Tumor Response to Neoadjuvant Chemotherapy Correlates with the Expression of P-Glycoprotein and PCNA but Not GST-π in the Tumor Cells of Cervical Carcinoma

Objective.To identify the clinicopathological and chemoresistant factors predicting the response to neoadjuvant chemotherapy and the patient prognosis in high-risk cervical carcinomas.Methods.We retrospectively reviewed 47 patients with locally advanced or bulky cervical carcinoma treated with two courses of intraarterial infusion of cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil (5-FU), followed by radical hysterectomy at our hospital between 1988 and 1995. Expressions of the chemoresistance-related proteins, such as P-glycoprotein, glutathioneS-transferase π (GST-π), and proliferating cell nuclear antigen (PCNA) in the tumor cells, were examined by immunohistochemistry using pretreatment biopsy specimens. These results were compared with the chemotherapeutic response, which was evaluated by magnetic resonance imaging (MRI) and histopathology. Outcome of the patients was also studied.Results.Chemotherapeutic effect of either complete (CR) or partial (PR) response on MRI was obtained in 36 of the 47 (86%) patients. Poor response to chemotherapy was significantly correlated with P-glycoprotein expression (P< 0.005) and low PCNA labeling (P< 0.05), but not GST-π expression in the tumor cells. Independent prognostic factors for patient survival were parametrial involvement and lymph node metastasis. Neither the expression of GST-π nor PCNA was correlated with the patient survival.Conclusion.Assessment of the expression of P-glycoprotein and PCNA is potentially useful for the prediction of tumor response to neoadjuvant chemotherapy for cervical carcinomas.     

Clinical studies on the transabdominal resection of esophagocardial cancer and cervical anastomosis using bypass methods. Analysis of data on 76 patients

Transabdominal resection for esophagocardial cancer and reestablishment of alimentary continuity using bypass methods were performed in 76 patients. Thirteen underwent a bypass with a gastric tube and in 30, a colonic segment was prepared. In the remaining 33, a jejunal segment was used as a bypass organ, with considerable success. The 5 year survival rates were 68.8 per cent in those with stages (I+II), 16.5 per cent in those with stage III, 12.6 per cent in those with stage IV and 22.5 per cent in all cases, indicating similar results compared to those with cancer located in the upper third of the stomach with the limited proximal extension within the esophagocardial junction and operated on during the same period.     

Abdominal vagotomy attenuates interleukin-1β-induced nitric oxide release in the paraventricular nucleus region in conscious rats

Nitric oxide (NO) has recently been shown to modulate the hypothalamic–pituitary–adrenal axis response to interleukin-1β (IL-1β). We measured levels of nitrite (NO₂⁻) and nitrate (NO₃⁻) in the hypothalamic paraventricular nucleus (PVN) region using an in vivo brain microdialysis technique in conscious rats. Intraperitoneally administered IL-1β produced a significant increase in both NO₂⁻ and NO₃⁻ levels in the PVN region. We also examined the possible involvement of the abdominal vagal afferent nerves in this effect. In abdominal-vagotomized rats, the increase was significantly attenuated compared to that in sham-operated rats. Our results suggest that the abdominal vagal afferent nerves are involved in intraperitoneally administered IL-1β-induced NO release in the PVN region.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Characterization of a 34-kDa soybean binding protein for the syringolide elicitors

Syringolides are water-soluble, low-molecular-weight elicitors that trigger defense responses in soybean cultivars carrying the Rpg4 disease-resistance gene but not in rpg4 cultivars. ¹²⁵I-syringolide 1 previously was shown to bind to a soluble protein(s) in extracts from soybean leaves. A 34-kDa protein that accounted for ¹²⁵I-syringolide 1 binding activity was isolated with a syringolide affinity-gel column. Partial sequences of internal peptides of the 34-kDa protein were identical to P34, a previously described soybean seed allergen. In soybean seeds, P34 is processed from a 46-kDa precursor protein and was shown to have homology with thiol proteases. P34 is a moderately abundant protein in soybean seeds and cotyledons but its level in leaves is low. cDNAs encoding 46-, 34-, and 32-kDa forms of the soybean protein were cloned into the baculovirus vector, pVL1392, and expressed in insect cells. The resulting 32- and 34-kDa proteins, but not the 46-kDa protein, exhibited ligand-specific ¹²⁵I-syringolide binding activity. These results suggest that P34 may be the receptor that mediates syringolide signaling.     

