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1.
J Cancer Educ ; 39(4): 360-367, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38506985

ABSTRACT

A critical shortage of skilled healthcare workers is a primary cause of disparate global cancer outcomes. We report participant evaluation of a multidisciplinary preceptorship program. In collaboration with the city of Kumasi, Ghana, Mayo Clinic and the City Cancer Challenge hosted a preceptorship program for comprehensive multidisciplinary breast and cervix cancer training. A total of 14 healthcare workers from Kumasi received two weeks of training at Mayo Clinic in November and December 2021. Each participant and preceptor were requested to complete an anonymous post-participation survey. Of the 14 trainee participants, 10 (71%) completed the survey. All respondents found the program "valuable and applicable to their clinical practice." Ninety percent reported they were able to "review effective and critical elements in the development and expansion of the multidisciplinary team" and able to "solve practical clinical cases as a team". General themes of satisfaction included: (1) organization and administration, (2) clinical observations and demonstrations, (3) guidelines development, and (4) recognizing the central importance of cultivating a team-based approach. Of the 40 preceptors, 16 (40%) completed the survey. All respondents reported they felt the training would meaningfully "influence patient care in Ghana", that participation "added value or joy to their clinical practice," and all wished to "participate in future preceptorship programs". After a focused two-week program, trainees reported high satisfaction, usefulness from observing specialized cancer care, and value in closely observing a multidisciplinary oncology team. Preceptors reported the experience added joy and perspective to their clinical practice and wished to participate in future programs.


Subject(s)
Medical Oncology , Preceptorship , Humans , Ghana , Medical Oncology/education , Female , Health Personnel/education , Patient Care Team , Surveys and Questionnaires , Male , Program Evaluation , Adult , Breast Neoplasms
2.
Breast Cancer Res Treat ; 196(1): 229-237, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36045271

ABSTRACT

PURPOSE: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is), in combination with endocrine therapy (ET), are standard either in the first (1L) or second-line (2L) setting for the treatment of hormone receptor (HR) positive, HER2-negative metastatic breast cancer (MBC). However, the optimal sequencing of treatments after progression on CDK4/6i remains unknown. We performed a single-institution analysis to identify treatments and outcomes after progression on a CDK4/6i. METHODS: We identified patients with HR-positive, HER2-negative MBC prescribed a CDK4/6i in the 1L or 2L settings from December 2014 to February 2018 at Mayo Clinic in Rochester, Minnesota. Outcomes were collected through September 30, 2020. RESULTS: Palbociclib, in combination with letrozole or fulvestrant, was the most prescribed CDK4/6i. The 1L and 2L CDK4/6i cohorts exhibited comparable overall survival (OS), but progression-free survival (PFS) was longer in the 1L than the 2L cohort [28.2 months (95% CI 19.6-34.9) vs 19.8 months (95% CI 15.7-29.6)]. The most common post-CDK4/6i treatments were PI3K/mTOR inhibitors (PI3K/mTORi), single-agent ET, or chemotherapy. PFS in the 1L CDK4/6i cohort following PI3K/mTORi was 8.5 months (95% CI 5.5 months-NE), single-agent ET was 6.0 months (95% CI 3.3-14.0 months), and chemotherapy PFS was 5.4 months (95% CI 3.3 months-NE). CONCLUSIONS: Following progression on a CDK 4/6i, mPFS was short, with similar PFS times comparing chemotherapy and ET, with slightly longer PFS for targeted strategies (PI3K/mTOR). These results highlight a major need to better understand the mechanisms of CDK4/6i resistance and identify new therapeutic strategies for these patients.


Subject(s)
Breast Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Cyclin-Dependent Kinase 4 , Cyclin-Dependent Kinase 6 , Female , Fulvestrant/therapeutic use , Humans , Letrozole/therapeutic use , Phosphatidylinositol 3-Kinases , Protein Kinase Inhibitors , Receptor, ErbB-2/genetics , Retrospective Studies , TOR Serine-Threonine Kinases
3.
Environ Res ; 204(Pt A): 111915, 2022 03.
Article in English | MEDLINE | ID: mdl-34419472

