scholarly journals Biological characteristics of rt181T/sW172* HBV are similar among distinct genotypes

2020 ◽  
Author(s):  
Wang Huaqiang ◽  
Ai Jun ◽  
Zhang Jiajuan ◽  
Zheng Wenkai ◽  
Wang Maorong ◽  
...  
Keyword(s):  
Hbv Dna ◽  
Biological Characteristics ◽  
Wild Type ◽  
Hbv Genotypes ◽  
Mutational Pattern ◽  
Significant Difference ◽  
Positive Rate ◽  
The Impact ◽  
Type Strains ◽  
Genotype A

Abstract Background: The influence of genotypes on disease progression and clinical outcome of HBV infection is noted. The impact of HBV genotypes on rtA181T/sW172* mutation remains unclear. Patients and Methods: Clinical characteristics of 69 patients with rtA181T/sW172* mutation and 39 patients with rtA181V mutation were analyzed in this study. Fifteen serum specimens with rtA181T/sW172* mutation from different genotypes were collected for cloning and sequence analysis. HBV markers in HepG2 cells encoding different proportions of rtA181T/sW172* mutation and wild type strains were detected in genotype A, B, C and D, respectively.Results: No statistically difference was detected between rtA181T and rtA181V group regarding mean age, sex ratio, liver functions, HBV DNA load and HBeAg positive rate, except for HBsAg level (rtA181T group = 3.07±0.54 lg IU/ml vs rtA181V group = 3.29±0.43 lg IU/ml, P=0.037). Among 69 patients with rtA181T/sW172* mutation, HBV genotypes B and C accounted for 17.0% and 83.0%, respectively. The rate of genotype B was lower in rtA181T group (10.1%) than that in rtA181V group (29.7%), whereas genotype C was higher in rtA181T group (89.9%) than that in rtA181V group (70.3%). HBV rtA181T/sW172* mutant coexisted with wild type strains, accounted for 25% to 90% in all HBV strains. The distribution proportion showed no statistical difference between genotype B and C (59.2%±24.3% vs. 61.2%±19.1% , P=0.86). In transfection experiments, the level of HBV DNA was the highest for genotype B, while HBsAg was expressed in the highest level for genotype A. HBsAg and virus particle were barely detected in the supernatants of rtA181T/sW172* HBV clones in all genotypes. As the proportion of wild type HBV plasmid increased, deficiency of rt181T/sW172* mutation was complemented in all genotypes. No significant difference of the relative expression was found among distinct genotypes (P >0.05).Conclusions: HBV rtA181T/sW172* mutational pattern may be influenced by genotypes, but biological characteristics of this mutation is similar among distinct genotypes.

scholarly journals CTNI-22. RETROSPECTIVE ANALYSIS OF THE COMBINED TREATMENT OF VINCRISTINE, ACNU, CARBOPLATIN AND INTERFERON-β PLUS RADIOTHERAPY (VAC-FERON-R)IN PATIENTS WITH DIFFUSE ASTROCYTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii47-ii47
Author(s):  
Yoshiki Arakawa ◽  
Yasuhide Makino ◽  
Takeshi Kawauchi ◽  
Masaharu Tanji ◽  
Yohei Mineharu ◽  
...  
Keyword(s):  
Combined Treatment ◽  
Diffuse Astrocytoma ◽  
Wild Type ◽  
Interferon Β ◽  
Mutant Type ◽  
Who Grade ◽  
Integrated Diagnosis ◽  
Significant Difference ◽  
Favorable Clinical Outcome ◽  
The Impact

