. Advances in the use of photosensitizers for detection and treatment of malignant tumors during the previous reviews in this journal have been mainly in the areas of development of potentially useful new photosensitizers (e.g. phthalocyanines and chlorins), further understanding of the mechanisms of photodynamic therapy (PDT), and in dosimetry of light delivery in tissue. Perhaps the most significant advance during the past year has been the initiation of Phase III clinical trials of PDT vs standard therapy in treatment of superficial bladder cancer and obstructive endobronchial tumors. In the final analysis, only such clinical trials can determine the future of this new modality for cancer treatment.

Photosensitizers: therapy and detection of malignant tumors

The Biochemistry of glycoproteins and proteoglycans

The effect of hematoporphyrin derivative photoradiation on tumor and normal tissue microcirculation was studied microscopically in vivo on rats with mammary carcinomas transplanted into subcutis in transparent observation chambers. One day after i.p. injection of hematoporphyrin derivative (15 mg/kg), chambers were exposed to red light (632 ± 2 nm, eight light dose values, 0 to 270 J/cm2). After an initial blanching (ischemia) of the tumor accompanied by apparent vasoconstriction, reperfusion was observed with a slowing down of the tumor circulation, vasodilatation, and eventually a complete stasis, together with diffuse hemorrhages and subsequent necrosis. Besides, in large normal tissue vessels, platelet aggregates were observed, but no hemorrhage. Tumor regrowth occurred unless the tumor circulation and the adjacent normal tissue circulation were both destroyed. Tumor cell viability after treatment was assessed by transplanting the tumor from the chamber into the flank of the same animal. Even after a combined porphyrin and light dose 4 times the lethal dose for all tissues in the chamber, five of five transplanted tumors did regrow. This leads to the conclusion that, in our model system, tumor cell death after photoradiation occurs secondary to destruction of the microcirculation. In order to obtain additional information on normal tissue damage, rat ears were also irradiated. For the same light dose, the biological effect was only slightly larger than that of the normal tissue in the observation chambers, even though the measured ratio of porphyrin concentrations in ears and normal tissue in the chambers (subcutis) was about six.

https://cancerres.aacrjournals.org/content/canres/46/5/2532.full.pdf

Destruction of rat mammary tumor and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers.

P-glycoprotein—A mediator of multidrug resistance in tumour cells

Many inherited polymorphisms in plasma proteins and in enzyme activities of red blood cells are now available as genetic markers to differentiate bloods within a species (see Giblett, 1969, and Harris, 1975). However, the term “blood groups” is still usually retained to describe antigenic differences detected on the red cell surface by means of specific antibodies. Macromolecules occurring in secretions of the same or different species which carry serological specificities related to the red cell antigens are called blood group substances; these substances are designated by the letter or symbol assigned to the corresponding antigen on the red cell surface. In man fifteen well-defined independent blood group systems are recognized, each comprising antigens believed to be the products of alleles at one gene locus or of closely linked gene loci. In addition, there are some very frequent (“public”) and infrequent (“private”) antigens which may belong to established systems or may be parts of new systems (see Race and Sanger, 1975). For only three blood group systems, namely ABO, Lewis, and P, is the chemical nature of the antigens unequivocally established, and this review will be primarily concerned with these systems.

Biochemistry and Genetics of the ABO, Lewis, and P Blood Group Systems

Synthetic and analytical approaches were used to characterize the tumor-localizing components of the porphyrin preparation, hematoporphyrin derivative. From studies involving aqueous and nonaqueous gel exclusion and reverse-phase chromatography, we conclude that localization is mediated by hematoporphyrin derivative components which are among the most hydrophobic in the preparation. This apparent hydrophobicity may derive from hydrogen-bonding phenomena, rather than from absence of hydrophilic functional groups.

https://cancerres.aacrjournals.org/content/canres/43/5/1994.full.pdf

Tumor-localizing Components of the Porphyrin Preparation Hematoporphyrin Derivative

