Persistent sciatic artery aneurysm associated with the development of angiosarcoma: a case report

Persistent sciatic artery (PSA) is a very rare, but clinically significant, congenital anomaly. PSA is known to undergo aneurysmal formation; however, there have been no previous reports of a soft-tissue sarcoma arising from a PSA. We describe a 79-year-old woman with a 10 year history of a slowly growing mass on her right buttock. Physical examination revealed a painful, firm, pulsatile mass with a maximum diameter of 13 cm. Computed tomography angiography revealed that the mass arose from the PSA. We successfully excised the mass lesion with no postoperative circulatory disturbances. The final pathological diagnosis was aneurysmal PSA that focally developed secondary angiosarcoma.     

Effects of flavoxate hydrochloride on voltage-dependent Ba<Superscript>2+</Superscript> currents in human detrusor myocytes at different experimental temperatures

The inhibitory effects of flavoxate hydrochloride (piperidinoethyl-3-methylflavone-8-carboxylate; hereafter referred as flavoxate) on voltage-dependent nifedipine-sensitive inward Ba²⁺ currents (I _Ba) in human detrusor myocytes were investigated at different temperatures using conventional whole-cell patch-clamp techniques. When the bath-solution temperature was increased from 22°C to 30°C, I _Ba peak amplitude was enhanced by approximately twice at several test potentials. Neither the I _Ba threshold nor the membrane potentials for the I _Ba maximum peak amplitude was affected by the temperature change. The concentration-response curves of flavoxate at both 30°C (K _i  = 5.1 μM) and 37°C (K _i  = 4.6 μM) were slightly shifted to the left in comparison with that at 22°C (K _i  = 10.3 μM). Similar results were also obtained in the presence of nifedipine (K _i  = 14 nM at 22°C vs. K _i  = 2.5 nM at 30°C and K _i  = 2.1 nM at 37°C). Altering the bath-solution temperature from 22°C to 30°C shifted the steady-state inactivation curve of I _Ba at −90 mV to the left. At 30°C, the steady-state inactivation curve of I _Ba in the presence of flavoxate was also shifted to the left in comparison with that in the absence of flavoxate. Either 3-isobutyl-1-methylxanthine (IBMX) or theophylline, a phosphodiesterase inhibitor, caused little effects on I _Ba, although cyclic nucleotides (dibutyryl cAMP and 8-Br-cGMP) inhibited I _Ba. These results suggest that the inhibitory actions of flavoxate on I _Ba in human detrusor myocytes were slightly changed at different experimental temperatures and that flavoxate directly blocked voltage-dependent L-type Ca²⁺ channels, not through the inhibition of phosphodiesterase activity pathway.     

The roles of copper transporters in cisplatin resistance

Platinum-based antitumor agents have been effective in the treatments of many human malignancies but the ultimate success of these agents is often compromised by development of drug resistance. One mechanism associated with resistance to platinum drugs is reduced intracellular accumulation owing to impaired drug intake, enhanced outward transport, or both. Mechanisms for transporting platinum drugs were not known until recent demonstrations that import and export transporters involved in maintenance copper homeostasis are also involved in the transport of these drugs. Ctr1, the major copper influx transporter, has been convincingly demonstrated to transport cisplatin and its analogues, carboplatin, and oxaliplatin. Evidence also suggests that the two copper efflux transporters ATP7A and ATP7B regulate the efflux of cisplatin. These observations are intriguing, because conventional thinking of the inorganic physiologic chemistry of cisplatin and copper is quite different. Hence, understanding the underlying mechanistic aspects of these transporters is critically important. While the mechanisms by which hCtr1, ATP7A and ATP7B transport copper ions have been studied extensively, very little is known about the mechanisms by which these transporters shuffle platinum-based antitumor agents. This review discusses the identification of copper transporters as platinum drug transporters, the structural-functional and mechanistic aspects of these transporters, the mechanisms that regulate their expression, and future research directions that may eventually lead to improved efficacy of platinum-based-based drugs in cancer chemotherapy through modulation of their transporters’ activities.     

DNA index as a significant indicator of lymph node metastasis and local recurrence of rectal cancer

To confirm the prognostic significance of the DNA index (DI) in cases of rectal cancer, the nuclear DNA content of tumor cells was examined in 184 cases of rectal cancer treated with curative surgery, and the incidence of lymph node metastasis and recurrence of the cancer was analyzed. The incidence of lymph node metastasis was 43.9 percent in cases with aneuploidy (DI above 1.5), being statistically different from the 18.0 percent incidence in cases with diploidy (P <0.001). Although the extent of lymph node metastasis was limited to adjacent lymph nodes in cases with diploidy, distant lymph node metastases were frequent in cases with aneuploidy, especially in those with a DI above 1.5. Furthermore, the incidence of recurrence of cancer, and especially of local recurrence, was significantly higher (P <0.001) in cases with aneuploidy (DI above 1.5) than in cases with diploidy and aneuploidy (DI below 1.4). These findings indicate the significant value of the DNA index for the prediction of lymph node metastasis and local recurrence in patients with rectal cancer.     

Antiactin-targeted immunoliposomes ameliorate tissue plasminogen activator-induced hemorrhage after focal embolic stroke.

Thrombolytic stroke therapy with tissue plasminogen activator (tPA) is limited by serious risks of intracerebral hemorrhage. In this study, the authors show that a novel antiactin-targeted immunoliposome significantly reduced tPA-induced hemorrhage in an established rat model of embolic focal stroke. Spontaneously hypertensive rats were subjected to focal ischemia using homologous blood clot emboli. Delayed administration of tPA (10 mg/kg, 6 hours after ischemia) induced intracerebral hemorrhage at 24 hours. In control rats treated with tPA plus vehicle, hemorrhage volumes were 9.0 +/- 2.4 uL (n = 7). In rats treated with tPA plus antiactin immunoliposomes, hemorrhage volumes were significantly reduced to 4.8 +/- 2.7 uL (n = 8, P < 0.05). No significant effects were seen when rats were treated with tPA plus a nontargeted liposome (7.8 +/- 2.1 uL, n = 9). Fluorescent immunohistochemistry showed that rhodamine-labeled targeted liposomes colocalized with vascular structures in ischemic brain that stained positive for endothelial barrier antigen, a marker of cerebral endothelial cells. These data suggest that immunoliposomes may ameliorate vascular membrane damage and reduce hemorrhagic transformation after thrombolytic therapy in cerebral ischemia.