RADI-15. Radiotheranostic Approach in Brain Tumor

Abstract Purpose The aim of this study is feasibility and potential treatment of targeted radionuclide theranostic approach for patients with brain tumors. Methods For the period 2020–2021, 6 child and adult patients who had been diagnosed with brain tumors were treated using theranostic approach followed by refractory to conventional therapy. Two patients that were presented with HER-2 positive, ER and PR negative breast cancer and brain metastases as well as a history of several cycles of chemotherapy sessions and radiotherapy using gamma knife were treated with 177Lu-Trastuzumab (Herceptin). Three other patients with primary brain tumor underwent peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. The last case was a patient with refractory primary cerebral lymphoma to standard therapy with confirmed CD20-positive B-cell lymphoma who underwent 177Lu-Rituximab. Results A two women with HER-2 positive breast cancer and brain metastasis underwent two cycles of 177Lu-trastuzumab. Post-therapy assessment showed some improvement. Next, a man with a high-grade glioma tumor in the left frontal lobe with history of debunking surgery in combination with chemoradiation received 177Lu-DOTATATE that resulted in a short-term stable situation. Another patient presented with a right cerebellopontine angle meningioma underwent PRRT with 177Lu-DOTATATE. She had a stable disease with some improvement in the clinical status. Also, a girl with an astrocytoma in suprasellar cistern underwent 2 cycles of 177Lu-DOTATATE. The complete response was designed. Finally, a patient with refractory primary cerebral lymphoma received 177Lu-Rituximab. Conclusion Nuclear oncology in the field of neuro-oncology (neuroradiotheranostics) has been toward a personalized approach, effective and safe therapy. These preliminary studies might demonstrate feasibility and therapeutic potential of theranostics in patients with primary, relapsed or metastasis brain tumors. Further studies preferentially well-designed multicenter international clinical trial is warranted.

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Nigella sativa and Cancer: A Review Focusing on Breast Cancer, Inhibition of Metastasis and Enhancement of Natural Killer Cell Cytotoxicity

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200430120453 ◽

2020 ◽

Vol 21 (12) ◽

pp. 1176-1185 ◽

Cited By ~ 1

Author(s):

Tuğcan Korak ◽

Emel Ergül ◽

Ali Sazci

Keyword(s):

Breast Cancer ◽

Natural Killer Cells ◽

Natural Killer ◽

Therapeutic Potential ◽

Nigella Sativa ◽

Killer Cell ◽

B Cell Lymphoma ◽

Killer Cells ◽

Natural Killer Cell Cytotoxicity ◽

Endothelial Growth Factor

Background: In the last decade, there have been accumulating data that the use of medicinal plants could bring additional benefits to the supportive treatment of various diseases. Nigella sativa (N. sativa, family Ranunculaceae) is one of these plants that has attracted considerable interest. The extracts and seeds of N. sativa and its active component thymoquinone have been studied extensively and the results suggest that N. sativa might carry some therapeutic potential for many diseases, including cancer. Methods: The selection criteria for references were applied through Pubmed with “N. sativa and cancer”, “N. sativa and breast cancer”, “N. sativa and metastasis”, “N. sativa and cytotoxicity of natural killer cells”. The pathway analysis was performed using the PANTHER tool by using five randomly selected N. sativa affected genes (Cyclin D1, P53, p21 protein (Cdc42/Rac) activated kinase 1 (PAK1), B-cell lymphoma 2 (Bcl-2) and vascular endothelial growth factor (VEGF)) in order to elucidate further potentially affected signaling pathways. Results: The aim of this review was to summarize studies regarding the effects of N. sativa in cancer generally, with a focus on breast cancer, its anti-metastatic effects, and how N. sativa modulates the cytotoxicity of Natural Killer cells that play a crucial role in tumor surveillance. Conclusion: In summary, the data suggest that N. sativa might be used for its anti-cancer and antimetastatic properties and as an immune system activator against cancer.

