Search

A 31‐year‐old primiparous woman underwent non‐invasive prenatal testing. The result was trisomy 13 (T13) positive. The chromosome 13 t‐statistics (Z‐score) was significantly high. The result of amniocentesis was normal karyotype (46,XX). Detailed ultrasound showed no fetal structural abnormalities. We suspected T13 confined placental mosaicism (CPM) and observed the course naturally. From the late second trimester, severe fetal growth restriction manifested followed by proteinuria and hypertension, diagnosing her with preeclampsia (PE). At 35 + 5 weeks, emergent cesarean section was required, yielding a 1480 g female infant. We sampled five locations of chorionic villi in the placenta. T13 cells dominated cells with normal karyotypes in all parts and the rate of trisomic cells ranged from 57% to 96%, which were generally high rate. None developed PE in reported T13 CPM cases and this is the first case of PE. The dominancy of T13 cells can be associated with PE development. [ABSTRACT FROM AUTHOR]

Pulmonary neuroendocrine (NE) cells are rare airway epithelial cells. The balance between Achaete‐scute complex homolog 1 (ASCL1) and hairy and enhancer of split 1, one of the target molecules of the Notch signaling pathway, is crucial for NE differentiation. Small cell lung cancer (SCLC) is a highly aggressive lung tumor, characterized by rapid cell proliferation, a high metastatic potential, and the acquisition of resistance to treatment. The subtypes of SCLC are defined by the expression status of NE cell‐lineage transcription factors, such as ASCL1, which roles are supported by SRY‐box 2, insulinoma‐associated protein 1, NK2 homeobox 1, and wingless‐related integration site signaling. This network reinforces NE differentiation and may induce the characteristic morphology and chemosensitivity of SCLC. Notch signaling mediates cell‐fate decisions, resulting in an NE to non‐NE fate switch. The suppression of NE differentiation may change the histological type of SCLC to a non‐SCLC morphology. In SCLC with NE differentiation, Notch signaling is typically inactive and genetically or epigenetically regulated. However, Notch signaling may be activated after chemotherapy, and, in concert with Yes‐associated protein signaling and RE1‐silencing transcription factor, suppresses NE differentiation, producing intratumor heterogeneity and chemoresistance. Accumulated information on the molecular mechanisms of SCLC will contribute to further advances in the control of this recalcitrant cancer. [ABSTRACT FROM AUTHOR]

Background: Biliary confluence is sometimes involved in colorectal liver metastasis (CRLM), and therefore bile duct resection (BDR) is occasionally necessary for complete resection. However, the utility of hepatectomy with combined BDR is unclear. The safety and survival outcome of hepatectomy with combined BDR for CRLM was assessed. Methods: Patients who underwent hepatectomy for CRLM between 2002 and 2017 were identified from a prospectively compiled database. Postoperative outcomes were compared between patients undergoing hepatectomy alone and with combined BDR for CRLM. Results: A total of 734 patients who underwent hepatectomy for CRLM were included. Hepatectomy with combined BDR was performed in 16 (2.1%) patients. The postoperative complications rate (Clavien–Dindo ≥ 3) of patients undergoing hepatectomy with BDR was 31.2%, which was higher than that without BDR (P = 0.001) for CRLM. The mortality rate of surgery for CRLM was 0%. The 5- and 10-year relapse-free survival (RFS) rates for hepatectomy with BDR were 45.0% and 30.0%, respectively. Patients undergoing hepatectomy with BDR had a similar RFS to those without BDR for CRLM (P = 0.351). The 5- and 10-year overall survival (OS) rates for hepatectomy with BDR were 62.6% and 62.6%, respectively. Patients undergoing hepatectomy with BDR had a similar OS to those without BDR for CRLM (P = 0.738). Conclusions: In conclusion, hepatectomy with combined BDR was a potentially feasible treatment option that obtained favorable survival outcomes in patients with invasion of the biliary confluence by CRLM, although BDR with hepatectomy for CRLM was associated with a high rate of morbidity. [ABSTRACT FROM AUTHOR]

Purpose This work studies the detective quantum efficiency ( DQE) of a-Se-based solid state x-ray detectors for medical imaging applications using ARTEMIS, a Monte Carlo simulation tool for modeling x-ray photon, electron and charged carrier transport in semiconductors with the presence of applied electric field. Methods ARTEMIS is used to model the signal formation process in a-Se. The simulation model includes x-ray photon and high-energy electron interactions, and detailed electron-hole pair transport with applied detector bias taking into account drift, diffusion, Coulomb interactions, recombination and trapping. For experimental validation, the DQE performance of prototype a-Se detectors is measured following IEC Testing Standard 62220-1-3. Results Comparison of simulated and experimental DQE results show reasonable agreement for RQA beam qualities. Experimental validation demonstrated within 5% percentage difference between simulation and experimental DQE results for spatial frequency above 0.25 cycles/mm using uniform applied electric field for RQA beam qualities ( RQA5, RQA7 and RQA9). Results include two different prototype detectors with thicknesses of 240 μm and 1 mm. Conclusions ARTEMIS can be used to model the DQE of a-Se detectors as a function of x-ray energy, detector thickness, and spatial frequency. The ARTEMIS model can be used to improve understanding of the physics of x-ray interactions in a-Se and in optimization studies for the development of novel medical imaging applications. [ABSTRACT FROM AUTHOR]

Background: The American Joint Committee on Cancer (AJCC) has recommended that cancers with liver involvement be graded T2b and those with portal vein involvement be graded T3, although the value of staging as prognostic factors remains unclear. We evaluated the current definition of the T2/3 tumors for perihilar cholangiocarcinoma. Methods: A total of 202 patients with perihilar cholangiocarcinoma who underwent hepatectomy without vascular resection were enrolled. Clinicopathologic data about invasion of the liver and the unilateral portal vein were evaluated. Results: The liver and the unilateral portal vein were involved in 100 (49.5 %) and 38 (18.8 %) patients, respectively. The survival rates were not significantly different between patients with and without liver invasion (48.6 vs. 52.2 %, respectively, at 5 years, P = 0.157) and between patients with or without unilateral portal vein invasion (43.2 vs. 52.1 %, respectively, at 5 years, P = 0.363). The survival rate of patients with tumors staged pT2b was not significantly different from the rate of patients with pT2a (63.4 vs. 55.6 % at 5 years, P = 0.912), and the pT2b tumor patient survival rate was better than the rate of patients with pT3 (34.9 % at 5 years, P = 0.011). Using multivariate analysis, nodal metastasis ( P = 0.003), positive surgical margin ( P = 0.010), and Bismuth type IV tumor ( P = 0.039) were identified as independent prognostic factors. Conclusions: The liver and the unilateral portal vein are frequently involved in perihilar cholangiocarcinoma. The determinants of the current AJCC T2/3 tumor classifications are rational; however, subdivision of T2 tumors may be of less clinical value. [ABSTRACT FROM AUTHOR]

