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1.
Cancer Med ; 13(1): e6720, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38111983

ABSTRACT

BACKGROUND: Although adjuvant chemotherapy (ACT) is widely used to treat patients with Stage II/III colorectal cancer (CRC), administering ACT to specific patients remains a challenge. The decision to ACT requires an accurate assessment of recurrence risk and absolute treatment benefit. However, the traditional TNM staging system does not accurately assess a patient's individual risk of recurrence. METHODS: To identify recurrence risk-related genetic factors for Stage II/III CRC patients after radical surgery, we conducted an analysis of whole-exome sequencing of 47 patients with Stage II/III CRC who underwent radical surgery at five institutions. Patients were grouped into non-recurrence group (NR, n = 24, recurrence-free survival [RFS] > 5 years) and recurrence group (R, n = 23, RFS <2 years). The TCGA-COAD/READ cohort was employed as the validation dataset. RESULTS: A recurrence-predictive model (G8plus score) based on eight gene (CUL9, PCDHA12, HECTD3, DCX, SMARCA2, FAM193A, AATK, and SORCS2) mutations and tumor mutation burden/microsatellite instability (TMB/MSI) status was constructed, with 97.87% accuracy in our data and 100% negative predictive value in the TCGA-COAD/READ cohort. For the TCGA-COAD/READ cohort, the G8plus-high group had better RFS (HR = 0.22, p = 0.024); the G8plus-high tumors had significantly more infiltrated immune cell types, higher tertiary lymphoid structure signature scores, and higher immunological signature scores. The G8plus score was also a predict biomarker for immunotherapeutic in advanced CRC in the PUCH cohort. CONCLUSIONS: In conclusion, the G8plus score is a powerful biomarker for predicting the risk of recurrence in patients with stage II/III CRC. It can be used to stratify patients who benefit from ACT and immunotherapy.


Subject(s)
Colorectal Neoplasms , Microsatellite Instability , Humans , Prognosis , Colorectal Neoplasms/therapy , Colorectal Neoplasms/drug therapy , Neoplasm Staging , Biomarkers, Tumor/genetics
2.
Genome Biol ; 24(1): 247, 2023 10 30.
Article in English | MEDLINE | ID: mdl-37904244

ABSTRACT

Genomic abnormalities are strongly associated with cancer and infertility. In this study, we develop a simple and efficient method - multiple genetic abnormality sequencing (MGA-Seq) - to simultaneously detect structural variation, copy number variation, single-nucleotide polymorphism, homogeneously staining regions, and extrachromosomal DNA (ecDNA) from a single tube. MGA-Seq directly sequences proximity-ligated genomic fragments, yielding a dataset with concurrent genome three-dimensional and whole-genome sequencing information, enabling approximate localization of genomic structural variations and facilitating breakpoint identification. Additionally, by utilizing MGA-Seq, we map focal amplification and oncogene coamplification, thus facilitating the exploration of ecDNA's transcriptional regulatory function.


Subject(s)
DNA Copy Number Variations , Oncogenes , Genomics/methods , Gene Expression Regulation , DNA
3.
Opt Lett ; 48(19): 5093-5096, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37773393

ABSTRACT

A dual-wavelength DFB laser array based on four phase-shifted grating and equivalent chirp technology is first proposed, fabricated, and experimentally demonstrated. The dual-wavelength emitting is achieved by symmetrically introducing two π phase shifts into a chirped four phase-shifted sampled grating cavity. Meanwhile, the beating signal of the dual-wavelength output is stabilized by applying an electro-absorption modulator integrated at the rear of the cavity. Under different grating chirp rates, a series of RF signals from 66.8 GHz to 73.6 GHz with a linewidth of less than 210 kHz is obtained.

