TGF-β/SMAD signaling US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for TGF-β/SMAD signaling. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
TGF-β/SMAD signaling US Medical PG Question 1: A 33-year-old woman comes to the physician 1 week after noticing a lump in her right breast. Fifteen years ago, she was diagnosed with osteosarcoma of her left distal femur. Her father died of an adrenocortical carcinoma at the age of 41 years. Examination shows a 2-cm, firm, immobile mass in the lower outer quadrant of the right breast. A core needle biopsy of the mass shows adenocarcinoma. Genetic analysis in this patient is most likely to show a defect in which of the following genes?
- A. BRCA1
- B. KRAS
- C. TP53 (Correct Answer)
- D. Rb
- E. PTEN
TGF-β/SMAD signaling Explanation: ***TP53***
- This patient's presentation with **early-onset breast cancer**, a history of **osteosarcoma** at a young age, and a father's death from **adrenocortical carcinoma** at 41 years strongly suggests **Li-Fraumeni syndrome**.
- Li-Fraumeni syndrome is an autosomal dominant disorder caused by a germline mutation in the **tumor suppressor gene TP53**, increasing the risk for multiple primary cancers at a young age.
*BRCA1*
- While **BRCA1 mutations** are associated with an increased risk of breast and ovarian cancer, they are not typically linked to osteosarcoma or adrenocortical carcinoma.
- The constellation of cancers in this patient is more indicative of Li-Fraumeni syndrome than solely a BRCA1-related cancer syndrome.
*KRAS*
- **KRAS** is an oncogene commonly mutated in several cancers, including pancreatic, colorectal, and lung cancer, but is not primarily associated with either Li-Fraumeni syndrome or the specific tumors seen in this family history.
- Mutations in KRAS are typically somatic mutations acquired during a person's lifetime, not germline mutations causing inherited cancer syndromes like the one suggested here.
*Rb*
- Mutations in the **retinoblastoma (Rb) gene** are associated with retinoblastoma and an increased risk of osteosarcoma, but not typically with adrenocortical carcinoma or breast cancer as part of a classic inherited syndrome.
- The combination of breast cancer, osteosarcoma, and adrenocortical carcinoma points more specifically to TP53.
*PTEN*
- **PTEN mutations** are associated with Cowden syndrome, which increases the risk for breast cancer, thyroid cancer, and endometrial cancer, along with benign growths.
- However, Cowden syndrome does not typically include osteosarcoma or adrenocortical carcinoma as prominent features, making PTEN less likely than TP53 for this specific family history.
TGF-β/SMAD signaling US Medical PG Question 2: A 57-year-old man comes to the physician because of a 4-week history of constipation, episodic bloody stools, progressive fatigue, and a 5-kg (10.2-lb) weight loss. Digital rectal examination shows a hard, 1.5-cm rectal mass. A biopsy confirms the diagnosis of colorectal carcinoma. The patient begins treatment with a combination chemotherapy regimen that includes a drug that is also used in the treatment of wet age-related macular degeneration. This drug most likely acts by inhibiting which of the following substances?
- A. Vascular endothelial growth factor (Correct Answer)
- B. Interferon-alpha
- C. Metalloproteinase
- D. Fibroblast growth factor
- E. Epidermal growth factor
TGF-β/SMAD signaling Explanation: ***Vascular endothelial growth factor***
- The drug described is likely **bevacizumab**, a monoclonal antibody that targets **VEGF**.
- **VEGF** plays a crucial role in **angiogenesis**, promoting tumor growth and the abnormal blood vessel formation seen in **wet age-related macular degeneration**.
*Interferon-alpha*
- **Interferon-alpha** is an **immunomodulatory cytokine** used in treating certain cancers (e.g., melanoma, renal cell carcinoma) and viral infections (e.g., hepatitis B and C).
- It does not have a role in the direct treatment of **wet age-related macular degeneration**.
*Metalloproteinase*
- **Metalloproteinases** are enzymes involved in **extracellular matrix remodeling** and can contribute to tumor invasion and metastasis, but are not the primary target for the drug described.
