2024 Flashcards

Question

What is CD45?

Answer 1

CD45 is a protein tyrosine phosphatase expressed on leukocytes (white blood cells) and plays a role in leukocyte development, activation, and trafficking.

Answer 2

CD5 is a cell surface protein expressed on mature T cells, involved in T cell activation and development.

Answer 3

CD204, also known as dendritic cell-specific intercellular adhesion molecule-3 (DC-SIGN), is a lectin expressed on dendritic cells and other immune cells, involved in cell-cell adhesion and the uptake of pathogens.

Answer 4

CD11b, also known as integrin alphaM, is an integrin expressed on myeloid cells such as macrophages, neutrophils, and granulocytes, playing a crucial role in leukocyte adhesion, migration, and immune responses.

Answer 5

HO is a generalized osteoproductive disorder of the periosteum that affects the long bones of the extremities, typically beginning on the digits and progressing proximally.

Answer 6

Lesions are bilaterally symmetric and involve all four limbs.

Answer 7

It is most commonly associated with primary lung tumors or tumors that have metastasized to the lungs.

Answer 8

The most common tumor type reported is osteosarcoma.

Answer 9

Paraneoplastic HO has been reported in dogs with renal transitional cell carcinoma, nephroblastoma, urinary bladder botryoid rhabdomyosarcoma, hepatocellular carcinoma, esophageal adenocarcinoma, prostatic carcinoma, and malignant schwannoma derived from the vagus nerve.

Answer 10

Nonneoplastic diseases include infectious/inflammatory lung disease, Dirofilaria immitis infection, bacterial endocarditis, patent ductus arteriosus with right-to-left shunting, Spirocera lupi esophageal granulomas, esophageal foreign body, and congenital megaesophagus.

Answer 11

Yes, idiopathic HO has been reported in cats.

Answer 12

Yes, cats with primary lung tumors can develop digital metastasis, which can have a similar clinical presentation to HO.

Answer 13

mTOR, or mechanistic target of rapamycin, is a protein kinase that regulates cell growth, metabolism, and survival.

Answer 14

mTOR regulates protein synthesis, cell cycle progression, metabolism, cell survival, and is implicated in aging.

Answer 15

A protein kinase is an enzyme that adds phosphate groups to other proteins, which can activate or deactivate them.

Answer 16

mTOR controls cell growth and proliferation, protein synthesis, metabolism, and cell survival.

Answer 17

mTOR exists in two complexes: mTORC1 and mTORC2, each with different functions and regulatory mechanisms.

Answer 18

mTOR plays a crucial role in growth during development and maintaining cellular homeostasis.

Answer 19

mTOR is often overactive in cancer cells, leading to uncontrolled growth and survival; inhibiting mTOR can be a cancer therapy strategy.

Answer 20

mTOR dysregulation is linked to obesity, type 2 diabetes, neurodegenerative disorders, and aging.

Answer 21

mTORC1 regulates protein synthesis, cell growth, and inhibits autophagy; mTORC2 plays a role in cell survival and actin cytoskeleton organization.

Answer 22

Rapamycin is a drug that binds to mTOR and inhibits its activity.

Answer 23

mTOR inhibitors are used as immunosuppressants in organ transplants and are being investigated for cancer treatment.

Answer 24

Major Complications: - Postoperative dehiscence (suture failure) - not a high risk: in cats with alimentary lymphoma after full-thickness GI surgery, according to a study from NIH - Bile peritonitis (infection of the abdominal cavity with bile) is a rare but serious complication. - Pancreatitis

Answer 25

- In a retrospective 2024 study in Can J. Vet Med, phenoxybenzamine pretreatment did not offer any cardiovascular benefits based on the measured variables, and may be associated with more intraoperative hypertensive episodes. - In a retropective 2022 Vet Surg study, most dogs survived the immediate postoperative period and achieved long-term survival with a low reported incidence of tumor recurrence or metastasis. Preoperative alpha-blocker therapy was not associated with increased survival.

Answer 26

- Cats in both arms had similar response rates, PFS, and Lymphoma specific response (LSS) (48 versus 64 days, P = .87; 139 versus 136 days, P = .96). - Cats that received vincristine were significantly more likely to switch arms based on gastrointestinal toxicity than cats that received vinblastine (44.4 versus 10.5%, P = .02). - Lower baseline weight was significantly negatively associated with PFS and LSS (P = .01, P = .003, respectively). - Baseline anemia was significantly negatively associated with LSS (P = .04)

Answer 27

- MST 12-19 months - Two major studies showed no prognostic value of mastocytosis

Answer 28

Fluorodeoxyglucose (FDG) This tracer is a sugar molecule (glucose analog) that is tagged with a radioactive isotope. FDG is taken up by cells that are actively using glucose, such as cancer cells. When FDG decays, it emits positrons, which are detected by the PET scanner. The scanner generates an image showing where the FDG has concentrated, indicating areas of high metabolic activity

Answer 29

- Eight cats with lymphoblastic gastrointestinal or multicentric lymphoma confined to the abdominal cavity were treated with a 6-week combination chemotherapy protocol followed 2 weeks later by whole-abdomen radiation therapy consisting of 10 daily fractions of 1.5 Gy. - Combination chemotherapy is standard care with response rates ranging from 30 to 65% and remission duration from 6 to 10 months - The remaining five cats remain in remission at least 266 days afterstarting therapy; median remission duration has not been reached (range, 4266 to 41332 days). ## Footnote - Treatment was well tolerated; renal insufficiency documented in one cat at the start of radiation therapy progressed to stable chronic renal failure. - One cat not in complete remission at the time of radiation therapy relapsed 2 weeks later, one cat with multicentric lymphoma relapsed with hepatic large granular lymphoma, and one cat was euthanatized 3 weeks following completion of radiation therapy for other reasons

Answer 30

Canine: When mediastinal masses are composed of a lymphocyte-rich population, FC of the lymphoid population is considered an excellent tool to distinguish mediastinal lymphoma from non-neoplastic normal lymphocytes, thus supporting thymoma. A cutoff value of 10% of double positive CD4+CD8+ thymocytes and small cell size (similar to that of a circulating lymphocyte) is strongly supportive of thymoma (14). Cat: Forward scatter (FSC) of lymphoid cells was higher in the lymphoma group. Double positive CD4+CD8+ T-cells were the dominant population in eight out of 12 lymphomas, whereas non-lymphomatous lesions showed no dominant lymphoid population in five out of eight cases. Unlike dogs, the high prevalence of CD4+CD8+ lymphomas in cats it makes difficult to differentiate lymphoma from non-lymphomatous lesions using FC alone. F

Answer 31

CD3: A key marker for T cells, indicating T cell lineage. CD4: Found on T-helper cells, which play a role in immune responses. CD8: Found on cytotoxic T-cells, which are responsible for eliminating infected or cancerous cells. CD5: Another T cell marker that is often co-expressed with CD4 and CD8. CD21: A marker of B cells, helps distinguish LGLs from B cells. ## Footnote Other relevant markers: TCRαβ and TCRγδ: T cell receptor markers used to further subclassify T cells. CD25: Associated with activated T cells, including regulatory T cells (Tregs). FoxP3: A nuclear marker used to identify Tregs. NKp46 (NCR1): A marker suggested for canine NK cells, although not a universal marker. CD11d: Sometimes expressed on splenic or intestinal origin T cells.

Answer 32

CD21, CD5, CD19, CD23, and CD20, along with other markers like CD38, ZAP70, and CD49d/VLA-4

Answer 33

- In canine neutrophils, surface markers like CD15 and CD16/FcγRIII are used to differentiate them from other granulocytes, while the lack of CD14 helps distinguish them from monocytes. - Other markers like CD66b, CD11b, CD33, and myeloperoxidase are also useful for neutrophil identification. - Neutrophils also express CD11b and CADO48A as myeloid cell markers. Elaboration: ## Footnote CD15 and CD16/FcγRIII: These markers help distinguish neutrophils from other granulocytes like eosinophils and basophils. Lack of CD14: This helps differentiate neutrophils from monocytes and macrophages, which express CD14. CD66b, CD11b, CD33, and Myeloperoxidase: These are additional markers that can be used to identify and characterize neutrophils, particularly in flow cytometry studies. CADO48A: This is a canine neutrophil monoclonal antibody that is used to identify neutrophils in various assays. CD11b and CADO: These are myeloid cell markers used for more precise detection of neutrophils and monocyte/macrophage subsets.

