scholarly journals Sulphur metabolism in colon cancer tissues: a case report and literature review

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110599
Author(s):  
Hironori Fukuoka ◽  
Tomohiro Andou ◽  
Takeo Moriya ◽  
Koji Narita ◽  
Ken Kasahara ◽  
...  

Sulphur-containing compounds have been linked to colorectal cancer by factors such as the presence of methyl mercaptan in intestinal gas and long-term dietary intake associated with sulphur-metabolizing microbiota. Therefore, this current case report hypothesized that active sulphur metabolism in colorectal cancer results in the formation of sulphur compounds in the intestine and, thus, examined sulphur metabolites possibly associated with sulphur respiration in colon cancer tissues. The patient was a 73-year-old female that underwent laparoscopic right hemicolectomy for ascending colon cancer. During the surgery, colon cancer tissues and normal intestinal mucosa samples were collected. After optimizing the sample concentrations for homogenization (pre-treatment), the samples were stabilized using a hydroxyphenyl-containing derivative and the relevant metabolites were quantified using liquid chromatography with tandem mass spectrometry. The results showed that cysteine persulfide and cysteine trisulfide levels were higher in colon cancer tissues than in normal mucosal tissues. Thus, sulphur metabolism, possibly sulphur respiration, is enhanced in colon cancer tissues.

2020 ◽  
pp. 107815522093416
Author(s):  
Jasmine Giani ◽  
Michael B Sawyer ◽  
Carole Chambers

Colorectal cancer is one of the most common malignancies diagnosed in Canada. Currently, adjuvant colorectal cancer treatment primarily includes chemotherapeutic regimens such as FOLFOX6 (5-fluorouracil, leucovorin, oxaliplatin) or CAPOX (capecitabine, oxaliplatin), as well as alternative regimens such as TOMOX (raltitrexed, oxaliplatin). However, the prevalence of drug shortages in today’s society may make these preferred regimens inaccessible. The purpose of this case report is to highlight the tolerability of an alternative adjuvant regimen (pemetrexed plus oxaliplatin) that has undergone both phase I and II clinical trials for the treatment of colorectal cancer. The patient presented in this case report is a 57-year-old female diagnosed with Stage III colon cancer. This patient received seven cycles of pemetrexed plus oxaliplatin and experienced several adverse events, with the majority of them being mild in nature including fatigue and cold dysesthesia. However, the patient also experienced progressive neuropathy which required a dose reduction and subsequent discontinuation of oxaliplatin. Overall, pemetrexed and oxaliplatin’s tolerability seems comparable to other regimens used to treat colorectal cancer and could potentially be an option to consider in the future for alternative treatment of colorectal cancer pending further trials.


2020 ◽  
Author(s):  
Fuda Huang ◽  
Mingwei Wei ◽  
Anmin Wang ◽  
Ya Zhang ◽  
Zebang Qin ◽  
...  

Abstract BackgroundCalponin was first defined as a striated muscle troponin T-like protein that binds actin thin filaments to regulate smooth muscle contraction. There are few studies of CNN1 and CNN2 in colorectal cancer, and the roles these two genes play in colorectal cancer cell lines and the mechanisms by which they act are unknown.MethodsWe used immunohistochemistry to identify expression of the two genes in the cancer tissues. RT-PCR was used to measure expression levels of microRNA. W performed western blots to measure changes in signaling pathways in the context of expression interference.Meanwhile, the same method was used to measure binding relationship between the two genes and key pathway proteins. To determine the relationship between microRNA and gene mRNA, we used the reporter gene method. We used the chi-square and t-test methods to analyze the significance and correlations of the data.Results and conclusionsExpression levels of CNN1 were lower in colon cancer tissues than in normal mucosal tissues. After downregulating CNN1, the cell cycle in colon cancer cell lines progressed quickly, and the expression of related pathway proteins also increased. Expression levels of CNN2 were higher in colon cancer tissues, and its downregulation significantly inhibited cell cycle progression in colon cancer cell lines. We confirmed correlations between the expression of microRNA and CNN2 using data analysis.Bars indicate ± standard errors.*p < 0.05; **p < 0.01 compared with the control. The inhibition of the expression of CNN2 mRNA using microRNA was confirmed using western blot. The combination of the two at the mechanism level was also demonstrated using the reporter gene method.