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Brain tumors and indications for brain imaging in patients with psychiatric manifestations: a case report

Middle East Current Psychiatry ◽

10.1186/s43045-021-00136-2 ◽

2021 ◽

Vol 28 (1) ◽

Author(s):

Seyed Alireza Haji Seyed Javadi ◽

Bahare Rezaei

Keyword(s):

Brain Tumor ◽

Brain Tumors ◽

Psychiatric Symptoms ◽

Relevant Information ◽

History Of ◽

Response To Stress ◽

The Right ◽

Occipital Lobes ◽

Psychiatric Manifestations ◽

The Relationship

Abstract Background Studies on the relationship between psychiatric symptoms and brain tumors are ambiguous, as it is not clear whether these symptoms are due to the direct effect of the tumor or a secondary psychological response to stress, resulting from the diagnosis and treatment of the disease; therefore, it is difficult to analyze and retrieve relevant information. Case presentation We present the case of a 43-year-old male patient, who was admitted to a psychiatric emergency room with psychiatric symptoms, such as restlessness and extreme talkativeness, but normal neurological examinations. He showed no response to outpatient treatment and had no history of psychiatric disorders. The onset of symptoms was 2 months before his visit. On neuroimaging, a brain tumor was observed in the right temporal and occipital lobes. Accordingly, the patient was transferred to the neurosurgery ward. Conclusion Factors, such as increased internal pressure on the brain due to a brain tumor or the effect of tumor area, contribute to the occurrence of symptoms, such as restlessness and talkativeness. However, further studies are needed to confirm these findings.

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Difficulty Diagnosing a Brain Tumor during Clinical Maintenance of a Complete Response to anti-HER2 Treatments for Metastatic Breast Cancer: A Case Report

Case Reports in Oncology ◽

10.1159/000511051 ◽

2020 ◽

Vol 13 (3) ◽

pp. 1311-1316

Author(s):

Ryoko Semba ◽

Yoshiya Horimoto ◽

Atsushi Arakawa ◽

Yoko Edahiro ◽

Tomoiku Takaku ◽

...

Keyword(s):

Breast Cancer ◽

Brain Tumor ◽

Ductal Carcinoma ◽

Metastatic Breast ◽

Stage Iv ◽

B Cell Lymphoma ◽

High Dose ◽

Her2 Positive ◽

Stage Iv Breast Cancer ◽

The Right

A 46-year-old woman with erythema of the right breast presented to our hospital and was diagnosed with stage IV breast cancer (HER2-positive invasive ductal carcinoma). She received 4 courses of anthracycline-based regimens and 4 courses of trastuzumab + pertuzumab + docetaxel (Tmab + Pmab + DTX). Since she responded well to these therapies, only Tmab + Pmab was continued thereafter. Twenty-three months after starting treatment, she developed a headache. A tumor was identified in the right temporal lobe. Craniotomy was performed for definitive diagnosis. Intraoperative pathological assessment suggested the tumor to be brain metastasis of breast cancer. However, the final pathological diagnosis was diffuse large B-cell lymphoma of central nervous system (DLBCL-CNS) based on re-assessment with immunohistochemical examinations. Therefore, the Tmab + Pmab was discontinued, and 6 courses of high-dose methotrexate therapy were administered. This case highlights the importance of considering rare entities, such as DLBCL, when diagnosing a solitary brain tumor in a patient with a primary cancer, based on imaging and pathological findings.

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Hyperoside Induces Breast Cancer Cells Apoptosis via ROS-Mediated NF-κB Signaling Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms21010131 ◽

2019 ◽

Vol 21 (1) ◽

pp. 131 ◽

Cited By ~ 8

Author(s):

Jinxia Qiu ◽

Tao Zhang ◽

Xinying Zhu ◽

Chao Yang ◽

Yaxing Wang ◽

...

