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At least 1,387 records · Page 77Linked to original sources
PubMed2004

Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma.

BACKGROUND: Mortality rates associated with pancreatic resection for cancer have steadily decreased with time, but improvements in long-term survival are less clear. This prospective study evaluated risk factors for survival after resection for pancreatic adenocarcinoma. METHODS: Data from 366 consecutive patients recorded prospectively between November 1993 and September 2001 were analysed using univariate and multivariate models. RESULTS: Fifty-eight patients (15.8 per cent) underwent surgical exploration only, 97 patients (26.5 per cent) underwent palliative bypass surgery and 211 patients (57.7 per cent) resection for pancreatic adenocarcinoma. Stage I disease was present in 9.0 per cent, stage II in 18.0 per cent, stage III in 68.7 per cent and stage IV in 4.3 per cent of patients who underwent resection. Resection was curative (R0) in 75.8 per cent of patients. Procedures included pylorus-preserving Whipple resection (41.2 per cent), classical Whipple resection (37.0 per cent), left pancreatic resection (13.7 per cent) and total pancreatectomy (8.1 per cent). The in-hospital mortality and cumulative morbidity rates were 2.8 and 44.1 per cent respectively. The overall actuarial 5-year survival rate was 19.8 per cent after resection. Survival was better after curative resection (R0) (24.2 per cent) and in lymph-node negative patients (31.6 per cent). A Cox proportional hazards survival analysis indicated that curative resection was the most powerful independent predictor of long-term survival. CONCLUSION: Resection for pancreatic adenocarcinoma can be performed safely. The overall survival rate is determined by the radicality of resection. Patients deemed fit for surgery who have no radiological signs of distant metastasis should undergo surgical exploration. Resection should follow if there is a reasonable likelihood that an R0 resection can be obtained.

Adenocarcinoma↗
PubMed2000

Feeding dendritic cells with tumor antigens: self-service buffet or à la carte?

Adoptive transfer of autologous dendritic cells (DC) presenting tumor-associated antigens initiate and sustain an immune response which eradicate murine malignancies. Based on these observations, several clinical trials are in progress testing safety and efficacy with encouraging preliminary reports. In these approaches, ex vivo incubation of DC with a source of tumor antigens is required to load the relevant antigenic epitopes on the adequate antigen presenting molecules. Recent data show that in some instances exogenous DC artificially injected into malignant tissue or endogenous DC attracted to the tumor nodule by means of gene transfer of GM-CSF and CD40L into malignant cells result in efficacious antitumor immunity. In the case of intratumoral injection of DC the procedure is curative only if DC had been genetically engineered to produce IL-12, IL-6 or to express CD40L. Evidence has been obtained showing that intratumoral DC can capture and process tumor antigens to be presented to T-lymphocytes. Although the exact mechanisms of tumor antigen acquisition by DC are still unclear, available data suggest a role for heat shock proteins released from dying malignant cells and for the internalization of tumor-derived apoptotic bodies. Roles for tumor necrosis versus apoptosis are discussed in light of the 'danger theory'. Gene Therapy (2000) 7, 1167-1170.

Adenoviridae↗
PubMed1999

Cumulative prognostic value of p53 mutations and bcl-2 protein expression in head-and-neck cancer treated by radiotherapy.

We investigated the prognostic significance of p53-gene mutation (exon 5-9) and bcl-2-protein expression in primary squamous-cell carcinoma of the head and neck (HNSCC) treated by curative radiotherapy (RT). Primary squamous-cell carcinomas for analysis were obtained from 85 consecutive head-and-neck-cancer patients, with complete follow-up data. We detected bcl-2 protein in 24% (20/85) of HNSCC studied; 38 (45%) of the 85 tumours had cells bearing p53 mutations. A strong association was observed between tobacco exposure and bcl-2-protein expression (p = 0.003), an association also evident in those patients who had a p53-mutated carcinoma (p = 0.049). Moreover, we found that most of the bcl-2-positive cancers (70%) were also mutated in the p53 gene (p = 0.010). In univariate and in multivariate analyses, the simultaneous detection of bcl-2 expression and a p53-gene mutation in a tumour biopsy specimen was associated with greater risk of locoregional failure (p = 0.002 and 0.001 respectively) and worse survival (p = 0. 045 and 0.033) within 5 years in HNSCC patients treated by RT. The present study shows a cumulative prognostic value of simultaneous detection of bcl-2 over-expression and p53-gene aberration in some primary HNSCC treated with conventional RT, and provides further evidence for cross-talk between p53 and bcl-2, suggesting that these genes are important determinants of radiation-induced apoptosis, thereby modulating resistance to RT. Int. J. Cancer (Pred. Oncol.) 84:573-579, 1999.

