[A case of a giant rectal gastrointestinal stromal tumor radically resectable after treatment with neoadjuvant imatinib mesylate].

A 64-year-old male patient was diagnosed with rectal gastrointestinal stromal tumor(GIST)by prostate biopsy, because of high PSA. We considered that a radical operation was impossible because the tumor occupied the pelvis, and we suspected prostate invasion. After neoadjuvant chemotherapy(imatinib mesylate 400 mg/day), the tumor size was reduced(90×85 mm→60×50mm), and we could thus perform radical resection. The patient is currently receiving adjuvant chemotherapy (imatinib mesylate 400 mg/day), without recurrence.

[A case of carcinoma associated with anal fistula resected after preoperative chemoradiotherapy].

A 66-year-old man with a 39-year history of anal fistula was admitted to our hospital for anal pain and bleeding. Fistulectomy was carried out for anal fistula. Histological examination of the specimen revealed carcinoma associated with anal fistula. A computed tomography showed that the tumor had invaded the prostate. Therefore, preoperative chemoradiotherapy(S-1 plus radiation 40 Gy/body)for locally advanced cancer was performed. Magnetic resonance imaging showed that the boundary between the tumor and the prostate was unclear, but we performed an abdominoperineal resection and the prostate was fully preserved. Histopathologically, no cancer cell existed on the surgical margin. The histological effect of chemoradiotherapy was judged as grade 2. This case suggested that surgical treatment combined with preoperative chemoradiotherapy may be effective for locally advanced carcinoma associated with anal fistula, in which preservation of adjacent organs is considered to be difficult.

[Long-term results of chemoradiation therapy for the patients with locally advanced (T4) esophageal cancer].

The prognosis of patients with advanced esophageal cancer is still poor. Recently, concurrent chemoradiation therapy for esophageal cancer is being utilized with increasing frequency. In this study, we reported concurrent chemoradiation for patients with T4 esophageal cancer. From July 2000, we treated 21 consecutive patients with radiation and concurrent chemotherapy using intermittent low-dose FP chemoradiation (40 Gy radiation, 2 Gy/day, for 4 weeks 280/m(2) 5-FU intermittent 24 continuous, CDDP 8 mg/m(2)/intermittent). All patients who underwent the treatment with concurrent CRT completed the planned chemoradiation. Out of 21 patients, 2 (9.5%) showed a complete response and 9 patients (42.8%) showed a partial response. The 5-year survival rate of the T4 patients with CRT was almost the same as for those who underwent surgery alone. Concurrent chemoradiation therapy for T4 esophageal cancer patients is feasible and seems to be a standard treatment for T4 esophageal cancer patients. The results indicated that CRT is an effective therapy for advanced esophageal cancer.

Adenoendocrine cell carcinoma of the gallbladder: report of a case.

Adenoendocrine cell carcinoma of the gallbladder is an uncommon form of cancer. We treated a 36-year-old woman who came to us with a chief complaint of abdominal pain. The abnormality was diagnosed to be a tumor-like mass in the gallbladder, and adenomyomatosis of the gallbladder was strongly suspected. A laparoscopic cholecystectomy was successfully performed, and the histopathological finding was adenoendocrine cell carcinoma of the gallbladder. The tumor cells of the small round cell carcinoma partly stained positively for synaptophysin, neuron-specific enolase, and CD 56, while adenocarcinoma cells showed positive reactions to keratin, which was thus suggestive of adenoendocrine cell carcinoma. The patient is alive and doing well at 12 months after the treatment.

[A case of liver metastases from cecal cancer successfully treated with fluorouracil and folinic acid (UFT/LV)].

A 76-year-old man had undergone a right hemicolectomy for cecal cancer. Oral UFT (450 mg/day) administration alone was started 2 months following the operation. From a CT scan of the abdomen performed 3 months postoperatively, he was diagnosed with liver metastasis. Because the liver metastasis had progressed, combination oral administration of UFT+LV was started (UFT 450 mg/day, LV 75 mg/day, 4 weeks of therapy followed by a 1-week treatment break). After 1 cycle, a good partial response of that lesion was achieved. The pulmonary metastasis had almost disappeared to within normal limits. In conclusion, this treatment was very safe and effective.

