Intriguing issues of EGFR targeting in head and neck cancer

We have read the recent comprehensive review by Cruz et al.[1] regarding the targeting of receptor tyrosine kinases andtheir therapeutic perspectives in head and neck squamous cellcarcinomas (HNSCC). The major focus of this report was epidermalgrowth factor receptor (EGFR) biology and targeting. However,we feel     

Myelin thickenings in val 102/fs null mutation of MPZ gene

Painful sensory neuropathies consist of a wide range of neuropathies that can involve large as well as small nerve fibres. Even if most cases remain of unknown cause, some of them may be associated with an underlying disorder such as diabetes, HIV, infections, amyloidosis, and Sjogren's syndrome. Since in some cases an autoimmune mechanism has been postulated, we investigated a panel of circulating autoantibodies including anti‐gliadin (AGA), anti‐endomysium (EmA), anti‐transglutaminase (tTGA) and anti‐nuclear (ANA) antibodies in the sera of patients with unexplained painful sensory neuropathies in order to identify other potentially treatable disorders. We tested the sera of 10 patients (4M; 6F) previously investigated for other causes of neuropathies, including anti‐nerve, onconeural, anti‐extractable nuclear, anti‐neutrophil cytoplasmic, anti‐thyroglobulin (TgA) and anti‐peroxidase (TPOA) antibodies. We found the presence of AGA positivity in 4 patients (40%), ANA in 7 (70%) and AGA + ANA in 4 (40%), two of whom were negative for celiac disease by gastrointestinal biopsy. None of the patients had EmA positivity. Three (30%) had TgA and TPOA and none had anti‐nerve or onconeural antibodies. Whether the presence of circulating autoantibodies in patients with unexplained painful neuropathy reflects an autoimmune involvement which may be amenable to immune therapy and not only to symptomatic treatment remains to be established.     

Early macrophage and cytokine response during the growth of immunogenic and non-immunogenic murine tumors

Very little data exist on the mechanisms of innate immunity during the first days after syngeneic tumor inoculation. Nonspecific macrophage reaction precedes the development of specific immune response and is important for further tumor growth and stroma formation. We investigated two lymphoma cell lines of the same origin, differing in immunogenicity: non-immunogenic parental strain P388 and its highly immunogenic subline P388/adria. Early systemic inflammatory response resulted in the enhancement of nitric oxide (NO) and superoxide production by peritoneal macrophages which was at a maximum on the first day after s.c. tumor inoculation and was observed in mice bearing either of these tumors independently of immunogenicity. It was followed by a transient elevation of the serum levels of pro-inflammatory cytokines: TNF-alpha IL-6. In order to evaluate the role of inflammatory response, vaccinations with lethally irradiated lymphoma cells were performed. After two weekly injections, the mice were challenged s.c. with live tumor cells of the same subline. Effective vaccination with P388/adria lymphoma cells induced retardation of tumor growth in parallel with down-regulation of peritoneal macrophage activity and abrogation of serum cytokine release. Non-effective immunization with P388 cells influenced neither tumor growth nor macrophage functions and cytokine level. Thus, a positive correlation was found between down-regulation of the inflammatory response and inhibition of tumor growth. We suppose that, in efficiently immunized mice, special mechanisms exist which are responsible for down-regulation of the inflammatory reaction. Macrophage products may facilitate tumor cell survival by preventing apoptosis or participate in the activation of tumor neoangiogenesis. Suppression of these activities may serve as an important tool for the inhibition of tumor growth at the early stages of malignant transformation.     

NK and NKT cells in liver injury and fibrosis

The innate immune mechanisms of the liver represent an important first line of defense against bacterial products, toxins, and food antigens coming from the intestine. Natural Killer (NK) and Natural Killer T cells (NKT) are components of the innate immune system with increased presence in the liver compared to other organs and have been reported to participate in the inflammatory processes during hepatic diseases. However significant confusion has been noted in this field mainly due to changes in the characterization of these cells as new knowledge accumulates and due to differences in the approaches used for their study. Both cell types can mediate hepatic injury in several models but studies in human liver diseases have not managed to fully explain their functions. However accumulating evidence supports an antifibrotic role of NK cells mainly via an inhibitory effect on hepatic stellate cells by inducing apoptosis and via production of interferon-gamma. Therefore, downregulation of NK cells during most types of liver injury may facilitate liver fibrosis. Data about the role of NKT cells in liver fibrosis are limited. This review will summarize the studies about the role of NK and NKT cells in liver diseases with a special interest in hepatic injury and liver fibrosis.     

Molecular and biological properties of hamster tumor cell lines transformed with B77 virus: expression of v-src does not correlate with metastatic potential.

Three hamster tumor cell lines (B77Hep, B77H1De and ML cl 3.1) were investigated with the aim to determine some biological and molecular properties of cells which are connected with invasive and metastatic ability. Except B77H1De all cell lines exhibited high metastatic capacity in syngeneic adult animals. Analysis of cell lines revealed a relationship between metastatic ability and growth properties (growth rate, saturation density and colony formation in soft agar). Southern blot analysis of genomic DNA samples from high metastatic cell line (B77Hep) and low metastatic (B77H1De) showed that the metastatic potential of these cell lines did not depend on the number of integrated proviral copies. Northern blot analysis was used to determine the level of mRNA encoded by v-src gene in B77Hep and B77H1De cell lines. We found a good correlation between the number of integrated proviral copies and the level of v-src gene expression in investigated cell lines, but not with their metastatic potential. No proviral sequences were found in genomic DNA isolated from ML cl 3.1 cell line. In cell lines used in this study we found differences in expression of endogenous proto-oncogenes c-myc and c-fos.     

Acquired immunodeficiency syndrome-associated non-Hodgkin's lymphomas and other malignancies in patients with hemophilia

Non-Hodgkin's lymphoma (NHL) is the most common human immunodeficiency virus (HIV)-associated malignancy in hemophiliacs. We studied the incidence and clinicopathologic features of NHL in 3,041 hemophiliacs followed at 18 US Hemophilia Centers between 1978 and 1989. Of the 1,295 (56.6%) who were HIV(+), 253 (19.5%) developed acquired immunodeficiency syndrome (AIDS), of whom 14 (5.5%) developed NHL. Three NHL occurred in HIV(-) hemophiliacs, for a 36.5-fold greater risk in HIV(+) than HIV(-) hemophiliacs (P < .001). The NHL incidence rate was 29-fold greater than in the US population by Surveillance, Epidemiology, and End Results (SEER) estimates (P < .001). Between 0 and 4 lymphomas have been observed per year between 1978 and 1989. At presentation 13 (92.9%) of the HIV(+) NHL were extranodal. Ten were stage IV, 1 stage II, and 3 stage IE. Ten (71.4%) were high-grade, 3 (21.4%) intermediate-grade, and 1 (7.1%) was a low-grade B-cell lymphoma. Epstein-Barr virus (EBV) DNA was detected in 36% by in situ hybridization, including one central nervous system (CNS) lymphoma. The mean CD4 cell count at NHL diagnosis was 64/mm3, the mean latency from initial HIV infection was estimated to be 59 months, and the median survival was 7 months. The incidence of basal cell carcinoma in HIV(+) hemophiliacs was 18.3-fold greater than in HIV(-) hemophiliacs (P < .001) and 11.4-fold greater than in the US population (P < .001). In conclusion, incidence rates of NHL and basal cell carcinoma in HIV(+) hemophiliacs are significantly increased over rates in HIV(-) hemophiliacs and over rates in the US population. Clinicopathologic presentation of NHL in HIV(+) hemophiliacs is similar to that in HIV(+) homosexual men.