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1.
Int J Biol Sci ; 20(7): 2748-2762, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38725859

RESUMEN

Abnormal nuclear enlargement is a diagnostic and physical hallmark of malignant tumors. Large nuclei are positively associated with an increased risk of developing metastasis; however, a large nucleus is inevitably more resistant to cell migration due to its size. The present study demonstrated that the nuclear size of primary colorectal cancer (CRC) cells at an advanced stage was larger than cells at an early stage. In addition, the nuclei of CRC liver metastases were larger than those of the corresponding primary CRC tissues. CRC cells were sorted into large-nucleated cells (LNCs) and small-nucleated cells (SNCs). Purified LNCs exhibited greater constricted migratory and metastatic capacity than SNCs in vitro and in vivo. Mechanistically, ErbB4 was highly expressed in LNCs, which phosphorylated lamin A/C at serine 22 via the ErbB4-Akt1 signaling pathway. Furthermore, the level of phosphorylated lamin A/C was a negative determinant of nuclear stiffness. Taken together, CRC LNCs possessed greater constricted migratory and metastatic potential than SNCs due to ErbB4-Akt1-mediated lamin A/C phosphorylation and nuclear softening. These results may provide a potential treatment strategy for tumor metastasis by targeting nuclear stiffness in patients with cancer, particularly CRC.


Asunto(s)
Neoplasias Colorrectales , Lamina Tipo A , Proteínas Proto-Oncogénicas c-akt , Receptor ErbB-4 , Transducción de Señal , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Receptor ErbB-4/metabolismo , Receptor ErbB-4/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Lamina Tipo A/metabolismo , Animales , Línea Celular Tumoral , Ratones , Núcleo Celular/metabolismo , Movimiento Celular , Masculino , Femenino , Fosforilación , Metástasis de la Neoplasia , Ratones Desnudos
3.
World J Gastrointest Surg ; 15(8): 1751-1760, 2023 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-37701694

RESUMEN

BACKGROUND: Early gastric cancer (EGC) is typically treated with endoscopic submucosal dissection (ESD). However, recurrence may occur after ESD, requiring surveillance. AIM: To examine the knowledge, attitude, and practice (KAP) of EGC survivors following ESD regarding gastric cancer recurrence. METHODS: This cross-sectional study was conducted between June 1, 2022 and October 1, 2022 in Zhejiang, China. A total of 400 EGC survivors who underwent ESD at the Affiliated Jinhua Hospital, Zhejiang University School of Medicine participated in this study. A self-administered questionnaire was developed to assess KAP monitoring gastric cancer after ESD. RESULTS: The average scores for KAP were 3.34, 23.76, and 5.75 out of 5, 30, and 11, respectively. Pearson correlation analysis revealed positive and significant correlations between knowledge and attitude, knowledge and practice, and attitude and practice (r = 0.405, 0.511, and 0.458, respectively; all P < 0.001). Multivariate logistic regression analysis showed that knowledge, attitude, 13-24 mo since the last ESD (vs ≤ 12 mo since the last ESD), and ≥ 25 mo since the last ESD (vs ≤ 12 mo since the last ESD) were independent predictors of proactive practice (odds ratio = 1.916, 1.253, 3.296, and 5.768, respectively, all P < 0.0001). CONCLUSION: EGC survivors showed inadequate knowledge, positive attitude, and poor practices in monitoring recurrences after ESD. Adequate knowledge, positive attitude, and a longer time since the last ESD were associated with practice.

