Biomedical subjects

C Fontolliet

Publications and source records attributed to C Fontolliet.

At least 19 recordsLinked to original sources

PubMed2003

Endoscopic fluorescence detection of intraepithelial neoplasia in Barrett's esophagus after oral administration of aminolevulinic acid.

BACKGROUND AND STUDY AIMS: Barrett's esophagus is strongly associated with adenocarcinoma. Early malignant transformation of the Barrett's mucosa is often not visible endoscopically and may remain undetected until the invasive adenocarcinoma stage. Endoscopic surveillance is currently carried out on random four-quadrant biopsies at 1-2 cm intervals. Endoscopic fluorescence detection of protoporphyrin IX induced by 5-aminolevulinic acid can identify premalignant lesions. This study evaluates endoscopic fluorescence detection in patients having Barrett's esophagus and compares the results to those of standard endoscopy with random four-quadrant biopsies. PATIENTS AND METHODS: The study included 30 examinations in 28 patients (22 men, 6 women; age range 37-78 years, mean age 60 years,), with five patients having known intraepithelial neoplasia. A dose of 20 mg/kg of 5-aminolevulinic acid was given orally 5 hours before examination. Random four-quadrant biopsies were performed 4-6 weeks before endoscopic fluorescence detection. RESULTS: Of the biopsies taken during the endoscopic fluorescence detection procedure, 28 % (23/81) were true positives. More than one-third of the false-positive results were due to inflammation. None of the 97 control biopsies taken on nonfluorescing areas during endoscopic fluorescence detection were dysplastic. Endoscopic fluorescence detection showed low-grade intraepithelial neoplasia in five patients which was not diagnosed with random four-quadrant biopsies, while random four-quadrant biopsies alone showed three low-grade intraepithelial neoplasias that were invisible during endoscopic fluorescence detection. All high-grade intraepithelial neoplasias or adenocarcinomas (2/2) were detected with both methods. CONCLUSIONS: Fluorescence detection achieved a similar performance when compared with four-quadrant random biopsy, but resulted in fewer biopsies (81 for endoscopic fluorescence detection vs 531 for random four-quadrant biopsies).

Administration, Oral↗

PubMed2001

Localization of tetra(m-hydroxyphenyl)chlorin (Foscan) in human healthy tissues and squamous cell carcinomas of the upper aero-digestive tract, the esophagus and the bronchi: a fluorescence microscopy study.

To date, little is known about precise time-dependent distribution and histological localization of tetra(m-hydroxyphenyl)chlorin (mTHPC) in human healthy tissues and squamous cell malignancies in the upper aero-digestive tract. A fluorescence microscopy study was performed on 50 healthy tissue biopsies and on 13 tumors (graded from Tis to T1 SCC) from 30 patients. Tissue samples were taken between 4 h and 11 days following injection of 0.15 mg/kg mTHPC. A fairly comparable distribution pattern in various tissues was observed over time in different patients. Vascular localization of mTHPC fluorescence predominates at a short delay, whereas the dye is essentially located in the tumoral and healthy mucosa after longer delays. A much lower uptake and retention of mTHPC fluorescence was noted in striated muscle and cartilage as compared to neoplastic lesions. No significant selectivity was found between healthy and tumoral mucosa. The obtained data are important to confirm drug-light interval that have been selected for effective PDT for early SCC malignancies while minimizing the risks of over- or under-treatment. The low fluorescence level in striated muscle provides the opportunity to develop interstitial PDT as a treatment modality for invasive SCC of unfavorable locations in the oral cavity or pharynx, such as the base of the tongue.

Aged↗

PubMed2001

p53 gene mutation and protein accumulation during neoplastic progression in Barrett's esophagus.