Keyword(s):

Breast Cancer ◽

Mouse Model ◽

Cancer Cells ◽

Signaling Pathway ◽

Breast Cancer Cells ◽

Caspase 3 ◽

Therapeutic Potential ◽

B Cell Lymphoma ◽

Flavonoid Glycosides

Hyperoside (quercetin 3-o-β-d-galactopyranoside) is one of the flavonoid glycosides with anti-inflammatory, antidepressant, and anti-cancer effects. But it remains unknown whether it had effects on breast cancer. Here, different concentrations of hyperoside were used to explore its therapeutic potential in both breast cancer cells and subcutaneous homotransplant mouse model. CCK-8 and wound healing assays showed that the viability and migration capability of Michigan Cancer Foundation-7 (MCF-7) and 4T1 cells were inhibited by hyperoside, while the apoptosis of cells were increased. Real-time quantitative PCR (qRT-PCR) and western blot analysis were used to detect mRNA and the protein level, respectively, which showed decreased levels of B cell lymphoma-2 (Bcl-2) and X-linked inhibitor of apoptosis (XIAP), and increased levels of Bax and cleaved caspase-3. After exploration of the potential mechanism, we found that reactive oxygen species (ROS) production was reduced by the administration of hyperoside, which subsequently inhibited the activation of NF-κB signaling pathway. Tumor volume was significantly decreased in subcutaneous homotransplant mouse model in hyperoside-treated group, which was consistent with our study in vitro. These results indicated that hyperoside acted as an anticancer drug through ROS-related apoptosis and its mechanism included activation of the Bax–caspase-3 axis and the inhibition of the NF-κB signaling pathway.

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Outcome of Patients (pts) with Chronic Myeloid Leukemia (CML) Treated with Tyrosine Kinase Inhibitors (TKI) Who Have a History of Prior Malignancies,

Blood ◽

10.1182/blood.v118.21.3787.3787 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3787-3787

Author(s):

Paul B Koller ◽

Hagop M Kantarjian ◽

Charles Koller ◽

Elias Jabbour ◽

Susan O'Brien ◽

...