4.
Aging (Albany NY) ; 15(16): 7933-7955, 2023 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-37589508

RESUMEN

Tumor oncogenesis, cancer metastasis, and immune evasion were substantially impacted by the mammalian target of the rapamycin complex 1 (mTORC1) pathway. However, in hepatocellular carcinoma (HCC), no mTORC1 signaling-based gene signature has ever been published. mTORC1 scores were computed employing a single sample gene set enrichment analysis based on databases including the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). The PAG1, LHFPL2, and FABP5 expression levels were obtained to construct a mTORC1 pathway-related model. In two databases, the overall survival (OS) rate was shorter for high-mTORC1 score patients compared to those with low scores. The activation of TFs in the group with high risk was enhanced, such as the HIF-1 pathway. Additionally, it was discovered that a high mTORC1 score was linked to an immune exclusion phenotype and enhanced immunosuppressive cell infiltration. Notably, it was discovered that high-mTORC1 scores patients had poorer immunotherapeutic results and might not gain benefit from immunotherapy. When compared to the low HCC metastatic cell lines, the high HCC metastatic cell lines have overexpressed levels of PAG1, LHFPL2, and FABP5 expression. The expression of PAG1, LHFPL2, and FABP5 was inhibited by the MAPK and mTORC1 pathway inhibitors. Our study identified mTORC1 score signature can aid in the development of individualized immunotherapy protocols and predict the HCC patients' prognoses.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Pronóstico , Carcinogénesis , Inmunoterapia , Diana Mecanicista del Complejo 1 de la Rapamicina , Proteínas de Unión a Ácidos Grasos , Proteínas de la Membrana , Proteínas Adaptadoras Transductoras de Señales
6.
Int J Biol Macromol ; 250: 126104, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37536412

RESUMEN

Since inflammatory cytokines cause stress to chondrocytes and the failure of cartilage defects repair with cartilage tissue engineering, it is necessary to develop a scaffold to maintain cartilage regeneration under inflammatory factors caused stress. Following a berberine-oleanolic acid (OA) complex salt (BOA) was grafted to hyaluronic acid (HA) to obtain water soluble BOA-g-HA, it mixed with silk fibroin (SF) to prepared 4 solutions, which contained 30 mg/mL SF and 0.75, 1.5, 2.25, and 3.0 mg/mL BOA-g-HA respectively. They were lyophilized to fabricate BOA-g-HA/SF-1, BOA-g-HA/SF-2, BOA-g-HA/SF-3, and BOA-g-HA/SF-4 composite scaffolds respectively. All prepared scaffolds displayed porous network structure and exhibited promising mechanical properties for tissue engineering applications. Among them, the BOA-g-HA/SF-3 composite scaffold showed the highest influence on maintaining chondrocytic phenotype of chondrocytes under IL-1ß induced stress. Following SF, HA/SF, and BOA-g-HA/SF-3 composite scaffolds with seeded chondrocytes were treated with IL-1ß induction for 1 week, specimens were incubated with cell culture medium for 3 week or were subcutaneously implanted into nude mice for 4 weeks. The results demonstrated that the BOA-g-HA/SF-3 composite scaffold promotes cartilage tissue regeneration in vitro and in vivo under IL-1ß caused stress, suggesting that it can be potential applied for repairing cartilage defects in osteoarthritis patients.


Asunto(s)
Berberina , Fibroínas , Ácido Oleanólico , Ratones , Animales , Humanos , Fibroínas/farmacología , Fibroínas/química , Ácido Hialurónico/farmacología , Ácido Hialurónico/química , Andamios del Tejido/química , Ácido Oleanólico/farmacología , Ratones Desnudos , Cartílago , Ingeniería de Tejidos/métodos
7.
Rev Esp Enferm Dig ; 2023 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-37350661

RESUMEN

A 25-year-old man presented with 3-day history of abdominal pain, vomiting, diarrhea, and bloody stools. The contrast-enhanced CT examination of the abdomen detected thickening and edema of intestinal canal wall. The complete colonoscopy showed hyperemia, dropsy and erosion in the sigmoid colon and rectum. The biopsies revealed obvious bleeding points in mucosa. Then, wireless capsule endoscopy (OMOM ® JS-ME-I) was carried out and showed multiple lesions in the entire small intestine with diffused hyperemia, dropsy and erosion, even multiple and large ulcers. Subsequently, symmetrical scattered purpura distributed over the extensor surfaces of the lower limbs. Hence, a firm diagnosis of adult mixed-type Henoch-Schönlein purpura (HSP) was made. With the use of methylprednisolone, the patient was recovered. The patient remained well during our follow-up.