4.
Opt Lett ; 48(19): 5113-5116, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37773398

ABSTRACT

Integrated microring resonator structures based on silicon-on-insulator (SOI) platforms are promising candidates for high-performance on-chip sensing. In this work, a novel sidewall grating slot microring resonator (SG-SMRR) with a compact size (5 µm center radius) based on the SOI platform is proposed and demonstrated experimentally. The experiment results show that the refractive index (RI) sensitivity and the limit of detection value are 620 nm/RIU and 1.4 × 10-4 RIU, respectively. The concentration sensitivity and minimum concentration detection limit are 1120 pm/% and 0.05%, respectively. Moreover, the sidewall grating structure makes this sensor free of free spectral range (FSR) limitation. The detection range is significantly enlarged to 84.5 nm in lab measurement, four times that of the FSR of conventional SMRRs. The measured Q-factor is 3.1 × 103, and the straight slot waveguide transmission loss is 24.2 dB/cm under sensing conditions. These results combined with the small form factor associated with a silicon photonics sensor open up applications where high sensitivity and large measurement range are essential.

5.
Methods ; 218: 48-56, 2023 10.
Article in English | MEDLINE | ID: mdl-37516260

ABSTRACT

Drug repurposing, which typically applies the procedure of drug-disease associations (DDAs) prediction, is a feasible solution to drug discovery. Compared with traditional methods, drug repurposing can reduce the cost and time for drug development and advance the success rate of drug discovery. Although many methods for drug repurposing have been proposed and the obtained results are relatively acceptable, there is still some room for improving the predictive performance, since those methods fail to consider fully the issue of sparseness in known drug-disease associations. In this paper, we propose a novel multi-task learning framework based on graph representation learning to identify DDAs for drug repurposing. In our proposed framework, a heterogeneous information network is first constructed by combining multiple biological datasets. Then, a module consisting of multiple layers of graph convolutional networks is utilized to learn low-dimensional representations of nodes in the constructed heterogeneous information network. Finally, two types of auxiliary tasks are designed to help to train the target task of DDAs prediction in the multi-task learning framework. Comprehensive experiments are conducted on real data and the results demonstrate the effectiveness of the proposed method for drug repurposing.


Subject(s)
Drug Development , Drug Repositioning , Drug Discovery
6.
Opt Express ; 31(12): 20034-20048, 2023 Jun 05.
Article in English | MEDLINE | ID: mdl-37381406

ABSTRACT

We simulate and demonstrate experimentally an inner-wall grating double slot micro ring resonator (IG-DSMRR) with a center slot ring radius of only 6.72 µm based on the silicon-on-insulator platform. This novel photonic-integrated sensor for optical label-free biochemical analysis boosts the measured refractive index (RI) sensitivity in glucose solutions to 563 nm/RIU with the limit of detection value being 3.7 × 10-6 RIU (refractive index units). The concentration sensitivity for sodium chloride solutions can reach 981 pm/%, with a minimum concentration detection limit of 0.02%. Using the combination of DSMRR and IG, the detection range is enlarged significantly to 72.62 nm, three times the free spectral range of conventional slot micro ring resonators. The measured Q-factor is 1.6 × 104, and the straight strip and double slot waveguide transmission losses are 0.9 dB/cm and 20.2 dB/cm, respectively. This IG-DSMRR combines the advantages of a micro ring resonator, slot waveguide, and angular grating and is highly desirable for biochemical sensing in liquids and gases offering an ultra-high sensitivity and ultra-large measurement range. This is the first report of a fabricated and measured double-slot micro ring resonator with an inner sidewall grating structure.

7.
Biomed Opt Express ; 14(3): 1216-1227, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36950230

ABSTRACT

Quantitative detection of virus-like particles under a low concentration is of vital importance for early infection diagnosis and water pollution analysis. In this paper, a novel virus detection method is proposed using indirect polarization parametric imaging method combined with a plasmonic split-ring nanocavity array coated with an Au film and a quantitative algorithm is implemented based on the extended Laplace operator. The attachment of viruses to the split-ring cavity breaks the structural symmetry, and such asymmetry can be enhanced by depositing a thin gold film on the sample, which allows an asymmetrical plasmon mode with a large shift of resonance peak generated under transverse polarization. Correspondingly, the far-field scattering state distribution encoded by the attached virus exhibits a specific asymmetric pattern that is highly correlated to the structural feature of the virus. By utilizing the parametric image sinδ to collect information on the spatial photon state distribution and far-field asymmetry with a sub-wavelength resolution, the appearance of viruses can be detected. To further reduce the background noise and enhance the asymmetric signals, an extended Laplace operator method which divides the detection area into topological units and then calculates the asymmetric parameter is applied, enabling easier determination of virus appearance. Experimental results show that the developed method can provide a detection limit as low as 56 vp/150µL on a large scale, which has great potential in early virus screening and other applications.

