-
Shigeyuki Yamada, Hideo Saito,
Shinya Ohara,
Shinichi Yamashita,
Koji Mitsuzuka,
Shunichi Namiki,
Minoru Miyazato,
Yasuhiro Kaiho,
Akihiro Ito,
Haruo Nakagawa,
Shigeto Ishidoya,
Yoichi Arai
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVE: We investigated the efficacy and toxicity of a docetaxel, ifosfamide and nedaplatin regimen as salvage therapy for patients with advanced testicular germ cell tumor. METHODS: Eleven patients with advanced germ cell tumor refractory or relapsed after cisplatin-based chemotherapy were treated using docetaxel, ifosfamide and nedaplatin. The docetaxel, ifosfamide and nedaplatin regimen comprised docetaxel (75 mg/m(2)) on Day 1, ifosfamide (2 g/m(2)) on Days 1-3 and nedaplatin (75 mg/m(2)) on Day 2 of a 3-week cycle. RESULTS: Ten (91%) of the 11 patients achieved favorable responses, including complete response in one case and partial response in nine cases. Nine (81%) of the 11 patients have continued to show no evidence of disease after docetaxel, ifosfamide and nedaplatin therapy followed by subsequent surgical resection, with a median follow-up period of 52 months. One patient died of the disease 3 months after completing docetaxel, ifosfamide and nedaplatin chemotherapy. One patient was lost to follow-up with a status of alive with disease. Ten (91%) of the 11 patients developed Grade 4 leukopenia, which was managed using granulocyte colony-stimulating factor. No patients developed sensory neuropathy or renal dysfunction. CONCLUSIONS: The docetaxel, ifosfamide and nedaplatin regimen was efficacious and well-tolerated as salvage chemotherapy for patients with advanced germ cell tumor.
Japanese Journal of Clinical Oncology 04/2013; · 1.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A right renal cyst was found in a 69-year-old man with stage IV chronic kidney disease on abdominal ultrasonography performed to investigate a right upper abdominal swelling. Aspiration cytology of the cyst revealed no malignancy, but malignancy could not be ruled out on magnetic resonance imaging because of the cyst's wall thickness and heterogeneous contents. At one-year of follow-up, emergent abdominal surgery was performed due to incidental perforation of ascending colon diverticulitis. At that time, cystic fenestration was performed because the large renal cyst obstructed the operative procedure. Pathological examination showed type-1 papillary renal cell carcinoma, and radical nephrectomy was performed after the patient's general condition improved. Hemodialysis was started after the operation, and there has been no disease recurrence for two years.
Hinyokika kiyo. Acta urologica Japonica 12/2012; 58(12):679-682.
-
[show abstract]
[hide abstract]
ABSTRACT: To assess the surgical and oncological outcomes of laparoscopic retroperitoneal lymph node dissection (RPLND) after chemotherapy.
Twenty patients with metastatic nonseminomatous testicular germ-cell tumor underwent extraperitoneal laparoscopic RPLND after chemotherapy. The procedure was not indicated for patients with a pre-chemotherapy mass larger than 5 cm. Morbidity and oncological outcome were reviewed retrospectively. Surgical complications were graded according to the Clavien classification system.
Laparoscopic RPLND was completed in all patients, and there was no conversion to open surgery. The median operating time was 223 min (range, 137-399 min). The median blood loss was 20 ml (range, 10-520 ml). There were no intraoperative complications. Postoperatively, 4 patients (20 %) had prolonged lymphorrhea (grade I) and 9 (45 %) had chyle leakage (grade I). Histological examination of the residual mass revealed necrosis in 16 (80 %) and the presence of teratoma with/without viable tumor in 4 (20 %). With a median follow-up of 45 months (range, 24-112), no patient has had disease recurrence. Normal antegrade ejaculation was preserved in all of the 14 patients studied.
Extraperitoneal laparoscopic RPLND can be performed with acceptable morbidity and excellent cancer control in select patients. Surgeons should be aware of relatively high incidence of chyle leakage following this procedure.
