Treatment results and prognostic factors in 101 men treated for squamous carcinoma of the penis

PURPOSE: This retrospective study was performed to assess the treatment outcome and prognostic factors in 101 men with invasive squamous carcinoma of the penis treated at the Royal Marsden Hospital between 1960-1990. METHODS AND MATERIALS: The tumor was confined to the glans penis (T1) in 79 patients, 82 were node negative (N0), and two patients had distant metastases at presentation. The histology was Grade 1 (G1) in 36, Grade 2 (G2) in 18, Grade 3 (G3) in 28, and unknown in 19 patients. Node-positive disease was commoner in patients with G3 (p = 0.02) or T2/3/4 tumors (p = 0.007). Treatment for the primary tumor was external beam radiotherapy (EBRT) in 59, interstitial brachytherapy in 13, and partial or total penectomy in 29 patients. The median dose, dose/fraction, and treatment time for EBRT was 60 Gy, 2 Gy/fraction, and 46 days, respectively. Eighty patients received no inguinal node treatment, 13 had EBRT (4 with chemotherapy), and 8 underwent groin dissection at presentation. RESULTS: During a median follow-up of 5.2 years (2 months-22 years), 56 patients died (penile cancer 31, intercurrent illness 23 and unknown cause 2), giving 10 year overall and cause-specific survival (CSS) of 39 and 57%, respectively. Adverse prognostic factors for CSS on univariate analysis were G3, ulcerative/fungating or T2/3/ 4 tumors, node positive, Jackson's Stage 2/3/4, and surgical treatment for the primary. All but the last two were significant independent prognostic factors for CSS on multivariate analysis. Penile or perineal recurrence or residual disease after initial treatment was seen in 36 out of 98 evaluable patients, giving a 10-year local failure rate (LFR) of 45%. Local failure after initial treatment was successfully salvaged in the majority (26 out of 36) of patients with further surgery or radiotherapy, and local control was achieved ultimately in 74 out of 77 T1, 7 out of 12 T2; 3 out of 3 T3, and 3 out of 5 T4 tumors. In the 44 evaluable patients with T1 tumors treated by EBRT the only adverse RT parameter approaching prognostic significance (p = 0.052) was a BED value corrected for recovery of <60 Gy (alpha/beta 10, K = 0.5 Gy/day, mean = 21 days). CONCLUSION: Invasive squamous carcinomas of the penis carry a significant risk of loco-regional recurrence after initial radiotherapy and this can be successfully salvaged in most patients with further treatment. This mandates close follow-up to detect loco regional recurrence early.     

A differential scanning calorimetric study of Newcastle disease virus: identification of proteins involved in thermal transitions

The spatial and temporal pattern of expression of enhancer trap lines reporting on the wingless (wg) and engrailed (en) genes was characterized in the adult antenna of Drosophila melanogaster. The time courses of expression seen for wg and en, although different from each other, reveal a complex well-controlled pattern of temporal expression, providing evidence that regulatory mechanisms are preserved throughout the life span of the adult fly. Altering the life span demonstrates that the temporal patterns of expression of both wg and en are linked to life span. These studies suggest that the expression of wg and en in the adult antenna is controlled by age-dependent mechanisms.     

Hprt- mutation spectrum in a closely related pair of human bladder tumour cell lines after gamma-irradiation at different dose-rates

Inactivation of p53 gene and overexpression of MDR1 gene are both associated with drug resistance. Previous studies have suggested that p53 gene can modulate the expression activity of MDR1 gene promoter in a promoter-CAT system. In the present study, wild-type p53 gene cDNA was introduced into a multidrug-resistant cell line, KBv200, in which endogenous p53 gene is aberrant. In wt-p53 transfected cells, the expression of MDRI gene was significantly increased, accumulation of adriamycin (ADM) was decreased, and the sensitivity to vincristine (VCR), ADM and 5-fluorouracil (5-FU) was increased compared with the parent KBv200 cells. After treatment with ADM and VCR, the p53-transfectants were more susceptible to apoptosis. The results suggest that the increase in drug sensitivity of the cells may be, at least in part, due to p53-dependent apoptosis induced by anticancer agents.     

