scholarly journals NEW PYRALIDS

1876 ◽  
Vol 8 (5) ◽  
pp. 98-99 ◽  
Author(s):  
A. R. Grote
Keyword(s):  
Dark Spot ◽  
Lemon Yellow ◽  
Second Line ◽  
The Third ◽  
Small Spot ◽  
Base Form ◽  
Internal Margin

♂ ♀. This species in ornamentation approaches partialis Led., Taf.9, fig. 8. Both wings clear pale lemon yellow. Primaries crossed by four equidistant lines, of which the first three from the base form brown spots narrowly outlined in black on the costal region. The third spot coalesces with an inferior spot on the line. The second line widens into a small spot on internal margin. The fourth line has a small dark spot on costa and one on internal margin.

scholarly journals Pegvisomant and Pasireotide LAR as second line therapy in acromegaly: clinical effectiveness and predictors of response

2021 ◽  
Vol 184 (2) ◽  
pp. 217-229
Author(s):  
Sabrina Chiloiro ◽  
Antonella Giampietro ◽  
Federica Mirra ◽  
Federico Donfrancesco ◽  
Tommaso Tartaglione ◽  
...  
Keyword(s):  
First Generation ◽  
Third Ventricle ◽  
Free Time ◽  
Second Line ◽  
Tumor Extension ◽  
The Third ◽  
Clinical Biomarkers ◽  
Predictors Of Response ◽  
Igf I ◽  
Pre Treatment

Background The treatment of acromegaly resistant to first-generation somatostatin receptor ligands (SRLs) is often difficult. Pegvisomant and Pasireotide LAR are mostly used in these subset of patients, as second line therapies. Choice of the type of second line therapies is difficult, since predictors of response are still unclear, impairing personalized therapy. We aimed to investigate predictors of response to Pegvisomant and Pasireotide LAR. Methods Seventy-four acromegaly patients entered this observational, cross-sectional and retrospective study if (i) resistant to high dose first-generation SRLs and (ii) treated with Pegvisomant and Pasireotide LAR for at least 12 consecutive months. Patients treated with radiotherapy in the previous 10 years were excluded. Results Fourty-one patients were treated with Pegvisomant and 33 with Pasireotide LAR. At the end of the study, acromegaly was controlled in 35 patients treated with Pegvisomant (85.4%) and in 23 treated with Pasireotide LAR (69.7%). In this cohort, a poor Pegvisomant response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (P = 0.004, HR: 1.6, 95%CI: 1.2–4.6), with a Ki67-Li >4% (P = 0.004, HR: 3.49, 95%CI: 1.4–4.0) and with pre-treatment IGF-I >3.3×ULN (P=0.03, HR: 1.3, 95%CI: 1.1–6.0). A poor Pasireotide LAR response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (P=0.025, HR: 1.6 95%CI: 1.4–3.4), pre-treatment IGF-I >2.3×ULN (P=0.049, HR: 2.4, 95%CI: 1.4–8.0), absent/low SST5 membranous expression (P=0.023 HR: 4.56 95%CI: 1.3–6.4) and in patients carried the d3-delated GHR isoform (P=0.005, HR: 11.37, 95%CI: 1.3–20.0). Conclusion Molecular and clinical biomarkers can be useful in predicting the responsiveness to Pegvisomant and Pasireotide LAR.

Aromatase Inhibitors in the Treatment and Prevention of Breast Cancer

2001 ◽  
Vol 19 (3) ◽  
pp. 881-894 ◽  
Author(s):  
Paul E. Goss ◽  
Kathrin Strasser
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Clinical Status ◽  
Phase Iii ◽  
Type I ◽  
Third Generation ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
The Third

PURPOSE: The purpose of this article is to provide an overview of the current clinical status and possible future applications of aromatase inhibitors in breast cancer. METHODS: A review of the literature on the third-generation aromatase inhibitors was conducted. Some data that have been presented but not published are included. In addition, the designs of ongoing trials with aromatase inhibitors are outlined and the implications of possible results discussed. RESULTS: All of the third-generation oral aromatase inhibitors—letrozole, anastrozole, and vorozole (nonsteroidal, type II) and exemestane (steroidal, type I)—have now been tested in phase III trials as second-line treatment of postmenopausal hormone-dependent breast cancer. They have shown clear superiority compared with the conventional therapies and are therefore considered established second-line hormonal agents. Currently, they are being tested as first-line therapy in the metastatic, adjuvant, and neoadjuvant settings. Preliminary results suggest that the inhibitors might displace tamoxifen as first-line treatment, but further studies are needed to determine this. CONCLUSION: The role of aromatase inhibitors in premenopausal breast cancer and in combination with chemotherapy and other anticancer treatments are areas of future exploration. The ongoing adjuvant trials will provide important data on the long-term safety of aromatase inhibitors, which will help to determine their suitability for use as chemopreventives in healthy women at risk of developing breast cancer.