8.
Ear Nose Throat J ; : 1455613231182661, 2023 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-37341102

RESUMEN

Objective: To compare the graft success rate and hearing outcomes of endoscopic cartilage reinforcement perichondrium-cartilage composite graft and push-through techniques for the treatment of large marginal perforations. Study Design: Randomized controlled trial. Materials and Methods: A total of 57 large marginal perforations were prospectively randomized to cartilage reinforcement (n = 29) and cartilage push-through technique (n = 28) groups. The graft success rate, audiometric outcomes, and complications were compared between the 2 groups at 6 months. Results: All patients completed 6 months of follow-up. The graft success rate in the cartilage reinforcement group was significantly higher compared to that in the push-through group (100.0% vs 78.6%, P < .01). Residual perforation was observed in 5 (17.9%) patients, and re-perforation in 1 (3.6%) patient, in the push-through group. The preoperative air-bone gap (ABG) was 17.6 ± 3.5 dB in the cartilage reinforcement group and 16.8 ± 8.4 dB in the push-through group (P > .05). Postoperatively, although the postoperative ABG in the cartilage reinforcement group was higher than that in the push-through group, no significant difference was observed (11.8 ± 4.3 dB vs 8.9 ± 2.5 dB, P > .05). Additionally, no significant difference was found in ABG closure between the 2 groups (6.6 ± 1.9 dB vs 7.9 ± 4.7 dB, P > .05). Conclusion: Cartilage reinforcement myringoplasty is a simpler and more useful technique to achieve graft success compared to cartilage-perichondrium push-through for the treatment of large marginal perforations, and it does not affect hearing levels.

9.
Plant Cell Physiol ; 64(2): 258-268, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36525532

RESUMEN

We show that the knockout of a sugar transporter gene OsSWEET15 led to a significant drop in rice fertility with around half of the knockout mutant's spikelets bearing blighted or empty grains. The rest of the spikelets bore fertile grains with a slightly reduced weight. Notably, the ovaries in the blighted grains of the ossweet15 mutants expanded after flowering but terminated their development before the endosperm cellularization stage and subsequently aborted. ß- glucuronidase (GUS) and Green Fluorescent Protein (GFP) reporter lines representing the OsSWEET15 expression showed that the gene was expressed in the endosperm tissues surrounding the embryo, which supposedly supplies nutrients to sustain embryo development. These results together with the protein's demonstrated sucrose transport capacity and plasma membrane localization suggest that OsSWEET15 plays a prominent role during the caryopsis formation stage, probably by releasing sucrose from the endosperm to support embryo development. By contrast, the empty grains were probably caused by the reduced pollen viability of the ossweet15 mutants. Investigation of ossweet11 mutant grains revealed similar phenotypes to those observed in the ossweet15 mutants. These results indicate that both OsSWEET15 and OsSWEET11 play important and similar roles in rice pollen development, caryopsis formation and seed-setting, in addition to their function in seed-filling that was demonstrated previously.


Asunto(s)
Oryza , Oryza/genética , Semillas/metabolismo , Endospermo/genética , Transporte Biológico , Glucuronidasa/metabolismo , Sacarosa/metabolismo , Proteínas de Plantas/metabolismo
10.
Cell Death Dis ; 13(7): 651, 2022 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-35896535

