Biomedical subjects

Naoko Kinukawa

Publications and source records attributed to Naoko Kinukawa.

At least 19 recordsLinked to original sources

PubMed2003

Interhemispheric functional desynchronization in the human vibratory system.

We examined the differences in interhemispheric functional correlation in the somatosensory system using coherence (Coh) analysis. Ten healthy adult volunteers served as subjects for this experiment. Vibratory stimulation (modulation frequency, 21 Hz) was given to each palm to record vibratory steady-state somatosensory evoked potentials (S-SEPs). S-SEPs were recorded from four electrodes placed at 2 cm posterior and anterior to C3 and C4, referred to an electrode at Fpz, respectively. For comparison, unstimulated S-SEPs were also recorded. A total of 50 responses of 1-s epochs was averaged and subjected to discrete fast Fourier transforms to yield the amplitudes of major harmonic components and Coh value. The Coh value between the two signals, x and y at each frequency f, was calculated as [Coh(xy)(f)](2)=[S(xy)(f)](2)/[S(xx)(f)xS(yy)(f)]. The amplitude at 21 Hz in the contralateral somatosensory area was significantly larger than that in the other electrodes. The interhemispheric Coh of the somatosensory area at 21 Hz was significantly lower than that in the unstimulated condition or intrahemispheric Coh. The initial somatosensory information is desynchronized. These findings indicate less significance of interhemispheric correlation as the first step of the vibratory information processing in the somatosensory cortex.

Adult↗

PubMed2003

Nuclear expression of Y-box-binding protein-1 correlates with P-glycoprotein and topoisomerase II alpha expression, and with poor prognosis in synovial sarcoma.

Nuclear expression of the Y-box-binding protein (YB-1) has been reported to correlate with the expression of P-glycoprotein in breast cancer and osteosarcoma. Overexpression of the ATP-binding cassette (ABC) superfamily, such as P-glycoprotein/multi-drug resistance (MDR) 1 and MDR-associated protein (MRP) 1, 2 and 3, has been reported in various malignant neoplasms. Fifty-four surgically resected synovial sarcomas were examined immunohistochemically for nuclear expression of YB-1 and intrinsic expression of P-glycoprotein, MRP1, MRP2, and topoisomerase II alpha, and the findings were compared with clinicopathological parameters, proliferative activities as evaluated by MIB-1 labelling index (LI), and the patients' prognoses. In addition, MDR1, MRP1, MRP2, and MRP3 mRNA levels were assessed using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method in 22 concordant frozen specimens from these cases and the findings were compared with six control skeletal muscle tissues. Independent prognostic factors were investigated using the Cox proportional hazards regression model. Nuclear expression of YB-1 protein correlated with P-glycoprotein expression (p = 0.0126). Moreover, cases with nuclear expression of YB-1 correlated with poor survival (p = 0.0495) and showed a high topoisomerase II alpha labelling index (topo II alpha LI) (p = 0.0056) and a high MIB-1 LI (p = 0.01). Multivariate Cox analysis showed that only the nuclear expression of YB-1 (p = 0.0136) and high American Joint Committee on Cancer (AJCC) stage (ie stage III or IV) (p < 0.0001) were independent factors for poor prognosis, while the expression of the YB-1 responsive gene products examined was not. These results indicate that the nuclear expression of YB-1 protein is associated with P-glycoprotein expression and proliferative activity as shown by the topo II alpha LI and the MIB-1 LI, and that expression of this protein is an important independent prognostic factor in synovial sarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Clinical significance of serum RCAS1 levels detected by monoclonal antibody 22-1-1 in patients with cholangiocellular carcinoma.

BACKGROUND/AIMS: The tumor-associated antigen, RCAS1, has been reported to be expressed in various types of cancer, including cholangiocarcinoma. We measured serum RCAS1 levels in patients with intrahepatic cholangiocellular carcinoma (CCC) and other hepatobiliary diseases, and examined the clinical significance of serum RCAS1 as a tumor marker. METHODS: Sera collected from the patients and healthy volunteers were used for ELISA for RCAS1. The values of RCAS1 for CCC patients were compared to those of other tumor marker proteins. RESULTS: Serum RCAS1 levels exceeded the normal limit in a high percentage (73.9%) of CCC patients. The positivity rate was higher than those of CA19-9 and CEA. No correlation was found between the RCAS1 and CA19-9 concentrations. Serum RCAS1 was positive in many cases that were negative for CA19-9. Surgical resection of CCC reduced the RCAS1 level to within the normal range. On the other hand, serum RCAS1 levels were elevated in very few cases of benign hepatobiliary disease. CONCLUSIONS: As a tumor marker in CCC, RCAS1 is, at least, of complementary value to CA19-9 and CEA. Measuring serum RCAS1 contributes to the diagnostic accuracy, and is useful for estimating tumor progression or therapeutic effect.

