Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Strontium-89 is an established alternative for the alleviation of bone pain in prostate cancer. There are few data evaluating the effect on pain of palliative chemotherapy. The aim of this randomized phase II study was to assess and compare the analgesic efficacy of strontium-89 and chemotherapy (FEM=5-FU, epirubicin, and mitomycin C) in 35 patients with disseminated, hormone-refractory prostate cancer suffering from persisting bone pain despite analgesic treatment. In order to minimize the risk for imbalances regarding the two patient groups, a double-blind randomization was performed. A significant reduction in pain intensity and pain frequency was registered in both patient groups (P < 0.01 in both groups after 3 weeks). Side effects were generally mild in the strontium-89 group and significantly more severe in the FEM group. The effect of FEM on pain is surprising as chemotherapy has generally only limited effect on tumor growth in bone metastases due to prostate cancer. A possible explanation is that FEM has an inhibitory activity on the inflammatory component of metastases.
J Pain Symptom Manage 2005 Apr
PMID:Palliation of bone pain in prostate cancer using chemotherapy and strontium-89. A randomized phase II study. 1585 38

Octreotide is one of the somatostatin analogue used for the treatment of endocrine tumors principally to suppress hormone secretion and to inhibit tumor growth. We experienced a case with multiple endocrine neoplasia type 1 who small amount of octreotide dramatically relieved the lumber pain caused by metastatic bone tumor. He had recurrent bronchial carcinoid tumors that metastasized to liver and bones. The spontaneous and radiated pain by bone tumors subsided within a few minutes after the initial injection of octreotide and the effect persisted for several hours. Combination therapy of octreotide and interferon alpha-2b significantly reduced the size of metastatic liver tumors and inhibited further growth of metastatic bone tumors for the last 27 months. The use of octreotide may be a good option for controlling pain by metastatic bone disease and combination therapy of octreotide and interferon alpha-2b is worth to try for patients with inoperable metastatic carcinoid tumor.
 ...
PMID:Octreotide as a rapid and effective painkiller for metastatic carcinoid tumor. 1586 61

The three main organs affected by metastasis of all cancers include lungs, liver, and bone. Clinical confirmation of tumor spread to these organs is a negative prognostic sign that marks the stage when disease is rarely curable. Today, treatment of bone metastases is primarily palliative. The aims of treatment are to relieve pain, prevent development of pathologic fractures, improve mobility and function, and if possible, prolong survival. Significant improvements in our understanding of tumor biology along with early tumor detection has led to the discovery of few innovative approaches aimed to treat bone metastases. The most promising treatment modalities include combination of anti-cancer therapies (surgery, radiation therapy, citostatic therapy) with bone antiresorptive therapies (bisphosphonate) that specifically target osteoclasts, bone resorbing cells. The osteoclast, whose increased activity is induced by the tumor, is responsible for the deterioration of bone mass and structure along with the release of grow factors that feed back and support further tumor growth. The current pharmaceutical approach is to target bone metastases by developing drugs that specifically target tumor cells in bone in addition to bone stroma since skeletal metastases are more resistant to treatment, present the highest bulk of tumor mass in the body, serve as site for secondary spread of tumor cells, and are associated with significant morbidity. There is a real need for a more effective modified release of newer anti-cancer drugs such as gene therapy and immunotherapy by using established and novel delivery platforms that will improve therapy and reduce side effects as a result of more appropriate plasma profiles. Overall, however, developments regarding treatment of cancer metastases to bone are encouraging. The scope of future advancements is immense and includes innovative therapeutics and delivery systems aimed to improve skeletal affinity, selectivity, and efficacy of drugs.
 ...
PMID:Targeting of therapeutic agents to bone to treat metastatic cancer. 1587

To determine whether ATP and P2X3 receptors contribute to bone-cancer pain in a mouse model, immunohistochemical techniques were used to identify whether changes in the labeling of P2X3 receptors on epidermal nerve fibers (ENFs) occurred during tumor development. C3H mice were injected with osteolytic fibrosarcoma cells in and around the calcaneus bone. These mice exhibited mechanical hyperalgesia by day 10 post-implantation as assessed using von Frey monofilaments. Biopsies of the plantar skin overlying the tumor were obtained at days 10, 14, and 18 post-implantation. Confocal images were analyzed for the number of PGP 9.5, P2X3, and CGRP immunoreactive (ir) ENFs. The overall ENF population (PGP-ir) decreased progressively over time, whereas the subsets of P2X3-ir fibers demonstrated a modest increase and CGRP-ir nerve fibers remained fairly constant. Importantly, the proportion of CGRP-ir fibers that labeled for P2X3 increased from approximately 6% in control animals to nearly 30% at day 14 following tumor cell implantation. These studies demonstrate increased expression of P2X3 receptors on CGRP-ir ENFs during tumor growth and suggest a role for ATP in cancer-related pain.
 ...
PMID:Re-organization of P2X3 receptor localization on epidermal nerve fibers in a murine model of cancer pain. 1588 18