RESUMEN

Uneven oxygen supply in solid tumors leads to hypoxic and normoxic regions. Hypoxic cells exhibit increased secretion of lactate, which creates an acidic tumor microenvironment (TME). This acidic TME is positively associated with tumor metastasis. Despite the increased metastatic capacity of hypoxic cells, they are located relatively further away from the blood vessels and have limited access to the circulatory system. Studies have shown that cancer stem cells (CSCs) are enriched for tumor metastasis-initiating cells and generally undergo aerobic respiration, which could be enhanced by lactate. We therefore hypothesized that TME-derived lactate may promote the metastasis of normoxic CSCs. In the present study, the abundance of hypoxic and normoxic CSCs was analyzed in primary CRC tumors. It was found that the proportion of normoxic CSCs was positively associated with tumor stage. Using two human CRC cell lines, LoVo and SW480, and a patient-derived xenograft (XhCRC), it was found that treatment with lactate promoted normoxic CSC metastasis. Metabolism analysis indicated that, upon treatment with lactate, oxidative phosphorylation (OXPHOS) activity in normoxic CSCs was enhanced, whereas hypoxic CSCs were rarely altered. At the molecular level, the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of lactate oxidation, was found to be elevated in normoxic CSCs. Furthermore, PGC-1α knockdown markedly reduced the metastatic potential of normoxic CSCs. Notably, both the PGC-1α-mediated OXPHOS activity and metastatic potential were impaired when hypoxia-inducible factor-1α (HIF-1α) was activated in normoxic CSCs. Together, these findings provide a therapeutic strategy against tumor metastasis through the targeting of PGC-1α and, thus, the suppression of lactate-feeding OXPHOS in normoxic CSCs may improve the therapeutic benefit of patients with cancer, particularly CRC.


Asunto(s)
Neoplasias Colorrectales , Fosforilación Oxidativa , Línea Celular , Neoplasias Colorrectales/patología , Humanos , Hipoxia/patología , Ácido Láctico , Células Madre Neoplásicas/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Microambiente Tumoral
11.
Fish Shellfish Immunol ; 121: 305-315, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35031476

RESUMEN

Ichthyophthirius multifiliis is a protozoan ciliate that causes white spot disease (also known as ichthyophthiriasis) in freshwater fish. Holland's spinibarbel (Spinibarbus hollandi) was less susceptible to white spot disease than grass carp (Ctenopharyngodon Idella). In this study, grass carp and Holland's spinibarbel are infected by I. multifiliis and the amount of infection is 10,000 theronts per fish. All grass carp died within 12 days after infection, and the survival rate of Holland's spinibarbel was more than 80%. In order to study the difference in sensitivity of these two fish species to I. multifiliis, transcriptome analysis was conducted using gill, skin, liver, spleen and head kidney of Holland's spinibarbel and grass carp at 48 h post-infection with I. multifiliis. A total of 489,296,696 clean reads were obtained by sequencing. A total of 105 significantly up-regulated immune-related genes were obtained by Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis in grass carp. Cluster of differentiation 40 (CD40), cluster of differentiation 80 (CD 80), tumor necrosis factor-alpha (TNF-α), toll-like receptor 4 (TLR-4), interleukin 1 beta (IL-1ß) and other inflammatory-related genes in grass carp were enriched in the cytokine-cytokine receptor interaction pathway and toll-like receptor pathway. In Holland's spinibarbel, a total of 46 significantly up-regulated immune-related genes were obtained by GO classification and KEGG pathway enrichment analysis. Immune-related genes, such as Immunoglobin heavy chain (IgH), cathepsin S (CTSS), complement C1q A chain (C1qA), complement component 3 (C3) and complement component (C9) were enriched in phagosome pathway, lysosome pathway and complement and coagulation concatenation pathway. C3 was significantly up-regulated in gill and head kidney. Fluorescence in situ hybridization (FISH) showed that the C3 gene was highly expressed in gill tissue of Holland's spinibarbel infected with I. multifiliis. A small amount of C3 gene was expressed in the gill arch of grass carp after infected with I. multifiliis. In conclusion, the severe inflammatory response in vivo after infecting grass carp with I. multifiliis might be the main cause of the death of grass carp. The extrahepatic expression of the gene of Holland's spinibarbel might play an important role in the immune defense against I. multifiliis.


