In Silico Design of CT26 Polytope and its Surface Display by ClearColi™-Derived Outer Membrane Vesicles as a Cancer Vaccine Candidate Against Colon Carcinoma.

Simultaneous targeting of several mutations can be useful in colorectal cancer (CRC) due to its heterogeneity and presence of somatic mutations. As CT26 mutations and expression profiles resemble those of human CRC, we focused on designing a polyepitope vaccine based on CT26 neoepitopes. Due to its low immunogenicity, outer membrane vesicles (rOMV) as an antigen delivery system and adjuvant was applied. Herein, based on previous experimental and our in silico studies four CT26 neoepitopes with the ability to bind MHC-I and MHC-II, TCR, and induce IFN-α production were selected. To increase their immunogenicity, the gp70 and PADRE epitopes were added. The order of the neoepitopes was determined through 3D structure analysis using ProSA, Verify 3D, ERRAT, and Ramachandran servers. The stable peptide-protein docking between the selected epitopes and MHC alleles strengthen our prediction. The CT26 polytope vaccine sequence was fused to the C-terminal of cytolysin A (ClyA) anchor protein and rOMVs were isolated from endotoxin-free ClearColi™ strain. The results of the C-ImmSim server showed that the ClyA-CT26 polytope vaccine could induce T and B cells immunity.The ClyA-CT26 polytope was characterized as a soluble, stable, immunogen, and non-allergen vaccine and optimized for expression in ClearColi™ 24 h after induction with 1 mM IPTG at 25 °C. Western blot analysis confirmed the expression of ClyA-CT26 polytope by ClearColi™ and also on ClearColi™-derived rOMVs. In conclusion, we found that ClearColi™-derived rOMVs with CT26 polytope can deliver CRC neoantigens and induce antitumor immunity, but in vivo immunological studies are needed to confirm vaccine efficacy.

Codelivery of methotrexate and silibinin by niosome nanoparticles for enhanced chemotherapy of CT26 colon cancer cells.

Colon cancer (CC) is one of the most prevalent cancers in the world, and chemotherapy is widely applied to combat it. However, chemotherapy drugs have severe side effects and emergence of multi drug resistance (MDR) is common. This bottleneck can be overcome by niosome nanocarriers that minimize drug dose/toxicity meanwhile allow co-loading of incompatible drugs for combination therapy. In this research, silibinin (Sil) as a hydrophobic drug was loaded into the lipophilic part, and methotrexate (MTX) into the hydrophilic part of niosome by the thin film hydration (TFH) method to form Nio@MS NPs for CT26 colon cancer therapyin vitro. Our results indicated synthesis of ideal niosome nanoparticles (NPs) with spherical morphology, size of ∼100 nm, and a zeta potential of -10 mV. The IC50value for Nio@MS was determined ∼2.6 µg ml-1, which was significantly lower than MTX-Sil (∼6.86 µg ml-1), Sil (18.46 µg ml-1), and MTX (9.8 µg ml-1). Further, Nio@MS significantly reduced cell adhesion density, promoted apoptosis and increased gene expression level of caspase 3 and BAX while promoted significant downregulation of BCL2. In conclusion, the design and application of niosome to co-administer Sil and MTX can increase the drugs cytotoxicity, reduce their dose and improve anti-cancer potential by combating MDR.

Ascending colon cancer metastasized to the right testicle: a case report.

BACKGROUND: Testicular metastasis from malignant solid tumors is extremely rare. It is usually found by chance during autopsy or pathological examination of testicular specimens. Therefore, we consider it necessary to report our patient's case of testicular metastasis from colon cancer. CASE PRESENTATION: We report a 61-year-old Han Chinese male patient who presented to our clinic with progressive painless swelling of the right testicle for 2 years. Positron emission tomography-computed tomography scans showed increased 18F-fluorodeoxyglucose metabolism in the right testicle, possibly owing to distant metastasis. His previous medical history suggested that he had undergone laparoscopic-assisted right hemicolectomy for ascending colon cancer 4 years ago. Considering the ascending colon cancer metastasis to the right testicle, we performed a right radical testicular resection through an inguinal approach. Postoperative histological examination showed intestinal metastatic adenocarcinoma. CONCLUSION: Colon cancer metastasis to the testes is uncommon. The clinical and imaging manifestations of this tumor are nonspecific, so the diagnosis relies on postoperative pathology. If testicular metastasis is found, treatment principles for advanced colon cancer should be followed.