Adult↗

PubMed2003

Cytokine imbalance in hyper-IgE syndrome: reduced expression of transforming growth factor beta and interferon gamma genes in circulating activated T cells.

Hyper-IgE syndrome (HIES) is a primary immunodeficiency disease characterized by recurrent infections and marked immunoglobulin (Ig)E elevation. To assess the proper T-cell defects of HIES, the cytokine profile of naturally activated T cells was compared between HIES, atopic dermatitis and chronic granulomatous disease (CGD). Intracellular flow cytometric analysis after in vitro stimulation showed no difference in the proportion of interferon (IFN)gamma- or interleukin 4 (IL-4)-producing T cells among these diseases. Quantitative polymerase chain reaction (PCR) for the cytokine genes was performed using circulating highly fractionated HLA-DR+ and HLA-DR- T cells. The IFNgamma/IL-4 or IFNgamma/IL-10 ratios were lower in HLA-DR+ T cells of HIES than in CGD (P = 0.0106, 0.0445), but did not differ between HIES and atopy. The transforming growth factor-beta (TGFbeta)/IL-4 ratio in HLA-DR+ T cells of HIES was lower than that of atopy (0.0106) or CGD (0.0062). The TGFbeta/IL-4 ratio in HLA-DR- T cells of HIES was also lower than that of atopy (0.0285). Stepwise logistic regression analysis identified TGFbeta/IL-4 ratios in HLA-DR+ (0.0001) or HLA-DR- (0.0086) T cells as the most powerful parameters to distinguish HIES from atopy and/or CGD. Serum IgE levels negatively correlated with IFNgamma/IL-4 (0.0108), IFNgamma/IL-10 (0.0254), or TGFbeta/IL-4 (0.0163) ratios in HLA-DR+, but not HLA-DR-, T cells. These results suggested that the in vivo activated T cells of HIES did not sufficiently express the IFNgamma and TGFbeta genes, which could affect IL-4-dependent IgE production. The reduced TGFbeta expression may involve the indigenous T-cell defects of HIES.

Adolescent↗

PubMed2003

[Factors related to functional capacity in community dwelling elderly people].

PURPOSE: To clarify the content of support for healthy aging, we analyzed age-related changes in functional capacity and factors affecting the maintenance based on a health status survey in elderly people, and also evaluated the results of a survey on functional capacity, living habits, and health in leaders in elderly people's clubs. METHODS: A questionnaire survey was carried out with (1) 1,000 randomly selected elderly subjects aged > or = 65 years and (2) 122 leaders in elderly people's clubs to evaluate functional capacity according to The Tokyo Metropolitan Institute of Gerontology Index of Competence, feeling of happiness according to the morale scale established by Lawton, living habits, and health. Factors affecting functional capacity were identified by stepwise multiple longistic regression analysis. In addition, the elderly people's club leader group and an age- and sex-matched control group were compared. RESULTS: 1) Functional capacity decreased with age, this being more marked in the females than in the males. In particular, Instrumental Activities of Daily Living markedly decreased in the females at late ages. 2) Stepwise multiple logistic regression analysis revealed the following positive and negative factors associated with the maintenance of a high functional capacity (functional capacity score > or = 12). The positive factors were: 1. hobbies, 2. living with the spouse, 3. habitual exercise, 4. positive acceptance of aging, 5. psychological stability, 6. diets with consideration of nutritional balance, 7. busy life, and 8. talking with friends and acquaintances once a week or more. The negative factors were: 1. belonging to a higher age groups, 2. living alone, and 3. smoking. 3) In the elderly people's club leader group, the age-related decline was gradual, and functional capacity was maintained at later ages. The group leaders typically 1. had hobbies, 2. went out almost everyday, 3. exercised almost every day, 4. talked with friends and relatives almost every day, 5. had active roles, 6. were busy, and 7. considered themselves to be healthy more frequently than the control group. The leader group also showed 8. a higher total morale scale score and 9. a higher score for positive acceptance of aging as a subscale than the control group. CONCLUSIONS: Our results suggest that nutrition balance, habitual exercise, hobbies, social roles, frequent contacts with others, positive acceptance of aging, and psychological stability are important for maintaining functional capacity in the maintenance of functional capacity. Early preventive measures are necessary to combat decline in functional capacity, particularly regarding Instrumental Activities of Daily Living, in females at later ages.

