FXYD3 was originally identified as one of the gene products (mRNAs) highly expressed in murine mammary tumors induced by the transgenic neu or ras but not induced by myc or int-2 oncogenes.1) In human, FXYD3 mRNA was overexpressed in breast cancer cell lines and primary breast cancers, 2) and also in prostate and pancreatic cancers. [3][4][5] Suppression of FXYD3 expression by the small interfering RNA (siRNA) or antisense transfection caused a significant decrease in cellular proliferation of prostate and pancreatic cancer cell lines, respectively. 4,5) Therefore, FXYD3 is involved in proliferation, and is expected to be a tumor marker.FXYD3 is a member of the "FXYD" family proteins, which consist of seven members of small proteins that have a single transmembrane segment, and share a signature sequence of four amino acids "FXYD" (Phe-Xaa-Tyr-Asp) located in the ectodomain close to the transmembrane segment.6) Among the seven members of FXYD proteins, only FXYD2 (Na ϩ ,K ϩ -ATPase g-subunit) and FXYD3 have two isoforms which encode two proteins of different amino acid sequences, respectively. The FXYD3 short-form (FXYD3a) mRNA has an in-frame deletion of 78 nucleotides in the coding sequence compared to the FXYD3 long-form (FXYD3b) mRNA. As a result, the FXYD3b protein has 26 more amino acids in the cytoplasmic domain compared to the FXYD3a protein ( Fig. 1). FXYD family proteins perform fine tuning of ion transport by associating with and modulating the activity of Na ϩ ,K ϩ -ATPase molecule and modifying the activity of ion channels.2,7) FXYD3a slightly decreased the apparent affinity both for intracellular Na ϩ (up to 40%) and extracellular K ϩ (15 to 40%) of Na ϩ ,K ϩ -ATPase whereas FXYD3b slightly increased the apparent affinity for intracellular Na ϩ (about 15%) and decreased the apparent affinity for extracellular K ϩ (up to 50%). 8,9) Both FXYD3 isoforms induced a hyperpolarization-activated chloride current in Xenopus oocytes.2,9) However, physiological roles of FXYD3 isoforms have not been fully understood yet. The expression pattern of FXYD3a and FXYD3b mRNAs has not been cleared. Moreover, it remains to be clear whether the FXYD3 proteins are overexpressed in breast cancers or not. Here, we quantified FXYD3a and FXYD3b mRNAs in human normal tissues and many human cancer cell lines by quantitative reverse transcription polymerase chain reaction (RT-PCR). We prepared two kinds of antibodies against human FXYD3 protein (one antibody against both FXYD3a and 3b; the other against FXYD3b) and examined the expression pattern of FXYD3 proteins in human cancer cell lines and human breast tissues. We also suppressed the expression of FXYD3 proteins by the treatment of siRNA to study the role of FXYD3 on cellular proliferation of a breast cancer cell line, MCF-7. FXYD3, also known as Mat-8 (Mammary tumor 8 kDa), is one of mRNAs highly expressed in mouse and human breast cancers. Here, we newly found that FXYD3 protein was also overexpressed in human breast cancer specimens; invasive ductal carcinomas and intr...

This paper reports an autopsy case of a 5‐year and 11‐month‐old girl with generalized subcutaneous lipomatosis, megalencephaly, and macrodactyly. Marked emaciation and poor prognosis were the characteristic findings of this case. We thought that this case was identical with a rare syndrome which was initially reported by Bannayan in 1971. Autopsy disclosed diffuse lipomatosis in the thoracic and abdominal cavity, and infiltration of fat tissue to the pancreas. Hyperplasia of the small intestinal mucosa and Peyer's patch, and a pedunculated polyp of the sigmoid colon were the unique findings which could not be seen in the previously reported cases.

We present herein an usual case of primary malignant melanoma of the gallbladder in a 51-year-old man in whom an exploratory laparotomy for melena revealed six malignant melanoma lesions located in the gallbladder, main pancreatic duct, stomach, duodenum, jejunum, and a mesenteric lymph node. Total pancreatectomy was performed and histologically, junctional activity was seen only in the gallbladder, suggesting that this was the primary site. No melanotic lesions were found on the skin or eyes. The metastases to the main pancreatic duct and gastrointestinal tract appeared likely to have occurred as a consequence of the mucosal dissemination of the tumor cells shed into the bile. The post-operative course was uneventful and combined chemotherapy was administered for 16 months. No new metastatic lesions were found until 21 months postoperatively, when metastases were detected in the brain and thoracic spinal cord. These metastatic tumors were removed surgically, but the patient died from cerebral disturbance 26 months after the initial operation. Thus, we consider that aggressive surgical therapy was effective for extending the survival time and improving the quality of life of this patient.

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.

No abstract