Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 15 de 15
Filter
Add more filters










Publication year range
1.
Folia Med (Plovdiv) ; 66(2): 213-220, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38690816

ABSTRACT

INTRODUCTION: The density of breast tissue, radiologically referred to as fibroglandular mammary tissue, was found to be a predisposing factor for breast cancer (BC). However, the stated degree of elevated BC risk varies widely in the literature.


Subject(s)
Breast Density , Breast Neoplasms , Mammography , Humans , Female , Breast Neoplasms/epidemiology , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Egypt/epidemiology , Incidence , Middle Aged , Adult , Aged
2.
Cancer ; 124(15): 3118-3126, 2018 08 01.
Article in English | MEDLINE | ID: mdl-29905927

ABSTRACT

BACKGROUND: Regorafenib, a multikinase inhibitor that inhibits angiogenesis, growth, and proliferation, prolongs survival as monotherapy in patients with refractory colorectal cancer. This international, double-blind, placebo-controlled, multicenter trial assessed the efficacy of regorafenib with folinic acid, fluorouracil, and irinotecan (FOLFIRI) as a second-line treatment for metastatic colorectal cancer. METHODS: Patients with metastatic colorectal cancer who progressed on first-line oxaliplatin and fluoropyrimidine enrolled at 45 sites in the United States and Ireland. Patients, stratified by prior bevacizumab use, were randomized 2:1 to regorafenib or placebo. The treatment consisted of FOLFIRI on days 1 and 2 and days 15 and 16 with 160 mg of regorafenib or placebo on days 4 to 10 and days 18 to 24 of every 28-day cycle. Crossover was not allowed. The primary endpoint was progression-free survival (PFS). Under the assumption of a 75% event rate, 180 patients were required for 135 events to achieve 90% power to detect a hazard ratio (HR) of 0.65 with a 1-sided α value of .1. RESULTS: One hundred eighty-one patients were randomized (120 to regorafenib-FOLFIRI and 61 to placebo-FOLFIRI) with a median age of 62 years. Among these, 117 (65%) received prior bevacizumab or aflibercept. PFS was longer with regorafenib-FOLFIRI than placebo-FOLFIRI (median, 6.1 vs 5.3 months; HR, 0.73; 95% confidence interval [CI], 0.53-1.01; log-rank P = .056). The median overall survival was not longer (HR, 1.01; 95% CI, 0.71-1.44). The response rate was higher with regorafenib-FOLFIRI (34%; 95% CI, 25%-44%) than placebo-FOLFIRI (21%; 95% CI, 11%-33%; P = .07). Grade 3/4 adverse events with a >5% absolute increase from regorafenib included diarrhea, neutropenia, febrile neutropenia, hypophosphatemia, and hypertension. CONCLUSIONS: The addition of regorafenib to FOLFIRI as second-line therapy for metastatic colorectal cancer only modestly prolonged PFS over FOLFIRI alone. Cancer 2018. © 2018 American Cancer Society.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Camptothecin/analogs & derivatives , Colorectal Neoplasms/drug therapy , Phenylurea Compounds/administration & dosage , Pyridines/administration & dosage , Adult , Aged , Camptothecin/administration & dosage , Colorectal Neoplasms/pathology , Double-Blind Method , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Fluorouracil/administration & dosage , Humans , Irinotecan/administration & dosage , Kaplan-Meier Estimate , Leucovorin/administration & dosage , Male , Middle Aged , Progression-Free Survival
3.
Theranostics ; 7(11): 2914-2923, 2017.
Article in English | MEDLINE | ID: mdl-28824725

ABSTRACT

Background: Cancers related to tobacco use and African-American ancestry are under-characterized by genomics. This gap in precision oncology research represents a major challenge in the health disparities in the United States. Methods: The Precision Oncology trial at the Wake Forest Baptist Comprehensive Cancer Center enrolled 431 cancer patients from March 2015 to May 2016. The composition of these patients consists of a high representation of tobacco-related cancers (e.g., lung, colorectal, and bladder) and African-American ancestry (13.5%). Tumors were sequenced to identify mutations to gain insight into genetic alterations associated with smoking and/or African-American ancestry. Results: Tobacco-related cancers exhibit a high mutational load. These tumors are characterized by high-frequency mutations in TP53, DNA damage repair genes (BRCA2 and ATM), and chromatin remodeling genes (the lysine methyltransferases KMT2D or MLL2, and KMT2C or MLL3). These tobacco-related cancers also exhibit augmented tumor heterogeneities. Smoking related genetic mutations were validated by The Cancer Genome Atlas dataset that includes 2,821 cases with known smoking status. The Wake Forest and The Cancer Genome Atlas cohorts (431 and 7,991 cases, respectively) revealed a significantly increased mutation rate in the TP53 gene in the African-American subgroup studied. Both cohorts also revealed 5 genes (e.g. CDK8) significantly amplified in the African-American population. Conclusions: These results provide strong evidence that tobacco is a major cause of genomic instability and heterogeneity in cancer. TP53 mutations and key oncogene amplifications emerge as key factors contributing to cancer outcome disparities among different racial/ethnic groups.


