Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 42
Filter
1.
Cell Death Dis ; 6: e1947, 2015 Oct 29.
Article in English | MEDLINE | ID: mdl-26512957

ABSTRACT

Neutral sphingomyelinase-2 (nSMase2) is a ceramide-generating enzyme that has been implicated in growth arrest, apoptosis and exosome secretion. Although previous studies have reported transcriptional upregulation of nSMase2 in response to daunorubicin, through Sp1 and Sp3 transcription factors, the role of the DNA damage pathway in regulating nSMase2 remains unclear. In this study, we show that doxorubicin induces a dose-dependent induction of nSMase2 mRNA and protein with concomitant increases in nSMase activity and ceramide levels. Upregulation of nSMase2 was dependent on ATR, Chk1 and p53, thus placing it downstream of the DNA damage pathway. Moreover, overexpression of p53 was sufficient to transcriptionally induce nSMase2, without the need for DNA damage. DNA-binding mutants as well as acetylation mutants of p53 were unable to induce nSMase2, suggesting a role of nSMase2 in growth arrest. Moreover, knockdown of nSMase2 prevented doxorubicin-induced growth arrest. Finally, p53-induced nSMase2 upregulation appears to occur via a novel transcription start site upstream of exon 3. These results identify nSMase2 as a novel p53 target gene, regulated by the DNA damage pathway to induce cell growth arrest.


Subject(s)
Doxorubicin/pharmacology , Sphingomyelin Phosphodiesterase/physiology , Tumor Suppressor Protein p53/physiology , Up-Regulation , DNA Damage , Gene Expression Regulation/drug effects , Gene Knockdown Techniques , Humans , MCF-7 Cells , RNA, Messenger/drug effects , Sphingomyelin Phosphodiesterase/genetics , Sphingomyelin Phosphodiesterase/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
2.
Clin Radiol ; 70(12): 1382-7, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26392317

ABSTRACT

AIM: To evaluate the association of quantitative computed tomography (CT) measures of emphysema with the occurrence of pneumothorax after CT-guided needle lung biopsy (NLB) accounting for other risk factors. MATERIALS AND METHODS: One hundred and sixty-three CT-guided NLBs performed between 2008 and 2013 with available complete chest CT within 30 days were reviewed for the occurrence of post-procedure pneumothorax. Percent emphysema was determined quantitatively as the percentage of lung voxels below -950 HU on chest CT images using automated software. Multivariable regression was used to assess the association of percent emphysema volume with the occurrence of post-procedure pneumothorax. The association of percent emphysema volume with the pneumothorax size and need for chest tube placement after NLB was also explored. RESULTS: Percent emphysema was significantly associated with the incidence of post-NLB pneumothorax (OR=1.10 95% confidence interval: 1.01-1.15; p=0.03) adjusting for lower-lobe lesion location, needle path length, lesion size, number of passes, and pleural needle trajectory angle. Percent emphysema was not associated with the size of the pneumothorax, nor the need for chest tube placement after NLB. CONCLUSION: Percent emphysema determined quantitatively from chest CT is a significant predictor of post-NLB pneumothorax.


Subject(s)
Pneumothorax/diagnostic imaging , Pneumothorax/pathology , Radiography, Interventional , Biopsy, Needle/methods , Cross-Sectional Studies , Female , Humans , Image-Guided Biopsy/methods , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Predictive Value of Tests , Reproducibility of Results , Risk Factors , Tomography, X-Ray Computed
3.
Cancer Chemother Pharmacol ; 75(1): 207-14, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25428516

ABSTRACT

PURPOSE: The purpose of this study was to measure the frequency of three CYP2B6 [CYP2B6*4 (rs2279343), CYP2B6*5 (rs3211371) and CYP2B6*9 (rs3745274)] alleles in patients with breast cancer receiving cyclophosphamide (CP) therapy and test whether these variants are predictors of CP-associated toxicity and efficacy. METHODS: A total of 145 female breast cancer patients admitted to the American University of Beirut Medical Center for breast cancer-related therapy were included. Chart review was performed for collection of toxicity data. A time-to-event analysis was performed with a subset of 38 patients. RESULTS: The minor allele frequencies of CYP2B6*9, CYP2B6*4 and CYP2B6*5 were 0.27, 0.29 and 0.07, respectively. CYP2B6 *5/*6, *6/*9 or *6/*6 haplotypes were associated with a significantly shorter time to recurrence of the disease. There were no significant associations with myelo-toxicity. CONCLUSIONS: This is the first report on the pharmacogenetic profile of patients with breast cancer and the therapeutic and myelo-toxic behavior of CP in women from an Arab Middle Eastern country. Our results show that genotyping for these CYP2B6 alleles does not help in personalizing therapy from a toxicity perspective, and the association of shorter survival in these subjects with homozygous variants is interesting yet insufficient to justify routine genotyping prior to therapy, or to consider using a higher CP dose. Larger future studies or meta-analyses will be needed to further clarify the potential implication of these genetic polymorphisms.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Cyclophosphamide/therapeutic use , Cytochrome P-450 CYP2B6/genetics , Polymorphism, Genetic , Adult , Alleles , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast/drug effects , Breast/metabolism , Breast/pathology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cohort Studies , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Cytochrome P-450 CYP2B6/metabolism , Female , Gene Frequency , Genetic Association Studies , Humans , Lebanon , Middle Aged , Myelopoiesis/drug effects , Neoplasm Grading , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/metabolism , Neoplasm Staging , Polymorphism, Single Nucleotide , Retrospective Studies , Survival Analysis
4.
Epilepsy Behav ; 12(1): 145-9, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17950673

