scholarly journals Pharmacogenetic Aspects of Type 2 Diabetes Treatment

2020 ◽  
Vol 5 (3) ◽  
pp. 13-23
Author(s):  
N. O. Pozdnyakov ◽  
I. N. Kagarmanyan ◽  
A. E. Miroshnikov ◽  
E. S. Emelyanov ◽  
A. A. Gruzdeva ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Poor Response ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Pharmacokinetic Parameters ◽  
Average Decrease ◽  
Kcnj11 Gene ◽  
Personalized Approach ◽  
A Minor ◽  
Pparγ Gene

In this article, we analyze the role of different variants of the KCNJ11, TCF7L2, SLC22A1, SLC22A3, CYP2C9, CYP2C8, PPARγ genes polymorphisms in efficacy of diabetes mellitus pharmacotherapy. T allele of the KCNJ11 rs2285676 gene polymorphism and G allele of KCNJ11 rs5218 gene polymorphism are associated with the response to IDPP-4 therapy; the presence of KCNJ11 gene rs5210 polymorphism A allele is a predictor of poor response. The effect of rs7903146 polymorphism of TCF7L2 gene was evaluated on the response to treatment of patients taking linagliptin. Linagliptin significantly reduced HbA1c levels for all three rs7903146 genotypes (CC: –0.82 %; CT: –0.77 %; TT: –0.57 %). A significantly smaller effect of therapy was observed with the genotype with ТТ. The rs622342 polymorphism of SLC22A1 gene was studied in effectiveness of metformin. The researches demonstrated that carriers of variant AA had an average decrease of HbA1c of 0.53 %, heterozygous – decrease of 0.32 %, and carriers of a minor variant of SS had an increase of 0.2 % in the level of HbA1c. A significant effect of CYP2C9 polymorphisms on the pharmacokinetic parameters of PSM was noted. When studying the kinetics of glibenclamide, it was found that carriage of the allele *2 significantly reduces glibenclamide metabolism: homozygous carriers had clearance 90 % lower than homozygous carriers of the wild variant. The studies confirmed the association of the allelic variants of Thr394Thr and Gly482Ser of PPARγ gene with higher efficacy of the rosiglitazone. The data obtained from the analysis of the association of the Pro12Ala polymorphism of PPARγ gene and the response to therapy is contradictory. Thus the personalized approach, based on the knowledge of polymorphism options, will allow choosing the most effective drug with transparent kinetics for each individual patient.

scholarly journals Primary Biliary Cholangitis: Predictors of Poor Response to Ursodeoxycholic Acid after 1 Year of Treatment in Moroccan Patients

2021 ◽  
pp. 990-995
Author(s):  
Hakima Abid ◽  
Inssaf Akoch ◽  
Maria Lahlali ◽  
Nada Lahmidani ◽  
Mounia El Yousfi ◽  
...  
Keyword(s):  
Ursodeoxycholic Acid ◽  
Biological Response ◽  
Poor Response ◽  
Overlap Syndrome ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Decompensated Cirrhosis ◽  
Primary Biliary Cholangitis ◽  
Biliary Cirrhosis ◽  
Average Value

Introduction: Primary biliary cholangitis (PBC), the new dominance of primary biliary cirrhosis, is a cholestatic disease of autoimmune etiology and represents the leading cause of intra-hepatic cholestasis. Treatment is mainly based on ursodeoxycholic acid. The biological response to treatment is the main predictor of survival without liver transplantation. The Globe-score has been recently validated as the main prognostic factor. Materials and methods: This is a retrospective study carried out in our department collating all cases of PBC followed in consultation. The aim of our work is to research the predictors of poor response to UDCA. Results: 46 patients were collected. The mean age of the patients was 58.82 years, with a predominance of women (n = 43, 93.5%). 34.78% of patients were in the stage of cirrhosis. Anti-M2 mitochondria antibodies were positive in 44 patients (95.65%). An overlap syndrome was found in 11 patients (23.9%). Treatment was based on UDCA combined with corticosteroid therapy and immunosuppressant for overlap syndrome. A biochemical response at 1 year of treatment according to the Paris II criteria was found in 47.8%. The average value of the globe score was 1.35. A score greater than 0.30 was objectified in 20 cases (43.47%). Nineteen cirrhotic patients (41.30%) had a globe score> 0.30. Factors associated with poor response to therapy were: stage of decompensated cirrhosis, elevated pre-therapy total bilirubin greater than 30 g / l and hypoalbunemia less than 35 g / l. The study of the correlation between Globe score and Paris II showed a strong and significant association with a correlation coefficient estimated at 67%. The Paris II score was significantly correlated with the response to treatment (p = 0.001). Conclusion: In accordance with the data in the literature, the globe-score and Paris II are two similar predictive means for evaluating the response at 1 year of treatment in Moroccan context. Keywords: Morocco, Predictors of response, Primary biliary cholangitis, Ursodeoxycholic acid

scholarly journals Treatment of bone pain secondary to metastases using samarium-153-EDTMP