To investigate the possibility of‘de novo’ prostate cancer by analyzing the relationship between high grade prostatic intraepithelial neoplasia (HGPIN) and latent prostate cancer.Latent prostate cancers found at autopsy were examined and 55 cancer foci with a poorly (Gleason grade 4 and 5) or moderately (Gleason grade 3) differentiated component were selected. The 55 foci were separated into two groups: (i) foci with either a poorly or moderately differentiated component only (single differentiation group, SDG); and (ii) mixed foci with two or more types of differentiation components (mixed differentiation group, MDG). High grade intraepithelial neoplasia was defined as positive if it was observed within 2 mm from the edge of the cancer focus and the relationship between HGPIN and the two groups was investigated.The MDG had 39 cancer foci (71.0%) and there were 16 in the SDG (29.0%). There were 31 foci that were small-volume cancers (<0.2 mL). In the MDG, 13 small-volume cancer foci were HGPIN positive, but in the SDG, none of the small-volume cancers were HGPIN positive.Small-volume cancer foci without HGPIN in the SDG may be candidates for de novo prostate cancers. [ABSTRACT FROM AUTHOR]

To investigate retrospectively whether the eight-core biopsy method improves the prostate cancer detection rate when compared with the standard sextant biopsy method in patients with prostate specific antigen (PSA) levels of 4.1–10 ng/mL. Of 437 patients whose PSA levels ranged from 4.1 to 10 ng/mL, 237 underwent a transrectal ultrasound guided sextant biopsy (sextant group), and 200 underwent an eight-core biopsy (eight-core group). Eight core samples were obtained from each of the far lateral regions in addition to the standard sextant biopsy cores. None of the patients had a previous history of prostate biopsy. Of the 237 patients in the sextant group, prostate cancer was detected in 47 patients (19.8%) and in 50 of the 200 patients in the eight- core group (25.0%). The rates of detection in the two methods were not statistically significant. However, in patients whose PSA density was less than 0.1 ng/mL per cc, the cancer detection rates in the sextant group and the eight-core group were 4.5% and 18.8%, respectively ( P = 0.046). The morbidity and complications of the eight-core biopsy method were not notable. Only in patients with PSA levels of 4.1–10 ng/mL and density of less than 0.1 ng/mL per cc was the eight-core biopsy method an improvement on the sextant biopsy method in terms of prostate cancer detection rate. Accordingly, a number of cores greater than eight will be required to improve the cancer detection rates in patients with PSA levels of 4.1–10 ng/mL and PSA densities of more than 0.1 ng/mL per cc. [ABSTRACT FROM AUTHOR]

Rcd1, initially identified as a factor essential for the commitment to nitrogen starvation-invoked differentiation in fission yeast, is one of the most conserved proteins found across eukaryotes, and its mammalian homolog is expressed in a variety of differentiating tissues. Here we show that mammalian Rcd1 is a novel transcriptional cofactor and is critically involved in the commitment step in the retinoic acid-induced differentiation of F9 mouse teratocarcinoma cells, at least in part, via forming complexes with retinoic acid receptor and activation transcription factor-2 (ATF-2). In addition, antisense oligonucteotide treatment of embryonic mouse lung explants suggests that Rcd1 also plays a role in retinoic acid-controlled lung development. [ABSTRACT FROM AUTHOR]

Background: In oral lichen planus (OLP), destruction of the basal cell layer, which is one of the characteristic histological features, is seen and many changes in cell proliferation, cell repair and cell death occur in the injured mucosal epithelium.Methods: We studied mucosal tissues from 19 patients of OLP and 10 controls, with immunohistochemistry for Ki-67, p53, cyclin dependent kinase inhibitors (CDKI) and cyclins. Mitotic count was calculated. TUNEL assay was also performed for evaluation of apoptotic cell death.Results: Mitotic count, Ki-67 and cyclin D1 labeling indices in the basal and parabasal layers of OLP mucosa were elevated in comparison with those of controls. p53, p21Cip1 and TUNEL indices of OLP mucosa were also increased.Conclusions: These complex changes, which concomitantly occur in the injured mucosal epithelium, could contribute to the development and maintenance of characteristic mucosal epithelial architectures seen in OLP. [ABSTRACT FROM AUTHOR]

Abstract Background: M1 prostate cancer, which is invasive, is usually associated with a serum level of prostate-specific antigen (PSA) greater than 10 ng/mL, but cases are occurring where the serum PSA level is less than this. The present study investigated the clinical and pathologic characteristics of these cases of M1 prostate cancer. Methods: Between April 1989 and March 1998, 167 cases of M1 prostate cancer were diagnosed by transrectal needle biopsy and eight of these with a serum PSA level less than 10 ng/mL were investigated. The patients' ages ranged from 57 to 79 years (median, 73) and the serum PSA levels ranged from less than 4.0 to 9.8 ng/mL. In all cases except one, the distal metastasis was to bones only. All cases had received hormonal therapy as the initial therapy. Immunostaining of PSA, chromogranin A, neuron-specific enolase, carcinoembryonic antigen and vimentin were performed in five of the eight cases. Results: Four cases were poorly differentiated, two were undifferentiated, one was a mixture of poorly differentiated and undifferentiated and one case was moderately differentiated. Of the five cases in the immunohistochemical study, three cases with an undifferentiated carcinoma component showed negative staining reactions for PSA and all cases were positive for carcinoembryonic antigen. Four of the patients died of prostate cancer. In two of these four cases, hormonal therapy was ineffective, but systemic chemotherapy and irradiation therapy had been moderately effective. The overall 3-year survival rate was 33.3%. Conclusions: The cases of M1 prostate cancer with a serum PSA less than 10 ng/mL are almost always poorly differentiated or undifferentiated and have a poor prognosis compared with the usual M1 prostate cancer. Because hormonal therapy is ineffective in these cases, systemic chemotherapy and irradiation therapy should be chosen as the initial therapy. [ABSTRACT FROM AUTHOR]

