摘要:

Ninety-three patients underwent a potentially curative abdominoperineal resection (APR) with a wide perineal dissection to the ischial tuberosities and excision of the entire mesorectum. There were 56 males and 37 females. The median follow-up was 67 months (range 7–240 months). The lymph node clearing technique was used and the median number of lymph nodes cleared was 35 (range 6–89). Eighteen of 93 patients (19%) developed a local recurrence, 12 of whom (13%) developed local recurrence only as the first site of recurrence. In 10 of 18 patients (56%) the distal rectum was the site of the primary rectal cancer. Of the 18 patients, 1 patient had stage I disease, 5 stage II, and 12 stage III. Five of the 18 patients (28%) who developed a local recurrence received adjuvant therapy. The median survival from the time of diagnosis of a local recurrence was 12 months. Histological grade (p =. 001), patient age (p =. 006), and presence of positive lymph nodes (p =. 005) had a statistically significant adverse effect on survival. We believe the surgical technique of abdominoperineal resection with wide perineal resection to the ischial tuberosities and total excision of the mesorectum allowed us to achieve a low local recurrence rate (13%) in a high-risk group of patients. Clearly, the best form of prevention for local recurrence from rectal adenocarcinoma is radical surgical therapy of the primary tumor.

ISSN:0735-7907    

DOI:10.3109/07357909609018432

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Because most cancer deaths result from disseminated disease, understanding the regulation of tumor invasion and metastasis is a central theme in tumor cell biology. Interactions between extracellular matrices (ECM) and cellular microenvironment play a crucial role in this process. We have tested selected amino acids andpolyamines for their ability to regulate RL95–2 cell invasion through both intact human amniotic basement membrane and a novel human ECM (Amgel). Three major systems for neutral amino acid transport, systems L, A, and ASC, are operational in these neoplastic cells. Amino acids entering the cell via transport system A or N, i.e., (methyl amino)-isobutyrate (MeAIB) orAsn, markedly enhanced invasiveness of these human adenocarcinoma cells as measured by a standard 72-hr amnion or Amgel invasion assay. Addition of 2-amino-2-norborane carboxylic acid (BCH; 1 mM), a model substrate of the L transport system, caused a significant decrease in invasive activity when tested in the Amgel assay. Interestingly, Val lowers steady-state levels of MeAIB uptake and blocks the increase in cell invasion elicited by MeAIB. At the same time, these amino acids do not influence cell proliferation activity. Neither the charged amino acid Lys or Asp (not transported by A/N/L systems) nor the polyamines putrescine, spermidine, or spermine modulate invasiveness under similar experimental conditions. Moreover, the observed time-dependent stimulation of system A activity (cellular influx of MeAIB) by substrate depletion is prevented by the addition of actinomycin D (5μM) or cycloheximide (100μM), suggesting the involvement of de novo RNA and protein synthesis events in these processes. MeAIB treatment of tumor cells selectively increased the activities of key invasion-associated type IV collagen-ases/gelatinases. These results indicate that in the absence of defined regulators (growth factors or hormones), certain amino acids may contribute to the epigenetic control of human tumor cell invasion and, by extension, metastasis. We propose that amino acids, acting via specific signaling pathways, modulate phenotypic cell behavior by modulating the levels of key regulatory enzymatic proteins.

ISSN:0735-7907    

DOI:10.3109/07357909609018433

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

The effect of 3′-deoxyadenosineN1-oxide (3′-dANO) on Ehrlich ascites tumor and a human squamous lung cell carcinoma was investigated. The 3′-dANO concentration that inhibited the cell growth 50% (IC50) in Ehrlich ascites tumor cells in vitro was 0.15 mM, and the killing efficiency concentration (concentration of the drug that kills all cells) was 1 mM. By simultaneous administration of 3′-dANO and the adenosine deaminase inhibitor erythro-9-(2-hydroxyl-3-nonyl) adenine (EHNA), the IC50of 3′-dANO was unchanged, but the killing efficiency concentration of 3′-dANO was reduced to 0.3 mM. When mice bearing Ehrlich ascites tumor were treated i.p. with 3′-dANO doses of 200 mg/kg daily for 4 days, the mean increased life span (ILS) was 200%. 3′-dANO in combination with EHNA did not further increase the life span of the tumor-bearing mice. The specific growth delay (SGD) of the Ehrlich tumor and of a human squamous lung cell carcinoma growing subcutaneously in 3′-dANO-treated mice were calculatedfrom Gomperts tumor growth curves. The Ehrlich tumor-bearing mice received 3′-dANO i.p. at doses of 250 mg/kg daily for 4 days, and the nude mice bearing human carcinoma received 3′-dANO i.p. at doses of 225 mg/kg daily for 5 days. The SGD for the investigated tumors were calculated to be 1.0 and 1.1, respectively.

ISSN:0735-7907    

DOI:10.3109/07357909609018434

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909609018435

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909609018436

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

An outgrowth of classic nucleic acid interaction studies, oligonucleotide-directed triple helix formation is a unique method for creating highly specific chemical ligands that recognize and bind to particular sequences of duplex DNA. Under permissive conditions, these oligonucleotide-based compounds can approach or exceed the binding affinity and sequence specificity of natural DNA-binding proteins. Triple helix recognition has been found to be useful in certain cell-free applications including precise chromosome fragmentation. It has been proposed that such oligonucleotides could also form the basis for gene-targeted (antigene) drugs that might repress transcription from undesired genes in living cells. However, current strategies for oligonucleotide-directed triple helix formation suffer from important constraints involving requirements for stabilizing binding conditions, restrictions on permitted target sequences, and inefficient nuclear delivery of oligonucleotides. Implementation of oligonucleotide-directed triple helix formation as a viable approach to cancer therapy must therefore await clever solutions to a series of fascinating problems.

ISSN:0735-7907    

DOI:10.3109/07357909609018437

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909609018438

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909609018439

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor