LYVE-1 immunohistochemical assessment of lymphangiogenesis in endometrial and lung cancer.

Aims/methods: Normal and malignant pulmonary and endometrial tissues were analysed for lymphatic vessels to assess the process of lymphangiogenesis and its role at these sites, using specific immunostaining for LYVE-1 and the panendothelial marker CD31.

Results: Lymphatics were clearly demonstrated in some normal tissues (myometrium, bronchial submucosa, and intestinal submucosa), but not in others (endometrium and alveolar tissue). LYVE-1 positive lymphatic vessels were detected at the tumour periphery of endometrial and lung carcinomas, but not within the main tumour mass.

c-erbB-2 related aggressiveness in breast cancer is hypoxia inducible factor-1alpha dependent.

c-erbB-2-positive breast carcinomas are highly aggressive tumors. In vitro data on breast cell lines showed that c-erbB-2 enhanced translational efficiency of hypoxia inducible factor-1alpha (HIF1alpha) production (Laughner et al., Mol Cell Biol 2001;21:3995-4005).

Tumour angiogenesis: vascular growth and survival.

Angiogenesis starts at the edge of a malignant epithelial tumour concurrently with tumour cell invasion and stromatogenesis, i.e. the formation of specific connective tissue stroma amenable to easy penetration by endothelial and tumour cells.

VEGF gene sequence variation defines VEGF gene expression status and angiogenic activity in non-small cell lung cancer.

Different vascular endothelial growth factor (VEGF) gene polymorphisms have been shown to result in different VEGF gene responsiveness to various stimuli and different capacity for VEGF protein production. In the present study, we examined four VEGF gene polymorphisms in thirty-six individuals with non-small cell lung cancer (NSCLC). Gene polymorphisms were correlated with the VEGF protein expression in cancer cells and the tumor angiogenic activity.

Conformal hypofractionated and accelerated radiotherapy with cytoprotection (HypoARC) for high risk prostatic carcinoma: rationale, technique and early experience.

Recent radiobiological analysis of the radiotherapy results for prostate cancer revealed that prostate carcinoma behaves as a late responding tissue, sharing an alpha/beta ratio lower than 2Gy. These findings suggest that hypofractionation may be more effective. Reduction of the overall treatment time could further increase response by abrogating the effect of rapid tumor repopulation.

Angiogenesis and vascular survival ability in ovarian adenocarcinomas.

This study was designed to investigate the prognostic relevance of ovarian tumour angiogenesis in terms of tumour angiogenic activity (TAA) and vascular survival ability (VSA), i.e. the ability of newly formed vessels to survive once incorporated into the main tumour mass.

Assessment and management of cutaneous reactions with amifostine administration: findings of the ethyol (amifostine) cutaneous treatment advisory panel (ECTAP).

Purpose: To review reports of severe skin reactions during amifostine treatment.

Methods And Material: The expert panel reviewed postmarketing reports of skin reactions and discussed strategies for evaluation and management.

Results: Between 1994 and April 2002, 35 events were classified as severe skin reactions worldwide: erythema multiforme (8), Stevens-Johnson syndrome (10), toxic epidermal necrolysis (11), toxicoderma (3), and bullae (3).

BNIP3 expression is linked with hypoxia-regulated protein expression and with poor prognosis in non-small cell lung cancer.

BNIP3 is a proapoptotic protein regulated by hypoxia-inducible factor 1. We analyzed BNIP3 expression in 105 tumor samples from early operable, non-small lung cancer and the relationship of expression to hypoxia-inducible factor 1alpha, other hypoxia-regulated pathways, and prognosis. There was strong cytoplasmic expression in >10% of cells in 40 of 105 cases.

Interferon regulatory factor-1 (IRF-1) suppression and derepression during endometrial tumorigenesis and cancer progression.

Interferon regulatory factor-1 (IRF-1) is a tumor suppressor gene presumed to be involved in the control of cellular proliferation and transformation. Given that the IRF-1 is consistently expressed in the normally cycling endometrium, the question was raised of the possible role of IRF-1 in the genesis of endometrial adenocarcinoma. A series of 25 normal and 86 malignant endometria was investigated using immunohistochemical techniques and the anti-IRF-1 polyclonal antibody c-20.

