Phase II study of twice-daily high-dose thoracic radiotherapy alternating with cisplatin and vindesine for unresectable stage III non-small-cell lung cancer: Japan Clinical Oncology Group Study 9306.

PURPOSE: To evaluate the efficacy and toxicity of high-dose thoracic radiotherapy (TRT) alternating with chemotherapy (CH) for unresectable stage III non--small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-one patients received TRT with 1.5 Gy twice daily, 5 days a week, on weeks 1, 2, 5, 6, and 9, up to a total dose of 66 to 72 Gy, alternating with cisplatin 80 mg/m(2) on day 1 and vindesine 3 mg/m(2) on days 1 and 8, repeated every 4 weeks, for two or three courses beginning on week 3. RESULTS: The median (range) total dose of TRT and number of CH courses were 72 Gy (16.5 to 72 Gy) and three (zero to three), respectively. Delay in TRT > or = 5 days was observed in 24 (75%) of 32 patients who completed the projected treatment, due to leukopenia in 12, esophagitis in seven, infection in two, and other causes in three patients. Partial responses were obtained in 36 patients (88%). The median survival time and 3- and 5-year survival rates were 18.4 months, 24%, and 10%, respectively. Grade 3 or 4 leukopenia and esophagitis developed in 32 and seven patients, respectively. Grade 3 or 4 late esophageal toxicity developed in two patients. CONCLUSION: Alternating high-dose TRT and CH for stage III NSCLC produced a high response rate with median and long-term survival comparable to prior trials utilizing standard approaches in this population. Acute and late esophageal toxicity was observed and interruption of TRT was required in most of the patients.     

Macrophage infiltration correlates with tumor stage and angiogenesis in human malignant melanoma: possible involvement of TNFalpha and IL-1alpha

We examined whether macrophage infiltration is associated with angiogenesis in cutaneous melanoma. The numbers of macrophages and microvessels increased significantly with increasing depth of tumor and with tumor angiogenesis. Macrophage infiltration thus appeared to provide a useful diagnostic marker for the progression of cutaneous melanoma. We further examined whether human melanoma cells produce angiogenic factors in response to macrophage-derived cytokines, tumor necrosis factor alpha (TNFalpha) and interleukin-1 alpha (IL-1alpha). Treatment of melanoma cells with TNFalpha and IL-1alpha in vitro enhanced the production of interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF), and of basic fibroblast growth factor (bFGF) to a lesser degree, in human melanoma cells. Lipopolysaccharide (LPS)-activated human monocytes enhanced production of IL-8, VEGF, TNF alpha, as well as IL-1alpha, but not bFGF. Co-culture of human monocytes and human melanoma cells was also found to significantly enhance production of IL-8 and VEGF in the absence and presence of LPS, compared with either monocytes or melanoma cells alone. The production of IL-8 and VEGF from co-cultured melanoma cells and LPS-activated monocytes was blocked when anti-TNF-alpha antibody or anti-IL-1alpha antibody was co-administrated. This is direct evidence that production of the potent angiogenic factors IL-8 and VEGF from melanoma cells is up-regulated through TNFalpha and/or IL-1alpha secreted by activated monocytes/macrophages, influencing both tumor growth and angiogenesis in melanomas.     

A case of primary adenosquamous carcinoma of the stomach preoperatively diagnosed by endoscopic biopsy

A 53-year-old complained of upper abdominal pain. A diagnosis of Borrmann III type gastric cancer in the posterior part of the corpus region was made by X-ray and endoscopy, and primary adenosquamous carcinoma was preoperatively diagnosed by endoscopic biopsy. Subtotal gastrectomy was performed. The part of the adenocarcinoma adjacent to squamous-cell carcinoma was poorly differentiated. Adenosquamous carcinoma of the stomach is rare. Furthermore, preoperative diagnosis by endoscopic biopsy is extremely unusual, having been reported in 7 cases in Japan including ours. And in 5 cases out of 6, region of the adenocarcinoma was the poorly differentiated type.     