Reducing the effective dose of cisplatin using cobalt modified silver nano-hybrid as a carriers on MCF7 and HCT cell models.

Cancer is a deadly illness with a convoluted pathogenesis. The most prevalent restrictions that frequently result in treatment failure for cancer chemotherapy include lack of selectivity, cytotoxicity, and multidrug resistance. Thus, considerable efforts have been focused in recent years on the establishment of a modernistic sector termed nano-oncology, which offers the option of employing nanoparticles (NPs) with the objective of detecting, targeting, and treating malignant disorders. NPs offer a focused approach compared to conventional anticancer methods, preventing negative side effects. In the present work, a successful synthetic process was used to create magnetic cobalt cores with an AgNPs shell to form bimetallic nanocomposites CoAg, then functionalized with Cis forming novel CoAg@Cis nanohybrid. The morphology and optical properties were determined by TEM, DLS, FTIRs and UV-vis spectroscopy, furthermore, anticancer effect of CoAg and CoAg@Cis nanohybrids were estimated using MTT assay on MCF7 and HCT cell lines. Our results showed that Co@Ag core shell is about 15 nm were formed with dark CoNPs core and AgNPs shell with less darkness than the core, moreover, CoAg@Cis has diameter about 25 nm which are bigger in size than Co@Ag core shell demonstrating the loading of Cis. It was observed that Cis, CoAg and CoAg@Cis induced a decline in cell survival and peaked at around 65%, 73%and 66% on MCF7 and 80%, 76%and 78% on HCT at 100 µg/ml respectively. Compared to Cis alone, CoAg and CoAg@Cis caused a significant decrease in cell viability. These findings suggest that the synthesized CoAg can be used as a powerful anticancer drug carrier.

IL-6 promotes tumor growth through immune evasion but is dispensable for cachexia.

Various cytokines have been implicated in cancer cachexia. One such cytokine is IL-6, deemed as a key cachectic factor in mice inoculated with colon carcinoma 26 (C26) cells, a widely used cancer cachexia model. Here we tested the causal role of IL-6 in cancer cachexia by knocking out the IL-6 gene in C26 cells. We found that the growth of IL-6 KO tumors was dramatically delayed. More strikingly, while IL-6 KO tumors eventually reached the similar size as wild-type tumors, cachexia still took place, despite no elevation in circulating IL-6. In addition, the knockout of leukemia inhibitory factor (LIF), another IL-6 family cytokine proposed as a cachectic factor in the model, also affected tumor growth but not cachexia. We further showed an increase in the infiltration of immune cell population in the IL-6 KO tumors compared with wild-type controls and the defective IL-6 KO tumor growth was rescued in immunodeficient mice while cachexia was not. Thus, IL-6 promotes tumor growth by facilitating immune evasion but is dispensable for cachexia.

Investigating the effectiveness of iron nanoparticles synthesized by green synthesis method in chemoradiotherapy of colon cancer.

Current methods of colon cancer treatment, especially chemotherapy, require new treatment methods due to adverse side effects. One important area of interest in recent years is the use of nanoparticles as drug delivery vehicles since several studies have revealed that they can improve the target specificity of the treatment thus lowering the dosage of the drugs while preserving the effectiveness of the treatment thus reducing the side effects. The use of traditional medicine has also been a favorite topic of interest in recent years in medical research, especially cancer research. In this research work, the green synthesis of Fe nanoparticles was carried out using Mentha spicata extract and the synthesized nanoparticles were identified using FT-IR, XRD, FE-SEM and EDS techniques. Then the effect of Mentha spicata, Fe nanoparticles, and Mentha spicata -loaded Fe nanoparticles on LS174t colon cancer cells, and our result concluded that all three, especially Mentha spicata -loaded Fe nanoparticles, have great cytotoxic effects against LS174t cells, and exposure to radiotherapy just further intensified these results. The in vitro condition revealed alterations in the expression of pro-apoptotic BAX and anti-apoptotic Bcl2, suggesting a pro-apoptotic effect from all three components, particularly the Mentha spicata-loaded Fe nanoparticles. After further clinical trials, these nanoparticles can be used to treat colon cancer.