Breast cancer metastasis to the bone occurs frequently, causing numerous complications including severe pain, fracture, hypercalcemia, and paralysis. Despite its prevalence and severity, few effective therapies exist. To address this, we examined whether the heat shock protein 90 (Hsp90) inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), would be efficacious in inhibiting breast cancer metastasis to bone. Utilizing the human breast cancer subline, MDA-MB-231SA, previously in vivo selected for its enhanced ability to generate osteolytic bone lesions, we determined that 17-AAG potently inhibited its in vitro proliferation and migration. Moreover, 17-AAG significantly reduced MDA-MB-231SA tumor growth in the mammary-fat pad of nude mice. Despite these findings, 17-AAG enhanced the incidence of bone metastasis and osteolytic lesions following intracardiac inoculation in the nude mouse. Consistent with these findings, 17-AAG enhanced osteoclast formation 2- to 4-fold in mouse bone marrow/osteoblast cocultures, receptor activator of nuclear factor kappaB ligand (RANKL)-stimulated bone marrow, and RAW264.7 cell models of in vitro osteoclastogenesis. Moreover, the drug enhanced osteoclastogenesis in human cord blood progenitor cells, demonstrating that its effects were not limited to mouse models. In addition to 17-AAG, other Hsp90 inhibitors, such as radicicol and herbimycin A, also enhanced osteoclastogenesis. A pro-osteolytic action of 17-AAG independent of tumor presence was also determined in vivo, in which 17-AAG-treated tumor-naive mice had reduced trabecular bone volume with an associated increase in osteoclast number. Thus, HSP90 inhibitors can stimulate osteoclast formation, which may underlie the increased incidence of osteolysis and skeletal tumor incidence caused by 17-AAG in vivo. These data suggest an important contraindication to the Hsp90 targeted cancer therapy currently undergoing clinical trial.
 ...
PMID:The heat shock protein 90 inhibitor, 17-allylamino-17-demethoxygeldanamycin, enhances osteoclast formation and potentiates bone metastasis of a human breast cancer cell line. 1593 Mar 15

The present study was conducted to evaluate the pain development and bone destruction during bone cancer growth in a murine model of bone cancer pain and to evaluate the analgesic efficacy of fentanyl, sufentanil, and morphine in this model. C3H/HeNCrl mice were inoculated into the intramedullary space of the femur with osteolytic NCTC 2472 fibrosarcoma cells, and followed during a 3-week period to assess pain behaviors (spontaneous lifting and limb-use during forced ambulation on rotarod) and bone destruction (parameters indicative of bone lesions determined by microCT-scans of the tumor-bearing bones) during bone cancer growth. The results showed that in this murine model of cancer-induced bone pain, behavioural manifestations of pain emerge in parallel with the progression of bone destruction. The subcutaneous administration of fentanyl (0.025-0.64 mg/kg), sufentanil (0.005-0.04 mg/kg), and morphine (2.5-40 mg/kg) on the test days 15 and 22 post-inoculation reduced pain-related behaviors in a dose dependent manner. A complete relief from pain-related behaviors was achieved with the following doses: > or =0.16 mg/kg fentanyl, 0.02 mg/kg sufentanil, and 20 mg/kg morphine. In conclusion, the results showed a clear link between tumor growth-induced bone destruction and behavioral pain manifestations, the latter was effectively controlled by the opioids fentanyl, sufentanil, and morphine.
 ...
PMID:Evaluation of pain-related behavior, bone destruction and effectiveness of fentanyl, sufentanil, and morphine in a murine model of cancer pain. 1612 59

The most used treatment for bone cancer pain is radiation; however, the mechanism responsible for analgesia after irradiation is unknown. The mechanistic influence of a single, localized 10-, 20- or 30-Gy dose of radiation on painful behaviors, osteolysis, histopathology and osteoclast number was evaluated in mice with painful femoral sarcomas. Dramatic reductions in pain behaviors (P < 0.05) and osteolysis (P < 0.0001) were seen in mice irradiated with 20 and 30 Gy. Irradiation reduced the tumor area by more than 75% (P < 0.05) but did not affect osteoclast frequency per mm2 tumor. Treatment with 20 Gy prior to tumor injection had no effect on tumor growth or pain behaviors, suggesting that radiation reduces osteolysis and pain through direct tumor effects. To demonstrate that tumor elimination was responsible for reduction in osteolysis and pain, sarcoma cells containing the suicide gene cytosine deaminase (CD) were inoculated into femora. After onset of bone cancer pain, mice were treated with the prodrug 5-fluorocytosine (5-FC). 5-FC treatment significantly reduced both osteolysis (P < 0.0005) and bone cancer pain (P < 0.05). The findings in this study demonstrate that one mechanism through which radiation decreases bone cancer pain is by direct effects on tumor cells.
 ...
PMID:Radiation treatment decreases bone cancer pain through direct effect on tumor cells. 1618 42