- While inhibitors of MMPs have been explored, they are not the class of drugs recognized for dual use in **colorectal cancer** and **wet AMD**.
*Fibroblast growth factor*
- **Fibroblast growth factor (FGF)** is involved in diverse cellular processes including **cell growth, proliferation, and angiogenesis**.
- While FGF signaling can promote tumor growth, it is not the main target of the drug used for both **colorectal carcinoma** and **wet AMD**.
*Epidermal growth factor*
- **Epidermal growth factor (EGF)** and its receptor **EGFR** are targets for certain cancer therapies (e.g., cetuximab, panitumumab) that inhibit cell proliferation and survival.
- However, **EGFR inhibitors** are not used in the treatment of **wet age-related macular degeneration**.
TGF-β/SMAD signaling US Medical PG Question 3: A 30-year-old woman presents to her physician for her annual checkup. She has diabetes mellitus, type 1 and takes insulin regularly. She reports no incidents of elevated or low blood sugar and that she is feeling energetic and ready to face the morning every day. Her vital signs and physical are normal. On the way home from her checkup she stops by the pharmacy and picks up her prescription of insulin. Later that night she takes a dose. What is the signaling mechanism associated with this medication?
- A. Increased concentration intracellular cAMP
- B. Increased permeability of the cell membrane to negatively charged molecules
- C. Activation of tyrosine kinase (Correct Answer)
- D. Rapid and direct upregulation of enzyme transcription
- E. Increased permeability of the cell membrane to positively charged molecules
TGF-β/SMAD signaling Explanation: ***Activation of tyrosine kinase***
- **Insulin** primarily binds to the **insulin receptor**, which is a **receptor tyrosine kinase**.
- Upon insulin binding, the intrinsic tyrosine kinase activity of the receptor is activated, leading to **autophosphorylation** and phosphorylation of downstream signaling proteins like **IRS-1**.
*Increased concentration intracellular cAMP*
- This mechanism is characteristic of signaling pathways involving **G protein-coupled receptors** that activate adenylyl cyclase, such as those for **glucagon** or **catecholamines**.
- Insulin does not primarily signal through **cAMP** as a second messenger.
*Increased permeability of the cell membrane to negatively charged molecules*
- Changes in membrane permeability to negatively charged molecules are usually associated with **GABAergic** or **glycinergic neurotransmission**, leading to inhibitory postsynaptic potentials.
- This is not a primary mechanism for **insulin signaling**.
*Rapid and direct upregulation of enzyme transcription*
- While insulin does influence gene expression over longer periods, its immediate effects involve **protein phosphorylation** and translocation, not direct, rapid transcriptional changes at the moment of receptor binding.
- Steroid hormones typically mediate more direct transcriptional regulation.
*Increased permeability of the cell membrane to positively charged molecules*
- This mechanism is characteristic of **ligand-gated ion channels** that allow influx of ions like **Na+** or **Ca2+**, important in neuronal excitation or muscle contraction.
- Insulin signaling primarily involves **kinase cascades** and not direct changes in membrane permeability to positive ions.
TGF-β/SMAD signaling US Medical PG Question 4: An 8-year old boy is brought into clinic for evaluation of possible scoliosis that was newly found on a routine exam at school. On exam, he is also noted to be in the 99th percentile for height and 70th percentile for weight. He appears to have abnormally long extremities as well as an upward lens dislocation on ophthalmologic exam. A mutation leading to a defect in which of the following proteins is the most likely cause of his condition?
- A. Type IV collagen
- B. Type I collagen
- C. Elastin
- D. Fibrillin (Correct Answer)
- E. ATP7A
TGF-β/SMAD signaling Explanation: ***Fibrillin***
- The patient's clinical features, including **scoliosis**, being in the **99th percentile for height**, having **abnormally long extremities** (arachnodactyly), and **upward lens dislocation**, are classic signs of **Marfan syndrome**.
- **Marfan syndrome** is an autosomal dominant disorder caused by a mutation in the *FBN1* gene, which codes for **fibrillin-1**, a glycoprotein essential for the formation of elastic fibers in connective tissue.
