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Biomedical subjects

A Paolicchi

Publications and source records attributed to A Paolicchi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Combined transcatheter arterial chemoembolization and percutaneous ethanol injection for the treatment of large hepatocellular carcinoma: local therapeutic effect and long-term survival rate.

The aim of our study was to investigate local therapeutic effects and long-term results of combined transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) in the treatment of large hepatocellular carcinoma (HCC). Eight-six patients (67 males and 19 females, age range 48-75 years, mean age 65.1 years) with Child-Pugh class A (n = 48) or B (n = 38) liver cirrhosis and a large HCC (main tumor 3.1-8 cm in diameter with no more than two daughter nodules) were enrolled in a prospective study. All patients underwent a single TACE session followed by PEI. Follow-up ranged from 4 to 65 months (mean 27.8 months, median 26 months). No major complication occurred. The local therapeutic effect, as assessed on the basis of findings at CT and MR imaging, was complete response in 71 of 86 patients (82 %) and partial response in 15 of 86. Overall survival rates by the Kaplan-Meier method were 92 % at 1 year, 83 % at 2 years, 69 % at 3 years, 58 % at 4 years, and 47 % at 5 years. Survival of Child-Pugh A patients (75 % at 3 years and 59 % at 5 years) was significantly longer (p < 0.01) than that of Child-Pugh B patients (61 % at 3 years and 35 % at 5 years). Combined TACE and PEI is an effective treatment for large HCC.

Actuarial Analysis↗
PubMed1998

Radio-frequency thermal ablation of liver metastases with a cooled-tip electrode needle: results of a pilot clinical trial.

The aim of this study was to evaluate feasibility, safety, and effectiveness of radio-frequency (RF) thermal ablation, performed by using a cooled-tip electrode needle, in the treatment of liver metastases. Twenty-nine patients (20 males and 9 females; age range 43-77 years) with one to four hepatic metastases 1.1-4.8 cm in diameter (mean 2.9 +/- 0.8 cm) from previously resected intra-abdominal primary malignancies were treated. All patients were excluded from surgery and had partial or no response to chemotherapy. Radio-frequency ablation was performed by using a 100-W generator and 17-gauge, dual-lumen, cooled-tip electrode needles with a 2- to 3-cm exposed tip. Exposure time was 12 min for each needle insertion. Findings at spiral CT were used to assess the therapeutic response. A total of 127 insertions were performed (mean 2.4 +/- 1.7 insertions/lesion) during 84 treatment sessions (mean 1.6 +/- 0.7 sessions/lesion) in absence of major complications. Complete tumor response (i. e., unenhancing area of thermal necrosis larger than the treated tumor) was seen in 41 (77 %) of 53 lesions, including 33 (87 %) of 38 lesions 3 cm or less in diameter. After a mean follow-up period of 6.5 +/- 2.1 months (range 3-9 months), recurrence of the treated lesion was seen in 5 (12 %) of the 41 cases. New metastatic lesions appeared in 7 patients. Two patients died after 6 and 8 months, respectively. Of the 27 patients still in follow-up, 14 are currently free of disease. Radio-frequency thermal ablation with a cooled-tip electrode needle is a safe and effective local treatment for hepatic metastases 3 cm or less in greatest dimension.

Adult↗
PubMed1998

Ovarian cancer cisplatin-resistant cell lines: multiple changes including collateral sensitivity to Taxol.