Adult↗
PubMed1993

Resection-line involvement in gastric cancer: a continuing problem.

Surgeons are aware of the adverse effect that resection-line disease has on anastomotic leakage, perioperative mortality and long-term survival. In an attempt to assess the effect of this knowledge on surgical practice, patients entered into the second British Stomach Cancer Group adjuvant therapy trial were studied. The presence of resection-line disease was compared with the operative stage. Of 555 patients for whom complete data were available, resection-line disease was present in 105 (19 per cent). Of 424 patients undergoing what the surgeon considered to be a potentially curative operation, 55 (13 per cent) had involvement of one or both resection lines, rendering the surgery palliative. Only 9 per cent of patients with stage I-III disease and resection-line involvement survived beyond 5 years, compared with 27 per cent of those with clear lines. Despite knowledge of the adverse effects of resection-line disease, surgeons continue to perform inadequate resections. This demonstrates the need for a more aggressive approach to assessment of resection margins at operation.

Gastrectomy↗
PubMed2002

Seminal vesicle involvement in patients with D1 disease predicts early prostate specific antigen recurrence and metastasis after radical prostatectomy and early androgen ablation.

BACKGROUND: Controversy persists regarding the management of patients who present with locally advanced metastatic prostate carcinoma. Although radical prostatectomy is not curative, there is growing evidence that survival may be prolonged when the surgery is combined with early androgen ablation. In the current study, the authors present data with which to evaluate and define factors for disease progression in patients undergoing radical prostatectomy with lymph node positive disease who are treated with early endocrine ablation. METHODS: Data from 40 patients undergoing radical prostatectomy and early androgen ablation between 1987-1998, all of whom had lymph node positive disease, were analyzed. Age, preoperative prostate specific antigen (PSA) level, clinical and pathologic Gleason score, surgical margin, seminal vesicle involvement (SVI), and the number and percentage of involved positive lymph nodes were analyzed to predict PSA progression, metastasis, and death using univariate and multivariate statistical techniques. RESULTS: Univariate analysis identified only SVI as a statistically significant predictor of PSA progression and metastasis. Twenty-seven patients (67.5%) were found to have SVI. Multivariate analysis failed to identify other factors that added significantly to the predictive ability of SVI. Kaplan-Meier estimates of time to PSA recurrence and metastasis demonstrated that SVI was highly predictive of disease progression. The median time to PSA progression for the 27 patients with SVI was 7.5 years compared with no progression reported in the 13 patients without SVI (P = 0.011). CONCLUSIONS: VI is a very powerful predictor of disease progression in patients with lymph node positive disease who undergo radical prostatectomy and early androgen ablation. In the current study, preoperative PSA, clinical or pathologic Gleason scores, and other clinical factors were not found to be predictive of disease outcome.

Adenocarcinoma↗
PubMed2001

Local excision of rectal cancer: what is the evidence?

PURPOSE: Although local excision of rectal cancers is a less morbid alternative to radical resection, its role as a curative procedure is unclear. The role of adjuvant therapy after local excision is also controversial. This review aims to examine current evidence on local excision of rectal cancers and how it fits into the management algorithm for rectal cancer. METHODS: A literature review was undertaken through the MEDLINE database and by cross-referencing previous publications, thus identifying 41 studies on curative local excision of rectal cancer published in English. Details of preoperative staging, surgical procedures, adjuvant therapy, follow-up, and outcome measures, including complications, survival data, recurrences, and salvage were examined. RESULTS: Preoperative staging of rectal cancers is variable. Digital rectal examination and computerized tomography are used in most studies. Endorectal ultrasound is used in some patients in 9 of 41 studies. Local excision preserves anorectal function, and seems to have limited morbidity (0-22 percent). Local excision alone is associated with local recurrences in 9.7 (range, 0-24) percent of T1, 25 (range, 0-67) percent of T2 and 38 (range, 0-100) percent of T3 cancers. The addition of adjuvant chemoradiotherapy after local excision yields local recurrence rates of 9.5 (range, 0-50) percent for T1, 13.6 (range, 0-24) percent for T2, and 13.8 (range, 0-50) percent for T3 cancers. Data on local excision after preoperative chemoradiotherapy for tumor down staging are limited. Factors other than T-stage that lead to higher local recurrence rates after local excision include poor histologic grade, the presence of lymphovascular invasion, and positive margins. Local recurrences after local excision can be surgically salvaged (84 of 114 patients in 15 studies), with a disease-free survival rates between 40 and 100 percent at a follow-up of 0.1 to 13.5 years. CONCLUSIONS: Local excision for rectal cancers is associated with a low morbidity and provides satisfactory local control and disease-free survival rates for T1 rectal cancers. There is, however, a need for a randomized, controlled trial for T2 cancers, comparing local excision with adjuvant chemoradiotherapy to radical resection.

