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1.
Ann Oncol ; 34(6): 531-542, 2023 06.
Article in English | MEDLINE | ID: mdl-37062416

ABSTRACT

BACKGROUND: In high-risk hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC), nanoparticle albumin-bound (nab)-paclitaxel showed promising efficacy versus solvent-based (sb)-paclitaxel in neoadjuvant trials; however, optimal patient and therapy selection remains a topic of ongoing research. Here, we investigate the potential of Oncotype DX® recurrence score (RS) and endocrine therapy (ET) response (low post-endocrine Ki67) for therapy selection. PATIENTS AND METHODS: Within the WSG-ADAPT trial (NCT01779206), high-risk HR+/HER2- EBC patients were randomized to (neo)adjuvant 4× sb-paclitaxel 175 mg/m2 q2w or 8× nab-paclitaxel 125 mg/m2 q1w, followed by 4× epirubicin + cyclophosphamide (90 mg + 600 mg) q2w; inclusion criteria: (i) cN0-1, RS 12-25, and post-ET Ki67 >10%; (ii) cN0-1 with RS >25. Patients with cN2-3 or (G3, baseline Ki67 ≥40%, and tumor size >1 cm) were allowed to be included without RS and/or ET response testing. Associations of key factors with pathological complete response (pCR) (primary) and survival (secondary) endpoints were analyzed using statistical mediation and moderation models. RESULTS: Eight hundred and sixty-four patients received neoadjuvant nab-paclitaxel (n= 437) or sb-paclitaxel (n = 427); nab-paclitaxel was superior for pCR (20.8% versus 12.9%, P = 0.002). pCR was higher for RS >25 versus RS ≤25 (16.0% versus 8.4%, P = 0.021) and for ET non-response versus ET response (15.1% versus 6.0%, P = 0.027); no factors were predictive for the relative efficacy of nab-paclitaxel versus sb-paclitaxel. Patients with pCR had longer distant disease-free survival [dDFS; hazard ratio 0.42, 95% confidence interval (CI) 0.20-0.91, P = 0.024]. Despite favorable prognostic association of RS >25 versus RS ≤25 with pCR (odds ratio 3.11, 95% CI 1.71-5.63, P ≤ 0.001), higher RS was unfavorably associated with dDFS (hazard ratio 1.03, 95% CI 1.01-1.05, P = 0.010). CONCLUSIONS: In high-risk HR+/HER2- EBC, neoadjuvant nab-paclitaxel q1w appears superior to sb-paclitaxel q2w regarding pCR. Combining RS and ET response assessment appears to select patients with highest pCR rates. The disadvantage of higher RS for dDFS is reduced in patients with pCR. These are the first results from a large neoadjuvant randomized trial supporting the use of RS to help select patients for neoadjuvant chemotherapy in high-risk HR+/HER2- EBC.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Epirubicin/therapeutic use , Neoadjuvant Therapy/methods , Solvents/therapeutic use , Ki-67 Antigen , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Paclitaxel/therapeutic use , Albumins/therapeutic use , Cyclophosphamide/therapeutic use , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism
2.
J Oncol Pharm Pract ; 27(7): 1766-1769, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33427037