Effects of calcium in continuous cardioplegia on myocardial protection

The effects of calcium (Ca) on a hyperkalemic cardioplegic solution for continuous cardioplegia were examined in an isolated perfused working rat heart model. The coronary arteries were perfused with a modified Krebs-Henseleit bicarbonate buffer (K-H) solution, containing various concentrations of Ca(0.1, 0.6, 1.2, and 2.5 mmol/l) and a high concentration of potassium (20 mmol/l), for 180 min, after which cardiac arrest was induced at 37°C for 180 min. Cardiac function and creatine kinase (CK) were measured. In the control group, K-H solution was infused in place of the cardioplegic solution, and cardiac arrest was not induced. No significant differences were observed between the groups infused with the K-H solution containing Ca concentrations of 0.6, 1.2, and 2.5 mmol/l in the percent recovery of aortic flow (82.1±2.9%, 80.6±2.0%, and 71.5±3.7% (mean±SEM) respectively) or in the recovery of other indices of cardiac function, or in CK leakage. There were also no significant differences in the recovery of cardiac function and CK leakage between these groups and the control group. In the Ca 0.1 mmol/l group, however, the characteristic Ca paradox was observed. These findings suggest that if the Ca concentration in a cardioplegic solution is higher than 0.6 mmol/l during continuous cardioplegia, excellent cardioprotective effects will be achieved.     

Isolation and Structure Elucidation of Neokadsuranic Acid A, the First Triterpenoid with the 14 (13-->12) abeo Lanostane Skeleton, and (24Z)-3-Oxo-lanosta-8,24-dien-26-oic Acid1

Neokadsuranic acid A, which is the first triterpenoid with the 14(13-->12) ABEO lanostane skeleton, was isolated from KADSURA HETEROCLITA together with (24 Z)-3-oxo-lanosta-8,24-dien-26-oic acid. The present paper deals with the isolation and structure elucidation of these two new compounds.     

Expression of Jun activation domain-binding protein 1 and p27 (Kip1) in thyroid medullary carcinoma

AIMS: p27 is a prominent regulator of cell proliferation by universally inhibiting the cell cycle, while Jun activation domain-binding protein 1 (Jab1), a multifunctional cell signaling protein, contributes to carcinoma progression by degrading p27. In this study, we investigated the expression of these proteins in medullary thyroid carcinoma. METHODS: We immunohistochemically examined Jab1 and p27 expression in 64 medullary thyroid carcinomas. RESULTS: Of the 64 cases examined, decreased p27 expression was observed in 38 cases (59.4%). The p27 expression level was inversely linked to tumour size as well as plasma calcitonin level. Jab1 expression level was generally high, and 46 cases (71.9%) were classified as overexpressing Jab1. The incidence was higher than those in papillary and follicular carcinomas, which were previously reported. Jab1 expression level was inversely linked to that of p27, and all five cases with only cytoplasmic but not nuclear staining of p27 overexpressed Jab1. CONCLUSIONS: These findings suggest that (1) decrease in p27 expression may contribute to local tumour growth; (2) Jab1 expression is related to the progression of medullary carcinoma by decreasing the amount of p27 in the cell and accelerating its degradation; and (3) Jab1 may play a more vital role in the pathogenesis of medullary carcinoma than papillary and follicular carcinomas.     

Diazepam reduces both arterial blood pressure and muscle sympathetic nerve activity in human

It is known that benzodiazepines have a hypotensive effect, but the mechanism has not been well elucidated yet. To clarify whether this effect is due to central or peripheral mechanism, we administered 5 mg of diazepam or saline intravenously to healthy volunteers and assessed the change in blood pressure, heart rate, muscle sympathetic nerve activity and heart rate variability. After diazepam administration, systolic and mean blood pressure decreased significantly. Muscle sympathetic nerve activity was also significantly reduced but heart rate did not change, whereas the variables of spectral analysis of heart rate variability did not show significant change. We concluded that the hypotensive effect of diazepam in human is mainly due to the central mechanism.     

Up-regulation of histamine H1 receptors in an allergic rat nasal mucosa model

Inflammation Research -