RON and MET Co-overexpression Are Significant Pathological Characteristics of Poor Survival and Therapeutic Targets of Tyrosine Kinase Inhibitors in Triple-Negative Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Triple-negative breast cancer (TNBC) is highly malignant and has poor prognosis and a high mortality rate. The lack of effective therapy has spurred our investigation of new targets for treating this malignant cancer. Here, we identified RON (macrophage-stimulating 1 receptor) and MET (MET proto-oncogene, receptor tyrosine kinase) as a prognostic biomarker and therapeutic targets for potential TNBC treatment. @*Materials and Methods@#We analyzed RON and MET expression in 187 primary TNBC clinical samples with immunohistochemistry. We validated the targeted therapeutic effects of RON and MET in TNBC using three tyrosine kinase inhibitors (TKIs): BMS-777607, INCB28060, and tivantinib. The preclinical therapeutic efficacy of the TKIs was mainly estimated using a TNBC xenograft model. @*Results@#Patients with TNBC had widespread, abnormal expression of RON and MET. There was RON overexpression, MET overexpression, and RON and MET co-overexpression in 63 (33.7%), 63 (33.7%), and 43 cases (23.0%), respectively, which had poor prognosis and short survival. In vivo, the TKI targeting RON ant MET inhibited the activation of the downstream signaling molecules, inhibited TNBC cell migration and proliferation, and increased TNBC cell apoptosis; in the xenograft model, they significantly inhibited tumor growth and shrank tumor volumes. The TKI targeting RON and Met, such as BMS-777607 and tivantinib, yielded stronger anti-tumor effects than INCB28060. @*Conclusion@#RON and MET co-overexpression can be significant pathological characteristics in TNBC for poor prognosis. TKIs targeting RON and MET have stronger drug development potential for treating TNBC.

Adult sacrococcygeal teratoma: a retrospective study over eight years at a single institution / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Objective: To determine the clinical, imaging, and histological features, and surgical resection modalities and outcomes of adult sacrococcygeal teratoma (SCT). Methods: Adult patients with histopathologically diagnosed SCT were enrolled in our hospital between August 2010 and August 2018. Each patient’s characteristics and clinical information were reviewed. Results: There were 8 patients in the study (2 males, 6 females) with a median age of 34 years (range, 18–67 years). The time to clinical symptoms was 14 d to 35 years, with a median time of 4 years. Six patients presented with symptoms of sacrococcygeal pain, and four with signs of sacrococcygeal mass and ulceration in the sacrococcygeal region. Six patients were evaluated using a combination of computed tomography (CT) and magnetic resonance imaging (MRI). All patients showed a presacral tumor with heterogeneous intensity on CT images. All patients underwent surgical treatment, including 6 parasacral, 1 transabdominal, and 1 combined anterior-posterior surgery cases. Seven patients were histopathologically diagnosed with benign mature SCT, and have shown no recurrence. One patient had malignant SCT, with recurrence at 84 months after surgery. After a second surgery, the patient had no recurrence within 6 months follow-up after re-resection. Conclusions: Our retrospective study demonstrated: (1) adult SCT is difficult to diagnose because of a lack of typical clinical symptoms and signs; (2) a combination of CT and MRI examination is beneficial for preoperative diagnosis; (3) the choice of surgical approach and surgical resection modality depends on the size, location, and components of the tumor, which can be defined from preoperative CT and MRI evaluation; (4) most adult SCTs are benign; the surgical outcome for the malignant SCT patient was good after complete resection. Even for the patient with recurrent malignant SCT, the surgical outcome was good after re-resection.

