Novel therapeutic diiminoquinone exhibits anticancer effects on human colorectal cancer cells in two-dimensional and three-dimensional in vitro models.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality. Cancer stem cells (CSCs) in CRC, which are spared by many chemotherapeutics, have tumorigenic capacity and are believed to be the reason behind cancer relapse. So far, there have been no effective drugs to target colon CSCs. Diiminoquinone (DIQ) has shown promising effects on targeting colon cancer. However, there is limited research on the effects of DIQ on eradicating CSCs in CRC. AIM: To investigate the anticancer potential of DIQ on colon CSCs in two-dimensional (2D) and three-dimensional (3D) models using colonospheres and patient-derived organoids. METHODS: Various 2D methods have been used to assess the effect and the mechanism of DIQ on HCT116 and HT29 cell lines including cell proliferation and viability assays, migration and invasion assays, immunofluorescence staining, and flow cytometry. The potency of DIQ was also assessed in 3D culture using the sphere formation assay and colon cancer patient-derived organoid model. RESULTS: Our results showed that DIQ significantly inhibited cell proliferation, migration, and invasion in HCT116 and HT29 cell lines. DIQ treatment induced apoptosis along with an accumulation of HCT116 and HT29 cancer cells in the sub-G1 region and an increase in reactive oxygen species in both CRC cell lines. DIQ reduced sphere-forming and self-renewal ability of colon cancer HCT116 and HT29 stem/progenitor cells at sub-toxic doses of 1 µmol/L. Mechanistically, DIQ targets CSCs by downregulating the main components of stem cell-related -catenin, AKT, and ERK oncogenic signaling pathways. Potently, DIQ displayed a highly significant decrease in both the count and the size of the organoids derived from colon cancer patients as compared to control and 5-fluorouracil conditions. CONCLUSION: This study is the first documentation of the molecular mechanism of the novel anticancer therapeutic DIQ via targeting CSC, a promising compound that needs further investigation.

Thymoquinone Radiosensitizes Human Colorectal Cancer Cells in 2D and 3D Culture Models.

Resistance of cancer cells and normal tissue toxicity of ionizing radiation (IR) are known to limit the success of radiotherapy. There is growing interest in using IR with natural compounds to sensitize cancer cells and spare healthy tissues. Thymoquinone (TQ) was shown to radiosensitize several cancers, yet no studies have investigated its radiosensitizing effects on colorectal cancer (CRC). Here, we combined TQ with IR and determined its effects in two-dimensional (2D) and three-dimensional (3D) culture models derived from HCT116 and HT29 CRC cells, and in patient-derived organoids (PDOs). TQ sensitized CRC cells to IR and reduced cell viability and clonogenic survival and was non-toxic to non-tumorigenic intestinal cells. TQ sensitizing effects were associated with G2/M arrest and DNA damage as well as changes in key signaling molecules involved in this process. Combining a low dose of TQ (3 µM) with IR (2 Gy) inhibited sphere formation by 100% at generation 5 and this was associated with inhibition of stemness and DNA repair. These doses also led to ~1.4- to ~3.4-fold decrease in organoid forming ability of PDOs. Our findings show that combining TQ and IR could be a promising therapeutic strategy for eradicating CRC cells.

Superior mesenteric arteriovenous fistula embolisation complicated by bowel ischaemia.

Superior mesenteric arteriovenous fistulas are rare, especially when iatrogenic in origin. Management of these fistulas can be surgical or endovascular. Endovascular embolisation is the preferred modality with a low rate of complications. Among the reported complications, bowel ischaemia is considered an unlikely occurrence. We report a case of a complex iatrogenic arterioportal fistula that was managed by endovascular embolisation and controlled through both its inflow and outflow, and was later complicated by bowel ischaemia.

Laparoscopic repair of a left paraduodenal hernia presenting with acute bowel obstruction: report of a case.

An internal hernia is any protrusion of a solid organ or a hollow viscus through a defect within the abdominal cavity. Paraduodenal hernias (PDHs) are rare; however, they are the most common form of internal hernias. We present a case of a left PDH in a 59-year-old healthy woman who presented with acute bowel obstruction. The PDH was diagnosed preoperatively using computed tomography scan. Laparoscopic exploration of the abdomen was then performed for reduction of the hernia. Using this approach, we managed to close the defect with intracorporeal continuous suturing with the aim of avoiding future incarceration. The patient was discharged 60 hours postoperation in a good condition, compared with 3 to 28 days postoperation reported in most of the literature. Our search of the english language literature revealed only 16 reported cases of laparoscopic repair of PDH. We believe that laparoscopic treatment of PDH in experienced hands is recommended in selected cases as it decreases the morbidity and significantly shortens the hospital stay.