International Urology and Nephrology 05/2012; 44(5):1389-95. · 1.47 Impact Factor
-
International Journal of Urology 12/2011; 19(3):277-8. · 1.75 Impact Factor
-
Hideo Saito,
Tadashi Matsuda,
Kazunari Tanabe,
Akihiro Kawauchi,
Toshiro Terachi,
Ken Nakagawa,
Masatsugu Iwamura,
Masanobu Shigeta,
Katsunori Tatsugami,
Akihiro Ito,
Jiro Machida,
Mutsushi Kawakita,
Hidefumi Kinoshita,
Nobuo Shinohara,
Naomasa Ioritani,
Toshimori Seki,
Yoichi Arai
[show abstract]
[hide abstract]
ABSTRACT: Despite clear trends toward minimally invasive surgery, information about laparoscopic partial nephrectomy (LPN) in Japan is sparse. We conducted a retrospective survey to clarify time trends for LPN and analyze surgical and oncologic outcomes. Patients and Methods: A nationwide survey was performed. Between 1998 and 2008, 1375 patients underwent LPN at 54 institutions. Complications, patterns of tumor recurrence, and recurrence-free survival were analyzed.
Renal pedicle clamping was used in 1031 (75%) cases, and renal cooling was performed in 64%. Median warm/cold ischemic time was 37/53 minutes. Median tumor size was 2.26 cm (interquartile range 1.6 to 2.7). Multivariate analysis identified total operative time, operative blood loss, and surgical margin status as independently associated with high grade (grade 3-5) urologic and nonurologic complications. Despite increases in central tumor, a trend was seen toward shorter warm/cold ischemic time in recent cases, and the overall complication rate did not change throughout the study period. With a median follow-up of 26 months for 1193 malignancies, recurrence occurred in 22 (1.7%) patients, including local recurrence in 7 (0.5%), lung in 8 (0.7%), lymph nodes in 2 (0.1%), and bone in 4 (0.3%). Of the 26 cases with positive surgical margins, local tumor recurrence occurred in only one.
This is the first nationwide survey of LPN in Japan to be reported. LPN could be performed with acceptable positive margins and complication rates. Most tumor recurrences occur as metastases, and surgical margin status appears to have little impact on oncologic outcomes.
Journal of endourology / Endourological Society 11/2011; 26(6):652-9. · 1.75 Impact Factor
-
International Journal of Urology 07/2011; 18(9):675-6. · 1.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the changes in split renal function after retroperitoneal laparoscopic partial nephrectomy with renal hypothermia using ice-cold saline.
From June 2002 to October 2009, 32 patients (median age 56 years) underwent retroperitoneal laparoscopic partial nephrectomy with hypothermia using ice-cold saline for the treatment of small renal tumors. The total renal function was monitored using the estimated glomerular filtration rate. Split renal function was evaluated using technetium-99m dimercaptosuccinic acid renal scintigraphy preoperatively and 3 months postoperatively.
The median renal ischemic time, including the initial 10 minutes for cooling, was 52 minutes (range 28-101). Of the patients whose renal temperature was monitored, the lowest renal temperature during cooling was 15-25°C. The median decrease in the estimated glomerular filtration rate was 7.2 mL/min/1.73 m(2) (range -16.3 to 33.7). The median decrease in the contribution of the affected kidney to global renal function was 5.3% (range 0.4%-21.1%). On multivariate analysis, a shorter ischemia duration was an independent predictor of a lesser decrease in the contribution of the affected kidney (P = .0032).
The methods we have described are simple and effective to facilitate suboptimal hypothermia. The decrease in the renal contribution of the affected kidney appeared to be minimal, although the ischemic time was relatively longer in our series.
