Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some locally advanced neoplastic diseases (i.e. head and neck cancer, breast cancer and osteogenic sarcoma), benefit from neoadjuvant chemotherapy with a resultant enhanced operability and a longer disease-free survival. The pharmacological study of the tissue distribution of adriamycin in patients affected by locally advanced breast cancer has shown a preferable tropism of the drug toward the primary tumor and axillary lymph nodes. Median concentrations of the drug in the tumor were: 9.68 micrograms/gr at 30 minutes, 8.71 micrograms/gr at 24 hours and 6.44 micrograms/gr at 48 hours. Median concentration in lymph nodes at 48 hours was 10.80 in normal and 16.62 in metastatic. Lower concentrations were found at 48 hours in the mammary gland (mean 1.72 micrograms/gr), skin (mean 0.59 micrograms/gr) and in muscle tissue (mean 1.83 micrograms/gr in normal and 2.41 micrograms/gr in metastatic). As regards acute toxicity, we observed that grade II-III leukopenia was associated with longer plasmatic T1/2 beta (3 out of 6 patients) and that grade II mucositis was related to high plasma AUC values (3 out of 6 patients). Nausea and vomiting and alopecia seem to be unrelated to plasma pharmacokinetics parameters. After a median follow-up of 36 months it is suggestive that high drug concentrations in carcinoma and in metastatic lymph nodes may be predictive of longer disease-free survival and overall survival. These data give a further rationale for the use of polychemotherapies containing adriamycin in the pre-operative treatment of locally advanced breast cancer.
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PMID:A pharmacological rationale for neoadjuvant chemotherapy with adriamycin in locally advanced breast cancer. 233 26

Clinical cancer research is at a crossroads. The major progress which has been achieved will continue, provided that factors which threaten the clinical cancer researcher are identified and corrected. These problems (with proposed solutions) include: the increasing number of clinical oncologists, particularly medical oncologists; the relationship of the practicing clinical oncologist to cancer centers; the relative attractions of clinical practice, on the one side, and basic science on the other, as compared to clinical cancer research; the lack of recognition that clinical cancer research provides an opportunity for high achievement and challenge, and originality; the threat of curtailment of research funding; jurisdictional and other conflicts between scientific and clinical disciplines; the emerging "establishment generation" of clinical oncology; and the bureaucratic and regulatory ambience that has increasingly enveloped the clinical cancer researcher. That opportunities for originality continue was illustrated by a new therapeutic surgery known as neoadjuvant or anterior chemotherapy. In this strategy, systemic treatment is employed prior to surgery and/or radiotherapy for patients with head and neck cancer has increased operability ("upstaged" the patient) and on preliminary analysis would appear to be increasing disease-free survival. A clinical trial in osteogenic sarcoma involving initial chemotherapy has indicated that such treatment not only provides substantial regression of the primary in the majority of patients but also results in a substantially improved disease-free and overall survival, particularly in patients with locally responsive disease.
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PMID:Clinical cancer research: an embattled species. 712 45

Between 1988 and 1994, 24 patients underwent 32 procedures for pulmonary metastases. Primary tumours were gastrointestinal, malignant melanoma, osteogenic sarcoma, renal cell carcinoma, head and neck cancer and finally testicular carcinoma. Age ranged from 16 to 78 years, with a female/male ratio of 7/17. Pulmonary metastasectomy was performed in 9 cases through median sternotomy, in 21 cases through thoracotomy and in 2 cases by thoracoscopy. In 9 cases repeated resection was necessary. Overall mortality was 0% (95% confidence limits are 0.00 +/- 14.25). Computed tomography of the chest in combination with tumour markers, were most important during follow-up to detect recurrent disease. The overall 5-year actuarial survival and disease-free survival were 0.56 +/- 0.17 and 0.30 +/- 0.14 respectively. With regard to testicular carcinoma 5-year actuarial survival was 100%. Pulmonary metastasectomy is a recommended procedure in the treatment of selected patients with metastatic pulmonary disease. Resections should be as conservative as possible and if necessary, repeated. In our study this procedure proved especially effective in case of testicular carcinoma.
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PMID:Pulmonary metastasectomy. 857 21

