Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 29
Filter
1.
Gynecol Oncol Rep ; 38: 100871, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34646930

ABSTRACT

OBJECTIVES: To assess telemedicine readiness of gynecologic oncology patients, particularly those at risk for care access disparities (increased distance to care, rural populations.). METHODS: Patients at all disease/treatment stages completed an anonymous survey during in-person outpatient appointments at an academic comprehensive cancer center from 1/6/2020 to 2/28/2020, conducted prior to the COVID-19 pandemic, before the introduction of telemedicine in this practice. RESULTS: Of 180 patients approached, 170 completed the survey (94.4%). Mean age was 59.6 years; 73.4% identified as White, 23.7% Black, and 2.9% other race. Ovarian cancer was most common (41.2%), followed by endometrial (27.1%), cervical (20.6%), and vaginal/vulvar (7.1%). Most patients traveled > 50 miles for appointments (63.8%); they were more likely from rural counties with significantly higher travel costs/visit ($60.77 vs $37.98, p = 0.026.) The majority expressed interest in using telemedicine (75.7%) or a smartphone app (87.5%) in their care. The majority of patients with difficulty attending appointments (88.9 vs 70.2%, p = 0.02) or from rural counties (88.7% vs 69.6%, p = 0.03) were interested in telemedicine; those with both characteristics reported 100% interest. The majority in both urban and rural counties had home internet access, and reported similarly high rates of daily use (79% vs 75%). Race and age were not associated with differences in internet access or use or telemedicine interest. CONCLUSIONS: Telemedicine is attractive to the majority of patients and may offer financial/logistical advantages. Patients have high internet use rates and comfort with using technology for healthcare. Telemedicine should be incorporated into standard practice beyond the COVID-19 pandemic to reduce healthcare access disparities.

2.
Gene Ther ; 15(16): 1156-66, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18401437

ABSTRACT

Intradermal administration of DNA vaccines via a gene gun represents a feasible strategy to deliver DNA directly into the professional antigen-presenting cells (APCs) in the skin. This helps to facilitate the enhancement of DNA vaccine potency via strategies that modify the properties of APCs. We have previously demonstrated that DNA vaccines encoding human papillomavirus type 16 (HPV-16) E7 antigen linked to calreticulin (CRT) are capable of enhancing the E7-specific CD+ T-cell immune responses and antitumor effects against E7-expressing tumors. It has also been shown that cluster (short-interval) DNA vaccination regimen generates potent immune responses in a minimal time frame. Thus, in the current study we hypothesize that the cluster intradermal CRT/E7 DNA vaccination will generate significant antigen-specific CD8+ T-cell infiltrates in E7-expressing tumors in tumor-bearing mice, leading to an increase in apoptotic tumor cell death. We found that cluster intradermal CRT/E7 DNA vaccination is capable of rapidly generating a significant number of E7-specific CD8+ T cells, resulting in significant therapeutic antitumor effects in vaccinated mice. We also observed that cluster intradermal CRT/E7 DNA vaccination in the presence of tumor generates significantly higher E7-specific CD8+ T-cell immune responses in the systemic circulation as well as in the tumors. In addition, this vaccination regimen also led to significantly lower levels of CD4+Foxp3+ T-regulatory cells and myeloid suppressor cells compared to vaccination with CRT DNA in peripheral blood and in tumor-infiltrating lymphocytes, resulting in an increase in apoptotic tumor cell death. Thus, our study has significant potential for future clinical translation.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Cancer Vaccines/analysis , Genetic Therapy/methods , Neoplasms/therapy , Papillomavirus E7 Proteins/immunology , Vaccines, DNA/analysis , Animals , Apoptosis , Biolistics , Calreticulin/genetics , Dendritic Cells/immunology , Humans , Injections, Intradermal , Lymphocyte Activation , Mice , Mice, Inbred C57BL , Neoplasms/immunology , Neoplasms/pathology , Papillomavirus Infections/immunology , Skin/immunology , Xenograft Model Antitumor Assays
3.
Br J Cancer ; 96(9): 1480-3, 2007 May 07.
Article in English | MEDLINE | ID: mdl-17437020