Answer 34

In dogs, approximately 95% of GISTs (Gastrointestinal Stromal Tumors) are positive for c-KIT/CD117. Immunohistochemical staining for c-KIT is a key diagnostic tool for GIST.

Answer 35

around 625 days significantly reduced to around 320 days

Answer 36

While the average survival time for untreated canine nasal lymphoma is typically 3-5 months, treatment can significantly improve survival and quality of life. With radiation therapy, some dogs may experience a median survival of 12-18 months or even longer, depending on the stage and subtype of the tumor.

Answer 37

Xeroderma pigmentosum is caused by defects in the nucleotide excision repair pathway, which is responsible for repairing DNA damage caused by ultraviolet (UV) radiation. This is a rare, inherited genetic disorder caused by mutations in genes involved in the nucleotide excision repair pathway. Individuals with XP have a very high sensitivity to UV radiation, leading to severe sunburns, skin cancer, and other skin problems. The defect in NER prevents the cells from effectively repairing DNA damage caused by UV exposure, leading to the accumulation of DNA damage and the clinical manifestations of XP.

Answer 38

Loss of heterozygosity (LOH) can be caused by various processes, including deletions, mitotic recombination, chromosome loss, and gene conversion. These mechanisms can lead to the loss of one allele at a specific locus, effectively rendering the individual homozygous for that region. Mechanisms of Loss of Heterozygosity (LOH): Deletions: 1. Direct or indirect deletions of a portion of a chromosome can remove one allele, leading to LOH. 2. Mitotic Recombination: Recombination between homologous chromosomes during cell division can result in LOH, where the recombined chromosome may segregate with an unrecombined chromosome. 3. Chromosome Loss: Loss of an entire chromosome (monosomy) or a segment of a chromosome can also cause LOH. This can be followed by duplication of the remaining chromosome or segment. 4. Gene Conversion: A process where one allele "converts" to the sequence of the other allele, often mediated by homologous recombination, can lead to LOH. 5. Acquired Uniparental Disomy (UPD): A person receives two copies of a chromosome (or part of a chromosome) from one parent and none from the other, often due to errors during meiosis. 6. Mitotic Nondisjunction: Failure of sister chromatids or chromosome pairs to separate properly during mitosis can lead to LOH, as one daughter cell may receive more chromosomes than the other. 7. Translocation: Recombination between fragments of nonhomologous chromosomes can result in LOH. 8. Break-Induced Replication (BIR): This mechanism can also lead to LOH, where a DNA break is repaired by copying DNA from the homologous chromosome, potentially leading to a change in the genetic material.

Answer 39

In a 2013 prospective study, dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin In a 2014 retrospective by Selmic, after adjustment for baseline characteristics and prognostic factors, neither of the protocols provided a significant reduction in risk of development of metastases or death.

Answer 40

In dogs, oral papillary squamous cell carcinoma (COPSCC) differs significantly from conventional oral squamous cell carcinoma (SCC) in several ways. COPSCC is characterized by exophytic growth, limited invasion, and a generally better prognosis compared to conventional SCC. Conventional SCC, on the other hand, often exhibits more aggressive growth, deeper invasion, and a higher tendency for metastasis. ## Footnote Key Differences: Growth Pattern: COPSCC tends to have a papillary, exophytic growth pattern, while conventional SCC often presents with more invasive growth patterns. Invasion: COPSCC typically shows limited invasion of surrounding tissues, whereas conventional SCC can exhibit deeper invasion into the underlying bone and soft tissues. Metastasis: COPSCC has a lower metastatic rate compared to conventional SCC. Metastasis from COPSCC is rare, while conventional SCC can metastasize to regional lymph nodes and even distant sites. Prognosis: COPSCC generally has a better prognosis due to its limited invasiveness and lower metastatic potential, according to the National Institutes of Health. Diagnosis: Diagnosing COPSCC can be challenging due to its exophytic nature, which may mimic benign oral lesions. Conventional SCC is usually easier to diagnose histologically. Treatment: COPSCC often responds well to surgical excision, while conventional SCC may require more aggressive treatments like surgery, radiation therapy, or chemotherapy.

Answer 41

Reactive Hyperplasia: - Infectious: Viral (e.g., cat scratch disease), bacterial (e.g., Bartonella), fungal (e.g., Cryptococcus), parasitic (e.g., Cytauxzoonosis). - Inflammatory/Immune-related: Autoimmune lymphoproliferative syndrome, drug reactions, etc. - Other: Reactive to vaccines, trauma, or other inflammatory conditions. Neoplastic Processes: - Lymphoma: Primary lymphoid neoplasia is a common cause, especially in older cats. - Metastatic Neoplasia: Cancers can spread from other locations to the lymph nodes, such as mammary gland carcinoma or oral squamous cell carcinoma. - Other: Mast cell tumor, etc. ## Footnote Options included: Hodgkins lymphoma, thymoma, parathyroid tumor, vascular endothelial proliferative disorder (plexiform vasculopathy?)

Answer 42

Plexiform vasculopathy refers to an endothelial proliferative disorder affecting cervical or inguinal lymph nodes of cats. The cause of this disorder and the origin of the proliferating endothelial cells are still unknown. In 4 cats with a history of a slowly growing, well-demarcated, nonpainful mass adjacent to the thyroid gland, an enlarged dark brown to red lymph node was removed. Histologically, the lymph nodes showed severe loss of lymphoid tissue with accumulations of erythrocytes. In addition, networks of capillary structures with well-differentiated endothelial cells on a collagen-rich stroma were observed, consistent with benign plexiform vasculopathy. Immunohistochemistry revealed the expression of the vascular endothelial markers CD31 and factor VIII-related antigen. In addition, immunolabeling with a Prox-1 antibody indicated a lymphendothelial origin. With respect to our findings, a lymphendothelial origin has to be considered in cases of intranodal vascular neoplasms.

Answer 43

Radiotherapy (RT) alone: Survival times can range from 1 to 2 years or more, especially if the cancer is localized and hasn't spread. Chemotherapy alone: Survival times can be shorter, with median survival times reported as 7-10 months, or even 3-6 months for some types of lymphoma, according to one study and another study. RT + Chemotherapy: This combination can potentially lead to longer survival times compared to either treatment alone. Some studies have reported median survival times ranging from 5.8 to 31.4 months. ## Footnote Lymphoma is sensitive to chemotherapy, and response rate of feline NL to chemotherapy is reported to be 67–73% [7, 19] and median survival time is 116–358 days when treated with chemotherapy alone [7, 19, 20]. Feline lymphoma is also sensitive to radiotherapy [2, 3]. Radiotherapy is suitable to treat feline NL with localized lesion. In fact, cats with NL treated with radiotherapy seem to have favorable prognosis and median survival time was reported to be 456–922 days [7, 10, 18]. In cats with NL that received a combination of radiotherapy and chemotherapy, median survival time was reported to be 174–955 days [7, 17]. Alth

