- Intestinal Obstruction of Uncommon Cause and Point-of-Care Ultrasonography - Where Do We Stand? [Journal Article]
- GPGE Port J Gastroenterol 2018; 25(1):38-41
- Malignant neoplasms of the small bowel, especially from the jejunum, are among the rarest types of cancer. Given its location, a delayed diagnosis is frequent and sometimes only made in an emergency ...
Malignant neoplasms of the small bowel, especially from the jejunum, are among the rarest types of cancer. Given its location, a delayed diagnosis is frequent and sometimes only made in an emergency context. The authors present a case of intestinal obstruction, where ultrasonography was pivotal in establishing a diagnosis. Point-of-care ultrasonography seems to be particularly sensitive in assessing emergency patients with abdominal pain, allowing effective orientation and saving human and technical resources.
- A case of small intestinal neuroendocrine carcinoma diagnosed using double-balloon endoscopy with long-term survival. [Journal Article]
- CJClin J Gastroenterol 2018 Feb 15
- Neuroendocrine neoplasms, including neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs), are rare epithelial tumors with a predominant neuroendocrine differentiation. Compared with NETs...
Neuroendocrine neoplasms, including neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs), are rare epithelial tumors with a predominant neuroendocrine differentiation. Compared with NETs, NECs have been reported to be rarer and have a poorer prognosis. We present a rare case of small bowel NEC diagnosed using double-balloon endoscopy (DBE) and the long-term survival accomplished via intensive therapy. DBE revealed an ulcerative tumor in the deep jejunum, and biopsy specimens showed large and highly dysplastic tumor cells; immuno-histological synaptophysin and chromogranin A tests were positive, and the Ki-67 index was more than 90%. Partial intestinal resection without complete lymph node dissection was performed and, postoperatively, chemotherapy was administered. The patient was observed for 3 years after chemotherapy, and complete remission was maintained.
- Anterior Approach to En Bloc Resection in Left-Sided Retroperitoneal Sarcoma with Adjacent Organ Involvement: A Study of 25 Patients in a Single Center. [Journal Article]
- MSMed Sci Monit 2018 Feb 16; 24:961-969
- CONCLUSIONS: In selected patients, left-sided retroperitoneal sarcoma associated with local organ involvement can be surgically managed using an anterior approach with en bloc resection of adjacent organs.
- Interaction of the Wnt/β-catenin and RAS-ERK pathways involving co-stabilization of both β-catenin and RAS plays important roles in the colorectal tumorigenesis. [Review]
- ABAdv Biol Regul 2018 Jan 10
- Cancer development is usually driven by multiple genetic and molecular alterations rather than by a single defect. In the human colorectal cancer (CRC), series of mutations of genes are involved in t...
Cancer development is usually driven by multiple genetic and molecular alterations rather than by a single defect. In the human colorectal cancer (CRC), series of mutations of genes are involved in the different stages of tumorigenesis. For example, adenomatous polyposis coli (APC) and KRAS mutations have been known to play roles in the initiation and progression of the tumorigenesis, respectively. However, many studies indicate that mutations of these two genes, which play roles in the Wnt/β-catenin and RAS-extra-cellular signal regulated kinase (ERK) pathways, respectively, cooperatively interact in the tumorigenesis in several different cancer types including CRC. Both Apc and Kras mutations critically increase number and growth rate of tumors although single mutation of these genes does not significantly enhance the small intestinal tumorigenesis of mice. Both APC and KRAS mutations even result in the liver metastasis with inductions of the cancer stem cells (CSCs) markers in a mice xenograft model. In this review, we are going to describe the history for interaction between the Wnt/β-catenin and RAS/ERK pathways especially related with CRC, and provide the mechanical basis for the cross-talk between the two pathways. The highlight of the crosstalk involving the stability regulation of RAS protein via the Wnt/β-catenin signaling which is directly related with the cellular proliferation and transformation will be discussed. Activation status of GSK3β, a key enzyme involving both β-catenin and RAS degradations, is regulated by the status of the Wnt/β-catenin signaling dependent upon extracellular stimuli or intracellular abnormalities of the signaling components. The levels of both β-catenin and RAS proteins are co-regulated by the Wnt/β-catenin signaling, and these proteins are overexpressed with a positive correlation in the tumor tissues of CRC patients. These results indicate that the elevation of both β-catenin and RAS proteins is pathologically significant in CRC. In this review, we also will discuss further involvement of the increments of both β-catenin and RAS especially mutant KRAS in the activation of CSCs and metastasis. Overall, the increments of β-catenin and RAS especially mutant KRAS by APC loss play important roles in the cooperative tumorigenesis of CRC.
- The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines. [Journal Article]
- EREndocr Relat Cancer 2018; 25(3):367-380
- Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. ...
Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We therefore performed immunophenotyping, copy number profiling, whole-exome sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype while three others, KRJ-I, L-STS and H-STS, did not. Instead, these three cell lines were identified as lymphoblastoid. Characterisation of remaining authentic GEPNET cell lines by copy number profiling showed that GOT1, among other chromosomal alterations, harboured losses on chromosome 18 encompassing theSMAD4gene, while P-STS had a loss on 11q. BON-1 had a homozygous loss ofCDKN2AandCDKN2B, and QGP-1 harboured amplifications ofMDM2andHMGA2Whole-exome sequencing revealed both disease-characteristic mutations (e.g.ATRXmutation in QGP-1) and, for patient tumours, rare genetic events (e.g.TP53mutation in P-STS, BON-1 and QGP-1). A large-scale inhibitor screening showed that cell lines from pancreatic NETs to a greater extent, when compared to small intestinal NETs, were sensitive to inhibitors of MEK. Similarly, neuroendocrine NET cells originating from the small intestine were considerably more sensitive to a group of HDAC inhibitors. Taken together, our results provide a comprehensive characterisation of GEPNET cell lines, demonstrate their relevance as neuroendocrine tumour models and explore their therapeutic sensitivity to a broad range of inhibitors.
- Gastrointestinal stromal tumor of the esophagus: current issues of diagnosis, surgery and drug therapy. [Review]
- TGTransl Gastroenterol Hepatol 2018; 3:6
- Gastrointestinal stromal tumors (GISTs) often arise in the stomach and small intestine, while esophageal GISTs are rare. Due to their rarity, clinicopathological data on esophageal GISTs are extremel...
Gastrointestinal stromal tumors (GISTs) often arise in the stomach and small intestine, while esophageal GISTs are rare. Due to their rarity, clinicopathological data on esophageal GISTs are extremely limited, and this results in a lack of clear recommendations concerning optimal surgical management for esophageal GISTs. It is difficult to distinguish esophageal GIST from leiomyoma, the most frequent esophageal mesenchymal tumor, prior to resection, because the two types of tumors appear similar on computed tomography (CT), endoscopic ultrasound (EUS), and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Fine-needle aspiration biopsy (FNAB) under EUS enables definitive diagnosis, but it is often avoided because scarring could make enucleation more difficult and increase the risk of tumor dissemination by capsule destruction. Esophageal segmental and wedge resections are not usually performed due to the anatomical peculiarity of the esophagus, and the surgical options are limited to the highly invasive esophagectomy or the much less invasive surgical tumor enucleation. The decision as to which surgical procedure should be performed for esophageal GISTs is still under debate. Tumor enucleation may be permitted for smaller tumors, and esophagectomy may be recommended for larger GISTs or high-risk tumors with a high mitotic rate. The purpose of neoadjuvant imatinib administration is downsizing of the GIST to reduce the extent of resection and to reduce the risk of intraoperative complications, including tumor rupture. The efficacy of neoadjuvant/adjuvant imatinib therapy for esophageal GISTs is poorly understood, because the reports are limited to case reports or case series with small numbers. More clinicopathological data and clinical trials for esophageal GIST are expected.
- Small bowel obstruction from distant metastasis of primary breast cancer: a case report. [Journal Article]
- ASAnn Surg Treat Res 2018; 94(2):102-105
- Gastrointestinal (GI) tract metastasis of primary breast cancer is very rare. We present a patient with small bowel obstruction from distant metastasis of primary breast cancer. Each characteristic f...
Gastrointestinal (GI) tract metastasis of primary breast cancer is very rare. We present a patient with small bowel obstruction from distant metastasis of primary breast cancer. Each characteristic features of concern of GI tract distant metastasis from many pervious studies has been reported differently. We should remember that GI tract metastasis may coexist when patients with breast cancer have intermittent or recurrent abdominal pain with or without obstructive symptoms.
- Ex vivo activity of cytotoxic drugs and targeted agents in small intestinal NETS. [Journal Article]
- EREndocr Relat Cancer 2018 Feb 12
- Small intestinal endocrine tumours (SI-NETs) are generally considered resistant to systemic treatment. To date, predictive markers for drug activity are lacking. Tumour samples from 27 patients with ...
