Malignant Tumors Of Gastrointestinal Tract Research Articles

Immunotherapies catering to the unmet medical need of cold colorectal cancer

As a common malignant tumor of gastrointestinal tract, the incidence of colorectal cancer (CRC) has gradually increased in recent years. In western developed countries, it has even become the second largest malignant tumor next to lung cancer. Immunotherapy is a hot topic in the field of cancer therapy, including immune checkpoint blockade (ICB), adoptive cell therapy (ACT), cancer vaccines and cytokines, aiming to improve the ability of the immune system to recognize, target and eliminate cancer cells. However, cold CRC, which accounts for a high proportion of CRC, is not so reactive to it. The development of immunotherapy to prevent cancer cells from forming “immune escape” pathways to the immune system in cold CRC, has been under increasing study attention. There is proof that an organic combination of radiotherapy, chemotherapy, and several immunotherapies can considerably boost the immune system’s capacity to eradicate tumor cells. In this review, we summarized the role of immunotherapy in colorectal cancer. In addition, we propose a breakthrough and strategy to improve the role of immunotherapy in cold CRC based on its characteristics.

PICALM exerts a role in promoting CRC progression through ERK/MAPK signaling pathway

BackgroundColorectal cancer (CRC) is a common malignant tumor in gastrointestinal tract with high incidence and mortality. In this study, the functions and potential mechanism of phosphatidylinositol-binding clathrin assembly protein (PICALM) in CRC were preliminarily explored.MethodsBased on the Cancer Genome Atlas database and immunohistochemistry staining, revealing that the expression level of PICALM in CRC tissues was higher than that in adjacent normal tissues.ResultsMoreover, loss-of-function and gain-of-function assays in HCT 116 and RKO cells found that PICALM promotes proliferation and migration of CRC cells and inhibits apoptosis. Consistently, knockdown of PICALM inhibited tumorigenicity of CRC cells in vivo. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that knockdown of PICALM resulted in the enrichment of MAPK signaling pathway. Treatment of CRC cells with MAPK inhibitor reversed the effects of PICALM overexpression on proliferation and apoptosis. In addition, overexpression of PICALM upregulated the protein levels of ERK1/2 (p-ERK1/2), MEK1/2 (p-MEK1/2), p38 (p-p38) and JNK (p-JNK), and these effects were partially alleviated by the treatment of MAPK inhibitor.ConclusionsIn summary, the study presented the new discovery that PICALM promoted CRC progression through ERK/MAPK signaling pathway, which drew further interest regarding its clinical application as a promising therapeutic target.

A Review of Emerging Biomarkers for Immune Checkpoint Inhibitors in Tumors of the Gastrointestinal Tract

In recent years, immune checkpoint inhibition (ICI) therapy has made a tremendous improvement in the treatment of malignant tumors of gastrointestinal tract, especially for those with metastatic or recurrent lesions. However, while some patients benefit from ICI, others do not. In fact, predictive biomarkers can play a crucial role in screening patients who may benefit from a selected or targeted treatment, including immunotherapies such as programmed death-1/programmed death-1 ligand 1 (PD-1/PD-L1) inhibitors. A variety of techniques can be used to detect and quantify tumor biomarkers, each of which has a specific clinical application scenario and limitations. Cancer biomarkers in the gastrointestinal system involve an extremely complex network that requires careful interpretation and analysis. Different prognostic or predictive biomarkers are playing important roles in various tumor types, stages, and pathology/molecular subgroups, sometimes overlapping. Expression levels of biomarkers vary between different tumor types and even between the different lesions in the same tumor, depending on the heterogeneity of the patient, the tumor types, and the techniques of detection. The present systematic review comprehensively summarizes the potential biomarkers of immunotherapy, such as PD-1/PD-L1, total mutation burden (TMB), and tumor-infiltrating lymphocytes (TILs) in various gastrointestinal tumors, including tumors of the colon, stomach, esophagus, liver, and pancreas, to assist future application of immunotherapy and patient selection in clinical practice.

