Biomedical subjects

R Jakesz

Publications and source records attributed to R Jakesz.

At least 19 recordsLinked to original sources

PubMed2006

Selective resection of colorectal liver metastases.

AIMS: Safety of liver surgery for colorectal cancer liver metastases after neoadjuvant chemotherapy has to be re-evaluated. PATIENTS AND METHODS: Two hundred Patients were prospectively analyzed after surgery for colorectal cancer liver metastases between 2001 and 2004 at our institution. Special emphasis was given to perioperative morbidity and mortality under modern perioperative care. RESULTS: There was no in-hospital mortality and the perioperative morbidity was 10% (20/200). Four patients had to be reoperated due to bile leak or intraabdominal abscess. The remainder either had infectious complications or pleural effusion and/or ascites requiring tapping. Variables strongly associated with decreased survival were T, N, G and UICC (International Union against cancer) classification of the primary, hepatic lesions>5 cm and elevated tumour markers. Short disease free interval and neoadjuvant chemotherapy without response predicted impaired recurrence free survival (RFS). Multivariate analysis revealed lymph node status and differentiation of the primary, presence of extrahepatic tumour and gender as factors associated with decreased survival. Administration of neoadjuvant chemotherapy was not associated with higher postoperative morbidity or prolonged hospital stay. CONCLUSIONS: Modern dissection techniques and improved perioperative care contributed to a very low rate of surgery-related morbidity (10%) and a zero percent mortality which was also observed in patients pretreated with neoadjuvant chemotherapy prior to resection. Liver resection in experienced hands has become a safe part in the potentially curative attempt of treating patients with metastatic colorectal cancer.

Adult↗

PubMed2006

Improved quality of life after sympathetic block for upper limb hyperhidrosis.

BACKGROUND: The aim of the study was to assess two disease-specific quality of life (QoL) instruments after limited endoscopic thoracic sympathetic block (TS) at T4 for upper limb hyperhidrosis. METHODS: : Between 2001 and 2005, 112 patients underwent 223 TS procedures in a prospective study. Some 103 patients (92.0 per cent) had palmar, 87 (77.7 per cent) had axillary and 75 (67.0 per cent) had combined hyperhidrosis. QoL questionnaires devised by Keller et al. and Milanez de Campos et al. were employed before and after treatment. Mean(s.d.) follow-up was 21.9(10.1) months. RESULTS: A total of 106 patients (94.6 per cent) were evaluated. All patients with palmar hyperhidrosis were completely or almost dry after surgery. Side-effects of compensatory sweating and gustatory sweating were observed in 17.0 and 28.3 per cent of patients respectively. QoL improved after TS in 100 per cent (Keller) and 97.3 per cent (Milanez de Campos) of patients illustrated by ameliorated scores of 78.7 and 67.8 per cent, respectively (both P < 0.001). Both questionnaires showed that compensatory sweating resulted in reduced postoperative QoL (P = 0.011, Keller; P = 0.032, Milanez de Campos). CONCLUSION: Endoscopic sympathetic block at T4 leads to improved QoL. Both current questionnaires fulfilled validation criteria for disease-specific QoL instruments in upper limb hyperhidrosis.

Adult↗

PubMed2006

An update on ovarian suppression/ablation.

Adjuvant ovarian function suppression is acknowledged today as effective therapy for premenopausal patients with early breast cancer. Various modalities have been applied to achieve this treatment option: First, early investigations comparing ovarian ablation with chemotherapy identified similar outcomes in terms of patients' rates of disease-free survival (DFS). Second, prospective randomized trials have more recently focused on luteinizing hormone-releasing hormone analogues (LHRHa) that induce medical ovarian suppression and avoid the morbidity and irreversibility associated with surgical ovariectomy or irradiation. These trials analyzed the value of treatment with goserelin or other LHRHa, with or without tamoxifen, as against chemotherapy. Goserelin was subsequently established as a valid alternative, and our own results demonstrated that goserelin + tamoxifen is more effective and better tolerated in hormone-responsive patients. Third, other multiple-arm studies have compared LHRHa + chemotherapy with chemotherapy alone. Addition of tamoxifen to goserelin + chemotherapy was shown to improve DFS, and significant benefits in goserelin-treated patients were seen irrespective of use of chemotherapy or tamoxifen. Finally, ongoing trials are addressing the appropriate duration of LHRHa therapy and other unresolved issues. In summary, combined ovarian suppression with adjuvant goserelin and tamoxifen is considered to be at least as effective as chemotherapy in premenopausal breast cancer patients. Published reports have demonstrated that ovarian suppression is a safe means of reducing risk of recurrence in estrogen receptor-positive women and underlined its use as a competitive alternative to chemotherapy in this patient subset.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Straight and colonic J-pouch reconstruction after low anterior resection.

