Colon Cancer Research Articles

Non-nucleophilic base promoted synthesis of azo-linked oxazolone-pyrazole hybrids: Antimicrobial, antitubercular, anticancer evaluations and in-silico modeling insights

Ten new non-nucleophilic base (DBU) catalyzed oxazolone-bearing pyrazole derivatives were created to treat infectious diseases caused by bacterial, mycobacterial strains, and cancerous cell lines. Compounds 7b and 7c showed excellent antibacterial and antifungal activity. Compound 7b was highly effective against M. tuberculosis H37Rv, with a MIC of 0.06 μg/mL and significant binding affinities to AcrB of E. coli (−12 Kcal/mol), TriABC of P. aeruginosa (−12.5 Kcal/mol), and MepR of S. aureus (−10.6 Kcal/mol). Based on the findings, compounds 7b, 7c, and 7e exhibit proficient binding affinity with two essential targets, namely Enoyl-[acyl-carrier-protein] reductase and Topoisomerase I, of M. tuberculosis. Compound 7b showed superior cytotoxic activity against all cancer types except leukemia with GI50 values of 1.26–1.83 µM and LC50 values of 5.36–7.88 µM. Compound 7a demonstrated remarkable anticancer activity against colon, melanoma, ovarian, renal, and breast cancer cell lines with GI50 values of 1.60–2.55 µM.

Efficacy of traditional Chinese medicine in the conservative management of complete small intestinal obstruction post-gastric cancer surgery: A case report

In this case report, we describe the successful treatment of a patient with complete small bowel obstruction following gastric cancer surgery, employing an integrated approach of traditional Chinese medicine and Western medicine. Initial treatment consisted of conventional biomedical interventions, including intestinal obstruction catheterization, but after 16 days without improvement, surgical intervention was recommended. The patient, however, refused surgery and opted for treatments based on traditional Chinese medicine. Comprehensive traditional Chinese medicine therapies such as acupuncture, moxibustion, flash cupping, oral administration of compound herbal formulas, and enemas using Chinese herbal medicine were implemented alongside modern medical care. The obstruction resolved, and the patient was discharged without requiring surgery. Follow-up revealed no recurrence of the condition. This case highlights the potential of integrating traditional Chinese medicine with Western medical practices in the conservative management of complete small bowel obstruction, offering a reference for clinical application.

GUCA2A dysregulation as a promising biomarker for accurate diagnosis and prognosis of colorectal cancer

Colorectal cancer is a leading cause of global mortality and presents a significant barrier to improving life expectancy. The primary objective of this study was to discern a unique differentially expressed gene (DEG) that exhibits a strong association with colorectal cancer. By achieving this goal, the research aims to contribute valuable insights to the field of translational medicine. We performed analysis of colorectal cancer microarray and the TCGA colon adenoma carcinoma (COAD) datasets to identify DEGs associated with COAD and common DEGs were selected. Furthermore, a pan-cancer analysis encompassing 33 different cancer types was performed to identify differential genes significantly expressed only in COAD. Then, comprehensively in-silico analysis including gene set enrichment analysis, constructing Protein–Protein interaction, co-expression, and competing endogenous RNA (ceRNA) networks, investigating the correlation between tumor-immune signatures in distinct tumor microenvironment and also the potential interactions between the identified gene and various drugs was executed. Further, the candidate gene was experimentally validated in tumoral colorectal tissues and colorectal adenomatous polyps by qRael-Time PCR. GUCA2A emerged as a significant DEG specific to colorectal cancer (|log2FC|> 1 and adjusted q-value < 0.05). Importantly, GUCA2A exhibited excellent diagnostic performance for COAD, with a 99.6% and 78% area under the curve (AUC) based on TCGA-COAD and colon cancer patients. In addition, GUCA2A expression in adenomatous polyps equal to or larger than 5 mm was significantly lower compared to smaller than 5 mm. Moreover, low expression of GUCA2A significantly impacted overall patient survival. Significant correlations were observed between tumor-immune signatures and GUCA2A expression. The ceRNA constructed included GUCA2A, 8 shared miRNAs, and 61 circRNAs. This study identifies GUCA2A as a promising prognostic and diagnostic biomarker for colorectal cancer. Further investigations are warranted to explore the potential of GUCA2A as a therapeutic biomarker.