Author(s):  
Yang zhi Jiang ◽  
Qing Guo Tao ◽  
fei yan Zhu

BACKGROUND AIM To explore the correlation between the expression of miRNA-135a and Bach1 in colorectal cancer tissue and the patient's clinical information.  Methods   60 patients with colorectal carcinoma were treated as a control group. Real-time quantitative PCR assays and immunohistochemistry method were performed to detect the expression of miRNA-135a and Bach1 in 60 colorectal carcinomas and adjacent normal tissues, and the clinical and pathological classifications had also been investigated. The SPSS 19.00 software was used. All data represented mean±SD of three independent experiments. P&lt;0.05 was considered statistically significant. Results  miRNA-135a expression levels increased significantly in the colon cancer tissues compared with the non-tumor control tissues(P&lt;0.01). miRNA-135a expression levels were higher in stage III/IV than in stage I/II colon cancer patients. The expression level of Bach1 in colorectal cancer was significantly lower(P&lt;0.01). Bach1 and miRNA-135a were negatively correlated.  Conclusions:  The levels of miRNA-135a and Bach1 were opposite, the over-expression of miRNA-135a might downregulated the expression of Bach1, which might be involved in the pathogenesis of colorectal cancer.


Author(s):  
Nandini Bhaduri Bhattacharyya ◽  
Anadi Roy Chowdhury ◽  
Susmita Mukhopadhyay ◽  
. Sneha

Introduction: Galectin-3 is a β-galactoside-binding lectin found in a considerable number of normal tissues and malignant neoplasms. It was found to be expressed in few thyroid tumours particularly follicular and papillary tumours. Lectins were found to be released in circulation and increased concentration was noted in colorectal cancers especially in metastatic colonic adenocarcinoma. Different types of galectins are expressed in normal colonic and rectal epithelium. Some types do increases in inflammation and cancers of these areas. It was seen that galectin-3 increases in colorectal tumourigenesis and it bears an important role in cancer progression and metastasis. Galectin-3 seems to have an important role in colorectal cancer. Some studies proved that galectin inhibitors could reduce tumour progression and metastasis and it may be a therapeutic target in metastatic colorectal adenocarcinoma. Aim: To evaluate colon cancer specimens received for biopsy, for galectin-3 expression and its relation with tumour stage, lymphovascular space invasion and tumour differentiation. Materials and Methods: The study was a cross-sectional observational study conducted in the Department of Pathology of RG Kar Medical College and Hospital from November 2018 to November 2019. It was an immunohistochemistry based assay performed to test the expression levels of galectin-3 in cancer tissues of 62 colorectal neoplasms with the help of galectin-3 primary antibody (mouse monoclonal antibody- clone 9C4). Statistical analysis was done using Statistical Package of Social Sciences (SPSS) version 19.0. Results: Out of 62 cases, 60 cases were colorectal adenocarcinoma and 2 cases were adenoma with age group between 40-75 years. Total 46 cases had cancer in caecum and ascending colon and rest were in recto-sigmoid colon. A 36/60 cases (60%) of cancer tissues were positive for galectin-3 expression. Strong association of lymphovascular space invasion (p=0.046) and depth of tumour (p=0.0078) with galectin positivity in colon carcinoma was noted. Conclusion: Evaluation of galectin-3 expression is helpful in the assessment of tumour staging and prognosis in colorectal cancer patients. It may have a therapeutic implication in the management of colon cancer in future.


2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Oluwatobi O Onafowokan ◽  
Kiran Khosa ◽  
Hugo Bonatti

Background. Morgagni hernias are rare in adults and may be asymptomatic but, nevertheless, require surgical repair, with laparoscopy offering an excellent option. The colon dislodged into the chest through diaphragmatic hernias may be affected by various disorders, including malignancies. Case Report. A 70-year-old obese male presented with fatigue and shortness of breath. CT scan showed the right colon lodged in the chest through a Morgagni hernia. He was anaemic, and colonoscopy revealed a colon cancer. He underwent combined laparoscopic hernia repair with bioabsorbable mesh and right hemicolectomy. Recovery was uneventful, but the patient died 5 months later from chemotherapy-associated cardiac failure. Literature review revealed eight similar published cases, and including ours, there were seven Morgagni hernias, one traumatic hernia, and one Bochdalek hernia. Median age of the five men and four women was 66 (range 49-85) years. Surgical approach was thoracotomy (2), laparotomy (5), and laparoscopy (2). Conclusion. Outcome of the rare condition is determined by the course of the colon cancer. Hernia repair was successful in ours and all other published cases. A combined laparoscopic approach can be safely done.


