Clinicopathological and surgical factors associated with long-term survival in patients with HER2-positive metastatic breast cancer.

Trastuzumab-based treatment has dramatically improved the outcomes of HER2-positive (HER2+) metastatic breast cancer (MBC) patients, with some patients achieving prolonged survival times. In this study, we aim to identify factors that are associated with long-term survival. Patients with HER2+ MBC treated with anti-HER2 target therapy were identified. Patients were grouped according to overall survival (OS) and categorized as long-term survivors (LTS, OS ≥ 5 years), or non-long-term survivors (non-LTS, OS < 5 years). Descriptive statistics and multivariable logistic regression modeling were used. A sensitivity analysis was carried out, including only patients diagnosed before 2007; therefore, 5 years of potential follow-up was possible. 1063 patients with HER2+ MBC diagnosed between 1994 and 2012 and treated with anti-HER2 therapy were identified. Among them, 154 (14.5 %) patients were categorized as LTS (median OS 92.2 months). Among LTS, 63.4 % were HR-positive and 32 % had de novo stage IV disease. Hormone receptor positivity (OR) 1.69; 95 % CI 1.17-2.44), resection of metastases (OR 2.38; 95 % CI 1.53-3.69), and primary breast surgery in patients with de novo stage IV (OR 2.88; 95 % CI 1.47-5.66) were associated with improved long-term survival. Greater number of metastatic sites (≥3 vs. 1, OR 0.41; 95 % CI 0.23-0.72) and visceral metastases (OR 0.61; 95 % CI 0.4-0.91) were associated with poor survival. Hormone receptor positivity, low burden of disease, metastasis to soft and bone tissues, and surgical management with resection of the metastatic site and the primary tumor were associated with long-term survival in patients with MBC who received anti-HER2 treatment.

Quality-of-life outcomes from a randomized phase III trial of dose-dense weekly paclitaxel and carboplatin compared with conventional paclitaxel and carboplatin as a first-line treatment for stage II-IV ovarian cancer: Japanese Gynecologic Oncology Group Trial (JGOG3016).

BACKGROUND: Dose-dense weekly paclitaxel (Taxol) and carboplatin (dd-TC) improved survival compared with conventional tri-weekly paclitaxel and carboplatin (c-TC) as a first-line chemotherapy for newly diagnosed stage II-IV ovarian cancer in the Japanese Gynecologic Oncology Group 3016 trial. We report the quality-of-life (QoL) results from this trial. PATIENTS AND METHODS: A total of 637 patients were randomly assigned to receive c-TC or dd-TC (c-TC, n = 319; dd-TC, n = 312) and were asked to complete a QoL assessment at baseline, just after the third and sixth chemotherapy cycles, and at 12 months after randomization. QoL was assessed using Functional Assessment of Cancer Therapy (FACT)-general (FACT-G), FACT-taxane subscale (FACT-T), and FACT-ovary subscale (FACT-Ov). The overall QoL and that according to each subscale were analyzed using mixed-effects models adjusted for treatment and time. RESULTS: Baseline QoL assessment was completed by 204 out of 319 (63.9%) and 200 out of 312 (64.1%) patients in the c-TC and dd-TC groups, respectively. In these groups, the compliance rates with regard to QoL assessment were 74.5% and 73.0%, respectively, after three chemotherapy cycles; 86.8% and 86.9%, respectively, after six chemotherapy cycles; and 74.2% and 71.6%, respectively, at 12 months after randomization. The overall QoL did not differ significantly between the two treatment groups up to 12 months after randomization (P = 0.46). However, QoL according to the FACT-T subscale was significantly lower in the dd-TC group than in the c-TC group (P = 0.02). CONCLUSION: dd-TC does not decrease overall QoL compared with c-TC.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer was published in 2022. It was therefore decided, by both the ESMO and the Indian Society of Medical and Paediatric Oncology (ISMPO), to convene a virtual meeting in July 2022 to adapt the ESMO 2022 guidelines to take into account the variations in the management of endometrial cancer in Asia. These guidelines represent the consensus opinion of a panel of Asian experts representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). Voting was based on scientific evidence and was conducted independently of the current treatment practices and treatment access constraints in the different Asian countries, which were discussed when appropriate. The aim of this guideline manuscript is to provide guidance for the optimisation and harmonisation of the management of patients with endometrial cancer across the different regions of Asia, drawing on the evidence provided by Western and Asian trials whilst respecting the variations in clinical presentation, diagnostic practices including molecular profiling and disparities in access to therapeutic options, including drug approvals and reimbursement strategies.