2004 ◽  
Vol 122 (5) ◽  
pp. 208-212 ◽  
Author(s):  
Elba Cristina Sá de Camargo Etchebehere ◽  
Carlos Araújo Cunha Pereira Neto ◽  
Mariana Cunha Lopes de Lima ◽  
Allan de Oliveira Santos ◽  
Celso Darío Ramos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Lung Cancer ◽  
Bone Metastases ◽  
Bone Pain ◽  
Poor Response ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Unknown Primary ◽  
Breast And Prostate Cancer

CONTEXT: More than 50% of patients with prostate, breast or lung cancer will develop painful bone metastases. The purpose of treating bone metastases is to relieve pain, reduce the use of steroids and to maintain motion. OBJECTIVE: To evaluate the use of samarium-153-EDTMP (153Sm-EDTMP) for the treatment of bone pain secondary to metastases that is refractory to clinical management. TYPE OF STUDY: Retrospective. SETTING: Division of Nuclear Medicine, Universidade Estadual de Campinas (Unicamp). METHODS: Fifty-eight patients were studied (34 males) with mean age 62 years; 31 patients had prostate cancer, 20 had breast cancer, three had lung cancer, one had lung hemangioendothelioma, one had parathyroid adenocarcinoma, one had osteosarcoma and one had an unknown primary tumor. All patients had multiple bone metastases demonstrated by bone scintigraphy using 99mTc-MDP,and were treated with 153Sm-EDTMP. Response to treatment was graded as good (pain reduction of 50-100%), intermediate (25-49%) and poor (0-24%). RESULTS: All patients showed good uptake of 153Sm-EDTMP by bone metastases. Among the patients with prostate cancer, intermediate or good response to therapy occurred in 80.6% (25 patients) and poor response in 19.4% (6). Among the patients with breast cancer, 85% (17) showed intermediate or good response to therapy while 15% (3) showed poor response. All three patients with lung cancer showed poor response to treatment. The lung hemangioendothelioma and unknown primary lesion patients showed intermediate response to treatment; the osteosarcoma and parathyroid adenocarcinoma patients showed good response to treatment. No significant myelotoxicity occurred. DISCUSSION: Pain control is important for improving the quality of life of patients with advanced cancers. The mechanism by which pain is relieved with the use of radionuclides is still not yet completely understood, however, the treatment is simple and provides a low risk of mielotoxicity. CONCLUSION: Treatment with 153Sm-EDTMP can control the pain secondary to bone metastases effectively in most patients with breast and prostate cancer without significant side effects.

Molecular Profiling of Carcinoma of Unknown Primary and Correlation With Clinical Evaluation

2008 ◽  
Vol 26 (27) ◽  
pp. 4442-4448 ◽  
Author(s):  
Gauri R. Varadhachary ◽  
Dmitri Talantov ◽  
Martin N. Raber ◽  
Christina Meng ◽  
Kenneth R. Hess ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Poor Response ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Unknown Primary ◽  
Cancer Center ◽  
Carcinoma Of Unknown Primary ◽  
University Of Texas ◽  
Pathologic Features ◽  
Tissue Of Origin

Purpose To evaluate the feasibility of a 10-gene reverse transcriptase polymerase chain reaction assay to identify the tissue of origin in patients with carcinoma of unknown primary (CUP) site. Patients and Methods Diagnostic biopsy formalin-fixed, paraffin-embedded (FFPE) specimens from 120 patients with CUP were collected retrospectively from Sarah Cannon Research Institute, Nashville, TN, and prospectively from The University of Texas M. D. Anderson Cancer Center, Houston, TX. Tissue of origin assignments by the assay were correlated with clinical and pathologic features and with response to therapy. Results The assay was successfully performed in 104 patients (87%), and a tissue of origin was assigned in 63 patients (61%). In the remaining 41 patients (39%), the molecular profiles were not specific for the six tumor types detectable by this assay. The tissues of origin most commonly identified were lung, pancreas, and colon; most of these patients had clinical and pathologic features consistent with these diagnoses. Patients with lung and pancreas profiles had poor response to treatment. Patients with colon cancer profiles had better response to colon cancer–specific therapies than they did to empiric CUP therapy with taxane/platinum regimens. Patients with ovarian cancer profiles were atypical, with widespread visceral metastases and a paucity of overt peritoneal involvement. Conclusion This gene expression profiling assay was feasible using FFPE biopsy specimens and identified a putative tissue of origin in 61% of patients with CUP. In most patients, the assigned tissue of origin was compatible with clinicopathologic features and response to treatment. Prospective studies in which assay results are used to direct therapy are indicated.