Primary squamous cell carcinoma of the breast: a case report.

Primary squamous cell carcinoma of the breast is a rare entity. We treated a 55-year old woman who came to us with bleeding from the left breast tumor. The tumor was 7 x 8 x 10 cm in size with ulceration and surgical biopsy results showed it to be squamous cell carcinoma of the breast, while metastatic work-up findings ruled out other sources of primary tumor. She also complained of nausea and vomiting, and brain CT disclosed cerebellar metastasis. The metastatic brain tumor was surgically removed, however, the symptoms became gradually exacerbated. The patient died 67 days after admission.

Alterations of the K-ras and p53 genes and microsatellite instability in sporadic colorectal carcinomas.

BACKGROUND: The international guidelines for the evaluation of microsatellite instability (MSI) in colorectal cancer were defined in 1997 by the National Cancer Institute (NCI). Here, the relationship between MSI, cancer-associated genes and their clinicopathological variables were revaluated using these guidelines. PATIENTS AND METHODS: Mutations of K-ras at exon 1 and p53 at exons 5, 6, 7 and 8 were analyzed in 43 cases of sporadic colorectal carcinoma. MSI was analyzed using the 5 markers recommended by the NCI reference panel. RESULTS: The proportion of p53 mutations in the MSI-H cases (0 out of 5; 0%) was lower than that of non-MSI-H cases (23 out of 38; 60.5%) (p=0.0117). The proportion of p53 mutations in microsatellite stable (MSS) cases (21 out of 34; 61.8%) was higher than that of non-MSS cases (2 out of 9; 22.2%) (p=0.0366). The proportion of K-ras mutations in MSI-H tumors (1 out of 5; 20.0%) was less frequent than in non-MSI-H tumors (19 out of 38; 50.0%) (p=0.2115). CONCLUSION: p53 mutations in MSI-H tumors were much less common than in non-MSI-H tumors. This result suggested that alterations of the p53 gene are not closely associated with carcinogenesis in MSI-H carcinomas.

Structure and photophysical properties of porphyrin-modified metal nanoclusters with different chain lengths.

Three-dimensional porphyrin-monolayer-protected gold clusters with different chain lengths (MPCs) have been prepared to examine the structure and photophysical properties, in comparison with self-assembled monolayers (SAMs) of the porphyrins on a flat gold surface. The three-dimensional porphyrin MPCs exhibit electrochemical and photophysical properties that are much closer to those of a porphyrin reference compound in solution than those of two-dimensional porphyrin SAMs on the flat gold surface. The three-dimensional architectures of porphyrin MPCs with large surface area have improved the light-harvesting efficiency relative to the corresponding porphyrin SAM on the two-dimensional flat gold surface. Time-resolved single photon counting fluorescence and transient absorption spectroscopic studies have demonstrated that undesirable quenching of the porphyrin excited singlet state via energy transfer to the gold surface of the three-dimensional MPCs is much suppressed, as compared to the quenching of the porphyrin SAMs on the two-dimensional flat gold surface. Both the quenching rate constants of the porphyrin excited singlet state by the surfaces of bulk gold and gold nanoclusters reveal weak chain length dependence of the energy transfer quenching.

BRAF mutations in papillary carcinomas of the thyroid.

BRAF is a serine/threonine kinase that receives a mitogenic signal from RAS and transmits it to the MAP kinase pathway. Recent studies have reported that mutations of the BRAF gene were detected with varying frequencies in several cancers, notably more than 60% in melanoma. We analysed mutations of BRAF and RAS genes in 100 cases of thyroid carcinoma to investigate genetic aberrations in the RAS/RAF/MEK/MAP kinase pathway. BRAF mutations were detected exclusively in papillary carcinomas (40 in 76 cases: 53%), and were exclusively V599E, a mutation frequently observed in other carcinomas. NRAS mutation was observed in six cases (6%), all in histological types other than papillary carcinoma, and was exclusively Q61R. No mutations were found in KRAS or HRAS. Our results suggest that BRAF mutations may play a critical role in the carcinogenesis of papillary carcinoma of the thyroid.

