Phase II trial of gallium nitrate,amonafide and teniposide in metastatic non-small cell lung cancer

Summary Fifty-five patients with metastatic non-small cell lung cancer (NSCLC) were entered into this phase II randomized study for evaluating three new agents: gallium nitrate, amonafide and teniposide. The patients had to have ECOG performance status 0 or 1, no prior chemotherapy, and adequate hematological, hepatic and renal functions. Forty-seven patients were eligible and evaluable. Fourteen were randomized to receive gallium nitrate, 18 to amonafide and 15 to teniposide. Seventy-four percent of eligible patients were male. The majority of patients (89%) had an ECOG performance status 1. ECOG grade 4 toxicity occurred twice in patients on gallium nitrate, seven times on amonafide and 18 times on teniposide. The cause of death was attributed to amonafide in one patient (from sepsis) and to teniposide in two patients (due to infection and leukopenia). There was no objective response in all the patients entered. The overall survival times ranged from 2 weeks to 156 weeks with a median of 23 weeks. There were no survival differences among the three treatment arms. We conclude that gallium nitrate, amonafide and teniposide are inactive in metastatic NSCLC and do not warrant any further testing in this disease.The contents of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.     

Effects of malnutrition on the acute phase response of plasma proteins in patients undergoing total gastrectomy

The serum level of six acute phase proteins (APP) has been evaluated preoperatively and for a few days in the postoperative period. Thirty patients undergoing total gastrectomy for gastric cancer have been studied in two subgroups according to their nutritional status. Those with gastric cancer had significantly higher baseline serum levels of alpha 1 acid glycoprotein (alpha1AGP) and C-reactive protein (CRP) than a control group. Malnourished patients also had reduced acute phase response for alpha1AGP and alpha 1 antitrypsin (alpha1AT) a higher increase of CRP and fibrinogen, and a lower decrease for transferrin and retinol binding protein (RBP).     

Provisional "normograms" for identifying adenocarcinomas of the prostate or colon and hepatocellular carcinoma derived from their distribution of proteins separated by two-dimensional electrophoresis

The distribution of proteins in samples from 8 prostate and 4 colon adenocarcinomas and 1 hepatoma was analyzed by 2-dimensional protein electrophoresis. Composite "normograms" based upon their distribution of proteins were developed from these patterns. Particular attention was paid to acidic proteins between pI 3.5 and 5.9. Of 161 proteins enumerated, 23 of the first 135 were present in prostate cancers, compared with 68 in colon cancer and 85 in the hepatoma. The 26 proteins denoted from nos. 135 to 161 were prostate associated, and none was evident in the colon or hepatoma samples. Twenty-seven prostate, 20 colon, and 48 liver cancer proteins were "unique" to each of the 3 cancers, respectively. The patterns of protein associated with each type of cancer were so dissimilar that with this technique no difficulty should be experienced in distinguishing these carcinomas originating from 3 different types of "stem" cells without obligatory recourse to microscopy.     

Systemic and pulmonary vascular resistance in brain death

BACKGROUND: Hemodynamic instability is known to affect brain dead subjects and it can be dangerous for the viability of transplantable organs. Aim of the present study was to assess the hemodynamic performance in brain dead subjects, the changes during the legal observation period and the results of therapeutic management. METHODS: The authors evaluated 28 consecutive adult brain dead subjects, all in intensive treatment, controlled ventilation, infusion therapy and/or dopamine administration and continuous direct monitoring of arterial pressure. Ten hemodynamic parameters have been registered by the thermodilution method and the Swann-Ganz catheter. The Legal Committee performed measurements at the beginning (T0) and the end (T6) of the observation period, which lasts 6 hours according to the current law on death certification (Law N. 578/93). RESULTS: Low systemic and pulmonary vascular resistances have been documented in the majority of subjects (75%), both treated only with fluids and with the additional dopamine administration (dosage lower than 10 ug/Kg/min). The above-mentioned reduction was similar at the two different monitored times (T0 and T6). CONCLUSIONS: This situation can be ascribed to the destruction of the cerebral vasoactive centers and the consequent hypotension is due to autonomic nervous system dysfunction. Hemodynamic instability must be treated by fluids and inotropic drugs, but they may cause cardiac and respiratory problems, thus it is suggested to use also low doses of vasoconstrictive drugs, provided that cardiac condition allows this therapeutic strategy.     