Prostate cancer is unique in that bone is often the only clinically detectable site of metastasis. Prostate tumors that have metastasized to bone frequently induce bone pain which can be difficult to fully control as it seems to be driven simultaneously by inflammatory, neuropathic, and tumorigenic mechanisms. As nerve growth factor (NGF) has been shown to modulate inflammatory and some neuropathic pain states in animal models, an NGF-sequestering antibody was administered in a prostate model of bone cancer where significant bone formation and bone destruction occur simultaneously in the mouse femur. Administration of a blocking antibody to NGF produced a significant reduction in both early and late stage bone cancer pain-related behaviors that was greater than or equivalent to that achieved with acute administration of 10 or 30 mg/kg of morphine sulfate. In contrast, this therapy did not influence tumor-induced bone remodeling, osteoblast proliferation, osteoclastogenesis, tumor growth, or markers of sensory or sympathetic innervation in the skin or bone. One rather unique aspect of the sensory innervation of bone, that may partially explain the analgesic efficacy of anti-NGF therapy in relieving prostate cancer-induced bone pain, is that nearly all nerve fibers that innervate the bone express trkA and p75, and these are the receptors through which NGF sensitizes and/or activates nociceptors. The present results suggest that anti-NGF therapy may be effective in reducing pain and enhancing the quality of life in patients with prostate tumor-induced bone cancer pain.
 ...
PMID:A blocking antibody to nerve growth factor attenuates skeletal pain induced by prostate tumor cells growing in bone. 1623 Apr 6

To begin to understand the relationship between disease progression and pain in pancreatic cancer, transgenic mice that develop pancreatic cancer due to the expression of the simian virus 40 large T antigen under control of the rat elastase-1 promoter were examined. In these mice precancerous cellular changes were evident at 6 weeks and these included an increase in: microvascular density, macrophages that express nerve growth factor and the density of sensory and sympathetic fibers that innervate the pancreas, with all of these changes increasing with tumor growth. In somatic tissue such as skin, the above changes would be accompanied by significant pain; however, in mice with pancreatic cancer, changes in pain-related behaviors, such as morphine-reversible severe hunching and vocalization only became evident at 16 weeks of age, by which time the pancreatic cancer was highly advanced. These data suggest that in mice as well as humans, there is a stereotypic set of pathological changes that occur as pancreatic cancer develops, and while weight loss generally tracks disease progression, there is a significant lag between disease progression and behaviors indicative of pancreatic cancer pain. Defining the mechanisms that mask this pain in early and mid-stage disease and drive the pain in late-stage disease may aid in earlier diagnosis, survival, and increased quality of life of patients with pancreatic cancer.
Pain 2005 Dec 15
PMID:Pancreatic cancer pain and its correlation with changes in tumor vasculature, macrophage infiltration, neuronal innervation, body weight and disease progression. 1629 91

Isolated recurrence of rectal carcinoma have been reported from 7% to 33% with a median of 15. Increasing recurrence is associated with increasing Dukes's stage. Patient who have recurrence after a low-anterior resection are more likely to present with non fixed, surgically correctable lesion versus recurrences after abdominoperineal resection. The most common symptom related to pelvic recurrence is pain, which may be perineal or radiate to the lower extremities. The diagnosis of a locally recurrent rectal cancer was obtained with CT; imaging is the first step to estimate the extent and location of the local tumor growth and the presence or absence of distant metastases. The most common location is at or around the anastomosis and the presacral region. Apart from distant metastases locoregional recurrence is the most important factor determining prognosis and survival. If an R0 resection can be performed, a 5-year survival rate of 20-30% can be achieved. Local or locoregional recurrence implies the reappearance of carcinoma after an intended complete removal of the tumor. For rectal cancer, the adjacent organs include the perineum, bladder and vagina, and LR failure includes perineal or pelvic lesions. Total pelvic exenteration is performed in patients with local recurrence of rectal cancer and a 5-year suvival rate of 30-40% was achieved. For patient with unresectable recurrence, chemotherapy and radiation contribute to a better quality of life and prolong survival. While radiotherapy may reduce recurrence, it is now apparent that total mesorectal excision is the most effective modality, with rates as low as 5%. The anastomotic recurrence that can be locally resected, the best approach for long-term survival is an extensive surgical procedure requiring en bloc removal of adjacent organs and pelvic structures so called composite resection. Intraoperative radiotherapy and brachytherapy, and/or preoperative chemoradiation may provide better results in future. While radioterapy remains the most common antineoplastic modality used for palliation of symptoms, surgical resection remains the mainstay of curative treatment for carcinoma of colon and rectum.
 ...
PMID:[Pelvic recurrence of rectal cancer: our experience]. 1643 80


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>