Trastuzumab in combination with AT-101 induces cytotoxicity and apoptosis in Her2 positive breast cancer cells

Bulut, Gulcan/0000-0001-7382-0972WOS: 000533256900008PubMed: 31829029Aim: AT-101 is a polyphenolic compound with potent anti-apoptotic effects in various cancers. in this study, the possible synergistic cytotoxic and apoptotic effect of trastuzumab/AT-101 combination was investigated in HER2-positive breast cancer cell lines. Materials & methods: SKBR-3, MDA-MB-453 and MCF-10A cell lines were treated with a trastuzumab/AT-101 combination. Synergistic cytotoxicity and apoptosis effects were shown and then PI3K and Akt protein levels were studied. Result: the trastuzumab/AT-101 combination induced synergistic cytotoxicity and apoptosis in both breast cancer cells but not in MCF-10A cells. Combination treatment induced cytotoxicity via inhibiting PI3K/AKT but not the MAPK/ERK pathway. Conclusion: the trastuzumab/AT-101 combination may be a good candidate for patients with trastuzumab-resistant Her2-positive breast cancer and inhibition of the PI3K/AKT pathway may be one of the underlying mechanisms.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [113S055]This project was supported by the Scientific and Technological Research Council of Turkey (TUBITAK, Project Number 113S055). the authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed

Leptomeningeal carcinomatosis of gastric adenocarcinoma

WOS: 000292752300014PubMed ID: 21796558Gastric cancer is the third most common malignancy among gastrointestinal malignancies. With the advance of new treatments, overall survival in gastric cancer is extending, and metastasis to atypical sites is seen more commonly. Leptomeningeal metastasis is one such atypical metastasis for gastric cancer. We report a case of gastric adenocarcinoma with leptomeningeal metastasis as an atypical involvement. A 39-year-old female, presenting with headache, vertigo, horizontal gaze palsy, visual disturbances, and seizures, was admitted to our hospital in August 2009. The funduscopic examination revealed the presence of bilateral papilledema. Magnetic resonance imaging of the brain showed diffuse leptomeningeal enhancement and biventricular dilatation. Cytological examination of the cerebrospinal fluid revealed malignant cells. These findings were consistent with leptomeningeal carcinomatosis. Six months before, she was diagnosed as having gastric cancer by upper gastrointestinal tract endoscopy, which was performed as a part of the diagnostic work-up to clarify the cause of her abdominal ascites. She received six cycles of docetaxel-cisplatin-5-fluorouracil for metastatic gastric cancer, and she developed the above-mentioned symptoms under chemotherapy. She was included in a craniospinal radiotherapy program and received intrathecal methotrexate treatment. We present this case report since leptomeningeal carcinomatosis of gastric cancers is a rare clinical entity, and treatment strategies remain challenging for clinicians

Electrochemotherapy with anti-PD-1 treatment induced durable complete response in heavily pretreated metastatic melanoma patient

WOS: 000427031000010Metastatic melanoma (MM) is one of the most lethal types of cancer. Although novel immunotherapeutics have been developed recently, still, these drugs fail to save the lives of a third of MM patients. Electrochemotherapy (ECT) is a local treatment of cancer based on a combination of electroporesis and low-dose chemotherapy. In this case report, we present the treatment history of a MM patient treated successfully with ECT and immunotherapy combination as a fifth-line treatment. Our patient was a 39 year-old woman who was diagnosed with nodulary melanoma stage II. Due to a local recurrence, she was given interferon- treatment. After 6 months, her disease relapsed in the axillary lymph nodes, and temozolamide treatment 150 mg/m2 was initiated. After six cycles on temozolamide, she progressed both in the axillary site and in the lungs. Her BRAF mutation analysis revealed V600E positivity. Hence, BRAF inhibitor-vemurafenib 24 tablets per day was initiated. Within 3 months, she responded dramatically both in the axillary site and in the lungs. At the ninth month of treatment, she progressed again, at which time ipilimumab 3 mg/kg was started as a fourth line treatment. However, shortly after, she progressed again and developed a solitary brain metastasis. She was operated and had whole brain radiotherapy. At that point, nivolumab, an antiprogrammed cell death ligand-1 blocker, was the only remaining option. She showed a biphenotypical response to nivolumab; a mass on the anterior axilla was progressing while the other lymph nodes had regressed. Owing to the accessibility of the subcutaneous lesion with external electrodes, ECT was performed using IGEA Cliniprator device through a hexagonal electrode on the progressive mass, while on nivolumab treatment. A complete response was achieved, with no evidence of disease at 4 years since her local recurrence. Eradication of symptomatic, refractory lesions using ECT meets an important clinical need. Whenever a disseminated disease presents with cutaneous/subcutaneous lesions, high efficacy of ECT should be deployed to augment tumor immunogenicity and complement systemic immunotherapies

Is it the time for metformin to take place in adjuvant treatment of Her-2 positive breast cancer? Teaching new tricks to old dogs

WOS: 000270374400041PubMed ID: 19560877Breast cancer is the most common malignancy diagnosed among women. According to the new molecular subclassification, basal like and Her-2 positive breast cancers have the worst outcome and these are the ones in which chemotherapy is a must as a part of adjuvant treatment. New treatment options that could be used as an adjuvant maintenance treatment are still being investigated. Insulin hormone is one of the reasons of breast cancer recurrence and death in breast cancer survivors. Targeting insulin as a therapeutic modality in breast cancer could be an option in the adjuvant treatment of breast cancer. It seems that insulin may signal to activate a cascade of proliferative and anti-apoptotic events in the cancer cell. Metformin, an oral anti-diabetic known for 50 years, may also have direct effects on cancer cells. Metformin causes Her-2 suppression via the inhibition of mTOR in breast cancer cells. Thus, we believe that the time has arrived both to target insulin reduction and to alter Her-2 oncogene based molecular pathogenetic steps in breast cancer by using metformin as an adjuvant therapy in breast cancer patients. (C) 2009 Elsevier Ltd. All rights reserved

Can gossypol be a hope for transsexual patients (male to female) before sex reassignment surgery? Just for adjusting the body to mind

WOS: 000270374400048PubMed ID: 1964794

Centro de investigación y observación de aves migratorias para los Pantanos de Villa

Un Centro de Investigación y Observación de Aves Migratorias ubicado en la zona de amortiguamiento de los Pantanos de Villa es un lugar para visitantes e investigadores que tiene como finalidad concientizar a la población de un área que merece ser cuidada y respetada, realzar el valor del entorno natural y recuperar el uso para la conservación del mismo. El énfasis está relacionado al vínculo que debe existir entre la arquitectura y el entorno natural cercano, con espacios que mantengan una relación amigable entre el visitante y la naturaleza, insertándose en el terreno con un bajo impacto ambiental y que ayude a darle mayor valor al área natural, hoy en día olvidada.Tesi