Multi-targeted screening of botanicals in food supplements by liquid chromatography with tandem mass spectrometry.

Safety, quality and composition assessments of food supplements based on botanical ingredients are of major concern, as they have usually not been through a rigorous testing process as required for the approval of therapeutic phytopreparations. Therefore, an efficient multi-targeted method was developed to screen selected botanicals of interest in herbal food supplements. Liquid chromatography coupled with a hybrid triple quadrupole linear ion trap was used for this purpose. Botanicals were characterised by means of appropriate biomarkers, which were unambiguously identified by mass spectrometry using an information dependent acquisition experiment which combined a multiple reaction monitoring survey with dependent enhanced product ion scans. During this procedure, product ion scans of targeted analytes were generated at three collision energies and compared with an in-house library of MS/MS spectra acquired from reference standards of all biomarkers. This generic method enables detection, identification and quantification of 98 biomarkers intended to characterise 79 selected plants.

Assessment of cardiac exposure in left-tangential breast irradiation.

PURPOSE: To assess the value of treatment-planning related parameters namely, the breast volume; the distance of the inferior field border to diaphragm; and the cardiothoracic ratio for left-tangential breast irradiation. PATIENTS AND METHODS: Treatment plans of 27 consecutively left-sided breast cancer patients after breast conserving surgery were evaluated for several parameters concerning heart-irradiation. We measured the heart distance respective to the cardiothoracic ratio and the distance of the inferior field border to diaphragm, as well as the breast volume in correlation with the irradiated heart volume. RESULTS: The mean heart and left breast volumes were 504 cm(3) and 672.8 cm(3), respectively. The mean heart diameter was 13.4 cm; the mean cardiothoracic ratio 0.51 and the mean distance of the inferior field border to diaphragm was 1.4 cm. Cardiothoracic ratio (p=0.01), breast volume (p=0.0002), distance of the inferior field border to diaphragm (p=0.02) and central lung distance (p=0.02) were significantly correlated with the measured heart distance. A significant correlation was also found between cardiothoracic ratio, breast volume and distance of the inferior field border to diaphragm with the irradiated heart volume measured by V10, V20 and V40. CONCLUSION: The verification of parameters like cardiothoracic ratio, distance of the inferior field border to diaphragm and breast volume in left-sided breast cancer patients may help in determining which patients could benefit from more complex planning techniques such as intensity-modulated radiotherapy to reduced risk of late cardiac injury.

Quality of life and social integration after allogeneic hematopoietic SCT.

In total, 124 adult patients in remission after allogeneic hematopoietic SCT (HSCT) participated in a cross-sectional study to assess health-related quality of life (HRQL). Assessment of HRQL was carried out using two questionnaires: the (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy (FACT) with specific modules for BMT (FACT-BMT). Transplanted patients differed from healthy controls in many HRQL-related dimensions in the EORTC QLQ-C30: social functioning 73.4 versus 85.8, P<0.0001; role functioning 74.6 versus 83.3, P<0.004; physical functioning 83.9 versus 89.9, P<0.001; emotional functioning 72.2 versus 82.8, P<0.0001 but were not significant for global HRQL 71.2 versus 75.3, P<0.03. In total, 60% of the patients returned to work after HSCT; 31% part time and 29% full time. Age at HSCT and employment status were significantly associated with HRQL. Other factors such as disease and disease stage and especially the occurrence of late complications did not impact the perception of HRQL. This study suggests that the perception of HRQL after HSCT differs from the general population. Issues to increase work-related capabilities and improve social support need to be addressed.

Pelvic excision of large aggressive angiomyxoma in a woman: irradiation for recurrent disease.