ABSTRACT

For the optimization of silver nanoparticle production, a central composite design was used with three parameters: AgNO3 concentration, green tea extract concentration, and temperature at three different levels. The size of the synthesized silver nanoparticle, its UV absorbance, zeta potential, and polydispersity index were set as the response parameters. Silver nanoparticles obtained in the optimization process were characterized and its efficacy on colorimetric detection of mercury was evaluated. The response variables were significant for the factors analyzed, and each variable had a significant model (P < 0.05). The ideal conditions were: 1 mM AgNO3, 0.5% green tea extract, and 80 °C temperature. To analyze the produced AgNPs under certain ideal conditions, Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray diffraction (XRD) were used. The UV-visible spectra of AgNPs revealed an absorption maxima at 424 nm. The XRD pattern reveals a significant diffraction peak at 38.25°, 44.26°, 64.43°, and 77.49°, which corresponds to the (111), (200), (220), and (311) planes of polycrystalline face-centered cubic (fcc) silver, respectively. The TEM and SEM analyses confirmed that the particles were spherical, and dynamic light scattering study determined the average diameter of AgNPs to be 77.4 nm. The AgNPs have a zeta potential of -62.6 mV, as determined by the zeta sizer analysis. The AgNPs detects mercury at a micromolar concentration. Furthermore, the environmentally friendly generated AgNPs were used to detect mercury in a colorimetric method that was effectively employed for analytical detection of Hg2+ ions in an aqueous environment for the purpose of practical application.


Subject(s)
Mercury , Metal Nanoparticles , Anti-Bacterial Agents , Colorimetry , Industrial Waste , Plant Extracts , Silver , Tea , Wastewater
4.
Environ Res ; 205: 112477, 2022 04 01.
Article in English | MEDLINE | ID: mdl-34863690

ABSTRACT

Green mediated biosynthesis of iron oxide nanoparticles utilising Rosa indica flower petal extracts (RIFP-FeONPs) was used in this investigation. The RIFP-FeONPs were evaluated by the UV-Visible Spectroscopy, FTIR, SEM, EDX, XRD, Zeta potentials, and DLS, and been engaged than for the elimination of Cr (VI) from the contaminated environments. At 269 nm, the RIFP-FeONPs surface plasmon vibration bands were observed, which attributed to the Fe3+. XRD patterns of RIFP-FeONPs depicted the intense diffraction peak of face-centered cubic (fcc) iron at a 2θ value of 45.33° from the (311) lattice plane indisputably revealed that the particles are constituted of pure iron. The fabricated nanomaterials are spherical and polydisperse with a diameter of 70-120 nm, and various agglomeration clusters are attributable to intermolecular interaction. Zeta potential measurement and particle size distribution of RIFP-FeONPs showed a mean average size of 115.5 ± 29 nm and a polydispersity index (PDI) of 0.420. The study aims to analyse the appropriateness of RIFP-FeONPs for removing hexavalent chromium from the aqueous environment and the application of adsorption isotherm and statistical models in the experiment. The sorption of Cr (VI) on RIFP-FeONPs was observed to fit well with the isothermal models (R2 = 0.98). The linear correlation between processing parameters and time demonstrated that the adsorption efficiency of Cr (VI) well correlated with the pseudo-first order kinetic model and isothermal adsorption with the Langmuir and Freundlich isothermal models, so that the RIFP-FeONPs could be a prospective nanosorbent for hexavalent chromium removal from industrial waste.


Subject(s)
Nanoparticles , Water Pollutants, Chemical , Adsorption , Chromium/analysis , Hydrogen-Ion Concentration , Iron/chemistry , Kinetics , Nanoparticles/chemistry , Prospective Studies , Water Pollutants, Chemical/analysis
5.
Environ Res ; 204(Pt A): 112030, 2022 03.
Article in English | MEDLINE | ID: mdl-34508771

ABSTRACT

The study was designed to determine the impact of acute toxicity of fumaronitrile exposure through tissue damaging, oxidative stress enzymes and histopathological studies in gills, liver and muscle cells of freshwater tilapia fish (Oreochromis mossambicus). In gill, liver, and muscle cells, biochemical indicators such as tissue damage enzymes (Acid Phosphatase (ACP), Alkaline Phosphatase (ALP), and Lactate Dehydrogenase (LDH)) and antioxidative enzymes (Superoxide Dismutase (SOD); Catalase (CAT); Glutathione-S-transferase (GST); Reduced Glutathione (GSH); Glutamate oxaloacetate transaminase (GOT) and Glutamate pyruvate transaminase (GPT) were quantified in the time interval of 30, 60 and 90 days exposure to the fumaronitrile. After 90 days, under 6 ppb exposure conditions, the acid phosphatase (ACP) levels of fish increased significantly in the gills (3.439 µmol/mg protein/min), liver (1.743 µmol/mg protein/min), and muscles (2.158 µmol/mg protein/min). After 90 days of exposure to the same concentration and days, ALP activity increased significantly in gills (4.354 µmol/mg protein/min) and liver (1.754 µmol/mg protein/min), but muscle cells had a little decrease in ALP activity (2.158 µmol/mg protein/min). The LDH concentration in gills following treatment with fumaronitrile over a period of 0-90 days was 3.573 > 3.521 > 2.245 µmol/mg protein/min over 30 > 60 > 90 days. However, at the same dose and treatment duration, a greater LDH level of 0.499 µmol/mg protein/min was found in liver and muscle cells. Histopathological abnormalities in the gills, liver, and muscle cells of treated fish were also examined, indicating that fumaronitrile treatment generated the most severe histological changes. The current study reveals that fumaronitrile exposure has an effect on Oreochromis mossambicus survival, explaining and emphasising the risk associated with this POP exposure to ecosystems and human populations.