Activities of Daily Living↗

PubMed2002

Distributions of diffuse intimal thickening in human arteries: preferential expression in atherosclerosis-prone arteries from an early age.

Diffuse intimal thickening (DIT) is a thickened intima present in human arteries before atherosclerosis develops and is considered to be related to atherogenesis. The purpose of this study was to clarify the systemic and age distributions of DIT. Coronary, cerebral, carotid, subclavian, iliac and abdominal organ arteries and the aorta were examined in 72 autopsy cases (aged 36 weeks of gestation to 30 years at death). DIT was found in the coronary arteries and aorta from 36 weeks of gestation and the first year of life, respectively. The intima/media (I/M) ratio of coronary arteries showed an age-dependent increase and was much greater than that of other muscular arteries, i.e., intracranial and extraparenchymal cerebral arteries and abdominal organ arteries. Aorta also demonstrated age-dependent as well as site-dependent increases of I/M ratio; the more distal the segments, the greater the ratio. Consequently, the abdominal aorta had the largest I/M ratio within the aorta. Other elastic arteries, i.e., carotid, subclavian and iliac arteries, showed trends similar to the distal portions of the aorta. Thus, DIT was strongly expressed from an early age in arteries that are considered to be prone to atherosclerosis. These findings suggest that the development of atherosclerosis depends at least partly on the degree of DIT.

Adolescent↗

PubMed2002

Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia. Fukuoka Atherosclerosis Trial (FAST).

OBJECTIVES: This study investigated the effect of reducing serum lipids on carotid artery intima-media thickness (IMT) in asymptomatic patients with hypercholesterolemia from Fukuoka, Japan. BACKGROUND: Carotid atherosclerosis is a strong, independent predictor of morbidity and mortality in patients with coronary heart disease (CHD). METHODS: A total of 246 asymptomatic hypercholesterolemic patients (mean age 66 years) were randomized to receive either probucol (500 mg/day, n = 82) or pravastatin (10 mg/day, n = 83) or to enter a control group (diet alone, n = 81); they were followed for two years. The change in IMT in the common carotid artery was the primary end point measure, and the incidence of major cardiovascular events was the secondary measure. RESULTS: Over the two-year period, serum low-density lipoprotein (LDL) cholesterol was significantly reduced in the pravastatin group (36%), the probucol group (29%) and the control group (12%) (p < 0.0001, p < 0.0001 and p < 0.05, respectively). After two years, the probucol and pravastatin groups showed a significant reduction in IMT (-13.9% and -13.9% and p < 0.01 and p < 0.01, respectively), but there was significant IMT thickening (23.2%; p < 0.05) in the control group. Probucol reduced the rate of IMT increase, independently of its reduction of LDL or high-density lipoprotein cholesterol. Moreover, there was a significantly lower incidence of cardiac events in the probucol group (2.4%) than in the control group (13.6%) (p = 0.0136). CONCLUSIONS: Probucol reduced cholesterol levels and stabilized plaque, leading to a lower incidence of cardiac events in these hypercholesterolemic patients.

Adult↗

PubMed2002

Prognostic significance of microvessel density, vascular cuffing and vascular endothelial growth factor expression in ovarian carcinoma: a special review for clear cell adenocarcinoma.

