[A case showing a complete response by weekly paclitaxel associated with severe empyema and mediastinal abscess caused by reduction of a recurrent lung metastatic tumor originating from adenocarcinoma of the esophagogastric junction after primary operation].

The patient was a 57-year-old man who presented with cancer of the esophagogastric junction. He underwent total gastrectomy, lower esophagectomy, distal pancreatectomy and splenectomy with para-aortic lymphnode dissection by the transthoracoabdominal approach. He was given a daily dose of 100 mg of S-1 as adjuvant chemotherapy. About one year after the operation, lung metastasis was recognized by enhanced CT examination. He began weekly paclitaxel as second-line chemotherapy. Paclitaxel was infused once a week. About two weeks after the first infusion therapy, he was admitted to our hospital with fever and dyspnea. A chest enhanced CT revealed remarkable empyema and mediastinal abscess. Chest drainage and mediastinal drainage were performed.After one month of drainage, the empyema and mediastinal abscess had improved. The metastastic tumor of the lung disappeared at the time of discharge. CR has been maintained for more than a year without chemotherapy.This case suggests that remarkable reduction of the tumor induced by chemotherapy may have caused the empyema and mediastinal abscess.

[A Case of gastric endocrine cell carcinoma successfully treated by FU plus irinotecan(CPT-11)adjuvant therapy against recurrent metastases].

A case of gastric endocrine cell carcinoma successfully treated by FU (5-FU/UFT) +irinotecan (CPT-11) adjuvant therapy against recurrent metastases is reported with some discussion. A 69-year-old man was admitted to our hospital with severe anemia. He was diagnosed with advanced gastric cancer, T3N1H0P0M0, Stage IIIa. Total gastrectomy with pancreato-splenectomy with D2 lymph node dissection was done for curative resection. The pathological diagnosis was gastric endocrine cell carcinoma because Grimelius and Chromogranin A stained positive histologically. Seven months after operation, recurrent liver metastases with tumor embolism of the portal vein were revealed by enhanced CT examination. FU (5-FU/UFT) +CPT-11 was done as the first-line adjuvant chemotherapy. Metastatic lesion of the liver and portal vein tumor embolism was decreased. Tumor marker CA19-9 level was also decreased and within normal limits. This therapy was evaluated as a partial response (PR) in twelve months and the patient died three years and eight months after operation. Gastric endocrine cell carcinoma is known as a potentially highly malignant tumor. But in our case FU+CPT-11 controlled growth of the recurrent tumor. Based on this finding, we recommend adjuvant chemotherapy by FU+CPT-11 for gastric endocrine cell carcinoma.

Computed tomography imaging of the neuronal structure of Drosophila brain.

The neural circuit of the central nervous system (CNS) primarily determines brain functions and, as a consequence, controls animal behavior. This paper describes an X-ray microtomographic analysis of the Drosophila larvae CNS, visualizing the neural network embedded in the three-dimensional structure of the nerve tissue. In fluorescence confocal microscopy, absorbance at emission or excitation wavelengths interferes with the fluorescence detection. In contrast, transparency of the nerve tissue to hard X-rays enables tomographic analysis of the intact CNS without sectioning. Yet the nerve tissue is composed of light elements that give little contrast in a hard X-ray transmission image. The contrast was enhanced by staining neuropils in the CNS with metal elements. The obtained structure revealed the internal architecture of the CNS. This metal-staining microtomographic analysis can be applied to any nerve tissues, thereby shedding light on the underlying structural basis of neural functions.

[A resected case of squamous cell carcinoma of the breast successfully treated by FU plus cisplatin (CDDP) adjuvant therapy against recurrent metastases].

A resected case of squamous cell carcinoma associated with ductal carcinoma in the hemilateral breast successfully treated by FU plus cisplatin (CDDP) adjuvant therapy against recurrent metastases is reported with some discussion. A 42-year-old woman was admitted to our hospital because of right breast tumor. By physical examination, mammography, ultrasound examination and aspirated cytology, we diagnosed squamous cell carcinoma of the right breast. Before operation SCC antigen was elevated. Standard mastectomy was performed, and SCC antigen was decreased within normal range. Then, a standard regimen of chemotherapy using docetaxel with anti-hormonal therapy by LH-RH analog and tamoxifen was done as first-line adjuvant therapy. Four months after operation the SCC antigen level was elevated again, and recurrence of cancer (skin and liver metastases) was recognized. Next, we tried 5-FU/UFT plus CDDP for squamous cell carcinoma of other organs such as the esophagus. These anti-tumor drugs proved effective, and no metastasis of the skin was detected thereafter, and liver metastatic lesion was decreased in ten months. The SCC antigen level was within the normal range again. Additionally, when metastases redeveloped, TS-1 plus CDDP controlled growth of tumors in seven months. Based on the present findings,we recommend adjuvant chemotherapy by FU plus CDDP for squamous cell carcinoma of the breast.

In vivo cross-linking of nucleosomal histones catalyzed by nuclear transglutaminase in starfish sperm and its induction by egg jelly triggering the acrosome reaction.

A histone heterodimer, designated as p28, which contains an Nepsilon(gamma-glutamyl)lysine cross-link between Gln9 of histone H2B and Lys5 or Lys12 of histone H4, is present in starfish (Asterina pectinifera) sperm. Treatment of sperm nuclei with micrococcal nuclease produced soluble chromatin, which was size-fractionated by sucrose-gradient centrifugation to give p28-containing oligonucleosome and p28-free mononucleosome fractions, indicating that the cross-link is internucleosomal. When sperm nuclei were incubated with monodansylcadaverine, a fluorescent amine, in the presence or absence of Ca(2+), histone H2B was modified only in the presence of Ca(2+). Gln9, in the N-terminal region, was modified, but the other Gln residues located in the internal region were not, suggesting that the modification takes place on the surface of the nucleosome core by the in situ action of a Ca(2+)-dependent nuclear transglutaminase. Treatment of sperm with the egg jelly, which activates Ca(2+) influx to induce the acrosome reaction, resulted in a significant elevation of the p28 content in the nucleus. This is the first demonstration of an in vivo activation of transglutaminase leading to the formation of a cross-link in intracellular proteins.

Aurora-B associated protein phosphatases as negative regulators of kinase activation.

The human serine/threonine kinase Aurora-B is structurally related to the protein kinase Ipl1p from S cerevisiae and aurora from Drosophila melanogaster, which are key regulators of mitosis. The present study shows that human Aurora-B is activated by okadaic acid and forms complexes with the protein serine/threonine phosphatase type 1 (PP1) or PP2A, but not with PP5. These data identified Aurora-B associated protein phosphatases as negative regulators of kinase activation. We then used a series of substrates based on a histone H3 phosphorylation site (residues 5-15) to determine the substrate specificity of human Aurora-B. We found that this enzyme is an arginine-directed kinase that can phosphorylate histone H3 at serines 10 and 28 in vitro, suggesting that human Aurora-B is a mitotic histone H3 kinase.