Anthracycline-induced cardiomyopathies evaluated by tissue Doppler tracking system and strain rate imaging.

OBJECTIVES: Anthracycline cardiotoxicity is known to occur from the subendocardial side of the left ventricular wall. Recent advances of tissue Doppler echocardiography may allow the evaluation of anthracycline cardiotoxicity by dividing the left ventricular wall into the subendocardial half and subepicardial half. The present study assessed the feasibility using the tissue Doppler echo tracking system (M-mode) and myocardial strain rate imaging (B-mode) to noninvasively detect anthracycline cardiotoxicity. METHODS: The tissue Doppler echo tracking system (M-mode) was used to measure systolic thickening of the subendocardial layer (delta Endo), subepicardial layer (delta Epi), and whole wall (delta Total) of the left ventricular posterior wall in 41 normal subjects and three groups of patients receiving anthracycline: 34 patients in the low dose group, 19 in the middle dose group, and 12 in the high dose group. Strain rate is the spatial gradient of local velocities, reflecting local compression and expansion rates not affected by overall heart motion. Myocardial strain rate imaging (B-mode) was used in 25 normal subjects, 9 patients in the low dose group, and 10 patients in the high dose group. The ratio of peak systolic strain rate of subendocardium to that of subepicardium (peak strain rate endo/epi), and the ratio of integrated strain rate during ejection time of subendocardium to that of subepicardium (integrated strain rate endo/epi) were measured. RESULTS: Tissue Doppler echo tracking system (M-mode) measurement of delta Endo/delta Epi showed the most distinct difference and the least overlap of the data between normal subjects and patients, whereas delta Total failed to show significant differences. Myocardial strain rate imaging (B-mode) measurement of integrated strain rate endo/epi showed the most distinct difference and the least overlap of the data between normal subjects and patients, but ejection fraction failed to show statistically significant differences. CONCLUSIONS: These methods are highly sensitive tools for monitoring anthracycline cardiotoxicity.

Activation of peroxisome proliferator-activated receptor gamma inhibits the growth of human pancreatic cancer.

OBJECTIVE: In the present study, we examined the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in human pancreatic cancer and the possible effects of its ligand engagement on cell growth. METHODS: Seven human pancreatic cancer cell lines and 7 surgically resected human pancreatic cancer tissues were used as samples. The expression of PPARgamma was analyzed with reverse transcription-polymerase chain reaction and immunoblotting. The interaction between PPARgamma and PPAR-responsive element (PPRE) was examined by gel shift assay. Growth inhibition by thiazolidinediones was confirmed with anchorage-dependent and anchorage-independent growth assays. RESULTS: PPARgamma was detected in all cell lines tested and in 5 out of 7 cancer tissues (71%), but was not found in adjacent normal pancreatic tissues. Gel shift analysis revealed that the proteins in nuclear extracts of the pancreatic cancer cell line PANC-1 specifically bind to the PPRE. Cell growth was significantly inhibited by treatment with troglitazone and rosiglitazone in a dose- and time-dependent manner (p < 0.01). In contrast, a nonfunctional metabolic analog of troglitazone did not affect cell growth. CONCLUSION: These observations suggest that PPARgamma plays an important role in human pancreatic cancer growth and that ligand-induced activation of PPARgamma would be a useful strategy for treatment of human pancreatic cancer.

Preparation of sterol-imprinted polymers with the use of 2-(methacryloyloxy)ethyl phosphate.

Steroid-selective polymers were prepared by the molecular imprinting technique, using 2-(methacryloyloxy)ethyl phosphate as functional monomer. The retentivity and selectivity of the obtained imprinted polymers were evaluated by liquid chromatography. The cholesterol-imprinted polymer showed higher affinity for cholesterol than that for cholesterol derivatives. The selectivity of the imprinted polymer was superior to the imprinted polymer prepared with the conventional functional monomer, 2-(trifluoromethyl)acrylic acid. Estradiol was also imprinted and gave similar results, demonstrating that 2-(methacryloyloxy)ethyl phosphate would be suitable for imprinted polymers of cholesterol and related compounds.

[Transmural heterogeneity of the left ventricular wall: subendocardial layer and subepicardial layer].

