Publications by authors named "Soki Kashima"

17 Publications

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[Complete Remission of Metastatic Renal Cell Carcinoma with Invasion of the Duodenum and Pancreas after Treatment with Nivolumab Plus Ipilimumab Followed by Axitinib and Surgery : A Case Report].

Hinyokika Kiyo 2021 May;67(5):197-203

The Department of Urology, Kyoto University Hospital.

A man in his 60s was diagnosed with clear cell carcinoma of the right kidney with multiple lung metastases, tumor thrombus of the inferior vena cava (IVC), and invasion of the duodenum and pancreas. Ipilimumab plus nivolumab was administered as first-line therapy. After 3 treatment courses, computed tomography (CT) demonstrated a slight decrease in the size of the primary tumor and lung metastases. However, the patient became hemodynamically unstable due to persistent duodenal bleeding during treatment despite frequent blood transfusions. Axitinib was then initiated as second-line therapy. The duodenal bleeding ceased 10 days after starting axitinib and his anemia remissed. Subsequent CT showed further decrease in the size of the primary tumor and lung metastases. The patient underwent right nephrectomy after improvement of nutrition. IVC thrombectomy, and pancreaticoduodenectomy. The lung metastases disappeared on postoperative imaging and no additional treatment was provided. Twelve months after surgery, he was in good health and showed no signs of recurrence.
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http://dx.doi.org/10.14989/ActaUrolJap_67_5_197DOI Listing
May 2021

[18F]FDG-labelled stem cell PET imaging in different route of administrations and multiple animal species.

Sci Rep 2021 May 25;11(1):10896. Epub 2021 May 25.

Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

Stem cell therapy holds great promise for tissue regeneration and cancer treatment, although its efficacy is still inconclusive and requires further understanding and optimization of the procedures. Non-invasive cell tracking can provide an important opportunity to monitor in vivo cell distribution in living subjects. Here, using a combination of positron emission tomography (PET) and in vitro 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) direct cell labelling, the feasibility of engrafted stem cell monitoring was tested in multiple animal species. Human mesenchymal stem cells (MSCs) were incubated with phosphate-buffered saline containing [18F]FDG for in vitro cell radiolabelling. The pre-labelled MSCs were administrated via peripheral vein in a mouse (n = 1), rats (n = 4), rabbits (n = 4) and non-human primates (n = 3), via carotid artery in rats (n = 4) and non-human primates (n = 3), and via intra-myocardial injection in rats (n = 5). PET imaging was started 10 min after cell administration using a dedicated small animal PET system for a mouse and rats. A clinical PET system was used for the imaging of rabbits and non-human primates. After MSC administration via peripheral vein, PET imaging revealed intense radiotracer signal from the lung in all tested animal species including mouse, rat, rabbit, and non-human primate, suggesting administrated MSCs were trapped in the lung tissue. Furthermore, the distribution of the PET signal significantly differed based on the route of cell administration. Administration via carotid artery showed the highest activity in the head, and intra-myocardial injection increased signal from the heart. In vitro [18F]FDG MSC pre-labelling for PET imaging is feasible and allows non-invasive visualization of initial cell distribution after different routes of cell administration in multiple animal models. Those results highlight the potential use of that imaging approach for the understanding and optimization of stem cell therapy in translational research.
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http://dx.doi.org/10.1038/s41598-021-90383-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149709PMC
May 2021

First-line axitinib therapy is less effective in metastatic renal cell carcinoma with spindle histology.

Sci Rep 2020 11 18;10(1):20089. Epub 2020 Nov 18.

Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.

Axitinib, a vascular endothelial growth factor receptor-tyrosine kinase inhibitor, will be used in combination first-line therapies against metastatic renal cell carcinoma (mRCC), but its effects as a first-line monotherapy are unclear. Thus, we aimed to elucidate pretreatment clinical factors that predict the prognosis of patients with mRCC receiving first-line axitinib therapy. We enrolled 63 patients with mRCC treated with axitinib as first-line therapy between Nov. 2003 and Jul. 2018. Progression-free survival (PFS) and overall survival (OS) were assessed using the Wald χ statistic in Cox proportional hazards regression. Median patient age was 67 (range: 25-85) years. Seven (11.1%) patients were classified as being at favorable risk, 33 (52.4%) at intermediate risk, and 23 (36.5%) at poor risk according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification system. Median follow-up duration after axitinib initiation was 14 (range: 1-72) months. Median PFS and OS were 18 months and 65 months, respectively. Cox regression analyses of clinical predictors revealed that high C-reactive protein (CRP) levels were significantly correlated with shorter PFS [hazard ratio (HR), 1.63; 95% confidence interval (CI) 1.7-4.0)], whereas spindle cells and poor IMDC risk scores were related to worse OS (HR, 2.87 and 2.88, respectively; 95% CI 1.4-11.0 and 1.1-8.5, respectively). Thus, patients with mRCC and spindle histology or poor IMDC risk scores had worse OS, and those with high CRP levels had shorter PFS in first-line axitinib treatment. Other therapies might be more suitable for initial management of such patients.
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http://dx.doi.org/10.1038/s41598-020-77135-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675987PMC
November 2020

