[Evaluation of direct administration of DDS-CDDP into the mediastinum for malignant esophageal cancer].
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
Y Kasai
Publications and source records attributed to Y Kasai.
[Antitumor effect of S-1 and cisplatin treatment against human gastric cancer xenografted in nude mice].
The enhanced effects due to the combined use of oral administration of S-1 and intraperitoneal administration of Cisplatin (CDDP) were examined with gastric cancer xenografts (NUGC 4). S-1, a new anticancer drug, was daily administered at 10 mg/kg (qld x 5 x 3 weeks). 5-FU level in blood was 1 microgram/ml at two hours after the treatment. Antitumor activity was not found in mice with only the CDDP treatment. But antitumor activity by S-1 and daily low-dose (1 mg/kg) or intermittent treatment (5 mg/kg) of CDDP showed better results than daily S-1 treatment. The daily low-dose CDDP treatment showed similar efficacy to the intermittent administration at the same total dose, but the daily low-dose CDDP treatment was better in the light of toxicities. These results suggest that treatment with S-1 and daily low-dose CDDP was effective for gastric cancer.
Administration, Oral↗
[Findings of genetic changes in small intestinal carcinomas].
There is now good evidence that a series of genetic lesions in both dominant oncogenes and tumor suppressor genes are involved in the pathogenesis of human digestive tract carcinomas. Small intestinal carcinomas are very rare, accounting for only about 0.19% of all primary gastrointestinal malignant tumors in Japan, so there are few reports investigating genetic changes of small intestinal carcinoma. We analyzed 3 microsatellite loci and the status of K-ras and p53 genes isolated from tumors and surrounding normal tissue samples obtained during surgery. The polymerase chain reaction (PCR) technique used frequent genetic instability to assess differences between tumor and matched DNAs. Replication errors (RERs) were observed in 3 of the 29 cases (10%) of gastric carcinoma and in 11 of the 72 cases (15%) of colorectal carcinoma. None of the 13 (0%) esophageal carcinoma cases showed any RER, but 5 of 11 cases of small intestinal carcinoma (45%) had RERs, reflecting a significantly high incidence. None of the 11 small intestinal carcinoma cases exhibited K-ras gene mutations. Of 7 case amplified successfully by polymerase chain reaction (PCR) in exon 5-8 loci in p53 gene, 2 exhibited abnormally migrated bands in polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. It is thus clear that the genetic carcinogenesis in the small intestine is different from other parts of the digestive tract. These results suggest that genetic instability plays an important role in the pathogenesis of small intestinal carcinomas.
Adenocarcinoma↗
Loss of H19 imprinting in esophageal cancer.
Recent articles have reported that loss of imprinting (LOI) of the endogenous gene H19 was frequently found in lung cancer and chorio-carcinoma, common adulthood cancers. Consequently, we examined the status of genomic imprinting of H19 in 29 esophageal and 48 colorectal cancer specimens, and studied its relation to the expression of H19. Of 12 esophageal cancer specimens heterozygous for the RsaI polymorphism, 6 (50%) exhibited LOI of H19, but none of the 18 colorectal cancer specimens heterozygous for the RsaI polymorphism exhibited LOI of H19. The present study suggests that LOI of H19 may play an important role in the pathogenesis of esophageal cancer. Moreover, H19 expression was frequently abundant in both cancers, and all six esophageal cancers carried LOI with overexpressed H19. Therefore, this overexpression of H19 seems to be an important phenomenon for the development of esophageal and colorectal cancer cells.
Base Sequence↗
Expression of MRP and mdr1 in human gastrointestinal cancer cell lines: a correlation with resistance against doxorubicin.
