Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 37-year-old woman presented with a neck mass that proved to be medullary thyroid carcinoma by histologic and immunoperoxidase examinations. Serum calcitonin values were greatly elevated (over 100,000 pg/ml). There were widespread metastases in bone and liver. As the peripheral lesions showed only slight response to chemotherapy and local radiation therapy, potential use of radioiodine was studied. The bone lesions showed uptake of both Tc-99m MDP and radioiodide (I-131). Metastatic lesions were similar to the primary tumor in terms of histology, presence of calcitonin, and absence of thyroglobulin. Hence, the patient had a medullary thyroid carcinoma that took up radioiodide in its metastases. Two large oral doses of radioiodide (over 100 mCi each) did not significantly alter the serum calcitonin values, although there was a slight response in the activity of bone lesions. The whole body turnover of radioiodide was rapid (T 1/2 = 0.7 days). Upon oral administration of lithium carbonate, whole-body radioiodide turnover slowed slightly (T 1/2 = 1 day). If this effect were reflected in greater tumor retention of radioiodide (slower release), then agents that block radioiodide egress might have a role to play in therapy.
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PMID:Medullary thyroid carcinoma with radioiodide transport. Effects of iodine-131 therapy and lithium administration. 315 60

Tumor cells are characterized by an increased rate of glucose consumption and glycolysis. This increased glucose consumption leads to tumor acidification, which represents a major obstacle for several therapeutic strategies. Tumor cells have adapted to this acidification by upregulation of several H(+)-extruding transporter systems and proteins to cope with this compromised situation. One of these proteins is carbonic anhydrase IX (CA IX), which catalyzes the reversible hydration of carbon dioxide to carbonic acid outside the cell, leading to an acidic extracellular pH and a physiological intracellular pH. The aim of this article was to study semiquantitatively the expression of CA IX in non-small cell lung cancer (NSCLC) and to assess the existence of a possible relationship between CA IX expression and tumor FDG uptake, reflecting glucose metabolism. The levels and the extent of CA IX expression were estimated in immunohistochemical stained, formalin-fixed, paraffin-embedded tissue samples from 18 patients with NSCLC and compared with FDG uptake in FDG-PET imaging. We found a statistically significant correlation between CA IX Hscores and SUVmax and SUVmean values of the primary tumor. This relationship provides indirect evidence for cotranscription of glucose transporters and hexokinases that drive tumor hyperglycolysis and for CA IX governed by hypoxia-inducible factor-1 and suggests that, in the future, it may be possible to identify NSCLC patients who are most likely to benefit from CA IX targeting therapy on the basis of FDG-PET imaging.
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PMID:Carbonic anhydrase IX expression correlates with FDG uptake by primary non-small cell lung cancer. 2042 27

Prostate cancer is the most common primary tumor and the second leading cause of cancer-related deaths in men in the United States. Prostate cancer bone metastases are characterized by abnormal bone remodeling processes and result in a variety of skeletal morbidities. Prevention of skeletal complications is a crucial element in prostate cancer management. This study investigated prostate cancer-induced alterations in the molecular composition and morphological structure of metastasis-bearing bones in a mouse model of prostate cancer using Raman spectroscopy and micro-computed tomography (microCT). LNCaP C4-2B prostate cancer cells were injected into the right tibiae of 5-week old male SCID mice. Upon sacrifice at 8weeks post tumor inoculation, two out of the ten tumor-bearing tibiae showed only osteoblastic lesions in the radiographs, 4 osteolytic lesions only and 4 mixed with osteoblastic and osteolytic lesions. Carbonate substitution was significantly increased while there was a marked reduction in the level of collagen mineralization, mineral crystallinity, and carbonate:matrix ratio in the cortex of the intact tumor-bearing tibiae compared to contralateral controls. MicroCT analysis revealed a significant reduction in bone volume/total volume, trabecular number and trabecular thickness, as well as significant increase in bone surface/volume ratio in tibiae with osteolytic lesions, suggesting active bone remodeling and bone loss. None of the changes in bone compositional properties were correlated with lesion area from radiographs or the changes in bone architecture from microCT. This study indicates that LNCaP C4-2B prostate cancer metastases alter bone tissue composition independent of changes in architecture, and altered bone quality may be an important contributor to fracture risk in these patients. Raman spectroscopy may provide a new avenue of investigation into interactions between tumor and bone microenvironment.
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PMID:Prostate cancer metastases alter bone mineral and matrix composition independent of effects on bone architecture in mice--a quantitative study using microCT and Raman spectroscopy. 2386 19

