Malvasia (Vitis vinifera L.) grapes were harvested at 17.8% of soluble solids content (SSC) and placed inside an innovative dehydration room where temperature, relative humidity, and air flow were maintained, respectively, at 15 degrees C, 40%, and 1-1.5 m s(-1). Weight loss of bunches reached approximately 33% in 29 days. SSC increased inversely proportionally with the weight decrease, reaching at the end of experiment 23%. Abscisic acid (ABA) increased rapidly from around 29 to 80 microg g(-1) of dry weight at 11.7% of bunch weight loss and then declined gradually. Lipoxygenase (LOX) showed the same behavior as ABA, whereas alcohol dehydrogenase (ADH), read in the way of ethanol oxidation, increased continuously when the weight loss reached approximately 19.5%. In parallel with the activity of LOX, C6 compound [hexanal, hex-1-enol, (E)-hex-2-enal] concentrations reached a peak at 11.7% of weight loss, whereas ethanol and acetaldehyde increased with the increase of ADH and successively decrease and ethyl acetate increased. Proline increased initially as ABA and successively with the increase of ADH, 5.3-fold increase versus 4.2-fold increase of proteins. Postharvest dehydration of Malvasia grapes shows a biphasic pattern: a first metabolic stress response up to 11.7% of bunch weight loss and a second stress response beyond 19.5% of weight loss. The metabolic mechanism of these postharvest water stress responses is discussed.

Recent progress in elucidating the complex and heterogeneous interactions between malignancy and coagulation or fibrinolysis reactions in humans has clarified the pathogenesis of disseminated intravascular coagulation that occurs with malignancy and has revealed evidence for two distinct pathways of growth regulation based on production by tumor cells of initiators of thrombin formation versus plasminogen activators. We have proposed a preliminary classification of tumors (see Table 2) based on these interactions. Type I tumors are those in which the tumor cells are associated with an intact coagulation pathway that leads to thrombin formation at the tumor periphery but in which the tumor cells lack u-PA. Examples of tumors in this category include SCCL, malignant melanoma, and renal cell carcinoma. Type II tumors are those in which the tumor cells express u-PA but lack an associated coagulation pathway leading to thrombin formation. Examples of type II tumors include prostate cancer, colon cancer, breast cancer, and N-SCLC. Type III tumors are those that express neither of these pathways, or exhibit some other pattern of interaction. Obviously, this formulation must be regarded as hypothetical. However, this concept fits with the limited data available to date from clinical trials. More importantly, this hypothesis can be tested further by means of intervention aimed at interrupting pathways relevant to specific tumor types. Characterization of additional tumor types by the methods described should permit amplification of this classification of tumors and other patterns of interaction may be defined. Exploration of the coagulation-cancer interaction holds considerable promise for gaining new understanding of both the coagulation mechanism and tumor biology. Most intriguing is the prospect that imaginative approaches to cancer treatment may be devised that are not only relatively nontoxic and low cost, but also effective.

SummaryPlatelet counts were evaluated in 714 patients with advanced non-small cell lung cancer (N-SCLC), small cell carcinoma of the lung (SCCL), and colon cancer entered to a clinical trial. Patients had not received prior chemotherapy. Platelet counts were not different in patients who had received radiation therapy prior to entry to the study. In comparison to the other tumor types, patients with N-SCLC demonstrated an increased prevalence of thrombocytosis (counts greater than 400,000/mm3), higher platelet counts at the time of entry to the study, higher over all mean platelet counts, relative preservation of high platelet levels during disease progression, and no relationship between platelet numbers and the amount of chemotherapy given. By contrast, platelet counts in patients with SCCL were negatively correlated with the absolute amount of cyclophosphamide and adriamycin given, and declined most dramatically with disease progression and death. Platelet numbers did not correlate with fibrinopep-tide A or fibrin split product levels suggesting that disseminated intravascular coagulation or fibrinolysis may have had less influence on platelet numbers than certain other factors. By contrast, significant correlations were found for all three tumor types between platelet numbers and other indicators of bone marrow function including anemia, total leukocyte count, and absolute neutrophil count; and the fibrinogen level. Based upon these findings, we postulate that the host response to malignancy, possibly in the form of production of bone marrow-stimulating cytokines, may play a prominent role in regulation of platelet counts in these (and perhaps other) neoplasms, and that a particularly prominent and persistent degree of marrow stimulation exists in patients with N-SCLC.

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A volume of data that has accumulated for over a century has suggested that fibrin may facilitate the persistence and progression of malignancy. Techniques that have been developed recently have shown that fibrin is indeed a component of the connective tissue stroma in human malignancy but in only a few tumor types. However, therapeutic intervention studies with drugs that limit thrombin activity or enhance fibrinolysis have shown favorable clinical effects in at least one such tumor type. These favorable findings affirm the concept that cause-and-effect relationships do, in fact, exist between thrombin generation with fibrin formation and tumor progression, and suggest that a rational basis exists for the design of future drug intervention trials that target reactions relevant to specific tumor types. These findings also provide a basis for the design of experiments capable of defining further the role of fibrin in the integrity of these tumor types. Because fibrinogen is found much more commonly than fibrin in the connective tissue of a variety of human malignancies, attention might reassumably be directed to determining the possible contribution of this molecule as well as of fibrin to tumor progression.

An extensive biomedical literature attests to the controversy regarding the significance of coagulation activation in cancer. It has been known for over a century that thromboembolism may complicate the course of malignancy (1) and that fibrin may occur in association with intravascular tumor deposits in humans (2). That peripheral blood coagulation changes, indicative of disseminated intravascular coagulation (DIC), occur regularly in cancer is common knowledge (3). However, the biological significance of such activation of blood coagulation is still not completely clear. Some investigators claim that it is only an insignificant epiphenomenon in a disease that often involves multiple organ systems and that uses the bloodstream for metastatic dissemination. However, other investigators, on the basis of recent clinical and experimental data, including therapeutic intervention studies with antithrombotic drugs, have argued that such activation of the coagulation mechanism might be capable of contributing to progression of malignancy (4-11). The purpose of this review is to evaluate critically the evidence that addresses the significance of blood coagulation activation in malignancy by analyzing the extent, pattern, and possible role of fibrin deposition in situ in tumor tissues. Particular emphasis will be placed on defining the evident heterogeneity that exists between tumor types in an attempt to interpret the existing literature on the coagulation-cancer interaction that is both intriguing and confusing. Fibrin Deposition in Solid Tumors O'Meara (12) first called attention to the possibility of fibrin deposition in solid tumors. However, more convincing evidence that fibrinogen-related proteins were localized in solid tumors came from the work of investigators who showed that systemic administration of fibrinogen together with antifibrinogen antibody leads to their sequestration in animal and human tumors (13, I4).Laki and Yancey (15) reviewed their earlier work that showed direct conversion of fibrinogen to fibrin by cultured malignant cells that were placed in a fibrinogen solution. Fibrin was observed by electron microscopy adjacent to these tumor cells following their innoculation into mice. Other investigators demonstrated fibrinogen-related proteins by immunofluorescence in several experimental and human neoplasms (15, 16). The conclusions derived from these early reports, the results of which Supported in part by the Italian Association for Cancer Research (A.I.R.C.), Milan, Italy (V.C.

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