A phase II study of combination chemotherapy using docetaxel and irinotecan for TC-refractory or TC-resistant ovarian carcinomas (GOGO-OV2 study) and for primary clear or mucinous ovarian carcinomas (GOGO-OV3 Study)

Objective

To analyze the efficacy and safety of combination chemotherapy of docetaxel and irinotecan for paclitaxel and carboplatin (TC) -refractory or -resistant ovarian carcinomas and for first treatment of primary clear cell and mucinous ovarian carcinomas.

Study design

Between 2002 and 2009, we conducted a prospective Phase II study of the efficacy and safety of combination chemotherapy using docetaxel and irinotecan in 62 patients with TC-refractory or -resistant ovarian carcinoma cases (GOGO-OV2) and 15 patients with primary clear cell and mucinous ovarian carcinoma cases (GOGO-OV3). The dose of docetaxel and irinotecan was determined during our previous Phase I study.

Results

A docetaxel plus irinotecan regimen provided a 53% response rate, 6 months progression-free survival (PFS), and 12 months overall survival (OS) for primary clear cell and mucinous ovarian carcinomas (similar to TC therapy). The differences of anti-tumor and survival effects between refractory and resistant cases were not statistically significant. The regimen also provided a 15% response rate, 5 months PFS, and 15 months OS for TC-refractory or TC-resistant cases, when used as a second-line chemotherapy. These data are similar to previous reports, however, our study provides the first data exclusively for the cases refractory or resistant to a gold standard TC therapy as a second-line chemotherapy. The regimen was demonstrated to be well tolerable.

Conclusion

Combination chemotherapy of docetaxel and irinotecan may be a useful option to treat TC-refractory/resistant cases and primary clear cell and mucinous adenocarcinoma cases of ovarian carcinoma.     

Reduction of oligodendrocyte myelin glycoprotein expression following facial nerve transection

Oligodendrocyte myelin glycoprotein (OMgp) has been thought to be expressed in the oligodendrocytes and inhibit the regeneration of the nerves by binding to the Nogo receptor expressed in neurons in the central nervous system (CNS). However, OMgp is expressed in the CNS in the neurons as well as oligodendrocytes. In order to help understanding the physiological role of neuronal OMgp, we examined the change of OMgp expression in the facial nucleus after the facial nerve transection. Real-time RT-PCR and Western blot analysis showed a down-regulation of OMgp expression in the facial nucleus 5-7 (mRNA) or 5-14 (protein) days after transection. Thereafter, expression of OMgp returned to the control level at 28 days after axotomy. Subsequent analysis using in situ hybridization histochemistry and immunohistochemistry established that the decrease of OMgp expression was attributable to the expression in facial motoneurons, but not in oligodendrocytes. These findings suggest a possibility that the change of neuronal OMgp expression might be involved in reconnection of neural circuit between axotomized facial neuron and upper motor neuron after transection.     

Wavelength Specificity of Photoparoxysmal Responses in Idiopathic Generalized Epilepsy

Summary: Using optic filters, we analyzed the wavelength specificity of photoparoxysmal responses (PPR) in photosensitive patients with idiopathic generalized epilepsy (ICE). We specified the wavelength spectrum ∼700 nm (660–720 nm) as the only visible spectrum essential for eliciting PPR in some normal trichromat IGE patients and showed that any flashing lights containing this essential wavelength spectrum could elicit PPR independent of the number of stimulated cones. Absorption of the wavelength spectrum -700 nm by optic filters eliminated PPR in normal trichromat ICE patients. In an IGE patient with deuteranomaly, intermittent flashing lights containing a part of the wavelength spectrum from 580 to 700 nm elicited PPR. These data suggest a new interpretation of wavelength specificity of PPR: Flashing lights containing the wavelength spectrum that does not produce antagonistic cone interactions at the level of retinal ganglion cells can elicit PPR in some photosensitive ICE patients.     

Andrology: Acrosome reaction induced in a limited population of human spermatozoa by progesterone (Ca2+-dependent) and ATP (Ca2+-independent)

We examined the kinetics of the acrosome reaction induced inhuman spermatozoa by progesterone (Ca²⁺-dependent) and adenosine5'-triphosphate (ATP; Ca²⁺-independent). ATP and progesteronedid not induce the acrosome reaction unless spermatozoa wereincubated in a capacitation medium. ATP exhibited a constantinduction of the acrosome reaction regardless of the incubationperiod, while progesterone began to induce the acrosome reactionafter >6 h of incubation. At 24 h of incubation, the percentagesof spermatozoa in which the acrosome reaction had been inducedby both progesterone and ATP were almost equal. To determinewhether a limited population of human spermatozoa was reactiveto both progesterone and ATP, we employed an MH61 bead bindingmethod. When the acrosome-reacted spermatozoa were removed withMH61 beads, their percentage in the sperm suspension was decreasedto <3%. At 24 h of incubation, progesterone and ATP inducedthe acrosome reaction in 12.0 and 10.0% of spermatozoa, respectively.After MH61 bead binding was performed, the remaining spermatozoadid not react to the other activator (progesterone -> ATP,ATP -> progesterone). These findings indicate that only alimited population of human spermatozoa has the potential toundergo the acrosome reaction when stimulated by both progesteroneand ATP.     

Endoscopic complete removal of the histologically unconfirmed gastric cancer with massive invasion as a giant biopsy

A 68-year-old man underwent upper GI endoscopy in a mass screening, which showed a suspicious tumor in the antral region of stomach. However, histologic examination of repeated endoscopic biopsy samples (15 samples) revealed no neoplastic change. Although all the examinations including endoscopy, endosonography, and barium study pointed to the diagnosis of gastric cancer, we did not have histologic evidence of malignancy. Hence, complete endoscopic removal of the lesion using a new method of endoscopic mucosal resection (EMR) was performed as a giant biopsy. Histologic assessment of the endoscopically resected specimen confirmed invasive adenocarcinoma of the stomach. He then underwent distal gastrectomy with regional lymphadenectomy. Endoscopic resection of the tumor in the digestive tract is also a very useful diagnostic modality of the lesion when malignancy cannot be revealed by endoscopic biopsy.     

Strip meniscometry: a new and simple method of tear meniscus evaluation

PURPOSE: To investigate the applicability and efficacy of a new and simple method of quantification of the volume of tear meniscus, termed "strip meniscometry," in the diagnosis of the dry eye syndromes in a prospective controlled study. METHODS: One hundred eyes of 50 patients with dry eye (19 males; 31 females) aged between 18 and 76 years (mean, 54.3 years), as well as 80 eyes of 40 normal subjects aged from 15 to 70 years (mean, 50.8 years; 12 males, 28 females) were recruited in this study. The patients and the control subjects underwent strip meniscometry for 5 seconds, tear film lipid layer interferometry, tear film break-up time measurement, and ocular surface vital staining with fluorescein and rose bengal dyes and the Schirmer-1 test. RESULTS: Strip meniscometry scores correlated with tear quantity and stability, ocular surface staining scores, and lipid layer interferometry grades and improved after 2 weeks of punctal plug occlusion. CONCLUSIONS: Strip meniscometry is a swift, noninvasive, promising new method that is expected to find application in the diagnosis and evaluation of the outcome of treatment of dry eye syndromes.