Radiotoxicity of h-R3 monoclonal antibody labeled with 188Re administered intracerebrally in rats

2000 ◽  
Vol 19 (12) ◽  
pp. 684-692 ◽  
Author(s):  
B Gonzalez ◽  
A Casaco ◽  
P Alvarez ◽  
M Leon ◽  
M Arteaga ◽  
...  
Keyword(s):  
Growth Factor ◽  
Behavioral Problems ◽  
Clinical Chemistry ◽  
Growth Factor Receptor ◽  
Systemic Toxicity ◽  
Intraventricular Administration ◽  
Intracerebral Administration ◽  
Histopathological Studies ◽  
The Right ◽  
Toxicity Effects

Brain tumors are often incurable despite current aggressive treatmentmodalities. Regional intracerebral administration of labeled monoclonal antibodies (Mabs) can maximize the radioisotope and Mab concentration to tumor sites while reducing systemic toxicity. h 3 is a humanized antiepidemal growth factor receptor Mab that successfully targets the epidermal growth factor receptor, which is overexpressed in glioblastomas. We studied the acute local and systemic toxicity effects of intraventricular 188Re 3 in rats. Forty rats were distributed into four groups with five animals of each sex in each group. A single 5-II dose (2.5 pl into the left and 2.5 MI into the right lateral ventricles) of neutral solution containing50pgofh-R31abeledwith49.5 t 1.7,284±13.7or 579±23.7 p Ci of 188Re were stereotactically administered to each animal. Control animals received vehicle alone. Each animal was observed twice daily for detection of toxicity signs. Bodyweights were recorded on days 0, 7 and 14. Blood samples for analysis of hematological and clinical chemistry parameters were taken on days 0 and 14. Necropsy and histopathological studies were carried out after completion of the study. All animals, but one, remained clinically stable. Toxicities included local radionecrosis, discrete increase in ALAT and creatinine blood values at higher dose level. We concluded that a single intraventricular administration of relatively large doses of 188Re 3 is tolerable and causes minimal local and systemic toxicity effects in rats. Nevetheless, further studies are necessary to discard learning and behavioral problems.

scholarly journals Trastuzumab-Based Combination Chemotherapy in Patients with Human Epidermal Growth Factor Receptor-2-Positive Metastatic Carcinoma ex Pleomorphic Adenoma

2018 ◽  
Vol 11 (3) ◽  
pp. 835-841 ◽  
Author(s):  
Yohei Arihara ◽  
Kazuyuki Murase ◽  
Kohichi Takada ◽  
Naotaka Hayasaka ◽  
Shogo Miura ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Case Report ◽  
Growth Factor ◽  
Combination Chemotherapy ◽  
Case Reports ◽  
Growth Factor Receptor ◽  
Carcinoma Ex Pleomorphic Adenoma ◽  
Her2 Positive ◽  
Epidermal Growth ◽  
The Right

Background: Carcinoma ex pleomorphic adenoma (CXPA) is a rare histologic subtype of lacrimal gland and submandibular gland cancer. Currently, there is no standard treatment for metastatic CXPA, although some case reports have explored the role of targeted agents in chemotherapy. A few histopathologic analyses have shown that some of these tumors overexpress human epidermal growth factor receptor-2 (HER2), suggesting a potential role for HER2-based therapy. We report here two cases of metastatic CXPA that were treated with trastuzumab-based chemotherapy (IRB approved) with rapid and significant responses. Case Report 1: A 66-year-old male was diagnosed as HER2-positive CXPA of the right lacrimal gland with multiple bone and lymph node metastases. Combination chemotherapy with trastuzumab (Tmab) and nanoparticle albumin-bound paclitaxel (nabPTX) was initiated. A rapid response was confirmed, and after seven cycles of treatment, CR(complete response) was achieved. Case Report 2: A 67-year-old female was diagnosed with HER2 positive CXPA of the right submandibular gland. Multiple pulmonary metastatic lesions were detected after surgery, and combination chemotherapy with Tmab and nab-PTX was initiated. A rapid partial response (PR) was confirmed, and she eventually became disease-free. Conclusion: In the absence of definitive clinical trials, which are unlikely to be performed due to the rarity of HER2-positive CXPA, therapeutic information must be obtained from case reports. Some reports, such as this one, have suggested a potential utility of trastuzumab-based chemotherapy.