*Type I collagen*
- Defects in **Type I collagen** are primarily associated with **osteogenesis imperfecta**, characterized by **bone fragility**, multiple fractures, blue sclera, and hearing loss.
- While it can present with skeletal abnormalities, it does not typically cause the extreme height, arachnodactyly, or lens dislocation seen in this patient.
*Type IV collagen*
- Defects in **Type IV collagen** are linked to conditions like **Alport syndrome**, which primarily affects the kidneys (glomerulonephritis), ears (hearing loss), and eyes (ocular defects including lenticonus), but not typically the skeletal features described.
- It is a major component of **basement membranes**, important for filtration and structural support in various organs.
*Elastin*
- Mutations in **elastin** are associated with conditions like **supravalvular aortic stenosis** (Williams syndrome) or cutis laxa, which affect the skin and cardiovascular system.
- It does not explain the characteristic skeletal and ocular findings of Marfan syndrome.
*ATP7A*
- A mutation in the *ATP7A* gene, which codes for an ATPase involved in copper transport, is responsible for **Menkes disease**.
- **Menkes disease** is characterized by **sparse, kinky hair**, failure to thrive, neurological degeneration, and connective tissue abnormalities due to copper deficiency, which does not align with the patient's presentation.
TGF-β/SMAD signaling US Medical PG Question 5: A 38-year-old man presents to his primary care practitioner for 2 months of rectal bleeding. He also reports occasional diarrhea and abdominal pain. His family history is relevant for his father and uncle, who died from complications of colorectal cancer. Colonoscopy shows more than 10 colorectal adenomas. Which of the following genes is most likely affected in this patient?
- A. RAS
- B. TP53
- C. hMLH1
- D. PPAR
- E. APC (Correct Answer)
TGF-β/SMAD signaling Explanation: ***APC***
- This patient's presentation with **numerous colorectal adenomas** (over 10), early-onset symptoms (38 years old), and a strong **family history of colorectal cancer** (father and uncle) is highly characteristic of **Familial Adenomatous Polyposis (FAP)**.
- FAP is an **autosomal dominant** condition caused by a germline mutation in the **APC tumor suppressor gene**, leading to the development of hundreds to thousands of adenomatous polyps in the colon, which inevitably progress to colorectal cancer if untreated.
*RAS*
- **RAS mutations** are commonly found in sporadic colorectal cancers and play a role in tumor growth and progression, but they are not typically associated with the **hereditary syndrome of multiple adenomas** seen in this patient.
- RAS activation leads to an increase in **cell proliferation** and can contribute to the development of many cancers, but not as the primary genetic defect in a polyposis syndrome.
*TP53*
- **TP53** is a well-known tumor suppressor gene, and mutations are involved in various cancers, including colorectal cancer (often in its later stages). However, germline mutations in TP53 are associated with **Li-Fraumeni syndrome**, which involves a broad spectrum of early-onset cancers and is not primarily characterized by numerous colonic adenomas.
- TP53 mutations are generally hallmarks of **genomic instability** and are more often seen in the progression of sporadic cancers rather than initiating a polyposis syndrome.
*hMLH1*
- **hMLH1** is a gene involved in **DNA mismatch repair**. Germline mutations in this gene, along with other mismatch repair genes (e.g., MSH2, MSH6, PMS2), are responsible for **Lynch syndrome (hereditary non-polyposis colorectal cancer - HNPCC)**.
- While Lynch syndrome is an important cause of hereditary colorectal cancer, it is characterized by fewer polyps (typically <10) that progress rapidly to cancer, and an increased risk of other cancers (e.g., endometrial), which differs from the presentation of **hundreds of adenomas** seen in FAP.
*PPAR*
- **PPARs (Peroxisome Proliferator-Activated Receptors)** are a group of nuclear receptor proteins that play roles in metabolism, cell differentiation, and inflammation.
- While PPAR pathways have been investigated for their potential role in cancer development and as therapeutic targets, **mutations in PPAR genes are not directly linked** to a common hereditary colorectal cancer syndrome characterized by numerous adenomas like FAP.