Aggressive angiomyxoma (AAM) is a rare tumor that preferentially involves the pelvis and perineal regions and arises from the connective tissue. Its cause and pathogenesis are unknown at present. Treatment typically involves surgery, and despite apparently complete resection, local recurrences are common. We describe a case of a large angiomyxoma of the left pelvis in a 59-year-old woman who underwent two surgical excisions. The first had been done in May 1998. She developed a local recurrence in December 1998. A palliative resection with macroscopic residuals was performed in February 2001, followed by radiation therapy with a total dose of 60 Gy. The diagnosis was revised at the time of the second operation. Initially, the tumor was diagnosed as angiomyofibroblastoma. Follow-up 3 years after the radiation treatment revealed no recurrence. The time of the local control achieved as yet is already longer than the former time to progression between the first two surgical procedures. This is, to our knowledge, the second description of a therapeutic irradiation of a recurrent AAM. Radiation therapy is able to control a recurrent AAM for at least 3 years.

Separation of four isomeric tropane alkaloids from Schizanthus grahamii by non-aqueous capillary electrophoresis.

The potential of non-aqueous capillary electrophoresis was investigated for the separation of four isomeric tropane alkaloids, namely 3alpha-senecioyloxy-7beta-hydroxytropane, 3alpha-hydroxy-7beta-senecioyloxytropane, 3alpha-hydroxy-7beta-angeloyloxytropane and 3alpha-hydroxy-7beta-tigloyloxytropane extracted from Schizanthus grahamii. The composition of the organic solvent and the nature of the electrolyte were of considerable importance with respect to selectivity. Different organic solvents (i.e. methanol, ethanol, acetonitrile, tetrahydrofuran) and mixtures thereof were investigated. Moreover, different electrolytes such as formate, acetate and trifluoroacetate were tested. After optimisation, an electrolyte consisting of 1 M trifluoroacetic acid and 25 mM ammonium trifluoroacetate in methanol:ethanol (40:60, v:v) was selected. It provided an efficient separation of the four positional isomers as well as a good repeatability of migration time (RSD < 0.2%). The method was successfully used with electrospray MS to confirm the molecular mass of the tropane alkaloids.

Sphincter-conserving treatment of carcinomas of the anal margin.

Between April 1982 and December 1997 24 patients with carcinoma of the anal margin were treated with radiation therapy (RT) (10 patients) or RT-chemotherapy (CT) (14 patients). External beam RT (EBRT) was delivered in 18 patients, combined with brachytherapy in 5 patients, while one patient was treated with brachytherapy alone. Inguinal nodes were irradiated in 17 patients. Chemotherapy was based on 5-fluorouracil and mitomycin-C. At 5 years, the overall survival rate was 56% and the locoregional rate was 69.5%. Anal sphincter was preserved in 16/24 treated patients. Grade 4 late complications were observed in 3 patients. This study reinforces the notion that radical RT +/- CT provides a high probability of cure and sphincter preservation in patients presenting with this rare condition. Major late toxicity is uncommon; a better adaptation of treatment technique to the individual clinical situation may prevent some of the more severe complications in the future.

Total body irradiation before allogeneic bone marrow transplantation: is more dose better?

PURPOSE: This study was performed to retrospectively assess the potential influence of total-body irradiation (TBI) dose on overall survival in patients undergoing allogeneic bone-marrow transplants (BMT) for hematologic malignancies. METHODS AND MATERIALS: Between October 1984 and December 1996, 116 patients were conditioned with high-dose chemotherapy and fractionated TBI before allogeneic BMT. The median age was 34 years (range 3-60). The TBI dose was given in 6 fractions, twice-a-day, over 3 days before BMT. The total dose was 10 Gy in 24 patients, 12 Gy in 66 patients, and 13.5 Gy in 26 patients. RESULTS: TBI dose was inversely correlated with overall survival. Five-year survival was 62% for patients conditioned with 10 Gy, 55% for patients conditioned with 12 Gy, and 46% for patients conditioned with 13.5 Gy. Age at BMT was also independently correlated with survival, with the best outcome for patients < 40 years old. CONCLUSION: A TBI dose (fractionated) > 10 Gy may not necessarily be associated with a better outcome in patients undergoing allogeneic bone-marrow transplant for hematologic malignancies.

Ion permeation and selectivity of wild-type recombinant rat CNG (rOCNC1) channels expressed in HEK293 cells.