Subject(s)
Tilapia , Water Pollutants, Chemical , Animals , Antioxidants/metabolism , Catalase/metabolism , Ecosystem , Fumarates , Gills , Industrial Waste , Lipid Peroxidation , Liver , Oxidative Stress , Persistent Organic Pollutants , Superoxide Dismutase/metabolism , Tilapia/metabolism , Wastewater , Water Pollutants, Chemical/metabolism
6.
Clin Cancer Res ; 30(15): 3147-3156, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38752717

ABSTRACT

PURPOSE: We previously reported that postmenopausal women with estrogen receptor-α-positive breast cancer receiving adjuvant anastrozole 1 mg/day (ANA1) with estrone (E1) ≥1.3 pg/mL and estradiol (E2) ≥0.5 pg/mL [inadequate estrogen suppression (IES)] had a threefold increased risk of a breast cancer event. The objective of this study was to determine if increasing anastrozole to 10 mg/day (ANA10) could result in adequate estrogen suppression (AES: E1 <1.3 pg/mL and/or E2 <0.5 pg/mL) among those with IES on ANA1. PATIENTS AND METHODS: Postmenopausal women with estrogen receptor-α-positive breast cancer planning to receive adjuvant ANA1 were eligible. E1 and E2 were assessed pre- and post-8 to 10 weeks of ANA1. Those with IES were switched to 8- to 10-week cycles of ANA10 followed by letrozole 2.5 mg/day. E1 and E2 were assessed after each cycle. Anastrozole concentrations were measured post-ANA1 and post-ANA10. Primary analyses included patients who documented taking at least 80% of the planned treatment (adherent cohort). RESULTS: In total, 132 (84.6%) of 156 eligible patients were ANA1 adherent. IES occurred in 40 (30.3%) adherent patients. Twenty-five (78.1%) of 32 patients who began ANA10 were adherent, and AES was achieved in 19 (76.0%; 90% confidence interval, 58.1%-89.0%) patients. Anastrozole concentrations post-ANA1 and post-ANA10 did not differ by estrogen suppression status among adherent patients. AES was maintained/attained in 21 (91.3%) of 23 letrozole-adherent patients. CONCLUSIONS: Approximately 30% of ANA1-adherent patients had IES. Among those who switched to ANA10 and were adherent, 76% had AES. Further studies are required to validate emerging data that ANA1 results in IES for some patients and to determine the clinical benefit of switching to ANA10 or an alternative aromatase inhibitor.


Subject(s)
Anastrozole , Breast Neoplasms , Nitriles , Postmenopause , Triazoles , Humans , Anastrozole/administration & dosage , Anastrozole/therapeutic use , Anastrozole/adverse effects , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Middle Aged , Aged , Triazoles/administration & dosage , Triazoles/adverse effects , Nitriles/administration & dosage , Nitriles/adverse effects , Estrogens/administration & dosage , Neoplasm Staging , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/adverse effects , Antineoplastic Agents, Hormonal/therapeutic use , Prospective Studies , Estradiol/administration & dosage , Estrone/blood , Estrone/administration & dosage , Aromatase Inhibitors/administration & dosage , Aromatase Inhibitors/adverse effects
7.
JAMA Oncol ; 9(6): 815-824, 2023 06 01.
Article in English | MEDLINE | ID: mdl-36892847

