Biomedical subjects
Publications and source records attributed to H Yokouchi.
A 56-year-old woman was seen with the clinical features of collapse of the right lower lobe. Intrabronchial extension of a tumor was demonstrated endoscopically. Sleeve bilobectomy was performed, and a diagnosis of bronchial neurofibrosarcoma was confirmed by light and electron microscopic and immunohistochemical studies.
Expression of pancreatic secretory trypsin inhibitor (PSTI) gene was examined by Northern blotting analyses in 31 human colorectal tumors that included two benign adenomas and 26 adenocarcinomas. Among the total of 28 cases which proved to be adequate for mRNA analyses, all but one showed the expression of PSTI at various levels. In contrast, PSTI expression was not detected in two malignant lymphomas of the rectum. The level of PSTI expression was not correlated with the patient's age, sex, tumor location or size, stage of differentiation, lymph node metastasis, or progression stage. Some colorectal adenocarcinomas were also shown to express genes that can hybridize with human trypsinogen cDNA probe. It looks as though in these tumors, a protease(s) and its inhibitor are produced simultaneously as part of a cellular self-defense mechanism.
We have previously reported concerning the existence of a third type of human alpha-amylase gene, AMY3 [Emi et al., Gene 62 (1988) 229-235; Tomita et al., Gene 76 (1989) 11-18], which is expressed in a lung carcinoid tissue, and differs in nucleotide sequence from the two previously characterized human alpha-amylase genes coding for salivary and pancreatic isozymes, termed AMY1 and AMY2, respectively. Here, we rename this gene AMY2B to coincide with the designation by Gumucio et al. [Mol. Cell Biol. 8 (1988) 1197-1205] and describe its genetic properties as revealed by sequencing studies. It consists of ten major exons whose sequences are highly homologous to those of AMY1 and AMY2. Not only the exons, but also most of the introns seem to be highly conserved, as judged from physical mapping data. The AMY2B gene identified from mRNA in a lung carcinoid tissue has at least two additional untranslated exons in its 5' region; hence the promoter lies far upstream relative to the other two AMY genes.
The human genome carries several endogenous retroviral sequences. One of them that we named 'HERV-A', carries almost the complete sequence of the long terminal repeat (LTR), and is located in the 5' region of the amylase genes (M.Emi, A.Horii, N.Tomita, T.Nishide, M.Ogawa, T. Mori and K.Matsubara, Gene 62: 229-235, 1988). Using this sequence as a probe, we found a 1.4 kb LTR transcript(s) in a lung cancer cell line. No corresponding transcript was observed in control cells. Two partial, but different cDNA clones were obtained, and each one was found to be a transcript starting within human sequences at 5' upstream from the LTR and ending within the LTR sequence.
Two types of cDNA, which code for the two types of rat pancreatic secretory trypsin inhibitors (PSTIs), were cloned and sequenced. Both predicted amino acid sequences consisting of 79 amino acids, with the secretion signal peptide consisting of 18 and 23 amino acids for PSTI-I and PSTI-II, respectively. The nucleotide sequences were 91% homologous between the two cDNAs, but 68% and 65% homologous, respectively, when compared with human PSTI cDNA. Northern blot analyses showed that PSTI-I is expressed in the pancreas, whereas PSTI-II is expressed in the pancreas and the liver using the same promoter. Southern blot analyses suggested that both PSTI-I and PSTI-II genes are single copy genes per haploid genome. Duplication of rat PSTI gene seems to have occurred recently, after the divergence of humans and rats.