ABSTRACT

In this first study comparing epilepsy-specific quality-of-life measures of children after epilepsy surgery (2.4 years after focal resection) with those of a matched comparison group of nonoperated patients, seizure severity, medication side effects, overall quality of life, general health, physical activity, and well-being were better in surgical patients (70.6% seizure free vs 8.3%). Cognitive, social, and behavioral functioning did not differ, suggesting that these may require additional interventions during postsurgical follow-up.


Subject(s)
Epilepsy , Health Status , Motor Activity/physiology , Outcome Assessment, Health Care , Quality of Life , Adolescent , Case-Control Studies , Child , Child, Preschool , Epilepsy/physiopathology , Epilepsy/psychology , Epilepsy/surgery , Female , Humans , Interviews as Topic , Longitudinal Studies , Male , Severity of Illness Index
6.
Int J Gynecol Cancer ; 16(5): 1933-5, 2006.
Article in English | MEDLINE | ID: mdl-17009994

ABSTRACT

Metastatic carcinoma of the spleen occurs in a setting of widespread malignant disease. Solitary parenchymal splenic metastasis of ovarian carcinoma is rare. We report a case of a 59-year-old woman who presented with an elevated serum CA125 level due to a solitary splenic metastasis after a long disease-free period. She was treated with laparoscopic splenectomy followed by chemotherapy. The literature contains 16 cases of solitary parenchymal splenic metastasis of ovarian carcinoma. Our case is the third case that was treated with laparoscopic splenectomy. We review the literature, and we focus on the laparoscopic approach in managing these cases.


Subject(s)
Cystadenocarcinoma, Serous/secondary , Ovarian Neoplasms/pathology , Splenic Neoplasms/secondary , CA-125 Antigen/blood , Cystadenocarcinoma, Serous/surgery , Female , Humans , Laparoscopy/methods , Middle Aged , Ovarian Neoplasms/therapy , Spleen/pathology , Spleen/surgery , Splenic Neoplasms/surgery
9.
Eur J Gynaecol Oncol ; 26(4): 443-5, 2005.
Article in English | MEDLINE | ID: mdl-16122199

ABSTRACT

Pure primary squamous cell carcinoma (SCC) of the breast is a rare condition. The exact histogenesis of this malignancy is unclear. The rarity of the condition makes it difficult to draw firm conclusions on the course of the disease and the overall prognosis. We report a case of pure primary SCC of the breast occurring in a 62-year-old woman and presenting as an enlarged breast lesion with bleeding. We also review the literature for all cases of pure primary SCC.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Female , Humans , Mastectomy , Middle Aged , Neoplasm Invasiveness , Radiotherapy, Adjuvant
14.
Am J Med Genet A ; 125A(3): 257-60, 2004 Mar 15.
Article in English | MEDLINE | ID: mdl-14994233

ABSTRACT

We have identified six individuals over three generations within a Lebanese-Arab family affected with Gaucher disease. This family is unusual and informative because affected members are homozygous for a previously unidentified mutation, L371V. Clinical symptoms begin in early childhood and progress to moderately severe involvement by young adulthood. There is significant anemia, thrombocytopenia, and bony involvement, but no mental deterioration. The phenotype is more severe than the phenotype observed in the common mutation associated with type 1 Gaucher disease, N370S. It is unknown whether L371V is a private mutation limited to this family, or will prove to be a common mutation within the Lebanese population.


