Postoperative radiation therapy for adenoid cystic carcinoma.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
S Sone
Publications and source records attributed to S Sone.
[Causative agents for lung carcinogenesis].
Lung cancer is a leading cause of malignancy-related death in Japan, and its incidence is still rising steeply. Various factors, including cigarette smoking, asbestos, and diet, have been reported to correlate with the development of lung cancer. Of these factors, cigarette smoking is believed as the major carcinogen for lung cancer. Recent studies indicate that cigarette smoke carcinogens cause genetic damages at both oncogenes(K-ras) and tumor suppressor genes(p53) of lung cancer, and hence initiate and promote the development of lung cancer. This article reviews recent advances in the molecular mechanisms of lung cancer carcinogenesis.
Air Pollution↗
[Clinical development of new molecular targeted therapeutics for cancer therapy].
Recently much attention has been paid to clinical development of new drugs targeting the important molecules involved in cell growth, motility, invasion, metastatic formation of cancer cells and tumor angiogenesis. Among them, several drugs are designed to inhibit those activities, by which cancer growth and/or metastasis may be controlled. A major problem in developing new molecular targeted therapeutics is determining the optimal biological dose in Phase I studies. Appropriate surrogate markers should be employed to evaluate their therapeutic efficacy before entering the Phase III study. A future strategy to evaluate the efficacy of new drugs in combination with conventional anticancer therapy (surgery, radiotherapy and chemotherapy) is required. For this, careful consideration must be given to the design of clinical Phase III trials. This paper discusses the present status and future strategy for development of new molecular targeted therapeutics in clinics.
Angiogenesis Inhibitors↗
Hepatopulmonary syndrome-discussion of cardiopulmonary parameters.
We report a 70-year-old man with hepatopulmonary syndrome (HPS) in C liver cirrhosis. Hypoxemia worsened markedly, especially on exertion, while the hepatic function was clinically stable. Contrast echocardiography, 99mTc macroaggregated albumin (99mTcMAA) lung scan, and pulmonary angiography were performed. The findings suggested the presence of both intrapulmonary vascular dilatation and substantial right-to-left shunt. The contribution of intrapulmonary vascular abnormalities in patients with severe liver cirrhosis without abnormal chest radiography and spirometry tests when marked hypoxemia is present should be investigated.
Aged↗
[Development of molecular targeting drugs for the treatment of cancer-therapeutic potential and issues to be addressed in global development].
A survey of cancer treatment in a sample of hospitals > 100 beds conducted in 1998 compared with experience in the US showed that good progress has been achieved in Japan in the screening and early treatment of gastric cancer, and that the prognosis for breast cancer is better than in the West. Although in the past, the cytotoxic therapies available to physicians in Japan vs the West have been different, recent acceleration of regulatory review will result in a convergence of treatment paradigms and some improvement in acute response in many tumour types. However, world wide there is a need for new improved therapies in all cancers evaluated. Particular needs are in the management of NSCLC, advanced disease and cancers which form micrometastases. The eventual hope is that cancer can be turned from a lethal disease into a chronic disease where patients maintain a good QOL. Apart from anti hormonal therapies, the usual approach has been to kill the cancerous cells. However, the new approaches to intervening in the growth and migration of cancerous cells or the host tissue response by molecular targeting offer the promise of achieving a step change in therapy. Although EGF tyrosine Kinase inhibitors such as ZD 1839 have been shown to cause a conventional tumour response in NSCLC, many of these new approaches are unlikely to show a short term response even if they have the capacity to affect tumour development and increase disease free survival. Some compounds will require combination therapy with a conventional cytotoxic or radiotherapy to show their full benefit. For conventional cytotoxics, the usual approach to development has been to select the maximum tolerated dose and then evaluate the efficacy in advanced disease. However, for the new approaches which will not have such severe dose limiting toxicities, it will be necessary to select a surrogate marker of the intended biological effect to select the optimal biological dose (OBD) and dose regimen in phase I/II studies for further evaluation in phase II or III studies which are designed to show the expected patient benefit. The tumour target, the stage of the disease and the possible need for concomitant therapy will also have to be considered according to the mechanism of action of the product.