Polymorphisms in the Promoter Region of the Mcl-1 Gene Are Associated with Ex Vivo Cytotoxicity but Not with Response to Treatment in Advanced Chronic Lymphocytic Leukemia (CLL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4991-4991
Author(s):  
Neus Villamor ◽  
Silvia Marce ◽  
Francesc Bosch ◽  
Anna Ferrer ◽  
Patricia Pérez-Galán ◽  
...  
Keyword(s):  
Promoter Region ◽  
Ex Vivo ◽  
Poor Response ◽  
Allelic Frequency ◽  
Response To Therapy ◽  
Lymphocytic Leukemia ◽  
Response To Treatment ◽  
Rna Expression ◽  
Wild Type

Abstract High levels of Mcl-1 have been related to a poor response to therapy in patients with CLL. Genetic polymorphisms in the promoter region of the Mcl-1 gene consisting in insertions of 6 (+6) or 18 (+18) bp have been described in 30% to 60% of patients with CLL. The biological and clinical translation of such polymorphisms is controversial. We have analysed this issue in a cohort of newly diagnosed patients with CLL (14 F/ 46 M; 80% in B or C Binet’s stage), treated with a combination of fludarabine (F), cyclophospamide (C) and mitoxantrone (M). Polymorphisms were correlated with: Mcl-1 RNA expression as assessed by quantitative PCR, ex vivo cytotoxicity against F, C, and M, alone or in combination, using the MTT assay, and clinical response to treatment. The frequency of the wild type (wt), +6, and +18 allel was 56%, 12%, and 32 %, respectively (table). Twenty-one of 60 (35%) patients were homozygous for wt allel. Quantification of Mcl-1 RNA expression was performed in 18 patients. Wt/wt patients (n=6) tended to have lower Mcl-1 gene expression than the remaining patients (1.0 AU ±0.4 vs 2.2 AU ±2.8). Ex vivo cytotoxicity was different according to the Mcl-1 genotypes for F, M, F+M, and C+F, but not for FCM. The highest cytotoxicity was observed in patients with +18/+18 genotype (n=7) while those with wt/wt (n=11) presented intermediate cytotoxicity and those with other genotypes (n=17) had the lowest cytotoxicity. Twenty-eight patients achieved CR, 22 PR, and 5 failed to respond. No relationship was found between Mcl-1 polymorphisms and response to therapy (table). Interestingly, however, the ex vivo response to F (58.2% ±16 vs 45.7% ±16, p=0.05) and F+M (87% ±9 vs 76% ±15.5, p=0.04) was greater in the 13 patients who achieved MRD-negative CR. After a median follow up of 28 months (range: 6–53), 16 of 38 patients have progressed. No relationship was found between Mcl-1 polymorphism and progression after treatment. In summary, in this series of patients with advanced CLL homogeneously treated the frequency of insertions in the promoter region of Mcl-1 gene was high. Although Mcl-1 polymorphisms were associated with the ex vivo response to antileukemic drugs, they did not correlate with response to treatment and disease progression. Distribution of Mcl-1 Polymorphisms and Response to Treatment Allel Allelic Frequency Genotype Patients CR (MRD- CR) wt/wt 21 (35%) 9 ( 4 ) wt 68 (56%) +6/+6 2 ( 3%) 0 ( 0 ) +18/+18 7 (12%) 4 ( 3 ) +6 14 (12%) wt/+6 6 (10%) 4 ( 2 ) wt/+18 20 (33%) 9 ( 3 ) +18 38 (32%) +6/+18 4 ( 7%) 2 ( 1 )

scholarly journals Μελέτη της απόπτωσης σε καρκίνωμα στομάχου

2015 ◽  
Author(s):  
Σουσάνα Αμπτουλάχ
Keyword(s):  
Gastric Cancer ◽  
Caspase 3 ◽  
Interleukin 1 ◽  
Stage Iv ◽  
Poor Response ◽  
Apoptotic Index ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tissue Samples