Pearls for counseling older adults on the indications for stopping colon cancer screening

Colorectal cancer remains a leading cause of mortality, making effective screening procedures like colonoscopy essential in reducing associated risks. The cessation of colorectal cancer screening in older adults presents complex challenges, particularly as guidelines recommend screening initiation at age 45 and emphasize individualized decision-making for older populations. Key considerations include balancing procedural risks, cancer risk, overall health prognosis, and patient preferences. The risks associated with colonoscopy are especially pertinent for older patients with comorbidities, necessitating the use of prognostic tools like ePrognosis and the Charlson Comorbidity Index to inform screening decisions. High-risk individuals may experience increased anxiety about cancer, complicating the decision-making process, as many have historically relied on regular surveillance. Perspectives from both physicians and patients reveal significant uncertainty regarding screening cessation, highlighting the importance of patient involvement in these discussions. Effective communication strategies are crucial, advocating for recommendations that align with patients' broader health goals rather than focusing solely on age-related actuarial data. Ultimately, navigating the intricacies of colorectal cancer screening cessation in older adults requires a patient-centered approach that minimizes risks while respecting individual values and health goals.

PLA/PLGA nanocarriers fabricated by microfluidics-assisted nanoprecipitation and loaded with Rhodamine or gold can be efficiently used to track their cellular uptake and distribution

This study represents a pioneering investigation into using microfluidic technology for manufacturing PLA and PLGA nanocarriers (NCs) loaded with tracer molecules or metals through a co-precipitation protocol that involves saturating the water phase. The effects of total flow rate (TFR), flow rate ratio (FRR), surfactant amount, and polymer concentration on particle sizes and distributions were examined. The average size of PLA-NCs varied from 349 ± 175 nm to 170 ± 64 nm, with surface charges ranging from −13 to −6 mV. In contrast, PLGA-NCs had an average size between 192 ± 46 nm and 100 ± 34 nm, with surface charges from –23 mV to −53 mV. Increasing the TFR from 6 to 10 mL/min with a fixed FRR of 1:1 and reducing polymer concentrations in the organic phase from 20 to 5 mg/mL generally resulted in smaller NC sizes and distributions (monodispersed), with PLGA-NCs consistently exhibiting smaller dimensions. Under these specific conditions, Rhodamine B (Rhod) and gold (Au) were successfully loaded, achieving encapsulation efficiencies exceeding 50 %. Electron microscopy analysis confirmed that the nanocarriers exhibited a consistent spherical shape with smooth surface morphology. X-ray energy-dispersive spectroscopy (EDX) revealed a uniform distribution of gold within the polymer matrix. PLA-NCs were effectively internalized by various cell types, including human Peripheral Blood Mononuclear Cells (PBMCs), HT-29 colon cancer cells, and C6 glioma cells. Uptake occurred in a dose-dependent manner for PLA-NCs sized at 260 ± 51 nm, with only 30 % internalization at 2 mg/mL concentration after 24 to 48 h. Notably, smaller PLA-NCs with a mean size of 170 ± 64 nm achieved nearly 100 % uptake across all tested cell types after 48 h, indicating that particle size significantly influenced cellular uptake

A rare incidence of signet ring cell carcinoma of the rectosigmoid junction: a case report