scholarly journals Oculo-auriculo-vertebral spectrum with craniosynostosis and osteo-cartilagineous multiple defects: a diffuse chondro-membranous-osteo-dysplasia

2015 ◽  
Vol 37 (3) ◽  
Author(s):  
Agostino Berio ◽  
Giacomo Garlaschi ◽  
Giuseppe Mangiante ◽  
Attilia Piazzi
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Cranial Base ◽  
Fibroblast Growth ◽  
X Ray ◽  
Lambdoid Synostosis ◽  
The Right ◽  
Multiple Abnormalities ◽  
Mastoid Antrum

We report on a female with oculo-auriculo-vertebral spectrum, low height, and on X-ray lambdoid suture synostosis, cerebral cyst/mild holoprosencephalia and cholesteatoma, and multiple abnormalities of bones of chondral origin. On the right side, maxillary, mandibular bones, external auditory canal, middle ear were hypoplastic as well as semicircular canal, cranial base, bones vestibule. On the left side, coclea, timpanic cavity, mastoid antrum were hypoplastic, while stapes was misshapen. Limbs bones were slender with thin metaphyses and some carpal bones were absent. Hand second phalanx was hypoplastic and fifth finger presented clynodactily. Lambdoid synostosis expressed membranous ossification abnormality. We hypothesize that during the blastogenesis a mutation of a factor responsible for abnormal generalized endochondral and connectival ossification (possibly fibroblast growth factor receptor) occurs.

scholarly journals Triple Mutation Epidermal Growth Factor Receptor (EGFR) Exon 18 (G719S), 20 (T790M) and 21 (L858R) in a Male Patient with Lung Adenocarcinoma: A Case Report

2020 ◽  
Vol 6 (1) ◽  
pp. 13
Author(s):  
Nur Marleta Riza ◽  
Daniel Maranatha
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Male Patient ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Epidermal Growth ◽  
The Right ◽  
Egfr Tki

Background: Lung cancer is one of the deadliest cancers in the world. The percentage of non small cell lung cancer (NSCLC) is about 80% of the incidence of lung cancer. The type of NSCLC, adenocarcinoma, is usually found in the presence of epidermal growth factor receptor (EGFR) mutations.Case. A male patient aged 70 years, an active smoker, works as a farmer. He has complained of shortness of breath, and chest pain for three months. There was no family history of suffering from malignancy. The cytology result of the right pleural fluid indicated adenocarcinoma. He was diagnosed with pulmonary adenocarcinoma (D) stage IV positive mutation of EGFR exon 18 (G719S), 20 (T790M) and 21 (L858R) carnofsky score 70. He could survive for more than 11 months with the treatment of EGFR TKI, and received a good therapeutic response. Initially, for the first six months it was such a progressive disease, and for the next eleven months it became stable.Conclusion: In addition to the exon mutations found in this case, the cells in the tumor will continue to grow and develop into new mutants that are immune such drugs and rapidly split themselves into new, different forms. The therapy for complex mutations is still being developed. EGFR TKI therapy in this patient had a relatively good response. Further understanding of the molecular biology of lung cancer is seriously required.

Cavernous Sinus and Leptomeningeal Metastases Arising from a Squamous Cell Carcinoma of the Face: Case Report

Neurosurgery ◽  
2004 ◽  
Vol 54 (2) ◽  
pp. 492-499 ◽  
Author(s):  
Jay-Jiguang Zhu ◽  
Osvaldo Padillo ◽  
John Duff ◽  
Bae-Li Hsi ◽  
Jonathan A. Fletcher ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cavernous Sinus ◽  
Cauda Equina ◽  
Growth Factor Receptor ◽  
Perineural Spread ◽  
Epidermal Growth ◽  
The Right