The permeation properties of adenosine 3', 5'-cyclic monophosphate (cAMP)-activated recombinant rat olfactory cyclic nucleotide-gated channels (rOCNC1) in human embryonic kidney (HEK 293) cells were investigated using inside-out excised membrane patches. The relative permeability of these rOCNC1 channels to monovalent alkali cations and organic cations was determined from measurements of the changes in reversal potential upon replacing sodium in the bathing solution with different test cations. The permeability ratio of Cl(-) relative to Na(+) (P(Cl)/P(Na)) was about 0.14, confirming that these channels are mainly permeable to cations. The sequence of relative permeabilities of monovalent alkali metal ions in these channels was P(Na) > or = P(K) > P(Li) > P(Cs) > or = P(Rb), which closely corresponds to a high-strength field sequence as previously determined for native rat olfactory receptor neurons (ORNs). The permeability sequence for organic cations relative to sodium was P(NH3OH) > P(NH4) > P(Na) > P(Tris) > P(Choline) > P(TEA), again in good agreement with previous permeability ratios obtained in native rat ORNs. Single-channel conductance sequences agreed surprisingly well with permeability sequences. These conductance measurements also indicated that, even in asymmetric bi-ionic cation solutions, the conductance was somewhat independent of current direction and dependent on the composition of both solutions. These results indicate that the permeability properties of rOCNC1 channels are similar to those of native rat CNG channels, and provide a suitable reference point for exploring the molecular basis of ion selectivity in recombinant rOCNC1 channels using site-directed mutagenesis.

NMR structure of a concatemer of the first and second ligand-binding modules of the human low-density lipoprotein receptor.

The ligand-binding domain of the human low-density lipoprotein receptor consists of seven modules, each of 40-45 residues. In the presence of calcium, these modules adopt a common polypeptide fold with three conserved disulfide bonds. A concatemer of the first and second modules (LB(1-2)) folds efficiently in the presence of calcium ions, forming the same disulfide connectivities as in the isolated modules. The three-dimensional structure of LB(1-2) has now been solved using two-dimensional 1H NMR spectroscopy and restrained molecular dynamics calculations. No intermodule nuclear Overhauser effects were observed, indicating the absence of persistent interaction between them. The near random-coil NH and H alpha chemical shifts and the low phi and psi angle order parameters of the four-residue linker suggest that it has considerable flexibility. The family of LB(1-2) structures superimposed well over LB1 or LB2, but not over both modules simultaneously. LB1 and LB2 have a similar pattern of calcium ligands, but the orientations of the indole rings of the tryptophan residues W23 and W66 differ, with the latter limiting solvent access to the calcium ion. From these studies, it appears that although most of the modules in the ligand-binding region of the receptor are joined by short segments, these linkers may impart considerable flexibility on this region.

Assessment of quality of life in patients treated with accelerated radiotherapy for laryngeal and hypopharyngeal carcinomas.

BACKGROUND: This study was conducted to evaluate quality of life (QOL) and functional outcome in patients with carcinomas of the larynx and hypopharynx treated with accelerated radiotherapy (RT). METHODS: Between January 1991 and September 1996, 21 patients treated with accelerated concomitant boost RT schedule (69.9 Gy in 5. 5 weeks) for laryngeal (n = 10) or hypopharyngeal (n = 11) carcinomas and who remained free of disease at 1-year minimum follow-up were evaluated. The functional outcome was assessed by the subjective Performance Status Scale for Head and Neck cancer (PSSHN) and general QOL by the European Organization for Research and Treatment of Cancer Core QOL questionnaire (EORTC QLQ-C30). The median length of follow-up was 37 months (range, 13 to 75). RESULTS: The PSSHN scores were 89, 84, and 86, respectively, for eating in public, understandability of speech and normalcy of diet (100 = normal function). Significantly lower scores for understandability of speech were observed in patients with advanced and laryngeal carcinomas. Normalcy of diet was affected negatively by the severity of xerostomia. All mean functional scale scores of the EORTC QLQ-C30 module were 20% to 25% below the higher score. Most of these scale scores were significantly affected by the severity of xerostomia. CONCLUSIONS: Patients treated with concomitant boost RT for laryngeal and hypopharyngeal carcinomas appear to have similar QOL and functional outcome to those reported for patients treated with conventional or hyperfractionated RT. As expected, many QOL scales were affected by the severity of xero- stomia.