Six Portraits of Political Ambition in Xenophon's Memorabilia

2014 ◽  
Vol 109 (1) ◽  
pp. 79-92 ◽  
Author(s):  
LEWIS FALLIS
Keyword(s):  
Political Community ◽  
Human Beings ◽  
Political Ambition ◽  
The Third ◽  
Dialectical Approach ◽  
Greek Philosopher ◽  
High Form ◽  
Base Form

In this article I claim that the Greek philosopher Xenophon, in the third book of his Memorabilia, catalogues six—and perhaps the six—essential and enduring forms of human ambition. Most treatments of ambition depict the phenomenon as monolithic; or, at best, as dichotomous. That is, ambition is understood as a single trait or passion shared by all ambitious people, its manifestations differing only according to circumstance; or, alternatively, as a trait or passion with one good (or high) form and one bad (or base) form. Little attention is paid to an enterprise of cataloguing various types of human beings as embodying distinct forms of ambition, forms which a political community must tolerate or encourage, channel or confront, in different ways. This enterprise is best carried out through the dialectical approach, in which the personality of a particular interlocutor emerges in light of, and in response to, Socratic scrutiny.

Outcome of Patients with CML Treated with Dasatinib or Nilotinib after Failure of Second Prior TKIs

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2294-2294
Author(s):  
Antonella Russo Rossi ◽  
Massimo Breccia ◽  
Fausto Castagnetti ◽  
Luigiana Luciano ◽  
Antonella Gozzini ◽  
...  
Keyword(s):  
Median Time ◽  
Conflicts Of Interest ◽  
Cell Uptake ◽  
Second Line ◽  
The Third ◽  
Line Therapy ◽  
Third Line ◽  
New Mutations

Abstract Abstract 2294 Background. The TKIs Nilotinib and Dasatinib offer additional therapeutic options for patients with CML who are resistant or intolerant to Imatinib. These agents, active against the majority of Imatinib resistant BCR-ABL mutated clones, have a different pattern of kinase target selectivity, pharmacokinetics parameters, cell uptake, efflux properties and adverse events profiles. Preliminary results suggest that some patients may respond to a second TKI used as third line therapy, but little is known about the long term benefit of such an approach.Aim of this collaborative Italian study was to verify the response (rate and duration) and the clinical outcome in patients with CML treated with a third TKI after sequential failure of the previous ones. Methods. We evaluated 66 patients with CML, resistant/intolerant to Imatinib and treated with Dasatinib or Nilotinib, then switched to a third- line TKI after treatment failure. Of these, 29 patients were treated with dasatinib after imatinib/nilotinib failure and 37 with nilotinib after imatinib/dasatinib failure. Patients were monitored with complete blood counts, cytogenetic analysis, bone marrow aspiration RT-PCR and mutational analysis. Results. A total of 66 patients (median age 63 years, range, 33–85 years) were treated with sequential TKIs; 40 (61%) patients had received interferon-a before starting Imatinib; 26 (39%) patients received imatinib as first line therapy. The median time on imatinib therapy was 47.5 months (range 4–101 months). At the start of nilotinib as second line, 27/29 (93%) patients were in CP, 1 (3.5%) in AP, and 1 (3.5%) in BP. 9 patients (31%) had developed mutations before starting treatment. The median time on second line TKI was 8 months (range 2–36 months). In the resistant patients 4 new mutations were identified (F359V in two patients, T315I, Y253H+F359V). At the start of dasatinib as second line, 33/37 (89.2%) patients were in CP, 4 (10.8%) in AP. 7 patients (18.9%) had developed mutations before starting treatment. The median time on second line TKI was 14 months (range 4–59 months).In the resistant patients 5 new mutations were identified (F137L in three pts, M318T, M244V+F317L). At the start of the third TKI, 60/66 (90.9%) patients were in CP, 5 (7.6%) in AP, and 1 (1.5%) in BP. Of these, 7 patients (18.9%) on dasatinib and 7 (24.1%) on nilotinib had mutations before starting treatment. The best response to the third line treatment with TKI was 10 (15.2%) MMR, 10 (15.2%) CCyR, 8 PcyR (12.1%), 5 (7.5%) mCyR, 24 (36.4%) CHR and 9 (13.6%) No Response (NR). In the dasatinib group, 9 (31%) patients discontinued treatment because of toxicity versus 17 (45.9%) patients in the nilotinib group.Two new mutations (F317L, E255V) emerged with dasatinib as third line therapy.After a median follow up of 13 months (range 2–37 months) 50 patients (48 CP, 2 AP) are continuing therapy (33 on nilotinib, 17 on dasatinib).Since the start of the third TKI, 61 patients (92.4%) are still alive for a median overall survival of 110 months (range 15–300) (52 CP, 7 AP, 2 NA); the 5 deaths (7.6%) were caused by disease progression and spread of the gene mutation T315I. Discussion. In our study, about one third of patients derived benefit from the use of three sequential TKIs; patients with better, longer response (28.7%) to third TKI were the same patients with a better response to the Imatinib and 2TKIs therapy. All these patients had taken interferon therapy before the Imatinib. In this subset of patients (good responders: CCyR and MMR) 5 patients developed mutations that were sensitive to the sequential treatment.The lack of a durable cytogenetic remission could be explained by the emergence of new kinase domain mutations as patients are exposed to sequential TKI; a change of therapy resulted in an adequate response. In our series, patients with poor prognosis showed mutations not sensitive to the TKIs treatment. Conclusions. Although allogeneic SCT is the treatment of choice in all patients failing 2 TKIs who are suitable candidates for this approach, alternative strategies are required for ineligible patients. The use of a third TKI after failure of two previous TKIs induces response in some patients. Longer follow up of a larger series of patients is needed to determine the long term impact of the response. Disclosures: No relevant conflicts of interest to declare.

