Abstract:
:The stress harbored by the solid phase of tumors is known as solid stress. Solid stress can be either applied externally by the surrounding normal tissue or induced by the tumor itself due to its growth. Fluid pressure is the isotropic stress exerted by the fluid phase. We recently showed that growth-induced solid stress is on the order of 1.3 to 13.0 kPa (10-100 mmHg)--high enough to cause compression of fragile blood vessels, resulting in poor perfusion and hypoxia. However, the evolution of growth-induced stress with tumor progression and its effect on cancer cell proliferation in vivo is not understood. To this end, we developed a mathematical model for tumor growth that takes into account all three types of stresses: growth-induced stress, externally applied stress, and fluid pressure. First, we conducted in vivo experiments and found that growth-induced stress is related to tumor volume through a biexponential relationship. Then, we incorporated this information into our mathematical model and showed that due to the evolution of growth-induced stress, total solid stress levels are higher in the tumor interior and lower in the periphery. Elevated compressive solid stress in the interior of the tumor is sufficient to cause the collapse of blood vessels and results in a lower growth rate of cancer cells compared with the periphery, independently from that caused by the lack of nutrients due to vessel collapse. Furthermore, solid stress in the periphery of the tumor causes blood vessels in the surrounding normal tissue to deform to elliptical shapes. We present histologic sections of human cancers that show such vessel deformations. Finally, we found that fluid pressure increases with tumor growth due to increased vascular permeability and lymphatic impairment, and is governed by the microvascular pressure. Crucially, fluid pressure does not cause vessel compression of tumor vessels.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Stylianopoulos T,Martin JD,Snuderl M,Mpekris F,Jain SR,Jain RKdoi
10.1158/0008-5472.CAN-12-4521subject
Has Abstractpub_date
2013-07-01 00:00:00pages
3833-41issue
13eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-12-4521journal_volume
73pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::In Sarcoma 180 and L1210 ascites tumor models, the initial rate of methotrexate accumulation in tumor cells in the peritoneal cavity and in small intestine (intracellularly) after s.c. doses up to 800 mg/kg, showed saturation kinetics. These results and the fact that initial uptake in these tissues within this dosage ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-12-01 00:00:00
abstract::We have examined a t(9;11)(p22;q23) chromosome translocation in an acute myeloid leukemia of an infant. The breakpoints on the two chromosomes occurred within introns of the involved genes: AF-9 on chromosome 9, and ALL-1 on chromosome 11. Sequence analysis identified heptamers flanking the breakpoints on both chromos...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-10-01 00:00:00
abstract::Akt activation has been implicated broadly in tumorigenesis, but the basis for its dysregulation in cancer cells is incompletely understood. In this study, we sought to clarify a regulatory role for the Akt-binding carboxy-terminal modulator protein (CTMP), which has been controversial. In evaluating CTMP expression i...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-0518
更新日期:2013-10-15 00:00:00
abstract::Two populations of nuclear androgen receptors have been characterized in human prostatic tissue, and the levels and proportions of each were found to differ in normal prostates, benign hyperplastic prostates (BPH), and malignant prostates. A significant percentage (35 to 50%) of total nuclear androgen receptors was as...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-03-01 00:00:00
abstract::The transforming growth factor-beta (TGF-beta) family of cytokines regulates cell proliferation, morphogenesis, and specialized cell functions in metazoans. Herein, we screened a compound library for modifiers of TGF-beta signaling in NMuMG epithelial cells using a cell-based assay to measure Smad2/3 nuclear transloca...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-2542
更新日期:2006-04-01 00:00:00
abstract::A glomerulopathy in hamsters bearing human epithelial tumors is described. The tumors resulted from the s.c. implantation of human heteroploid cells (MA160) derived originally from a benign prostatic adenoma. The renal immunomorphological and ultrastructural changes include expansion of mesangial matrix and cellularit...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-02-01 00:00:00
abstract::The mechanism whereby the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is silenced in repair-deficient (Mer-) human tumor cells is unknown. The role of methylation of the 5' CpG island in MGMT gene suppression is controversial. Although we previously showed by restriction enzyme analysis that CpG m...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-09-01 00:00:00
abstract::Occurrence of estrone, estradiol, and testosterone glucuronyltranferase activities was tested in a well-differentiated hepatoma, Reuber H35. Transferase activities for estrone and estradiol were found in the hepatoma. The Michaelis-Menten kinetics of these two microsomal glucuronyltransferase activities were similar i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-07-01 00:00:00