The aim of the present study was to characterize expression and mutation of p53 during the neoplastic progression from Barrett's esophagus to adenocarcinoma and to test the reliability of immunohistochemistry for p53 overexpression as an indicator of p53 mutation in this context. The association of both gene mutation and protein accumulation with clinicopathological findings and survival was also studied. A total of 77 samples from 30 esophagectomy specimens with Barrett's esophagus and adenocarcinoma of patients in longitudinal clinical follow-up were analyzed. Different lesions (intestinal metaplasia, dysplasia, and adenocarcinoma) as well as normal squamous-cell esophageal epithelia were sampled from formalin-fixed, paraffin-embedded tissues by microdissection. Mutations in p53 Exons 5 to 9 were detected by polymerase chain reaction-single-strand conformation polymorphisms (PCR-SSCP) and confirmed by direct DNA sequencing. Nuclear accumulation of p53 protein was analyzed immunohistochemically from tissue sections adjacent to those used for microdissection. p53 gene mutations were found in 17 and p53 protein accumulation were found in 20 tumor samples. Of the 17 adenocarcinomas with a p53 mutation, 16 stained positive for p53 protein. p53 mutations were detected significantly more frequently in high-grade dysplastic than in low-grade dysplastic lesions (77% versus 29%, P < 0.01). In contrast, nuclear accumulation of p53 was detected in 85% of high-grade and 71% of low-grade dysplastic lesions. In eight cases with p53 mutation, the mutation identified in the tumors was also detected in premalignant lesions, mainly in high-grade dysplasia. In four cases of p53-mutated tumors, clones with different p53 mutations were detected in premalignant lesions. Neither p53 mutations nor p53 protein accumulations were found in metaplastic lesions. In summary, we found that p53 mutations occurred mainly during the transition from low-grade to high-grade dysplasia in the neoplastic progression of Barrett's esophagus but not in the nondysplastic Barrett's mucosa. Mutational analysis of p53 by PCR-SSCP and p53 accumulation by immunohistochemistry were mostly concordant in adenocarcinoma and high-grade dysplastic lesions but frequently discordant in low-grade dysplastic lesions. No correlation between p53 gene mutation or p53 accumulation and clinicopathological findings was observed in this study.

Adenocarcinoma↗

PubMed2001

Primary neuroendocrine carcinoma of the liver: an autopsy case.

An autopsy case of primary hepatic neuroendocrine carcinoma is described. A 72-year-old man had a large tumor mass measuring 22 cm in its greatest diameter and localized to the right, left and caudal lobes of the non-cirrhotic liver. Microscopically, the tumor was composed of middle-sized pleomorphic cells organized in ribbons or trabeculae, with scanty intersecting fibrous septae. Immunohistochemically, the tumor cells were positive for multikeratin C11, chromogranin A and synaptophysin. The patient also had metastases in the bone marrow. No alternative primary source of endocrine tumor was detected. The patient died 4 days after presentation.

Aged↗

PubMed2001

Evolution of DNA ploidy during squamous cell carcinogenesis in the esophagus.

Image and flow cytometry was used to study the nuclear DNA content (ploidy) during the squamous cell carcinogenesis in the esophagus. The present retrospective study comprised 26 surgical specimens of squamous cell carcinomas (SCC) in patients who underwent surgery alone at the Department of Surgery in CHUV Hospital in Lausanne, between January 1992 and December 1999. We analyzed 53 healthy tissues, 43 tumors, and six lymph node metastases. Diploid DNA histogram patterns were observed in all non-pathologic tissues analyzed, either distant or proximal to the lesion. Aneuploidy was observed in 30 (70%) of 43 lesions; 20 (62.5%) of 32 early squamous-cell carcinomas; and 10 (91%) of 11 advanced carcinomas. In patients with various tumor stages or with multicentric synchronous or metachronous tumors, DNA content was not different among different tumor stages. Four of six lymph node metastases had the same DNA content as the primary tumor. In four patients, discordance between image and flow cytometry analysis was observed for malignant lesions only. Ploidy status was not statistically associated with the differentiation of the tumor, but it was associated with the stage of tumor (P < 0.001). These findings suggest that early malignant changes in the esophagus are already associated with alteration in DNA content, and aneuploidy tends to correlate with progression to invasive SCC. This cell kinetic information could help clinicians in selecting the optimal treatment for the individual patient.