8.
Opt Lett ; 48(2): 359-362, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36638457

ABSTRACT

We report, to the best of our knowledge, the first demonstration of a 1555-nm stepped-height ridge waveguide polarization mode converter monolithically integrated with a sidewall grating distributed-feedback (DFB) laser using the identical epitaxial layer scheme. The device shows stable single longitudinal mode (SLM) operation with the output light converted from TE to TM polarization with an efficiency of >94% over a wide range of DFB injection currents (IDFB) from 140 mA to 190 mA. The highest TM mode purity of 98.2% was obtained at IDFB = 180 mA. A particular advantage of this device is that only a single step of metalorganic vapor-phase epitaxy and two steps of III-V material dry etching are required for the whole integrated device fabrication, significantly reducing complexity and cost.

9.
Ann Surg ; 277(4): 557-564, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36538627

ABSTRACT

OBJECTIVE: To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia (MRF). BACKGROUND DATA: nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower-risk LARC patients with uninvolved MRF. METHODS: Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to nCT group with 4 cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported the results of secondary end points: histopathologic response, surgical events, and toxicity. RESULTS: Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathologic complete response rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm ( P =0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm ( P =0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P =0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P =0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a nonsurgical approach. Similar results were observed in subgroup analysis. CONCLUSIONS: nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.


Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Humans , Neoadjuvant Therapy/methods , Treatment Outcome , Capecitabine/therapeutic use , Rectal Neoplasms/pathology , Chemoradiotherapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Staging
10.
Pest Manag Sci ; 79(1): 55-67, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36067067

ABSTRACT

BACKGROUND: Acyrthosiphon pisum Harris is the most destructive pest worldwide because of its ability to feed on plants directly and transmit plant viruses as a vector. This study aims to identify triterpenoid saponins from Oxytropis hirta Bunge as biopesticides to control aphids. RESULTS: Three new azukisapogenol triterpenoid saponins (1-3), a new pinoresinol lignan glycoside (8), and four known saponins (4-7) were identified from the root of O. hirta. Compounds 4-7 displayed significant aphicidal activities against A. pisum with oral toxicities (LC50  = 51.10-147.43 µg/mL, 72 h), deterrent effects (deterrence index = 1.00, 100-200 µg/mL, 24 h), and aphid reproduction inhibitory effects (inhibition rates = 75.91-86.73%, 400 µg/mL, 24 h), respectively. The carboxyl groups at C-3 GlcA and C-30 were functional groups for their aphicidal activities. The toxic symptoms caused by the optimal 5 involved insect body-color changes from light green to dark or gray-green, and then brown until death. The intestinal cavity, apical microvilli, nuclei, mitochondria, and electron dense granules in the midgut tissues of A. pisum were the target sites showing aphicidal activity. The suppression of pepsin and α-amylase, and the activation of lipase and trypsin could be the signs of organelle damage in the midgut tissues. CONCLUSION: Azukisapogenol triterpenoid saponins from O. hirta could be used as biopesticides to control aphids for their multiple efficacies, including oral toxicity, deterrent activity, and reproduction inhibitory activity. The toxic symptoms involved insect body-color changes. Midgut tissues and their related enzymes were the targets for saponins showing aphicidal activities. © 2022 Society of Chemical Industry.


