Carbon tetrachloride when administered to animals in sufficient quantities causes liver cell injury. Earlier metabolic studies emphasized the effect of this poison on the tricarboxylic acid cycle and fatty acid oxidation. In both chemical and anatomical investigations, attention has been directed largely to the mitochondrion as the affected organelle: Christie and Judah (1) reported changes in the stability of several enzymes of the tricarboxylic acid cycle when examined 12 to 16 hours after the administration of the carbon tetrachloride. We were unable to find evidence of mitochondrial changes histochemically at earlier periods, 3 to 6 hours following carbon tetrachloride administration, when morphological evidence of cell injury is already apparent. Examination of the liver by electron microscopy at these early times following carbon tetrachloride administration also failed to reveal alterations in the mitochondria, but discernible changes were apparent in the endoplasmic reticulum. Similar changes in the endoplasmic reticulum had already been described by Oberling and Rouiller (2) and by Bassi (3) but no association of these with metabolic alterations was made.Since the rough endoplasmic reticulum is believed currently to participate in protein synthesis, the alterations produced by carbon tetrachloride suggested that there might be a defect in this process (4). The following report presents evidence that an early, and perhaps fundamental, manifestation of carbon tetrachloride is the altered relationship of the ribonucleoprotein (RNP) particles to the membranes of the rough endoplasmic reticulum and associated with this an impairment of protein synthesis within the liver cells.
Loss of heterozygosity affecting chromosome 17p has been detected at high frequencies in a variety of human tumors, including cancers ofthe colon, breast, lung, and brain. One presumed target of these losses is p53, a tumor suppressor gene located on 17p. To our knowledge, loss of heterozygosityhas not yet been reported at any locus, including p53, in human esophageal cancer. Moreover, current methods of detecting loss of heterozygosity depend on the availability of large amounts of high molecular weight DNA, making the study of small biopsy specimens or paraffin-embedded tissues problematic. We examined 52 primary human esophageal neoplasms for loss of heterozygosity affecting the p53 gene by using the polymerase chain reaction. Loss of one allele was detected in 52% of informative cases and was more common in squamous carcinomas than in adenocarcinomas. Southern blot analysis was used to confirm polymerase chain reaction-derived data.The identification of allelic loss in approximately half of the tumors analyzed supports the hypothesis that inactivation of p53 is involved in the pathogenesis of esophageal cancer.Esophageal carcinoma is a major cancer worldwide, ranked among the leading causes of cancer death (1). There are two main forms of this disease, squamous cell carcinoma and adenocarcinoma. Squamous esophageal cancer is associated with ethanol and tobacco consumption (1), whereas primary esophageal adenocarcinoma usually accompanies Barrett esophagus (2). Barrett esophagus denotes replacement of the normal squamous esophageal lining by metaplastic columnar mucosa in response to chronic gastroesophageal reflux (3). Patients with this condition are at increased risk of developing esophageal adenocarcinoma (4, 5). Despite the clinical importance of esophageal cancer, its molecular basis is not well understood. Recent studies have addressed the role of ras family protooncogene activation in this disease, but ras mutations were found rarely or not at all (6-9). Amplification of several protooncogenes has also been reported (6, 10-13).Loss of heterozygosity (LOH) occurring frequently at a specific locus is widely assumed to imply the existence of a tumor suppressor gene at or near that locus. The p53 gene encodes an evolutionarily conserved 53-kDa cellular protein implicated in the control of cell proliferation and tumor formation/progression (14)(15)(16)(17)(18)(19)(20)(21)(22). LOH at or near the p53 gene locus, shown to occur frequently in a variety of human tumor types (18,(23)(24)(25)(26)(27)(28)(29), is believed to favor malignancy by removing a normal copy of this tumor suppressor gene (30). The remaining p53 allele is often inactivated by point mutation (18)(19)(20)(31)(32)(33)(34). It is believed that this mutant p53 may exert a dominant negative effect by complexing with wild-type product (35,36). A recent study suggests involvement of the p53 gene by point mutation in esophageal cancers (34). LOH at any locus, including 17p, has not to our knowledge been reported in esophageal cancer.Curren...
Basaloid squamous carcinoma is believed to be a histologically distinct variant of squamous cell carcinoma of the neck region with 11 cases reported. Two cases arising in the pyriform fossa and vallecula are reported, both of which were associated with second primary malignant tumors: esophageal small cell carcinoma and palatal squamous cell carcinoma, respectively. The authors suggest that basaloid squamous carcinoma may be associated with a high incidence of second primary tumors in the upper gastrointestinal tract or larynx.
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