Adult sacrococcygeal teratoma: a retrospective study over eight years at a single institution / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#To determine the clinical, imaging, and histological features, and surgical resection modalities and outcomes of adult sacrococcygeal teratoma (SCT).@*METHODS@#Adult patients with histopathologically diagnosed SCT were enrolled in our hospital between August 2010 and August 2018. Each patient's characteristics and clinical information were reviewed.@*RESULTS@#There were 8 patients in the study (2 males, 6 females) with a median age of 34 years (range, 18-67 years). The time to clinical symptoms was 14 d to 35 years, with a median time of 4 years. Six patients presented with symptoms of sacrococcygeal pain, and four with signs of sacrococcygeal mass and ulceration in the sacrococcygeal region. Six patients were evaluated using a combination of computed tomography (CT) and magnetic resonance imaging (MRI). All patients showed a presacral tumor with heterogeneous intensity on CT images. All patients underwent surgical treatment, including 6 parasacral, 1 transabdominal, and 1 combined anterior-posterior surgery cases. Seven patients were histopathologically diagnosed with benign mature SCT, and have shown no recurrence. One patient had malignant SCT, with recurrence at 84 months after surgery. After a second surgery, the patient had no recurrence within 6 months follow-up after re-resection.@*CONCLUSIONS@#Our retrospective study demonstrated: (1) adult SCT is difficult to diagnose because of a lack of typical clinical symptoms and signs; (2) a combination of CT and MRI examination is beneficial for preoperative diagnosis; (3) the choice of surgical approach and surgical resection modality depends on the size, location, and components of the tumor, which can be defined from preoperative CT and MRI evaluation; (4) most adult SCTs are benign; the surgical outcome for the malignant SCT patient was good after complete resection. Even for the patient with recurrent malignant SCT, the surgical outcome was good after re-resection.

Induction of apoptosis in hormone-resistant human prostate cancer PC3 cells by inactivated Sendai virus / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Inactivated Sendai virus particle [hemagglutinating virus of Japan envelope (HVJ-E)] has a potential oncolytic effect due to its ability to induce apoptosis in tumor cells. However, the molecular mechanism of apoptosis induction in cancer cells mediated by HVJ-E has not been fully elucidated. This paper aims to investigate the underlying mechanism of apoptosis induction by HVJ-E in prostate cancer cells (PC3).</p><p><b>METHODS</b>PC3 cells were treated with HVJ-E at various MOI, and then interferon-β (IFN-β) production, and the cell viability and apoptosis were detected by ELISA, MTT-based assay and flow cytometry, respectively. Next, the roles of Jak-Stat, MAPK and Akt pathways played in HVJ-E-induced apoptosis in PC3 cells were analyzed by immunoblot assay. To further evaluate the cytotoxic effect of HVJ-E on PC3 cells, HVJ-E was intratumorally injected into prostate cancers on BALB/c-nude mice, and the tumor volume was monitored for 36 days.</p><p><b>RESULTS</b>HVJ-E induced IFN-β production and activated Jak-Stat signaling pathway, which resulted in the activation of caspase-8, caspase-3, and PARP in PC3 prostate cancer cells post HVJ-E treatment. Furthermore, we observed for the first time that p38 and Jnk MAPKs in PC3 cells contributed to HVJ-E-induced apoptosis. In addition, intratumoral HVJ-E treatment displayed a direct inhibitory effect in an in vivo BALB/c nude mouse prostate cancer model.</p><p><b>CONCLUSION</b>Our findings have provided novel insights into the underlying mechanisms by which HVJ-E induces apoptosis in tumor cells.</p>

The role of hand-assisted laparoscopic surgery in total colectomy for colonic inertia: a retrospective study / 대한외과학회지

PURPOSE: To compare and assess the efficacy, safety and utility of hand-assisted laparoscopic surgery (HALS) with open surgery (OS) in total colectomy with ileorectal for colonic inertia. METHODS: From January 2001 to February 2012, 56 patients diagnosed with colonic inertia who failed to respond to medical treatments underwent hand-assisted laparoscopic total colectomy with ileorectal anastomosis. Another 68 patients underwent laparotomy. Main parameters such as clinical manifestations, conversion to open procedure, operative time, incision length, pain score, intraoperative blood loss, time to first flatus and hospitalization, early postoperative complications and hospitalization cost were retrospectively analyzed. Postoperative defecating frequencies were followed up in both groups. RESULTS: All patients received successful operation, no surgical mortality happened and none of the patients required conversion to an exploratory laparotomy in HALS group. The clinical features, the estimated blood loss, incision length, pain score, first passing flatus time, and postoperative hospitalization time were superior in HALS group (P < 0.05). The early postoperative complications and frequency of defecation were similar. However, the mean operative time was longer and hospitalization cost was higher in HALS group than those in OS group (P < 0.05). CONCLUSION: HALS total colectomy can be a safe and efficient technique in the treatment of colonic inertia. HALS can result in a better cosmetic result and a quicker postoperative recovery, but requires higher direct cost.