Subject(s)
Colorectal Neoplasms/pathology , Lung Neoplasms/pathology , Mutation , Tobacco Smoking/adverse effects , Urinary Bladder Neoplasms/pathology , Black or African American , Humans , Pathology, Molecular , Sequence Analysis, DNA , Tumor Suppressor Protein p53/genetics , White People
4.
Diagn Cytopathol ; 45(2): 133-136, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27634114

ABSTRACT

A 30-year-old male presented to his doctor with complaints of abdominal pain and was found to have retroperitoneal as well as multiple hepatic masses. A serum alpha-fetoprotein (AFP) level was significantly elevated (17,373 ng mL-1 ), raising suspicions for a metastatic germ cell tumor. Fine needle aspiration biopsy of the pancreatic lesion revealed atypical epithelioid cells with round nuclei, large prominent nucleoli, and granular cytoplasm. The morphologic differential diagnosis included pancreatic neoplasm, metastatic germ cell tumor, other metastatic carcinoma, and melanoma. An extensive panel of immunohistochemical stains confirmed the diagnosis of acinar cell carcinoma. The diagnosis of acinar cell carcinoma could be confounded by the markedly increased AFP level, particularly in the setting of a retroperitoneal mass in a younger male. The increased AFP level in the setting of an acinar cell tumor is a potential pitfall to correct diagnosis by cytology. As the treatment for these two entities differs considerably, acute awareness of the phenomenon is important. We present a case of pancreatic ACC with an increased AFP level diagnosed on a cytology specimen. Diagn. Cytopathol. 2017;45:133-136. © 2016 Wiley Periodicals, Inc.


Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Acinar Cell/pathology , Neoplasms, Germ Cell and Embryonal/pathology , Pancreatic Neoplasms/pathology , alpha-Fetoproteins/metabolism , Adult , Biopsy, Fine-Needle , Carcinoma, Acinar Cell/blood , Diagnosis, Differential , Humans , Male , Neoplasm Metastasis , Neoplasms, Germ Cell and Embryonal/blood , Pancreatic Neoplasms/blood
6.
Complement Ther Med ; 25: 139-42, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26977123

ABSTRACT

OBJECTIVES: Fatigue and other treatment-related symptoms (e.g., sleep disturbance) are critical targets for improving quality of life in patients undergoing chemotherapy. Yoga may reduce the burden of such symptoms. This study investigated the feasibility of conducting a randomized controlled study of a brief yoga intervention during chemotherapy for colorectal cancer. DESIGN: We randomized adults with colorectal cancer to a brief Yoga Skills Training (YST) or an attention control (AC; empathic attention and recorded education). SETTING: The interventions and assessments were implemented individually in the clinic while patients were in the chair receiving chemotherapy. INTERVENTIONS: Both interventions consisted of three sessions and recommended home practice. MAIN OUTCOME MEASURES: The primary outcome was feasibility (accrual, retention, adherence, data collection). Self-reported outcomes (i.e., fatigue, sleep disturbance, quality of life) and inflammatory biomarkers were also described to inform future studies. RESULTS: Of 52 patients initially identified, 28 were approached, and 15 enrolled (age Mean = 57.5 years; 80% White; 60% Male). Reasons for declining participation were: not interested (n = 6), did not perceive a need (n = 2), and other (n = 5). Two participants were lost to follow-up in each group due to treatment changes. Thus, 75% of participants were retained in the YST and 71% in the AC arm. Participants retained in the study adhered to 97% of the in-person intervention sessions and completed all questionnaires. CONCLUSIONS: This study demonstrated the feasibility of conducting a larger randomized controlled trial to assess YST among patients receiving chemotherapy for colorectal cancer. Data collected and challenges encountered will inform future research.