Abstract OBJECTIVE Diffuse astrocytomas are classified as WHO grade II and its median overall survival (mOS) is 10 to 11 years. The efficacy of chemoradiation in the high-risk feature has been reported. The prognosis is associated with IDH and TERT promoter (TERTp) mutations. Here, we retrospectively analyzed the patients with diffuse astrocytoma treated with vincristine, ACNU, carboplatin and interferon-β plus radiotherapy (VAC-feron-R)in our institute. PATIENTS AND METHODS Between December 2003 to January 2016, 44 patients were diagnosed as diffuse astrocytoma with integrated diagnosis of histological and molecular analysis. The average age was 43.1 years (22–71 years). They received VAC-feron-R as initial treatment in our institute. We analyzed the IDH1/2 and the TERTp mutation using Sangar sequencing and determined the 1p/19q codeletion by the fluorescence in situ hybridization or the multiplex ligation-dependent probe amplification. RESULTS Median follow-up period was 76.5 months, mPFS was 126 months, mOS did not reach, and 10-year survival rate was 60%.IDH status was determined in 29 patients, 9 mutant and 20 wild types. There was no significant difference in PFS and OS between the two groups. TERTp status was determined in 18 patients with IDH wild type, 6 mutant and 12 wild types. mPFS of patients with TERTp wild type did not reach, but that with TERTp mutant type was 34.5 months (p = 0.0356). CONCLUSION Compared with previous clinical studies, VAC-feron-R showed a favorable clinical outcome in diffuse astrocytoma. The impact of TERTp status on prognosis was identified but not IDH status in this cohort.

Clinical characteristics of KRAS mutations in NSCLC and their impact on outcomes to first-line chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7588-7588
Author(s):  
Mohit Butaney ◽  
Jennifer Porter ◽  
Neal Ian Lindeman ◽  
Pasi A. Janne ◽  
Michael S. Rabin ◽  
...  
Keyword(s):  
Smoking Status ◽  
Egfr Mutations ◽  
Limited Information ◽  
Wild Type ◽  
First Line ◽  
Kras Mutations ◽  
Response To Chemotherapy ◽  
Significant Difference ◽  
The Impact ◽  
Line Chemotherapy

7588 Background: KRAS is one of the most commonly mutated oncogenes in non-small cell lung cancer (NSCLC). While the impact of EGFR mutations and EML4-alk translocations has been well-described, there is limited information about the impact of these somatic mutations on response to chemotherapy. Methods: We retrospectively reviewed the demographics and clinical outcomes of patients with KRAS mutations and compared these to patients who were KRAS wild-type (WT). Eligible pts received 1st-line IV chemo for stage IV NSCLC at DFCI and had known information about both KRAS and EGFR status. Since the biology and impact of EGFR mutations on response to chemo is well-described, we excluded such pts from the analysis. The primary endpoint was progression-free survival (PFS) with first-line chemo; secondary endpoints included radiographic response rate (RR) and overall survival (OS). Results: Between 2/05 and 8/11, there were 63 eligible KRAS pts and 97 eligible WT pts. The groups were similar in age (median 65yrs in both groups), % female (K 62, WT 54) race (K 89% white/6% black, 5% other; WT 86% white,/6% black/8% other), histology (K 90%adeno/8% NSCLC NOS; WT 86% adeno/9%NSCLC NOS), and % of pts receiving 1/2/3 agents in 1st line (K 11/56/33; WT 18/53/30). KRAS pts were less likely to be never or light smokers (4% vs 33% for WT). Nonsmokers were more likely to harbor KRAS transition rather than transversion mutations (3 transition, 1 transversion), while the converse held for smokers (51 transversions, 8 transitions). Median PFS was similar for KRAS vs WT (K .65 vs WT 4.8 months, p=0.81). RR (29% for both groups), disease control rates (K 73% vs WT 78%), and median OS (K 13.5 vs WT 12.1 months, p=.525) were also similar. Outcomes of KRAS pts to 2nd line chemotherapy (PFS 2.2, OS 8.6) are similar to those seen for WT patients in this setting. There was no significant difference in outcomes based on gender, smoking status, drug received (pemetrexed-based vs taxane based), or specific KRAS genotype. Conclusions: Pts with KRAS mutations experience similar outcomes to standard chemotherapy as those who are wild-type for EGFR and KRAS. Going forward, these data can serve as a reference for control arms of KRAS-specific randomized trials.

