Salivary glands secrete saliva which contains mucins, antimicrobial substances and growth factors. Since epidermal growth factor (EGF) and nerve growth factor (NGF) were demonstrated in murine submandibular glands (SMGs), several growth factors and biologically-active peptides have been studied in the human or other mammalian salivary glands and saliva. These growth factors may have a functional role in cell migration, proliferation and maturation within not only salivary glands but also other organs. In the SMGs of mice and rats, EGF, NGF and other known growth factors are usually synthesized in granular convoluted tubule cells (GCT). However, human SMGs are devoid of GCT cells, and growth factors in human salivary glands are usually produced in striated ducts. These findings suggest an evolutionary trace of ductal cells in mammals. The present review describes expression patterns of the following salivary gland growth factors: nerve growth factor (NGF); transforming growth factor α and β (TGF-α/β) bone morphogenetic protein (BMP); insulin-like growth factor (IGF); fibroblastic growth factor (FGF); and somatostatin, as well as their receptors. This review also discusses their cell biological roles in pathophysiological conditions.

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The kinetics of oxygenation and proliferative activity in mouse squamous cell carcinomas subjected to photodynamic therapy (PDT) were investigated in order to elucidate appropriate fractionation intervals between PDTs for enhanced anti-tumor effects. Tumor reoxygenation following PDT was evaluated in mice by immunohistochemical expression of hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). In addition, proliferative activity after PDT was assessed by the immunohistochemical expression of proliferating cell nuclear antigen (PCNA). Both the HIF-1α labeling indices (LIs) and VEGF LIs of tumor cells were increased at 0, 2.5, and 6 hrs after PDT but subsequently decreased at 24 hrs after PDT. The PCNA LI of tumor cells at 24 hrs after PDT was significantly lower than that of the control group but returned to the control level at 48 hrs. These results suggested that tumors subjected to PDT appeared to be hypoxic from immediately to 6 hrs after PDT but subsequently were reoxygenated at 24 hrs after PDT. In conclusion, we propose here that fractionated light exposure with a 24-hrs interval should be utilized in PDT for an enhanced anti-tumor effect.

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Ganglioneuroma of the head and neck is rare. The clinical, histopathological and immunohistochemical characteristics of 6 cases of cervical ganglioneuroma were analyzed. The average age of the patients in this study was 32.8 years (6-62 years). The tumors grew slowly and the patients were asymptomatic. Grossly, they were well encapsulated. Under the microscope, the tumors consisted of primarily Schwann cells, tangled masses of neurites in bundles, and variably-distributed large ganglion cells. The ganglion cells showed positive immunohistochemical reactivity to neuronspecific enolase, neurofilament, chromogranin A, and synaptophysin but negative for S100, the same as in the controlled normal sublingual ganglion cells. All the tumors were treated with surgical excision. There was no recurrence and metastasis during a follow-up time of 3-5 years.

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A rare case of hepatocellular carcinoma (HCC) that metastasized to the posterior mandible of a 74-year-old Japanese female is described. Computed tomography (CT) revealed buccolingual osteolytic masses. Histopathologically, the solid tumor nests were composed of cells with granular eosinophilic cytoplasm, oval nuclei and enlarged nucleoli. Immunohistochemically, the tumor cells were strongly positive for hepatocyte paraffin 1 (Hep Par 1) and cytokeratin 18 (CK18). Ultrastructurally, abundant mitochondria, rough endoplasmic reticulum, lysosome-like granules, ductal structures and intercellular junctional complexes were distinct in the tumor cells. At autopsy, multinodular tumor masses and cirrhosis were detected in the liver. Microscopically, the tumor cells had trabecular, solid and sarcomatous appearances with severe atypism. Metastatic foci were found in the spleen, stomach, lymph nodes and ribs, but not in the lungs. We finally diagnosed this as mandibular metastasis of HCC, which is a very rare cancer, 1 of only 5 known cases in a female.

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A case of multiple-drug-induced gingival overgrowth (GO) in a 46-year-old male is reported. The patient exhibited severe gingival enlargement throughout the entire mandible and maxilla with a history of multiple medications for psychiatric and internal diseases. A gingivectomy specimen was examined pathologically and further analyzed using immunohistochemical and molecular biological methods for the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Histologically, the gingival overgrowth was due to fibrous granulation tissue with hyperplastic collagen bundles and squamous epithelia, and the lesion was pathologically diagnosed as drug-induced gingival hyperplasia. An enhanced transcript level for TIMP-3 but reduced levels for MMPs and cathepsin L were quantitatively determined by RT-PCR. TIMP-3 was strongly immunohistochemically localized in fibroblasts and endothelial cells. DNA invader genotyping revealed that the patient carried one GO-related allele (α2 integrin +807C). These findings showed that, in this GO case, collagen accumulation in the gingival granulation tissue was associated with decreased MMPs and increased TIMP-3 expression, which was suggested to be synergistically induced by simultaneous and multiple medications, including nifedipine and antipsychotic drugs.

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