Small intestinal endocrine tumours (SI-NETs) are generally considered resistant to systemic treatment. To date, predictive markers for drug activity are lacking. Tumour samples from 27 patients with SI-NETs were analyzed ex vivo for sensitivity to a panel of cytotoxic drugs and targeted agents using a short-term total cell kill assay. Samples of renal cancer, colorectal cancer (CRC), ovarian cancer, and chronic lymphocytic leukemia (CLL) were included for comparison. For the SI-NET subset, drug sensitivity was analyzed in relation to clinico-pathological variables and pre-treatment biomarkers. For cytotoxic drugs, SI-NETs demonstrated similar or higher sensitivity to 5-FU, platinums, gemcitabine and doxorubicin compared with CRC. For several targeted kinase inhibitors, SI-NET was among the most sensitive solid tumour types. CLL and ovarian cancer were generally the most sensitive tumour types to both cytotoxic drugs and protein kinase inhibitors. SI-NET was more sensitive to the mTOR inhibitor sirolimus than the other solid tumour types tested. Individual SI-NET samples demonstrated great variability in ex vivo sensitivity for most drugs. Cross-resistance between different drugs also varied considerably, being higher among protein kinase inhibitors. Age, stage, grade, peritoneal carcinomatosis and extra-abdominal metastases as well as serum chromogranin A and urine 5-HIAA concentrations at diagnosis did not correlate to drug sensitivity ex vivo. SI-NETs exhibit intermediate sensitivity ex vivo to cytotoxic and targeted drugs. Clinico-pathological factors and currently used biomarkers are not clearly associated to ex vivo sensitivity, challenging these criteria for treatment decisions in SI-NET. The great variability in drug sensitivity calls for individualized selection of therapy.
- Anti-inflammatory drug resistance selects putative cancer stem cells in a cellular model for genetically predisposed colon cancer. [Journal Article]
- OLOncol Lett 2018; 15(1):642-648
- Mutations in the adenomatous polyposis coli (Apc) tumor suppressor gene represent the primary genetic defect in colon carcinogenesis. Apc+/- mouse models exhibit pre-invasive small intestinal adenoma...
Mutations in the adenomatous polyposis coli (Apc) tumor suppressor gene represent the primary genetic defect in colon carcinogenesis. Apc+/- mouse models exhibit pre-invasive small intestinal adenomas. Cell culture models exhibiting Apc defects in the colon and quantifiable cancer risk provide a novel clinically relevant approach. The tumor-derived Apc-/- colonic epithelial cell line 1638N COL-Pr1 represented the experimental model. The anti-inflammatory drugs sulindac (SUL) and celecoxib (CLX) represented the test compounds. Compared with non-tumorigenic Apc+/+ C57COL cells, the Apc+/- 1638N COL cells and Apc-/- 1638N COL-Pr1 cells exhibited progressive loss of homeostatic growth control. Compared with Apc+/- cells, Apc-/- cells displayed increased expression of biomarkers specific for hyper-proliferation. Treatment of Apc-/- cells with SUL and CLX resulted in inhibition of anchorage-independent colony formation in vitro, which is indicative of reduced cancer risk in vivo. Mechanistically, SUL and CLX suppressed the expression of the Apc target genes β-catenin, cyclin D1, c-Myc and cyclooxygenase-2. Long-term treatment with high concentrations of SUL and CLX led to the selection of hyper-proliferative drug-resistant phenotypes. The Apc-/- SUL-resistant phenotype displayed spheroid formation and enhanced the expression of the stem cell-specific molecular markers CD44, CD133 and c-Myc. These data demonstrated the growth-inhibitory efficacy of SUL and CLX and indicated that drug resistance leads to the selection of a putative cancer stem cell phenotype. The study outcome validates a stem cell-targeted mechanistic approach to identify testable alternative leads for chemotherapy-resistant colon cancer.
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- 92R Monoclonal Antibody Inhibits Human CCR9+ Leukemia Cells Growth in NSG Mice Xenografts. [Journal Article]
- FIFront Immunol 2018; 9:77
- CCR9 is as an interesting target for the treatment of human CCR9+-T cell acute lymphoblastic leukemia, since its expression is limited to immature cells in the thymus, infiltrating leukocytes in the ...
CCR9 is as an interesting target for the treatment of human CCR9+-T cell acute lymphoblastic leukemia, since its expression is limited to immature cells in the thymus, infiltrating leukocytes in the small intestine and a small fraction of mature circulating T lymphocytes. 92R, a new mouse mAb (IgG2a isotype), was raised using the A-isoform of hCCR9 as immunogen. Its initial characterization demonstrates that binds with high affinity to the CCR9 N-terminal domain, competing with the previously described 91R mAb for receptor binding. 92R inhibits human CCR9+ tumor growth in T and B-cell deficient Rag2-/- mice. In vitro assays suggested complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity as possible in vivo mechanisms of action. Unexpectedly, 92R strongly inhibited tumor growth also in a model with compromised NK and complement activities, suggesting that other mechanisms, including phagocytosis or apoptosis, might also be playing a role on 92R-mediated tumor elimination. Taken together, these data contribute to strengthen the hypothesis of the immune system's opportunistic nature.