The mRNA expression of mdr1 and MRP, each of which codes for a transport protein belonging to ATP-binding cassette superfamily and are reported to be responsible for multidrug resistance phenotype, were semi-quantified by RT-PCR in a panel of gastrointestinal cancer cell lines. Although the expression of MRP was predominant in esophageal cancer cell lines, expression of either or both of the genes was detected in all the cell lines tested. Expression of these two genes added together correlated significantly with chemosensitivity against doxorubicin, implicating that expression of both genes should be evaluated in the future analysis of multidrug resistance phenotype. The ID50 values for pirarubicin, although generally lower than the values for doxorubicin, correlated well with the latter, suggesting that the similar phenotype as that for doxorubicin might be responsible for drug resistance against this semisynthetic anthracycline glycoside.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Surgical treatment for the recurrence of colorectal cancer.
We report the results of a retrospective study conducted on patients who developed recurrence following surgery for colorectal cancer, and present a practical plan to improve the survival rates. Of 974 patients who underwent surgery for colorectal cancer in our hospital during the 20 years between 1974 and 1993, 152 developed recurrence, as local recurrence in 70 (7.2%), as liver metastasis in 47 (4.8%), and as pulmonary metastasis in 35 (3.6%). The number of patients who underwent reoperation or curative resection was 54 (77.1%) and 13 (24.1%), respectively, of those with local recurrence, 16 (34.0%) and 6 (37.5%) of those with liver metastasis, and 6 (17.1%) and 6 (100.0%) of those with pulmonary metastasis. The 3- and 5-year survival rates were 13.4% and 8.9%, respectively, after reoperation for local recurrence, 14.4% and 0%, after reoperation for liver metastasis, and 53.3% and 53.3% after reoperation for pulmonary metastasis. Although evaluation was difficult owing to the small number of patients with lung metastasis, resection of a pulmonary lesion resulted in a good outcome. Furthermore, a significant difference in 3- and 5-year survival rates was observed between patients who underwent reoperation and those who underwent conservative treatment, for whom the survival rates were 0% and 0% following local recurrence, 4.6% and 0% following liver metastasis, and 0% and 0% following lung metastasis, at 3 and 5 years, respectively. These findings indicate that aggressive surgery for recurrence may result in a better outcome.
Colorectal Neoplasms↗
Transient hepatofugal portal blood flow after hepatectomy in a patient with cirrhosis: report of a case.
We report herein the case of a 60-year-old man who developed hepatic failure with simultaneous transient hepatofugal portal blood flow after undergoing hepatectomy for hepatocellular carcinoma accompanied by cirrhosis with a splenorenal shunt. The transient hepatofugal portal blood flow was detected by color Doppler ultrasonography. Following this case report, the possibility of a relationship between hepatofugal portal blood flow, portal-systemic shunts, and postoperative hepatic failure is discussed.
Carcinoma, Hepatocellular↗
Causes of rectal incontinence after sphincter-preserving operations for rectal cancer.
PURPOSE: Low anterior resection (LAR) is the treatment of choice for middle and high rectal tumors. Even though the rectal sphincter is preserved, some patients show a postoperative loss of rectal continence that may be recovered during follow-up. The purpose of this study was to collect clinical and manometric data before and after LAR to find possible explanations for incontinence. METHODS: Seventeen continent patients with rectal tumors located 10 cm above the anal verge were selected. Manometry was performed before and three months after surgery and when stable frequency of bowel movement was achieved (mean, 7 months). RESULTS: Immediately after the operations, 14 of 17 patients showed a certain degree of incontinence but recovered during follow-up; at the end of the study, only two patients reported minor soiling. Resting and squeeze pressures were moderately reduced after surgery and increased during the following six months without regaining preoperative levels. Rectoanal inhibitory reflex was present in 94.4 percent of patients before the operations and in 25 percent of them after surgery, but it was not associated with incontinence. Rectal sensation was significantly reduced, and its recovery was well correlated with decrease in the frequency of bowel movements. CONCLUSIONS: After LAR, there is a reduction in rectal pressures, suggesting damage to sphincter muscle fibers or innervation. There is also a reduction in rectal sensation related to loss in reservoir capacity, all of which may contribute to incontinence.