In 12 patients with recurrences and metastases of different primaries (head and neck cancer, breast cancer, malignant melanoma, and osteosarcoma) who were treated with reactor fission neutrons the photon emission of irradiated tissue was measured after each radiotherapy fraction. Spectral analyses of the decay rates resulted in data for the exchange of sodium (Na) and chlorine (Cl) between the irradiated tissue and the body. About 60% of Na and Cl exchanged rapidly with a turnover half-life of 13 +/- 2 min. New defined mass exchange rates for Na and Cl amount to an average of 0.8 mval/min/kg of soft tissue. At the beginning of radiotherapy the turnover of the electrolytes in tissues with large tumor volumes was about twice that in tissues with small tumor volumes. Depending on the dose, neutron therapy led in all cases to variation in the metabolism. A maximum of Cl exchange and a minimum of Na exchange occurred after 10 Gy of neutrons (group of six previously untreated patients) or after 85 Gy (photon equivalent dose) of combined photon-neutron therapy. A significant increase in non-exchangeable fraction of Na from about 40 to 80% was observed in three tumors after a neutron dose of 10 Gy administered in five fractions correlated with a rapid reduction of tissue within 4 weeks after end of therapy. These results demonstrate for the first time the local response of the electrolyte metabolism to radiotherapy.
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PMID:In vivo neutron activation analysis of sodium and chlorine in tumor tissue after fast neutron therapy. 894 49

Pre-therapeutic evaluation of p53 gene is very important for treating patients with head and neck cancer. However, the analysis for p53 gene has generally been done by immunohistochemistry, polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) and direct sequencing. Functional analysis system for p53 transcriptional activity in mammalian cells is now required. We developed a functional analysis system for p53 transcriptional activity in cancer cells. We used two human head and neck cancer cell lines harboring mutated p53 gene, HSG (Asn30Ser) and TYS (Asp281His), and a human osteosarcoma cell line, Saos-2 as a control. We transfected these cells with luciferase reporter plasmids containing promoter sequence of p53 target genes (p21waf1, BAX, MDM2, p53AIP1 or PUMA). After treating the cells with chemotherapeutic drugs, alteration of the luciferase activity was measured. In HSG cells, none of the target gene promoters was activated by treatment with chemotherapeutic drugs. In TYS cells, p21waf1 promoter was markedly activated by treatment with chemotherapeutic drugs, but Bax and p53AIP1 promoter was not activated. This type of mutated-p53 in TYS cells prevents cell death from DNA damage, and probably accumulates genetic alterations and accelerates the malignant progression of the cells by DNA damaging therapy. Thus, analysis for the diverse function of mutated-p53 may help to determine the therapeutic strategy, especially for chemotherapy and radiation in the individual patients with head and neck cancer.
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PMID:Evaluation of the chemosensitivity of head and neck cancer cells based on the diverse function of mutated-p53. 1252 38

The aim of this study was to report our experience on the management of radiation-induced sarcomas (RISs). A retrospective study from 1994 to 2003 was done at our institution reviewing the medical records of 5 patients who had RISs. Five patients diagnosed of head and neck cancer received irradiation to treat their diseases. Later on, these patients developed new neoplasms in the irradiation fields (3 malignant fibrous histiocytoma, 1 osteosarcoma, and 1 angiosarcoma). The mean period of latency between irradiation and diagnosis of new tumors was 13 years. Early symptoms included neck or face swelling, odynophagia, or trigeminal hypoesthesia. All of the patients underwent surgical treatment. In 4 cases, regional and free flaps for head and neck reconstruction were required. Three patients also needed neoadjuvant chemotherapy. In the follow-up, 2 patients are alive and free of disease. Wide excision is the treatment of choice for RISs. Previous radiation therapy limits the dose that can be administered to the involved area, and the response rate to the chemotherapy is always poor.
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PMID:Radiation-induced sarcomas of the head and neck. 1881 53