ABSTRACT

INTRODUCTION: Kaposi sarcoma (KS) is an angioproliferative malignancy associated with HHV-8. It is mostly observed in patients affected by HIV and/or chronic immunosuppression, while classic KS without underlying immunosuppression are relatively rare. Systemic chemotherapy is used for advanced diseases, although there is no consensus in treatment algorithms. With the demonstration of PD-1 expression in KS, immune-checkpoint-inhibitors (ICI) emerged as possible treatment options. Notwithstanding, the data of ICIs is limited to case reports/series. Herein, we present a case of advanced classic KS, which has been treated successfully with nivolumab. CASE REPORT: 82-year-old male patient was investigated for erythematous lesions on thigh. Punch biopsy lead to KS diagnosis. Abdominal CT showed lymphadenopathies in the inguinal region. After radiotherapy follow-up, patient had shown vertebral & gastric metastases. Because of the PSA elevation patient was diagnosed with prostatic adenocarcinoma. Metastases were investigated for origin. The lesions showed no uptake in Ga-68 PET-CT, therefore accepted as KS metastases. Patient rejected chemotherapy options and consented to immunotherapy trial.Management and outcome: Nivolumab was initiated 3 mg/kg bi-weekly with 12-dose protocol. After nivolumab patient wellbeing is improved and control endoscopy shown no metastases. With these findings patient has been assessed as complete response. DISCUSSION: ICI on KS is still a blurred option to be included in standard regimens; but progressive understanding of PD-1 expression and its role in disease progression may be a milestone for further treatment algorithms on KS. Besides good efficacy, tolerability of ICIs could be helpful patients with comorbidities precluding the use of chemotherapy.


Subject(s)
Gallium Radioisotopes , Sarcoma, Kaposi , Aged, 80 and over , Humans , Immunotherapy , Male , Positron Emission Tomography Computed Tomography , Sarcoma, Kaposi/drug therapy
3.
BJOG ; 127(7): 859-865, 2020 06.
Article in English | MEDLINE | ID: mdl-32037645

ABSTRACT

OBJECTIVE: To evaluate the feasibility and effect of mesureteral preservation on urinary complications in the context of total mesometrial resection (TMMR), a surgical treatment for cervical cancer. DESIGN: Retrospective cohort study with historic control. SETTING: Single tertiary academic centre. POPULATION: Women older than 18 with primary cervical cancer staged FIGO IB1-IIB enrolled in the prospective Leipzig School MMR study and underwent total mesometrial resection (TMMR) without adjuvant radiation. METHOD: We retrospectively analysed 100 consecutive TMMR procedures which were performed for cancer of the uterine cervix and in which the mesureter was preserved (intervention group, 01/2014-06/2017). We compared this group with the previous 100 consecutive TMMRs, which were performed before the introduction of mesureteral preservation (control group, 09/2010-01/2014). MAIN OUTCOME MEASURES: The occurrence of urological and specifically ureteral complications. RESULTS: Mesureteral preservation was feasible and was associated with a significant decrease in ureteral complications (11% without mesureteral preservation versus 3% with mesureteral preservation, P = 0.049). Furthermore, we found a significant decrease in the number of postoperative percutaneous nephrostomies and re-operations (7% versus none, P = 0.014). There was also a trend towards a decrease in other urinary complications such as postoperative bladder atony and uretero-vaginal fistulas. CONCLUSION: The mesureter constitutes a convenient dissection plane enabling the preservation of lateral ureteral blood supply during TMMR. In our study, maintenance of mesureteral integrity was associated with a significant reduction in ureteral complications. Mesureteral preservation might also be useful in other types of pelvic surgeries that carry a high risk of ureteral damage. TWEETABLE ABSTRACT: Surgical preservation of the mesureter in cervical cancer patients was associated with a reduction in urinary complications.


Subject(s)
Intraoperative Complications/prevention & control , Mesentery/surgery , Organ Sparing Treatments/methods , Pelvic Exenteration , Postoperative Complications , Ureter/injuries , Ureteral Obstruction , Uterine Cervical Neoplasms , Female , Germany/epidemiology , Humans , Hysterectomy/adverse effects , Hysterectomy/methods , Lymph Node Excision/adverse effects , Lymph Node Excision/methods , Middle Aged , Neoplasm Staging , Organs at Risk , Outcome and Process Assessment, Health Care , Pelvic Exenteration/adverse effects , Pelvic Exenteration/methods , Postoperative Complications/diagnosis , Postoperative Complications/prevention & control , Ureteral Obstruction/diagnosis , Ureteral Obstruction/etiology , Ureteral Obstruction/prevention & control , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgery
4.
Eur J Cancer ; 117: 91-98, 2019 08.
Article in English | MEDLINE | ID: mdl-31276981

