Correlation between Dose and Tumor Response in the Radiotherapy of Lung Cancer of Various Histological Types

Correlation between dose and tumor response by cell types wasdetermined in 50 patients with lung cancer in order to predictthe possibility of further tumor regression. The TDF (time-dose-fractionation)concept was used as dose factor. The radiation source was a cobalt-60 -ray or linear accelerator10 MV X-ray. As a routine regime a fraction dose of 2 Gy fivetimes per week was given to 39 of the 50 patients, but a doseof 2 Gy three times per week or of 1.5 Gy five times per weekwas given to seven and four patients, respectively. Radiation response was the best in small cell carcinoma andbetter in adenocarcinoma than in squamous cell carcinoma, showinga tumor regression rate of 50% or more in 90%, 80% and 58% ofthe patients, respectively. The correlation between tumor regression rate and TDF valueswas good in squamous cell carcinoma (r=0.73) and small cellcarcinoma (r=- 0.72), but poor in adenocarcinoma (r=- 0.10).These results suggest that in squamous cell carcinoma improvementof tumor regression can be expected by increasing TDF values,and in adenocarcinoma and small cell carcinoma the optimal TDFvalues are about J00 and 60 to 80, respectively.     

"Flare" Followed by Successful Tamoxifen Therapy in Two Cases of Advanced Breast Cancer

An antiestrogen, tamoxifen, is an effective drug in the treatmentof advanced breast cancer. The drug is generally very well toleratedand serious side effects such as the so-called "flare in thetumor" have rarely been observed. We have had two patients withadvanced breast cancer who showed the "flare" soon after theinitiation of tamoxifen therapy, and both patients finally achievedpartial response to tamoxifen. It is important not to misinterpretthe "flare" as progressive disease during tamoxifen therapy.     

Usefulness of ultrasensitive prostate-specific antigen assay for early detection of biochemical failure after radical prostatectomy

BACKGROUND: In order to assess whether the prostate-specific antigen (PSA) nadir obtained with an ultrasensitive PSA assay can be used as a prognostic indicator for patients undergoing radical prostatectomy, we investigated it retrospectively. METHODS: Between October 1997 and July 2003, 46 patients underwent radical prostatectomy for prostate cancer at our institution. None of them received preoperative treatment. Levels of PSA were measured with an ultrasensitive PSA assay every 1-3 months after prostatectomy. Biochemical recurrence was defined as a PSA level of 0.2 ng/mL or higher. RESULTS: There was a significant difference in PSA nadir between the biochemical recurrence group and the no recurrence group (P < 0.001). The receiver operating characteristics (ROC) curve gave an optimal cut-off value for PSA nadir of 0.01 ng/mL, demonstrating a significant difference in biochemical recurrence after radical prostatectomy. No patient with a PSA nadir level <0.01 ng/mL showed biochemical failure, while 15 out of 22 patients with PSA nadir levels >or=0.01 ng/mL showed biochemical failure. CONCLUSION: The PSA nadir level obtained using an ultrasensitive PSA assay is an excellent predictor of biochemical recurrence after radical prostatectomy. Early detection of recurrence offers the possibility of early salvage therapy.     

EXCRETION OF BIKUNIN AND ITS FRAGMENTS IN THE URINE OF PATIENTS WITH RENAL STONES

PURPOSE: Bikunin is a Kunitz-type protease inhibitor found in serum and urine. It has been implicated in urinary stone formation. This study was designed to investigate the role of urinary bikunin in stone formation. MATERIALS AND METHODS: Urinary concentrations of bikunin were measured in 18 male formers of urinary stones 28 to 74 years old and in 77 healthy controls, including 39 males and 38 females, without urological abnormality. A sensitive competitive solid phase enzyme immunoassay was established for urinary bikunin. Bikunin was also qualitatively assessed by Western blot analysis. RESULTS: The mean urinary bikunin-to-creatinine ratio plus or minus standard deviation in stone formers was significantly elevated compared with that in healthy male and female controls (52.9 +/- 46.0 microg./mg. creatinine versus 28.0 +/- 30.4 and 26.5 +/- 21.7, p = 0.005 and 0.006, respectively). By Western blot analysis all urine samples contained authentic 40 kDa. bikunin species. However, a significantly higher proportion of patients was found to have aberrant 25 kDa. bikunin species compared with controls (10 of 18 or 55.6% versus 15 of 77 or 19.5%, p = 0.002). Experiments on de-glycosylation with chondroitinase ABC, amino acid sequencing of the aberrant bikunin species and calcium oxalate crystal growth inhibition assay demonstrated that the 25 kDa. bikunin fragment was identical to de-glycosylated bikunin and less inhibitory on calcium oxalate crystal growth. CONCLUSIONS: If urinary bikunin is important in the pathogenesis of urolithiasis, its effect is probably attributable to the concentration and degree of glycosylation.     