Sphincter-sparing surgery after preoperative radiotherapy for low rectal cancers: feasibility, oncologic results and quality of life outcomes.

The present study assesses the choice of surgical procedure, oncologic results and quality of life (QOL) outcomes in a retrospective cohort of 53 patients with low-lying rectal cancers (within 6 cm of the anal verge) treated surgically following preoperative radiotherapy (RT, median dose 45Gy) with or without concomitant 5-fluorouracil. QOL was assessed in 23 patients by using two questionnaires developed by the QOL Study Group of the European Organization for Research and Treatment of Cancer: EORTC QLQ-C30 and EORTC QLQ-CR38. After a median interval of 29 days from completion of RT, abdominoperineal resection (APR) was performed in 29 patients (55%), low anterior resection in 23 patients (20 with coloanal anastomosis) and transrectal excision in one patient. The 3-year actuarial overall survival and locoregional control rates were 71.4% and 77.5% respectively, with no differences observed between patients operated by APR or restorative procedures. For all scales of EORTC QLQ-C30 and EORTC QLQ-CR38, no significant differences in median scores were observed between the two surgical groups. Although patients having had APR tended to report a lower body image score (P = 0.12) and more sexual dysfunction in male patients, all APR patients tended to report better physical function, future perspective and global QOL. In conclusion, sphincter-sparing surgery after preoperative RT seems to be feasible, in routine practice, in a significant proportion of low rectal cancers without compromising the oncologic results. However, prospective studies are mandatory to confirm this finding and to clarify the putative QOL advantages of sphincter-conserving approaches.

Critical appraisal of a conformal head and neck cancer irradiation avoiding electron beams and field matching.

PURPOSE: In head and neck cancer patients, spinal chains are usually irradiated by a combination of photon and electron beams, requiring high precision in field matching. This study compares a conventional treatment approach where two lateral photon beams are combined to direct electron fields, to a conformal radiotherapy based on five photon fields, covering the whole neck. METHODS AND MATERIALS: A comparative analysis of dose distributions and dose-volume histograms was carried out in patients with locally advanced head and neck tumors, for which planning target volumes (PTV) were outlined from the base of the skull down to the supraclavicular region. The prescribed dose to PTV (excluding booster irradiation) was 54 Gy, with spinal dose constraint not exceeding 75% of the total dose, whatever the technique. RESULTS: For the new five-field technique, minimum and maximum point doses showed mean deviations, on five patients entered in the study, of 84% and 113% from the ICRU prescription point. In the conventional treatment, the corresponding figures were 73% and 112%, respectively. A positioning error analysis (isocenter displacement of 2 mm, in all directions) did not elicit any systematic difference in five-field treatment plans while hot spots were found with electron fields. CONCLUSIONS: The five-field technique appears routinely feasible and compares favorably with the conventional mixed photon- and electron-therapy approach, especially in regard to its better compliance with dose homogeneity requirements and a reduced risk in dose inhomogeneity related to field matching and patient positioning.

Primary mediastinal large B-cell lymphoma: the need for prospective controlled clinical trials.

Primary mediastinal large-B cell lymphomas (PMLCL) are considered to be a distinct clinicopathologic entity among the diffuse large B-cell lymphomas. This study evaluated the prognostic factors and therapeutic outcome of PMLCL in a single-institution series. Twenty seven patients were reviewed. Nineteen of the 27 had Stage I-II and 8 had Stage III-IV disease. B-symptoms were found in 11 (41%) and bulky disease in 10 (37%) patients. All were initially given combination chemotherapy (CT): doxorubicin-containing regimens to 23 patients (11 patients had CHOP, 12 received more intensive third-generation regimens) and 4 elderly (>70 years) patients received CVP. Eleven responders were consolidated with irradiation (RT) as part of their initial treatment, with a median total dose of 39 Gy. Nineteen patients (70%) achieved clinical remission (15 CR and 4 PR) with their initial therapy. Forty-four percent of patients remained progression-free and 59% are alive at 3 years. The actuarial 10-year time to progression (TTP) and overall survival (OS) were 44% and 50%, respectively. Age >60 years, performance status >1 and IPI intermediate-high to high risk were significantly associated with poorer OS and TTP by univariate analysis (log-rank test). A better outcome was associated with the use of more aggressive chemotherapy regimens or with the inclusion of RT in the first-line treatment. Our analyses suggest that the application of radiotherapy in combination regimens and the use of more aggressive chemotherapy in the treatment of this particular type of lymphoma should now be evaluated in prospective randomized trials.