ABSTRACT

BACKGROUND: Randomised trials comparing the efficacy of standard endocrine therapy (ET) versus experimental ET + bevacizumab (Bev) in 1st line hormone receptor-positive patients with metastatic breast cancer have thus far shown conflicting results. PATIENTS AND METHODS: We pooled data from two similar phase III randomised trials of ET ± Bev (LEA and Cancer and Leukemia Group B 40503) to increase precision in estimating treatment effect. Primary end-point was progression-free survival (PFS). Secondary end-points were overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety. Exploratory analyses were performed within subgroups defined by patients with recurrent disease, de novo disease, prior endocrine sensitivity or resistance and reported grades III-IV hypertension and proteinuria. RESULTS: The pooled sample consisted of 749 patients randomised to ET or ET + Bev. Median PFS was 14.3 months for ET versus 19 months for ET + Bev (unadjusted hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.66-0.91; p < 0.01). ORR and CBR with ET and ET + Bev were 40 versus 61% (p < 0.01) and 64 versus 77% (p < 0.01), respectively. There was no difference in OS (HR 0.96; 95% CI 0.77-1.18; p = 0.68). PFS was superior for ET + Bev for endocrine-sensitive patients (HR 0.68; 95% CI 0.53-0.89; p = 0.004). Grade III-IV hypertension (2.2 versus 20.1%), proteinuria (0 versus 9.3%), cardiovascular (0.5 versus 4.2%) and liver events (0 versus 2.9%) were significantly higher for ET + Bev (all p < 0.01). Hypertension and proteinuria were not predictors of efficacy (interaction test p = 0.33). CONCLUSION: The addition of Bev to ET increased PFS overall and in endocrine-sensitive patients but not OS at the expense of significant additional toxicity. TRIALS REGISTRATION: ClinicalTrial.Gov NCT00545077 and NCT00601900.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Neoplasms/drug therapy , Breast Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Soft Tissue Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Bevacizumab/administration & dosage , Bone Neoplasms/metabolism , Bone Neoplasms/secondary , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Evaluation Studies as Topic , Female , Follow-Up Studies , Fulvestrant/administration & dosage , Humans , Letrozole/administration & dosage , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Prognosis , Soft Tissue Neoplasms/metabolism , Soft Tissue Neoplasms/secondary , Survival Rate , Tamoxifen/administration & dosage
5.
Cancer Chemother Pharmacol ; 83(1): 131-143, 2019 01.
Article in English | MEDLINE | ID: mdl-30377778

ABSTRACT

PURPOSE: In this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients. METHODS: This study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers. RESULTS: Median age was 51 (22-82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure. CONCLUSIONS: Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/mortality , Carcinoma, Ductal, Breast/mortality , Carcinoma, Lobular/mortality , Practice Patterns, Physicians' , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/secondary , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/secondary , Docetaxel/administration & dosage , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Invasiveness , Neoplasm Metastasis , Paclitaxel/administration & dosage , Prognosis , Retrospective Studies , Survival Rate , Trastuzumab/administration & dosage , Young Adult
7.
Ann Oncol ; 28(3): 497-504, 2017 03 01.
Article in English | MEDLINE | ID: mdl-27831502