Abstract OBJECTIVE AND IMPORTANCE Invasion of trigeminal and facial perineural spaces is a recognized complication of cutaneous malignancies. Centripetal spread along the trigeminal nerve axis and into the cavernous sinus and the gasserian ganglion is rare. Metastasis to the leptomeninges and cauda equina has not been reported. We report a unique case of perineural spread and central dissemination from an epithelial squamous cell carcinoma (SCC) associated with a tumor biomarker. CLINICAL PRESENTATION After excision of multiple cutaneous SCCs and basal cell carcinomas of the head and neck, a 70-year-old male patient developed successive, right-side, V1 and V2 trigeminal neuropathies and complete right cavernous sinus syndrome during a 5-year period. Concurrently, the right face became paralyzed. Left facial paresis developed during the latter half of this period. Two months before admission, subacute left lower-extremity radicular weakness resulted in falls. Serial magnetic resonance imaging scans obtained in the previous 4 years were unrevealing. At the time of admission, enhancing masses were found in the 1) right cavernous sinus and dura, foramina ovale and rotundum, and Meckel's cave, 2) right subtemporal region and orbital rectus muscles, and 3) cauda equina. Cerebrospinal fluid analysis demonstrated mild pleocytosis and rare carcinoma cells. INTERVENTION Biopsy of the right cavernous sinus mass confirmed moderately differentiated, metastatic SCC. Immunohistochemical staining and fluorescence in situ hybridization revealed epidermal growth factor receptor overexpression and genomic amplification. CONCLUSION The indolent progression of cranial nerve palsy among patients with resected cutaneous SCCs of the head and neck must raise clinical suspicion of perineural spread, even in the absence of radiological changes. Biomarkers predicting aggressive SCC behavior, illustrated here by epidermal growth factor receptor amplification and central invasion, have the potential to guide early therapy.

Adhesion and growth factor receptor crosstalk mechanisms controlling cell migration

2019 ◽  
Vol 63 (5) ◽  
pp. 553-567 ◽  
Author(s):  
Joanna R. Thomas ◽  
Nikki R. Paul ◽  
Mark R. Morgan
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Mechanical Forces ◽  
Cellular Processes ◽  
Therapeutic Benefits ◽  
Intracellular Signals ◽  
Cytoskeletal Dynamics ◽  
Receptor Crosstalk ◽  
The Right

Abstract Cell migration requires cells to sense and interpret an array of extracellular signals to precisely co-ordinate adhesion dynamics, local application of mechanical force, polarity signalling and cytoskeletal dynamics. Adhesion receptors and growth factor receptors (GFRs) exhibit functional and signalling characteristics that individually contribute to cell migration. Integrins transmit bidirectional mechanical forces and transduce long-range intracellular signals. GFRs are fast acting and highly sensitive signalling machines that initiate signalling cascades to co-ordinate global cellular processes. Syndecans are microenvironment sensors that regulate GTPases to control receptor trafficking, cytoskeletal remodelling and adhesion dynamics. However, an array of crosstalk mechanisms exists, which co-ordinate and integrate the functions of the different receptor families. Here we discuss the nature of adhesion receptor and GFR crosstalk mechanisms. The unifying theme is that efficient cell migration requires precise spatial and temporal co-ordination of receptor crosstalk. However, a higher order of complexity emerges; whereby multiple crosstalk mechanisms are integrated and subject to both positive and negative feedbacks. Exquisite and sensitive control of these mechanisms ensures that mechanical forces and pro-migratory signals are triggered in the right place and at the right time during cell migration. Finally, we discuss the challenges, and potential therapeutic benefits, associated with deciphering this complexity.

scholarly journals Predictive Molecular Tumour Testing: What Are the Obstacles between Bench and Bedside?

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Linda Mileshkin ◽  
Bhaumik Shah ◽  
Michael Michael
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Clinical Practice ◽  
Growth Factor ◽  
Molecular Basis ◽  
Growth Factor Receptor ◽  
Potential Barriers ◽  
Molecular Tests ◽  
Epidermal Growth ◽  
Tissue Specimens ◽  
The Right

There have been many exciting new breakthroughs in understanding tumour biology. This has opened up the possibility of personalized treatment for people with certain tumours. The epidermal growth factor receptor (EGFR) and K-ras are two such targets that can help classify tumours on a molecular basis and guide treatment decisions. However, there are still questions about how best to implement new molecular tests like these to characterize tumours in clinical practice. Potential obstacles include availability of good quality tissue specimens, access to the right test, and consensus about interpretation, funding, and availability. In this paper, we review these issues, by discussing these two examples in detail and suggest some actions for addressing potential barriers.

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