Asunto(s)
Carpas , Infecciones por Cilióforos , Cyprinidae , Enfermedades de los Peces , Hymenostomatida , Animales , Carpas/genética , Carpas/parasitología , Infecciones por Cilióforos/genética , Infecciones por Cilióforos/veterinaria , Cyprinidae/genética , Cyprinidae/parasitología , Enfermedades de los Peces/parasitología , Proteínas de Peces/genética , Perfilación de la Expresión Génica , Hymenostomatida/patogenicidad , Países Bajos
12.
Plant Sci ; 314: 111065, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34895534

RESUMEN

Sucrose-proton symporters play important roles in carbohydrate transport during plant growth and development. Their physiological functions have only been partly characterized and their regulation mechanism is largely unclear. Here we report that the knockout of a sucrose transporter gene, OsSUT1, by CRISPR-Cas9 mediated gene editing resulted in a slightly dwarf size and complete infertility of the gene's homozygous mutants. Observation of caryopsis development revealed that the endosperm of OsSUT1 mutants failed to cellularize and did not show any sign of seed-filling. Consistently, OsSUT1 was identified to express strongly in developing caryopsis of wild-type rice, particularly in the nucellar epidermis and aleurone which are critical for the uptake of nutrients into the endosperm. These results indicate that OsSUT1 is indispensable during the rice reproductive stage particularly for caryopsis development. Interestingly, OsSUT1 possesses at least 6 alternative splicing transcripts, including the 4 transcripts deposited previously and the other two identified by us. The differences among these transcripts primarily lie in their coding region of the 3' end and 3' UTR region. Real-time PCR showed that 4 of the 6 transcripts had different expressional patterns during rice vegetative and reproductive growth stages. Given the versatility of the gene, addressing its alternative splicing mechanism may expand our understanding of SUT's function substantially.


Asunto(s)
Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Fertilidad/genética , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Oryza/genética , Oryza/metabolismo , Sacarosa/metabolismo , Empalme Alternativo , Productos Agrícolas/genética , Productos Agrícolas/metabolismo , Grano Comestible/genética , Grano Comestible/metabolismo , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Variación Genética , Genotipo , Semillas/crecimiento & desarrollo
13.
Int J Mol Sci ; 22(20)2021 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-34681858

RESUMEN

Sugar transporters play important or even indispensable roles in sugar translocation among adjacent cells in the plant. They are mainly composed of sucrose-proton symporter SUT family members and SWEET family members. In rice, 5 and 21 members are identified in these transporter families, and some of their physiological functions have been characterized on the basis of gene knockout or knockdown strategies. Existing evidence shows that most SUT members play indispensable roles, while many SWEET members are seemingly not so critical in plant growth and development regarding whether their mutants display an aberrant phenotype or not. Generally, the expressions of SUT and SWEET genes focus on the leaf, stem, and grain that represent the source, transport, and sink organs where carbohydrate production, allocation, and storage take place. Rice SUT and SWEET also play roles in both biotic and abiotic stress responses in addition to plant growth and development. At present, these sugar transporter gene regulation mechanisms are largely unclear. In this review, we compare the expressional profiles of these sugar transporter genes on the basis of chip data and elaborate their research advances. Some suggestions concerning future investigation are also proposed.


