated by paclitaxel with significant increases in protein levels for tumor necrosis factor-α (TNF-α) and stromal-derived cell factor 1 (SDF-1). Importantly, intrathecal injection of paclitaxel-activated astrocytes produced mechanical allodynia that was reversed by TNF-α and SDF-1 neutralizing antibodies. Conclusion Our results suggest for the first time that paclitaxel can directly activate astrocytes, which are sufficient to produce acute pain by releasing TNF-α and SDF-1. Targeting astrocytes and these cytokines may offer new treatments for P-APS.

Clinical effect of intra-arterial tumor necrosis factor-α for malignant glioma

1992 ◽  
Vol 77 (1) ◽  
pp. 78-83 ◽  
Author(s):  
Jun Yoshida ◽  
Toshihiko Wakabayashi ◽  
Masaaki Mizuno ◽  
Kenichiro Sugita ◽  
Tazuka Yoshida ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Malignant Glioma ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Tumor Regression ◽  
Malignant Gliomas ◽  
Human Tumor ◽  
Content Type ◽  
Factor Α ◽  
Necrosis Factor

✓ Recombinant human tumor necrosis factor-α was administered intra-arterially to treat 20 cases of malignant gliomas, mostly progressive or recurrent. The optimum dosage was determined to be 1 × 105 U/sq m/day. Among the 10 evaluable patients treated at this dosage, two responded (one completely and one partially), resulting in a 20% response rate. Side effects were mild and easily controllable. Improvement of neurological symptoms was noted in 47% of the patients a few days after treatment, even when computerized tomography showed no tumor regression. This might have been due to the pleiotypic biological activity of tumor necrosis factor-α. Neuroradiographic observations revealed narrowing of the tumor-feeding artery, a decrease in tumor staining ability, and necrosis in the central part of a tumor. The authors suggest that intra-arterial administration of tumor necrosis factor-α may be an effective treatment for malignant glioma, including recurrent cases.

Polymorphism of the 5′-flanking region of the human tumor necrosis factor (TNF)-α gene in Japanese

1998 ◽  
Vol 51 (6) ◽  
pp. 605-612 ◽  
Author(s):  
T. Higuchi ◽  
N. Seki ◽  
S. Kamizono ◽  
A. Yamada ◽  
A. Kimura ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Human Tumor ◽  
Human Tumor Necrosis Factor ◽  
Tnf Α ◽  
Flanking Region ◽  
Necrosis Factor

scholarly journals Serum Tumor Necrosis Factor-alpha and Interleukin-2 Concentrations in Newly Diagnosed ERBB2 (HER2/neu) Positive Breast Cancer Patients

2009 ◽  
Vol 24 (3) ◽  
pp. 142-146 ◽  
Author(s):  
Sezer Saglam ◽  
Rafi Suzme ◽  
Figen Gurdol
Keyword(s):  
Breast Cancer ◽  
Tumor Necrosis Factor ◽  
Cancer Patients ◽  
Tumor Necrosis ◽  
Interleukin 2 ◽  
Breast Cancer Patients ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Aim Cytokines have been associated with symptoms and adverse outcomes in breast cancer. Overexpression of ERBB2 (c-erb-b2; formerly HER2/neu), which is a member of the epidermal growth receptor family, is associated with involvement of lymph nodes, large tumor size, high grade, steroid receptor negativity, aneuploidy, high proliferation rate, and low overall survival in breast cancer. The aim of the study was to examine whether ERBB2 amplification has any effect on circulating levels of tumor necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2) in breast cancer patients. Material and methods Fifty patients with primary breast carcinoma, classified as either ERBB2 (+) or (-) by the fluorescence in situ hybridization (FISH) technique, were included in the study. Cytokines were studied by ELISA according to the procedure described in the commercial kit. Results IL-2 levels were found significantly higher in ERBB2+ patients than in controls (p<0.05). A significant negative correlation existed between ERBB2 positivity and estrogen receptor status (p=0.004). Plasma TNF-α and IL-2 levels were positively correlated in ERBB2+ breast cancer patients (p<0.01). Conclusion The increase in IL-2 concentrations observed in our study suggests an activation of T cells by ERBB2 peptides.

scholarly journals Influence of Vector-Encoded Cytokines on Anti-Salmonella Immunity: Divergent Effects of Interleukin-2 and Tumor Necrosis Factor Alpha

2001 ◽  
Vol 69 (6) ◽  
pp. 3980-3988 ◽  
Author(s):  
Basel K. al-Ramadi ◽  
Mariam H. Al-Dhaheri ◽  
Nada Mustafa ◽  
Mounir AbouHaidar ◽  
Damu Xu ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Interleukin 2 ◽  
Fine Tuning ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Attenuated Salmonella strains are of interest as new vaccine candidates and as vectors of cloned genes of other organisms. Attenuated strains expressing specific cytokines were constructed as a means of manipulating the immune response in various disease settings. In the present study, interleukin-2 (IL-2)-expressing (GIDIL2) or tumor necrosis factor alpha (TNF-α)-expressing (GIDTNF) strains were compared with the parent strain (BRD509) for the effect of cytokines on anti-Salmonella immunity. Expression of IL-2 resulted in a rapid clearance of the organism soon after vaccination. The reduction in GIDIL2 CFU was 50- to 300-fold higher than that of BRD509 and correlated with a markedly decreased splenomegaly. Furthermore, no evidence for any significant activation, including upregulation of surface markers and production of nitric oxide (NO), was observed in spleens of GIDIL2-injected mice. In contrast, the host response to GIDTNF was marked by an early, strong, splenic cellular influx, but surprisingly, the degree of induced splenomegaly and NO secretion was only 50% of that observed in BRD509-treated mice. Despite this, bacterial colonization of the spleen in GIDTNF-immunized animals was either slightly decreased from or equivalent to that of the BRD509-treated group, suggesting the induction of additional antimicrobial mechanisms by TNF-α. In vivo protection studies demonstrated that, at limiting doses, GIDIL2 was inferior to GIDTNF and BRD509 in its capacity to protect against virulent challenge. At high doses, however, all three strains exhibited equal protective efficacy. These results demonstrate that the immune response against intracellular bacteria can be manipulated by pathogen-expressed cytokines and open the way for further fine tuning of immune responses not only to Salmonella strains themselves but also to the heterologous gene(s) carried by them.

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