scholarly journals Association of PAX3 and TMTC2 gene polymorphism with the face morphology change after excision of skin tumors

2020 ◽  
Vol 77 (6) ◽  
pp. 631-636
Author(s):  
Sasa Milicevic ◽  
Zvonko Magic ◽  
Gordana Supic ◽  
Aleksandar Jevtic ◽  
Stevo Jovandic ◽  
...  
Keyword(s):  
Skin Tumor ◽  
Human Populations ◽  
Wild Type ◽  
Tumor Excision ◽  
Pax3 Gene ◽  
Significant Difference ◽  
The Face ◽  
Suture Closure ◽  
The Impact ◽  
Face Morphology

Background/Aim. The group of genes, known as PAX (paired box), has a great role in organogenesis, as well as in maintaining the normal function of certain cells after the birth. In addition to these genes, the impact on the organogenesis, at the cellular level, has a transmembrane tetratricopeptid group of genes (TMTC). The term polymorphism in the human genome implies variations in the hereditary basis that occur in human populations, the presence of two or more different alleles of one genome in the population. The aim of the work was to determine whether there is an association of PAX3 and TMTC2 genes polymorphism with changes of the face morphology after skin tumor excision and direct suture closure. Methods. The study included 130 patients of both sexes, older than 50 years, with the medical indication for the elliptical surgical excision of the skin tumor. DNA was isolated from 5 mL of peripheral blood. Gene polymorphisms were analyzed with pre-designed single nucleotide polymorphisms (SNP) assays, by allelic discrimination method on REAL-TIME apparatus. The patients were subjected to a laser scanning preoperatively, and 7 and 90 days postoperatively, in order to obtain x, y and z coordinates of 5 cephalometric points on the face, which determined the shape of the medial cheek region. The shape of the medial cheek region, as well as the coordinates of 5 cepahlometric points, were compared among genotypes of both genes preoperatively, as well as 7 days and 90 days postoperatively. Results. A statistically significant difference in the shape of the medial cheek region between wildtype and mutant of PAX3 gene was found preoperatively, while the statistically significant difference in the shape of the medial cheek region was not found between wild-type and heterozygote, nor between wild-type and heterozygote and mutant of PAX3 gene, nor among genotypes of TMTC2 gene. Seven days and 90 days postoperatively, there were no statistically significant differences in the shape of the examined region among genotypes of both genes. Conclusion. Polymorphisms of PAX3 and TMTC2 genes are not associated with the change in the face morphology after the skin tumor excision and direct suture closure of the defect.

Alpha-Catenin Is Dispensable for Normal Hematopoietic Stem Cell Function.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1438-1438
Author(s):  
Natallia Mikhalkevich ◽  
Michael W. Becker
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Conflicts Of Interest ◽  
Fusion Product ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
Myeloid Neoplasms ◽  
Increased Risk ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 1438 Poster Board I-461 We previously demonstrated the loss of expression of alpha-E-Catenin, the product of the CTNNA1 gene, in primary leukemic stem cells isolated from patients with advanced Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) associated with loss of all or part of the long arm of chromosome 5. To formally assess the impact of loss of Ctnna1 expression on hematopoiesis, we employed a murine model for the hematopoietic specific conditional loss of Ctnna1 expression. We demonstrate that Ctnna1 deficiency is associated with normal hematopoietic maturation and proliferation as assessed by peripheral blood examination and methycellulose colony assays. We assessed stem cell and early progenitor frequencies using both flow cytometry and functional assays. Ctnna1 deficiency was associated with equivalent frequencies of Sca1+C-Kit+CD135-Lineage- HSCs in both experimental animals and controls. Short term HSC and MPP frequencies were likewise unaltered. We assessed HSC function using transplantation studies. In competitive repopulation experiments, HSCs deficient for Ctnna1 maintained stable engraftment of recipient mice for up to 1 year. Limiting dilution analyses detected no significant difference in HSC frequency between wild type and Ctnna1 deficient mice. We examined the potential role of Ctnna1 deficient hematopoietic stem cells in two murine models for myeloid neoplasms 1.) exposure to mutagen ENU and 2.) a model for murine AML driven by the HoxA9-Nup98 fusion product. Following exposure of HSCs to ENU, loss of Ctnna1 was not associated with an increased risk of development of a myeloid neoplasm. Expression of the HoxA9-Nup98 fusion product by retroviral infection of Ctnna1 deficient and wild type Sca1+C-Kit+Lineage- cells resulted in no difference in time to development of the previously characterized myeloproliferative disorder or acute leukemia. Taken together, these data demonstrate that in the absence of specific genetic abnormalities, loss of Ctnna1 expression in primary murine HSCs is not associated with aberrant HSC function or the development of myeloid neoplasms. Further studies are necessary to define a role for of loss of Ctnna1 expression in human myeloid malignancies. Disclosures No relevant conflicts of interest to declare.