LINC00882 Plays a Tumor-promoter Role in Colorectal Cancer by Targeting miR-3619-5p to Up-regulate CTNNB1

Colorectal cancer (CRC) is a common malignant tumor in gastrointestinal tract around the world. Emerging evidence has confirmed that long non-coding RNAs (lncRNAs) are closely connected to cell progression in cancers, including CRC. RT-qPCR assays were applied to detect the expression of LINC00882, miR-3619-5p and CTNNB1. Western blot assays were performed to measure the protein level of E-cadherin, N-cadherin and CTNNB1. Transwell assay was conducted to test the cell migration. Immunofluorescence (IF) assay was performed to measure the connected protein of EMT process. LINC00882 was highly expressed in CRC tissues and cell lines. Knockdown of LINC00882 hindered the process of CRC. Studies on gain-of-function and loss-of-function further testified that knockdown of LINC00882 or up-regulation of miR-3619-5p hindered cell migration and EMT process in CRC cells. Moreover, rescue assay proved that the inhibition of migration ability and EMT process resulted from LINC00882 silencing could be rescued when miR-3619-5p inhibitor or pcDNA3.1/CTNNB1 was transfected into CRC cells. Our data suggested that LINC00882 promoted the progression of CRC as a ceRNA to regulate CTNNB1 via sponging miR-3619-5p. This finding would supply a novel insight for CRC therapy.

Evaluation of CEA,CA19-9, and CA242 Tumor Markers in Patients with Colorectal Cancer by ELISA Technique

Colorectal cancer (CRC) is one of the common malignant tumors of gastrointestinal tract (GIT). A total of 40 patients with CRC were studied preoperatively and postoperatively while only 20 healthy persons were studied. Their ages ranged between 18-78 years.This study was carried out to investigate the possible association of some risk factors with CRC such as (age, gender, smoking, inflammatory bowel disease, and ulcerative colitis). With application of ELISA technique, Serum levels of CEA, CA 19-9, and CA 242 was measured preoperatively and postoperatively. The results showed an increase in preoperative serum level of CEA in CRC patients when compared to both postoperative and control groups, There was a significant increase in the serum level of CEA (10.73 ± 4.01) comparison with the two other groups (postoperative 3.95 ± 1.55) and control (1.91 ± 0.27) at (P<0.05), but no significant differences between the two groups (postoperative and healthy) which have mean (3.95 ± 1.55 and 1.91 ± 0.27) respectively. Also showed a significant increase in serum level of CA19-9 in patients preoperative (23.28 ± 1.86), who were differed significantly from the mean of serum in patients postoperative (18.63 ± 1.40) and control group (19.11 ± 1.46) at (P<0.05), When compared the serum level of CA242 revealed a significant increase in serum level of patients preoperative (19.58 ± 3.46) as compared to postoperative(8.75 ± 1.77) and control group(9.85 ± 2.22) at (P<0.05).