abstract::Smoking prevention will decrease lung cancer incidence in time. However, early detection would improve lung cancer prognosis in subjects at risk provided that specific markers could be identified. We previously reported that retinoic acid receptor (RAR) and retinoid X receptor (RXR) expression was altered in lung tumo...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-06-01 00:00:00
abstract::In an effort to achieve high concentrations of 5-fluorouracil (5-FUra) in the hepatic circulation while minimizing systemic exposure, several routes of intrahepatic administration were compared in the canine model. To ascertain these data, 5-FUra (30 mg/kg) was given as a bolus into either a systemic vein (femoral vei...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-11-01 00:00:00
abstract::Biochemical quantitation of estrogen receptors has been used to predict prognosis in breast cancer. Immunocytochemical analysis of estrogen receptors correlates with biochemical analysis but has very few follow-up studies in the literature to validate it as a prognostic indicator. 257 patients were followed for up to ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-02-15 00:00:00
abstract::By applying a new and highly sensitive assay for measuring N-hydroxy metabolites, the biochemical properties of the microsomal N-hydroxylase from control and 3-methylcholanthrene-treated rat and hamster liver have been analyzed, and the following conclusions have been drawn. (a) Due to a difference in enzyme affinity,...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-10-01 00:00:00
abstract::Thirty-seven endometrial cancers were subjected to an allelotype analysis in an attempt to identify chromosomal regions that are lost in a significant portion of tumors and to identify tumors characterized by replication errors. Thirty-nine highly polymorphic microsatellite markers representing all chromosomal arms, e...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-05-01 00:00:00
abstract::In previous studies a clone of the gynogenetic fish, Poecilia formosa (the Amazon molly), was successfully used as a test animal to identify ultraviolet-induced damage. This work has been extended, and the fish system was used to detect damage caused byionizing radiation. Fish cells, exposed in vitro to 250 and 500 ra...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-12-01 00:00:00
abstract::Expression of some members of the cadherin family is reduced in several human tumors, and CDH13 (H-cadherin), located on chromosome 16q24.2-3, may function as a tumor suppressor gene. In human tumors, loss of expression of many tumor suppressor genes occurs by aberrant promoter region methylation. We examined the meth...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-06-01 00:00:00
abstract::Changes in the structure of the surface of mastocytoma cells were induced by hyperthermia and were investigated by means of cell electrophoresis. A decrease in the cell electrophoretic mobility was detected as early as 15 min after treatment at 42 degrees and progressed more rapidly under hypoxic conditions than under...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-10-01 00:00:00
abstract::Immunity to infectious agents involves a coordinated response of innate and adaptive immune cells working in concert, with many feed-forward and regulatory interactions between both arms of the immune system. In contrast, many therapeutic strategies to augment immunity against tumors have focused predominantly on stim...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-17-1340
更新日期:2017-10-01 00:00:00
abstract::We previously reported that intetumumab (CNTO 95), a fully human anti-αv integrin monoclonal antibody, is a radiosensitizer in mice with xenograft tumors. Because intetumumab does not cross-react with mouse integrins, but has cross-reactivity with rat integrins, we next studied the potential combined use of radiation ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-1639
更新日期:2010-10-01 00:00:00
abstract::Oligomerization of the nonreceptor tyrosine kinase c-Abl can activate its transforming potential. Domains mediating oligomerization within the BCR-ABL and TEL-ABL oncoproteins are required for transforming activity, and fusion of inducible dimerization domains to c-Abl can generate chimeric proteins with dimerization-...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-02-15 00:00:00
abstract::The retinoblastoma (Rb) family consists of the tumor suppressor pRb/p105 and related proteins p107 and pRb2/p130. Recent immunohistochemical studies of the retinoblastoma family of proteins in 235 specimens of lung cancer show the tightest inverse association between the histological grading in the most aggressive tum...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-01-15 00:00:00
abstract::DAB486IL-2, a recombinant fusion toxin in which the native receptor binding domain of diphtheria toxin has been replaced with interleukin-2 (IL-2), has displayed significant activity in patients with chemotherapy refractory hematological cancers. To further investigate the safety and antitumor effect of this agent, we...