Mating disruption by a synthetic sex pheromone in the white grub beetle Dasylepida ishigakiensis (Coleoptera: Scarabaeidae) in the laboratory and sugarcane fields.

A serious sugarcane pest, Dasylepida ishigakiensis, remains in the soil during most of its life cycle except for a short period for mating. Mating disruption by an artificial release of the sex pheromone (R)-2-butanol (R2B), therefore, may be a feasible method to control this pest. We examined the effects of artificial release of R2B and its related compounds, (S)-2-butanol (S2B) and the racemic 2-butanol (rac-2B), on the mating success of this beetle both in the laboratory and in the field. In flight tunnel experiments, almost all males orientated towards a R2B-releasing source and 40% of them landed on the source. When the atmosphere was permeated with R2B, the frequency of males landing on the model was significantly reduced. Both rac-2B and S2B were less effective, but substantial reduction in landing success by males was achieved at higher rac-2B concentrations. R2B released from polyethylene dispensers in sugarcane plots greatly reduced not only the proportion of females mated with males but also the number of males caught by R2B-baited traps, indicating that male mate-searching behaviour was strongly affected by the released R2B. Similar inhibitory effects on male behaviour were also observed when tube- or rope-type dispensers released high rac-2B concentrations in the field. These results indicate that it would be highly possible to control D. ishigakiensis through the disruption of the sexual communication by releasing either synthetic R2B or rac-2B.

Ultrahard diamond indenter prepared from nanopolycrystalline diamond.

Knoop indenters were prepared from nanopolycrystalline diamonds (NPDs) synthesized by direct conversion sintering from graphite under high pressure and high temperature. Owing to the fine structure (grain size: 10-100 nm) of NPD, high-accuracy sharp edges could be formed at the indenter tips. The indentation tests demonstrated that the NPD indenter can form normal (measurable) indentations on NPD samples without fracture or chipping even at high temperatures of up to 1000 degrees C, while conventional indenters made of single-crystal diamonds break easily above 600 degrees C. This suggests that the NPD indenter has greater potential in high-temperature hardness tests than the conventional single-crystal diamond indenters.

Note: Evaluation of microfracture strength of diamond materials using nano-polycrystalline diamond spherical indenter.

Ultra-hard and high-strength spherical indenters with high precision and sphericity were successfully prepared from nanopolycrystalline diamond (NPD) synthesized by direct conversion sintering from graphite under high pressure and high temperature. It was shown that highly accurate and stable microfracture strength tests can be performed on various super-hard diamond materials by using the NPD spherical indenters. It was also verified that this technique enables quantitative evaluation of the strength characteristics of single crystal diamonds and NPDs which have been quite difficult to evaluate.

gamma-Globin gene triplication and quadruplication in Japanese newborns. Evidence for a decreased in vivo expression of the 3'-A gamma-globin gene.

