Head and neck squamous cell carcinoma (HNSCC) remains difficult to treat, and despite of advances in treatment, the overall survival rate has only modestly improved over the past several years. Thus, there is an urgent need for additional therapeutic modalities. We hypothesized that treatment of HNSCC cells with a dietary product such as bitter melon extract (BME) modulates multiple signaling pathways and regresses HNSCC tumor growth in a preclinical model. We observed a reduced cell proliferation in HNSCC cell lines. The mechanistic studies reveal that treatment of BME in HNSCC cells inhibited c-Met signaling pathway. We also observed that BME treatment in HNSCC reduced phosphoStat3, c-myc and Mcl-1 expression, downstream signaling molecules of c-Met. Furthermore, BME treatment in HNSCC cells modulated the expression of key cell cycle progression molecules leading to halted cell growth. Finally, BME feeding in mice bearing HNSCC xenograft tumor resulted in an inhibition of tumor growth and c-Met expression. Together, our results suggested that BME treatment in HNSCC cells modulates multiple signaling pathways and may have therapeutic potential for treating HNSCC.
Damage to the bone marrow elements, as shown by cytoplasmic vacuolization, has been reported in patients with acute alcohol intoxication, drug reactions, nutritional deficiencies, myeloproliferative syndromes, malignant hematologic conditions, some metabolic conditions, and in those treated with chemotherapeutic agents. A case of zinc toxicity with anemia, leukopenia, and cytoplasmic vacuolization of both myeloid and erythroid precursors is described. The patient described was a 30-year-old quadriplegic man who was receiving oral zinc to promote the healing of and prevention of decubitus ulcers. In the gut, dietary zinc interacts with copper in a competitive manner, and high levels of zinc can lead to copper deficiency. Zinc-induced copper deficiency anemia can be morphologically identified in the bone marrow preparations by cytoplasmic vacuolization of both myeloid and erythroid precursor elements.
The relationship between the presence of the c-erbB-2 protein, demonstrated immunohistochemically with antibody 21N, and thymidine labelling index (TLI) has been studied in the in situ component of 70 cases of carcinoma of the breast. A significant association was found between high TLI and positive staining. Twenty of the 70 cases stained (29%) and of those that were stained 75% had a high TLI; 43% of those with a high TLI stained positively but only 14% of those with a low TLI stained positively. Strong correlations were seen between nuclear size and histological pattern and both 21N staining and TLI. The majority of carcinomas of comedo pattern with large nuclei were 21N positive and had a high TLI, whilst those with small nuclei and a predominantly cribriform/micropapillary appearance did not stain and had a low TLI. In tumours of mixed histological pattern there was less concordance between staining and TLI. The significance of these findings in relation to the biological behaviour of these tumours and their clinical management is discussed.
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