There is strong evidence that tumor growth is not only a result of uncontrolled cell proliferation but alsoof decreased apoptosis. Caspase-3 is a member of interleukin- 1 beta-converting enzyme which is involved in theinduction of apoptosis. Data on the expression of caspase-3 in patients with gastric cancer and its association with patient outcome are somewhat contradictory. We aimed to investigate the potential relation of the expression of caspase-3 protein with response to therapy and overall survival in patients with advanced noncardia gastric cancer. Tumor tissue samples collected from 359 consecutive patients with gastric cancer stage IV were retrospectively analyzed for the expression of caspase-3 in the primary tumor. The DNA apoptotic index assessed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling method. All patients were followed up until death. Caspase-3 was expressed in 43.5 % of tumors. Caspase-3 expression compared to no expression was related with a higher DNA apoptotic index (p\0.05). In multivariate analysis, tumor expression of caspase-3 was found to be an independent predictor of poor treatment response and survival (p\0.05). Expression of caspase-3 in advanced gastric cancer is a predictor of poor response to treatment and survival. Further studies are needed to fully elucidate the prognostic value of caspase-3 expression in these patients.

scholarly journals Relation of interleukin-1β gene to treatment response in chronic patients infected with HCV genotype 4

2013 ◽  
Vol 7 (11) ◽  
pp. 851-858 ◽  
Author(s):  
Moataza Hassan Omran ◽  
Noha E. Ibrahim ◽  
Samar S. Youssef ◽  
Basma E Fatouh ◽  
Wael Nabil ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Interferon Therapy ◽  
Strong Association ◽  
Response To Therapy ◽  
Interleukin 1Β ◽  
Response To Treatment ◽  
P Value ◽  
Chronic Patients ◽  
Genotype 4 ◽  
Chronic Hcv

Introduction: Hepatitis C virus (HCV) infection results in chronic hepatitis in more than 70% of infected patients, while 20-30% of patients recover spontaneously. This strengthens the role of the host genetic factors in either spontaneous or drug-induced viral clearance. The aim of this study was to investigate the relationship between interleukin-1β +3953 gene polymorphism and the response to interferon therapy in chronic HCV patients infected with genotype 4. Methodology: The interleukin-1β (+3953 C/T) (rs1143634) gene was amplified in 115 chronic HCV patients. Interleukin-1β single nucleotide polymorphism (SNP) plus several clinical and pathological factors were statistically analyzed in correlation with response to therapy. Results: Genotypes C/T and T/T had a significant association with non-response to treatment compared to genotype C/C, which had a strong association with response to treatment (95% confidence; 6.4884-48.5818, p = 0.0001). Furthermore, analysis of allele frequency in this cohort revealed that the T allele is associated with non-response, higher fibrosis, and higher hepatic activity, while the C allele had a significant association with sustained virologic response lower fibrosis, and lower hepatic activity (p value = 0.0001). Conclusion: This is the first study to examine the correlation between interleukin-1β (+3953 C/T) (rs1143634) gene polymorphism and the response of interferon therapy in genotype 4 HCV-infected patients. The results encourage further assessment of this SNP as a marker  to predict response to therapy and disease progression, which can have major implications in saving money, time, and in avoiding unnecessary adverse effects.

scholarly journals Management Of Childhood Lichen Planus

2016 ◽  
Vol 12 (1) ◽  
pp. 1-6
Author(s):  
DM Thapa ◽  
M Malathi
Keyword(s):  
Lichen Planus ◽  
Treatment Options ◽  
Poor Response ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Direct Immunofluorescence ◽  
Topical Steroids ◽  
Indian Children ◽  
Lichen Planopilaris ◽  
Oral Steroids

Childhood lichen planus (LP) is a rare entity, with less than 2–3% of all cases seen in patients under 20 years of age. LP in childhood is common in subtropical countries such as India. The most common clinical type of LP in Indian children is the classic form. Approximately 1–15% of patients with LP demonstrate nail involvement, but disease of the nails without skin involvement is rare. LP is diagnosed by historical and physical findings, biopsy results, and, in some cases, features on direct immunofluorescence (DIF). LP tends to have a chronic course. Depending on disease severity, however, LP may respond to a combination of topical or systemic therapies. The response to therapy may be similar to that seen in adults. Moderately potent or super potent steroids are the treatment of choice. Topical steroids can be combined with oral steroids in tapering doses over 2-12 weeks period. This is useful for children with widespread involvement or cutaneous LP lesions associated with significant morbidity. Intralesional steroid is effective for hypertrophic LP unresponsive to topical steroids. Topical steroids in adhesive base used several times a day for several months is a treatment of choice for symptomatic oral LP. Topical steroids in combination with systemic steroids can be given in a tapering dose over 3-6 weeks in very symptomatic cases in early stages. In severe unresponsive cases of both cutaneous and oral LP, oral retnoids are the preferred option. Treatment options for the nail LP in young children are oral steroids given as tapering dose over 4-12 weeks and oral retinoids. Intralesional steroids as nail matrix injection are the third option for older children. Most pediatric patients with LP respond to treatment with full clearance over 1-6 months. Poor response to treatment is a feature of hypertrophic LP and lichen planopilaris. DOI: http://dx.doi.org/10.3126/njdvl.v12i1.10588 Nepal Journal of Dermatology, Venereology & Leprology Vol.12(1) 2014 pp.1-6