Our purpose is to demonstrate the relationship between microvessel density (MVD), vascular cuffing (VC), vascular endothelial growth factor (VEGF) expression and clinicopathological parameters in ovarian cancer. Surgical specimens from 105 primary ovarian cancers were examined for vascularization and VEGF expression by immunohistochemical staining. The higher MVD group (MVD> or =70) and the positive VEGF group were associated with better progression-free survival only in early stages. The significant association of the MVD with better progression-free survival was recognized only in the patients with clear cell adenocarcinomas. The complete VC group showed a similar trend as MVD though there was no statistical difference. A multivariate analysis revealed MVD to correlate independently with progression-free survival. In ovarian carcinoma, MVD was found to be an independent prognostic factor. In addition, the higher MVD with clear cell adenocarcinoma had the better prognosis. The clinicopathological role of angiogenesis should be analyzed taking account of histologic type.

Adenocarcinoma, Clear Cell↗

PubMed2002

The prognostic significance of lymph node size in patients with squamous esophageal cancer.

BACKGROUND: The prognosis of patients with esophageal cancer remains dismal, and their care poses a great challenge of customizing therapeutic strategies for individual patients. Lymph node staging is still less than ideal in esophageal cancer patients. Therefore, we investigated a new approach to lymph node analysis. METHODS: One hundred eighty-seven patients curatively resected for squamous cell cancer of the esophagus were studied. The long diameter of the largest metastatic lymph node (MLN) was measured on a histopathologic slide and was considered as the MLN size. RESULTS: Patient survival decreased with each millimeter increment in MLN size. By using MLN size as the lymph node classification criterion, patients with MLN <10 mm had both a significantly better overall and cancer-specific survival than those with MLN >or=10 mm. Patients with fewer than four MLNs were separated into prognostic groups according to the MLN size. Among the several prognostic factors, MLN size remained the strongest independent predictor of survival by multivariate analysis. This nodal analysis allowed stratification of patients into four stages with distinctly different survivals. CONCLUSIONS: This approach supplements traditional nodal staging strategies and therefore has potential for guiding the development of treatment strategies in this carcinoma.

Aged↗

PubMed2002

Association of meteorological and day-of-the-week factors with emergency hospital admissions in Fukuoka, Japan.

We carried out a statistical study of the influence of meteorological and day-of-the-week factors on the intrinsic emergency patients transported to hospitals by ambulance. Multiple piecewise linear regression analysis was performed on data from 6,081 emergency admissions for 1 year between April 1997 and March 1998 in Fukuoka, Japan. The response variable was the daily number of emergency patients admitted with three types of disease: cerebrovascular, respiratory and digestive diseases. The results showed that the number of emergency patients admitted daily with cerebrovascular disease was significantly associated with temperature on the day of admission and whether the day was Sunday. As it became colder than 12 degrees C, emergency admissions of patients with cerebrovascular disease increased drastically, reaching a plateau at 4 degrees C. On the 3rd and 7th days after the temperature fell below 10 degrees C, the daily admission of patients with respiratory disease significantly increased. We also observed a weak association between emergency admissions of patients suffering from digestive disease and rising barometric pressure on the day of admission.

Atmospheric Pressure↗

PubMed2002

Different patterns of excitation and inhibition of the small hand and forearm muscles from magnetic brain stimulation in humans.

OBJECTIVES: The objective of the present study is to quantify the effects of voluntary muscle contraction of the small hand (abductor pollicis brevis, first dorsal interosseus (FDI)) and forearm muscles (extensor carpi radialis (ECR), extensor carpi ulnaris (ECU), flexor carpi radialis (FCR) and flexor carpi ulnaris (FCU)) on motor evoked potentials (MEPs). METHODS: MEPs were recorded in 12 healthy subjects by a circular coil placed over the vertex at 1.2 times the resting motor threshold at different levels of the muscle contraction (0-100% of maximum voluntary contraction (MVC)). The effects of transcranial magnetic stimulation (TMS) on the onset latency, MEP area and silent period (SP) as a function of the %MVC were evaluated using a piecewise linear regression analysis. RESULTS: The MEP areas for the small hand muscles were almost completely saturated at 20% of MVC. In contrast, the MEP areas for radial muscles (ECR, FCR) had a dual increase at 40% of MVC while the ulnar muscles (ECU, FCU) had a dual increase at 20% of MVC. A uniform latency shift (1.5-3 ms reduction) was observed in all muscles with a changing point at 10% of MVC. The SPs were the longest for FDI and were not significantly influenced by MVC for any muscles. CONCLUSIONS: The excitatory and inhibitory effects of TMS on the MEPs differed for the small hand and forearm muscles and also between the ulnar and radial muscles. These results probably resulted from the different degrees of direct corticomotoneuronal inputs to each muscle and the inherent properties of the spinal motoneurons.