BACKGROUND: Alteration in apoptosis pathways (in particular mutations of p53 gene) may result in resistance of ovarian carcinoma to cisplatin. However, cisplatin resistance is likely to be multifactorial. An understanding of the molecular alterations associated with the development of resistance may be of considerable relevance in an attempt to optimize the therapeutic approach. STUDY DESIGN: Two cisplatin-resistant sublines (IGROV-1/Pt0.5 and IGROV-1/Pt1), both characterized by mutant p53 (Cancer Res 1996; 56: 556-62), but with different degree of resistance were studied in terms of pattern of cross-resistance, susceptibility to drug-induced apoptosis, expression of gluthathione-dependent system, cellular pharmacokinetics, drug-induced DNA damage. The resistance index (ratio between the IC50 of resistant and sensitive cells) after a 96-hour drug exposure was 10 for IGROV-1/Pt0.5 and 14 for IGROV-1/Pt1 cells. RESULTS: Resistant cells were cross-resistant to DNA-damaging agents and, interestingly, they had a collateral sensitivity to Taxol. The cellular response to Taxol paralleled the drug ability to induce apoptosis. The intracellular glutathione level was significantly increased in IGROV-1/Pt cells compared to the sensitive counterpart. In contrast, glutathione S-transferase level was consistently reduced in both sublines. gamma-Glutamyl transpeptidase activity, which was lower in resistant than in sensitive cells, was not directly correlated with glutathione level, thus suggesting a complex regulation of cellular glutathione content. In the resistant cells with the highest glutathione content, a reduced level of cisplatin-induced cross-link was found. Analysis of DNA platination revealed a slight decrease of DNA-bound platinum only in IGROV-1/Pt1 cells. Again, this reduction is consistent with a protective role for glutathione. The expression of metallothionein IIa was increased in both resistant variants. CONCLUSIONS: Multiple changes are involved in acquired resistance of ovarian carcinoma cells including reduced susceptibility to apoptosis as consequence of inactivation of p53 and expression of defence mechanisms. The relative contribution is related to the degree of drug resistance. In particular, the glutathione-dependent system could have a role only in the development of a high degree of resistance. Finally, the finding that Taxol was very effective in inducing apoptosis in resistant sublines with p53 mutation supports the expression of an intact p53-independent pathway of apoptosis and suggests the pharmacological interest of Taxol in the treatment of p53-mutated tumors.

Adenocarcinoma↗
PubMed1998

Hepatocellular carcinoma treatment with percutaneous ethanol injection: evaluation with contrast-enhanced color Doppler US.

PURPOSE: To investigate the ability of contrast agent-enhanced color Doppler ultrasonography (US) in evaluating the response of hepatocellular carcinoma (HCC) to percutaneous ethanol injection (PEI). MATERIALS AND METHODS: Forty-two patients (36 men, six women; age range, 51-79 years) with 54 1.3-7.0-cm-diameter (mean +/- SD, 2.8 cm +/- 1.1) HCC lesions were examined with contrast-enhanced color Doppler US before and after PEI. Spiral computed tomography (CT) and percutaneous biopsy also were performed to establish the outcome of therapy. RESULTS: Before PEI, intratumoral color signals were demonstrated at contrast-enhanced color Doppler US in 47 (87%) lesions (in 40 patients). After PEI, blood flow signals were no longer detected in all 34 of the lesions that were found to be necrotic at spiral CT and biopsy. In 12 (92%) of 13 lesions containing residual viable tumor, intratumoral color signals corresponding to the enhancing areas at spiral CT were still identified at contrast-enhanced color Doppler US. These 12 lesions were retreated with PEI by targeting the areas of residual tumor with contrast-enhanced color Doppler US guidance. Complete necrosis was seen after the second PEI cycle in nine of 12 lesions. CONCLUSION: Contrast-enhanced color Doppler US shows promise in assessing the therapeutic effect of PEI on HCC and in guiding additional treatment in cases of incomplete response.

Aged↗
PubMed1997

The cell-specific anti-proliferative effect of reduced glutathione is mediated by gamma-glutamyl transpeptidase-dependent extracellular pro-oxidant reactions.

We have shown earlier that extracellular GSH can exert a cell-specific growth-inhibitory effect on human tumor cells. In the present study, 2 human ovarian carcinoma cell lines (A2780 and IGROV-1) were used to investigate the biochemical basis of the GSH growth-inhibitory effect. Whereas cells were resistant, A2780 cells were sensitive to a 1 hr exposure to GSH, as assessed by the growth inhibition assay. Analysis of relevant GSH-dependent enzymes indicated that A2780 cells had low level of GSH S-transferase, glutathione reductase and gamma-glutamyl transpeptidase (gamma-GT) activities in comparison with those of IGROV-1 cells, and GSH peroxidase activity was undetectable in A2780 cells. The GSH effect was reversed by catalase and by dithiothreitol, indicating the occurrence of oxidative phenomena resulting in the impairment of critical cellular thiols. Indeed treatment of cells with H(2)O(2) also resulted in growth inhibition, which was more marked in A2780 cells. The gamma-glutamyl acceptor glycylglycine, a co-substrate for gamma-GT, potentiated the growth-inhibitory effect of GSH, which in contrast was decreased by the gamma-GT inhibitors, serine-borate complex and acivicin, suggesting that the production of reactive forms of oxygen (probably H(2)O(2)) was mediated by cysteinyl-glycine after GSH hydrolysis. The results support that the growth-inhibitory effect of low GSH concentration is the result of oxidative damage related to extracellular GSH metabolism.

