High Positive Rate of pS2 Expression in Forefront Intraductal Cancerous Area in Breast Cancer

Multiple sections of 40 consecutive cases with invasive ductal carcinoma of the breast, all of which had wide intraductal cancerous extension, were examined by immunohistochemicsl analysis for evaluation of hormone dependency in several areas of breast cancer tissues. In this study, we examined the expression of pS2 protein in the central invasive area (CIV), central intraductal cancerous area (CDC) and forefront intraductal cancerous area (FDC). pS2 staining was positive in 52.5% (21/40) of CIV and a significant correlation was found between pS2 expression in CIV and the estrogen receptor status (ER). pS2 staining was positive in 77.5% of CDC and 85.0% of FDC, respectively. A majority (68.4%) of the cases that were negative pS2 in CIV were positive for pS2 in FDC. Moreover, the cases with noncomedo intraductal carcinoma in premenopausal status showed a higher positivity of pS2 expression in FDC than the cases with comedo-carcinoma, though the number of cases of comedo-carcinoma was limited. These findings suggest that endocrine therapy may be useful after breast conserving treatment regardless of the ER status of the primary tumor.     

Treatment of children with refractory acute lymphocytic leukemia with vincristine and diltiazem

Six children with refractory acute lymphocytic leukemia were treated with vincristine combined with diltiazem. In four of five children who took the drug as scheduled, a cytolytic effect was observed. One child showed massive cell destruction which caused hyperuricemic nephropathy. The only adverse effect was atrioventricular block in two children, which was completely reversible. Increased neurotoxicity was not observed in any child.     

Clinical Usefulness of Determining the Rate of Thermal Clearance within Heated Tumors

Between June 1987 and June 1988, 28 patients (28 tumors) withliver, retroperitoneal, intrapelvic, or superficial tumors weretreated with hyperthermia combined with radiotherapy and/orchemotherapy. Hyperthermia was administered once or twice aweek for 30-60 min per session, up to a total of 2–11sessions, with an 8-MHz RF capacitive heating device. Bloodflow in the tumors was evaluated from the rate of thermal clearance(TCR) using the bio-heat transfer equation. The TCR was measuredin the middle of the first heating session and at the end ofthe last heating session by turning off the output power ofthe heating device. For 9 patients, contrast-enhanced CT scanswere taken and CT numbers at the centers of tumors were measuredbefore and after the entire course of hyperthermia. Changesin TCR were closely related to average tumor center temperature,changes in CT number, and tumor response. When smaller and moresuperficial tumors were treated by hyperthermia combined withradiotherapy and/or chemotherapy that consisted of many heatingsessions and during which a high average tumor center temperaturewas achieved, a better tumor response was obtained. The betterthe tumor response, the higher the local control rate became.The cause-specific survival rate of patients who achieved goodtumor responses was higher than that of patients who showedpoor tumor responses. Changes in TCR and CT number in heatedtumors were useful and important indicators of tumor responseto hyperthermia.     

A phase I and II clinical trial of a newly developed ultrasound hyperthermia system with an improved planar transducer

: The clinical usefulness of a newly developed ultrasound hyperthermia system was evaluated.

: The hyperthermia system uses a modified planer transducer operated at frequencies of 0.5, 1.0, and 1.5 MHz. The transducer has a nonvibrating part at the center to reduce the central hot spot. Frequency sweeping technique is also used to eliminate the annular hot spot around the center. Thirty-eight tumors in 29 patients were examined in this study. In 35 tumors, hyperthermia was given in conjunction with irradiation and/or chemotherapy, and in the remaining 3 tumors, hyperthermia alone was given. In all, a total of 153 hyperthermia sessions were performed.

: The number of hyperthermia sessions per tumor ranged from 1 to 7 (mean, 4.0 ± 1.3). The number of intratumor thermometr points per session ranged from 1 to 8 (mean, 4.3 ± 1.5). The average intratumor temperature for tumors with a maximum depth of <3 cm, 3–6 cm, and >6 cm was 42.1 ± 1.2, 41.7 ± 1.4, and 39.9 ± 2.0°C, respectively. The percentage of monitored intratumor points with temperature exceeding 42°C was 56 ± 31%, 43 ± 34%, and 21 ± 24%, respectively. Of the 30 evaluable tumors treated with combined irradiation, 12 showed complete response, 14 partial response, and 4 no change. Observed complications included pain at the treatment site in 13 of the 153 treatment sessions and vesicle formation in 3 of the 38 treatment sites. No serious complication was seen.