Subject(s)
Colorectal Neoplasms/complications , Quality of Life , Sleep Wake Disorders/therapy , Yoga , Adult , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , Cytokines/blood , Female , Humans , Male , Middle Aged , Patient Compliance , Patient Satisfaction , Pilot Projects , Sleep Wake Disorders/etiology , Treatment Outcome
7.
Am Surg ; 79(4): 414-21, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23574853

ABSTRACT

Perioperative chemotherapy has been shown to improve disease-free survival compared with surgery alone for resectable colorectal liver metastases (CLM). We examined our experience with systemic chemotherapy in this clinical setting. A prospectively collected liver surgery database identified 210 patients treated for resectable CLM from 1996 to 2010. Results were correlated to four treatment groups: posthepatectomy adjuvant only, prehepatectomy preoperative only, perioperative (preoperative and adjuvant), and surgery only. Seventy-nine (37.6%) patients received posthepatectomy adjuvant only treatment, 33 (15.7%) received prehepatectomy preoperative only treatment, 46 (21.9%) received perioperative (preoperative and adjuvant) treatment, whereas 52 (24.8%) received surgery alone. Preoperative and adjuvant systemic chemotherapy regimens were as follows: 23 (29.1%) and 18 (14.4%) received a 5-fluorouracil monotherapy regimen, 19 (24.1%) and 31 (24.8%) received an irinotecan-based regimen, and 28 (35.4%) and 37 (29.6%) received an oxaliplatin-based regimen. Nine (11.4%) and 12 (9.6%) received some other unknown combination. Treatment groups showed no difference in gender, mean tumor size, number of tumors, margin status, or postoperative complications with the only difference being a higher incidence of metachronous tumors in the preoperative only and perioperative groups (P = 0.01). Median follow-up and overall survival were 25 and 41 months, respectively. The adjuvant, preoperative, perioperative, and surgery only groups had a median survival time of 48, 35, 39, and 29 months, respectively (log-rank P = 0.04). Independent predictors of overall survival on multivariate analysis included treatment algorithm used and postoperative complication status. Adjuvant only systemic therapy was associated with an improved survival in resectable CLM. Prospective randomized trials are needed to confirm these findings.


Subject(s)
Colorectal Neoplasms/drug therapy , Hepatectomy , Liver Neoplasms/surgery , Aged , Antineoplastic Agents/administration & dosage , Chemotherapy, Adjuvant , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Humans , Liver Neoplasms/mortality , Middle Aged , Multivariate Analysis , Neoadjuvant Therapy , Proportional Hazards Models , Survival Analysis
8.
Clin Colon Rectal Surg ; 25(2): 118-22, 2012 Jun.
Article in English | MEDLINE | ID: mdl-23730227

ABSTRACT

Colorectal cancer (CRC) is the second most common cancer in females and the third most common cancer diagnosed in males. Familial CRC comprises ~20 to 30% of all CRC cases. Lynch syndrome (LS), previously called hereditary nonpolyposis CRC (HNPCC), is the most common of the hereditary CRC syndromes. In this review, the oncological management of hereditary colorectal cancer from the medical oncologist perspective is discussed with special emphasis on Lynch syndrome. Lynch syndrome is characterized by the presence of germline mutations in the mismatch repair genes (MMR)-MSH2, MLH1, MSH6, and PMS2. The available data regarding the prognostic role of mismatch repair genes (MMR), the predictive role of MMR genes, and the implications of that in the management of patients with deficient MMR genes (dMMR/MSI-H) tumors including Lynch syndrome patients are also discussed.

9.
Anal Chim Acta ; 636(2): 218-23, 2009 Mar 23.
Article in English | MEDLINE | ID: mdl-19264171

ABSTRACT

A rapid immunoassay for sensitive detection of microcystin-LR using a portable chemiluminescence multichannel immunosensor (CL-MADAG) was developed. The sensor device is based on a capillary ELISA technique in combination with a miniaturized fluidics system and uses chemiluminescence as the detection principle. Minimum concentrations of at least 0.2 microgL(-1) microcystin-LR could be unambiguously measured in a spiked buffer system as well as in spiked real water samples. A single sample analysis for detection of microcystin-LR could be accomplished in just 13 min on the CL-MADAG. Besides providing a highly reproducible, fast and easy to perform test format, one major advantage of the newly established capillary immunoassay is represented by the feasibility of an internal retrospective quality control mechanism. Finally, simultaneous CL-MADAG measurements employing our inhibition immunoassay and a sandwich ELISA could be successfully demonstrated.


