The platinum coordination complex inhibits cell invasion-migration and epithelial-to-mesenchymal transition by altering the TGF-β-SMAD pathway in colorectal cancer

Introduction: There is a steady increase in colorectal cancer (CRC) incidences worldwide; at diagnosis, about 20 percent of cases show metastases. The transforming growth factor-beta (TGF-β) signaling pathway is one of the critical pathways that influence the expression of cadherins allowing the epithelial-to-mesenchymal transition (EMT), which is involved in the progression of the normal colorectal epithelium to adenoma and metastatic carcinoma. The current study aimed to investigate the impact of a novel coordination complex of platinum (salicylaldiminato) PT(II) complex with dimethyl propylene linkage (PT-complex) on TGF-β and EMT markers involved in the invasion and migration of the human HT-29 and SW620 CRC cell lines.Methods: Functional study and wound healing assay showed PT-complex significantly reduced cell motility and the migration and invasion of CRC cell lines compared to the untreated control. Western blot performed in the presence and absence of TGF-β demonstrated that PT-complex significantly regulated the TGF-β-mediated altered expressions of EMT markers.Results and Discussion: PT-complex attenuated the migration and invasion by upregulating the protein expression of EMT-suppressing factor E-cadherin and suppressing EMT-inducing factors such as N-Cadherin and Vimentin. Moreover, PT-complex significantly suppressed the activation of SMAD3 in both CRC cell lines. Further, the microarray data analysis revealed differential expression of genes related to invasion and migration. In conclusion, besides displaying antiproliferative activity, the PT complex can decrease the metastasis of CRC cell lines by modulating TGF-β-regulated EMT markers. These findings provide new insight into TGF-β/SMAD signaling as the molecular mechanism involved in the antitumoral properties of novel PT-complex

Microwave ablation of liver metastasis complicated by Clostridium perfringens gas-forming pyogenic liver abscess (GPLA) in a patient with past gastrectomy

Introduction: Gas-forming pyogenic liver abscess (GPLA) caused by C. perfringens is rare but fatal. Patients with past gastrectomy may be prone to such infection post-ablation. Presentation of case: An 84-year-old male patient with past gastrectomy had MW ablation of his liver tumors complicated by GPLA. Computerised tomography scan showed gas-containing abscess in the liver and he was managed successfully with antibiotic and percutaneous drainage of the abscess. Discussion: C. perfringens GPLA secondary to MW ablation in a patient with previous gastrectomy has not been reported in the literature. Gastrectomy may predispose to such infection. Even in high-risk patients, empirical antibiotic before ablation is not a standard of practice. Therefore following the procedure, close observation of patients’ conditions is necessary to allow early diagnosis and intervention that will prevent progression of infection. Conclusion: Potential complication of liver abscess following MW ablation can never be overlooked. The risk may be enhanced in patients with previous gastrectomy. Early diagnosis and management may minimise mortality and morbidity

Surveillance Compliance and Quality of Life Assessment Among Surgical Patients with Familial Adenomatous Polyposis Syndrome

Abstract Background Familial adenomatous polyposis (FAP) syndrome has a near-100% lifetime risk of colorectal cancer. Early surveillance and prophylactic surgery have been advocated to reduce this risk. However, the surveillance practices among FAP individuals in Saudi Arabia are unknown. We aimed to explore surveillance compliance in our population, as well as the disease impact on their quality of life (QoL). Methods All patients with FAP who underwent surgical resection at King Saud University Medical City between 2016 and 2022 were included. Demographic data, clinical features, family history, and compliance with surveillance were collected and analyzed. QoL questionnaires: Short-form health survey (SF-36) and European Organization for Research and Treatment (EORTC) were conducted by phone interview. Results A total of 14 patients were included with an average age of 25 years. Three patients (21.4%) were the first of their family members to develop FAP. Nine patients (64%) were untested for genetic mutation due to lack of referral to geneticists. The compliance rate toward both pre-operative colonoscopy and upper endoscopy were 78%. However, 38% and 27% compliance rates were observed toward initial and post-operative colonoscopy, respectively. The compliance rate was 14% toward thyroid ultrasound. QoL scores varied among patients, with a mean score above 60 across all SF-36 domains. Conclusion An overall poor compliance was observed among our participants, particularly toward thyroid ultrasound. Increased health awareness and patient education are essential. In addition, the importance of surveillance and genetic counseling should be emphasized among physicians treating these patients

