Synthesis of three cisplatin-conjugated asymmetric porphyrin photosensitizers for photodynamic therapy.

Photodynamic therapy provides a promising solution for treating various cancer types. In this study, three distinct asymmetric porphyrin-cisplatin complex photosensitizers (ZnPt-P1, ZnPt-P2, and ZnPt-P3) were synthesized, each having unique side chains. Through a set of experiments involving singlet oxygen detection and density functional theory, ZnPt-P1 was demonstrated to have excellent efficacy, exceeding that of ZnPt-P2 and ZnPt-P3. Notably, ZnPt-1 showed significant phototoxicity while maintaining low dark toxicity when tested on HepG2 cells. Additionally, further examination revealed that ZnPt-P1 had the capability to generate reactive oxygen species within cancer cells when exposed to light irradiation. Taken together, these results highlight the potential of ZnPt-P1 as a photosensitizer for use in photodynamic therapy. This study contributes to enhancing cancer treatment methodologies and provides insights for the future development of innovative drugs for photosensitization.

Long non-coding RNAs as epigenetic mediator and predictor of glioma progression, invasiveness, and prognosis.

Gliomas are aggressive brain tumors with high mortality rate. Over the past several years, non-coding RNAs, specifically the long non-coding RNAs (lncRNAs), have emerged as biomarkers of considerable interest. Emerging data reveals distinct patterns of expressions of several lncRNAs in the glioma tissues, relative to their expression in normal brains. This has led to the speculation for putative exploitation of lncRNAs as diagnostic biomarkers as well as biomarkers for targeted therapy. With a focus on lncRNAs that have shown promise as epigenetic biomarkers in the proliferation, migration, invasion, angiogenesis and metastasis in various glioma models, we discuss several such lncRNAs. The data from cell line / animal model-based studies as well as analysis from human patient samples is presented for the most up-to-date information on the topic. Overall, the information provided herein makes a compelling case for further evaluation of lncRNAs in clinical settings.

Ileocecal intussusception caused by two different tumors - which is the culprit lesion? A case report.

BACKGROUND: Ileocecal intussusception caused by two different tumors is rare, according to a literature review. We describe a case of a male patient with a cauliflower-like mass in the middle of the transverse colon observed by colonoscopy before surgery. It was considered to be intussusception caused by colon cancer. However, a substantial lipomatous mass was seen in the distal end of the intussusception by computed tomography before surgery, which posed a challenge in the preoperative diagnosis. CASE SUMMARY: We report a 72-year-old male patient with intussusception. The patient underwent right hemicolectomy and cholecystectomy in our hospital on April 29, 2019. During operation, the ileum was inserted into the ascending colon by about 15 cm, and a tumor with a diameter of approximately 3.0 cm was observed in the distal part of the intestine. An atypical liposarcoma/highly differentiated liposarcoma in the adipose tissue was suspected in the postoperative pathology, and a lipoma was diagnosed after MDM2 gene testing. A 4.0 cm × 5.0 cm polypoid mass was seen immediately adjacent to the mass, and the postoperative pathology report suggested a high-level tubular adenoma. The patient was eventually cured and discharged with an uneventful follow-up. CONCLUSION: Intussusception caused by two different types of masses is extremely rare. At present, surgery is the best treatment once intussusception is diagnosed.

Huge primary dedifferentiated pancreatic liposarcoma mimicking carcinosarcoma in a young female: A case report.

BACKGROUND: Pancreatic liposarcoma is a rare tumor. According to a literature review, the patient described in this study is the seventh case of pancreatic liposarcoma reported in the English literature and the third case of dedifferentiated liposarcoma. Furthermore, this case had the largest primary tumor volume, and a primary pancreatic liposarcoma was diagnosed based on sufficient evidence. CASE SUMMARY: We here report a rare case of a 28-year-old female with a huge dedifferentiated liposarcoma in the pancreatic tail. In June 2015, the patient underwent distal pancreatectomy with splenectomy. During the operation, a huge liposarcoma of approximately 28.0 cm × 19.0 cm × 8.0 cm was found, which had a yellow and white fish-like incisal surface. Based on both pathology and MDM2 gene amplification, the tumor was diagnosed as a dedifferentiated liposarcoma. The patient was treated with surgery but declined postoperative chemotherapy. She was well at the 26-mo follow-up, and no relapse was observed. CONCLUSION: Pancreatic liposarcoma has a low incidence. Chemotherapy should be included in the treatment regimens. Complete resection is the only effective treatment.

Recognition of the toxicity of aristolochic acid.