Introduction and importance: Signet ring cell carcinoma (SRCC) is a rare type of adenocarcinoma. SRCC comprises 1.0% of all colon cancer and 0.7% of all rectal cancer. The SRCC spreads both hematologically and through lymph nodes making it highly invasive. The pathophysiology of the colorectal SRCC involves an alteration in the function of the RNF43, CDH-1, and SMAD4 genes as well as TGF-B signaling pathways, which are responsible for epithelial-mesenchymal transitions and stem cell properties. This also shows a higher rate of BRAF mutation, microsatellite instability-high (MSI-H) and CpG island methylator phenotype positivity Case presentation: A 17-year-old female patient with no known comorbidities presented with copious, bright red colored per rectal bleeding along with painful defecation. Colonoscopy revealed an eccentric growth that led to luminal narrowing. Multiple biopsies confirmed a 4 cm × 6 cm neoplastic lesion with locoregional lymphadenopathy, but no metastasis. The patient underwent anterior resection of the rectum, colostomy, and rectal stump closure. The sigmoid colon was resected up to the middle up to the third mesorectum followed by multiple re-explorations. Discussion: SRCC presents at an advanced stage with a poor prognosis because signet ring cells infiltrate the mucosa without forming a significant mass, hindering early diagnosis of this carcinoma. Among the previously published large-scale studies, SRCC involves the proximal colon, i.e., the cecum, ascending, and transverse colon. However, our case presents a less common left-sided presentation in a less-commonly presented demographic, a 17-year-old girl. The patient’s non-specific symptoms contributed to a delayed diagnosis. Despite this, the absence of metastasis in our late-diagnosed case is atypical of SRCC. Conclusion: SRCC should be considered as a differential diagnosis for young adults presenting with per-rectal bleeding and other common symptoms often seen in frequently diagnosed conditions. Therefore, early diagnosis along with appropriate surgical intervention combined with supportive treatment are important for better patient outcomes.

Jing-Si Herbal Tea attenuates oral cancer cell viability, migration, and invasion by regulating epithelial-to-mesenchymal transition and reactive oxygen species accumulation

Background/purposeOral cancer is the sixth most common cancer worldwide and can be life-threatening if not diagnosed and treated in its early stages. Jing-Si Herbal Tea (JSHT), containing eight traditional Chinese medicine-based herbs, is known to suppress the malignancy, growth, and metastasis of several tumor cells, including breast, lung, and colon cancer cells. However, the pharmacological effect of JSHT on oral cancer progression is still unclear. Materials and methodsIn this study, we evaluated the potential of JSHT to arrest the development of oral cancer via induction of cell death by reactive oxygen species (ROS) accumulation and inhibition of migration, invasion, and epithelial-to-mesenchymal transition (EMT). For this purpose, we employed the human tongue squamous cell carcinoma SAS cell line, which we treated with different JSHT concentrations for 24 h, and assessed cell viability, migration, and wound healing capabilities, together with western blotting for measuring expression levels of EMT markers. ResultsSurvival, migration/invasion ability, EMT, and ROS production in the SAS human tongue squamous carcinoma and FaDu human pharynx squamous cell carcinoma cell line were decreased by JSHT treatment via Lon protease-independent mechanisms. ConclusionThis study demonstrates that JSHT could be regarded as a candidate new supplement to existing anticancer therapies and an alternative, orally administered healthcare product for treating oral squamous cell carcinoma.

Probiotic and Functional Characterization of Newly Isolated Lactiplantibacillus plantarum Strains from Human Breast Milk and Proliferative Inhibition Potential of Metabolites

Four Lactiplantibacillus plantarum strains newly isolated and identified from human breast milk in Turkey, have probiotic, functional and proliferative inhibition potential of metabolites against colon cancer cell lines (Caco-2 and HT-29) were evaluated. In simulated gastric (pH+pepsin) and intestinal (bile and pancreatin) media, all strains exhibited strong probiotic character by showing resistance, although decreasing with time and concentration. The strains were sensitive to penicillin G, rifampin and chloramphenicol and showed antibacterial effect on all pathogenic bacteria. Citric acid, malic acid, tartaric acid, pyruvic acid and fumaric acid were not detected in the strains, while the highest amount of acetic acid was detected. It was observed that all strains synthesized exopolysaccharide in similar amounts. Compared to standard antioxidants, the strains showed less DPPH activity and similar ABTS activity. High amounts of metabolites of the strains showed good antiproliferative effect on Caco-2, while lower amounts showed good antiproliferative effect on the HT-29 cell line. When all the data were considered, it was determined that the strains were close to each other, but the YAAS 23 strain showed slightly better properties. In conclusion, breast milk is a unique environment harboring beneficial bacteria such as L. plantarum for human health.

