Dual innervation of the submandibular gland by nerve to mylohyoid and chorda tympani.

The chorda tympani typically utilises the lingual nerve and submandibular ganglion to transmit parasympathetic fibres to the submandibular gland. During a routine anatomy dissection, the submandibular gland was found to be innervated by both the lingual nerve and the nerve to mylohyoid. The clinical implications of this variant dual innervation to the submandibular gland is not clear due to its rarity: however, recognising such a variation should be borne in mind during surgical intervention near the nerve to mylohyoid.

Relationships between squamous cell carcinoma antigen and cytokeratin 19 fragment values and renal function in oral cancer patients.

Squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragment (CYFRA) are used to screen and monitor oral cancer patients. However, recent studies have reported that tumour markers become elevated as renal function decreases, regardless of tumour progression. A retrospective study was performed of 423 oral cancer patients who underwent blood testing for these tumour markers and other blood analytes during a 10-year period. The values of SCC-Ag and CYFRA increased significantly with decreasing renal function (P < 0.01), and the values were abnormal at a median 2.6 ng/ml for SCC-Ag and 4.7 ng/ml for CYFRA in the group with estimated glomerular filtration rate (eGFR) values of< 30 ml/min/1.73 m2. The factors that were related to the variation in tumour markers were albumin and creatinine. The cut-off values of eGFR were 59.7 ml/min/1.73 m2 for SCC-Ag and 63.6 ml/min/1.73 m2 for CYFRA, and the cut-off age when the tumour markers might rise due to the effect of renal function were 72 years for SCC-Ag and 73 years for CYFRA. In conclusion, decreased renal function should be taken into account when evaluating tumour markers in oral cancer. In addition, tumour markers are likely to be overestimated in patients over the age of 72-73 years.

Inactivation of AMPK alters gene expression and promotes growth of prostate cancer cells.

AMP-activated protein kinase (AMPK) serves as a fuel-sensing enzyme that is activated by binding of AMP and subsequent phophorylation by upstream kinases such as the tumor suppressor LKB1, when cells sense an increase in the ratio of AMP to ATP. Acute activation of AMPK stimulates fatty acid oxidation to generate more ATP and simultaneously inhibits ATP-consuming processes including fatty acid and protein syntheses, thereby preserving energy for acute cell-surviving program, whereas chronic activation leads to inhibition of cell growth. The goal of the present study is to explore the mechanisms by which AMPK regulates cell growth. Toward this end, we established stable cell lines by introducing a dominant-negative mutant of AMPK alpha1 subunit or its shRNA into the prostate cancer C4-2 cells and other cells, or wild type LKB1 into the lung adenocarcinoma A549 and breast MB-MDA-231 cancer cells, both of which lack functional LKB1. Our results showed that the inhibition of AMPK accelerated cell proliferation and promoted malignant behavior such as increased cell migration and anchorage-independent growth. This was associated with decreased G1 population, downregulation of p53 and p21, and upregulation of S6K, IGF-1 and IGF1R. Conversely, treatment of the C4-2 cells with 5-aminoimidazole-4-carboxamide 1-D-ribonucleoside (AICAR), a prototypical AMPK activator, caused opposite changes. In addition, our study using microarray and RT-PCR revealed that AMPK regulated gene expression involved in tumor cell growth and survival. Thus, our study provides novel insights into the mechanisms of AMPK action in cancer cells and presents AMPK as an ideal drug target for cancer therapy.

Synthesis and secretion of an hEGF-like immunoreactive factor by human gastric cancer cells (MKN-45).

A large amount of an immunoreactive factor was detected in the medium conditioned by human gastric cancer cells, strain MKN-45, by our enzyme immunoassay system for human epidermal growth factor (hEGF) based on hEGF isolated from urine. However, the dose-response curve of the immunoreactive factor (designated as MKN-45 EGF) was not parallel with the standard curve of hEGF. The molecular weight of MKN-45 EGF was slightly larger than that of hEGF and was estimated to be 7,000-8,000 by gel filtration on Sephadex G-50. On isoelectric focusing analysis, MKN-45 EGF gave a major peak at pH 5.0 and a minor one at pH 4.3. These results demonstrate that MKN-45 cells synthesize and secrete into the culture medium a polypeptide immunologically related to hEGF.

Production of an hEGF-like immunoreactive factor by human gastric cancer cells depends on differentiational state of the cells.

We have extended our recent observation that human gastric cancer cells (MKN-45) synthesize and secrete an hEGF-like immunoreactive factor (designated as EGF-LI) by characterization of EGF-LI produced by five human gastric cancer cell lines in culture. Two cell lines (MKN-45 and KATO-III) derived from poorly differentiated adenocarcinoma synthesized and secreted a much larger amount of EGF-LI than three cell lines (MKN-1, MKN-28, and MKN-74) derived from well-differentiated adenocarcinoma. Treatment of MKN-45 cells by retinoic acid reduced significantly synthesis and secretion of EGF-LI, suggesting that production of EGF-LI is dependent on differentiational state of gastric cancer cells.