Urology 02/2011; 77(4):814-8. · 2.43 Impact Factor
-
Ken Takeda,
Keichi Jingu,
Masashi Koto,
Keisuke Fujimoto,
Kakutaro Narazaki,
Masaki Kubozono, Hideo Saito,
Shigeyuki Yamada,
Kohji Mitsuduka,
Shigeto Ishidoya,
Hisanori Ariga,
Yoichi Arai,
Shogo Yamada
[show abstract]
[hide abstract]
ABSTRACT: Prostate cancer is one of the common cancers in the world. In Japan, prostate brachytherapy (PB) with iodine-125 has become a treatment option for localized prostate cancer since 2003. Nevertheless, severe acute urinary toxicity (AUT) remains as one of the intractable side effects. We assessed AUT and the changes in international prostate symptom score (IPSS) before and after PB for localized prostate cancer. IPSS is a questionnaire tool for tracking the subjective urinary symptoms. Between 2006 and 2009, 104 eligible patients underwent PB with iodine-125 were analyzed. AUT was graded with the radiation therapy oncology group (RTOG) scale. Eligible patients filled out IPSS questionnaires before and after PB. Clinical and treatment-related factors were examined for correlation with the severity of AUT and the interval to IPSS resolution. AUT of RTOG Grade 0 (no changes) and Grade 2 was detected in one and 96 patients, respectively, whereas seven patients (6.7%) experienced AUT of Grade 3. Thus, the incidence of severe AUT (Grade 3) after PB was low. A greater number of needles (p = 0.012) were associated with AUT of RTOG Grade 3 on the univariate analysis. The median interval to IPSS resolution was 6 months (7 ± 6 months). Greater post-implant maximal IPSS (p < 0.001) was associated with slower IPSS resolution, whereas higher pre-implant IPSS (p < 0.001) was associated with faster IPSS resolution on the multivariate analysis. In conclusion, reducing the number of needles in PB may be helpful for decreasing the rate of severe AUT.
The Tohoku Journal of Experimental Medicine 01/2011; 223(1):55-60. · 1.24 Impact Factor
-
Xingfeng Bao,
E Ashley Moseman, Hideo Saito,
Bronislawa Petryniak,
Bronislawa Petryanik,
Aude Thiriot,
Shingo Hatakeyama,
Yuki Ito,
Hiroto Kawashima,
Yu Yamaguchi,
John B Lowe,
Ulrich H von Andrian,
Minoru Fukuda
[show abstract]
[hide abstract]
ABSTRACT: Heparan sulfate can bind several adhesion molecules involved in lymphocyte trafficking. However, the in vivo function of endothelial heparan sulfate in lymphocyte homing and stimulation of the immune response has not been elucidated. Here, we generated mutant mice deficient in the enzyme Ext1, which is required for heparan sulfate synthesis, in a Tek-dependent and inducible manner. Chemokine presentation was diminished in the mutant mice, causing the lack of appropriate integrin-mediated adhesion, and resulted in a marked decrease in lymphocyte sticking to high endothelial venules and in recruitment of resident dendritic cells through lymphatic vessels to the lymph nodes. As a consequence, mutant mice displayed a severe impairment in lymphocyte homing and a compromised contact hypersensitivity response. By contrast, lymphocyte rolling was increased because of loss of electrostatic repulsion by heparan sulfate. These results demonstrate critical roles of endothelial heparan sulfate in immune surveillance and immune response generation.