A rare case of hepatocellular carcinoma and colorectal liver metastasis

Abstract Hepatocellular carcinoma is the third leading cause of cancer deaths worldwide, with a 5-year survival rate of 20.3%, while colorectal cancer is a major cause of morbidity and mortality worldwide, being the third most common cancer in men and the second in women. In addition, multiple primary tumors, involving cancers at different sites and histologies, occur in 2.4% to 17% of cases. We report a case of a 74-year-old man with colon cancer presented at the Emergency Department with asymptomatic anemia post chemotherapy and surgical intervention two years ago. He reported experiencing paleness, dizziness, exertional dyspnea, and fatiguability for the past month. Therefore, chest computed tomography was performed to rule out pulmonary embolism; however, the image revealed an incidental finding of two hepatic lesions in segment II. After further investigations, the decision was to perform hepatic segmentectomy. Postoperative pathology revealed residual Hepatocellular carcinoma and metastatic colonic-type adenocarcinoma with mucinous differentiation.

Awareness of colon cancer screening among the general population: Community-based study from the Qassim Region of Saudi Arabia

ABSTRACT Introduction: Colorectal cancer (CRC) has surged to prominence as the leading cancer affecting men and the second most common affecting women in Saudi Arabia. The need for preventative screening is underscored by the rising prevalence of precancerous polyps, early-stage colorectal cancer, and the fact that these conditions often manifest without symptoms. Methods: This study utilized a cross-sectional descriptive design and employed data from a sample of 425 residents of Qassim region in Saudi Arabia. The participants guaranteed their confidentiality when completing self-administered online questionnaires. Results: Nearly half, 209 (49.2%), of the participants indicated that there were increasing incidences of colon cancer in Saudi Arabia. A considerable number [122 (28.7%)] of respondents believed that family history was the risk factor for colorectal cancer. A total of 203 (47.8%) knew that CRC could develop without symptoms. Common symptoms of CRC were cited as bleeding per rectum 300 (70.6%) and abdominal pain 259 (60.9%). The majority, 384 (90.4%), of the respondents believed that CRC could be prevented and cured if detected early, 415 (97.6%). The results noted that more females knew that there were increasing incidences of CRC in KSA (P = 0.03). Older participants were more likely to understand the function of the colon and rectum (P &lt; 0.001**), the risk factors (P &lt; 0.001**), and the symptoms of CRC (P &lt; 0.001**), as well as their willingness to choose colonoscopy to conduct colon follow-up screening even without symptoms (P &lt; 0.001**). Married participants had a higher likelihood of knowing the ranking of CRC among the most common tumors in both sexes in KSA (P = 0.027*). Participants with a higher education level were more likely to know the ranking of CRC among the common tumors in the KSA (P = 0.004**), the functions of colon and rectum (0.003**), and the symptoms of CRC (P &lt; 0.001**). Conclusion: The study revealed considerably below-average knowledge about the general public’s screening for CRC in the Qassim region of Saudi Arabia. Although a substantial proportion of participants demonstrated knowledge about the risk factors, symptoms, and prevention of CRC, there is limited knowledge about screening programs in the region. This underscores the need for public awareness campaigns and concerted efforts to eliminate the obstacles preventing more people from getting screened with colonoscopies for early detection and prevention of CRC.

