Medulloblastoma
Cerebellar Neoplasms
Neuroectodermal Tumors, Primitive
Hedgehog Proteins
Brain Neoplasms
Cranial Irradiation
Infratentorial Neoplasms
Cerebellum
Ependymoma
Basal Cell Nevus Syndrome
Veratrum Alkaloids
Cranial Fossa, Posterior
Chromosomes, Human, Pair 17
Gene Expression Regulation, Neoplastic
Combined Modality Therapy
Busulphan is active against neuroblastoma and medulloblastoma xenografts in athymic mice at clinically achievable plasma drug concentrations. (1/1008)
High-dose busulphan-containing chemotherapy regimens have shown high response rates in children with relapsed or refractory neuroblastoma, Ewing's sarcoma and medulloblastoma. However, the anti-tumour activity of busulfan as a single agent remains to be defined, and this was evaluated in athymic mice bearing advanced stage subcutaneous paediatric solid tumour xenografts. Because busulphan is highly insoluble in water, the use of several vehicles for enteral and parenteral administration was first investigated in terms of pharmacokinetics and toxicity. The highest bioavailability was obtained with busulphan in DMSO administered i.p. When busulphan was suspended in carboxymethylcellulose and given orally or i.p., the bioavailability was poor. Then, in the therapeutic experiments, busulphan in DMSO was administered i.p. on days 0 and 4. At the maximum tolerated total dose (50 mg kg(-1)), busulphan induced a significant tumour growth delay, ranging from 12 to 34 days in the three neuroblastomas evaluated and in one out of three medulloblastomas. At a dose level above the maximum tolerated dose, busulphan induced complete and partial tumour regressions. Busulphan was inactive in a peripheral primitive neuroectodermal tumour (PNET) xenograft. When busulphan pharmacokinetics in mice and humans were considered, the estimated systemic exposure at the therapeutically active dose in mice (113 microg h ml(-1)) was close to the mean total systemic exposure in children receiving high-dose busulphan (102.4 microg h ml(-1)). In conclusion, busulphan displayed a significant anti-tumour activity in neuroblastoma and medulloblastoma xenografts at plasma drug concentrations which can be achieved clinically in children receiving high-dose busulphan-containing regimens. (+info)Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children's Cancer Group 921 randomized phase III study. (2/1008)
PURPOSE: From 1986 to 1992, "eight-drugs-in-one-day" (8-in-1) chemotherapy both before and after radiation therapy (XRT) (54 Gy tumor/36 Gy neuraxis) was compared with vincristine, lomustine (CCNU), and prednisone (VCP) after XRT in children with untreated, high-stage medulloblastoma (MB). PATIENTS AND METHODS: Two hundred three eligible patients with an institutional diagnosis of MB were stratified by local invasion and metastatic stage (Chang T/M) and randomized to therapy. Median time at risk from study entry was 7.0 years. RESULTS: Survival and progression-free survival (PFS) +/- SE at 7 years were 55%+/-5% and 54%+/-5%, respectively. VCP was superior to 8-in-1 chemotherapy, with 5-year PFS rates of 63%+/-5% versus 45%+/-5%, respectively (P = .006). Upon central neuropathology review, 188 patients were confirmed as having MB and were the subjects for analyses of prognostic factors. Children aged 1.5 to younger than 3 years had inferior 5-year estimates of PFS, compared with children 3 years old or older (P = .0014; 32%+/-10% v 58%+/-4%, respectively). For MB patients 3 years of age or older, the prognostic effect of tumor spread (MO v M1 v M2+) on PFS was powerful (P = .0006); 5-year PFS rates were 70%+/-5%, 57%+/-10%, and 40%+/-8%, respectively. PFS distributions at 5 years for patients with M0 tumors with less than 1.5 cm2 of residual tumor, versus > or = 1.5 cm2 of residual tumor by scan, were significantly different (P = .023; 78%+/-6% v 54%+/-11%, respectively). CONCLUSION: VCP plus XRT is a superior adjuvant combination compared with 8-in-1 chemotherapy plus XRT. For patients with M0 tumors, residual tumor bulk (not extent of resection) is a predictor for PFS. Patients with M0 tumors, > or = 3 years with < or = 1.5 cm2 residual tumor, had a 78%+/-6% 5-year PFS rate. Children younger than 3 years old who received a reduced XRT dosage had the lowest survival rate. (+info)Prognostic value of cerebrospinal fluid cytology in pediatric medulloblastoma. Swiss Pediatric Oncology Group. (3/1008)