A naturally occurring p73 mutation in a p73-p53 double-mutant lung cancer cell line encodes p73 alpha protein with a dominant-negative function.

p73, a close homolog of p53 tumor suppressor, induces growth arrest and apoptosis. However, its role in cancers is controversial because of the rarity of p73 mutations, lack of tumors in p73-knockout mice, and the presence of multiple isotypes, among which Delta N isotypes inhibit the function of TA isotypes. We analyzed three naturally occurring p73 mutants found in lung cancer cell lines, NCI-H1155, DMS 92 and A427. NCI-H1155 is a cell line that has a p73 mutation [p73(G264W)] in the DNA-binding domain, as well as a p53 mutation [p53(R273H)], which is frequently found in human cancers and has a "gain-of-function" characteristic. p73 alpha(G264W) not only lacks transactivation activity itself, but also suppressed the transactivation activity of the wild-type p73 alpha in a dose-dependent manner, indicating that p73 alpha(G264W) is a dominant-negative mutant. p73 alpha(G264W) failed to suppress colony formation. We tested two other mutations, p73(Del418) in DMS 92 and p73(Del603) in A427. Both mutants retained similar levels of transactivation activity and suppression of colony formation to those of wild-type p73. The biological significance of these two mutations is unclear. In NCI-H1155 cells the coexistence of mutations that abrogate the normal functions of p73 and p53 may indicate that each mutation confers an additive growth advantage upon the cells.

Mouse SWAM1 and SWAM2 are antibacterial proteins composed of a single whey acidic protein motif.

Antibacterial proteins are important participants in the innate immunity system. Elafin and SLPI are the whey acidic protein (WAP) motif proteins with both antibacterial activity and antiprotease activity, and their role in innate immunity is under intense investigation. We cloned two novel antibacterial WAP motif proteins from mice, SWAM1 and SWAM2. SWAM1 and SWAM2 are composed of a signal sequence and a single WAP motif that has high homologies with the WAP motifs of elafin and SLPI. SWAM1 is constitutively expressed in kidney and epididymis, and is induced in the pneumonic lung. SWAM2 is constitutively expressed in tongue. SWAM1 and SWAM2 inhibit the growth of both Escherichia coli and Staphylococcus aureus at a IC(90) (concentration that achieves 90% inhibition) of 10 microM. Human genes LOC149709 and huWAP2 are considered to be human SWAM1 and SWAM2, respectively. These and several WAP motif proteins (WAP1, elafin, SLPI, HE4, eppin, C20orf170, LOC164237, and WFDC3) form a gene cluster on human chromosome 20, suggesting that they may be derived from the same ancestral gene by gene duplication. Our results underscore the role of the WAP motif as a skeletal motif to form antibacterial proteins, and warrant the study of antibacterial activity in other WAP motif proteins.

ELECTRON MICROSCOPIC OBSERVATIONS ON THE EXTRA-GRANULAR ZONE OF THE EMBRYO OF THE SEA URCHIN, HEMICENTROTUS PULCHERRIMUS.

"Extra-granular zone" proposed by Dan and Dan (3) was studied with the electron microscope. Two stages are noticed during the process of its formation; at first, a relatively yolk granule-free zone constitutes the egg periphery which should correspond to that observed by Dan and Dan, and later, this zone is occupied by a layer of the vacuoles (about 1.3 µm in mean diameter) with highly electron-transparent inclusions which migrated to the egg surface from the inner cytoplasm after fertilization. These vacuoles are scarcely found in the micromeres of 16-cell stage embryo.