Browsing by Author "Mandel, Nil Molinas"

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Efficacy of Palbociclib and Endocrine Treatment in Heavily Pretreated Hormone Receptor-positive/HER2-negative Advanced Breast Cancer: Retrospective Multicenter Trial
(GALENOS PUBL HOUSE, 2020-01-01) Demir, Atakan; Mandel, Nil Molinas; Paydas, Semra; Demir, Gokhan; Er, Ozlem; Turhal, Nazim Serdal; Bavbek, Sevil; Eralp, Yesim; Saip, Pinar Mualla; Guler, Emine Nilufer; Aydiner, Adnan; Uluc, Basak Oyan; Kilickap, Sadettin; Uskent, Necdet; Karadurmus, Nuri; Kaplan, Mehmet Ali; Yanmaz, Mustafa Teoman; Demir, Hacer; Alan, Ozkan; Korkmaz, Taner; Olgun, Polat; Uysal, Ozlem Sonmez; Altundag, Kadri; Gunduz, Seyda; Gunaldi, Meral; Sari, Murat; Beypinar, Ismail; Basaran, Gul
Background: The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood. Aims: To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed. Study Design: Multicenter retrospective observational cohort study. Methods: In this retrospective observational cohort study, we included 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2- metastatic breast cancer. Results: The median progression-free survival in our population was 7 months (25th-75th percentile, 4-10), and the median overall survival was 11 months (25th-75th percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14\%). Conclusion: The efficacy of palbociclib among heavily treated hormone receptor-positive/HER2- patients with advanced breast cancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population.
GnRH agonist leuprolide acetate does not confer any protection against ovarian damage induced by chemotherapy and radiation in vitro
(OXFORD UNIV PRESS, 2015-01-01) Bildik, Gamze; Akin, Nazli; Senbabaoglu, Filiz; Sahin, Gizem Nur; Karahuseyinoglu, Sercin; Ince, Umit; Taskiran, Cagatay; Selek, Ugur; Yakin, Kayhan; Guzel, Yilmaz; Ayhan, Cem; Alper, Ebru; Cetiner, Mustafa; Balaban, Basak; Mandel, Nil Molinas; Esen, Tarik; Iwase, Akira; Urman, Bulent; Oktem, Ozgur
STUDY QUESTION: Is there any in vitro evidence for or against ovarian protection by co-administration of a GnRH agonist with chemotherapy in human? SUMMARY ANSWER: The co-administration of GnRH agonist leuprolide acetate with cytotoxic chemotherapy agents does not preserve ovarian reserve in vitro. WHAT IS KNOWN ALREADY: Randomized controlled trials of the co-administration of gonadotrophin-releasing hormone (GnRH) agonists with adjuvant chemotherapy to preserve ovarian function have shown contradictory results. This fact, together with the lack of a proven molecular mechanism of action for ovarian protection with GnRH agonist (GnRHa) places this approach as a fertility preservation strategy under scrutiny. We therefore aimed in this study to provide in vitro evidence for or against the role of GnRHa in the prevention of chemotherapy-induced damage in human ovary. STUDY DESIGN, SETTINGS, SIZE AND DURATION: This translational research study of ex vivo and in vitro models of human ovary and granulosa cells was conducted in a university hospital between 2013 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian cortical pieces (n = 15, age 14-37) and mitotic non-luteinized (COV434 and HGrC1) and non-mitotic luteinized human granulosa cells (HLGC) expressing GnRH receptor were used for the experiments. The samples were treated with cyclophosphamide, cisplatin, paclitaxel, 5-FU, or TAC combination regimen (docetaxel, adriamycin and cyclophosphamide) with and without GnRHa leuprolide acetate for 24 h. DNA damage, apoptosis, follicle reserve, hormone markers of ovarian function and reserve (estradiol (E2), progesterone (P) and anti-mullerian hormone (AMH)) and the expression of anti-apoptotic genes (bcl-2, bcl-xL, bcl-2L2, Mcl-1, BIRC-2 and XIAP) were compared among control, chemotherapy and chemotherapy + GnRHa groups. MAIN RESULTS AND THE ROLE OF CHANCE: The greatest magnitude of cytotoxicity was observed in the samples treated with cyclophosphamide, cisplatin and TAC regimen. Exposure to these drugs resulted in DNA damage, apoptosis and massive follicle loss along with a concurrent decline in the steroidogenic activity of the samples. GnRHa co-administered with chemotherapy agents stimulated its receptors and raised intracellular cAMP levels. But it neither activated anti-apoptotic pathways nor prevented follicle loss, DNA damage and apoptosis induced by these drugs. LIMITATIONS, REASONS FOR CAUTION: Our findings do not conclusively rule out the possibility that GnRHa may offer protection, if any, through some other mechanisms in vivo. WIDER IMPLICATIONS OF THE FINDINGS: GnRH agonist treatment with chemotherapy does not prevent or ameliorate ovarian damage and follicle loss in vitro. These data can be useful when consulting a young patient who may wish to receive GnRH treatment with chemotherapy to protect her ovaries from chemotherapy-induced damage.
