For the purpose of analyzing the functions of regional lymph node lymphocytes (RLNL) in human lung cancer, we compared the response of RLNL to interleukin-2 (IL-2) with that of peripheral blood lymphocytes (PBL). With [3H]-thymidine incorporation, the entire RLNL population, including nonadherent RLNL and their E-rosette+ population, showed much stronger responses to IL-2, especially at low concentrations, than did PBL. After RLNL were cultured with IL-2 for 6 days, both IL-2 receptor (IL-2R) α and β chains on CD4+ cells and CD8+ cells were analyzed and compared to those of PBL by using a flow cytometer. Compared to PBL, the expression of the IL-2R α chain on the CD4+ cells of RLNL was more highly enhanced by the addition of IL-2. These data suggest that even in low concentrations RLNL show a higher response to IL-2. These findings might shed new light on immunotherapy using RLNL in lung cancer patients.
Colon cancer which represents a long segmental stenosis and has a cobblestone-like appearance is generally likely to be indistinguishable from inflammatory bowel disease. We treated two such cases in a 30-year-old woman and a 48-year-old man. The woman had a previous history of ulcerative colitis; she suffered from peritonitis due to a perforation of the sigmoid colon and underwent a simple closure of the perforation, a transverse colostomy and drainage. An enema performed after the operation showed a long segmental stenosis and fistula formation between the colon and ileum. Diagnosed as having inflammatory bowel disease, probably Crohn's disease, she was treated with conservative therapy. However, further examinations revealed the existence of colon cancer. The man was admitted to our hospital for melena. An enema and colonoscopy revealed a long segmental stenosis and the cobblestone appearance of the transverse colon. Diagnosed as having inflammatory bowel disease, probably Crohn's disease, he was treated with conservative therapy. However, his condition did not improve in spite of therapy. Tumor marker analysis showed an increased CEA level. A colonoscopy was performed again and revealed the existence of colon cancer. In both patients, the cancer was far advanced. They both underwent a segmented resection of the colon, and both died in spite of chemotherapy. The morphology of stenosis of inflammatory bowel disease is said to be smooth with tapering edges which gradually fuse into the nonstenotic bowel. However, as was the case with these patients, it is not always easy to distinguish stenosis of inflammatory bowel disease from cancer, especially when it coexists with a cobblestone appearance. Therefore, a careful examination and the suspicion of malignancy is essential in cases like this.
Factors affecting survival after resection in patients with gastric cancer and simultaneous distant metastases were examined in the present study. A total of 300 patients who had undergone resection of gastric cancer, and who had distant metastases, were retrospectively analyzed with respect to survival using a multivariate analysis. Significant differences in survival time were found when univariate analysis was used to examine extent of lymphadenectomy (p<0.0001), surgical resectability (p<0.0001), depth of the tumor invasion (p=0.016), size of tumor (p=0.027) and liver metastasis (p<0.0001). Multivariate analysis using Cox's hazard model indicated that lymphadenectomy (hazard ratio: 1.469), surgical resectability (hazard ratio: 1.525), depth of the tumor invasion (hazard ratio: 1.530) and liver metastasis (hazard ratio: 2.062) were independent prognostic factors. The results of the present study suggest that the potential for cure in gastric cancer patients with distant metastases varies among patterns of metastasis, and that radical surgery with extended lymphadenectomy in attempts at the curative resection may contribute to increased survival of some of such patients.
The aim of this study was to assess exon deletion in the hormone- and DNA-binding sites of the ER α gene in endometrial diseases. The frequencies of three ER α splice variants (del. 2/3, del. 5, and del. 7) in 41 endometrial specimens were assessed by reverse transcription-polymerase chain reaction (RT-PCR) analysis and correlations with their histological features were examined. All the PCR products that corresponded to splice variants were expressed by products that corresponded to the wild type (wt.) mRNAs, and none of the tissues expressed a splice variant alone. ER α splice variant expression was not uncommon, and 82.9% (34/41) of the endometrial samples expressed one or more aberrant variants. Del. 5 and 7 were expressed more frequently (63.4 and 68.3%, respectively) than del. 2/3 (26.8%), and there was no significant difference between the frequency of each ER α variant in benign and malignant lesions, nor in samples from menopausal and premenopausal patients. We concluded that rather than being an abnormal event, ER α splice variant expression in hormone- and DNA-binding domains is a physiological event that occurs with wt. mRNA expression and is not a feature peculiar to neoplastic change in human endometrial tissue.