Catalase↗
PubMed1997

Prediction of pathological tumor volume in clinically localized prostate cancer: value of endorectal coil magnetic resonance imaging.

The purpose of this study was to determine whether endorectal coil magnetic resonance imaging (MRI) enables accurate assessment of pathologic tumor volume in patients with clinically localized prostate carcinoma. Twenty-four patients with biopsy-proved prostate carcinoma underwent MRI at 0.5 T before radical prostatectomy. Tumor volumes were determined independently on axial fast-spin-echo (SE) T2-weighted MR images and whole-mount pathology slides of the surgical specimens. At pathology, tumor volumes ranged from 0.17 to 9.42 cm3 (mean +/- SD, 3.11 +/- 2.99 cm3). A strong correlation (r = .944) was found between measurements of tumor volume based on MR images and pathological specimens. The error was less than 0.5 cm3 in 14 cases, in the range of 0.5-1 cm3 in 7 cases, and more than 1 cm3 in 3 cases. By using an MR tumor volume of 2 cm3 as cutoff value, extracapsular tumor spread could be predicted with a sensitivity of 81.2%, a specificity of 100%, and an accuracy of 87.5%. Tumor volume determinations based on MR images seem to be accurate enough to be helpful in clinical decision-making.

Humans↗
PubMed1997

Differentiation of hepatocellular adenoma and focal nodular hyperplasia of the liver: comparison of power Doppler imaging and conventional color Doppler sonography.

The aim of our study was to compare the diagnostic efficacy of power Doppler imaging and conventional color Doppler sonography for differentiating between hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) of the liver. Thirty-one focal liver lesions (in 29 patients) with histologic proof of HCA (n = 9) or FNH (n = 22) were studied with power and color Doppler sonography according to a standardized examination protocol. The size of the lesions ranged between 1.5 and 14.5 cm (HCA, 3.5-14.5 cm, mean +/- SD 7.3 +/- 3.3 cm; FNH, 1.5-9.1 cm, mean +/- SD 5.1 +/- 2.1 cm). Intratumoral vessels with a venous Doppler spectrum, associated with either pulsatile or continuous peripheral flow, were detected in HCA (eight of nine lesions by power Doppler imaging and six of nine by color Doppler imaging) but not in FNH. In contrast, color signals with an arterial Doppler spectrum, radiating from the center to the periphery of the lesion, were depicted in FNH (20 of 22 cases by power Doppler imaging and 15 of 22 by color Doppler sonography) but not in HCA. Differentiation of HCA and FNH was achieved in 28 of 31 cases (90 %) by power Doppler imaging and in 21 of 31 (68 %) by color Doppler sonography (p < 0.01). Power Doppler imaging is superior to conventional color Doppler sonography in the depiction of the intratumoral flow characteristics of HCA and FNH, and enables a more accurate differential diagnosis than color Doppler sonography.

Adenoma, Liver Cell↗
PubMed1997

gamma-Glutamyl transpeptidase-dependent lipid peroxidation in isolated hepatocytes and HepG2 hepatoma cells.