TurkStream’s Balkan route to Europe is not guaranteed

2019 ◽  
Keyword(s):  
Middle East ◽  
Second Line ◽  
Network Operator ◽  
Content Type ◽  
Gas Network ◽  
The Third ◽  
Squeeze Out ◽  
The Government

Significance At the third attempt, Bulgarian state-owned gas network operator Bulgartransgaz has established market interest in filling a new pipeline extending the Russian-Turkish TurkStream pipeline into Europe. Russia’s Gazprom was the main bidder, along with Bulgarian state-owned gas supplier Bulgargaz and Swiss-based MET. Bulgartransgaz will now invest in a new pipeline taking TurkStream’s second line (TurkStream 2) through Bulgaria rather than Greece, supporting Sofia’s ambition to become a Balkan gas hub. Impacts If TurkStream 2 took the Bulgarian route it would help Russia cement relations with Serbia. Russia could squeeze out alternative gas supplies from Azerbaijan and the Middle East. Bulgartransgaz must now finance the investment and the government must finalise tenders and award contracts to meet construction deadlines.

scholarly journals Efficacy of Levofloxacin Based Triple and High-Dose PPI-Amoxicillin Dual Eradication Therapy for Helicobacter pylori after Failures of First- and Second-Line Therapies

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Kenichiro Okimoto ◽  
Makoto Arai ◽  
Keiko Saito ◽  
Shoko Minemura ◽  
Daisuke Maruoka ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Triple Therapy ◽  
Eradication Rate ◽  
Eradication Therapy ◽  
High Dose ◽  
Second Line ◽  
Intention To Treat ◽  
The Third ◽  
Significant Difference ◽  
Third Line

Objectives. The aim of this study was to investigate and compare the eradication rate of Helicobacter pylori as the third-line triple therapy with rabeprazole (RPZ) + amoxicillin (AMPC) + levofloxacin (LVFX) and high-dose RPZ + AMPC. Methods. 51 patients who failed Japanese first-line (proton pump inhibitor (PPI) + AMPC + clarithromycin) and second-line (PPI + AMPC + metronidazole) eradication therapy were randomly assigned at a 1 : 1 ratio to one of the following third-line eradication groups: (1) RAL group: RPZ 10 mg (b.i.d.), AMPC 750 mg (b.i.d.), and LVFX 500 mg (o.d.) for 10 days; (2) RA group: RPZ 10 mg (q.i.d.) and AMPC 500 mg (q.i.d.) for 14 days. Patients who failed to respond to third-line eradication therapy received salvage therapy. Results. The rates of eradication success, based on intention to treat (ITT) analysis, were 45.8% in the RAL group and 40.7% in the RA group. The overall eradication rates were 73.9% in the RAL group and 64.0% in the RA group. There was no significant difference between the two groups. Conclusions. The third-line triple therapy with RPZ, AMPC, and LVFX was as effective as that with high-dose RPZ and AMPC.

