Specific Radius Change of Quantum Dot inside the Lipid Bilayer by Charge Effect of Lipid Head-Group

We studied the quantum dot-liposome complex (QLC), which is the giant unilamellar vesicle with quantum dots (QDs) incorporated in its lipid bilayer. A spin coating method in conjunction with the electroformation technique yielded vesicles with highly homogeneous unilamellar structure. We observed QD size dependence of the QLC formation: QLCs form with blue, green and yellow-emission QD (core radius ~1.05 nm, 1.25 nm and 1.65 nm) but not with red-emission QD (core radius ~2.5 nm). In order to explain this size dependence, we made a simple model explaining the QD size effect on QLC formation in terms of the molecular packing parameter and the lipid conformational change. This model predicts that QDs below a certain critical size (radius ≈ 1.8 nm) can stably reside in a lipid bilayer of 4 - 5 nm in thickness for Egg-PC lipids. This is consistent with our previous experimental results. In the case of red-emission QD, QD-aggregations are only observed on the fluorescent microscopy instead of QLC. We expected that the reduction of packing parameter (P) would lead to the change of specific QD radius. This prediction could be verified by our experimental observation of the shift of the specific QD size by mixing DOPG

Prognostic Value of Postoperative CEA Clearance in Rectal Cancer Patients with High Preoperative CEA Levels

PURPOSE: We determined the prognostic value of carcinoembryonic antigen (CEA) clearance after tumor resection with serial evaluation of postoperative CEA levels in rectal cancer. METHODS: Between 1994 and 2004, we retrospectively reviewed 122 patients with rectal cancer whose serum CEA levels were measured on the preoperative day and postoperative days 7 and 30. Patients with preoperative CEA levels <5.0 ng/ml were excluded. An exponential trend line was drawn using the three CEA values. Patients were categorized into three groups based on R(2) values calculated through trend line, which indicates the correlation coefficient between exponential graph and measured CEA values: exponential decrease group (group 1: 0.9 < R(2) < or = 1.0), nearly exponential decrease group (group 2: 0.5 < R(2) < or = 0.9), and randomized clearance group (group 3: 0.5 < or = R(2)). We then analyzed the CEA clearance pattern as a prognostic indicator. RESULTS: With a median follow-up of 57 months, the 5-year overall survival was 62.3% vs. 48.1% vs. 25% and the 5-year disease-free survival was 58.6% vs. 52.7% vs. 25% among groups 1, 2, and 3 (P = 0.014, P = 0.027, respectively) in patients with stage III rectal cancer. For those with stage II rectal cancer, the 5-year overall survival rate of group 1 was significantly better than groups 2 and 3 (88.8% vs. 74.1%, respectively, P = 0.021). CONCLUSIONS: the postoperative pattern of CEA clearance is a useful prognostic determinant in patients with rectal cancer. Patients with a randomized pattern of CEA clearance after tumor resection should be regarded as having the possibility of a persistent CEA source and may require consideration of intensive follow-up or adjuvant therapy.ope

Efficacy of laparoscopic subtotal gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer: the protocol of the KLASS-02 multicenter randomized controlled clinical trial

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Despite the well-described benefits of laparoscopic surgery such as lower operative blood loss and enhanced postoperative recovery in gastric cancer surgery, the application of laparoscopic surgery in patients with locally advanced gastric cancer (AGC) remains elusive owing to a lack of clinical evidence. Recently, the Korean Laparoscopic Surgical Society Group launched a new multicenter randomized clinical trial (RCT) to compare laparoscopic and open D2 lymphadenectomy for patients with locally AGC. Here, we introduce the protocol of this clinical trial. Methods/design This trial is an investigator-initiated, randomized, controlled, parallel group, non-inferiority trial. Gastric cancer patients diagnosed with primary tumors that have invaded into the muscle propria and not into an adjacent organ (cT2–cT4a) in preoperative studies are recruited. Another criterion for recruitment is no lymph node metastasis or limited perigastric lymph node (including lymph nodes around the left gastric artery) metastasis. A total 1,050 patients in both groups are required to statistically show non-inferiority of the laparoscopic approach with respect to the primary end-point, relapse-free survival of 3 years. Secondary outcomes include postoperative morbidity and mortality, postoperative recovery, quality of life, and overall survival. Surgeons who are validated through peer-review of their surgery videos can participate in this clinical trial. Discussion This clinical trial was designed to maintain the principles of a surgical clinical trial with internal validity for participating surgeons. Through the KLASS-02 RCT, we hope to show the efficacy of laparoscopic D2 lymphadenectomy in AGC patients compared with the open procedure. Trial registration ClinicalTrial.gov, NCT01456598

Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer

microRNAs (miRNAs) play integral roles in diverse processes including tumorigenesis. miRNA gene loci are often found in close conjunction, and such clustered miRNA genes are transcribed from a common promoter to generate polycistronic primary transcript. The primary transcript (pri-miRNA) is then processed by two RNase III proteins to release the mature miRNAs. Although it has been speculated that the miRNAs in the same cluster may play related biological functions, this has not been experimentally addressed. Here we report that the miRNAs in two clusters (miR-106b∼93 ∼ 25 and miR-222 ∼ 221) suppress the Cip/Kip family members of Cdk inhibitors (p57Kip2, p21Cip1 and p27Kip1). We show that miR-25 targets p57 through the 3′-UTR. Furthermore, miR-106b and miR-93 control p21 while miR-222 and miR-221 regulate both p27 and p57. Ectopic expression of these miRNAs results in activation of Cdk2 and facilitation of G1/S phase transition. Consistent with these results, both clusters are abnormally upregulated in gastric cancer tissues compared to the corresponding normal tissues. Ectopic expression of miR-222 cluster enhanced tumor growth in the mouse xenograft model. Our study demonstrates the functional associations between clustered miRNAs and further implicates that effective cancer treatment may require a combinatorial approach to target multiple oncogenic miRNA clusters

Label-Free Quantitative Proteome Profiling of Cerebrospinal Fluid from a Rat Stroke Model with Stem Cell Therapy

Human adipose-derived mesenchymal stem cells (hAMSCs) are capable of immunomodulation and regeneration after neural injury. For these reasons, hAMSCs have been investigated as a promising stem cell candidate for stroke treatment. However, noninvasive experiments studying the effects of grafted stem cells in the host brain have not yet been reported. Cerebrospinal fluid (CSF), which can be collected without sacrificing the subject, is involved in physiological control of the brain and reflects the pathophysiology of various neurological disorders of the central nervous system (CNS). Following stem cell transplantation in a stroke model, quantitative analysis of CSF proteome changes can potentially reveal the therapeutic effect of stem cells on the host CNS. We examined hAMSC-secreted proteins obtained from serum-free culture medium by liquid chromatography-tandem mass spectrometry (LC-MS/MS), which identified several extracellular matrix proteins, supporting the well-known active paracrine function of hAMSCs. Subsequently, we performed label-free quantitative proteomic analysis on CSF samples from rat stroke models intravenously injected with hAMSC (experimental) or phosphate buffered saline (control). In total, 524 proteins were identified; among them, 125 and 91 proteins were increased and decreased with hAMSC treatment, respectively. Furthermore, gene set enrichment analysis revealed three proteins, 14-3-3 theta, MAG, and neurocan, that showed significant increases in the hAMSC-treated model; these proteins are core members of neurotrophin signaling, nerve growth factor (NGF) signaling, and glycosaminoglycan metabolism, respectively. Subsequent histological and neurologic function experiments validated proliferative neurogenesis in the hAMSC-treated stroke model. We conclude that (i) intravenous injection of hAMSCs can induce neurologic recovery in a rat stroke model and (ii) CSF may reflect the therapeutic effect of hAMSCs. Additionally, proteins as 14-3-3 theta, MAG, and neurocan could be considered as potential CSF biomarkers of neuroregeneration. These CSF proteome profiling results would be utilized as valuable resource in further stroke studies.1

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells

Undifferentiated carcinoma with osteoclast-like giant cells is a rare neoplasm of the exocrine pancreas. Some similar cases have been reported, but the histogenesis of these tumors varies and is controversial. We report here on a case of undifferentiated carcinoma of the pancreas with osteoclast-like giant cells. A 77-year old woman presented with abdominal pain and anorexia. Abdominal computed tomography and magnetic resonance imaging showed an approximately 10 × 5 cm highly attenuated mass arising from the tail of the pancreas and invading the spleen and adjacent bowel loop. The initial impression was a malignant endocrine tumor or solid-pseudopapillary tumor of the pancreas. The patient underwent a distal pancreatectomy with splenectomy and left hemicolectomy. The histopathology and immunohistochemistry helped make the diagnosis that of an undifferentiated carcinoma with osteoclast-like giant cells of the pancreas