2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Taro Fukui ◽  
Koichi Suzuki ◽  
Sawako Tamaki ◽  
Iku Abe ◽  
Yuhei Endo ◽  
...  

Abstract Background Anti-epidermal growth factor receptor (EGFR) antibody is widely used for the treatment of patients with metastatic colorectal cancer. Hypomagnesemia is a comparatively frequent adverse event of this drug, which is likely overlooked because it occurs later in treatment without symptoms. Furthermore, hypomagnesemia and hypomagnesemia-induced corrected QT (QTc) prolongation may lead to loss of consciousness (LOC), the onset of which is not generally considered associated with the treatment of anti-EGFR antibody because of its rare occurrence. Here, we present a colorectal cancer patient treated with anti-EGFR antibody, who suffered LOC during treatment while severe hypomagnesemia or QTc prolongation was not observed. Case presentation A 69-year-old man with metastatic colon cancer was treated with cetuximab (anti-EGFR antibody) plus irinotecan as third-line chemotherapy. His serum magnesium level gradually decreased, and grade 2 hypomagnesemia (a serum magnesium level of 0.9 mg/dL) was observed at the 12th administration of cetuximab. In light of this development, intravenous supplementation of 20 mEq magnesium sulfate began with careful blood monitoring despite the lack of clinical symptoms. Electrocardiogram (ECG) showed prolonged QT or corrected QT (QTc) intervals (grade 1). His serum magnesium level remained at 0.9 mg/dL, and no hypomagnesemia symptoms were observed by the 17th administration of cetuximab. After the treatment, however, he suddenly lost consciousness without symptoms related to infusion or allergic reactions. Circulatory collapse following dermatological reactions and respiratory events were not evident. Intravenous supplementation of magnesium sulfate was administered again. He awakened 2 min after the onset of temporary LOC without any other symptoms related to hypomagnesemia, such as lethargy, tremor, tetany, and seizures. No other etiology outside of the low level of serum magnesium was confirmed in further examinations. Cetuximab was discontinued, and his serum magnesium level returned to a level within the normal range after 6 weeks. Because of tumor progression, regorafenib and TAS-102 (trifluridine tipiracil hydrochloride) were introduced sequentially for 6 months. Five months after the final treatment of TAS-102, he died of his primary disease, which reflected a survival period of 4 years and 6 months since the beginning of treatment. Conclusions This case report reminds clinicians that LOC can be induced without severe hypomagnesemia or QTc prolongation, during anti-EGFR antibody treatment for metastatic colorectal cancer even while under carefully monitored magnesium supplementation.


2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 208s-208s
Author(s):  
S. Lian ◽  
L. Meng ◽  
Y. Yang ◽  
L. Qu ◽  
C. Shou