Gamma-glutamyltranspeptidase (GGT), a plasma membrane-bound enzyme, provides the only activity capable to effect the hydrolysis of extracellular glutathione (GSH), thus favoring the cellular utilization of its constituent amino acids. Recent studies have shown however that in the presence of chelated iron prooxidant species can be originated during GGT-mediated metabolism of GSH, and that a process of lipid peroxidation can be started eventually in suitable lipid substrates. The present study was undertaken to verify if a GGT-dependent lipid peroxidation process can be induced in the lipids of biological membranes, including living cells, and if this effect can be sustained by the GGT highly expressed at the surface of HepG2 human hepatoma cells. In rat liver microsomes (chosen as model membrane lipid substrate) exposed to GSH and ADP-chelated iron, the addition of GGT caused a marked stimulation of lipid peroxidation, which was further enhanced by the addition of the GGT co-substrate glycyl-glycine. The same was observed in primary cultures of isolated rat hepatocytes, where the lipid peroxidation process did not induce acute toxic effects. GGT-stimulation of lipid peroxidation was dependent both on the concentration of GSH and of ADP-chelated iron. In GGT-rich HepG2 human hepatoma cells, the exposure to GSH, glycyl-glycine, and ADP-chelated iron resulted in a nontoxic lipid peroxidation process, which could be prevented by means of GGT inhibitors such as acivicin and the serine-boric acid complex. In addition, by co-incubation of HepG2 cells with rat liver microsomes, it was observed that the GGT owned by HepG2 cells can act extracellularly, as a stimulant on the GSH- and iron-dependent lipid peroxidation of microsomes. The data reported indicate that the lipid peroxidation of liver microsomes and of living cells can be stimulated by the GGT-mediated metabolism of GSH. Due to the well established interactions of lipid peroxidation products with cell proliferation, the phenomenon may bear particular significance in the carcinogenic process, where a relationship between the expression of GGT and tumor progression has been envisaged.

Animals↗
PubMed1996

Localization of a GSH-dependent dehydroascorbate reductase in rat tissues and subcellular fractions.

A novel GSH-dependent dehydroascorbate (DHA) reductase from rat liver cytosol has been recently purified and partially characterized in our laboratory. A further characterization study has been carried out in order to determine intracellular and tissue distribution of the enzyme. A modified purification method, yielding a threefold increase in enzyme activity recovery, has been used. Polyclonal antibodies were obtained in rabbits and specific anti-DHA reductase IgG were purified by affinity chromatography employing the homogeneous enzyme as ligand. Immunoblotting analysis of subcellular fractions showed the exclusively cytosolic location of the enzyme. Immunotitration experiments, performed in order to determine the percentage of cytosolic DHA reductase activity ascribable to our enzyme, revealed that purified enzyme activity was completely titrable, while only 70% of DHA reducing activity was titrable in liver cytosol preparation. When immunoblotting analysis was employed to determine tissue distribution of the enzyme, liver, intestinal mucosa, kidney, adrenals, submaxillary gland, testis, and pancreas appeared most endowed with the enzyme, and lower levels were observed in all the other tissues examined. Immunohistochemical studies showed clear zonal distributions in kidney and intestinal tract and overall homogeneous patterns in the other tissues.

Adrenal Glands↗
PubMed1996

Single-cell investigation by laser scanning confocal microscopy of cytochemical alterations resulting from extracellular oxidant challenge.

Confocal laser scanning fluorescence microscopy coupled to image analysis was employed in order to develop and evaluate procedures for the appraisal at the single-cell level of: (1) protein-bound 4-hydroxynonenal, the specific product of membrane peroxidation (by means of immunocytochemistry with biotin-avidin revelation); (2) protein oxidation (by reaction of protein carbonyls with 2, 4-dinitrophenyl-hydrazine followed by immunocytochemistry of dinitrophenyl moieties); and (3) cellular protein thiols (by direct alkylation of sulfhydryl groups with thiol-specific fluorescent reagents possessing different cell permeabilities). The procedures proved able to reveal the subcellular distribution of cytochemical parameters useful as indices of oxidative stress conditions, and may allow "redox phenotyping" of isolated cells, which would provide an efficient tool in selected experimental models.

Aldehydes↗
PubMed1996

Selective colocalization of lipid peroxidation and protein thiol loss in chemically induced hepatic preneoplastic lesions: the role of gamma-glutamyltranspeptidase activity.