Diagnosis and treatment of suppurative complication of anaerobe etiology in trauma and orthopedic patients

An extensive study of road traffic accident cases occurring within eastern suburban Calcutta during April 1992 to March 1993 was done. Of which 276 fatal cases having minimum medical aids were taken into consideration to avoid erroneous interpretation. Male pedestrians of age group of 50 years and above were mostly involved during the time period of 5 A.M. to 12 Noon. Fatal Accidents mostly occurred during winter and on the broader roads (Highways) and in majority of cases victims were at fault.     

Anisotropy of radiance in tissue phantoms and Dunning R3327 rat tumors: radiance measurements with flat cleaved fiber probes

OBJECTIVE: To compare the prevalence of conduct problems (CP) according to level of urbanization and to determine which factors account for the potential difference in prevalence rates. METHOD: Study 1 used a questionnaire survey of a nationally representative sample of 10,462 Norwegian adolescents. Study 2 used a questionnaire survey of a representative sample of 1,346 adolescents living in Oslo. Self-reported CP included most DSM-III-R criteria for conduct disorder. RESULTS: CP rates were similar in all levels of urbanization, except for the only semimetropolitan city in the country, the capital Oslo, which had CP rates twice those of the rest of the country. This increase rate could not be explained by a series of commonly advocated explanations: family structure and parental practices, social network, socioeconomic status, integration in community activities, religious involvement, and race. However, involvement in "soft" drugs and associating with antisocial peers could explain the statistically differential rates. Furthermore, in the Oslo study, adolescents' CP did not vary according to density of population or region within the city. CONCLUSIONS: The results support previous studies showing increased rates of CP in urban areas. However, urbanization must pass a certain threshold before it has this effect. Moreover, the lack of support for commonly advocated explanations for the difference between urban and nonurban areas suggests that investigations specifically addressing potential explanations for this difference should be conducted. The results indicate that the increased rates of substance use in highly urbanized areas may account for the difference in CP rates by prolonging and aggravating CP.     

Cloning, expression and sequence analysis of the SphI restriction-modification system

SphI, a type II restriction-modification (R-M) system from the bacterium Streptomyces phaeochromogenes, recognizes the sequence 5'-GCATGC. The SphI methyltransferase (MTase)-encoding gene, sphIM, was cloned into Escherichia coli using MTase selection to isolate the clone. However, none of these clones contained the restriction endonuclease (ENase) gene. Repeated attempts to clone the complete ENase gene along with sphIM in one step failed, presumably due to expression of SphI ENase gene, sphIR, in the presence of inadequate expression of sphIM. The complete sphIR was finally cloned using a two-step process. PCR was used to isolate the 3' end of sphIR from a library. The intact sphIR, reconstructed under control of an inducible promoter, was introduced into an E. coli strain containing a plasmid with the NlaIII MTase-encoding gene (nlaIIIM). The nucleotide sequence of the SphI system was determined, analyzed and compared to previously sequenced R-M systems. The sequence was also examined for features which would help explain why sphIR unlike other actinomycete ENase genes seemed to be expressed in E. coli.     

Interaction between proteins containing homeodomains associated to leucine zippers from sunflower

A strategy based on the use of PCR with one degenerate oligonucleotide deduced from conserved sequences and lambda gt10 primers was used to isolate homeobox containing sequences from sunflower stem and root cDNA libraries. Six different partial cDNAs coding for the first 48 amino acids of homeodomains and amino terminal sequences were analyzed and found to be members of the HD-Zip superfamily, which contain a homeobox linked to a leucine zipper coding region. A full-length cDNA clone, Hahb-10, was isolated and characterized. The leucine zipper portions of Hahb-10 and of the previously reported Hahb-1 have been utilized to construct fusions with the N-terminal domain of the lambda repressor. These fusions were tested for their ability to bind to lambda promoters in vivo. The expression of a protein containing an active dimerization domain, but not capable of DNA binding, exerts a dominant negative effect on the ability of repressor-zipper fusions to bind to its target DNA. From these experiments, it was concluded that Hahb-1 and -10, when co-expressed, form preferentially homodimers. Exchange of conserved threonines and leucines at positions a1 and d1 of both zippers reduces dimerization efficiency and allows the formation of heterodimers, suggesting that these residues are, among others, determinants of the specificity of interaction, most likely through changes in hydrophobic packing interactions at the dimer interface. The results imply that a great number of interacting molecular entities compose this protein superfamily which is presumably involved in regulating plant developmental responses.