Adult↗

PubMed2002

A simple method for calculating the financial balance of a hospital, based on proportional dividing.

It is necessary to estimate financial status to determine hospital management policy. The costs and revenues (financial balance) of each hospital division are one good index. However, it is difficult to calculate the financial balance for each division, since clinics and central services are intricately involved with each other There are no reports on a pragmatic method for calculating the financial balance. We devised a simple method based on proportional dividing. Consequently, one individual was able to complete the calculation for our hospital, which consists of 1300 beds and 23 clinics, without using the central hospital computer system.

Accounting↗

PubMed2002

Hepatitis C virus (HCV) RNA level determined by second-generation branched-DNA probe assay as predictor of response to interferon treatment in patients with chronic HCV viremia.

Using first- and second-generation branched-DNA probe assays (1st- and 2nd-bDNA), we investigated the predictors of favorable clinical response to interferon (IFN) treatment in patients with chronic HCV viremia. A total of 122 patients (85 genotype lb and 37 genotype 2a) with chronic HCV viremia received 24-week IFN-alpha treatment. Patients with sustained clearance of serum HCV RNA by polymerase chain reaction at six months after IFN treatment were defined as having a sustained response (SR). HCV RNA level was determined by 1st- and 2nd-bDNA assays prior to treatment. Mean HCV RNA level by 1st-bDNA was significantly higher in genotype lb patients [5.4 x 10(6) HCV genome equivalent (Meq)/ ml] than in genotype 2a patients (0.9 Meq/ml) (P < 0.05). There was no significant difference between patients with these genotypes in the level by 2nd-bDNA (1b: 5.2 Meq/ml and 2a: 3.1 Meq/ml). SR was achieved by 43 (35.2%) of 122 patients. Mean HCV RNA levels by both the 1st- and 2nd-bDNA of SR patients (1.0 and 1.9 Meq/ml) were significantly lower than those of non-SR patients (5.3 and 6.0 Meq/ml) (both P < 0.05). The SR rate in genotype 2a patients (59.5%) was significant higher than in genotype lb patients (24.7%) (P < 0.05). Stepwise logistic regression analysis showed that HCV RNA level < or = 1.0 Meq/ml by 2nd-bDNA (odds ratio = 7.6, compared to level > 1.0 Meq/ml, P < 0.05) was a significant predictive cutoff for SR. Using 2nd-bDNA, a significantly higher rate of SR was found in genotype lb patients with level < or = 1.0 Meq/ml (57.6%) than in those with level > 1.0 Meq/ml (3.8%) (P < 0.05). The SR rate of genotype 2a patients with level >1.0 Meq/ml (68.6%) was somewhat higher than for those with level < or = 1.0 Meq/ml (52.4%). These findings suggested that, using 2nd-bDNA, a low HCV RNA level of < or = 1.0 Meq/ml was the most favorable marker of successful IFN treatment and that patients with genotype 2a, even those with level >1.0 Meq/ml, had a high rate of SR to IFN treatment.

Adult↗

PubMed2002

Risk-directed treatment of infant acute lymphoblastic leukaemia based on early assessment of MLL gene status: results of the Japan Infant Leukaemia Study (MLL96).

We studied the effectiveness of risk-directed therapy for infants younger than 13 months of age with acute lymphoblastic leukaemia (ALL). Fifty-five infants were assigned to different treatment programs (from December 1995 to December 1998) on the basis of their MLL gene status at diagnosis. Forty-two cases (76.3%) had a rearranged MLL gene (MLL+) and were treated with remission induction therapy followed by sequential intensive chemotherapy, including multiple genotoxic agents (MLL9601 protocol). Haematopoietic stem cell transplantation (HSCT) was attempted if suitable donors were available. Thirteen infants (23.7%) were classified as MLL- and treated for 2.5 years with intensive chemotherapy for high-risk B-ALL (MLL9602 protocol). Complete remission was induced in 38 of the 42 infants (90.5%) with MLL+ ALL and in all 13 patients (100%) with MLL- disease. In the MLL+ subgroup, the estimated event-free survival (EFS) rate at 3 years post diagnosis was 34.0% +/- 7.5%, compared with 92.3% +/- 7.4% in the MLL- subgroup (overall comparison, P = 0.001 by log-rank analysis). Both age less than 6 months (hazard ratio = 6.87, 95% CI = 0.91-52.3; P = 0.013) and central nervous system (CNS) involvement at diagnosis (hazard ratio = 2.92 95% CI = 1.29-6.63; P = 0.015) were significant independent predictors of an inferior outcome. These findings indicate a strategic advantage in classifying infant ALL as either MLL+ or MLL- early in the clinical course and selecting therapy accordingly. Standard chemotherapy for high-risk B-lineage ALL appeared adequate for MLL- cases. Novel therapeutic initiatives are warranted for infants with MLL+ disease, particularly those with initial CNS leukaemic involvement or age less than 6 months, or both.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Reassessment and clinicopathological prognostic factors of malignant fibrous histiocytoma of soft parts.