Targeting fibroblast activation protein with chimeric antigen receptor macrophages

Under the rapid advancement of chimeric antigen receptor T cell (CAR-T) technology, CAR-macrophages (CAR-Ms) are also being developed currently in the pre-clinical stage and have been shown to inhibit tumor growth in several mouse tumor models. Fibroblast activation protein (FAP) is a type II transmembrane serine protease, which is expressed in stromal fibroblasts of over 90 % of common human epithelial cancers and is upregulated in fibrotic diseases of the liver, lung and colon, etc. In this study, we firstly constructed FAP-CAR macrophages to target FAP+ cells through in vitro phagocytosis assays. In subsequent in vivo assays, we discovered that FAP-CAR-ΔZETA bone marrow-derived macrophages (BMDMs) rather than FAP-CAR BMDMs, exhibited a pronounced anti-tumor effect in mouse subcutaneous MC38 colon cancer model. In addition, FAP-CAR and FAP-CAR-ΔZETA BMDMs therapy could effectively improve CCl4-induced liver fibrosis in mice. Collectively CAR-Ms targeting FAP demonstrated great therapeutic potential in cancer and liver fibrosis therapy.

A hydrogen sulfide-activated Pd@Cu2O nanoprobe for NIR-II photoacoustic imaging of colon cancer and photothermal-enhanced ferroptosis therapy

A hydrogen sulfide-activated Pd@Cu2O nanoprobe for NIR-II photoacoustic imaging of colon cancer and photothermal-enhanced ferroptosis therapy

Neoadjuvant chemoradiotherapy in locally advanced and locally recurrent colon cancer

Neoadjuvant chemoradiotherapy in locally advanced and locally recurrent colon cancer

Assessment of drug treatment response using primary human colon cancer cell spheroids cultivated in a microfluidic mixer chip

Assessment of drug treatment response using primary human colon cancer cell spheroids cultivated in a microfluidic mixer chip

Conjugation of Doxorubicin and Carbon-based-nanostructures for Drug Delivery against HT-29 Colon Cancer Cells.

A drug delivery system is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. Such systems release the drugs at specific amounts in a specific site. The carbon based-nanomaterials have been actively used as drug carriers to treat various cancer. This study aimed to evaluate the cytotoxic effects of DOX-GO, DOX-OMC and DOXCNT in colon cancer cells (HT29). We reported platforms based on graphene oxide (GO), ordered mesoporous carbon (OMC) and carbon nanotubes (CNT) to conjugate with doxorubicin (DOX). The conjugation of DOX with carbon nanomaterial was investigated by UV-Vis spectroscopy, field emission scanning electron microscope (FE-SEM) and cyclic voltammetry (CV) methods. We showed that graphene oxide was a highly efficient matrix. Efficient loading of DOX, 89%, 78%, and 73.5% at pH 7.0 was seen onto GO, OMC and CNT, respectively. Upon pH 4. 0 after 15 h, 69%, 61% and 61% of DOX could be released from the DOX-GO, DOX-OMC and DOX-CNT, respectively, which illustrated the significant benefits of the developed approach for carbon nanomaterial applications. In vitro cytotoxicity analysis showed greater cytotoxicity of DOX/GO, DOX/OMC and DOX/CNT in comparison with GO, OMC and CNT against HT29 colon cancer cells with cell viability of 22%, 40% and 44% after 48 h for DOX-GO, DOX-OMC and DOX-CNT, respectively. The nanohybrids based on DOX-carbon nanomaterial, because of their unique physical and chemical properties, will remarkably enhance the anti-cancer activity.

Cordycepin enhances the Anticancer efficacy of PD-L1 blockade by modulating the tumor microenvironment of colon cancer

BackgroundPD-L1 blockade has been found to be effective in treating multiple malignancies. Combined therapy is proposed to provide better therapeutic effects. Cordycepin, a prominent bioactive compound found in cordyceps, can inhibit the development of various cancers. PurposeThis study aimed to determine the efficacy of combined anti-PD-L1 antibody and cordycepin in tumor treatment. MethodsA single-cell RNA sequencing was used to analyze the mechanism of combined treatment. ResultsCombination therapy of anti-PD-L1 and cordycepin significantly inhibited tumor growth by regulating the T cell ratio and improving the function of CD8+T cells. Furthermore, cordycepin promoted the reprogramming of type-II macrophages into type-I macrophages, a process confirmed through flow cytometry analysis of the underlying mechanism. ConclusionOur findings demonstrate that the combination of anti-PD-L1 and cordycepin effectively suppressed tumor growth by regulating the proportion of T cells and reprograming type-II macrophages.