[Retracted] Tunicamycin inhibits colon carcinoma growth and aggressiveness via modulation of the ERK­JNK­mediated AKT/mTOR signaling pathway.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell invasion and migration assay data shown in Fig. 1B and C were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes, which had either already been published or were under consideration for publication at around the same time. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 4203­4212, 2018; DOI: 10.3892/mmr.2018.8444].

Three cancers in the renal pelvis, bladder, and colon: A case report.

BACKGROUND: Multiple primary cancers are rare occurrences that can involve either metachronous or synchronous development. It is particularly rare for an individual to have more than two primary cancers. In this report, we present a case study of an elderly man who was diagnosed with three heterochronous cancers in the renal pelvis, bladder, and colon. CASE SUMMARY: On December 30, 2014, a 51-year-old Chinese man was admitted to our hospital with complaints of intermittent painless gross hematuria for the preceding week. A computed tomography (CT) scan revealed wall thickening in the left ureter's upper segment, while a CT urography revealed a left renal pelvis tumor. A successful laparoscopic radical resection of the left renal pelvis tumor was subsequently performed at Shanghai Zhongshan Hospital in January 2015. The pathological findings after the surgery revealed a low-grade papillary urothelial carcinoma of the renal pelvis. The final pathological tumor stage was pT1N0M0. After surgery, this patient received 6 cycles of intravenous chemotherapy with gemcitabine and carboplatin, as well as bladder infusion therapy with gemcitabine. On December 18, 2017, the patient was admitted once again to our hospital with a one-day history of painless gross hematuria. A CT scan showed the presence of a space-occupying lesion on the posterior wall of bladder. Cystoscopic examination revealed multiple tumors in the bladder and right cutaneous ureterostomy was performed under general anesthesia on December 29, 2017. The postoperative pathological findings disclosed multifocal papillary urothelial carcinoma of the bladder (maximum size 3.7 cm × 2.6 cm). The bladder cancer was considered a metastasis of the renal pelvis cancer after surgery. The pathological tumor stage was pT1N0M1. The patient refused chemotherapy after surgery. After another six years, the patient returned on February 28, 2023, complaining of periumbilical pain that had lasted six days. This time, a CT scan of the abdomen showed a tumor in the ascending colon, but a subsequent colonoscopy examination indicated a tumor in the descending colon. On March 12, 2023, a subtotal colectomy and an ileosigmoidal anastomosis were carried out under general anesthesia. Postoperative pathological findings revealed that all three tumors were adenocarcinomas. The final pathological tumor stage was pT3N0M0. The patient had an uneventful postoperative recovery and was discharged without complications. CONCLUSION: The case of this elderly man presents a rare occurrence of metachronous primary cancers in the renal pelvis and colon. Bladder cancer is considered a metastasis of renal pelvis cancer after surgery. Optimal treatment can be implemented by evaluating the patient's histological features, clinical history, and tumor distribution correctly.

Tumefactive Crohn's Disease Mimicking Colon Carcinoma in a Young Female: A Case Report.

Tumefactive Crohn's disease is a rare form of Crohn's disease that may mimic colon carcinoma macroscopically. This case report describes a 28-year-old female who presented with right-sided abdominal pain and a palpable abdominal mass that had persisted for over a month. Multiple hospitalizations failed to provide an accurate diagnosis until an exploratory laparotomy revealed that the "mass" was the cecum and a perforated ascending colon. A partial right colectomy was performed, sending the specimen for biopsy. The microscopic description showed dense and confluent chronic inflammation in the colonic mucosa and wall, extending to the serosa in some regions. The infiltration comprised lymphocytes and plasma cells, with an admixture of some neutrophils. Aphthous mucosal ulcerations, intramural fissures, and fistulas were present. Immunostains for pan-keratin demonstrated no intramural epithelial elements. The characteristics of this lesion represent tumefactive Crohn's disease. This case highlights the key microscopic characteristics that pathologists look for when differentiating Crohn's disease from colon carcinoma in a patient presenting with abdominal pain and a colon mass.

Primary Papillary Colonic Adenocarcinoma With PDGFRA Mutation. A New Morphological Subtype? A Case Report and Review of Literature.