Angiogenesis Inhibitors↗
[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).
Adenocarcinoma↗
Increased incidence of autoantibodies to interleukin-1a in rheumatoid arthritis with interstitial lung disease.
OBJECTIVE: To clarify the clinical significance of autoantibodies (auto-Ab) to interleukin-1alpha (IL-1alpha) in rheumatoid arthritis (RA) with interstitial lung disease (ILD), we examined the IL-1alpha auto-Ab level in serum of patients with RA with/without ILD. METHODOLOGY: We investigated the level of IL-1alpha auto-Ab in serum of 70 patients with RA with/without ILD and 40 control patients (CP). Levels of IL-1alpha auto-Ab were measured by radioimmunoassay, and serum was regarded as IL-1alpha auto-Ab positive at an auto-Ab level of more than 5 ng/mL. RESULTS: Interleukin-1alpha auto-Ab was detected in the serum of 30 out of 70 RA patients (42.9%), and six out of 40 CP (15%) (P < 0.05). Interleukin-1alpha auto-Ab were detected in the serum of 18 out of 32 patients with RA with ILD (56.2%) and 12 out of 38 patients with RA without ILD (31.5%). The positive rate of these autoantibodies in RA with ILD was significantly higher than that in RA without ILD (P < 0.05). Although C-reactive protein, immunoglobulin G, rheumatoid factor and rheumatoid arthritis particle agglutination levels in serum from patients with RA with ILD were not significantly different between the IL-1alpha auto-Ab-positive and -negative groups, the lactate dehydrogenase level (LDH) and AaDO, in the IL-1alpha auto-Ab-positive group were significantly higher than those in the negative group (LDH: P < 0.001, AaDO2: P < 0.05). CONCLUSION: These results suggest that IL-1alpha auto-Ab are generated in response to the immunoinflammatory process of ILD in RA, and these autoantibodies may neutralize and regulate the IL-1alpha activity.
Adult↗
[Immunologic pleuritis].
Explore the source record for details and available documents.
Arthritis, Rheumatoid↗
[Idiopathic interstitial pneumonia, idiopathic pulmonary fibrosis].
Explore the source record for details and available documents.
Biomarkers↗
Apoptosis induction of human lung cancer cell line in multicellular heterospheroids with humanized antiganglioside GM2 monoclonal antibody.
The chimeric antiganglioside GM2 monoclonal antibody (MAb) KM966, which showed high effector functions such as complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC), potently suppressed growth and metastases of GM2-positive human cancer cells inoculated into mice. To further improve the therapeutic efficacy of the anti-GM2 MAb in humans, we constructed a humanized anti-GM2 MAb, KM8969. The humanized KM8969 was more efficient in supporting ADCC against GM2-positive human cancer cell lines than the chimeric KM966, whereas complement-dependent cytotoxicity was slightly reduced in the humanized KM8969. In addition, the humanized KM8969 was shown to exert potent ADCC mediated by both lymphocytes and monocytes. To investigate the effect of the humanized KM8969 on the biological function of GM2 in the condition physiologically mimicking formation and growth of cancer masses, the heterospheroids composed of normal human dermal fibroblasts and GM2-positive human lung cancer cells were developed. Interestingly, the humanized KM8969 gave rise to growth inhibition of heterospheroids without dependence of the effector functions. Morphological and immunocytochemical analysis suggested that the inhibitory effect was due to the apoptosis of GM2-positive cancer cells in the heterospheroids. The result indicates that GM2 captured by the antibody on the cell surface loses its physiological function that plays a critical role in maintaining the three-dimensional growth of cancer cells in contact with its own cells or other type of cells in a microenvironment. The humanized KM8969, which can destroy the cancer cells via blocking functional GM2 on the cell surface as well as the effector functions, would have extraordinary potential in human cancer therapy.
Animals↗
Radiotherapy following mastectomy: indication and contraindication of chest wall irradiation.
