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1.
J Exp Clin Cancer Res ; 23(1): 127-33, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15149161

ABSTRACT

The clinical significance of cyclin A expression, which has been known to act in the mitotic phase of the cell cycle, as an indicator of malignant potential in human tumors, has been suggested. The aim of this study was to elucidate the significance of immunohistochemical expression of cyclin A in colorectal carcinomas based on a larger study population. Immunohistochemical staining for cyclin A was performed for 167 colorectal carcinomas and the correlation between cyclin A expression and the clinicopathological characteristics was analyzed. One hundred and two carcinomas (61.1%) had cyclin A expression and the other 65 (38.9%) did not. The mean size of the tumors with cyclin A expression was significantly larger than that of tumors without cyclin A expression (p = 0.012). Survival in patients with cyclin A-expressing carcinomas was significantly worse than that in patients with carcinomas without cyclin A expression (p = 0.004). Cyclin A expression (p = 0.030), as well as lymph node metastasis (p = 0.007) and Dukes' stage of the tumors (p < 0.0001) were found to be factors independently associated with unfavorable prognosis in patients with colorectal carcinoma. Our results demonstrated that immunohistochemical expression of cyclin A is an independent prognostic indicator in patients with colorectal carcinoma.


Subject(s)
Carcinoma/metabolism , Colorectal Neoplasms/metabolism , Cyclin A/biosynthesis , Adult , Aged , Aged, 80 and over , Carcinoma/pathology , Cell Differentiation , Colorectal Neoplasms/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Multivariate Analysis , Prognosis , Time Factors
2.
J Cancer Res Clin Oncol ; 129(9): 498-502, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12884029

ABSTRACT

PURPOSE: The significance of p34(cdc2) expression in human tumors has not been fully explained. The aim of the current study was to elucidate the clinicopathologic significance of immunohistochemical p34(cdc2) expression in carcinoma of the colon and rectum. METHODS: The immunohistochemical expression of p34(cdc2) was examined in 90 consecutive colorectal tumor cases, and p34(cdc2) expression and the clinicopathologic features of the patients and their tumors were compared. RESULTS: Lymph node metastasis was significantly more frequent in tumors expressing p34(cdc2) (47.8%, 11 of 23 tumors) than in tumors not expressing p34(cdc2) (22.4%, 15 of 67 tumors; P=0.020). Multivariate analysis demonstrated that tumor depth ( P=0.008) and p34(cdc2) expression ( P=0.022) were independently associated with lymph node metastases of colorectal carcinomas. CONCLUSIONS: The immunohistochemical expression of p34(cdc2) is independently associated with lymph node metastasis in colorectal carcinoma.


Subject(s)
Biomarkers, Tumor/analysis , CDC2 Protein Kinase/analysis , Carcinoma/pathology , Colorectal Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Lymph Nodes/pathology , Aged , Carcinoma/chemistry , Colorectal Neoplasms/chemistry , Female , Humans , Immunohistochemistry , Lymph Nodes/chemistry , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness , Odds Ratio
3.
Eur Surg Res ; 35(1): 22-5, 2003.
Article in English | MEDLINE | ID: mdl-12566783

ABSTRACT

PURPOSE: Administration of anticancer drugs may damage gastrointestinal epithelium, thereby increasing the permeability of the gastrointestinal mucosa. We estimated the usefulness of oral lactulose and mannitol (L/M) test for assessment the extent of mucosal damage following postoperative chemotherapy for human malignant disease. METHODS: The permeability index (PI): the urinary recovery ratio of excreted L to M was measured before and after chemotherapy in 31 patients with gastrointestinal cancers who underwent surgical resection. These findings were compared with data on 12 patients with breast cancer. The effect of chemotherapy was evaluated by the ratio of increase in PI, which was designed as post-chemotherapy value on day 7 divided by pre-chemotherapy value. RESULTS: The mean PIs before chemotherapy in patients who underwent gastrectomy or colectomy were significantly higher than the value in those treated with mastectomy (p < 0.05). In the gastrointestinal cancer patients, the mean PIs significantly increased after chemotherapy compared with the pre-chemotherapeutic value (p < 0.01), however no significant difference was seen in breast cancer patients. When the ratios of increase in PI were calculated among gastric cancer patients, the total gastrectomy group showed a significantly higher increase in PI compared with the partial gastrectomy group (p < 0.05). CONCLUSIONS: Since the oral L/M absorption test is useful for assessing the degree of mucosal damage and measurement of intestinal permeability, this analysis should be recommended to determine the optimum timing and the adequate dosage of the anticancer drug administration.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Camptothecin/therapeutic use , Colonic Neoplasms/drug therapy , Intestinal Mucosa/metabolism , Stomach Neoplasms/drug therapy , Breast Neoplasms/surgery , Cisplatin/therapeutic use , Colonic Neoplasms/surgery , Combined Modality Therapy , Cyclophosphamide/therapeutic use , Fluorouracil/therapeutic use , Humans , Methotrexate/therapeutic use , Permeability/drug effects , Stomach Neoplasms/surgery
4.
Eur Surg Res ; 34(5): 351-6, 2002.
Article in English | MEDLINE | ID: mdl-12364819