PURPOSE: A complication after restorative rectal surgery with a straight anastomosis is low-anterior resection syndrome with a postoperatively deteriorated anorectal function. The colonic J-reservoir is sometimes used with the purpose of reducing these symptoms. An alternative method is to use a simple side-to-end anastomosis or a coloplasty. MATERIAL AND METHODS: Three-hundred fiftyseven patients with rectal cancer undergoing total mesorectal excision (TME). Three-hundred (84.0%) received a low anterior resection with primary anastomosis and colo-rectal n = 194 (64.6%) or colo-anal anastomosis n = 106 (35.3%). A colonic pouch using the descending colon was created in 24 patients and in 75 patients respectively. Surgical results and complications were recorded. Patients were followed with a functional evaluation at 6 and 12 months postoperatively. RESULTS: Patient characteristics in both groups were very similar regarding gender, age, tumor level, and Dukes' stages. A large proportion of the patients received short-term preoperative radiotherapy (72%). There was no significant difference in surgical outcome between the 2 techniques with respect to anastomotic height, perioperative blood loss, postoperative complications, reoperations, hospital stay or pelvic sepsis rates except the anastomotic stricture rate in the colonic J-Pouch group after coloanal anastomosis (p < 0.02). CONCLUSIONS: These data show that either a colonic J-pouch or a straight anastomosis performed on the descending colon in low-anterior resection with TME are methods that can be used with similar expected surgical and functional results.

Anal Canal↗

PubMed2005

Fulvestrant ('Faslodex') in pre-treated patients with advanced breast cancer: a single-centre experience.

Fulvestrant ('Faslodex') is a new oestrogen receptor (ER) antagonist with no agonist effects. This report describes the experience of a single centre including 126 postmenopausal women with advanced breast cancer (ABC) in a fulvestrant Compassionate Use Programme. All patients had previously received endocrine treatment for early or ABC. Patients received fulvestrant as first- (n=7), second- (n=51), third- (n=50) or fourth-line endocrine therapy (n=18) for ABC (median duration of treatment: 4 months [range 3-27(+) months], follow-up: 13 months [range 1-38(+) months]). Twelve patients had partial responses (PR) and 43 patients experienced stable disease (SD) > or = 6 months (objective response rate: 9.5%; clinical benefit [CB] rate: 43.6%). Ten of 12 patients with a PR had HER2-negative tumours, and 9/12 had ER-positive and progesterone receptor (PgR)-positive disease (two patients had unknown HER2 status and one had unknown ER and PgR status). Nine of the 18 patients with HER2-positive tumours experienced CB with fulvestrant. Although CB rates were similar when fulvestrant was given as first- to fourth-line endocrine treatment, the proportion of those experiencing CB who had a PR appeared to decrease when fulvestrant was used later in the sequence. Fulvestrant was well tolerated; six patients experienced adverse events (all grade I/II). These data demonstrate that fulvestrant is an effective and well-tolerated therapy for patients with ABC progressing on prior therapies.

Adult↗

PubMed2005

A prospective randomised trial to study the role of levamisole and interferon alfa in an adjuvant therapy with 5-FU for stage III colon cancer.