We have measured plasma levels of an alpha-2-L-fucosyltransferase in 18 patients with acute adult leukemia at various clinical stages along with simultaneous bone marrow aspirations and biopsies Patients in remission had significantly lower levels of this enzyme than did nonresponding or relapsing patients Furthermore, plasma levels were correlated with percentage of marrow blast cells This enzyme may serve as a biological marker for monitoring patients with acute leukemia receiving chemotherapy It is particularly helpful as a guide to chemotherapy in patients on whom bone marrow aspirates are technically difficult to obtain

Variation of levels of plasma guanosine diphosphate L-fucose:beta-D-galactosyl alpha-2-L-fucosyltransferase in acute adult leukemia.

Levels of two fusosyltransferases were measured in plasmas of patients with non-Hodgkin's lymphoma at different phases of the disease. The level of a GDP-fucose: galactoside fucosyltransferase (EC 2.4.1.69) was found elevated in nonresponding patients and was correlated with estimated tumor burden. Enzyme levels in the normal range were found in patients in remission, maintained on chemotherapy, or unmaintained. The plasma level of a GDP-fucose; N-acetylglucosaminide fucosyltransferase (EC 2.4.1.68) was elevated in all individuals receiving drug therapy regardless of diesease status, but returned to normal levels during unmaintained remissions.

Evaluation of two plasma fucosyltransferases as marker enzymes in non-Hodgkin's lymphoma.

We have measured the plasma level of a fucosyltransferase in patients with acute myelogenous leukemia and non-Hodgkin's lymphoma at various stages of the disease and in normal controls. This enzyme transfers the sugar fucose from a guanosine diphosphate-l-fucose donor to high-molecular-weight acceptors with a terminal N -acetylglucosamine residue. The enzyme levels of fucosyltrans ferase in individuals free from disease and in patients with untreated leukemia or lymphoma were comparable. A substantial increase in plasma enzyme level was measured during drug-induced remissions, three weeks after drug therapy. The enzyme level fell to the normal range during unmaintained remissions in patients with lymphomas; comparable information for the leukemia is not available since all remissions were durg maintained. These data, together with microscopic examination of marrow samples, indicate that the level of this fucosyltransferase is correlated with regeneration of a normal marrow population after chemotherapy. The enzyme assay may prove useful in defining normal bone marrow recovery and in timing cyclic combination chemotherapy in patients with neoplastic disease.

https://cancerres.aacrjournals.org/content/canres/38/1/181.full.pdf

Guanosine diphosphate-L-fucose plasma: N-acetylglucosaminide fucosyltransferase as in index of bone marrow hyperplasia after chemotherapy.

Fucosyltransferase activity was measured in plasma samples obtained from patients with chronic granulocytic leukemia in different disease stages. Total enzyme activity was generally elevated in untreated and in stable disease; a marked further elevation was noted 30 to 60 days before development of blast crisis. Electrofocusing studies indicate the presence of three major enzymes. The level of enzyme which focused at pH 5.6 was elevated in untreated disease and rose markedly during blastic transformation. A second enzyme focused at pH 5.1 and appeared to be related to marrow erythroid turnover. A third enzyme with pi = 4.7 was elevated only during marrow regeneration which followed myelosuppressive therapy. These data suggest the enzyme with pi = 5.6 to be a specific marker

Ta-Hsu Chou

Papers

Tumor-localizing Components of the Porphyrin Preparation Hematoporphyrin Derivative

Variation of levels of plasma guanosine diphosphate L-fucose:beta-D-galactosyl alpha-2-L-fucosyltransferase in acute adult leukemia.

Evaluation of two plasma fucosyltransferases as marker enzymes in non-Hodgkin's lymphoma.

Guanosine diphosphate-L-fucose plasma: N-acetylglucosaminide fucosyltransferase as in index of bone marrow hyperplasia after chemotherapy.

Electrofocusing patterns of fucosyltransferase activity in plasma of patients with chronic granulocytic leukemia.