Algorithms↗
PubMed1998

Staging of colorectal cancer: biology vs. morphology.

PURPOSE: An accurate determination of the extent or staging of a disease is critical, because it provides the basis for making therapeutic decisions. Staging is a collaborative effort by the surgeon and the pathologist. Radioimmunoguided surgery has been evaluated for its ability to help surgeons determine the extent of disease during surgery, when management decisions have the most impact on patient care. This study was done to compare radioimmunoguided surgery "biostaging" with traditional pathologic staging (TNM) as predictors of survival in patients undergoing curative resections for colorectal cancer. METHODS: Ninety-seven patients with colorectal cancer were prospectively enrolled in radioimmunoguided surgery protocols. Evaluation of follow-up survival data was performed. All patients underwent exploratory laparotomy and radioimmunoguided surgery with resection of their primary colorectal tumor. Survival data were analyzed with the Kaplan-Meier method with log-rank comparisons. RESULTS: Of 97 patients enrolled in the study, 59 were evaluable and completely resectable by radioimmunoguided surgery. Mean follow-up was 62 months, with a range of 34 to 89 months. By traditional staging 13 patients were pStage I, 18 patients were pStage II, and 28 patients were pStage III. By radioimmunoguided surgery biostaging, 24 patients were radioimmunoguided surgery-negative whereas 35 patients were radioimmunoguided surgery-positive. Survival rates by pathologic stage approached a significant difference, but did not, as of the conclusion of the study period, reach it (P = 0.12). Survival rates based on radioimmunoguided surgery status demonstrated a highly significant difference (P = 0.0002). CONCLUSIONS: Radioimmunoguided surgery biostaging provides new information intraoperatively on cancer staging that has not been available before. This may lead to new strategies for therapy that can be individualized and optimized for each patient with cancer.

Adult↗
PubMed2003

Oncologic results following abdominoperineal resection for adenocarcinoma of the low rectum.

PURPOSE: The role of abdominoperineal resection for rectal cancer has changed because of advances in sphincter-preserving surgery. Our aim was to evaluate the results of this operation in the five-year period following introduction of the concept of total mesorectal excision METHODS: Data on all patients undergoing abdominoperineal resection for very low rectal cancer between 1992 and 1997 were collected prospectively. All patients had had total mesorectal excision. Curative resection was defined as absence of macroscopic disease after resection and local recurrence as any infiltration or tumor identified in the pelvis, alone or combined with distant disease. Survival and local recurrence rates were calculated using the Kaplan-Meier method and log-rank analysis. RESULTS: Of 165 abdominoperineal resections performed, 106 were for primary adenocarcinoma of the rectum. The male:female ratio was 50:56, with a median age of 65 (range, 33-85) years. There was one postoperative death. Twenty-seven patients received short-course preoperative radiotherapy (25 Gy over 1 week), whereas 22 had a longer course, with concomitant chemotherapy in 2. Postoperative chemotherapy was administered in 29, postoperative radiotherapy in 4, and combined therapy in 8. After curative resection (n = 91), survival at five years was 76 percent and differed significantly by stage. Recurrence at any site was 7 percent (3/34) for Stage I, 27 percent (6/26) for Stage II, and 53 percent (16/31) for Stage III. Nine patients presented with local recurrence, with an overall rate at five years of 10 percent. Isolated locale recurrence was observed in only 5 percent of patients CONCLUSIONS: After abdominoperineal resection and total mesorectal excision, good rates of local control may be achieved provided surgical technique is meticulous.

Adenocarcinoma↗
PubMed1990

Radiotherapy in the treatment of pancreatic cancer.

