Role of Wnt5b-Ror1 signaling in the proliferation of pancreatic ductal adenocarcinoma cells.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most refractory cancers with the worst prognosis. Although several molecules are known to be associated with the progression of PDAC, the molecular mechanisms underlying the progression of PDAC remain largely elusive. The Ror-family receptors, Ror1 and Ror2, which act as a receptor(s) for Wnt-family ligands, particularly Wnt5a, are involved in the progression of various types of cancers. Here, we show that higher expression of Ror1 and Wnt5b, but not Ror2, are associated with poorer prognosis of PDAC patients, and that Ror1 and Wnt5b are expressed highly in a type of PDAC cell lines, PANC-1 cells. Knockdown of either Ror1 or Wnt5b in PANC-1 cells inhibited their proliferation significantly in vitro, and knockout of Ror1 in PANC-1 cells resulted in a significant inhibition of tumor growth in vivo. Furthermore, we show that Wnt5b-Ror1 signaling in PANC-1 cells promotes their proliferation in a cell-autonomous manner by modulating our experimental setting in vitro. Collectively, these findings indicate that Wnt5b-Ror1 signaling might play an important role in the progression of some if not all of PDAC by promoting proliferation.

Autonomous and intercellular chemokine signaling elicited from mesenchymal stem cells regulates migration of undifferentiated gastric cancer cells.

Accumulating evidence demonstrates that bone marrow (BM)-derived mesenchymal stem cells (MSCs) play critical roles in regulating progression of various types of cancer. We have previously shown that Wnt5a-Ror2 signaling in MSCs induces expression of CXCL16, and that CXCL16 secreted from MSCs then binds to its cognate receptor CXCR6 on the surface of an undifferentiated gastric cancer cell line MKN45 cells, eventually leading to proliferation and migration of MKN45 cells. However, it remains unclear about a possible involvement of another (other) cytokine(s) in regulating progression of gastric cancer. Here, we show that CXCL16-CXCR6 signaling is also activated in MSCs through cell-autonomous machinery, leading to upregulated expression of CCL5. We further show that CCR1 and CCR3, receptors of CCL5, are expressed on the surface of MKN45 cells, and that CCL5 secreted from MSCs promotes migration of MKN45 cells presumably via its binding to CCR1/CCR3. These data indicate that cell-autonomous CXCL16-CXCR6 signaling activated in MSCs upregulates expression of CCL5, and that subsequent activation of CCL5-CCR1/3 signaling in MKN45 cells through intercellular machinery can promote migration of MKN45 cells. Collectively, these findings postulate the presence of orchestrated chemokine signaling emanated from MSCs to regulate progression of undifferentiated gastric cancer cells.

[Multidisciplinary Therapy for Hepatocellular Carcinoma with Peritoneal Dissemination].

We report a case of bilobar multiple hepatocellular carcinoma(HCC)with peritoneal dissemination successfullytreated by dual treatment with reductive surgeryplus percutaneous isolated hepatic perfusion(PIHP). A 73-year-old man had sudden abdominal pain and was diagnosed bilobar multiple HCC through some examinations. The abdominal CT scan demonstrated onlya peritoneal dissemination under the liver. We performed partial hepatectomyof the lateral segment and the Spiegel lobe, and resected a peritoneal dissemination. Subsequently, we underwent PIHP twice. The tumor marker was normalized, and CT images demonstrated complete response according to the RECIST. Dual treatment is considered to be a unique therapeutic modalityfor severe advanced HCC.

Clinical Significance of Early Recurrence After Curative Resection of Colorectal Cancer.

BACKGROUND/AIM: Although survival in cases with early recurrence after curative resection of colorectal cancer has been persistently poor, the risk factors for early recurrence remain unknown. PATIENTS AND METHODS: A total of 1,043 patients with stage I-III colorectal cancer underwent curative resection at Kobe University Hospital between April 2007 and September 2020. Of these, 122 patients developed recurrence: 57 had early recurrence (<1 year after surgery) and 65 patients had late recurrence (≥1 year after surgery). The clinicopathological features were compared between the groups and the risk factors for early recurrence were analyzed. RESULTS: Overall survival both from the date of recurrence and from the date of surgery were significantly worse in the early recurrence group. The proportion of the patients with ≥100 g of intraoperative blood loss, blood transfusion, and postoperative complications were significantly higher in the early recurrence group. R0 resection was achieved more frequently in the late recurrence group. Multivariate analysis revealed that no adjuvant chemotherapy, elevated preoperative CA19-9, blood transfusion, and the occurrence of the postoperative complication were independent risk factors for early recurrence. CONCLUSION: Early recurrence after curative resection of colorectal cancer was associated with worse overall survival. Adjuvant chemotherapy might be beneficial for patients with risk factors of early recurrence to improve prognosis.