Immunoexpression of Matrix Metalloproteinase-9 in Colorectal Adenocarcinoma

Colorectal carcinoma is one of the most common malignant tumors of gastrointestinal tract and is a contributing factor of cancer mortality in Myanmar. Matrix metalloproteinase-9 is a proteolytic enzyme which breaks down extracellular matrix leading to tumor progression, contri-buting as a potential prognostic marker nowadays. The study was aimed to determine MMP-9 immunoexpression in colorectal adenocarcinoma and its association with Astler-Coller staging. A cross-sectional descrip-tive study was done on 42 specimens of colorectal adenocarcinoma. All tissue specimens were studied with haematoxylin and eosin to categorize histological types and grades. Out of 42 cases, 21.4% were well differentiated, 57.2% were moderately differentiated and 21.4% were poorly differentiated. According to Astler-Coller staging, 11.9% were found to be in stage B1, 40.5% in stage B2, 7.1% in stage C1, 33.3% in stage C2 and 7.1% in stage D. 81% (34/42) of colorectal carcinoma showed positive MMP-9 immunoexpression. Positive MMP-9 immuno-expression was seen in 91% of conventional adenocarcinoma, 40% of mucinous carcinoma and no cases signet ring carcinoma. The findings of the study pointed out that MMP-9 immunoexpression was positively associated with histological types of colorectal adenocarcinoma (p=0.001). MMP-9 immunoexpression was positive in 88.9% of well differentiated adenocarcinoma, 91.7% of moderately differentiated adenocarcinoma and 44.4% of poorly-differentiated adenocarcinoma (p=0.007). Regarding the immunoexpression of MMP-9 in different Astler-Coller staging, positive MMP-9 immunoexpression was seen in 60% of the cases in stage B1, 76.5% in stage B2, 66.7% in stage C1, 92.9% in stage C2 and 100% in stage D. The findings of the study can be extrapolated to predict prognosis and help in better management of colorectal adenocarcinoma by introducing targeted therapy against MMP-9 in future.

Modern Nanomaterials and Nanotechnology in Diagnosis and Treatment of Malignant Tumors of Gastrointestinal Tract

Modern Nanomaterials and Nanotechnology in Diagnosis and Treatment of Malignant Tumors of Gastrointestinal Tract

MiR-1307–3p overexpression inhibits cell proliferation and promotes cell apoptosis by targeting ISM1 in colon cancer

Backgroundcolon adenocarcinoma (COAD) is the most common malignant tumor of gastrointestinal tract. Our study attempts to explore the effect of miR-1307–3p on biological function of COAD cells and its connection with isthmin 1 (ISM1). MethodsThe miRNA dataset and clinical information of patients with COAD were downloaded from The Cancer Genome Atlas (TCGA) database. The survival prognosis was analyzed by GGSURV package from R. MicroRNA (miR)-1307–3p was identified by identifying overlapping miRNAs that target ISM1, across two databases (miRDB and Targetscan). Dual luciferase reporter assay was employed to scrutinize the relationship between miR-1307–3p and ISM1. RT-PCR was used to quantify miR-1307–3p and ISM1 expression of colon cancer tissues and cell lines. Western blot was performed to quantify related protein expression. Flow Cytometry, CCK8 and colony formation assays were performed to evaluate the apoptosis, cell cycle, cell viability and proliferation of COAD cells. ResultsmiR-1307–3p mRNA level decreased in both COAD tissues and cell lines. Overexpression of miR-1307–3p suppressed the proliferation, promoted apoptosis and arrested cell cycle at G1 phase, meanwhile, downregulation of ISM1 accelerated the proliferation, inhibited apoptosis and promote cell cycleprogression. The result of dual luciferase reporter assay indicated that miR-1307–3p targeted ISM1 directly and inhibited its expression. The functions of miR-1307–3p regulating cleaved caspase-3, cyclinD1, Ki67 protein levels and activation of Wnt3a/β-catenin signaling pathway were reversed by ISM1. ConclusionsmiR-1307–3p inhibited activation of Wnt3a/β-catenin signaling through targeting downregulation of ISM1, thereby inhibited proliferation and promote apoptosis of COAD cells.