A novel type of alpha-amylase was detected in a lung carcinoid tissue after surveying the cDNA library constructed from this tumor mRNA. Nucleotide sequence analysis showed that the amylase expressed in this carcinoid tumor has 13 and 6 amino acid substitutions when compared with salivary amylase (Amy1) and pancreatic amylase (Amy2), respectively. The nucleotide sequence homologies of cDNAs between this carcinoid amylase and amy1, amy2 are 97.5% and 98.2%, respectively. The nucleotide sequence comparison strongly suggests that this new amylase is the product of the amy3 gene that has been detected in human genome [Emi et al., Gene 62 (1988) 229-235]
The cDNA clone encoding human prechymotrypsinogen was isolated from a human pancreas cDNA library and its nucleotide sequence was determined. The sequence consists of a 16 bp 5' non-coding region, a 789 bp amino acid coding region and a 60 bp 3' non-coding region. The predicted product consists of 263 amino acids, including 18 amino acids for a signal peptide and 15 amino acids possible for an activation peptide. Southern blot analyses using the cloned cDNA as a probe revealed that human genomic DNA carries at least two genes that are related to chymotrypsinogen.
The author experienced two model cases of long-lasting SPCN (smear positive and culture negative) status. The both cases having no prior chemotherapy, which were suggestive of relationship of SPCN to the use of RFP and the presence of huge cavity wherein tuberculous bacilli were most abundant. In these two cases, the laboratory examination showed resistance of the bacillus against INH which was most effective in tuberculous chemotherapy and the bacillus were sensitive against RFP. The SPCN continued for more than half a year. The both cases had huge cavity in the lung. The culture of bacillus was continued for 16 weeks, and no growth of colony was observed. Moreover, in one case, RFP was prescribed 1.2 g/day, much higher than the ordinary dose. The case was a medical doctor, and this dose was prescribed according to his wish. As mentioned above, these two SPCN cases were very suggestive of the model of explaining mechanisms of SPCN with simultaneous presence of huge cavity, resistance against INH and sensitivity to RFP.
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BACKGROUND: The significance of intraoperative pleural lavage cytology (PLC) in lung cancer patients without malignant effusion remains undetermined in terms of staging, prognosis, and local management. METHODS: PLC was performed both after thoractomy and before closure of the thoracic cavity in 325 patients with lung cancer without malignant pleurisy. RESULTS: According to the PLC results (positive [+] or negative [-] after thoracotomy/before closure), the patients were classified as follows: group A (-/-), 262 patients; group B (+/-), 19; group C (-/+), 22; and group D (+/+), 22. In comparison with group A, group C showed more advanced stage with aggressive nodal involvement, and group D showed more advanced lung cancer related to pleural and nodal involvement, whereas group B showed characteristics similar to those of group A. The rate of pleural recurrence in group D was the highest (26%). In particular, pleural recurrence was seen in the patients with a relatively large number of adenocarcinoma cells in PLC after thoractomy. The patients in groups C and D, especially those with adenocarcinoma, showed poorer prognosis, but in a multivariate analysis, PLC status was not an independent prognostic factor. CONCLUSIONS: PLC status after thoractomy provides useful information in the detection of high-risk subgroup for pleural recurrence. Although PLC status is closely associated with survival, its prognostic value is not independent.
Several analyses of the retinoblastoma (RB) gene in lung cancer at the DNA, mRNA and protein levels have recently been reported. In particular, small cell lung carcinoma shows a high incidence of RB gene abnormalities, suggesting that alterations of this gene may participate in tumor development. In the present study, we used an immunohistochemical technique with a monoclonal antibody raised against RB protein (PMG3-245) to detect its expression in representative paraffin sections of tissues obtained from 108 patients with various types of lung cancer treated by surgical resection of the primary tumor. While deletion of RB protein expression was observed in 7 (88%) of small cell lung carcinomas, only 17 (17%) of 100 non-small cell lung carcinomas showed decreased RB protein levels and 6 (6%) showed no RB protein expression. This low incidence of RB protein expression abnormalities in non-small cell lung carcinomas was significant (p < 0.0001). Thus, in contrast to small cell lung carcinoma, abnormalities in RB protein expression may be minor events in non-small cell lung carcinoma. In addition, no significant correlation was found between abnormalities in RB protein expression and clinical factors such as stage, tumor size, and nodal involvement in non-small cell lung carcinoma. However, abnormalities in RB protein expression in squamous cell carcinoma were observed only in the less differentiated types (p = 0.144), and there was a weak but not statistically significant association in non-small cell lung carcinoma between RB protein status and prognosis (p = 0.09). Therefore, in non-small cell lung carcinoma, although abnormalities in RB protein appear not to be closely associated with tumor development, further studies on a larger scale and with a longer-term follow-up are required to determine the clinicopathological significance of RB gene abnormalities, in particular the relationship between abnormalities of RB protein and differentiation or prognosis.