Background Previously, we reported that Sema3A, one of the secreted repulsive axon guidance molecules, CRMP (collapsin response mediator protein)-2, a putative intracellular signalling molecule for Sema3A and Sema3A receptor neuropilin-1 are expressed in the developing lung. Sema3A inhibits branching morphogenesis of embryonic lung in organ culture. Results We examined the gene expression of Sema3A, Sema3C, Sema3F and their receptors, NP-1, NP-2 and plexin-A1 by in situ hybridization. Transcripts of all six genes were detected in mouse lung from embryonic day E11.5 to E17.5, and displayed highly specific spatiotemporal distributions. The distribution of the receptor genes was detected in patterns which were consistent with known receptor usage of the semaphorins. In contrast to Sema3A, we found that the other class 3 semaphorins, Sema3C and Sema3F, stimulated branching morphogenesis. This stimulatory effect of Sema3C or Sema3F was accompanied by a moderate increase in the incorporation of bromodeoxyuridine (BrdU) into DNA in the terminal epithelial cells. Conclusion The coordinated expression patterns of different semaphorins and their receptors, together with the specific activities affecting branching morphogenesis, suggest that the semaphorins act as both positive and negative regulators of branching morphogenesis in the developing lung. [ABSTRACT FROM AUTHOR]

Abstract A case of primary signet-ring cell carcinoma of the urinary bladder that was found to have induced renal failure is the second such case reported in the world. Primary signet-ring cell carcinoma of the urinary bladder is a rare histologic variant of adenocarcinoma. The patient died of distant metastasis 8 months after undergoing total cystectomy. The neoplasm had a high stage at diagnosis, so the prognosis was very poor. To improve the prognosis, earlier diagnosis and establishing a regimen of chemotherapy is necessary. [ABSTRACT FROM AUTHOR]

We report a case of malignant phyllodes tumor of the prostate which is the eleventh reported case in the world. Phyllodes tumor of the prostate is extremely rare and histologically resembles mammary phyllodes tumor. Phyllodes tumor of the prostate is classified into benign, borderline and malignant, but health professionals should carefully follow up the borderline cases in case they take a malignant clinical course. This case was the first to be treated by pre- and postoperative radiation therapy. Although the patient had a slight response to radiation therapy, he eventually developed metastasis. Because malignant phyllodes tumor of the prostate is a very aggressive tumor, people with the condition should undergo systemic chemotherapy as adjuvant therapy. [ABSTRACT FROM AUTHOR]

Myoepithelioma of the lacrimal gland is extremely rare and only four cases, one of which was malignant, have been reported in detail. The present report describes a case of lacrimal gland myoepithelioma in a Japanese male with histological features suggestive of potentially malignant transformation. The excised tumor consisted of two components, a central nodular component and a peripheral component surrounding the former. These components were separated by a fibrous tissue. Microscopically, both components were comprised almost entirely of spindle-shaped cells, but with some epithelioid cells containing glycogen granules. Extracellular spaces in the peripheral component were filled with eosinophilic materials with the occasional crystalloid structures, which were immunoreactive for collagen type I. Neoplastic cells were immunoreactive focally for vimentin and S-100, but negative for cytokeratins, epithelial membrane antigen, muscle actin, smooth muscle actin, desmin, myosin, and glial fibrillary acidic protein. The neoplastic cells in the central component showed nuclear pleomorphism and atypia with a higher frequency of mitotic figures, and higher labelings of proliferation markers than those in the peripheral component. Neither invasion, necrosis, nor hemorrhage was observed in the tumor. From these findings we proposed a diagnosis of potentially malignant myoepithelioma. [ABSTRACT FROM AUTHOR]

Twenty-four specimens of squamous cell carcinoma of the tongue were immunostained for heat shock proteins (HSPs) to reveal differences in stainability among normal epithelium, dysplasia and carcinoma and to clarify the prognostic significance of HSPs in comparison with survival period, clinical stage, lymph node metastasis, histological grade, and p53 immunostaining. Normal epithelium was positively stained in the suprabasal layer for HSP60 and HSP70, but was negative for HSP27 and HSP90. Dysplastic lesions were positive for HSP27, HSP70 and HSP90, but stained variously for HSP60. In squamous cell carcinoma, the cytoplasm of suprabasal tumor cells was often positive for HSP27 and HSP90 (18/24, 17/24, respectively). Although HSP immunohistochemistry has revealed changes in HSP expression during tumorigenesis of squamous epithelium of the tongue, there was no correlation between HSP staining and survival period, stage, lymph node metastasis, histological grade or p53 immunostaining. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the characteristics of recent male and female patients diagnosed with interstitial cystitis (IC), then investigated which therapy was chosen by the attending urologist. Methods: Materials were 282 IC patients diagnosed and treated during the past 3 years (sampling from Japanese IC database). Gender, age, medical history and predominant symptoms were investigated. In addition, we investigated the interval before a diagnosis was established. In laboratory findings, we investigated voided volume, urinalysis findings and cystoscopic findings. Regarding therapy, we investigated which therapy was chosen as the first line. Results: The gender ratio was about 1.0:5.6 (male : female). Regarding age distribution, patients in their 60s were the most frequent (65 cases, 31.3%). The interval before diagnosis of IC was 36.5 months on average (1–360 months). Regarding medical history, intrapelvic surgery was the most common and repeated urinary tract infection was next. The most frequent symptom was urinary frequency (295 cases, 98.3%). Urinary urgency was noted in 186 cases (62%) and supra-pubic pain was noted in 125 cases (41.6%). The once voided volume was 104.3 mL on average (50–200 mL). The most common cystoscopic finding was glomerulation (158 cases). Ulcer was present in only 19 cases. The most widely carried out therapy was hydrodistension (208 cases, 67.9%). Oral suplatast tosilate (197 cases, 65.6%), antihistamine (77 cases, 25.6%) and intravesical dimethylsulfoxide (69 cases, 23%) followed. Conclusions: Regarding characteristics, the age distribution was older than other countries. The most frequent symptom was urinary frequency. Oral suplatast tosilate was one of the popular therapies in Japan. [ABSTRACT FROM AUTHOR]

