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Biomedical subjects

N Shinohara

Publications and source records attributed to N Shinohara.

At least 91 records · Page 5Linked to original sources

Osteosarcoma versus malignant fibrous histiocytoma of bone in patients older than 40 years. A clinicopathologic and immunohistochemical analysis with special reference to malignant fibrous histiocytoma-like osteosarcoma.

BACKGROUND: It is often difficult to discriminate between osteosarcoma and malignant fibrous histiocytoma (MFH) of bone, especially in older patients because of the clinical similarities, including the lytic radiologic appearance. A histologic analysis of MFH-like osteosarcoma, which closely resembles MFH of bone both clinically and radiologically, has not yet been conducted thoroughly, and therefore this issue remains controversial. METHODS: Using clinicopathologic and immunohistochemical techniques, the authors studied 24 cases of osteosarcoma arising in patients older than 40 years of age and compared them with 20 cases of MFH of bone from similarly aged patients. RESULTS: Radiography revealed that 68.2% of the osteosarcoma cases were predominantly lytic, whereas all cases of MFH of bone showed either a predominantly or purely lytic pattern. Histologically, osteosarcoma was subclassified as conventional osteoblastic (54.2%), MFH-like (29.2%) containing various amounts of tumor osteoid and/or bone in each of the cases, and conventional fibroblastic (4.2%), whereas all the cases of MFH of bone had a storiform-pleomorphic pattern. Immunohistochemically, no overexpression of p53 protein was found in MFH-like osteosarcoma, whereas it tended to occur more frequently in osteoblastic osteosarcoma (66.7%) and MFH of bone (50.0%). The Ki-67 labeling index was significantly lower in MFH-like osteosarcoma than in MFH of bone. The 5-year survival rate was 18.2% in patients with osteoblastic osteosarcoma, 66.7% in patients with MFH-like osteosarcoma, and 21.5% in patients with MFH of bone. A significant difference in the survival curve was observed between osteoblastic and MFH-like osteosarcoma. CONCLUSIONS: It is proposed that MFH-like osteosarcoma, which shows characteristically different clinical and histologic features from that of conventional osteosarcoma, thus may be considered a variant of osteosarcoma.

Adult↗

Gelsolin: a candidate for suppressor of human bladder cancer.

Human transitional cell carcinomas of the bladder frequently reveal chromosomal abnormalities that span a range between chromosome 9p12 and 9qter, even at early stages of bladder carcinogenesis. Because the gene that encodes an actin-regulatory protein, gelsolin, is localized in chromosome 9q33, we examined the expression of gelsolin in a number of human bladder cancer cell lines and tissues. In all 6 cell lines and in 14 of the 18 tumor tissues (77.8%), gelsolin expression was undetectable or extremely low in comparison with its expression in normal bladder epithelial cells. Furthermore, upon the introduction of the exogenous human or mouse authentic gelsolin cDNA into a human bladder cancer cell line, UMUC-2, gelsolin transfectants of UMUC-2 greatly reduced the colony-forming ability and the tumorigenicity in vivo. These results suggest that gelsolin plays a key role as a tumor suppressor in human urinary bladder carcinogenesis.

Base Sequence↗

The role of MR imaging in the diagnosis of alveolar soft part sarcoma: a report of 10 cases.

OBJECTIVE: The objective of this study was to analyze the characteristics of alveolar soft part sarcoma using magnetic resonance imaging (MRI). DESIGN: MRI studies of pathologically proven alveolar soft part sarcomas (ASPS) in ten patients were reviewed and compared with computed tomographic (CT) studies and angiograms. PATIENTS: Ten patients presented with a soft tissue mass of the extremities, neck, axilla, or buttocks. MR images were obtained in all patients prior to surgical intervention, chemotherapy, or irradiation. RESULTS AND CONCLUSION: Although most soft tissue sarcomas are isointense relative to muscle or MRI T1-weighted images (T1WI), nine of the ten alveolar ASPS in the present study demonstrated high signal intensity on both T2 and T1WI. Flow voids were observed both at the core and at the margins of the tumors studied. Recognition of these characteristic MRI findings may lead to the early diagnosis of ASPS, especially when the clinical presentation is that of a slow-growing soft tissue mass in a young adult patient.

Adult↗

Establishment and characterization of a new cell line from human bladder cancer (JMSU1).