ABSTRACT

Background: The neoadjuvant phase III GeparSepto study showed that substituting nab-paclitaxel for standard solvent-based paclitaxel significantly improved the pathologic complete response (pCR) rate achieved with a sequential neoadjuvant chemotherapy regimen of paclitaxel, epirubicin, and cyclophosphamide for high-risk primary breast cancer. Recent trials demonstrated that in HER2+ breast cancer pCR can be increased by using pertuzumab in addition to trastuzumab and chemotherapy. The present analysis focuses on efficacy and safety data from the subset of patients with HER2+ tumors from the GeparSepto trial (n = 396) in comparison to the HER2- cohort. Patients and methods: Patients with histologically confirmed breast cancer (n = 1206) received four cycles of weekly paclitaxel [either solvent-based (Pac) or nab-paclitaxel (nab-Pac), according to randomization] followed by 4 cycles of epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 q3w, with concurrent trastuzumab and pertuzumab q3w for those with HER2+ tumors. The primary endpoint was pCR defined as ypT0 ypN0. Results: Higher rates of pCR were achieved in HER2+ than in HER2- tumors (57.8% versus 22.0%, P < 0.0001), with the highest rate in the HER2+/HR- cohort (71.0%; 66.7% Pac, 74.6% nab-Pac). In HER2+/HR+ tumors, the pCR rate was 52.9% (49.7% Pac, 56.4% nab-Pac). Grade ≥3 toxic effects were significantly more common in HER2+ than in HER2- patients, with grade 3-4 diarrhea in 7.6% versus 0.9% (P < 0.001) and febrile neutropenia in 6.3% versus 3.3% (P = 0.023) of patients. Left ventricular ejection fraction decreases from baseline were uncommon, with 2.0% versus 0.4% of patients showing decreases to <50% along with a ≥10% decrease from baseline. Conclusion: In HER2+ early breast cancer, a dual HER2-targeted combination of pertuzumab and trastuzumab, together with taxane-epirubicin-cyclophosphamide neoadjuvant chemotherapy, achieved high rates of pCR.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Receptor, ErbB-2/antagonists & inhibitors , Aged , Albumins/administration & dosage , Anthracyclines/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Paclitaxel/administration & dosage , Receptor, ErbB-2/genetics , Trastuzumab/administration & dosage
8.
Rev Sci Instrum ; 87(10): 106103, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27802690

ABSTRACT

This article is focused on a novel and practical production method for a uniform magnetic field generator. The method involves building of a surface coil template using a desktop 3D printer and winding of a conducting wire onto the structure using surface grooves as a guide. Groove pattern was based on the parametric spheroidal helical coil formula. The coil was driven by a current source and the magnetic field inside was measured using a Hall probe placed into the holes on the printed structure. The measurements are found to be in good agreement with our finite element analysis results and indicate a fairly uniform field inside.

9.
Front Immunol ; 7: 283, 2016.
Article in English | MEDLINE | ID: mdl-27499755

ABSTRACT

The integrated endoplasmic reticulum stress response (IERSR) is an evolutionarily conserved adaptive mechanism that ensures endoplasmic reticulum (ER) homeostasis and cellular survival in the presence of stress including nutrient deprivation, hypoxia, and imbalance of Ca(+) homeostasis, toxins, and microbial infection. Three transmembrane proteins regulate integrated signaling pathways that comprise the IERSR, namely, IRE-1 that activates XBP-1, the pancreatic ER kinase (PERK) that phosphorylates the eukaryotic translation initiation factor 2 and transcription factor 6 (ATF6). The roles of IRE-1, PERK, and ATF4 in viral and some bacterial infections are well characterized. The role of IERSR in infections by intracellular parasites is still poorly understood, although one could anticipate that IERSR may play an important role on the host's cell response. Recently, our group reported the important aspects of XBP-1 activation in Leishmania amazonensis infection. It is, however, necessary to address the relevance of the other IERSR branches, together with the possible role of IERSR in infections by other Leishmania species, and furthermore, to pursue the possible implications in the pathogenesis and control of parasite replication in macrophages.