ABSTRACT

BACKGROUND: S-1 is a new antitumor agent which was developed based on biochemical modulation of fluorouracil. S-1 consists of tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1. S-1 has been reported to enhance therapeutic effects and to reduce the gastrointestinal toxicity as compared with 5-fluorouracil. In this study performed in rats, S-1 was used to assess the relationship between gastrointestinal mucosal toxicity and changes in intestinal barrier function. METHODS: Fifteen rats were equally divided into three groups: group A (untreated controls), group B (FT and CDHP mixture), and group C (FT and CDHP in combination with Oxo). The animals in groups B and C received equitoxic doses of the drugs in their food for 14 consecutive days. The intestinal permeability was determined on the basis of the urinary recovery of orally administered lactulose and mannitol (L/M). Injury to the small intestines was evaluated by light microscopy. The cell surface expression of CD44 was evaluated immunohistochemically. RESULTS: Recovery of L/M in urine (expressed as a fraction of the dose administered) was 0.15 +/- (SE) 0.08, 0.23 +/- 0.13, and 0.09 +/- 0.04 in groups A, B, and C, respectively. The intestinal permeability in group B was significantly higher than that in group C (p < 0.05). Treatment with FT and CDHP (groups B and C) induced injury to the small intestine and decreased expression of CD44 within the intestinal mucosa, but the extent of damage was reduced by coadministration of Oxo (group C). CONCLUSION: This experimental study suggested that the gastrointestinal toxicity resulting from administration of anticancer drugs is accompanied by an impaired gut barrier function measurable as an increase in intestinal permeability to L/M.


Subject(s)
Antimetabolites, Antineoplastic/toxicity , Intestinal Absorption/drug effects , Tegafur/toxicity , Animals , Fluorouracil/analogs & derivatives , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Male , Oxonic Acid/toxicity , Pyridines/toxicity , Rats , Rats, Sprague-Dawley
5.
Oncol Rep ; 8(6): 1313-5, 2001.
Article in English | MEDLINE | ID: mdl-11605056

ABSTRACT

The aim of the current study was to elucidate the histopathological characteristics of obstructing carcinoma of the colon and rectum. We studied 72 patients with colorectal carcinoma, including 13 with obstructing carcinoma. The obstruction carcinomas occurred in sigmoid colon significantly more frequently than did non-obstructing carcinomas (p=0.007). The mean size of the obstructing carcinomas was 3.7+/-0.9 cm, which was significantly smaller than that of non-obstructing carcinomas (5.4+/-1.9 cm, p=0.003). The proportion of lymph node metastasis in obstructing carcinomas was 66.9%, which was significantly higher than that in non-obstructing carcinomas (42.4%, p=0.021). The proportion of carcinomas classified into Dukes' C or D in obstructing carcinomas was 84.6% and was significantly higher than that in non-obstructing carcinomas (52.5%, p=0.026). The pathogenesis of obstruction in colorectal carcinoma can be also derived from the contraction of the intestinal lumen caused by the condensation of cancer cells.


