leptin levels increase (answer a).Leptin inhibits hypothalamic synthesis and
secretion of neuropeptide Y, an appetite (orexigenic) peptide (answer d).
103.The answer is b.(Kumar, pp 309–313.)The patient is diagnosed with
transitional cell carcinoma (TCC) that is highly aggressive having penetrated
the muscle of the bladder (T3a), with lymph node involvement and metas-
tases (M2). TCC metastasizes primarily to the lymph nodes, lung, bone, liver
and brain. The tumor cells normally adhere to the basement membrane. To
undergo metastasis they must dissolve the basement membrane and extracel-
lular matrix in order to reach the bloodstream and subsequently migrate to a
new site, where they reaggregate and reestablish cell-cell and cell-basal lamina
interactions. Metalloproteinases such as the serine, cysteine, and metallopro-
teinases (MMPs), including type IV collagenase (MMP-2), play a key role in
freeing tumor cells to migrate to metastatic sites. Lysyl oxidase (answer a)is
an extracellular enzyme that is responsible for cross-linking of collagen by
deamination of lysine and hydroxylysine residues to form aldehydes. Those
aldehydes then interact with each other or with other lysyl side chains to form
collagen cross-links. A similar process occurs in the synthesis of elastin. Plas-
minogen(answer c)is an inactive form of plasmin that occurs in plasma and
is converted to plasmin by organic solvents. SERPINS (answer d)are serine
protease inhibitors. Members of that gene family regulate cell division and
migration, neurite extension, tumor cell metastasis, and blood coagulation.
The SERPINS act as specific inhibitors of cell-surface and extracellular matrix
serine proteases that participate in cascade mechanisms in those biological
processes. TIMPs (answer e),are the tissue inhibitors of the metalloproteases
and, like SERPINS, inhibit the degradation of the extracellular matrix.
192 Anatomy, Histology, and Cell Biology