Takashi Hatano

Incidence of bone fracture in patients receiving luteinizing hormone-releasing hormone agonists for prostate cancer

Objective To investigate the incidence of bone fractures in patients receiving luteinizing hormone‐releasing hormone agonists (LHRH‐a) for prostate cancer (in whom a continued low testosterone level after the long‐term administration of these drugs reduces bone mineral density), and thus determine the risk of secondary osteoporosis.

Cytotoxic effect of the protein-doxorubicin conjugates on the multidrug-resistant human myelogenous leukemia cell line, K562, in vitro

In vitro studies were performed to examine the antitumor effect of protein-doxorubicin (DXR) conjugate on the growth of the multidrug-resistant human chronic myelogenous leukemia cell line, K562/DXR. The 50% inhibitory concentration (IC50) for DXR in the K562/DXR cell line was 20 nM (in the K562 parental cell line, IC50 was 3.2 nM). Treatment of both types of cells with various concentrations of DXR or conjugates at equivalent concentrations of DXR was carried out. One type of the conjugates used was human serum albumin (HSA)-DXR conjugate and human transferrin (Tf)-DXR conjugate via a glutaraldehyde bridge (HSA-ga-DXR, Tf-ga-DXR, respectively) and another type used was HSA-DXR conjugate with a dextran bridge (HSA-dex-DXR). All of these conjugates showed potent dose-dependent inhibition of cell growth against the K562/DXR cells as compared with the cells treated with DXR or other controls. IC50 for HSA-ga-DXR, Tf-ga-DXR and HSA-dex-DXR conjugates in the K562/DXR cell line was 2.4, 3.6 and 1.0 (equivalent DXR) nM, respectively, which were approximately similar to the value of the K562 treated with DXR. Through the treatment of K562/DXR cells with HSA-DXR conjugate, the intracellular drug concentration increased as a function of time up to 24 h compared with the cells treated with DXR. Intracellular DXR effluxed rapidly from K562/DXR cells, but HSA-ga-DXR as well as HSA-dex-DXR conjugates remained in the cells at a relatively high concentration for a long time. These results indicate that it may be possible to overcome multidrug resistance by chemically modifying DXR, such as by conjugation of the drug with proteins.

Clear cell carcinoma of the human ovary synthesizes and secretes a transferrin with microheterogeneity of lectin affinity.

Human ovarian clear cell carcinoma cell line (transferrin (Tf)‐non‐producer), HAC 2, cells were adapted to grow in chemically defined synthetic medium when the cells were cultured with medium containing 10 of insulin at least for 6 months. They synthesized and secreted constantly the 80 kDa protein immunologically similar to human serum Tf(15 ± 12 /107 cells/3 days). By sensitive lectin‐affinity electrophoresis followed by antibody‐affinity blotting technique, a concanavalin A weakly bound or unbound, lentil lectin, a strongly reactive abnormal band, which was rarely found in human serum Tf, was detectable in the Tf synthesized by HAC 2 cells (HACTf). These findings suggest that the HACTf may act as one of the autocrine growth factors and that this heterogeneity of HACTf for lectin affinity is ascribed to differences in the carbohydrate moiety of the Tf.

Case of gonadoblastoma in a 9‐year‐old boy without physical abnormalities

Background: A 9‐year‐old boy was admitted to Jikei University Hospital complaining of gradual enlarging of the left scrotal contents.

Growth of a human yolk sac tumor cell line with yolk sac-derived functions in selenium-supplemented chemically defined synthetic medium.

SummaryA human yolk sac tumor cell line, TG1, which was established from a testicular yolk sac tumor, was found to replicate continuously in a chemically defined medium supplemented with Na2SeO3 (ISRPMI). TG1 produced several plasma proteins and growth factors: albumin, alpha-fetoprotein (AFP), ferritin, carcinoembryonic antigen, beta-2-microglobulin, polyamine, neuron specific enolase, tissue polypeptide antigen, transferrin (Tf), epidermal growth factor, and platelet derived growth factor. By analysis of lectin (LcHA)-affinity electrophoresis, to examine the microheterogeneity of carbohydrate chains of synthetic glycoproteins, TG1 cells cultured with ISRPMI produced only LcHA reactive Tf and AFP based on core fucose attached to asparagine-linkedN-acetylglucosamine residues instead of LcHA-nonreactive Tf and AFP produced by TG1 cells cultured with fetal bovine serum (FBS)-containing medium.α1-6 Fucosyltransferase activity was significantly greater in the TG1 cells cultured with ISRPMI (39.9±1.5 pmol · h−1 · mg−1 protein) than cultured with FBS-containing media (18.2±1.2 pmol · h−1 · mg−1 protein). These results have indicated that the selective increase ofα1-6 fucosyltransferase occurred when the cells were cultured with the FBS-free synthetic media.