Subject(s)
Colorectal Neoplasms/complications , Colorectal Neoplasms/pathology , Intestinal Obstruction/etiology , Adult , Aged , Aged, 80 and over , Female , Humans , Lymphatic Metastasis , Male , Middle Aged
6.
Hepatogastroenterology ; 48(41): 1389-92, 2001.
Article in English | MEDLINE | ID: mdl-11677971

ABSTRACT

BACKGROUND/AIMS: The factors influencing the development of small intestinal obstruction following gastric surgery are controversial. METHODOLOGY: Univariate and multivariate analyses were carried out on data from 48 patients with gastric cancer who underwent total gastrectomy and Roux-en-Y reconstruction for a potential cure. RESULTS: Of these 48 patients, 11 (22.9%) presented with mechanical obstruction in the small intestine postoperatively. There were no statistically significant differences with regard to age, sex, and the presenting pathology. The development of obstruction was not related to a longer operation time, a greater estimated blood loss during surgery, an extensive lymph node dissection and a combined resection of adjacent organs. The probability that the antecolic anastomosis would cause obstruction was significant when compared with findings in case of the retrocolic anastomosis (P < 0.05). In the multivariate logistic regression analysis, the significant risk factors related to the development of small intestinal obstruction proved to be reconstructive route of jejunal loop. CONCLUSIONS: In potentially curative patients undergoing total gastrectomy, retrocolic anastomosis should be attempted to prevent the development of postoperative intestinal obstruction.


Subject(s)
Anastomosis, Roux-en-Y/methods , Gastrectomy/methods , Intestinal Obstruction/etiology , Intestine, Small , Postoperative Complications/etiology , Stomach Neoplasms/surgery , Aged , Aged, 80 and over , Anastomosis, Surgical/methods , Female , Humans , Male , Middle Aged , Multivariate Analysis , Risk Factors
7.
Bioorg Med Chem ; 8(3): 515-21, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10732967

ABSTRACT

A series of new platinum(IV) complexes of the type [PtIV(DACH)trans(L)2Cl2] (where DACH = trans-1R,2R-diaminocyclohexane, and L = acetate, propionate, butyrate, valerate, hexanoate, or heptanoate) bearing the carboxylate groups in the axial positions have been synthesized and characterized by elemental analysis, IR, and 195Pt NMR spectroscopy. The crystal structure of the analogue [PtIV(DACH)trans(acetate)2Cl2] was determined by single crystal X-ray diffraction method. There were two crystallographically independent molecules, both of which lie on crystallographic two-fold axes. The bond lengths and bond angles of both the molecules were the same within the experimental error. The compound crystallizes in the monoclinic space group C2, with a = 11.180(2) A, b = 14.736(3) A, c = 10.644(2) A, beta = 112.38(3) degrees, Z = 4 and R = 0.0336, based upon a total of 1648 collected reflections. In this complex, the platinum had a slightly distorted octahedron geometry owing to the presence of a geometrically strained five-member ring. The two adjacent corners of the platinum plane were occupied by the two amino nitrogens of DACH, whereas the other two equatorial positions were occupied by two chloride ions. The remaining two axial positions were occupied by the oxygens of acetate ligands. The DACH ring was in a chair configuration. An intricate network of intermolecular hydrogen bonds held the crystal lattice together. These analogues were evaluated in vitro and demonstrated cytotoxic activity against the human ovarian 2008 tumor cell line (IC50 = 0.001-0.06 microM). Structure-activity study revealed that activity was highest for the analogue where L = butyrate.


Subject(s)
Carboxylic Acids/chemistry , Organoplatinum Compounds/chemistry , Organoplatinum Compounds/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Survival/drug effects , Cisplatin/analogs & derivatives , Cisplatin/chemistry , Crystallography, X-Ray , Humans , Hydrogen Bonding , Inhibitory Concentration 50 , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Organoplatinum Compounds/chemical synthesis , Platinum , Spectrophotometry, Infrared , Stereoisomerism , Structure-Activity Relationship , Tumor Cells, Cultured
8.
Pharmacogenetics ; 8(4): 315-23, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9731718

