[The aging of adrenaline-containing local anesthetic solutions. II. Preservation of local anesthetics. Changes in local anesthetic activity and toxicity].
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Aging↗
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Treatment algorithm for locally recurrent osteosarcoma based on local disease-free interval and the presence of lung metastasis.
BACKGROUND: Local recurrence in osteosarcoma is clinically distinct from metastasis, although associated with a similar reduction in survival. The prognostic factors in locally recurrent osteosarcoma were investigated and these factors were translated into a management strategy. METHODS: In all, 407 consecutive patients with skeletal osteosarcoma between 1977 and 2002 were analyzed. Twenty-three patients with resectable local recurrence were analyzed. Clinical and tumor-related factors were assessed for significance in relation to survival and a management strategy was formulated based on factors found to be independently significant for survival. RESULTS: Seventeen of the 23 patients underwent primary resections and initial treatment, yielding an overall local recurrence rate of 4.2% for resectable cancer. Median time to local recurrence was 13 months (95% confidence interval, 9-16 months). The 5-year and 10-year survival rates in the recurrent cases were 29% and 10%, respectively. All patients received chemotherapy both for their primary and recurrent disease. Increased risk of local recurrence (P < .0001) was strongly correlated with positive margins of resection. The rate of local recurrence was not related to chemotherapy-associated necrosis in the primary tumor. Nevertheless, neoadjuvant therapy halved the risk of local recurrence (odds ratio, 1.92; P = .3, power 10%). The strongest correlate with poor survival was local recurrence within the first year after primary resection (P = .001), followed by metastasis at the time of first local recurrence (P = .04) and failure to achieve clinical remission after disease recurrence (P = .04). Chemotherapy-associated necrosis and margins of resection of the primary tumor were not significant prognostic variables for survival. Survival differed significantly among patients defined by local disease-free interval and lung metastasis (P = .0001). They required an individualized approach as captured in the management algorithm. CONCLUSION: There is a residual risk of local recurrence in patients despite favorable chemotherapy-associated necrosis and negative margins of resection. A treatment strategy emphasizing clinical remission at all identifiable sites offers the highest likelihood of survival in this patient population.
Adolescent↗
The influence of histopathologic criteria on the long-term prognosis of locally excised pT1 rectal carcinomas: results of local excision (transanal endoscopic microsurgery) and immediate reoperation.
PURPOSE: Local excision of early rectal cancer is a controversial issue, which is in part because of differences in the evaluation of histopathologic criteria. This prospective study was designed to determine prognostic factors for recurrences and the need for reoperation. METHODS: In 105 of 118 patients with pT1 carcinomas and local excision, results of recurrence rates and ten-year cancer-free survival were studied separately according to different histologic criteria (R0, R1, Rx, R < or = 1 mm, high-/low-risk situation), tumor localization (anterior, posterior, lateral wall and third of rectum), size, and degree of resection (full-thickness/partial wall). Patients were grouped into local excision (n = 89) and local excision followed by reoperation (n = 21). Risk classification was performed by division into "low-risk" carcinomas after local R0-resection (Group A) and unfavorable histologic results after local resection (R1, Rx, R < or = 1 mm, high-risk situation; Group B). RESULTS: Local recurrence rates after local R0-resection of low-risk carcinomas were 6 percent, whereas patients in Group B with local resection were 39 percent. The recurrence risk in those patients was significantly reduced to 6 percent by reoperation (P = 0.015). In addition, ten-year, cancer-free survival was 93 percent in Group B after reoperation compared with 89 percent in patients of Group A after local excision alone. CONCLUSIONS: Local R0-resection in cases with low-risk pT1 carcinomas represents an oncologically adequate therapy, which results in similar survival rates compared with primary radical surgery of pT1N0M0 rectal carcinomas. High recurrence rates are observed in tumors with unfavorable histologic result (Group B) requiring further treatment. In these cases immediate reoperation reduces the recurrence rate to 6 percent.
Adult↗
Local recurrence in patients with large and locally advanced breast cancer treated with primary chemotherapy.