In the last two decades, we have witnessed revolutionary advances in pancreatic imaging as well as increased availability of megavoltage radiotherapy equipment and sophisticated radiotherapy planning devices. Several advances in the radiotherapy of pancreatic cancer have been made for the patient with resectable disease. Postoperative radiotherapy combined with chemotherapy confers a survival advantage after 'curative' resection. Preoperative and intraoperative intraoperative radiotherapy may do the same, but this requires further evaluation. Preoperative irradiation may improve the resectability rate, but the clinical data are still very limited. For locally unresectable disease, PHD radiotherapy with adjuvant 5-FU should now be the standard treatment in suitable cases with a median survival time of about one year. High LET radiation beams have failed to produce improved survival in two prospective randomized studies. Intraoperative radiotherapy is an effective means of pain control and enhances control of local disease, but has not been shown to improve survival rate significantly. Interstitial radiotherapy also improves local control, but it is associated with a high mortality rate and an even higher major complication rate. Wide-area radiation therapy and preoperative radiotherapy both seem to show promise in this group of patients. Patients with metastatic disease should be treated palliatively on an individual basis.

Combined Modality Therapy↗
PubMed2004

Large cell neuroendocrine carcinoma of the lung: an aggressive disease potentially treatable with surgery.

BACKGROUND: Assessment of clinical and pathologic features of large cell neuroendocrine carcinoma to confirm its specificity in the setting of high grade neuroendocrine pulmonary tumors. METHODS: From 1989 to 2001, 123 patients with a neuroendocrine carcinoma were surgically treated in a curative intent at a single institution. According to the 1999 World Health Organization classification, 20 patients were reviewed as having a large cell neuroendocrine carcinoma. Clinical data as well as detailed pathologic analysis and survival were collected. RESULTS: There were 18 men and 2 women. The median age was 62 years. Four patients had a preoperative diagnosis of large cell neuroendocrine carcinoma. The resections consisted of 14 lobectomies and 6 pneumonectomies. There was no operative death. Complications occurred in 7 patients (35%). Four patients had a stage I of the disease, 4 had stage II, 9 had stage III, and 3 had stage IV. At follow-up (median, 46 months), 13 patients died from general recurrence and 7 patients were still alive. Median time to progression was 9 months (range, 1 to 54 months). The 5-year survival rate was 36% (median, 49 months) and it seemed to be negatively influenced by the disease stage (54% for stage I-II vs 25% for stage III-IV; p = 0.07), the presence of metastatic lymph node (45% for N0/N1 vs 17% for N2; p = 0.12), or vessel invasion (66 vs 25%; p = 0.18). CONCLUSIONS: Large cell neuroendocrine carcinoma predominantly occurred in men. An accurate tissue diagnosis was rarely obtained preoperatively. Although overall survival after resection was substantial, large cell neuroendocrine carcinoma frequently showed pathologic features of occult metastatic disease, such as lymph node or vessel invasion, or both.

Adult↗
PubMed1987

Neuroanatomical approach to radical cystoprostatectomy with preservation of sexual function.

The technique for radical cystoprostatectomy has been modified to avoid injury to the branches of the pelvic plexus that innervate the corpora cavernosa. Although the course of the neurovascular bundles in the region of the prostate and urethra has been well charted, the exact relationship of the cavernous nerves to the seminal vesicles and bladder has remained unclear. In an effort to delineate this anatomy more clearly, detailed anatomical dissections were performed on 9 male human cadavers. This study demonstrated that the pelvic plexus is located retroperitoneally on the lateral wall of the rectum 5 to 11 cm. from the anal verge with its midpoint related to the tip of the seminal vesicle. The cavernous branches travel in a direct route from the pelvic plexus toward the posterolateral base of the prostate, gradually coalescing from a group of fibers approximately 12 mm. wide to a more organized bundle approximately 6 mm. wide at the level of the prostate. Because the bulk of the pelvic plexus and its important branches are located lateral and posterior to the seminal vesicles, the seminal vesicles can be used as a landmark intraoperatively to avoid injury to the pelvic plexus when ligating the posterior pedicle. During the last 5 years 25 men have undergone radical cystoprostatectomy. Pathological evaluation of all specimens demonstrated negative surgical margins and no patient has had locally recurrent tumor. Of the patients undergoing cystectomy alone 83 per cent are potent. Although all patients undergoing urethrectomy were able to have erections postoperatively, only 40 per cent have erections that are sufficient for intercourse. These data indicate that to date it is possible to perform radical cystoprostatectomy with preservation of sexual function in the majority of patients without compromise to the curative aspects of the radical operation.