Activation of autophagy, paraptosis, and ferroptosis by micheliolide through modulation of the MAPK signaling pathway in pancreatic and colon tumor cells

Micheliolide (MCL), a naturally occurring sesquiterpene lactone, has demonstrated significant anticancer properties through the induction of various programmed cell death mechanisms. This study aimed to explore MCL's effects on autophagy, paraptosis, and ferroptosis in pancreatic and colon cancer cells, along with its modulation of the MAPK signaling pathway. MCL was found to substantially suppress cell viability in these cancer cells, particularly in MIA PaCa-2 and HT-29 cell lines. The study identified that MCL induced autophagy by enhancing the levels of autophagy markers such as Atg7, p-Beclin-1, and Beclin-1, which was attenuated by the autophagy inhibitor 3-MA. Furthermore, MCL was found to facilitate paraptosis, indicated by decreased Alix and in-creased ATF4 and CHOP levels. It also promoted ferroptosis, as demonstrated by the reduced expression of SLC7A11, elevated TFRC levels, and increased intracellular iron. Additionally, MCL activated the MAPK signaling pathway, marked by the phosphorylation of JNK, p38, and ERK, linked with an increase in ROS production that is vital in regulating these cell death mechanisms. These findings propose that MCL is a versatile anticancer agent, capable of activating various cell death pathways by modulating MAPK signaling and ROS levels. These results emphasize the therapeutic promise of MCL in treating cancer, pointing to the necessity of further in vivo investigations to confirm these effects and determine its potential clinical uses.

Affordable Care Act May Increase Access to Colon Cancer Care

Affordable Care Act May Increase Access to Colon Cancer Care

Effect of Acacia concinna Extract on Apoptosis Induction Associated with Endoplasmic Reticulum Stress and Modulated Intracellular Signaling Pathway in Human Colon HCT116 Cancer Cells.

Colorectal cancer (CRC) stands as one of the most prevalent cancer types and among the most frequent causes of cancer-related death globally. Acacia concinna (AC) is a medicinal and edible plant that exhibits a multitude of biological properties, including anticancer properties. This study aimed to investigate the impact of the AC extract on apoptosis induction and the underlying mechanisms associated with this effect in KRAS-mutated human colon HCT116 cells. The effect of AC extract on cell cytotoxicity was evaluated using MTT assay. Nuclear morphological changes were visualized with Hoechst 33342 staining, while mitochondrial membrane potential (MMP) was assessed via JC-1 staining. Flow cytometry was employed for cell cycle analysis, and intracellular ROS levels were determined using DCFH-DA staining. The results showed that HCT116 cells exposed to AC extract showed reduced cell growth and prompted apoptosis, as indicated by an increase in chromatin condensation, apoptotic bodies, the sub-G1 apoptotic cell population, and disrupted MMP. Expression levels of apoptosis mediator proteins determined by Western blot analysis showed an increase in pro-apoptotic proteins (Bak and Bax) while decreasing anti-apoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1), leading to caspase-7 activation and PARP inactivation. AC extract was also found to enhance intracellular reactive oxygen species (ROS) levels and stimulate endoplasmic reticulum (ER) stress. Furthermore, AC extract increases the phosphorylation of ERK1/2, p38, and c-Jun while downregulating PI3K, Akt, β-catenin, and their downstream target proteins. These results demonstrate that AC extract could inhibit cancer cell growth via ROS-induced ER stress associated with apoptosis and regulate the MAPK, PI3K/Akt, and Wnt/β-catenin signaling pathways in HCT116 cells. Therefore, AC extract may be a novel candidate for natural anticancer resources for colon cancer treatment.

Quercetin inhibits malignant progression of high metastatic advanced colon cancer in hypoxia via suppressing ROS and PI3K/AKT pathway

Quercetin inhibits malignant progression of high metastatic advanced colon cancer in hypoxia via suppressing ROS and PI3K/AKT pathway