TGF-β/SMAD signaling US Medical PG Question 6: A 55-year-old woman has a total thyroidectomy for papillary thyroid carcinoma. She complains of tingling around the mouth 11 hours after the operation. Her condition rapidly deteriorates with difficulty breathing and chest tightness. Which of the following best represent the signaling pathway of the deficient hormone responsible for this patient’s symptoms?
- A. Cyclic guanosine monophosphate (cGMP)
- B. Cyclic adenosine monophosphate (cAMP) (Correct Answer)
- C. Intracellular receptors
- D. Receptor tyrosine kinase
- E. Inositol trisphosphate (IP3)
TGF-β/SMAD signaling Explanation: ***Cyclic adenosine monophosphate (cAMP)***
- The patient's symptoms of perioral tingling, difficulty breathing, and chest tightness after total thyroidectomy suggest **hypocalcemia**, likely due to accidental removal or damage to the **parathyroid glands** during surgery.
- The deficient **parathyroid hormone (PTH)** acts primarily through the **cAMP second messenger system** to increase serum calcium levels.
*Cyclic guanosine monophosphate (cGMP)*
- **cGMP** is a second messenger system primarily involved in mediating the effects of hormones like **atrial natriuretic peptide (ANP)** and **nitric oxide**, which are unrelated to calcium homeostasis and parathyroid function.
- This pathway is not the primary mechanism of action for **PTH**.
*Intracellular receptors*
- **Intracellular receptors** are typically used by **steroid hormones** (e.g., cortisol, estrogen) and **thyroid hormones**, which are lipid-soluble and can cross the cell membrane.
- **PTH** is a peptide hormone and acts on cell surface receptors.
*Receptor tyrosine kinase*
- **Receptor tyrosine kinases (RTKs)** are transmembrane receptors involved in signaling pathways for hormones like **insulin** and **growth factors**, promoting cell growth, differentiation, and metabolism.
- This is not the primary signaling pathway for **PTH**.
*Inositol trisphosphate (IP3)*
- The **IP3/DAG (diacylglycerol)** pathway is another common second messenger system used by various hormones (e.g., **vasopressin, oxytocin, TRH**), leading to the release of intracellular calcium.
- While it involves calcium signaling, it is not the primary or most characteristic pathway for **PTH** action, which predominantly utilizes **cAMP**.
TGF-β/SMAD signaling US Medical PG Question 7: A 78-year-old man receives chemotherapy for advanced hepatocellular carcinoma. Despite appropriate therapy, he dies 4 months later. Histopathological examination of the cancer cells shows the presence of a transmembrane efflux pump protein that is known to cause decreased intracellular concentrations of chemotherapeutic drugs. Which of the following best describes this membrane protein?
- A. G protein
- B. Cadherin
- C. P-glycoprotein (Correct Answer)
- D. Tyrosine receptor
- E. Channel protein
TGF-β/SMAD signaling Explanation: **P-glycoprotein**
- **P-glycoprotein** (also known as **MDR1**) is a well-known **efflux pump** that actively transports many chemotherapy drugs out of cancer cells, leading to **multidrug resistance**.
- Its presence explains the **decreased intracellular concentrations** of chemotherapy drugs and the poor response to treatment in this patient.
*G protein*
- **G proteins** are intracellular signaling molecules that mediate responses to various extracellular stimuli, not primarily involved in drug efflux.
- They are typically associated with **G protein-coupled receptors** and downstream signaling pathways, not direct drug transport.
*Cadherin*
- **Cadherins** are cell adhesion molecules that play a crucial role in cell-cell binding and maintaining tissue structure.
- They are not involved in the active transport of drugs across the cell membrane.
*Tyrosine receptor*
- **Tyrosine kinase receptors** are transmembrane proteins that bind to growth factors and initiate intracellular signaling cascades, promoting cell growth and differentiation.
- They are involved in signaling, not in the active transport of chemotherapy drugs out of the cell.
*Channel protein*
- **Channel proteins** facilitate the passive diffusion of ions or small molecules across the cell membrane, typically down their electrochemical gradient.