Classic colon carcinomas are defined as adenocarcinomas, characterized by groups of medium/large cells with basophilic and polymorphous nuclei and an eosinophilic elongated cytoplasm, that rearrange on glandular structures. Signs of poor prognosis include high tumor budding, lymphovascular and perineural invasion, poor differentiation, positive margins, and CDX2 loss. Less frequent colon carcinoma subtypes are: mucinous, medullary, signet-ring cell, squamous cell, small cell and undifferentiated carcinoma, among others. In the following case report, we present a 65-year-old woman with a T2N0Mx colon carcinoma with a remarkable papillary and follicular histological appearance. The immunohistochemical stains confirmed an intestinal origin (CDX2+) and excluded a thyroid, gynecological, and urological metastasis, with tumor cells negative for GATA3, PAX8, TTF-1, and thyroglobulin. There was no loss of mismatch repair proteins and p53 showed a wild-type staining. next generation sequencing showed a platelet-derivated growth factor receptor alpha (PDGFRA) mutation. To the best of our knowledge, there have been only two examples of primary papillary colon carcinoma reported in the literature, and neither of them with a PDGFRA mutation. We describe one tumor and discuss its pathological features.

SMARCB1/INI1-Deficient Poorly Differentiated Carcinoma of the Colon With Rhabdoid Features-A Rare Tumor With Serrated Phenotype: Case Report and Review of Literature.

Poorly differentiated colonic carcinoma with rhabdoid features is a rarely described entity. Our knowledge regarding the molecular phenotype of the tumor is evolving. We herein report a similar tumor with rhabdoid differentiation identified in the splenic flexure, which on histological examination showed a poorly differentiated phenotype with epithelioid to spindled morphology, tumor giant cells, and rhabdoid differentiation. The tumor was mismatch repair-proficient, deficient of INI1/SMARCB1, KRAS mutated (A146×), BRAFV600E mutated (c.1799T > A), and NRAS wild-type, indicating serrated differentiation in the tumor. The patient died after 3.5 months post-surgery. INI1-deficient poorly differentiated carcinoma of the colon is a rare, aggressive colonic malignancy showing a serrated phenotype. Routine identification and subtyping are important keeping in mind the distinct tumor phenotype, resistance to conventional chemotherapy, and dismal prognosis.

[Retracted] Rotenone restrains colon cancer cell viability, motility and epithelial­mesenchymal transition and tumorigenesis in nude mice via the PI3K/AKT pathway.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the immunofluorescence staining data shown in Fig. 3C, and the migration and invasion assay data shown in Figs. 4C and 4D were strikingly similar to data appearing in different form in other research articles written by different authors at different research institutes that had either already been published, or were submitted for publication at around the same time, one of which has been retracted. In addition, the western blotting data shown for the E­cadherin and AKT protein bands in Fig. 5 were strikingly similar, albeit the bands had been flipped vertically. Owing to the fact that contentious data in the above article had already been submitted for publication elsewhere prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 44: 700­708, 2020; DOI: 10.3892/ijmm.2020.4637].

Anti-Proliferative Potential of Cynaroside and Orientin-In Silico (DYRK2) and In Vitro (U87 and Caco-2) Studies.

Luteolin derivates are plant compounds with multiple benefits for human health. Stability to heat and acid hydrolysis and high resistance to (auto)oxidation are other arguments for the laden interest in luteolin derivates today. The present study was designed to compare the in silico and in vitro anti-proliferative potential of two luteolin derivates, luteolin-7-O-glucoside/cynaroside (7-Lut) and luteolin-8-C-glucoside/orientin (8-Lut). In silico investigations were carried out on the molecular target, namely, the human dual specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) in association with its natural ligand, curcumin (PDB ID: 5ZTN), by CLC Drug Discovery Workbench v. 1.5.1. software and Molegro Virtual Docker (MVD) v. MVD 2019.7.0. software. In vitro studies were performed on two human tumor cell lines, glioblastoma (U87) and colon carcinoma (Caco-2), respectively. Altogether, docking studies have revealed 7-Lut and 8-Lut as effective inhibitors of DYRK2, even stronger than the native ligand curcumin; in vitro studies indicated the ability of both luteolin glucosides to inhibit the viability of both human tumor cell lines, up to 85% at 50 and 100 µg/mL, respectively; the most augmented cytotoxic and anti-proliferative effects were obtained for U87 exposed to 7-Lut (IC50 = 26.34 µg/mL). The results support further studies on cynaroside and orientin to create drug formulas targeting glioblastoma and colon carcinoma in humans.

Enhancement of Radiation Sensitivity by Cathepsin L Suppression in Colon Carcinoma Cells.

