Role of 12-lipoxygenase in regulation of ovarian cancer cell proliferation and survival

Purpose  

Eicosanoid-related enzymes have been implicated in the pathogenesis of various cancers. Little is known about the relevance of lipoxygenase pathway to ovarian cancer growth. In this study, we examined the role of 12-lipoxygenase (12-LOX), the main human 12-HETE generating enzyme, in the regulation of proliferation and survival in epithelial ovarian cancer.     

Prognostic significance of keratinization in squamous cell cancer of uterine cervix: a population based study

Purpose  To determine the influence of keratinization on prognosis in squamous cell cancer (SCC) of the uterine cervix. Methods  Patients with keratinized squamous cell carcinoma (KSCC) and non-keratinized squamous cell carcinoma (NKSCC) of the cervix were identified from the Limited Use SEER database from 1988 to 2004. A subgroup of patients who did not have radiation or surgery formed the basis to study the natural history of the disease. Data were analyzed using Pearson Chi-square, Student’s T tests. Kaplan–Meier and Cox Regression Proportional Hazards survival analysis was conducted in SPSS and SEER-Stat software. Results  The KSCC group had 3,102 and the NKSCC had 3,751 patients with mean age being 51 and 49 years, respectively (P = 0.001). In general, patients with KSCC were more likely to have advanced stage (FIGO III and IV) disease while patients with NKSCC were more likely to have poorly differentiated neoplasms (P < 0.001). The prevalence of lymph node metastasis remained similar in both histology types (P > 0.05). Overall, the 5-year survival in KSCC was 63.4% as compared to 65.3% in the NKSCC group (P = 0.04). Patients treated by surgery had no difference in survival; however, patients treated by radiation had a median survival in KSCC of 33 months (n = 928, 95% CI 27.7–38.3) as compared to 38 months (n = 1,140, 95% CI 32.1–43.8) in NKSCC (P = 0.03). A total of 165 KSCC and 147 NKSCC patients did not receive treatment. Within this subgroup, the median survival was 10 months (95% CI 5.93–14.07) as compared to 28 months (95% CI 17.9–38.0; P = 0.001) respectively for the two cohorts. In multivariate analysis stage, treatment status, nodal metastasis and keratinization were independent predictors of survival (P < 0.05). Conclusion  This is the largest study reporting on the prognostic importance of keratinization in SCC. KSCC may be less radiosensitive and associated with shorter overall survival. Also, in the natural history of the SCC, keratinization signifies striking reduction in survival.     

Effects of Fluid Rehydration Strategy on Correction of Acidosis and Electrolyte Abnormalities in Children With Diabetic Ketoacidosis

OBJECTIVEFluid replacement to correct dehydration, acidosis, and electrolyte abnormalities is the cornerstone of treatment for diabetic ketoacidosis (DKA), but little is known about optimal fluid infusion rates and electrolyte content. The objective of this study was to evaluate whether different fluid protocols affect the rate of normalization of biochemical derangements during DKA treatment.RESEARCH DESIGN AND METHODSThe current analysis involved moderate or severe DKA episodes (n = 714) in children age <18 years enrolled in the Fluid Therapies Under Investigation in DKA (FLUID) Trial. Children were assigned to one of four treatment groups using a 2 × 2 factorial design (0.90% or 0.45% saline and fast or slow rate of administration).RESULTSThe rate of change of pH did not differ by treatment arm, but Pco₂ increased more rapidly in the fast versus slow fluid infusion arms during the initial 4 h of treatment. The anion gap also decreased more rapidly in the fast versus slow infusion arms during the initial 4 and 8 h. Glucose-corrected sodium levels remained stable in patients assigned to 0.90% saline but decreased in those assigned to 0.45% saline at 4 and 8 h. Potassium levels decreased, while chloride levels increased more rapidly with 0.90% versus 0.45% saline. Hyperchloremic acidosis occurred more frequently in patients in the fast arms (46.1%) versus the slow arms (35.2%).CONCLUSIONSIn children treated for DKA, faster fluid administration rates led to a more rapid normalization of anion gap and Pco₂ than slower fluid infusion rates but were associated with an increased frequency of hyperchloremic acidosis.     

Ultrastructural study of the effect of acid etching on different dentin adhesives

We study the behavior of several dentinal adhesives in shielding dentine against acid insult. Durafill, Ionosit, Visiobond, Heliobond and Prismabond provide little protection against acids, leaving the dentinal tubules uncovered, more or less open. Scotchbond, which, forms a layer thicker than any of the other adhesives, endures acid engraving a little better, leaving less dentinal tubules unprotected, which are thinner than those left bare by any of the other adhesives studied here.     

