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Biomedical subjects

E Shin

Publications and source records attributed to E Shin.

At least 55 records · Page 3Linked to original sources

[Combination with intra-hepatic arterial infusion of low-dose cisplatin and oral administration of high-dose doxyfluridine in patients with liver metastases of gastric cancer].

Two cases of gastric cancer with multiple liver metastases were treated with 5'-DFUR and CDDP after the surgery. The first case, a 79-year-old male, was administered 1,200 mg/day of 5'-DFUR orally, 6 mg/day of CDDP continuously for 2 weeks, then 20 mg once a week for 5 months by intra-hepatic arterial infusion. This case showed 95% tumor reduction by CT. The other case, a 78-year-old female, was administered 1,200 mg/day of 5'-DFUR orally and 20 mg of CDDP once a week through the hepatic artery. Following several intra-hepatic arterial infusions, it was changed to intra-venous infusion of 20 mg of CDDP twice a week because of trouble with the vascular access system. Two months after, CT showed a 46% tumor reduction in her liver. Neither complained of diarrhea nor nausea, but there was a mild degree of appetite loss. Combination with high-dose 5'-DFUR and low-dose intra-hepatic arterial infusion of CDDP is considered a very effective chemotherapy which can be performed ambulatorily while maintaining the quality of life of patients with liver metastases of gastric cancer.

Administration, Oral↗

[Evaluation of prophylactic intra-hepatic-arterial infusion chemotherapy after resection of hepatic metastases from colorectal primaries].

To prevent recurrence in the residual liver after surgical treatment for colorectal metastases, the efficacy of intermittent or continuous intra-hepatic-arterial chemotherapy was analyzed. The three- and five-year survival rate of patients with intermittent infusion of ADM or MMC (n = 11) was 36.4% and 36.4%, respectively, while the survival rate of the patients without the regional chemotherapy (n = 32) was 41.9% and 23.3%, respectively, indicating no statistical significance. On the other hand, one patient out of 8 with continuous infusion of 5-FU and 2 patients out of 6 without local chemotherapy developed recurrent disease during the median follow-up time of 12 months. No serious complication such as sclerotic cholangitis or hepatic necrosis was observed. Although the follow-up was not long enough to accurately evaluate the efficacy, local chemotherapy with continuous infusion of 5-FU could be a promising method as an adjuvant chemotherapy after hepatic resection for colorectal metastases.

Administration, Oral↗

[Intra-arterial infusion chemotherapy for recurrent breast cancer via an implantable system--the second report].

Intra-arterial infusion chemotherapy via an implantable port catheter has been applied in 16 patients with locally recurrent breast cancer. The regimen consisted of induction and subsequent maintenance: intra-arterial infusion of epirubicin (EPI). Non-responders were entered into the second-line regimen consisting of Methotrexate and 5-FU (MF). The results were as follows: 1) The response rate (CR+PR) of EPI to locoregional lesions was 50%, and the median duration of response was 5.7 months. 2) The response rate and the duration of response of MF were 25% and 3 months, respectively. 3) Patients with ER-rith, no previous therapy and a long disease-free interval tended to have a high rate of response to intra-arterial infusion therapy. 4) Improvements of QOL, such as intractable pain, infection and severe lymphedema were recognized in 68.6% of the cases. In more than half of the cases, these treatments were carried out in an outpatient clinic. 5) Leucopenia and catheter or portal problems were encountered in 68.6% and 25.0%, respectively. We conclude that intra-arterial infusion chemotherapy via implantable system is a promising modality with regard to therapeutic effect and improvement of quality of life.

Adult↗

[Neoadjuvant intra-arterial infusion chemotherapy for the treatment of locally advanced breast cancer with remote metastases].

Intra-arterial infusion chemotherapy (I.A.) before the operation was performed in 7 advanced breast cancers with remote metastases. The locations of remote metastases were bone (6 cases), lung (one case), and brain (one case). The response rate of primary lesions to I.A. was 71% and the responders of remote metastases were two cases, of which one was CR (lung). After the chemotherapy, all cases underwent standard radical mastectomy, and five of seven cases are alive at this writing without local recurrence. We have performed I.A. for locally advanced breast cancer with remote metastases on the grounds that the effect of this treatment is "semi-local and semisystemic," I.A. bring down-staging to the primary lesions and can control local recurrence. The effect of the drug which leaks from I.A. is expected to the metastatic lesions. I.A. was considered to be useful too for the treatment of locally advanced breast cancer with remote metastases in terms of the excellent control effect of the local lesions and the effect on the metastatic lesions.