ABSTRACT

We screened 145 HIV-infected non-pregnant women at a tertiary care centre in Lusaka, Zambia. Liquid-based cytology and human papillomavirus (HPV) genotyping with PGMY09/11 biotinylated primers (Roche Linear Array HPV genotyping test) maximised sensitivity of cytology and HPV assessments. Among high-risk (HR) types, HPV 52 (37.2%), 58 (24.1%) and 53 (20.7%) were more common overall than HPV 16 (17.2%) and 18 (13.1%) in women with high-grade squamous intraepithelial lesions or squamous cell carcinoma (SCC) on cytology. High-risk HPV types were more likely to be present in women with CD4+ cell counts <200 microl(-1) (odds ratios (OR): 4.9, 95% confidence intervals (CI): 1.4-16.7, P=0.01) and in women with high-grade or severe cervical cytological abnormalities (OR: 8.0, 95% CI: 1.7-37.4, P=0.008). Human papillomavirus diversity in high-grade lesions and SCC on cytology suggests that HPV 16- and 18-based vaccines may not be adequately polyvalent to induce protective immunity in this population.


Subject(s)
HIV Infections/epidemiology , Papillomaviridae/genetics , Papillomavirus Infections/epidemiology , CD4 Lymphocyte Count , Confidence Intervals , Female , HIV Infections/immunology , Humans , Odds Ratio , Papillomaviridae/isolation & purification , Zambia/epidemiology
4.
Eur J Dermatol ; 17(2): 130-2, 2007.
Article in English | MEDLINE | ID: mdl-17337395

ABSTRACT

A Japanese newborn male with an unremarkable family history presented at birth with verrucous papules on the left side of the trunk and limbs, distributed along Blaschko's lines. Histological examination showed mild acantholytic dyskeratosis, consistent with Darier's disease; however, search for mutations of the SERCA gene, performed on DNA extracted from cells from involved and uninvolved skin and peripheral blood proved negative. The absence of detectable SERCA mutations did not allow confirmation of the diagnosis of (segmental) Darier's disease, and a tentative diagnosis of congenital acantholytic dyskeratotic epidermal nevus was considered. The relationship between the two conditions is briefly discussed.


Subject(s)
Acantholysis/diagnosis , Nevus/diagnosis , Skin Neoplasms/diagnosis , Acantholysis/pathology , Darier Disease/diagnosis , Darier Disease/pathology , Diagnosis, Differential , Humans , Infant, Newborn , Male , Nevus/pathology , Skin Neoplasms/pathology
5.
Int J Gynecol Cancer ; 17(5): 998-1002, 2007.
Article in English | MEDLINE | ID: mdl-17367322

ABSTRACT

The aim is to evaluate disease-free (DFS) and overall survival (OS) of patients with fallopian tube carcinoma (FTCA) treated with adjuvant chemotherapy. An Institutional Review Board approved retrospective review identified 38 patients with FTCA that received adjuvant chemotherapy following primary surgery from 1975 to 2001. Median age was 56 (range 36-78) and 95% of patients were white. Twenty patients (53%) had FIGO stage III/IV FTCA. Seventeen patients underwent second-look laparotomy, 8 (47%) patients were found to have disease. Adjuvant chemotherapeutic regimens consisted of melphalan in 11 patients, platinum-based chemotherapy without paclitaxel in 17 patients, and the combination of paclitaxel and platinum in 10 patients. Although DFS was similar for the three chemotherapy cohorts (P= 0.19), patients receiving paclitaxel had superior OS compared to patients receiving either melphalan (P= 0.02) or platinum without paclitaxel (P= 0.04). Of the twenty patients with stage III/IV disease, 55% of patients had optimal cytoreduction performed at their initial surgery. Both median DFS, 68 versus 50 months (P= 0.14) and OS, 73 versus 50 months (P= 0.12) were greater in patients with optimal cytoreduction. When compared to historical chemotherapeutic regimens, the combination of paclitaxel and platinum has superior efficacy for the management of patients with FTCA. Although not statistically significant in our study, optimal cytoreduction likely improves both DFS and OS and should be the goal of all patients surgically managed for FTCA.