Subject(s)
Biosensing Techniques/instrumentation , Luminescent Measurements/instrumentation , Luminescent Measurements/methods , Microcystins/analysis , Water Pollutants, Chemical/analysis , Biosensing Techniques/methods , Enzyme-Linked Immunosorbent Assay , Marine Toxins , Reproducibility of Results , Sensitivity and Specificity , Silicon Dioxide/chemistry , Time Factors
10.
J Ky Med Assoc ; 106(11): 520-4, 2008 Nov.
Article in English | MEDLINE | ID: mdl-19058477

ABSTRACT

Mucormycosis is an acute fungal infection in humans that is often fulminant and potentially fatal. It occurs most frequently in immunocompromised individuals. We report a diabetic patient who presented in ketoacidosis with lacrimal sac infection from this organism. To the best of our knowledge, this is only the second patient with dacryocystitis caused by this fungus described in the medical literature. Our patient is unique in that she had no evidence of concurrent sinus involvement. Surgical debridement and antifungal therapy were combined to ensure a successful outcome.


Subject(s)
Dacryocystitis/diagnosis , Mucorales/isolation & purification , Mucormycosis/diagnosis , Adult , Anti-Bacterial Agents/therapeutic use , Dacryocystitis/drug therapy , Dacryocystitis/microbiology , Dacryocystitis/surgery , Enzyme Inhibitors/therapeutic use , Female , Humans , Mucormycosis/drug therapy , Mucormycosis/microbiology , Mucormycosis/surgery , Penicillanic Acid/analogs & derivatives , Penicillanic Acid/therapeutic use , Piperacillin/therapeutic use , Tazobactam , Tobramycin/therapeutic use , Vancomycin/therapeutic use
11.
Tenn Med ; 101(3): 35-7, 40, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18459646

ABSTRACT

The occurrence of glomerular disease as a paraneoplastic manifestation of malignancy is well documented in the medical literature. The strongest association is between membranous glomerulonephritis and solid tumors. We report a patient with IgA nephropathy associated with small cell lung cancer. To our knowledge, this is the second documented occurrence of an IgA nephropathy with a casual association with small cell bronchogenic cancer. This observation leads to the hypothesis that IgA nephropathy might be a paraneoplastic manifestation of this histiologic type of lung cancer.


Subject(s)
Carcinoma, Small Cell/complications , Glomerulonephritis, IGA/etiology , Lung Neoplasms/complications , Paraneoplastic Syndromes , Humans , Male , Middle Aged
12.
Biosens Bioelectron ; 22(7): 1368-75, 2007 Feb 15.
Article in English | MEDLINE | ID: mdl-16839755

ABSTRACT

The automated 10-channel capillary chip immunodetector (10K-IDWG) is a prototype, which has been developed for automatically operated biological agents (BA) point detection. The current technology uses a chemiluminescence capillary immunoassay (EIA) technique in combination with integrated microfluidics and allows the highly sensitive and rapid detection and preliminary identification of multiple BA in aqueous solutions in the laboratory. The chemiluminescence capillary EIA are performed within a disposable capillary chip containing 10 fused-silica capillaries arranged in parallel coated with selected capture antibodies. A multianode-photomultiplier array is used to detect chemiluminescence intensity in each capillary. Reservoirs for reagents and buffers and a waste disposal reservoir are integrated. This paper describes the technology of the 10K-IDWG and its evaluation with three different BA, the toxin staphylococcal enterotoxin B (SEB), the bacterial analyte Escherichia coli (E. coli) O157:H7 as a model for bacterial pathogens, and the bacteriophage M13 as a model for virus pathogens. The 10K-IDWG is able to detect the above mentioned three BA in an aqueous sample within 29 min (single analyte-detection and multiplexing). Limits of detection (LOD) are 0.1 ng/ml for SEB, 10(4)cfu/ml for E. coli O157:H7, and 5x10(5) pfu/ml for M13. Cross reactivities between the three assays were not observed.