scholarly journals The impact of epidermal growth factor receptor mutations on patterns of disease recurrence after chemoradiotherapy for locally advanced non–small cell lung cancer: a literature review and pooled analysis

2016 ◽  
Vol 57 (5) ◽  
pp. 449-459 ◽  
Author(s):  
Satoru Ochiai ◽  
Yoshihito Nomoto ◽  
Yui Watanabe ◽  
Yasufumi Yamashita ◽  
Yutaka Toyomasu ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Disease Recurrence ◽  
Wild Type ◽  
Mutation Status ◽  
Locally Advanced Nsclc ◽  
Significant Difference ◽  
Epidermal Growth ◽  
The Impact

Abstract The purpose of this review was to evaluate the impact of epidermal growth factor receptor (EGFR) mutation status on disease recurrence in patients treated with chemoradiotherapy (CRT) for locally advanced non–small cell lung cancer (NSCLC). A literature search was conducted and a total of three studies were analyzed. There was no significant difference in the objective response rate between the EGFR mutation group and the EGFR wild-type group (odds ratios [OR] 1.46, 95% CI, 0.79–2.70, P = 0.228), and there was no significant difference in the incidence of disease recurrence (OR 1.37, 95% CI, 0.68–2.75, P = 0.379) between the two groups. There were significant difference in the incidence of local/locoregional progression (LP) (OR 0.35, 95% CI, 0.18–0.71, P = 0.003) and distant progression (DP) (OR 2.97, 95% CI, 1.59–5.54, P < 0.001). Brain metastasis (BM) was one of the main recurrence patterns of DP, and the incidence was significantly higher in the EGFR mutant group (OR 2.75, 95% CI, 1.43–5.31, P = 0.003). There were no statistically significant heterogeneities in these pooled analyses. The patterns of recurrence after CRT for locally advanced NSCLC were different according to EGFR mutation status. LP after CRT in patients with EGFR mutation was less frequent, but the high incidence of DP, especially BM, continued to be the major problem. On the other hand, LP continued to be the major problem in EGFR wild-type patients. In multimodality treatment for inoperable locally advanced NSCLC, we may need to consider different treatment strategies according to EGFR mutation status.

scholarly journals Applicability of Endobronchial Ultrasound and Virtual Bronchoscopic Navigation Combined with Rapid On-Site Evaluation in Diagnosing Peripheral Lung Lesions

2021 ◽  
Author(s):  
Jia-Chao Qi ◽  
Liping Liao ◽  
Zhiwei Zhao ◽  
HuiXue Zeng ◽  
Tiezhu Wang ◽  
...  
Keyword(s):  
Diagnostic Yield ◽  
Endobronchial Ultrasound ◽  
Average Procedure ◽  
Procedure Time ◽  
Significant Difference ◽  
Positive Rate ◽  
Site Evaluation ◽  
Medical University ◽  
The Impact ◽  
Average Procedure Time