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Patient Outcome ◽

Median Time ◽

Cancer Diagnosis ◽

Research Funding ◽

B Cell Lymphoma ◽

Excellent Outcome ◽

History Of ◽

Prior Malignancy

Abstract Abstract 3787 Background: The natural history of CML has been irrevocably changed since the advent of TKIs with pts living longer than they ever have. Some patients have a history of previous cancers by the time they are diagnosed with CML. These pts' long-term prognosis has never been previously described. Aims: To determine the effect of prior malignancy on patient outcome after diagnosis of CML. Methods: The primary objective was to determine outcome of pts with a previous diagnosis of malignancy (PM) vs a group without (nPM). Patients included in clinical trials of TKI as initial therapy for CML in chronic phase from July 2000 to January 2011 were reviewed. Results: Of the 471 CML pts treated with frontline TKIs 47 (10%) had a PM before their CML diagnosis and 5 (1%) pts PM status could not be obtained. The median age of the patients with a PM was 60 (30–84) compared to 46 (15–86) for those with no PM. There were no significant differences in clinical characteristics between PM and nPM patients. The median from diagnosis of a PM and a diagnosis of CML was 69 months (mo) (7 mo to 707 mo). The five most common PMs were: non-melanoma skin cancer in 14 (30%), breast cancer in 10 (21%), melanoma in 5 (11%), colorectal cancer in 5 (11%), and prostate cancer in 5 (11%). “Six pts (13%) had more than one PM and 2 of those 6 had 3 PM before the diagnosis of CML, the other 4 pts had 2 PM. The PMs were treated prior to the diagnosis of CML in the following ways: 17 (36%) pts received chemotherapy for their PM, 17 (36%) received radiotherapy, and 43 (91%) received surgery. At the time of CML diagnosis 3 (6%) pts had active cancer, while the remainder of the pts with a PM were thought to be in remission. Two (4%) pts were on active therapy for their prior cancer diagnosis at the time they started on CML therapy (Tamoxifen for breast cancer in both). After the diagnosis of CML, 6 (13%) pts had a recurrence of their PM including 2 pts with basal cell cancer, and 1 each with melanoma, breast cancer, prostate cancer, and lymphoma. These recurrent malignancies were treated as follows: 3 with radiation, 2 had surgery, and 2 with chemotherapy. Five of these 6 pts continued TKI while receiving therapy for PM. The median time between diagnosis of CML and relapse of PM was 18 months. Median remission of the PM was 151 months. Also, 6 (13%) pts had a new malignancy after CML diagnosis: 2 pts with squamous skin carcinoma, and 1 each with chronic lymphocytic leukemia, papillary thyroid carcinoma, mucoepidermoid carcinoma, and large B-cell lymphoma. Treatments for the new onset malignancy after the diagnosis of CML include: surgery (4), chemotherapy (2), radiation (1), and observation (1). The median time between diagnosis of CML and a new malignancy was 39 months. Six of the 47 pts are deceased: 2 died of their PM, 2 died secondary to treatment complications for their PM, 2 died of cardiovascular issues unrelated to a cancer diagnosis. None died of CML. Initial treatment for CML was imatinib 400mg in 4/47 (9%) PM and 69/419 (16%) nPM, imatinib 800mg in 15/47 (33%) PM and 189/419 (45%) nPM, dasatinib in 11/47 (24%) PM and 78/419 (19%) nPM, and nilotinib in 16/47 (35%) PM, and 83/419(20%) nPM. The outcome of pts with PM and nPM is presented in Table 1. There was no significant different in patient outcome between pts with PM and nPM. Conclusion: Pts with CML who have prior malignancies have the same excellent outcome as patients with no prior malignancies. In the few instances in which concomitant therapy for other malignancies was required during therapy with TKI this could be accomplished with no significant toxicity. Thus, the history of prior malignancy in a patient who develops CML should not affect the decision to treat with TKI. Disclosures: Cortes: Pfizer Inc: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.

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Spontaneous Intracranial Hemorrhage Caused by Brain Tumor

Neurosurgery ◽

10.1227/00006123-198204000-00004 ◽

1982 ◽

Vol 10 (4) ◽

pp. 437-444 ◽

Cited By ~ 200

Author(s):

Susumu Wakai ◽

Kenta Yamakawa ◽

Shinya Manaka ◽

Kintomo Takakura

Keyword(s):

Brain Tumor ◽

Pituitary Adenoma ◽

Brain Tumors ◽

Intracranial Hemorrhage ◽

Embryonal Carcinoma ◽

Clinical Symptoms ◽

Massive Bleeding ◽

The Past ◽

History Of ◽

Spontaneous Intracranial Hemorrhage

Abstract Hemorrhage from brain tumor was confirmed clinically, surgically, or on autopsy in 94 of 1861 cases (5.1%) treated during the past 18 years: 49 of 311 pituitary adenomas (15.8%) and 45 of 1550 other brain tumors (2.9%). The higher incidence of hemorrhage from pituitary adenoma was statistically significant (Neurosurgery < 0.001). In brain tumors other than pituitary adenoma, the incidence of hemorrhage was significantly higher in the patients under 14 years old (17 of the 322 cases, 5.3%) than in the patients over 15 years old (28 of the 1228 cases; 2.3%) (Neurosurgery < 0.001). Nineteen patients showed no evidence of clinical symptoms related to bleeding. Twenty-six patients had a definite history of an acute episode that suggested sudden bleeding. In 11 of these, the apoplectic syndrome was the initial presenting symptom. The incidence of hemorrhage was not statistically correlated with sex. The hemorrhage was intratumoral in 30 cases, intracerebral in 7, subarachnoid in 7, and subdural in 1. The tumors were supratentorial in 36 cases, pineal in 1, and infratentorial in 8. Primary and metastatic choriocarcinoma and primary embryonal carcinoma seemed to cause hemorrhage most frequently. The following precipitating factors were found in 7 of the 17 patients aged under 14: ventricular drainage in 2, ventriculoperitoneal shunt in 2, carotid angiography in 1, head injury in 1, and leukemia in 1. Seven of the 17 patients under 14 years old died of massive bleeding from the tumor. Unless there is evidence of vascular disease such as cerebral aneurysm, vascular malformation, or hypertensive cerebrovascular disease, intracranial hemorrhage should be suspected of being due to a brain tumor.