Direct mediastinal injection of Cisplatin (CDDP) with activated charcoal or of CDDP powder with Lipiodol (DDS-CDDP) was performed in advanced esophageal cancer patients (Stage III and IV) from 1989 to 1995. Curative tumor resection with extended lymphadenectomy was performed in 45 cases, and 22 patients received the direct mediastinal injection (DMI) combined with additional postoperative systemic chemotherapy (DMI group); these two treatments were assigned by block randomization. CDDP was injected into the mediastinum in two forms: CDDP+FM127 (activated charcoal) and CDDP powder+Lipiodol. Complications related to mediastinal injection occurred in only 1 patient (mediastinitis). Mediastinal local recurrence was not determined in patients with DMI treatment. In conclusion, direct injection of DDS-CDDP to the mediastinum might be a safe and effective postoperative treatment for prevention of local recurrence in the mediastinum.
The relationship between apoptosis induction by X-ray and by cell cycle regulation remains not well understood. In this study, using EL-4 mouse lymphoma cells we demonstrate that the majority of apoptotic cell death following X-irradiation is induced after G2/M arrest. When cells were irradiated at a dose of 20Gy, their viability began to decrease at 24h. Gel electrophoresis of the extracted DNA showed multimers of 200bp fragments, which are characteristic of apoptosis. An increase in the apoptotic fraction was observed when the X-irradiated cells began to accumulate in the G2/M phase. The apoptotic rate was remarkably augmented by caffeine that inhibits the G2 checkpoint system; this effect was clearly demonstrated by a suppression of the cyclin B1: cdc2 ratio. A remarkable decrease in bcl-2 expression may also be ascribed to the apoptosis-enhancing effect by caffeine. In contrast, an antimitotic drug, colchicine, did not affect the rate of DNA fragmentation. These results suggest that G2/M is a critical phase in the regulation of apoptotic cell death and that X-ray-induced apoptosis can be triggered if mitotic events progress without repair of the damaged DNA. Despite X-irradiation's usual effect in increasing p53 expression, intracellular p53 levels in irradiated cells were significantly suppressed in the presence of caffeine. This demonstrates that the mechanism of X-ray-induced apoptosis is involved in the increased expression of p53 proteins, whereas enhancement of apoptotic cell death by caffeine is independent of p53 status.
To evaluate the effectiveness of immunotherapy using PSK, an immunomodulator, a controlled study was implemented from February 1987 to November 1989 at 16 institutions in Japan. Postoperative adjuvant therapy completely accomplished was continued for at least 3 months until to the tumor progression. The aim of the present retrospective study was to evaluate the indications for PSK therapy by using 653 patients drawn from this controlled study, who were completely accomplished therapies. Two hundred twenty-two patients underwent surgery alone, 184 received gastrectomy plus complete PSK therapy, 146 received gastrectomy plus complete chemotherapy, and 101 received gastrectomy plus complete chemotherapy plus PSK. There was a significant difference in survival between patients receiving gastrectomy alone and PSK, but not between those receiving chemotherapy and chemotherapy + PSK. There was also a significant difference in survival between patients with and without PSK. Among CEA-negative patients, there was a significant difference in survival between patients receiving gastrectomy alone and those receiving PSK, while among CEA-positive patients, there was a significant difference in survival between both gastrectomy alone and PSK, and chemotherapy and chemotherapy + PSK. Using the Cox's proportional-hazard model, we identified that PSK therapy prolonged survival times in patients with abnormal levels of IAP, ASP, SA, and CEA, while in those with normal level of ACT with statistical significance, and that the stata of CEA and SA levels might be best predictive values of response to PSK treatment in gastric cancer.