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Biomedical subjects

Shigeru Sasaki

Publications and source records attributed to Shigeru Sasaki.

35 records · Page 2Linked to original sources

Clinical presentation and management of molar pregnancy.

We can now detect molar pregnancy at a much earlier gestational age than before by using high resolution vaginal ultrasonography. As a result, the current clinical presentation of complete hydatidiform moles has clearly changed compared to that of the classic type of mole. The diagnosis of molar pregnancy is nearly always made by ultrasonography. Ultrasonography does not, however, always lead to diagnosis in the very early stages of gestation, before the chorionic villi have attained the characteristic vesicular pattern. Therefore, a histopathological examination of the products of conception should be required in all such cases. Hydatidiform moles should be treated by evacuating the uterus surgically as soon as possible after diagnosis. The patients must be followed up until their serial weekly serum human chorionic gonadotrophin (hCG) titre has fallen to an undetectable level.

Biomarkers↗

Patterns of care study in Japan: analysis of patients subjected to mastectomy followed by radiotherapy.

BACKGROUND: Two prospective studies reported in 1997 demonstrated that postoperative radiotherapy after mastectomy was not only associated with a higher loco-regional control rate but also with a higher overall survival rate. The purpose of this study is to clarify the processes of care for patients undergoing mastectomy and postoperative radiotherapy in Japan. METHODS: A national survey carried out in 1998-2000, involving 79 Japanese institutions by two-stage cluster sampling of institutions and patients, disclosed that 1124 patients with breast cancer had been treated between 1995 and 1997. Mastectomy followed by radiotherapy was performed on 258 patients. RESULTS: The compliance rates for pre-treatment evaluation, including history, physical examination and mammography, averaged approximately 50% (24-81%). The chest wall was irradiated in only 19% of the patients and regional node irradiation was carried out for 70-86%. Radiation treatment planning with the aid of computed tomography was done in only 29% of patients (university hospitals or cancer centers, 39%; other hospitals, 17%; P = 0.001). Hormonal therapy was administered to 56% of the patients who showed no endocrine responsiveness. Non-intensive chemotherapy, which did not include the use of anthracycline or taxol, was used in 55% of the patients who received chemotherapy. CONCLUSIONS: There is room for improvement regarding some aspects of radiotherapy and adjuvant systemic therapies. Especially in the field of radiotherapy, significant differences were found among the treatment techniques employed in various institutions.

Adult↗

Risk factors for local-regional recurrence following preoperative radiation therapy and surgery for head and neck cancer (stage II-IVB).

PURPOSE: To discover possible risk factors for local-regional recurrence (LRR) following preoperative radiation therapy and curative surgery for head and neck squamous cell carcinoma (SCC) (stage II-IVB). MATERIALS AND METHODS: Clinical records from 1987 to 1999 of 161 patients with head and neck SCC (oral cavity, 80 patients; larynx, 50; hypopharynx, 19; oropharynx, 12) who underwent preoperative radiation therapy and surgery were retrospectively reviewed. One hundred thirty-two (82%) of the patients had stage III or IV cancer. The median radiation dose was 38 Gy. RESULTS: The 5-year overall survival rate and LRR rate were 58% and 35%, respectively. At multivariate analysis, oral cavity cancer (P =.020), clinical T stage (P =.016), clinical N stage (P =.017), and status of surgical margins (P =.008) emerged as variables that were significantly associated with LRR. The analysis of only those patients with lymph node involvement showed that oral cavity cancer (P =.008), advanced N-stage cancer (P =.045), and long interval between the start of preoperative radiation therapy and surgery (> or =7 weeks) (P =.019) emerged as variables that were significantly associated with LRR. CONCLUSION: Oral cavity cancer, advanced T or N stage of disease, and unsatisfactory margins were risk factors for LRR. A long interval (> or =7 weeks) was a risk factor for LRR in patients with lymph node involvement.

Aged↗

[Impact of treatment extending to 60 Gy on the outcome of radiotherapy for nasopharyngeal carcinoma].

PURPOSE: To clarify the impact of treatment duration on the outcome of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Forty-three patients with NPC were treated with definitive radiotherapy from January 1980 through May 1996. The male-to-female ratio was 32:11, and median age was 58 years (10-78 years). According to the fifth UICC classification, 4 patients were stage I, 12 were stage II, 6 were stage III, and 21 were stage IV. Twenty-nine patients received chemotherapy. Each patient was treated to various doses according to their disease extension. Thus, treatment duration was defined as the duration from the start of radiotherapy to the end of 60 Gy. The median follow-up period was 63 months (2-164 months). RESULTS: The 5-year overall and disease-free survival rates of all patients were 66% and 59%, respectively. The 5-year disease-free survival rates of the patients treated with the short treatment duration (< or = 8 weeks) and those treated with the long treatment duration (> 8 weeks) were 76% and 38%, respectively (p = 0.008). CONCLUSION: Long treatment duration may lead to poor treatment outcome in NPC.