WHAT IS KNOWN AND OBJECTIVE: Aristolochic acid (AA) is an abundant compound in Aristolochia plants and various natural herbs. In the 1990s, a slimming formula used in Belgium that contains Aristolochia fangchi was reported to cause kidney damage and bladder cancer, and aristolochic acid nephropathy (AAN) is now well recognized worldwide. In October 2017, researchers reported an AA signature that is closely associated with hepatocellular carcinoma (HCC) worldwide. COMMENT: There are differing opinions on the toxicity of AA, and different countries have taken different measures to address the issue. There is a lack of clarity on the causal role of AA in hepatocarcinogenesis and on the potential underlying mechanisms for the reported nephrotoxicity and carcinogenicity. The toxicity of AA differs depending on gender and age, and other risk factors that could explain the variability in the toxicity of AA remain to be identified. WHAT IS NEW AND CONCLUSION: Whether preparations containing AA, such as many Chinese medicines, should be used remains controversial, and this issue warrants further investigation before definite conclusions can be drawn.

[Prevention and treatment of biliary complications following orthotopic liver transplantation].

OBJECTIVE: To study the prevention and treatment of biliary complications after orthotopic liver transplantation. METHODS: Clinical data of 183 recipients who had received liver transplantation between May 1995 and December 2006 were retrospectively analyzed. RESULTS: Biliary complications occurred in 15 patients (15/183, 8.2%). The incidence for short-term and long-term complication were 6.0% (11/183) and 2.2% (4/183) respectively. No biliary complications was due to hepatic artery thrombosis(HAT). Four cases who received PTC(percutaneous transhepatic cholangiography) with stent insertion,8 cases who received ERCP( endoscopic retrograde cholangiopancreatography) with stent insertion and 1 who received Roux-en-Y choledochojejunostomy for anastomotic stricture were successfully cured. Two cases required relaparotomy died for fungus infection eventually. The mortality due to biliary complications was 1.1%. CONCLUSIONS: The rapid combined abdominal organ harvesting technique could shorten the ischemia time and ameliorate the injury due to vascular and bile duct variances, which could reduce the incidence of biliary complication. PTC and (or) ERCP combined with stent insertion were main procedure for biliary complications not related to HAT after liver transplantation.

Prevention and treatment of rejection after simultaneous pancreas-kidney transplantation.

OBJECTIVE: To explore methods of preventing and reversing rejection after simultaneous pancreas-kidney (SPK) transplantation. METHODS: Seventeen patients underwent SPK transplantation from September 1999 to September 2003 were reviewed retrospectively. Immunosuppression was achieved by a triple drug regimen consisting of cyclosporine, mycophenolate mofteil (MMF), and steroids. Three patients were treated with anti-CD3 monoclone antibody (OKT3, 5 mg x d(-1)) for induction therapy for a mean period of 5-7 days. One patients received IL-2 receptor antibodies (daclizumab) in a dose of 1 mg x kg(-1) on the day of transplant and the 5th day posttransplant. One patient was treated with both OKT3 and daclizumab for induction. RESULTS: No primary non-functionality of either kidney or pancreas occurred in this series of transplantations. Function of all the kidney grafts recovered within 2 to 4 days after transplantation. The level of serum creatinine was 94 +/- 11 micromol/L on the 7th day posttransplant. One patient experienced the accelerated rejection, resulting in the resection of the pancreas and kidney grafts because of the failure of conservative therapy. The incidence of the first rejection episodes at 3 months was 47.1% (8/17). Only the kidney was involved in 35.3% (6/17); and both the pancreas and kidney were involved in 11.8% (2/17). All these patients received a high-dose pulse of methylprednisone (0.5 g x d(-1)) for 3 days. OKT3 (0.5 mg x d(-1)) was administered for 7-10 days in two patients with both renal and pancreas rejection. All the grafts were successfully rescued. CONCLUSION: Rejection, particularly acute rejection, is the major cause influencing graft function in SPK transplantation. Monitoring renal function and pancreas exocrine secretion, and reasonable application of immunosuppressants play important roles in the diagnosis and treatment of rejection.

Influence of hepatitis B and hepatitis C virus infection on the outcome of kidney transplantation.

