Comparative Transcriptomic Analysis of the Flavor Production Mechanism in Yogurt by Traditional Starter Strains.

Synergistic fermentation of milk by Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus is one of the key factors that determines the quality of yogurt. In this study, the mechanism whereby yogurt flavor compounds are produced by mixture of S. thermophilus SIT-20.S and L. delbrueckii ssp. bulgaricus SIT-17.B were investigated by examining these strains' flavor production, growth, and gene transcription. The results showed that yogurt produced by a 10:1 mixture of the aforementioned strains had the highest abundance of acetoin, whereas yogurt produced by a 1:1 mixture had the highest abundance of diacetyl and acetaldehyde. In addition, the growth of S. thermophilus SIT-20.S was enhanced in the 10:1 mixture. Transcriptomic analysis revealed differentially expressed genes in the flavor-compound-related pathways of S. thermophilus SIT-20.S and L. delbrueckii ssp. bulgaricus SIT-17.B in yogurts produced by 10:1 and 1:1 mixture compared with those produced by either strain alone. Mixed fermentations regulated the expression of genes related to glycolysis, resulting in an increase of pyruvate, which is an important precursor for diacetyl and acetoin synthesis. The gene encoding the acetoin reductase (SIT-20S_orf01454) was decreased in S. thermophilus SIT-20.S, which ensured the accumulation of acetoin. Besides, gene encoding the acetaldehyde dehydrogenase (SIT-20S_orf00949) was upregulated in S. thermophilus SIT-20.S, and the expression of alcohol dehydrogenase (SIT-20S_orf01479; SIT-17B_orf00943) was downregulated in both strains, maintaining the abundance of acetaldehyde. In addition, the gene encoding the NADH oxidase (SIT-17B_orf00860) in L. delbrueckii ssp. bulgaricus SIT-17.B were upregulated, which promoted the accumulation of diacetyl and acetoin. In conclusion, we characterized the mechanism by which S. thermophilus and L. delbrueckii ssp. bulgaricus synergistically generated yogurt flavor compounds during their production of yogurt and highlighted the importance of appropriate proportions of fermentation starters for improving the flavor of yogurts.

[Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma].

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

[The expression level of secretory mature B cell surface antigen in primary diagnosed multiple myeloma and its clinical significance].

Objective: To explorer Secretory mature B cell surface antigen (sBCMA) expression level, changes during treatment and clinical significance in newly diagnosed MM patients. Methods: Clinical data of 158 MM patients admitted to the Department of Hematology, the First Affiliated Hospital of Soochow University from August 2018 to September 2020 were analyzed retrospectively. The concentration of sBCMA in the patients was determined by BCMA ELISA and compared with the normal range. The results were compared with clinical efficacy, age, type, R-ISS stage, renal impairment, and humoral immune function. Results: The median age of the patients was 57 (31-73 years old), 86 (54.5%) males and 72 (45.5%) females, mainly IgG type, 81 patients(51.2%). SBCMA value M(Q1,Q3) was 76.50 (55.50, 94.40) µg/L, 100% higher than the upper limit of normal value. According to the efficacy evaluation, the patients were divided into complete remission(CR) group, very good partial remission(VGPR) group, partial remission(PR) group and ineffiecacy group, the results showed the level of sBCMA in CR group[80.10 (58.05, 96.90) vs 15.70 (9.85, 28.65) µg/L] and VGPR group[74.60 (52.20, 93.00) vs 17.20 (13.30, 38.80) µg/L]was significantly higher than that before treatment(all P<0.001), and there was no significant difference in PR group and ineffective group before and after treatment (all P>0.05).The amount of serum intact protein M protein was positively correlated with the level of sBCMA expression in newly diagnosed patients (r=0.22, P=0.040), and there was no correlation between the proportion of bone marrow plasma cells and sBCMA expression (r=0.07, P=0.449).The correlation between sBCMA levels at initial diagnosis and MM type[IgG type, IgA type vs light chain type:(78.6±3.5), (72.4±5.4) vs (83.8±6.9)µg/L], age[≥65 vs<65 years: (73.6±5.5)vs (79.3±3.1)µg/L], R-ISS stage[stage Ⅰ, Ⅱ vs Ⅲ:(80.2±3.1) vs (69.4±6.1)µg/L], renal impairment [Creatinine clearance rate (Ccr) ≤30 vs>30 ml/min:(81.6±4.8) vs (76.5±3.4)µg/L], and high-risk karyotype[high-risk vs standard-risk:(73.6±5.7) vs (80.2±3.2)µg/L] were not associated (all P>0.05). Expression levels of sBCMA were negatively correlated with IgM levels in MM patients (r=-0.39, P=0.002) and after treatment (r=-0.25, P=0.015). Conclusions: The expression of sBCMA in MM patients is a reliable indicator of the clinical efficacy of MM and is related to the occurrence of MM immune deficiency and recovery after treatment. sBCMA can be used as a new independent marker for monitoring and predicting the efficacy of MM patients.