Recently, the category of malignant fibrous histiocytoma (MFH) has been under discussion and new entities resembling MFH have appeared. To clarify the recent situation regarding MFH, we reassessed previously diagnosed MFH cases in accordance with the most up-to-date diagnostic criteria, which included allied tumors. We carefully reassessed 428 cases that had been diagnosed in our institute during the past 28 years. Moreover, we searched for clinicopathological prognostic factors among the cases that were finally diagnosed as MFH. Among the 428 cases, 138 cases had their diagnoses changed. The revised cases included 78 leiomyosarcomas (57%; ordinary leiomyosarcoma, 45 cases; pleomorphic leiomyosarcoma, 23 cases; myxoid leiomyosarcoma, 10 cases), 12 liposarcomas (9%; pleomorphic liposarcoma, 11 cases; dedifferentiated liposarcoma, one case), seven dermatofibrosarcoma protuberans (5%), six unclassified sarcomas (4%), five primary or metastatic carcinomas (4%), four low-grade fibromyxoid sarcomas (3%), four inflammatory myofibroblastic tumors (3%), three rhabdomyosarcomas (2%), three malignant peripheral nerve sheath tumors (2%), three acral myxoinflammatory fibroblastic sarcomas (2%) and two atypical fibroxanthomas (1.5%). Among the 1974 soft tissue sarcomas registered in our institute, MFH (428 cases) had been the most common sarcoma, followed by liposarcoma, leiomyosarcoma and rhabdomyosarcoma. However, after reassessment, leiomyosarcoma proved to be the most common soft tissue sarcoma (322 cases), followed by 290 MFH, 273 liposarcomas and 202 rhabdomyosarcomas. Among these 290 cases finally diagnosed as MFH, survival data were available in 189 cases. Tumor location in the abdominal cavity, the retroperitoneum or the head and neck (P = 0.0024), tumor size of 5 cm or more (P < 0.0001), deep tumor location (P < 0.0001), high histological grade (grade 3) based on the French Federation of Cancer Centers' grading system (P = 0.0007), and high stage (stage III or IV) based on the American Joint Committee on Cancer (AJCC) staging system (P < 0.0001) were significantly worse prognostic factors by univariate analysis. In multivariate analysis, deep tumor location and high AJCC stage were independent adverse prognostic factors. We conclude that leiomyosarcoma is the most important differential diagnosis for MFH, especially pleomorphic leiomyosarcoma from storiform-pleomorphic type and myxoid leiomyosarcoma from myxoid type. Tumor depth and AJCC stage are the most important predictive prognostic factors in MFH.

Data Interpretation, Statistical↗

PubMed2002

Clinicopathologic relevance of apoptotic and proliferative factors in human lung adenocarcinoma: Fas expression correlates with the histologic subtype, but not with the degree of apoptosis.

