polyposis coli
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BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Georgia Sofia Karachaliou ◽  
Rached Alkallas ◽  
Sarah B. Carroll ◽  
Chongshan Caressi ◽  
Danny Zakria ◽  
...  

Abstract Background Melanoma-intrinsic activated β-catenin pathway, the product of the catenin beta 1 (CTNNB1) gene, has been associated with low/absent tumor-infiltrating lymphocytes, accelerated tumor growth, metastases development, and resistance to anti-PD-L1/anti-CTLA-4 agents in mouse melanoma models. Little is known about the association between the adenomatous polyposis coli (APC) and CTNNB1 gene mutations in stage IV melanoma with immunotherapy response and overall survival (OS). Methods We examined the prognostic significance of somatic APC/CTNNB1 mutations in the Cancer Genome Atlas Project for Skin Cutaneous Melanoma (TCGA-SKCM) database. We assessed APC/CTNNB1 mutations as predictors of response to immunotherapies in a clinicopathologically annotated metastatic patient cohort from three US melanoma centers. Results In the TCGA-SKCM patient cohort (n = 434) presence of a somatic APC/CTNNB1 mutation was associated with a worse outcome only in stage IV melanoma (n = 82, median OS of APC/CTNNB1 mutants vs. wild-type was 8.15 vs. 22.8 months; log-rank hazard ratio 4.20, p = 0.011). APC/CTNNB1 mutation did not significantly affect lymphocyte distribution and density. In the 3-melanoma institution cohort, tumor tissues underwent targeted panel sequencing using two standards of care assays. We identified 55 patients with stage IV melanoma and APC/CTNNB1 genetic aberrations (mut) and 169 patients without (wt). At a median follow-up of more than 25 months for both groups, mut compared with wt patients had slightly more frequent (44% vs. 39%) and earlier (66% vs. 45% within six months from original diagnosis of stage IV melanoma) development of brain metastases. Nevertheless, time-to-development of brain metastases was not significantly different between the two groups. Fortunately, mut patients had similar clinical benefits from PD-1 inhibitor-based treatments compared to wt patients (median OS 26.1 months vs. 29.9 months, respectively, log-rank p = 0.23). Less frequent mutations in the NF1, RAC1, and PTEN genes were seen in the mut compared with wt patients from the 3-melanoma institution cohort. Analysis of brain melanoma tumor tissues from a separate craniotomy patient cohort (n = 55) showed that melanoma-specific, activated β-catenin (i.e., nuclear localization) was infrequent (n = 3, 6%) and not prognostic in established brain metastases. Conclusions APC/CTNNB1 mutations are associated with a worse outcome in stage IV melanoma and early brain metastases independent of tumor-infiltrating lymphocyte density. However, PD1 inhibitor-based treatments provide comparable benefits to both mut and wt patients with stage IV melanoma.


2021 ◽  
Author(s):  
Larissa Dayelle Osternack ◽  
Júlia Ciola Kapfenberger ◽  
Juliane Kaori Saito ◽  
Magali Akemi Osiro ◽  
Samya Hamad Mehanna