Cancer is one of the main causes of death globally. Radiotherapy/Radiation therapy (RT) is one of the most common and effective cancer treatments. RT utilizes high-energy radiation to damage the DNA of cancer cells, leading to their death or impairing their proliferation. However, radiation resistance remains a significant challenge in cancer treatment, limiting its efficacy. Emerging evidence suggests that cathepsin L (cath L) contributes to radiation resistance through multiple mechanisms. In this study, we investigated the role of cath L, a member of the cysteine cathepsins (caths) in radiation sensitivity, and the potential reduction in radiation resistance by using the specific cath L inhibitor (Z-FY(tBu)DMK) or by knocking out cath L with CRISPR/Cas9 in colon carcinoma cells (caco-2). Cells were treated with different doses of radiation (2, 4, 6, 8, and 10), dose rate 3 Gy/min. In addition, the study conducted protein expression analysis by western blot and immunofluorescence assay, cytotoxicity MTT, and apoptosis assays. The results demonstrated that cath L was upregulated in response to radiation treatment, compared to non-irradiated cells. In addition, inhibiting or knocking out cath L led to increased radiosensitivity in contrast to the negative control group. This may indicate a reduced ability of cancer cells to recover from radiation-induced DNA damage, resulting in enhanced cell death. These findings highlight the possibility of targeting cath L as a therapeutic strategy to enhance the effectiveness of RT. Further studies are needed to elucidate the underlying molecular mechanisms and to assess the translational implications of cath L knockout in clinical settings. Ultimately, these findings may contribute to the development of novel treatment approaches for improving outcomes of RT in cancer patients.

Transcription Factor FOSL1 Promotes Angiogenesis of Colon Carcinoma by Regulating the VEGF Pathway Through Activating TIMP1.

Angiogenesis is the critical media for tumor growth and migration. Tissue Inhibitor Matrix Metalloproteinase-1 (TIMP1) acts as an oncogene in colon carcinoma (CC), but the biological effects of TIMP1 on angiogenesis remain an open issue. This study sought to explore the exact function and mechanism of TIMP1 in the angiogenesis of CC. Bioinformatics methods were utilized to analyze the expression of TIMP1 and its upstream transcription factor FOS-like antigen 1 (FOSL1) in the tumor tissue of CC. Meanwhile, in CC cell lines, real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot were utilized to verify the expression of TIMP1 and FOSL1. Cell counting kit-8 and tube formation assays were utilized to analyze the proliferation and angiogenesis abilities of human umbilical vein endothelial cells (HUVECs). Western blot was used to detect the protein expression of VEGFA, VEGFR-2, and VEGFR-3. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were carried out to explore the specific interaction between FOSL1 and TIMP1. The present study discovered that TIMP1 and FOSL1 were evidently up-regulated in CC tissue and cells. Meanwhile, TIMP1 was found to participate in regulating the signaling pathway of vascular endothelial growth factor (VEGF). Silenced TIMP1 conspicuously suppressed the proliferation and angiogenesis of HUVECs and reduced the protein expression of VEGFA, VEGFR-2, and VEGFR-3. Moreover, FOSL1 could promote TIMP1 transcription by binding with its promoter and the inhibition of TIMP1 expression obviously reversed the promotion effects of FOSL1 overexpression on the proliferation and angiogenesis of HUVECs. FOSL1 activated VEGF pathway by up-regulating TIMP1 expression, thereby advancing CC angiogenesis. We provided theoretical basis that the FOSL1/TIMP1/VEGF pathway might be a novel option for anti-angiogenesis therapy of CC.

The modulation of local and systemic anti-tumor immune response induced by methotrexate nanoconjugate in murine MC38 colon carcinoma and B16 F0 melanoma tumor models.