Subject(s)
Aphids , Oxytropis , Saponins , Animals , Aphids/drug effects , Oxytropis/chemistry , Triterpenes/chemistry , Saponins/chemistry , Saponins/pharmacology , Insecticides/chemistry , Insecticides/pharmacology
11.
Opt Lett ; 47(23): 6237-6240, 2022 Dec 01.
Article in English | MEDLINE | ID: mdl-37219216

ABSTRACT

A four-laser array based on sampled Bragg grating distributed feedback (DFB) lasers in which each sampled period contains four phase-shift sections is proposed, fabricated, and experimentally demonstrated. The wavelength spacing between adjacent lasers is accurately controlled to 0.8 nm ± 0.026 nm and the lasers have single mode suppression ratios larger than 50 dB. Using an integrated semiconductor optical amplifier, the output power can reach 33 mW and the optical linewidth of the DFB lasers can be as narrow as 64 kHz. This laser array uses a ridge waveguide with sidewall gratings and needs only one metalorganic vapor-phase epitaxy (MOVPE) step and one III-V material etching process, simplifying the whole device fabrication process, and meeting the requirements of dense wavelength division multiplexing systems.

12.
Medicine (Baltimore) ; 100(34): e27011, 2021 Aug 27.
Article in English | MEDLINE | ID: mdl-34449472

ABSTRACT

RATIONALE: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Common sites for metastasis are the liver and peritoneum, whereas skeletal muscle metastases are rare. PATIENT CONCERNS: A 59-year-old man with skeletal muscle metastasis was diagnosed during a period of adjuvant imatinib therapy following the recurrence of GIST of the small intestine. DIAGNOSIS: The patient was diagnosed with skeletal muscle metastasis of GIST based on immunohistochemistry and molecular pathology analysis results. INTERVENTION: Extensive resection of the left thigh tumor was performed. The patient underwent whole-exome sequencing of tissue examination. The results suggest that resistance to imatinib may have been developed, and the patient was therefore administered sunitinib instead. OUTCOMES: Complete remission was observed following sunitinib therapy. LESSONS: In cases of skeletal muscle metastasis diagnosed during a period of adjuvant imatinib therapy following the recurrence of a GIST of the small intestine, whole exome sequencing may be used to discover more gene variations.


Subject(s)
Gastrointestinal Neoplasms/pathology , Gastrointestinal Stromal Tumors/pathology , Muscle Neoplasms/secondary , Muscle, Skeletal/pathology , Drug Resistance, Neoplasm/genetics , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Stromal Tumors/drug therapy , Humans , Imatinib Mesylate/therapeutic use , Male , Middle Aged , Muscle Neoplasms/drug therapy , Muscle Neoplasms/surgery , Sunitinib/therapeutic use , Thigh/pathology , Exome Sequencing
13.
Pest Manag Sci ; 77(11): 5268-5277, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34310837

ABSTRACT

BACKGROUND: Tobacco mosaic virus (TMV) is a disreputable plant pathogen that causes a decline in the quality and yield of various economic crops. Natural products are important potential sources of biopesticides to control TMV. This study focuses on the discovery of anti-TMV active flavonoid glycosides and their mode of action on TMV particles from Clematis lasiandra Maxim. RESULTS: A new benzoyl acylated flavonoid glycoside, kaempferol 3-O-(2''-benzoyl)-ß-d-glucopyranosyl-7-O-α-l-rhamnopyranoside (1), and nine known flavonoids (2-10) were identified first from C. lasiandra. The hydroxyl group at C-7, E-p-coumarate at C-6'' in the Glc of C-6, and the glucuronic acid at C-3 were functional groups for the antiviral flavonoid glycosides. Flavonoids 2, 5, and 6 showed higher inactivation efficacies of 64.62% to 82.54% compared with ningnanmycin at 500 µg ml-1 . The protective and curative efficacies for 2 and 5 were 57.44-59.00% and 41.17-43.92% at 500 µg ml-1 , respectively. Compound 5 showed higher TMV systemic resistance with control efficacies of 41.64%, 36.56% and 27.62% at concentrations of 500, 250 and 125 µg ml-1 compared with ningnanmycin in K326 tobaccos, respectively. Compound 5 can directly fracture TMV particles into small fragments combining with the fusion phenomena, and TMV-CP was an important target for 5 to break TMV particles. CONCLUSION: Flavonoid glycosides from C. lasiandra showed potent antiviral activities against TMV with multiple modes of action including inactivation, protective and curative effects, and inducing systemic resistance. TMV-CP was an important target for active flavonoid glycosides to fracture TMV particles. The results provided evidence that flavonoid glycosides from C. lasiandra have the potential to control TMV.