Studies on paediatric head and neck cancer are limited in the medical literature. Most studies have been restricted to specific histological types such as rhabdomyosarcoma, osteogenic sarcoma or Burkitt's lymphoma. This study describes the relative frequency of cancers seen in the head and neck region of children below 16 years of age at the University College Hospital, Ibadan, Nigeria. A total of 281 cases of paediatric head and neck tumours were diagnosed within the study period, out of which 84 cases were malignant. Fifty-four of these cases were males while 30 were females, giving a male to female ratio of 1.8:1. The age range for these cases was 3 days to 15 years with a mean age of 9.03 +/- 4.63 years. The most frequently diagnosed tumours were haematopoietic malignancies, accounting for 47.6% of cases, followed by sarcomas (27.4%) and carcinomas (21.4%). Burkitt's lymphoma constituted 28.6%, followed by rhabdomyosarcoma accounting for 17.9% of cases. Malignant neoplasms of the head and neck region are rare in the paediatric age group. The pattern of these neoplasms also differs from that in the adult population. However, malignant head and neck neoplasms in the paediatric age group also showed the male preponderance characteristic of head and neck malignancies in the adult population.
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PMID:Paediatric head and neck malignancies in Ibadan, Nigeria. 1972 29

Recently, several new and non-invasive methods have been introduced for the treatment of skin cancers. Topical creams using the immune modulator imiquimod or the COX inhibitor diclofenac (with hyaluronic acid) are now registered for use against neoplasms such as basal or squamous cell carcinoma. Another modern treatment option is photodynamic therapy (PDT). A refined version of PDT, namely photochemical internalisation, is currently subject to a first clinical trial in patients with osteosarcoma, squamous cell carcinoma, head and neck cancer as well as adenocarcinoma of the breast. Preliminary results from this trial suggest that PCI seems to be a promising treatment.
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PMID:[Photochemical internalisation (PCI): a further development of photodynamic therapy for the treatment of skin cancer]. 2108 95

Dihydrofolate reductase (DHFR) is an essential enzyme involved in de novo purine and thymidine biosynthesis. For several decades, selective inhibition of DHFR has proven to be a potent therapeutic approach in the treatment of various cancers including acute lymphoblastic leukemia, non-Hodgkin's lymphoma, osteogenic sarcoma, carcinoma of the breast, and head and neck cancer. Therapeutic success with DHFR inhibitor methotrexate (MTX) has been compromised in the clinic, which limits the success of MTX treatment by both acquired and intrinsic resistance mechanisms. We report that benzamide riboside (BR), via anabolism to benzamide adenine dinucleotide (BAD) known to potently inhibit inosine monophosphate dehydrogenase (IMPDH), also inhibits cell growth through a mechanism involving downregulation of DHFR protein. Evidence to support this second site of action of BR includes the finding that CCRF-CEM/R human T-cell lymphoblasic leukemia cells, resistant to MTX as a consequence of gene amplification and overexpression of DHFR, are more resistant to BR than are parental cells. Studies of the mechanism by which BR lowers DHFR showed that BR, through its metabolite BAD, reduced NADP and NADPH cellular levels by inhibiting nicotinamide adenine dinucleotide kinase (NADK). As consequence of the lack of NADPH, DHFR was shown to be destabilized. We suggest that, inhibition of NADK is a new approach to downregulate DHFR and to inhibit cell growth.
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PMID:A second target of benzamide riboside: dihydrofolate reductase. 2295 84

Epithelial-to-mesenchymal transition (EMT) facilitates tumor metastasis. Twist is a basic helix-loop-helix protein that modulates many target genes through E-box-responsive elements. There are two twist-like proteins, Twist-1 and Twist-2, sharing high structural homology in mammals. Twist-1 was found to be a key factor in the promotion of metastasis of cancer cells, and is known to induce EMT. Twist-1 participation in carcinoma progression and metastasis has been reported in a variety of tumors. However, controversy exists concerning the correlation between Twist-1 and prognostic value with respect to carcinoma. A systematic review and meta-analysis were performed to determine whether the expression of Twist-1 was associated with the prognosis of carcinoma patients. This analysis included 17 studies: four studies evaluated lung cancer, three evaluated head and neck cancer, two evaluated breast cancer, two evaluated esophageal cancer, two evaluated liver cancer and one each evaluated osteosarcoma, bladder, cervical and ovarian cancer. A total of 2006 patients were enrolled in these studies, and the median trial sample size was 118 patients. Twist-1 expression was associated with worse overall survival (OS) at both 3 years (hazard ratio "HR" for death = 2.13, 95% CI = 1.86 to 2.45, p < 0.001) and 5 years (HR for death = 2.01, 95% CI = 1.76 to 2.29, p < 0.001). Expression of Twist-1 is associated with worse survival in carcinoma.
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PMID:Twist-1 up-regulation in carcinoma correlates to poor survival. 2542 25


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