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Biomedical subjects

H Inohara

Publications and source records attributed to H Inohara.

25 records · Page 2Linked to original sources

Effects of natural complex carbohydrate (citrus pectin) on murine melanoma cell properties related to galectin-3 functions.

Citrus pectin (CP) and pH-modified citrus pectin (MCP) are highly branched and non-branched complex polysaccharides, respectively, rich in galactoside residues, capable of combining with the carbohydrate-binding domain of galectin-3. We reported previously that intravenous injection of B16-F1 murine melanoma cells with CP or MCP into syngeneic mice resulted in a significant increase or decrease of lung colonization, respectively (Platt D, Raz A (1992) J Natl Cancer Inst 84:438-42). Here we studied the effects of these polysaccharides on cell-cell and cell-matrix interactions mediated by carbohydrate-recognition. MCP, but not CP, inhibited B16-F1 melanoma cells adhesion to laminin and asialofetuin-induced homotypic aggregation. Both polysaccharides inhibited anchorage-independent growth of B16-F1 cells in semisolid medium, i.e. agarose. These results indicate that carbohydrate-recognition by cell surface galectin-3 may be involved in cell-extracellular matrix interaction and play a role in anchorage-independent growth as well as the in vivo embolization of tumour cells.

Animals↗

Endoscopic examination of the upper gastrointestinal tract for the presence of second primary cancers in head and neck cancer patients.

Endoscopic examination of the upper gastro-intestinal tract with Lugol's solution staining was performed on 150 patients with head and neck cancer treated at the Departments of Otolaryngology and Radiology, Osaka University Hospital, between June 1987 and December 1991. Thirteen second primary cancers (11 esophageal and 2 gastric cancers) were found endoscopically, although prior fluoroscopy had found only 4 (3 esophageal and one gastric cancer). All of the 9 second primary cancers which were not detected by fluoroscopy were in the early stage. Both Brinkman's and Alcohol indices of double primary cancer cases were significantly higher than those of single head and neck cancer cases. These results indicate that head and neck cancer patients who smoke and/or drink heavily require thorough examination of their upper gastro-intestinal tract with endoscopy, using Lugol's solution staining, as well as with fluoroscopy.

Adenocarcinoma↗

Reduction of leaky lymphocyte clones producing immunoglobulins and thymic lymphocytic leukemia by selective inbreeding of SCID (severe combined immunodeficiency) mice.

Selective inbreeding of C.B17-scid/scid mouse pairs showing undetectable IgG and IgM has been carried out in order to reduce the mortality of mice by early occurrence of thymic lymphocytic leukemia and abnormal lymphocyte clones producing immunoglobulins, both of which inhibit the successful heterotransplantation of normal and neoplastic human tissues. Although the majority of C.B17-scid/scid mice showed undetectable (< 1 microgram/ml) or low level (< or = 25 micrograms/ml) of serum IgG and IgM, some produced abnormally high concentrations of IgG and IgM (> 25 micrograms/ml). The incidence of such mice showing higher levels of IgG was very high at F1 and F2 generation (10/55, 18.2%), but significantly low after the F3 generation (18/446, 4.0%, p << 0.001). Although leukemia incidence was very high at F4 to F5 generations (8/40, 20.0%), death from leukemia was not observed early in life (4-6 months after birth) at F7 to F10 generations (0/36, 0%, p < 0.01) and was very low during the age of 6-10 months after the F8 generation (11/66, 16.7% at F4 and F5 vs 4/93, 4.3% at F8-10), p < 0.01). Scid mice improved by the selective inbreeding will provide an invaluable experimental system for the heterotransplantation of normal and neoplastic human tissues.

Animals↗

Growth and metastasis of fresh human benign and malignant tumors in the head and neck regions transplanted into scid mice.