Subject(s)
Carcinoma/therapy , Fallopian Tube Neoplasms/therapy , Adult , Aged , Carcinoma/drug therapy , Carcinoma/surgery , Chemotherapy, Adjuvant , Fallopian Tube Neoplasms/drug therapy , Fallopian Tube Neoplasms/surgery , Female , Humans , Middle Aged , Retrospective Studies , Survival Analysis , Treatment Outcome , Universities
6.
Int J Gynecol Cancer ; 17(4): 886-9, 2007.
Article in English | MEDLINE | ID: mdl-17309665

ABSTRACT

The objective of this study was to evaluate the treatment outcomes and risk factors of women with surgical stage I endometrial adenocarcinoma who were initially treated with surgery alone and subsequently developed isolated vaginal recurrences. Patients with surgical stage I endometrial adenocarcinoma diagnosed from 1975 to 2002 were identified from tumor registry databases at seven institutions. All patients were treated with surgery alone including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic (+/- para-aortic) lymph node dissection, and peritoneal cytology and did not receive postoperative radiation therapy. Vaginal recurrences were documented histologically. Metastatic disease in the chest and abdomen was excluded by radiologic studies. Overall survival was calculated by the Kaplan-Meier method. Sixty-nine women with surgical stage I endometrial cancer with isolated vaginal recurrences were identified. Of the 69 patients, 10 (15%) were diagnosed with stage IA disease, 43 (62%) were diagnosed with stage IB disease, and 16 (23%) were diagnosed with stage IC disease. Patients diagnosed with grade 1 disease were 22 (32%), grade 2 disease were 26 (38%), and grade 3 disease were 21 (30%). Among women, 81% with isolated vaginal recurrences were salvaged with radiation therapy. The mean time to recurrence was 24 months, and the mean follow-up was 63 months. Among women, 18% died from subsequent recurrent disease. The 5-year overall survival was 75%. The majority of isolated vaginal recurrences in women with surgical stage I endometrial cancer can be successfully salvaged with radiation therapy, further questioning the role of adjuvant therapy for patients with uterine-confined endometrial cancer at the time of initial diagnosis.


Subject(s)
Adenocarcinoma/radiotherapy , Adenocarcinoma/surgery , Endometrial Neoplasms/surgery , Neoplasm Recurrence, Local/radiotherapy , Salvage Therapy , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Endometrial Neoplasms/pathology , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Risk Factors , Treatment Outcome
7.
Br J Dermatol ; 150(5): 904-9, 2004 May.
Article in English | MEDLINE | ID: mdl-15149502

ABSTRACT

BACKGROUND: Granulysin is a recently identified antimicrobial protein expressed on cytotoxic T cells, natural killer (NK) cells and NKT cells. It has been shown that granulysin contributes to the defence mechanisms against mycobacterial infection. Superficial microbial folliculitis is a common skin disease. In a previous report, we showed that, as a first line of defence, alpha-defensin, a human neutrophil peptide, and beta-defensin (human beta-defensin-2) were expressed in infiltrating neutrophils and in lesional epidermal keratinocytes, respectively, in superficial folliculitis. As we also observed many infiltrating lymphocytes in lesional dermis, we hypothesized that infiltrating lymphocytes may possess antimicrobial substances, such as granulysin, and play a role in the defence mechanism as a second line of defence. OBJECTIVES: Seven specimens of superficial microbial folliculitis diagnosed clinically and histologically were examined by means of immunohistochemistry. To identify the phenotype of cells expressing granulysin, confocal laser microscopic examination was performed. RESULTS: A dense lymphoid cell infiltrate was observed in pustules, in the perivascular regions. A large number of these lymphoid cells were positive for granulysin. Phenotypically, cells consisted of CD3+ T cells, CD8+ T cells and UCHL-1+ T cells. CD20+ cells and CD56+ cells were not observed. Microscopic examination with a confocal laser showed that the lymphocytes producing granulysin were CD3+ and CD4+ T cells but not CD8+ T cells. CONCLUSIONS: We showed that many granulysin-bearing T cells infiltrated affected follicles and perilesional dermis in superficial microbial folliculitis. However, few granulysin-positive lymphoid cells were observed in sterile pustular lesions. Our observations indicated that adaptive immunity such as granulysin, a lymphocyte-produced antimicrobial protein, may play an important role in the cutaneous defence mechanism.


