Cartilage is a type of tough, flexible connective tissue (see Question 1).
Cartilage from cows (bovine cartilage) and sharks has been studied as a treatment for people with cancer and other medical conditions for more than 30 years (see Question 2).
Laboratory and animal studies have looked at whether bovine and shark cartilage products can kill cancer cells, make the immune system more active against cancer, and prevent the body from making the new blood vessels that a tumor needs to grow...
Medulloblastoma (commonly referred to as classic medulloblastoma).
Large cell medulloblastoma.
Medulloblastoma with extensive nodularity (MBEN).
Significant attention has been focused on medulloblastomas that display anaplastic features, including increased nuclear size, marked cytological pleomorphism, numerous mitoses, and apoptotic bodies.[3,4] Using the criteria of anaplasia is subjective because most medulloblastomas have some degree of anaplasia. Foci of anaplasia may appear in tumors with histologic features of both classic and large cell medulloblastomas, and there is significant overlap between the anaplastic and large cell variant.[3,4] One convention is to consider medulloblastomas as anaplastic when anaplasia is diffuse (variably defined as anaplasia occurring in 50% to 80% of the tumor).
The incidence of medulloblastoma with the desmoplastic variant is higher in infants, is less common in children, and increases again in adolescents and adults. The desmoplastic variant subtype is different from MBEN; the nodular variant has an expanded lobular architecture. The nodular subtype occurs almost exclusively in infants and carries an excellent prognosis.[5,6]
Biologically/molecularly defined subtypes of medulloblastoma
Multiple medulloblastoma subtypes have been identified based on gene expression profiles.[7,8,9,10,11,12,13,14,15,16,17,18,19,20,21] As of 2012, there was a general consensus that medulloblastoma can be molecularly separated into at least four subtypes; however, it is likely that further subclassification will occur.[20,21,22]
The following four core subtypes of medulloblastoma have been identified:[20,21,23]
Subtype 1: WNT tumors (medulloblastoma with aberrations in the WNT signaling pathway). Subtype 1 shows a WNT signaling gene expression signature and beta-catenin nuclear staining. They are usually histologically classified as classic medulloblastoma tumors and rarely have a large cell/anaplastic appearance. They are infrequently metastasized at diagnosis. Genetically, these tumors have 6q loss and CTNNB1 mutations and have activated WNT signaling; there may be occasional MYC overexpression.
The WNT subset is primarily observed in older children, adolescents, and adults and does not show a male predominance. The subset is believed to have brain stem origin, from the embryonal rhombic lip region. Subtype 1 tumors are associated with a very good outcome.
Subtype 2: Sonic hedgehog (SHH) tumors (medulloblastoma with aberrations in the SHH pathway). Subtype 2 tumors are characterized by chromosome 9q deletions, desmoplastic/nodular histology, and mutations in SHH pathway genes including PTCH1, as well as PTCH2, SMO, and SUFU.
The SHH subset shows a bimodal age distribution and is observed primarily in children younger than 3 years, as well as in older adolescents and adults. The tumors are believed to emanate from the external granular layer of the cerebellum. Prognosis for patients with SHH medulloblastoma appears to be negatively affected by additional factors such as chromosome 17p loss, chromosome 3q gain, chromothripsis, p53 amplification, and the finding of large cell/anaplastic histology. Outcome in this group is relatively favorable, especially for children younger than 3 years. For adolescents and young adults, outcome is not different from non-WNT pathway activated tumors.
Subtype 3 (Group 3): Histology of Subtype 3 tumors is either classic or large cell/anaplastic and these tumors are frequently metastasized at the time of diagnosis. A variety of different mutations have been noted in these tumors including the presence of i17q and, most characteristically, MYC amplification.
Subtype 3 tumors occur throughout childhood and may occur in infants. Males outnumber females in a 2:1 ratio in this medulloblastoma subtype. Subtype 3 patients have the least favorable outcome among the molecularly defined medulloblastoma subtypes.
Subtype 4 (Group 4): Subtype 4 tumors are either classic or large cell/anaplastic tumors. Metastasis at diagnosis is common, but not as frequent as is seen in Subtype 3 tumors. Molecularly, they have a CDK6 amplification and MYCN amplification and may also have an i17q abnormality.
Subtype 4 tumors occur throughout infancy and childhood and into adulthood. They also predominate in males. The prognosis is better than Subtype 3 tumors but not as good as Subtype 1 tumors. Prognosis for Subtype 4 patients is affected by additional factors such as the presence of metastatic disease and chromosome 17p loss.[20,21]