Answer 44

Treatment for tumor lysis syndrome (TLS) in dogs primarily involves aggressive fluid therapy, electrolyte management, and the use of medications like allopurinol or rasburicase to lower uric acid levels. The goal is to prevent complications like kidney failure and cardiac arrhythmias. Detailed Treatment Steps: 1. Aggressive Hydration: IV fluids are administered to increase urine output and flush out the byproducts of tumor breakdown, according to the Veterinary Information Network® (VIN). 2. Electrolyte Correction: Blood samples are analyzed, and electrolytes like potassium, calcium, and phosphate are monitored and corrected as needed to prevent life-threatening arrhythmias or other complications 3. Medications (in humans): Allopurinol: This medication helps to reduce uric acid production by inhibiting the enzyme xanthine oxidase, Rasburicase: This medication rapidly lowers uric acid levels by converting uric acid into a more soluble form, which is then excreted in the urine ## Footnote Administering calcium gluconate is a major step in treatment although it does not alter the level of circulating potassium. When administered IV, calcium gluconate makes the charge outside of the cardiac cells more positive, thereby stabilizing the cell membrane and correcting ECG abnormalities. Regular insulin (0.5U/kg IV) and intravenous dextrose are also administered to combat hyperkalemia. As insulin allows for glucose to be utilized intracellularly, it will also force potassium to enter the cell thereby reducing the circulating levels. Dextrose is administered as a bolus IV and then as a CRI until blood glucose levels normalize. Beta-adrenergic agonists like terbutaline (0.01mg/kg slow IV) and albuterol (1–3 puffs from an inhaler) will have the effect of driving potassium intracellularly by increasing sodium and potassium ATPase activity. Lastly, sodium bicarbonate (1–2mEq/kg slow IV) can be administered. As H+ is moved out of cells to decrease the pH after sodium bicarbonate infusion, potassium will be moved intracellularly. Patients must be able to ventilate appropriately as sodium bicarbonate is changed into CO2 which the patient needs to be able to remove via the respiratory system.

Answer 45

Tumor lysis syndrome (TLS) is defined by the triad of hyperuricemia, hyperkalemia, and hyperphosphatemia. It results from the release of the intracellular contents of tumor cells. Increased lactate dehydrogenase, uric acid, and creatinine and decreased urine output are predictors of increased severity of TLS and increased risk of acute renal and end-organ failure.

Answer 46

p53, p21, p16, and mTOR The interplay between p53, p21, p16, and mTOR can influence the cell fate decision between cell cycle arrest (quiescence), senescence, or apoptosis.

Answer 47

p53: Tumor Suppressor: . p53 is a central tumor suppressor protein that regulates various cellular processes, including cell cycle arrest, DNA repair, and apoptosis, all crucial in preventing cancer. Cell Cycle Arrest: . p53 induces the expression of p21, a protein that inhibits cyclin-dependent kinases (CDKs), leading to cell cycle arrest, especially during the G1 phase, to allow for DNA repair. Senescence: . p53 can also induce senescence, a state of irreversible cell cycle arrest, in response to various stressors, including DNA damage or oncogene activation.

Answer 48

p21: Cell Cycle Arrest: p21 is a key component of the p53-p21 pathway, directly inhibiting CDKs, which are essential for cell cycle progression. Senescence: p21 can contribute to senescence, but its role can be complex. While it can induce senescence on its own, it can also cooperate with p53 or other factors to drive cell cycle arrest and senescence.

Answer 49

p16: Cell Cycle Arrest: p16, specifically p16INK4, inhibits CDKs 4 and 6, which are involved in the phosphorylation of the Retinoblastoma protein (Rb), a key regulator of cell cycle progression. Senescence: p16 can induce senescence by inhibiting cell cycle progression through the p16-RB pathway, leading to a permanent cell cycle arrest.

Answer 50

mTOR: Cellular Metabolism and Growth: mTOR is a central regulator of cellular metabolism, protein synthesis, and cell growth. Senescence: mTOR activation can drive senescence, a process known as geroconversion. Inhibition of mTOR, particularly by rapamycin, can suppress geroconversion and promote quiescence. Interactions with p53 and p21: mTOR's activity can be influenced by p53 and p21. For example, p53 can suppress mTOR activity, while mTOR can promote senescence even in the presence of p21. Interplay and Implications:

Answer 51

In dogs, metoclopramide treatment can lead to an increase in the hormone prolactin. This is because metoclopramide blocks dopamine receptors in the brain, and dopamine normally inhibits prolactin release. By blocking dopamine, metoclopramide allows prolactin levels to rise. | Options were histamine, dopamine, NK1, prolactin

Answer 52

Amantadine (A) antagonizes the N-methyl-D-aspartate (NMDA) receptor on the postsynaptic side of the cleft, thereby blocking transmission of pain signals from those receptors. Both of these actions decrease the number of pain impulses that are transmitted from the spinal cord to the brain.

Answer 53

In general, both human splenic Marginal Zone LSA and Mantle Cell LSA are positive for CD45, CD20, CD79a, Bcl-2, and Pax-5 and negative for CD3, CD23, BCL-6, and CD10.* In addition, MCL is generally positive for CD5, CD38, cyclin D1, and sex-determining region Y box 11 (SOX-11) while MZL is generally positive for Bcl-10 and MUM-1. In canines, CD3, CD10, CD20, CD45, CD79a, Bcl-2, Bcl-6, Pax-5, and MUM-1 have been routinely used

Answer 54

No CRs for chlorambucil in rescue setting 2015 study: Overall response rates were 71% and 83% for melphalan- and cyclophosphamide-treated cats, respectively. Discontinuation of melphalan due to toxicity was common. Survival times for cats initially treated with melphalan or cyclophosphamide were not significantly different (median 252 and 394 days, respectively), and no statistically significant prognostic factors were identified. This study suggests that the combination of cyclophosphamide and corticosteroids is well tolerated and may be considered as first-line therapy for cats with systemic MRD. ## Footnote chlorambucil is sometimes used as a rescue therapy, but it hasn't shown to achieve complete clinical responses (CRs). Melphalan and prednisone, or cyclophosphamide, are more commonly used as first-line treatments,

Answer 55

For dogs with multiple myeloma and splenic involvement, the treatment approach typically involves a combination of chemotherapy and supportive care. While surgery (splenectomy) is not a cure, it can be part of the treatment plan, especially for splenic masses that are not part of the systemic myeloma but may be complications. Here's a more detailed look at the treatment options: 1. Chemotherapy: First-line treatment: Chemotherapy is often the initial treatment for multiple myeloma, and melphalan, often combined with prednisone, is a common choice. Response rate: A significant number of dogs (80-95%) show a positive response to melphalan/prednisolone within a few weeks. Dosage: Melphalan can be given in various dosing protocols, such as daily for 10 days followed by a lower maintenance dose, or in a "pulse-dose" schedule. Other chemotherapy options: In some cases, other chemotherapy drugs like chlorambucil, cyclophosphamide, or doxorubicin might be used, either alone or in combination.

Answer 56

The mechanism of action of pamidronate, as well as other bisphosphonates, stems from its chemical structure as a derivative of inorganic pyrophosphate (PPi). Bisphosphonates mimic PPi and bind with high affinity to hydroxyapatite crystals found within areas of remodeling bone. The bound drug is released from its bound hydroxyapatite as osteoclasts begin to resorb bone. The freed drug then leads to apoptosis of osteoclasts via inhibition of the enzyme farnesyl pyrophosphate synthase. This enzyme is involved in metabolic pathways responsible for the production of cholesterol and other lipids. Despite the ubiquitous nature of this enzyme, bisphosphonate-induced apoptosis via inhibition of farnesyl pyrophosphate only appears in osteoclasts. Pamidronate and the other newer (nitrogen-containing) bisphosphonates induce osteoclast apoptosis via this mechanism, while earlier (non-nitrogen-containing) bisphosphonates do so via disruption of several intracellular ATP-dependent processes.[9][1]

Answer 57

- inhibition of cancer cell metastases and angiogenesis and the inhibition of proliferation and apoptosis in vitro. - Additionally, the inhibition of matrix metalloproteinase activity, altered cytokine and growth factor expression, as well as reductions in parameters of pain have also been reported. - Notwithstanding, BPs are used widely in small animal veterinary practice for the medical management of hyperparathyroidism, idiopathic hypercalcemia in cats, as well as for the palliative care of bone tumors which are common in dogs, and in particular, primary bone tumors such as osteosarcoma. Palliative BP treatment has also recently increased in veterinary oncology to alleviate tumor-associated bone pain.