Immunity 11/2010; 33(5):817-29. · 21.64 Impact Factor
-
Shingo Hatakeyama,
Atsushi Kyan,
Hayato Yamamoto,
Akiko Okamoto,
Naoki Sugiyama,
Yuichiro Suzuki,
Takahiro Yoneyama,
Yasuhiro Hashimoto,
Takuya Koie,
Shigeyuki Yamada, Hideo Saito,
Yoichi Arai,
Minoru Fukuda,
Chikara Ohyama
[show abstract]
[hide abstract]
ABSTRACT: We studied orchiectomy specimens from 130 patients immuhistochemically with testicular germ cell tumor (TGCT) using anti-core 2 N-acetylglucosaminyltransferase-1 (C2GnT-1) antibody. The incidence of C2GnT-1 positivity in stage I disease (29.5%, 21/71) was significantly lower than that in higher stages (84.7%, 50/59) (P < 0.001, chi(2) test). This significant difference was also found when the cases were divided into seminoma and NSGCT according to histopathological classification. Kaplan-Meier plots and the log rank test showed that in the patients with stage I seminoma, C2GnT-1-positive cases had a higher risk for recurrence (P < 0.001). This was also the case with the patients with stage I NSGCT (P < 0.001). To determine whether C2GnT-1 promotes aggressive behavior of cancer cells, a C2GnT-1-negative human TGCT cell line, JKT-1, was stably transfected with a mammalian expression vector containing C2GnT-1 cDNA. In vitro assays revealed that JKT-1-C2 cells are more invasive than mock transfectants, although there are no differences in proliferation activity. When orthotopically inoculated into athymic nude mice, JKT-1-C2 cells produced larger testicular tumors extending to the retroperitoneum with mesenteric metastasis, while mock transfectants produced small tumors without metastasis (P < 0.01, Mann-Whitney's U-test). When injected via the tail vein, JKT-1-C2 cells produced a number of metastatic lung foci. In contrast, mock transfectants produced a small number of nodules (p < 0.01, Mann-Whitney's U-test). These results strongly suggest that C2GnT-1 enhances the metastatic potential of TGCT and may be a reliable biomarker for aggressive potential of TGCT.
International Journal of Cancer 12/2009; 127(5):1052-9. · 5.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the biochemical outcome following radical prostatectomy alone in patients with high-risk prostate cancer.
Between January 2002 and August 2007, 252 patients underwent radical retropubic prostatectomy. Those who received neoadjuvant hormone therapy were excluded from this analysis. Based on pre-operative data, we stratified the patients into low, intermediate, and high-risk groups according to the risk criteria of the National Comprehensive Cancer Network in 2003, respectively. Prostate-specific antigen (PSA) failure was defined as any detectable PSA level higher than 0.2 ng/mL.
The PSA failure-free survival rate for the high-risk group (n = 46) was 64.5% after a median follow-up period of 39 months. Among patients with high-risk disease, none with pathologically organ-confined cancer (n = 19) and a negative surgical margin had PSA failure. The PSA failure-free rate in patients with non organ-confined cancer (n = 27) was 39.5%. Among the pretreatment variables, a positive biopsy core percentage (the number of positive biopsy cores/total biopsy core) >or=30 was a significant independent predictor of extra prostatic extension.
Radical prostatectomy is feasible in high-risk prostate cancer patients, only if they have a pathologically organ-confined disease.
International Journal of Urology 09/2009; 16(9):733-8. · 1.75 Impact Factor
-
Junya Mitoma,
Tatsuo Miyazaki,
Mark Sutton-Smith,
Misa Suzuki, Hideo Saito,
Jiunn-Chern Yeh,
Takehiro Kawano,
Ole Hindsgaul,
Peter H Seeberger,
Maria Panico,
Stuart M Haslam,
Howard R Morris,
Richard D Cummings,
Anne Dell,
Minoru Fukuda
[show abstract]
[hide abstract]
ABSTRACT: E-, P- and L-selectins critically function in lymphocyte recirculation and recruiting leukocytes to inflammatory sites. MECA-79 antibody inhibits L-selectin-mediated lymphocyte adhesion in several species and does not require sialic acid in its epitope. Many other antibodies, however, recognize human selectin ligands expressing N-acetylneuraminic acid but not mouse selectin ligands expressing N-glycolylneuraminic acid, suggesting that difference in sialic acid in sialyl Lewis X leads to differential reactivity. We found that HECA-452 and FH6 monoclonal antibodies bind Chinese hamster ovary (CHO) cells expressing N-acetylneuraminyl Lewis X oligosaccharide but not its N-glycolyl form. Moreover, synthetic N-acetylneuraminyl Lewis X oligosaccharide but not its N-glycolyl oligosaccharide inhibited HECA-452 and FH6 binding. By contrast, E-, P- and L-selectin bound to CHO cells regardless of whether they express N-acetyl or N-glycolyl form of sialyl Lewis X, showing that selectins have a broader recognition capacity than HECA-452 and FH-6 anti-sialyl Lewis x antibodies.