Subject(s)
Clematis , Tobacco Mosaic Virus , Antiviral Agents/pharmacology , Flavonoids/pharmacology , Glycosides/pharmacology , Virion
14.
Opt Express ; 29(2): 1221-1231, 2021 Jan 18.
Article in English | MEDLINE | ID: mdl-33726341

ABSTRACT

Optical-matter interactions and photon scattering in a sub-wavelength space are of great interest in many applications, such as nanopore-based gene sequencing and molecule characterization. Previous studies show that spatial distribution features of the scattering photon states are highly sensitive to the dielectric and structural properties of the nanopore array and matter contained on or within them, as a result of the complex optical-matter interaction in a confined system. In this paper, we report a method for shape characterization of subwavelength nanowells using photon state spatial distribution spectra in the scattering near field. Far-field parametric images of the near-field optical scattering from sub-wavelength nanowell arrays on a SiN substrate were obtained experimentally. Finite-difference time-domain simulations were used to interpret the experimental results. The rich features of the parametric images originating from the interaction of the photons and the nanowells were analyzed to recover the size of the nanowells. Experiments on nanoholes modified with Shp2 proteins were also performed. Results show that the scattering distribution of modified nanoholes exhibits significant differences compared to empty nanoholes. This work highlights the potential of utilizing the photon status scattering of nanowells for molecular characterization or other virus detection applications.


Subject(s)
Microscopy, Polarization/instrumentation , Nanostructures/chemistry , Scattering, Radiation , Silicon Compounds/chemistry , Equipment Design , Light , Photons
15.
Nanoscale Adv ; 3(24): 6882-6887, 2021 Dec 07.
Article in English | MEDLINE | ID: mdl-36132363

ABSTRACT

A parallel four-quadrant sensing method utilizing a specially designed gold nanodot array is created for sensing virus-like particles with a sub-diffraction limit size (∼100 nm) in a wide-field image. Direct label-free sensing of viruses using multiple four-quadrant sensing channels in parallel in a wide-field view enables the possibility of high-throughput onsite screening of viruses.

16.
Medicine (Baltimore) ; 99(21): e20026, 2020 May 22.
Article in English | MEDLINE | ID: mdl-32481270

ABSTRACT

RATIONALE: Cutaneous metastases from colorectal cancer are extremely rare and generally appear several years after diagnosis or resection of the primary colorectal tumor. Although cutaneous metastasis is unusual, it often indicates a poor prognosis. PATIENT CONCERNS: We treated a 62-year-old woman with multiple cutaneous metastatic nodules on the chest, back, and armpit 7 months after resection of ascending colon cancer. DIAGNOSES: The patient was diagnosed with cutaneous metastasis of ascending colon cancer with BRAF V600E mutation. INTERVENTIONS: After 6 cycles of fluorouracil, leucovorin, oxaliplatin, cetuximab, and emurafenib, most of the metastatic lesions had begun to shrink, and no new metastases were observed. Serum tests showed that the levels of several tumor markers were decreased. OUTCOMES: The patient responded well to treatment and survived for 6.5 months after presentation with skin metastasis. LESSONS: Cutaneous metastasis of colorectal cancer with BRAF V600E mutation is a rare but important phenomenon that should not be ignored. Cutaneous metastasis of colorectal cancer frequently indicates advanced disease and poor prognosis. The SWOG 1406 program is one of the treatment options, but this needs further exploration.