ABSTRACT

Because aryl hydrocarbon hydroxylase (AHH) is considered to be responsible for the activation of benzo(a)pyrene and other polyaromatic hydrocarbons in cigarette smoke to carcinogens, it is important to examine CYP1A1 (AHH) activity in the determination of susceptibility to lung cancer. We investigated AHH activity in peripheral mitogen-treated lymphocytes in 108 lung cancer patients and 95 healthy control individuals. Non-induced AHH activity was detectable in all the samples. AHH inducibility (3-methylcholanthrene-induced/non-induced AHH activity) showed a very wide interindividual variation as well as non-induced AHH activity. No significant associations were found between adjusted AHH activity and histologic type of tumor among lung cancer patients. Adjusted AHH inducibility of genotype C [geometric mean and 95% confidence interval (CI); 15.56 and 11.69-20.71] in MspI polymorphism was significantly higher than those of the other two genotypes (P = 0.0001), while no significant difference was observed between genotypes A (4.76 and 3.82-5.93) and B (5.60 and 4.57-6.86). On the other hand, non-induced AHH activity of genotype Val/Val (0.121 and 0.082-0.178 pmol/min/10(6) cells) in isoleucine-valine (Ile-Val) polymorphism was significantly higher than those of genotypes Ile/Ile (0.042 and 0.034-0.052 pmol/min/10(6) cells) and Ile/Val (0.040 and 0.030-0.053 pmol/min/10(6) cells) (P < 0.0001). Even after controlling for age, cigarettes smoked per day and season of the year, high AHH inducibility (7.0 < versus 0 < < or = 3.0: OR and 95 %CI, 12.4 and 2.88-53.4) was an independent risk factor for lung cancer. The data indicate that high AHH inducibility may strongly associate with the susceptibility to lung carcinogenesis.


Subject(s)
Aryl Hydrocarbon Hydroxylases/metabolism , Cytochrome P-450 CYP1A1/genetics , Lung Neoplasms/enzymology , Adult , Aged , Aged, 80 and over , Aryl Hydrocarbon Hydroxylases/biosynthesis , Cytochrome P-450 CYP1A1/metabolism , Enzyme Induction , Female , Gene Frequency , Genotype , Humans , Japan , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Phenotype , Polymorphism, Genetic , Regression Analysis , Smoking/adverse effects
9.
Cancer Chemother Pharmacol ; 42(3): 194-200, 1998.
Article in English | MEDLINE | ID: mdl-9685054

ABSTRACT

MST-16, a derivative of bis(2,6-dioxopiperazine), is a newly developed anticancer agent that is potentially effective in combination with anthracyclines. It has a structural similarity to ICRF-187. The effects of MST-16 and its active form, ICRF-154, on the cytotoxic activities of six anthracyclines were investigated both in vitro and in vivo. Adriamycin (ADM), therarubicin (THP) and ME2303 (ME) showed synergistic cytotoxicity against colon 26 cells, when combined with MST-16. Epirubicin (EPI) and menogaril (TUT-7) and daunomycin (DM) all had a combination index of less than 1.0 only in the lower fraction affected range and, so there were probably no synergistic interactions between these drugs and MST-16. In colon 26 tumor-bearing mice, a significant delay in tumor growth was noted in the mice treated with ADM (7.5 mg/kg) and MST-16 (750 mg/kg) compared with mice given either drug alone. Similarly, tumor growth in mice treated with THP (10 mg/kg) or ME (10 mg/kg) with MST-16 (750 mg/kg) was significantly delayed. To elucidate the mechanism of synergy between these anthracyclines and MST-16, the concentration of anthracyclines in the treated cells was measured by flow cytometry. No increased intracellular accumulation of ADM. THP or ME was evident even when combined with MST-16. Cell cycle analysis revealed that MST-16 enhanced the accumulation of cells in G2M induced by ADM, THP and ME 1.6, 1.4, and 1.5 times, respectively. We thus conclude that the administration of ADM, THP and ME combined with MST-16 is synergistic and that the mechanism may not include an increase in the intracellular drug uptake but rather an increase in G2M accumulation.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Piperazines/pharmacology , Animals , Body Weight/drug effects , Cell Division/drug effects , Colonic Neoplasms/pathology , Drug Synergism , Female , Mice , Mice, Inbred BALB C , Tumor Cells, Cultured/drug effects
10.
Gan To Kagaku Ryoho ; 25 Suppl 3: 464-8, 1998 Apr.
Article in Japanese | MEDLINE | ID: mdl-9589054

ABSTRACT

BACKGROUND: The present study was done to determine if carcinoembryonic antigen (CEA) concentration doubling time can predict the course of disease in patients with adenocarcinoma of the gastrointestinal tract and characterize tumor biology. METHODS: CEA doubling times were determined from semilogarithmic plots of CEA concentration time courses in 20 patients with recurrent gastric cancer and 17 with recurrent colorectal cancer. RESULTS: Gastric and colorectal carcinomas showed mean CEA doubling times of 229 days and 85 days, respectively. There were no significant differences with regard to patient age, tumor size, gross appearance and histological differentiation. However, women had shorter CEA doubling times than did men. Flow cytometric analysis showed that tumors with a higher proportion of cells in S-phase (> or = 15%) had significantly shorter CEA doubling times than those with a lower S-phase fraction (< 15%). There was a significant correlation between the CEA doubling time and the length of survival after the initial CEA concentration increase in patients with recurrent gastric and colorectal carcinomas. CONCLUSIONS: CEA doubling time predicts life expectancy in patients with adenocarcinoma of the gastrointestinal tract. Differences in survival time are closely associated with variations in the biological aggressiveness of individual tumors.