Glycoconjugate Journal 01/2009; 26(5):511-23. · 2.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent microanatomical studies have identified a significant amount of nerve fibers along the ventral circumference of the prostate capsule and confirmed the concept of a periprostatic nerve network. However, functional investigations have not yet proved whether nerve fibers distributed on the prostate capsule, particularly those outside the neurovascular bundle (NVB), contribute to erection.
To confirm whether nerve fibers distributed on the prostate capsule contribute to erectile function, the present study was performed using electrophysiologic testing.
The circumference of the prostate capsule was electrically stimulated during radical retropubic prostatectomy (RRP) in 12 patients with clinically localized prostate cancer (PCa). We defined the ventromedian circumference of the prostate capsule as the 12 o'clock position and the posterolateral position of the typical NVB as the 5 o'clock position. Periprostatic nerve fibers at the 12, 1, 2, 3, 4, and 5 o'clock positions of the midprostate were stimulated using bipolar electrodes.
Changes in pressure at the middle of the urethra were measured using an inserted balloon catheter to detect increases in cavernosal pressure.
Although the study included only 12 patients, every stimulation at all positions between 1 and 5 o'clock evoked urethral pressure responses in all patients. Mean pressure response was most powerful for 5 o'clock stimulation and decreased with stimulated points further from the 5 o'clock position.
We demonstrated that electrostimulation at not only the posterolateral but also the anterior and lateral circumference of the prostate capsule can increase cavernosal pressure. These findings indicate that the periprostatic nerve network contributes to erections.
European urology 10/2008; 55(1):148-54. · 7.67 Impact Factor
-
Junya Mitoma,
Xingfeng Bao,
Bronislawa Petryanik,
Patrick Schaerli,
Jean-Marc Gauguet,
Shin-Yi Yu,
Hiroto Kawashima, Hideo Saito,
Kazuaki Ohtsubo,
Jamey D Marth,
Kay-Hooi Khoo,
Ulrich H von Andrian,
John B Lowe,
Minoru Fukuda
[show abstract]
[hide abstract]
ABSTRACT: Lymphocyte homing is mediated by specific interaction between L-selectin on lymphocytes and the carbohydrate ligand 6-sulfo sialyl Lewis X on high endothelial venules. Here we generated mice lacking both core 1 extension and core 2 branching enzymes to assess the functions of O-glycan-borne L-selectin ligands in vivo. Mutant mice maintained robust lymphocyte homing, yet they lacked O-glycan L-selectin ligands. Biochemical analyses identified a class of N-glycans bearing the 6-sulfo sialyl Lewis X L-selectin ligand in high endothelial venules. These N-glycans supported the binding of L-selectin to high endothelial venules in vitro and contributed in vivo to O-glycan-independent lymphocyte homing in wild-type and mutant mice. Our results demonstrate the critical function of N-glycan-linked 6-sulfo sialyl Lewis X in L-selectin-dependent lymphocyte homing and recruitment.
Nature Immunology 05/2007; 8(4):409-18. · 26.01 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Spinal cord compression is a skeletal-related event in advanced malignancies and is associated with serious morbidity and poor prognosis. Despite the palliative nature of laminectomy treatment, it is important to prevent neurological deficits and relieve pain as a means to improve quality of life. Here we report on a prostate cancer patient with spinal cord compression who became ambulant from paraparesis after he underwent a decompression laminectomy; he survived for 9.5 years with good quality of life.
International Journal of Clinical Oncology 01/2005; 9(6):520-2. · 1.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Testicular tumors are not common pediatric solid tumors, especially in Asian children. There have been few reviews of cases in Japan to date. We present the clinical features of 14 pediatric testicular tumor patients.
Clinical features of 14 testicular tumor patients, such as chief complaints, age at diagnosis, pathology, stages, treatments and prognosis, were examined from medical records. Two patients had their semen tested at adolescence.