Rectal cancer and chemoradiation in Iraq: systematic review and meta-analysis

BackgroundRectal cancer is one of the most common malignant tumors of gastrointestinal tract. Combining chemotherapy with radiotherapy has a sound effect on its management. ObjectivesAssessment the patterns of characterizations of rectal cancer. Evaluation of the efficacy, and long-term survival of pre-/ postoperative chemoradiation. Collecting all eligible evidence articles and summarize the results. MethodsBy this systematic review and meta-analysis study, we include data of chemoradiation of rectal cancer articles from 2015 until 2019. The research was carried out at Baghdad Medical City oncology centers. Accordance with the PRISMA guidelines, and the Newcastle–Ottawa Scale used. ResultsStarting with gender distribution as M:F ratio of 0.94:1.06. Regarding the age, recorded mean±SD of 48.7±14.2 years. Rectosigmoid represented the most common site as 50(49.5%), and adenocarcinoma was common histopathology as 76(75.2%) of patients, with localized stage in 50(49.5%). The moderate differentiation was most grade as 65(64.4%). The distant from anal verge mostly seen was 5–10cm in 59(58.4%). The pulmonary was commonest site of metastasis in 11(10.9%). Most patients undergo APR operation, which has done in 41(40.6%). Adjuvant chemoradiation received by 40(39.6%) patients, whereas neoadjuvant chemoradiation gave to 25 patients. A total of 2609 articles from 12 databases met our search strategies. The highest Newcastle–Ottawa score (8) demonstrated in three studies, and median score (7) calculated in five studies. ConclusionsThe incidence belonged to 5th and 6th decade of life. Rectosigmoid represented the most common site. Mostly, the 5–10cm distant of tumor from anal verge was common finding. The pulmonary was most site of metastasis. We concluded the formulation of a novel point that survival benefit found in many pre or postoperative chemoradiation trials in rectal cancer.

Rare cause of small bowel obstruction: Metastatic squamous cell carcinoma with occult primary

Only 1% to 2% of all malignant tumors of gastrointestinal tract occur in the small bowel. Metastatic tumors are more common than primary tumors of small bowel. In case of metastatic small bowel disease most common primary is melanoma followed by adenocarcinoma and rarely squamous cell carcinoma. Isolated metastatic disease presenting with stricture is further a rare presentation and very few case has been reported. Most common presentation is obstruction. It represents a metastatic disease with poor prognosis. Due to aggressive nature and resistance to chemotherapy overall survival of these patients are 6 to 9 months.

Evaluation of CK20 and CD8 Tumor Markers in Patients with Colorectal Cancer by Using Immunohistochemical Technique

Colorectal cancer (CRC) is one of the common malignant tumors of gastrointestinal tract (GIT). The incidence rate of this cancer increased in frequency in the last few years. This study was carried out to investigate the possible association of some risk factors with CRC such as (age, gender, smoking, inflammatory bowel disease, and ulcerative colitis). In this study we analyzed using immunohistochemistry technique of the following markers for 30 selected cases: cytokeratin 20 (CK20), and cytotoxic T-lymphocyte (CD8), the results showed that CD8 and CK20 are positive immunostaining markers.

MicroRNAs in colorectal cancer potential biomarkers and therapeutic targets

Colorectal Cancer (CRC) is one of the most common malignant tumors of gastrointestinal tract. The occurrence, development, diagnosis and prognosis have become a hot topic in current clinical research. However, current diagnosis and treatment still depend on the results of tumor imaging or pathology test. Therefore, to reveal the biological pathogenesis of CRC and to discover specific biomarkers for early diagnosis and better prognosis assessment of CRC have become key roles in current studies. Recent literature has revealed that aberrant expression of microRNAs (miRNAs) could contribute to the development and progression of CRC through the regulation of several critical pathways, including apoptosis, epithelial-mesenchymal transition, angiogenesis and signal transduction. These findings have also indicated that miRNAs could be a novel biomarker for early clinical diagnosis and prognosis evaluation of CRC. In this review, we have summarized the recent studies of miRNAs on the diagnosis, treatment and prognosis clinical biomarker of CRC. We also discussed the regulatory mechanisms of miRNAs in CRC, which may guide the future treatment for CRC.