Adenocarcinoma↗
Induction of E-selectin expression on vascular endothelium by digestive system cancer cells.
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Digestive System Neoplasms↗
Preoperative embolization of gastric arteries for esophageal cancer.
BACKGROUND: We developed a novel treatment of preoperative embolization therapy in an attempt to prevent anastomotic leakage after esophageal resection. We report the results of this new treatment. METHODS: Preoperative embolization therapy (PET) was performed in 24 cases of esophageal carcinoma. The femoral artery was punctured, and celiac angiography was performed. The left gastric artery and splenic artery underwent embolization. The right gastric artery then underwent embolization at a site beyond the second or third branch to the gastric wall. With a laser flow meter the stomach tissue blood flow was measured before and after construction of the gastric tube, and the change in blood flow was compared. RESULTS: The average decrease in gastric blood flow was 23% in patients with PET and 65% in patients without PET. Twenty-one (88%) of 24 cases maintained more than 50% tissue blood flow in patients with PET and in 1 (8%) of 12 in patients without PET (p < 0.001 by t test). No serious complications occurred. CONCLUSIONS: Preoperative embolization therapy is a safe and uncomplicated technique, and tissue blood flow in the stomach was better preserved. This new technique is expected to reduce the frequency of anastomotic leakage after esophageal operation.
Adult↗
Seasonal variation in blood pressure in normotensive women studied by home measurements.
1. The factors influencing the seasonal variation in blood pressure measured at home in normotensive women were examined. 2. Sixteen female subjects (56.3 +/- 7.9 years old, mean +/- SD) measured their blood pressure and pulse rate at home each morning for more than 20 times per month for at least 1.5 years. Blood pressure and body weight were also determined in the office once or twice a month in that period. Monthly means of outdoor and indoor temperatures and daytime length were obtained from the Meteorological Observatory. The single cosinor method was used to evaluate circannual rhythm. 3. We observed a biphasic seasonal variation in self-recorded blood pressure measured at home, environmental temperature and daytime length but found no apparent seasonal variation in body weight and blood pressure measured in the office. The lowest levels of systolic and diastolic blood pressure measured at home were observed in July. The longest daytime length was recorded in June, while the highest outdoor temperature and indoor temperature were recorded in August, indicating that the longest daytime length preceded and the highest environmental temperature lagged behind the lowest level of blood pressure. The shortest daytime length is in December. The lowest outdoor and indoor temperature were observed in January, while the highest levels of self-recorded systolic blood pressure and diastolic blood pressure were in January and December, respectively. Half-amplitudes of self-recorded systolic and diastolic blood pressure were 2.6 +/- 1.0 mmHg and 2.0 +/- 0.8 mmHg, respectively. 4. These findings indicate the importance of a seasonal effect, i.e. daytime length and the environmental temperature, on the blood pressure of individuals.
Adult↗
Detection of ras gene mutations in perioperative peripheral blood with pancreatic adenocarcinoma.
Surgeons wish to know of any correlation between an operation and the incidence of metastasis. In perioperative periods, pancreatic cancer cells were identified by detecting mutant K-ras gene by two-step PCR and RFLP analysis in blood samples taken from peripheral blood. In no case was K-ras point mutation detected in blood before operation, although the mutant hand was observed in all cases at the time the lesion was resected. Surprisingly, in five of ten cases, positive bands were identified just after laparotomy, before we had reached the primary lesion. In almost all cases, mutant K-ras was detected until the fourteenth postoperative day. These findings suggest that cancer cells exist in the circulation, and have a potential for hematogenous metastasis during the perioperative period. In conclusion, surgical stress causes hematogenous dissemination of pancreatic cancer cells, and surgeons should employ the appropriate anti-metastasis therapy in the perioperative period.
Adenocarcinoma↗
[Neoadjuvant chemotherapy in high-grade advanced gastric cancer with protracted infusional 5-fluorouracil and consecutive low-dose cisplatin].