Pathological complete response after nivolumab therapy following angiogenesis inhibitors in a patient with metastatic renal cell carcinoma.

IJU Case Rep 2020 Nov 5;3(6):287-290. Epub 2020 Oct 5.

Department of Urology Hyogo Prefectural Amagasaki General Medical Center Amagasaki Hyogo Japan.

Introduction: Nivolumab is effective for advanced renal cell carcinoma; however, reports are limited wherein nivolumab is combined with sequential therapy of angiogenesis inhibitors and metastasectomy.

Case Presentation: A 65-year-old man was diagnosed with left renal cell carcinoma of cT2aN0M1 with lung metastasis. The patient underwent nephrectomy and sequential therapy with interferon-α and angiogenesis inhibitors. Lung metastasis decreased by angiogenesis inhibitors, but new right adrenal gland metastasis appeared. Nivolumab as the fifth systemic therapy remarkably shrank the metastasis. After discontinuing nivolumab therapy, the metastasis continued to shrink. The patient underwent adrenalectomy, and pathological analysis revealed no remnant cancer cells in the specimen, confirming a pathological complete response. Twenty months postoperatively, he remains in good health without recurrence.

Conclusion: We report a rare case with renal cell carcinoma of a pathological complete response by nivolumab after angiogenesis inhibitors.
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http://dx.doi.org/10.1002/iju5.12220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609183PMC
November 2020

Does the Addition of Abiraterone to Castration Affect the Reduction in Bone Mineral Density?

In Vivo 2020 Nov-Dec;34(6):3291-3299

Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.

Background/aim: The in vivo effect of abiraterone on bone mineral density (BMD) in addition to androgen deprivation therapy was examined using a murine model.

Materials And Methods: The mice were separated into the following groups: control, abiraterone, castration, and castration+abiraterone. The percentage change in the ratio of bone to tissue volume (BV/TV), number of osteoblasts and osteoclasts, and the serum level of bone markers were compared on day 21.

Results: The BV/TV ratio of the abiraterone, castration, and castration+abiraterone groups was lower than that of the control group. However, the change in the BV/TV ratio in the castration+abiraterone group was not significantly different from that in the castration group. There was no significant difference in the serum TRAP5b level and the number of osteoclasts and osteoblasts between the castration+abiraterone and the castration groups.

Conclusion: The addition of abiraterone to castration did not affect BMD in the murine model.
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http://dx.doi.org/10.21873/invivo.12167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811634PMC
June 2021

[Mass-Production of Cytotoxic T Lymphocytes Regenerated from Pluripotent Stem Cells-To Target Solid Tumors].

Gan To Kagaku Ryoho 2020 Oct;47(10):1415-1420

Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University.

Current adoptive T cell therapies conducted in an autologous setting are costly, time consuming, and depend on the quality of the patient's T cells. To address these issues, we developed a strategy in which T cells are regenerated from induced pluripotent stem cells (iPSCs) that were originally derived from T cells, and succeeded in regenerating cytotoxic T lymphocytes (CTLs) specific for the WT1 antigen, which exhibited therapeutic efficacy in a xenograft model of leukemia. We recently have extended our strategy to solid tumors. To make our method more generally applicable, we developed an allogeneic approach by transducing HLA-haplotype homozygous iPSCs with WT1-specific TCR α/β genes that had been tested clinically. The regenerated CTLs antigen-specifically suppressed tumor growth in a patient-derived xenograft model of renal cell carcinoma, demonstrating the feasibility of our strategy against solid tumors.
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October 2020

Regeneration of Tumor-Antigen-Specific Cytotoxic T Lymphocytes from iPSCs Transduced with Exogenous TCR Genes.