Background: Right hepatectomy with caudate lobectomy (RHx) is considered an appropriate procedure for Bismuth type I/II perihilar cholangiocarcinoma in terms of its anatomical and oncological aspect. However, validity of left hepatectomy with caudate lobectomy (LHx) concomitant with arterial resection and reconstruction (AR) is not fully evaluated.Methods: The patients who underwent surgical resection for Bismuth type I/II perihilar cholangiocarcinoma between 2002 and 2013 were studied. The standard procedure for Bismuth type I/II cholangiocarcinoma in the institute was RHx, while in patients who had insufficient functional reserve of the left liver, LHx was selected, irrespective of the necessity of AR. The clinicopathologic and perioperative outcomes after LHx + AR were compared with those after RHx.Results: The surgical procedures comprised LHx + AR in 12 and RHx in 24. The left liver volume and left liver functional reserve were significantly lower with LHx + AR than with RHx (left liver volume: 28.0 vs. 33.7%, p = 0.026; estimated indocyanine green clearance of the left liver: 0.036 vs. 0.046, p < 0.001). The rate of surgical morbidity was almost identical between the two procedures. No arterial reconstruction-related complications occurred. The overall 3- and 5-year survival rates and median survival time were 66.7%, 41.7% and 44 months for LHx + AR and 70.8%, 49.0% and 57 months for RHx (p = 0.640).Conclusion: LHx + AR for Bismuth type I/II perihilar cholangiocarcinoma is considered to be a valid alternative to RHx in patients with an insufficient left liver functional reserve. [ABSTRACT FROM AUTHOR]

Background and aim: Previous studies have shown that microscopic vessel invasion (MVI) occurs in hepatocellular carcinoma (HCC) with a treatment history due to its poorer malignant behavior in comparison with primary HCC. The aim of the present study was to determine the predictors of MVI and overall survival in HCC patients with a treatment history.Methods: This retrospective study included 580 patients who underwent hepatectomy and whose preoperative imaging showed no evidence of macroscopic vessel invasion. The patients were classified into two groups: primary HCC (n = 425) and HCC with a treatment history (n = 155). MVI was defined as the presence of either microscopic portal vein invasion or venous invasion, which was invisible on preoperative imaging.Results: MVI was identified in 34 (21.9%) patients with a treatment history. A multivariate analysis showed that a high des-gamma-carboxy prothrombin (odds ratio [OR] 5.16, P = 0.002) and a large tumor diameter (OR 2.57, P = 0.030) were the significant predictor of MVI in HCC with a treatment history. Moreover, the presence of MVI (hazard ratio [HR] 2.27, P = 0.001) and tumor diameter >27 mm (HR 2.04, P = 0.006) remained significant predictors of the overall survival in HCC with a treatment history. The tumor diameter cutoff value for predicting MVI (27 mm) in HCC with a treatment history was smaller than in primary HCC (37 mm).Conclusions: The presence of MVI was a significant predictor in the HCC patients with a treatment history. The tumor diameter is an important factor that can be used to predict the presence of MVI, especially in HCC with a treatment history. [ABSTRACT FROM AUTHOR]

Tumor‐initiating cells are major drivers of chemoresistance and attractive targets for cancer therapy, however, their identity in human pancreatic ductal adenocarcinoma (PDAC) and the key molecules underlying their traits remain poorly understood. Here, we show that a cellular subpopulation with partial epithelial‐mesenchymal transition (EMT)‐like signature marked by high expression of receptor tyrosine kinase‐like orphan receptor 1 (ROR1) is the origin of heterogeneous tumor cells in PDAC. We demonstrate that ROR1 depletion suppresses tumor growth, recurrence after chemotherapy, and metastasis. Mechanistically, ROR1 induces the expression of Aurora kinase B (AURKB) by activating E2F through c‐Myc to enhance PDAC proliferation. Furthermore, epigenomic analyses reveal that ROR1 is transcriptionally dependent on YAP/BRD4 binding at the enhancer region, and targeting this pathway reduces ROR1 expression and prevents PDAC growth. Collectively, our findings reveal a critical role for ROR1high cells as tumor‐initiating cells and the functional importance of ROR1 in PDAC progression, thereby highlighting its therapeutic targetability. Synopsis: Cancer cell diversity and contribution of tumor‐initiating cells to pancreatic ductal adenocarcinoma (PDAC) progression remain poorly defined. In this work, single‐cell RNA sequencing and functional analyses uncovered targetable tumor‐initiating cells in PDAC. Heterogeneous tumor cells in PDAC arise from a subpopulation with partial EMT signature characterized by high expression of ROR1.Intratumoral ROR1high cells are tumor‐initiating cells with increased tumorigenic capacity.ROR1 functionally promotes PDAC tumor growth, relapse after chemotherapy, and metastasis.ROR1 induces the expression of AURKB via activation of AKT/c‐Myc/E2F signaling, thereby enhancing PDAC proliferation.ROR1 transcription is dependent on the YAP/BRD4 axis. [ABSTRACT FROM AUTHOR]

Background: Gastroenterostomy and stent placement are the most common palliative procedures for patients with a gastric outlet obstruction caused by advanced pancreatic adenocarcinoma. Gastroenterostomy is regarded as the optimum treatment for patients in whom a longer survival is expected, while stent placement is preferred for patients whose survival is likely to be relatively short. However, prognosis of such patients has not been fully evaluated. Methods: This study included patients undergoing gastroenterostomy or duodenal stent placement for gastric outlet obstruction caused by advanced pancreatic adenocarcinoma between 2002 and 2015. Prognostic factors found to be significant based on a multivariate analysis were given a prognostic score according to their hazard ratios (HR). The overall survivals stratified according to the total prognostic score were compared. Results: The median survival time of all cohorts was 4.2 months. The multivariate analyses demonstrated a neutrophil-to-lymphocyte ratio (NLR) ≥ 4 (HR = 4.01, p < 0.001), presence of liver metastases (HR = 1.90, p = 0.002), and presence of cancer pain (HR = 2.08, p < 0.001) to be significant prognostic factors. Regarding the HR, NLR ≥ 4, liver metastases and cancer pain were subsequently scored as 2, 1, and 1, respectively. The median survival time was 9.4 months in patients with a score of 0 or 1 and 3.3 months in patients with a score of 2-4, respectively. Conclusion: The scoring system clearly demonstrates the patient survival. Patients with scores of 0 or 1 are favorable candidates for gastroenterostomy, while patients with scores of 2-4 are candidates for stent placement. [ABSTRACT FROM AUTHOR]

Background: The survival impact of distal pancreatectomy (DP) with celiac axis resection for locally advanced pancreatic body/tail cancer remains unclear. Methods: A total of 16 patients underwent DP with celiac axis resection, while 76 underwent standard DP for pancreatic body/tail cancer. The indications for DP with celiac axis resection included: (a) tumor invasion of either the celiac axis or common hepatic artery or both [CA/CHA (+)] and (b) tumor invasion of the root of the splenic artery, which is difficult to dissect without securing an adequate surgical margin [CA/CHA (−)]. Results: DP with celiac axis resection presented longer operative time and greater amount of blood loss than DP. The median survival time was 17.5 months in the DP with celiac axis resection group and 43.1 months in the DP group ( p = 0.040). Among the patients who underwent DP with celiac axis resection, the median survival time was 35.1 months in the CA/CHA (−) group and 13.2 months in the CA/CHA (+) group ( p = 0.001). Comparing the patients undergoing standard DP and DP with celiac axis resection with a CA/CHA (−) status, there were no significant differences in either disease-free or overall survival times. The CA19-9 value, CA/CHA (+) status, and microscopic venous infiltration were revealed independent significant prognostic factors. Conclusions: DP with celiac axis resection should therefore be indicated in patients with a CA/CHA (−) status. However, it is difficult to justify the use of DP with celiac axis resection in patients with CA/CHA (+) status due to the poor survival. [ABSTRACT FROM AUTHOR]

Focuses on clinical symptom scales for interstitial cystitis for diagnosis and for following the course of the disease. Quantification of patients; Measurement of treatment outcome.