Adolescent↗

Synthesis, structure, and redox properties of the extremely crowded triarylpnictogens: tris(2,4,6-triisopropylphenyl)phosphine, arsine, stibine, and bismuthine.

A series of the extremely crowded triarylpnitogens, tris(2,4,6-triisopropylphenyl)phosphine (1), arsine (2), stibine (3), and bismuthine (4), were synthesized by the reaction of 2,4,6-triisopropylphenylcopper(I) with the corresponding pnictogen trichlorides. Introduction [corrected] of the three bulky aryl groups resulted in the unusual structures and redox properties, which were studied by X-ray crystallography and cyclic voltammetry. The triarylpnictogens 1, 2, and 3 had extremely large bond angles around pnictogen atoms (1: 111.5 degrees , 2: 109.2 degrees , 3: 106.7 degrees ), and not only 1 and 2, but also stibine 3 displayed a reversible redox wave in the cyclic voltammograms at very low potentials (1: 0.16 V, 2: 0.50 V, 3: 0.57 V vs Ag/Ag+), which suggests considerable stability of the corresponding cation radicals.

Journal Article↗

Prevalent involvement of illegitimate V(D)J recombination in chromosome 9p21 deletions in lymphoid leukemia.

To understand molecular pathways underlying 9p21 deletions, which lead to inactivation of the p16/CDKN2A, p14/ARF, and/or p15/CDKN2B genes, in lymphoid leukemia, 30 breakpoints were cloned from 15 lymphoid leukemia cell lines. Seventeen (57%) breakpoints were mapped at five breakpoint cluster sites, BCS-LL1 to LL5, each of <15 bp. Two breakpoint cluster sites were located within the ARF and CDKN2B loci, respectively, whereas the remaining three were located >100 kb distal to the CDKN2A, ARF, and CDKN2B loci. The sequences of breakpoint junctions indicated that deletions in the 11 (73%) cell lines were mediated by illegitimate V(D)J recombination targeted at the five BCS-LL and six other sites, which contain sequences similar to recombination signal sequences for V(D)J recombination. An extrachromosomal V(D)J recombination assay indicated that BCS-LL3, at which the largest number of breakpoints (i.e. five breakpoints) was clustered, has a V(D)J recombination potential 150-fold less than the consensus recombination signal sequence. Three other BCS-LLs tested also showed V(D)J recombination potential, although it was lower than that of BCS-LL3. These results indicated that illegitimate V(D)J recombination, which was targeted at several ectopic recombination signal sequences widely distributed in 9p21, caused a large fraction of 9p21 deletions in lymphoid leukemia.

Base Sequence↗

MYO18B, a candidate tumor suppressor gene at chromosome 22q12.1, deleted, mutated, and methylated in human lung cancer.

Loss of heterozygosity on chromosome 22q has been detected in approximately 60% of advanced nonsmall cell lung carcinoma (NSCLC) as well as small cell lung carcinoma (SCLC), suggesting the presence of a tumor suppressor gene on 22q that is involved in lung cancer progression. Here, we isolated a myosin family gene, MYO18B, located at chromosome 22q12.1 and found that it is frequently deleted, mutated, and hypermethylated in lung cancers. Somatic MYO18B mutations were detected in 19% (14/75) of lung cancer cell lines and 13% (6/46) of primary lung cancers of both SCLC and NSCLC types. MYO18B expression was reduced in 88% (30/34) of NSCLC and 47% (8/17) of SCLC cell lines. Its expression was restored by treatment with 5-aza-2'-deoxycytidine in 11 of 14 cell lines with reduced MYO18B expression, and the promoter CpG island of the MYO18B gene was methylated in 17% (8/47) of lung cancer cell lines and 35% (14/40) of primary lung cancers. Furthermore, restoration of MYO18B expression in lung carcinoma cells suppressed anchorage-independent growth. These results indicate that the MYO18B gene is a strong candidate for a novel tumor suppressor gene whose inactivation is involved in lung cancer progression.

Cell Division↗

Mucin phenotype and microsatellite instability in early multiple gastric cancers.