Optimizing the Personalized Care for the Management of Rectal Cancer: A Consensus Statement
(AVES, 2022-01-01) Aytac, Erman; Ozer, Leyla; Baca, Bilgi; Balik, Emre; Kapran, Yersu; Taskin, Orhun Cig; Uluc, Basak Oyan; Abacioglu, Mehmet Ufuk; Gonenc, Murat; Bolukbasi, Yasemin; Cil, Barbaros E.; Baran, Bulent; Aygun, Cem; Yildiz, Mehmet Erdem; Unal, Kemal; Erkol, Burcak; Yalti, Tunc; Ozbek, Ugur; Attila, Tan; Tozun, Nurdan; Gurses, Bengi; Erdamar, Sibel; Er, Ozlem; Bese, Nuran; Bilge, Orhan; Ceyhan, Guralp Onur; Mandel, Nil Molinas; Selek, Ugur; Yakicier, Cengiz; Karabey, Hulya Kayserili; Saruc, Murat; Ozben, Volkan; Esen, Eren; Ozoran, Emre; Vardareli, Erkan; Guner, Levent; Hamzaoglu, Ismail; Bugra, Dursun; Karahasanoglu, Tayfun; Grp, Istanbul
Colorectal cancer is the third most common cancer in Turkey. The current guidelines do not provide sufficient information to cover all aspects of the management of rectal cancer. Although treatment has been standardized in terms of the basic principles of neoadjuvant, surgical, and adjuvant therapy, uncertainties in the management of rectal cancer may lead to significant differences in clinical practice. In order to clarify these uncertainties, a consensus program was constructed with the participation of the physicians from the Acibadem Mehmet Ali Aydinlar and Koc Universities. This program included the physicians from the departments of general surgery, gastroenterology, pathology, radiology, nuclear medicine, medical oncology, radiation oncology, and medical genetics. The gray zones in the management of rectal cancer were determined by reviewing the evidence-based data and current guidelines before the meeting. Topics to be discussed consisted of diagnosis, staging, surgical treatment for the primary disease, use of neoadjuvant and adjuvant treatment, management of recurrent disease, screening, follow-up, and genetic counseling. All those topics were discussed under supervision of a presenter and a chair with active participation of related physicians. The consensus text was structured by centralizing the decisions based on the existing data.
Prognostic Significance of Tumor Tissue NeuGcGM3 Ganglioside Expression in Patients Receiving Racotumomab Immunotherapy
(HINDAWI LTD, 2020-01-01) Uskent, Necdet; Ayla, Sule; Mandel, Nil Molinas; Ozkan, Metin; Teomete, Mehmet; Baloglu, Huseyin; Aydincer, Cenk; Yergok, Hale; Dogan, Ender; Berk, Barkin; Yazar, Aziz
Expression ofN-glycolyl GM3 (NeuGcGM3) ganglioside was detected in the tumor specimens of patients who were on Racotumomab anti-idiotype vaccine maintenance treatment, and prognostic significance as a biomarker was investigated. No statistically significant association was observed in the multivariate analysis between overall survival and tissue NeuGcGM3 IHC levels. Although numerically there was a difference favoring less intense IHC for better prognosis, this did not reach statistical power. However, there was a strong correlation between Racotumomab doses and overall survival (OS). Mean OS of the patient with more than 10 Racotumomab application was significantly longer than the patient who had less than 10 injections (70.7 months vs. 31.1 months, p<0.001). We propose that, regardless of staining intensity, the presence of NeuGcGM3 in patient tissues might be an indicator of benefit in Racotumomab treatment.