BACKGROUND: Primary chemotherapy is being given in the treatment of large and locally advanced breast cancers, but a major concern is local relapse after therapy. This paper has examined patients treated with primary chemotherapy and surgery (either breast-conserving surgery or mastectomy) and has examined the role of factors which may indicate those patients who are subsequently more likely to experience local recurrence of disease. METHODS: A consecutive series of 173 women, with data available for 166 of these, presenting with large and locally advanced breast cancer (T2>/=4 cm, T3, T4, or N2) were treated with primary chemotherapy comprising cyclophosphamide, vincristine, doxorubicin, and prednisolone and then surgery (either conservation or mastectomy with axillary surgery) followed by radiotherapy were examined. RESULTS: The clinical response rate of these patients was 75% (21% complete and 54% partial), with a complete pathological response rate of 15%. A total of 10 patients (6%) experienced local disease relapse, and the median time to relapse was 14 months (ranging from 3 to 40). The median survival in this group was 27 months (ranging from 13 to 78). In patients having breast conservation surgery, local recurrence occurred in 2%, and in those undergoing mastectomy 7% experience local relapse of disease. Factors predicting patients most likely to experience local recurrence were poor clinical response and residual axillary nodal disease after chemotherapy. CONCLUSIONS: Excellent local control of disease can be achieved in patients with large and locally advanced breast cancers using a combination of primary chemotherapy, surgery and radiotherapy. However, the presence of residual tumor in the axillary lymph nodes after chemotherapy is a predictor of local recurrence and patients with a better clinical response were also less likely to experience local disease recurrence. The size and degree of pathological response did not predict patients most likely to experience recurrence of disease.
Adult↗
Is there a progression of histologic grade from radical prostatectomy to local recurrence in patients with clinically isolated local recurrence following surgery?
OBJECTIVE: To evaluate whether there is any histologic progression from radical prostatectomy (RP) to local recurrence in patients with clinically isolated local recurrence following RP. METHODS AND MATERIALS: A total of 43 patients with clinically isolated, biopsy proven, local recurrence following RP were retrospectively analyzed with respect to the change in Gleason score (GS) from RP to local recurrence. Central pathology review was undertaken for both RP and local recurrence biopsy specimens. The changes in primary and secondary Gleason grade (GG), and any potential correlation between the extent of GS change and other variables were also examined. RESULTS: Median age at the time of local recurrence was 67 years (range: 55-78). Median interval between RP and local recurrence was 3.6 years (range: 0.3-17.7). Eight had a short course (<3 months) of hormone therapy prior to RP. Initial GS of RP specimens was 5, 6, 7, 8, and 9 in 1, 3, 29, 1, and 9 patients, respectively. At the time of local recurrence, GS was upgraded in 13, unchanged in 23, and downgraded in 7. The extent of GS change was correlated with the interval between RP and local recurrence, but not with pathological T stage or age. CONCLUSION: There was no statistically significant change in GS from RP to local recurrence, although there was a trend toward a higher GS at the time of local recurrence. The extent of GS change was associated positively with the elapsed time to local recurrence.
Adenocarcinoma↗
[Local treatment of locally recurrent breast cancers].
For the treatment of recurrent breast cancer, surgical treatment of the local lesion is only of limited significance, leaving a major role for systemic treatment such as chemotherapy and endocrine therapy. Therefore, a new method of local treatment other than surgical removal alone, or systemic treatment of these locally recurrent breast cancers is required. For the treatment of locally recurrent breast cancer, intra-arterial infusion chemotherapy was performed through both the internal mammary artery and subclavian artery or individually. Fourteen cases of locally recurrent breast cancer in our hospital were treated with this therapy. Continuous infusion of 5-fluorouracil and intermittent injections of mitomycin, adriamycin or 4'-epi-adriamycin were jointly or individually done into each artery. Regression of the locally recurrent mass was periodically measured from 4 to 6 weeks after infusion. The percentage of patients with PR was 35.7%. Intra-arterial infusion chemotherapy is a useful preliminary procedure for systemic treatment of local lymph node recurrence from breast cancer. A treatment involving local infusion of the non-specific immuno-activators, OK-432 and PSK, has also been performed for local recurrent lesions of breast cancers. We injected OK-432 and 5% PSK solution into patients with locally recurrent breast cancers and studied their suppressive effect on tumor proliferation. Macroscopically, PR was noted in 3 of 12 patients given OK-432. CR+PR were obtained in 9 of 12 patients given PSK. These results suggest that local injection of OK-432 and PSK solution is beneficial in the management of nodular or scattered-type locally recurrent tumors except for infiltrating type.