Answer 58

Progression free survival (PFS) was 1318 days and disease-related median survival time (MST) was 1845 days

Answer 59

Hypofractionated radiation therapy (HFRT) for osteosarcoma, especially 4 fractions, has shown a higher fracture rate compared to 2 fractions. In a study, dogs receiving finer fractionated RT (F-RT) had a higher fracture rate (83%) compared to those receiving coarser fractionated RT (C-RT) (30%). For osteosarcoma pain control, both 2-fraction and 4-fraction hypofractionated radiation therapy (RT) can be effective, and there's not a significant difference in pain relief between the two regimens. However, research suggests that 2-fraction hypofractionated RT might offer slightly better pain relief and local control compared to 4-fraction regimens.

Answer 60

Thymidine kinase 1 (TK1) is an enzyme that plays a crucial role in DNA synthesis by converting thymidine to its monophosphate form (dTMP), a key component of DNA. It's primarily found in the cytoplasm and its levels are tightly regulated during the cell cycle, peaking during the S phase when DNA replication is most active. TK1's activity is essential for maintaining the intracellular thymidine pool and is involved in both DNA synthesis and DNA repair.

Answer 61

The tumor suppressor p53 is one of the most important proteins for protection of genomic stability and cancer prevention. Cancers often inactivate it by either mutating its gene or disabling its function. Thus, activating p53 becomes an attractive approach for the development of molecule-based anti-cancer therapy. MDM2 Inhibitors: Small molecules that target MDM2, a protein that regulates p53 degradation, can increase p53 levels and activity by preventing its degradation. Ex. Nutlin-3 has an antitumor effect on feline lymphoma cell lines harboring the wt-p53 gene through accumulation and activation of P53 leading to cell cycle arrest and apoptosis. p53 Reactivators: Some compounds, like those targeting mutant p53, can restore or reactivate p53's function, even in cells with a mutated p53 gene.

Answer 62

Traditionally, wide lateral surgical margins of 3 cm and one fascial plane deep have been recommended for resection of canine cutaneous mast cell tumor (MCT). Despite the low quality of the overall body of evidence, a recommendation can be made that resection of canine cutaneous MCTs (< 4 cm) of Patnaik grade I and II with 2 cm lateral margins and 1 fascial plane deep results in low rates of incomplete excision and local tumor recurrence.

Answer 63

In veterinary oncology, cancer stem cell (CSC) markers are used to identify and characterize cells within a tumor that possess the ability to initiate and maintain tumor growth, potentially contributing to tumor recurrence and chemoresistance. Some common markers used in veterinary medicine to identify CSCs in various canine tumor types include CD44, CD133, CD34, CD90, Lgr5, Lgr6, Sox9, and Nestin. Here's a more detailed look at some key markers: CD44: A cell surface glycoprotein involved in cell adhesion and migration, often upregulated in CSCs. CD133: A cell surface marker associated with stem cells in various tissues, including tumors. CD34: A hematopoietic stem cell marker also found in some cancer stem cells, particularly in lymphoma. CD90: Another surface marker associated with stem cells, including those found in lymphoma. Lgr5, Lgr6, and Sox9: These are stem cell markers specifically studied in canine hair follicle and skin tumors, with Lgr5 and Lgr6 involved in the Wnt signaling pathway and Sox9 expressed in sebaceous and sweat glands. Nestin: A marker for undifferentiated cells, often expressed in glioma stem cells. Aldh1: Aldehyde dehydrogenase activity and expression are indicators of stem cells in normal and cancer cells.

Answer 64

- The alpha/beta (α/β) ratio in radiation oncology is a measure of a tissue's intrinsic radiosensitivity, indicating how much a tissue responds to different doses and fractionation schemes of radiation therapy. - A low α/β ratio, typically around 3 Gy, suggests a late-responding tissue, while a high ratio, often above 10 Gy, indicates an early-responding tissue. What the α/β Ratio Represents: Fractionation Sensitivity: The α/β ratio reflects how much a tissue's response to radiation is influenced by the size of individual radiation doses (fractions). Linear-Quadratic Model: It's a parameter in the linear-quadratic (LQ) model, a mathematical model used to describe cell survival after radiation exposure. Balance of Damage: The ratio represents the balance between single-hit damage (alpha) and double-hit damage (beta). How it's Used in Radiotherapy: Optimizing Treatment Plans: Understanding the α/β ratio of a tumor and surrounding tissues helps optimize radiation treatment plans by considering different fractionation schemes. Hypofractionation: Tissues with low α/β ratios, like some late-responding normal tissues, might be better treated with fewer, larger doses (hypofractionation) as they are more sensitive to changes in fraction size. Hyperfractionation: Conversely, tissues with high α/β ratios, like many tumors, might benefit from more frequent, smaller doses (hyperfractionation) as they are less sensitive to changes in fraction size. B iological Equivalent Dose (BED): The α/β ratio is used to calculate BED, which compares the biological effect of different fractionation schedules. Examples: Normal tissues: Late-responding tissues like the rectum have a low α/β ratio (around 3 Gy), making them more sensitive to fraction size changes. Tumors: Early-responding tumors, like some head and neck cancers, have a higher α/β ratio (around 8-10 Gy), making them less sensitive to fraction size changes. Factors Influencing α/β Ratio: Cell Proliferation: Rapidly proliferating cells (tumors) tend to have higher α/β ratios, while slowly proliferating cells (late-responding tissues) have lower ratios. Cell Cycle: The stage of the cell cycle can influence radiation sensitivity. Other Factors: Hypoxia (lack of oxygen), radiation dose rate, and certain drugs can also affect the α/β ratio.

Answer 65

Surgery Even though surgical removal remains the most widely accepted treatment option for feline mammary tumors, it is usually not curative. Complete removal of neoplastic tissue is hampered by the degree of invasion and ulceration. Most cats require unilateral or bilateral chain mastectomy with removal of draining lymph nodes. **While more radical procedures are associated with longer disease-free intervals, they do not have a significant effect on overall survival rates.** In cases requiring bilateral mastectomy the procedure should be performed in two stages, with a 2-week interval between surgeries. The inguinal lymph node is always removed with the A2 gland, whereas the axillary lymph node is removed only if it is enlarged or cytologically positive for tumor. Prophylactic removal of axillary lymph nodes is unlikely to have a therapeutic benefit. Because the histological completeness of resection has been correlated with survival, the surgeon should submit the entire specimen with the surgical margins inked for histological review to ensure that complete margins have been obtained. Survival times for cats with mammary gland adenocarcinomas treated with surgery alone depend on the stage of disease when the cat is presented. Stage is directly related to tumor size and the presence or absence of metastases (see prognostic factors). The average time between detection of primary tumor and death in untreated cats is 12 months. Chemotherapy Opinions differ among veterinarians regarding the value of postsurgical chemotherapy. While some recommend it as adjunct therapy in cats with tumors showing evidence of invasion into the blood vessels or lymphatic vessels, others recommend chemotherapy in all cases. Regardless, it is important to note that the response of mammary tumors to chemotherapy is usually poor once metastases have occurred.

Answer 66

Prognostic factors Tumor size The most important prognostic factor in cats with mammary gland neoplasia is tumor size, which significantly affects both disease-free interval and survival time. MacEwen et al reported that cats diagnosed with mammary tumors smaller than 2 cm survived for an average of 54 months, while those with tumors 2–3 cm in diameter survived for an average of 24 months. Histopathology grade An association between survival time and histopathology grade has been demonstrated. The rate of death 1 year after surgery was 0% in cats with well-differentiated carcinoma, and 100% in those with poorly differentiated carcinoma. Mitotic count The number of mitotic figures found in tumor tissue has been shown to be of prognostic value. Longer survival times were seen in animals with tumors exhibiting fewer than two mitotic figures per high power field. Disease stage Clinical stage at presentation is another factor that has been shown to be significantly associated with survival time. Median survival times of cats with stage I, II, III and IV disease were 29, 12.5, 9 and 1 month(s), respectively. Surgical approach MacEwen et al compared the results of conservative surgery and radical mastectomy in cats with malignant mammary adenocarcinoma and found that cats that had undergone radical mastectomy had a significantly reduced rate of local recurrence compared with cats that had undergone conservative surgery.

