Protective effects of conditioned media of immortalized stem cells from human exfoliated deciduous teeth on pressure ulcer formation.

Pressure ulcers (PUs) are increasing with aging worldwide, but there is no effective causal therapy. Although mesenchymal stem cells (MSCs) promote cutaneous wound healing, the effects of the conditioned medium (CM) of MSCs on cutaneous PU formation induced by ischemia-reperfusion injury have been poorly investigated. To address this issue, herein, we first established an immortalized stem cell line from human exfoliated deciduous teeth (SHED). This cell line was revealed to have superior characteristics in that it grows infinitely and vigorously, and stably and consistently secretes a variety of cytokines. Using the CM obtained from the immortalized SHED cell line, we investigated the therapeutic potential on a cutaneous ischemia-reperfusion mouse model for PU formation using two magnetic plates. This is the first study to show that CM from immortalized SHEDs exerts therapeutic effects on PU formation by promoting angiogenesis and oxidative stress resistance through vascular endothelial growth factor and hepatocyte growth factor. Thus, the CM of MSCs has potent therapeutic effects, whereas these therapies have not been implemented in human medicine. To try to meet the regulatory requirements for manufacturing and quality control as much as possible, it is necessary to produce CM that is consistently safe and effective. The immortalization of stem cells could be one of the breakthroughs to meet the regulatory requirements and consequently open up a novel avenue to create a novel type of cell-free regenerative medicine, although further investigation into the quality control is warranted.

A Chaperone-Like Role for EBI3 in Collaboration With Calnexin Under Inflammatory Conditions.

The interleukin-6 (IL-6)/IL-12 family of cytokines plays critical roles in the induction and regulation of innate and adaptive immune responses. Among the various cytokines, only this family has the unique characteristic of being composed of two distinct subunits, α- and ß-subunits, which form a heterodimer with subunits that occur in other cytokines as well. Recently, we found a novel intracellular role for one of the α-subunits, Epstein-Barr virus-induced gene 3 (EBI3), in promoting the proper folding of target proteins and augmenting its expression at the protein level by binding to its target protein and a well-characterized lectin chaperone, calnexin, presumably through enhancing chaperone activity. Because calnexin is ubiquitously and constitutively expressed but EBI3 expression is inducible, these results could open an avenue to establish a new paradigm in which EBI3 plays an important role in further increasing the expression of target molecules at the protein level in collaboration with calnexin under inflammatory conditions. This theory well accounts for the heterodimer formation of EBI3 with p28, and probably with p35 and p19 to produce IL-27, IL-35, and IL-39, respectively. In line with this concept, another ß-subunit, p40, plays a critical role in the assembly-induced proper folding of p35 and p19 to produce IL-12 and IL-23, respectively. Thus, chaperone-like activities in proper folding and maturation, which allow the secretion of biologically active heterodimeric cytokines, have recently been highlighted. This review summarizes the current understanding of chaperone-like activities of EBI3 to form heterodimers and other associations together with their possible biological implications.

Carcinomatous meningitis from recurrent glassy cell carcinoma of the uterine cervix-A case report.

Carcinomatous meningitis presents with a variety of neurological symptoms and has a poor prognosis. We encountered a case of carcinomatous meningitis from cervical cancer. A 30-year-old patient was diagnosed with cervical cancer (glassy cell carcinoma), stage IIB. She underwent radical hysterectomy and chemoradiotherapy. Nine months later, the disease recurred with iliac lymph node and right lung metastases. The patient received chemotherapy; however, after seven cycles, the lung lesions increased. The patient responded to supportive care; nevertheless, symptoms including headaches developed and were followed by diplopia. A contrast-enhanced magnetic resonance image of the head confirmed the diagnosis of carcinomatous meningitis. She was transferred to the palliative care unit and died approximately 1 week later. Carcinomatous meningitis has a poor prognosis and is difficult to treat; however, early diagnosis may provide meaningful time to patients. Therefore, attention must be paid to meningeal irritation and neurological symptoms.

Efficacy of palonosetron plus dexamethasone in preventing chemotherapy-induced nausea and emesis in patients receiving carboplatin-based chemotherapy for gynecologic cancers: a phase II study by the West Japan Gynecologic Oncology Group (WJGOG 131).

OBJECTIVE: Palonosetron is effective for the management of acute and delayed chemotherapy-induced nausea and vomiting (CINV). While emetogenic carboplatin-based chemotherapy is widely used to treat gynecologic cancers, few studies have evaluated the antiemetic effectiveness of palonosetron in this setting. METHODS: A multicenter, single-arm, open-label phase II trial was conducted to evaluate the safety and effectiveness of palonosetron in controlling CINV in patients with gynecologic cancer. Chemotherapy-naïve patients received intravenous palonosetron (0.75 mg/body) and dexamethasone before the infusion of carboplatin-based chemotherapy on day 1. Dexamethasone was administered (orally or intravenously) on days 2-3. The incidence and severity of CINV were evaluated using the patient-completed Multinational Association of Supportive Care in Cancer Antiemesis Tool and treatment diaries. The primary endpoint was the proportion of patients experiencing complete control (CC) of vomiting, with "no rescue antiemetic medication" and "no clinically significant nausea" or "only mild nausea" in the delayed phase (24-120 hours post-chemotherapy). Secondary endpoints were the proportion of patients with a complete response (CR: "no vomiting" and "no rescue antiemetic medication") in the acute (0-24 hours), delayed (24-120 hours), and overall (0-120 hours) phases, and CC in the acute and overall phases. RESULTS: Efficacy was assessable in 77 of 80 patients recruited. In the acute and delayed phases, the CR rates the primary endpoint, were 71.4% and 59.7% and the CC rates, the secondary endpoint, were 97.4% and 96.1%, respectively. CONCLUSION: While palonosetron effectively controls acute CINV, additional antiemetic management is warranted in the delayed phase after carboplatin-based chemotherapy in gynecologic cancer patients (Trial registry at UMIN Clinical Trials Registry, UMIN000012806).