PURPOSE: To determine in which cases radiotherapy of the chest wall following mastectomy is indicated, based on the local recurrent rate in patients with locally advanced breast cancer. METHODS AND MATERIALS: From 1984 until 1994, 105 patients who had four or more histopathologically confirmed axillary nodes metastases, or T3-4Nany, were subjected to mastectomy and were administered radiotherapy postoperatively using the hockey-stick field, which included the ipsilateral supraclavicular fossa and internal mammary nodes, except the chest wall. Median age was 51 years old (range, 23 to 82 years old). Eighty-five patients underwent radical mastectomy, 18 modified radical mastectomy, and 2 extended radical mastectomy. Fraction size was 2 Gy/day, the weekly fraction size was 10 Gy and the total dose ranged from 44 Gy to 54 Gy (median 50 Gy). Seventy-four patients were administered adjuvant chemotherapy, and 61 patients were administered hormone therapy. RESULTS: The 5-year disease-free survival rates of the whole study population were 66%. The 5-year chest wall recurrence rates were 10%. The 5-year chest wall recurrence rates of the patients who had no vascular invasion (n = 19) and the patients who had definite vascular invasion (n = 38) were 0% and 24%, respectively (p = 0.036). All the patients who presented chest wall recurrence had four or more axillary nodes metastases. Nine of the 10 patients who presented chest wall recurrence had definite vascular invasion, while there was no information about vascular invasion for the remaining patient. Factors such as age, pathological subtypes, tumor location, estrogen receptors, extent of resection, chemotherapy, and hormone therapy did not influence the development of chest wall recurrence. CONCLUSION: Among patients with breast cancer who have four or more positive axillary nodes or T3-4Nany, those who have no vascular invasion or less than 4 axillary nodes metastases do not need to be subjected to chest wall irradiation after radical mastectomy.
Adult↗
Combined therapy with anti-P-glycoprotein antibody and macrophage colony-stimulating factor gene transduction for multiorgan metastases of multidrug-resistant human small cell lung cancer in NK cell-depleted SCID mice.
Our aim was to determine the antimetastatic potential of anti-P-glycoprotein (P-gp) antibodies (Abs) against multidrug-resistant (MDR) human small cell lung cancer (SCLC) cells expressing P-gp. Human SCLC cells H69 (P-gp negative) and its etoposide-resistant variant H69/YP (P-gp positive) were used. H69 and H69/VP cells injected i.v. metastasized to the liver, kidneys and systemic lymph nodes of NK cell-depleted severe combined immunodeficient (SCID) mice. H69/VP cells, but not H69 cells, were resistant to treatments with vindesine. Treatment with mouse-human chimeric anti-P-gp Ab (MH162) and its mouse counterpart (MRK-16) reduced metastasis of H69/VP cells in various organs and prolonged the survival of tumor-bearing mice, although they were less effective if injected at late times (after 28 days). Treatment with another mouse anti-Pgp Ab, MRK-17, was effective only against liver metastasis. MH162 and MRK-16 efficiently induced Ab-dependent cellular cytotoxicity (ADCC) by peritoneal macrophages against H69/VP cells in vitro, but MRK-17 was less effective, in accordance with their in vivo antimetastatic potential. Gene transfection of macrophage colony-stimulating factor (M-CSF) into H69/VP cells to augment macrophage-mediated ADCC resulted in inhibition of metastasis to the liver and lymph nodes, but not kidneys. Combined treatment with a low dose of MRK-16 completely cured metastasis of M-CSF transfectant, but not of the mock transfectant. Our findings suggest that while anti-P-gp Abs had antimetastatic potential against SCLC cells expressing P-gp, combined treatment with M-CSF gene transduction to augment the therapeutic efficacy of anti-P-gp Abs may be beneficial for eradicating metastatic MDR SCLC in humans.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Monocyte chemoattractant protein-1 gene modification of multidrug-resistant human lung cancer enhances antimetastatic effect of therapy with anti-P-glycoprotein antibody in SCID mice.