Introdução: Adenomas são lesões precursoras com potencial evolutivo para malignidade entre 5 e 15 anos. Doenças como a polipose adenomatosa familiar (PAF) aumentam o risco de desenvolvimento do câncer colorretal. Objetivos: Descrever a histologia colorretal, correlacionando à PAF e sua evolução para adenocarcinoma colorretal. Material e métodos: Pesquisa bibliográfica nas bases Pubmed e Scielo, com os descritores: “familial adenomatous polyposis” e “colorectal neoplasms”. Foram utilizados: Robbins Patologia Básica 9ª Ed.; Junqueira e Carneiro Histologia Básica 13ª Ed. Resultados: O intestino grosso possui mucosa de tecido epitelial simples cilíndrico com células caliciformes e criptas de Lieberküng, lâmina própria de tecido conjuntivo frouxo e muscular da mucosa. A submucosa contém tecido conjuntivo denso e plexo de Meissner. A muscular própria possui duas subcamadas musculares lisas: circular interna, longitudinal externa, e plexo de Auerbach. Por fim, a serosa/adventícia possui tecido conjuntivo frouxo e adiposo. A PAF é uma doença autossômica dominante caracterizada pelo desenvolvimento de adenomas entéricos. Ela resulta da mutação no supressor tumoral adenomatous polyposis coli, responsável pela estabilidade genômica e apoptose. Se não tratados precocemente, 100% dos pacientes acometidos desenvolverá câncer colorretal. Na forma clássica, apresenta inúmeros adenomas, que evoluem para câncer rapidamente. Na atenuada, há menos adenomas, menor agressividade e progressão lenta. Estruturalmente, os adenomas são tubulares, vilosos ou túbulo-vilosos, classificação essencial para conhecimento do potencial maligno. A displasia epitelial de baixo grau nos adenomas possui núcleos alongados e pseudoestratificados, com pequenos nucléolos, enquanto a de alto grau apresenta núcleos redondos, estratificação e nucléolo proeminente. No cólon proximal, os adenocarcinomas são polipóides e exofíticos, raramente causando obstrução. Já no distal, são lesões anulares com estreitamento luminal e oclusão. Clinicamente, no cólon direito ocorre anemia ferropriva e no esquerdo sangramento oculto, alterações intestinais e cólicas. Microscopicamente, os adenocarcinomas bem diferenciados possuem células colunares altas, semelhantes aos adenomas, com componente invasivo causador de resposta desmoplásica, ocasionando consistência firme. Os pouco diferenciados formam glândulas e produzem mucina. Ainda, estas neoplasias podem apresentar diferenciação neuroendócrina. Conclusão: As características da PAF explicam sua correlação com o desenvolvimento de carcinomas colorretais. Assim, destaca-se a importância do estudo histopatológico, facilitando a compreensão evolutiva adenomas-câncer neste grupo populacional.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Younis Mohd ◽  
Parvinder Kumar ◽  
Haripriya Kuchi Bhotla ◽  
Arun Meyyazhagan ◽  
Balamuralikrishnan Balasubramanian ◽  
...  

Colorectal cancer (CRC) is one of the globally prevalent and virulent types of cancer with a distinct alteration in chromosomes. Often, any alterations in the adenomatosis polyposis coli (APC), a tumor suppressor gene, and methylenetetrahydrofolate reductase (MTHFR) gene are related to surmise colorectal cancer significantly. In this study, we have investigated chromosomal and gene variants to discern a new-fangled gene and its expression in the southern populations of India by primarily spotting the screened APC and MTHFR variants in CRC patients. An equal number of CRC patients and healthy control subjects ( n = 65 ) were evaluated to observe a chromosomal alteration in the concerted and singular manner for APC and MTHFR genotypes using standard protocols. The increasing prognosis was observed in persons with higher alcoholism and smoking ( P < 0.05 ) with frequent alterations in chromosomes 1, 5, 12, 13, 15, 17, 18, 21, and 22. The APC Asp 1822Val and MTHFR C677T genotypes provided significant results, while the variant alleles of this polymorphism were linked with an elevated risk of CRC. Chromosomal alterations can be the major cause in inducing carcinogenic outcomes in CRCs and can drive to extreme pathological states.


PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255738
Author(s):  
Emily M. Astarita ◽  
Sara M. Maloney ◽  
Camden A. Hoover ◽  
Bronwyn J. Berkeley ◽  
Monica K. VanKlompenberg ◽  
...  

Adenomatous Polyposis Coli (APC) is lost in approximately 70% of sporadic breast cancers, with an inclination towards triple negative breast cancer (TNBC). TNBC is treated with traditional chemotherapy, such as paclitaxel (PTX); however, tumors often develop drug resistance. We previously created APC knockdown cells (APC shRNA1) using the human TNBC cells, MDA-MB-157, and showed that APC loss induces PTX resistance. To understand the mechanisms behind APC-mediated PTX response, we performed cell cycle analysis and analyzed cell cycle related proteins. Cell cycle analysis indicated increased G2/M population in both PTX-treated APC shRNA1 and parental cells, suggesting that APC expression does not alter PTX-induced G2/M arrest. We further studied the subcellular localization of the G2/M transition proteins, cyclin B1 and CDK1. The APC shRNA1 cells had increased CDK1, which was preferentially localized to the cytoplasm, and increased baseline CDK6. RNA-sequencing was performed to gain a global understanding of changes downstream of APC loss and identified a broad mis-regulation of cell cycle-related genes in APC shRNA1 cells. Our studies are the first to show an interaction between APC and taxane response in breast cancer. The implications include designing combination therapy to re-sensitize APC-mutant breast cancers to taxanes using the specific cell cycle alterations.