Cord blood samples of 113 Japanese babies from Kurashiki, Japan, were analyzed for the presence of possible modifications in gamma-globin gene arrangements and for changes in the relative quantities of the gamma chains G gamma, A gamma, and its variant A gamma T. As many as 9 babies had the gamma-globin gene triplication, one a gamma-globin gene quadruplication, and two a gamma-globin gene deletion. The triplication and quadruplication involved cross-overs within the G gamma- and A gamma-globin genes resulting in a hybrid gene with the 5'-segment being derived from the A gamma and the 3'-segment from the G gamma-globin gene (-AG gamma-). The G gamma value of the 9 babies with the -G gamma-AG gamma-A gamma-globin gene arrangement averaged approximately 80% and that of the baby with -G gamma-AG gamma-AG gamma-A gamma- was 78%. Four of the 9 babies with the triplication and the baby with the quadruplication had an A gamma T mutation in trans; in these babies, the A gamma chain level (from the A gamma-globin gene in 3'-position in the tri- and quadruplication arrangements) was decreased to about one-third and one-sixth of the level observed in the simple A gamma T heterozygote. This observation supports the suggestion that transcription beginning at the 5'-gamma-globin gene interferes with that of the 3'-gamma-globin gene.

A new hemoglobin variant, Hb Mito [beta 144(HC 1) Lys----Glu], with increased oxygen affinity.

A new abnormal hemoglobin, Hb Mito [beta 144(HC 1) Lys----Glu], with an amino acid substitution in the 2,3-DPG pocket, was discovered in a Japanese female. This hemoglobin showed increased oxygen affinity, and decreased organic phosphate and Bohr effects, while the Hill constant n was normal.

Hemoglobin Okayama [beta 2 (NA 2) His replaced by Gln]: a new 'silent' hemoglobin variant with substituted amino acid residue at the 2,3-diphosphoglycerate binding site.

A new 'silent' abnormal hemoglobin, Hb Okayama [beta 2 (NA 2) His replaced by Gln], happened to be discovered in a diabetic Japanese female living in Okayama Prefecture, Japan, in the course of glyco-Hb measurement of the blood samples of diabetic patients. This variant did not differ from Hb A by conventional electrophoretic tests. Only the isoelectric focusing on PAG plate for the determination of glyco-Hb and the cation exchanger chromatography were successful in the separation of this abnormal variant from Hb A and glyco-Hb. Functional study of the whole blood demonstrated a slight increase of oxygen affinity.

Hemoglobin Aichi [alpha 50(CE8) His----Arg]: a new slightly unstable hemoglobin variant discovered in Japan.

A new abnormal hemoglobin, Hb Aichi [alpha 50(CE8) His----Arg], was discovered in a young Japanese man. This variant was isoelectrofocussed between Hb A and Hb A2 and amounted to about 21% of the total hemoglobin in the hemolysate. This hemoglobin showed normal oxygen affinity but slight instability.

Hb Okazaki [beta 93(F8) Cys----Arg], a new hemoglobin variant with increased oxygen affinity and instability.

A new abnormal hemoglobin, Hb Okazaki [beta 93(F9) Cys----Arg], with an amino acid substitution at the tyrosine pocket of the beta chain as well as at the alpha 2 beta 1 contact of the quaternary structure of molecule, was discovered in a Japanese man. This hemoglobin showed increased oxygen affinity and molecular instability.

Hemoglobin Kariya [alpha 40 (C5) Lys leads to Glu]: a new hemoglobin variant with an increased oxygen affinity.

A new abnormal hemoglobin, Hb Kariya [alpha 40 (C5) Lys leads to Glu], with an amino acid substitution at the alpha 1 beta 2 contact was discovered in a young Japanese man. This variant migrated to the anode faster than Hb A, being nearly the same as Hb I in electrophoretic mobility. It amounted to about 6% of the total hemoglobin of the hemolysate. This hemoglobin showed an increased oxygen affinity, decreased heme-heme interaction and a lowered 2,3-DPG effect.

An antiserum to a synthetic fimbrial peptide of Actinobacillus actinomycetemcomitans blocked adhesion of the microorganism.