Background and aim: Several papers have shown that preoperative inflammation-based prognostic scores and/or immunonutritional status are associated with survival in patients with hepatocellular carcinoma (HCC). However, the validity of prognostic factors of these scores remains controversial. This study aimed to validate the power of prognostic scores based on the preoperative inflammatory and immunonutritional indices of patients who underwent hepatectomy for HCC with curative intent. Methods: Clinicopathological parameters and inflammation-based prognostic scores and immunonutritional status, including the Glasgow Prognostic Score, neutrophil to lymphocyte ratio (NLR), and prognostic nutritional index (PNI), were retrospectively analyzed to identify the predictors of overall and recurrence-free survival in 256 patients. Results: In multivariate analysis, NLR was an independent prognostic factor for overall, and recurrence-free survival (hazard ratio [HR] 2.59, 95 % confidence interval [CI] 1.56-4.31, P < 0.001, and HR 2.11, 95 % CI 1.44-3.11, P < 0.001, respectively). Additionally, PNI was an independent predictor of overall survival (HR 2.01, CI 1.21-3.36, P = 0.007). Conclusions: The present study shows that the NLR and PNI based on preoperative inflammatory and immunonutritional indices are predictors of overall survival in patients who undergo hepatectomy for HCC with curative intent. [ABSTRACT FROM AUTHOR]

Introduction: The genomic characteristics of hepatocellular carcinoma (HCC) after a sustained virological response (SVR) and its differences according to whether an SVR was achieved by treatment with direct‐acting antivirals (DAA) or interferon (IFN) are still not fully understood. Methods: Sixty‐nine surgically resected HCCs from patients with hepatitis C virus infection were analyzed by gene expression profiling and whole‐exome sequencing. Results: Among the 69 HCC patients, 34 HCCs in which an SVR was not achieved at the time of surgery were classified as HCV‐positive, and 35 HCCs in which an SVR was achieved at the time of surgery were classified as HCV‐SVR. According to the HCV treatment, 35 HCV‐SVR HCCs were classified into two groups: eight tumors with DAA (HCV‐SVR‐DAA) and 24 tumors with interferon (HCV‐SVR‐IFN). The frequency of samples with ARID2 mutations was significantly lower in HCV‐SVR than in HCV‐positive tumors (p = 0.048). In contrast, the frequency of samples with PREX2 mutations was significantly higher in HCV‐SVR samples than in HCV‐positive samples (p = 0.048). Among the patients with HCV‐SVR, the frequency of samples with TP53 mutations was significantly higher in HCV‐SVR‐DAA tumors than in HCV‐SVR‐IFN tumors (p = 0.030). TP53 inactivation scores in HCV‐SVR‐DAA tumors were found to be significantly enhanced in comparison to HCV‐SVR‐IFN tumors (p = 0.022). In addition, chromosomal instability and PI3K/AKT/mTOR pathway signatures were enhanced in HCV‐SVR‐DAA tumors. HCV‐SVR‐DAA was significantly associated with portal vein invasion (p = 0.003) in comparison to HCV‐SVR‐IFN. Conclusion: Our dataset potentially serves as a fundamental resource for the genomic characteristics of HCV‐SVR‐DAA tumors. Our comprehensive genetic profiling by WES revealed significant differences in the mutation rate of several driver genes between HCV‐positive tumors and HCV‐SVR tumors. Furthermore, it was revealed that the frequency of samples with mutations in TP53 was significantly higher in HCV‐SVR‐DAA tumors than in HCV‐SVR‐IFN tumors. [ABSTRACT FROM AUTHOR]

Interstitial cystitis (IC) is a disease of the urinary bladder with lower urinary tract symptoms such as urinary frequency, bladder hypersensitivity and/or bladder pain and resultant serious impairment of quality of life. In Japan, assuming that IC is very rare, research activity and medical care of IC have been sparse until 2001, when the Society of Interstitial Cystitis of Japan (SICJ) and a patient support group were founded. 1,2 Subsequently the International Consultation on Interstitial Cystitis Japan (ICICJ) was held in Kyoto in 2003. 3 On the other hand, the etiology of IC has not been well clarified, which complicates its diagnosis and treatment at clinical settings. We have thus developed the Japanese Clinical Guideline, 4 which is targeted at healthcare professionals including specialists in urology and women's health care who may engage in the diagnosis and treatment of IC. This article is the English translation of a shortened version of the Guideline for convenience of readers worldwide. [ABSTRACT FROM AUTHOR]

Background: Several indicators of systemic inflammation and nutritional status were recently shown to serve as novel prognostic factors for certain cancers. Here, we aimed to investigate the prognostic impact of preoperative indicators of systemic inflammation and nutritional status associated with the survival of patients with resected ampulla of Vater carcinoma (AC). Methods: We retrospectively analyzed the records of 91 patients who underwent pancreatoduodenectomy (PD) for AC from January 2002 through December 2018. Indices for systemic inflammation and nutritional status (Systemic immune-inflammation index [SII], Prognostic nutritional index [PNI], modified Glasgow prognostic score [mGPS], and Controlling nutritional status score [CONUT]) were determined using preoperative blood tests. Clinicopathological factors and these indices were analyzed to identify predictors of overall survival (OS). Results: The median preoperative SII and PNI values were 456.7 and 47.5, respectively, and their optimal cut-off values were 670.0 and 50.0, respectively. Univariate analysis revealed that high SII, low PNI, mGPS ≥ 1, and malnutrition, assessed using the CONUT, were significant predictors of shorter OS. Multivariate analysis revealed that high SII (HR = 2.71, p = 0.023) and malnutrition assessed using the CONUT (hazard ratio = 3.98, p = 0.006) were independent predictors of shorter OS. Conclusion: SII and the CONUT predicted the survival of patients with AC after radical resection. These indicators are easily calculated using preoperative blood tests and may contribute to the development of improved strategies to treat AC. [ABSTRACT FROM AUTHOR]