Subject(s)
Adenocarcinoma/pathology , Skin Neoplasms/pathology , Skin Neoplasms/secondary , Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Fatal Outcome , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Middle Aged , Proto-Oncogene Proteins B-raf , Skin Neoplasms/drug therapy
17.
Gene ; 704: 103-112, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-30974197

ABSTRACT

Lynch syndrome (LS) is a common cancer syndrome that is inherited in an autosomal dominant manner. Its pathogenesis is thought to be closely related to germline mutations of mismatch repair (MMR) genes such as the MLH1, MSH2, PMS2 and MSH6 genes. This study identifies a Chinese family with LS clinically diagnosed according to the Amsterdam II criteria. In these patients, immuno-histochemical staining showed negative MSH6 expressions but positive MLH1, MSH2, and PMS2 expressions. In order to further explore the molecular biology of this LS family, we used targeted next-generation sequencing (NGS) and Multiplex ligation dependent probe amplification (MLPA) to identify the mutation and verify the authenticity of the mutation in 15 family members. For NGS, two panels have been used, one is of MLH1, MSH2, PMS2 and MSH6 genes, the other one is of 139 cancer genetic susceptibility genes. And for the large deletions/duplications can also be identified by NGS panel, an adjusted data analysis strategy of NGS has been used. As a result, we identified a novel heterozygous large deletion in MSH6 gene that was found to be co-segregated among affected family members. This deletion results in the loss of a 3246 bp-sized fragment in MSH6 gene exons 5-9 which represents the coding regions of the MSH6 ATPase domain. This novel mutation has yet to be documented in the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) database. This mutation resulted in MSH6 protein losing gene mismatch repair function, and further caused the microsatellite instable. We speculate that this mutation may significantly impact MMR function through impaired ATP domain function. Theoretically, this proband would likely benefit from PD-1 immune check-point blockade therapy, but conversely, we observed that tumors appeared to rapidly progress after 4 sessions of anti-PD-1 treatment. Further studies to validate the effectiveness of anti-PD-1 treatments in carriers of this mutation are necessary.


Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA-Binding Proteins/genetics , Germ-Line Mutation , Sequence Deletion , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adult , Asian People/genetics , China , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , DNA Mismatch Repair/genetics , Family , Female , Genetic Testing , Heterozygote , Humans , Male , Microsatellite Instability , Pedigree
18.
Medicine (Baltimore) ; 98(3): e14060, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30653116

ABSTRACT

RATIONALE: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract and is characterized by KIT mutations. Patientsresistant to 1st-line imatinib therapy are usually given sunitinib assecond-line treatment, which provides a median progression-free survival of 8 to 12 months. We report the 1st case of metastatic jejunum GIST with a KIT exon 11 deletion that showed complete response (CR) to sunitinib for more than 3 years. PATIENT CONCERNS: A 34-year-old man with advanced jejunum GIST was surgically treated upon initial diagnosis, and was histologically found to carry a high recurrence risk. Genetic testing revealed a KIT exon 11 deletion, and adjuvant therapy with imatinib was administered. The imatinib dose was escalated following recurrence in the abdomen, but the mass continued to grow. DIAGNOSIS: He was diagnosed with abdominal recurrence of GIST based on his medical history and histopathological results. INTERVENTION: Second-line sunitinib therapy was given. OUTCOMES: The mass disappeared, and CR was seen following 7 months of sunitinib therapy; this CR was sustained for more than 45 months. LESSONS: In cases of metastatic jejunum GIST with a KIT exon 11 deletion, sunitinib as second-line therapy can be used to achieve CR for more than 3 years.


Subject(s)
Antineoplastic Agents/administration & dosage , Gastrointestinal Stromal Tumors/drug therapy , Jejunal Neoplasms/drug therapy , Sunitinib/administration & dosage , Adult , Drug Administration Schedule , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , Exons , Gastrointestinal Stromal Tumors/genetics , Humans , Induction Chemotherapy , Jejunal Neoplasms/genetics , Male , Mutation , Proto-Oncogene Proteins c-kit/drug effects , Proto-Oncogene Proteins c-kit/genetics , Time Factors , Treatment Outcome
19.
Medicine (Baltimore) ; 96(34): e7768, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28834880