scholarly journals THE NEWLY DISCOVERED PERSIAN INSCRIPTION OF THE XII CENTURY IN THE FORTRESS OF BJNI

2019 ◽  
pp. 324-331
Author(s):  
TIGRAN MIKAYELYAN
Keyword(s):  
Horizontal Line ◽  
Second Line ◽  
National Academy Of Sciences ◽  
First Line ◽  
Stone Fragment ◽  
The Third ◽  
Arabic Characters ◽  
Third Line ◽  
Academy Of Sciences

In 2007 during its excavations within the citadel of Bjni fortress the expedition of the Institute of Archaeology and Ethnology of the National Academy of Sciences of Armenia discovered a stone with an inscription in Arabic characters. We have read this Persian inscription in five lines sculpted on a stone fragment showing missing parts from all sides. The first line is damaged and is unreadable, the second line mentions the name of some Isfahsalar Muhammad/Mohammad طوسي... Tusi محمد سلار] سفه ا ....[ The third line is also unclear, except for the guessable word ‘Islam’. The fourth line reads ‘May the God bless all’ in Persian. The fifth line communicates the date, which is ... [ئه [ما خمس و عين ...The date is incomplete, however it is definitely the 500th year of Hijra or the XII century AD. To define the decade we need to offer numbers ending with عين ..These are forty اربعين seventy سبعين or ninety تسعين . From these figures we prefer seventy سبعين because of a few considerations: if it is forty اربعين horizontal line of alif would be visible even if it is damaged; there is a dot over عين... even though ‘ba’s dot has been put over and not under the letter. سبعين or ninety also has no dots. So by choosing seventy, we can date the inscription to the period of 1175-1183. We can’t offer a more precise date as the first number before seventy is lost. We also believe that this inscription is not an epitaph as there are no Islamic formulas for the deceased put right before the name; also the sculpted characters are too big for a gravestone and in addition they are positioned perpendicularly to the stone unlike Armenia’s Muslim gravestones. Therefore, this must be a fragment of an inscription commemorating some construction or maybe a repair or strengthening of the Bjni fortress or citadel executed by the order of Isfahsalar Muhammad Tusi. Unfortunately the inscription does not communicate the dynasty to which it belongs. However, there is another Arabic inscription of 1174 by Shaddadids carved on a citadel of Nerkin Talin/Dashtadem (Aragatsotn region of Armenia). The newly discovered Persian inscription is evidence that Muslim military had some presence during the last decades of the XII century in the Armenian fortress of Bjni.

scholarly journals Rapid Hematologic and Organ Responses with Daratumumab, Bortezomib and Dexamethasone in Patients with Relapsed/Refractory AL Amyloidosis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2009-2009 ◽  
Author(s):  
Sarah S Lee ◽  
Nathaniel Rosko ◽  
Bhumika J. Patel ◽  
Madeline Waldron ◽  
Jackie Tomer ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stable Disease ◽  
Cardiac Response ◽  
Al Amyloidosis ◽  
Molecular Heterogeneity ◽  
Line Treatment ◽  
Second Line ◽  
Newly Diagnosed ◽  
The Third ◽  
Highly Effective