Subject(s)
Bacterial Infections/immunology , Folliculitis/immunology , Receptors, Immunologic/biosynthesis , T-Lymphocyte Subsets/immunology , Adult , Aged , Antigens, Differentiation, T-Lymphocyte , Bacterial Infections/pathology , CD3 Complex/analysis , CD8-Positive T-Lymphocytes/immunology , Female , Folliculitis/microbiology , Folliculitis/pathology , Humans , Immunophenotyping , Leukocyte Common Antigens/analysis , Male , Microscopy, Confocal , Middle Aged , Receptors, Immunologic/immunology , Skin/immunology
8.
Ann Acad Med Singap ; 32(5): 590-5; quiz 596, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14626785

ABSTRACT

INTRODUCTION: The recent development of affordable human papillomavirus (HPV) testing has prompted consideration of its use as adjuvant and primary screening for cervical dysplasia. This review focuses on the use of HPV testing in triage management of atypical squamous cells of undetermined significance (ASC-US) Pap smears. MATERIALS AND METHODS: A Medline search was performed for articles relevant to HPV testing as a triage strategy for ASC-US Paps. Key references from other papers that were not included in the search were also reviewed. Findings from the major randomised trials were then summarised. RESULTS: Reflex HPV testing with hybrid capture is at least as effective and potentially cheaper than repeat cytology for evaluation of an ASC-US Pap. It also avoids 50% of colposcopies that would normally be performed if immediate colposcopy were done for all ASC-US Paps, while retaining excellent negative predictive value. CONCLUSION: Reflex HPV testing using liquid-based cytology is the preferred management strategy for triage of ASC-US Paps.


Subject(s)
Carcinoma, Squamous Cell/virology , Papillomaviridae/isolation & purification , Papillomavirus Infections/diagnosis , Uterine Cervical Dysplasia/virology , Uterine Cervical Neoplasms/virology , Adult , Aged , Carcinoma, Squamous Cell/pathology , Colposcopy/methods , DNA, Viral/analysis , Female , Humans , Mass Screening , Middle Aged , Papanicolaou Test , Papillomavirus Infections/complications , Polymerase Chain Reaction/methods , Prognosis , Sensitivity and Specificity , Singapore , Triage , Uterine Cervical Dysplasia/pathology , Uterine Cervical Neoplasms/pathology , Vaginal Smears
9.
Br J Dermatol ; 148(3): 526-32, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12653745

ABSTRACT

BACKGROUND: Glycocalyx collapses during dehydration to produce electron-dense accretions. Confocal laser scanning microscopy (CLSM) may be used to visualize fully hydrated microbial biofilms. OBJECTIVES: Using CLSM, to analyse glycocalyx production by Staphylococcus aureus cells in skin lesions of bullous impetigo, atopic dermatitis and pemphigus foliaceus. A second objective was to compare numbers of S. aureus cells in tissue sections prepared by different methods for routine light microscopy. METHODS: S. aureus cells in skin lesions of impetigo, atopic dermatitis and pemphigus were stained with safranin, and positive staining with fluorescein isothiocyanate-conjugated concanavalin A was considered to indicate the presence of glycocalyx. RESULTS: All S. aureus cells tested in skin lesions of impetigo, atopic dermatitis and pemphigus were covered with glycocalyx and formed microcolonies. The numbers of S. aureus cells in a routine light microscopy section were significantly lower than those in a frozen section that had not been dehydrated with ethanol. CONCLUSIONS: S. aureus cells generally produce glycocalyx in skin lesions of bullous impetigo, atopic dermatitis and pemphigus foliaceus, which accounts for the difficulty of removing S. aureus cells from these skin lesions. The glycocalyx may collapse during dehydration and most of the S. aureus cells may be carried away during preparation of routine light microscope sections.


Subject(s)
Biofilms/growth & development , Dermatitis, Atopic/microbiology , Glycocalyx/metabolism , Impetigo/microbiology , Microscopy, Confocal/methods , Pemphigus/microbiology , Staphylococcus aureus/physiology , Acetic Acid/pharmacology , Adolescent , Adult , Aged , Child , Child, Preschool , Colony Count, Microbial , Female , Fibrin , Fusidic Acid/pharmacology , Humans , Hydrochloric Acid/pharmacology , Male , Middle Aged , Staphylococcus aureus/drug effects
11.
Br J Dermatol ; 147(5): 879-85, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12410696