Subject(s)
Biosensing Techniques/instrumentation , Immunoenzyme Techniques , Microfluidics , Luminescence
13.
Anticancer Res ; 24(1): 43-51, 2004.
Article in English | MEDLINE | ID: mdl-15015574

ABSTRACT

Human kallikreins are a cluster of 15 serine protease genes located in the chromosomal band 19q13.4, a non-randomly rearranged region in many solid tumors, including pancreatic cancer. We utilized the SAGE and EST databases of the Cancer Genome Anatomy Project to perform in-silico analysis of kallikrein gene expression in normal and cancerous pancreatic and colon tissues and cell lines using virtual Northern blotting (VNB), digital differential display (DDD) and X-profiler. At least two kallikreins, KLK6 and KLK10, are significantly up-regulated in pancreatic cancer. We probed 2 normal and 6 pancreatic cancer SAGE libraries with gene-specific tags for each of these kallikreins. KLK6 was found to be expressed in 5/6 cancer libraries and showed the most marked (5-fold) increase in average expression levels in cancer vs. normal. These data were verified by screening the EST databases, where all mRNA clones isolated were from cancerous libraries, with no clones detected in normal pancreatic tissues or cell lines. X-profiler comparison of two pools of normal and cancerous pancreatic libraries further verified the significant increase of KLK6 expression levels in pancreatic cancer. DDD data showed a 13-fold increase in KLK10 expression in pancreatic cancer. Three kallikrein genes, KLK6, 8 and 10 are overexpressed in colon cancer compared to normal colon, while one kallikrein, KLK1, is down-regulated. While no expression of KLK6 was detected in normal colon, KLK6-specific tags were detectable in 2 cancer libraries. Similar results were obtained by EST screening; no KLK6 clones were detected in any of the 28 normal libraries examined, while 10 KLK6 EST clones were found in colon adenocarcinoma. KLK10 was not detectable in normal colon. Gene-specific tags were, however, detectable with high density in colon cancer and 7 EST clones were found to be expressed in colon Adenocarcinoma.


Subject(s)
Adenocarcinoma/metabolism , Colonic Neoplasms/metabolism , Kallikreins/biosynthesis , Pancreatic Neoplasms/metabolism , Adenocarcinoma/genetics , Blotting, Northern , Colonic Neoplasms/genetics , Expressed Sequence Tags , Gene Expression , Gene Expression Profiling , Humans , Kallikreins/genetics , Pancreatic Neoplasms/genetics , RNA, Messenger/biosynthesis , RNA, Messenger/genetics
14.
Cancer Res ; 63(9): 2223-7, 2003 May 01.
Article in English | MEDLINE | ID: mdl-12727843

ABSTRACT

Recent evidence suggests that many members of the human kallikrein (KLK) gene family are differentially regulated in ovarian cancer and have potential as diagnostic and/or prognostic markers. We used the serial analysis of gene expression and expressed sequence tag databases of the Cancer Genome Anatomy Project to perform in silico analyses of the expression pattern of the 15 human KLK genes in normal and cancerous ovarian tissues and cell lines. We found that seven KLK genes (KLK5, KLK6, KLK7, KLK8, KLK10, KLK11, and KLK14) are up-regulated in ovarian cancer. Probing 2 normal and 10 ovarian cancer serial analysis of gene expression libraries with gene-specific tags for each KLK indicated that whereas no expression was detected in any normal libraries (with the exception of KLK10 and KLK11), these KLKs were found to be expressed with moderate densities (103-408 tags per million) in 40-60% of the ovarian cancer libraries analyzed. These data were verified by screening the expressed sequence tag databases, where 78 of 79 mRNA clones isolated for these genes were from ovarian cancer libraries. X-profiler comparison of the pools of normal and cancerous ovaries identified a significant difference in expression levels for six of the seven KLKs. We experimentally verified the overexpression of six KLK proteins in cancer versus normal or benign tissues with highly sensitive and specific immunofluorometric assays. A statistically significant stepwise increase in protein levels was found among normal, benign, and cancerous ovarian tissues. The expression of five KLKs showed a strong degree of correlation at the protein level, suggesting the existence of a common mechanism or pathway that controls the expression of this group of adjacent genes during ovarian cancer progression.


Subject(s)
Kallikreins/genetics , Ovarian Neoplasms/genetics , Computational Biology/methods , Female , Gene Expression Regulation, Neoplastic , Humans , Kallikreins/biosynthesis , Ovarian Neoplasms/metabolism , Reproducibility of Results , Tumor Cells, Cultured , Up-Regulation
SELECTION OF CITATIONS
SEARCH DETAIL
...