Genetic Risk Factors Associated With Antiemetic Efficacy of Palonosetron,Aprepitant, and Dexamethasone in Japanese Breast Cancer Patients Treated With Anthracycline-based Chemotherapy

Introduction

Breast cancer patients often receive anthracycline-based chemotherapy, and chemotherapy-induced nausea and vomiting (CINV) remains one of the most uncomfortable and distressing adverse reactions. Poor control of CINV reduces the relative dose intensity of chemotherapy agents, which has been associated with poor clinical outcomes and shorter survival. The aim of the present study was to identify genetic risk factors associated with anthracycline-based CINV.

Area-specific substratification of deep layer neurons in the rat cortex

Gene markers are useful tools to identify cell types for fine mapping of neuronal circuits. Here we report area‐specific sublamina structure of the rat cerebral cortex using cholecystokinin (cck) and purkinje cell protein4 (pcp4) mRNAs as the markers for excitatory neuron subtypes in layers 5 and 6. We found a segregated expression, especially pronounced in layer 6, where corticothalamic and corticocortical projecting neurons reside. To examine the relationship between gene expression and projection target, we injected retrograde tracers into several thalamic subnuclei, ventral posterior (VP), posterior (PO), mediodorsal (MD), medial and lateral geniculate nuclei (MGN and LGN); as well as into two cortical areas (M1 and V1). This combination of tracer‐in situ hybridization (ISH) experiments revealed that corticocortical neurons predominantly express cck and corticothalamic neurons predominantly express pcp4 mRNAs in all areas tested. In general, cck(+) and pcp4(+) cells occupied the upper and lower compartment of layer 6a, respectively. However, the sublaminar distribution and the relative abundance of cck(+) and pcp4(+) cells were quite distinctive across areas. For example, layer 6 of the prelimbic cortex was almost devoid of cck(+) neurons, and was occupied instead by corticothalamic pcp4(+) neurons. In the lateral areas, such as S2, there was an additional layer of cck(+) cells positioned below the pcp4(+) compartment. The claustrum, which has a tight relationship with the cortex, mostly consisted of cck(+)/pcp4(?) cells. In summary, the combination of gene markers and retrograde tracers revealed a distinct sublaminar organization, with conspicuous cross‐area variation in the arrangement and relative density of corticothalamic connections. J. Comp. Neurol. 520:3553–3573, 2012. © 2012 Wiley Periodicals, Inc.     

Phase I/II study of docetaxel and S-1 in patients with advanced gastric cancer

The aims of this phase I/II study of docetaxel and S-1 were to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and recommended dose (RD) in the phase I part and to explore the tumour response, survival and safety in the phase II part. Patients with histologically- or cytologically confirmed unresectable or recurrent gastric cancer were eligible. Treatment consisted of intravenous docetaxel on day 1 (starting dose 50 mg m(-2)) and oral S-1 at a fixed dose of 40 mg m(-2) twice daily on days 1-14, every 4 weeks up to six cycles. Nine patients took part in the phase I portion of the study. The MTD of docetaxel was determined to be 50 mg m(-2), with the DLTs of grade 3 infection associated with grade 3 neutropenia and grade 4 neutropenia during S-1 administration. The RD of docetaxel was 40 mg m(-2) in combination with S-1 40 mg m(-2) b.i.d. The efficacy and safety of this regimen was therefore assessed in 46 patients with at least one measurable lesion. The overall response rate and estimated median overall survival were 46% (95% CI, 31-61%) and 14.0 months (8.3-17.3 months), respectively. The most common grade 3/4 toxicity was neutropenia (67% of patients), which was predictable and manageable. This regimen showed promising activity with moderate toxicities in advanced gastric cancer.     

Age-related changes in the interactive mobility of the hip and knee joints: a geometrical analysis

This study examined any systematic age-related change in the passive range of motion (PROM) of the hip and knee joints. Seventy-seven healthy male volunteers ranging in age from 15 to 73 years were assessed. A geometrical range of motion (ROM) analysis was applied, which could evaluate the effects of both monoarticular and biarticular muscles. The PROM of the hip joint decreased progressively with advancing age, whereas that of the knee joint remained unchanged. In addition, the interactive PROM of the hip and knee joint associated with biarticular rectus femoris and hamstring muscles also showed an age-related reduction. The progressive reduction of the ROM is probably caused by shortening of muscles or connective tissues due to reduced compliance of joint structures and degenerative changes in spinal alignment, as well as by diminished muscle stretching resulting from a decrease in daily physical activities with advancing age.     

