Performance of degree of accumulation with 201Tl-SPECT in 13 cases of lung cancer smaller than 2 cm

The aim of this study was to determine the sensitivity of 201Tl-chloride for small lung cancers. The study subjects consisted of 13 cases of surgically verified lung cancer smaller than 2 cm who had undergone 201Tl-SPECT prior to surgery, owing to the difficulty of establishing a diagnosis of lung cancer based on diagnostic CT. Among 13 cases, four showed positive accumulation in early and delayed SPECT, and nine negative, with a degree of accumulation of 31% (4/13).     

Correlation of Glut-1 glucose transporter expression with

Positron emission tomography (PET) with [18F]2-fluoro-2-deoxy-D-glucose (FDG) may show negative results for bronchioloalveolar lung carcinoma. We investigated the correlation of Glut-1 glucose transporter expression with [18F]FDG uptake in non-small cell lung cancer. Thirty-two patients with 34 non-small cell lung cancers (7 bronchioloalveolar carcinomas, 23 non-bronchioloalveolar adenocarcinomas, 3 squamous cell carcinomas, and 1 adenosquamous cell carcinoma) were studied. Final diagnoses were established by histology (via thoracotomy) in all patients. [18F]FDG PET was performed 40 min after i.v. injection of 185 MBq [18F]FDG. For semi-quantitative analysis of [18F]FDG uptake, standardized uptake values (SUVs) were calculated. Glut-1 expression was studied in terms of the immunohistochemistry of paraffin sections using anti-Glut-1 antibody to determine the intensity (0-3) of Glut-1 immunoreactivity and percentage of the Glut-1-positive area. Of seven bronchioloalveolar carcinomas, six (85.7%) were negative for the expression of Glut-1, while only one (4.3%) of 23 non-bronchioloalveolar adenocarcinomas was negative (P < 0.0001). The percentages of Glut-1-positive area, as well as the SUVs, were significantly lower in bronchioloalveolar carcinomas (n = 7) (2.86% +/- 7.56% and 1.25 +/- 0.75, respectively) than in non-bronchioloalveolar adenocarcinomas (n = 23) (54.83% +/- 25.64%, P < 0.0001, and 3.94 +/- 1.93, P = 0.001, respectively). The degree of cell differentiation correlated with the percentage of Glut-1-positive area and SUVs in adenocarcinoma of the lung. Correlations between SUVs and the intensity of Glut-1 immunoreactivity were also significant (intensities 0 and 1, n = 11, SUV 1.47 +/- 0.63; intensities 2 and 3, n=23, SUV 4.78 +/- 2.13; P < 0.0001). The percentage of Glut-1-positive area correlated significantly with SUVs (n = 34, r = 0.658, P < 0.01). Overexpression of Glut-1 correlated with high [18F]FDG uptake. These findings suggest that Glut-1 expression is related to [18F]FDG uptake in non-small cell lung cancer. Glut-1 expression, as well as [18F]FDG uptake, correlated with the degree of cell differentiation in adenocarcinomas, and both Glut-1 expression and [18F]FDG uptake were significantly lower in bronchioloalveolar carcinomas than in non-bronchioloalveolar carcinomas.     

Calponin h1 Suppresses Tumor Growth of Src-induced Transformed 3Y1 Cells in Association with a Decrease in Angiogenesis