Adult↗
PubMed2003

Early neoplasias of the gallbladder and bile duct: an "unstable" biliary epithelium?

Benign tumours of the biliary tree are rare. In particular, only anecdotal cases of intraductal villous adenomas have been reported. The polyp-cancer sequence has not been observed in the biliary epithelium, in contrast to the paradigm of colorectal carcinogenesis. This report presents the case of a 64-year-old woman with a past history of cholelithiasis who had two early neoplasias involving the biliary epithelium: an adenocarcinoma in situ of the gallbladder and a common bile duct (CBD) villous adenoma with high-grade dysplasia. The tumours presented 4 years apart. The clinical features and combined radiological, cytological, and surgical modalities leading to the diagnosis of intraductal villous adenoma are presented. The endoscopic ultrasound (EUS) characteristics of villous adenoma of the CBD are described. While the prognosis on both occasions appears excellent following curative resections of both tumours detected at an early stage, it is possible that further neoplasia involving the biliary tree may recur. There are currently no data on optimal surveillance modalities. It may be hypothesized that the gallbladder and biliary epithelium share a similar mechanism for carcinogenesis to that observed in the colonic adenomacarcinoma sequence.

Adenoma, Villous↗
PubMed1994

MHCPEP: a database of MHC-binding peptides.

MHCPEP is a curated database comprising over 4000 peptide sequences known to bind MHC molecules. Entries are compiled from published reports as well as from direct submissions of experimental data. Each entry contains the source protein (when known), an estimate of binding affinity and critical anchor residues (if identified), and is fully referenced. The present format of the database allows test string matching searches. The database can be accessed via Internet using gopher.

Binding Sites↗
PubMed1996

MHCPEP--a database of MHC-binding peptides: update 1995.

MHCPEP is a curated database comprising over 6000 peptide sequences known to bind MHC molecules. Entries are compiled from published reports as well as from direct submissions of experimental data. Each entry contains peptide sequence, MHC specificity and when available, experimental method, observed activity, binding affinity, source protein, anchor positions, as well as publication references. The present format of the database allows text string matching searches but can easily be converted for use in conjunction with sequence analysis packages. The database can be accessed via Internet using Gopher, FTP or WWW.

Computer Communication Networks↗
PubMed1997

MHCPEP, a database of MHC-binding peptides: update 1996.

MHCPEP is a curated database comprising over 9000 peptide sequences known to bind MHC molecules. Entries are compiled from published reports as well as from direct submissions of experimental data. Each entry contains the peptide sequence, its MHC specificity and, when available, experimental method, observed activity, binding affinity, source protein, anchor positions and publication references. The present format of the database allows text string matching searches but can easily be converted for use in conjunction with sequence analysis packages. The database can be accessed via Internet using WWW, FTP or Gopher.

Amino Acid Sequence↗
PubMed2006

Loco-regional recurrence from colon cancer: a population-based study.

BACKGROUND: The survival after colon cancer surgery has not improved to the same extent as after rectal cancer treatment and studies on loco-regional recurrence after colon cancer surgery are scarce. The aim of this study was to assess the problem of loco-regional recurrence after potentially curative resections for colon cancer, regarding incidence, risk factors, management, and outcome. METHODS: All 1,856 patients submitted to potentially curative surgery for colon cancer in the Stockholm/Gotland region in Sweden between 1996 and 2000 were followed until January 2005 or until death. Follow-up data were prospectively collected. Risk factors for loco-regional recurrences were analyzed, treatment and outcome for patients with recurrence was studied. RESULTS: The cumulative 5-year incidence of loco-regional recurrence was 11.5%. Tumor locations in the right flexure and in the sigmoid colon, bowel perforation and emergent surgery were identified as independent risk factors for loco-regional recurrence. The risk also increased with increasing T- and N-stage. The median survival for all 192 patients with loco-regional recurrence was 9 months. Surgery was performed in 110 (57%) patients. In 23 (12%) patients a complete tumor clearance was achieved and the estimated 5-year survival in this group was 43%. CONCLUSION: Loco-regional recurrence from colon cancer is a significant clinical problem. A multidisciplinary treatment approach, including preoperative staging, a complete resection of the recurrence and more effective adjuvant treatments may improve the outcome.

Adenocarcinoma↗
PubMed1998

Dose-intensive therapy in small cell lung cancer.