Abstract Introduction: Multi-organ dysfunction remains a major cause of morbidity and mortality with light chain amyloidosis (AL) especially for patients not achieving hematologic complete response. Approval of daratumumab (DARA) has revolutionized the care of multiple myeloma and its therapeutic implications have shown to be safe and highly effective in relapsed/refractory AL amyloidosis. This analysis demonstrates the activity of the combination of DARA, bortezomib, and dexamethasone in AL amyloidosis patients somewhat refractory to cyclophosphamide, bortezomib, and dexamethasone (CyBorD). Methods: Patients (pts) were identified via our IRB-approved plasma cell disorder registry. Pt selection included those who did not achieve at least a hematologic VGPR with first line treatment and who went on to receive a DARA containing second-line treatment for AL amyloidosis. Results: Since the approval of DARA for multiple myeloma, we have seen 159 pts with newly diagnosed AL amyloidosis, of which we identified 10 pts who failed to achieve a VGPR with initial treatment (CyBorD). The median age of our cohort was 67 (range, 38-75), with 80% males. At the time of diagnosis, 50% of the pts had more than one organ involvement (cardiac, renal, GI, lung, and/or bone marrow). All pts were initially treated with CyBorD with average of 4 cycles (range, 2-6), of which 60% achieved a PR and 40% had stable disease. The most common second line regimen was DARA, bortezomib, and dexamethasone (70%) followed by DARA monotherapy. The median number of cycles was 5 (range 1-9) with 50% of pts still undergoing treatment at the time of analysis. The median time to first response was 1.5 cycles (range, 1-3), with 50% achieving a PR, 30% VGPR, 10% CR and the other 10% with stable disease. The overall hematologic response rate was 90% (5 pts achieved at least a VGPR and 2 pts achieved a CR). Organ response was noted in 70% of pts by average of 2 cycles (range, 1-5). Five pts had a cardiac response by NT-proBNP criteria and 2 pts had renal response with 50% reduction in 24 hour urine protein. Toxicity included 40% of pts with a grade 2 infusion reaction with first dose DARA, grade 1-2 fatigue in 60% of pts, and there were no hospitalizations and/or deaths attributed to therapy. Notably, our institutional policy in amyloidosis pts has been to eliminate dexamethasone as a premedication after 3 DARA doses to minimize the risk of volume overload. Six out of 10 pts had dexamethasone discontinued before the end of cycle 2, and of those, half had dexamethasone stopped after the third DARA dose. One additional pt had dexamethasone stopped after the third cycle. No pts had infusion reactions after the discontinuation of dexamethasone. Of the 10 pts, only 2 pts had disease progression. Notably, 1 of the 2 patient's progressed while off therapy, but within 1 additional cycle of DARA monotherapy hematologic CR was achieved. Conclusion: Daratumumab is safe and highly effective in patients with AL amyloidosis who failed to achieve a deep hematological response with CyBorD. From our clinical experience, we have noted that DARA can induce rapid hematologic and organ responses which is critical to prevent irreversible organ damage. Monotherapy with DARA or in combination is well tolerated. Ongoing studies are investigating CyBorD with or without DARA in newly diagnosed patients. An unanswered question is whether or not CyBorD is needed at all when DARA is used in newly diagnosed patients. Exploring the molecular heterogeneity of these patients may also help identify a subset of patients that will benefit from DARA monotherapy upfront. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Efficacy of targeted therapy (TT) after checkpoint inhibitors (CPI) in metastatic renal cell carcinoma (mRCC): Results from the Canadian Kidney Cancer Information System (CKCis).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 568-568 ◽  
Author(s):  
Austin Kalirai ◽  
Lori Wood ◽  
Aly-Khan A. Lalani ◽  
Daniel Yick Chin Heng ◽  
Sunita Ghosh ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Mammalian Target Of Rapamycin ◽  
Cancer Information ◽  
Second Line ◽  
First Line ◽  
The Third ◽  
Factor Inhibitor ◽  
On Line ◽  
Third Line ◽  
Line Of Therapy

568 Background: While the use of CPI has demonstrated clinical benefit in patients with mRCC, data showing the efficacy of subsequent TT is limited. This real-world analysis evaluated the efficacy of TT post CPI in mRCC patients. Methods: Data was collected and analyzed from CKCis. Patients with mRCC who received TT after CPI were identified and analyzed based on line of therapy. Time to treatment failure (TTF – time from starting first subsequent TT to stopping TT) and overall survival (OS) were calculated. Hazard Ratio (HR) calculations were adjusted for IMDC group and age. Results: 102 patients were treated with TT post CPI (table). Those who received first-line ipilimumab + nivolumab (I/N) versus a vascular endothelial growth factor inhibitor (VEGFi) + CPI combination prior to second-line TT had a median TTF of 8.0 vs 5.2 months (m) (HR=0.43, 95% CI: 0.13-1.44) and median OS of 16.5 m vs not reached (HR=0.76, 95% CI: 0.11-5.24). Patients who received a VEGFi versus a mammalian target of rapamycin inhibitor (mTORi) as third-line TT had a median TTF of 7.6 vs 4.4 m (HR=0.52, 95% CI: 0.24-1.10) and median OS of 21.7 vs 16.2 m (HR=0.41, 95% CI: 0.16-1.08). All third-line TT patients received first-line VEGFi and second-line nivolumab. Of the third-line VEGFi TT patients, 24 received axitinib (TTF 7.1 m, OS 21.7 m) and 22 received cabozantinib (data immature). Conclusions: Activity of TT in mRCC patients after CPI is demonstrated in multiple lines. In second-line, VEGFi TT had numerically better outcomes after I/N than after VEGFi+CPI combination. Efficacy of third-line TT was seen with a trend favoring VEGFi over mTORi. Axitinib in the third-line has notable activity after CPI, while data on cabozantinib and fourth-line TT are maturing. These results support the use of VEGFi after CPI in mRCC patients. [Table: see text]

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