ABSTRACT

RATIONALE: Metastasis to the small intestine from a primary lung cancer is rare, and is associated with a poor prognosis. Early diagnosis of small intestine metastasis is difficult because of the low incidence of clinically apparent symptoms. PATIENT CONCERNS: Clinical data and treatment of a 59-year-old man with small intestine metastasis from primary solid subtype lung adenocarcinoma are summarized. DIAGNOSES: A man who was previously diagnosed with stage IIIA (T3N2M0) lung adenocarcinoma (solid subtype) came to our hospital for postoperative radiotherapy. Laboratory tests indicated anemia and melena. The patient was initially believed to have digestive ulcer and was treated with omeprazole, which proved to be ineffective. We conducted an abdominal computed tomography (CT) contrast scan and discovered a mass in the small intestine mass. Further positron emission tomography-computed tomography (PET-CT) imaging indicated the small intestine mass with fluorodeoxyglucose uptake. INTERVENTIONS: The patient underwent an enterectomy and anastomosis. Pathological analysis confirmed the diagnosis of small intestinal metastasis from lung cancer with concomitant mesenteric lymph node metastasis. OUTCOMES: One month after the operation, hemoglobin levels became normal, and the patient had good quality of life. However, 3 months after the operation, the patient suffered from anemia again. An abdominal CT scan indicated a new small intestine mass. Progression continued rapidly, and the patient died of hemorrhagic shock 5.5 months after the resection of the small intestine mass. LESSONS: Although uncommon, if lung cancer patients present with anemia and melena, enteric metastasis should be part of the differential diagnosis. Abdominal CT scans and PET-CT are effective for early diagnosis. The prognosis of metastatic spread of solid subtype lung adenocarcinoma to the small intestine with mesenteric lymph node metastasis is poor. Subgroups of patients benefitting from metastasectomy and more effective systemic therapy need to be further investigated.


Subject(s)
Adenocarcinoma/pathology , Anemia/etiology , Intestinal Neoplasms/complications , Intestinal Neoplasms/secondary , Lung Neoplasms/pathology , Melena/etiology , Adenocarcinoma of Lung , Humans , Middle Aged
20.
Aging (Albany NY) ; 8(9): 2023-2038, 2016 09 18.
Article in English | MEDLINE | ID: mdl-27654478

ABSTRACT

LncRNAs play critical roles in gastric cancer (GC). In this study, the expression of fourteen cancer related lncRNAs were investigated in paired tissues of 66 patients with GC, real-time RT-PCR revealed that ZFAS1 was significantly upregulated. We then examined the expression of ZFAS1 in plasmas derived from 77 GC patients before- and post-operations and 60 healthy individuals, and found that circulating ZFAS1 was also upregulated in GC patients and operation can reduce its presence in plasma. To investigate the potential mechanisms, we compared the expression of ZFAS1 in multiple gastric cell lines and one normal cell line and found that ZFAS1 was up-regulated in GC cell lines. Furthermore, circulating tumor cells (CTC) were simulated by mixing GC cells with peripheral blood. After EpCAM antibody-based cell sorting, we found that the expression of ZFAS1 was positively correlated with EMT property of CTCs. In GC patient tissue samples, we found that Twist was positively correlated with ZFAS1 by immunohistochemical staining. Taken together, our results suggested that ZFAS1 was up-regulated in both tissues and plasmas of GC patients, and may be involved in regulation of EMT in GC progression. Thus, ZFAS1 might serve as a potential diagnostic marker and/or therapeutic target for GC.


Subject(s)
Cell Proliferation/genetics , Epithelial-Mesenchymal Transition/genetics , RNA, Long Noncoding/metabolism , Stomach Neoplasms/metabolism , Up-Regulation , Cell Line, Tumor , Disease Progression , Female , Humans , Male , Middle Aged , RNA, Long Noncoding/blood , RNA, Long Noncoding/genetics , Stomach Neoplasms/blood , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Twist-Related Protein 1/genetics , Twist-Related Protein 1/metabolism
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