A new human bladder cancer cell line designated JMSU1 has been established from malignant ascitic fluid of a 75-year-old Japanese man with bladder cancer, and maintained in culture for more than 7 years and over 240 passages. Inverted phase-contrast microscopy revealed that JMSU1 was composed of morphologically distinct cells (polygonal to spindle-shaped cells), showing morphological heterogeneity in vitro. Histological examination of xenografts showed poorly differentiated transitional cell carcinoma, resembling the original tumor. Immunohistochemical staining for cytokeratin and electron microscopic examination suggested that JMSU1 was of epithelial origin. Chromosome analysis gave a modal number of 69 with no Y chromosome. Isozyme analysis (LDH, G6PD, and NP) showed the mobility pattern of human type B. DNA fingerprint analysis demonstrated that there was no cross-culture contamination of JMSU1 during the passages. In conclusion, a newly established and well-characterized cell line, JMSU1, offers promising material for the investigation of the biological properties of bladder cancer.

Aged↗

Predominance of the mutation at 1138 of the cDNA for the fibroblast growth factor receptor 3 in Japanese patients with achondroplasia.

Fibroblast growth factor receptor 3 (FGFR3) has recently been identified as a putative gene for achondroplasia. Since a guanine to adenine mutation at 1138 of the cDNA for FGFR3 had been identified in most of the patients in Western population, we examined 13 Japanese patients to see if they also share the same mutation. Specific endonuclease digestion of the amplified coding sequence for the transmembrane domain of the FGFR3 revealed that the 12 patients have the G to A change at 1138, while the other had the G to C substitution at the same point, both of which result in G380A substitution. As far as we studied, the homogeneity of the point mutation at 1138 is also authentic to Japanese patient as well as Western patients.

Achondroplasia↗

Effect of maternal diabetes on longevity in offspring of spontaneously hypertensive rats.

We studied the effect of maternal diabetes induced by neonatal streptozotocin treatment on the longevity of the male offspring in spontaneously hypertensive rats (SHR). Maternal diabetes significantly decreased the survival in the offspring as compared with the control (p < 0.01). Mean age at death was 14.9 +/- 0.6 months in the offspring from the diabetic dams and 17.9 +/- 1.1 months in that from the control. The life span was significantly correlated with the birth weight (rs = 0.55, p = 0.009). These findings suggest that a diabetic pregnancy may accelerate an age-related degenerative process of the offspring in SHR.

Animals↗

Squamous cell carcinoma of the ureter with marked leukocytosis producing granulocyte colony-stimulating factor.

This paper describes a case of squamous cell carcinoma (SCC) of the ureter which showed marked leukocytosis without any evidence of infection and hematologic malignancies. The level of serum granulocyte colony-stimulating factor (G-CSF) assayed by enzyme immunoassay increased and the immunohistochemical staining of the ureter tumor showed the presence of G-CSF in tumor cells. These findings indicate that SCC of the ureter produced G-CSF which stimulated leukocyte production in bone marrow and resulted in leukocytosis. To our knowledge, this is the first report of ureter tumor with leukocytosis producing G-CSF.

Aged↗

[Clinicopathological evaluation of etoposide or estramustine phosphate in castrated patients with advanced prostatic cancer].

BACKGROUND: We conducted a multicentric randomized trial to compare bilateral orchiectomy versus bilateral orchiectomy plus etoposide or estramustine phosphate as first-line therapy for advanced prostatic cancer (stage D2). METHODS: From January 1991 to December 1992 a total of 46 newly diagnosed cases (registered cases) of advanced (stage D2) prostatic cancer was randomized into 3 groups as follows; Group A: bilateral orchiectomy and 25 mg/day of etoposide every 2 weeks for 6 months. Group B: bilateral orchiectomy and 560 mg/day of estramustine phosphate for 6 months. Group C: bilateral orchiectomy alone. One of group A and one of group B were ineligible cases, so 44 were eligible. In the eligible cases, ages were ranged from 54 to 90 (mean of 71.2) years old. No significant difference of patients' characteristics was found among 3 groups and median follow-up period was 25 months. Response was evaluated based on the response criteria according to Japanese urological association. Specifically, a central pathologist who blinded to the treatment was employed for evaluating pathological response at six months. RESULTS: Of the 44 eligible patients, 33 and 25 were evaluated for clinically and pathological analyses, respectively. Clinical response rates were 80% (12/15) of group A, 100% (4/4) of group B and 78.6% (11/14) of group C. No significant difference in the clinical response and survival rate was shown among the three groups. Significantly higher frequencies of side effects were noted in the grop B compared to the other two groups (p < 0.05) and cardiovascular complications were the most frequent in group B. Favorable pathological response was obtained in all of group B, but not statistically significant compared with 7/21 (33.3%) of response rate in group A and C. The pathological response was significantly correlated with the clinical one in all patients (p < 0.01). While 8 of 11 patients (73%) with pathological response grade 1, 2 and 3 achieved clinical PR (partial response) or CR (complete response), only 5 of 14 (36%) with grade 0 received PR or CR. CONCLUSIONS: We conclude that low dose administration of etoposide or estramustine phosphate dose not improve clinical response and survival in a short term in castrated patients, but increases the adverse effects due to the drugs in these patients. In addition, the pathological evaluation at 6 months after treatment appears to reflect the clinical response at that time in newly diagnosed patients with advanced prostatic cancer.