Aged↗

[A case of advanced gastric cancer successfully treated with resection after FEP (5-FU, epirubicin, CDDP) combined chemotherapy].

We reported an experience with an advanced gastric cancer patient with direct invasion into liver and metastases to liver, who had responded extremely well to an FEP combined chemotherapy. He had curatively undergone total gastrectomy with partial hepatectomy and enlarged lymph node dissection. The patient received three courses of 5-FU (750 mg/m2/day, for four days, continuous infusion), epirubicin (30 mg/m2, on day 1, i.v.), CDDP (17.5 mg/m2/day, on days 1, 2, 3, 4 i.v.) every 3 weeks in our hospital. No remarkable side effect was encountered. Partial response in the primary and invasive lesions was observed by X-P, endoscopy and CTscan. Accordingly, we could perform curative resection of the stomach with lymph nodes and parts of liver. The effect (partial response) of neoadjuvant chemotherapy was confirmed by histological examinations. FEP combined chemotherapy appears useful as a neoadjuvant approach to advanced gastric cancer.

Adenocarcinoma↗

Construction of radiation-reduced hybrids and their use in mapping of microclones from chromosome 10p11.2-q11.2.

Radiation-reduced hybrids for mapping of DNA markers in the pericentromeric region of chromosome 10 were developed. A Chinese hamster/human somatic cell hybrid (762-8A) carrying chromosomes 10 and Y as the only human material were exposed to 40,000 rads of irradiation and then rescued by fusion with non-irradiated recipient Chinese hamster cells (GM459). Southern hybridization analyses revealed that 10 of 128 HAT-resistant clones contained human chromosomal fragments corresponding to at least one marker locus between FNRB (10p-11.2) and RBP3 (10q11.2). These hybrids were then used to map micro-dissection clones previously isolated and roughly mapped to this chromosomal region by fluorescence in situ hybridization (FISH). Two of the six microclones studied could be mapped to the proximity of the D10-S102 locus. These radiation hybrids are useful for the construction of refined genetic maps of the pericentromeric region of chromosome 10.

Animals↗

Deletion mapping of chromosome 1p and 22q in pheochromocytoma.

To identify the localization of tumor suppressor genes, 22 pheochromocytomas (9 hereditary and 13 sporadic) were examined for loss of heterozygosity (LOH) on the short arm of chromosome 1 and on the long arm of chromosome 22 by using 11 polymorphic DNA markers on each chromosome arm. LOH on 1p was observed in 12 of 22 informative cases (55%) and on 22q in 8 of 20 informative cases (40%). There was no significant difference in the frequency of LOH on 1p or 22q between hereditary and sporadic cases. We could localize the commonly deleted regions as distal to D1S73 and proximal to D1S63 on 1p and distal to D22S24 and proximal to D22S1 on 22q. In addition, the relationship between LOH on 1p and 22q was studied in 20 pheochromocytomas which were informative for probes on both chromosome arms. Of eight tumors that showed LOH on 22q, allelic loss on 1p was also detected in seven. Thus, LOH on 22q was correlated significantly with LOH on 1p (P = 0.0249; Fisher's exact test). These results suggest that inactivation of multiple tumor suppressor genes may be required for development and progression of hereditary and non-hereditary pheochromocytoma.

Adrenal Gland Neoplasms↗

[A case of locally advanced breast cancer successfully treated with intra-arterial infusion of high-dose epirubicin].

A 43-year-old female with locally advanced breast cancer was treated with preoperative intra-arterial infusion chemotherapy using an implantable port catheter. The therapeutic regimen was comprised of two cycles at 3-week intervals. One cycle consisted of 50 mg of epirubicin which was administered on day 1, 4 and 7. A remarkable loco-regional response was confirmed only after two repeated cycles of the regimen. The side effects such as hair loss, general fatigue and leukopenia (nadir 1,700) were encountered, but these were moderate and had no influence on the patient's quality of life. These findings suggested that intra-arterial infusion of high-dose epirubicin via an implantable system was an efficient modality for the treatment of breast cancer.

Adult↗

[Intra-arterial infusion chemotherapy for recurrent breast cancer via an implantable system].

Intra-arterial infusion chemotherapy via implantable port catheter has been applied in 14 patients suffering from recurrent breast cancer. The regimen consisted of at least 2 cycles of epirubicin (1 cycle: 150 mg) and subsequent maintenance infusion (30 mg/2 weeks). The results were as follows: 1) The response rate (CR+PR) was 50%: 42.9% CR, 7.1% PR, 14.3% MR, and the median duration of response was 6 months. 2) Intractable pain, severe lymphedema and infection were reduced in 42.9% (6/14). 3) Leucopenia was the dose-limiting factor, and it appeared with an incidence of 78.8%. Catheter or portal trouble was observed in 28.6% of the patients. Despite the existence of several unanswered questions, intra-arterial infusion chemotherapy via implantable system is promising with regard to therapeutic effect and quality of life.