Asunto(s)
Proteínas de Transporte de Membrana/fisiología , Oryza/fisiología , Proteínas de Plantas/fisiología , Regulación de la Expresión Génica de las Plantas , Interacciones Huésped-Patógeno/genética , Oryza/microbiología , Estrés Fisiológico/fisiología , Sacarosa/metabolismo , Azúcares/metabolismo
14.
Exp Biol Med (Maywood) ; 246(24): 2559-2569, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34514884

RESUMEN

In breast cancer, tumor-associated macrophages with activated phenotypes promote tumor invasion and metastasis. The more aggressive mesenchymal-like breast cancer cells have a selective advantage, skewing macrophages toward the more immunosuppressive subtype. However, the mechanism underlying this shift is poorly understood. Cyclin D1b is a highly oncogenic variant of cyclin D1. Our previous study showed that non-metastatic epithelial-like breast cancer cells were highly metastatic in vivo when cyclin D1b was overexpressed. The present study determined whether cyclin D1b contributed to the interaction between breast cancer cells and macrophages. The results showed that cyclin D1b promoted the invasion of breast cancer cells in vitro. Specifically, through overexpression of cyclin D1b, breast cancer cells regulated the differentiation of macrophages into a more immunosuppressive M2 phenotype. Notably, tumor cells overexpressing cyclin D1b activated macrophages and induced migration of breast cancer cells. Further investigations indicated that SDF-1 mediated macrophage activation through breast cancer cells overexpressing cyclin D1b. These results revealed a previously unknown link between aggressive breast cancer cells and Tumor-associated macrophages, and highlighted the importance of cyclin D1b activity in the breast cancer microenvironment.


Asunto(s)
Neoplasias de la Mama/patología , Ciclina D1/inmunología , Metástasis de la Neoplasia/patología , Microambiente Tumoral/inmunología , Macrófagos Asociados a Tumores/inmunología , Animales , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Ciclina D1/metabolismo , Femenino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Metástasis de la Neoplasia/inmunología , Fenotipo , Macrófagos Asociados a Tumores/metabolismo
15.
Cancer Treat Res Commun ; 25: 100211, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33113437

RESUMEN

PURPOSE: Triple-negative breast cancer (TNBC) is known for its higher recurrence rate in short-term (3-5 years) follow-up and limited systemic therapeutic methods (chemotherapy). Current literature debates over whether chemotherapy should be given to TNBC with a very early disease stage (T1a/bN0). This meta-analysis aimed to compare short-term recurrence rate between patients receiving adjuvant chemotherapy or not for this population. METHODS: We performed a comprehensive search in databases including PubMed, Web of Science, Embase, and Cochrane library from January 2008 to December 2019. Raw data on local or distance recurrence events was extracted, odds ratio (OR) values, 95% confidence interval (CI) values, and P values were then calculated. RESULTS: 9 studies out of 426 were included in the meta-analysis. Our main results showed that breast cancer recurrence rate in T1a/bN0 TNBC patients receiving chemotherapy was significantly lower than those without chemotherapy (OR 0.54, 95% CI 0.37-0.78, P = 0.001). Similar results were detected in the T1b group (OR 0.45, 95% CI 0.26-0.78). The main result remained stable after sensitivity analysis. No significant publication bias was found. CONCLUSIONS: Our results revealed that adjuvant chemotherapy reduced recurrence rate for T1mi/a/bN0 TNBC, especially for T1bN0. The benefit of chemotherapy for T1mi/aN0 disease is still debated.


Asunto(s)
Quimioterapia Adyuvante/métodos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Humanos , Recurrencia Local de Neoplasia , Neoplasias de la Mama Triple Negativas/patología
16.
Cancer Lett ; 493: 236-244, 2020 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-32898601