The purpose of this trial was to examine the efficacy of the addition of levamisole (LEV) or interferon alfa (IFN) to an adjuvant chemotherapy with 5-fluorouracil (5-FU) in patients with stage III colon cancer. According to a 2 x 2 factorial study design, 598 patients were randomly assigned to one of four adjuvant treatment arms. Patients in arm one received 5-FU weekly for 1 year, patients in arm two 5-FU plus LEV, in arm three 5-FU plus IFN and patients in arm four 5-FU, LEV and IFN. The relative risk of relapse and the relative risk of death were significantly higher for patients treated with LEV compared with those without LEV treatment (HR 1.452, 95% CI 1.135-1.856, P=0.0028; HR 1.506, 95% CI 1.150-1.973, P=0.0027, respectively). No significant impact on survival was observed for therapy with IFN in the univariate analysis. The addition of LEV to adjuvant 5-FU significantly worsened the prognosis of patients with stage III colon cancer. Interferon alfa had no significant influence on survival when combined with adjuvant 5-FU, but increased the toxicity of therapy substantially.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Preoperative short-term radiation therapy (25 Gy, 2.5 Gy twice daily) for primary resectable rectal cancer (phase II).

To evaluate the feasibility, effectiveness, and long-term bowel function of preoperative hyperfractionated accelerated radiotherapy in primary resectable rectal cancer. A total of 184 consecutive patients (median age 65 years, male : female=2 : 1) with clinical T3Nx rectal adenocarcinoma received preoperative pelvic radiation therapy with single fractions of 2.5 Gy twice daily (interval 6 h between fractions) to a total dose of 25 Gy within 1 week. Surgery was conducted the following week. Postoperative histology revealed UICC stage I in 33%, stage II in 26%, stage III in 34%, and stage IV in 7% of the patients. Median follow-up was 43 months (53 months for surviving patients). The actuarial 4-year-local-recurrence rate was 2.1%, overall recurrence 23%. Disease-specific and disease-free survivals at 4 years (excluding stage IV) were 82 and 69%, respectively. Overall survival for 4 years was 68%. Postoperative mortality was 0.5% (one patient), early anastomotic leakage occurred in 11.4%, and anastomotic stenosis requiring treatment in 6%, of 132 patients with primary anastomosis. Seven of 184 patients (3.8%) died of abdominal complications, all within the first year. Bowel function was satisfactory after more than 5 years. Local control in primarily resectable rectal cancer after 10 x 2.5 Gy is excellent, warranting further evaluation of this treatment.

Adenocarcinoma↗

PubMed2004

High nuclear grade and negative estrogen receptor are significant risk factors for recurrence in DCIS.

INTRODUCTION: Recommendations for adjuvant treatment of DCIS after breast conservation are controversial. We tried to identify further risk factors in a retrospective study of our own practice. PATIENTS AND METHODS: Three hundred and thirty-two patients treated by breast conservation between 1978 and 2001 at the Department of General Surgery, University of Vienna were analysed. Tumour size, nuclear grade, hormone receptors, p53, her-2/neu, multifocality, microinvasion and post-operative therapy (irradiation, tamoxifen or combination) were analysed for their influence on breast recurrence. RESULTS: Overall recurrence rate was 6.1% (8/132). For patients with DCIS showing high nuclear grade or negative estrogen receptor the risk for development of ipsilateral breast recurrence is significantly higher. Newer factors like p53 and her-2/neu do not have any prognostic significance. No recurrence was observed in patients treated by post-operative irradiation and tamoxifen. CONCLUSION: Nuclear grade remains the most significant factor for breast recurrence after DCIS. Hormone receptor status identifies a subset of patients with more favourable prognosis.

Adult↗

PubMed2003

Limited endoscopic thoracic sympathetic block for hyperhidrosis of the upper limb: reduction of compensatory sweating by clipping T4.