Prospective pilot study of sildenafil for treatment of postradiotherapy erectile dysfunction in patients with prostate cancer.

PURPOSE: Erectile dysfunction is a common late complication patients may experience after external-beam radiotherapy for prostate cancer. The efficacy and safety of oral sildenafil to correct sexual dysfunction caused by external-beam radiotherapy was studied in patients participating in our prospective trial. PATIENTS AND METHODS: Thirty-five assessable patients participated in this prospective pilot study. Using a 25-point scale based on the International Index of Sexual Function, erectile dysfunction was assessed weekly, during which time patients received sildenafil 100 mg orally once a week for 6 consecutive weeks. Response was defined as a score of 18 or more, corresponding to at least one successful attempt at sexual intercourse per week. RESULTS: Thirty patients (86%) completed the 6-week study. Seventy-seven percent of these patients had significantly improved erectile function, allowing recovery of full capacity for sexual intercourse. Of 27 patients not receiving concomitant hormone treatment, failure to respond was observed in only four patients (15%) compared with four (50%) of eight patients receiving hormonal treatment during the study. The time course of response was gradual, with 40%, 57%, 66%, 69%, and 74% responding at weeks 1 through 5, respectively. Therapy was generally well tolerated. The most frequently reported side effects in patients were flushing (37%), transient headache (17%), and dyspepsia (9%). No patient reported priapism, and no cardiovascular event or death was observed. After response, 12 patients (34%) reported the ability to achieve and maintain an erection sufficient for intercourse in the absence of sildenafil (ie, 24 hours to 6 days after taking the medication). CONCLUSION: This study suggests that oral sildenafil is well tolerated and can reverse erectile dysfunction after radiotherapy in a substantial proportion of prostate cancer patients.

Primary mediastinal large B-cell lymphoma (PMLCL): the need for prospective controlled clinical trials.

Primary mediastinal large-B cell lymphomas (PMLCL) are considered to be a distinct clinicopathologic entity among the diffuse large B-cell lymphomas. This study evaluated the prognostic factors and therapeutic outcome of PMLCL in a single-institution series. Twenty seven patients were reviewed. Nineteen of the 27 had Stage I-II and 8 had Stage III-IV disease. B-symptoms were found in 11 (41%) patients and bulky disease in 10 (37%). All patients were initially given combination chemotherapy (CT): doxorubicin-containing regimens to 23 patients (11 patients had CHOP, 12 more intensive third-generation regimens) and 4 elderly (>70 years) patients received CVP. Eleven responders were consolidated with irradiation (RT) as part of their initial treatment, with a median total dose of 39 Gy. Nineteen patients (70%) achieved clinical remission (15 CR and 4 PR) with their initial therapy. Forty-four percent of patients remained progression-free and 59% are alive at 3 years. The actuarial 10-year TTP and OS were 44% and 50%, respectively. Age >60 years, performance status >1 and IPI intermediate-high to high risk were significantly associated with poorer OS and TTP by univariate analysis (log-rank test). A better outcome was associated with the use of more aggressive chemotherapy regimens or with the inclusion of RT in the first-line treatment. In conclusion our analyses suggest that the application of radiotherapy in combination regimens and the use of more aggressive chemotherapy in the treatment of this particular lymphoma entity should be evaluated in prospective randomized trials.

Altered apoptotic profiles in irradiated patients with increased toxicity.