ABSTRACT

Importance: Aurora A kinase (AURKA) activation, related in part to AURKA amplification and variants, is associated with downregulation of estrogen receptor (ER) α expression, endocrine resistance, and implicated in cyclin-dependent kinase 4/6 inhibitor (CDK 4/6i) resistance. Alisertib, a selective AURKA inhibitor, upregulates ERα and restores endocrine sensitivity in preclinical metastatic breast cancer (MBC) models. The safety and preliminary efficacy of alisertib was demonstrated in early-phase trials; however, its activity in CDK 4/6i-resistant MBC is unknown. Objective: To assess the effect of adding fulvestrant to alisertib on objective tumor response rates (ORRs) in endocrine-resistant MBC. Design, Setting, and Participants: This phase 2 randomized clinical trial was conducted through the Translational Breast Cancer Research Consortium, which enrolled participants from July 2017 to November 2019. Postmenopausal women with endocrine-resistant, ERBB2 (formerly HER2)-negative MBC who were previously treated with fulvestrant were eligible. Stratification factors included prior treatment with CDK 4/6i, baseline metastatic tumor ERα level measurement (<10%, ≥10%), and primary or secondary endocrine resistance. Among 114 preregistered patients, 96 (84.2%) registered and 91 (79.8%) were evaluable for the primary end point. Data analysis began after January 10, 2022. Interventions: Alisertib, 50 mg, oral, daily on days 1 to 3, 8 to 10, and 15 to 17 of a 28-day cycle (arm 1) or alisertib same dose/schedule with standard-dose fulvestrant (arm 2). Main Outcomes and Measures: Improvement in ORR in arm 2 of at least 20% greater than arm 1 when the expected ORR for arm 1 was 20%. Results: All 91 evaluable patients (mean [SD] age, 58.5 [11.3] years; 1 American Indian/Alaskan Native [1.1%], 2 Asian [2.2%], 6 Black/African American [6.6%], 5 Hispanic [5.5%], and 79 [86.8%] White individuals; arm 1, 46 [50.5%]; arm 2, 45 [49.5%]) had received prior treatment with CDK 4/6i. The ORR was 19.6%; (90% CI, 10.6%-31.7%) for arm 1 and 20.0% (90% CI, 10.9%-32.3%) for arm 2. In arm 1, the 24-week clinical benefit rate and median progression-free survival time were 41.3% (90% CI, 29.0%-54.5%) and 5.6 months (95% CI, 3.9-10.0), respectively, and in arm 2 they were 28.9% (90% CI, 18.0%-42.0%) and 5.4 months (95% CI, 3.9-7.8), respectively. The most common grade 3 or higher adverse events attributed to alisertib were neutropenia (41.8%) and anemia (13.2%). Reasons for discontinuing treatment were disease progression (arm 1, 38 [82.6%]; arm 2, 31 [68.9%]) and toxic effects or refusal (arm 1, 5 [10.9%]; arm 2, 12 [26.7%]). Conclusions and Relevance: This randomized clinical trial found that adding fulvestrant to treatment with alisertib did not increase ORR or PFS; however, promising clinical activity was observed with alisertib monotherapy among patients with endocrine-resistant and CDK 4/6i-resistant MBC. The overall safety profile was tolerable. Trial Registration: ClinicalTrials.gov Identifier: NCT02860000.


Subject(s)
Breast Neoplasms , Humans , Female , Middle Aged , Fulvestrant , Breast Neoplasms/pathology , Estrogen Receptor alpha , Aurora Kinase A/therapeutic use , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Antineoplastic Combined Chemotherapy Protocols/adverse effects
8.
Gynecol Oncol ; 124(2): 210-5, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22047770

ABSTRACT

OBJECTIVE: To evaluate the efficacy and biological effects of the gemcitabine/tanespimycin combination in patients with advanced ovarian and peritoneal cancer. To assess the effect of tanespimycin on tumor cells, levels of the chaperone proteins HSP90 and HSP70 were examined in peripheral blood mononuclear cells (PBMC) and paired tumor biopsy lysates. METHODS: Two-cohort phase II clinical trial. Patients were grouped according to prior gemcitabine therapy. All participants received tanespimycin 154 mg/m(2) on days 1 and 9 of cycle 1 and days 2 and 9 of subsequent cycles. Patients also received gemcitabine 750 mg/m(2) on day 8 of the first treatment cycle and days 1 and 8 of subsequent cycles. RESULTS: The tanespimycin/gemcitabine combination induced a partial response in 1 gemcitabine naïve patient and no partial responses in gemcitabine resistant patients. Stable disease was seen in 6 patients (2 gemcitabine naïve and 4 gemcitabine resistant). The most common toxicities were hematologic (anemia and neutropenia) as well as nausea and vomiting. Immunoblotting demonstrated limited upregulation of HSP70 but little or no change in levels of most client proteins in PBMC and paired tumor samples. CONCLUSIONS: Although well tolerated, the tanespimycin/gemcitabine combination exhibited limited anticancer activity in patients with advanced epithelial ovarian and primary peritoneal carcinoma, perhaps because of failure to significantly downregulate the client proteins at clinically achievable exposures.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasms, Glandular and Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Benzoquinones/administration & dosage , Benzoquinones/adverse effects , Biomarkers, Tumor/metabolism , Carcinoma, Ovarian Epithelial , Cell Line, Tumor , Cohort Studies , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Female , HSP70 Heat-Shock Proteins/metabolism , HSP90 Heat-Shock Proteins/metabolism , Humans , Lactams, Macrocyclic/administration & dosage , Lactams, Macrocyclic/adverse effects , Middle Aged , Neoplasms, Glandular and Epithelial/metabolism , Ovarian Neoplasms/metabolism , Peritoneal Neoplasms/metabolism , Survival Rate , Gemcitabine
9.
Gynecol Oncol ; 127(1): 55-62, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22664059