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The Real Impact of Target Therapy in Breast Cancer Patients: Between Hope and Reality

Current Cancer Drug Targets ◽

10.2174/1568009617666170209100322 ◽

2018 ◽

Vol 18 (5) ◽

pp. 480-498

Author(s):

Sebastiano Bordonaro ◽

Massimiliano Berretta ◽

Antonino Carmelo Tralongo ◽

Silvia Clementi ◽

Brigida Stanzione ◽

...

Keyword(s):

Breast Cancer ◽

Mapk Pathway ◽

Target Therapy ◽

Breast Cancer Patients ◽

Luminal A ◽

Over Expression ◽

History Of ◽

Her 2 ◽

Intracellular Signal

Over the last 15 years, we have seen a huge expansion of the development of drugs directed against biomolecular targets within breast cancer cells. The over-expression of certain receptors (ER, PgR, HER-2, VEGF-R), as well as alteration of several intracellular signal transduction pathways (the PI3K-AKT-mTOR pathway, MEK-MAPK pathway, loss of PTEN, etc ...) has a great impact on the likelihood of recurrence and progression of the disease, influencing the natural history of breast cancer. The recent biomolecular classification of breast cancer (Luminal A / B, HER2- driven, Basal Like) allowed finally to identify specific treatments against molecular target to associate or not to traditional chemotherapy, and to use in relation to the prognosis of the disease. In the following paragraphs, we will set out the major targeted drug that have received indications in breast cancer, both in the localized and in advanced disease, referring to the specific target (hormonal receptors, HER2, VEGF, m-TOR, PARP etc ...).

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CLINICAL ASPECTS OF ASYMPTOMATIC ARRHYTHMIA IN ELDERLY PATIENTS WITH LEFT BREAST CANCER AT THE STAGE OF RADIATION THERAPY

Успехи геронтологии ◽

10.34922/ae.2020.33.5.016 ◽

2021 ◽

pp. 940-944

Author(s):

В. Н. Федорец ◽

Р. М. Жабина ◽

К. Л. Козлов ◽

И. В. Вологдина ◽

Л. А. Красильникова

Keyword(s):