[A clinical retrospective analysis of newly diagnosed multiple myeloma patients with systemic light chain amyloidosis].

Objective: To analyze the clinical characteristics, treatment response, and prognosis of newly diagnosed symptomatic multiple myeloma (MM) patients with systemic light chain amyloidosis (AL) . Methods: The clinical data of 160 patients with newly diagnosed MM treated at the First Affiliated Hospital of Soochow University from January 1, 2017 to October 31, 2018, were retrospectively analyzed. According to the histopathological biopsy results of bone marrow, skin, and other tissues, the patients were divided into two groups according to whether amyloidosis was combined or not, namely, the MM+AL group and the MM group. The clinical characteristics and treatment responses of the two groups were compared. Results: Among the 160 patients with newly diagnosed MM, there were 42 cases in the MM+AL group and 118 cases in the MM group. In terms of clinical features, the involved light chain and non-involved light chain (dFLC) in the MM+AL group was significantly higher than that in the MM group (P=0.039) . After induction treatment, the MM+AL group had a higher overall response rate (85.7%vs 79.7%, P<0.05) and higher excellent partial response (76.2%vs 55.1%, P<0.05) . After a median follow-up of 26 (0.25-41) months, there was no significant difference in the progression free survival and overall survival (OS) between the two groups (P>0.05) . The OS of patients in autologous hematopoietic stem cell transplantation group was better than that in non transplantation group (P<0.05) .The prognosis of patients with cardiac involvement in the MM+AL group was significantly worse than that in the MM group and MM+AL group without cardiac involvement (P<0.001) , with a median OS of only 13 months. Conclusion: The differential diagnosis between the MM+AL and MM groups requires histopathology, particularly for patients with significantly increased dFLC. The overall remission rate of patients in MM+AL group after 4 courses of induction chemotherapy was higher than that in MM group. The prognosis of patients with cardiac involvement in MM+AL group was poor.

[Efficacy and safety of lenalidomide combined with bortezomib and dexamethasone induction therapy in newly diagnosed patients with multiple myeloma].

Objective: This study aimed to evaluate the efficacy and safety of lenalidomide combined with bortezomib and dexamethasone (VRD) in the treatment of newly diagnosed multiple myeloma (MM) . Methods: A total of 150 newly diagnosed patients with MM diagnosed in The First Affiliated Hospital of Soochow University from November 2018 to February 2021 and received VRD as the induction regimen were included to evaluate the safety and efficacy of VRD induction therapy for newly diagnosed MM. Results: The median follow-up was 22 months, two patients (1.3%) died early after treatment, and 148 patients (98.7%) completed induction therapy. 116 patients (77.3%) were mobilized to collect autologous hematopoietic stem cells, 101 cases (87.1%) were qualified in the collection, of which 48 cases (41.4%) were excellent in the collection. The 3-year progression-free survival (PFS) rate was 59%, and the 3-year overall survival (OS) rate was 83%. After induction, complete remission (CR) /stringent CR rate was 54.4%, ≥ very good partial remission rate was 77.3%, overall response rate was 86.0%, and minimal residual disease negative rate was 46.0%. There was no statistically significant difference in the efficacy of cytogenetic high-risk patients compared with standard risk patients (P=0.456) . The median PFS time of cytogenetic high-risk patients was shorter than that of standard risk patients (not reached vs 33 months, P=0.014) . There was no statistically significant difference in the median OS time (not reached vs not reached, P=0.072) . The highest incidence of hematological adverse events was thrombocytopenia (72%) , followed by neutropenia (42%) and anemia (20%) . The highest incidence of non-hematological adverse events was peripheral neuritis (56.7%) . The main digestive tract symptoms include constipation (30.0%) and diarrhea (17.3%) . Upper respiratory tract infection (23.3%) and lung infection (7.3%) are the main infections. The incidence of adverse thrombocytopenia (90.0% vs 63.7%, P=0.001) , neutropenia (54.2% vs 36.3%, P=0.038) , anemia (33.3% vs 13.7%, P=0.005) , diarrhea (27.1% vs 12.7%, P=0.030) , limb edema (20.8% vs 3.9%, P=0.030) , fever (20.8% vs 4.9%, P=0.006) , thrombosis (8.3% vs 0, P=0.016) , and renal function deterioration (20.8% vs 3.9%, P=0.030) in patients with renal insufficiency was higher than that in patients with normal renal function. Conclusion: The VRD regimen has a significant effect on newly diagnosed MM, does not affect the hematopoietic stem cell collection, and has controllable adverse events; however, the incidence of adverse events was higher in patients with renal insufficiency.

