Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040.

BACKGROUND: Patients with advanced hepatocellular carcinoma (aHCC) have a poor prognosis and high mortality. Nivolumab monotherapy demonstrated clinical benefit with an acceptable safety profile in patients with aHCC in the CheckMate 040 study. Five-year follow-up of the sorafenib-naive and sorafenib-experienced groups of CheckMate 040 is presented here. PATIENTS AND METHODS: Patients received nivolumab monotherapy at dose levels of 0.1-10.0 mg/kg (dose-escalation phase) or 3 mg/kg (dose-expansion phase) every 2 weeks until disease progression or unacceptable toxicity. Primary endpoints were safety and tolerability (dose escalation), and objective response rate (ORR) by blinded independent central review (BICR) and by investigator as per RECIST version 1.1 (dose expansion). RESULTS: Eighty sorafenib-naive and 154 sorafenib-experienced patients were treated. Minimum follow-up in both groups was 60 months. ORR as per BICR was 20% [95% confidence interval (CI) 12% to 30%] and 14% (95% CI 9% to 21%) in the sorafenib-naive and sorafenib-experienced groups, respectively. Responses occurred regardless of HCC etiology or baseline tumor cell programmed death-ligand 1 (PD-L1) expression levels. Median overall survival (OS) was 26.6 months (95% CI 16.6-30.6 months) and 15.1 months (95% CI 13.0-18.2 months) in sorafenib-naive and sorafenib-experienced patients, respectively. The 3-year OS rates were 28% in the sorafenib-naive and 20% in the sorafenib-experienced groups; 5-year OS rates were 14% and 12%, respectively. No new safety signals were identified; grade 3/4 treatment-related adverse events were observed in 33% and 21% of patients in the sorafenib-naive and sorafenib-experienced groups, respectively. Biomarker analyses showed that baseline PD-L1 expression ≥1% was associated with higher ORR and longer OS compared with PD-L1 <1%. In the sorafenib-naive group, patients with OS ≥3 years exhibited higher baseline CD8 T-cell density compared with those with OS <1 year. CONCLUSION: With 5 years of follow-up, nivolumab monotherapy continued to provide durable clinical benefit with manageable safety in sorafenib-naive and sorafenib-experienced patients with aHCC.

EVITA-a double-blind, vehicle-controlled, randomized phase II trial of vitamin K1 cream as prophylaxis for cetuximab-induced skin toxicity.

Background: Acne-like skin rash is a frequently occurring adverse event associated with drugs against the epidermal growth factor receptor. This randomized vehicle-controlled study investigated the addition of vitamin K1 cream to doxycycline in patients with metastatic colorectal cancer treated with cetuximab. Patients and methods: Patients receiving first-line cetuximab + FOLFIRI were randomly assigned to prophylactic treatment with doxycylin and vitamin K1 cream or doxycycline and the vehicle. The primary end point of the study was the incidence of grade ≥ 2 skin rash (NCI CTCAE version 4.02) during 8 weeks of skin treatment. Secondary end points comprised skin rash according to a more thorough tripartite skin toxicity score (WoMo), quality of life, efficacy, and compliance. The study had 80% power to show a 20% reduction of the incidence of grade ≥ 2 skin rash. Results: A total of 126 patients were analyzed. The incidence of skin rash grade ≥ 2 was comparable between the arms. Likewise, no difference was seen in the WoMo score with respect to the percentage of skin affected. However, starting in week 5 and increasing over time patients treated with vitamin K1 cream had less severe rash and fewer fissures. Quality of life as well as efficacy and compliance with study medication and anticancer treatment was comparable in both arms. Conclusion: The primary end point of decreasing grade ≥ 2 skin rash was not met. However, using vitamin K1 cream as part of prophylactic treatment decreased the severity of acne-like skin rash according to WoMo, an alternative and more thorough skin toxicity scoring tool.

Identifying indications for percutaneous (PTC) vs. endoscopic ultrasound (EUS)- guided "rendezvous" procedure in biliary obstruction and incomplete endoscopic retrograde cholangiography (ERC).