- While they are transmembrane proteins, they do not actively pump drugs out against a concentration gradient, which is characteristic of multidrug resistance.
TGF-β/SMAD signaling US Medical PG Question 8: A 15-year-old boy presents with shortness of breath on exertion for the past 2 weeks. Although he does not have any other complaints, he is concerned about not gaining much weight despite a good appetite. His height is 188 cm (6 ft 2 in) and weight is 58 kg (124 lb). His blood pressure is 134/56 mm Hg and his pulse rate is 78/min. On cardiac auscultation, his apex beat is displaced laterally with a diastolic murmur lateral to the left sternal border. Slit-lamp examination shows an upward and outward displacement of both lenses. Synthesis of which of the following proteins is most likely defective in this patient?
- A. Fibronectin
- B. Elastin
- C. Fibrillin (Correct Answer)
- D. Reticular fibers
- E. Laminin
TGF-β/SMAD signaling Explanation: ***Fibrillin***
- The patient's presentation with **tall stature**, **arachnodactyly** (implied by tall, thin build), **ectopia lentis** (upward and outward lens displacement), and a **diastolic murmur** (suggesting aortic root dilation or dissection, or mitral valve prolapse) are classic features of **Marfan syndrome**.
- **Marfan syndrome** is caused by a defect in the gene encoding **fibrillin-1**, a glycoprotein essential for the formation of elastic fibers and connective tissue integrity.
*Fibronectin*
- **Fibronectin** is involved in cell adhesion, growth, migration, and differentiation, and plays a crucial role in wound healing and embryonic development.
- While essential for connective tissue, defects in fibronectin are not typically associated with the constellation of symptoms seen in Marfan syndrome.
*Elastin*
- **Elastin** works in conjunction with fibrillin to provide elasticity to tissues like the skin, lungs, and blood vessels.
- While Marfan syndrome affects elastic fibers, the primary defect is in fibrillin, which then impairs the proper formation and function of elastin-containing microfibrils.
*Reticular fibers*
- **Reticular fibers** are fine collagen fibers (primarily type III collagen) that form a delicate supporting network in various tissues and organs.
- Defects in reticular fibers are not characteristic of Marfan syndrome; Marfan syndrome is specifically linked to fibrillin defects.
*Laminin*
- **Laminins** are major proteins of the **basal lamina**, essential for cell adhesion and differentiation in epithelial and endothelial tissues.
- Genetic defects in laminin components are often associated with muscular dystrophies or epidermolysis bullosa, not the Marfanoid features presented.
TGF-β/SMAD signaling US Medical PG Question 9: An 8-year-old boy is brought to the physician by his parents for blurry vision for the past 2 months. He is at the 97th percentile for height and 25th percentile for weight. Physical examination shows joint hypermobility, a high-arched palate, and abnormally long, slender fingers and toes. Slit lamp examination shows superotemporal lens subluxation bilaterally. This patient's findings are most likely caused by a defect in which of the following structural proteins?
- A. Keratin
- B. Fibrillin (Correct Answer)
- C. Laminin
- D. Type I collagen
- E. Type III collagen
TGF-β/SMAD signaling Explanation: ***Fibrillin***
- The patient's features—tall stature, **joint hypermobility**, high-arched palate, **arachnodactyly** (long, slender fingers and toes), and **superotemporal lens subluxation**—are classic signs of **Marfan syndrome**.
- Marfan syndrome is caused by a defect in the *FBN1* gene, which codes for **fibrillin-1**, a glycoprotein essential for the formation of elastic fibers in connective tissue.
*Keratin*
- **Keratins** are intermediate filament proteins primarily found in epithelial cells, providing structural integrity to skin, hair, and nails.
- Defects in keratin are associated with conditions like **epidermolysis bullosa simplex** and various **ichthyoses**, which manifest as skin fragility and blistering, not the systemic connective tissue issues seen here.
*Laminin*
- **Laminins** are major components of the **basement membrane**, providing structural support and mediating cell adhesion, differentiation, and migration.