Answer 67

1. Immunohistochemistry: Vimentin: A common marker for mesenchymal cells, often used to identify tumor origin in a wide range of mesenchymal tumors. E-cadherin: While primarily associated with epithelial cells, E-cadherin can be downregulated in some mesenchymal neoplasms, indicating epithelial-to-mesenchymal transition (EMT). CD34: A vascular marker used in the identification of hemangiosarcoma and other vascular tumors. S-100 protein: Can be used to identify tumors of neural origin. Other markers: Depending on the specific type of mesenchymal tumor, other markers like desmin (for muscle tumors), lysozyme, and alpha-1-antichymotrypsin (for histiocytic tumors) can be helpful.

Answer 68

The main negative prognostic factors are the size of the primary tumor, metastatic regional lymphadenopathy at first presentation, the size and the number of the metastatic lymph nodes, distant metastases at the time of diagnosis, and the histological characteristics of the primary tumor. Hypercalcemia is sometimes noted to be and sometimes not.

Answer 69

Thymoma and lymphoma

Answer 70

This study suggests no difference in outcome for dogs treated with and without bisphosphonates in addition to hypofractionated RT. (Thamm 2019) There are studies that show single agent pamidronate does have good pain control in some dogs with OSA.

Answer 71

RANKL, or Receptor Activator of Nuclear Factor-κB Ligand, is a protein that plays a crucial role in bone remodeling and immune function. It's a member of the TNF (Tumor Necrosis Factor) superfamily and acts as a ligand for its receptor, RANK, which is found on osteoclast precursors and mature osteoclasts. ## Footnote RANKL binds to RANK on osteoclast precursors, triggering their differentiation into mature osteoclasts and stimulating their activation. Bone Resorption: Osteoclasts, once activated by RANKL, are responsible for breaking down bone tissue, a process crucial for bone remodeling and repair. Immune System Development and Function: RANKL is also involved in the development and function of immune cells, including T cells, dendritic cells, and lymph nodes. Osteoprotegerin (OPG): . OPG is a decoy receptor that binds to RANKL, preventing it from interacting with RANK and inhibiting osteoclast activity. Other Factors: . Various factors can influence RANKL expression, including parathyroid hormone (PTH), vitamin D, and prostaglandins. Implications of RANKL Dysregulation: Bone Diseases: . Dysregulation of RANKL signaling can lead to bone diseases like osteoporosis, characterized by excessive bone loss, and other conditions like osteopetrosis. Cancer: . RANKL can influence the behavior of cancer cells within the bone microenvironment, potentially promoting bone metastasis. Other Diseases: . RANKL dysregulation has also been implicated in other diseases, including multiple myeloma, rheumatoid arthritis, and Charcot joint. Therapeutic Targeting of RANKL: Denosumab: A monoclonal antibody that blocks the interaction between RANKL and RANK, is approved for the treatment of osteoporosis and other bone diseases.

Answer 72

Median progression-free interval was 78 days (range, 20 to 112 days). Median survival time was 307 days (range, 29 to 929 days). Moderate to severe renal toxicosis and moderate to severe gastrointestinal toxicosis developed in 5 and 8 dogs, respectively. Because of minimal efficacy and associated renal and gastrointestinal toxicosis, administration of cisplatin (40 to 50 mg/m²) with piroxicam cannot be recommended for treatment of dogs with TCC of the urinary bladder

Answer 73

In cats, serum iohexol clearance was an accurate predictor of CLPT and can be used to calculate the carboplatin dose as follows: dose = AUCTarget X ([1.3 X GFRIohexol] + 1.4) X body weight. (Am J Vet Res 2009;70:1135–1140)

Answer 74

Surgery with margins is likely curative, no follow up other than watching for regrowth. If higher grade on histopath could consider chemo.

Answer 75

The Wnt/β-catenin signaling pathway is significantly involved in the development and progression of osteosarcoma (OS). Abnormal activation of this pathway can promote cell proliferation, invasion, and migration, as well as tumor angiogenesis and chemoresistance in OS. Targeting the Wnt/β-catenin pathway may offer potential therapeutic strategies for OS. Here's a more detailed look: Wnt/β-catenin and Osteosarcoma Development: The Wnt/β-catenin pathway is a crucial signaling pathway that plays a role in various cellular processes, including cell growth, differentiation, and apoptosis. In osteosarcoma, this pathway is often abnormally activated, leading to the dysregulation of these processes and the promotion of tumor development. Targeting Wnt/β-catenin in Osteosarcoma: Researchers are exploring various strategies to target the Wnt/β-catenin pathway in osteosarcoma, including: MicroRNAs (miRNAs): Some miRNAs have been shown to inhibit the Wnt/β-catenin pathway and potentially decrease osteosarcoma progression. Zinc: Zinc has been shown to inhibit osteosarcoma cell proliferation and invasion by activating the Wnt-3a/β-catenin signaling pathway. Wnt Inhibitors: Inhibiting the Wnt pathway can lead to decreased osteosarcoma cell growth. Wnt Activators: Conversely, some Wnt pathway activators have also been shown to inhibit osteosarcoma growth. Clinical Significance: Studies have indicated that β-catenin overexpression in osteosarcoma is associated with a higher risk of metastasis and poorer prognosis. However, some studies have produced conflicting results, and a consensus on the prognostic value of β-catenin overexpression in osteosarcoma is still lacking. In essence, the Wnt/β-catenin signaling pathway is a key player in osteosarcoma development, and targeting this pathway holds promise for developing more effective treatments for this bone malignancy.

Answer 76

Hallmarks of Cancer: The hallmarks of cancer are a set of six fundamental biological capabilities that are acquired by cells as they progress from normal to malignant states. These capabilities are: Sustaining proliferative signaling: Normal cells have a tight control over their growth and proliferation, but cancer cells acquire the ability to generate their own growth signals, becoming self-sufficient in their growth. Evading growth suppressors: Normal cells have mechanisms to prevent uncontrolled growth, including tumor suppressor genes like p53. Cancer cells develop ways to evade these growth suppressors. Resisting cell death: Normal cells undergo apoptosis (programmed cell death) when damaged or at the end of their life cycle. Cancer cells develop mechanisms to resist cell death, allowing them to survive and proliferate. Enabling replicative immortality: Normal cells have a limited lifespan due to telomere shortening, but cancer cells can acquire mechanisms to maintain their telomeres, allowing them to divide indefinitely. Inducing angiogenesis: Cancer cells require a constant supply of nutrients and oxygen to grow and spread. They induce the formation of new blood vessels through angiogenesis, which is visualized using PET scans. Activating invasion and metastasis: Cancer cells can invade surrounding tissues and metastasize to distant sites, spreading the disease.

Answer 77

Incidence: Measures the likelihood of a person developing a disease or condition within a specific timeframe. It's a dynamic measure, reflecting the rate at which new cases are appearing in the population. For example, if 500 people in a population of 100,000 develop a new case of a disease within a year, the incidence rate would be 5 per 1,000 people per year. Prevalence: Provides a snapshot of how many people in a population have a disease or condition at a particular time, regardless of when they first developed it. It's a static measure, reflecting the total burden of the disease in the population at a given point. For example, if 1,500 people in a population of 100,000 have a disease at a specific time, the prevalence rate would be 15 per 1,000 people. Key Difference: Incidence focuses on the rate of new cases, while prevalence considers both new and existing cases. This means that a disease with a high incidence but a short duration might have a relatively low prevalence, while a disease with a low incidence but a long duration might have a high prevalence.