Oncological outcomes of elective versus emergency surgery for colon cancer: A tertiary academic center experience

Background: In this study, we aimed to identify the oncological outcomes in colon cancer patients who underwent elective versus emergency curative resection. Methods: All patients who underwent curative resection for colon cancer between July 2015 and December 2019 were retrospectively reviewed and analyzed. Patients were divided into two groups based on the presentation into elective and emergency groups. Results: A total of 215 patients with colon cancer were admitted and underwent curative surgical resection. Of those, 145 patients (67.4%) were elective cases, and 70 (32.5%) were emergency cases. Family history of malignancy was positive in 44 patients (20.5%) and significantly more common in the emergency group (P = 0.016). The emergency group had higher T and TNM stages (P = 0.001). The 3-year survival rate was 60.9% and significantly less in the emergency group (P = 0.026). The mean duration from surgery to recurrence, 3-year disease-free survival, and overall survival were 1.19, 2.81, and 3.11, respectively. Conclusion: Elective group was associated with better 3-year survival, longer overall, and 3-year disease-free survival compared to the emergency group. The disease recurrence rate was comparable in both groups, mainly in the first two years after curative resection

Bioactivities of the Green Synthesized Silver Nanoparticles Reduced Using Allium cepa L Aqueous Extracts Induced Apoptosis in Colorectal Cancer Cell Lines

Allium cepa L (A. cepa) extract is frequently used as an adjuvant food in cancer treatment. We hypothesized that it contains a source of anticancer activity. There is a need to synthesize the silver nanoparticles (AgNPs) using an environment-friendly green synthesis reduction method using an aqueous extract of A. cepa. The AgNPs-CEPA were prepared by reduction method using the aqueous extract of A. cepa. The formed AgNPs-CEPA were characterized for their sizes and charge distribution. The AgNP-CEPA was investigated for its antioxidant and anticancer properties. Cell viability was evaluated by MTT assay. Gene expression was evaluated by real-time polymerase chain reaction (RT-PCR), and apoptosis measurement was carried out by flow cytometry in AgNP-CEPA-treated cells. The results showed a uniform size for AgNPs-CEPA of 155 & PLUSMN;2.1 nm with a zeta potential of -37.3 & PLUSMN;-2.92 mv. The produced AgNPs-CEPA are biocompatible with anticancer action and a moderate level of antioxidant reactivity. AgNPs-CEPA showed better reducing activity for A. cepa extract compared to the AgNPs-CEPA. AgNP-CEPA treatment of human colorectal cancer cell lines (HT-29 and SW620) inhibited cell proliferation and altered Bcl2 family gene expression. Moreover, exposure of cell lines to AgNPs-CEPA resulted in the significant induction of apoptosis compared to A. cepa and AgNO3. These findings indicate that AgNP-CEPA induces apoptosis by inhibiting Bcl2 family gene expression, suggesting that this formula is a promising anticancer agent for treating colorectal cancer

Discovery and Mechanistic Studies of Dual-Target Hits for Carbonic Anhydrase IX and VEGFR‑2 as Potential Agents for Solid Tumors: X‑ray, <i>In Vitro</i>, <i>In Vivo</i>, and <i>In Silico</i> Investigations of Coumarin-Based Thiazoles

A dual-targeting approach is predicted to yield better cancer therapy outcomes. Consequently, a series of coumarin-based thiazoles (5a–h, 6, and 7a–e) were designed and constructed as potential carbonic anhydrase (CA) and VEGFR-2 suppressors. The inhibitory actions of the target compounds were assessed against CA isoforms IX and VEGFR-2. The assay results showed that coumarin-based thiazoles 5a, 5d, and 5e can effectively inhibit both targets. 5a, 5d, and 5e cytotoxic effects were tested on pancreatic, breast, and prostate cancer cells (PANC1, MCF7, and PC3). Further mechanistic investigation disclosed the ability of 5e to interrupt the PANC1 cell progression in the S stage by triggering the apoptotic cascade, as seen by increased levels of caspases 3, 9, and BAX, alongside the Bcl-2 decline. Moreover, the in vivo efficacy of compound 5e as an antitumor agent was evaluated. Also, molecular docking and dynamics displayed distinctive interactions between 5e and CA IX and VEGFR-2 binding pockets