Administration, Oral↗

[5-Fluorouracil and alpha-2a interferon in patients with hormone-refractory prostate cancer].

BACKGROUND: Hormone-refractory metastatic prostate cancer remains a disease for were limited therapeutic options are available. Therefore, the establishment of newly, more effective chemotherapy is expected. Experimental data suggest that PC-3, a human hormone refractory prostate cancer cell line, showed a 2-fold increase in 5-Fluorouracil (5FU) sensitivity in the presence of alpha-2a Interferon (IFN alpha 2a) at 100 IU/ml, compared to that without IFN alpha 2a. Based on this data, we treated 11 patients with 5FU and IFN alpha 2a in order to determine the clinical response and toxicity of this combination chemotherapy. METHODS: One course of this combination chemotherapy consisted of a continuous intravenous infusion of 5FU at 600 mg/m2/day for 5 days (D1-D5) with IFN alpha 2a 3 million units (MU) intramuscularly 3 times weekly (D1, D3, D5) followed by a bolus injection of 5FU at 600 mg/m2 and IFN alpha 2a at 3 MU/day on D15 and D22. RESULTS: Based on the Response Criteria for Prostate cancer Treatment, one of 9 patients with bony metastasis had partial response, 2 patients with nodal disease on the CT scan obtained partial response. Six of 11 patients had more than 50% decrease in post-therapy prostatic antigen levels, 3 of whom obtained complete response. Significant myelosuppression did not occur. There were no chemotherapy-related deaths. CONCLUSION: These results suggest that the combination of 5FU and IFN alpha 2a, although preliminary, is an active regimen against hormone-refractory metastatic prostate cancer.

Aged↗

Nephron sparing surgery for renal cell carcinoma in von Hippel-Lindau disease.

PURPOSE: We evaluated the technical feasibility and followup outcomes of a nephron sparing operation for localized renal cell carcinoma and von Hippel-Lindau disease. MATERIALS AND METHODS: Our 5 patients underwent initial nephron sparing surgery followed by serial computerized tomography. RESULTS: All but 1 renal lesion was resected in 9 initial nephron sparing operations. Postoperative computerized tomography revealed 35 lesions of which 8 had enlarged. Four patients underwent secondary renal surgery and adequate renal function was preserved. CONCLUSIONS: Even with the high risk of local recurrence nephron sparing surgery is an appropriate approach for these patients.

Adult↗

[Endourology update].

In urology, endoscopic surgery and laparoscopic surgery are generally named as endourology. Transurethral endoscopic surgery was originated in mid 19th century, and established by 1950s. At present, transurethral resection of the prostate, transurethral resection of the bladder tumor, transurethral incision of the urethral stricture, transurethral vesicolithotripsy, and transurethral ureterolithotripsy, were commonly performed in many urological clinics. Percutaneous nephrolithotripsy and extracorporeal shock wave lithotripsy were introduced in 1980s, and now, open operation for urolithiasis are rarely performed. In 1990s, as a new endourologic procedure, laparoscopic operations are being increasingly applied to the treatment of urological diseases; for example, laparoscopic pelvic lymphadenectomy, laparoscopic varicocelectomy, laparoscopic exploration of non-palpable testis, laparoscopic nephrectomy, and laparoscopic adrenalectomy etc. Of the variety of treatment modalities available, the most effective and least invasive method should be selected appropriately. So, we anticipate the further advancement in minimally invasive therapy, interdependently with our sufficient experience and skills.

Endoscopy↗

Prognostic factors in synovial sarcoma: a clinicopathologic study of 18 cases.