[Clinical and prognostic values of TP53 mutation in patients with B-lineage acute lymphoblastic leukemia].

Objective: To investigate the survival and prognosis of B-lineage acute lymphoblastic leukemia (B-ALL) patients with TP53 mutation. Methods: The clinical data of 479 newly diagnosed B-ALL patients treated in the First Affiliated Hospital of Soochow University from January 2016 to December 2019 were retrospectively analyzed. Results: Among 479 B-ALL patients, 34 cases (7.1%) were positive for TP53 gene mutation, and a total of 36 TP53 mutations were detected, including 10 frameshift gene mutations (27.8%) , 23 missense mutations (63.9%) and 3 nonsense mutations (8.3%) . A total of 34 (94.4%) mutations were located in the DNA binding domain (exons 5-8) .The average number of mutated genes in patients with TP53 gene mutation (2.3) and the group without TP53 gene mutation (1.1) were statistically different (P<0.001) . The proportion of Ph positive and Ph-like positive patients in the TP53 gene mutation negative group was significantly higher than that of the TP53 mutation positive group, and the difference was statistically significant (P<0.001) . The 3-year OS and EFS rates of the TP53 gene mutation negative group were significantly higher than those of the TP53 gene mutation positive group. The differences in OS and EFS rates between the two groups were statistically significant (χ(2)= 4.694, P = 0.030; χ(2)= 5.080, P= 0.024) . In the multivariate analysis, failure to achieve remission (CR) after one course of induction chemotherapy was an independent adverse prognostic factor affecting OS.Of the 34 patients with TP53 mutation, 16 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the CR(1) state, and 2 patients with recurrence after transplantation obtained CR(2) after infusion of donor-derived anti-CD19 chimeric antigen receptor T (CAR-T) cells. Among the 11 patients with TP53 gene mutation who relapsed during consolidation chemotherapy, 6 received anti-CD19 CAR T cell therapy, 4 patients achieved remission and minimal residual disease (MRD) turned negative, followed by bridging allo-HSCT, and 2 of them sustained CR. Conclusion: Missense mutations are the most common in B-ALL patients with TP53 gene mutation, and the majority of mutations were located in the DNA binding domain. B-ALL patients with TP53 gene mutation should undergo allo-HSCT as soon as possible after CAR-T cell therapy has cleared the MRD after recurrence. B-ALL patients with TP53 gene mutation still have a higher recurrence rate after allo-HSCT, and the infusion of donor-derived CAR-T cells can achieve better sustained remission.

[Source investigation on a familiar cluster of coronavirus disease 2019 in Dandong city of Liaoning Province].

To Track the source of the infection through an investigation of a clustering of coronavirus disease 2019(COVID-19), and provide scientific basis and Strategy for the effective control of the aggregated epidemic situation of COVID-19. Field epidemiological method was used to survey the cases and related close contacts in a family clustering epidemic of COVID-19 in Dandong city of Liaoning Province. We obtained survey data for a descriptive analysis.Real time RT-PCR technique was used to detect 2019-nCoV nucleic acid in samples collected from cases and related close contacts combined with serum specific antibody detection. A total of 3 confirmed cases and 2 asymptomatic infection cases were discovered in the clustering epidemic, with 34 close contacts.Of eight close family contacts visiting from other province, one patient was on the same flight as the confirmed case, and her antibody IgG was positive. The family clustering was caused by past infection case who visited her friend through Wuhan from other provinces to local area.

[Clinical implication of minimal residual disease monitoring by 10-color flow cytometry in multiple myeloma].