Subject(s)
Gaucher Disease/genetics , Mutation/genetics , Adolescent , Adult , Anemia/pathology , Bone and Bones/pathology , Child , DNA Mutational Analysis , Female , Gaucher Disease/enzymology , Gaucher Disease/pathology , Genotype , Glucosylceramidase/genetics , Homozygote , Humans , Lebanon , Male , Pedigree , Polymerase Chain Reaction , Thrombocytopenia/pathology
15.
Eur J Gynaecol Oncol ; 24(6): 539-40, 2003.
Article in English | MEDLINE | ID: mdl-14658598

ABSTRACT

The association of ovarian carcinoma with idiopathic thrombocytopenic purpura (ITP) is rare. There have been different case reports indicating an association between solid tumors and ITP. We report a case of a 47-year-old woman diagnosed with ovarian cancer who presented with abdominal distention and thrombocytopenia. Her clinical course and the mechanisms of thrombocytopenia are discussed.


Subject(s)
Carcinoma, Endometrioid/diagnosis , Ovarian Neoplasms/diagnosis , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Carcinoma, Endometrioid/complications , Carcinoma, Endometrioid/surgery , Diagnosis, Differential , Fallopian Tubes/surgery , Female , Humans , Hysterectomy , Middle Aged , Ovarian Neoplasms/complications , Ovarian Neoplasms/surgery , Ovariectomy , Prednisone/therapeutic use , Purpura, Thrombocytopenic, Idiopathic/complications , Purpura, Thrombocytopenic, Idiopathic/drug therapy
16.
Dermatol Online J ; 9(3): 15, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12952762

ABSTRACT

A 70-year-old woman with non-small-cell lung cancer developed severe nail toxicity while she was being treated with docetaxel at three-week intervals. Docetaxel is a chemotherapeutic agent of the taxane family. Taxanes are well known to cause nail changes, but mainly when used on a weekly basis.


Subject(s)
Antineoplastic Agents, Phytogenic/adverse effects , Nail Diseases/chemically induced , Paclitaxel/analogs & derivatives , Paclitaxel/adverse effects , Taxoids , Aged , Antineoplastic Agents, Phytogenic/administration & dosage , Docetaxel , Female , Humans , Lung Neoplasms/drug therapy , Nails/drug effects , Paclitaxel/administration & dosage
17.
Clin Lab Haematol ; 25(3): 187-90, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12755797

ABSTRACT

Multiple myeloma represents a malignant proliferation of plasma cells derived from a single clone within the bone marrow. While the cause of myeloma is not known, interleukin 6 may play a role in driving myeloma cell proliferation. Waldenstrom's macroglobulinemia (WM) is a proliferative disease of B-lymphocytes. The cells have lymphoplasmacytoid features and secrete IgM. It is important to distinguish between IgM myeloma and WM as they have distinct clinical courses and prognoses, and treatment strategies are therefore different. The clinical characteristics of a patient diagnosed with IgM myeloma, and his excellent response to treatment are reported here.


Subject(s)
Immunoglobulin M/blood , Multiple Myeloma/diagnosis , Waldenstrom Macroglobulinemia/diagnosis , Chromosome Aberrations , Diagnosis, Differential , Humans , Immunophenotyping , Male , Middle Aged , Multiple Myeloma/immunology , Multiple Myeloma/therapy , Treatment Outcome , Waldenstrom Macroglobulinemia/immunology
18.
Eur J Gynaecol Oncol ; 24(2): 163-8, 2003.
Article in English | MEDLINE | ID: mdl-12701970

ABSTRACT

PURPOSE: The value of neoadjuvant chemotherapy in squamous cell carcinomas of the cervix has not been proven. It has been suggested that the potential benefit of this therapy on local and occult metastatic disease could be offset by delaying effective radiation therapy and selection of more aggressive tumor clones. This report examines the potential impact of short duration neoadjuvant chemotherapy on the response and outcome of advanced carcinoma of the cervix. MATERIALS AND METHODS: Between 1993 and 1997, 37 patients with advanced squamous cell carcinoma of the cervix (FIGO Stages IIB to IV) were enrolled in a prospective nonrandomized study using short duration neoadjuvant chemotherapy. Median age was 57 years (range: 34-70). Twenty-one patients (57%) had Stage IIB disease, one (3%) had Stage IIIA, 11 (30%) Stage IIIB, and four (11%) had Stage IV disease. The average tumor diameter at presentation assessed by physical examination and by CT scan measurements was 5.3 + 1.9 cm and 5.3 + 1.4 cm, respectively. Patients received three cycles of chemotherapy consisting of cisplatin 50 mg/m2 and vincristine 1 mg/m2 for 1 dose and bleomycin 25 mg/m2 daily for three days. Cycles were repeated every ten days. All patients started definitive radiotherapy within a week from the end of chemotherapy. Radiation therapy consisted of whole pelvis radiotherapy followed by 1-3 sessions of low dose rate brachytherapy. RESULTS: Response to neoadjuvant chemotherapy was as follows: seven patients (19%) had minor or no response, one patient had progressive disease, and 28 (76%) had more than 50% tumor reduction; 14 of them (38%) had no clinical evidence of residual tumor. Chemotherapy was discontinued in one patient after the second cycle because of significant changes in pulmonary function tests (PFT), and one patient developed a grade 4 urinary complication after radiotherapy. Median follow-up time for the whole group was 24 months (range: 1-67). Five-year actuarial rates of local control and disease-free survival were 47 and 42%, respectively. At three years, 20 patients (54%) were alive or had died without evidence of disease, and 17 (46%) had succumbed to their disease, with a median time to recurrence of 25 months. Stage and response to neoadjuvant chemotherapy had significant impact on survival, while age. tumor size, and menopausal status did not influence survival. CONCLUSIONS: Our data indicate that short duration chemotherapy followed by definitive radiotherapy is well tolerated and feasible. However, despite a high rate of objective response (76%), and improved survival for responders, there was no obvious long-term survival benefit for the entire group.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/radiotherapy , Bleomycin/administration & dosage , Carcinoma, Squamous Cell/pathology , Cisplatin/administration & dosage , Combined Modality Therapy , Feasibility Studies , Female , Humans , Middle Aged , Prognosis , Survival Analysis , Treatment Outcome , Uterine Cervical Neoplasms/pathology , Vincristine/administration & dosage
19.
Int J Gynecol Cancer ; 13(1): 88-9, 2003.
Article in English | MEDLINE | ID: mdl-12631227