We report an extremely rare case of primary lung cancer showing various histological elements diagnosed as the collision of an adenosquamous carcinoma and a large cell neuroendocrine carcinoma by loss of heterozygosity (LOH) analysis of the human androgen receptor (AR) and phosphoglycerate kinase (PGK-1) genes. The tumor exhibited a tiny ground-glass opaque shadow suggesting atypical adenomatous hyperplasia 18 months prior to surgery. However, the tumor grew rapidly, and the resected tumor consisted of two closely located nodules. The larger nodule was composed of well-differentiated adenocarcinomatous and moderately to poorly differentiated squamous cell carcinomatous elements, while the smaller nodule consisted of a large cell neuroendocrine carcinomatous element with partial squamoid differentiation having focal continuity with the adenocarcinomatous element. Both the adenocarcinomatous and squamous cell carcinomatous elements revealed transitional features and LOH of AR and PGK-1 genes, while the large cell neuroendocrine carcinomatous element showed a monoclonal pattern but possessed both alleles of AR and PGK-1 genes. From these clinical and pathological results, the parental cell of the large cell neuroendocrine carcinomatous element was considered to be different from that of the adenosquamous carcinomatous element. [ABSTRACT FROM AUTHOR]

Elucidates the incidence of histiocytoid breast carcinoma (HBC) in Japan. Review of histological specimen from breast cancer patients; Foci of in situ lobular carcinoma in cases of pure HBC; Presence of targetoid and Indian file invasive patterns in all cases of pure HBC.

To elucidate interactions between the glucose transport system and hepatic glucose production in the tumour-bearing state, glycogen storage, expression of glucose transporter isoform 2 (Glut 2) and activities of glucose-6-phosphatase (G-6-Pase) and hexokinase were histochemically examined in hepatocytes of tumour-bearing rats. Five male F344 rats, subcutaneously inoculated with methylcholanthrene(MCA)-induced sarcoma cells were compared with five pair-fed animals and four ad libitum fed controls. Glycogen storage was markedly decreased in liver cells of tumour-bearing rats compared to in those of control animals. Glut 2 immunoreactivity was uniformly seen in the cellular membrane of hepatocytes from control animals. In rats bearing sarcoma, the staining intensity was significantly decreased, suggesting that Glut 2 with its bi-directional transport capacity was down-regulated in the tumour-bearing state. Positive staining for hexokinase activity was located in the perivenous area in livers from control animals and was more diffusely located and more intense in livers from tumour-bearing animals. G-6-Pase activity, limited to the peripheral area in livers from controls, extended to the intermediate area and had stronger reactivity in livers from tumour-bearing animals. In the tumour-bearing cachectic condition, glucose may be partially consumed by a futile cycle, hepatic metabolic zonation was disturbed, and the release of glucose from the liver may not be mediated by a facilitative glucose transporter-2. [ABSTRACT FROM AUTHOR]

Background: The absence of the portal bifurcation (APB) is a rare anatomic variation, in which the horizontal part of the left portal vein (PV) is missing. The aim of this study was to identify the vascular architecture in livers with APB. Methods: Computed tomography data for 17,651 patients were reviewed; five patients (0.03%) were found to present with APB. The liver volume and anatomy of APB patients were compared with those of 30 patients with normal livers. Results: All the APB patients exhibited an independent posterior branch of the PV. The intrahepatic left PV (LPV) ran through either the ventral (n = 2, 40%) or dorsal side (n = 3, 60%) of the middle hepatic vein. The frequency of medial branches diverging from the LPV was higher in patients with APB than in normal patients (p < 0.001). The left hepatic duct (LHD) ran through the inside of the left lobe along the left PV in 40% of the patients with APB, whereas in the remaining 60% of the patients with APB, the LHD ran on the outside of the liver separately from the left PV and joined the right hepatic duct. The liver volume of the left lateral section was significantly smaller (p = 0.014), and the posterior section was significantly larger (p = 0.014) in patients with APB than in patients with normal livers. Conclusion: The unique anatomical characteristics and the positional relation of the vessels should be considered preoperatively in patients with APB. [ABSTRACT FROM AUTHOR]

Background: Surgical resection in patients with extrahepatic cholangiocarcinoma (EHCC) with paraaortic lymph node metastasis (PALNM) remains controversial. The objective of this study was to investigate the prognostic impact of PALNM in resected EHCC. Methods: The present retrospective study included 410 patients, including 16 patients with PALNM, who underwent surgical resection of EHCC between September 2002 and December 2018. These were compared to 9 patients in whom EHCC was not resected due to PALNM. The clinicopathological features and survival outcomes were investigated to identify the prognostic factors in resected EHCC. Results: The overall survival in the resected patients with PALNM was significantly better than that in unresected patients (median survival time [MST] 33.7 vs. 16.7 months, p=0.009) and was not significantly worse than that of patients with regional lymph node metastasis (LNM) (MST 33.7 vs 36.0 months, p=0.278). The multivariate analysis identified age > 70 years, male sex, tumor location (perihilar), residual tumor status, histological grade, microscopic venous invasion, and regional LNM as independent prognostic factors. Conclusions: There was no significant difference in survival between the resected patients with PALNM and patients with regional LNM, and PALNM was not a significant prognostic factor in the multivariate analysis. Surgical resection may be considered an acceptable approach for EHCC with PALNM in selected patients. [ABSTRACT FROM AUTHOR]

Background: Lymph node metastasis (LNM) has been regarded as one of the prognostic factors in patients with ampulla of Vater carcinoma (AC). However, the consensus about an optimal cutoff value of the number of LNMs and the definition of the regional lymph nodes (RLNs) has not been achieved. Methods: This study included 114 consecutive patients who underwent pancreatoduodenectomy for AC between January 2002 and March 2019. Results: The minimum p value approach for the greatest difference in the overall survival classified the number of LNM into none (N0, n = 66), from 1 to 2 (N1, n = 32), and ≥3 LNM (N2, n = 11) (p = 0.004). Distant LNM was defined as M1 (n = 5). Significant differences in relapse-free survival (RFS) were found between N0 and N1 (p < 0.001), N1 and N2 (p = 0.047), and N1 and M1 (p = 0.044) but not between N2 and M1 (p = 0.683). Moreover, the patients with regional LNM were classified into two groups: Np group (n = 35, LNM only in pancreatic head region) and Nd group (n = 8, LNM in other regional location). Significant differences in the RFS were found between N0 and Np (p < 0.001), Np and Nd (p = 0.004), and Np and M1 (p = 0.033) but not between Nd and M1 (p = 0.883). A Cox proportional hazards analysis for RFS revealed that ≥ 3 LNMs (hazards ratio [HR], 3.22) and LNM except for pancreatic head region (HR, 4.27) were individually independent worse prognostic factors. Conclusions: ≥3 LNMs and regional LNM except for pancreatic head region were associated with poor prognosis comparable to that of the patients with M1. [ABSTRACT FROM AUTHOR]

