Recurrence prediction in clear cell renal cell carcinoma using machine learning of quantitative nuclear features.

The recurrence of non-metastatic renal cell carcinoma (RCC) may occur early or late after surgery. This study aimed to develop a recurrence prediction machine learning model based on quantitative nuclear morphologic features of clear cell RCC (ccRCC). We investigated 131 ccRCC patients who underwent nephrectomy (T1-3N0M0).

Prediction of non-muscle invasive bladder cancer recurrence using machine learning of quantitative nuclear features.

Non-muscle invasive bladder cancer (NMIBC) generally has a good prognosis; however, recurrence after transurethral resection (TUR), the standard primary treatment, is a major problem. Clinical management after TUR has been based on risk classification using clinicopathological factors, but these classifications are not complete. In this study, we attempted to predict early recurrence of NMIBC based on machine learning of quantitative morphological features.

Giant retroperitoneal schwannoma in a 52-year-old man.

Schwannoma in the retroperitoneal space is rare, and it is extremely rare in patients with no history of neurofibromatosis. We present a case of giant retroperitoneal schwannoma in a 52-year-old man who did not have neurofibromatosis. Because malignant transformation would be extremely rare in this circumstance, close imaging follow-up could avert the necessity for complete resection.

Molecular targeted therapies of renal cell carcinoma considering life stage of the patient: Two case reports.

Molecular targeted therapies have markedly improved the prognosis of metastatic renal cell carcinoma (RCC) and patients are able to receive specific treatments depending on their condition. The cases of two patients who presented with large RCC with very different statuses were examined in the current study. One of the patients was elderly with numerous comorbidities, and the other was young and had Case 1 was an elderly female with various comorbidities including a history of cerebral infarction and impaired eyesight.

Incidental Presacral Myelolipoma Resembling the Liposarcoma: A Case Report and Literature Review.

Presacral myelolipomas are rare, benign, asymptomatic tumors composed of mature adipose tissue and hematopoietic elements, but fewer than 50 cases have been reported in the literature. They are usually discovered incidentally during imaging studies and are often misdiagnosed as liposarcoma, which have a malignant nature, because the imaging findings of myelolipoma can be similar to those of liposarcoma. It is challenging to distinguish presacral myelolipomas from other presacral fat-containing tumors without performing a histological examination.

Annular rectal constriction caused by infiltrating bladder cancer: A case report.

A 69-year-old man was referred to our hospital with chief complaints of urinary incontinence, pollakiuria, thin stools and edema of the left lower extremity. Computed tomography and magnetic resonance imaging revealed bilateral hydronephrosis, thickening of the rectal and posterolateral bladder walls, and enlargement of the left obturator lymph nodes, suggesting metastasis. The carcinoembryonic antigen and carbohydrate antigen 19-9 levels were 5.

Individual and combining effects of anti-RANKL monoclonal antibody and teriparatide in ovariectomized mice.

We examined the individual and combined effects of teriparatide and anti-RANKL (receptor activator of nuclear factor κB ligand) monoclonal antibody in ovariectomized mice. Three-month-old female C57BL/6 mice were ovariectomized (OVX) or sham operated. Four weeks after OVX, they were assigned to 3 different groups to receive anti-RANKL monoclonal antibody (Ab) alone (5 mg/kg single injection at 4 weeks after OVX, Ab group), teriparatide alone (80 μg/kg daily injection for 4 weeks from 4 weeks after OVX, PTH group), or mAb plus teriparatide (Ab + PTH group).

Genomewide comprehensive analysis reveals critical cooperation between Smad and c-Fos in RANKL-induced osteoclastogenesis.

We have previously reported that transforming growth factor β (TGF-β) plays an essential role in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. However, the detailed underlying molecular mechanisms still remain unclear. Formaldehyde-assisted isolation of regulatory elements (FAIRE) and chromatin immunoprecipitation (ChIP) followed by sequencing (FAIRE-seq and ChIP-seq) analyses indicated the cooperation of Smad2/3 with c-Fos during osteoclastogenesis.

[Updates of denosumab, anti-RANKL antibody for osteoporosis].

Osteoporosis and osteoporosis-related fractures tend to increase year by year around the world including Japan. Denosumab, a fully human monoclonal antibody to receptor activator of NF-κB ligand (RANKL) , a cytokine member of the TNF family essential for osteoclast differentiation has recently been approved in Japan, Europe and the US for the treatment of postomenopausal osteoporosis as well as bone metastasis. In some large clinical trials, denosumab significantly decreased bone resorption, increased bone mineral density (BMD) , and reduced the risk of vertebral, nonvertebral and hip fractures in postmenopausal women.

Bone resorption is regulated by cell-autonomous negative feedback loop of Stat5-Dusp axis in the osteoclast.

Signal transducer and activator of transcription 5 (Stat5) is essential for cytokine-regulated processes such as proliferation, differentiation, and survival in hematopoietic cells. To investigate the role of Stat5 in osteoclasts, we generated mice with an osteoclast-specific conditional deletion of Stat5 (Stat5 conditional knockout [cKO] mice) and analyzed their bone phenotype. Stat5 cKO mice exhibited osteoporosis caused by an increased bone-resorbing activity of osteoclasts.

Anti-apoptotic Bcl-2 family member Mcl-1 regulates cell viability and bone-resorbing activity of osteoclasts.

Myeloid cell leukemia sequence 1 (Mcl-1) is an anti-apoptotic Bcl-2 family protein and an immediate early gene expressed during myeloid leukemia cell line differentiation. We analyzed the expression and function of Mcl-1 in osteoclasts. Mcl-1 protein exhibited a short half-life in osteoclasts caused by its degradation in the ubiquitin-proteasome system.

Regulation of bone resorption and sealing zone formation in osteoclasts occurs through protein kinase B-mediated microtubule stabilization.

We investigated the role of protein kinase B (Akt), a downstream effector of phosphatidylinositol 3-kinase, in bone-resorbing activity of mature osteoclasts. Treatment with a specific Akt inhibitor disrupted sealing zone formation and decreased the bone-resorbing activity of osteoclasts. The normal microtubule structures were lost and the Akt inhibitor reduced the amount of acetylated tubulin, which reflects stabilized microtubules, whereas forced Akt activation by adenovirus vectors resulted in the opposite effect.

[Cytokines in bone diseases. Genetic disorders of RANKL-RANK-OPG system].

It is now widely recognized that the RANKL-RANK-OPG signaling system plays an important role in the differentiation, activation and cell death of osteoclasts. Recently, several genetic disorders involving the RANKL-RANK-OPG system have been discovered. In this article, we would like to show a brief review on a genetic disorder familial expansile osteolysis (FEO) , in which RANK gene mutation was identified, and other genetic disorders of the RANKL-RANK-OPG system.