Breast Cancer ◽

Radiation Therapy ◽

Cardiac Arrhythmias ◽

Elderly Women ◽

Conformal Radiotherapy ◽

Left Breast ◽

Clinical Aspects ◽

Knowledge Age ◽

History Of ◽

Her 2

Недостаточная изученность возрастных особенностей клинического течения бессимптомных нарушений сердечного ритма у женщин с раком молочной железы на этапе лучевой терапии определяет высокую востребованность посвященных данной проблеме исследований. Цель исследования - выявление и оценка нарушений сердечного ритма, протекающих бессимптомно, у женщин пожилого возраста [средний возраст - 67 (64; 69) лет] с раком левой молочной железы на этапе лучевой терапии. Обследованы 48 женщин без тяжелой сердечнососудистой патологии в анамнезе с HER 2- neu отрицательным раком левой молочной железы на этапе 3D конформной лучевой терапии. Всем пациенткам на предшествующих этапах была проведена мастэктомия по Маддену с последующей терапией доксорубицином. Обследование включало регистрацию ЭКГ, мониторирование ЭКГ по Холтеру и эхо-КГ. Бессимптомные нарушения ритма были выявлены до начала лучевой терапии у 43 (89,6 %) пациенток. После лучевой терапии выявлено увеличение количества патологической наджелудочковой и желудочковой аритмии, что можно объяснить кардиотоксичностью. Insufﬁcient knowledge age peculiarities of the clinical course of cardiac arrhythmias occurring asymptomatically as a manifestation of cardiotoxicity in women with breast cancer at the stage of radiation therapy, determines the high demand for research on this problem. The aim of the study was to identify and evaluate asymptomatic cardiac arrhythmias in elderly women with left breast cancer at the stage of radiation therapy. 48 women without a history of severe cardiovascular disease with HER 2 neu negativecancer of the left breast at the stage of 3D conformal radiotherapy were examined. Mean age 67 (64; 69). All patients at the previous stages were carried out mastectomy Madden followed by therapy with doxorubicin. The examination included ECG registration, 24-hour ECG monitoring and echocardiography. Before radiation therapy, asymptomatic arrhythmias were detected in 43 (89,6 %) patients. After radiation therapy signiﬁcantly increased the number of pathological supraventricular and ventricular arrhythmias as a manifestation of cardiotoxicity.

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Current Clinical Brain Tumor Imaging

Neurosurgery ◽

10.1093/neuros/nyx103 ◽

2017 ◽

Vol 81 (3) ◽

pp. 397-415 ◽

Cited By ~ 68

Author(s):

Javier E. Villanueva-Meyer ◽

Marc C. Mabray ◽

Soonmee Cha

Keyword(s):

Brain Tumor ◽

Brain Tumors ◽

Tumor Imaging ◽

Tumor Patient ◽

Therapy Assessment ◽

Noninvasive Characterization ◽

Magnetic Resonance Imaging Mri ◽

The Brain ◽

Post Therapy

Abstract Neuroimaging plays an ever evolving role in the diagnosis, treatment planning, and post-therapy assessment of brain tumors. This review provides an overview of current magnetic resonance imaging (MRI) methods routinely employed in the care of the brain tumor patient. Specifically, we focus on advanced techniques including diffusion, perfusion, spectroscopy, tractography, and functional MRI as they pertain to noninvasive characterization of brain tumors and pretreatment evaluation. The utility of both structural and physiological MRI in the post-therapeutic brain evaluation is also reviewed with special attention to the challenges presented by pseudoprogression and pseudoresponse.

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Homogeneity of antibody-drug conjugates critically impacts the therapeutic efficacy in brain tumors

10.1101/2021.12.23.474044 ◽

2021 ◽

Author(s):

Yasuaki Anami ◽

Yoshihiro Otani ◽

Wei Xiong ◽

Summer Y. Y. Ha ◽

Aiko Yamaguchi ◽

...

Keyword(s):

Brain Tumor ◽

Brain Tumors ◽

Therapeutic Potential ◽

Xenograft Model ◽

Antitumor Effects ◽

Antibody Drug Conjugates ◽

Cancer Management ◽

Drug Conjugates ◽

Therapeutic Benefits ◽

Antibody Drug

Glioblastoma multiforme (GBM) is characterized by aggressive growth and the poorest prognosis of all brain tumor types. Most therapies rarely provide clinically meaningful improvements in outcomes of patients with GBM. Antibody-drug conjugates (ADCs) are emerging chemotherapeutics with stunning success in cancer management. Although promising, clinical studies of three ADCs for treating GBM, including Depatux-M, have been discontinued because of safety concerns and limited therapeutic benefits. Here, we report that ADC homogeneity is a critical parameter to maximize the therapeutic potential in GBM therapy. We demonstrate that homogeneous conjugates generated using our linker show enhanced drug delivery to intracranial brain tumors. Notably, compared to heterogeneous ADCs, including a Depatux-M analog, our ADCs provide greatly improved antitumor effects and survival benefits in orthotopic brain tumor models, including a patient-derived xenograft model of GBM. Our findings warrant the future development of homogeneous ADCs as promising molecular entities toward cures for intractable brain tumors.

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