Subject(s)
Carcinoembryonic Antigen/blood , Colonic Neoplasms/pathology , Life Expectancy , Neoplasm Recurrence, Local/pathology , Stomach Neoplasms/pathology , Aged , Cell Cycle , Colonic Neoplasms/immunology , DNA, Neoplasm/analysis , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/immunology , Neoplastic Cells, Circulating/pathology , Stomach Neoplasms/immunology
11.
Cancer Chemother Pharmacol ; 41(6): 453-6, 1998.
Article in English | MEDLINE | ID: mdl-9554588

ABSTRACT

PURPOSE: A phase II trial combining cisplatin, carboplatin and etoposide was conducted in previously untreated patients with stage IIIB and IV small-cell lung cancer, in an attempt to increase response rates and prolong survival. METHODS: Previously untreated patients with small-cell lung cancer, with measurable disease, aged < or = 72 years, performance status < or = 2, and adequate hematologic, hepatic and renal function were enrolled in the study. They were treated with 80 mg/m2 cisplatin on day 1, 100 mg/m2 carboplatin on days 2, 3 and 8, and 50 mg/m2 etoposide on days 1, 2, 3 and 8. RESULTS: A total of 46 patients (20 with stage IIIB and 26 with stage IV disease) were enrolled in the study. A total of 186 courses of chemotherapy were given, and the dose was reduced in 27 courses (15%). The chemotherapy was repeated for four or more courses in 30 patients. There were 10 complete responses and 32 partial responses, for a total response rate of 91% (95% confidence interval, 79% to 98%). The median survival time and 2-year survival rates were 18 months and 22% for stage IIIB disease, and 14 months and 15% for stage IV disease. Major side effects were hematologic: leukopenia, anemia, and thrombocytopenia of grade 3 or more occurred in 48%, 46%, and 43% of patients, respectively. CONCLUSIONS: The three-drug regimen of cisplatin, carboplatin and etoposide is feasible and active against small-cell lung cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Small Cell/drug therapy , Lung Neoplasms/drug therapy , Aged , Alopecia/chemically induced , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/adverse effects , Carboplatin/therapeutic use , Carcinoma, Small Cell/mortality , Carcinoma, Small Cell/pathology , Cisplatin/adverse effects , Cisplatin/therapeutic use , Etoposide/adverse effects , Etoposide/therapeutic use , Female , Hematologic Diseases/chemically induced , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Nausea/chemically induced , Neoplasm Staging , Survival Rate , Treatment Outcome , Vomiting/chemically induced
12.
Anticancer Drugs ; 8(8): 778-83, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9396622

ABSTRACT

Flavone acetic acid (FAA) has shown the effectiveness of vasoactive drugs in the selective reduction of tumor blood flow. A FAA-mediated decrease in tumor blood flow may produce sufficient hypoxic conditions within the tumor. Carboquone (CQ), a naturally occurring prototype bioreductive alkylating agent like mitomycin C (MMC), has been shown to be selectively more cytotoxic toward hypoxic tumor cells. We have reported enhancement of the combined antitumor effects of MMC plus FAA and hyperthermia (HT). In this study, we examined the combined effects of FAA, CQ and HT. In vitro, although HT (43 degrees C, 60 min) reduced the colonogenicity to 0.58 in CQ (0.01 microg/ml) alone, the combined cytotoxicity of CQ and HT was not enhanced with exposure to FAA at a concentration of 100 microg/ml. In vivo, the tumor growth time, calculated as the time required to reach twice the initial tumor volume, for CQ (2 mg/kg) alone, FAA (150 mg/kg) alone, CQ+FAA, CQ+HT (43 degrees C, 15 min), FAA+HT and FAA+CQ+HT was 6.1, 5.1, 7.1, 8.0, 7.6 and 13.4 days, respectively. A significant enhancement of antitumor effects by trimodality therapy with CQ, FAA and HT was observed, when compared to the treatment with CQ and FAA (p < 0.05). The possible mechanisms of an increased antitumor response achieved with the combination of CQ, FAA and HT may be explained in the following way: the FAA-mediated decrease in tumor blood flow produced sufficient hypoxic conditions within the tumor, and these resulted in a significant increase of the antitumor effects of CQ and HT.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hyperthermia, Induced , Melanoma, Experimental/therapy , Animals , Carbazilquinone/administration & dosage , Cell Hypoxia , Combined Modality Therapy , Drug Synergism , Flavonoids/administration & dosage , Male , Mice , Tumor Cells, Cultured/drug effects
13.
Am J Clin Oncol ; 20(4): 393-7, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9256897