scholarly journals Effectiveness of Injection of Trigger Points with Platelet Rich Plasma as A Pain Management Method in Rotator Cuff Syndrome: إدارة الآلام المزمنة في متلازمة الكفة المدورة بواسطة زرق نقاط التوتر بالبلازما الغنية بالصفائح الدموية

2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Hayder Ghali Algawwam, Abdullah Ahmed Mohammad
Keyword(s):  
Chronic Pain ◽  
Pain Management ◽  
Rotator Cuff ◽  
Platelet Rich Plasma ◽  
Poor Response ◽  
Trigger Points ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Significant Difference ◽  
Management Method

Objective The aim of the current study is to evaluate the effectiveness of the injection of trigger points with platelet-rich plasma as a pain management method in chronic pain resulting from rotator cuff syndrome. Methodology A retrospective study was designed for the period from August 1, 2016, until July 31, 2019, 36 patients (21 females and 15 males) visited our private clinic in Kirkuk, Iraq because of chronic shoulder pain, they received trigger points PRP injections. The PRP was prepared by centrifuging the patient's own blood. The response to therapy was graded: excellent, good, fair and poor. Results The mean age was 52.3± 1.9 years. Most of the patients (n: 33, 92%) had either overweight or obesity and (n: 16, 44.6%) had hypertension either alone or in combination with diabetes mellitus. Most of the patients (n: 30, 83.3%) received three sessions while (n: 6, 16.7%) received one session of PRP injections. Most of the patients (n: 28, 77.8%) yielded either good or excellent response to treatment, while (n: 8, 22.2%) from the patient had an either fair or poor response to treatment, there was a statistically significant difference (p˂0.01) between the 2 groups. Conclusion PRP injections of trigger points in patients complaining from chronic pain as a result of rotator cuff syndrome seem to be an effective, safe and cheap pain management method.

scholarly journals INTERNATIONAL MULTICENTER EXPERIENCE IN THE TREATMENT OF INVASIVE ASPERGILLOSIS IN IMMUNOCOMPROMISED CANCER PATIENTS

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
R. Hachem ◽  
Marjorie Batista ◽  
Souha S Kanj ◽  
Saaed El Zein ◽  
Sara Haddad ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Cancer Patients ◽  
Amphotericin B ◽  
Multivariate Logistic Regression Analysis ◽  
Poor Response ◽  
Primary Treatment ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Primary Therapy ◽  
American University

BACKGROUND: Invasive aspergillosis (IA) is a life-threatening infection in immunocompromised patients. In this study, we compared the efficacy of voriconazole containing regimen vs non-voriconazole containing regimen in patients with IA. METHODS: In this retrospective study, we reviewed the medical records of all immunocompromised cancer patients diagnosed with proven or probable IA between February 2012 and March 2018. This trial included 26 patients from the American University of Beirut,  Lebanon, 20 patients from  Hospital das Clinicas da Faculdade de Medicina, Universidade de  São Paulo, Brazil, and 10 patients from St. Luke's International Hospital Tokyo, Japan. RESULTS:  A total of 56 patients were analyzed. They were divided into 2 groups voriconazole containing regimen and non-voriconazole containing regimen (90% Amphotericin B  based regimen) . Both groups had similar characteristic, age, gender, and immunocompromised status. The majority of patients had underlying leukemia 53%, lymphoma 18%, myeloma 15% and solid tumor 13%. Antifungal primary therapy with voriconazole-containing regimen was associated with better response to treatment (P = 0.003). Survival analysis showed that primary therapy with a voriconazole containing regimen was significantly associated with improved survival (p =0.006). By multivariate logistic regression analysis, mechanical ventilation was predictor of worse outcome (poor response to therapy and increased mortality at 6 weeks), whereas primary treatment with voriconazole containing regimen was associated with improved outcome (OR=0.14; 95% CI 0.03-0.64, P=0.01). CONCLUSIONS: Based on international experience in immunocompromised cancer patients with IA, primary therapy with voriconazole-containing regimen is associated with improved response and survival compared with non-voriconazole amphotericin B based regimen.

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