Calponin h1 (CNhl) is a basic actin-binding protein that is abundantly expressed in smooth muscle cells and involved in smooth muscle contraction by inhibiting actomyosin MgATPase. In recent studies, CNhl was noted to suppress cell proliferation and tumorigenicity in leiomyosarcoma and tumor growth in fibrosarcoma cell lines. To further investigate the function of CNhl as a tumor suppressor, we transfected the human CNhl gene into a v- src -transformed rat fibroblast cell line SR–3Y1. The volume of the tumors derived from one randomly selected CNh1 -transfectant (C1) in nude mice was reduced to 34.1% of that from a randomly selected vector transfectant (VI). A similar tendency was observed in another independent pair (C2, V2). Pathological analysis showed a significant decrease in the number of mitotic cells in the CNh1 -transfectants. Further, a marked reduction in the number of vessels in the CNhl -transfectant was observed. DNA synthesis under conditions without serum was significantly reduced in the CNhl -transfectant (C1) compared with the control transfectant (VI), while no significant difference was seen in the cellular growth in the presence of 10% serum. A slight but significant reduction in in vitro cellular motility in the CNhl -transfectant was also observed. While the suppression of growth potential and cell motility by CNhl transfer was significant but partial, a marked reduction in vascular endothelial growth factor (VEGF) mRNA and the secretion of VEGF protein was observed in the CNhl -transfectant. These results suggest that CNhl plays a role as tumor suppressor in SR–3Y1 mainly by decreasing VEGF expression and angiogenesis in vivo and partially through reducing cellular proliferative potential and cell motility.     

Treatment of superficial esophageal cancer by external radiation therapy alone: results of a multi-institutional experience

PURPOSE: To assess the effectiveness and toxicity of external radiation therapy for superficial esophageal cancer. METHODS AND MATERIALS: During the period from March 1979 to November 1996, 78 patients with superficial esophageal cancer received radiation therapy without intracavitary irradiation at nine radiotherapy institutions in Japan. All patients had histologically-proven squamous cell carcinoma. Endoscopic ultrasonography was performed in 34 patients to discriminate mucosal from submucosal cancer. Most of the patients had received radiation therapy using conventional fractionation at an average dose of 65.5 Gy. RESULTS: The survival rates at 1, 2, and 5 years were 88%, 73%, and 45%, respectively. The local control rates at 1, 2, and 5 years were 85%, 79%, and 66%, respectively. Although the difference was not significant, the survival rate of cancer patients with a tumor invading the submucosa was lower than that of the other patients. In 6 mucosal cancer patients, local recurrence was observed in 1 patient with extensive cancer. Regional lymph node recurrence and distant failure were not observed in mucosal cancer patients, while in 28 submucosal cancer patients, the 5-year survival rate and relapse free rate were only 49% and 43%, respectively. Univariate and multivariate analysis identified age as the only significant prognostic factor. Severe late injury, such as esophageal ulcer, perforation, and bleeding, was not observed. CONCLUSION: External radiation therapy is effective for mucosal cancer. However, further investigation is needed to establish a better standard treatment protocol for submucosal cancer.     

Tumor bulk as a prognostic factor for the management of localized aggressive non-Hodgkin's lymphoma: a survey of the Japan Lymphoma Radiation Therapy Group

PURPOSE: To identify the prognostic factors that specifically predict survival rates of patients with localized aggressive non-Hodgkin's lymphoma (NHL). METHODS AND MATERIALS: The survey was carried out at 25 radiation oncology institutions in Japan in 1998. The 5-year event-free (EFS) and overall survival rates (OAS) were calculated, and univariate and multivariate analyses were done to identify which of the following factors, namely, gender, age, performance status (PS), serum lactate dehydrogenase (LDH) level, Stage (I vs. II), tumor bulk (maximum diameter), and treatment, were significant from the viewpoint of prognosis. RESULTS: A total of 1141 patients with Stage I and II NHL were treated by the Japanese Lymphoma Radiation Therapy Group between 1988 and 1992. Of them, 787 patients, who were treated using definitive radiotherapy with or without chemotherapy for intermediate- and high-grade lymphomas in working formulation, constituted the core of this study. Primary tumors arose mainly from extranodal organs (71%) in the head and neck (Waldeyer's ring: 36% and sinonasal cavities: 9%). The factors associated with poorer prognosis were age over 60 years old (p < 0. 0001), radiation therapy alone (p < 0.0001), PS = 2-4 (p = 0.0011), (sex male, p = 0.0078), a bulky tumor more than 6 cm in maximum diameter (p = 0.0088), elevated LDH (p = 0.0117), and stage II (p = 0.0642). A median dose of 42 Gy was delivered mainly to the involved fields. Short-course chemotherapy was provided in 549 (70%) patients. The 5-year OAS and EFS rates for all patients were 71% and 67%, respectively. According to the stage-modified International Prognostic Index, the 5-year EFS of the patients with risk factors from 0 to 1 was 76%, 61% for patients with two risk factors, and 26% for patients with three or more risk factors. CONCLUSION: Extranodal presentation, especially Waldeyer's ring and sinonasal cavities, is encountered more frequently in Japan than in Western countries. Tumor bulk is an important prognostic factor in patients with localized aggressive extranodal NHL. Short course chemotherapy followed by radiation therapy was associated with prolonged survival in patients with localized aggressive NHLs of extranodal origin and 0-1 risk factor.     