A number of studies indicate that cell proliferation can be modulated by changes in the redox balance of (soluble and protein) cellular thiols. Free radical processes, including lipid peroxidation (LPO), can affect such a balance, and a role for LPO in multistage carcinogenesis has been envisaged. The present study was aimed to assess the relationships between the protein thiol redox status and the LPO process in chemically induced preneoplastic tissue. The Solt-Farber's initiation-promotion model of chemical carcinogenesis in the rat liver was used. In fresh cryostat sections, preneoplastic lesions were identified by the reexpression of gamma-glutamyltranspeptidase (GGT) activity. In serial sections, different classes of protein thiols were stained; in additional sections, LPO was elicited by various prooxidant mixtures and determined thereafter by the hydroxynaphthoic hydrazide-Fast Blue B procedure. The incubation of sections in the presence of chelated iron plus substrates for GGT activity leads to the development of LPO in selected section areas closely corresponding to GGT-positive lesions, indicating the ability of GGT activity to initiate LPO. Protein-reactive thiols, as well as total protein sulfur, were decreased by 20-25% in cells belonging to GGT-positive preneoplastic nodules, suggesting the occurrence of oxidative conditions in vivo. The incubation of additional adjacent sections with the prooxidant mixture H2O2 plus iron(II), in order to induce the complete oxidation of lipid present in the section, showed a decreased basal concentration of oxidizable lipid substrate in GGT-rich areas. The decreased levels of both protein thiols and lipid-oxidizable substrate in GGT-positive nodules suggest that the observed GGT-dependent pathway of LPO initiation can be chronically operative in vivo during early stages of chemical carcinogenesis, in cells expressing GGT as part of their transformed phenotype.

2-Acetylaminofluorene↗
PubMed1996

Glomerular and tubular effects of contrast media diatrizoate and iopromide.

The aim of this study is to evaluate the nephrotoxicity of two contrast media (CM), with different physicochemical characteristics: diatrizoate (ionic high-osmolar), iopromide (nonionic low-osmolar). Intravenous urography was performed in 34 patients: 17 were examined with diatrizoate and 17 with iopromide, randomly assigned. Different parameters of glomerular and tubular function were measured before and at 6, 24, and 48 h after urography. Both contrast media induced a reversible increase of urine enzymes, which was significantly higher after diatrizoate. In particular, diatrizoate determined a relevant increase of brush border enzymes gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) and of cytosolic enzyme lactate dehydrogenase (LDH), while, after iopromide increases of urinary enzymes were less evident and were significant only for GGT and ALP. In addition, diatrizoate affected other tubular functions (clearances of phosphorus and uric acid) and slightly decreased glomerular function in a few patients. In no case did these glomerular and tubular effects have a clinical relevance. In conclusion, the nonionic low-osmolar contrast medium iopromide appeared less nephrotoxic than diatrizoate. The cost-benefit ratio needs further examination.

Alkaline Phosphatase↗
PubMed1995

Treatment of small hepatocellular carcinoma with percutaneous ethanol injection. Analysis of prognostic factors in 105 Western patients.

BACKGROUND: Percutaneous ethanol injection (PEI) has been used in the Far East for treating small, unresectable hepatocellular carcinoma (HCC). To clarify when treatment with PEI may be best indicated for Western patients with HCC, the authors performed a retrospective analysis of the clinicopathologic factors influencing prognosis. METHODS: From December 1987 to August 1994, 105 patients with cirrhosis with HCC received PEI as the sole anticancer treatment. Eighty-two patients had uninodular tumors smaller than 5 cm, and 23 patients had multiple lesions (2-4) smaller than or equal to 3 cm each. All patients were in Child-Pugh class A (n = 64) or B (n = 41). Survival was analyzed according to patient- and tumor-related factors by means of the Kaplan-Meier method. RESULTS: The estimated survival rates of all 105 patients were 96% at 1 year, 86% at 2 years, 68% at 3 years, 51% at 4 years, 32% at 5 years, and 24% at 6 years. Survival was not affected by sex, age, etiology of cirrhosis, or hepatitis B surface antigen or anti-hepatitis C virus positivity, but depended on Child-Pugh class (P = 0.006) and presence of ascites (P = 0.009). Patients with a pretreatment alpha-fetoprotein level of 200 ng/ml or less had a better prognosis than patients with an alpha-fetoprotein level higher than 200 ng/ml (P = 0.007). Patients with unmodular HCC of 3 cm or less had significantly better long term survival (P = 0.04) than patients with uninodular HCC of 3.1-5 cm or with multinodular tumors. Tumor grade according to Edmondson and Steiner and tumor volume, in contrast, did not significantly influence prognosis (P > 0.1). CONCLUSIONS: For Western patients with HCC treated with PEI, the prognosis was highly dependent on the severity of the underlying cirrhosis. Treatment with PEI is best indicated for patients with uninodular tumors of 3 cm or less in greatest dimension and an alpha-fetoprotein level lower than 200 ng/ml.

