Intracellular lipid droplets (LDs) are found in a wide variety of cell types and have been recognized as organelles with unique spherical structures. Although LDs are not stable lipid-depots, they ...are active sites of neutral lipid metabolism, and comprise neutral lipid or cholesterol cores surrounded by phospholipid monolayers containing specialized proteins. However, sizes and protein compositions vary between cell and tissue types. Proteins of the perilipin family have been associated with surfaces of LDs and all carry a conserved 11-mer repeat motif. Accumulating evidence indicates that all perilipins are involved in LD formation and that all play roles in LD function under differing conditions. In this brief review, we summarize current knowledge of the roles of perilipins and lipid metabolizing enzymes in a variety of mammalian cell types.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study analyzed outcomes of systemic chemotherapy for advanced neuroendocrine carcinoma (NEC) of the digestive system. Clinical data from 258 patients with unresectable or recurrent NEC of the ...gastrointestinal tract (GI) or hepato‐biliary‐pancreatic system (HBP), who received chemotherapy, were collected from 23 Japanese institutions and analyzed retrospectively. Patients had primary sites in the esophagus (n = 85), stomach (n = 70), small bowel (n = 6), colorectum (n = 31), hepato‐biliary system (n = 31) and pancreas (n = 31). Median overall survival (OS) was 13.4 months the esophagus, 13.3 months for the stomach, 29.7 months for the small bowel, 7.6 months for the colorectum, 7.9 months for the hepato‐biliary system and 8.5 months for the pancreas. Irinotecan plus cisplatin (IP) and etoposide plus cisplatin (EP) were most commonly selected for GI‐NEC and HBP‐NEC. For patients treated with IP/EP (n = 160/46), the response rate was 50/28% and median OS was 13.0/7.3 months. Multivariate analysis among patients treated with IP or EP showed that the primary site (GI vs HBP; hazard ratio HR 0.58, 95% confidence interval CI 0.35–0.97) and baseline serum lactate dehydrogenase levels (not elevated vs elevated; HR 0.65, 95% CI 0.46–0.94) were independent prognostic factors for OS, while the efficacy of IP was slightly better than for EP (HR 0.80, 95% CI 0.48–1.33; P = 0.389). IP and EP are the most common treatment regimens for NEC of the digestive system. HBP primary sites and elevated lactate dehydrogenase levels are unfavorable prognostic factors for survival. A randomized controlled trial is required to establish the appropriate chemotherapy regimen for advanced NEC of the digestive system. This study was registered at UMIN as trial number 000005176.
Clinical data from patients with unresectable or recurrent NEC of the gastrointestinal tract (GI) or hepato‐biliary‐pancreatic system (HBP), who received chemotherapy, were collected from 23 Japanese institutions and analyzed retrospectively. This study included 258 patients. Multivariate analysis among the patients treated with IP or EP showed that the primary site (GI vs. HBP; HR 0.58, 95% CI 0.35–0.97) and baseline serum lactate dehydrogenase (LDH) levels (not elevated vs elevated; HR 0.65, 95% CI 0.46–0.94) were independent prognostic factors for OS, while the efficacy of IP was slightly better than EP (HR 0.80, 95% CI 0.48–1.33; P = 0.389).
Background
Advanced low rectal cancer has a non-negligible risk of lateral pelvic lymph node (LPLN) metastasis (LPLNM) and lateral local recurrence (LR) after neoadjuvant (chemo)radiotherapy and ...total mesorectal excision. LPLN dissection (LPLND) reduces LR but increases postoperative complications and sexual/urinary dysfunction.
Objective
The aim of this study was to develop a new radiomics-based prediction model for LPLNM in patients with rectal cancer.
Methods
A total of 247 patients with rectal cancer and enlarged LPLNs treated by (chemo)radiotherapy and LPLND were enrolled in this retrospective, multicenter study. LPLN radiomic features were extracted from pretreatment portal venous-phase computed tomography images. A radiomics score of LPLN was constructed based on the least absolute shrinkage and selection operator regression in a primary cohort of 175 patients. Model performance was assessed in terms of discrimination, calibration, and decision curve analysis, and was externally validated in 72 patients.