Aged↗

PubMed2001

Promoter methylation analysis on microdissected paraffin-embedded tissues using bisulfite treatment and PCR-SSCP.

Methylation-sensitive single-strand conformation analysis (MS-SSCA) is a new method of screening for DNA methylation changes. The combination of bisulfite modification and PCR results in the conversion of unmethylated cytosines to thymines, whereas methylated cytosines remain unchanged. This sequence conversion can lead to methylation-dependent alterations of single-strand conformation, which can be detected by SSCA. An analysis of mixtures of methylated and unmethylated DNA at known ratios revealed that the relative intensities of the corresponding bands following MS-SSCA were maintained. MS-SSCA was applied for methylation analysis of human p16 promoter region using genomic DNA obtained from either frozen, fixed, or microdissected fixed tissue sections. MS-SSCA is a rapid, specific, and semiquantitative approach that allows the detection of methylation of the p16 gene promoter. In reconstruction experiments, the method permits the detection of 10% or less of cells harboring a methylated p16 promoter. We have been successful in analyzing by MS-SSCA almost all (96%) tumor samples microdissected from archival paraffin-embedded fixed tissue sections and obtaining reproducible results. In addition, when microdissection was performed, the clonality of this genetic alteration could be identified.

DNA↗

PubMed2001

[Twelve years of liver transplantation in Lausanne].

From 1988 to June 2000 138 transplantations were performed in 129 adult patients. Actuarial patient and graft survivals have been 80.7% and 75.4% at one year and 67.8% and 63.5% at 10 years. This compares favourably with the statistics of the European Liver Transplant Registry that collected data from more than 30,000 grafts. Over the twelve years of activity, the indications have become more liberal and the techniques have been simplified. The waiting list has therefore grown and some patients are now unfortunately dying before a graft can be found because the number of brain dead donors remains stable. In order to palliate this shortage, older donors are now being accepted even with co-morbidities and/or moderate alterations of the liver function tests. The use of live donors and the split of the best cadaveric grafts for two recipients will also reduce the gap between the demand and the offer.

Actuarial Analysis↗

PubMed2000

Prognostic value of postoperative carcinoembryonic antigen concentration and extent of invasion of resection margins after hepatic resection for colorectal metastases.

OBJECTIVE: To evaluate the prognostic value of postoperative concentration of carcinoembryonic antigen (CEA) and extent of surgical margins after resection of liver metastases from colorectal cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Switzerland. SUBJECTS: 49 patients with hepatic metastases after primary colorectal cancer. INTERVENTIONS: Resection of hepatic metastases MAIN OUTCOME MEASURES: Assessment of prognostic value of variables by univariate and multivariate analysis. RESULTS: Median survival was 24 months (range 5-86 months). Resection margins were clear (> 1-cm) in 10, close (< 1-cm) in 25 and invaded in 9 patients. On univariate analysis, a postoperative concentration of CEA of <4ng/ml was correlated with prolonged survival (p < 0.001), but the width of the resection margin was not of prognostic importance. There was no correlation between width of resection margins and postoperative concentration of CEA (p = 0.5). On multivariate analysis, postoperative concentrations of CEA of 4 ng/ml or more were associated with increased risk of death (relative risk 7.3; 95% confidence interval (CI) 2.8-18.7, p < 0.001). CONCLUSION: Postoperative CEA offers better prognostic discrimination than the width of resection margins after resection of liver metastases from colorectal tumours. Some patients with invaded resection margins did survive for 3 years, but no patient did whose CEA concentration was 4 ng/ml or more. The definition of a potentially curative hepatic resection should include a postoperative CEA concentration of <4 ng/ml (within the reference range).

Carcinoembryonic Antigen↗

PubMed2000

Nuclear accumulation of beta-catenin is a common and early event during neoplastic progression of Barrett esophagus.