Solid papillary carcinoma (SPC) is a histological subtype of breast carcinomas. At least 50% of SPC show neuroendocrine differentiation. Insulinoma‐associated protein 1 (INSM1) is a transcription factor now employed as a useful neuroendocrine marker. It is suppressed by the Notch signaling pathway in other neuroendocrine tumors. However, the usefulness of INSM1 as a neuroendocrine marker and the relationships between INSM1 and NOTCH receptors in SPC of the breast currently remain unclear. To clarify the usefulness of INSM1 as a neuroendocrine marker and the relationships between INSM1 and NOTCH receptors in SPC, we performed immunohistochemistry using 19 tissue specimens of SPC of the breast. We complementarily analyzed public RNA sequencing data on breast carcinomas. Immunohistochemical examinations revealed that the staining intensity of INSM1 was significantly higher in the neuroendocrine group than in the non‐neuroendocrine group. Positive correlations were observed between INSM1 and synaptophysin (SYP), or chromogranin‐A (CHGA). In all cases, NOTCH 2 and 3 were positive, while NOTCH 1 and 4 were negative. According to public RNA data analyses, there were positive correlations between INSM1 and SYP, or CHGA, and negative correlations between INSM1 and NOTCH1–3. INSM1 is useful as a diagnostic marker for SPC with neuroendocrine differentiation in the breast. [ABSTRACT FROM AUTHOR]

Background: The long-term patency of the portal vein (PV) in patients who survive after pancreaticoduodenectomy (PD) remains unclear. The aim of the present study was to investigate the clinical features and risk factors for benign PV stenosis after PD. Methods: We retrospectively analyzed the patients who underwent PD from September 2002 and December 2015 at our institution without intraoperative radiation therapy or concomitant PV resection. The postoperative computed tomography of each patient was evaluated, and PV stenosis was defined as the shortest diameter of the PV being <3 mm. The patients with PV stenosis due to local recurrence were excluded. Results: Of the 458 patients, PV stenosis occurred in 57 (12.4%), including benign PV stenosis in 28 (6.1%) and PV stenosis due to local recurrence in 29 (6.3%). Of the 28 patients with benign PV stenosis, 7 (25%) developed symptoms related to portal hypertension, namely recurrent gastrointestinal bleeding in 5 and refractory ascites in 2. Six patients were treated with percutaneous transhepatic PV stent placement, and all of their symptoms improved. A multivariate analysis found that a postoperative pancreatic fistula was an independent risk factor for benign PV stenosis after PD (odds ratio, 4.36; p = 0.005). Conclusions: Postoperative pancreatic fistula was a significant risk factor for benign PV stenosis after PD. Stent placement for benign PV stenosis was effective for the patients with symptoms due to portal hypertension. [ABSTRACT FROM AUTHOR]

Background: The efficacy of infrahepatic inferior vena cava (IVC) semi-clamping for reducing blood loss during hepatic resection and its safety remain unclear. The aim of this study was to validate the effectiveness of IVC semi-clamping for reducing blood loss during hepatic resection and to confirm its safety. Methods: Patients who underwent anatomical hepatic resection between January 2011 and May 2018 were analysed by propensity score-matched and multivariate analyses. Results: Of 437 patients who underwent anatomical hepatic resection, IVC semi-clamping was performed in 196 patients (44.9%; clamping group). A propensity score-matched analysis demonstrated that even though there was no significant difference in the characteristics of the 141 patients in each group, IVC semi-clamping reduced the blood loss during hepatic resection (clamping group versus non-clamping group: 836 ± 123 vs. 1198 ± 124 ml, P = 0.04). Regarding post-operative complications, the multivariate analysis identified IVC semi-clamping as an independent risk factor for acute kidney injury on post-operative day 1 (P = 0.01, odds ratio = 9.23). A significant positive correlation was found between the duration of IVC semi-clamping and an increased level of serum creatinine (sCre) (P = 0.03), and a significant inverse correlation was found between the blood pressure after clamping and an increased level of sCre (P = 0.02). A receiver operating characteristic analysis revealed the duration and mean blood pressure after clamping that indicated a high risk of acute kidney injury to be 116 min and 65 mmHg, respectively. Conclusion: IVC semi-clamping can reduce blood loss during hepatic resection but still necessitates monitoring in order to avoid acute kidney injury. [ABSTRACT FROM AUTHOR]

Background: Insulinoma‐associated protein 1 (INSM1) has been reported to be a useful marker for diagnosing pancreatic neuroendocrine tumours (PNETs). However, INSM1 expression in endoscopic ultrasound‐guided fine needle aspiration cytology has not been examined. We evaluated INSM1 expression in the cytology of cases diagnosed with PNETs. Methods: We immunocytochemically stained INSM1 and Ki‐67 in 14 PNET cases, and according to the 2017 World Health Organisation criteria, seven PNET Grade 1 cases, four Grade 2 cases and three Grade 3/neuroendocrine carcinoma cases were identified. As a control for INSM1 and Ki‐67 expression, we used cytological specimens from 15 cases of pancreatic ductal adenocarcinoma. Results: In PNET cases, INSM1‐expressing tumour cells were identified in all cytological specimens of PNET. The median INSM1 expression rate in Grade 1 cases was 49.8% (mean ± standard deviation: 55.1 ± 12.5%, min: 39.3%, max: 74.1%), and in Grade 2 and Grade 3/neuroendocrine carcinoma cases was 81.1% (mean ± standard deviation: 77.6 ± 18.6%, min: 50.3%, max: 100%). However, there was no correlation between INSM1 and Ki‐67 expression (r = −0.15). The median expression rate in PNET cases was 64.3%, which was significantly higher than that in pancreatic ductal adenocarcinoma cases (P < 0.0001). Conclusion: INSM1 immunocytochemistry of cytological specimens obtained from endoscopic ultrasound‐guided fine needle aspiration cytology can accurately diagnose PNETs; therefore, INSM1 could be an important diagnostic tool in assessing therapeutic strategies, including molecular‐targeted therapy. Recently, neuroendocrine markers such as SYP, CGA, and NCAM have been used with high specificity and sensitivity for PNETs. However, there are similarities in cell structure and immunocytochemistry between pancreatic solid tumors. We reported INSM1 positivity in all histological specimens of PNETs examined including high grade PNETs. This can be considered a useful biomarker. [ABSTRACT FROM AUTHOR]

