Aortic root subadventitial hematoma

A 51-year-old woman was operated on for aortic valve regurgitation 3 months after experiencing chest tightness awakening her from sleep. Intraoperative findings included turbid dark brown pericardial fluid and a nipple-shaped protrusion on the external aspect of the noncoronary sinus of Valsalva. Histologically, the lesion was enclosed by intact media and adventitia, and represented an organized hematoma. Dilated venules noted adjacent to the lesion were suggestive of an intramural hemangioma. The etiology of this lesion is unclear, but it might be an unusual type of intramural hematoma (IMH) and gives us a hint of an origin of IMH.     

A case of metastatic colon cancer in which repetition of standard treatment proved effective

In palliative chemotherapy, a focus on palliative treatment is recommended in cases that are unresponsive to multiple drugs. Careful judgment is needed, however, because when treatment is inadequate, cases that are considered to be unresponsive may include some in which chemotherapy would be effective. We treated a patient with metastatic colon cancer who was judged to be unresponsive to multiple drugs at another hospital, yet repetition of standard therapy proved effective. We report this case as an instructive example of the importance of maintaining dose intensity. The patient was a 60-year-old man. Lung metastasis appeared after he had undergone proctectomy and received adjuvant chemotherapy by his previous doctor. Low-dose intensity IFL therapy, FOLFOX4 therapy (once a month), and FOLFIRI therapy (once only) had been performed, but the patient's condition worsened and he was referred to our hospital. This case could not be considered unresponsive to multiple drugs because the treatment had been insufficient, and so we restarted FOLFIRI treatment with the international standard dose and obtained control of the disease. Treatment was then continued, and the patient died 2 years and 11 months after he was first examined at our hospital. Simple palliative treatment alone should not be given unthinkingly when patients are referred for outpatient palliative care. Full consideration of the dosing and schedule is needed.     

Validation of the histone methyltransferase EZH2 as a therapeutic target for various types of human cancer and as a prognostic marker

The emphasis in anticancer drug discovery has always been on finding a drug with great antitumor potential but few side-effects. This can be achieved if the drug is specific for a molecular site found only in tumor cells. Here, we find the enhancer of zeste homolog 2 (EZH2) to be highly overexpressed in lung and other cancers, and show that EZH2 is integral to proliferation in cancer cells. Quantitative real-time PCR analysis revealed higher expression of EZH2 in clinical bladder cancer tissues than in corresponding non-neoplastic tissues (P < 0.0001), and we confirmed that a wide range of cancers also overexpress EZH2, using cDNA microarray analysis. Immunohistochemical analysis showed positive staining for EZH2 in 14 of 29 cases of bladder cancer, 135 of 292 cases of non-small-cell lung cancer (NSCLC), and 214 of 245 cases of colorectal cancer, whereas no significant staining was observed in various normal tissues. We found elevated expression of EZH2 to be associated with poor prognosis for patients with NSCLC (P = 0.0239). In lung and bladder cancer cells overexpressing EZH2, suppression of EZH2 using specific siRNAs inhibited incorporation of BrdU and resulted in significant suppression of cell growth, even though no significant effect was observed in the normal cell strain CCD-18Co, which has undetectable EZH2. Because EZH2 expression was scarcely detectable in all normal tissues we examined, EZH2 shows promise as a tumor-specific therapeutic target. Furthermore, as elevated levels of EZH2 are associated with poor prognosis of patients with NSCLC, its overexpression in resected specimens could prove a useful molecular marker, indicating the necessity for a more extensive follow-up in some lung cancer patients after surgical treatment.     