Of the 14 prepubescent patients, 12 (85.7%) patients were diagnosed before 3 years of age. Ten cases (71.4%) were diagnosed as yolk sac tumors, three (21.4%) as mature teratomas and one case as an epidermoid cyst. Nine cases (90.0%) among the 10 cases of yolk sac tumor were diagnosed as stage I and one case was stage IV. One stage I yolk sac tumor patient developed lung metastasis later. Eventually, two yolk sac tumor patients died, despite chemotherapy. While all the cases with a diagnosis before 2 years of age survived, 67% (2/3) of cases with a diagnosis after the age of 2 died of tumors. Semen analysis in two patients showed normospermia.
In the present study, the most common testicular tumors were yolk sac tumors and the patients diagnosed before 2 years of age showed favorable results. Age could be a relapse risk factor in yolk sac tumors. Guidelines for handling testicular tumors in children is not yet well established in Japan. An organized system seems necessary to gather and accumulate the results of the cases in Japan in order to develop better guidelines for treatment.
International Journal of Urology 11/2004; 11(10):890-3. · 1.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A retrospective study was conducted to examine the host factors of 240 testicular germ cell tumor patients. This study was performed to address a new theory proposed by Skakkebaek called testicular dysgenesis syndrome which claims that cryptorchism, hypospadias, poor semen quality and testicular germ cell tumors are symptoms of an underlying testicular dysgenesis in uterus.
The past health histories and familial episodes of 240 testicular germ cell tumor patients were examined. The past health histories included cryptorchism, hypospadias, infertility, atrophic testis and inguinal hernia.
Of the 240 patients, 13 (5.4%) had a history of cryptorchism or orchidopexy. Two (0.8%) showed existence of hypospadias or had experienced urethroplasty. Among 129 married couples, 104 (80.6%) couples were fertile. Three (1.3%) patients developed testicular tumors after they were diagnosed as infertile or came to the hospital with the complaints of infertility. Four (1.7%) had contralateral atrophic testis. 19 (7.9%) had experienced inguinal herniorrhaphy before age 15. Three (1.3%) had testicular germ cell tumor patients among their family or relatives.
The testicular germ cell tumor patients showed a considerable incidence of complications such as cryptorchism, hypospadias and incomplete closure of processus vaginalis. Cryptorchism, perinatal factors and familial factors could be risks for developing testicular germ cell tumors.
International Journal of Urology 09/2004; 11(8):640-6. · 1.75 Impact Factor
-
Yasuo Inaba,
Chikara Ohyama,
Tetsuro Kato,
Makoto Satoh, Hideo Saito,
Shigeru Hagisawa,
Toshiko Takahashi,
Mareyuki Endoh,
Michiko N Fukuda,
Yoichi Arai,
Minoru Fukuda
[show abstract]
[hide abstract]
ABSTRACT: Elevated expression of sialyl Lewis X has been postulated to be a prognostic indicator of prostate cancer. However, direct evidence for the relationship between increased expression of sialyl Lewis X and malignancy of prostate cancer is still lacking. To determine whether increased levels of sialyl Lewis X leads to malignancy in prostate tumor, we transfected the human prostate cancer cell line PC-3 with alpha1,3-fucosyltransferase III (FTIII) to obtain stable transfectants, PC-3-FTIII lines, that highly express sialyl Lewis X. When inoculated in the prostate of nude mice, PC-3-FTIII cells produced large prostate tumors, while mock-transfected PC-3 cells, which are negative for sialyl Lewis X antigen, produced small prostate tumors. The aggressive tumor formation by PC-3-FTIII cells was inhibited by preincubation of the tumor cells with anti-sialyl Lewis X antibody, by the presence of sialyl Lewis X oligosaccharide or by selectin ligand mimic peptide but not by control peptide. PC-3-FTIII cells and mock-transfected PC-3 cells exhibited no significant difference in cell numbers when cultured in vitro. Remarkably, PC-3-FTIII adhered to prostatic stromal cells in vitro with higher affinity than mock-transfected PC-3. Such adhesion was inhibited by preincubation of PC-3-FTIII cells with antisialyl Lewis X antibody, by the addition of sialyl Lewis X oligosaccharide or by selectin ligand mimic peptide. However, anti-E-selectin, anti-P-selectin or anti-L-selectin antibodies did not inhibit the adhesion of PC-3-FTIII cells to the stromal cells. These results suggest that prostate cancer cells gain aggressiveness through adhesive interaction with prostatic stromal cells by a novel mechanism involving sialyl Lewis X.