BACKGROUND: Although the demonstration of leptomeningeal dissemination is the most important predictor of poor outcome in children with medulloblastoma, there is lack of consensus on the prognostic value of a positive cerebrospinal fluid (CSF) cytology (i.e., stage M1). PATIENTS AND METHODS: Eighty-six pediatric medulloblastoma patients treated in Switzerland between 1972-1991 were retrospectively studied regarding the influence of M-stage on prognosis. 39 were M0, 13 M1, 15 Mx, 17 M2, and 2 M3. RESULTS: Five- and 10-year overall survival rates were 76% and 54% for M0, 68% and 50% for Mx, 36% and 25% for M1, and 22% and 22% for M2-3 (P < 0.001), respectively. No significant survival differences were observed between M1 and M2-3 patients. Among 26 patients with only postoperative CSF cytologies, seven were positive. Their outcome was similar to that of six preoperatively staged M1 and significantly different from that of M0 patients (P = 0.001). In 14 patients both pre- and postoperative CSF cytology was performed. Total agreement was observed between the pre- and postoperative results (six positive and eight negative). Among the 19 M2-3 patients CSF cytology was positive in eight, negative in five, and unknown in six. CONCLUSIONS: A positive CSF cytology either pre- or postoperatively predicts for a poor outcome, similar to that observed in stage M2-3 patients. A postoperative cytology is likely to be concordant with cytologic results obtained preoperatively, and seems to have the same prognostic significance. A negative cytology, however, does not exclude a more advanced stage. (+info)Activation of the CD95 (APO-1/Fas) pathway in drug- and gamma-irradiation-induced apoptosis of brain tumor cells. (4/1008)
Chemotherapeutic agents and gamma-irradiation used in the treatment of brain tumors, the most common solid tumors of childhood, have been shown to act primarily by inducing apoptosis. Here, we report that activation of the CD95 pathway was involved in drug- and gamma-irradiation-induced apoptosis of medulloblastoma and glioblastoma cells. Upon treatment CD95 ligand (CD95-L) was induced that stimulated the CD95 pathway by crosslinking CD95 via an autocrine/paracrine loop. Blocking CD95-L/receptor interaction using F(ab')2 anti-CD95 antibody fragments strongly reduced apoptosis. Apoptosis depended on activation of caspases (interleukin 1beta-converting enzyme/Ced-3 like proteases) as it was almost completely abrograted by the broad range caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone. Apoptosis was mediated by cleavage of the receptor proximal caspase FLICE/MACH (caspase-8) and the downstream caspase CPP32 (caspase-3, Apopain) resulting in cleavage of the prototype caspase substrate PARP. Moreover, CD95 was upregulated in wild-type p53 cells thereby increasing responsiveness towards CD95 triggering. Since activation of the CD95 system upon treatment was also found in primary medulloblastoma cells ex vivo, these findings may have implications to define chemosensitivity and to develop novel therapeutic strategies in the management of malignant brain tumors. (+info)Comparative genomic hybridization detects many recurrent imbalances in central nervous system primitive neuroectodermal tumours in children. (5/1008)
A series of 23 children with primitive neuroectodermal tumours (PNET) were analysed with comparative genomic hybridization (CGH). Multiple chromosomal imbalances have been detected in 20 patients. The most frequently involved chromosome was chromosome 17, with a gain of 17q (11 cases) and loss of 17p (eight cases). Further recurrent copy number changes were detected. Extra copies of chromosome 7 were present in nine patients and gains of 1q were detected in six patients. A moderate genomic amplification was detected in one patient, involving two sites on 3p and the whole 12p. Losses were more frequent, and especially involved the chromosomes 11 (nine cases), 10q (eight cases), 8 (six cases), X (six patients) and 3 (five cases), and part of chromosome 9 (five cases). These recurrent chromosomal changes may highlight locations of novel genes with an important role in the development and/or progression of PNET. (+info)Cicatricial fibromatosis mimics metastatic medulloblastoma. (6/1008)