Objective: To evaluate the prognostic significance of minimal residual disease (MRD) monitoring by 10-color flow cytometry in multiple myeloma (MM) patients after treatment. Methods: 150 patients with MM who were admitted to the First Affiliated Hospital of Soochow University from July 2015 to July 2017 were retrospectively analyzed. Clinical data, MRD data monitoring by 10-color flow cytometry and prognosis were analyzed. Results: 39.1% (34/87) patients were MRD negative after induction chemotherapy, and 49.3% (34/69) patients were MRD negative within 1 year after autologous hematopoietic stem cell transplantation (ASCT) . MRD-negative patients after induction chemotherapy or after transplantation have better progress-free survival (PFS) than MRD-positive patients (P=0.022 and P<0.001) . According to the changes of MRD pre-ASCT and after ASCT, the patients were divided into 4 groups: patients with MRD continued negativity,improved from MRD positive to MRD negative, MRD continued positivity, transformed from MRD negative to MRD positive. The two-year PFS of the four groups were 83%, 82%, 44%, 0, respectively, (P=0.002) . Multivariate analysis showed that the level of MRD after induction chemotherapy was an independent factor for PFS (P=0.002) , HR=4.808 (95%CI 1.818-12.718) . Conclusion: Patients with MRD negative after treatment is a better prognosis marker than complete remission or even the best marker, which can evaluate prognosis by combining R-ISS and cytogenetic changes.

[Comparison of visual effects after LASIK in myopia between centered on the coaxially sighted corneal light reflex and line of sight].

OBJECTIVE: To compare visual acuity, refractive outcome, high order aberrations, contrast sensitivity and subjective symptom of myopia with laser in situ keratomileusis (LASIK) centered on the coaxially sighted corneal light reflex (CSCLR group) and the conventional ablation of line of sight (LOS group). METHODS: With prospective, double-blind, randomized, controlled trial, the right eyes of patients were included and divided into two groups according to random stratified grouping. Two hundred and ten myopic eyes were treated with centration on the coaxially sighted corneal light reflex and 210 myopic eyes treated with centration on pupil center(line of sight). The parameters of visual acuity, refractive outcome, ablation center distance from visual axis, corneal high order aberrations, subjective discomfort glare and shadowing incidence rate, contrast sensitivity between the two groups were measured and compared up to 6months post operation. Consistent with the measurement data, normal distribution using the group t-test, non-normal distribution of measurement data using the group wilcoxon rank-sum test and count data using chi-square test. RESULTS: The data of postoperative UCVA, BCVA, MRSE efficacy index and safety index showed no statistical difference between the CSCLR and the LOS group up to 6months post operation(P> 0.05). 3% lost one line or more of BCVA in the CSCLR group,and 9% in the LOS group postoperatively, χ(2)= 6.38, P=0.01. The ablation center deviation was (0.19±0.15) mm from visual axis(pentacam system default setting) in CSCLR group and (0.43±0.22) mm in the LOS group. Ablation center deviation was statistically significantly shorter in the CSCLR group (t=-2.59, P<0.01). The postoperative increased total cornea higher order aberrations was 0.150 µm in CSCLR group and 0.193 µm in LOS group, the difference was statistically significant, Z=3.21, P=0.03. The increased corneal vertical coma of CSCLR group was 0.321 µm,smaller than in the LOS group(0.464 µm), Z=4.33, P<0.01. The increased horizontal coma was 0.242 µm in CSCLR group and also smaller than the LOS group(0.353 µm), Z=4.54,P<0.01. Subjective discomfort glare and shadowing incidence rates were 8.5% and 17.5% respectively in the CSCLR and LOS group, χ(2)=7.16,P< 0.01. The one month postoperative contrast sensitivity visual acuity in the CSCLR was 1.157 ± 0.253, significantly higher than the LOS group (0.797±0.218) on 18 c/d spatial frequency, t=- 2.55, P=0.01, but with no significant difference between the two groups at 3 and 6 months. CONCLUSIONS: Myopic LASIK centered on the CSCLR achieved significant lower induction of lost of BCVA, lower induction of high order aberrations, lower risk of subjective discomfort glare and shadowing and lower decline of early contrast sensitivity by comparison to centration on the LOS, improving the quality of vision after operation. (Chin J Ophthalmol, 2016, 52: 499-506).

Age-related changes in anatomic bases for the insertion of zygomatic implants.