Abstract Background To investigate the value of endobronchial ultrasound (EBUS) and virtual bronchoscopic navigation (VBN) combined with rapid on-site evaluation (ROSE) in diagnosing peripheral pulmonary lesions (PPLs). Methods Between January 1st 2019 to September 1st 2021, EBUS and VBN examination were performed in 250 consecutive patients with PPLs who were admitted to Zhangzhou Affiliated Hospital of Fujian Medical University (Fujian, China). Finally, 198 eligible patients were randomly divided into ROSE group (100 cases) and non-ROSE group (98 cases). The diagnostic yield of brushing and biopsy, the complications, the procedure time, the diagnosis time and expense during diagnosis were analyzed. Results In the ROSE group, the positive rate of EBUS brushing and biopsy were 68%, 84%, repectively. The average procedure time and diagnosis time were 18.6 ± 6.8 min, 3.84 ± 4.28 days, repectively, and the average expense was 4093.15 ± 4494.67 yuan. In the controls, the positive rate of brushing and biopsy were 44%, 74%, repectively. The average procedure time and diagnosis time were 15.4 ± 5.7 min, 6.46 ± 3.66 days, repectively. And the average expense during diagnosis was 6420.28 ± 4541.33 yuan. There was significant difference in the positive rate of EBUS brushing and biopsy, diagnosis time and expense during diagnosis between both groups. And no significant difference was observed in the complications and the procedure time. Additionally, the impact of ROSE on diagnostic yield in right upper lobe and the size of lesion ≤2 cm in diameter was significant. Conclusion In combination with ROSE, EBUS could significantly improve the positive rate of diagnosing PPLs, shorten diagnosis time and reduce expense during diagnosis. ROSE will be of great importance in the diagnosis of PPLs and medical resource.

scholarly journals Varied Contribution of Phospholipid Shedding From Membrane to Daptomycin Tolerance in Staphylococcus aureus

2021 ◽  
Vol 8 ◽  
Author(s):  
Tianwei Shen ◽  
Kelly M. Hines ◽  
Nathaniel K. Ashford ◽  
Brian J. Werth ◽  
Libin Xu
Keyword(s):  
Staphylococcus Aureus ◽  
Wild Type ◽  
Bacterial Membranes ◽  
Strain Pair ◽  
Time Kill ◽  
The Impact ◽  
Growth Controls ◽  
Type Strains ◽  
Spent Media

It has been suggested that daptomycin can be inactivated by lipids released by Staphylococcus aureus and that this effect is antagonized by phenol soluble modulins (PSMs), which bind to the shed lipids. PSM production is regulated by the Agr system, and others have shown that loss of the Agr function enhances S. aureus survival in the presence of daptomycin. Here we assessed the impact of Agr function on daptomycin activity and lipid metabolism under various conditions. Daptomycin activity was evaluated against three sets of isogenic strain series with wild-type or dysfunctional Agr using static daptomycin time-kills over 24 h and against one strain pair using in vitro pharmacokinetic/pharmacodynamic (PK/PD) models simulating clinical daptomycin exposure for 48 h. We performed comprehensive lipidomics on bacterial membranes and the spent media to correlate lipid shedding with survival. In static time-kill experiments, two agr-deficient strains (SH1000- and USA300 LAC ΔagrA) showed improved survival for 8 h compared with their corresponding wild-type strains as seen in previous studies, but this difference did not persist for 24 h. However, four other agr-deficient strains (SH1001 and JE2 agr KOs) did not demonstrate improved survival compared to isogenic wild-type strains at any time in the time-kills. Lipidomics analysis of SH1000, SH1001, and SH1000- strains showed daptomycin exposure increased lipid shedding compared to growth controls in all strains with phosphatidylglycerols (PGs), lysylPGs and cardiolipins predominating. In the cell pellets, PGs and lysylPGs decreased but cardiolipins were unchanged with daptomycin exposure. The shed lipid profiles in SH1001 and SH1000- were similar, suggesting that the inability to resist daptomycin by SH1001 was not because of differences in lipid shedding. In the PK/PD model, the agr mutant SH1000- strain did not show improved survival relative to SH1000 either. In conclusion, inactivation of daptomycin by shed lipids may be dependent on genetic background, the specific agr mutations, or the techniques used to generate these KOs rather than the overall function of the Agr system, and its contribution to daptomycin tolerance seems to be varied, transient, and growth-condition dependent.