Our aim was to characterize expression and mutation of beta-catenin in the progression of Barrett esophagus to adenocarcinoma. Immunohistochemical analysis of beta-catenin was performed on paraffin-embedded tissue from 30 cases with adenocarcinomas and premalignant lesions. To determine whether there is a correlation between beta-catenin nuclear accumulation and exon 3 mutation of this gene, mutational analysis by polymerase chain reaction-single-strand conformation polymorphism was performed on DNA extracted from the same 30 adenocarcinomas. As a result, the prevalence of reduced expression of beta-catenin on the membrane, with or without nuclear staining, increased significantly from low-grade (LG) to high-grade (HG) dysplasia. Focal nuclear staining for beta-catenin was present in 19 cases of adenocarcinoma, and nuclear staining was associated significantly with progression from metaplasia to LG dysplasia. In addition, in glands with clear histologic transition from metaplasia to LG dysplasia, nuclear accumulation of beta-catenin was found only in the LG dysplastic areas. No mutation in exon 3 of the beta-catenin gene was detected in adenocarcinomas. These results demonstrate that disturbance of the APC/beta-catenin pathway, as indicated by nuclear accumulation of beta-catenin, is a common and early event during neoplastic progression in Barrett esophagus.

Adenocarcinoma↗

PubMed2000

Time-dependent biodistribution of tetra(m-hydroxyphenyl)chlorin and benzoporphyrin derivative monoacid ring A in the hamster model: comparative fluorescence microscopy study.

The pharmacokinetics of the photosensitizer used play a key role in the understanding of the mechanism of photodynamic therapy-induced damage. Fluorescence microscopy was used to compare time-dependent biodistribution of tetra(m-hydroxyphenyl)chlorin (mTHPC) and benzoporphyrin derivative monoacid ring A (BPD-MA) in different hamster tissues, including an early, chemically induced, squamous cell carcinoma. Following injection of 0.5 mg/kg body weight of mTHPC and 2.0 mg/kg BPD-MA, groups of three animals were sacrificed at different time points and a series of fluorescence micrographs from different excised organs were analyzed. The highest fluorescence intensities of mTHPC were observed at 96 h for squamous epithelia and skin and at 48 h for smooth muscle. There is no real peak of BPD-MA fluorescence between 30 min and 3 h in the basal epithelial layers, fibroconnective tissue, muscles or blood vessels. At 4 h after injection, the fluorescence level of BPD-MA decreased and at 24 h it had returned to background level in all observed tissues. The significantly faster clearance of BPD-MA is the principal advantage as compared to mTHPC. However, similar localization patterns in different tissues with essentially vascular affinity represent a possible disadvantage for treating early malignancies with BPD-MA as compared to mTHPC, which is mainly localized in various epithelia. For both photosensitizers no significant selectivity between early squamous cell carcinoma and healthy mucosae is seen. Pharmacokinetic studies of different photosensitizers in an appropriate animal model are essential for selecting new-generation photosensitizers with the most favorable localization for photodynamic therapy of early malignancies in hollow organs.

Animals↗

PubMed1999

[Monolobar Caroli's disease. Apropos of 12 cases].