Results
The radiomics score showed significantly better discrimination compared with pretreatment short-axis diameter measurements in both the primary (area under the curve AUC 0.91 vs. 0.83,
p
= 0.0015) and validation (AUC 0.90 vs. 0.80,
p
= 0.0298) cohorts. Decision curve analysis also indicated the superiority of the radiomics score. In a subanalysis of patients with a short-axis diameter ≥ 7 mm, the radiomics nomogram, incorporating the radiomics score and LPLN shrinkage to ≤ 4 mm, had better discrimination compared with a model incorporating only LPLN shrinkage in both cohorts.
Conclusions
Radiomics-based prediction modeling provides individualized risk estimation of LPLNM in rectal cancer patients treated with (chemo)radiotherapy, and outperforms measurements of pretreatment LPLN diameter.
Background
The aim of the present study was to clarify the advantages of robotic-assisted laparoscopic lateral lymph node dissection (RALLD) for rectal cancer by comparing its short-term outcomes ...with those of open lateral lymph node dissection (OLLD) in a large series from a single center. In terms of RALLD for advanced lower rectal cancer, there are only a few reports with a small number of cases in retrospective, non-comparative studies.
Methods
From April 2010 to July 2014, a total of 177 patients underwent rectal cancer surgery with lateral lymph node dissection. Four patients who underwent conventional laparoscopic lateral lymph node dissection were excluded. Thus, 173 patients were enrolled, with 85 RALLD and 88 OLLD cases. Perioperative outcomes, postoperative complications, and pathological results were compared between the groups.
Results
No conversion to open surgery was necessary in the RALLD group. The rate of sphincter-preserving procedure was significantly higher in the RALLD group than in the OLLD group (
p
= 0.007). Operative time was significantly longer in the RALLD group than in the OLLD group (
p
= 0.007). Blood loss was significantly less in the RALLD group than in the OLLD group (
p
< 0.001). The rates of wound infection, small bowel obstruction, anastomotic leakage, and urinary retention were significantly lower in the RALLD group than in the OLLD group. Numbers of harvested lymph nodes and positive resection margin rates showed no significant differences.
Conclusions
The short-term outcomes of RALLD may be superior to those of OLLD for advanced lower rectal cancer.
P-glycoprotein extrudes a large variety of xenobiotics from the cell, thereby protecting tissues from their toxic effects. The machinery underlying unidirectional multidrug pumping remains unknown, ...largely due to the lack of high-resolution structural information regarding the alternate conformational states of the molecule. Here we report a pair of structures of homodimeric P-glycoprotein: an outward-facing conformational state with bound nucleotide and an inward-facing apo state, at resolutions of 1.9 Å and 3.0 Å, respectively. Features that can be clearly visualized at this high resolution include ATP binding with octahedral coordination of Mg
; an inner chamber that significantly changes in volume with the aid of tight connections among transmembrane helices (TM) 1, 3, and 6; a glutamate-arginine interaction that stabilizes the outward-facing conformation; and extensive interactions between TM1 and TM3, a property that distinguishes multidrug transporters from floppases. These structural elements are proposed to participate in the mechanism of the transporter.
The surfaces of lipid droplets (LDs) constitute major sites of regulated accumulation and degradation of lipid in cells, and hence play important roles in lipid homeostasis of the whole body. CGI-58 ...(also called α/β hydrolase domain-containing protein 5 (ABHD5)) is a member of the α/β-hydrolase family of proteins and is a product of the causal gene of Chanarin–Dorfman syndrome (CDS), which is characterized by excessive storage of triacylglycerol (TG) in various tissues. CGI-58 is distributed predominantly on the surface of LDs and plays a crucial role in TG degradation in cells. In the process of lipolysis, CGI-58 coordinates with several proteins, including perilipin, a member of the PAT family of proteins, and adipose triglyceride lipase (ATGL), a putative rate-limiting enzyme for TG degradation in adipocytes. Besides its role in adipocytes, CGI-58 is involved in lipid degradation in various tissues, including those of skin and liver. This review focuses on the functions and protein interactions of CGI-58 on the surface of LDs in the regulation of fat mobilization in cells.
Purposes
Several retrospective studies have demonstrated the safety and technical feasibility of robotic-assisted laparoscopic surgery (RALS). The aim of the present study was to clarify the ...advantages of RALS for rectal cancer by comparing its short-term outcomes with those of conventional laparoscopic surgery (CLS).