The objectives of this study were to verify whether Chinese patients are well-suited for zygomatic implantation and to observe age-related changes in the linear and angular anatomic bases of the maxilla and zygoma. Using three-dimensional images selected from maxillofacial cone beam computed tomography (CBCT) scans generated by SimPlant, linear and angular measurements were obtained by simulating zygomatic implantation. The edentulous group comprised 40 subjects aged between 62 and 65 years. A total of 120 dentate cases were divided into three groups based on age: the established occlusion group (n=40; 12-15 years old), the adult group (n=40; 37-40 years old), and the elderly group (n=40; 62-65 years old). The mean potential insertion length of the ordinary and additional zygomatic implants became longer with age in the dentate groups. For both zygomatic implant insertion areas, the anteroposterior lengths of the maxilla and zygoma were thicker in the older dentate groups (P<0.05). Significant differences were verified in the installation direction among the dentate groups. Gender was not a significant factor. The zygomatic skeleton changes with age, which results in linear and angular variations in the zygomatic implant insertion area. Therefore, the anatomic bases in Chinese adults are suitable for zygomatic implants.

Human papillomavirus infection in Shenyang City, People's Republic of China: A population-based study.

To investigate the prevalence of, and risk factors for, cervical infection with human papillomavirus (HPV) in Shenyang City, People's Republic of China, we interviewed and obtained cervical cell samples from 685 women aged 15-59 years enumerated from local population lists. Human papillomavirus DNA was detected in cervical cell samples using a GP5+/6+-based PCR assay for 44 HPV types. Human papillomavirus prevalence was 16.8% overall and 13.6% among women without cervical abnormalities (16.6% and 12.4%, respectively, age-standardised to the world standard population), with no significant trends in HPV prevalence by age group. Of the 32 types identified, high-risk HPV types predominated in all age groups, HPV16 being the most common (3.4% of all women), followed by HPV52 (2.5%) and 58 (1.9%). Multiple-type infections accounted for 31.3% of all infected women. Not being married, reporting multiple sexual partners and husband's extramarital sexual relationships were all significantly associated with being HPV-positive. The disclosure of a relatively high HPV prevalence in Shenyang, in comparison with other worldwide populations, raises important questions concerning the prevention of cervical cancer in China, especially given the promising efficacy of prophylactic HPV vaccines.

Association of haemoglobin level with morbidity and mortality of patients with locally advanced oesophageal carcinoma undergoing radiotherapy--a secondary analysis of three consecutive clinical phase III trials.

AIMS: To investigate the strength of association between anaemia and overall survival, locoregional control, and late radiation complications in patients with locally advanced oesophageal carcinoma undergoing radiotherapy with or without chemotherapy and hyperthermia. MATERIALS AND METHODS: Between March 1996 and December 2002, 303 patients with locally advanced squamous cell carcinoma of oesophagus enrolled in three consecutive prospective phase III trials conducted in our department were included in this study. These patients received one of the following four irradiation schedules: late course accelerated hyperfractionated (LCAF) radiotherapy alone, LCAF combined with concurrent chemotherapy, LCAF combined with hyperthermia, and continuous accelerated hyperfractionated (CAHF) radiotherapy according to each protocol. According to the haemoglobin levels measured before radiotherapy, patients were stratified to normal haemoglobin group (> or = 12.0 g/dl for men, or > or = 11.0 g/dl for women) or anaemic group (< 12.0 g/dl for men, or < 11.0 g/dl for women). Overall survival, locoregional control rate and late irradiation toxicity were estimated by Kaplan-Meier method. RESULTS: Of 303 eligible patients, 243 patients (80.2%) had normal haemoglobin level and 60 patients (19.8%) were anaemic. The 5-year overall survival was 39% in patients with normal haemoglobin level, whereas, 22%, with anaemia patients (P = 0.001). The 5-year locoregional control rate at 5 years was 68% in patients with normal haemoglobin, versus 62%, with anaemia patients (P = 0.050). The 5-year rate of radiation toxicity of grade 3 or greater was 29% in patients with normal haemoglobin level, but it was 8%, with anaemic patients (P = 0.033). From multivariate analyses, T stage, location of tumour and haemoglobin level were found to be independent predictors for survival. T stage, gender and haemoglobin level were independent predictors for locoregional control. It was also detected that age and haemoglobin level played as independent predictors for development of radiation toxicity. CONCLUSIONS: For patients with locally advanced oesophageal carcinoma undergone irradiation, anaemia associated a statistically significant reduction in survival and locoregional control rates, but also decreased radiation toxicity rates. Therefore, haemoglobin level should be considered as a stratification variable in prospective clinical trials.