The role of positron emission tomography in selecting patients with metastatic cancer for adrenalectomy

Metastases to the adrenal glands usually signal disseminated disease. However, isolated metastases do occur that may be curable with adrenalectomy. Functional imaging with positron emission tomography (PET) can differentiate benign from malignant pathology and isolated from disseminated metastases. The purpose of this study was to determine whether PET scanning can influence the outcome of adrenalectomy for metastatic disease. We conducted a retrospective review of eight patients undergoing adrenalectomy for presumed isolated metastatic disease from 1985 through 1997. The patients included six women and two men with an average age of 58 (range, 36-74). Their primary tumors were six lung carcinomas, one renal cell carcinoma, and one colon carcinoma. The adrenal masses were located on the right in six patients, on the left in one, and bilaterally in one. Before operation, all patients were evaluated by chest and abdominal CT. Four patients were also evaluated by PET scan. Six right, one left, and one bilateral adrenalectomies were performed. Associated organ resections included two right partial nephrectomies and one right total nephrectomy, one left partial nephrectomy, two distal pancreatectomies, one splenectomy, and two partial hepatic resections. All eight patients survived operation. There were no major perioperative complications, but one patient required readmission for congestive heart failure. Three of the four patients who did not have PET scanning died from 4 to 48 months after operation with disseminated disease from lung, colon, and renal carcinoma respectively. The remaining patient who did not have PET scanning is alive and well 11 years later. Two of the four patients who had PET scans showing isolated disease are alive at 28 and 43 months after operation, whereas the other two died of disseminated disease at 29 and 36 months after operation. We conclude that 1) adrenalectomy can provide survival benefit in patients with isolated metastases, and 2) PET scanning is useful in confirming isolated metastatic disease and selecting patients for adrenalectomy.     

Prognostic Significance of Skeletal Muscle Loss During Early Postoperative Period in Elderly Patients with Esophageal Cancer

Annals of Surgical Oncology -     

Begelomab for severe refractory dermatomyositis: A case report

Rationale:Severe refractory idiopathic inflammatory myopathy (IIM) represents a challenge for the clinician. The lack of efficacy of available tools reflects our incomplete insight into the molecular events sustaining the inflammatory tissue damage in these patients. We present the first case of refractory IIM treated with anti-dipeptidyl peptidase-4 (DPP-4)/cluster of differentiation 26 (CD26) monoclonal antibody.Patient concerns:A 55-year old man presented with proximal muscle weakness, diffuse erythematous skin lesions which rapidly evolved into ulcerations, dysphagia and dysphonia.Diagnosis:Increased serum creatine kinase levels and histological findings at muscle and skin biopsies were compatible with the diagnosis of dermatomyositis (DM). Several lines of treatment failed to control the disease including steroids, mycophenolate mofetil, tacrolimus, intravenous immunoglobulins and rituximab. Despite therapy, the patient also had recurrent intestinal vasculitis causing bowel perforation. Concurrently, DPP-4/CD26 expression in the patient''s skin and skeletal muscle was observed.Interventions:The patient was treated with begelomab, a murine immunoglobulin G2b monoclonal antibody against DPP-4/CD26.Outcomes:Dysphagia, skin lesions and intestinal vasculitis resolved and the patient experienced a significant improvement of his quality of life.Conclusion:Blockade of DPP-4/CD26, which is expressed on T cells and mediates T cell activation and function, is safe and might be effective in patients with refractory DM.     

Long pentraxin‐3 as an epithelial–stromal fibroblast growth factor‐targeting inhibitor in prostate cancer

Fibroblast growth factors (FGFs) exert autocrine/paracrine functions in prostate cancer by stimulating angiogenesis and tumour growth. Here dihydrotestosterone (DHT) up‐regulates FGF2 and FGF8b production in murine TRAMP‐C2 prostate cancer cells, activating a FGF‐dependent autocrine loop of stimulation. The soluble pattern recognition receptor long pentraxin‐3 (PTX3) acts as a natural FGF antagonist that binds FGF2 and FGF8b via its N‐terminal domain. We demonstrate that recombinant PTX3 protein and the PTX3‐derived pentapeptide Ac‐ARPCA‐NH₂ abolish the mitogenic response of murine TRAMP‐C2 cells and human LNCaP prostate cancer cells to DHT and FGFs. Also, PTX3 hampers the angiogenic activity of DHT‐activated TRAMP‐C2 cells on the chick embryo chorioallantoic membrane (CAM). Accordingly, human PTX3 overexpression inhibits the mitogenic activity exerted by DHT or FGFs on hPTX3_TRAMP‐C2 cell transfectants and their angiogenic activity. Also, hPTX3_TRAMP‐C2 cells show a dramatic decrease of their angiogenic and tumourigenic potential when grafted in syngeneic or immunodeficient athymic male mice. A similar inhibitory effect is observed when TRAMP‐C2 cells overexpress only the FGF‐binding N‐terminal PTX3 domain. In keeping with the anti‐tumour activity of PTX3 in experimental prostate cancer, immunohistochemical analysis of prostate needle biopsies from primary prostate adenocarcinoma patients shows that parenchymal PTX3 expression, abundant in basal cells of normal glands, is lost in high‐grade prostatic intraepithelial neoplasia and in invasive tumour areas. These results identify PTX3 as a potent FGF antagonist endowed with anti‐angiogenic and anti‐neoplastic activity in prostate cancer. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.