A case of peripancreatic plexiform schwannoma.

BACKGROUND: Plexiform schwannoma is one of the least common variants of schwannoma, accounting for only 5% of all schwannoma cases. It generally occurs in the skin and subcutaneous tissues and is uncommon in deep soft tissue or viscera. We present an extremely rare case of plexiform schwannoma arising from the peripancreatic plexus. CASE PRESENTATION: A 29-year-old man presented with hyperglycemia detected during a medical checkup. He was diagnosed with type 1 diabetes based on the clinical findings and laboratory tests. During the diagnostic process for diabetes, a 2.5 cm mass was incidentally detected in the pancreas by abdominal ultrasound. Contrast-enhanced computed tomography revealed a mass that was gradually enhanced at the body and tail of the pancreas. Magnetic resonance imaging revealed low signal intensity of the mass on T1-weighted images and high signal intensity on T2-weighted and diffusion-weighted images. Magnetic resonance cholangiopancreatography showed no abnormal findings in the main pancreatic duct. Endoscopic ultrasonography (EUS) showed a lobulated, low-echoic mass with a clear boundary. EUS-guided fine needle biopsy was performed, and spindle-shaped cells that were diffusely immunopositive for S-100 and negative for c-kit and desmin were detected, resulting in a diagnosis of a neurogenic tumor arising from the pancreas or the peripancreatic nerve plexus. The patient underwent laparoscopic spleen-preserving distal pancreatectomy. Although the tumor was connected to the splenic plexus, the splenic artery could be divided along its adventitial plane. Macroscopic findings of the excised tumor consisted of multiple yellowish-white nodules, and its histopathological features were consistent with plexiform schwannoma. There was no pancreatic tissue on the dorsal surface of the tumor, which suggested that the tumor arose from the peripancreatic nerve plexus. CONCLUSIONS: The findings documented herein can aid in the differential diagnosis of peripancreatic schwannoma and in planning appropriate treatment.

Intussusception caused by a small intestinal lipoma with ectopic gastric mucosa containing gastric cystica profunda component cells within the inverted Meckel's diverticulum: a case report.

BACKGROUND: Lipomas are the most common cause of intussusception in adults. To our knowledge, however, no cases of lipoma and ectopic gastric mucosa with gastritis cystica profunda (GCP) have been reported. We report a case of intussusception caused by a small intestinal lipoma with ectopic gastric mucosa containing GCP-component cells within the inverted Meckel's diverticulum. CASE PRESENTATION: A female in her 40s underwent computed tomography for postoperative follow-up of left breast cancer. A tumor, suspected to be a lipoma, was found in the ileum. Since there were no symptoms, the patient underwent regular follow-up. However, gradual enlargement was observed, and surgery was recommended due to the risk of intussusception. After reduction via the Hutchinson technique, laparoscopically assisted partial resection of the small intestine was performed due to suspicion that the tumor was causing intussusception starting from the ileum. Histopathologic examinations revealed proliferation of mature adipose tissue in the subserosal layer, which was diagnosed as lipoma. Furthermore, adipose tissue was found in the stem area and accordingly, we diagnosed lipoma associated with the inverted Meckel's diverticulum. Moreover, gastric mucosa-like crypt epithelium and proper glandular tissue were identified in the mucosal membrane at the area of onset, and signs of gastric pit dilatation over the submucosa and crypt epithelium hyperplasia were observed. Diagnosis was ectopic gastric mucosa containing GCP component tissue. CONCLUSIONS: Intussusception in the small intestine complicated with lipoma and ectopic gastric mucosa with GCP within the Meckel's diverticulum has not been reported, demonstrating the rarity of our case.