The purpose of this study is to certify the importance of the fimbriae as an attachment factor of Actinobacillus actinomycetemcomitans, a human periodontopathic bacterium, and the significance of anti-fimbrial antibody function as an attachment inhibitor. Fimbrial antigen was prepared from the A. actinomycetemcomitans 310-a strain. Oligopeptides were synthesized according to the amino acid sequence of the fimbrial protein. The peptide antigen was conjugated with branched lysine polymer resin beads. The peptide antigen was suspended in PBS emulsified with incomplete Freund's adjuvant and used to immunize rabbits. A rabbit antiserum reacted with an approximately 54 kDa protein of the fimbriae protein from A. actinomycetemcomitans 310-a and with those of other fimbriated strains. This antiserum strongly inhibited the attachment of fimbriated A. actinomycetemcomitans strains to saliva-coated hydroxyapatite beads, buccal epithelial cells, and a fibroblast cell line, Gin-1. Such a synthetic fimbrial peptide antigen may be effective in inducing antibodies which inhibit adhesion and subsequent colonization by A. actinomycetemcomitans.

Hemoglobin Pitié-Salpétrière [beta 34 (B16) Val-->Phe] showing erythrocytosis and mild hemolysis in a Japanese man.

We report the first case of Hemoglobin Pitié-Salpétrière (Hb P-S) identified among the Japanese population. The patient was a 33-year-old man referred to us because of severe erythrocytosis and mild hemolysis. DEAE high-performance liquid chromatography showed an abnormal broad peak around Hb A2 peak. Isoelectrofocusing detected abnormal Hb at the position of the Hb F band, and the content of abnormal Hb was estimated at about 25%. An instability test according to the isopropanol precipitation method was positive, and the beta/alpha ratio of biosynthesized globin was slightly reduced. Structural analyses demonstrated the substitution of phenylalanine for valine at beta 34, which was also confirmed by DNA sequencing; that is a single base substitution of GTC-->TTC at codon 34 of beta chain. From these findings, the abnormal Hb was identified as being a high-oxygen-affinity variant, Hb P-S (beta 34 [B16] Val-->Phe). Hb P-S was detected in the patient's mother but not in his father, suggesting that the inheritance pattern is autosomal dominant. It was suggested that the slightly unstable state of Hb P-S caused by the looseness of alpha 1 beta 1 contact could result in mild hemolysis.

Band 4.2 Komatsu: 523 GAT-->TAT (175 Asp-->Tyr) in exon 4 of the band 4.2 gene associated with total deficiency of band 4.2, hemolytic anemia with ovalostomatocytosis and marked disruption of the cytoskeletal network.

A novel mutation of 523 GAT-->TAT (175 Asp-->Tyr) in exon 4 of the band 4.2 gene was detected in a 37-year-old Japanese patient with total lack of band 4.2 protein, designated as allele 4.2 Komatsu. In this patient, moderate uncompensated hemolytic anemia (red cell count 3.38 x 10(6)/microliters, hemoglobin 10.8 g/dl, hematocrit 30.9%, reticulocytes 12.4%, indirect bilirubin 1.84 mg/dl) with ovalostomatocytosis and increased osmotic fragility had been noted since birth. Family studies revealed no overt hemolytic anemia in other family members, essentially normal red cell morphology, and a normal profile of red cell membrane proteins including band 4.2. Genetic studies proved that the proband was homozygous and all the family members studied were heterozygous with respect to the mutation of 523 GAT-->TAT of the band 4.2 gene. Although band 4.2 was completely absent in the proband, trace amounts of 72 kDa and 74 kDa peptides were detected in the red cells of all the family members, in which the mutation of 424 GCT-->ACT at exon 3 of the band 4.2 gene (Nippon type) was not present. Electron microscopic studies with the surface replica method and the quick-freeze deep-etching method showed the most marked disorganization of the cytoskeletal network in the patient's red cells in situ among the cases of band 4.2 deficiencies we have studied. This suggests that the amino acid of the band 4.2 protein, which was affected by the present mutation in exon 4, is much more crucial for the functioning of band 4.2 protein than that at codon 142 in exon 3. The cytoplasmic domain of band 3 in the proband's red cells was essentially normal in protein chemistry and in gene analysis with single-stranded conformation polymorphism (SSCP).

Prevention by ulinastatin of decreased carbonic anhydrase activity induced by PMN elastase in vitro.