Laparoscopic donor nephrectomy: The Middle East experience.

OBJECTIVES: To summarize the experience of the Middle East in laparoscopic donor nephrectomy (LDN), to discuss the associated advantages and salient problems, to examine the learning curve encountered compared with that of the pioneering centres in the West, and the contribution of the regional centres to the worldwide experience. METHODS: We searched Medline and PubMed for all centres performing LDN in the Middle East. Questionnaires were e-mailed to the regional transplantation centres, and programme directors, and leading urological and transplant surgeons were contacted by telephone. RESULTS: LDN in the Middle East was first introduced in 2000; this approach has been pioneered and practised at seven transplant centres within five countries in the region, and was restricted to only three Arab countries, i.e. Lebanon, Egypt and Kuwait. Data collection yielded a total of 888 procedures over one decade, representing only 2% of the total of ≈50,000 transplants during the same period. Despite variability of accurate reporting the overall outcomes were similar to those of open DN. The spectrum of complications was comparable to that from major centres in the USA during their learning curve. CONCLUSIONS: The introduction of LDN in the Middle East has been gratifying. The relative hesitancy in introducing LDN in the rest of the Arab Middle East is multifaceted. The advantages conferred to the donor underscore the need for further expansion of this approach for kidney retrieval.

Evaluation of right versus left laparoscopic donor nephrectomy.

OBJECTIVES: With the advent of laparoscopic donor nephrectomy, there has been a general underuse of right laparoscopic donor nephrectomy versus left because of concerns regarding higher complication rates and poorer outcomes. We performed a retrospective analysis of our laparoscopic donor nephrectomy series with an emphasis on the side of the kidney retrieved and the outcomes of donors and recipients. MATERIALS AND METHODS: Data on 94 consecutive donor-recipient pairs (188 patients) were reviewed. All donor nephrectomies were performed by pure laparoscopy. There were 74 left laparoscopic donor nephrectomies and 20 right laparoscopic donor nephrectomies. Intraoperative parameters and graft outcome were recorded and the data were analyzed to compare right laparoscopic donor nephrectomy versus left laparoscopic donor nephrectomy using a computer software system. Follow-up ranged from 1 to 6 years (mean, 3.4 y). RESULTS: There were no significant differences in any intraoperative or postoperative parameters, except in a slightly higher warm ischemia time in right laparoscopic donor nephrectomy versus left laparoscopic donor nephrectomy, but this did not translate into an adverse effect on renal recovery. Acute graft rejection was observed in 2 of 74 patients who had a left laparoscopic donor nephrectomy (2.7%) and none of the patients who had a right laparoscopic donor nephrectomy. Chronic graft loss was observed in 2 of 74 patients who had a left laparoscopic donor nephrectomy (2.7%); 1 of recurrent pyelonephritis and sepsis and 1 renal oxalosis. No graft losses were observed in any patient who had a right laparoscopic donor nephrectomy. Mean serum creatinine levels in recipients at 1, 3, 6, 9, and 12 months were equivalent for right laparoscopic donor nephrectomy versus left laparoscopic donor nephrectomy; they were 120, 110, 110, 110, 110 µmol/L, versus 110, 110, 110, 110, 110 µmol/L. (1.35, 1.21, 1.24, 1.21, 1.26 mg/dL versus 1.22, 1.17, 1.17, 1.17, 1.23 mg/dL). CONCLUSIONS: This single center study demonstrates equivalent results with left laparoscopic donor nephrectomy and right laparoscopic donor nephrectomy with no adverse effects of right laparoscopic donor nephrectomy on donor-recipient outcome or renal function.

Isolated splenic metastasis from colorectal cancer.

Splenic metastases are unusual, arising in less than 1% of all metastases. Isolated solitary splenic metastasis from colorectal carcinoma is considered exceptional. This rarity has been explained by several hypotheses relating to the anatomical, histological, and immunological features of the spleen. We review the reported cases of isolated solitary splenic metastasis from colorectal carcinoma and discuss the diagnostic and therapeutic options for this entity. We searched the English-language medical literature, using the Medline and Pubmed databases from January 1966 through July 2010, for articles reporting isolated splenic metastasis from colorectal carcinoma. Only 26 cases have been reported; four cases had synchronous splenic metastasis. Fifteen patients had regional lymph node involvement on diagnosis of primary carcinoma. The primary tumor was located in the left colon or in the rectum in 18 cases. Carcinoembryonic antigen (CEA) level was elevated in 73% of cases. All patients underwent curative splenectomy; only one patient had laparoscopic resection of the spleen. Mean reported survival interval was 19.5 months; only three patients were deceased at last follow-up. Solitary splenic metastasis from colorectal carcinoma is very rare; clinicians are advised to pay close attention when routinely evaluating patients with serial CEA levels and abdominal scans. Splenectomy seems to be the preferred treatment modality with improvement of long-term survival. However, definitive conclusions cannot be drawn from the small number of case reports available.