Basic to curative treatment for small cell lung cancer (SCLC) are the principles of dose response, combination chemotherapy, and combined-modality therapy. Theory and experimental and clinical data suggest that solid tumors recur, despite initially responding to chemotherapy due to drug resistance. Resistance to chemotherapy is potentially overcome by using 5- to 10-fold higher doses. To decrease the emergence of drug resistance, combinations of active non-cross-resistant agents are used. Hematopoietic stem cell support provides the opportunity to test dose response to the limits of organ tolerance. Dose-intensive therapy for lung cancer patients is complicated by the fact that this disease most often occurs in an older-aged population (median, 60 to 65 years) with underlying smoking-related comorbid disease, early metastatic spread, and enhanced risk of secondary smoking-related malignancies. In a phase II feasibility trial just activated, patients younger than 60 years of age with limited-stage SCLC are being treated with four cycles of cisplatin and etoposide and concurrent twice-daily chest radiotherapy to 45 Gy (150-cGy fractions). Those patients achieving complete or near-complete response will receive high-dose cyclophosphamide/cisplatin/ carmustine with autologous stem cell support. Upon recovery, prophylactic cranial irradiation will be given. Results could lead to a phase III trial testing the concept of dose intensification. This article reviews evidence for the contribution of dose intensification to response and survival in the treatment of SCLC, the adequacy of the clinical trial's design to address these relationships, and suggestions for future directions. The strategies of dose-intensive induction therapy, multicycle dose-intensive combination therapies, chest radiography, and stem cell purging trials will be discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Selective COX-2 inhibitors and dual acting anti-inflammatory drugs: critical remarks.

Non steroidal anti-inflammatory drugs (NSAIDs) are still the most commonly used remedies for rheumatic diseases. But NSAIDs produce serious adverse effects, the most important being gastric injury up to gastric ulceration and renal damage. Several strategies have been adopted in order to avoid these shortcomings, especially gastrointestinal toxicity. So, non steroidal anti-inflammatory drugs have been associated with gastroprotective agents that counteract the damaging effects of prostaglandin synthesis suppression: however, a combination therapy introduces problems of pharmacokinetics, toxicity, and patient s compliance. Also incorporation of a nitric oxide (NO)-generating moiety into the molecule of several NSAIDs was shown to greatly attenuate their ulcerogenic activity: however, several findings suggest a possible involvement of NO in the pathogenesis of arthritis and subsequent tissue destruction. A most promising approach seemed to be the preparation of novel NSAIDs, specific for the inducible isoform of cyclooxygenase (COX-2): they appear to be devoid of gastrointestinal toxicity, in that they spare mucosal prostaglandin synthesis. However, a number of recent studies raised serious questions about the two central tenets that support this approach, namely that the prostaglandins that mediate inflammation and pain are produced solely via COX-2 and that the prostaglandins that are important in gastrointestinal and renal function are produced solely via COX-1. So, increasing evidence shows that COX-2 (not only COX-1) also plays a physiological role in several body functions and that, conversely, COX-1 (not only COX-2) may also be induced at sites of inflammation. Moreover, COX-2 selective NSAIDs have lost the cardiovascular protective effects of non-selective NSAIDs, effects which are mediated through COX-1 inhibition (in addition, COX-2 has a role in sustaining vascular prostacyclin production). The products generated by the 5-lipoxygenase pathway (leukotrienes) are particularly important in inflammation: indeed, leukotrienes increase microvascular permeability and are potent chemotactic agents; moreover, inhibition of 5-lipoxygenase indirectly reduces the expression of TNF-alpha (a cytokine that plays a key role in inflammation). This explains the efforts to obtain drugs able to inhibit both 5-lipoxygenase and cyclooxygenases: the so-called dual acting anti-inflammatory drugs. Such compounds retain the activity of classical NSAIDs, while avoiding their main drawbacks, in that curtailed production of gastroprotective prostaglandins is associated with a concurrent curtailed production of the gastro-damaging and bronchoconstrictive leukotrienes. Moreover, thanks to their mechanism of action, dual acting anti-inflammatory drugs could not merely alleviate symptoms of rheumatic diseases, but might also satisfy, at least in part, the criteria of curative drugs. Indeed, leukotrienes are pro-inflammatory, increase microvascular permeability, are potent chemotactic agents and attract eosinophils, neutrophils and monocytes into the synovium. Finally, recent data strongly suggest that dual inhibitors may have specific protective activity also in neurodegeneration.

Animals↗