Effect of everolimus treatment for renal angiomyolipoma associated with tuberous sclerosis complex: an evaluation based on tumor density

BackgroundThe aim of this study was to evaluate the influence of components of angiomyolipoma (AML) on the efficacy of everolimus.MethodsWe investigated a total of 40 patients with tuberous sclerosis complex (TSC) who had AML ≥4xa0cm in diameter. The components of the AML were determined using abdominal computed tomography (CT) images. The AML density was measured as the mean Hounsfield unit (HU) values of the whole area of the AML on axial CT images. We classified them into two groups, i.e., a lipid group with a predominant lipid component (HUxa0≤xa0−50) and a solid group with predominant vascular and muscle components (HUxa0≥30). For each patient, we measured the AML reduction rate and transition of the mean HU value.ResultsThe mean reduction rate of AML in the lipid group was 24%, whereas it was 68% in the solid group (Pxa0<xa00.001). The mean tumor density after 6xa0months was decreased in both groups. In particular, the density significantly decreased compared to the baseline in the solid group (Pxa0<xa00.001). The tumor density did not change after 6xa0months in either group.ConclusionThe effect of everolimus on TSC–AML is mainly a reduction of the solid components consisting of angioma and leiomyoma. The tumor density at the start of treatment might be a predictive marker for the response to everolimus in TSC–AML.

Shrinkage of Prostate Volume in Sunitinib-treated Patients with Renal Cell Carcinoma

Sunitinib is widely used to treat patients with advanced renal cell carcinoma; however, its influences on the prostate volume and lower urinary tract symptoms remain unclear. To investigate the influence of sunitinib on clinical findings of urinary tract, we recruited a total of 20 male patients with advanced renal cell carcinoma who are treated with sunitinib. We evaluated clinical findings during clinical visits over 24 weeks: International Prostate Symptom Score, urine flow rate, residual urine volume, serum prostate-specific antigen level and prostate volume. Residual urine and prostate volumes were significantly decreased at Week 24. The residual urine volume was especially decreased in patients with a high residual volume at baseline. No differences were observed in the International Prostate Symptom Score total score, International Prostate Symptom Score quality of life score, maximal urinary flow rate or prostate-specific antigen level. We observed a reduction in prostate volume and an improvement in urinary symptoms through relief from urinary tract obstruction during sunitinib treatment. Careful attention to urinary functions and drug dose adjustment seems to be necessary in patients with comorbid benign prostatic hyperplasia or dysuria.

Effect of everolimus treatment for regrown renal angiomyolipoma associated with tuberous sclerosis complex after transcatheter arterial embolization

BackgroundThe aim of this study was to evaluate the effects and the utility of second-line everolimus treatment for regrown renal angiomyolipoma (AML) with tuberous sclerosis complex (TSC) after transcatheter arterial embolization (TAE).MethodsWe investigated a total of 14 patients who underwent second-line everolimus treatment for TSC–AML that regrew after TAE, and assessed their effects and adverse events. Everolimus treatment was performed for AML with a maximum diameter of 4xa0cm. To determine the reduction ratio of AML, the volume of AML was measured using multislice helical computed tomography. Adverse events were evaluated according to CTCAE v4.0-JCOG. We further compared the treatment effect and adverse events with those in patients receiving first-line everolimus treatment.ResultsThe AML volume decreased in all patients, with au2009≥u200950% volume decrease in 57% (8 of 14) of the cases, and the mean reduction rate was 53%. We observed no significant difference in the mean reduction rate of AML between second-line everolimus treatment for regrown TSC–AML after TAE and first-line everolimus treatment for TSC–AML. The adverse events were mild and consistent with those reported in our previous study.ConclusionAlthough further studies are needed, everolimus appears to be effective as second-line treatment for TSC–AML that regrew after TAE and a beneficial treatment option for TSC–AML.

スニチニブ不応であったpapillary type2の転移性腎癌に対しsecond lineのアキシチニブ投与が奏功を示した一例

According to previous studies, papillary renal cell carcinoma (pRCC) type 2 is known to have a poor prognosis, especially in cases with metastases. We report a case of pRCC that responded well to axitinib administered as second line therapy. The patient was a 52-year-old woman who presented at our hospital with an incidental tumor on the left kidney. She underwent laparoscopic radical nephrectomy, and the pathological diagnosis was pRCC type 2, grade 3 pT1b. Multiple lung and bone metastases were observed following the four months, and histological findings of lung metastases was metastatic RCC. Although sunitinib was administered as first line therapy, tumor progression was observed after the first cycle of treatment. Therefore, axitinib (10 mg/day) was administrated as second-line therapy and was gradually increased to 14 mg/day. Five months after the administration of axitinib, the maximum tumor diameter of the lung metastases reduced by 83%. At present, eight months have passed since the start of axtinib administration, but the response was still maintained and the adverse events were generally tolerable.

A clinical study of secondary osteoporosis induced by endocrine therapy for prostate cancer

PURPOSEnThere is one of the big problems that endocrine therapy for prostate cancer causes to induce secondary osteoporosis. The risk factors and future treatments for osteoporosis were investigated.nnnMATERIALS AND METHODSn31 patients treated with luteinizing hormone releasing hormone agonists (LHRH-a) or combination of chlormadinone acetate (CMA) and LHRH-a, and 19 patients with no treatments for prostate cancer were included in the analysis. Lumber spine bone mineral density (BMD) was measured by quantitative computed tomography.nnnRESULTSnAging had much influence on decreases of BMD than the other risk factors (p < 0.01). There were statistically decreases of BMD in the patients with CMA + LHRH-a compared with no treatments (p < 0.05). Adrenal androgen which had an important role of maintenance in BMD was statistically decreased by the administration of CMA (p < 0.01).nnnCONCLUSIONSnMeasurement of BMD before endocrine therapy is necessary for the patients with prostate cancer. It is important for the patients with decreases of BMD that CMA is not combined or the therapy for osteoporosis is preventively employed.