Hypoxia-activated tumor pathways of angiogenesis and pH regulation independent of anemia in head-and-neck cancer.

Purpose: Anemia is considered a major factor that counteracts the efficacy of radiotherapy, presumably because of reduced oxygen availability that leads to tumor hypoxia. Nevertheless, anemia is not the only factor defining oxygen availability, because a poor and/or immature vascular network may prevent blood flow and tumor oxygenation. Furthermore, the ability of tumors to upregulate hypoxia-regulated molecular pathways may affect radiosensitivity by mechanisms independent of the traditional concept of "oxygen effect.

Association of -634G/C and 936C/T polymorphisms of the vascular endothelial growth factor with spontaneous preterm delivery.

Background: There is convincing evidence for a central role of vascular endothelial growth factor (VEGF) in fetal and placental angiogenesis. Our present study was undertaken to examine the possible relationship between two common functional VEGF gene polymorphisms (- 634G/C and 936C/T), linked with altered VEGF gene responsiveness, and spontaneous preterm delivery.

Methods: Genomic DNA was extracted from whole blood from 54 women with preterm labor and 79 menopausal women with at least two term spontaneous labors.

Vascular endothelial growth factor gene polymorphisms and pre-eclampsia.

Vascular endothelial growth factor (VEGF) plays a crucial role in physiological vasculogenesis and vascular permeability and has been implicated in the pathogenesis of pre-eclampsia. Our present study was undertaken to identify associations between three functional VEGF gene polymorphisms, linked with altered VEGF gene responsiveness, and pre-eclampsia. The study involved 42 pre-eclamptic and 73 healthy control women who were genotyped for the -2578C/A, -634G/C and 936C/T polymorphisms of the VEGF gene.

Phytobezoars as a cause of small bowel obstruction associated with a carcinoid tumor of the ileocecal area.

Carcinoid tumors are slowly growing malignant neoplasms associated with an indolent clinical course. About 60% of such tumors are located within the gastrointestinal tract. We describe an unusual case of small bowel obstruction associated with a carcinoid tumor of the ileum.

Tumour angiogenic activity and vascular survival ability in bladder carcinoma.

Background: Tumour angiogenic activity (TAA) is an important prognostic factor in many human tumours, including transitional cell carcinomas of the urinary bladder. The new tumour vessels are formed in the invading tumour front. This peripheral tumour area is internalised as soon as the growing tumour forms a new front.

"Stromatogenesis" and tumor progression.

"Stromatogenesis" is the formation of new stroma occurring, in parallel with the neoplastic process, at sites of active tumor invasion, i.e., at the free surface of a developing exophytic tumor, at the invading tumor front of an advancing endophytic tumor, and at sites of tumor metastasis, wherein the newly formed stroma disrupts the continuity of normal structures, cleaving paths for the invading tumor cells.

Amifostine: is there evidence of tumor protection?

A large body of experimental evidence suggests that amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD) is a selective cytoprotector of normal tissues. Nevertheless, several experimental studies, most of which were conducted in the early 1980s, suggest that amifostine may protect tumor tissues, although to a much lower degree than its protective effect on normal tissues. Based on a critical literature review, we conclude that any experimental evidence suggesting tumor protection is weak.

Assessment of highly angiogenic and disseminated in the peripheral blood disease in breast cancer patients predicts for resistance to adjuvant chemotherapy and early relapse.

The assessment of tumor molecular features in combination with the detection of occult malignant cells may provide important clinical information, beyond the standard staging of breast cancer. Using a nested RT-PCR technique, we assessed prospectively the presence of cytokeratin-19 (CK19) mRNA positive cells in the blood of 100 operated patients with breast cancer before the initiation of adjuvant chemotherapy and local radiotherapy. Tissue samples were prospectively collected and analyzed for estrogen (ER) and progesterone (PgR) receptor, c-erbB-2 overexpression, mutant-p53 and bcl-2 protein accumulation, proliferation index and microvessel density (MVD).