Frequency of KRAS mutations in female colorectal cancer (CRC) patients: Findings of a Brazilian cohort of 8,234 cases.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14101-e14101
Author(s):  
Carlos G. M. Ferreira ◽  
Mariano Zalis ◽  
Ilana Zalcberg-Renault ◽  
Martin H Bonamino ◽  
Marcos Barcelos de Pinho ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Kras Mutation ◽  
Direct Sequencing ◽  
Reference Laboratory ◽  
Wild Type ◽  
Kras Mutations ◽  
Significant Difference ◽  
Exon 1 ◽  
The Impact ◽  
Brazilian Cohort

e14101 Background: Although major advances in the last decades, there are still important gaps in our understanding of CRC carcinogenesis, particularly whether sex-linked factors play any role. Some groups, including ours, observed that KRAS mutation may be more frequent in female than male (Ferreira C.G. et al. J Clin Oncol 28: 2010 suppl abstr 3614; Uetake H. et al. J Clin Oncol 29: 2011 suppl abstr 3605). Methods: Between July 2008 and July 2011, we analyzed 8,234 consecutive patient samples sent to a reference laboratory for KRAS genotyping as a screening for cetuximab use. DNA was extracted from paraffin-embedded tissue, exon 1 was amplified by PCR and submitted to direct sequencing. Codons 12 and 13 were analyzed. Results: The median age was 59 years and well balanced according to gender with 51.9% of male and 48.1% female patients. The percentage of wild-type and mutated KRAS was 66.4 and 33.6%, respectively. Corroborating previous findings a significant difference in the percentage of mutated KRAS patients was observed between female and male (34.8% versus 32.5%, p = 0.03). However there were no differences in the distribution of any specific KRAS mutation according to gender. Among the 2,626 mutated cases, 83% were in codon 12 versus 17% in codon 13. Mutation Gly12Asp was the most common being detected in 36% of the mutated cases. Conclusions: This is one of the largest cohorts of KRAS genotyping in CRC patients. In line with previous data our present findings indicate that KRAS-mutations are more frequent in female than male. Further research is required to better address the impact of gender differences and/or hormones as potential drivers of CRC carcinogenesis.

Metastases resection after FOLFIRI-aflibercept (FA) in oxaliplatin-refractory colorectal cancer patients (ORF-CRC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 862-862 ◽  
Author(s):  
Andres J. Muñoz Martín ◽  
Silvia Garcia Adrian ◽  
Carles Pericay ◽  
Ana Ruíz ◽  
Patricia Ibeas ◽  
...  
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Real Life ◽  
Colorectal Metastases ◽  
Second Line ◽  
Surgical Mortality ◽  
Wild Type ◽  
Mortality And Morbidity ◽  
Number Of Patients ◽  
Significant Difference ◽  
The Impact