ABSTRACT

Most patients with advanced or recurrent uterine sarcoma experience disease progression and ultimately die. We present a case of uterine sarcoma with lung metastasis treated with systemic chemotherapy and with no evidence of disease for more than 5 years. A 77-year-old woman underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy for carcinosarcoma of the uterus followed by external pelvic radiotherapy. Ten months later, the tumor recurred in the apex of the vagina and was treated with brachytherapy. After 6 months of remission, she presented with pulmonary metastasis. After four cycles of systemic chemotherapy with cisplatin and ifosfamide, the pulmonary nodules completely disappeared. Currently she is still in complete remission after more than 5 years, but unfortunately she has developed myelodysplastic syndrome. This is the first reported case in the literature of cured metastatic uterine carcinosarcoma to lungs, with long-term survival of 5 years.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinosarcoma/drug therapy , Carcinosarcoma/secondary , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Uterine Neoplasms/pathology , Aged , Carcinosarcoma/therapy , Cisplatin/administration & dosage , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Ifosfamide/administration & dosage , Uterine Neoplasms/therapy
20.
Eur J Obstet Gynecol Reprod Biol ; 100(1): 77-80, 2001 Dec 10.
Article in English | MEDLINE | ID: mdl-11728662

ABSTRACT

PURPOSE: To prospectively follow a group of women with breast cancer on tamoxifen for the development of ovarian cysts. METHODS: 72 women were followed every 6 months with pelvic examination and vaginal ultrasound. Chi square and Student's t-test were used for statistical analysis. RESULTS: The duration of treatment was 31.5+/-20 months. The mean age was 51.2+/-9.8 years. 55.6% were post-menopausal. Out of 72 women, 18 (25%) developed ovarian cysts. The mean age of women who developed ovarian cysts was significantly lower than in those who did not (47.0+/-7.0 and 52.5+/-10.2 years, respectively, P=0.03), however, the mean duration of treatment was not significantly different (33.3+/-17.4 and 29.3+/-20 months, respectively, P=0.45). Out of 32, 14 (43.8%) pre-menopausal and out of 40, 4 (10%) post-menopausal women developed ovarian cysts (P=0.003). They developed the cysts after an average duration of 33.3+/-18 and 50.7+/-6.2 months, respectively (P=0.7). The average diameter of the cysts was 2.8+/-1.2 cm. All cysts were simple except for one pre-menopausal women. All the cysts in post-menopausal women resolved spontaneously. One pre-menopausal patient had a multi-loculated cyst, was operated and had a serious cystadenoma. In nine patients, the cysts resolved spontaneously and in three after discontinuation of tamoxifen, and one patient was lost to follow-up. All cysts were asymptomatic. CONCLUSION: Ovarian cysts frequently develop in women with breast cancer on tamoxifen. The majority of the cysts resolve spontaneously, therefore an expectant management with follow-up ultrasonography is recommended.


Subject(s)
Estrogen Antagonists/adverse effects , Ovarian Cysts/chemically induced , Tamoxifen/adverse effects , Adult , Breast Neoplasms/drug therapy , Female , Humans , Middle Aged , Ovarian Cysts/diagnostic imaging , Postmenopause , Premenopause , Prospective Studies , Time Factors , Ultrasonography
SELECTION OF CITATIONS
SEARCH DETAIL
...