The usefulness of the in vitro chemosensitivity test, the collagen gel droplet embedded culture drug- sensitivity test (CD-DST, Int J Oncol 11: 449, 1997), in cisplatin-based combined chemotherapy for postoperative recurrent tumors in non-small cell lung cancer (NSCLC) patients was retrospectively analyzed. CD-DST data for cisplatin (or carboplatin), etoposide, 5-fluorouracil, mitomycin C, and vindesine were obtained in 311 surgically resected primary lesions. Of them, 25 patients were practically treated with first-line cisplatin- or carboplatin-based chemotherapy for postoperative initial recurrence. Nine (36%) of them responded to the combined chemotherapy for recurrent lesions, including one with complete remission, whereas 16 did not, with no change in 5 and progression in 11. Seven (70%) of 10 patients receiving combined chemotherapy using two or three in vitro sensitive chemoagents showed good responses, whereas there was no responder among the patients receiving chemotherapy including no in vitro sensitive chemoagents. In particular, of 11 patients showing good sensitivity to cisplatin or carboplatin on CD-DST, 8 (73%) responded to chemotherapy, whereas only one (7%) of 14 patients showing cisplatin- or carboplatin-resistance on CD-DST was a responder. Thus, CD-DST results for the chemoagents, especially cisplatin or carboplatin, correlated with chemotherapeutic response, indicating that the CD-DST analysis of surgically resected primary NSCLC tumors is a practically useful indicator of the clinical effect of first-line cisplatin-based combined chemotherapy for postoperative recurrence.
Although adrenal metastases from lung cancer are frequently detected during the late clinical stage or at autopsy, they are rarely surgically treated following pulmonary resection for lung cancer. We detected adrenal lesions as initial clinical recurrence in 9 (1%) of 904 patients who underwent pulmonary resection for lung cancer at our institute between 1980 and 1992. Adrenalectomy was performed in five who had developed unilateral adrenal metastasis. One underwent simultaneous operation for primary and metastatic lesions, and 4 underwent adrenal surgery following pulmonary resection. The adrenal tumor was removed via laparotomy in three patients, and via posterolateral non laparotomic approach in two. Co-metastatic lesions which were detected incidentally at operation included intestinal metastasis in two patients and regional lymph node metastasis in two; these were simultaneously resected. Following adrenalectomy, all these patients were treated with adjuvant chemotherapy or radiotherapy. Two patients have remained free of relapse for 40 and 26 months, respectively, after adrenal surgery, while three died of other distant metastases more than 9 months after adrenalectomy. In contrast, the four patients who received chemotherapy or radiation therapy died less than 6 months after palliative therapy. Thus, we consider that surgical treatment for adrenal metastases following pulmonary resection for lung cancer is effective in selected cases. The indications for adrenalectomy are presented in comparison with those for palliative therapy, and several difficulties in the surgical management of adrenal metastases are discussed.
Bcl-2 oncoprotein, a member of a new category of oncogenes associated with the regulation of programmed cell death (apoptosis), has been considered to be involved in biological processes such as tumorigenesis and tumor development. To determine the role of bcl-2 oncoprotein in lung cancer, we preliminarily examined the expression of this protein in various histological types. Immunohistochemical staining using monoclonal bcl-2 oncoprotein antibody was performed in surgically resected frozen specimens. Bcl-2 staining was seen in nine of 13 small cell lung cancers (69%), while only 18 out of 69 non-small cell lung cancers (26%) expressed bcl-2 oncoprotein, showing a significantly increased incidence of bcl-2 oncoprotein expression in the former histological type. Considering the greater aggressiveness of small cell lung cancer compared to non-small cell lung cancer, the possibility exists that the high prevalence of bcl-2 oncoprotein expression in small cell lung cancer is closely associated with tumorigenesis and tumor development.