ABSTRACT

PURPOSE: Based upon promising preclinical and phase 1 trial results, combined flavopiridol and cisplatin therapy was evaluated in patients with ovarian and primary peritoneal cancers. METHODS: A two cohort phase 2 trial of cisplatin (60 mg/m2 IV) immediately followed by flavopiridol (100 mg/m2 IV, 24 h infusion; 21 day cycles) was undertaken in patients with recurrent platin-sensitive or platin-resistant disease (progression>vs. ≤6 months following prior platin-based therapy). Measurable disease (RECIST)--or evaluable disease plus CA125>2X post-treatment nadir--and ECOG performance≤2 were required. RESULTS: Forty-five patients were enrolled between December 23, 2004 and February 25, 2010: 40 platin-resistant (Group 1), and 5 platin-sensitive (Group 2). In Group 1, the median number of treatment cycles was 3 (range 2-12). Only 10% of patients incurred grade 4 toxicities, but grade 3 toxicities were common (65%): neutropenia (17.5%); nausea (12.5%); vomiting, fatigue, thrombosis, anemia (10% each). Seven patients (17.5%) achieved a confirmed response (1 CR, 6 PR; median duration 118 days); ten additional patients (25%) attained maintained stable disease. Median time to progression was 4.3 months; overall survival was 16.1 months. Pilot translational studies assessed ascites flavopiridol level; surrogate marker studies were uninformative. In Group 2, although 4 of 5 patients responded (2 confirmed PRs with median time to progression, 10.8 months and median overall survival 20.6 months) the cohort was closed due to poor accrual. CONCLUSIONS: The assessed flavopiridol and cisplatin regimen displayed clinical activity in platin resistant and sensitive ovarian/primary peritoneal cancers, meriting further study.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ovarian Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cell Survival/drug effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cohort Studies , Disease-Free Survival , Drug Resistance, Neoplasm , Female , Flavonoids/administration & dosage , Flavonoids/adverse effects , Humans , Middle Aged , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/pathology , Piperidines/administration & dosage , Piperidines/adverse effects , Young Adult
10.
Gynecol Oncol ; 122(1): 116-20, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21514634

ABSTRACT

OBJECTIVE: Resistance to chemotherapy is a major challenge in the treatment of ovarian/peritoneal cancer. One purported mechanism of topotecan resistance is the breast cancer resistance protein (BCRP) and P-glycoprotein (Pgp). We designed a phase II clinical trial evaluating the efficacy and adverse event profile of concomitant topotecan and lapatinib, a small molecule pan-erbB inhibitor that can block BCRP/Pgp efflux of topotecan. METHODS: Patients with platinum-refractory or resistant epithelial ovarian/peritoneal cancer were treated with topotecan 3.2 mg/m² IV on Day 1, 8 and 15 and lapatinib 1250 mg PO daily, continuously in 28 day cycles. The primary endpoint was response rate. For correlative studies, archived tissue was assessed for expression of EGFR, HER2, HIF-1α, CD31, and BCRP. RESULTS: Eighteen patients were enrolled and treated. Four experienced evidence of clinical benefit: one partial response and three with stable disease. Using a two-stage Simon design, the trial was stopped after the first stage due to insufficient activity. Grades 3+ and 4+ adverse events (AE) were experienced in 14 and 4 patients, respectively. The most common grade 3/4 AE were neutropenia (56%), thrombocytopenia (28%), and diarrhea (22%). CONCLUSIONS: The combination of lapatinib plus topotecan for the treatment of platinum refractory/resistant epithelial ovarian cancer lacks sufficient activity to warrant further investigation. In particular, hematologic adverse events were substantial. Expression of correlative study markers did not reveal patterns of predicted benefit or toxicity. Disruption of erbB signaling and BCRP/Pgp efflux with lapatinib was insufficient for overcoming topotecan resistance, suggesting alternative mechanisms of resistance are involved.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ovarian Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , ATP Binding Cassette Transporter, Subfamily G, Member 2 , ATP-Binding Cassette Transporters/biosynthesis , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/metabolism , Disease-Free Survival , Drug Resistance, Neoplasm , ErbB Receptors/biosynthesis , Female , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis , Lapatinib , Middle Aged , Neoplasm Proteins/biosynthesis , Organoplatinum Compounds/pharmacology , Platelet Endothelial Cell Adhesion Molecule-1/biosynthesis , Quinazolines/administration & dosage , Quinazolines/adverse effects , Receptor, ErbB-2/biosynthesis , Survival Rate , Topotecan/administration & dosage , Topotecan/adverse effects
11.
J Cancer Educ ; 26(3): 474-7, 2011 Sep.
Article in English | MEDLINE | ID: mdl-20857352