The prognostic factors for synovial sarcoma were analyzed retrospectively in 18 patients. Variables evaluated for their use in predicting survival included the location of the primary tumor, tumor size, local recurrence, completeness of surgical resection, and histologic subtype. Chemotherapy was not evaluated because the patients received various regimens and/or inadequate doses. Tumor size was the most significant prognostic factor, and a diameter of more than 10 cm was associated with a significantly worse prognosis (risk ratio: 5.38) (P = 0.012). We conclude that complete surgical resection of tumors less than 5 cm in maximum diameter may be curative and that adjuvant chemotherapy may not be necessary for such patients, because the value of chemotherapy for synovial sarcoma is still controversial.

Adolescent↗

Origin of a T cell clone with a mismatched combination of MHC restriction and coreceptor expression.

Although the existence of a large number of CD8+ class II MHC-specific CTLs had long been noticed, the origin of such T cells with a discordant combination of specificity and phenotype has been a mystery in the positive selection model. Recent reports suggesting the independency of the positive selection of T cells from coreceptor-mediated signals raised a possibility that they might be the progeny of putative transitional, mismatched, single-positive cells appearing before positive selection as proposed in the stochastic/selective model. By developing transgenic mice carrying TCR alpha and beta chain genes of a CD8+ class II MHC Ag-specific allogeneic CTL clone QM11, the origin of such T cells with mismatched TCR specificity and coreceptor expression was studied. The results indicate that QM11 belongs to a conventional CD8+ T cell population whose maturation is dependent on a class I (or class I-like) MHC product. Consequently, the reactivity of QM11 to I-Ak can be considered to be an accidental cross-reaction.

Animals↗

Acidification is essential for maintaining the structure and function of lytic granules of CTL. Effect of concanamycin A, an inhibitor of vacuolar type H(+)-ATPase, on CTL-mediated cytotoxicity.

An inhibitor of vacuolar type H(+)-ATPase, concanamycin A (CMA), inhibited the specific cytolytic activity of a CD8+ CTL clone, OE4. The inhibitory effect was observed when the effector cells, and not the target cells, were pretreated with CMA. CMA did not seem to inhibit early events, inasmuch as effector/target conjugate formation remained unaffected. Although CMA treatment of OE4 resulted in a slight decrease in the efficiency of granule exocytosis in response to anti-CD3 stimulation, the most prominent effect was a marked reduction of perforin activity and DNA degradation activity in lytic granules. Western blotting analysis indicated a drastic decrease in the amount of perforin in CMA-treated cells. Fluorescent microscopic observation of OE4 stained with acridine orange indicated that CMA raised the pH of the lytic granules. Under transmission electron microscopy, striking morphologic changes in cytoplasmic granular structures were observed after CMA treatment of OE4. The lytic granules of OE4 had homogeneously stained large cores and numerous small vesicles that filled peripheral areas. In contrast, the lytic granules of CMA-treated OE4 showed irregular shapes with no small vesicles, but with cores that became rough and loose. Vacuoles with no structure in them were seen occasionally. These results suggest that acidification through vacuolar type H(+)-ATPase is essential to maintain the structure and function of lytic granules.

Acid-Base Equilibrium↗

Differential Na+,K(+)-ATPase activity and cisplatin sensitivity between transformants induced by H-ras and those induced by K-ras.

We examined the differential effects of the H-ras oncogene and the K-ras oncogene on cisplatin sensitivity in murine NIH/3T3 cells transfected with these oncogenes. Although the NIH/3T3 cells transformed with H-ras oncogenes (EJ-NIH/3T3 and Ha8-21) showed an increased resistance to cisplatin compared to the parental NIH/3T3, the cell lines transformed with K-ras oncogenes (DT and 1,8DNP2-2-5) did not. Compared with NIH/3T3, the 2 H-ras transformants reduced both the accumulation of cisplatin and the Na+,K(+)-ATPase activity in the membrane fraction. On the other hand, we observed no significant difference in cellular accumulation of cisplatin or in Na+,K(+)-ATPase activity between parental NIH/3T3 and the K-ras transformants. Since these ras transformants did not affect the cellular metallothionein content, transcriptional level of DNA polymerase beta or activity of glutathione-S-transferase which is not associated with cisplatin sensitivity, these results suggest that cisplatin resistance is brought about by the H-ras oncogene, but not by K-ras, and that induction of cisplatin resistance by H-ras is mainly due to a reduction of cisplatin accumulation and an impairment of Na+,K(+)-ATPase activity in the membrane fraction.

3T3 Cells↗