ABSTRACT

BACKGROUND: Bacteria that adhere to damaged tissues encase themselves in a hydrated matrix of polysaccharides, forming a slimy layer known as a biofilm. This is the first report of detection of glycocalyx production by Staphylococcus aureus using confocal laser scanning microscopy (CLSM) on damaged skin tissues. OBJECTIVES: To analyse glycocalyx production by S. aureus cells on damaged skin tissues and the influence of polymorphonuclear leucocytes (PMNs) and various antimicrobial agents on its production using CLSM in cyclophosphamide (Cy)-treated (neutropenic) or non-Cy-treated (normal) mice. METHODS: S. aureus cells were inoculated on damaged skin tissues in neutropenic or normal mice with or without topical application of antimicrobial agents. S. aureus cells were stained with safranine, and positive staining with fluorescein isothiocyanate-conjugated concanavalin A was considered to indicate the presence of glycocalyx. RESULTS: All S. aureus cells tested on damaged skin tissues formed microcolonies encircled by glycocalyx. The colony counts of S. aureus cells on croton oil dermatitis in normal mice treated with 2% fusidic acid ointment were about 100 times lower than those in neutropenic mice (control). CONCLUSIONS: As S. aureus cells can generally produce a biofilm on damaged skin tissues, antimicrobial agents may not eradicate S. aureus cells without the help of PMNs. S. aureus glycocalyx may play a crucial role in colonization and adherence to damaged skin tissues.


Subject(s)
Biofilms/growth & development , Glycocalyx/microbiology , Skin/microbiology , Staphylococcal Infections/microbiology , Staphylococcus aureus/physiology , Animals , Anti-Infective Agents, Local/therapeutic use , Colony Count, Microbial , Dermatitis, Contact/complications , Female , Fusidic Acid/therapeutic use , Glycocalyx/drug effects , Glycocalyx/pathology , Mice , Microscopy, Confocal , Neutropenia/complications , Opportunistic Infections/complications , Opportunistic Infections/prevention & control , Povidone-Iodine/therapeutic use , Staphylococcal Infections/complications , Staphylococcal Infections/prevention & control
12.
Chemotherapy ; 48(3): 122-8, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12138327

ABSTRACT

BACKGROUND: Heavy colonization of atopic dermatitis (AD) with Staphylococcus aureus is well documented. The isolation rate of methicillin-resistant S. aureus is high in strains from AD in Japan. Our objective in the present study was to investigate the actions of farnesol and xylitol against S. aureus for the control of AD skin lesion-colonizing S. aureus. METHODS: We examined the actions of farnesol on plasma coagulation and superantigenic exotoxin production by S. aureus, the antimicrobial activity of beta-lactam antibiotics combined with farnesol at concentrations below the minimal inhibitory concentration (MIC) and the effect of xylitol on glycocalyx production. RESULTS: Coagulation by S. aureus cells was inhibited in plasma containing farnesol at a concentration of 1/12 of the MIC (100 microg/ml) after incubation for 24 h. The production of superantigenic exotoxins by S. aureus cells with farnesol (100 microg/ml) was about 10 times lower than that by S. aureus cells alone. The MICs of ampicillin and cefdinir against S. aureus were reduced to < or =0.06 microg/ml in Mueller-Hinton agar plates with farnesol (100 microg/ml). We suggest that farnesol at concentrations above the MIC had a suppressive effect against S. aureus cells in the exponential and stationary phase and acted on the cell wall of S. aureus cells in both phases. CONCLUSIONS: Farnesol is a promising adjuvant agent against S. aureus skin infections treated with beta-lactam antibiotics. Further, 5% xylitol inhibited glycocalyx production by S. aureus cells and consequently had a suppressive effect on the colonization of S. aureus on the horny cells of AD lesions.


Subject(s)
Farnesol/pharmacology , Staphylococcal Infections/drug therapy , Staphylococcus aureus/drug effects , Xylitol/pharmacology , Dermatitis, Atopic/complications , Dermatitis, Atopic/microbiology , Humans , Methicillin Resistance , Staphylococcus aureus/pathogenicity
13.
J Dermatol Sci ; 29(1): 54-61, 2002 May.
Article in English | MEDLINE | ID: mdl-12007722

ABSTRACT

We used a scanning confocal laser microscope to study the effects of various agents on sugar production by Staphylococcus aureus in vitro. S. aureus cells attached to coverslips in Pl-TSB (plasma:tryptic soy broth=1:1) were stained with fluorescein isothiocyanate-conjugated concanavalin A (FITC-conA) and were more strongly stained over time. We considered that the materials that stained positive for FITC-conA consistent with S. aureus cells were sugars, probably glycocalyx, produced by the S. aureus cells. Since the cells in the stationary growth phase alone were strongly stained with FITC-conA, all S. aureus cells attached to the coverslips in Pl-TSB were considered to be in this phase (low growth rate). The positive staining for FITC-conA was markedly reduced when fibrin was not formed in Pl-TSB with plasmin and sucrose, and was also markedly reduced when the fibrin in Pl-TSB was destroyed with plasmin. In conclusion, the results of the present study indicate that the existence of fibrin is essential for glycocalyx production and biofilm formation of S. aureus cells to aid in the attachment of S. aureus cells in vitro, because S. aureus cells attached on coverslips and fibrin alone produce glycocalyx. Of the antimicrobial agents tested, sulfadiazine silver most strongly inhibited the production of FITC-conA-positive materials by S. aureus cells at a sub-MIC concentration. Plasmin, sucrose, and sulfadiazine silver may be useful topical applications for use on clinical dermatology for the prevention and the treatment of staphylococcal biofilms. We consider that this simple method is very useful for the detection of S. aureus glycocalyx on dermatology field.