ABSTRACT

This study examined how the lay electronic media covers poly-ADP-ribose polymerase, or "PARP," inhibitors, a class of cancer agents currently under clinical investigation. Of 771 internet links, 51 targeted the lay public. Independent review by two investigators yielded the following categorizations: 36 (71%) were "overly positive", 15 (29%) "neutral", and none "overly negative". "Overly positive" articles used: (l) overstated benefit, (2) included quotations from enthusiastic scientists, and (3) discussed single or small patient subsets. They used such phrases as "the holy grail of cancer research", "the most exciting development in cancer research in a decade or more…. it could save thousands of lives", and "we were surprised and delighted…. it's the kind of thing you don't really think will happen". Healthcare providers should be aware of the foregoing when discussing PARP inhibitors-and perhaps other novel therapies-with cancer patients.


Subject(s)
Advertising , Antineoplastic Agents/therapeutic use , Choice Behavior , Enzyme Inhibitors/therapeutic use , Neoplasms/drug therapy , Poly(ADP-ribose) Polymerase Inhibitors , Humans , Internet , Neoplasms/enzymology , Television
12.
Indian Dermatol Online J ; 11(1): 68-71, 2020.
Article in English | MEDLINE | ID: mdl-32055513

ABSTRACT

Perforating dermatoses are characterized by transepidermal elimination of altered dermal components or foreign particles. Owing to their common clinical presentation as umbilicated papules with a keratotic plug, histopathology and special staining play a very crucial role in the diagnosis. Perforating calcific elastosis, (periumbilical perforating pseudoxanthoma elasticum), an uncommon acquired localized cutaneous dermatoses, is characterized by transepidermal elimination of modified elastic fibres. It is usually seen in middle-aged obese multiparous women as well-defined periumbilical hyperpigmented atrophic plaques. We report a case of a 66-year-old female who presented with a mildly pruritic hyperpigmented periumbilical plaque of 2 years duration. Histopathology studies revealed multiple fragmented, thick, short, and curly eosinophilic fibers; along with granular basophilic material in the dermis, which stained positive for calcium and elastin, thus clinching the diagnosis of perforating calcific elastosis. There were no features of hereditary pseudoxanthoma elasticum. We report this case for its rarity.

13.
J Clin Oncol ; 38(13): 1409-1418, 2020 05 01.
Article in English | MEDLINE | ID: mdl-32125938

ABSTRACT

PURPOSE: To determine the sensitivity and specificity of genetic testing criteria for the detection of germline pathogenic variants in women with breast cancer. MATERIALS AND METHODS: Women with breast cancer enrolled in a breast cancer registry at a tertiary cancer center between 2000 and 2016 were evaluated for germline pathogenic variants in 9 breast cancer predisposition genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53). The performance of the National Comprehensive Cancer Network (NCCN) hereditary cancer testing criteria was evaluated relative to testing of all women as recommended by the American Society of Breast Surgeons. RESULTS: Of 3,907 women, 1,872 (47.9%) meeting NCCN criteria were more likely to carry a pathogenic variant in 9 predisposition genes compared with women not meeting criteria (9.0% v 3.5%; P < .001). Of those not meeting criteria (n = 2,035), 14 (0.7%) had pathogenic variants in BRCA1 or BRCA2. The sensitivity of NCCN criteria was 70% for 9 predisposition genes and 87% for BRCA1 and BRCA2, with a specificity of 53%. Expansion of the NCCN criteria to include all women diagnosed with breast cancer at ≤ 65 years of age achieved > 90% sensitivity for the 9 predisposition genes and > 98% sensitivity for BRCA1 and BRCA2. CONCLUSION: A substantial proportion of women with breast cancer carrying germline pathogenic variants in predisposition genes do not qualify for testing by NCCN criteria. Expansion of NCCN criteria to include all women diagnosed at ≤ 65 years of age improves the sensitivity of the selection criteria without requiring testing of all women with breast cancer.