862 Background: Recent data suggest resection of colorectal metastases after second-line chemotherapy offers similar overall survival (OS) benefit compared to what described in first-line. The improvement in response rate with FA in second-line may increase the number of patients eventually undergo metastases resection. Methods: We performed a retrospective analysis of 32 patients from 26 Spanish hospitals who underwent surgical resection after FA in ORF-CRC in real-life setting. Our aim was to analyze the impact of metastases resection in different organs (liver, lung, etc.) in terms of OS and progression-free survival (PFS) and post-surgical mortality and morbidity. Results: Clinical characteristics: Median age: 65 years (43-83). Sex: 78.1% male, 21.9% female. ECOG 0/1 53.1/46.9%. Ras: wild-type/mutated 25/75%. Type of tumor: colon 75.0%, rectal 25.0%. Location: right 28.1%, transverse 9.4%, and left-side 62.5%. Previous treatment: oxaliplatin combinations (100%), bevacizumab 37.5%, cetuximab 21.97%. Ras wild-type patients received previous anti-EGFR therapy. FA in second-line 93.7% and beyond second-line 6.3%. Median FA cycles before surgery: 6.5 (range 3-44). Type of surgery: liver metastases 46.9%, lung metastases 25.0%, cytoreductive surgery for peritoneal carcinomatosis 15.6%, supraadrenalectomy 3.1%, simultaneous liver and peritoneal carcinomatosis 9.4%. Better tumor response with FA (RECIST1.1): partial response 56.3%, complete response 3.1%, stable disease 40.6%. Median follow-up: 20.9 months [m] (range 3.8-57.3 m). Median PFS from surgery: 8.0 m (confidence interval [CI] 95% 2.5-13.5 m). Median OS from surgery: 37.3 m (CI 95% 23.3-51.4 m). No significant difference between right and left-side tumors in OS or PFS were observed. 90-day postoperative mortality/morbidity: 18.8/0% Reoperation rate: 9.4%. Resection rates: R0 75.0%, R1 15.6%, R2 9.4%. Aflibercept after surgery: 22% patients. Conclusions: Metastases resection following FA in ORF-CRC offers encouraging OS with favorable surgical mortality and morbidity. Salvage surgery should be considered in highly selected patients in second-line setting with oligometastatic disease.

scholarly journals Vibrational spectroscopic analysis of hydroxyapatite in HYP mice and individuals with X-linked hypophosphatemia

2018 ◽  
Vol 9 (12) ◽  
pp. 268-281 ◽  
Author(s):  
Eva Amenta ◽  
Helen E. King ◽  
Holger Petermann ◽  
Vuk Uskoković ◽  
Steven M. Tommasini ◽  
...  
Keyword(s):  
Neutral Endopeptidase ◽  
Permanent Teeth ◽  
Wild Type ◽  
Ionic Substitution ◽  
Carbonate Ion ◽  
Physiological Properties ◽  
Significant Difference ◽  
Human Dentin ◽  
Ion Substitution ◽  
The Impact

Background: X-linked hypophosphatemia (XLH) is the most common form of familial phosphate-wasting disorders, due to an inactivating mutation in the phosphate-regulating neutral endopeptidase, X-linked gene. Persistent osteomalacia, enthesophytes, osteophytes, degenerative arthritis and dental abscesses/periodontal disease dominate the adult disorder. However, the impact of insufficient phosphate on hydroxyapatite composition, the major inorganic component of bone and teeth, is unknown in individuals with XLH. Methods: Using Raman spectroscopy, the carbonate (CO32−) to phosphate (PO43−) ion ratio was measured in HYP and wild-type mice and in primary and permanent teeth from XLH individuals and unaffected controls. Results: There was a significant difference in carbonate ion substitution between the HYP and wild-type femoral cortical bone (0.36 ± 0.08 versus 0.24 ± 0.04; p < 0.001). Carbonate ion substitution levels were also higher in permanent XLH teeth compared with unaffected individuals (0.39 ± 0.12 versus 0.23 ± 0.04; p < 0.001), but not in primary teeth (0.29 ± 0.11 versus 0.26 ± 0.02; p = 0.29). Complementary Fourier transform infrared analyses demonstrated higher relative intensities of the four major vibrational bands originating from the carbonate anion in XLH teeth compared with unaffected controls. Conclusion: Ionic substitution within the crystal lattice is a common feature of hydroxyapatite and one that confers the physiological properties of bone that impact mechanical strength and the process of bone remodeling. Our data demonstrating anionic substitution in human dentin from individuals with XLH validate the use of dentin as a proxy for bone and to better understand the molecular adaptations that occur in the biochemical milieu of XLH.

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