10.
Acta Gastroenterol Belg ; 79(2): 216-21, 2016.
Article in English | MEDLINE | ID: mdl-27382941

ABSTRACT

BACKGROUD AND STUDY AIM: The role of immunoglobulin (Ig) G4 in the etiopathogenesis of inflammatory bowel disease (IBD) and its association with endoscopic and pathological activity are not yet completely understood. The purpose of this study was to determine the possible relationship between IgG4 status and IBD. PATIENTS AND METHODS: Endoscopic colon biopsies of 55 patients with ulcerative colitis (UC) and of 17 patients with Crohn's disease (CD) were examined. Numbers of IgG4-positive plasma cells stained immunohistochemically were counted in a minimum of 5 high power fields (HPFs) for each specimen. The presence of > 10 cells/HPF IgG4-positive PCs was considered positive. RESULTS: he prevalence of IgG4-positive plasma cells in the lamina propria of the colonic mucosa was significantly higher in patients with UC than in those with CD (p :0.01). Additionally, the prevalence of IgG4-positive plasma cells increased in line with endoscopic and pathological activity in UC patients. Conversely, we determined no significant correlation between IgG4 positivity and pathological activity in the CD group. IgG4-positive UC patients also exhibited findings of more severe disease compared to IgG4-negative UC patients. CONCLUSION: Immunohistochemical IgG4 staining may predict disease severity in UC and may be a useful marker for distinguishing between UC and CD.


Subject(s)
Colitis, Ulcerative/metabolism , Colon/metabolism , Crohn Disease/metabolism , Immunoglobulin G/metabolism , Intestinal Mucosa/metabolism , Plasma Cells/metabolism , Adult , Aged , Biopsy , Colitis, Ulcerative/immunology , Colitis, Ulcerative/pathology , Colon/immunology , Colon/pathology , Crohn Disease/immunology , Crohn Disease/pathology , Female , Humans , Immunoglobulin G/immunology , Immunohistochemistry , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/pathology , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Male , Middle Aged , Plasma Cells/immunology , Severity of Illness Index
11.
Eur J Cancer Care (Engl) ; 25(3): 502-15, 2016 May.
Article in English | MEDLINE | ID: mdl-25828949

ABSTRACT

In this study, we aimed to determine the personal, social and economic burden and the frequency of depression, as well as in caregivers of cancer patients who are being treated with chemotherapy in Turkey. The study is designed as a cross-sectional survey study using a 5-point Likert-type response scale, and the last part of the questionnaire includes the Beck Depression Inventory. The depression rate was found to be 64% (n = 476) among all subjects (n = 968), with 91% of those with depression demonstrating signs of mild depression. In this study, a significant difference was found between the presence of depression and age (young), sex (female), educational level (high), economic status (low), financial loss during treatment, patient's lack of knowledge about his/her diagnosis, metastatic disease and short survival time. In addition, 64% of all subjects had concerns of getting cancer, and 44% of all subjects had feelings of anger/rage against other people. In a multivariate regression analysis, the patient's lack of knowledge of the diagnosis was the independent risk factor. In conclusion, depression incidence and burden rate increased among cancer caregivers, and care burden was highly associated with depression. Accordingly, approaches to reducing the psycho-social effects of cancer should focus intensively on both the patients and their caregivers in Turkey.


Subject(s)
Caregivers/psychology , Depressive Disorder/etiology , Neoplasms/psychology , Adolescent , Adult , Aged , Cancer Care Facilities , Cost of Illness , Cross-Sectional Studies , Emotions , Female , Humans , Male , Middle Aged , Neoplasms/drug therapy , Palliative Care/psychology , Pilot Projects , Socioeconomic Factors , Turkey , Young Adult
12.
Andrologia ; 48(5): 532-5, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26302884

ABSTRACT

This study measured the serum folic acid (FA) level in patients with erectile dysfunction (ED) and evaluated the possible association between the serum FA level and erectile function. The study divided 120 patients with ED into 3 groups of 40 patients each: those with severe, moderate and mild ED. Forty healthy men served as controls. Fasting serum samples were obtained, and the total testosterone, cholesterol and FA levels were measured using chemiluminescent immunoassays. There were no significant differences in the mean age, mean body mass index or mean serum total testosterone and cholesterol levels among the three ED groups and controls (P > 0.05). The mean serum FA concentrations were 7.2 ± 3.7, 7.1 ± 3.2, 10.2 ± 4.6 and 10.7 ± 4.6 ng ml(-1) in the severe, moderate and mild ED and control groups respectively. The mean serum FA concentration was significantly higher in the control group than in the severe and moderate ED groups (both P < 0.001), but not the mild ED group (P = 0.95). Considering the significant differences in the serum FA levels between the control and ED groups, serum FA deficiency might reflect the severity of ED.


