Melphalan-prednisone versus alternating combination VAD/MP or VND/MP as primary therapy for multiple myeloma: final analysis of a randomized clinical study.

Background And Objectives: In the absence of a cure for multiple myeloma (MM) with standard-dose therapy, any strategy that can be expected to increase tumor reduction and to extend survival duration is likely to be of clinical relevance. The primary end-point of the present study was to investigate whether the alternating combination of vincristine-doxorubicin-dexamethasone (VAD) and melphalan-prednisone (MP) or vincristine-mitoxantrone-dexamethasone (VND) and MP could improve the clinical outcome of MM patients thus treated in comparison with those receiving MP alone.

Design And Methods: Between November 1990 and April 1994, 527 previously untreated, stage I-III, MM patients from 29 Italian institutions were randomized to receive one of three remission induction chemotherapy regimens consisting of 8-monthly courses of either MP alone or alternating VAD/MP or VND/MP.

Expression of RB2/p130 tumor-suppressor gene in AIDS-related non-Hodgkin's lymphomas: implications for disease pathogenesis.

In this study we examined 21 cases of AIDS-related lymphomas for genomic organization and expression of RB2/p130 oncosuppressor gene and compared the results with the proliferative features of these neoplasms. We found no mutations in the RB2/p130 gene and unusually high percentages of cells expressing nuclear pRb2/p130 in tumors with a high proliferative activity, such as AIDS-related lymphomas. These findings might suggest that a molecular mechanism usually observed in viral-linked oncogenesis could be involved.

Cell kinetics and cell cycle regulation in lymphomas.

The proliferative indices of non-Hodgkin's lymphomas are useful prognostic indicators and provide information independent of other histological and clinical variables. However, proliferative indices alone do not suffice to characterise cell growth. A high cell production rate may be compensated, almost or fully, by a high cell deletion rate.

Apoptosis in the peripheral blood mononuclear cells as a self-limitation process in human acute pancreatitis.

Background/aim: Acute pancreatitis is primed and sustained by a chain of immuno-inflammatory factors. In this study, we investigated the possible existence of peripheral blood mononuclear cell apoptosis as a self-limitation mechanism in acute pancreatitis.

Methods: Peripheral blood mononuclear cell apoptosis was determined cytofluorometrically daily for 10 days from the onset of the illness in 27 consecutive patients (18 having mild uncomplicated acute pancreatitis and 9 having pancreatitis with complications) and was related to peripheral blood counts, including reticulocytes and reticulocyte fractions, and albumin, fibrinogen, and C-reactive protein levels.

Expression of urocortin mRNA and peptide in the human prostate and in prostatic adenocarcinoma.

Background: Urocortin (UCN) is a recently described neuropeptide member of the CRF family, responsible for the secretion of the proopiomelanocortin-derived peptides from the pituitary gland. Although previous results have demonstrated the synthesis of several neuroendocrine factors in the prostate, no studies have been carried out on the expression of UCN in the human gland.

Methods: UCN expression was evaluated in benign prostatic hyperplasia and prostatic tumor tissues by RT-PCR and immunohistochemistry.

p53 mutation in breast cancer. Correlation with cell kinetics and cell of origin.

Aim: Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factor receptor (EGFR), the oestrogen receptor (ER), and the progesterone receptor (PgR), in breast cancer, but no study has directly compared p53 mutations with these phenotypic and differentiation markers in the same case. The present study was designed to provide some of this information.

Methods: The expression of the p53 and bcl-2 proteins was evaluated by immunohistochemistry in relation to phenotypic characteristics and cellular kinetic parameters (mitotic index and apoptotic index) in 37 cases of ductal carcinoma in situ (DCIS) and 27 cases of infiltrating ductal carcinoma (IDC) of the breast.

Salvage therapy with thalidomide in patients with advanced relapsed/refractory multiple myeloma.

Background And Objectives: Few therapeutic options are presently available for patients with multiple myeloma (MM) who relapse after autologous or allogeneic stem cell transplantation, or for patients who are refractory to conventional chemotherapy and not eligible for salvage high-dose therapy. Thalidomide, a glutamic acid derivative with anti-angiogenic properties, has been recently proposed as an effective therapy for patients with advanced refractory disease. The aim of this study was to evaluate the activity of thalidomide in a large series of MM patients.

Cytokeratin expression patterns as an indicator of tumour progression in oesophageal squamous cell carcinoma.