BACKGROUND: The variety of rendezvous (RV) procedures has recently been extended by EUS- and PTCD-guided procedures as a complementary means to conventional ERCP. We have identified indication criteria and the potential of biliary PTCD-guided vs. EUS-guided RV. METHODS: Consecutive patients with bile duct obstruction who underwent RV were included. In all, ERCP alone was unable to achieve treatment success. Indication, technical success, and outcome in PTCD- vs. EUS-guided RV were retrospectively compared to identify criteria that indicate preference of RV technique. Site of obstruction, clinical scenario (stenosis with abscess vs. no abscess) and reason for previous failure of ERC were evaluated. RESULTS: In 32 patients, three different indications for RV procedures were identified: First, a one-step access to assist in failed ERCP (type 1, intra-ductal RV); second, temporary drainage for prolonged treatment of complex biliary disease (type 2, intra-ductal RV), and drainage of cholangio-abscess with re-establishing bile outflow (type 3, intra-abscess RV). Indication of PTCD- vs. EUS-guided rendezvous was competitive in type 1, but exclusive in favor of PTCD in types 2 and 3. The site of biliary obstruction indicated the anatomic location of RV procedures. CONCLUSIONS: This classification may help to define inclusion criteria for prospective studies on biliary RV procedures. Choice of therapeutic strategy depends on the anatomic location of the biliary obstruction and the type of the biliary lesion. PTCD-guided RV might improve outcome in cholangio-abscess.

Self-expandable metal stent for malignant colonic obstruction: outcome in proximal vs. left sided tumor localization.

INTRODUCTION: The aim of this study was to evaluate the outcome of through-the-scope (TTS) implanted self-expanding metal stent (SEMS) comparing left-sided vs. proximal placement with regard to complications and outcome in palliation of malignant colorectal obstruction. MATERIAL AND METHODS: All patients were consecutively retrospectively enrolled to this study between January 2009 and February 2012 due to impending or prevalent complete malignant colorectal obstruction. TTS applicable uncovered nitinol SEMS with unique flexible properties were used (Taewoong Medical, South Korea). Left-sided obstruction (aboral from the left flexure) was compared to proximal (from the ileo-cecal valve to the left flexure) localization. All patients have been discussed in the interdisciplinary tumor conference and the recommendation to treat by endoscopic stent placement was given in consensus. RESULTS: A total of 15 patients was enrolled to this study (10 male and 5 female; mean age 68.3 ± 15.4 years, range 48 - 94), five patients with obstructions located in the proximal hemicolon whereas ten patients had a left-sided malignancy. Technical success was achieved in all cases and there was no early complication noticed. Three late complications included tumor overgrowth (n = 1), stent occlusion (1), and dislocation (1). Stent-in-stent insertion achieved, again, clinical success. The site of SEMS implantation (proximal vs. left colon) had no impact on patient outcome or complication rate. SEMS patency duration was 269.8 ± 175.2 days (range 30 - 570) and mean survival of the patients was 305.1 ± 279.3 days (range 16 - 990). CONCLUSION: TTS application of flexible, non-covered SEMS seems to be safe and effective for palliation of malignant colorectal obstruction independent of localization of the tumor in the colon.

S-1 maintenance therapy in Caucasian patients with metastatic esophagogastric adenocarcinoma-final results of the randomized AIO MATEO phase II trial.

PURPOSE: Platinum-fluoropyrimidine combinations are standard of care for treatment of metastatic esophagogastric adenocarcinoma. The optimal duration of first-line chemotherapy is unknown, however, and maintenance strategies have not yet been established. DESIGN: MATEO is an international randomized phase II trial exploring efficacy and safety of S-1 maintenance therapy in human epidermal growth factor receptor 2 (HER2)-negative advanced esophagogastric adenocarcinoma. After 3 months of first-line platinum-fluoropyrimidine-based induction therapy, patients without progression were randomized in a 2 : 1 allocation to receive S-1 monotherapy (arm A) or to continue combination chemotherapy (arm B). The primary objective was to show non-inferiority of overall survival in the S-1 maintenance group. Progression-free survival, adverse events, and quality of life were secondary endpoints. RESULTS: From 2014 to 2019, 110 and 55 patients were randomized in arm A and arm B, respectively (recruitment closed prematurely). Median overall survival from randomization was 13.4 months for arm A and 11.4 months for arm B [hazard ratio 0.97 (80% confidence interval 0.76-1.23), P = 0.86]. Median progression-free survival from randomization was 4.3 and 6.1 months for arm A versus arm B, respectively [hazard ratio 1.10 (80% confidence interval 0.86-1.39), P = 0.62]. Patients in arm A had numerically fewer treatment-related adverse events (84.9% versus 93.9%) and significantly less peripheral sensory polyneuropathy ≥grade 2 (9.4% versus 36.7%). CONCLUSIONS: S-1 maintenance following platinum-based induction therapy leads to non-inferior survival outcomes compared with the continuation of platinum-based combination. Toxicity patterns favor a fluoropyrimidine maintenance strategy. These data challenge the continued use of platinum combination chemotherapy after response to 3 months induction therapy in patients with advanced human epidermal growth factor receptor 2-negative esophagogastric adenocarcinoma.