BACKGROUND: Endoscopic thoracic sympathicotomy of T2 to T4 (ETS 2-4) has evolved into an effective treatment for severe hyperhidrosis of the upper limb. Complications such as bleeding or Horner's syndrome are rare, but side effects such as compensatory and gustatory sweating occur in 30-50% of patients. Following the Lin-Telaranta classification, we aimed to reduce these side-effects by clipping T4 solely [endoscopic thoracic sympathetic block (ESB 4)]. We present our experience and clinical results using this method, with emphasis on patients' quality of life. METHODS: A total of 176 procedures (91 patients) were carried out in the ETS 2-4 group and 103 procedures (53 patients) in the ESB 4 group: 60.4 and 43.4% had palmar hyperhidrosis, 8.8 and 5.7% had isolated axillary, and 30.8 and 50.9% had combined manifestations, respectively. Follow-up was 22.1 months (obtained from 79.1% of patients) for the ETS 2-4 group and 7.5 months for the ESB 4 group (obtained from 88.7%). RESULTS: The success rate was similar for both groups: 87.9 and 64.5% had completely dry limbs, 9.9 and 35.5% ( p < 0.0002) were nearly dry, and 2.1 and 0% remained wet. (ETS 2-4 vs ESB 4). Although the armpits remained slightly humid in more patients in the ESB 4 group, 100% stated full satisfaction. Complications did not differ significantly. However, compensatory sweating (55.6 vs 8.5%, p = 0.0002) and gustatory sweating (33.3 vs 2.1%, p = 0.0019) were markedly reduced (ETS 2-4 vs ESB 4). Quality of life was assessed by a hyperhidrosis index, which significantly improved in most patients. CONCLUSIONS: ETS 2-4 and ESB 4 have similar success rates in the treatment of upper limb hyperhidrosis. The major side effects of compensatory and gustatory sweating were effectively reduced by the limited method of clipping T4, and patients' satisfaction and improvement in quality of life were remarkable.

Adult↗

PubMed2003

Dendritic cell-based vaccination in solid cancer.

PURPOSE: Dendritic cell (DC)-based immunotherapy is rapidly emerging as a viable tool in cancer treatment. This approach has been used mostly in patients in the presence of defined tumor antigens such as melanoma. In this study, cancer patients with advanced disease that lacks defined tumor antigens were vaccinated with tumor lysate-pulsed DCs. PATIENTS AND METHODS: Twenty patients (pancreatic, hepatocellular, cholangiocellular, and medullary thyroid carcinoma) with stage IV disease were enrolled in the study. In 3-week intervals, freshly isolated autologous CD14 magnetic bead-selected monocytes were cultured in granulocyte-macrophage colony-stimulating factor and interleukin-4 to obtain immature DCs. These cells were pulsed with autologous tumor lysate and matured with tumor necrosis factor alpha. Mature DCs were applied into a groin lymph node, under ultrasound guidance. Adjuvant interleukin-2 (20,000 U/kg) was given subcutaneously daily, for 12 days, after each vaccination. Toxicity, tumor marker profile, immune response, and clinical response were determined. RESULTS: Vaccination was well tolerated. No physical signs of autoimmunity were detected. DC vaccination induced delayed-type hypersensitivity reactivity in 18 patients. Tumor marker responses were observed in eight patients. In addition, in three patients the generation of interferon gamma-positive T cells was induced during the vaccination. Objective changes in measurable lesions or tumor markers were evident in seven of 20 assessed patients. None of the patients was found to meet the criteria for partial or complete responses. CONCLUSION: These data indicate that vaccination with autologous tumor-pulsed DCs generated from peripheral blood is safe and can induce tumor-specific cellular cytotoxicity. Clinical responses are achievable, even in patients with advanced disease.

Adult↗

PubMed2003

Treatment and reconstruction after disconnection of the failed cervical esophagogastric anastomosis.

Reconstruction of the esophageal passage after severe complications of the esophagogastric anastomosis (disconnection, long stenosis) remains a surgical challenge. We describe the course of five patients with cervical defects (n = 4) or stenosis (n = 1) after complications of the cervical esophagogastric anastomosis and successful reconstruction by free jejunal transfer. Cause of failure of the anastomosis was ischemia in two, and compression, bleeding and unknown reasons in the other three patients respectively. In four patients, subsequent treatment consisted of disconnection of the anastomosis. In all cases, reconstruction by free jejunal transfer was done between 8 weeks and 12 months after primary surgery. A perforation of the graft was observed in one patient (decubital ulcer from the split sternum). All patients regained normal swallowing function. Free jejunal transfer is a safe method for reconstruction of short defects with a satisfactory functional result and minimal surgical trauma.

Anastomosis, Surgical↗

PubMed2003

Randomised trial: One cycle of anthracycline-containing adjuvant chemotherapy compared with six cycles of CMF treatment in node-positive, hormone receptor-negative breast cancer patients.