Non-randomized study on the effects of preoperative radiotherapy and daily administration of low-dose cisplatin against those of radiotherapy alone for oral cancer--effects on local control, control of metastases, and overall survival

Cisplatin is a known radiation modifier. Our previous study suggested that daily administration of low-dose cisplatin enhanced the efficacy of radiotherapy against primary oral squamous carcinoma. In this paper, we follow the patients who participated in the previous study and survey the benefit of combination low-dose cisplatin in improving local control, prevention of metastases, and overall survival. This study included patients with surgically resectable advanced oral tumors. Ten patients underwent preoperative radiotherapy of 30-40 Gy/15-20 days with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m2). Ten other patients received external radiotherapy alone. All patients then underwent a planned radical tumor resection. No significant difference was see in loco-regional control rates (primary: 86 vs. 88%, neck: 83 vs. 78% at 48 months) or incidence of metastasis (70 vs. 64%) between the two groups. Nor was there a significant difference in the overall survival rate (60 vs. 66%). The results of this study suggest that the concomitant use of daily administration of low-dose cisplatin with preoperative radiation brings no statistically significant benefit in improving local control and survival rate in patients with advanced resectable oral cancer.     

Value of renal biopsy in the prognosis of liver transplantation in familial amyloid polyneuropathy ATTR Val30Met patients.

Liver transplantation for familial amyloid polyneuropathy (FAP) patients has been carried out worldwide and the outcomes seem to be promising. To clarify the severity of amyloid deposits on visceral organs, we evaluated the histopathological findings of biopsied renal and sural nerve specimens in 13 FAP patients with ATTR Val30Met by quantitative analysis, and compared them with the outcome of transplantation. Renal dysfunction with proteinuria seemed to correlate with the degree of amyloid deposits in glomeruli, not with that in medullary tissues. The severity of renal amyloid deposition did not consistently parallel that of myelinated nerve fiber loss in sural nerve. Three patients with proteinuria and severe amyloid deposits in glomeruli were considered to be unsuitable for transplantation. Ten patients underwent living donor liver transplantation and three resulted in unfavorable outcomes. These three had heavy amyloid deposits on renal tissues, especially in glomerular areas, but the severity of myelinated nerve fiber loss in their sural nerves was very similar to that in patients who made a good recovery. The prognosis after operation might be closely related to the severity of amyloid deposits in renal glomeruli. Renal biopsy is, therefore, recommended when determining the indications and contraindications for liver transplantation in FAP patients, although this biopsy is not routinely required.     

Antitumor effect of K18 on metastatic models

K18 is a newly synthesized antitumor agent which is the conjugate form of human immunoglobulin with p-di (2-chloroethyl)-amino-L-phenylalamine (melphalan). The antitumor effect of K18 on two animal metastatic models was investigated: (a) Lewis lung carcinoma was transplanted into thigh muscle of mice, followed by the reaction of the primary lesion, or the tumor was transplanted through the tail vein: (b) a renal model was also created, where colon-26 was inoculated into the renal capsule of BALB/c mice. Oral administration of K18 resulted in the decrease in the number of nodules in the lung in the case of tumor transplantation through tail vein.