State of the art in oncologic imaging of Lymphoma.
Author and Curator: Dror Nir, PhD
This is the last post in a series in which I will address the state of the art in oncologic imaging based on a review paper; Advances in oncologic imaging†‡ that provides updates on the latest approaches to imaging of 5 common cancers: breast, lung, prostate, colorectal cancers, and lymphoma. This paper is published at CA Cancer J Clin 2012. © 2012 American Cancer Society.
The paper gives a fair description of the use of imaging in interventional oncology based on literature review of more than 200 peer-reviewed publications. In this post I summaries the chapter on imaging used in management of Lymphoma.
The traditional tasks of imaging in the management of lymphoma include: staging, assessing response to therapy and confirming it reaching an end-point and detecting recurrence. The leading imaging modality is PET/CT. In their literature review the authors include several references claiming that the clinical outcome of lymphoma patients has improved significantly due to better prognosis – largely related to better disease characterization and identification of prognostic markers in recent years. Adoption of functional imaging that improved pre-treatment staging and assessment of the response to treatment contributed as well to this outcome 178 .179 “Most of the recent progress in management of lymphoma occurred after the widespread introduction of [18F]FDG PET and PET/CT. Accordingly, [18F]FDG PET is now part of the revised lymphoma response criteria.180 “
![A 46-year-old male with diffuse large B cell lymphoma, stage IV was studied. Baseline maximum intensity projection (MIP) positron emission tomography (PET) image with [18F]fluorodeoxyglucose ([18F]FDG) (A) shows widespread disease, which is essentially resolved on interim scan after 4 cycles of chemotherapy (B). The interim scan also shows increased [18F]FDG uptake in bone marrow related to administration of granulocyte colony-stimulating factor (GCSF). (C,D) Transaxial CT and PET/CT fusion images at baseline show abnormal [18F]FDG uptake in extensive mediastinal and hilar lymphadenopathy as well as in bone lesions in a right rib and the right scapula. On interim scan (E,F) abnormal [18F]FDG uptake at all of these sites has resolved although residual enlarged lymph nodes remain. The sites are better seen on a contrast-enhanced CT (G) and measure up to 5.3 cm × 3.6 cm. Chemotherapy was continued for a total of 8 cycles. At the time of writing, the patient remained disease-free after 9 years of follow-up.](https://i0.wp.com/pharmaceuticalintelligence.com/wp-content/uploads/2013/02/nfig019.jpg)
A 46-year-old male with diffuse large B cell lymphoma, stage IV was studied. Baseline maximum intensity projection (MIP) positron emission tomography (PET) image with [18F]fluorodeoxyglucose ([18F]FDG) (A) shows widespread disease, which is essentially resolved on interim scan after 4 cycles of chemotherapy (B). The interim scan also shows increased [18F]FDG uptake in bone marrow related to administration of granulocyte colony-stimulating factor (GCSF). (C,D) Transaxial CT and PET/CT fusion images at baseline show abnormal [18F]FDG uptake in extensive mediastinal and hilar lymphadenopathy as well as in bone lesions in a right rib and the right scapula. On interim scan (E,F) abnormal [18F]FDG uptake at all of these sites has resolved although residual enlarged lymph nodes remain. The sites are better seen on a contrast-enhanced CT (G) and measure up to 5.3 cm × 3.6 cm. Chemotherapy was continued for a total of 8 cycles. At the time of writing, the patient remained disease-free after 9 years of follow-up.
Subsequent to their acknowledgment of PET/CT as the most promising imaging modality for management of Lymphoma, the authors focused their review to on its role in this disease pathway. It being well understood that the clinical utility of [18F]FDG PET in lymphoma “depends on the intensity of radiotracer uptake in disease sites, which will affect the test accuracy for staging and characterizing residual masses after completion of therapy, as well as the role of the test in response assessment. The intensity of [18F]FDG uptake in lymphoma is determined by tumor histology, grade (eg, indolent versus aggressive NHL)”,181, 182 At the end of their extensive review the authors do mention that PET/MRI might become an important player in the management of this disease, especially in pediatric cases.
Other research papers related to the management of Lymphoma were published on this Scientific Web site:
Imatinib (Gleevec) May Help Treat Aggressive Lymphoma: Chronic Lymphocytic Leukemia (CLL)
Paradigm Shift in Human Genomics – Predictive Biomarkers and Personalized Medicine – Part 1
Predicting Tumor Response, Progression, and Time to Recurrence
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PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.