A patient with 17 primary tumours and a germ line mutation in TP53: tumour induction by adjuvant therapy?

We report the case history of a woman with a germ line mutation in the TP53 gene who developed 17 separate primary tumours. The incidence of new tumours rose steeply after adjuvant tamoxifen treatment for breast cancer and adjuvant vaginal vault radiotherapy for endometrial cancer. This increase could be due to cumulative genetic damage from environmental agents and the fact that the patient lived to the relatively late age of 60 years, or to a high inherent deleterious somatic mutation rate, which could represent the inability of cells from patients with TP53 mutations to repair therapy-induced genetic damage.

Combined single course carboplatin with radiotherapy in treatment of stage IIA,B seminoma--a preliminary report.

Twenty-one patients with Stage IIA or B seminoma have been treated post orchidectomy by a single course of carboplatin prior to conventional radiotherapy in either the Royal Marsden Hospital or the Norwegian Radium Hospital during 1989-1993. Follow-up ranged from 8 months to 51 months with a mean of 36 months and median 34 months. All patients achieved complete remission and remain disease free. The main side-effects were nausea and vomiting while haematological toxicity was slight. There was no symptomatic peripheral neuropathy, ototoxicity or deterioration of renal function. This combined modality approach is rational, feasible, and effective, although a larger number of patients with longer term follow-up are needed for reasonable comparison with the use of infradiaphragmatic radiotherapy alone.

Application of 2-chlorotrityl resin in solid phase synthesis of (Leu15)-gastrin I and unsulfated cholecystokinin octapeptide. Selective O-deprotection of tyrosine.

The carboxyl terminal dipeptide amide, Fmoc-Asp-Phe-NH2, of gastrin and cholecystokinin (CCK) has been attached in high yield through its free side chain carboxyl group to the acid labile 2-chlorotrityl resin. The obtained peptide resin ester has been applied in the solid phase synthesis of partially protected (Leu15)-gastrin I utilising Fmoc-amino acids. Quantitative cleavage of this peptide from resin, with the t-butyl type side chain protection intact is achieved using mixtures of acetic acid/trifluoroethanol/dichloromethane. Under the same conditions complete detritylation of the tyrosine phenoxy function occurs simultaneously. Thus, the solid-phase synthesis of peptides selectively deprotected at the side chain of tyrosine is rendered possible by the use of 2-chlorotrityl resin and Fmoc-Tyr(Trt)-OH. The efficiency of this approach has been proved by the subsequent high-yield synthesis of three model peptides and the CCK-octapeptide.

[Inhibitory effects of jian pi li qi Chinese medicinal herbs on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in rats].

Chinese medicinal herbs with Jian Pi Li Qi action were tested for their effects in inhibiting the precancerous lesions, gamma-GT positive hepatocellular foci and the expression of oncogenes (N-ras, Ha-ras) in male SD rats. The rats were given one i.p. dose of initiator DEN within 24 hours after 2/3 partial hepatectomy. The livers of sacrificed rats were processed to gamma-GT histochemical staining and measuring of oncogenic expression. The results of these two parameters showed that Chinese medicinal herbs with Jian Pi Li Qi action are effective in inhibiting the precursory lesions of liver cancer in rats.

DNA flow cytometric analysis of human nasopharyngeal carcinoma in nude mice.

The tissue from a patient with nasopharyngeal carcinoma has been transferred to nude mice (BALB/c), and has successfully been growing through twenty passages. The tumors in the nude mice and primary human tumor have been examined for the cellular DNA content by FCM and also conventional pathological examination, chromosome analysis, and EBV test. The tumor take rate varied markedly in different passages with a mean value of approximately 70%, and showing a tendency to increase. The tumor doubling time within 6-12 weeks after transplantation of six tumors in 18 and 20 passages were 14.8 and 9.3 days respectively. However, the tumor volume at 12 weeks varied significantly, ranging from 438 to 1998 mm3. By FCM, it has been found that the values of DNA index were about the same in both primary tumor and the tumors in nude mice. The distribution of various phase cells in cell cycle was also about the same in both. In conclusion, the application of FCM to examine the cellular DNA content of the tumor in nude mice is a rapid and sensitive method, useful in the investigation on the stability of biological characteristics of human NPC in nude mice and in further studies on the effects by various therapeutic methods.