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Sufficient folate intake confers positive health benefits, while deficiency is linked with many health problems. Although the US policy of dietary folic acid fortification has reduced the incidence of these deficiency-related health problems, recent evidence has demonstrated an association between folic acid supplementation and increased colorectal cancer incidence. Few studies have explored the possibility that folate affects other slowly developing cancers. This study sought to determine whether folic acid supplementation is sufficient to alter the growth and development of existing oral cancers. A series of in vitro growth, viability, and adhesion assays were performed using the well-characterized human oral squamous cell carcinoma cell lines, CAL27 and SCC25, to determine the effects of folic acid supplementation. Folic acid administration significantly stimulated CAL27 and SCC25 proliferation in a dose-dependent manner, but it was not sufficient to increase proliferation at any concentration tested in the normal control cell line, HGF-1. Neither oral cancer cell line harbored the common C677T DNA polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene, which might reduce folate bioavailability. Overexpression of p53 mRNA was observed in both cancerous cell lines, but it was differentially altered by folic acid administration in only SCC25 cells. These findings suggest folic acid administration may significantly alter growth of oral cancers in vitro via p53-dependent and p53-independent pathways. As oral cancer rates continue to rise in specific geographic areas, and among specific subsets of the US population, understanding environmental mediators, such as folic acid supplementation, becomes increasingly important for nutrition and public health scientists.

Proanthocyanidins, compounds highly concentrated in dietary fruits, such as cranberries and grapes, demonstrate significant cancer prevention potential against many types of cancer. The objective of this study was to evaluate cranberry and grape seed extracts to quantitate and compare their anti-proliferative effects on the most common type of oral cancer, oral squamous cell carcinoma. Using two well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC25, assays were performed to evaluate the effects of cranberry and grape seed extract on phenotypic behaviors of these oral cancers. The proliferation of both oral cancer cell lines was significantly inhibited by the administration of cranberry and grape seed extracts, in a dose-dependent manner. In addition, key regulators of apoptosis, caspase-2 and caspase-8, were concomitantly up-regulated by these treatments. However, cranberry and grape seed extracts elicited differential effects on cell adhesion, cell morphology, and cell cycle regulatory pathways. This study represents one of the first comparative investigations of cranberry and grape seed extracts and their anti-proliferative effects on oral cancers. Previous findings using purified proanthocyanidin from grape seed extract demonstrated more prominent growth inhibition, as well as apoptosis-inducing, properties on CAL27 cells. These observations provide evidence that cranberry and grape seed extracts not only inhibit oral cancer proliferation but also that the mechanism of this inhibition may function by triggering key apoptotic regulators in these cell lines. This information will be of benefit to researchers interested in elucidating which dietary components are central to mechanisms involved in the mediation of oral carcinogenesis and progression.

To the Editor.— Fifteen patients with herpes gestationis have been studied with immunofluorescence, and the findings reported, 1,2 since Provost and Tomasi, 3 have demonstrated C3 at the basement membrane zone in two cases in 1973. In all 17 cases, C3 was found at the basement membrane zone, while 11 showed IgG at the basement membrane zone by direct test, and only two showed circulating serum antibodies to the basement membrane zone (Table). These findings show herpes gestationis has distinct immunofluorescent characteristics, closer to bullous pemphigoid than it is to dermatitis herpetiformis, a concept that was previously based on clinical descriptions. Interesting atypical fluorescent findings have recently been reported in the bullous diseases. 4-6 We now describe a unique case that was diagnosed as herpes gestationis on clinical grounds but with features of pemphigus and herpes gestationis on immunofluorescence testing. Report of a Case.— A maculopapular pruritic eruption developed on

• Previous reports showed that cyclophosphamide used late in the treatment of patients with pemphigus vulgaris reduced the complications due to steroids. In this study, cyclophosphamide was used in the initial treatment of five patients with pemphigus vulgaris in combination with prednisone to avoid side-effects of prednisone. Two patients had no prior treatment with steroids for pemphigus. Results indicate that the initial combined program may be a highly effective treatment method for pemphigus vulgaris. Followup from one to four years after treatment shows all five patients in remission; four require no medication. ( Arch Dermatol 114:889-894, 1978)