OBJECTIVE: To investigate the impact of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the long-term survival of renal transplantation recipients. METHODS: A total of 443 patients who received renal allografts from 1992 to 2002 were analyzed. Outcome and survival were compared among four groups retrospectively. RESULTS: Twelve patients were positive for both hepatitis B surface antigen (HBsAg) and HCV antibody (anti-HCV) (group 1), 18 were HBsAg-positive and anti-HCV-negative (group 2), 26 were HBsAg-negative and anti-HCV-positive (group 3) and 387 were negative for both markers (group 4). The mean follow-up period was 6.1 +/- 2.8 years (range, 0.5-10 years) for all patients. Group 2 had significantly higher liver-related complications (38.9%) and liver-related death (16.7%) than did group 4 (0%, P < 0.01). Among all patients, 4 HBsAg-positive patients had fulminant hepatitis and died within two years of transplantation. Three patients (group 2) who died were seropositive for HBeAg and/or HBV DNA and none had a history of or positive serologic marker to indicate hepatitis of other etiologies. One (group 1), two (group 2), and one patient (group 3) developed liver cirrhosis respectively, and hepatocellular carcinoma occurred in two patients (group 2) and one patient (group 3). Despite high liver-related mortality in HBV-infected patients, no significant differences among the four groups in the long-term graft and patient survivals were demonstrated. The presence of HBsAg or anti-HCV was not associated with poor prognosis as determined by Cox regression analysis. CONCLUSION: HBV or HCV infection is not a contraindiction to kidney transplantation in Chinese patients. However, it should be noted that serious liver-related complications may occur and limit survival in patients infected with HBV and/or HCV after kidney transplantation.

[Analysis of rejection after simultaneous pancreas-kidney transplantation].

OBJECTIVE: To explore methods of preventing and reversing rejection after simultaneous pancreas-kidney transplantation (SPK). METHODS: Seventeen patients performed SPK operation from Sep, 1999 to Sep, 2003 were reviewed retrospectively. Immunosuppression was achieved by triple regimen consisting of cyclosporine, mycophenolate mofetil (MMF)/azathioprine and steroid. 2 patients were treated with Dalizumab, the other three patients used OKT3 as immune induction. RESULTS: 1 patient experienced the accelerated rejection, the pancreas and kidney grafts were resected because of failure of conservative therapy. 8 patients experienced renal acute rejection, 2 cases suffered from pancreas acute rejection at the same time. All these patients received daily high dose pulse steroid for 3 days. OKT3 was administered in 2 patients with steroid resistance rejection. All the grafts were successfully rescued. CONCLUSIONS: Reasonable application of immunosuppression after SPK operation and adoption of systemic measures which can reduce sensitivity of high risk receptor before SPK operation are the effective methods of preventing and treating rejection.

[The changes of Oddi sphincter motility after canine pancreas transplantation with bladder drainage].

OBJECTIVE: To study the changes of canine Oddi sphincter (SO) function after pancreas transplantation with bladder drainage and the effect on the graft function. METHODS: Normal canine SO, transplant canine SO and canine SO in vitro manometry were performed by triple lumen catheter. At the same time, pancreas endocrine and exocrine function after transplantation were determined. After transplantation, anti-reflux function of graft SO was also measured. RESULTS: Endocrine and exocrine function of all the transplanted dogs showed that pancreas graft function was good. Basal pressure of SO in control group was (18.5 +/- 2.8) mm Hg (1 mm Hg = 0.133 kPa). The contraction frequency was (9.7 +/- 1.5) per min, the contraction amplitude was (47.1 +/- 5.5) mm Hg, the motility index was (236 +/- 56). After transplantation, basal pressure increased to (27.8 +/- 2.8) mm Hg, frequency increased to (13.1 +/- 1.9) per min, amplitude decreased significantly to (8.3 +/- 1.8) mm Hg. There was no significant difference of motility index. Basal pressure of SO in vitro increased significantly to (37.2 +/- 5.1) mm Hg. Phasic contraction was not absent. After transplantation, the pressure in the bile duct residual did not increase in accordance with the increase of bladder pressure. CONCLUSIONS: After pancreas transplantation with bladder drainage, Basal pressure and frequency of canine SO could increase while amplitude could decrease, which provide the anti-reflux function of graft SO and may serve as an obstacle to pancreatic juice flow.

Protective effects of L-arginine on reperfusion injury after pancreaticoduodenal transplantation in rats.