Treatment of hepatocellular carcinoma with sorafenib - focus on special populations and adverse event management.

Sorafenib, a receptor tyrosine kinase-inhibitor with anti-proliferative and anti-angiogenic activity, is currently the only approved systemic treatment for patients with hepatocellular carcinoma. It inhibits downstream signaling of VEGFR-2, PDGFR, c-Kit receptors and BRAF. Over the last four years comprehensive experience with sorafenib in this indication has been accumulated. In this review we discuss the current data on the use of sorafenib in patients with advanced HCC including special patient populations such as patients with impaired liver function, patients after transplantation, and others. The most frequent side-effects and practical tips on how to manage them are discussed in detail. In addition, we summarize the current experimental data on the use of sorafenib in combination treatment, e. g., together with transarterial chemoembolisation or other targeted agents.

KRAS mutation in metastatic pancreatic ductal adenocarcinoma: results of a multicenter phase II study evaluating efficacy of cetuximab plus gemcitabine/oxaliplatin (GEMOXCET) in first-line therapy.

BACKGROUND: Genetic alterations within the epidermal growth factor receptor (EGFR) pathway, including KRAS mutations, have been demonstrated to be associated with response to EGFR inhibitors like cetuximab in colorectal cancers. Mutations in the KRAS gene have been found in 70-90% of pancreatic cancers. Unfortunately, the addition of cetuximab to chemotherapy did not increase response or survival in patients with advanced pancreatic cancer in phase II and phase III studies. The aim of this study was to evaluate the relationship between KRAS mutations and response or survival in patients with metastatic pancreatic cancer treated with cetuximab plus chemotherapy. METHODS: Within a multicenter phase II trial, 64 patients with metastatic pancreatic cancer were treated with cetuximab in combination with gemcitabine and oxaliplatin until disease progression. Analyses of the EGFR pathway, including KRAS mutations, could be performed in 25 patients. Analyses were carried out following microdissection of the tumor. RESULTS: Fourteen (56%) of the 25 patients examined harbored a point mutation in codon 12 of the KRAS gene. No differences between the groups were noted in median progression-free survival (104 days in KRAS wild-type patients vs. 118 days in patients with KRAS mutations). Overall survival was longer in wild-type patients compared to patients with KRAS mutations (263 vs. 162 days), but the difference did not reach statistical significance. A further analysis of our clinical phase II trial showed that the presence of a rash was significantly correlated with overall survival. CONCLUSIONS: KRAS mutation in codon 12 may be associated with reduced survival compared to KRAS wild type. The role of KRAS mutations for cetuximab therapy in pancreatic cancer warrants further investigation in larger trials to exclude an epiphenomenon. Furthermore, the development of a rash is indicative of clinical benefit.

Peroral cholangioscopy for diagnosis and therapy of biliary tract disease using an ultra-slim gastroscope.

High-resolution video cholangioscopy is expected to improve diagnostic validity for diseases of the biliary tract. We report our experience in using an ultra-slim gastroscope for diagnosis and treatment of biliary tract disease. Cholangioscopy was attempted in 25 cases (22 patients) and succeeded in 22 cases (success rate 88%; 19 patients). Cholangiocellular carcinoma (CCC) was diagnosed by cholangioscopy in five of 10 cases (histopathologically confirmed in four), or ruled out in five. Cholangioscopy was used to detect stones in mega-choledochus (n=3), to clarify the postoperative condition of the bile ducts (n=2), to diagnose bile duct varices (n=1), and to release a dislodged self-expanding metal stent (n=1), and others. Argon plasma coagulation was successfully completed in a patient with mucin-producing adenomatosis of the bile ducts. One case of non-fatal air embolism occurred before replacing air with CO2 insufflation. In summary, peroral cholangioscopy with an ultra-slim gastroscope is feasible and helpful in selected patients, improving diagnostic validity, and offering new therapeutic interventions. This technique should only be performed using CO2 insufflation.