PURPOSE: A retrospective study of radiation-induced apoptosis in CD4 and CD8 T-lymphocytes, from 12 cancer patients who displayed enhanced toxicity to radiation therapy and 9 ataxia telangiectasia patients, was performed to test for altered response compared to healthy blood-donors and normal cancer patients. METHODS AND MATERIALS: Three milliliters of heparinized blood from each donor was sent via express post to the Paul Scherrer Institute (PSI) for subsequent examination. The blood was diluted 1:10 in RPMI medium, irradiated with 0-, 2-, or 9-Gy X-rays, and incubated for 48 h. CD4 and CD8 T-lymphocytes were then labeled using FITC-conjugated antibodies, erythrocytes were lysed, and the DNA stained with propidium iodide. Subsequently, cells were analyzed using a Becton Dickinson FACScan flow cytometer. Radiation-induced apoptosis was recognized in leukocytes as reduced DNA content attributed to apoptosis-associated changes in chromatin structure. Apoptosis was confirmed by light microscopy, electron microscopy, and by the use of commercially available apoptosis detection kits (in situ nick translation and Annexin V). Data from hypersensitive individuals were compared to a standard database of 105 healthy blood-donors, and a database of 48 cancer patient blood donors who displayed normal toxicity to radiation therapy. To integrate radiosensitivity results from CD4 and CD8 T-lymphocytes after 2 and 9 Gy, z-score analyses were performed. RESULTS: A cohort of 12 hypersensitive patients was evaluated; 8 showed enhanced early toxicity, 3 showed enhanced late toxicity, and 1 showed both. The cohort displayed less radiation-induced apoptosis (-1.8 sigma) than average age-matched donors. A cohort of 9 ataxia telangiectasia homozygotes displayed even less apoptosis (-3.6 sigma). CONCLUSION: The leukocyte apoptosis assay appears to be a useful predictor of individuals likely to display increased toxicity to radiation therapy; however, validation of this requires a prospective study.

Avoidance of treatment interruption: an unrecognized benefit of accelerated radiotherapy in oropharyngeal carcinomas?

PURPOSE: To assess the impact of treatment interruption on the potential gain in locoregional control obtained with accelerated radiotherapy (RT) compared with conventionally fractionated RT in patients with oropharyngeal carcinomas. METHODS AND MATERIALS: 152 patients treated with radical RT for oropharyngeal carcinomas between 1979 and 1996 were retrospectively analyzed. According to the American Joint Committee on Cancer (AJCC) staging system, there were 6/30/43/73 stages III/III/IV. Sixty-one patients were treated with a conventional RT schedule (median dose 70 Gy in 35 fractions), and 91 patients with either of two 5/5.5-week accelerated RT schedules (median dose 69.6-69.9 Gy in 41 fractions). Discounting weekends, RT was interrupted for 2 consecutive days or more in 53 patients (median duration 11 days, range 2-97), including 67% of the patients in the conventional RT group and 13% in the accelerated RT group. Median follow-up for surviving patients was 55 months (range 23-230). The Cox proportional hazards model was used for the multivariate analysis of factors influencing locoregional control. RESULTS: In univariate analysis, factors associated with a significant decrease in locoregional control included WHO performance status > or =1, advanced AJCC stages (III and IV), conventional RT fractionation, overall treatment time > or =44 days (median), and RT interruption. In the multivariate analysis, when introduced into the model individually, the three significant therapeutic factors remained significant after adjustment for the forced clinical variables. However, when the three therapeutic factors were introduced together into the model, beside the AJCC stage (P = 0.017), only RT interruption remained a significant independent adverse prognostic factor (P = 0.026). CONCLUSIONS: This multivariate analysis highlights the potential negative impact of treatment gaps on locoregional control in oropharyngeal carcinomas. This suggests that treatment interruption may be an even more important parameter than the type of RT schedule per se. Thus, when assessing the relative merit of two RT schedules, inclusion of the other therapeutic factors in a multivariate model is mandatory in order to avoid misinterpretation of the results.

Seminoma of the testis: is scrotal shielding necessary when radiotherapy is limited to the para-aortic nodes?