Distant metastases and multidrug resistance are critical problems in the therapy of human small cell lung cancer (SCLC). In this study, we investigated whether transduction of the monocyte chemoattractant protein-1 (MCP-1) gene into multidrug-resistant (MDR) human lung cancer cells affected the formation of metastases or their inhibition by the anti-P-glycoprotein (P-gp) monoclonal antibody (MAb) MRK16. MDR human SCLC (H69/VP) cells were transduced with the human MCP-1 gene inserted into the expression vector BCMGSNeo. MCP-1 gene transduction had no effect on drug sensitivity, the expression of surface antigens or the in vitro proliferation of H69/VP cells. Using the metastatic model of NK cell-depleted SCID mice, H69/VP cells transduced with the MCP-1 gene were inoculated intravenously (i.v.) and formed metastatic colonies in the liver, kidneys and lymph nodes, similar to those formed by parent or mock-transduced cells. However, systemic treatment of the mice with MRK16 reduced the metastases of H69/VP cells in the liver, kidneys and lymph nodes, and was significantly more effective in inhibiting the metastases of MCP-1 producing H69/VP than those of mock-transduced cells. MCP-1 gene transduction significantly prolonged the survival of tumor-bearing mice treated with MRK16. Our findings suggest that local production of MCP-1 in the tumor site increases the anti-P-gp antibody-dependent cell-mediated cytotoxicity, and the MCP-1 gene-induced modification of MDR human SCLC cells thereby enhances the antimetastatic effect of therapy with anti-P-gp antibody. Thus, the accumulation of effector cells in the tumor site is a very important factor in the therapy using the anti-P-gp antibody.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Presence and potent immunosuppressive role of interleukin-10 in malignant pleural effusion due to lung cancer.
The presence and possible role of interleukin (IL)-10 were examined in malignant pleural effusion due to lung cancer. In 37 out of 55 cases examined, IL-10 was detectable in pleural effusion and the mean level with standard error was 62.1+/-12.1 pg/ ml. Spontaneous and lipopolysaccharide-induced production of anti-tumor cytokines such as IL-1beta and tumor necrosis factor (TNF)-alpha, by pleural macrophages, obtained from five patients with malignant pleurisy, were suppressed by IL-10. These findings suggest that IL-10 is present in the tumor-growing site and acts as a suppressive factor of local anti-tumor immunity in humans.
Aged↗
Detection of medullary thyroid carcinoma and regional lymph node metastases by magnetic resonance imaging.
OBJECTIVES: To evaluate the usefulness of magnetic resonance imaging in detecting primary medullary thyroid carcinoma (MTC) and regional metastasis to the lymph nodes, and to correlate magnetic resonance signal intensity to pathologic changes. MATERIALS AND METHODS: Magnetic resonance images in 14 patients with MTC (9 with primary disease, 5 with recurrent disease) were reviewed for signal intensities, tumor morphologic characteristics, and tumor invasion with spin-echo T1-weighted images (T1WIs), T2-weighted images (T2WIs), and gadolinium-enhanced T1WIs. Multiple regression analysis was used to examine the correlation between T2-weighted signal intensity and pathologic findings. Lymph nodes were evaluated based on signal and morphologic characteristics. RESULTS: Magnetic resonance imaging detected tumors in 9 (90%) of the 10 patients who had MTC in the thyroid gland. Extrathyroidal spread of the tumors was correctly predicted using this procedure. Most tumors were hyperintense or markedly hyperintense on T2WI. T2-weighted signal intensity of the tumor was associated with increased amyloid deposition and high tumor cellularity and low level of fibrosis (r = 0.91, P = .01). Lymph node metastasis was present in 38 (23%) of 168 surgically dissected nodes. The combined use of 4 criteria (nodule size, a minimum-maximum diameter ratio of 0.80 or greater, marked hyperintensity on T2WI, and necrosis in the node) yielded a high detection accuracy (93%) for nodal metastasis, with 74% sensitivity and 98% specificity. CONCLUSIONS: Magnetic resonance imaging is useful for detecting primary and recurrent MTC, and its signal intensity reflects the underlying pathologic changes.
Adult↗
Parotid gland lesions: diagnosis of malignancy with MRI and flow cytometric DNA analysis and cytology in fine-needle aspiration biopsy.