Subject(s)
Erectile Dysfunction/blood , Folic Acid/blood , Adult , Aged , Case-Control Studies , Cholesterol/blood , Erectile Dysfunction/etiology , Erectile Dysfunction/physiopathology , Folic Acid Deficiency/blood , Folic Acid Deficiency/complications , Folic Acid Deficiency/physiopathology , Humans , Male , Middle Aged , Severity of Illness Index , Testosterone/blood
13.
Andrologia ; 48(7): 787-92, 2016 Sep.
Article in English | MEDLINE | ID: mdl-26685713

ABSTRACT

Recent studies have shown that ED is an early symptom of atherosclerosis. Fetuin-A, a glycoprotein secreted by the liver, kidneys and choroid plexus, has been linked to systemic fibrosis and calcification in human and rat studies. Deficiency of this compound may play a role in atherosclerosis and cardiovascular disease progression. The aim of the study was to examine whether serum fetuin-A level is related to erectile function or severity of ED. Sixty ED patients without cardiovascular disease were assigned to one of the three groups (mild, moderate or severe ED) depending on ED severity. Twenty healthy volunteers were included as the control group. The International Index of Erectile Function-5 questionnaire was used to measure erection quality in all four groups. Mean age, body mass index, total testosterone, low- and high-density lipoprotein cholesterol, and triglyceride levels did not significantly differ between the three erectile dysfunction and control groups (P > 0.05). The group with severe ED had a significantly lower mean fetuin-A level than the mild ED and control groups. For both mild and moderate ED groups, the mean serum fetuin-A level was significantly lower in comparison with the control group (P < 0.001). Serum fetuin-A level may be used as a supplemental biochemical parameter in preliminary evaluation of ED.


Subject(s)
Erectile Dysfunction/blood , Erectile Dysfunction/diagnosis , alpha-2-HS-Glycoprotein/analysis , Adult , Animals , Healthy Volunteers , Humans , Male , Middle Aged , Risk Factors , Surveys and Questionnaires
14.
Dalton Trans ; 44(28): 12526-9, 2015 Jul 28.
Article in English | MEDLINE | ID: mdl-26103060

ABSTRACT

Engineering a copper coordination sphere with organoimine ligands and tuning the organophosphonate protonation states produced [{Cu(2,2'-bpy)}2(HO3P(CH2)8PO3H2)4] (1) and [{Cu(terpy)}2(2,7-FDA-H2)2]·(2,7-FDA-H4)(2H2O) (2) (2,7-FDA-H4 = 2,7-fluorenonediphosphonic acid) macrocyclic copper-organophosphonate building blocks. 1 exhibits high temperature magnetic ordering, while 2 is paramagnetic. The structures were characterized by single crystal X-ray diffraction.


Subject(s)
Coordination Complexes/chemistry , Copper/chemistry , Organophosphonates/chemistry , Magnetic Phenomena , Temperature , Thermogravimetry , X-Ray Diffraction
15.
Breast Cancer Res Treat ; 148(3): 477-88, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25395317

ABSTRACT

The functional redundancy of metabolic enzyme expression may present a new strategy for developing targeted therapies in cancer. To satisfy the increased metabolic demand required during neoplastic transformations and proliferation, cancer cells may rely on additional isoforms of a metabolic enzyme to satisfy the increased demand for metabolic precursors, which could subsequently render cancer cells more vulnerable to isoform-specific inhibitors. In this review, we provide a survey of common isoenzyme shifts that have been reported to be important in cancer metabolism and link those to metabolic pathways that currently have drugs in various stages of development. This phenomenon suggests a potentially new therapeutic strategy for the treatment of cancer by identifying shifts in the expression of metabolic isoenzymes between cancer and normal cells. We also delineate other putative metabolic isoenzymes that could be targets for novel targeted therapies for cancer. Changes in isoenzyme expression that occur during neoplastic transformations or in response to environmental pressure in cancer cells may result in isoenzyme diversity that may subsequently render cancer cells more vulnerable to isoform-specific inhibitors due to reliance on a single isoform to perform a vital enzymatic function.