Administration, Cutaneous↗
PubMed1995

The role of the glutathione-dependent system in tumor sensitivity to cisplatin: a study of human tumor xenografts.

BACKGROUND: Glutathione, the most important intracellular thiol, has been implicated in modulating tumor cell sensitivity to alkylating agents and cisplatin. However, the role of the glutathione-dependent detoxification system in mediating cisplatin resistance of human tumors remains unclear. DESIGN: Glutathione content and related enzyme activities were assessed in a series of human tumor xenografts representative of responsive (i.e., small-cell lung cancer and ovarian carcinoma) and resistant tumor types (i.e., non-small-cell lung cancer and colorectal carcinoma), in an attempt to establish a correlation with response to cisplatin treatment. RESULTS: The pattern of tumor response to cisplatin treatment for tumors selected in the two panels corresponded to the one expected from the clinical experience, since drug-induced tumor growth inhibition ranged from 70% to 100% in the group of sensitive tumors and from 20% to 60% in the group of resistant tumors. No correlation was observed between glutathione level and cisplatin response in the resistant tumor panel. An inverse correlation was found for glutathione-S-transferase activity level and tumor response only in the panel of chemoresponsive tumors. In the latter panel, the only unresponsive tumor (POCS) showed the highest glutathione level in the entire series investigated. No significant correlation was found between other enzymes investigated and tumor response to cisplatin treatment. In addition, a very low activity of gamma-glutamyltranspeptidase was found to be associated with sensitive tumors. CONCLUSIONS: Although glutathione may have a role in modulating cisplatin cell sensitivity, it is unlikely that alteration in glutathione level and metabolism is a primary mechanism of cisplatin resistance in human tumors, since: a) no significant correlations were found between glutathione level and response to cisplatin treatment in a series of chemosensitive and chemoresistant human tumor xenografts; b) a marked increase in glutathione level might be responsible for cisplatin resistance but, in contrast to findings on cell systems selected in vitro for resistance, it is not a frequent event in human tumors.

Animals↗
PubMed1995

[High-resolution computed tomography compared with the thoracic radiogram and respiratory function tests in assessing workers exposed to silica].

To compare the usefulness of high-resolution computed tomography (HRCT) and chest radiography in the functional evaluation of silica-exposed workers, 27 workers were submitted to posteroanterior and lateral chest radiographs, apex to base HRCT scans and pulmonary function tests. Two experienced readers studied plain films independently to assess small opacities profusion (ILO-UC, Geneva 1980): from 0/- to 3/+. HRCT grading and extent of silicotic nodules and associated emphysema were scored on a four-point scale. Inter-reader analysis showed better agreement for HRCT (K = 0.49) than chest radiography (K = 0.29). Poor agreement was observed between chest radiography and HRCT classes, particularly in the early stages of silicosis. No correlation was observed between chest radiography score and pulmonary function tests, while a significant correlation was observed between HRCT classes (grade and extent of the nodules) and FEV1, MEF50, MEF75, RV and FRC. In conclusion, HRCT exhibited better reproducibility and higher accuracy than chest radiography in identifying the absence of silicotic nodules and in depicting functionally important lesions. To this purpose, HRCT can be considered a useful support to conventional chest radiography.

Aged↗
PubMed1994

Influence of rat strain on P-glycoprotein expression in cultured hepatocytes.

The amount and activity of the multi-drug transporter P-glycoprotein (Pgp) have been measured in cultured hepatocytes derived from different rat strains. A marked increase in Pgp, as revealed by Western blotting, occurred 48 h after seeding in hepatocytes from Sprague-Dawley, Wistar and Fischer 344 rats, the last showing the highest value. The addition of dexamethasone (DEX) to culture medium delayed Pgp overexpression in all the strains, proportionally to the protein amount in the absence of hormone. The R-123 functional test for Pgp showed that Fischer 344 hepatocytes had the lowest ability to extrude the fluorescent dye as compared with Sprague-Dawley or Wistar rats. These results suggest that the Fischer 344 rat is more prone than other strains to culture stressing conditions, leading to an overexpression of Pgp that is not necessarily functional.

ATP Binding Cassette Transporter, Subfamily B, Mem↗