Twenty-one evaluable patients with primary gastric cancer/local invasion, liver metastasis and peritoneal metastasis were entered in a pilot study of neoadjuvant chemotherapy that used continuous 24-hour infusion 5-FU, 330 mg/m2/day plus low dose CDDP, 6 mg/m2 daily by bolus infusion d1-5. This regimen was repeated for 4 weeks. The overall response rate was 52%, including one complete and ten partial responses. The response rate of differentiated adenocarcinomas was significantly higher than that of poorly differentiated adenocarcinomas. In 15 patients (71%), gastrectomy and lymphadenectomy could be done after this regimen. chemotherapy-induced downstaging from the initial clinical stage was pathologically found in 5 patients who underwent gastrectomy. Toxicity was primarily hematologic. Leukopenia and thrombocytopenia of grade 3 or 4 occurred in 19% and 14% of patients, respectively. The patients were able to take meals during therapy and preserved good quality of life. Median survival time was 11 months for the cancers with liver metastasis and five of the 8 locally advanced cancers are alive 11 months after the therapy. This therapy was effective for patients with high-grade advanced gastric cancer.
Adenocarcinoma↗
Stretch-induced enhancement of contractions in uterine smooth muscle of rats.
1. We studied the effect of servo-controlled stretch of smooth muscle strips from rat uterus on tension and intracellular Ca2+ concentration ([Ca2+]i, using fura-2 as an indicator) at 30 degrees C. 2. When quiescent uterine muscle strips were stretched at a ramp time of 0.5 s by multiples of 5% of the resting muscle length (L0) up to 40%, forty-two out of sixty muscle strips responded with a transient active contraction and a [Ca2+]i increase. The minimum excursion of stretch required for contraction was 26.3 +/- 7.5% of L0 (mean +/- S.D.). The peak response had an all-or-none property and was almost independent of the duration of stretch. 3. Stretches of 30 or 35% of L0 induced contraction in most cases when rapidly applied in 0.2-0.5 s, but slowly applied stretch (ramp duration of 5-10 s) rarely induced contraction. 4. The stretch-induced response was inhibited by the removal of extracellular Ca2+ or by the addition of 10 nM nicardipine. However, it was unaffected by 1 microM tetrodotoxin, 1 microM atropine or by 10 microM cyclopiazonic acid, an inhibitor of Ca2+-ATPase in intracellular Ca2+ stores. 5. When a stretch of 15-35% of L0 was applied during the relaxation phase of 10 nM oxytocin-induced rhythmic contractions, the first contraction after the stretch occurred earlier than that expected from the control rhythm. However, the frequency of the subsequent rhythm returned to almost the control level even during continued application of stretch, although the half-width of rhythmic contractions was increased during stretch. 6. The present study demonstrates that stretch of uterine muscle induces a transient contraction due to Ca2+ influx, which is myogenic and dependent on the excursion and velocity of stretch. The all-or-none property of the stretch-induced contractions suggests initiation of Ca2+ spikes. Furthermore, stretch modulates the oxytocin-induced rhythmic contractions.
Animals↗
Low activity of branched-chain alpha-keto acid dehydrogenase complex in human liver.
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3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
Detection of hepatic micrometastasis in pancreatic adenocarcinoma patients by two-stage polymerase chain reaction/restriction fragment length polymorphism analysis.