We immunohistochemically examined 141 surgically resected peripheral lung adenocarcinomas for the expression of Fas, single stranded (ss-) DNA and Ki-67, and statistically evaluated the relationship of these parameters with other clinicopathologic variables, including clinical stage, nodal involvement, and histopathologic subtypes classified according to WHO criteria. Fas expression by cancer cells was characteristically localized in the cytoplasm, and the extent of expression correlated well with the degree of Ki-67 reactivity (p = 0.0004), but not with the degree of apoptic occurrence, as assessed by ss-DNA reactivity. Cancer cells of the bronchioloalveolar carcinoma (BAC) subtype without invasive growth exhibited a significantly lower Fas expression than those of other subtypes (p < 0.0001). Positive expression of Fas was frequently associated with a high incidence of nodal involvement and advanced clinical stage, as compared with cases of negative expression (p = 0.0111 and p = 0.0439, respectively). Multivariate analysis revealed that Fas expression significantly correlated with the histologic subtype, but not with tumor size, nodal involvement, or clinical stage. Survival analysis determined by the log-rank test revealed that clinical stage and Ki-67 reactivity were poor prognostic variables, and Fas expression was not statistically significant. Based on these data, intracytoplasmic expression of Fas in cancer cells may participate in the development of resistance to fas-mediated apoptosis.

Adenocarcinoma↗

PubMed2002

ATP-binding cassette superfamily transporter gene expression in human primary ovarian carcinoma.

PURPOSE: The purpose of this study is to attempt to characterize patients with unfavorable clinical outcome by the relative mRNA levels of ABC transporter expression in their tumor samples and to examine whether relative mRNA levels of each of the ABC transporters can be a useful predictor of progression-free survival in advanced ovarian carcinoma. EXPERIMENTAL DESIGN: We examined tumor samples taken from 30 patients with primary serous papillary adenocarcinoma of the ovary for the expression of MDR1 and MRP1, MRP2, and MRP3 mRNA by using real-time reverse transcription-PCR, and we evaluated its correlation with clinical outcome. All 30 patients were divided into three groups according to clinical outcome after debulking surgery and platinum-based chemotherapy: 8 patients were classified into the unfavorable group; 11 were classified into the favorable group; and 11 were classified into intermediate group. RESULTS: The relative mRNA levels of MRP1 and MRP3 were significantly different among the three groups, and the mRNA levels of MRP1 and MRP3 in the unfavorable group were significantly higher than those in the favorable group by multiple comparison. The relative mRNA levels of MRP1 expression were significantly correlated with those of MRP3 expression. In the 30 patients with serous papillary adenocarcinoma, univariate and multivariate analysis demonstrated that the high relative mRNA levels of MRP1 expression were significantly correlated with a short period of progression-free survival. CONCLUSIONS: In patients with advanced ovarian serous papillary adenocarcinoma, these results suggest that patients with an unfavorable clinical outcome are characterized by increased levels of coordinated MRP1 and MRP3 mRNA expression in their tumor samples. Furthermore, a higher level of MRP1 mRNA expression can be a candidate for a useful predictor of a shorter period of progression-free survival.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Gastric cancer with extragastric lymph node metastasis: multivariate prognostic study.

BACKGROUND: Although many authors have investigated the prognostic factors of gastric cancer, there are few comprehensive studies on the prognosis of patients with extensive lymph node metastasis. The aim of this study was to clarify the prognostic factors of gastric cancer with extragastric lymph node metastasis, using multivariate analysis.METHODS: The study population consisted of 121 patients who had undergone radical gastrectomy and extended lymph node dissection (D2, D3) for gastric cancer with extragastric lymph node metastasis. We examined 18 clinicopathologic factors, including the type of gastrectomy, tumor size, depth of wall invasion, status of lymph node metastasis, and stage of disease. Survival rates were analyzed by the Kaplan-Meier and Mantel-Cox methods, and multivariate analysis was done using the Cox proportional hazards model.RESULTS: The overall 5-year survival rate was 32%, and the 5-year survival rate after curative gastrectomy was 37%. Overall survival rate was associated with the type of gastrectomy, stage of disease, operative curability, tumor size, depth of wall invasion, and anatomical distribution of positive nodes, whereas the survival rate after curative gastrectomy was correlated with the type of gastrectomy, stage of disease, tumor size, gross type, and depth of wall invasion. Independent prognostic factors were operative curability and depth of wall invasion, and survival after curative gastrectomy was influenced only by the depth of wall invasion (mucosa and submucosa [T1], muscularis and subserosa [T2] vs serosa [T3]).CONCLUSION: In patients with gastric cancer with extragastric lymph node metastasis, independent prognostic factors after gastrectomy were operative curability and depth of wall invasion. Long-term survival can be achieved when the patients have no serosal invasion (T1, T2) and are treated by curative gastrectomy.

Journal Article↗