Adult↗
A report of RTOG 8206: a phase III study of whether the addition of single dose hemibody irradiation to standard fractionated local field irradiation is more effective than local field irradiation alone in the treatment of symptomatic osseous metastases.
Hemibody irradiation (HBI) in a single exposure is an effective and safe technique for palliation of symptoms due to widespread bony metastases (RTOG 78-10). The present study (82-06) sought to explore the possibility that HBI added to local-field irradiation might delay the onset of metastases in the hemibody effected, as assessed by bone scans and X rays, and decrease the frequency of further treatment. The results of this clinical trial establish that 800 cGy of HBI is indeed causes micro-metastases to regress, perhaps completely. A total of 499 patients were randomized to receive either HBI or no further treatment following completion of standard palliative local field irradiation (300 cGy x 10) to the symptomatic site. Improvement was seen in time-to-disease progression at one year, 35% for local + HBI versus 46% on the local-only control arm. Time-to-new disease in the targeted hemibody was also improved. At one year, 50% of patients on the local + HBI arm showed new disease compared to 68% on the local-only arm. Furthermore, the median time-to-new disease within the targeted HBI area was 12.6 months for the local + HBI arm versus 6.3 months for patients in the local-only arm. Time-to-new treatment within the hemibody segment was also delayed. At one year, 76% of the local only group had been retreated versus 60% in the local + HBI arm. There were no fatalities and no radiation pneumonitis was seen in the local + HBI arm. Overall, the incidence of toxicities was low (5-15%). The occurrence of severe hematopoetic toxicities were significantly different in the local + HBI arm, but they were transitory. One life-threatening thrombocytopenia occurred, for a limited time, indicating excellent tolerance to HBI. This clinical trial demonstrates that HBI has the potential to be used to treat systemic and occult metastases, particularly if both halves of the body can be treated.
Aged↗
Electroanatomical Mapping (CARTO) of ectopic atrial tachycardia: impact of bipolar and unipolar local electrogram annotation for localization the focal origin.
UNLABELLED: Electroanatomical Mapping (CARTO) allows a tridimensional localization of ectopic atrial tachycardia (EAT). No standardized recommendation exists for annotation the local activation time in EAT using this new technology. In the present study bipolar local electrogram were used for CARTO guided RF ablation of EAT. In comparison the same maps were retrospectively analyzed by annotation the unipolar local electrogram. METHODS: In 15 consecutive patients (6m, 51+/-14 y) with EAT CARTO mapping was guided by annotation the earliest onset of the bipolar local electrogram. Following successful RF ablation the obtained EAT maps were subsequently evaluated by annotation of the earliest steepest negative intrinsic deflection of the unipolar local electrogram. Both CARTO maps were compared with regard to the region of focal EAT origin. RESULTS: RF ablation of all 15 EAT foci guided by annotation the bipolar local electrogram with CARTO was successful with a median of 3 [1-18] pulses and a median fluoroscopy time of 10 min [4-25]. All but one focus was located in the right atrium: posterior to posteroinferior region of the terminal crest in 6, septal region in 5, anterior superior region in 3 cases. One left sided EAT was located at the septum. The bipolar CARTO map demonstrated a "small territory" location of earliest activation (extension of the focus < or =0.4 cm(2)) in 14 out of 15 patients. In a single patient the bipolar map showed several sites of earliest local activation (extension >0.4 cm(2)). On the other side the retrospectively achieved unipolar maps demonstrated an extended region of earliest local activation in 6 out of 15 patients (>0.4 cm(2)). CONCLUSIONS: CARTO maps of EAT by annotation the earliest onset of the bipolar local electrogram provide an efficacious guide for location the focal origin. Extended regions of earliest local activation in EAT might be rather determined by annotation the unipolar in comparison to the bipolar local electrogram.