Enzymatic semisynthesis of [Leu B30] insulin

Experimental conditions for the preparation of [Leu^B30] insulin by coupling of des-Ala^B30 insulin with Leu-OBu^t were determined using Achromobacter protease I and trypsin as catalysts. Successful coupling required a large excess of the amine component (0.8 M), a high concentration of organic cosolvent (35–50%) and neutral pH of the reaction mixture. The coupling yield of Achromobacter protease I after 24 h at 37°C was almost the same or a little higher than that at 25°C. With trypsin, the coupling yield at 37°C after 24 h was considerably lower than at 25°C. This was partly ascribed to the difference in concentration of organic cosolvent at 37°C and 25°C; 35% and 50%, respectively, or possibly of enzyme stability at these temperatures. The maximum product yield was about 90% with both enzymes under optimal conditions. A preparative scale experiment was performed with Achromobacter protease I; the yield of [Leu^B30] insulin was 51% using porcine insulin as the starting material. This semisynthetic insulin was identified by HPLC and amino acid analysis. No difference was observed in CD spectra between [Leu^B30] insulin and human insulin.     

Comparison of Survival of Patients With Lung Cancer Between Elderly (greater double equals70) and Younger (70>) Age Groups

Results of radiotherapy for lung cancer in the elderly werecompared with those in younger patients. A total of 129 patientswere treated by radiation therapy with or without chemotherapy.Fifty-six patients (43.4%) were 70 years old or more (elderlygroup) at the time of treatment, and the remaining 73 patientswere below age 70 (younger group). Treatment results in the elderly group were nearly the sameas those in the younger group in all stages of the disease.Survival time was longer for patients with performance status(PS) of 0 to 2 than for those with PS 3 or 4 regardless of age(p < 0.05). The survival time of the elderly group was nearlythe same as that of the younger group for squamous cell carcinoma,but somewhat shorter for adenocarcinoma although the differencewas not statistically significant. There was no difference insurvival between the two groups when they were treated by combinedradiation therapy and chemotherapy. Our results suggest thatelderly patients can be treated as safely as younger patientsby radiotherapy alone or combined radiation therapy and chemotherapy.     

Colony-Stimulating Factor Producing Carcinoma of the Gallbladder

A patient with an anaplastic carcinoma of the gallbladder accompaniedby marked neutrophilia was found to have high colony-stimulatingfactor (CSF) activity in the urine and serum. The supernatantof the cultured tumor cells (6th passage) showed high and specificCSF activity. These specimens induced the formation of granulocytecolonies, macrophage colonies or granulocyte macrophage mixedcolonies by both human and C57BL mouse bone marrow cells insoft agar. These results suggest that this tumor is a human granulocyte-macrophage(GM)-CSF producing tumor.     

Ovarian mixed germ cell tumor composed of dysgerminoma, endodermal sinus tumor, choriocarcinoma and mature teratoma in a 44-year-old woman: Case report and literature review

A case of ovarian mixed germ cell tumor In a 44-year-old woman was examined. The tumor was well circumscribed, measured 15 times 11 times 10cm and appeared solid and partly cystic on the cut surface. Light microscopic examinations revealed that the tumor was composed of four different neoplastic germ cell elements, Intermingled with each other. They are: (i) choriocarcinoma, immunohistochemically positive for human placental lactogen (hPL) and human chorionic gonadotropin (hCG); (ii) dysgerminoma, positive for placental alkaline phosphatase; (iii) endodermal sinus tumor positive for α-fetoproteln (AFP); and (lv) mature teratoma. Among these histological types, dysgermlnoma occupied more than 50% of the neoplasm. The patient was diagnosed as a stage la ovarian mixed germ cell tumor and was subsequently treated with chemotherapy. A second-look laparotomy after completion of chemotherapy revealed no residual tumors in the abdomen and the patient Is alive and well 15 months after operation. This Is the fourth reported case of ovarian mixed germ cell tumor arising In patients over 40 years old.