Clinicopathologically, multiple gastric cancers (MGCs) are reported to involve predominantly intestinal-type adenocarcinoma and frequently to be associated with severe intestinal metaplasia. However, there are few reports concerning the characteristic biomarkers of early MGCs. The aim of our study was to identify the cellular lineage defined by mucin phenotypes and the relationships among mucin phenotypes, background mucosa and microsatellite instability (MSI) of early MGCs. We examined mucin phenotypes of 63 surgically resected carcinomas from 25 patients with early MGCs and 39 early solitary gastric cancers (SGCs) by immunohistochemical analysis using a panel of monoclonal antibodies. MSI and the degree of intestinal metaplasia (IM) on the background mucosa were also examined. In early MGCs, the incidence of cancer exhibiting the gastric phenotype (G-type) was 59% (37 of 63 cancers), which was higher than that in early SGCs (23%, 9 of 39 cancers). There was a significant difference between the distributions of mucin phenotypes in early MGCs and early SGCs (p = 0.001). Whereas half of the G-type cancers in early MGCs were related to severe IM, none of the G-type cancers in early SGCs were related to severe IM. In the early MGCs, MSI was observed in 21 of 63 cancers (33.3%). In contrast, MSI was observed in only 3 of the 39 (7.7%) early SGCs, indicating a significant difference between these 2 groups (p < 0.01). Our results suggest that the characteristic features of early MGCs are the gastric mucin dominant phenotype and high frequency of MSI.

Aged↗

Preparation and characterization of anti-anti-idiotypic monoclonal antibody ("Ab1-like Ab3") in relation to carcinoembryonic antigen.

In order to analyze the epitope structure of carcinoembryonic antigen (CEA) and the idiotype network system, seven anti-idiotypic monoclonal antibodies (anti-Id MoAbs) were generated from a BALB/c mouse immunized with anti-CEA MoAb P1-356, which recognized a synthetic peptide P1 of CEA, domain I. These MoAbs were divided into four groups. The anti-Id MoAbs specifically reacted with MoAb P1-356, but not with any MoAb, and inhibited the binding of MoAb P1-356 to CEA, indicating that all of these anti-Id MoAbs recognized private idiotopes at the combining sites of MoAb P1-356. Polyclonal anti-anti-idiotypic antiserum (Ab3) generated with anti-Id MoAbs M315 (Ab2), blocked the binding of MoAb P1-356 (Ab1) to CEA and reacted with CEA(Ag) and synthetic peptide P1. The analysis of serological assays suggested that it contains "Ab1-like Ab3." Therefore, we prepared anti-anti-Id MoAbs using anti-Id MoAb M315. Among 13 candidates, anti-anti-Id MoAb 11B2 was selected, because it competed with MoAb P1-356 (Ab1) binding to CEA. A direct binding assay using MoAb11B2 showed that it reacted with purified CEA and with CEA synthetic peptide P1. In addition, MoAb 11B2 (Ab3) reacted with both CEA-producing cultured cells and colonic cancerous tissues in immunostaining. These results indicate that anti-anti-Id MoAb 11B2 is "Ab1-like Ab3." Therefore, it is suggested that anti-Id MoAb M315 bears an "internal image" of the MoAb P1-356-defined epitope on CEA.

Animals↗

Analysis of gene expression in human colorectal cancer tissues by cDNA array.

BACKGROUND: The development and progression of cancer are accompanied by complex changes in patterns of gene expression. The purpose of this study was to clarify the relevance of macroarray analysis of human colorectal cancer tissues. METHODS: Hybridization of cDNA macroarray filters on which 550 genes had been spotted was performed with biotin-labeled cDNA targets that were prepared from mRNA extracted from 20 pairs of colorectal cancer and corresponding noncancerous tissues. Expression of differentially expressed genes was further studied by semiquantitative RT-PCR. RESULTS: Fourteen (2.5%) of the 550 genes were differentially expressed and up- or downregulated in cancer tissues by at least threefold compared with matched noncancerous tissues in 10 or more of the 20 patients. The genes that were upregulated in cancer tissues were associated with transcription, cell cycle, growth factor receptor, cell adhesion, extracellular matrix-degrading enzymes, and angiogenesis, and the downregulated genes were those involved in apoptosis and immune recognition. Semiquantitative RT-PCR analysis of these differentially expressed genes gave results consistent with those by cDNA array analysis. CONCLUSIONS: Although the macroarray used in this study contained only a small number of genes, our results support the feasibility and usefulness of this approach to study variation in gene expression patterns in human colorectal cancer tissues. The results also suggest the possibility of a diagnostic application of cDNA macroarrays in daily clinical settings.

Biopsy, Needle↗

[Monoclonal antibody induces apoptosis against cancer cells].

ErbB-2, a member of the epidermal growth factor(EGF) receptor tyrosine kinase family, is often overexpressed and/or amplified in breast, ovarian and gastric cancers, and other malignancies. ErbB-2 is a candidate as one of the best target molecules for cancer therapy. Many anti-ErbB-2 monoclonal antibodies(MoAbs) have been developed. An inhibitory humanized MoAb shows clinical responses in some breast cancer patients, both with MoAb alone and in combination with Cisplatinum or other anti-cancer drugs. A mouse-human chimeric anti-ErbB-2 MoAb CH401 was established and characterized in our laboratory. CH401 is able to kill cancer cells overexpressing ErbB-2 both in vitro and in vivo. The analysis of this tumor growth inhibition by CH401 made it clear that the cytotoxicity was induced by apoptosis. These results may suggest that CH401 has a therapeutic potential for ErbB-2 overexpressing cancers. This approach may be particularly valuable as a new type of cancer therapy.