Background: The indication of surgery in intrahepatic cholangiocarcinoma (ICC) patients with lymph node metastasis (LNM), macroscopic periductal infiltration (PI), and intrahepatic metastasis (IM) remains unclear.Methods: Patients who underwent resection for mass-forming (MF) dominant ICC and unresected patients caused by LNM, IM, or locally advanced tumors (UR group) were enrolled. The significance of CA19-9 was investigated in advanced ICC.Results: Seventy-three patients who underwent resection and 20 UR patients were analyzed. Using the minimum p value approach based on the overall survival, the optimal CA19-9 cutoff value was 300 U/mL. The OS of the patients with CA19-9 < 37 U/mL (n = 26; MST, 49.6 months) and 37-300 U/mL (n = 28; MST, 45.1 months) was comparable (P = 0.842); however, the OS of the patients with CA19-9 = 37-300 U/mL was significantly better than that with CA19-9 ≥ 300 U/mL (n = 19; MST, 15.3 months; P < 0.001). CA19-9 > 300 U/mL, MF + PI, and IM were independently associated with OS. The OS of the patients with CA19-9 < 300 U/mL who developed LNM (MST, 34.0 months), MF + PI (MST, 32.9 months), or IM (MST, 35.2 months), or who required major vascular resection (MST, 45.1 months) was better than those with CA19-9 ≥ 300 U/mL who developed LNM (MST, 8.7 months; P = 0.005), MF + PI (MST, 7.5 months; P = 0.040), or IM (MST, 8.7 months; P = 0.001), or who required major vascular resection (MST, 14.8 months; P = 0.015); their prognosis was similar with the UR group.Conclusions: Even if patients had ICC developing LNM, PI, or IM, or require major vascular resection, surgical resection can be indicated for patients with CA19-9 < 300 U/mL. However, the indications for either adjuvant therapy or resection should be carefully determined in patients with CA19-9 ≥ 300 U/mL. [ABSTRACT FROM AUTHOR]

Background Small cell lung carcinoma ( SCLC) is characterized by a high rate of relapse and failure of chemotherapy because of the emergence of drug resistant cells. Notch signaling controls carcinogenesis in several human malignancies and could be involved in the resistance of cells to several chemotherapeutic agents. Herein, we analyzed the role of Notch1 signaling in the resistance of human SCLC cells to doxorubicin. Methods Small interfering ribonucleic acid technology was used to knock down ( KD) Notch1 in H69 AR and SBC-3 SCLC cells. We detected the effect of inhibiting Notch1 on the expression of drug resistant related molecules: multidrug resistance-associated protein ( MRP-1) and anti-apoptotic factor B-cell lymphoma-2, as well as to cell adhesion molecule E-cadherin, which contributes to the adhesion of SCLC cells to the extracellular matrix and confers chemoresistance in a process known as cell adhesion-mediated drug resistance ( CAM-DR). We also observed the effect of KD Notch1 on cell survival under high concentrations of doxorubicin treated media. Results H69 AR and SBC-3 cells expressed Notch1 protein and grew as adherent aggregates, which confer resistance to high concentrations of doxorubicin. On inhibiting Notch1, we observed activation of the apoptotic pathway in cells, possibly resulting from the loss of CAM-DR and, thus, SBC-3 cells showed a loss of chemoresistant ability. However, in H69 AR cells with KD Notch1, the expression of MRP-1 was increased and, thus, sustained the chemoresistant ability of cells. Conclusion The Notch1 signaling pathway is involved in mediating the drug resistance phenotype of SCLC cells. [ABSTRACT FROM AUTHOR]

Reported herein is a 57-year-old man infected by Sparganum mansoni, a kind of tapeworm, showing a solitary nodule of the middle lobe of the right lung. Because a transbronchial biopsy could not diagnose the nodule, a right middle lobectomy was performed on suspicion of malignant tumor. The lesion was diagnosed as sparganosis by histological and immuno-serological examinations. Histological examination revealed granulomatous inflammation with neutrophil and eosinophil infiltration around the worm and interstitial pneumonia surrounding the nodule. Moreover, vasculitis with foreign body giant cell was seen around the lesion. To the authors' knowledge this is the second case of sparganosis limited in the lung, and the current report presents the first detailed histological description of a pulmonary sparganosis case. [ABSTRACT FROM AUTHOR]

Brefeldin A induces a rapid redistribution of cost proteins associated with clathrin-coated vesicles that bud from the tans-Golgi network but not of those associated with vesicles derived from the plasma membrane. Its effect on glucose transport and the subcellular distribution of the glucose transporter CLUT4 were therefore investigated in the absence or in the presence of insulin in order to characterize the mechanism of insulin-induced GLUT4 recycling. Exposure of rat adipose cells to befeldin A in the absence of insulin resulted in a slight increase both in 3-O-methyl-D-glocose transport and in the amount of GLUT4 in the plasma membrane as determined by immunoblot analysis. In contrast, it had no effect on the insulin-induced increase in 3-O-methyl-glucose transport and plasma-membrane-associated GLUT4. Immunohistochemical analysis revealed clathrin immunoreactivity in the juxtanuclear region and in the cell periphery, and the staining in the perinuclear region decreased after exposure of cells to 35 μM brefeldin A. However, it had no effect on the basal pattern of GLUT4 staining or on the insulin-induced redistribution of GLUT4 staining to the cell periphery. These results suggest that basal recycling of GLUT4 responsible for maintaining the intracellular location of the transporter may include a membrane budding step sensitive to brefeldin A, possibly associated with clathrin-coated vesicles, but that the insulin-stimulated GLUT4 recycling pathway is mediated predominatly by a brefeldin A-insensitive mechanism. [ABSTRACT FROM AUTHOR]

Explores the role of CCR8 in innate immune response during septic peritonitis induced by cecal ligation and puncture (CLP). Expression of CCR8 in peritoneal macrophages during CLP; Resistane of CCR8 mice to CLP-induced lethality; Increased bacterial clearance in CCR8; Augmented innate immune response in CCR8 macrophages; Altered cytokine response and prevention of renal injury in CCR8 mice.