ABSTRACT

We conducted a phase II trial of a regimen that combined cisplatin (CDDP), carboplatin (CBDCA), and vindesine (VDS) in previously untreated patients with non-small cell lung cancer (NSCLC) to evaluate the efficacy and safety of the regimen. Thirty-five patients with inoperable NSCLC entered the study. Cisplatin (CDDP 80 mg/m2) was administered on day 1, and CBDCA 100 mg/m2 and VDS 2 mg/m2) were administered on days 2, 3, and 8. We observed one complete response (CR) and 16 partial responses (PR), with a total response rate of 49% [95% confidence interval (CI) 31-66%]. The overall median survival was 58 weeks; the 1-year survival rate was 60%, and the 2-year survival rate was 23%. Major toxicities were hematologic; leukopenia of grades 3 and 4 occurred in 66% patients, and thrombocytopenia occurred in 23%. Therefore, the dose-intensified regimen of CDDP, CBDCA, and VDS was active in treating patients with inoperable NSCLC, with demonstration of a favorable median survival time.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin/administration & dosage , Lung Neoplasms/drug therapy , Vindesine/administration & dosage , Adult , Aged , Alopecia/chemically induced , Anemia/chemically induced , Antineoplastic Agents/adverse effects , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/adverse effects , Cisplatin/adverse effects , Female , Follow-Up Studies , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Leukopenia/chemically induced , Male , Middle Aged , Nausea/chemically induced , Recombinant Proteins , Remission Induction , Safety , Survival Rate , Thrombocytopenia/chemically induced , Vindesine/adverse effects , Vomiting/chemically induced
14.
Neoplasma ; 44(1): 69-72, 1997.
Article in English | MEDLINE | ID: mdl-9201284

ABSTRACT

Fuyuan Country, in Yunnan Province, China has an extremely high lung cancer mortality both in males and non-smoking females. Out of 5768 deaths, 588 patients died of malignant diseases. Lung cancer was the number one cause of death among malignant diseases both in males and females. The rate of lung cancer death to the whole of malignant diseases was 56.2% for males and 55.0% for females. Indoor soot and combustion emission derived from smoky coal produced in northern Fuyuan exhibited high mutagenic activities against Salmonella typhimurium TA98 strain in Ames test. Resected lung tissues derived from the patients with lung cancer in Fuyuan contained significantly higher concentrations of benzo(a)pyrene than those in Japan, both in males and females (i.e., 608.7 +/- 477.1 pg/dry weight for samples of the patients in Fuyuan, 180.1 +/- 104.5 for Japanese non-smokers, and 207.5 +/- 98.8 for Japanese heavy smokers, respectively). These results suggest that mutagenic chemicals contained in coal as well as indoor environment may have a great influence on lung carcinogenesis in Fuyuan, Yunnan Province, China.


Subject(s)
Air Pollution, Indoor/adverse effects , Benzo(a)pyrene/adverse effects , Carcinogens, Environmental/adverse effects , Coal , Environmental Pollutants/adverse effects , Lung Neoplasms/mortality , Benzo(a)pyrene/analysis , Carcinogens, Environmental/analysis , China/epidemiology , Female , Humans , Incidence , Lung/chemistry , Lung Neoplasms/chemistry , Lung Neoplasms/etiology , Male , Mutagenicity Tests , Salmonella typhimurium
15.
Surg Today ; 27(6): 550-3, 1997.
Article in English | MEDLINE | ID: mdl-9306550

ABSTRACT

We report herein the rare case of a 15-year-old girl with chronic appendicitis in whom the appendix was clearly depicted by a barium enema (BE) examination. The patient presented with a 4-month history of diffuse abdominal pain and tenderness in the lower abdomen. Neither computed tomography nor ultrasonography showed any abnormal findings in the lower abdomen or pelvic cavity. Furthermore, BE examination depicted an appendix filled with the contrast medium. However, at elective surgery, she was found to have chronic appendicitis which was later confirmed histologically. Following this case report, a discussion on the value and limitations of BE examination for the diagnosis of acute and chronic appendicitis is presented.