Methods
Between April, 2010 and April, 2015, a total of 974 patients underwent proctectomy for rectal cancer. After the exclusion of those who underwent open surgery, high anterior resection, lateral lymph node dissection, or multiple resection, 442 patients were enrolled in this study, including 203 who underwent RALS and 239 who underwent CLS. We compared the short-term outcomes of these two groups.
Results
There was no case of conversion to open surgery in the RALS group, but 8 (3.3 %) cases in the CLS group (
p
= 0.009). Operative time was not significantly different, but blood loss was significantly less in the RALS group than in the CLS group (
p
< 0.001). The postoperative hospital stay was shorter in the RALS group than in the CLS group (
p
< 0.001). The rate of urinary retention was significantly lower in the RALS group than in the CLS group (
p
= 0.018).
Conclusion
The short-term outcomes in this series provide further evidence that RALS may be superior to CLS for rectal cancer.
Purpose
The purpose of this study was to evaluate the advantages of robot-assisted laparoscopic surgery (RALS) for lower rectal cancer and for visceral obesity cases, which have been regarded as ...challenging situations in rectal cancer surgery, comparing their surgical outcomes with those of conventional laparoscopic surgery (CLS).
Methods
Patients who underwent robotic or laparoscopic total mesorectal excision for rectal cancer were included in this retrospective study. Surgical outcomes including perioperative, postoperative, and pathological data were compared between the RALS and CLS groups. Patients were stratified into obese and non-obese groups according to visceral fat area (VFA). Obesity was defined by VFA ≥130 cm
2
.
Results
Two hundred thirty-six patients were enrolled, including 127 cases in the RALS group and 109 cases in the CLA group. A total of 82 (34.7 %) cases were categorized as VFA obese, including 52 cases in the RALS and 30 cases in the CLS groups. RALS for lower rectal cancer was associated with less blood loss (
p
= 0.007), a lower overall complication rate (9.4 % in RALS vs 23.9 % in CLS,
p
= 0.003), and shorter postoperative stay (
p
< 0.01) than CLS, with similar operative time and pathological results. The overall complication rate was significantly lower in the RALS group with VFA obesity; blood loss was significantly less and the postoperative stay was shorter in the RALS group with visceral obesity.
Conclusions
The present study demonstrated that RALS has some advantages in terms of surgical outcomes over CLS in challenging situations of rectal cancer surgery, such as lower rectal cancer cases and visceral obesity cases.
BACKGROUND:Mesorectal excision with lateral lymph node dissection is the standard treatment for locally advanced low rectal cancer in Japan. However, the safety and feasibility of laparoscopic ...lateral lymph node dissection remain to be determined.
OBJECTIVE:The purpose of this study was to evaluate the safety and feasibility of laparoscopic versus open lateral lymph node dissection for locally advanced low rectal cancer.
DESIGN:This was a retrospective cohort study using an exact matching method.
SETTING:We conducted a multicenter study of 69 specialized centers in Japan.
PATIENTS:Patients with consecutive midrectal or low rectal adenocarcinoma cancer stage II to III who underwent mesorectal excision with curative intent between 2010 and 2011 were recruited.
MAIN OUTCOME MEASURES:Short-term and oncological outcomes were compared between the laparoscopic and open-surgery groups.
RESULTS:Of the 1500 eligible patients, 676 patients who underwent lateral lymph node dissection were analyzed, including 137 patients who were treated laparoscopically and 539 patients who were treated with open surgery. After matching, the patients were stratified into laparoscopic (n = 118) and open-surgery (n = 118) groups. Operative times in the overall cohort were significantly longer (461 vs 372 min) in the laparoscopic versus the open-surgery group. In the laparoscopic group, the blood loss volume was significantly smaller (193 vs 722 mL), with fewer instances of blood transfusion (7.3% vs 25.5%) compared with the open-surgery group. The postoperative complication rates were 35.8% and 43.6% for the laparoscopic and open-surgery groups (p = 0.10). The 3-year relapse-free survival rates were 80.3% and 72.6% for the laparoscopic and open-surgery groups (p = 0.07).
LIMITATIONS:The study was limited by its retrospective design and potential selection bias.
CONCLUSIONS:Laparoscopic lateral lymph node dissection is safe and feasible for cancer stage II to III low rectal cancer and is associated with similar oncological outcomes as open lateral lymph node dissection. See Video Abstract at http://links.lww.com/DCR/A334.
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