Subject(s)
Fluorescein-5-isothiocyanate/analogs & derivatives , Glycocalyx/drug effects , Glycocalyx/ultrastructure , Staphylococcus aureus/metabolism , Biofilms/drug effects , Concanavalin A , Fibrin/metabolism , Fibrinolysin/pharmacology , Microscopy, Confocal , Silver Sulfadiazine/pharmacology , Staphylococcus aureus/drug effects , Sucrose/pharmacology
14.
Clin Exp Dermatol ; 26(6): 504-6, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11678876

ABSTRACT

We describe a rare case of pemphigus foliaceus associated with familial myasthenia gravis (MG). A 35-year-old woman developed MG during oral corticosteroid treatment for pemphigus foliaceus. She had been operated on for a thyroid gland tumour that was confirmed histopathologically to be papillary carcinoma without metastasis. At the time of treatment, her mother had had MG for 30 years and undergone thymectomy 22 years ago. A specific ELISA technique showed that antidesmoglein 1 antibody was present in the daughter. There are many reports of multiple diseases such as pemphigus, thymoma, malignancy, and other autoimmune diseases associated with MG. However, familial MG following pemphigus foliaceus has not been reported previously.


Subject(s)
Carcinoma, Papillary/complications , Myasthenia Gravis/genetics , Pemphigus/complications , Thyroid Neoplasms/complications , Adult , Ambenonium Chloride/therapeutic use , Antibodies/analysis , Carcinoma, Papillary/drug therapy , Carcinoma, Papillary/immunology , Cholinesterase Inhibitors/therapeutic use , Complement C3/analysis , Cytoskeletal Proteins/immunology , Desmoplakins , Drug Therapy, Combination , Epidermis/immunology , Female , Fluorescent Antibody Technique, Direct , Humans , Immunoglobulin G/analysis , Myasthenia Gravis/drug therapy , Myasthenia Gravis/immunology , Pemphigus/drug therapy , Pemphigus/immunology , Prednisolone/therapeutic use , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/immunology
15.
Gynecol Oncol ; 83(2): 370-7, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11606099

ABSTRACT

OBJECTIVE: The transfer of tumor suppressor genes has been shown to revert the malignant phenotype. In this regard, bax is a pro-apoptotic molecule that also functions as a tumor suppressor. The purpose of this study was to evaluate bax as a gene therapeutic in the context of cervical cancer. METHODS: Efficiency of viral transduction in cervical cancer cell lines and primary cervical cancer cells was evaluated with an adenoviral vector encoding green fluorescent protein and luciferase, respectively. We generated a recombinant adenoviral vector that encodes the bax gene under inducible conditions. To this end, expression of this pro-apoptotic gene was controlled by a Cre-LoxP system. Following infection with the recombinant bax adenovirus, the viability of cervical cancer cell lines and primary cervical cancer cells was evaluated using crystal violet staining and FACS analysis. Apoptotic cell death was monitored using annexin V staining. RESULTS: High levels of viral infection were observed in all cervical cancer cell lines (>85%) and primary cervical cancer cells. Significant cytotoxicity was seen in all cervical cancer cells lines and, more importantly, patient-derived primary cervical cancer cells. Moreover, bax-mediated cell death occurred via an apoptotic pathway. CONCLUSIONS: Our results indicate that a bax recombinant adenoviral vector causes cell death mediated via an apoptotic pathway in multiple cervical cancer cell lines and primary cervical cancer cells. These data suggest that bax may be a candidate for human gene therapy in the setting of cervical carcinoma.