Cicatricial fibromatoses usually occur in the anterior abdominal wall or in the extremities, but rarely in the scalp or the soft tissues of the neck. We report a case of desmoid fibromatosis that developed in a 15-year-old boy 8 months after surgery for cerebellar medulloblastoma. (+info)Unexpected stomach uptake of technetium-99m-MDP. (7/1008)
Two pediatric cases are described in which the results of each patient's bone scan demonstrated abnormal stomach uptake. There have been a number of reports in the literature describing stomach uptake of bone agents, however, it is an uncommon finding. (+info)Medullomyoblastoma: A case report. (8/1008)
Medullomyoblastoma is a rare tumour seen in childhood. We report a medullomyoblastoma occurring in the cerebellar vermis of a 4 year old boy. The light microscopic features, immunohistochemistry and histogenesis are described. (+info)Medulloblastoma is a type of malignant brain tumor that originates in the cerebellum, which is the part of the brain located at the back of the skull and controls coordination and balance. It is one of the most common types of pediatric brain tumors, although it can also occur in adults.
Medulloblastomas are typically made up of small, round cancer cells that grow quickly and can spread to other parts of the central nervous system, such as the spinal cord. They are usually treated with a combination of surgery, radiation therapy, and chemotherapy. The exact cause of medulloblastoma is not known, but it is thought to be related to genetic mutations or abnormalities that occur during development.
Cerebellar neoplasms refer to abnormal growths or tumors that develop in the cerebellum, which is the part of the brain responsible for coordinating muscle movements and maintaining balance. These tumors can be benign (non-cancerous) or malignant (cancerous), and they can arise from various types of cells within the cerebellum.
The most common type of cerebellar neoplasm is a medulloblastoma, which arises from primitive nerve cells in the cerebellum. Other types of cerebellar neoplasms include astrocytomas, ependymomas, and brain stem gliomas. Symptoms of cerebellar neoplasms may include headaches, vomiting, unsteady gait, coordination problems, and visual disturbances. Treatment options depend on the type, size, and location of the tumor, as well as the patient's overall health and age. Treatment may involve surgery, radiation therapy, chemotherapy, or a combination of these approaches.
Neuroectodermal tumors, primitive (PNETs) are a group of highly malignant and aggressive neoplasms that arise from neuroectodermal cells, which are the precursors to the nervous system during embryonic development. These tumors can occur anywhere in the body but are most commonly found in the central nervous system, particularly in the brain and spinal cord.
PNETs are characterized by small, round, blue cells that have a high degree of cellularity and mitotic activity. They are composed of undifferentiated or poorly differentiated cells that can differentiate along various neural lineages, including neuronal, glial, and epithelial. This feature makes their diagnosis challenging, as they can resemble other small round blue cell tumors, such as lymphomas, rhabdomyosarcomas, and Ewing sarcoma.
Immunohistochemical staining and molecular genetic testing are often required to confirm the diagnosis of PNETs. These tests typically reveal the expression of neural markers, such as NSE, Synaptophysin, and CD99, and the presence of specific chromosomal abnormalities, such as the EWS-FLI1 fusion gene in Ewing sarcoma.