Disturbed carbon dioxide (CO2) elimination in adult respiratory distress syndrome (ARDS) has been considered to result from the dead space created by microthrombosis and vasoconstriction. However, another disturbance factor in CO2 elimination has been reported; the chemical dead space resulting from the inhibition of carbonic anhydrase (CA). This experiment was conducted to quantify the inhibition of CA activity by polymorphonucleocyte (PMN) elastase, which increases in ARDS. Different flasks containing solutions of CA, buffer, elastase, ulinastatin (an elastase antagonist), CA with PMN elastase, and CA with both PMN elastase and ulinastatin were prepared. Each flask was injected with sodium bicarbonate labeled with radioactive carbon (14C) and was shaken for 20 minutes; CA activity in each flask was measured by calculating the decrease in the coefficient (K) of 14C. It was observed that CA activity was inhibited dose-dependently by PMN elastase and that the inhibited activity was recovered by ulinastatin, which can inhibit PMN elastase. These findings indicate that CA activity in vitro could be inhibited by PMN elastase, which increases in ARDS, and suggests that disturbance of CO2 elimination could be reduced by using ulinastatin. It was concluded that ulinastatin could prevent the CA activity induced by PMN elastase in vitro.

Methoxylation of 3beta,7alpha-dihydroxychol-5-en-24-oic acid, a key intermediate of chenodeoxycholic acid biogenesis, compared with that of its 7beta-epimer.

The conventional methods of gas liquid chromatography or mass spectrometry failed to be useful for the identification of the biliary 3beta,7alpha-dihydroxychol-5-en-24-oic acid, a key intermediate of chenodeoxycholic acid biogenesis. It has been preliminarily reported that this acid in human bile was successfully identified by gas chromatography-mass spectrometry, after the methoxylation of its allyl alcohol group. Physical as well as spectral properties of the methoxylation products derived from the acid were reported, compared with those from its 7beta-epimer.

3alpha-Hydroxy-5beta,14beta-chol-8-en-24-oic acid and its isomer, dehydration products of chenodeoxycholic acid obtained by treatment with concentrated HC1.

3alpha, 7alpha-Dihydroxy-5beta-cholan-24-oic acid in acetic acid was treated with concentrated hydrochloric acid at room temperature. Two of the dehydration products thus obtained proved to correspond to the beta- and gamma-acids reported (5). One (gamma-acid) of these was identified as 3alpha-hydroxy-5beta, 14beta-chol-8-en-24-oic acid (IIa) by means of several spectral measurements of itself and its OsO4 oxidation products. Chemical structure of the other (beta-acid) remains undetermined.

High prevalence of antibody to Toxoplasma gondii among humans in Surabaya, Indonesia.

Infection with Toxoplasma gondii is of medical importance in relation to a recent increase in cases of acquired immunodeficiency syndrome (AIDS). In the present study, we surveyed antibody to Toxoplasma among 1,761 people in Surabaya, Indonesia. The overall prevalence was 58% with significant differences between males (63%) and females (52%; P < 0.001). Although antibody prevalences at 0-9 years in both genders were less than 10%, those at ages over 10 years were more than 50% in males or more than 40% in females, suggesting an extremely high transmission rate of the parasite to humans in this area. A bimodal pattern in the frequency distribution of Toxoplasma antibody levels suggested a persistent feature of Toxoplasma infection in humans.

Hb Ube-2 in a diabetic case with an abnormally low HbA1C value.

A 69-year-old male diabetic patient had an abnormally low HbA1C value of 2.8%, which was inconsistent with his elevated fasting plasma glucose of 8.2 mmol/l. Hb analysis disclosed that the abnormal Hb was Hb Ube-2 [alpha68 (E17) Asn --> Asp] and it accounted for 21.5% of the total Hb. Since the glycated abnormal Hb emerged at the same position as did HbF on high performance liquid chromatography, the HbA1C value was falsely low. The present case demonstrates that Hb Ube-2 is one of the abnormal Hbs in which caution should be exercised when monitoring diabetic control.