Subject(s)
Apoptosis/genetics , Genetic Therapy/methods , Proto-Oncogene Proteins c-bcl-2 , Proto-Oncogene Proteins/genetics , Uterine Cervical Neoplasms/therapy , Adenoviridae/genetics , Female , Genes, Tumor Suppressor , Genetic Vectors/genetics , HeLa Cells , Humans , Transduction, Genetic , Tumor Cells, Cultured , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , bcl-2-Associated X Protein
16.
Biochim Biophys Acta ; 1527(1-2): 31-8, 2001 Jul 02.
Article in English | MEDLINE | ID: mdl-11420140

ABSTRACT

The relevance of NADH-cytochrome b(5) reductase to the NADH-dependent reduction of D-erythroascorbyl free radical was investigated in Saccharomyces cerevisiae. MCR1, which is known to encode NADH-cytochrome b(5) reductase in S. cerevisiae, was disrupted by the insertion of URA3 gene into the gene of MCR1. In the mcr1 disruptant cells, the activity of NADH-D-erythroascorbyl free radical reductase almost disappeared and the intracellular level of D-erythroascorbic acid was about 11% of that of the congenic wild-type strain. In the transformant cells carrying MCR1 in multicopy plasmid, the intracellular level of D-erythroascorbic acid and the activity of NADH-D-erythroascorbyl free radical reductase increased up to 1.7-fold and 2.1-fold, respectively. Therefore, it indicated that the MCR1 product, mitochondrial NADH-cytochrome b(5) reductase, plays a key role in the NADH-dependent reduction of D-erythroascorbyl free radical in S. cerevisiae. On the other hand, the mcr1 disruptant cells were hypersensitive to hydrogen peroxide and menadione, and overexpression of MCR1 made the cells more resistant against oxidative stress. These results suggested that the mitochondrial NADH-cytochrome b(5) reductase functions as NADH-D-erythroascorbyl free radical reductase and plays an important role in the response to oxidative damage in S. cerevisiae.


Subject(s)
Ascorbic Acid/metabolism , Cytochrome Reductases/metabolism , Mitochondria/enzymology , Saccharomyces cerevisiae/enzymology , Cytochrome-B(5) Reductase , Free Radicals/metabolism , Oxidation-Reduction , Oxidative Stress/physiology , Saccharomyces cerevisiae/metabolism
17.
Infect Immun ; 69(6): 3939-46, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11349062

ABSTRACT

In some lower eukaryotes, D-erythroascorbic acid, a five-carbon analog of L-ascorbic acid, is present instead of L-ascorbic acid. We have cloned ALO1, the gene encoding D-arabinono-1,4-lactone oxidase, which catalyzes the final step of D-erythroascorbic acid biosynthesis in Candida albicans. The ALO1 gene contained a continuous open reading frame of 1,671 bp that encodes a polypeptide consisting of 557 amino acids with a calculated molecular mass of 63,428 Da. To investigate the functional roles of D-erythroascorbic acid in C. albicans, we disrupted or overexpressed the ALO1 gene. In the alo1/alo1 null mutants, the activity of D-arabinono-1,4-lactone oxidase was completely lost and D-erythroascorbic acid could not be detected. When ALO1 on a multicopy plasmid was transformed in C. albicans, the enzyme activity and the intracellular D-erythroascorbic acid level were increased up to 3.4-fold and 4.0-fold, respectively. The alo1/alo1 null mutants of C. albicans showed increased sensitivity towards oxidative stress. Overexpression of ALO1 made the cells more resistant to the same stress. The alo1/alo1 mutants showed defective hyphal growth and attenuated virulence. Taken together, our results suggest that D-erythroascorbic acid functions as an important antioxidant and can be considered one of the virulence factors enhancing the pathogenicity of C. albicans.


Subject(s)
Ascorbic Acid/biosynthesis , Candida albicans/growth & development , Candida albicans/pathogenicity , Candidiasis/microbiology , Sugar Alcohol Dehydrogenases/metabolism , Amino Acid Sequence , Animals , Candidiasis/physiopathology , Cloning, Molecular , Female , Gene Deletion , Mice , Mice, Inbred BALB C , Molecular Sequence Data , Oxidative Stress , Sequence Analysis, DNA , Sugar Alcohol Dehydrogenases/genetics , Virulence
18.
Biochem J ; 356(Pt 2): 595-604, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11368790