Adult↗
fatvg encodes a new localized RNA that uses a 25-nucleotide element (FVLE1) to localize to the vegetal cortex of Xenopus oocytes.
Vegetally localized transcripts have been implicated in a number of important biological functions, including cell fate determination and embryonic patterning. We have isolated a cDNA, fatvg, which encodes a localized maternal transcript that exhibits a localization pattern reminiscent of Vg1 mRNA. fatvg is the homologue of a mammalian gene expressed in adipose tissues. The fatvg transcript, unlike Vg1 which localizes strictly through the Late pathway, also associates with the mitochondrial cloud that is characteristic of the METRO or Early pathway. This suggests that fatvg mRNA may utilize both the METRO and Late pathways to localize to the vegetal cortex during oogenesis. We have dissected the cis-acting localization elements of fatvg mRNA and compared these elements with Vg1 mRNA. Our results indicate that, like most localized RNAs, in a variety of systems, transcripts of fatvg contain localization elements in the 3'UTR. The 3'UTR of fatvg mRNA contains multiple elements that are able to function independently; however, it functions most efficiently when all of the elements are present. We have defined a short 25-nucleotide element that can direct vegetal localization as a single copy. This element differs in sequence from previously described Vg1 localization elements, suggesting that different localization elements are involved in the localization of RNAs through the Late pathway.
3' Untranslated Regions↗
The effect of systemic therapy on local-regional control in locally advanced breast cancer.
One hundred and seven patients with locally advanced breast cancer were prospectively referred for multimodality treatment on protocol using chemohormonal therapy to maximal response followed by local treatment and maintenance therapy. Forty-eight patients (45%) were diagnosed with Stage IIIA disease, 46 (43%) with Stage IIIB inflammatory cancer, and 13 (12%) with Stage IIIB non-inflammatory disease. Induction therapy consisted of cyclophosphamide, doxorubicin, methotrexate, and 5-fluorouracil with hormonal synchronization using tamoxifen and conjugated estrogens. Local treatment was determined by response to chemotherapy. Patients with a clinical parital response underwent mastectomy followed by local-regional radiotherapy while patients with a clinical complete response were biopsied for pathologic correlation. Those with residual disease received mastectomy followed by radiotherapy while those with a pathologic complete response received radiation only to the intact breast and regional nodes. With a median follow-up of 64 months, patients with IIIA disease had a significantly lower local-regional failure rate compared to IIIB inflammatory patients, with the 5-year actuarial local-regional failure rate as only site of first failure 3% for IIIA disease versus 21% for IIIB inflammatory cancer (p = .02), and local-regional failure as any component of first failure 12% versus 36% (p = .01), respectively. When local-regional failure was analyzed by repeat biopsy, 5/31 (16%) patients with a pathologic complete response treated with radiation only developed a local-regional failure versus 2/53 (4%) with residual disease treated with mastectomy and postoperative radiotherapy. The 5-year actuarial local-regional failure rate as first site of failure was 23% for radiation only versus 5% for mastectomy and post-operative radiotherapy (p = .07). The response to chemotherapy did not reliably predict local-regional control. Both relapse-free survival and overall survival were significantly better for IIIA versus IIIB patients; stratification by repeat biopsy did not however, significantly affect either relapse-free or overall survival.
Adult↗
Neoadjuvant chemotherapy for localized Ewing's sarcoma of the extremities: preliminary results of a protocol which uses surgery (alone or followed by radiotherapy) for local control.