Author(s):  
Nicole Winkler ◽  
Michael Peterson ◽  
Rachel Factor

Abstract Fibromatosis of the breast is a rare, benign locally infiltrative tumor without metastatic potential. Patients typically present with a painless, palpable, firm breast mass, which may be mobile or fixed to the pectoralis muscle. While some cases are related to familial mutations in the adenomatous polyposis coli (APC) gene, the majority are sporadic due to somatic mutations or prior injury to the breast tissue. On mammography, fibromatosis is typically seen as an irregular, dense, spiculated mass. US demonstrates a hypoechoic, irregular mass with indistinct margins. Fibromatosis is indistinguishable from breast cancer on imaging, and core biopsy is required for definitive diagnosis. Wide local excision is the historical standard for treatment; however, recurrence rates are high, and other emerging therapies are being explored. This article reviews the clinical features, imaging and histopathologic findings, along with brief overview of management.


2021 ◽  
Vol 22 (3) ◽  
pp. 197-201
Author(s):  
Kamer Tomaoğlu ◽  
Hasan Ökmen
Keyword(s):  

2021 ◽  
Author(s):  
M Grossgut ◽  
B Schaefer ◽  
A Pircher ◽  
N Baumgartner ◽  
L Obholzer ◽  
...  

Author(s):  
Mahesh Nepal ◽  
Sravani Lokineni ◽  
Le Yu Naing ◽  
Jay Bapaye ◽  
Erik Olson

Serrated polyposis syndrome (SPS) is the most common form of polyposis syndrome and has been shown to increase the risk of colorectal cancer (CRC). The genetic pathway of CRC in SPS is different from the classic adenomatous polyposis coli (APC) pathway, which accounts for 70–80% of cases of CRC. Most commonly, SPS mutations include BRAF and KRAS, with activation of the RAS-RAF-MAP kinase pathway involved in the pathogenesis of serrated lesions. We present a rare case of SPS in a 32-year-old woman with MSH6 and SMARCA4 variants, which have not previously been reported in the literature.


2021 ◽  
Vol 22 (14) ◽  
pp. 7330
Author(s):  
Hwani Ryu ◽  
Ky-Youb Nam ◽  
Hyo Jeong Kim ◽  
Jie-Young Song ◽  
Sang-Gu Hwang ◽  
...  

More than 80% of colorectal cancer patients have adenomatous polyposis coli (APC) mutations, which induce abnormal WNT/β-catenin activation. Tankyrase (TNKS) mediates the release of active β-catenin, which occurs regardless of the ligand that translocates into the nucleus by AXIN degradation via the ubiquitin-proteasome pathway. Therefore, TNKS inhibition has emerged as an attractive strategy for cancer therapy. In this study, we identified pyridine derivatives by evaluating in vitro TNKS enzyme activity and investigated N-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-1-(2-cyanophenyl)piperidine-4-carboxamide (TI-12403) as a novel TNKS inhibitor. TI-12403 stabilized AXIN2, reduced active β-catenin, and downregulated β-catenin target genes in COLO320DM and DLD-1 cells. The antitumor activities of TI-12403 were confirmed by the viability of the colorectal cancer cells and its lack of visible toxicity in DLD-1 xenograft mouse model. In addition, combined 5-FU and TI-12403 treatment synergistically inhibited proliferation to a greater extent than that in a single drug treatment. Our observations suggest that TI-12403, a novel selective TNKS1 inhibitor, may be a suitable compound for anticancer drug development.


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