- Disorders involving laminin typically affect organs with prominent basement membranes, such as certain muscular dystrophies or nephropathies, which do not align with the patient's symptoms.
*Type I collagen*
- **Type I collagen** is the most abundant collagen in the body, found in bone, skin, tendons, and ligaments, providing tensile strength.
- Defects in type I collagen are characteristic of **osteogenesis imperfecta**, leading to fragile bones, blue sclerae, and hearing loss, which are not described in this patient.
*Type III collagen*
- **Type III collagen** is found in distensible tissues like blood vessels, skin, and intestines, contributing to their elasticity and strength.
- Defects in type III collagen are associated with **Ehlers-Danlos syndrome, vascular type**, which typically presents with arterial rupture, thin skin, and easy bruising, distinct from the patient's presentation.
TGF-β/SMAD signaling US Medical PG Question 10: A 28-year-old man is brought in by ambulance to the ER, barely conscious, after feeling drowsy and falling to the floor during a presentation several hours ago. His colleague who accompanied him says he has had similar episodes 5 times in the past 3 months. No significant past medical history. His blood pressure is 110/80 mm Hg and pulse is 114/min. His capillary blood glucose is 15 mg/dL. Immediate IV dextrose with thiamine is started, and he rapidly regains consciousness. A contrast CT of the abdomen is performed which reveals a tumor in the pancreas. Which of the following relative laboratory findings would you most likely expect to find in this patient?
- A. Glucose: ↑, Insulin: ↓, C-Peptide: ↓, Ketoacidosis: Present
- B. Glucose: Normal, Insulin: Normal, C-Peptide: Normal, Ketoacidosis: Absent
- C. Glucose: ↓, Insulin: ↑, C-Peptide: ↑, Ketoacidosis: Absent (Correct Answer)
- D. Glucose: ↓, Insulin: ↑, C-Peptide: ↓, Ketoacidosis: Absent
- E. Glucose: ↑, Insulin: ↑/Normal, C-Peptide: ↑/Normal, Ketoacidosis: Absent
TGF-β/SMAD signaling Explanation: ***Glucose: ↓, Insulin: ↑, C-Peptide: ↑, Ketoacidosis: Absent***
- The patient's **hypoglycemia (15 mg/dL)**, coupled with a pancreatic tumor and recurrent episodes, strongly suggests an **insulinoma**.
- An **insulinoma** is an insulin-secreting tumor, leading to **high insulin** and **C-peptide** levels in the presence of low glucose, and typically no ketoacidosis because insulin inhibits ketogenesis.
*Glucose: ↑, Insulin: ↓, C-Peptide: ↓, Ketoacidosis: Present*
- This profile describes **Type 1 Diabetes Mellitus** or severe insulin deficiency, where high glucose is due to lack of insulin production and subsequent diabetic ketoacidosis.
- The patient's symptoms (hypoglycemia) and the presence of a pancreatic tumor producing insulin are contradictory to this profile.
*Glucose: Normal, Insulin: Normal, C-Peptide: Normal, Ketoacidosis: Absent*
- This profile represents a **healthy individual** with normal metabolic function, which is inconsistent with the patient's severe hypoglycemia and recurrent collapses.
- It would not explain the patient's symptoms or the pancreatic tumor's function.
*Glucose: ↓, Insulin: ↑, C-Peptide: ↓, Ketoacidosis: Absent*
- This finding would be typical of **exogenous insulin administration** (e.g., insulin overdose) where insulin levels are high, but C-peptide (which is co-secreted with endogenous insulin) is low.
- While hypoglycemia is present, the low C-peptide contradicts the presence of an endogenous insulin-secreting pancreatic tumor.
*Glucose: ↑, Insulin: ↑/Normal, C-Peptide: ↑/Normal, Ketoacidosis: Absent*
- These findings could be seen in conditions like **Type 2 Diabetes** with **insulin resistance** or Cushing's syndrome where glucose and insulin might be elevated, but the patient's primary presentation is severe hypoglycemia.
- This profile does not align with the patient's profound hypoglycemia and clinical picture of an insulinoma.
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