PURPOSE: To evaluate the influence of different shielding conditions and field geometry on the scatter dose to the remaining testicle during postoperative radiotherapy (RT) in seminoma. MATERIALS AND METHODS: Testicular dose measurements were made with LiF thermoluminescent dosimeters (TLD) in 29 patients with stage I and IIA seminoma. The target volume consisted of para-aortic (PA) and para-aortic and homolateral iliac (PAI) lymph nodes in 14 and 15 patients, respectively. All patients had a scrotal shield as well as an additional block extending 7 cm inferiorly from the caudal field edge to shield the testicle from external scatter and collimator leakage. Doses with and without testicular blocks were measured for all patients. In seven patients treated exclusively to the PA region the gonadal dose was assessed according to four different shielding conditions: without any protection, with a gonadal shield alone, with the addition of an inferior field border block to the gonadal shield, and with the field border block alone. RESULTS: For patients treated with PAI fields the mean testicular doses per fraction were 3.89 cGy (S.D. +/- 1.44) and 1.48 cGy (S.D. +/- 0.51) without and with gonadal shielding, respectively (P-value < 0.001); the corresponding values for PA fields were 1.86 cGy (S.D. +/- 0.86) and 0.65 cGy (S.D. +/- 0.35). For the patients treated to the PA region and assessed according to the four different shielding conditions, the additional external block to the testicular shield did not reduce significantly the measured dose on the testis. CONCLUSIONS: These results suggest a benefit of gonadal shielding even in seminoma patients undergoing radiotherapy limited to the para-aortic region.

Upstream and downstream sequence elements determine the specificity of the rice tungro bacilliform virus promoter and influence RNA production after transcription initiation.

The contribution of sequences upstream and downstream of the transcription start site to the strength and specificity of the promoter of rice tungro bacilliform virus was analysed in transgenic rice plants. The promoter is strongly stimulated by downstream sequences which include an intron and is active in all vascular and epidermal cells. Expression in the vascular tissue requires a promoter element located between -100 and -164 to which protein(s) from rice nuclear extracts bind. Elimination of this region leads to specificity for the epidermis. Due to the presence of a polyadenylation signal in the intron, short-stop RNA is produced from the promoter in addition to full-length primary transcript and its spliced derivatives. The ratio between short-stop RNA and full-length or spliced RNA is determined by upstream promoter sequences, suggesting the assembly of RNA polymerase complexes with different processivity on this promoter.

A conservation approach to pharyngeal carcinoma with advanced neck disease: optimizing neck management.

BACKGROUND: Surgical management of advanced neck disease remains controversial when a conservative approach based on radiotherapy is retained for primary tumors. The objective of this study was to evaluate retrospectively treatment results in pharyngeal cancers presenting with N2-N3 neck disease, using neck dissection followed by radical locoregional radiotherapy (RT) and to compare these results with those obtained in patients treated by radical RT alone. METHODS: From August 1991 to November 1996, 41 patients with carcinomas of the oro- or hypopharynx were staged as T1-T3 N2-N3 M0 (American Joint Committee on Cancer [AJCC] stage IV). Twenty-four patients were treated with neck dissection followed by RT (group 1) and 17 patients with radical RT (group 2) using a progressively accelerated concomitant boost schedule. Chemotherapy was delivered to 6 patients in group 1 and 8 in group 2 partially concomitantly with RT. RESULTS: Three-year actuarial locoregional control was 73% and 55% for groups 1 and 2, respectively (p = .52). The corresponding 3-year actuarial overall survival rates were 37% and 50% (p = .42). Severe postoperative complications were observed after neck dissection in four patients (16%). Acute toxicity during RT was similar in the two groups. Late toxicities were also similar, except for two patients in group 1 who developed severe laryngeal edema. CONCLUSIONS: Neck dissection followed by radical RT to the primary tumor and neck represents a valid treatment option in this subset of patients, allowing good control of advanced neck disease, while at the same time conserving pharyngolaryngeal function. However, for patients who are at high risk of severe postoperative complications, radical RT can be considered a worthy alternative, particularly for oropharyngeal carcinomas.