Background: Phosphatase of regenerating liver (PRL-3) promotes cell invasiveness, but its role in genomic integrity remains unknown. We have reported that PRL-3 recruits to telomeric DNA by RAP1/TRF2 protein. Overexpression of PRL-3 in colon cancer cells and primary fibroblasts promotes structural abnormalities of telomere, telomere deprotection, DNA damage response, chromosomal instability. Aim: To substantiate the previous results and further assess the physiologic relevance of PRL-3 in tumorigenesis, also to explore the prediction role PRL-3 in clinical patients. We detected the expression of PRL-3, telomere length, H3K9me and p-H2AX in the colon cancer and thyroid cancer samples. Methods: We collected 273 colorectal cancer patients and stained with PRL-3 antibody and counterstained with HE. Semiquantitative scoring was performed. Microscopic analysis was done by 2 of the authors. Tissues-chips were obtained from Alenabio (Th802a, thyroid). Results: We retrospectively analyzed a cohort of colorectal cancer tissues (n = 269) stained with anti-PRL-3 (clone 3B6). Although the majority of mitotic cells were bipolar, more multipolar mitoses, an indicator of chromosomal missegregation and chromosomal instability, was observed in PRL-3 positive tissues than in negative tissues (Fig 1A). Also in the PRL-3 positive tissues, more anaphase bridges were detected ( Fig 1A ). These results suggest that PRL-3 levels positively correlate with chromosomal instability in colon cancer tissues. Next, we analyzed 12 freshly dissected colon cancer tissues, with WI38 control and PRL-3-overexpressing cells as reference samples. We detected varying levels of PRL-3 proteins in these tissues, and the level of stably overexpressed PRL-3 in WI38 cells was comparable to some of these tissues. An inverse correlation between PRL-3 and telomere length was revealed, while PRL-3 showed positive correlations with gamma-H2AX and H3K9me3 ( Fig 1B ). We also performed quantitative FISH (qFISH) analysis of telomere length and immunohistochemical staining of PRL-3 with thyroid tissue chips containing 80 samples. We found decreased telomere staining in adenocarcinoma tissues (n = 40) with positive PRL-3 expression, particularly in those of stage I (n = 23) ( Fig 1C ). No correlation was observed in thyroid adenoma (n = 40) or stage II/III/IV adenocarcinoma (n = 17) ( Fig 1C ). With the same thyroid tissue-chip, we evaluated association between PRL-3 and senescence. In stage I thyroid adenocarcinoma tissues, positive staining of PRL-3 correlated with positive H3K9me3 staining, but such correlation was not observed in thyroid adenoma or Stage II/III/IV adenocarcinoma ( Fig 1D ). Conclusion: These results raise the possibility that PRL-3-promoted telomere deprotection and senescence are early events during the development and progression of cancer. Our results uncover a novel role of PRL-3 in tumor development through its adverse impact on telomere homeostasis.[Figure: see text]


2021 ◽  
Vol 11 ◽  
Author(s):  
Zugui Li ◽  
Minying Zheng ◽  
Hao Zhang ◽  
Xiaohui Yang ◽  
Linlin Fan ◽  
...  

Arsenic trioxide (ATO) has been used to treat acute promyelocytic leukemia. However, it is not effective in treating solid tumors such as colorectal cancer. We have previously reported that polyploid giant cancer cells (PGCCs) exhibiting the characteristics of cancer stem cells can be generated by various inducers. In this study, ATO was used to induce the formation of PGCCs in LoVo and Hct116 colon cancer cell lines. The migration, invasion, and proliferation abilities of colon cancer cells with and without ATO treatment were assessed by wound-healing, transwell, and plate colony formation assays. The expression of epithelial to mesenchymal transition-related proteins and erythroid differentiation-related proteins in colon cancer cells was further evaluated by western blot and immunocytochemical assays. LoVo and Hct116 cells were transfected with a eukaryotic expression vector for green fluorescent protein (GFP), red fluorescent protein (RFP), H2B-GFP, and H2B-mCherry to study PGCCs formation via cell fusion. WB and ICC assays were performed to assess the expression of cell fusion-related proteins. MG132, small interfering RNA-glial cell missing 1 (GCM1), and chromatin immunoprecipitation-polymerase chain reaction assays were performed to study the role of GCM1/syncytin-1-mediated cell fusion. Clinically, the significance of cell fusion-related proteins and erythroid differentiation-related proteins expression in human colorectal cancer tissues was evaluated. Results of our study showed that ATO induced the formation of PGCCs, and the daughter cells derived from PGCCs gained a mesenchymal phenotype and exhibited strong migration, invasion, and proliferation abilities. PGCCs also produced embryonic hemoglobin-delta and -zeta with strong oxygen-binding ability and erythroid differentiation-related proteins after ATO treatment. In addition, cell fusion was observed during the formation of PGCCs, indicated by the presence of yellow fluorescence via the GCM1/syncytin-1 signaling pathway. Clinically, the expression of cell fusion-related and erythroid differentiation-related proteins gradually increased with the progression of human colorectal cancer tissues. In conclusion, ATO can promote tumor progression by inducing the formation of PGCCs via GCM1/syncytin-1-mediated cell fusion. PGCCs can produce daughter cells with high invasion and migration abilities and embryonic hemoglobin with strong oxygen binding ability, promoting survival of tumor cells in a hypoxic microenvironment.


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