Animals↗

Differential roles of alterations of p53, p16, and SMAD4 expression in the progression of intraductal papillary-mucinous tumors of the pancreas.

Intraductal papillary-mucinous tumors (IPMTs) of the pancreas are characterized by dilated pancreatic ducts and ductules that are lined by tall columnar mucin-producing neoplastic epithelial cells. IPMTs have been suggested to be distinct neoplasms with a less aggressive phenotype than that of conventional ductal adenocarcinomas of the pancreas. Molecular mechanisms underlying tumorigenesis of IPMTs are beginning to be characterized. Allelic losses have frequently been detected at 9p, 17p, and 18q, suggesting that inactivation of tumor suppressor genes at these loci play a role in tumorigenesis of IPMTs. Using immunohistochemistry, we analyzed 38 IPMTs, including 9 hyperplasia, 16 adenoma, and 13 carcinoma tissues, for expression of p53, Ki-67, p16, and SMAD4. Nuclear p53 expression was observed in 5 (38%) of 13 carcinoma tissues but not in hyperplasia or adenoma tissues. Partial loss of p16 expression was observed in 9 (56%) and 12 (92%) of the 16 adenoma and 13 carcinoma tissues, respectively. Partial loss of p16 expression was observed even in adenomas with mild atypia. Partial loss of SMAD4 expression was observed in 6 (38%) and 12 (92%) of the 16 adenoma and 13 carcinoma tissues, respectively. The SMAD4 negative index was significantly higher in invasive carcinomas than in non-invasive carcinomas. Our results suggest that loss of p16 is an early event and p53 alteration is a late event during the progression of IPMTs. SMAD4 inactivation appears to be an early event but also involved in invasive tumor growth. Our results suggest that these alterations accumulate during the progression of IPMTs, reflecting results of analysis of allelic losses that showed a stepwise accumulation of genetic changes during progression.

Adenocarcinoma, Mucinous↗

Utility of serosal stamp cytology as an indicator for high-risk peritoneal metastasis in colorectal cancer surgery.

BACKGROUND/AIMS: Although peritoneal lavage cytology is widely performed during surgery for gastric cancer and the results have been reported to provide an accurate prognostic factor, its value has not been well established in colorectal cancer. In this study, we demonstrated the utility of serosal stamp cytology from the viewpoint of cell adhesion molecules. METHODOLOGY: Between 1997 and 1999, peritoneal lavage cytology and serosal stamp cytology were performed in 34 patients with resectable colorectal cancer. Epithelial cadherin (E-cadherin) was examined as an index of the progress degree of peritoneal metastasis. RESULTS: Although peritoneal lavage cytology was positive in one case, serosal stamp cytology was positive in 10 cases. E-cadherin expression was lost in all peritoneal lavage cytology and/or serosal stamp cytology positive patients. CONCLUSIONS: Our data indicate that serosal stamp cytology is more sensitive and simple than peritoneal lavage cytology. Serosal stamp cytology may be useful in identifying patients at high risk for peritoneal recurrence.

Adult↗

Results of radiation therapy for superficial esophageal cancer using the standard radiotherapy method recommended by the Japanese Society of Therapeutic Radiology and Oncology (JASTRO) Study Group.

BACKGROUND: Superficial esophageal cancer (SEC) is defined as esophageal cancer limited to the submucosal layers, including mucosal cancer and submucosal cancer, and is squamous cell carcinoma in most patients. In 2000, the Japanese Society of Therapeutic Radiology and Oncology (JASTRO) Study Group for SEC published a consensus guideline of standard radiotherapy methods. In this study, the interim treatment outcomes of SEC patients, who had received radiation therapy following the standard radiotherapy methods, were investigated. PATIENTS AND METHODS: From 2000 to 2003, a total of 141 SEC patients were treated in 24 institutions in Japan. RESULTS: The 1-, 2- and 3-year survival rates were 95%, 90% and 90%, respectively, for patients with mucosal cancer and 90%, 81% and 70%, respectively, for patients with submucosal cancer. The overall survival was better in patients who had undergone chemotherapy than in patients who had received radiation therapy alone, though the difference was not statistically significant. The clinical target volume (CTV) did not influence overall survival and intracavitary irradiation did not influence the local control rate in either patients with mucosal or submucosal cancer. Radiation-induced esophageal ulcer was not observed in this series. CONCLUSION: The standard radiotherapy methods are safe and effective for treating SEC. However, the usefulness of chemotherapy and intracavitary irradiation and the optimal setting of the CTV should be clarified by future randomized trials.

Aged↗