Cisplatin therapy for adenocarcinoma of the stomach.

Cisplatin-based chemotherapy has most recently emerged as among the most active combinations for patients with disseminated or locally unresectable adenocarcinoma of the stomach. This article provides the historical framework for understanding these trials. It reviews the results of clinical trials using cisplatin alone or in combination in almost 600 patients. Because a recent German trial has suggested that cisplatin in combination with etoposide and doxorubicin increases gastric cancer resection rates, the rationale for cisplatin combination therapy in the neoadjuvant setting now has a foundation. Preliminary results from such a neoadjuvant approach used at the University of Southern California Medical Center are discussed. Finally, new areas of clinical and laboratory research in the treatment of gastric cancer are outlined as possibilities for future studies of the therapy of gastric cancer.

Experience with cisplatin in treatment regimens for esophageal cancer.

This article reviews the rationale for chemotherapy (especially cisplatin-based treatments) in the management of epidermoid tumors of the esophagus. It focuses on the history of cisplatin and cisplatin-based combinations in the treatment of metastatic and localized esophageal cancers. The seminal chemotherapy trials of investigators at Memorial Sloan Kettering Cancer Center are reviewed and placed into perspective as a body of work that systematically measured the effects of chemotherapy in the treatment of primary tumors within the esophagus. The Wayne State University (Detroit, MI) program and subsequent similar programs, combining chemotherapy with concomitant radiation, are also reviewed and placed into historical context. Recently completed prospectively randomized cooperative group trials have now shown that chemotherapy in addition to radiation improves survival of patients with localized esophageal cancers versus radiation alone. While no standard chemotherapeutic regimen has come to the fore, chemotherapy clearly has a role in the curative treatment of epidermoid tumors of the esophagus.

Nucleotide sequence and distinctive characteristics of the env gene of endogenous feline leukemia provirus.

Nucleotide sequence analysis of the env gene of two different endogenous feline leukemia virus (FeLV) loci, CFE-6 and CFE-16, of domestic cats revealed the following characteristics. (i) Both proviruses contain an open reading frame in the env region; (ii) whereas the full complement of the exogenous FeLV env is generally present in CFE-6 DNA, it is truncated in CFE-16 DNA such that the 5' half of the gp70 domain and the untranslated region 3' to the p15E domain have been fused by an internal deletion, resulting in loss of the C-terminal half of the gp70- and all of the p15E-coding sequences; (iii) endogenous env is highly homologous to large sequence domains conserved in all three exogenous FeLV subgroups (A, B, and C) but is similar to FeLV-B sequence domains in the variable regions detected in these viruses; and (iv) there are four other sequence domains, one residing at the C terminus of gp70 and three scattered in p15E, which are unique for the endogenous env, thereby distinguishing it from the FeLV-B gene.

Structure and function of endogenous feline leukemia virus long terminal repeats and adjoining regions.

The nucleotide sequence of the 5' long terminal repeat (LTR) of three independent loci (CFE-6, CFE-16, and CF-14) of endogenous feline leukemia virus (FeLV) DNAs of the domestic cat genome was determined. The 3' LTR of the CFE-6 clone was also sequenced. The endogenous FeLV LTRs, which were very similar to each other in sequence and in organization of the functional domains, differed considerably from the exogenous FeLV LTR in the U3 region. The major differences in U3 included variations in sets of small (14 to 19 base pair) direct repeats, altered location of the simian virus 40 core enhancer-like sequence, and occurrence of three segments of largely nonhomologous sequences. There was extensive homology between endogenous and exogenous FeLV LTRs in sequences beginning from the TATA box through the R region down to the 3' end of the U5 region. The DNA sequence downstream of the 5' LTR encompassing the primer-binding site, leader, and almost to the end of the p15gag coding region, a point up to which the sequencing was carried out, also revealed a high degree of conservation. However, the detection of frameshift and nonsense mutations in this region of a nearly full-length endogenous provirus sequence (CFE-6) predicted its defectiveness and correlated with the lack of infectivity of this DNA. The functional studies of the endogenous LTRs, based on linkage to the bacterial cat gene and transient expression in feline cell lines, indicated that although the basic characteristics for promotion and enhancement of transcription were retained in each LTR, there was a significant variation in the activity of the cat constructs. Reconstruction and deletion analyses with the CFE-6 5' LTR revealed the presence of strong transcription regulatory sequences in the 702-base-pair region immediately upstream of the 5' boundary of the endogenous LTR. These and related data suggest that in addition to the transcription-modulating elements occurring within the LTR, the cis-acting nucleotide sequences in the upstream cellular DNA may determine the overall efficiency of transcription of the defective endogenous FeLV provirus loci of the felid genome.