BACKGROUND: Caroli's disease is the dilatation of the segmental intrahepatic bile ducts. It usually affects the entire liver but can occasionally involve only one lobe, commonly the left. This study included 12 cases of unilobular disease, nine localised in the left lobe and three in the right lobe, which were all treated by liver resection. PATIENTS AND METHODS: These 12 patients underwent surgery between 1974 and 1997. There were six men and six women (mean age: 51 years). The initial presentation and diagnosis were reported. The mean interval between the first symptoms and diagnosis was 12.5 years. Eight of the 12 patients had undergone 22 surgical or endoscopic procedures prior to liver resection. In the present series a preoperative ultrasonogram or CT scan established the diagnosis in all cases. Six patients did not have stones in the gallbladder. RESULTS: Surgical treatment consisted in seven left lobectomies, two left hepatectomies and three right hepatectomies (Couinaud's classification). A intrahilar cholangiojejunostomy was performed in five cases. Pathological examination showed cystic dilatation of the intrahepatic segmental and subsegmental bile ducts, measuring from a few millimetres to 4 cm, which contained calculi. Two cases were associated with congenital hepatic fibrosis. An intrahepatic focus of ectopic pancreatic tissue was seen in one case. There were no cases with cholangiocarcinoma. One patient developed a biliary fistula which required reoperation. All patients had an uneventful long term postoperative course except for one patient who died of colon carcinoma 3 years postoperatively. CONCLUSION: When associated with other malformations, most notably congenital hepatic fibrosis, this commonly diffuse disease is called Caroli's syndrome. The unilobar form, most usually involving the left lobe of the liver, is called Caroli's disease. Both monolobar and diffuse types are often characterised by recurrent bouts of cholangitis and, in over half of the cases, by common bile duct stones without gallbladder stones.

Adult↗

PubMed1998

Interstitial photodynamic therapy with tetra(m-hydroxyphenyl)chlorin: tumor versus striated muscle damage.

PURPOSE: The present study was initiated to determine the conditions under which a single photodynamic treatment would induce maximal damage to a tumor with no or at least minimal reversible damage to a normal striated muscle. METHODS AND MATERIALS: The technique of interstitial light delivery was used after prior 0.5 mg/kg tetra(m-hydroxyphenyl)chlorin administration in a hamster model. After having estimated the threshold light doses required for minimal muscle damage, the same light doses were applied to squamous cell carcinomas to evaluate the efficiency of interstitial photodynamic therapy. Sixteen and 96 h after the injection, irradiation at 650 nm was performed on the thigh muscle of the left hind leg. The applied light doses ranged between 0.3-15 J and were delivered at an intensity of 44 mW per cm of diffuser length. RESULTS: The threshold of muscle damage was obtained using light doses of 1.5-3 J at two drug-light intervals of 16 and 96 h, respectively. More than 85% of the tumor mass was destroyed when lesions were illuminated using these threshold conditions. In terms of immediate short-term tumor response, this means that for the given irradiation conditions, a relatively low threshold energy of only 1.5 or 3 J, depending on the drug-light interval, is sufficient to induce massive tumor destruction with minimal muscle damage. CONCLUSION: These results have implications for evaluating interstitial PDT for squamous cell cancers in unfavorable localization in the oral cavity or pharynx, such as at the base of the tongue.

Animals↗

PubMed1998

Clinical photodynamic therapy for superficial cancer in the oesophagus and the bronchi: 514 nm compared with 630 nm light irradiation after sensitization with Photofrin II.

Photodynamic therapy (PDT) for cancer in the oesophagus and bronchi with red (630 nm) light may occasionally lead to wall perforation and fistula. Therefore, we investigated the clinical use of a less penetrating wavelength (514 nm) for the curative treatment of nine superficial carcinomas in the oesophagus and bronchi after photosensitization with Photofrin II. Tumours without infiltration beyond the submucosa in the oesophagus and beyond the lamina propria in the bronchi were considered as superficial cancers. The outcome and complications were compared with those of 13 superficial cancers treated with PDT and 630 nm light. In addition, we evaluated histologically the extent of the long-term tissue damage and scarring following treatment of six oesophageal cancers with either green or red light. At first endoscopic control, 7-10 days after PDT, tissue necrosis simply matched the illuminated area, without evidence of selective tumour damage. Six of nine tumours treated with 514 nm light had a complete response compared with nine of 13 after 630 nm irradiation. No perforation or fistula occurred in either treatment group. However, severe chest pain and fever with or without pleural effusion, consistent with occult perforation, were observed in three patients after 630 nm illumination in the oesophagus. Histologically, fibrous scarring in the three distinct sites treated with green light was limited to the superficial layers of the oesophagus. After red light treatment, transmural fibrosis with marked thinning of the oesophageal wall was evident in two of the three specimens available for inspection. These results indicate that PDT with 514 nm light has the potential to cure superficial cancer in the oesophagus and bronchi with essentially the same probability of success as red light. In the oesophagus, green light prevents deep tissue damage, thus reducing the risk of perforation.