Subject(s)
Appendicitis/diagnosis , Barium Sulfate , Contrast Media , Enema , Abdominal Pain/etiology , Adolescent , Appendicitis/pathology , Appendicitis/surgery , Appendix/pathology , Chronic Disease , Female , Humans , Recurrence
16.
Nihon Kyobu Shikkan Gakkai Zasshi ; 35(11): 1179-85, 1997 Nov.
Article in Japanese | MEDLINE | ID: mdl-9493443

ABSTRACT

We immunohistochemically examined the expression of CD44 standard (CD44 st) and CD44 variant 6 (CD44 v6) in 112 cases of primary lung cancer, and their relationship to the clinical milieu, including the clinical stage. In 46 cases of squamous cell carcinoma, expression of CD44 st was observed in 45.7% of the cases, and expression of CD44 v6 was observed in 60.9%. In 43 cases of adenocarcinoma, positive staining of CD44 st and CD44 v6 was seen in 2.3% and 4.7% of the cases, respectively. None of 21 small cell carcinomas was positive for CD44 st or CD44 v6. In squamous cell carcinomas, the expression of CD44 st and CD44 v6 was observed at a rate significantly higher than in other histologic type. Most specimens positive for CD44 st stained positively for CD44 v6. Therefore, it seems likely that the CD44 expression observed in squamous cell carcinoma of the lung was a variant CD44 containing the domain encoded by variant exon 6. The expression of CD44 v6 was not related to the clinical stage. Significant association between CD44 v6 and differentiation of squamous cell carcinoma was seen; 2/7 (28.6%) for poorly differentiated, 19/31 (61.3%) for moderately differentiated, and 7/8 (87.5%) for well differentiated squamous cell carcinomas (p = 0.02 by trend test). It was previously reported that CD44 st and CD44 v6 were expressed in both normal bronchial epithelium and squamous cell metaplasia. These results suggest that the expression of CD44 v6 in squamous cell carcinoma of the lung may reflect the immunohistochemical characteristics of the tissue from which such carcinoma emerge.


Subject(s)
Hyaluronan Receptors/metabolism , Lung Neoplasms/immunology , Adenocarcinoma/immunology , Aged , Aged, 80 and over , Antibodies, Monoclonal , Antigenic Variation , Carcinoma, Small Cell/immunology , Carcinoma, Squamous Cell/immunology , Female , Humans , Immunohistochemistry , Male , Middle Aged
17.
Jpn J Cancer Res ; 87(1): 18-24, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8609043

ABSTRACT

We examined the relationship between aryl hydrocarbon hydroxylase (AHH) and the frequency of a MspI mutation in the 3'-flanking region of cytochrome P450 (CYP) 1A1 (MspI polymorphism) and another mutation in exon 7 (Ile-Val polymorphism) in 84 healthy male subjects in Fukuoka, Japan. AHH inducibility (3-methylcholanthrene (MC)-induced AHH activity/non-induced AHH activity) was correlated with the MspI polymorphism (P < 0.0001) and age class (P = 0.015), whereas no correlation was found for the Ile-Val polymorphism (P = 0.509). Age-adjusted AHH inducibility (mean +/- SE) of the predominant homozygote (genotype A), the heterozygote (genotype B) and a homozygote rare allele (genotype C) genotypes was 4.89 +/- 0.36, 4.82 +/- 0.29 and 13.61 +/- 1.44, respectively. The genotype C showed much higher AHH inducibility than genotypes A and B (P < 0.001), while no significant difference was observed between genotypes A and B. Non-induced AHH activity was also correlated with these polymorphisms. The AHH activity of a homozygous mutant Val/Val genotype (0.076 +/- 0.010 pmol/min/10(6) cells) was significantly higher (P < 0.05) than that of the wild-type homozygous Ile/Ile (0.044 +/- 0.004 pmol/min/10(6) cells) and heterozygous Ile/Val (0.047 +/- 0.007 pmol/min/10(6) cells) genotypes. Our study suggests that the genotypes C and Val/Val, which are more frequent in smoking-related lung cancer, are closely related with high AHH inducibility and high non-induced AHH activity, respectively. Thus, the positive relationship between AHH inducibility and lung cancer is supported by our study. If our results are confirmed and the assessment of genotype becomes feasible on a population basis, identification of smokers who have genetically high susceptibility to lung cancer (genotype C or Val/Val) may become important for the prevention of lung cancer.