BACKGROUND: The purpose of this study was to assess the capability of magnetic resonance imaging (MRI) and cytology and flow cytometric (FCM) deoxyribonucleic acid (DNA) analysis in fine-needle aspiration biopsy (FNAB)-derived materials for diagnosing malignancy of the parotid lesions and the efficacy of FCM analysis in FNAB. METHODS: Magnetic resonance imaging findings and FCM results (ploidy and S + G2 + M phases [S + G2M] fraction) and cytology in FNAB-derived materials in 26 patients with 26 parotid lesions (12 benign lesions, 14 malignancies) were assessed for predicting malignancy. Flow cytometric results in aspirates were compared with those in surgically resected tissues. RESULTS: When a single predictor was used, cytology (92% accuracy) was most accurate for malignancy, followed by ill-defined margin (88% accuracy) and aneuploidy (88% accuracy). The combination of FCM and cytology raised the rate of sufficient materials from 92% to 100% and accuracy from 92% to 96% compared with cytology alone. The same highest accuracy (96%) was obtained with the combination of the ill-defined margin or other findings such as cytology, aneuploidy, or a high (S + G2M) fraction (6% <). Deoxyribonucleic acid ploidy in the FNAB showed full agreement with that in the surgical specimens. Receiver operating characteristic curves showed that the diagnosis of malignancy with (S + G2M) fraction in FNAB was superior to that in surgical specimens, but no significant difference was noted. CONCLUSIONS: A combination of MRI findings, cytology, and FCM results is optimal for diagnosing malignancies of the parotid lesions, and FNAB may replace the surgical specimens in FCM analysis.
Adolescent↗
Comparison of suppressive effects of a new anti-inflammatory compound, FR167653, on production of PGE2 and inflammatory cytokines, human monocytes, and alveolar macrophages in response to endotoxin.
FR167653 [1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8 (4-pyridyl) pyrazoro [5-1-c] [1,2,4] triazin-2-yl]-2-phenylethanedion sulfate monohydrate] was developed to inhibit proinflammatory cytokine production. However, the effects of FR167653 on prostanoid production are unclear. We investigated the effect of FR167653 on proinflammatory cytokine and prostaglandin (PG) production by lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes and alveolar macrophages (AM) from the same individuals, and compared the effects in monocytes and AM. FR167653 inhibited interleukin-1beta and tumor necrosis factor alpha production. The effect on PGE2 production was assessed by four parameters. FR167653 inhibited PGE2 synthesis and LPS induction of cyclooxygenase activity. Western and Northern blot analyses revealed that LPS induction of cyclooxygenase-2 expression was attenuated by this compound. The suppression in monocytes was greater than that in AM. We concluded that the reduction of LPS-induced PGE2 synthesis by FR167653 was due to inhibition of cyclooxygenase-2 production. These results show that FR167653 may be therapeutically useful for inhibiting production of both inflammatory cytokines and PG production in inflammatory diseases.
Anti-Inflammatory Agents, Non-Steroidal↗
Cytolysis of human dendritic cells by autologous lymphokine-activated killer cells: participation of both T cells and NK cells in the killing.
Dendritic cells (DC) play a key role in the initiation of immune response by stimulating the naive T cells. The fate of DC after the initiation of immune response is not clearly understood. Although there are few reports implicating natural killer (NK) cells in the elimination of DC, killing of DC by LAK cells, and specifically by T cells, has not been studied. In this study, we observed that DC, generated from monocytes, in vitro in the presence of granulocyte-macrophage colony-stimulating factor, interleukin-4 (IL-4), and tumor necrosis factor alpha were susceptible to cytolysis by lymphokine-activated killer (LAK) cells induced in the presence of IL-2 and IL-15 but not IL-12 alone. However, LAK cells induced by a combination of IL-12 and suboptimal dose of IL-2 were cytotoxic to DC. When purified lymphocytes were activated with IL-2, the CD8+/CD57- fraction (T-LAK), but not the CD8-/CD57+ fraction (NK-LAK) was cytotoxic to autologous DC. However, when unseparated peripheral blood mononuclear cells were used to generate LAK cells, both T-LAK and NK-LAK fractions showed equal cytotoxicity against autologous DC. Monoclonal antibodies against CD54, CD11a, and CD18 significantly inhibited the cytolysis, indicating that the killing involves the engagement of CD54 with its ligands.
Antibodies, Blocking↗