From June 1983 to December 1985, thirty-eight patients with localized Ewing's sarcoma of the extremities were treated with a protocol that consisted of an initial nine week period of polychemotherapy (vincristine, adriamycin and cyclophosphamide) followed by local therapy and additional chemotherapy (vincristine, adriamycin, cyclophosphamide and dactinomycin) for one year. As local treatment all patients were offered surgery; thirty-two accepted and six refused. These six patients were locally treated with radiotherapy alone (50 Gy). In the remaining patients an amputation was performed in one case and a resection in thirty-one. In resected patients when a wide margin was achieved (24 cases) no further local treatment was performed; when it was marginal (5 cases) or intralesional (2 cases) radiotherapy at lower doses (40 Gy) followed. At mean follow-up of thirty-seven months the percentage of continuously disease-free patients was 50% for those treated with radiotherapy, 76% with surgery, and 85% with surgery and radiotherapy. Eight patients developed metastatic disease and two patients had local recurrence and metastases. The local recurrences were seen in one patient locally treated with surgery and in one locally treated with radiotherapy. Nine major local complications were observed: three in patients treated with radiotherapy, five in patients treated with surgery, and one in a patient treated with surgery and radiotherapy. These results indicate that after induction chemotherapy conservative surgery is possible in almost all cases of Ewing's sarcoma of the extremities and that such treatment is better than radiotherapy alone as local therapy.
Adolescent↗
Local administration of monoclonal antibody-drug conjugate: a new strategy to reduce the local recurrence of colorectal cancer.
This report investigates the application of monoclonal antibody A7 and its drug conjugate in locally controlling colorectal cancer. The experimental protocol consisted of local retention, lymphatic delivery, normal organ distribution, systemic toxicity, and tumoricidal effects. When 125I-labeled monoclonal antibody (Mab) A7 was injected into the pelvis and the thigh of Balb/c mice, a high local retention unrelated to antigen-antibody interaction was observed at the injected site for 24 h after injection. An analysis of local retension properties related to antigen-antibody interaction, conducted by intratumorally or peritumorally injecting 125I-Mab A7 into the tumor-bearing athymic nude mice, revealed a significantly higher tumor localization of Mab A7 in comparison to i.v. injection. 125I-Mab A7 accumulated to a great extent in the ipsilateral regional lymph node but not in the contralateral regional lymph node. Normal organ accumulation of Mab A7 was lower in the locally injected group than in the i.v. injected group. Intratumoral injection of Mab A7-neocarzinostatin (A7-NCS) led to the complete remission of established tumor in 5 of 6 antigen-positive xenograft-bearing mice but exhibited a complete remission in only 1 of 6 antigen-negative xenograft-bearing mice. A single local injection of A7-NCS inhibited tumor development in 12 of 16 and 5 of 15 antigen-positive tumor-bearing mice and antigen-negative tumor-bearing mice, respectively, whereas neither a systemic injection of A7-NCS and NCS nor a local injection of NCS and saline had a notable inhibitory effect on tumor development. Systemic toxicity of NCS was markedly reduced when it was locally administered in the antibody-conjugated form. These findings indicate that local injection of immunoconjugate is a promising new field for controlling the local recurrence of colorectal cancer.
Animals↗
Exploring local and non-local interactions for protein stability by structural motif engineering.
In order to probe the relative contribution of local and non-local interactions to the thermodynamic stability of proteins, we have devised an experimental approach based on a combination of motif engineering and sequence shuffling. Candidate chain segments in an immunoglobulin V(L) domain were identified whose conformation is proposed to be dominated by non-local interactions. Locally interacting structural motifs of a different conformation were then constructed as replacements, by introducing motif consensus sequences. We find that all nine replacements we constructed systematically reduce the folding cooperativity. By comparing this destabilising effect with the folding transitions of shuffled sequences for three of these motifs, we estimate the contribution of local, native interactions to the free energy of folding. Our results suggest that local and non-local interactions contribute to stability by an approximately equal amount, but that local interactions stabilise by increasing the resistance to denaturation while non-local interactions increase folding cooperativity. The systematic loss of stability by sequence shuffling in these host-guest experiments suggests that the designed interactions indeed are present in the native state, thus consensus sequence engineering may be a useful tool in structure design, but non-local interactions must be taken into account for global stability engineering. Statistical approaches are powerful tools for engineering protein structure and stability, but an analysis based on local sequence propensities alone does not adequately represent the balance of sequence and context in protein structures.