Subject(s)
Aryl Hydrocarbon Hydroxylases/metabolism , Cytochrome P-450 Enzyme System/genetics , Polymorphism, Genetic , Adult , Analysis of Variance , Aryl Hydrocarbon Hydroxylases/biosynthesis , Deoxyribonuclease HpaII/genetics , Enzyme Induction , Humans , Isoleucine/metabolism , Lymphocytes/enzymology , Lymphocytes/physiology , Male , Middle Aged , Mutation , Phenotype , Sensitivity and Specificity , Valine/metabolism
18.
Am J Surg ; 169(2): 261-4, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7840390

ABSTRACT

PURPOSE: We examined the efficacy of extended lymph node dissection for prolonging survival in macroscopically or histologically proven incurable gastric cancer. PATIENTS AND METHODS: We analyzed clinico-pathologic data on 119 patients with serosally invasive gastric cancer who underwent noncurative gastrectomy, with respect to the relation between the extent of lymphadenectomy and survival benefit. RESULTS: The 5-year survival rate was significantly higher among patients treated with extensive lymphadenectomy (R2/3) compared to simple gastrectomy (R1). Extensive lymphadenectomy significantly prolonged survival time even after noncurative gastrectomy in cases where there was no evidence of hepatic metastasis, peritoneal seeding, or extensive nodal metastasis beyond the tertiary lymph node, and regardless of the extent of direct invasion to adjacent organs. CONCLUSIONS: Gastrectomy combined with extended lymphadenectomy and/or resection of adjacent organs is recommended for gastric cancer patients without distant metastasis, even when the operation is histologically noncurative. Gastrectomy and perioperative intensive chemotherapy are called for when patients have distant metastasis.


Subject(s)
Adenocarcinoma/surgery , Gastrectomy , Lymph Node Excision , Stomach Neoplasms/surgery , Adenocarcinoma/mortality , Gastrectomy/mortality , Humans , Stomach Neoplasms/mortality , Survival Rate
19.
Surgery ; 117(2): 165-9, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7846620

ABSTRACT

BACKGROUND: Our objective was to evaluate the long-term benefit of R2/3 lymph node dissection compared with that of R1, even in node-negative cases. METHODS: We analyzed clinicopathologic data on 373 surgically treated patients with early gastric cancer and without microscopic nodal involvement. RESULTS: Five- and 10-year survival rates for patients treated with R2/3 gastrectomy were 97.3% and 95.4%, respectively. These values were significantly higher than the 90.1% and 81.1% noted for R1 gastrectomy (p < 0.01). Although no difference was found in morbidity and mortality, the incidence of death from a recurrence of the gastric cancer was significantly higher in patients treated with R1 gastrectomy than those with R2/3. Multivariate analysis with the Cox's proportional hazard model revealed patients' age and R2/3 gastrectomy to be independent prognostic factors in patients with node-negative early gastric cancer. CONCLUSIONS: These data show that prophylactic lymph node dissection can potentially prolong the survival time of patients with node-negative early gastric cancer by preventing a recurrence of the gastric cancer.


Subject(s)
Gastrectomy/methods , Lymph Node Excision , Neoplasm Recurrence, Local/prevention & control , Stomach Neoplasms/mortality , Stomach Neoplasms/surgery , Age Factors , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Prognosis , Proportional Hazards Models , Risk Factors , Stomach Neoplasms/pathology , Survival Rate , Time Factors
20.
J Am Coll Surg ; 178(4): 404-6, 1994 Apr.
Article in English | MEDLINE | ID: mdl-8149042

ABSTRACT

Instead of a linear stapler or manual pursestring suture onto the lower part of the rectum, we placed a No. 2-0 Prolene suture on the edge of the rectal stump, using 12 to 16 clips and a disposable skin stapler. This technique is satisfactory for very low anterior resection.


Subject(s)
Rectum/surgery , Surgical Staplers , Suture Techniques , Humans , Sutures
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