Primary leiomyosarcoma of the pancreas

Primary sarcomas of the pancreas are extremely rare, accounting for 0.1% of malignant pancreatic (non-islet) neoplasms. Pancreatic leiomyosarcoma is a highly aggressive malignancy that spreads in a similar manner to gastric leiomyosarcoma, i.e., by adjacent organ invasion, hematogenous spread, and lymph node metastasis. These tumors are large at the time of diagnosis and are usually found at an advanced stage. We report a case of a 70-year-old female with intermittent right upper quadrant abdominal discomfort. Radiological, histopathological, and immunohistochemical studies revealed the tumor to be a primary leiomyosarcoma of the pancreas. Herein, we describe a patient with a primary leiomyosarcoma of the pancreas who presented with clinical and radiological findings indicative of a mass in the pancreatic head

Efficacy of Imatinib Mesylate Neoadjuvant Treatment for a Locally Advanced Rectal Gastrointestinal Stromal Tumor

Surgery is the standard treatment for a primary gastrointestinal stromal tumor (GIST); however, surgical resection is often not curative, particularly for large GISTs. In the past decade, with imatinib mesylate (IM), management strategies for GISTs have evolved significantly, and now IM is the standard care for patients with locally advanced, recurrent or metastatic GISTs. Adjuvant therapy with imatinib was recently approved for use, and preoperative imatinib is an emerging treatment option for patients who require cytoreductive therapy. IM neoadjuvant therapy for primary GISTs has been reported, but there is no consensus on the dose of the drug, the duration of treatment and the optimal time of surgery. These are critical because drug resistance or tumor progression can develop with a prolonged treatment. This report describes two cases of large rectal malignant GISTs, for which a abdominoperineal resection was initially anticipated. The two patients received IM preoperative treatment; we followed-up with CT or magnetic resonance imaging to access the response. After 9 months of treatment, a multi-disciplinary consensus that maximal benefit from imatinib had been achieved was reached. We determined the best time for surgical intervention and successfully performed sphincter-preserving surgery before resistance to imatinib or tumor progression occurred. We believe that a multidisciplinary team approach, considerating the optimal duration of therapy and the timing of surgery, is required to optimize treatment outcome

Inflammatory and Tumor Stimulating Responses after Laparoscopic Sigmoidectomy

PURPOSE: Laparoscopic colectomy has clinical benefits such as short hospital stay, less postoperative pain, and early return of bowel function. However, objective evidence of its immunologic and oncologic benefits is scarce. We compared functional recovery after open versus laparoscopic sigmoidectomy and investigated the effect of open versus laparoscopic surgery on acute inflammation as well as tumor stimulation. MATERIALS AND METHODS: A total of 57 patients who were diagnosed with sigmoid colon cancer were randomized for elective conventional or laparoscopically assisted sigmoidectomy. Serum samples were obtained preoperatively and on postoperative day 1. C-reactive protein (CRP) and interleukin-6 (IL-6) were measured as inflammation markers, and vascular endothelial growth factor (VEGF) and insulin-like growth factor binding protein-3 (IGFBP-3) were used as tumor stimulation factors. Clinical parameters and serum markers were compared. RESULTS: Postoperative hospital stay (p=0.031), the first day of gas out (p=0.016), and the first day of soft diet (p<0.001) were significantly shorter for the laparoscopic surgery group than the open surgery group. The levels of CRP, IL-6, and VEGF rose significantly, and the concentration of IGFBP-3 fell significantly after both open and laparoscopic surgery. However, there were no significant differences in the preoperative and postoperative levels of CRP, IL-6, VEGF, and IGFBP-3 between the two groups. CONCLUSION: Our data suggest that both open and laparoscopic surgeries are accompanied by significant changes in IL-6, CRP, IGFBP-3, and VEGF levels. Acute inflammation markers and tumor stimulating factors may not reflect clinical benefits of laparoscopic surgery.ope