: These results indicate that the newly developed ultrasound hyperthermia system is clinically useful for the treatment of localized superficial and subsurface tumors with a maximum tumor depth of no more than 6 cm.     

Radiation therapy for T1,2 glottic carcinoma: impact of overall treatment time on local control

Purpose: Local control probabilities of T1,2 glottic laryngeal cancer were evaluated in relation to dose and fractionation of radiation therapy (RT). Materials and methods: Between 1975 and 1993, 96 T1N0M0 glottic cancers and 32 T2N0M0 glottic cancers were treated with definitive RT. Total RT dose was 60–66 Gy/2 Gy for most of the T1 and T2 tumors, although 10 T2 tumors were treated with hyperfractionation (72–74.4 Gy/1.2 Gy bid). Of the 128 patients, 90 T1 glottic tumors and 30 T2 glottic tumors were followed for >2 years after treatment. Multivariate analyses using the Cox proportional hazards model and a logistic regression analysis were performed to evaluate the significance of prognostic variables on local control. Results: The 5-year local control probability for T1 tumors was 85%, whereas that for T2 tumors was 71%. Multivariate analyses demonstrated that only overall treatment time (OTT) was a significant variable for local control. Total RT dose, normalized total doses at a fraction size of 2 Gy, and fraction size were not significant. Local control probability of T1 tumors with an OTT of 42–49 days was significantly higher than that of tumors with an OTT of >49 days (P < 0.02). Only a 1-week interruption of RT, due to holidays, significantly reduced the 5-year local control probability of T1 glottic tumors from 89 to 74% (P < 0.05). Conclusions: These results indicate that OTT is a significant prognostic factor for local control of T1 glottic tumors.     

Down-regulation of telomerase activity by anticancer drugs in human ovarian cancer cells

Maintenance of telomere length is crucial for survival of cells. Telomerase, an enzyme that is responsible for elongation of shortened telomeres, is active in human germ cells as well as most tumor tissues and experimentally immortalized cells. In contrast, most mature somatic cells in human tissues express undetectable or low telomerase activity, implying the existence of a stringent and negative regulatory mechanism. In this study we report the effects of anticancer drugs on telomerase activity in human cancer cells. In assaying for telomerase activity, we basically followed the original TRAP assay system, but with some modifications. A down-regulation of telomerase activity was found when cells of a human ovarian cancer cell line, A2780, were treated with;cis-diamminedichloroplatinum(II) (CDDP; cisplatin). However, down-regulation of telomerase activity was not found in cells of a cisplatin-resistant cell line, A2780CP, treated with cisplatin. On the other hand, telomerase activity in both the cell lines A2780 and A2780CP was reduced when A2780 or A2780CP was treated with adriamycin, an anthracycline antibiotic having a broad spectrum of antineoplastic activity. The different effects on the telomerase activity of the two types of anticancer drugs may be due the distinct chemical functions of these drugs. The present results may indicate a positive relationship between anticancer effects and down-regulation of telomerase activity by anticancer drugs.     

Neuroradiological study of patients with amyotrophic lateral sclerosis and parkinsonism-dementia complex on the Kii peninsula of Japan

BACKGROUND: The Kii peninsula of Japan, together with Guam and West New Guinea, has one of the highest incidences of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) in the world. OBJECTIVE: To perform neuroimaging studies on patients with ALS and PDC on the Kii peninsula. METHODS: Results of computed tomography, magnetic resonance imaging, and single-photon emission computed tomography were studied in 4 patients with ALS and in 10 patients with PDC from the Hohara village on the Kii peninsula of Japan. RESULTS: In patients with PDC, there was mild to severe atrophy of the frontal and temporal lobes on computed tomography and magnetic resonance imaging and a marked decrease in cerebral blood flow on single-photon emission computed tomography. In contrast, in patients with ALS, there was a decrease in cerebral blood flow of the frontal and temporal lobes, although the patients did not show signs of clinical dementia or obvious brain atrophy on computed tomography or magnetic resonance imaging. CONCLUSION: The finding of an obvious decrease in cerebral blood flow of the frontal and temporal lobes in patients with PDC and ALS with or without cerebral atrophy supports the concept that the 2 conditions are different manifestations of a single frontotemporal tauopathy.     