[Gangliocytic paraganglioma--a rare differential diagnosis of a submucosal duodenal tumor]. / Gangliozytisches Paragangliom--eine seltene Differenzialdiagnose eines submukösen duodenalen Tumors.

We report on the case of a 36-year-old male patient who was found to have a submucosal duodenal tumour during the diagnostic work-up of gastrointestinal bleeding. After exclusion of other tumour manifestations complete endoscopic resection was performed. Histologically a gangliocytic paraganglioma was diagnosed, a very rare type of a duodenal neuroendocrine tumour. This case report discusses the epidemiology, diagnostic work-up and therapeutic options for this rare tumour type.

[Colorectal cancer--current screening, treatment and follow-up standards]. / Kolorektales Karzinom--aktuelle Standards der Früherkennung, Diagnostik, Therapie und Nachsorge.

Colorectal cancer is the second most prevalent cancer in Germany. Following the nationwide introduction of the screening colonoscopy at the age of 55 years, more patients are currently diagnosed at an earlier and therefore potential curable stage. The aim for the coming years will be to further accelerate the acceptance of colorectal cancer screening. Furthermore, the treatment of patients with colorectal cancer has become more effective due to interdisciplinary approaches as well as the introduction of new anti-cancer drugs. The current comprehensive treatment standards were communicated in the form of a guideline in 2008. This article will summarise the most important standards for colorectal cancer screening as well as for treatment and follow-up as a guide for insurance purposes.

Cetuximab plus gemcitabine/oxaliplatin (GEMOXCET) in first-line metastatic pancreatic cancer: a multicentre phase II study.

Targeting the epidermal growth factor receptor pathway in pancreatic cancer seems to be an attractive therapeutic approach. This study assessed the efficacy of cetuximab plus the combination of gemcitabine/oxaliplatin in metastatic pancreatic cancer. Eligible subjects had histological or cytological diagnosis of metastatic pancreatic adenocarcinoma. The primary end point was response according to RECIST. Patients received cetuximab 400 mg m(-2) at first infusion followed by weekly 250 mg m(-2) combined with gemcitabine 1000 mg m(-2) as a 100 min infusion on day 1 and oxaliplatin 100 mg m(-2) as a 2-h infusion on day 2 every 2 weeks. Between January 2005 and August 2006, a total of 64 patients (22 women (34%), 42 men (66%); median age 64 years (range 31-78)) were enrolled at seven study centres. On October 2007, a total of 17 patients were alive. Sixty-two patients were evaluable for baseline and 61 for assessment of response to treatment in an intention-to-treat analysis. Six patients had an incomplete drug combination within the first cycle of the treatment plan (n=4 hypersensitivity reactions to the first cetuximab infusion, n=2 refused to continue therapy). Reported grade 3/4 toxicities (% of patients) were leukopaenia 15%, anaemia 8%, thrombocytopaenia 10%, diarrhoea 7%, nausea 18%, infection 18% and allergy 7%. Cetuximab-attributable skin reactions occurred as follows: grade 0: 20%, grade 1: 41%, grade 2: 30% and grade 3: 10%. The intention-to-treat analysis of 61 evaluable patients showed an overall response rate of 33%, including 1 (2%) complete and 19 (31%) partial remissions. There were 31% patients with stable and 36% with progressive disease or discontinuation of the therapy before re-staging. The presence of a grade 2 or higher skin rash was associated with a higher likelihood of achieving objective response. Median time to progression was 118 days, with a median overall survival of 213 days. A clinical benefit response was noted in 24 of the evaluable 61 patients (39%). The addition of cetuximab to the combination of gemcitabine and oxaliplatin is well tolerated but does not increase response or survival in patients with metastatic pancreatic cancer.

Treatment and prevention of rat glioblastoma by immunogenic C6 cells expressing antisense insulin-like growth factor I RNA.

Rat C6 glioma cells express insulin-like growth factor I (IGF-I) and form rapidly growing tumors in syngeneic animals. When transfected with an episome-based vector encoding antisense IGF-I complementary DNA, these cells lost tumorigenicity. Subcutaneous injection of IGF-I antisense-transfected C6 cells into rats prevented formation of both subcutaneous tumors and brain tumors induced by nontransfected C6 cells. The antisense-transfected cells also caused regression of established brain glioblastomas when injected at a point distal to the tumor. These antitumor effects result from a glioma-specific immune response involving CD8+ lymphocytes. Antisense blocking of IGF-I expression may reverse a phenotype that allows C6 glioma cells to evade the immune system.