RESUMEN

Tumors harbor diverse compartments of cells with distinct metabolic properties and phenotypes, but the mechanism by which metabolic commensalism among distinct subsets of cancer cells affects tumor progression remains unclear. Colorectal cancer (CRC) has been reported to consist of cancer stem cells (CSCs) and differentiated cancer cells (non-CSCs). In the present study, organoid models were employed to show that CSCs and non-CSCs in CRC were characterized by distinct metabolic phenotypes. Treatment with either non-CSC-derived conditioned medium or exogenous lactate enhanced organoid-forming and tumor-initiating capacity of CSCs. In tumor regeneration assays with co-implanted CSCs and non-CSCs, the tumor-initiating activity was reduced when either monocarboxylate transporter (MCT)4 in non-CSCs or MCT1 in CSCs was silenced or inhibited. Mechanistically, oxiadative phosphorylation-derived reactive oxygen species in CSCs activated AKT-Wnt/ß-catenin signaling, which could be induced by lactate from non-CSCs. Overall, these results suggest that CSCs and non-CSCs possess distinct metabolic profiles and, unexpectedly, non-CSC-originated lactate promotes self-renewal of CSCs and thus contributes to CRC progression. Our findings establish a rationale for developing novel therapies targeting the metabolic commensalism between different cell populations in CRC.


Asunto(s)
Neoplasias Colorrectales/patología , Ácido Láctico/metabolismo , Células Madre Neoplásicas/patología , Organoides/trasplante , Animales , Diferenciación Celular , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Trasplante de Neoplasias , Células Madre Neoplásicas/metabolismo , Organoides/citología , Organoides/metabolismo , Fosforilación Oxidativa , Células Tumorales Cultivadas , Vía de Señalización Wnt
17.
Cryobiology ; 96: 45-49, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32861699

RESUMEN

Patient derived xenograft (PDX) models provide an efficient way to study anti-tumor drug efficacy. In this respect, it is essential to study the optimal method needed to cryopreserve the starting cells obtained from tumor samples for PDX model generation. Cryopreservation of cells prior to xenografting is necessary for cross-verification of results obtained by xenografting and also for practical planning of experiments. In the present work, we studied the cryopreservation of colorectal carcinoma (CRC) cells isolated from patient tumor samples for generating their patient derived xenograft models. CRC therapeutics study is essential for early stage intervention and treatment of the disease. CRC cell lines do not ideally depict the molecular characteristics of patient CRC tumor samples. This necessitates the generation of CRC PDX models for drug discovery. We show that CRC cells isolated from patient tumor samples have comparable recovery, viability and growth with both conventional cryopreservation methods as well as Fibulas BioFlash Drive™. However, xenograft tumor formation was much more effective with Fibulas BioFlash Drive™ cryopreserved cells than with cells cryopreserved with conventional methods. Therefore, we put forward an effective way to cryopreserve primary cells obtained from patient tumor samples for PDX model generation in this study.


Asunto(s)
Neoplasias Colorrectales , Criopreservación , Animales , Neoplasias Colorrectales/tratamiento farmacológico , Criopreservación/métodos , Composición Familiar , Xenoinjertos , Humanos , Ensayos Antitumor por Modelo de Xenoinjerto
18.
Cell Death Dis ; 11(7): 610, 2020 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-32737283

RESUMEN

Tumor heterogeneity is an important feature of malignant tumors, and cell subpopulations may positively interact to facilitate tumor progression. Studies have shown that hypoxic cancer cells possess enhanced metastatic capacity. However, it is still unclear whether hypoxic cancer cells may promote the metastasis of normoxic cells, which have greater access to the blood circulation. When cocultured with hypoxic CRC cells or treated with hypoxic CRC cell-derived CM, normoxic CRC cells possessed increased metastatic capacity. Furthermore, hypoxic CRC cell-derived CM was enriched in interleukin 8. Hypoxic CRC cell-derived CM and recombinant human IL-8 both enhanced the metastatic capacity of normoxic cells by increasing the phosphorylation of p65 and then by inducing epithelial-mesenchymal transition. Knockdown of IL-8 in hypoxic CRC cells or the use of an anti-IL-8 antibody attenuated the CM- or rhIL-8-induced prometastatic capacity of normoxic CRC cells. Inhibition or knockdown of p65 abrogated IL-8-induced prometastatic effects. Most importantly, hypoxia-treated xenograft tumors enhanced the metastasis of normoxic CRC cells. Hypoxic CRC cell-derived IL-8 promotes the metastatic capacity of normoxic cells, and novel therapies targeting the positive interactions between hypoxic and normoxic cells should be developed.