Subject(s)
Breast Neoplasms/genetics , Genetic Predisposition to Disease/genetics , Genetic Testing/methods , Germ-Line Mutation , Hospitals , Adult , Aged , Aged, 80 and over , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/diagnosis , Breast Neoplasms/prevention & control , Fanconi Anemia Complementation Group N Protein/genetics , Female , Humans , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Young Adult
14.
Microbiol Res ; 164(1): 105-13, 2009.
Article in English | MEDLINE | ID: mdl-17207981

ABSTRACT

Response surface methodology was employed for the optimization of different nutritional and physical parameters for the production of laccase by the filamentous bacteria Streptomyces psammoticus MTCC 7334 in submerged fermentation. Initial screening of production parameters was performed using a Plackett - Burman design and the variables with statistically significant effects on laccase production were identified. Incubation temperature, incubation period, agitation rate, concentrations of yeast extract, MgSO(4)7H(2)O, and trace elements were found to influence laccase production significantly. These variables were selected for further optimization studies using a Box-Behnken design. The statistical optimization by response surface methodology resulted in a three-fold increase in the production of laccase by S. psammoticus MTCC 7334.


Subject(s)
Bacterial Proteins/metabolism , Culture Techniques/methods , Laccase/metabolism , Streptomyces/metabolism , Biomass , Fermentation , Temperature
15.
Lett Appl Microbiol ; 46(3): 338-43, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18266642

ABSTRACT

AIM: The present study was aimed at evaluating the effects of the three crucial factors, galactose concentration, inoculum size and moisture content, on alpha-galactosidase production by the filamentous actinobacterium Streptomyces griseoloalbus in solid-state fermentation. METHODS AND RESULTS: Central Composite design was adopted to derive a statistical model for the optimization of fermentation conditions. Maximum alpha-galactosidase yield (117 U g(-1) of dry fermented substrate) was obtained when soya bean flour supplemented with 1.5% galactose and with initial moisture content of 40% was inoculated with 1.9 x 10(6) CFU g(-1) initial dry substrate. CONCLUSIONS: The model was valid and could result in considerably enhanced enzyme yield. SIGNIFICANCE AND IMPACT OF THE STUDY: The results indicated a cost effective method for the production of alpha-galactosidase using soya bean flour. This is the first report on exploitation of the potential of filamentous bacterium for the production of alpha-galactosidase, an enzyme having versatile applications.


Subject(s)
Bioreactors , Biotechnology/methods , Models, Biological , Streptomyces/enzymology , Streptomyces/growth & development , alpha-Galactosidase/biosynthesis , Biomass , Culture Media , Fermentation , Galactose/metabolism , Humidity , Glycine max/metabolism
16.
Bioresour Technol ; 99(14): 6697-701, 2008 Sep.
Article in English | MEDLINE | ID: mdl-17996445

ABSTRACT

Polygalacturonase produced by Streptomyces lydicus was purified to homogeneity by ultrafiltration and a combination of ion exchange and gel filtration chromatographic procedures. The purified enzyme was an exo-polygalacturonase with a molecular weight of 43 kDa. It was optimally active at 50 degrees C and pH 6.0. The enzyme was stable from pH 4.0 to 7.0 and at or below 45 degrees C for 90 min. K(m) value for polygalacturonic acid was 1.63 mg/mL and the corresponding V(max) was 677.8 microM min(-1) mg(-1). The inhibition constant (K(i)) for gluconic acid d-lactone was 20.75 mM. Purified enzyme had been inhibited by N-bromosuccinimide, while l-tryptophan could induce enzyme activity, indicating the involvement of tryptophan at the active site.


Subject(s)
Polygalacturonase/isolation & purification , Streptomyces/enzymology , Chromatography, Gel , Chromatography, Ion Exchange , Electrophoresis, Polyacrylamide Gel , Hydrogen-Ion Concentration , Kinetics , Polygalacturonase/chemistry , Polygalacturonase/metabolism , Substrate Specificity , Temperature , Ultrafiltration
17.
Bioresour Technol ; 99(9): 3325-30, 2008 Jun.
Article in English | MEDLINE | ID: mdl-17904364

ABSTRACT

Streptomyces griseoloalbus was immobilized in calcium alginate gel and the optimal immobilization parameters (concentrations of sodium alginate and calcium chloride, initial biomass and curing time) for the enhanced production of alpha-galactosidase were determined. The immobilization was most effective with 3% sodium alginate and 0.1M calcium chloride. The optimal initial biomass for immobilization was approximately 2.2g (wet wt.). The alginate-entrapped cells were advantageous because there was a twofold increase in the enzyme yield (55 U/ml) compared to the highest yield obtained with free cells (23.6 U/ml). Moreover, with immobilized cells the maximum yield was reached after 72 h of incubation in batch fermentation under optimal conditions, whereas in the case of free cells the maximum enzyme yield was obtained only after 96 h of incubation. The alginate beads had good stability and also retained 75% ability of enzyme production even after eight cycles of repeated batch fermentation. It is significant that this is the first report on whole-cell immobilization for alpha-galactosidase production.