PNETs are aggressive tumors with a poor prognosis, and their treatment typically involves a multimodal approach that includes surgery, radiation therapy, and chemotherapy. Despite these treatments, the five-year survival rate for patients with PNETs is less than 30%.
Hedgehog proteins are a group of signaling molecules that play crucial roles in the development and regulation of various biological processes in animals. They are named after the hedgehog mutant fruit flies, which have spiky bristles due to defects in this pathway. These proteins are involved in cell growth, differentiation, and tissue regeneration. They exert their effects by binding to specific receptors on the surface of target cells, leading to a cascade of intracellular signaling events that ultimately influence gene expression and cell behavior.
There are three main types of Hedgehog proteins in mammals: Sonic hedgehog (Shh), Indian hedgehog (Ihh), and Desert hedgehog (Dhh). These protecules undergo post-translational modifications, including cleavage and lipid modification, which are essential for their activity. Dysregulation of Hedgehog signaling has been implicated in various diseases, including cancer, developmental abnormalities, and degenerative disorders.
Brain neoplasms, also known as brain tumors, are abnormal growths of cells within the brain. These growths can be benign (non-cancerous) or malignant (cancerous). Benign brain tumors typically grow slowly and do not spread to other parts of the body. However, they can still cause serious problems if they press on sensitive areas of the brain. Malignant brain tumors, on the other hand, are cancerous and can grow quickly, invading surrounding brain tissue and spreading to other parts of the brain or spinal cord.
Brain neoplasms can arise from various types of cells within the brain, including glial cells (which provide support and insulation for nerve cells), neurons (nerve cells that transmit signals in the brain), and meninges (the membranes that cover the brain and spinal cord). They can also result from the spread of cancer cells from other parts of the body, known as metastatic brain tumors.
Symptoms of brain neoplasms may vary depending on their size, location, and growth rate. Common symptoms include headaches, seizures, weakness or paralysis in the limbs, difficulty with balance and coordination, changes in speech or vision, confusion, memory loss, and changes in behavior or personality.
Treatment for brain neoplasms depends on several factors, including the type, size, location, and grade of the tumor, as well as the patient's age and overall health. Treatment options may include surgery, radiation therapy, chemotherapy, targeted therapy, or a combination of these approaches. Regular follow-up care is essential to monitor for recurrence and manage any long-term effects of treatment.
Cranial irradiation is a medical treatment that involves the use of radiation therapy to target the brain. It is often used to treat various conditions affecting the brain, such as brain tumors, leukemia, and certain neurological disorders. The radiation is directed at the skull and can be focused on specific areas of the brain or delivered more broadly, depending on the nature and location of the condition being treated.
The goal of cranial irradiation may be to destroy cancer cells, reduce the size of tumors, prevent the spread of cancer, or provide symptomatic relief for patients with advanced disease. However, it is important to note that cranial irradiation can have side effects, including hair loss, fatigue, memory problems, and cognitive changes, among others. These side effects can vary in severity and duration depending on the individual patient and the specific treatment regimen.
Infratentorial neoplasms refer to tumors that originate in the region of the brain called the posterior fossa, which is located below the tentorium cerebelli (a membranous structure that separates the cerebrum from the cerebellum). This area contains several important structures such as the cerebellum, pons, medulla oblongata, and fourth ventricle. Infratentorial neoplasms can be benign or malignant and can arise from various cell types including nerve cells, glial cells, or supportive tissues. They can cause a variety of symptoms depending on their location and size, such as headache, vomiting, unsteady gait, weakness, numbness, vision changes, hearing loss, and difficulty swallowing or speaking. Treatment options may include surgery, radiation therapy, and chemotherapy.
The cerebellum is a part of the brain that lies behind the brainstem and is involved in the regulation of motor movements, balance, and coordination. It contains two hemispheres and a central portion called the vermis. The cerebellum receives input from sensory systems and other areas of the brain and spinal cord and sends output to motor areas of the brain. Damage to the cerebellum can result in problems with movement, balance, and coordination.