Answer 78

In veterinary medicine, the BRAF V595E mutation test for canine urothelial carcinoma (UC) and prostatic carcinoma (PCa) typically exhibits a high specificity, with values reported above 99%, and a sensitivity ranging from 71% to 95%. The overall sensitivity of the BRAF and BRAF-PLUS test combined is reported to be 95%.

Answer 79

The adaptive immune system defends against tumors by identifying and targeting tumor-specific antigens, leading to the activation of various immune cells that can kill or control tumor growth. This process involves the recognition of tumor-associated antigens (TAAs), priming of T cells, their activation and migration to the tumor microenvironment (TME), and ultimately, the elimination of malignant cells. Here's a more detailed look at how it works: 1. Antigen Presentation and T Cell Priming: Dendritic cells (DCs): These cells act as "antigen-presenting cells" (APCs) by capturing and processing tumor antigens. MHC molecules: DCs present tumor antigens on their surface using major histocompatibility complex (MHC) molecules, which allows T cells to recognize them. T cell activation: In lymph nodes, DCs interact with naïve T cells, initiating their activation and clonal expansion. Helper T cells: Activated T helper cells (CD4+ T cells) can activate other immune cells, including cytotoxic T cells (CD8+ T cells). Cytotoxic T cells: These T cells (CD8+ T cells) directly kill tumor cells. 2. T Cell Trafficking and Elimination of Tumor Cells: T cell migration: Activated T cells migrate from lymph nodes to the tumor microenvironment. Infiltration and destruction: T cells infiltrate the tumor, recognize and bind to tumor cells, and then eliminate them through various mechanisms like apoptosis and necrosis. Other immune cells: Besides T cells, other immune cells like NK cells and γδ T cells can also recognize and kill tumor cells. 3. The Role of Antibodies: B cells: B cells, another type of adaptive immune cell, produce antibodies that recognize and bind to tumor cells. Antibody-mediated destruction: These antibodies can mark tumor cells for destruction by other immune cells or directly kill them. 4. The Cancer-Immunity Cycle: The process described above is often referred to as the "Cancer-Immunity Cycle" and involves the coordinated interaction between innate and adaptive immunity to eliminate tumor cells. This cycle includes antigen presentation, T cell priming, trafficking, infiltration, and ultimately, the elimination of malignant cells. 5. Immune Evasion by Tumors: Tumors can evolve mechanisms to evade the immune system, including inhibiting antigen presentation, downregulating MHC molecules, and producing immunosuppressive cytokines. This "adaptive immune resistance" can lead to tumor growth and metastasis. 6. Therapeutic Applications: Understanding how the immune system interacts with tumors has led to the development of various immunotherapies, including checkpoint inhibitors, which can reverse immune evasion by tumors. Other immunotherapies include tumor vaccines and cytokines, which can help to boost the immune response against tumors.

Answer 80

Conclusion and clinical importance: The number of dose delays was minimized with a prechemotherapy ANC cutoff of 1.5 × 103 /μL, and the prechemotherapy ANC class 1.5-1.99 × 103 /μL was not associated with an increased toxicity. Further investigation of an ANC cutoff near 0.75 × 103 /μL in which to prescribe prophylactic antibiotics is indicated.

Answer 81

An ANC cut-off of <0.75 × 109 /l for antimicrobial prophylaxis appears to be well tolerated and minimizes the prescription of antimicrobials.

Answer 82

Background: Canine osteosarcoma (OSA) causes focal malignant osteolysis leading to severe pain. Despite the documented efficacy of radiotherapy or IV aminobisphosphonates for managing cancer bone pain, their potential combined therapeutic value has not been reported in OSA-bearing dogs. Hypothesis: Pamidronate combined with standardized palliative therapy will improve pain control and bone biologic effects in OSA-bearing dogs. Animals: Fifty dogs with appendicular OSA treated with standardized palliative therapy and either pamidronate or sterile saline. Methods: Randomized, prospective, double-blinded, placebo-controlled study. Treatment responses for dogs receiving standardized palliative therapy with (n = 26) or without (n = 24) adjuvant pamidronate were serially evaluated for changes in subjective pain scores, urine N-telopeptide (NTx) excretion, primary tumor relative bone mineral density (rBMD), and computerized pressure platform gait analysis. Results: Median duration of subjective pain relief for dogs treated with adjuvant pamidronate or placebo was 76 and 75 days, respectively (P= .39). Forty percent (20/50; pamidronate [11/26] and placebo [9/24]) of dogs experienced durable analgesia, defined by pain alleviation > or =112 days. For patients achieving durable pain control, dogs treated with pamidronate achieved greater reductions in NTx excretion and larger increases in rBMD compared with placebo controls. Changes in peak vertical force assessed by computerized pressure platform gait analysis correlated with pain alleviation in OSA-bearing dogs. Conclusions and clinical importance: Combining pamidronate with standardized palliative therapy is safe, but does not clearly improve pain alleviation. However, in dogs achieving durable pain control, adjuvant pamidronate appears to decrease focal bone resorption in the local tumor microenvironment.

Answer 83

CDKN2A (cyclin dependent kinase inhibitor 2A)/CFA11 Goldens, Rotties

Answer 84

In addition to the CFA11 major locus, this study identified other HS loci on CFA2, CFA5, CFA14, and CFA20.

Answer 85

Viral interference assays and sequencing of different env genes have revealed five subgroups of FeLV: FeLV-A, FeLV-B, FeLV-C, FeLV-D, and FeLV-T. These subgroups arise when a cat is previously infectedwith FeLV-A, which mutates or recombines with endogenous retroviral sequences Almost all naturally infected cats are originally infected with A which is the least pathogenic subtype since it has been ID'd in most asymptomatic animals (although can be associated with development of LSA). FeLV-B primarily occurs in cats diagnosed with lymphoma and leukemia and FeLV-C infection is associated with severe non-regenerative anemia. The present study highlighted that the FeLV-B subgroup, in association with FeLV-A, is prevalent in cats with lymphoma and leukemia secondary to FeLV infection, particularly in animals with mediastinal lymphoma and myeloid leukemia.

Answer 86

decreased lymphocytes Findings from this study shows that local irradiation can be associatedwith systemic decreases in circulating lymphocyte counts with the mean Absolute Lymphocyt Count significantly decreasing and the mean Neutrophil to Lymphocyte Ratio increasing from the pre-treatment CBC to the mid-treatment CBC.

Answer 87

A Kaplan-Meier curve is a type of survival analysis plot that visually represents the survival function over time. It's used to estimate the probability of an event occurring (like death or relapse) within a specific group of individuals. The x-axis represents time, and the y-axis represents the survival probability. Here's how to interpret a Kaplan-Meier curve: 1. Understanding the Axes: The x-axis (horizontal) represents time. The units of time can be days, months, years, etc., depending on the study. The y-axis (vertical) represents the survival probability, typically ranging from 0 to 1 or 0% to 100%. 2. The Shape of the Curve: A steeper slope indicates a higher event rate (e.g., more deaths), suggesting worse survival. A flatter slope indicates a lower event rate, meaning better survival. 3. Estimating Survival Probability at Specific Time Points: To find the survival probability at a specific time, locate the time on the x-axis, drop a vertical line to the curve, and then read the survival probability from the y-axis. 4. Comparing Curves (if multiple curves are plotted): If the curves are close together, the survival probabilities are similar between the groups. If the curves diverge, it suggests a difference in survival between the groups, with the curve higher up representing better survival. 5. Median Survival: The median survival time is the time at which 50% of the individuals in the group are still alive. It can be found where the curve crosses the 0.5 (or 50%) survival probability line on the y-axis.