AIM: A randomised, controlled clinical trial was initiated in 1984 to test whether 1 cycle of anthracycline-containing adjuvant chemotherapy improves the outcome of breast cancer patients presenting with stage II disease and negative oestrogen and progesterone receptors (ER, PgR), as compared with 6 cycles of dose-reduced CMF. PATIENTS AND METHODS: Within 7 years 263 women with stage II breast cancer were randomised either to receive 1 cycle of doxorubicin, vinblastine, cyclophosphamide, methotrexate and 5- fluorouracil (AV-CMF) or to receive 6 cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients were stratified for tumour stage, nodal stage, menopausal status, type of surgery and participating centre. RESULTS: After a median follow-up of 100 months, neither disease-free (DFS) nor overall survival (OS) differed significantly between the two groups. CONCLUSIONS: Compared to 6 cycles of a non-standard low-dose CMF regimen 1 cycle of anthracycline- containing adjuvant chemotherapy failed to improve the outcome in women with stage II receptor-negative breast cancer in terms of DFS and OS.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Sequential steroid hormone receptor measurements in primary breast cancer with and without intervening primary chemotherapy.

The objective of this analysis was to determine the accuracy of steroid receptor measurement in large core needle biopsies compared with surgically removed specimens and the influence of preoperative chemotherapy on hormone receptor status. We consecutively performed 722 large core needle biopsies in palpable lesions of the breast. The diagnosis of breast cancer was confirmed upon biopsy in 450 patients; 236 women underwent immediate surgery, and 214 patients received preoperative chemotherapy. We assessed estrogen (ER) and progesterone receptor (PR) in biopsy tissue and surgically removed specimens and calculated accuracy, sensitivity, specificity, the weighted kappa value and Spearman's rank correlation. The modulation of steroid receptor status in preoperatively treated patients was tested by Cochran-Mantel-Haenszel statistics. The accuracy of ER evaluation in the biopsy material of patients without intervening chemotherapy was 91%, sensitivity and specificity were 94% and 80% respectively. Accuracy, sensitivity and specificity were 86% in patients treated preoperatively. In terms of PR assessment, we obtained slightly inferior results: accuracy, sensitivity and specificity were 80%, 73% and 85% respectively in patients without preoperative treatment, and 79%, 48% and 92% respectively in patients undergoing preoperative therapy. Following preoperative chemotherapy, patients showed a significant increase in ER-negative (P=0.02) and PR-negative (P=0.0005) measurements. We have concluded from our results that ER and PR receptor measurement in core needle biopsy is a reliable basis in clinical practice for selecting patients for neoadjuvant endocrine treatment. Preoperative cytotoxic chemotherapy induced a significant extent of variation in the steroid receptor expression of breast cancer cells.

Adult↗

PubMed2002

[Transhiatal laparoscopic approach in epiphrenic esophageal diverticulum].

Epiphrenic diverticula are rare. The exact prevalence of this condition is unknown because asymptomatic patients are usually not discovered. Symptoms are more often the result of an esophageal motility disorder than the diverticulum itself and no correlation exists between the size of the diverticulum and the severity of symptoms. We present a patient suffering from dysphagia, chest pain, food retention and regurgitation because of an epiphrenic diverticulum. The current treatment of choice for symptomatic epiphrenic diverticula is diverticulectomy via a left thoracic approach. We performed a successful abdominal laparoscopic approach.

Deglutition Disorders↗

PubMed2002

Chemotherapy versus hormonal adjuvant treatment in premenopausal patients with breast cancer.

Comparisons between the effects exerted by adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF)-based polychemotherapy and endocrine treatment in premenopausal breast cancer patients are validly drawn in the presence of steroid hormone receptor responsiveness. First, ovarian ablation still remains to show activity compared with chemotherapy in large patient groups. Second, tamoxifen is at least as active in this cohort and, by comparison, produces a significant effect in mortality reduction. Third, induction of reversible amenorrhoea by LHRH analogue administration has shown comparable effects in terms of recurrence-free survival. Finally, recent European investigations have indicated significant recurrence reductions with LHRH analogue-tamoxifen combination strategies. In conclusion, various endocrine treatment modalities have been substantiated as equiefficient to polychemotherapy. Tamoxifen added to a LHRH analogue further diminishes the recurrence rates and now appears to be a valid treatment alternative. We argue that selection of adjuvant systemic therapy for premenopausal breast cancer patients be increasingly guided by knowledge of the steroid hormone receptor levels.