Inactivated Sendai virus suppresses murine melanoma growth by inducing host immune responses and down-regulating β-catenin expression / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>This paper aims to investigate the anti-tumor mechanism of inactivated Sendai virus (Hemagglutinating virus of Japan envelope, HVJ-E) for murine melanoma (B16F10).</p><p><b>METHODS</b>The murine dendritic cells (DCs) were treated with HVJ-E, and then the cytokines secreted from DCs and costimulation-related molecules on DCs were measured. Meanwhile, the expression of β-catenin in HVJ-E treated murine melanoma cells was detected. In addition, HVJ-E was intratumorally injected into the melanoma on C57BL/6 mice, and the immune cells, CTL response and tumor volume were analyzed.</p><p><b>RESULTS</b>HVJ-E injected into B16F10 melanoma obviously inhibited the growth of the tumor and prolonged the survival time of the tumor-bearing mice. Profiles of cytokines secreted by dendritic cells (DCs) after HVJ-E stimulation showed that the number of cytokines released was significantly higher than that elicited by PBS (1P<0.05). The co-stimulation-related molecules on DCs were comparable to those stimulated by LPS. Immunohistochemical examinations demonstrated the repression of β-catenin in B16F10 melanoma cells after HVJ-E treatment. Meanwhile, real-time reverse transcription PCR revealed that HVJ-E induced a remarkable infiltration of CD11c positive cells, chemokine ligand 10 (CXCL10) molecules, interleukin-2 (IL-2) molecule, CD4(+) and CD8(+) T cells into HVJ-E injected tumors. Furthermore, the mRNA expression level of β-catenin in the HVJ-E injected tumors was also down-regulated. In addition, B16F10-specific CTLs were induced significantly after HVJ-E was injected into the tumor-bearing mice.</p><p><b>CONCLUSION</b>This is the first report to show the effective inhibition of melanoma tumors by HVJ-E alone and the mechanism through which it induces antitumor immune responses and regulates important signal pathways for melanoma invasion. Therefore, HVJ-E shows its prospect as a novel therapeutic for melanoma therapy.</p>

Clinical study of hand-assisted laparoscopic total colectomy for colonic inertia / 中华外科杂志

<p><b>OBJECTIVE</b>To compare the efficacy of hand-assisted laparoscopic surgery (HALS) with that of open surgery (OS) in total colectomy, and to evaluate the feasibility of hand-assisted laparoscopic total colectomy for colonic inertia.</p><p><b>METHODS</b>A total of 42 patients of colonic inertia received total colectomy from January 2001 to June 2006 were randomly allocated to OS group (n = 22) and HALS group (n = 20). Data as clinical manifestation, perioperative features including operative time, intraoperative blood loss and incision length, postoperative features including first flatus-passing time, first fluid-feeding time, hospitalization time, early postoperative complications, and hospitalizing expense were recorded and compared in the two groups. Postoperative defecating frequency was followed up in both groups.</p><p><b>RESULTS</b>All patients underwent total colectomy successfully and no death of operation occurred. The clinical features, operative time and blood loss were similar for the two groups. Incision length, first flatus-passing time, first fluids-feeding time, hospitalization time were better in HALS group than those in OS group. But mean hospitalizing expense in HALS group was higher than that in OS group. One case of incision infection and one intestinal obstruction occurred in OS group. No complication occurred in HALS group. Patients were followed up for 2 - 14 months, in the meantime the average defecating frequency was 3.55 +/- 1.80/d.</p><p><b>CONCLUSIONS</b>HALS and open total colectomy are safe, rapid and effective surgical procedures for colonic inertia. HALS can result in a better cosmetic effect and a quicker postoperative recovery.</p>