Amino Acid Motifs↗
Breast conservation therapy: local tumor control in patients with pathologically clear margins who receive 5000 cGy breast irradiation without local boost.
A retrospective study was performed to determine the value of pathological evaluation of inked primary tumor specimen margins in the local control of patients with stage I and II breast cancer. In 150 patients with 153 invasive breast cancers, treatment involved surgical resection of the primary tumor, pathological determination of tumor-free inked specimen margins, and 5000 cGy whole breast radiation therapy (RT) without tumor bed RT local boost. This approach yielded an actuarial five-year local control rate of 95%. The local control rate was 96% for T-1 cases and 93% for T-2 cases. The local control rate was 96% for patients with clear margins achieved at initial resection and 94% for patients with clear margins achieved at re-excision. Among patients with clear margins at re-excision, the local control rate was 97% for those with no residual cancer and 88% for those with residual cancer. Patients with surgical margins clear by 3 mm or less had a local control rate of 92% at five years. Local control rates appear to be comparable to other breast conservation approaches which routinely employ local RT boosts. In omitting the local RT boost in patients with clear margins, the overall RT course will be briefer and the cosmetic changes associated with high-dose, large volume local RT boosts can be avoided.
Breast Neoplasms↗
Local therapy in localized Ewing tumors: results of 1058 patients treated in the CESS 81, CESS 86, and EICESS 92 trials.
PURPOSE: The impact of different local therapy approaches on local control, event-free survival, and secondary malignancies in the CESS 81, CESS 86, and EICESS 92 trials was investigated. METHODS AND MATERIALS: The data of 1058 patients with localized Ewing tumors were analyzed. Wherever feasible, a surgical local therapy approach was used. In patients with a poor histologic response or with intralesional and marginal resections, this was to be followed by radiotherapy (RT). In EICESS 92, preoperative RT was introduced for patients with expected close resection margins. Definitive RT was used in cases in which surgical resection seemed impossible. In CESS 81, vincristine, adriamycin, cyclophosphamide, and actinomycin D was used. In CESS 86, vincristine, adriamycin, ifosfamide, and actinomycin D was introduced for patients with central tumors or primaries >100 cm(3). In CESS 92, etoposide, vincristine, adriamycin, ifosfamide, and actinomycin D was randomized against vincristine, adriamycin, ifosfamide, and actinomycin D in patients with primaries >100 cm(3). RESULTS: The rate of local failure was 7.5% after surgery with or without postoperative RT, and was 5.3% after preoperative and 26.3% after definitive RT (p = 0.001). Event-free survival was reduced after definitive RT (p = 0.0001). Irradiated patients represented a negatively selected population with unfavorable tumor sites. Definitive RT showed comparable local control to that of postoperative RT after intralesional resections. Patients with postoperative RT had improved local control after intralesional resections and in tumors with wide resection and poor histologic response compared with patients receiving surgery alone. Patients with marginal resections with or without postoperative radiotherapy showed comparable local control, yet the number of patients with good histologic response was higher in the latter treatment group (72.2% vs. 38.5%). CONCLUSION: Patients with resectable tumors after initial chemotherapy had a low local failure rate. With preoperative RT, local control was comparable. RT is indicated to avoid intralesional resections. After intralesional or marginal resections and after a poor histologic response and wide resection, postoperative RT may improve local control.
Clinical Trials as Topic↗
Local structure prediction with local structure-based sequence profiles.