Methotrexate (MTX) which is one of the longest-used cytostatics, belongs to the group of antimetabolites and is used for treatment in different types of cancer as well as during autoimmune diseases. MTX can act as a modulator enable to create the optimal environment to generate the specific anti-tumor immune response. A novel system for MTX delivery is its conjugation with high-molecular-weight carriers such as hydroxyethyl starch (HES), a modified amylopectin-based polymer applied in medicine as a colloidal plasma volume expander. Such modification prolongs the plasma half-life of the HES-MTX nanoconjugate and improves the distribution of the drug in the body. In the current study, we focused on evaluating the dose-dependent therapeutic efficacy of chemotherapy with HES-MTX nanoconjugate compared to the free form of MTX, and examining the time-dependent changes in the local and systemic anti-tumor immune response induced by this therapy. To confirm the higher effectiveness of HES-MTX in comparison to MTX, we analyzed its action using murine MC38 colon carcinoma and B16 F0 melanoma tumor models. It was noted that HES-MTX at a dose of 20 mg/kg b.w. was more effective in tumor growth inhibition than MTX in both tumor models. One of the main differences between the two analyzed tumor models concerned the kinetics of the appearance of the immunomodulation. In MC38 tumors, the beneficial change in the tumor microenvironment (TME) landscape, manifested by the depletion of pro-tumor immune cells, and increased influx of cells with strong anti-tumor activity was noted already 3 days after HES-MTX administration, while in B16 F0 model, these changes occurred 10 days after the start of therapy. Thus, the immunomodulatory potential of the HES-MTX nanoconjugate may be closely related to the specific immune cell composition of the TME, which combined with additional treatment such as immunotherapies, would enhance the therapeutic potential of the nanoconjugate.

Colocutaneous fistula due to an infected sigmoid adenocarcinoma: A case report of an unusual revelation.

INTRODUCTION AND IMPORTANCE: As revealed as a colocutaneous fistula with an abscess in the abdominal wall, colon cancer is rare. It should be suspected in case of a painful abdominal wall mass in elderly patients. This case presentation of an infected sigmoid adenocarcinoma aims to highlight this uncommon presentation presenting some therapeutic issues. CASE PRESENTATION: A 90-year-old woman with a past medical history of hypertension and major depressive disorder consulted the Emergency Department for lower left quadrant abdominal pain. The physical examination objectified a mild fever; lower left abdominal quadrant guarding, and abdominal mass of 10 cm with inflammatory signs. The abdominal CT scan showed a concentric thickness of the sigmoid colon with an abdominal wall abscess. She underwent an emergent laparotomy. Intraoperatively, we found an infected sigmoid tumour that invades the abdominal wall and is associated with a peritumoral abscess. This tumour was at the origin of the abdominal wall fistula. She underwent surgical drainage of the abscess, sigmoid colectomy, and colostomy. The postoperative follow-up was uneventful. The pathological examination of the operative specimen concluded with a colonic adenocarcinoma with lymph node invasion classified as pT4N2M0. CASE DISCUSSION: Despite initial medical and radiological interventions, emergent surgery became necessary to address the infected sigmoid tumour invading the abdominal wall. Pathological examination revealed advanced cancer, but timely intervention and adjuvant therapy resulted in a positive outcome with no recurrence after two years. This case emphasizes the importance of recognizing unusual colon cancer presentations and the need for swift diagnosis and intervention. CONCLUSIONS: The diagnosis of colon cancer complicated with a colocutaneous fistula remains based on pathological examination after surgical management. These tumours presented an advanced stage and correlated to a poor prognosis. This highlights the interest in screening colonoscopy in front of any digestive symptoms in elderly patients.

Proteomics analysis of C2C12 myotubes treated with atrophy inducing cancer cell-derived factors.

Cancer-associated cachexia is a wasting syndrome that results in dramatic loss of whole-body weight, predominantly due to loss of skeletal muscle mass. It has been established that cachexia inducing cancer cells secrete proteins and extracellular vesicles (EVs) that can induce muscle atrophy. Though several studies examined these cancer-cell derived factors, targeting some of these components have shown little or no clinical benefit. To develop new therapies, understanding of the dysregulated proteins and signaling pathways that regulate catabolic gene expression during muscle wasting is essential. Here, we sought to examine the effect of conditioned media (CM) that contain secreted factors and EVs from cachexia inducing C26 colon cancer cells on C2C12 myotubes using mass spectrometry-based label-free quantitative proteomics. We identified significant changes in the protein profile of C2C12 cells upon exposure to C26-derived CM. Functional enrichment analysis revealed enrichment of proteins associated with inflammation, mitochondrial dysfunction, muscle catabolism, ROS production, and ER stress in CM treated myotubes. Furthermore, strong downregulation in muscle structural integrity and development and/or regenerative pathways were observed. Together, these enriched proteins in atrophied muscle could be utilized as potential muscle wasting markers and the dysregulated biological processes could be employed for therapeutic benefit in cancer-induced muscle wasting.