Answer 88

Fc Trunk of the Y Made of constant domains from the heavy chains. Fab fragment is a region on an antibody that binds to antigens. It is composed of one constant and one variable domain of each of the heavy and the light chain. These domains shape the paratope — the antigen-binding site — at the amino terminal end of the monomer. Fc region is the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system. This property allows antibodies to activate the immune system. The Fc regions of immunoglobulin Gs bear a highly conserved N-glycosylation site.

Answer 89

The recommended dosage of doxorubicin to treat horses is 70 mg/m(2) given at 3-week intervals as single agent.

Answer 90

Internal Signals: DNA damage: Irreparable DNA damage can trigger cell death pathways. Oxidative stress: High levels of reactive oxygen species (ROS) can damage cellular components and initiate cell death. Loss of survival signals: Cells lacking essential growth factors or signals can initiate apoptosis to prevent overgrowth or ensure proper development. Mitochondrial damage: Damage to the mitochondria, including the mitochondrial outer membrane permeabilization (MOMP), releases pro-apoptotic factors like cytochrome c, which triggers apoptosis. External Signals: Death receptor activation: Binding of ligands like TNF, FasL, or TRAIL to death receptors initiates the extrinsic apoptotic pathway. Granzyme A and B: Released by cytotoxic cells, these enzymes can induce cell death through caspase-independent pathways. Toxins and injuries: Certain toxins, injuries, or treatments can damage cells and trigger cell death pathways. Calcium-dependent signaling: Increased intracellular calcium concentrations can activate calpains, a family of proteases that contribute to cell death. Cell Death Pathways: Apoptosis: A programmed cell death process involving a series of molecular events, often mediated by caspases, a family of proteases. Necroptosis: A form of regulated cell death that involves a lytic process where caspase-8 is inhibited. Autophagy: A cellular process of degrading intracellular components, which can also lead to cell death under certain circumstances. Ferroptosis: A regulated cell death process characterized by lipid peroxidation and iron accumulation. Molecular Mechanisms: Caspases: Proteases that are activated in apoptotic pathways and cleave specific proteins, leading to cell death. Bcl-2 family: A family of proteins that regulate apoptosis, with pro-apoptotic members like Bax and Bak and anti-apoptotic members like Bcl-2 and Bcl-xL. Death-inducing signaling complex (DISC): A complex formed upon activation of death receptors that recruits and activates caspase-8. Death receptors: Cell surface receptors that bind to ligands and initiate apoptosis through DISC formation.

Answer 91

3. Methotrexate

Answer 92

4. At an energy of 10 MeV, photons primarily interact with matter through pair production. This process involves a photon converting into an electron and a positron. The energy of the photon is converted into the mass of this electron-positron pair, with the threshold energy being 1.022 MeV. At 10 MeV, the probability of pair production is significantly higher than at lower energies.

Answer 93

Function: Tregs suppress the activity of other T cells and other immune cells, helping to maintain a balance in the immune system. This balance is crucial for preventing autoimmune diseases where the immune system mistakenly attacks the body's own tissues. Identification: Tregs are characterized by their expression of specific molecules, including CD4 and CD25. They also express a transcription factor called FOXP3, which is crucial for their development and function. Development: Tregs can develop either in the thymus (natural Tregs) or in the periphery from naive CD4+ T cells (induced Tregs). Regulation of Immune Responses: Tregs can suppress immune responses by interacting with other immune cells, secreting molecules that suppress activity, or competing for resources that other immune cells need to function. Implications for Disease: A deficiency or dysfunction of Tregs can contribute to autoimmune diseases, while an overabundance can hinder anti-tumor and anti-pathogen responses. Researchers are exploring the use of Tregs in therapies for autoimmune diseases, allergies, and even cancer.

Answer 94

Lipid soluble Lipid-soluble drugs: These drugs are readily absorbed and distributed because they can pass through cell membranes easily. This also means they can be stored in fatty tissues, further delaying their elimination. Water-soluble drugs: These drugs are less readily absorbed and distributed, and they are typically eliminated more rapidly by the kidneys.

Answer 95

In bisphosphonates, the R1 side chain primarily determines binding affinity to bone, while the R2 side chain influences anti-resorptive potency. A hydroxyl (OH) group on R1 enhances bone binding, and an amino (NH2) group on R2 increases the anti-resorptive effect. These modifications can lead to more effective drugs, particularly those with nitrogen in the R2 group, which are more potent. R1 Side Chain: The R1 side chain is often referred to as the "bone hook". It interacts with bone mineral, especially hydroxyapatite, and influences how well the bisphosphonate binds to the bone surface. A hydroxyl (OH) group at the R1 position is particularly effective at increasing binding affinity. R2 Side Chain: The R2 side chain plays a crucial role in determining the anti-resorptive potency of the bisphosphonate. Bisphosphonates with a nitrogen atom in the R2 group (amino-bisphosphonates) are generally more potent than those without (non-amino bisphosphonates). The amino group enhances binding to bone and contributes to the anti-resorptive effect. Impact of R1 and R2 Modifications: Nitrogen in R2: Increases potency and binding affinity due to the ability of the amino group to form additional hydrogen bonds with the bone mineral. Hydroxyl Group in R1: Enhances binding to bone mineral, contributing to the drug's effectiveness. Classification of Bisphosphonates: Bisphosphonates are categorized into two main groups: Nitrogen-containing bisphosphonates (N-BPs): These include alendronate, pamidronate, and zoledronic acid. Non-nitrogen-containing bisphosphonates (N-NBPs): Examples include clodronate and etidronate.

Answer 96

Inhibits DNA polymerases α, δ and ε, which results in DNA synthesis arrest and induction of programmed cell death

Answer 97

Several BH3-only proteins are known to induce autophagy, including BNIP3, BNIP3L (also known as NIX), and Beclin 1. - BNIP3 and NIX are induced by hypoxia and promote autophagy through their BH3 domains. - Beclin 1 is a key initiator of autophagy, and its interaction with Bcl-2 or Bcl-XL can be disrupted by BH3-mimetic compounds, leading to autophagy induction. Elaboration: BNIP3 and NIX: These proteins are induced by hypoxia and act as key regulators of autophagy. They contain BH3 domains that bind to Bcl-2 family proteins, promoting autophagy. Beclin 1: This protein is an essential initiator of autophagy and interacts with several other proteins to form the core autophagic complex. Beclin 1's BH3 domain can also bind to anti-apoptotic Bcl-2 family members, inhibiting autophagy. BH3-mimetic compounds: These compounds can disrupt the interaction between Beclin 1 and Bcl-2, leading to the activation of autophagy. Other BH3-only proteins: While BNIP3, NIX, and Beclin 1 are the most well-studied, other BH3-only proteins like Bad, Bim, and Bik have also been implicated in autophagy.

Answer 98

Iridociliary tumors in dogs are relatively common intraocular neoplasms, specifically iridociliary epithelial tumors (ICETs), that arise from the pigmented or non-pigmented epithelium of the ciliary body and iris. They are the second most frequent primary ocular tumor in dogs, after melanocytic tumors. ICETs can be either benign adenomas or malignant adenocarcinomas. Elaboration: Origin: ICETs develop from the cells that make up the pigmented and non-pigmented epithelium of the ciliary body and iris, which are of neuroectodermal origin. Frequency: In dogs, ICETs are the second most common primary intraocular tumor, following melanocytic tumors. Types: ICETs can be either benign adenomas or malignant adenocarcinomas. Diagnosis: A veterinary ophthalmologist may recommend an ultrasound of the eye to assess for a tumor, determine its location, and extent of growth. Further diagnosis can be made through enucleation (surgical removal of the eye) and histopathology, or by fine-needle aspiration. Treatment: Treatment options may include surgery, chemotherapy, or radiation therapy, depending on the type and stage of the tumor. Prognosis: The prognosis for canine iridociliary tumors, especially malignant ones, can be guarded, with a higher risk of recurrence and metastasis if the tumor invades the sclera (the white outer layer of the eye). The average survival time for dogs with cancer can range from one to three months with surgery alone, or five to seven months with surgery and chemotherapy, but many dogs will die within a year of diagnosis.