Subject(s)
Isoenzymes/biosynthesis , Metabolic Networks and Pathways/genetics , Molecular Targeted Therapy , Neoplasms/genetics , Databases, Protein , Energy Metabolism/drug effects , Energy Metabolism/genetics , Enzyme Inhibitors/therapeutic use , Gene Expression Regulation, Neoplastic , Glycolysis/genetics , Humans , Isoenzymes/antagonists & inhibitors , Isoenzymes/metabolism , Metabolic Networks and Pathways/drug effects , Neoplasms/pathology , Neoplasms/therapy
16.
Dis Esophagus ; 25(5): 437-41, 2012 Jul.
Article in English | MEDLINE | ID: mdl-21951971

ABSTRACT

Incidence of the esophagus adenocarcinoma has been dramatically increasing in Western countries since the last decade. Gastroesophageal reflux disease and Barrett's esophagus are risk factors for adenocarcinoma. Methylenetetrahydrofolate reductase (MTHFR) genes play a key role not only in folate metabolism but also in esophagus, stomach, pancreatic carcinoma, and acute leukemias. Studies have suggested that genetic polymorphisms of MTHFR (C677T) may clarify the causes and events involved in esophageal carcinogenesis. In this study, we evaluated MTHFR C677T and A1298C polymorphisms, and vitamin B12, folate, and plasma homocystein levels in patients with esophageal adenocarcinoma (EAC), Barrett's esophagus (BE), chronic esophagitis, and healthy controls (n = 26, n = 14, n = 30, and n = 30, respectively). The mean age of patients in the EAC and BE groups was significantly higher compared with the control group (P < 0.001, P = 0.003, respectively). In all patient groups, serum folate levels were significantly lower than that of the control group (P < 0.01, P < 0.05, and P < 0.01, respectively). There was no statistically significant association between folate levels and MTHFR gene polymorphisms. No differences were found in terms of MTHFR gene polymorphisms, homocystein, and B12 levels among the groups. MTHFR gene polymorphisms and folate deficiency are not predictors of early esophageal carcinoma. However, further studies using larger series of patients are needed to evaluate the effect of genetic polymorphisms in the folate metabolic pathway and to clarify the role of folate deficiency and folate metabolism in the development of esophagus adenocarcinoma.


Subject(s)
Adenocarcinoma/genetics , Barrett Esophagus/genetics , Esophageal Neoplasms/genetics , Esophagitis, Peptic/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Adenocarcinoma/etiology , Adult , Aged , Barrett Esophagus/etiology , Case-Control Studies , Esophageal Neoplasms/etiology , Esophagitis, Peptic/etiology , Female , Folic Acid/blood , Folic Acid Deficiency/complications , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Polymorphism, Genetic
17.
Int J Impot Res ; 24(1): 44-8, 2012.
Article in English | MEDLINE | ID: mdl-21938007

ABSTRACT

This study aimed to investigate the predictive accuracy of carotid and cavernosal Doppler ultrasound findings for discriminating patients with vasculogenic erectile dysfunction (ED). Fifty patients with complaints of ED were included. B-mode ultrasound of bilateral carotid arteries were performed and peak systolic velocity (PSV), end-diastolic velocity (EDV) and intima-media thickness (IMT) values were measured. Afterwards, corresponding values of cavernosal arteries were obtained by penile color duplex ultrasonography (P-CDU). Of total 50 patients, 29 (58%) were included in vasculogenic ED group and 21 (42%) in non-vasculogenic ED group according to P-CDU findings. There was a significant difference between groups for cavernosal IMT (P=0.012) but not for carotid IMT (P=0.601). When patients were reclassified according to carotid IMT values (IMT of the first group <0.9 mm and the second ≥0.9 mm), carotid PSV and EDV values were different (P=0.033 and 0.018, respectively). Cavernosal PSV and EDV displayed no difference (P=0.816 and 0.123) while cavernosal IMT and percent change of cavernosal caliper were significantly different (P=0.014 and 0.018). Carotid PSV and EDV successfully mirrored respective measurements in cavernosal artery. However, carotid IMT failed to demonstrate such a correlation. Cavernosal IMT seems promising as an additional tool in the evaluation of cavernosal function.