Lead encephalo-myelopathy of the suckling rat and its implications on the porphyrinopathic nervous diseases

Summary Experimental lead encephalo-myelopathy of the suckling rat is the signpost on the tortuous road of uncovering prolonged metabolic dysoxidosis as the major pathogenetic principle in lead encephalopathy and in the other porphyrinopathic encephalopathies. This principle rests on the specific skill of the capillary endothelium of the nervous system to act as regulator of the blood-brain and blood-spinal cord barriers and on the extreme susceptability of this skill to chronic metabolic dysoxidosis. This same pathogenetic principle lies at the root of a group of neurological diseases for which we propose the name systembound dysoric encephalopathies. In contrast to lead encephalopathy of the suckling rat, human lead encephalopathy does not belong to this group because of added hemodynamic disorders. Such disorders prevent a pathoclitic distribution of the lesions.

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Zusammenfassung Die experimentelle Bleiencephalomyelopathie der Saugratte ist der entscheidende Schritt auf dem verschlungenen Wege zur Aufdeckung der chronischen Wirkstoffmangeldysoxydose als pathogenetischer Faktor der porphyrinopathischen Encephalopathien und überhaupt als ein grundlegendes Prinzip der Neuropathologie. Dieses Prinzip brruht auf der den Capillarendothelien des Nervensystems eigenen Fähigkeit, die Bluthirn- bzw. die Blutrückenmarksscharanke zu regulieren, und andererseits auf der extremen Anfälligkeit dieser Fähigkeit gegenüber chronischer Wirkstoffmangeldysoxydose. Der Verlust dieser Fähigkeit reduziert die Capillaren auf die Stufe der weniger spezialisierten Capillaren der meisten übrigen Organe. Die Folge ist zunächst rein funktioneller Natur und äußert sich in psychischen Störungen mit oder ohne Krämpfe oder in motorischen Lähmungen. Diese Störungen sind in diesem Anfangsstadium reversibel, weil nach Beseitigung der Noxe die Capillaren ihre hoch-spezialisierte Fähigkeit wiedererlangen können. Bei längerer Dauer der Wirkstoffmangeldysoxydose jedoch kommt es zu einem breiten Spektrum von Strukturveränderungen dysorischer Art, an dessen äußerstem Ende Transudationen und Höhlenbildungen stehen.Die chronische Wirkstoffmangeldysoxydose ist die Grundursache einer großen Gruppe neurologischer Erkrankungen mit der Wernickeschen Encephalopathie als Protagonist, für welche die Bezeichnung systemgebundene dysorische Encephalopathien angebracht erscheint. Im Gegensatz zur Bleiencephalopathie der Saugratte gehört die menschliche Bleiencephalopathie nicht zu dieser Gruppe, weil sich bei ihr zum Versagen der Blutgehirnschranke Störungen der Durchblutung hinzugesellen. Die Anwesenheit solcher Störungen ist aber mit einer pathoklitischen Ausbreitung der Hirnschäden unvereinbar.

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Julius Hallervorden (1882–1965) in memoriam.

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This investigation was supported by a Research Grant NB-02275 from the National Institute of Neurological Diseases and Blindness, National Institutes of Health, Bethesda, Md.     

Loss of heterozygosity and microsatellite instability at the Xq28 and the A/G heterozygosity of the QM gene are associated with ovarian cancer

The QM gene is located at Xq28 of the X chromosome. QM may act as a tumor suppressor and may also participate in the 60S ribosomal subunit assembly. We studied loss of heterozygosity (LOH) and microsatellite instability (MSI) of microsatellite markers DXS15A, DXS1107, WI12360 and WI9327 for the Xq28 region in 29 ovarian cancer biopsies. The results showed that the LOH frequencies were 18.2%, 30%, 26.3% and 20.8% for WI12360, WI9327, DXS1107 and DXS15A, respectively, whereas the MSI rates were 18.2%, 50.0%, 31.6% and 12.5%, respectively. All tumors showed LOH or MSI for at least one of these markers. Sequencing the QM cDNA did not identify any mutation other than the adenine (A)/guanine (G) replacement at the 605th nucleotide which changes the coding from serine to asparagine. In 17 (58.6%) of the 29 tumors, both A and G types of QM mRNA were detected, indicating that the QM was A/G heterozygous and escaped X-inactivation. However, cDNA and genomic DNA sequencing revealed that the adjacent normal tissues showed the A/G heterozygosity in only 3 of the 17 cases, while in the remaining 14 cases, four had no more adjacent tissue available and ten revealed either G or A at the 605th nt, indicating an A/G point mutation in these tumors. The allele distribution was 32.8% for the A and 67.2% for the G type QM gene. The frequencies of A/A, G/G and A/G homo- or hetero-zygosity were 3.5%, 37.9% and 58.6%, respectively in cancer tissues but they were 26.1%, 52.2% and 21.7%, respectively in the adjacent tissues, indicating a higher heterozygous rate in cancer (58.6% vs 21.7%, p < 0.01). These results suggest that high frequencies of LOH and MSI at the Xq28 and of the A/G heterozygosity at the 605th nt of the QM gene may be associated with ovarian cancer.