BACKGROUND: Post-transplantation pancreatitis and graft thrombosis are two major complications of pancreas transplantation that contribute to morbidity, mortality, and graft loss. Nitric oxide(NO) is a potent vasodilator agent formed when L-arginine (L-Arg) is converted to L-citrulline by the action of NO synthase (NOS), and plays a major role in microcirculatory changes. We therefore investigated the effect of L-Arg on reperfusion injury following pancreaticoduodenal transplantation in rats. METHODS: The homologous male Wistar rat model of heterotopic total pancreaticoduodenal transplantation was used. The L-Arg-treated rats received the intravenous injection of L-Arg 5 minutes before and after reperfusion at a dose of 200 mg/kg while the N-Nitro-L-arginine methyl ester (L-NAME)-treated rats at a dose of 10 mg/kg. The amount of NO in the pancreas graft was measured. Serum concentration of cytokine-induced neutrophil chemoattractant (CINC) was determined by enzyme-linked immunosorbant assay, the expression of CINC mRNA was detected by Northern blot assay in the pancreas graft, and the activity of myeloperoxidase (MPO) was measured. Histological examination was performed. RESULTS: The amount of NO was higher in the L-Arg group than in the control group, while it was lower in the L-NAME group than in the control group (P<0.05). The peak of serum CINC concentration occurred 3 hours after reperfusion with the difference among the groups being significant. The expression peak of CINC mRNA in the pancreas graft occurred 3 hours after reperfusion. The expression level in the L-Arg group (7.66+/-1.53 microg/L) was lower than in the control group (26.31+/-2.01 microg/L), while in the L-NAME group (34.18+/-3.12 microg/L) it was higher than that in the control group (P<0.05). The activity of MPO in the L-Arg group was obviously decreased as compared with in the other groups. The pancreas inflammation was ameliorated when L-Arg was administered, whereas the pancreas damage was aggravated when L-NAME was administered. CONCLUSIONS: L-Arg can increase the amount of NO and inhibit the elevation of CINC, the CINC mRNA expression and early neutrophil accumulation in the pancreas. NO has protective effects on ischemia/reperfusion injury in pancreaticoduodenal transplantation.

Evaluation of the viability and energy metabolism of canine pancreas graft subjected to significant warm ischemia damage during preservation by UW solution cold storage method.

AIM: To evaluate the viability and energy metabolism of long warm ischemically damaged pancreas during preservation by the UW solution cold storage method. METHODS: The pancreas grafts subjected to 30-120 min warm ischemia were preserved by the UW solution cold storage method for 24 h. The tissue concentrations of adenine nucleotides (AN) and adenosine triphosphate (ATP) and total adenine nucleotides (TAN) were determined by using high performance liquid chromatography (HPLC) and the viability of the pancreas graft was tested in the canine model of segmental pancreas autotransplantation. RESULTS: The functional success rates of pancreas grafts of groups after 30 min, 60 min, 90 min, 120 min of warm ischemia were 100%, 100%, 67.7%, 0%, respectively. There was an excellent correlation between the posttransplant viability and tissue concentration of ATP and TAN at the end of preservation. CONCLUSION: The UW solution cold storage method was effective for functional recovery of the pancreas suffering 60-min warm ischemia. The tissue concentration of ATP and TAN at the end of 24 h preservation by the UW solution cold storage method would predict the posttransplant outcome of pancreas graft subjected to significant warm ischemia.

Oddi sphincter function after canine auto-pancreas transplantation with bladder drainage.

AIM: Several neural and hormonal factors are known to affect motility of sphincter of Oddi (SO). The major roles of SO are to regulate the flow of bile and pancreatic juice into the duodenum and to prevent the reflux of duodenal contents into the biliary and pancreatic duct. After pancreas transplantation, graft SO was denervated and graft pancreatitis might have relations to SO motility. The motility of SO after canine pancreas transplantation with bladder drainage was investigated. METHODS: Normal canine SO manometry and pancreas graft SO manometry after pancreas transplantation with bladder drainage were performed in seven dogs respectively before and after cholecystokinin (CCK) administration. Data of SO basal pressure, contraction frequency, amplitude and motility index after transplantation and CCK administration were compared with that in controls and before CCK administration. RESULTS: SO showed regular contractions with a certain basal pressure in control dogs. After transplantation, the graft SO basal pressure and contraction frequency were higher than that in controls, but the amplitude decreased (P<0.01). There was no great difference in SO motility index. CCK administration could relax normal SO but stimulate graft SO after pancreas transplantation with bladder drainage. After CCK administration, SO basal pressure, frequency and motility index were increased significantly (P<0.05), in comparison with that before administration. The amplitude remained unchanged (P>0.05), in comparison with that before CCK administration. CONCLUSION: After auto-pancreas transplantation with bladder drainage, canine SO motility was inhibited. Basal pressure and frequency increased but amplitude decreased. CCK administration after transplantation had an inhibitory effect on canine SO instead of a relaxation effect observed in normal canine SO. This will increase the resistance of SO to the pancreatic juice flow and induce pancreatic juice stagnation and can not prevent reflux of urine and duodenal contents when the bladder pressure is increased to a certain extent, which may cause graft pancreatitis.