Recent studies point out that cytokeratins (CKs) are involved in dynamic cell remodeling during cancer progression and particularly, CK expression patterns have been associated with invasion and metastasis. In oesophageal squamous cell cancer (ESCC), lymph node (LNN) metastasis is an important step in disease progression, invariably associated with an ominous prognosis. To assess whether specific CK expression patterns could represent reliable markers of tumor progression, a series of 111 ESCCs (59 lymph node-positive, 52-negative) derived from the high- incidence area of Linxian (Northern China), were subjected to immunohistochemical (IHC) analysis with an extensive panel of CK antibodies.

Increased mouse survival, tumor growth inhibition and decreased immunoreactive p53 after exposure to magnetic fields.

The possibility that magnetic fields (MF) cause antitumor activity in vivo has been investigated. Two different experiments have been carried out on nude mice bearing a subcutaneous human colon adenocarcinoma (WiDr). In the first experiment, significant increase in survival time (31%) was obtained in mice exposed daily to 70 min modulated MF (static with a superimposition of 50 Hz) having a time average total intensity of 5.

Immunoglobulin gene rearrangement analysis in composite hodgkin disease and large B-cell lymphoma: evidence for receptor revision of immunoglobulin heavy chain variable region genes in Hodgkin-Reed-Sternberg cells?

Immunoglobulin heavy chain gene (IgH) rearrangement was studied in a patient showing the occurrence of classical Hodgkin disease and large B-cell lymphoma (LBCL) in the same lymph node. The VHDHJH region was amplified by polymerase chain reaction, the template being the DNA extracted from single Hodgkin and Reed-Sternberg and LBCL cells, microdissected on hematoxylin-eosin-stained sections by laser capture. A repeated VH4DH3JH4 segment was found in Reed-Sternberg cells, whereas a repeated VH3DH3JH4 segment was observed in LBCL cells.

Antiangiogenic therapy in multiple myeloma.

In the recent years, several pieces of evidence have pointed out that disease progression in multiple myeloma (MM) is characterized by an increased bone marrow neovascularization. Targeting the mechanisms that control angiogenesis could thus represent an innovative therapeutic approach to MM. Thalidomide, a glutamic acid derivative with sedative properties, is able to inhibit angiogenesis in murine models; this compound has recently demonstrated to be effective in relapsed/refractory MM, leading to a 30-40% response, coupled with mild systemic toxicity.

The RET/PTC oncogene is frequently activated in oncocytic thyroid tumors (Hurthle cell adenomas and carcinomas), but not in oncocytic hyperplastic lesions.

Hurthle cell adenomas and carcinomas, characterized by the presence of oncocytic cells, are unusual thyroid neoplasms, the treatment of which is still controversial. We analyzed specimens from 49 patients with oncocytic cell nodular lesions including 20 adenomas, 19 carcinomas, and 10 hyperplasias for RET/PTC (papillary thyroid carcinoma) activation, which is the most frequent genetic alteration in PTCs. RET/PTC activation was detected in a significant number of cases of Hurthle cell adenomas and carcinomas, but in 0 of 10 patients with hyperplastic nodules.

Predictive value of skin color for illness severity in the high-risk newborn.

The relationship between skin color and illness severity in the newborn remains untested. We have evaluated the predictive value of skin color readings for illness severity in a population of high-risk newborn infants. A prospective study was conducted on 107 white newborns in the intensive care unit, which were categorized as either high or low severity of illness, defined by the presence of severe neonatal morbidity.

Inactivation of the E-cadherin gene in sporadic diffuse-type gastric cancer.

Loss of the cell adhesion molecule E-cadherin has been observed in a variety of human carcinomas, and germline E-cadherin mutations have been found in several familial cases of diffuse gastric cancer. We sought to determine the prevalence and nature of E-cadherin alterations in "sporadic" gastric carcinomas. We performed comprehensive sequencing of the coding region, loss of heterozygosity (LOH) analysis, and immunohistochemical protein expression determination on 40 sporadic gastric adenocarcinomas.

Molecular therapy for multiple myeloma.

Background And Objectives: Several molecular and cytogenetic advances have suggested novel therapeutic strategies that could help reach an eventual cure for multiple myeloma (MM).

Evidence And Information Sources: Identification of novel, "MM-specific" molecular targets should pave the way for drugs that can specifically attack the neoplastic cells while sparing the normal ones. Drugs that alter the marrow microenvironment--such as bisphosphonates, proteasome inhibitors (e.