Aged↗

PubMed1998

Therapeutic potential of the anti-angiogenesis drug TNP-470.

Neovessel formation is a pre-requisite for tumour growth and dissemination. Inhibition of angiogenesis is a promising approach for the treatment of neoplasms. In recent years, antiangiogenic drugs, such as TNP-470, have entered clinical trials. In this paper, we review the key experimental and clinical data on the role of TNP-470 in anti-tumour treatment.

Animals↗

PubMed1998

Photodynamic therapy of early squamous cell carcinomas of the esophagus: a review of 31 cases.

BACKGROUND AND STUDY AIMS: Patients with cancers of the head and neck have a strong tendency to develop early synchronous and metachronous carcinomas of the esophagus. In many of these patients, whose general condition is poor as a result of alcohol and tobacco abuse, the second primary cancers require minimally invasive treatment. The aims of this study were to evaluate the efficacy of photodynamic therapy for the treatment of early esophageal carcinomas and to compare the results obtained with three different photosensitizers (hematoporphyrin derivative), porfimer sodium (Photofrin II), and meta-(tetrahydroxyphenyl)chlorin (m-THPC). PATIENTS AND METHODS: Thirty-one early squamous cell carcinomas (Tis or T1a) of the esophagus were treated by photodynamic therapy in 24 patients. Nine tumors were treated with hematoporphyrin derivative, eight with Photofrin II and 14 with m-THPC. RESULTS: The early cancers were cured in 84% of patients after a mean follow-up period of 2 years. Because the number of cases included in each group was small, the differences in recurrence rates for the different photosensitizers could not be evaluated statistically, but m-THPC was more phototoxic, induced a shorter period of photosensitization of the skin, and had better selectivity than either of the other photosensitizers. There were four major complications: two stenoses and two esophagotracheal fistulas. CONCLUSIONS: Photodynamic therapy eradicates early squamous cell carcinomas (Tis and T1a) of the esophagus efficiently. Transmural necroses leading to fistulas can be avoided by using a low-penetrating wavelength of laser light (green light at 514.5 m instead of red light at 630 or 652 nm). Stenoses always result from circumferential irradiation of the esophageal wall, and this can be avoided by using a 180 degrees or 240 degrees windowed cylindrical light distributor.

Adult↗

PubMed1997

Field cancerisation and polyclonal p53 mutation in the upper aero-digestive tract.

Field cancerisation of the aerodigestive tract is caused by chronic exposure to alcohol and tobacco, but the nature of the genetic alterations preceding overt malignancy is unknown. To identify potential field changes we have used a functional assay which tests the transcriptional competence of human p53 expressed in yeast. To increase the sensitivity and reliability of the technique for samples containing under 20% mutant p53, the 5' and 3'-ends of the p53 cDNA were examined separately. With this split form of the assay the tissue p53 mRNA acts as its own control for RNA quality. Mutations were detected in 87% (46/53) of tumours, reflecting the high sensitivity of the technique. Multiple biopsies of histologically normal tissue from the upper aero-digestive tract were tested and clonal p53 mutations were identified in 76% (38/50) of biopsies from patients presenting with multiple tumours compared with 32% (38/117) of biopsies from patients presenting with single tumours (P<0.000001). All patients (16/16) presenting with multiple tumours had at least one positive biopsy, compared with only 53% (19/36) of patients presenting with single tumours (P <0.001). This defines expansion of multiple clones of mutant p53-containing cells as an important biological mechanism of field cancerisation, and provides a means to identify patients likely to benefit from intensive screening for the development of new head and neck tumours.