International Journal of Cancer 01/2004; 107(6):949-57. · 5.44 Impact Factor
-
Yasuo Inaba,
Chikara Ohyama,
Tetsuro Kato,
Makoto Satoh, Hideo Saito,
Shigeru Hagisawa,
Toshiko Takahashi,
Mareyuki Endoh,
Michiko N. Fukuda,
Yoichi Arai,
Minoru Fukuda
[show abstract]
[hide abstract]
ABSTRACT: Elevated expression of sialyl Lewis X has been postulated to be a prognostic indicator of prostate cancer. However, direct evidence for the relationship between increased expression of sialyl Lewis X and malignancy of prostate cancer is still lacking. To determine whether increased levels of sialyl Lewis X leads to malignancy in prostate tumor, we transfected the human prostate cancer cell line PC-3 with α1,3-fucosyltransferase III (FTIII) to obtain stable transfectants, PC-3-FTIII lines, that highly express sialyl Lewis X. When inoculated in the prostate of nude mice, PC-3-FTIII cells produced large prostate tumors, while mock-transfected PC-3 cells, which are negative for sialyl Lewis X antigen, produced small prostate tumors. The aggressive tumor formation by PC-3-FTIII cells was inhibited by preincubation of the tumor cells with anti-sialyl Lewis X antibody, by the presence of sialyl Lewis X oligosaccharide or by selectin ligand mimic peptide but not by control peptide. PC-3-FTIII cells and mock-transfected PC-3 cells exhibited no significant difference in cell numbers when cultured in vitro. Remarkably, PC-3-FTIII adhered to prostatic stromal cells in vitro with higher affinity than mock-transfected PC-3. Such adhesion was inhibited by preincubation of PC-3-FTIII cells with antisialyl Lewis X antibody, by the addition of sialyl Lewis X oligosaccharide or by selectin ligand mimic peptide. However, anti-E-selectin, anti-P-selectin or anti-L-selectin antibodies did not inhibit the adhesion of PC-3-FTIII cells to the stromal cells. These results suggest that prostate cancer cells gain aggressiveness through adhesive interaction with prostatic stromal cells by a novel mechanism involving sialyl Lewis X. © 2003 Wiley-Liss, Inc.
International Journal of Cancer 12/2003; 107(6):949 - 957. · 5.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The gene coding for microphthalmia-associated transcription factor (Mitf) contains many promoters that could generate multiple Mitf isoforms with distinct amino-termini, such as ubiquitously expressed Mitf-A and Mitf-H. To gain further insight into Mitf isoform multiplicity and the regulation of the promoter usage of the Mitf gene, we have analyzed the function of the amino-terminal domains of Mitf isoforms and the expression of Mitf mRNA in mouse postnatal testis, which is characterized by spermatogenesis and by a cool temperature because of its unique location. Here we show that the amino-terminal domain of Mitf-A possesses a transactivation activity, as judged by yeast expression analysis. We also show the expression of Mitf-A and Mitf-D mRNAs in testis by PCR-based methods. Moreover, in situ hybridization analysis revealed that an Mitf mRNA, probably representing Mitf-A and/or Mitf-D, is expressed in germ cells, including spermatogonia, spermatocytes that undergo meiosis, and round spermatids with the haploid genome, but is undetectable in elongated spermatids with remodeled and condensed chromatin. Notably, Mitf mRNA is undetectable in somatic Leydig cells and peritubular cells. Therefore, multiple promoters may direct differential expression of the Mitf gene in the testis and contribute to functional diversity of Mitf isoforms.
Journal of Biochemistry 08/2003; 134(1):143-50. · 2.37 Impact Factor