Polymorphisms in the methylenetetrahydrofolate reductase gene are determinant for vascular complications after liver transplantation.

OBJECTIVE: The aim of this study was to evaluate the role of the C677T-MTHFR (methylenetetrahydrofolate reductase)-polymorphism (CC, CT and TT) for vascular complications in liver transplant recipients. DESIGN: Retrospective study. SETTING: Hepatology-Transplantation-Unit, Johann Wolfgang Goethe-University, Frankfurt am Main. SUBJECTS: 48 liver transplant recipients were included, no dropouts. METHODS: MTHFR polymorphism was detected by PCR amplification and digestion with Hinfl restriction enzyme. Vascular complications after liver transplantation were detected from the patients' records. The total serum homocysteine (HCY) was analyzed with high-pressure liquid chromatography. RESULTS: In the wild-type group (CC), the HCY levels were slightly high (14.0+/-1 micro M). Among the patients with the CT polymorphism, the HCY values were elevated (22.5+/-3 micro M). In the homozygous TT group, there was a significant increase (31.2+/-6 micro M, P<0.01) of the HCY values. The percentage of vascular complications was higher in the heterozygous CT (47%) and homozygous TT (62.5%) group compared with wild-type CC (21%). Patients with a homozygous TT genotype of the MTHFR polymorphism with a vascular complication had a highly significant elevated HCY level compared to the other genotype groups, both with and without any vascular complications (P<0.001). Recipients with an elevated HCY and the TT polymorphism have a higher probability of developing a vascular complication after transplantation (odds ratio: 4.3 and 11.0; 95% confidence interval: 1.15, 12.25 and 1.41, 85.24). CONCLUSIONS: The C677T polymorphism in the MTHFR gene and subsequent elevation of the total serum HCY is significantly associated with an increased incidence of vascular complications in liver transplant recipients.

Insulin-like growth factor type I biology and targeting in malignant gliomas.

Growth factors such as insulin-like growth factor type I (IGF-I), epidermal growth factor (EGF), vascular-endothelial growth factor (VEGF) and transforming growth factor beta (TGF-beta) are present during the development of the CNS. When they reappear in the mature brain they are overexpressed in neoplastic glia, participating in the development of the most common human brain malignant tumor, glioblastoma multiforme, which is invariably fatal. Progress in treatment of this disease involves an increase in median survival from 8 to 11 months to an average of 15 months, rarely to 18 months. We do not know any therapy, which can make a complete stop of this neoplasm. To inhibit this process various anti-growth factor therapies have been proposed. We describe actual applications of growth factor inhibitors and antisense approaches. The review highlights results obtained with the promising treatment of glioblastoma multiforme: using inhibitors and antisense targeting growth factors, including IGF-I, their receptors, and their downstream signaling effectors including glycogenesis and oncogenes. The antisense strategies have been the subject of many clinical trials, especially the IGF-I antisense approach. Such antisense therapies, already introduced in clinical trial in the USA, Europe and Asia, will soon become the preferred alternative treatment for human glioblastoma multiforme. The inhibition of signal transduction pathways common to growth factors and glycogenesis appears as a parallel challenge to glioblastoma multiforme inhibition studies.

Visually induced analgesia during massage treatment in chronic back pain patients.

BACKGROUND: Previous findings suggest that watching sites of experimental and chronic pain can exert an analgesic effect. Our present study investigates whether watching one's back during massage increases the analgesic effect of this treatment in chronic back pain patients. METHODS: Twenty patients with chronic back pain were treated with a conventional massage therapy. During this treatment, patients received a real-time video feedback of their own back. Watching a neutral object, a video of another person of the same sex being massaged, a picture of the own back, and keeping one's eyes closed were used as controls. These conditions were presented in randomized order on five separate days. RESULTS: All conditions yielded significant decreases in habitual pain intensity. The effect of real-time video feedback of the own back on massage treatment was the strongest and differed significantly from the effect of watching a neutral object, but not from the other control conditions, which may have induced slight effects of their own. CONCLUSIONS: Repeated real-time video feedback may be useful during massage treatment of chronic pain. SIGNIFICANCE: This study shows that inducing visual induced analgesia during massage treatment can be helpful in alleviating chronic pain.