Clinical Utility of Endometrial Cell Block Cytology in Postmenopausal Women.

OBJECTIVE: To investigate the diagnostic utility of endometrial (EM) cell block (CB) cytology for the detection of intrauterine malignancy in postmenopausal women. METHODS: We reviewed the medical records of 104 postmenopausal women between January 2012 and November 2014. We reviewed symptoms upon admission, body mass index, parity, transvaginal ultrasonographic findings, and histopathological results based on CB and conventional cytology. RESULTS: The mean age was 62.6 (range 48-95) years. The mean menopausal age was 50.8 years and the mean duration of menopause was 12.0 years. The sensitivity of CB and conventional cytology was 82.3% (29/35) and 85.7% (30/35) and the specificity was 98.6% (68/69) and 94.2% (65/69), respectively. The sensitivity and specificity of CB cytology combined with conventional cytology were 82.3% (29/35) and 94.2% (65/69), respectively. The predictive values for EM hyperplasia and type-II carcinoma were 100 and 85.7%, respectively. CONCLUSION: CB cytology provides specimens for examination in a single outpatient session. Additionally, immunohistochemical staining can provide useful information for histological diagnosis. A combination of CB and conventional cytology can improve the diagnostic accuracy of EM lesions and may be a valid method for screening in postmenopausal women.

Two cases of acute limbic encephalitis in which symptoms improved as a result of laparoscopic salpingo-oophorectomy.

Anti-N-methyl-D-aspartate (NMDA) receptor antibody encephalitis is an autoimmune form of limbic encephalitis. Eighty percent of patients with anti-NMDA receptor (NMDAR) encephalitis are women, and 39% of those women are reported to have an ovarian teratoma also. When a tumor is also present, prompt surgery can prevent the development of more severe symptoms or the prolongation of symptoms of encephalitis. The current authors encountered two cases in which anti-NMDAR encephalitis was suspected. In these cases, abdominal computed tomography (CT) revealed an ovarian teratoma and both patients underwent a laparoscopic salpingo-oophorectomy. Both patients underwent surgery before a definitive diagnosis was made. Findings in one case did not lead to a diagnosis of anti-NMDAR encephalitis, but symptoms rapidly improved after surgery in both cases. Laparoscopic surgery is minimally invasive, so this approach may be the first step in a treatment algorithm for treatment of a tumor in a patient with anti-NMDAR encephalitis.

Detection of serous precursor lesions in resected fallopian tubes from patients with benign diseases and a relatively low risk for ovarian cancer.

The frequency of ovarian cancers in Japan has increased; however, doubts have been raised concerning the mechanism by which high-grade serous adenocarcinomas (HGSCs) arise. Conventionally, HGSC is thought to originate from the ovarian surface epithelium or epithelial inclusion cyst. However, recent data indicate that HGSCs may in fact develop from precursor lesions in the fallopian tube, including epithelia with a p53 signature, serous tubal intraepithelial carcinomas (STICs), secretory cell outgrowths (SCOUTs), and tubal intraepithelial lesions in transition (TILT). Here, we determined the frequency of these fallopian tube precursors in surgically excised samples from 123 patients with benign pelvic diseases. We identified 12 cases with a p53 signature (9.7%), 26 with observable SCOUTs (21.1%), and 4 with TILT (3.2%), but no STIC cases. Although the lifetime risk for developing ovarian cancer is only around 1.4% for women without germ-line mutations, it is important to evaluate the presence of precursor lesions to understand HGSC pathogenesis better. Taken together, salpingectomy appears to be an option for women who are past their childbearing age and plan to undergo elective pelvic surgery. To our knowledge, this is the first study to investigate the presence of these specific precursors post-salpingectomy in low-risk patients.

Desmoplastic small round cell tumor in the ovary: Report of two cases and literature review.

Desmoplastic small round cell tumor (DSRCT) is a rare intra-abdominal tumor of uncertain histogenesis that occurs predominantly in young males. We report two cases of DSRCT in young women that presented clinically as ovarian tumor with extensive pelvic and abdominal dissemination. Both patients underwent debulking surgery and combined chemotherapy. After primary therapy, the tumors recurred and both women died of the disease. The clinical presentation and differential diagnosis, as well as the treatment, including surgical debulking and combined chemotherapy are discussed.