The myocardium of the left ventricular wall is not homogeneous, but demonstrates transmural heterogeneity in myocardial blood flow, myocardial metabolism, and contraction and relaxation dynamics. Reimer and colleagues recognized that irreversible injury of the ischemic myocardium develops as a transmural wavefront, occurring first in the subendocardial myocardium, and with longer periods of ischemia, the wavefront of necrosis moves from the subendocardial zone across the wall to progressively involve more of the transmural thickness of the ventricular wall, ultimately becoming nearly transmural. This phenomenon was named the "wavefront phenomenon", and is the morphological counterpart of the transmural heterogeneity of the metabolism and blood flow. Autoregulation of myocardial blood flow is accomplished by changes in intramyocardial vascular resistance and intramyocardial pressure. It is more difficult to maintain the autoregulation in the subendocardial myocardium because contraction is greater, oxygen demand is greater, and myocardial pressure is higher in the subendocardium than in the subepicardial layer. In the normal myocardium, contraction is greater in the subendocardial layer, as is wall stress, accounting for the higher subendocardial energy requirements. Consistent with these findings, higher rates of metabolic activity and greater oxygen extraction are found in this region. As a consequence, ischemia becomes more severe and myocardial cells undergo necrosis first in the subendocardium. Under normal conditions, production and utilization of high-energy phosphates [adenosine triphosphate(ATP) and creatine phosphate] in the subendocardial myocardium are more active than in the subepicardial myocardium, but decline more easily in the subendocardium during ischemia, which induces the subendocardial ischemic injury. Lower production of Ca(2+)-ATPase in the subendocardium might also contribute to the subendocardial injury. Wavefront necrosis starts from the subendocardium, but the production of high-energy phosphates in the subepicardium is known to increase and compensate for the reduction in high-energy phosphate production in the subendocardium. Animal experiments have shown that systolic thickening of the endocardial half of the ventricular wall is double that in the epicardial half. Today, this can be confirmed in humans with the tissue Doppler tracking method which is completely noninvasive. Furthermore, the subepicardial half of the ventricular wall is known to compensate for the decreased systolic thickening of the subendocardial half in the case of subendocardial injury, which is called vertical compensation and is the mechanical counterpart of the concept of metabolic compensation. Many new technologies, including the tissue Doppler tracking method, magnetic resonance imaging tagging, and myocardial contrast echocardiography, will give more accurate information about the myocardial heterogeneity of layer-by-layer motion and blood flow, and will contribute to early detection and quantitative estimation of ischemia and other diseases of which the main lesion is in the subendocardium.

A Case of Esophageal Squamous Cell Carcinoma Metastatic to the Breast.

Metastasis to the breast from extramammary malignancies is rare. There are especially few reports of metastasis from esophageal cancer. We report the pathological and autopsy findings of a 44-year-old man with advanced esophageal cancer and a left breast tumor. Squamous cell carcinoma invading the mammary glands wasdemonstrated histologically. Immunostains for ER, PgR, and ErbB-2 were negative. At autopsy, metastatic lesions were found in lung, liver, diaphragm, peritoneum, spine, and mediastinal lymph nodes, with no evidence of metastasis to the skin. While metastatic breast tumors are rarely the initial sign of malignancy, it isimportant to distinguish a metastasis from primary breast cancer to avoid unnecessary conflicting treatments.

Dedifferentiated chondrosarcoma of the rib with a malignant mesenchymomatous component: an autopsy case report.

A rare variant of dedifferentiated chondrosarcoma with malignant mesenchymomatous component in a 57-year-old male is reported. The patient presented with a posterior mediastinal mass arising from the left eighth and ninth ribs showing well differentiated, low-grade chondrosarcoma. Five years later, local recurrence occurred and an excised specimen also showed the same histological features as the primary tumor. Another 6 years later, the tumor recurred and metastasized to the multiple organs, the patient dying 4 months later. Autopsy revealed that the recurrent and metastatic tumors showed malignant mesenchymomatous 'dedifferentiation' of chondrosarcoma composed of rhabdomyosarcoma, angiosarcoma, chondrosarcoma, osteosarcoma, and leiomyosarcoma, in addition to fibrosarcomatous areas. Although the less differentiated component of dedifferentiated chondrosarcoma usually shows the histological features of malignant fibrous histiocytoma and fibrosarcoma, multilineage differentiation can occur in that component. The phenomenon of 'dedifferentiation' in chondrosarcoma and the relationship to and distinction from malignant mesenchymoma of soft tissue and bone are discussed.

[Epidemiologic studies on multiple cancers in Japan].

During a 21-year period, 3040 patients with malignant tumors were treated at the Division of Surgery, Fukuyama National Hospital. Of these 86 (2.8%) were diagnosed as having double cancers. The simultaneous double cancer rate was 27.3%. Statistical study showed that the etiology had a relation to family history and previous therapy, but not to immunology. The prognosis was good and diagnosis by RI was non-specific.