Watching your pain site reduces pain intensity in chronic back pain patients.

BACKGROUND: Chronic back pain (CBP) is a frequent debilitating and often treatment-resistant disorder. The awareness of one's own body seems to be essential in pain reduction through visual input. Visual feedback of the back reduces experimental pain perception in CBP at this site and watching the back during repeated lumbar spine movements reduces movement-evoked pain. In this study, we tested whether visual feedback alone can reduce habitual pain in CBP. METHODS: In a within-subject design, 19 CBP patients participated in an online visual feedback condition, watching one's own back. This was compared to several control conditions, such as watching a neutral object (book), a video of another person of the same sex, a picture of the own back, and keeping one's eyes closed in randomized order on five separate days. In each experimental session, participants rated habitual pain intensity and unpleasantness before and after the experimental manipulation. RESULTS: We present evidence that visual feedback by watching the site of chronic pain on a video screen alone is sufficient to reduce habitual chronic pain. No additional manipulation or movement was necessary. CONCLUSIONS: These results suggest that online video feedback may be helpful in alleviating chronic pain.

Prism adaptation contrasts perceptual habituation for repetitive somatosensory stimuli.

Prism adaptation (PA) is a non-invasive procedure that requires performing a visuo-motor pointing task while wearing prism goggles inducing a visual displacement of the pointed target. This procedure involves a reorganization of sensorimotor coordination, and induces long-lasting effects on numerous higher-order cognitive functions in healthy volunteers and neglect patients. Prismatic displacement (PD) of the visual field can be induced when prisms are worn but no sensorimotor task is required. In this case, it is unlikely that any subsequent reorganization takes place. The effects of PD are short-lived in the sense that they last as long as prisms are worn. In this study we aimed, to the best of our knowledge for the first time, at investigating whether PA and PD induce changes in the perception of intensity of nociceptive and non- nociceptive somatosensory stimuli. We induced, in healthy volunteers, PD (experiment 1), or PA (experiment 2) and asked participants to rate the intensity of the stimuli applied to the hand undergoing the visuo-proprioceptive conflict (experiment 1) or adaptation (experiment 2). Our results indicate that: 1) the visuo-proprioceptive conflict induced by PD does not reduce the perceived intensity of the stimuli, 2) PA prevents perceptual habituation for both nociceptive and non-nociceptive somatosensory stimuli. Moreover, to investigate the possible underlying mechanisms of the effects of PA we conducted a third experiment in which stimuli were applied both at the adapted and the non-adapted hand. In line with the results of experiment 2, we found that perceptual habituation was prevented for stimuli applied onto the adapted hand. Moreover, we observed the same finding for stimuli applied onto the non-adapted hand. This result suggests that the detention of habituation is not merely driven by changes in spatial attention allocation. Taken together, these data indicate that prisms can affect the perceived intensity of somatosensory stimuli, but only when PA is induced.

Activation of an alpha-fetoprotein/receptor pathway in human normal and malignant peripheral blood mononuclear cells.

Alpha-fetoprotein (AFP) is mainly synthesized by the fetal liver and the yolk sac with minor contributions of several non-hepatic fetal tissues, variable according to the species considered. Most fetal cells, whatever their origin, possess the ability to bind and to endocytose the protein. This property, which is considered to be lost in differentiated cells of the adult, may be resumed in tumoral cells and is due to the expression of specific AFP receptors at the cell surface. Cytochemical and immunological approaches, combined with in situ hybridization, were used to investigate the specific uptake and synthesis of human AFP in several classes of peripheral blood mononuclear cells (PBMC) and in several malignant cell lines of hematopoietic origin. With the exception of quiescent T lymphocytes, all cells investigated specifically bound AFP. Both normal and malignant blood mononuclear cells expressed mRNA transcripts of AFP which were translated into the protein during a well established period of cellular growth. These results suggest that an AFP/receptor autocrine system might operate in normal and malignant blood mononuclear cells. Its physiological role is discussed in relation to recent work from our laboratory--providing experimental evidence that AFP, throughout its interaction with specific cell receptors, regulates and facilitates the entry of fatty acids into living cells undergoing growth and differentiation.