Complications of adjustable gastric banding, a radiological pictorial review.

OBJECTIVE: The purpose of this article is to review the radiologic appearance of complications of the adjustable gastric band. CONCLUSION: Continuous progress in surgical technique of adjustable gastric banding and the increasing experience of surgeons have decreased the rate of complications. However, because different complications may have the same clinical presentation but require different treatment, to give a definitive diagnosis, the radiologist must be aware of the surgical procedures and possible sequelae.

Tetrazolo[1,5-a] quinoline derivatives as anti-inflammatory and antimicrobial agents [1].

Tetrazolo[1,5-a]quinoline derivatives bearing in the 4-position various thiazolidinone 3a-c, 5a-c and 7a-c, thiazinone 8a,b, thiazoline 9a-d and thiadiazoline 10a,b moieties have been synthesized and evaluated for anti-inflammatory activity and antimicrobial properties. The synthetic routes involved the reaction of tetrazolo[1,5-a]quinoline-4-carboxaldehyde 1 with amines and hydrazines to give the corresponding aniles 2a-c and hydrazones 4a-c respectively The latter compounds when treated with thioglycolic acid, furnished the corresponding thiazolidinone derivatives 3a-c and 5a-c. Moreover; thiosemicarbazone 6a-c derivatives were subsequently cyclized by various reagents giving rise the title compounds. Some of the products proved to possess potent anti-inflammatory and antimicrobial properties.

Clear cell sarcoma (malignant melanoma of soft parts): fine-needle aspiration cytology of a highly pigmented tumor.

Diagnosis of clear cell sarcoma by fine-needle aspiration is difficult, as melanin is usually absent. Here we describe a case of a primary clear cell carcinoma with abundant melanin, making diagnosis definitive.

Synthesis of some novel quinoline-3-carboxylic acids and pyrimidoquinoline derivatives as potential antimicrobial agents.

The synthesis and in vitro antimicrobial evaluation of several quinoline and pyrimidoquinoline derivatives are described. Treatment of 7-substituted quinolin-2(1H)-one-3-carboxylic acids 2a-c with phosphoryl chloride or thionyl chloride gave rise to the 7-substituted 2-chloroquinoline-3-carboxylic acids 3a-c and 7-substituted 2-chloro-3-chlorocarbonylquinolines 5a-c respectively. The 2-chloro function in compounds 3a-c was replaced by 2-aminothiazole or 2-aminopyridine to give 2-(thiazol-2-yl)aminoquinoline-3-carboxylic acids 4a-c or 2-(pyrid-2-yl)aminoquinoline-3-carboxylic acids 4d-f. Treatment of 5a-c with the same heterocyclic amines at room temperature furnished the corresponding 7-substituted 2-chloro-3-heteryl-aminocarbonylquinolines 6a-f. The tetracyclic 9-substituted thiazolo[3', 2':1, 2]-pyrimido[4, 5-b]quinolin-5-ones 7a-c and 10-substituted pyrido[1', 2':1, 2]-pyrimido[4, 5-b]quinolin-6-ones 7d-f were synthesized by heating 5a-c with the heterocyclic amines in toluene or by heating 6a-f under reflux in dimethylformamide. The products were evaluated in vitro for potential antimicrobial activity.

Novel 4-aminopyrimido[4,5-b]quinoline derivatives as potential antimicrobial agents.

Two series of 4-aminopyrimido[4,5-b]quinoline derivatives substituted in the 2-position 6a-c and/or in 1-position 9a-e have been prepared by facile routes starting from 2-amino-3-cyanoquinoline 2,2-chloro-3-cyanoquinoline 4 and 2-arylamino-3-cyanoquinolines 8a-d. The reactions involved simple fusion with thiourea or urea and, in some cases, with guanidine. The prepared compounds were in vitro tested for antimicrobial activities against some selected Gram-positive, Gram-negative bacteria and fungi. The products containing the thio-function were the most active followed by those containing the imino-function while the carbonyl containing derivatives were without significant antimicrobial effect.