Anaplasia is a term used in pathology to describe the loss of differentiation and cellular organization in malignant tumors. It is characterized by the presence of large, pleomorphic cells with high mitotic activity, absence of mature tissue architecture, and lack of functional specialization. Anaplastic tumors are often aggressive and have a poor prognosis due to their rapid growth and tendency to metastasize. The term "anaplasia" is derived from the Greek words "ana," meaning "back" or "against," and "plasis," meaning "formation" or "molding."
Ependymoma is a type of brain or spinal cord tumor that develops from the ependymal cells that line the ventricles (fluid-filled spaces) in the brain, or the central canal of the spinal cord. These tumors can be benign or malignant, and they can cause various symptoms depending on their location and size.
Ependymomas are relatively rare, accounting for about 2-3% of all primary brain and central nervous system tumors. They most commonly occur in children and young adults, but they can also affect older individuals. Treatment typically involves surgical removal of the tumor, followed by radiation therapy or chemotherapy, depending on the grade and location of the tumor. The prognosis for ependymomas varies widely, with some patients experiencing long-term survival and others having more aggressive tumors that are difficult to treat.
Basal Cell Nevus Syndrome (BCNS), also known as Gorlin-Goltz Syndrome, is a rare genetic disorder that is characterized by the development of multiple basal cell carcinomas (BCCs), which are skin cancer tumors that arise from the basal cells in the outermost layer of the skin.
The syndrome is caused by mutations in the PTCH1 gene, which regulates the hedgehog signaling pathway involved in embryonic development and tissue growth regulation. The condition is inherited in an autosomal dominant manner, meaning that a child has a 50% chance of inheriting the mutated gene from an affected parent.
Individuals with BCNS typically develop hundreds to thousands of BCCs over their lifetime, often beginning in childhood or adolescence. They may also have other benign and malignant tumors, such as medulloblastomas (brain tumors), fibromas, and rhabdomyosarcomas.
Additional features of BCNS can include:
1. Facial abnormalities, such as a broad nasal bridge, widely spaced eyes, and pits or depressions on the palms and soles.
2. Skeletal abnormalities, such as spine deformities, rib anomalies, and jaw cysts.
3. Developmental delays and intellectual disabilities in some cases.
4. Increased risk of other cancers, including breast, ovarian, and lung cancer.
Early detection and management of BCCs and other tumors are crucial for individuals with BCNS to prevent complications and improve their quality of life. Regular dermatological examinations, sun protection measures, and surgical removal of tumors are common treatment approaches.
A cell line that is derived from tumor cells and has been adapted to grow in culture. These cell lines are often used in research to study the characteristics of cancer cells, including their growth patterns, genetic changes, and responses to various treatments. They can be established from many different types of tumors, such as carcinomas, sarcomas, and leukemias. Once established, these cell lines can be grown and maintained indefinitely in the laboratory, allowing researchers to conduct experiments and studies that would not be feasible using primary tumor cells. It is important to note that tumor cell lines may not always accurately represent the behavior of the original tumor, as they can undergo genetic changes during their time in culture.
Veratrum alkaloids are a group of steroidal alkaloids found in plants belonging to the genus Veratrum, such as Veratrum album (white hellebore) and Veratrum viride (American false hellebore). These compounds have complex structures and can be divided into several types, including veratrine, jervine, and cevadine. They have various pharmacological effects, such as being anticholinergic, antiarrhythmic, and emetic. Veratrum alkaloids are used in traditional medicine, but they can also be highly toxic if ingested or handled improperly.