Bupivacaine attenuates contractility by decreasing sensitivity of myofilaments to Ca2+ in rat ventricular muscle

BACKGROUND: Bupivacaine exhibits a cardiodepressant effect, the molecular mechanism(s) of which have yet to be fully understood. Bupivacaine may directly act on contractile proteins and thereby decrease myofibrillar Ca2+ sensitivity. METHODS: Rat ventricular muscle was used. First, the effect of bupivacaine was examined on tetanic contractions in isolated intact myocytes. Next, Triton X-100-treated ventricular trabeculae were used to investigate the effect of bupivacaine on the pCa (= -log [Ca2+ ])-tension relation as well as on maximal Ca2+ -activated tension. Furthermore, to test whether bupivacaine inhibits the pathway downstream from Ca2+ binding to troponin C, tension was elicited in the skinned preparations by lowering the Mg-adenosine triphosphate (MgATP) concentration in the absence of Ca2+. The effect of bupivacaine on the pMgATP (= -log [MgATP])-tension relation was examined. RESULTS: In myocytes, 3 microm bupivacaine significantly (P < 0.01) increased intracellular Ca2+ concentration required for 5% cell shortening from the resting cell length. In skinned preparations, bupivacaine shifted the pCa-tension relation to the lower pCa side; the midpoint of the pCa curve (pCa50) was significantly (P < 0.05) changed by 10 and 100 microm bupivacaine. A highly correlated linear relation (R = 0.81; P< 0.0005) was present between pCa50 and maximal Ca2+ -activated tension. Bupivacaine (10 and 100 microm) significantly (P < 0.05) shifted the midpoint of the pMgATP-tension relation to the higher pMgATP side. CONCLUSIONS: Bupivacaine decreases myofibrillar Ca2+ sensitivity in ventricular muscle, and this is coupled with the compound's inhibitory effect on the pathway beyond Ca2+ binding to troponin C, possibly on the actomyosin interaction. The current results may partly explain the overall cardiodepressant effect of bupivacaine in vivo.     

Platelet-sparing effect of paclitaxel in heavily pretreated ovarian cancer patients

 Carboplatin has proven to be effective in the treatment of patients with recurrent ovarian cancer who have responded to platinum-based first-line chemotherapy. However, thrombocytopenia is a problem in heavily pretreated patients. Paclitaxel has a so-called platelet-sparing effect, but until now it was unknown whether this effect could be obtained in heavily pretreated patients. We treated four patients with recurrent epithelial ovarian cancers who had previously undergone heavy chemotherapy. Because these patients had responded to platinum-based first-line therapy, single carboplatin administration was employed. Although satisfactory tumor marker responses were obtained, thrombocytopenia occurred. When paclitaxel was administered before the carboplatin infusion in the subsequent treatments, the thrombocytopenia became milder. It was concluded that a platelet-sparing effect was also observed in patients who had undergone heavy prior chemotherapy. Received: January 9, 2002 / Accepted: March 29, 2002 Correspondence to:H. Ishikawa     

Brain metastases from esophageal carcinoma: natural history, prognostic factors, and outcome

BACKGROUND: Brain metastases from esophageal carcinoma are extremely rare, and information regarding the natural history, results of treatment, and possible prognostic factors in these patients is limited. METHODS: The records of 36 patients with brain metastases from esophageal carcinoma who were treated between 1986 and 2000 were reviewed. For brain metastases, 12 patients (33%) were treated with surgical resection followed by radiation therapy (S+RT), and the remaining 24 patients were treated with radiation therapy alone. RESULTS: At the initial diagnosis of esophageal carcinoma, the median primary tumor length was 8 cm (range, 2-19 cm), and 26 of 32 available patients (81%) had clinical Stage III-IV tumors according to the International Union Against Cancer 1997 criteria. At time brain metastases appeared, lung metastases were not demonstrated in 25 of 36 patients (69%) who were assessed by chest computed tomography (CT) scans. The overall median survival for all patients was 3.9 months (range, 0.6-36.8 months), and the actuarial survival rates at 12 months and 24 months were 14% and 3%, respectively. In univariate analysis, treatment modality, Karnofsky performance status (KPS), and extracranial disease status each had a statistically significant impact on survival, and, in multivariate analysis, treatment modality and KPS were statistically significant prognostic factors for survival. Five patients (14%) survived more than 1 year, all of whom were treated with S+RT. These five patients had inactive extracranial disease and, four of five patients (80%) had a 90-100% KPS. CONCLUSIONS: Brain metastases from esophageal carcinoma tended to occur in patients with a large primary tumors and/or disease in advanced clinical stages. With the appearance of brain metastases, an absence of lung metastasis frequently was observed on chest CT scans. The prognoses for these patients were generally poor, although selected patients may survive longer with intensive brain tumor treatment.