Hepatic metastasis and retroperitoneal recurrence generally are considered to be the two primary modes of recurrence in pancreatic cancer. The goal of this study was to determine if patients with pancreatic adenocarcinoma have hepatic and peritoneal micrometastasis at operation. Pancreatic adenocarcinomas are known to have a high incidence of K-ras gene mutations. Liver tissue specimens were obtained from 30 patients (17 with pancreatic adenocarcinoma and 13 with other diseases) with a biopsy needle at operation. Peritoneal washings were obtained during operation from 20 patients with pancreatic adenocarcinoma. Two-stage polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis were used to detect K-ras oncogene mutation at codon 12. Thirteen of 17 pancreatic adenocarcinoma patients had K-ras gene mutations in the liver, whereas all 13 patients with other diseases did not. However, only two of 20 pancreatic adenocarcinoma patients revealed K-ras gene mutation in peritoneal lavage fluids. These results indicate the feasibility of detecting hepatic micrometastasis in patients with pancreatic adenocarcinoma, and imply that PCR/RFLP analysis may be of value in the diagnosis, treatment and follow-up of hepatic metastasis of pancreatic adenocarcinoma.
Adenocarcinoma↗
Protective effects of kampo medicines and baicalin against intestinal toxicity of a new anticancer camptothecin derivative, irinotecan hydrochloride (CPT-11), in rats.
In clinical use, irinotecan hydrochloride (CPT-11; 7-ethyl-10-[4-(piperidino)-1-piperidino]carbonyloxycamptothecin), a novel antitumor agent, causes a relatively high incidence of severe forms of diarrhea. We investigated whether baicalin, an inhibitor of beta-glucuronidase, which deconjugates the glucuronide of the active metabolite of CPT-11, SN-38 (7-ethyl-10-hydorxycamptothecin), and Japanese herbal medicines (Kampo medicines) which contain baicalin can ameliorate CPT-11-induced intestinal toxicity in rats. CPT-11 (60 mg/kg i.v. once daily for 4 consecutive days) induced intestinal toxicity characterized by diarrhea, loss of body weight, anorexia and disruption of intestinal epithelium. Treatment with baicalin (25 mg/kg p.o. twice daily) or Kampo medicines (TJ-14 and TJ-114; 1 g/kg p.o. twice daily) from the day before to 4 or 10 days after the start of CPT-11 administration resulted in significantly decreased weight loss, improved anorexia and delayed onset of diarrheal symptoms. Histological examination revealed that Kampo medicine-treated animals had less damage to the intestinal epithelium and that damage was repaired more rapidly than in control rats. These results suggest that the prophylactic use of Kampo medicines (TJ-14 and TJ-114) may be of value against CPT-11-induced intestinal toxicity.
Animals↗
[Study on the mechanisms of diarrhea induced by a new anticancer camptothecin derivative, irinotecan hydrochloride (CPT-11), in rats].
We investigated the mechanisms of CPT-11-induced diarrhea. 1) CPT-11 (80 mg/kg, i.v.) induced watery diarrhea within 1 hr after dosing in saline-loaded (10 ml/kg, p.o.) rats. This was partially inhibited by subcutaneous injection of atropine (1 mg/kg) or ondansetron (1 mg/kg) and almost completely inhibited by a combination of atropine and ondansetron or by clonidine (0.3 mg/kg) or morphine (10 mg/kg) alone. 2) CPT-11 at the same dose reduced intestinal fluid absorption, which was blocked by the anti-diarrheal agents mentioned above. Intraluminal injection of CPT-11 (20 mg/2 ml) inhibited fluid absorption and induced fluid secretion. 3) CPT-11, 60 mg/kg, by single intravenous injection induced fewer enzymological and histological changes in the small intestine than 5-FU at 270 mg/kg, while 4 consecutive dosings of CPT-11 induced delayed diarrhea (days 5-7) associated with disruption of intestinal integrity. Co-administration with anti-diarrheal agents, except for ondansetron, protected against watery diarrhea appearing within 1 hr after CPT-11 on days 3 and 4, but worsened delayed diarrhea. These results suggest that single injection of higher doses of CPT-11 causes watery diarrhea at an acute phase at least partly by reducing fluid absorption or increasing secretion, and that while conventional anti-diarrheal agents protect against watery diarrhea, their co-administration in repeated CPT-11 administration has no ameliorative effect on CPT-11-induced delayed diarrhea.
Animals↗