High metabolic and proliferative rates in cancer cells lead to production of large amounts of H+ and CO2 , and as a result, net acid extruding transporters are essential for the function and survival of cancer cells. We assessed protein expression of the Na+ /H+ exchanger NHE1, the Na+ - HCO3- cotransporter NBCn1, and the lactate-H+ cotransporters MCT1 and -4 by immunohistochemical analysis of a large cohort of breast cancer samples. We found robust expression of these transporters in 20, 10, 4 and 11% of samples, respectively. NHE1 and NBCn1 expression both correlated positively with progesterone receptor status, NHE1 correlated negatively and NBCn1 positively with HER2 status, whereas MCT4 expression correlated with lymph node status. Stable shRNA-mediated knockdown (KD) of either NHE1 or NBCn1 in the MDA-MB-231 triple-negative breast cancer (TNBC) cell line significantly reduced steady-state intracellular pH (pHi ) and capacity for pHi recovery after an acid load. Importantly, KD of any of the three transporters reduced in vivo primary tumor growth of MDA-MB-231 xenografts. However, whereas KD of NBCn1 or MCT4 increased tumor-free survival and decreased in vitro proliferation rate and colony growth in soft agar, KD of NHE1 did not have these effects. Moreover, only MCT4 KD reduced Akt kinase activity, PARP and CD147 expression and cell motility. This work reveals that different types of net acid extruding transporters, NHE1, NBCn1 and MCT4, are frequently expressed in patient mammary tumor tissue and demonstrates for the first time that they promote growth of TNBC human mammary tumors in vivo via distinct but overlapping mechanisms.
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PMID:The net acid extruders NHE1, NBCn1 and MCT4 promote mammary tumor growth through distinct but overlapping mechanisms. 2936 34

Tumor growth and metastasis are the major causes of high mortality in breast cancer. In this study, a water-responsive phospholipid-calcium-carbonate hybrid nanoparticle (PL/ACC-DOX&ICG) surface modified with a phospholipid shell is designed and covered with a shielding polymer polyethylene glycol; this development is loaded with the photosensitizer indocyanine green (ICG) and the chemotherapeutic drug doxorubicin (DOX) for near-infrared (NIR) imaging and chemophotothermal combination therapy against breast cancer. PL/ACC-DOX&ICG exhibits satisfactory stability against various aqueous environments with minimal drug leakage and can readily decompose to facilitate quick drug release into cancer cells. In vivo biodistribution studies, PL/ACC-DOX&ICG demonstrated strong tumor-homing properties. Interestingly, the in vitro cellular uptake and intratumoral penetration depth of PL/ACC-DOX&ICG are significantly enhanced under NIR laser irradiation, owing to ICG-induced hyperthermia, which not only enhances cell permeability and fluidity but also disrupts the dense tumor extracellular matrix. Compared to chemotherapy or photothermal therapy alone, chemophotothermal combination therapy synergistically induces apoptosis and death in 4T1 cells. Moreover, compared with the phosphate buffer saline group, the combined treatment suppress primary tumor growth at a rate of approximately 94.88% and decrease the number of metastatic nodules by about 93.6%. Therefore, PL/ACC-DOX&ICG may be a promising nanoplatform for breast cancer treatment.
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PMID:Water-Responsive Hybrid Nanoparticles Codelivering ICG and DOX Effectively Treat Breast Cancer via Hyperthermia-aided DOX Functionality and Drug Penetration. 3085 96

S-(-)-Oleocanthal (OC), a naturally occurring phenolic secoiridoid exclusively found in extra-virgin olive oil (EVOO), is a potential nutraceutical therapeutic for inflammation, neurodegenerative diseases, and many malignancies, especially breast cancer (BC). The oral delivery of OC is challenging because of its irritative, bitter, and pungent taste and exceptional chemistry, including two reactive aldehydes, phenolic, and ester groups. OC irritation did not correlate with CO2-induced irritation, and hence, OC was not exerting generalized acid-sensing irritation. The objective of this study was to develop an effervescent formulation of OC with an effective CO2-induced masked taste maintaining the efficacy against the estrogen receptor (ER) and HER2 positive BC. Several ratios of acid and carbonate sources were screened, and five effervescent formulations EF1-EF5 were selected and prepared based on their pH and effervescence time. OC formulations were characterized using differential scanning calorimetry, FT-IR spectroscopy, and scanning electron microscopy analyses. OC formulations exhibited acceptable flowability and effervescence time. Based on physical characteristics and improved OC release, formulation EF-2 was selected for subsequent studies. EF-2 showed effective OC taste masking, as suggested by electronic artificial tongue and mouse preference tests. EF-2 suppressed more than 70% of the hormone and HER2-positive BT-474 BC cell growth in a nude mouse xenograft model. Furthermore, EF-2 demonstrated significant inhibition of BT-474 tumor cell locoregional recurrence after primary tumor surgical excision. EF-2-treated mouse sera had significantly reduced CA 15-3 levels, the human BC recurrence marker, compared to the placebo control group at the end of the study. These results highlight the potential of the OC formulation EF-2 as a prospective nutraceutical for the control and prevention of ER+/HER+ BC progression and locoregional recurrence.
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PMID:Optimization of Taste-Masked (-)-Oleocanthal Effervescent Formulation with Potent Breast Cancer Progression and Recurrence Suppressive Activities. 3159 Mar 82