Lactate dehydrogenase isoenzymes 1 and 5: differential expression by neoplastic and stromal cells in non-small cell lung cancer and other epithelial malignant tumors.

Background/aims: Lactate dehydrogenase-5 (LDH-5), an isoenzyme composed of 4 M-polypeptide chains, catalyzes the conversion of pyruvate to lactate with an unparalleled efficiency (anaerobic oxidation), but this function of LDH gradually fades away as the number of H over M chains increases. Thus, LDH-1, another component isoenzyme made up of 4 H-polypeptide chains, favors aerobic oxidation of pyruvate by pyruvate dehydrogenase.

Methods: Using immunohistochemistry in this study, we explored the expression of LDH-1 and LDH-5 in a variety of normal and malignant tissues, including lung, breast, endometrium, urinary bladder and large intestine.

Vascular endothelial growth factor (VEGF) expression in operable gallbladder carcinomas.

Aim: To investigate the angiogenic and prognostic role of vascular endothelial growth factor (VEGF) in operable gallbladder carcinomas.

Methods: Sixty patients with early gallbladder carcinomas, treated with surgery alone, were investigated immunohistochemically for the expression of VEGF, thymidine phosphorylase (TP) and new blood vessel formation. The results were correlated with clinico-pathological features and prognosis.

Amifostine induces anaerobic metabolism and hypoxia-inducible factor 1 alpha.

Purpose: The cytoprotective mechanism of amifostine (WR-2721) implies free radical scavenging and DNA repair activities. We investigated additional cytoprotective pathways involving intracellular hypoxia and the activation of the hypoxia-inducible factor (HIF) pathway, a key transcription factor regulating glycolysis, angiogenesis and apoptosis, which is also linked with radioresistance.

Materials And Methods: The glucose and oxygen levels in the peripheral blood of patients receiving 1000 mg amifostine were determined at various time-points in order to investigate the metabolic changes induced by amifostine.

The vascular network of tumours--what is it not for?

It is becoming almost a dogma that tumours cannot grow beyond 1-2 mm(3) unless they are supported by a rich vascular supply 1. It is true that tumours promote angiogenesis and that highly vascularized carcinomas have, in general, a more aggressive clinical course than carcinomas of low vascularization 23. However, a study of intratumoral angiogenesis reveals that the newly formed vessels are commonly deprived of those structural qualities that would allow them to perform an optimal oxygenation function 3.

Neoplastic stroma and epithelium show up-regulation of platelet-derived endothelial cell growth factor/thymidine phosphorylase in colorectal carcinomas but not adenomas.

Tumor angiogenesis, a crucial step in tumor growth and progression, is regulated by an increasing number of angiogenic factors. One of those is platelet-derived endothelial cell growth factor, recently shown to bethymidine phosphorylase (TP), which reversibly catalyzes the phosphorylation of thymidine to deoxyribose-1-phosphate and thymine. TP overexpression in tumors has been reported, but the differential expression of this enzyme in the colorectal adenoma-carcinoma sequence has not been examined in detail.

Hypoxia-inducible factors 1alpha and 2alpha are related to vascular endothelial growth factor expression and a poorer prognosis in nodular malignant melanomas of the skin.

Hypoxia is a key regulatory factor in tumour growth, activating angiogenesis, glycolysis and cell migration. It is readily recognized by the intracellular accumulation of hypoxia-inducible factor 1alpha (HIF1alpha) and HIF2alpha. Accumulation of HIF1alpha and HIF2alpha was detected immunohistochemically in a series of 46 nodular malignant melanomas of the skin (epithelioid cell variant), treated with wide local excision.

Enhanced expression of SPARC/osteonectin in the tumor-associated stroma of non-small cell lung cancer is correlated with markers of hypoxia/acidity and with poor prognosis of patients.

Secreted Protein Acidic and Rich in Cystein (SPARC)/osteonectin is a nonstructural matricellular protein involved in cell-matrix interaction during tissue remodeling and embryonic development. Using a novel monoclonal antibody (10-255), we examined immunohistochemically the patterns of SPARC expression in non-small cell lung cancer (NSCLC). High levels of SPARC in normal lung were confined exclusively to the bronchial cartilage.