Subject(s)
Biotechnology/methods , Cells, Immobilized/enzymology , Streptomyces/enzymology , alpha-Galactosidase/biosynthesis , Alginates/pharmacology , Calcium Chloride/pharmacology , Cells, Immobilized/drug effects , Glucuronic Acid/pharmacology , Hexuronic Acids/pharmacology , Streptomyces/drug effects , Time Factors
18.
Bioresour Technol ; 99(11): 4583-9, 2008 Jul.
Article in English | MEDLINE | ID: mdl-17765539

ABSTRACT

The process parameters influencing the production of extracellular laccases by Streptomyces psammoticus MTCC 7334 were optimized in submerged fermentation. Coffee pulp and yeast extract were the best substrate and nitrogen source respectively for laccase production by this strain. The optimization studies revealed that the laccase yield was maximum at pH 7.5 and temperature 32 degrees C. Salinity of the medium was also observed to be influencing the enzyme production. An agitation rate of 175 rpm and 15% inoculum were the other optimized conditions for maximum laccase yield (5.9 U/mL). Pyrogallol and para-anisidine proved to be the best inducers for laccase production by this strain and the enzyme yield was enhanced by 50% with these inducers. S. psammoticus was able to decolourize various industrial dyes at different rates and 80% decolourization of Remazol Brilliant Blue R (RBBR) was observed after 10 days of incubation in dye based medium.


Subject(s)
Coloring Agents/metabolism , Laccase/biosynthesis , Streptomyces/enzymology , Biomass , Color , Copper Sulfate/pharmacology , Hydrocarbons, Aromatic/pharmacology , Hydrogen-Ion Concentration/drug effects , Lignin/metabolism , Nitrogen/pharmacology , Salinity , Spectrum Analysis , Streptomyces/drug effects , Temperature , Time Factors
19.
Microbiol Res ; 163(5): 538-44, 2008.
Article in English | MEDLINE | ID: mdl-16962301

ABSTRACT

Sediment samples were collected from different estuarine and marine areas along the West coast of India. Eighteen actinomycete cultures were isolated using starch casein agar and were screened for polygalacturonase activity by growing them on pectin-agar plates. Clear zones were visualized using 1% cetrimide. Out of the 18 strains screened ten cultures could effect hydrolysis of pectin. The above cultures were subjected to secondary screening under submerged fermentation. The actinomycete strain of Streptomyces lydicus was found to be a potent producer of polygalacturonase. Different growth media were screened for enzyme production and the best medium was selected for further studies. The crude enzyme was used for the treatment of raw banana fibers.


Subject(s)
Actinobacteria/enzymology , Fungal Proteins/metabolism , Geologic Sediments/microbiology , Musa/metabolism , Pectins/metabolism , Polygalacturonase/metabolism , Actinobacteria/isolation & purification , Culture Media/chemistry , Hydrolysis , India , Musa/microbiology
20.
Bioresour Technol ; 98(3): 485-90, 2007 Feb.
Article in English | MEDLINE | ID: mdl-16844369

ABSTRACT

The present study aimed at optimization of culture condition for the enhanced production of extra cellular thermostable cellulase-free xylanase from Bacillus pumilus by solid-state fermentation. Batch studies were carried out to evaluate various agro-industrial residues such as rice bran, rice husk, rice straw, sawdust, coconut pith, sugarcane bagasse and wheat bran for enzyme production by the bacterial culture. The endoxylanase production was highest on wheat bran media (5582 U/gds), which was enhanced 3.8-fold (21,431 U/gds) by optimization of cultivation conditions. The enzymatic extracts was used in mixed wastepaper recycling, which resulted in a considerable improvement of the paper strength with high drainage and easy drying up. The results of enzyme application with recycled paper clearly indicated that the effective use of enzymes in fiber separation could reduce the cost of carton paper production.


Subject(s)
Bacillus/enzymology , Conservation of Natural Resources , Endo-1,4-beta Xylanases/metabolism , Paper , Cellulase/metabolism , Fermentation , Hot Temperature , Hydrogen-Ion Concentration , Refuse Disposal/methods
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