The objective of this Phase II study was to evaluate the pharmacodynamic and immune effects of intratumorally administered recombinant human interleukin-12 (IL-12) on regional lymph nodes, primary tumor, and peripheral blood. Ten previously untreated patients with head and neck squamous cell carcinoma were injected in the primary tumor two to three times, once/week, at two dose levels of 100 or 300 ng/kg, before surgery. We compared these patients with 20 control (non-IL-12-treated) patients. Toxicity was high, with unexpected dose-limiting toxicities at the 300 ng/kg dose level. Dose-dependent plasma IFN-␥ and IL-10 increments were detected. These cytokine levels were higher after the first injection than after the subsequent injections.
The objective of this study was to evaluate the histologic and immunohistopathologic effects of intratumorally given recombinant human interleukin-12 on the immune cells in the primary tumors and regional lymph nodes. Ten previously untreated patients with head and neck squamous cell carcinoma (HNSCC) were injected in the primary tumor twice to thrice, once weekly, at two dose levels of 100 or 300 ng/kg, before surgery. These patients were compared with 20 non-IL-12-treated control HNSCC patients. In the primary tumor, the number of CD56 + natural killer (NK) cells was increased in IL-12-treated patients compared with control patients. In some IL-12-treated patients, an impressive peritumoral invasion of CD20 + B cells was noticed. No differences were seen in the CD8 + or CD4 + T lymphocytes. Interestingly, major differences were apparent in the architecture of the enlarged lymph nodes of IL-12-treated patients; in particular, the distribution of B cells differed and fewer primary and secondary follicles with smaller germinal centers were observed. In addition, a decrease of dendritic cell lysosyme-associated membrane glycoprotein -positive cells in the paracortex was noted, resulting in a reduction of paracortical hyperplasia. In the lymph nodes, especially the CD56 + NK cells but also the CD8 + and CD4 + T lymphocytes, produced a high amount of IFN-;. Patients, irrespectively of IL-12 treatment, with a high number of CD56 + cells in the primary tumor had a better overall survival than those with a low number. In conclusion, after i.t. IL-12 treatment in HNSCC patients, the largest effect was seen on the NK cells, with a higher number in the primary tumor and a high IFN-; mRNA expression in the lymph nodes. Significant effects were noted on B cells, with altered lymph node architecture in every IL-12-treated patient and excessive peritumoral infiltration in some patients.
Summary We studied the relation between tumour vascular density and tumour growth rate, metastatic incidence and vascular permeability factor (VPF) mRNA levels in a human xenograft model described previously. Vascular density was determined by automated image analysis.Xenografts derived from cell lines BLM and MV3 showed the highest mean vascular density (MVD), the highest in vivo growth rate, high VPF mRNA levels and rapid development of lung metastases. Xenografts of cell lines M14, Mel57 and MV1 showed a significantly lower degree of vascularization, lower in vivo growth rates and lower levels of VPF mRNA, but formed lung metastases with a similar incidence as those of BLM and MV3. Xenografts from cell line 1 F6 did not form lung metastases, whereas tumours derived from a spontaneous mutant of 1 F6, designated 1 F6m, gave rise to lung metastases to the same extent as Mel57, M14 and MV1 tumours. MVD values in 1 F6 and 1 F6m xenografts, VPF mRNA levels and in vivo growth rates of 1 F6 and 1 F6m xenografts, however, were similar. In conclusion, in the melanoma xenograft model vascular density is correlated with in vivo growth rate and with in vitro VPF mRNA levels, but not with the ability to metastasize.
Sjögren's syndrome (SS) is a chronic autoimmune disease characterised by specific lesions in exocrine glands, so sublabial minor salivary gland biopsy (SLGB) plays an important part in its diagnosis. The extent and composition of the lymphocytic infiltrate in SLGB specimens can be considered as target organ specific parameters. They are quantified after histological and immunohistological examination by a focus score (describing the extent of the infiltrate) and IgA% score (describing the composition of the infiltrate), respectively. However, little is known about the factors that contribute to the extent and composition of the infiltrate and whether these features are reversible as repeated SLGBs are rarely performed. A patient with SS is described who underwent SLGBs before and after treatment with high dose corticosteroids. After treatment there was not only clinical improvement, but also improvement in the histological and immunohistological parameters. Although these findings need to be confirmed in further studies, this suggests that histopathological changes may be reversible in SS. Furthermore, it shows that the potential eVects of corticosteroid use should be taken into account when interpreting SLGB specimens. When clinical changes do parallel histological changes, repeated SLGBs might oVer a marker for disease activity in patients with SS.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.