Adult↗

Loss of heterozygosity on the long arm of chromosome 22 in pheochromocytoma.

To identify the putative common deleted region on the long arm of chromosome 22 in pheochromocytoma, restriction fragment length polymorphism analysis was performed in 17 pheochromocytomas. All cases were heterozygous for at least one of the eight marker loci on 22q. Loss of heterozygosity (LOH) was observed in nine pheochromocytomas, of which eight were hereditary and one nonhereditary. Three pheochromocytomas had interstitial deletions that enabled us to localize the commonly deleted region as distal to D22S10 and proximal to D22S22. Hereditary pheochromocytoma frequently occurs in association with medullary thyroid carcinoma (MTC). Therefore, we also studied allelic loss on 22q in 23 hereditary MTCs. Only one of the MTCs showed LOH on 22q. Recent studies have mapped tumor suppressor loci associated with meningioma and neurofibromatosis type 2 (NF2) to 22q. The commonly deleted region in pheochromocytoma found by us encompasses the regions to which tumor suppressor genes associated with NF2 and meningioma have been mapped. The exact role of the pheochromocytoma tumor suppressor gene on 22q and its relationship to the suppressor genes involved in NF2 and meningioma remain unknown.

Adrenal Gland Neoplasms↗

The retinoblastoma protein region required for interaction with the E2F transcription factor includes the T/E1A binding and carboxy-terminal sequences.

Recent experiments in understanding the mechanism of the retinoblastoma protein (RB) function have revealed the existence of several cellular proteins that are complexed with RB. One of these cellular proteins is the E2F transcription factor, which was originally identified due to its inducibility by E1A during an adenovirus infection. The E2F recognition sequence is found in the promoters of several cellular genes involved in growth control, including several oncogenes. In this report, we provide evidence that the interaction of E2F and RB is mediated through a region on RB where viral oncogenes such as SV40 T antigen and adenovirus E1A bind and where tumorigenic mutations also cluster. Additional carboxy-terminal sequences are also required for the interaction with E2F. These observations provide evidence for a direct connection between tumor suppressor function and the gene expression program leading to cellular growth regulation.

Adenovirus E1A Proteins↗

Inactivation of the p53 gene is not required for tumorigenesis of medullary thyroid carcinoma or pheochromocytoma.

A polymerase chain reaction (PCR)-mediated RNase protection analysis was performed to detect subtle genetic alterations of p53 in medullary thyroid carcinoma (MTC) and pheochromocytoma. None of the 30 pheochromocytomas showed abnormal RNase protection patterns. Only one of 32 MTCs showed an abnormal pattern, and subsequent DNA sequencing of the PCR product revealed that it had a G to C transversion in codon 49 that resulted in a change from aspartic acid to histidine. However, this was a sporadic MTC with no specific clinicopathological characteristics. On the basis of a previous report that genes on chromosome 17p were not deleted in MTCs and were relatively infrequently deleted in pheochromocytomas, our results suggest that the p53 gene is not involved in tumorigenesis of MTC or pheochromocytoma.

Adrenal Gland Neoplasms↗

p53 gene mutations associated with anaplastic transformation of human thyroid carcinomas.

Anaplastic carcinoma of the thyroid gland, which is one of the most aggressive, malignant tumors in humans, is considered to originate from preexisting differentiated thyroid cancer. To define the genetic alterations associated with such progression, we examined nine cases of anaplastic thyroid carcinoma for mutation in exons 4-9 of the p53 tumor suppressor gene. Preliminary screening for mutation by RNase protection analysis demonstrated that two out of nine anaplastic carcinomas contained sequence alterations in the p53 gene. Subsequent DNA sequencing identified the mutated nucleotides in these two cases; one was a nonsense mutation at codon 165, and the other was a single-base deletion at codon 176 resulting in the creation of a stop codon downstream due to frameshift. The fact that no mutations were detected in coexisting foci of papillary carcinomas from the same patients shows that these mutations of the p53 gene occurred after development of papillary carcinomas. These results suggest that p53 gene mutation triggers the progression from differentiated into anaplastic carcinoma in the human thyroid gland.

Base Sequence↗

Expression of the ret proto-oncogene in human medullary thyroid carcinomas and pheochromocytomas of MEN 2A.