Discovery and Mechanistic Studies of Dual-Target Hits for Carbonic Anhydrase IX and VEGFR‑2 as Potential Agents for Solid Tumors: X‑ray, <i>In Vitro</i>, <i>In Vivo</i>, and <i>In Silico</i> Investigations of Coumarin-Based Thiazoles

A dual-targeting approach is predicted to yield better cancer therapy outcomes. Consequently, a series of coumarin-based thiazoles (5a–h, 6, and 7a–e) were designed and constructed as potential carbonic anhydrase (CA) and VEGFR-2 suppressors. The inhibitory actions of the target compounds were assessed against CA isoforms IX and VEGFR-2. The assay results showed that coumarin-based thiazoles 5a, 5d, and 5e can effectively inhibit both targets. 5a, 5d, and 5e cytotoxic effects were tested on pancreatic, breast, and prostate cancer cells (PANC1, MCF7, and PC3). Further mechanistic investigation disclosed the ability of 5e to interrupt the PANC1 cell progression in the S stage by triggering the apoptotic cascade, as seen by increased levels of caspases 3, 9, and BAX, alongside the Bcl-2 decline. Moreover, the in vivo efficacy of compound 5e as an antitumor agent was evaluated. Also, molecular docking and dynamics displayed distinctive interactions between 5e and CA IX and VEGFR-2 binding pockets

Discovery and Mechanistic Studies of Dual-Target Hits for Carbonic Anhydrase IX and VEGFR‑2 as Potential Agents for Solid Tumors: X‑ray, <i>In Vitro</i>, <i>In Vivo</i>, and <i>In Silico</i> Investigations of Coumarin-Based Thiazoles

A dual-targeting approach is predicted to yield better cancer therapy outcomes. Consequently, a series of coumarin-based thiazoles (5a–h, 6, and 7a–e) were designed and constructed as potential carbonic anhydrase (CA) and VEGFR-2 suppressors. The inhibitory actions of the target compounds were assessed against CA isoforms IX and VEGFR-2. The assay results showed that coumarin-based thiazoles 5a, 5d, and 5e can effectively inhibit both targets. 5a, 5d, and 5e cytotoxic effects were tested on pancreatic, breast, and prostate cancer cells (PANC1, MCF7, and PC3). Further mechanistic investigation disclosed the ability of 5e to interrupt the PANC1 cell progression in the S stage by triggering the apoptotic cascade, as seen by increased levels of caspases 3, 9, and BAX, alongside the Bcl-2 decline. Moreover, the in vivo efficacy of compound 5e as an antitumor agent was evaluated. Also, molecular docking and dynamics displayed distinctive interactions between 5e and CA IX and VEGFR-2 binding pockets

Discovery and Mechanistic Studies of Dual-Target Hits for Carbonic Anhydrase IX and VEGFR‑2 as Potential Agents for Solid Tumors: X‑ray, <i>In Vitro</i>, <i>In Vivo</i>, and <i>In Silico</i> Investigations of Coumarin-Based Thiazoles

A dual-targeting approach is predicted to yield better cancer therapy outcomes. Consequently, a series of coumarin-based thiazoles (5a–h, 6, and 7a–e) were designed and constructed as potential carbonic anhydrase (CA) and VEGFR-2 suppressors. The inhibitory actions of the target compounds were assessed against CA isoforms IX and VEGFR-2. The assay results showed that coumarin-based thiazoles 5a, 5d, and 5e can effectively inhibit both targets. 5a, 5d, and 5e cytotoxic effects were tested on pancreatic, breast, and prostate cancer cells (PANC1, MCF7, and PC3). Further mechanistic investigation disclosed the ability of 5e to interrupt the PANC1 cell progression in the S stage by triggering the apoptotic cascade, as seen by increased levels of caspases 3, 9, and BAX, alongside the Bcl-2 decline. Moreover, the in vivo efficacy of compound 5e as an antitumor agent was evaluated. Also, molecular docking and dynamics displayed distinctive interactions between 5e and CA IX and VEGFR-2 binding pockets