Adult↗

PubMed1997

Photodynamic therapy for early squamous cell carcinomas of the esophagus, bronchi, and mouth with m-tetra (hydroxyphenyl) chlorin.

OBJECTIVE: To clinically evaluate a new photosensitizer, m-tetra(hydroxyphenyl) chlorin (m-THPC), for the photodynamic therapy of early squamous cell carcinomas of the upper aerodigestive tract. DESIGN: Phase 1 included evaluation of the innocuousness of the compound after intravenous injection (control of vital parameters and blood analysis before and after injection) and evaluation of the duration of skin photosensitization. Phase 2 included assessment of optimal conditions for treatment (injected dose, drug-light interval, light dose, wavelength, etc), on 33 early squamous cell carcinomas of the mouth, esophagus, and bronchi, with a mean follow-up of 14 months; irradiation tests on healthy and neoplastic mucosae to determine the irradiation conditions that lead to tumor eradication with minimal damage to the surrounding normal mucosa and muscle layers; and localization of the dye in various tissue compartments and cells at different time intervals after the injection of the photosensitizer, by using a fluorescence microscope to analyze 46 biopsy specimens taken during the treatment sessions and 8 resected specimens of early cancers, excised with the carbon dioxide laser. SETTING: Endoscopic medical center of an otolaryngology-head and neck surgery department. PATIENTS: Twenty-five patients treated previously for a head and neck cancer with a synchronous or metachronous early second primary cancer. Patients with porphyria were excluded from the trial. RESULTS: The best results in the bronchi and mouth were obtained with an injected dose of 0.15 mg of m-THPC per kilogram of body weight 4 days before irradiation. The fluence was 7 to 16 J/cm2, and the fluence rate was between 100 and 150 mW/cm2 using red light at 652 nm. In the esophagus, green light at 514 nm is preferred to the red light to avoid fistulas. Optimal irradiation conditions at this wavelength, which was also used in the trachea, were found at a fluence of 75 to 100 J/cm2 and a fluence rate between 70 and 100 mW/cm2. Of 33 lesions treated thus far by photodynamic therapy with m-THPC, 28 show no recurrence with a mean follow-up of 14 months. Photosensitivity to sunlight does not exceed 6 weeks. CONCLUSIONS: m-Tetra(hydroxyphenyl) chlorin is a second-generation photosensitizer that has several significant advantages as compared with the first-generation porphyrin mixtures hematoporphyrin derivative and porfimer sodium (Photofrin II). It is a pure compound that is 100 times more phototoxic at 652 nm and 10 times more photoxic at 514 nm, has better selectivity for early carcinomas, and a shorter duration of skin photosensitivity. The therapeutic results indicate a recurrence rate that is similar to that obtained with Photofrin II, ie, about 15%.

Antineoplastic Agents↗

PubMed1997

Germ-line mutations of the p16INK4(MTS1) gene occur in a subset of patients with hepatocellular carcinoma.

The molecular mechanisms of hepatocarcinogenesis are poorly understood. Only very recently has there been a suggestion of familial hepatocellular carcinoma (HCC). We have analyzed the status of the p16INK4(MTS1) gene, a cyclin-dependent kinase inhibitor, in 26 patients with HCC of different etiologies. Four patients carried hemizygous germ-line point mutations of the p16INK4(MTS1) gene, suggesting the existence of familial HCC involving this gene. The wild-type allele was lost in the tumor in 2 of these 4 patients. Three of the patients carrying a germ-line mutation had non-cirrhosis-associated HCC. No somatic mutations of p16INK4(MTS1) were observed in the 26 cases of HCC. The most common somatic alteration of the p16INK4(MTS1) gene in HCC was de novo methylation, which was detected in 48% of the cases. Low levels (21%) of p16INK4(MTS1) gene allele loss were observed. Altogether, these results indicate that alteration of the p16INK4(MTS1) gene plays an important role in the genesis of HCC.

Adult↗