MOTIVATION: A large body of experimental and theoretical evidence suggests that local structural determinants are frequently encoded in short segments of protein sequence. Although the local structural information, once recognized, is particularly useful in protein structural and functional analyses, it remains a difficult problem to identify embedded local structural codes based solely on sequence information. RESULTS: In this paper, we describe a local structure prediction method aiming at predicting the backbone structures of nine-residue sequence segments. Two elements are the keys for this local structure prediction procedure. The first key element is the LSBSP1 database, which contains a large number of non-redundant local structure-based sequence profiles for nine-residue structure segments. The second key element is the consensus approach, which identifies a consensus structure from a set of hit structures. The local structure prediction procedure starts by matching a query sequence segment of nine consecutive amino acid residues to all the sequence profiles in the local structure-based sequence profile database (LSBSP1). The consensus structure, which is at the center of the largest structural cluster of the hit structures, is predicted to be the native state structure adopted by the query sequence segment. This local structure prediction method is assessed with a large set of random test protein structures that have not been used in constructing the LSBSP1 database. The benchmark results indicate that the prediction capacities of the novel local structure prediction procedure exceed the prediction capacities of the local backbone structure prediction methods based on the I-sites library by a significant margin. AVAILABILITY: All the computational and assessment procedures have been implemented in the integrated computational system PrISM.1 (Protein Informatics System for Modeling). The system and associated databases for LINUX systems can be downloaded from the website: http://www.columbia.edu/~ay1/.
Amino Acid Sequence↗
Salvage surgery for locally advanced and locally recurrent breast cancer.
OBJECTIVE: To determine if local control of breast cancer can be regained in patients with locally advanced and recurrent tumors using aggressive surgical treatment and reconstruction. DESIGN: A retrospective review of 15 consecutive patients. Patients were followed up from 8 to 32 months. SETTING: A university tertiary care facility in a metropolitan area. PATIENTS: All patients with locally advanced or recurrent breast cancer without known metastatic disease who underwent radical surgical resection of locally advanced breast cancer with reconstruction. MAIN OUTCOME MEASURES: Primary outcome measures were pathological findings, type of surgery, length of hospital stay, complications, local recurrence, and survival. RESULTS: Pathological findings showed 12 adenocarcinomas (80%) and three sarcomas (20%). Thirteen patients (86.7%) had undergone previous surgery, 11 (73.3%) had undergone previous radiation therapy, and all adenocarcinomas were progressing while patients were receiving chemotherapy. Full-thickness chest wall resection that included bone was required in 46.7%. The average hospital stay was 11.5 days. While 10 patients (66.7%) eventually manifested metastatic disease, local recurrence developed in only one. Minor complications occurred in six patients (40%) and major complications occurred in three (20%). There were no perioperative deaths. CONCLUSIONS: Patients presenting to our service had locally aggressive tumors that were recalcitrant to maximal medical management. With radical surgical treatment and reconstruction, there were no deaths, significant morbidity was low, and all but one patient regained local control. We found that aggressive surgical treatment and reconstruction is not only feasible in patients with locally advanced breast cancer but may be the only hope for local control in these patients who are difficult to treat.
Adenocarcinoma↗
Nuclear-localization-signal-dependent and nuclear-export-signal-dependent mechanisms determine the localization of 5-lipoxygenase.
5-Lipoxygenase (5-LO) metabolizes arachidonic acid to leukotriene A4, a key intermediate in leukotriene biosynthesis. To explore the molecular mechanisms of its cell-specific localization, a fusion protein between green fluorescent protein (GFP) and human 5-LO (GFP-5LO) was expressed in various cells. GFP-5LO was localized in the cytosol in HL-60 cells and in both the nucleus and the cytosol in RBL (rat basophilic leukaemia) cells, similarly to the native enzyme in these cells. The localization of GFP fusion proteins for mutant 5-LOs in a putative bipartite nuclear localization signal (NLS), amino acids 638-655, in Chinese hamster ovary (CHO)-K1 and Swiss3T3 cells revealed that this motif is important for the nuclear localization of 5-LO. A GFP fusion protein of this short peptide localized consistently in the nucleus. Leptomycin B, a specific inhibitor of nuclear export signal (NES)-dependent transport, diminished the cytosolic localization of 5-LO in HL-60 cells and that of GFP-5LO in CHO-K1 cells, suggesting that an NES-system might also function in determining 5-LO localization. Analysis of the localization of 5-LO during the cell cycle points to a controlled movement of this enzyme. Thus we conclude that a balance of NLS- and NES-dependent mechanisms determines the cell-type-specific localization of 5-LO, suggesting a nuclear function for this enzyme.
Active Transport, Cell Nucleus↗