Subject(s)
Arteries/diagnostic imaging , Carotid Arteries/diagnostic imaging , Erectile Dysfunction/diagnostic imaging , Penis/blood supply , Tunica Intima/diagnostic imaging , Tunica Media/diagnostic imaging , Adult , Aged , Carotid Arteries/pathology , Erectile Dysfunction/pathology , Humans , Impotence, Vasculogenic/diagnostic imaging , Impotence, Vasculogenic/pathology , Male , Middle Aged , Penis/diagnostic imaging , Tunica Intima/pathology , Tunica Media/pathology , Ultrasonography, Doppler, Color
18.
J Magn Reson ; 193(1): 49-53, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18455453

ABSTRACT

Our experimental and theoretical studies show that using two-frequency excitation of (14)N nuclei it is possible to observe secondary NQR signals at one of the three possible transitions due to irradiation of another adjacent transition. As a result of the pulse sequence applied to the adjacent transition the spin-echo signals on the detected transition are observed after essential time interval from the initial single pulse on this frequency. Experiments have been performed on the (14)N nuclei in the sodium nitrite (NaNO(2)) and the military explosive hexahydro-1,3,5-trinitro-s-triazine C(3)H(6)N(6)O(6) (RDX).

19.
J Nanosci Nanotechnol ; 8(2): 841-5, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18464416

ABSTRACT

Ferromagnetic monolayers Co90Fe10 thin films with individual layer thicknesses 2, 6, and 8 nm were grown on thermally oxidized Si substrate and magnetic properties of these were investigated with Ferromagnetic resonance (FMR) technique at room temperature. The magnetoresistance (MR) of the samples were measured as a function of applied DC magnetic field and the thickness dependence of the MR was plotted. The FMR spectra were recorded for both parallel and perpendicular geometry. The X-band (9.5 GHz) FMR spectra and resonance field of samples were analyzed and fitted theoretically by using the Landau-Lifshits dynamic equation of motion for magnetization with the Bloch-Bloembergen type damping term. The computer programs have been written to extract the effective magnetization (M), g-values and spin-spin relaxation time (T2) fitting parameters. The thickness dependence of magnetic parameters has been obtained from experimental data by mean of a theoretical model.

20.
Article in English | MEDLINE | ID: mdl-16843048

ABSTRACT

Ni++ ions doped inorganic CuGeO3 sample has been studied by using electron spin resonance (ESR) technique in the temperature range of 3-300 K. The ESR spectrum of Cu++ ion has been observed to be strongly temperature dependent for inorganic spin-Peierls (SP) Cu0.96Ni0.04GeO3 samples. The ESR line width and ESR amplitude exponentially vanishes below a critical temperature, Tsp=14 K. The one-dimensional (1D) antiferromagnetic (AF) spin chain formed of Cu++ is broken by Ni++ (spin-1) ion, giving uncoupled spins at the end of the chains that give extra contribution to the spectra at lower temperature and stabilizes a Néel state. The g-factor is much smaller than the expected value for isolated Cu++ and Ni++ ions and is much more anisotropic than for undoped samples [O. Yalçin, B. Aktas, J. Magn. Magn. Mater. 258/259 (2003) 137 (reference therein)]. It is shown that the ground state of dimerized spins is singlet. The spin-flop (SF) phenomenon is obtained from AF state mixed condition and then ferromagnetic (FM) state. The spin-flop field slightly increases when increasing temperature in the temperature range 100-300 K. The SF transition is showed almost AF order for Cu0.96Ni0.04GeO3.


Subject(s)
Copper/chemistry , Germanium/chemistry , Nickel/chemistry , Electron Spin Resonance Spectroscopy , Temperature
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