journal_title:Cancer research
pub_type: 临床试验,杂志文章
doi:
更新日期:1993-09-01 00:00:00
abstract::Patients with lung cancer often present with metastatic disease and therefore have a very poor prognosis. The recent discovery of several novel ROS receptor tyrosine kinase molecular alterations in non-small cell lung cancer (NSCLC) presents a therapeutic opportunity for the development of new targeted treatment strat...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-3990
更新日期:2012-08-01 00:00:00
abstract::When compared to normal esophageal epithelium, marked alterations in keratin protein and cross-linked envelope expression were found in human esophageal carcinomas. Examination of the pattern of keratin proteins extracted from either several primary esophageal tumors or carcinomas xenotransplanted in nude mice reveale...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-03-01 00:00:00
abstract::Skeletal muscle wasting is a devastating consequence of cancer that contributes to increased complications and poor survival, but is not well understood at the molecular level. Herein, we investigated the role of Myocilin (Myoc), a skeletal muscle hypertrophy-promoting protein that we showed is downregulated in multip...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-19-1558
更新日期:2020-05-01 00:00:00
abstract::Expression of death-associated protein (DAP) kinase, a proapoptotic serine/threonine protein kinase, is frequently lost in human tumors. In a study of 134 primary breast cancer specimens hypermethylation of the DAP kinase gene was found in 13% of cases. A highly significant difference (P < 0.001) of DAP kinase inactiv...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-11-15 00:00:00
abstract::Subcutaneous inoculation of Epstein-Barr virus (EBV) transformed peripheral blood B-lymphocytes (PBL) from an untreated chronic lymphocytic leukemia (CLL) patient produced progressively growing lethal tumors in 4 of 11 whole body irradiated (440 rads) nude mice. In one tumor bearing mouse there was splenomegaly and ge...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-05-01 00:00:00
abstract::Increased sialylation and branching of asparagine-linked oligosaccharides have recently been associated with both neoplastic transformation and the metastatic phenotype. Swainsonine, an inhibitor of Golgi alpha-mannosidase II blocks the synthesis of sialylated tri- and tetraantennary asparagine-linked oligosaccharides...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-10-01 00:00:00
abstract::Several genome-wide searches for common cancers have lead to the identification of a small number of loci that harbor low-risk cancer susceptibility markers. One marker, rs6983267 on chromosome 8q24, has been linked to both colon and prostate cancer, and is therefore a good candidate for a multicancer susceptibility m...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-1838
更新日期:2008-12-01 00:00:00
abstract::Addition of the tumor promoter of 12-O-tetradecanoylphorbol-13-acetate (TPA) to C3H/10T1/2 cells after exposure to either X-rays or to fission-spectrum neutrons increases significantly the frequency of transformation without any effect on cell survival. However, treatment of unirradiated cells with 0.1 micrograms of T...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-02-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF)-C is a lymphangiogenic factor implicated in lymphatic metastasis. In this study, we investigated the role of the type I insulin-like growth factor receptor (IGF-IR) in the regulation of VEGF-C expression. We used Lewis lung carcinoma subline M-27 cells transfected with human I...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-03-15 00:00:00