Surgically resected fresh human tumors (16 malignant and 1 benign) in the head and neck regions were s.c. transplanted into scid mice. All malignant tumors (12 squamous cell carcinomas, 2 papillary adenocarcinomas and 1 adenoid cystic carcinoma) except one heavily irradiated squamous cell carcinoma could grow in scid mice. However, all of three squamous cell carcinomas of the maxillary sinus grew only in 50% of scid mice, and two of them failed to grow in the second transfer. The remainder were successfully transplantable for further generations, except one accidental case. A benign tumor, a follicular adenoma of the thyroid gland, was also accepted in scid mice and was transplantable for further generations, though its growth was very slow. Distant metastases were found in the lung only when poorly differentiated carcinomas were transplanted into scid mice, but did not occur until 90 days after the transplantation of well and moderately differentiated carcinomas. The histological characteristics of both malignant and benign tumors were retained well in all of the xenografts and metastatic lesions. Thus, scid mice seem useful to investigate not only the properties of benign and malignant human tumors but also the metastatic spread of tumors which threaten the life of cancer patients.

Adenocarcinoma, Papillary↗

Rapid growth and spontaneous metastasis of human germinal tumors ectopically transplanted into scid (severe combined immunodeficiency) and scid-nudestreaker mice.

Xenograft acceptance, growth and spontaneous metastasis of ectopically transplanted human germinal tumors were compared among scid mice, athymic nude mice and F2 hybrids constructed from scid and nude mice, in relation to the impairments of T and B cell functions in these mice. In scid mice which are deficient in T and B cell functions, human yolk sac tumor (YST-2) that originated from the ovary grew to enormous sizes in 100% of the animals after both subcutaneous and intraperitoneal transplantation, while only half (59.1% and 51.9%) of the subcutaneous and none of the intraperitoneal transplants were accepted in usual athymic nude mice (BALB/c-nu/nu and CD1-nu/nu). The YST-2 grew rapidly in scid mice, developing 3 to 10 times larger tumors compared to nude-streaker (AKR/J-nustr/nustr) and usual nude mice, respectively. Furthermore, ectopically transplanted tumors spontaneously metastasized to distant organs (mostly to the lung) in scid mice (but less frequently in leaky scid mice), while metastases have never been found in nude mice. Although a xenograft of human classic (typical or pure) seminoma of the testis has never been established in nude mice, it grows slowly in one-third (36.4%) of scid mice and very rapidly in all of scid-nustr (scid/scid; nustr/nustr) double mutant mice. Spontaneous metastases of xenografted seminomas were also observed in distant organs (lymph node, lung, liver, spleen, and kidney). The metastastic distribution of the two human germinal tumors in scid and scid-nustr mice mimics that found in human. These results (xenograft acceptance, growth of transplanted tumors and degree of metastatic spread) were compatible with the level of T and B cell impairments indicated by FACS analysis, as well as mitogen responses, serum IgG and morphological features of the thymus.

Animals↗

SCID (severe combined immunodeficiency) mice as a new system to investigate metastasis of human tumors.

In severe combined immunodeficiency (scid) mice which are deficient in T and B cell functions, human yolk sac tumor (YST-2) grew rapidly to enormous sizes in all of the animals after both subcutaneous and intraperitoneal transplantation, while only half of the subcutaneous and none of the intraperitoneal transplants were accepted in usual athymic nude mice. Furthermore, transplanted tumors metastasized spontaneously to distant organs such as lung, liver, kidney, pancreas, and spleen in scid mice, while metastases were not found in athymic nude mice. Similar results were observed in scid mice and scid-nude (streaker) double mutant mice with human classic (typical) seminoma which has been neither transplantable nor metastatic in athymic nude mice. Thus, scid mice provide an invaluable experimental system to investigate the mechanism of metastasis which is the most important and life-threatening problem in cancer patients.

Animals↗

Production of transgenic fish: introduction and expression of chicken delta-crystallin gene in medaka embryos.

To produce a model of transgenic fish, recombinant plasmids containing chicken delta-crystallin gene were microinjected into the oocyte nucleus of a small teleost, medaka (Oryzias latipes). About 50% of the microinjected oocytes developed to 7-day-old embryos. By Southern blotting delta-crystallin gene was detected in 4 of 8 embryos, and, by Western blotting, delta-crystallin polypeptides in 5 of 16. In 1 of 6 examined histologically, delta-crystallin DNA was detected in all the tissues, and delta-crystallin polypeptides, in many of the tissues including the lens. Thus, the exogenous gene and/or its products were detected in 10 of 30 embryos examined. This is the first report of successful production of transgenic fish.

Animals↗