A Rare Presentation: Duodenal Leiomyosarcoma with Pulmonary Metastasis

Purpose: Duodenal Leiomyosarcoma (LMS) is a very rare malignant tumor of gastrointestinal tract. We present an interesting case of duodenal leiomyosarcoma with metastasis to lungs which is extremely rare. Case: A 60-year-old female with presented with abdominal distension and melena for few weeks. Esophagogastroduodenoscopy (EGD) showed a large friable purplish colored mass extending from second to third part of duodenum (figure). Biopsy showed malignant cells with high NC ratio, pleomorphism and increased mitoses (60/50 HPF). Immunohistological staining for S100, CK7, CK20, CD34, KIT (GIST marker), pancytokeratin, mucicarmine, myogenin, and lymphoma markers (CD3, CD20, CD30) was negative. It was positive for desmin and smooth muscle actin (SMA). These findings were compatible with poorly differentiated leiomyosarcoma. Further, CT scan confirmed large duodenal mass along with extensive metastatic lesions in liver and lungs. As she was not a surgical candidate due to extensive metastasis, she was started on chemotherapy. Unfortunately patient's condition gradually declined and she died within a few months after diagnosis.FigureDiscussion: Classically, duodenal leiomyomas and leiomyosarcomas are classified under gastrointestinal stromal tumors (GIST) because most of them express a protein KIT, also called CD117. But it is important to recognize LMS as a separate entity as they have a worse prognosis. The exact incidence of KIT negative tumors is not known while KIT positive tumors of duodenum have an incidence of 10% of all GISTs. Duodenal LMS can present with abdominal pain, GI bleed, anemia or obstructive jaundice in 50-70 year age group. Diagnosis is made by histology and immunochemical staining using which our patient was diagnosed with KIT negative poorly differentiated LMS. Most common sites of metastasis include liver, pancreas and peritoneal cavity. Our patient showed extensive pulmonary metastasis along with liver metastasis, which is rarely, if ever reported in the literature. The primary treatment option is surgical resection. Metastatic disease, KIT negative on immunostaining and non resectable lesion confer poor prognosis. Conclusion: Duodenal leiomyosarcoma should be differentiated from GIST and treated accordingly.

The basic strategy and consideration of surgery treatment for pancreatic head cancer

Pancreatic head cancer is one of the most malignant tumor in gastrointestinal tract, which has the characteristics of rapid progression and low resection rate due to the involving of superior mesenteric vessels and portal vein. Pancreaticoduodenectomy still plays the center role in surgical management of pancreatic head cancer, however it remains some controversial in operative methods choice and extended pancreatectomy procedure. Surgeons should take sufficient considerations and make appropriate strategy preoperatively to ensure the safety, resectability and radical resection of surgery treatment. Key words: Pancreatic cancer; Pancreaticoduodenectomy

The study of RNA markers in blood of patients with malignant tumors of gastrointestinal tract

In order to develop a diagnostic panel, mRNA levels of tumor marker genes have been evaluated in capillary blood of patients with various malignant tumors of the gastrointestinal tract (GIT) by means of the method of reverse transcription combined with real-time PCR with detection of reaction products using TaqMan probes. Use of small volumes of capillary blood did not decrease sensitivity of this method. RNA expression of telomerase (mhTERT), alpha-fetoprotein (mAFP), carcinoembryonic antigen (mCEA) and cytokeratin-20 (mCK-20) was higher in most patients with tumors. Blood of donors or non-oncological patients contained much lower (trace) amounts of the RNA markers. The RNA markers are characterized by reasonably high specificity and sensitivity acceptable for diagnostic application. The mhTERT marker was the most universal one and exhibited the highest specificity and sensitivity. Combined determination of several RNA markers increased sensitivity of this method. It is concluded that determination of RNA markers in small volumes of capillary blood may be used for screening, primary diagnostics, and postoperative monitoring.