Adult↗

PubMed2002

Teaching laparoscopic cholecystectomy: do beginners adversely affect the outcome of the operation?

OBJECTIVE: To evaluate the safety of elective laparoscopic cholecystectomy (LC) as a supervised teaching procedure. DESIGN: Prospectively documented series, retrospective analysis. SETTING: University teaching hospital, Austria. SUBJECTS: 581 consecutive patients who underwent elective LC for symptomatic cholelithiasis between January 1993 and December 1997. INTERVENTIONS: LC were allocated to three groups: the first (n = 91) were done by supervised beginners (who had done fewer than 11 LC), the second (n = 249) by supervised trainees who had a little experience (they had done more than 10 but fewer than 51 LC), and the third group (n = 241) who were experienced surgeons (they had done more than 50 LC). MAIN OUTCOME MEASURES: Minor and major complications, conversion and reoperation rate, length of operation and postoperative hospital stay. RESULTS: The minor intraoperative complication rates were 36/91 (40%), 115/249 (46%) and 49/241 (20%), respectively (p < 0.001 when experienced surgeons were compared with the 2 trainees' groups). There were no significant differences between the three groups regarding major complications (1/91, 4/249 and 4/241), conversions (5/91, 21/249, and 17/241) and reoperation rate (1/91, 3/249 and 3/241), median (range) length of operation 82 (24-159), 84 (25-249) and 82 (21-234) minutes and hospital stay 4 (3-19), 4 (3-11) and 4 (2-15) days. CONCLUSION: Elective LC for symptomatic cholelithiasis done by trainees under supervision does not increase surgical morbidity.

Austria↗

PubMed2002

Stimulation of autologous antitumor T-cell responses against medullary thyroid carcinoma using tumor lysate-pulsed dendritic cells.

Dendritic cells (DCs) have attracted wide interest because of their unique capacity to elicit primary and secondary antitumor responses. We have generated autologous tumor lysate-pulsed DCs from three patients with medullary thyroid carcinoma (MTC) and tested them for their ability to stimulate cytotoxic T-cell responses against autologous MTC tumor cells in vitro. The aim of our investigations was to evaluate the potential efficacy of DC-based immunotherapy in patients with MTC. DCs were generated from peripheral blood monocytes using GM-CSF and IL-4 (immature DCs) or GM-CSF, IL-4, and TNFalpha (mature DCs). Our results indicate that mature tumor lysate-pulsed DCs are able to elicit a human leukocyte antigen class I-restricted cytotoxic T-cell response against autologous MTC tumor cells, whereas immature tumor lysate-pulsed DCs do not stimulate significant antitumor activity. We feel that our data may be relevant for future clinical trials of active immunotherapy using tumor lysate-pulsed DCs in patients with MTC who have residual or distant disease after surgical treatment. The fact that mature DCs displayed a substantially higher capacity to stimulate autologous antitumor T-cell responses than immature DCs underlines the importance of a maturation step in immunotherapy protocols based on DCs.

Adult↗

PubMed2001

A genetically engineered influenza A virus with ras-dependent oncolytic properties.

The NS1 protein of influenza virus is a virulence factor that counteracts the PKR-mediated antiviral response by the host. As a consequence, influenza NS1 gene knockout virus delNS1 (an influenza A virus lacking the NS1 open reading frame) fails to replicate in normal cells but produces infectious particles in PKR-deficient cells. Because it is known that oncogenic ras induces an inhibitor of PKR, we addressed the question of whether the delNS1 virus selectively replicates in cells expressing oncogenic ras. We show that upon transfection and expression of oncogenic N-ras, cells become permissive for productive delNS1 virus replication, suggesting that the delNS1 virus has specific oncolytic properties. Viral growth in the oncogenic ras-transfected cells is associated with a reduction of PKR activation during infection. Moreover, treatment of s.c. established N-ras-expressing melanomas in severe combined immunodeficiency mice with the delNS1 virus revealed that this virus has tumor-ablative potentials. The delNS1 virus does not replicate in nonmalignant cell lines such as melanocytes, keratinocytes, or endothelial cells. The apathogenic nature of the delNS1 virus combined with the selective replication properties of this virus in oncogenic ras-expressing cells renders this virus an attractive candidate for the therapy of tumors with an activated ras-signaling pathway.

Animals↗