We studied the expression of the ret proto-oncogene (proto-ret) in human medullary thyroid carcinomas (MTCs) and pheochromocytomas of multiple endocrine neoplasia type 2A (MEN 2A) by Northern blot analysis. Expression of the normal-sized transcripts was detected in all 12 MTCs and in 6 of 8 pheochromocytomas. In situ localization of proto-ret mRNA revealed that the signal was confined to the cytoplasm of MTC cells. By Southern blot analysis neither amplification nor gross genetic changes of proto-ret were found in the tumors. Although no transcripts were detected in the normal portion of the thyroid from one MEN 2A patient, faint signals were detected in normal adrenal glands by Northern blot analysis, probably due to minor populations of C-cells and chromaffin cells in specimens from which MTC and pheochromocytoma might later develop. Proto-ret may play an important role in differentiation of a specific cell lineage from neuroectoderm, and it may be involved in development of MEN 2A tumors.

Adrenal Gland Neoplasms↗

Tight linkage of the ret proto-oncogene with the multiple endocrine neoplasia type 2A locus.

The ret proto-oncogene has been mapped to 10q11.2 near the MEN2A locus by in situ hybridization. We carried out a linkage study of Japanese multiple endocrine neoplasia type 2A (MEN2A) families using a cosmid clone containing the ret proto-oncogene as probe. Two polymorphic alleles (A1 and A2) could be detected by digesting DNA with EcoRI: allele A1 was detected as a 10 kb fragment and A2 as 5.4 and 4.6 kb fragments. Of 11 Japanese MEN2A families analysed, four were informative, and the maximum lod score was 4.23 at a recombination fraction of 0.00. This result suggests the ret proto-oncogene to be close to the MEN2A gene and therefore possibly to be a useful DNA marker for cloning the latter.

Chromosome Mapping↗

[Tumor suppressor gene: implication in the clinical medicine].

Several genetic events are necessary for a cell to become malignant. Some of these events are activation of proto-oncogenes, and other events are loss of normal function of tumor suppressor gene(s). Two or more different tumor suppressor genes may be inactivated in some tumors, and the same suppressor gene may be involved in different types of tumors. Loss of constitutional heterozygosity (LOH) in the tumor suggests that a certain tumor suppressor gene may reside near the locus of the probe by which the LOH was demonstrated. However, LOH is not necessarily found when a tumor suppressor gene is inactivated. The frequency of LOH found by a probe depends upon the distance between the probe and the tumor suppressor gene. Moreover, inactivation of the suppressor gene by point mutation or very small deletion does not cause any change in electrophoretic mobility of the DNA fragment detected by the probe. Treatment of a cancer by tumor suppressor gene(s) is not possible until a technique by which we can introduce the gene into all the tumor cells is established. At present, clinicians should cooperate with basic scientists in the search for tumor suppressor genes. The comparison of clinical features and the genetic alterations in the tumor will shed light on the malignant behavior of the tumor cells such as rapid growth and/or tendency to metastasis.

Adenomatous Polyposis Coli↗

A case control study on risk factors involved in inflammatory breast recurrence after breast-conserving surgery.

Recurrence that poses the biggest problem after breast-conserving surgery is local recurrence. Particularly, in the case of inflammatory breast recurrence which is rare but has a specific pathologic nature, it is important to elucidate the pathology and risk factors and to consider appropriate countermeasures. In the present study, we classified 133 cases of recurrence following breast-conserving surgery, collected from 18 key hospitals/institutes in Japan. Recurrence types were divided into three groups, namely, inflammatory breast recurrence, noninflammatory breast recurrence and distant metastasis only, and the risk factors involved in recurrence were investigated by the case control study allotting 2 controls to each case. The study population consisted of 9 cases of the inflammatory type, 64 cases of the noninflammatory type and 60 cases of distant metastasis. The significant risk factor for inflammatory breast recurrence was positive lymph node metastasis, which was significantly more frequent in lymphatic invasion-positive cases unlike in the distant metastasis group. The positive surgical margin and nonradiation therapy which have been shown to be significant risk factors for noninflammatory breast recurrence were entirely unrelated with inflammatory breast recurrence. In addition, the inflammatory-type recurrence time was as short as about 12 months irrespective of whether radiation therapy was performed or not. The inflammatory type was accompanied with local wide extension (cancerous embolus of the dermal lymphatic vessels), and distant metastasis (lymphangitis carcinomatosa) at the time of recurrence, and further surgery was impossible in most cases, with a significantly poorer prognosis than the other recurrence types. These findings suggest that this recurrence corresponds to the so-called 'occult' case of primary inflammatory breast carcinoma. We think it important to predict this recurrence by close pathological examination, particularly in patients with lymph node metastasis, and to consider appropriate measures.

Adenocarcinoma↗