Mol Ther Methods Clin Dev 2020 Dec 20;19:250-260. Epub 2020 Sep 20.

Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.

In the current adoptive T cell therapy, T cells from a patient are given back to that patient after activation, expansion, or genetic manipulation. However, such strategy depends on the quality of the patient's T cells, sometimes leading to treatment failure. It would therefore be ideal to use allogeneic T cells as "off-the-shelf" T cells. To this aim, we have been developing a strategy where potent tumor-antigen-specific cytotoxic T lymphocytes (CTLs) are regenerated from T-cell-derived induced pluripotent stem cells (T-iPSCs). However, certain issues still remain that make it difficult to establish highly potent T-iPSCs: poor reprogramming efficiency of T cells into iPSCs and high variability in the differentiation capability of each T-iPSC clone. To expand the versatility of this approach, we thought of a method to produce iPSCs equivalent to T-iPSCs, namely, iPSCs transduced with exogenous T cell receptor (TCR) genes (TCR-iPSCs). To test this idea, we first cloned TCR genes from WT1-specific CTLs regenerated from T-iPSCs and then established WT1-TCR-iPSCs. We show that the regenerated CTLs from TCR-iPSCs exerted cytotoxic activity comparable to those from T-iPSCs against WT1 peptide-loaded cell line in model. These results collectively demonstrate the feasibility of the TCR-iPSC strategy.
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http://dx.doi.org/10.1016/j.omtm.2020.09.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566080PMC
December 2020

Solitary recurrence of prostate cancer surrounded by seminal vesicle/vas deferens-like epithelium.

IJU Case Rep 2020 Sep 30;3(5):171-173. Epub 2020 Jul 30.

Department of Nephro-urologic Surgery Mie University Hospital Tsu Japan.

Introduction: Clinical recurrence of prostate cancer after curative treatment with a limited number of metastases is often termed as oligorecurrence. We report a case of solitary recurrence of prostate cancer surrounded by epithelium of the seminal vesicle or vas deferens.

Case Presentation: A 54-year-old man diagnosed with localized prostate cancer underwent radiation therapy. Six years later, imaging studies detected a solitary recurrence. We performed metastasectomy, and histopathological examination revealed the metastatic lesion surrounded by the epithelium of the seminal vesicle or vas deferens. Surgical resection achieved a complete biochemical response.

Conclusion: We presented with a case of prostate cancer metastasis surrounded by the epithelium of the seminal vesicle or vas deferens.
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http://dx.doi.org/10.1002/iju5.12168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469812PMC
September 2020

Cytotoxic T Lymphocytes Regenerated from iPS Cells Have Therapeutic Efficacy in a Patient-Derived Xenograft Solid Tumor Model.

iScience 2020 Apr 6;23(4):100998. Epub 2020 Apr 6.

Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address:

Current adoptive T cell therapies conducted in an autologous setting are costly, time consuming, and depend on the quality of the patient's T cells. To address these issues, we developed a strategy in which cytotoxic T lymphocytes (CTLs) are regenerated from iPSCs that were originally derived from T cells and succeeded in regenerating CTLs specific for the WT1 antigen, which exhibited therapeutic efficacy in a xenograft model of leukemia. In this study, we extended our strategy to solid tumors. The regenerated WT1-specific CTLs had a strong therapeutic effect in orthotopic xenograft model using a renal cell carcinoma (RCC) cell line. To make our method more generally applicable, we developed an allogeneic approach by transducing HLA-haplotype homozygous iPSCs with WT1-specific TCR α/β genes that had been tested clinically. The regenerated CTLs antigen-specifically suppressed tumor growth in a patient-derived xenograft model of RCC, demonstrating the feasibility of our strategy against solid tumors.
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http://dx.doi.org/10.1016/j.isci.2020.100998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188741PMC
April 2020

High Frequency Production of T Cell-Derived iPSC Clones Capable of Generating Potent Cytotoxic T Cells.

Mol Ther Methods Clin Dev 2020 Mar 24;16:126-135. Epub 2019 Dec 24.

Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.