Autoantibodies to RNA helicase A: a new serologic marker of early lupus

OBJECTIVE: To investigate the clinical and immunologic significance of autoantibodies to RNA helicase A (RHA) in patients with systemic rheumatic diseases. METHODS: The study group comprised 1,119 individuals enrolled in the University of Florida Center for Autoimmune Diseases registry from 2000 to 2005. Diagnoses were based on standard criteria. Autoantibodies were analyzed by immunoprecipitation and Western blot assays. RESULTS: Anti-RHA was observed in 17 (6.2%) of 276 patients with systemic lupus erythematosus (SLE), 2 patients with antiphospholipid antibodies, and 3 other patients, but anti-RHA was not observed in any patient with polymyositis/dermatomyositis, systemic sclerosis, rheumatoid arthritis, or Sj?gren's syndrome. Anti-RHA was present in only 2.9% of African American patients, compared with 6.0% of white patients and 12-25% of patients of other races; this was in striking contrast to the frequency of anti-Sm in African American patients (27.2%). Among patients with SLE, anti-RHA was common in young patients (26% of those whose initial visit was at an age younger than 20 years versus 3-4% of those who were initially seen at ages 20-49 years) and at an early stage of disease (23% of those whose first clinic visit was within 1 year of disease onset versus 2-8% of those whose first visit was at least 1 year after disease onset). In 9 of 11 patients, levels of anti-RHA decreased to <10% of the initial value within 9-37 months, while levels of coexisting anti-Ro or anti-Su remained the same. New specificities developed in 2 patients (anti-nuclear RNP and anti-Sm, and anti-ribosomal P, respectively). These data suggest that the level of anti-RHA diminishes over time, and that anti-RHA is regulated via a mechanism different from that for other lupus-related autoantibodies. CONCLUSION: Anti-RHA is a new serologic marker for SLE. It is produced mainly in young non-African Americans at an early stage of their disease. Anti-RHA has a unique tendency to diminish over time. The production of anti-RHA may depend on a process restricted to early SLE, or it may be highly sensitive to treatment.     

Angiotensin II decreases glucose uptake by downregulation of GLUT1 in the cell membrane of the vascular smooth muscle cell line A10

Recent evidence suggests a crosstalk between angiotensin II (Ang II) and insulin. However, whether this crosstalk affects glucose uptake, particularly in terms of actin filament involvement, has not yet been studied in vascular smooth muscle cells. Pretreatment of cells with either Ang II or cytochalasin D disarranged actin filaments in a time-dependent manner and inhibited glucose uptake. However, insulin increased actin reorganization and glucose uptake. Membrane fractionation studies showed that Ang II decreased GLUT-1 at the cell membrane, whereas it increased GLUT-1 in the cytoplasm, indicating that Ang II may cause internalization of GLUT-1 via actin disorganization, consequently decreasing glucose uptake. The effects of Ang II on glucose uptake and actin reorganization were blocked by AT1 receptor antagonist, but not by AT2 antagonist. Either P38 or ERK1/2 inhibitors partially reversed the Ang II-inhibited actin reorganization and glucose uptake, suggesting that MAPK signaling pathways could be involved as downstream events in Ang II signaling, and this signaling may interfere with insulin-induced actin reorganization and glucose uptake. These data imply that Ang II induces insulin resistance by decreasing glucose uptake via disarrangement of actin filaments, which provides a novel insight into understanding of insulin resistance by Ang II at the molecular level.     

Regressive effect of intralesional injection of a moderate dose of recombinant interleukin-2 on carcinoma erysipeloides from gastric carcinoma

Cutaneous metastatic diseases remain nearly incurable and a major medical challenge. It has been shown that interleukin-2 (IL-2) has potential as a therapeutic agent for various neoplastic diseases such as melanoma, renal cell carcinoma and myeloid leukaemia. However, IL-2 therapy for metastatic skin lesions has not been established yet. In the present study, we investigated the effect of recombinant IL-2 in a 79-year-old Japanese man with carcinoma erysipeloides, a rare type of cutaneous metastasis from gastric cancer. He was treated with an intralesional injection of rIL-2 (200 000 JRU) daily. Ten days after treatment, an erythematous plaque was eliminated almost completely leaving light brown pigmentation. A skin biopsy from the pigmented area revealed the absence of obvious tumour cells. These findings suggest that this cytokine should be considered for the clinical treatment of several inoperative metastatic cutaneous diseases, including gastric cancer.