Comparison of treatment outcomes between squamous cell carcinoma and adenocarcinoma in locally advanced cervical cancer

Objective

To compare the treatment outcomes between squamous cell carcinoma (SCC) and adenocarcinoma (ACA) in locally advanced cervical cancer patients.

Methods

All medical records of stages IIB-IVA of cervical cancer patients who had completed treatment between 1995 and 2008 were reviewed. ACA 1 case was matched for SCC 2 cases with clinical stage, tumor size, treatment modalities (radiation therapy (RT) vs concurrent chemoradiation (CCRT)). Treatment outcomes including response to RT/CCRT, time to complete response (CR), patterns of treatment failure and survival outcomes were analyzed.

Results

A total of 423 patients with stages IIB-IVA (141 ACA: 282 SCC) were included. Most of the patients (about 60%) had stage IIB. The overall complete responses (CR) between ACA and SCC were 86.5% and 94.7%, respectively (p = 0.004). Median time to clinical CR from RT/CCRT of ACA were 2 months (0-5 months) compared with 1 month (0-4 months) for SCC (p = 0.001). Pelvic recurrence and distant failure were found in 2.1% and 14.9% in ACA, and corresponding with 3.9% and 15.6% in SCC. The 5-year overall survival rates of ACA compared to SCC were 59.9% and 61.7% (p = 0.191), respectively. When all prognostic factors are adjusted, clinical staging was the only factor that influenced overall survival.

Conclusion

ACA in locally advanced cervical cancer had poorer response rate from treatment and also used longer time to achieve CR than SCC. However, these effects were not determinants of survival outcomes.     

Acute effect of Russell's viper (Vipera russelli siamensis) venom on renal hemodynamics and autoregulation of blood flow in dogs

Renal hemodynamics and autoregulation of blood flow were investigated following intravenous injection of Russell's viper venom (0.1 mg/kg) in dogs anesthetized with sodium pentobarbital. After venom injection, the glomerular filtration rate fell significantly throughout the experimental period of three hr. Urine flow rate and renal blood flow also decreased and the filtered load of electrolytes declined significantly. The fractional excretion of sodium, potassium and phosphorus increased following venom administration. These data suggest that the venom may depress both glomerular and tubular functions. The renal autoregulation of blood flow was maintained during the experimental reduction of renal arterial pressure. We conclude that the ability of renal vasculature to autoregulate renal blood flow is not inhibited by Russell's viper venom, even though renal function is depressed.     

Effect of poly(lactide-co-glycolide) molecular weight on the release of dexamethasone sodium phosphate from microparticles

The objective of this study was to investigate the effect of poly(lactide-co-glycolide) (PLGA) molecular weight (Resomer RG 502H, RG 503H, and RG 504H) on the release behavior of dexamethasone sodium phosphate-loaded microparticles. The microparticles were prepared by three modifications of the solvent evaporation method (O/W-cosolvent, O/W-dispersion, and W/O/W-methods). The encapsulation efficiency of microparticles prepared by the cosolvent- and W/O/W-methods increased from approximately 50% to >90% upon addition of NaCl to the external aqueous phase, while the dispersion method resulted in lower encapsulation efficiencies. The release of dexamethasone sodium phosphate from PLGA microparticles (>50 microm) was biphasic. The initial burst release correlated well with the porosity of the microparticles, both of which increased with increasing polymer molecular weight (RG 504H > 503H > 502H). The burst was also dependent on the method of preparation and was in the order of dispersion method > WOW method > consolvent method. In contrast to the higher molecular weight PLGA microparticles, the release from RG 502H microparticles prepared by cosolvent method was not affected by volume of organic solvent (1.5-3.0 ml) and drug loading (4-13%). An initial burst of approximately 10% followed by a 5-week sustained release phase was obtained. Microparticles with a size <50 microm released in a triphasic manner; an initial burst was followed by a slow release phase and then by a second burst.     

Serotonin depletion, cortical spreading depression, and trigeminal nociception

BACKGROUND: The attack of migraine has been observed to be associated with low level of serotonin (5-HT). Although the mechanism underlying this relationship is still unclear, change in cortical excitability or susceptibility of trigeminal system is a possible explanation. Objectives: The aim was to study the effect of 5-HT depletion on the development of cortical spreading depression (CSD) and CSD-evoked trigeminal nociception. METHODS: Wistar rats were separated into low 5-HT and control groups (eight rats each). 5-HT was depleted by administration of para-chlorophenylalanine, a tryptophan hydroxylase inhibitor. CSD was induced by applying 3 mg of potassium chloride on parietal cortex. Cortical activity was monitored for 1 hour. Trigeminal nociception was determined using number of Fos-immunoreactive (Fos-IR) neurons in trigeminal nucleus caudalis as the indicator. RESULTS: Application of KCl led to the development of series of depolarization shift characteristics for CSD. The development of these CSD waves was enhanced in low 5-HT state. The area under curve of each CSD wave and the number of CSD waves occurring within 1 hour were greater in low 5-HT group. No significant change in peak amplitude and duration of CSD wave was observed. The numbers of Fos-IR cells on ipsilateral and contralateral trigeminal nucleus caudalis were significantly greater in the low 5-HT group than those of the controls. CONCLUSION: Our findings indicate that 5-HT depletion enhances CSD-induced trigeminal nociception by increasing the cortical excitability and sensitivity of trigeminal nociceptive system. These findings may provide a better understanding regarding the relationship between low 5-HT and clinical headaches.     