Current adoptive T cell therapies conducted in an autologous setting are costly, time-consuming, and depend on the quality of the patient's T cells, and thus it would be highly beneficial to develop an allogeneic strategy. To this aim, we have developed a method by which cytotoxic T lymphocytes (CTLs) are regenerated from induced pluripotent stem cells that are originally derived from T cells (T-iPSCs). In order to assess the feasibility of this strategy, we investigated the frequency of usable T-iPSC clones in terms of their T cell-generating capability and T cell receptor (TCR) affinity. We first established eight clones of T-iPSCs bearing different MART-1-specific TCRs from a healthy volunteer. Whereas all clones were able to give rise to mature CTLs, cell yield varied greatly, and five clones were considered to be usable. TCR affinity in the regenerated CTLs showed a large variance among the eight clones, but functional avidities measured by cytotoxic activity were almost equivalent among three selected clones representing high, medium, and low TCR affinity. In a total of 50 alloreactivity tests using five CTL clones versus ten target cells, alloreactivity was seen in only three cases. These findings collectively support the feasibility of this T-iPSC strategy.
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http://dx.doi.org/10.1016/j.omtm.2019.12.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965501PMC
March 2020

Faithful preclinical mouse models for better translation to bedside in the field of immuno-oncology.

Int J Clin Oncol 2020 May 12;25(5):831-841. Epub 2019 Aug 12.

Department of Urology, Kyoto University, Kyoto, Japan.

The success of immunotherapy using immune checkpoint inhibitors has changed the practice of cancer treatment tremendously. However, there are still many clinical challenges, such as drug resistance, predictive biomarker development, exploration of combination therapies, and prediction of immune-related adverse events in preclinical settings. To overcome these problems, it is essential to establish faithful preclinical mouse models that recapitulate the clinical features, molecular genetics, biological heterogeneity, and immune microenvironment of human cancers. Here we review the advantages and disadvantages of current preclinical mouse models, including syngeneic murine tumor cell lines, autochthonous tumor models, cancer cell line-derived xenografts, patient-derived-xenografts, and various kinds of immunologically humanized mice. We discuss how these models should be characterized and applied in preclinical settings, and how we should prepare preclinical studies for successful translation from bench to bedside.
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http://dx.doi.org/10.1007/s10147-019-01520-zDOI Listing
May 2020

[Outcome of Resection of Inferior Vena Cava Superior to the Renal Vein in Renal Cell Carcinoma with Vena Caval Tumor Thrombus].

Hinyokika Kiyo 2016 Jun;62(6):287-94

The Department of Urology, Akita University Graduate School of Medicine.

Surgical management with radical nephrectomy and thrombectomy has often been performed in renal cell carcinoma (RCC) with tumor thrombus infiltrating the inferior vena cava (IVC). We retrospectively reviewed the outcomes of IVC resection without venous reconstruction in patients with RCC and IVC thrombus at our institution. Eight patients with right RCC underwent radical nephrectomy and IVC resection superior to the level of the renal vein without venous reconstruction from August 2005 to February 2015. Thoracotomy, liver mobilization, and extracorporeal circulation were performed based on the IVC thrombus level. We assessed surgical outcomes, perioperative complications, and survival. At presentation, four patients had level IIIa IVC thrombus, three had level IIIb IVC thrombus, and one had level IV IVC thrombus. Perioperative imaging showed that three of the four patients who underwent neoadjuvant molecular targeting therapy achieved down-staging of the tumor thrombus level. The median operative time was 406 min, and the median estimated blood loss was 3,135 ml. With regard to IVC resectionassociated perioperative complications, one patient needed extracorporeal circulation with IVC ligation and Pringle maneuver owing to low blood pressure. Another patient underwent temporary hemodialysis for 8 days after surgery. There were no perioperative deaths, and none of the patients required permanent hemodialysis. Three patients survived the mean observation period of 25 months, including one patient with no recurrence. Three patients achieved long-term survival of more than 2 years. IVC resection without venous reconstruction may be a feasible option for patients with RCC and IVC tumor thrombus. Further study is needed to determine the most appropriate candidates for this procedure.
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June 2016

COMPARISON BETWEEN EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY AT 120 AND 60 SHOCKWAVES PER MINUTE FOR TREATMENT OF URINARY STONES.

Nihon Hinyokika Gakkai Zasshi 2016 ;107(2):93-99

Department of Urology, Akita Red Cross Hospital.