Answer 99

Ocular lymphomas can cause inflammation of the eye (uveitis), swelling of the iris (uveal thickening), lesions on the cornea, and involvement of the conjunctiva or third eyelid.

Answer 100

Most of the biomarkers highlighted to date are protein-based, including CEA, CA15-3, AFP, LDH, AMH and **TK1**

Answer 101

Rare side effects of bisphosphonates – azotemia, distal limb swelling, hypocalcemia, necrosis of jaw, hypophosphatemia

Answer 102

Background: Transitional cell carcinoma is the most common bladder cancer of dogs. Cisplatin combined with piroxicam provides superior response rates, but unacceptable rates of nephrotoxicity. Tavocept is a chemoprotectant that has mitigated cisplatin toxicity and decreased the required infusion/diuresis volume in clinical trials in humans. Hypothesis/Objectives: We hypothesized that Tavocept would decrease diuresis volume and time and facilitate safe administration of a cisplatin/piroxicam protocol to dogs with bladder cancer. Secondary objectives were to compare response rate and survival times to an historical comparator group treated without Tavocept. Animals: Fourteen client-owned dogs were prospectively enrolled. Methods: Tumor volume was measured by computed tomography at days 0, 42, and 84. Dogs received combination Tavocept/cisplatin with a shortened diuresis protocol. A total of 4 doses was planned, with concurrent administration of piroxicam. Serial biochemical analyses were evaluated for azotemia. Results: A 90-minute infusion/diuresis time was used for all dogs. Three dogs (21%) had concurrent increases in serum creatinine (>2.0 mg/dL) and BUN (>42 mg/dL) concentrations; 2 of these dogs were isosthenuric. This frequency of nephrotoxicity is significantly less (P = 0.0406) than that of an historical control group treated without Tavocept. Overall response rate was 27%. Median survival time was comparable to historical controls (253 vs. 246 days). Conclusions and Clinical Importance: Tavocept decreased the required diuresis time with cisplatin from > 6 hours to 90 minutes, while also decreasing occurrence of azotemia. Survival time was comparable, but the response rate was inferior to an historical comparator group. Further evaluation in other tumors susceptible to platinum agents is warranted. Key words: Chemoprotectant; Neoplasia; Nephrotoxicity; Urogenital.

Answer 103

One study says supportive care, filgrastim, and abx, however in the study, high grade neutropenia was common and did not appear to be mitigated by the administration of filgrastim.

Answer 104

For chemotherapy extravasation (leakage of medication outside the vein), sodium thiosulfate is an antidote for mechlorethamine (Mustargen), while hyaluronidase is used for vinca alkaloids (like vincristine and vinblastine). For anthracyclines like doxorubicin, dexrazoxane (Totect) or topical dimethyl sulfoxide (DMSO) with low-dose hydrocortisone, can be used. For actinomycin D, topical DMSO is recommended. Cold is only recommended for vinca alkyloids.

Answer 105

Dexrazoxane is an iron chelator that prevents anthracycline-iron complexes and free radical formation causing oxidative damage. Furthermore, dexrazoxane has a protective effect on healthy tissue by stabilizing topoisomerase II, thereby preventing damage from anthracycline. This mechanism of action is responsible for its ability to reduce the cardiotoxicity associated with anthracyclines, such as doxorubicin.

Answer 106

Dexrazoxane was administered IV in a three-day schedule (1000, 1000, and 500 mg/m2 on respective days) starting no later than 6 hr after the extravasation event

Answer 107

Dexrazoxane may cause local injection-site reaction (pain, superficial phlebitis), and it is recommended that dexrazoxane be infused in a large vein.

Answer 108

Li-Fraumeni syndrome (LFS) is a rare, inherited genetic condition that significantly increases the risk of developing various types of cancer, particularly in childhood and young adulthood. It's caused by a mutation in the TP53 gene, which is a tumor suppressor gene that normally helps prevent cancer. Key Features of Li-Fraumeni Syndrome: Hereditary: . LFS is passed down through families, meaning if one parent has the mutation, there's a 50% chance their child will inherit it. Increased Cancer Risk: . Individuals with LFS have a greatly elevated lifetime risk of developing several cancers, including soft-tissue sarcomas, osteosarcomas, brain tumors, breast cancer, and adrenocortical carcinomas. TP53 Gene Mutation: . The underlying cause of LFS is a mutation in the TP53 gene, which impairs its ability to function properly as a tumor suppressor. Early Onset Cancers: . Cancers associated with LFS often develop at younger ages compared to cancers in the general population. Multiple Cancers: . Individuals with LFS can develop multiple primary cancers over their lifetime. Autosomal Dominant Inheritance: . This means that only one copy of the mutated TP53 gene is needed to be at risk for LFS.

Answer 109

Homologous recombination repair attempts occur in DNA before the cell enters mitosis (M phase shown) during the S and G2 phases of the cell cycle.

Answer 110

Among the options, homologous recombination (HR) is generally considered the most error-free DNA repair pathway. While nucleotide excision repair (NER) and mismatch repair (MMR) are also highly accurate, HR's reliance on a homologous template for repair makes it exceptionally precise. Non-homologous end-joining (NHEJ), on the other hand, is more error-prone as it directly joins broken DNA ends without a template

Answer 111

he Rb protein primarily blocks the G1 phase of the cell cycle, specifically the transition from G1 to S phase. This is achieved by inhibiting the activation of E2F transcription factors, which are crucial for driving cells into S phase.

Answer 112

Currently, bilateral excisional biopsy of mandibular and retropharyngeal nodes for staging is advocated. However, the therapeutic value of lymph node dissection in canine melanoma has not been studied systematically. Based on the evidence available, lymph node biopsy is more likely a diagnostic rather than a therapeutic procedure and may not offer a survival advantage. Surgical excision of tributary lymph nodes in oral, subungual, footpad and cutaneous melanoma is recommended. It adds important information regarding the clinical stage of the disease and it improves local tumor control.

Answer 113

unpredictable patterns of nodal metastasis for MHNT havebeen documented, with contralateral dissemination in up to 24%–62% of dogs and involvement of mandibular nodes, which are mostcommonly sampled due to their superficial location, reported in only54%–87% of cases.1

Answer 114

43-61 days

Answer 115

Pro-apoptotic phenotypes in cancer refer to cellular characteristics that promote programmed cell death (apoptosis), often triggered by the activation of pro-apoptotic pathways or the loss of anti-apoptotic pathways. These phenotypes are crucial in cancer treatment, as targeted therapies often aim to induce apoptosis in cancer cells. Key Pro-Apoptotic Phenotypes and Mechanisms: p53 Pathway: The p53 tumor suppressor gene plays a major role in inducing apoptosis in response to DNA damage or other cellular stress. It activates pro-apoptotic proteins like PUMA and NOXA, leading to cell death. TNF Signaling Pathway: Tumor Necrosis Factor (TNF) signaling can activate pro-apoptotic pathways, including the death receptor pathway, leading to caspase activation and cell death. Bcl-2 Family: The Bcl-2 family of proteins regulates apoptosis. Pro-apoptotic members like Bax and Bak can promote mitochondrial membrane permeabilization, leading to cell death, while anti-apoptotic members like Bcl-2 can inhibit this process. The balance between pro- and anti-apoptotic Bcl-2 proteins determines a cell's response to apoptotic stimuli. Death Receptor Pathway: This pathway is triggered by death receptors on the cell surface, such as Fas and TNF-R1, which activate intracellular signaling cascades that ultimately lead to caspase activation and apoptosis. Autophagy Pathway: Autophagy, a cellular self-eating process, can be triggered in response to stress and can contribute to cell death in some cancer contexts. Other Pathways: Other signaling pathways, such as the MAPK/ERK pathway, p38 MAPK signaling pathway, and Autophagy Pathway, can also influence pro-apoptotic phenotypes in cancer.

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