Asunto(s)
Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Interleucina-8/metabolismo , Transducción de Señal , Factor de Transcripción ReIA/metabolismo , Hipoxia Tumoral , Hipoxia de la Célula , Línea Celular Tumoral , Humanos , Invasividad Neoplásica , Metástasis de la Neoplasia , Comunicación Paracrina
19.
Medicine (Baltimore) ; 99(22): e20511, 2020 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-32481473

RESUMEN

BACKGROUND AND PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) usually experience recurrent acute exacerbations. These patients, especially those with stable COPD, require an effective intervention for treating exacerbations. This study aimed to evaluate the efficacy of Compound Caoshi silkworm granules (CCSGs) in stable COPD patients and to investigate their potential mechanism. METHODS: A randomized controlled trial was performed at Jinhua Hospital, Zhejiang University. Patients were enrolled in this study if they met the criterion of stable COPD. A total of 40 patients were randomly divided into the following 2 groups: Group A (n = 20, routine treatment (RT) group) and Group B (n = 20, RT plus CCSGs [RT plus CCSGs] group). The duration of treatment was 3 months. Stool samples were collected from all patients on day 0 and the gut microbiota was analyzed using 16s rRNA sequencing. The St. George's Respiratory Questionnaire (SGRQ) scores and lung function were assessed at month 0 and month 3. RESULTS: The components of gut microbiota differed between stable COPD patients and the healthy population. The RT plus CCSGs group showed improved SGRQ scores compared to the RT group. There was no difference in forced expiratory volume-one second, forced vital capacity, and forced expiratory volume-one second/forced vital capacity between the two groups. Furthermore, the abundance of gut microbiota in patients with the top 10 SGRQ scores (Group N) differed from the abundance of gut microbiota in those with the lowest 10 SGRQ scores (Group T). CONCLUSION: CCSGs have beneficial effects in the improvement of symptoms in stable COPD patients over a 3-month treatment period. The potential underlying mechanism may be attributable to the difference in gut microbiota among patients. However, more research is needed to confirm this conclusion.


Asunto(s)
Bombyx , Microbioma Gastrointestinal , Proteínas de Insectos/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Adulto , Anciano , Anciano de 80 o más Años , Animales , Femenino , Humanos , Masculino , Pruebas de Función Respiratoria
20.
World J Clin Cases ; 8(4): 798-805, 2020 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-32149063

RESUMEN

BACKGROUND: Mesenteric phlebosclerosis (MP) is a rare disease of the colon. The clinical manifestations of this disease are nonspecific and it may easily be misdiagnosed. We report a case of MP with amyloidosis in the colonic vessel walls in a patient with hypertension who had been consuming Chinese medicinal liquor for 10 years. We also review the relevant literature and summarize the characteristics of MP in patients in mainland China. CASE SUMMARY: A 64-year-old man was referred to our department from his primary hospital because of abdominal pain, diarrhea, and fever for almost 10 d. Computed tomography showed colon wall thickening, with threadlike calcifications in the mesenteric vein in the transverse colon. Colonoscopy revealed purple-blue mucosa with multiple ulcers in the ascending and transverse colon. Biopsy showed thickening and calcification of the vein walls, perivascular and mucosal collagen degeneration, and amyloidosis. The patient had been consuming Chinese medicinal liquor, mainly that made from gardenia fruit, for 10 years. Based on these results, a diagnosis of MP with amyloidosis was made. After conservative treatment, the patient's discomfort subsided and he was followed closely. The use of Chinese herbal medicine was suspected to play a role in the pathogenesis of MP. CONCLUSION: The clinical manifestations of MP are nonspecific. Recognition of its typical imaging findings, including multiple calcifications on computed tomography and purple-blue mucosal discoloration on colonoscopy, is vital.

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