(Purpose) It has recently been suggested that a slow delivery rate of shockwaves by extracorporeal shock wave lithotripsy (SWL) improved treatment outcomes for urinary stones. We retrospectively analyzed the treatment outcomes of different shockwave delivery rates at 120 and 60 shockwaves per minute. (Patients and method) A total of 88 patients were treated at a fast delivery rate of 120 shockwaves per minute between July 2010 and April 2012, and 139 patients were treated at a slow delivery rate of 60 shockwaves per minute between May 2012 and May 2014 (n=227) using a Sonolith Praktis lithotripter. The treatment outcome of stone-free rate (SFR) after one SWL session was assessed at four weeks. (Result) SWL at 60 shockwaves per minute resulted in a significantly higher SFR compared with SWL at 120 shockwaves per minute (39.8% and 59.0%, respectively, p=0.0047), particularly for upper ureter (U1) stones (53.1% and 72.0%, respectively, p=0.028). Multivariate analysis showed that younger age, stone sizes of 10 mm or less, U1 stones, and slow delivery rate were significant predictors of a stone-free outcome. There were fewer adverse events after the delivery rate of 60 shockwaves per minute (p=0.058). (Conclusion) Our study suggests that SWL at 60 shockwaves per minute should be recommended to successfully treat urinary stones using the Sonolith Praktis lithotripter.
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http://dx.doi.org/10.5980/jpnjurol.107.93DOI Listing
August 2018

[PRIMARY MEDIASTINAL GERM CELL TUMOR ARISING IN A PATIENT WITH NEUROFIBROMATOSIS TYPE 1].

Nihon Hinyokika Gakkai Zasshi 2015 Jul;106(3):178-84

Neurofibromatosis type 1 (NF1) is a distinct genetic disorder due to the NF1 gene mutation which induces the aberrant activation of the RAS-signaling. Because RAS-related proteins function as oncogenic factors, NF1 patients frequently develop malignant tumors, especially of neural crest origin, such as peripheral nerve sheath. In addition, malignant tumors of the pancreas, colorectum, and lung have been reported to frequently arise in NF1 patients. However, the association between germ cell tumor and NF1 has not been clarified yet. A 29-year-old male with dyspnea was referred to our hospital because of the large mass in the anterior mediastinum and cervical lymph node swelling. The diagnosis was extragonadal germ cell tumor with cervical lymph node metastasis, and complete remission was obtained by multidisciplinary treatment consisted of combination chemotherapy and surgical resection. To our acknowledgement, this is the first case of extragonadal germ cell tumor in NF1 patients. We discuss the relevance between activation of the RAS-signaling and the development of germ cell tumor.
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http://dx.doi.org/10.5980/jpnjurol.106.178DOI Listing
July 2015

Tocilizumab and adalimumab in an 18q deletion syndrome patient with chronic arthritis.

Clin Exp Rheumatol 2015 Jan-Feb;33(1):130-1. Epub 2015 Feb 9.

Department of Paediatrics, Akita City Hospital, Japan, Akita City, Akita, Japan.

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April 2015

Renal subcapsular fluid collection caused by penetration of a pancreatic pseudocyst.

Urology 2014 Nov 24;84(5):e23-4. Epub 2014 Oct 24.

Department of Urology, Akita University School of Medicine, Akita, Japan.

A 63-year-old man presented with left flank pain and spiked fever. Computed tomography revealed a pancreatic cyst and left renal subcapsular fluid collection that appeared to be connected to the cyst. High levels of amylase and lipase were observed in a test puncture of renal fluid collection. The cause of the fluid collection was diagnosed as penetration of the pancreatic pseudocyst. Endoscopic nasobiliary drainage was used to drain the pancreatic pseudocyst and renal subcapsular fluid collection. The present case demonstrated that renal subcapsular fluid collection may be caused by penetration of a pancreatic pseudocyst.
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http://dx.doi.org/10.1016/j.urology.2014.07.048DOI Listing
November 2014

[An intravesical foreign body by migration of remnant gauze into the bladder: a case report].

Hinyokika Kiyo 2014 Feb;60(2):83-6

The Department of Urology, Akita University Graduate School of Medicine.

A 35-year-old female, who had undergone Caesarean sections in 2000 and 2001, presented with repeated candida vaginitis and cystitis. She reported that a piece of gauze was excreted through the urethra in 2005. The patient visited an outpatient clinic, but no foreign body was identified by cystoscopy. She again visited the clinic in 2012 complaining of miction pain, and a calcified mass was identified in the bladder. The patient was then referred to our hospital. During a transurethral operation, crushed stones, which included the gauze, were removed from the bladder. We concluded that remnant gauze left in the abdominal cavity during the previous pelvic surgery, had migrated into the bladder and formed a calcified mass.
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February 2014
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