The posterior cranial fossa is a term used in anatomy to refer to the portion of the skull that forms the lower, back part of the cranial cavity. It is located between the occipital bone and the temporal bones, and it contains several important structures including the cerebellum, pons, medulla oblongata, and the lower cranial nerves (IX-XII). The posterior fossa also contains the foramen magnum, which is a large opening through which the spinal cord connects to the brainstem. This region of the skull is protected by the occipital bone, which forms the base of the skull and provides attachment for several neck muscles.
Human chromosome pair 17 consists of two rod-shaped structures present in the nucleus of each human cell. Each chromosome is made up of DNA tightly coiled around histone proteins, forming a complex called chromatin. Chromosomes carry genetic information in the form of genes, which are segments of DNA that contain instructions for the development and function of an organism.
Human cells typically have 23 pairs of chromosomes, for a total of 46 chromosomes. Pair 17 is one of the autosomal pairs, meaning it is not a sex chromosome (X or Y). Chromosome 17 is a medium-sized chromosome and contains an estimated 800 million base pairs of DNA. It contains approximately 1,500 genes that provide instructions for making proteins and regulating various cellular processes.
Chromosome 17 is associated with several genetic disorders, including inherited cancer syndromes such as Li-Fraumeni syndrome and hereditary nonpolyposis colorectal cancer (HNPCC). Mutations in genes located on chromosome 17 can increase the risk of developing various types of cancer, including breast, ovarian, colon, and pancreatic cancer.
Neoplastic gene expression regulation refers to the processes that control the production of proteins and other molecules from genes in neoplastic cells, or cells that are part of a tumor or cancer. In a normal cell, gene expression is tightly regulated to ensure that the right genes are turned on or off at the right time. However, in cancer cells, this regulation can be disrupted, leading to the overexpression or underexpression of certain genes.
Neoplastic gene expression regulation can be affected by a variety of factors, including genetic mutations, epigenetic changes, and signals from the tumor microenvironment. These changes can lead to the activation of oncogenes (genes that promote cancer growth and development) or the inactivation of tumor suppressor genes (genes that prevent cancer).
Understanding neoplastic gene expression regulation is important for developing new therapies for cancer, as targeting specific genes or pathways involved in this process can help to inhibit cancer growth and progression.
Cell proliferation is the process by which cells increase in number, typically through the process of cell division. In the context of biology and medicine, it refers to the reproduction of cells that makes up living tissue, allowing growth, maintenance, and repair. It involves several stages including the transition from a phase of quiescence (G0 phase) to an active phase (G1 phase), DNA replication in the S phase, and mitosis or M phase, where the cell divides into two daughter cells.
Abnormal or uncontrolled cell proliferation is a characteristic feature of many diseases, including cancer, where deregulated cell cycle control leads to excessive and unregulated growth of cells, forming tumors that can invade surrounding tissues and metastasize to distant sites in the body.
Combined modality therapy (CMT) is a medical treatment approach that utilizes more than one method or type of therapy simultaneously or in close succession, with the goal of enhancing the overall effectiveness of the treatment. In the context of cancer care, CMT often refers to the combination of two or more primary treatment modalities, such as surgery, radiation therapy, and systemic therapies (chemotherapy, immunotherapy, targeted therapy, etc.).
The rationale behind using combined modality therapy is that each treatment method can target cancer cells in different ways, potentially increasing the likelihood of eliminating all cancer cells and reducing the risk of recurrence. The specific combination and sequence of treatments will depend on various factors, including the type and stage of cancer, patient's overall health, and individual preferences.
For example, a common CMT approach for locally advanced rectal cancer may involve preoperative (neoadjuvant) chemoradiation therapy, followed by surgery to remove the tumor, and then postoperative (adjuvant) chemotherapy. This combined approach allows for the reduction of the tumor size before surgery, increases the likelihood of complete tumor removal, and targets any remaining microscopic cancer cells with systemic chemotherapy.
It is essential to consult with a multidisciplinary team of healthcare professionals to determine the most appropriate CMT plan for each individual patient, considering both the potential benefits and risks associated with each treatment method.