Cell proliferation, cell death, E-cadherin, metalloproteinase expression and angiogenesis in gastric cancer precursors and early cancer of the intestinal type.

The aim of this study was to analyse the morphological, kinetic and molecular characteristics of low-grade (LGD) and high-grade dysplasias (HDG) in comparison with intestinal metaplasia type III (IM III) and normal mucosa (NM) as well as with early gastric cancer of the intestinal type (EGC). Based on this it was verified whether these categories are distinct, progressive proliferative steps from IM III to LGD, HGD and EGC, according to Correa's sequence of events. The morphology, mitotic index (MI), and the apoptotic index (AI) were assessed.

Salvage therapy with thalidomide in multiple myeloma patients relapsing after autologous peripheral blood stem cell transplantation.

Background And Objectives: The introduction of high-dose therapy with stem cell support has significantly improved the outcome of patients with multiple myeloma (MM) in terms of increased complete remission (CR) rate and extended survival, both disease-free and overall. Few options, however, are presently available for patients who relapse after single or double autologous stem cell transplantation (SCT). Thalidomide, a glutamic acid derivative with anti-angiogenetic properties, has been recently proposed as salvage treatment for such patients.

Evaluation of HPV, CMV, HSV and EBV in esophageal squamous cell carcinomas from a high-incidence area of China.

Background: Certain viruses, notably human papillomavirus (HPV), cytomegalovirus (CMV), herpes simplex virus (HSV) and Epstein-Barr virus (EBV), are known to produce tumors in animals and cell transformation in vitro and they have been implicated in the pathogenesis of human cancers. All these viruses are also known to infect the esophagus. This study was aimed to determine whether these viruses play any causal role in the etiology of esophageal squamous cell carcinoma.

Quantitative image analysis of oesophageal squamous cell carcinoma from the high-incidence area of China, with special reference to tumour progression and papillomavirus (HPV) involvement.

Background: Despite much research effort, the major prognostic factor of oesophageal squamous cell cancer (ESCC) remains the pathological stage of the disease as defined by the TNM classification, whereas tumour grading is of limited value in this respect, mainly due to its low reproducibility. A better means for disease prognostication based on improved understanding of the pathogenetic mechanisms is urgently required.

Materials And Methods: Among the cohort of 700 ESCC patients from the high-incidence area of China, previously subjected to extensive testing for Human papillomavirus (HPV) involvement by in situ hybridization (ISH) and PCR, a group of 273 patients was randomly selected for analysis of the primary tumour, adjacent mucosa and regional lymph nodes, by histopathology and quantitative image analysis.

Autoantibodies against oxidized LDL in chronic renal failure: role of renal function, diet, and lipids.

Lipid peroxidation (LP) has recently been suggested to trigger the atherosclerotic process as well as to worsen the progression of renal disease. Autoantibodies against oxidized low-density lipoproteins (Ox-LDLAb) were considered to provide a sensitive marker to detect LDL oxidation in vivo. To date few studies have been reported on Ox-LDLAb levels in patients with different degrees of renal failure.

Altered glutathione anti-oxidant metabolism during tumor progression in human renal-cell carcinoma.

It has been proposed that oxidative stress develops in tumors, with important consequences for growth and progression. To investigate this hypothesis, we measured low m.w.

Chemotherapy of secondary leukemias.

Chemotherapy of secondary leukemias is currently still considered to be associated with poor results. However, recent data suggest that the response to remission induction may substantially differ according to the previous medical history of the patients. Therapy related leukemia, arising following exposure to previous alkylating agents or radiotherapy, is often associated with chromosomal abnormalities involving chromosomes 5 and 7 and has a particularly bad response, whereas AML after exposure to epipodophyllotoxins or topoisomerase-II active agents could have a somewhat better response.

All-trans retinoic acid significantly reduces the incidence of early hemorrhagic death during induction therapy of acute promyelocytic leukemia.

Early hemorrhagic death (within the first 10 d of treatment [EHD]) is reported as the main cause of death during induction therapy for acute promyelocytic leukemia (APL). In order to evaluate possible differences in the incidence of EHD during induction regimens based on all-trans retinoic acid (ATRA), we retrospectively analyzed a consecutive series of 86 APL patients, diagnosed and treated at our Institution from 1982. Forty-three patients received combination chemotherapy with anthracyclines and cytosine arabinoside (January 1982 to December 1991), while induction of the remaining 43 was based on ATRA alone or on a combination of ATRA and anthracyclines (January 1992 to October 1996).