The study of RNA markers in blood of patients with malignant tumors of gastrointestinal tract

In order to develop a diagnostic panel, mRNA levels of tumor marker genes have been evaluated in capillary blood of patients with various malignant tumors of the gastrointestinal tract (GIT) by means of the method of reverse transcription combined with real-time PCR with detection of reaction products using TaqMan probes. Use of small volumes of capillary blood did not decrease sensitivity of this method. RNA expression of telomerase (mhTERT), alpha-fetoprotein (mAFP), carcinoembryonic antigen (mCEA) and cytokeratin-20 (mCK-20) was higher in most patients with tumors. Blood of donors or non-oncological patients contained much lower (trace) amounts of the RNA markers. The RNA markers are characterized by reasonably high specificity and sensitivity acceptable for diagnostic application. The mhTERT marker was the most universal one and exhibited the highest specificity and sensitivity. Combined determination of several RNA markers increased sensitivity of this method. It is concluded that determination of RNA markers in small volumes of capillary blood may be used for screening, primary diagnostics, and postoperative monitoring.

Voluminous gastric fibrosarcoma in a 75-year-old patient

Background Gastrointestinal stromal tumors are mesenchymal neoplasms of the gastrointestinal tract, arising from the muscular layer. Revent immunohistochemical studies have shown that up to 94% of GISTs express 117, and 60–70% of GISTs stain for CD 34. GISTs account for 1% of all malignant tumors of gastrointestinal tract; they arise from stomach in the 40–60% of cases whereas they account only for 3% of gastric malignant neoplasms. GISTs can occur at any age but onset most commonly in the sixth and the seventh decades of life.

Early diagnosis and treatment of multiple primary malignant tumors in gastrointestinal tract in the elderly

Early diagnosis and treatment of multiple primary malignant tumors in gastrointestinal tract in the elderly

Relationship between expression of CD105 and growth factors in malignant tumors of gastrointestinal tract and its significance.

Angiogenesis is an important step in the growth of solid malignant tumors. A number of angiogenic factors have been found such as transforming growth factor beta1 (TGF-beta1) and vascular endothelial growth factor (VEGF). However, the roles of TGF-beta1 and VEGF in gastrointestinal carcinogenesis are still unclear. This study was to investigate the expressions of TGF-beta1 and VEGF in gastrointestinal tract malignant tumors, as well as their association with microvessel density (MVD). At the same time, we also observed the localization of TGF-beta1 and its receptor CD105 in gastric malignant tumors. The expressions of TGF-beta1 and CD105 were detected in 55 fresh specimens of gastric carcinoma and VEGF and CD105 in 44 fresh specimens of colorectal carcinoma by immunohistochemical staining (S-ABC). TGF-beta1 and CD105 in 55 gastric carcinoma tissues on the same slide were detected by using double-stain Immunohistochemistry (DS-ABC). Among the 55 cases of gastric carcinoma tissues, 30 were positive for TGF-beta1 (54.55%). The MVD of TGF-beta1 strong positive group (++ approximately +++ 23.22 +/- 5.8) was significantly higher than that of weak positive group (+17.56 +/- 7.2) and negative group (- 17.46 +/- 3.9) (q=4.5, q=5.3207, respectively, P<0.01). In the areas of high expression of TGF-beta1, MVD and the expression of CD105 were also high. Among the 44 cases of colonic carcinoma tissues, 26 were positive for VEGF (59.1%). The expressions of both VEGF and CD105 (MVD) were related with the depth of invasion (F=5.438, P<0.05; F=4.168, P=0.05), lymph node metastasis (F=10.311, P<0.01; F=20.282, P<0.01) and Dukes stage (F=6.196, P<0.01; F=10.274, P<0.01), but not with histological grade (F=0.487, P>0.05). There was a significant correlation between the expression of VEGF and CD105 (MVD) (r=0.720, P<0.01). Over-expression of TGF-beta1 and VEGF acts as stimulating factors of angiogenesis in gastrointestinal tumors. CD105, as a receptor of TGF-beta1, can regulate the biological effect of TGF-beta1 in tumor angiogenesis. MVD marked by CD105 is more suitable for detecting newborn blood vessels.