Glycosaminoglycan and collagen distribution in the developing human vitreous

· Background: We determined the distribution of glycosaminoglycans and collagens in the developing human vitreous. · Methods: Eighty human eyes from 5 gestational weeks to 2 postnatal years of age were used. Glycosaminoglycan components were determined by enzyme digestion with hyaluronidase or chondroitinase AC and ABC and immunohistochemistry for chondroitin, chondroitin-4-sulfate, chondroitin-6-sulfate, and dermatan sulfate. Collagen distribution was determined by immunohistochemistry for types I, II, and III collagens. · Results: Enzyme digestion showed that throughout development hyaluronic acid is the main glycosaminoglycan in the vitreous and in the extraocular space at 5–7 gestational weeks. Both areas were filled with mesenchymal cells. Immunohistochemistry showed chondroitin-6-sulfate in the vitreous between 6 and 40 gestational weeks, and chondroitin-4-sulfate between 12 and 40 gestational weeks. Hyaluronic acid and chondroitin sulfate appeared in the retina and around the hyaloid vessels at 12–40 weeks. Immunohistochemistry showed type III collagen in the vitreous and around the mesenchymal cells at 5–7 weeks that was replaced by type II collagen after 8 weeks. · Conclusions: Hyaluronic acid is the major glycosaminoglycan in the vitreous throughout development, except for the transient appearance of chondroitin sulfate at 6–40 gestational weeks. Type III is the main collagen in the early developing vitreous that converts to type II collagen at 8 weeks. The primary and secondary vitreous has the same components as these macromolecules. These vitreous glycosaminoglycans and collagens seem to be produced by mesenchymal cells at an early stage and by the retina and hyaloid vessels during middle and late development. Received: 7 November 1997 Revised version received: 5 January 1998 Accepted: 7 January 1998     

Application of PDT for Uterine Cervical Cancer

We have been performing PDT using Excimer Dye Laser (EDL) or YAG-OPO laser, a type of low power laser, both of which have a considerably higher degree of tissue penetration even when compared to PDT using Argon Dye Laser (ADL).PDT is a relatively simple procedure without any bleeding and does not require anesthesia since it causes no pain. PDT is performed 48 h after intravenous injection of 1.5-2.0 mg/kg of PHE (Photofrin((R))). Precise spot irradiation is possible using a colposcope with an optical laser path. We also use a cervical probe which enables photoirradiation of the entire cervical canal.We have performed PDT on 131 cases (95 CIS, 31 dysplasia, 1 vulval dysplasia (VIN), 3 squamous cell carcinoma, microinvasion, and 1 CIS + endocervical adenocarcinoma, microinvasion). Of these cases, 127 became CR (96.9%). The first CR case was 10 years ago and no recurrence has been observed yet.PDT is extremely effective to preserve fertility. Except for sensitive reactions to sunlight, there are no noticeable side effects or difficulties related to pregnancy or delivery. We expect that in the near future PDT will be performed using diode lasers and without hospitalization due to new photosensitizers which have shorter retention times.     

Serum placental alkaline phosphatase (PLAP) in gynecologic malignancies--with special reference to the combination of PLAP and CA54/61 assay

Serum placental alkaline phosphatase (PLAP) levels in patients with gynecological tumors were measured by two kinds of enzyme-antigen immunoassay kits provided by Innogenetics (PLAP-I) and Sangtec Medical (PLAP-S), and the combination assays for PLAP with other tumor markers were studied. None of the healthy women studied were PLAP positive, and the positive rate in patients with benign ovarian tumors was less than 6%. The positive rate in patients with ovarian cancers was about 35%, which was higher than the rates for other cancers. It was significantly higher in patients with ovarian serous cystadenocarcinoma (60%). Remarkably high PLAP-I values were observed in patients with dysgerminoma. By the combination assay for PLAP with CA54/61 antigen in ovarian cancers, the diagnostic efficiency increased compared with that for PLAP and CA125. We conclude that PLAP is useful in the diagnosis of ovarian serous cystadenocarcinoma and dysgerminoma and that CA54/61 is the better partner for the combination assay.     

Anti-cyclic citrullinated peptide antibody in the cerebrospinal fluid in patients with rheumatoid arthritis who have central nervous system involvement

Clinical Rheumatology - Central nervous system (CNS) involvement, including encephalopathy, encephalitis, leptomeningitis, and pachymeningitis, in rheumatoid arthritis (RA) is rather rare. We...     

Renal cyst puncture under ultrasound guidance: complications of ethanol injection

Under ultrasound guidance, we treated 25 cases of renal cyst with 99% ethanol instillation to prevent the recurrence of this disease from January 1985 to June 1987. Patients' age was from 17 to 85 years old with the average age of 63 years. Twelve cases were men, and 13 cases were women. Among the 25 cases, eleven were asymptomatic and 14 showed clinical features of lumbago, microhematuria, hypertension or proteinuria. The aspirated site was the right side in 9, left side in 14 and bilateral kidneys in 2 cases. Subsequently, cyst puncture was carried out 27 times. We encountered 12 complications following puncture. These complications were derived from the puncture itself or caused by the ethanol instillation. Flank pain caused by the injection of ethanol, nausea, causalgia or a feeling of drunkenness appeared immediately after the inoculation procedure. However, no serious complications such as pneumothorax, perirenal hematoma or infection were recognized. Some complications arose in 7 cases of 9 examples (77.8%) following more than 50 ml of ethanol injection, but the complications were observed in only 5 cases of 18 examples (22.8%) following less than 50 ml of administration. Based on these findings, ethanol injection in renal cysts appears to be useful for the treatment of this disease. In case of huge cysts when more than 50 ml of ethanol, is instilled the case should be followed up carefully after the instillation procedure.