Assessment of the neurotoxicity of oral dihydroartemisinin in mice

High doses of the oil-soluble antimalarial artemisinin derivatives artemether and arteether, given by intramuscular injection to experimental mammals, produce an unusual pattern of selective damage to brainstem centres predominantly involved in auditory processing and vestibular reflexes. We have shown recently, in adult Swiss albino mice, that constant exposure either from depot intramuscular injection of oil-based artemisinin derivatives, or constant oral intake carries relatively greater neurotoxic potential than other methods of drug administration. Using the same model, oral dihydroartemisinin suspended in water was administered once or twice daily at different doses ranging from 50 to 300 mg/kg/day for 28 days. The neurotoxic potential of the oral dihydroartemisinin was assessed and compared to that of oral artemether and artesunate. Oral artemether, artesunate, and dihydroartemisinin had similar neurotoxic effects with no significant clinical or neuropathological evidence of toxicity at doses below 200 mg/kg/day. These data indicate that once and twice daily oral administration of artemether, artesunate and dihydroartemisinin is relatively safe when compared to intramuscular administration of the oil-based compounds.     

Laparoscopic radical nephrectomy: long-term outcomes

BACKGROUND: Although more than a decade of experience with laparoscopic radical nephrectomy indicates it is an alternative to open surgery for localized renal-cell carcinoma (RCC), the long-term oncologic effectiveness of this procedure remains to be established. MATERIALS AND METHODS: A thorough MEDLINE and PubMed literature research on long-term outcomes of laparoscopic radical nephrectomy was performed, and all pertinent articles were reviewed in detail. This review was formulated on the current cancer indication, the oncologic basis, the oncologic efficacy, and the longterm oncologic effectiveness of the procedure, including laparoscopic cytoreductive nephrectomy, with regard to metastasis, port-site tumor recurrence, and the relation to laparoscopic partial nephrectomy. Furthermore, the authors' previous report on the intermediate-term efficacy of laparoscopic radical nephrectomy was updated. RESULTS: With increasing experience, the indications for laparoscopic radical nephrectomy continue to expand. There were many reports of intermediate-term, two reports of long-term, and our up-to-date outcomes analyzing the management of localized RCC that showed effective cancer control with no statistically significant difference between laparoscopic and open radical nephrectomy in the true 5- and 10-year survival analysis. CONCLUSION: Long-term data, critical in the evaluation of any treatment for cancer, are currently available with respect to laparoscopic radical nephrectomy for localized RCC.     

N-acetyl serotonin derivatives as potent neuroprotectants for retinas

N-acetylserotonin (NAS) is synthesized from serotonin by arylalkylamine N-acetyltransferase (AANAT), which is predominantly expressed in the pineal gland and retina. NAS activates TrkB in a circadian manner and exhibits antidepressant effects in a TrkB-dependent manner. It also enhances neurogenesis in hippocampus in sleep-deprived mice. Here we report the identification of NAS derivatives that possess much more robust neurotrophic effects with improved pharmacokinetic profiles. The compound N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC) selectively activates TrkB receptor with greater potency than NAS. It potently protects retinas from light-induced retinal degeneration (LIRD), which is tightly coupled with pronounced TrkB activation in retinas. Pharmacokinetic studies demonstrate that this compound is stable in serum and liver microsomes. It can pass the blood-brain barrier and blood-retinal barrier. Hence, HIOC is a good lead compound for further drug development for treating retinal degenerative diseases.     

Suppression of RelB-mediated manganese superoxide dismutase expression reveals a primary mechanism for radiosensitization effect of 1alpha,25-dihydroxyvitamin D(3) in prostate cancer cells

Nuclear factor-kappaB provides an adaptive response to protect cancer cells against cytotoxicity induced by redox active therapeutics. RelB is uniquely expressed at a high level in prostate cancer with high Gleason scores. Recently, we showed that the level of RelB rapidly increases in androgen-independent prostate cancer cells after exposure to ionizing radiation (IR), leading to a reduction in intrinsic radiosensitivity. Here, we show that interaction of 1alpha,25-dihydroxyvitamin D(3) [1alpha,25-(OH)(2)D(3)] with the vitamin D receptor significantly enhances radiosensitivity of prostate cancer cells at clinically relevant radiation doses. The radiosensitization effect of 1alpha,25-(OH)(2)D(3) is mediated, at least in part, by selectively suppressing IR-mediated RelB activation, leading to a reduced expression of its target gene MnSOD, a primary antioxidant enzyme in mitochondria. These results suggest that suppression of manganese superoxide dismutase is a mechanism by which 1alpha,25-(OH)(2)D(3) exerts its radiosensitization effect and that 1alpha,25-(OH)(2)D(3) may serve as an effective pharmacologic agent for selectively sensitizing prostate cancer cells to IR via suppression of antioxidant responses in mitochondria.