Intrathecal or dietary glycine inhibits bladder and urethral activity in rats with spinal cord injury

PURPOSE: We examined the influence of intrathecal or dietary glycine on bladder and urethral activity in rats with spinal cord injury. MATERIALS AND METHODS: A total of 20 female Sprague-Dawley rats were used 4 weeks after lower thoracic spinal cord injury. The rats were divided into standard and 1% glycine diet groups. In the standard diet group isovolumetric cystometry and urethral pressure measurement were performed before and after intrathecal injection of glycine. In the 1% glycine diet group bladder and urethral activity were compared with control recordings in the standard diet group. RESULTS: In the standard diet group intrathecal injection of glycine prolonged the interval and decreased the amplitude of bladder contractions, decreased baseline urethral pressure and altered urethral activity during bladder contraction from a pattern of detrusor-sphincter dyssynergia to detrusor-sphincter synergy at 100 mug glycine. In the 1% glycine diet group the interval and amplitude of bladder contractions were prolonged and decreased, respectively, compared with those in the standard diet group. Baseline urethral pressure was lower than in the standard diet group even after intrathecal injection of 100 mug glycine. Urethral pressure did not change during bladder contraction and it was the same as baseline pressure. Residual urine volume was lower than in the standard diet group. CONCLUSIONS: Intrathecal or dietary glycine inhibits bladder and urethral activity, and improves detrusor hyperreflexia and detrusor-sphincter dyssynergia.     

Small intestinal mucins are secreted in proportion to the settling volume in water of dietary indigestible components in rats

The aim of this study was to clarify the effect of dietary indigestible components on small intestinal mucin secretion. We prepared polystyrene foam (PSF) with different expansion ratios (PSF-30, -60 and -90) in which powders had different settling volumes in water (SV). Rats were fed a purified diet containing 0, 10, 30, or 90 g of PSF-60/kg for 10 d. After 8 h of food deprivation, rats were refed 3 g of their respective diets within 90 min. Small intestinal mucin fractions were prepared, and periodic acid/Schiff-reactive substances and O-linked oligosaccharide chains were determined as mucin markers. Feeding of PSF-60 increased the small intestinal mucin secretion dose dependently (control vs. 30 or 60 g of PSF-60/kg, P < 0.05). When rats were fed either purified diet or diets containing PSF-30, 60, or 90 at 10 g/kg for 7 d, small intestinal mucins were greatly affected by the SV of the respective PSF tested. Rats fed the diet containing PSF-90 with the highest SV had the highest amount of mucins (vs. control, P < 0.05). In some natural dietary fibers, the small intestinal mucins and SV were correlated (r = 0.967, P = 0.002). Finally, rats were fed a purified diet or that diet containing 50 g of PSF-60/kg for 7 d. Then, each dietary group was further divided into 2 groups. After 8 h of food deprivation, rats were refed 3 g of purified or PSF diet. Greater mucins in the small intestine were manifest only in rats previously fed the PSF diet whether they were refed purified or PSF diet (control vs. PSF, P < 0.05). These results suggest that the small intestinal mucins are secreted in proportion to the SV of dietary indigestible components, and chronic ingestion of indigestible components is required for the appearance of enhanced mucin secretion.     

Esophagocardioplasty with gastric patch in the treatment of achalasia

Result of operative treatment in 196 cases of achalasia was reviewed. The procedures employed include cardiolysis, Heller's extramucosal myotomy, Wendel's cardioplasty, Heyrovsky's esophagocardiostomy, with and without pyloroplasty, cardiac resection and esophagocardioplasty with gastric patch. Follow-up study on 166 cases revealed that the result was classified as good in 99 cases or 59.6 per cent and improved in 46 cases or 27.7 per cent. Overall satisfactory result was obtained in 87.3 per cent. When the result was broken down to groups following three classifications, i. e. according to X-ray, endoscopic and manometric findings, the interesting correlation emerged. Heller's myotomy and esophagocardioplasty with gastric patch gave best results in early stage of achalasia, while in later stage the latter procedure seems to be the operation of choice.     

Co-expression of Y box-binding protein-1 and P-glycoprotein as a prognostic marker for survival in epithelial ovarian cancer

OBJECTIVES: This study aimed to observe the expressions of Y box-binding protein-1 (YB-1) and P-glycoprotein (P-gp) in primary ovarian tumor and to determine whether they act as biomarkers for survival in epithelial ovarian cancer. METHODS: The expressions of YB-1 and P-gp were examined immunohistochemically in 59 patients who were treated from 1997 to 2000 at Kurume University Hospital. Samples were paraffin-embedded primary ovarian cancer tissue taken from the surgical specimens. RESULTS: Of the 59 primary ovarian tumors examined, 32 (54.2%) and 18 (30.5%) were positive for YB-1 and P-gp, respectively. Co-expression of these two proteins was observed in 20.3% (12/59) cases. Patients showing this co-expression had a worse 3-year survival than those without co-expression (40.0% vs. 73.1%, P = 0.0447). This co-expression significantly correlated with poor prognosis according to multivariate analysis (P = 0.0007). CONCLUSION: Co-expression of YB-1 and P-gp emerged as a promising relevant biomarker for unfavorable prognosis in ovarian cancer.