ABSTRACT

Candida albicans possesses a cyanide-resistant respiratory pathway mediated by alternative oxidase (AOX), which seems to be encoded by a gene family with two members. Cloning and expression of AOX1a, one of the genes encoding alternative oxidase from C. albicans, has previously been reported [Huh and Kang (1999) J. Bacteriol. 181, 4098-4102]. In the present study we report the isolation of another gene coding for alternative oxidase, designated AOX1b. AOX1b contains a continuous open reading frame that encodes a polypeptide consisting of 365 amino acids. Interestingly, AOX1a and AOX1b were found to be located in tandem on one of the chromosomes of C. albicans. The presence of cyanide in the culture medium remarkably retarded the growth of the aox1a/aox1a mutants. The growth of the aox1b/aox1b mutants and the aox1a/aox1a aox1b/aox1b double mutants was almost completely inhibited in the same medium. beta-Galactosidase reporter assays indicated that, whereas AOX1a was expressed constitutively, the expression of AOX1b was dependent on growth phase and was induced by treatment with cyanide, antimycin A, H(2)O(2), menadione and paraquat. Growth of the cells in media with non-fermentable carbon sources also enhanced the expression of AOX1b. CaSLN1, which encodes a histidine kinase, seems to be involved in the regulation of AOX expression in C. albicans on the basis of the observation that the activity of cyanide-resistant respiration and the expression level of AOX in the casln1/casln1 mutants were found to be significantly low under normal conditions and slightly increased in the presence of respiratory inhibitors compared with the wild-type strain. Like AOX1a, AOX1b could also be functionally expressed in AOX-deficient Saccharomyces cerevisiae and confer cyanide-resistant respiration on the organism.


Subject(s)
Candida albicans/enzymology , Candida albicans/genetics , Genes, Fungal , Multigene Family , Oxidoreductases/genetics , Amino Acid Sequence , Base Sequence , Candida albicans/drug effects , Candida albicans/growth & development , Cyanides/pharmacology , DNA Primers/genetics , Gene Expression , Genes, Reporter , Mitochondrial Proteins , Molecular Sequence Data , Mutation , Plant Proteins , Restriction Mapping , Saccharomyces cerevisiae/enzymology , Saccharomyces cerevisiae/genetics , Sequence Homology, Amino Acid , beta-Galactosidase/genetics
19.
Am J Contact Dermat ; 12(1): 35-7, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11244139

ABSTRACT

Antimicrobial coating of household products has gained wide acceptance in Japan in the past several years. Pyridine derivatives, used as antifungal or antibacterial agents in many common products, are known to cause contact dermatitis. We present a case of severe contact dermatitis caused by a pyridine derivative used as an antifungal agent in the polyvinyl chloride (PVC) leather of a chair. An open patch test was performed with each ingredient of the PVC leather. Other products were previously eliminated from consideration based on a series of negative patch tests. The PVC leather obtained from the patient's chair gave a ++ reaction with evident blistering, according to the International Contact Dermatitis Research Group standard. Fifteen ingredients of the PVC leather were open patch tested; a positive reaction was found with 2,3,5,6-tetrachloro-4 (methylsulphonyl) pyridine (1% in petrolatum). Clinicians should be aware that antifungal or antibacterial agents may be increasingly incorporated into common household products and should be suspected in cases of contact dermatitis.


Subject(s)
Allergens/adverse effects , Antifungal Agents/adverse effects , Dermatitis, Allergic Contact/diagnosis , Pyridines/adverse effects , Adult , Dermatitis, Allergic Contact/etiology , Dermatitis, Allergic Contact/pathology , Diagnosis, Differential , Humans , Interior Design and Furnishings , Leg , Male , Patch Tests , Polyvinyl Chloride
20.
Curr Treat Options Oncol ; 2(2): 129-35, 2001 Apr.
Article in English | MEDLINE | ID: mdl-12057131

ABSTRACT

Endometrial cancer is a common tumor of the female genital tract. The majority of women diagnosed with endometrial cancer present with early-stage disease. Although the optimal treatment for these patients requires hysterectomy, the use of lymphadenectomy is controversial. Growing scientific data support the use of lymphadenectomy in all patients diagnosed with endometrial cancer. When performed by an experienced surgeon, pelvic and para-aortic lymphadenectomy is a safe and potentially therapeutic procedure that provides prognostic information to the patient and physician. This information allows appropriate, cost-effective treatment strategies to be created for all women with endometrial cancer.


Subject(s)
Endometrial Neoplasms/surgery , Aorta, Thoracic , Endometrial Neoplasms/pathology , Female , Humans , Hysterectomy , Lymph Node Excision , Practice Guidelines as Topic
SELECTION OF CITATIONS
SEARCH DETAIL
...